Podcasts about crispr therapeutics

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Best podcasts about crispr therapeutics

Latest podcast episodes about crispr therapeutics

ASCO Daily News
Practice-Informing Research Across GU Oncology: Highlights From GU25

ASCO Daily News

Play Episode Listen Later Feb 27, 2025 28:18


Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium?  Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18?  Dr. Neeraj Agarwal: Yes, Peter, I agree with you. It was such an exciting conference overall and thank you for your leadership of this conference. So, let's talk about the TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients.  Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment.   Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang?  Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract?  Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:   Dr. Neeraj Agarwal    @neerajaiims    Dr. Peter Hoskin Follow ASCO on social media:      @ASCO on Twitter      ASCO on Bluesky  ASCO on Facebook      ASCO on LinkedIn      Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers  

Business Of Biotech
Biotech Story Time With Tal Zaks, M.D. (Part 2)

Business Of Biotech

Play Episode Listen Later Jan 6, 2025 54:04 Transcription Available


We love to hear from our listeners. Send us a message. Dr. Tal Zaks is back, along with Advancing RNA's Anna Rose Welch, for part 2 of "Story Time With Tal." On this week's episode, we turn from his time navigating medical affairs as CMO at Moderna during the COVID 19 pandemic to learn about his latest venture, an mRNA startup called Exsilio Therapeutics. We cover the foundational aspects of the company's start, from the science it's developing, who's been recruited to the team, and how Exsilio charted its way to an $82 million Series A co-led by Novartis Venture Fund and Delos Capital, with participation from OrbiMed, Insight Partners, J.P. Morgan Life Sciences Private Capital, CRISPR Therapeutics, Innovation Endeavors, Invus, Arc Ventures, and Deep Insight.Access this and hundreds of episodes of the Business of Biotech videocast under the Listen & Watch tab at bioprocessonline.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: matt.pillar@lifescienceconnect.comFind Matt Pillar on LinkedIn: https://www.linkedin.com/in/matthewpillar/

BioSpace
Highlights From ASH, Lilly and Novo's Manufacturing Boon, Momentum in Neuro, More

BioSpace

Play Episode Listen Later Dec 11, 2024 10:00


This week, GSK and Gilead and Arcellx presented key data at the American Society of Hematology (ASH) annual meeting as they vie for a competitive advantage in multiple myeloma. Meanwhile, Vertex unveiled positive long-term data for its CRISPR Therapeutics–partnered gene therapy Casgevy in sickle cell disease—results BMO Capital Markets analysts said should help Casgevy keep its edge over bluebird bio's Lyfgenia. On that note, Casgevy and Lyfgenia have a new outcomes-based payment model after the Centers for Medicare and Medicaid Service (CMS) said both companies have agreed to participate in a voluntary program to improve access to the gene therapies. Speaking of access, Eli Lilly and Novo Nordisk both announced significant manufacturing investments aimed at shoring up production of their diabetes and weight loss blockbusters tirzepatide and semaglutide. And in related news, the European Commission gave its blessing to Novo Holdings' controversial acquisition of contract manufacturing firm Catalent. Elsewhere, AbbVie got a much-needed win for Cerevel-acquired Parkinson's disease therapy tavapadon—a month after the deal's cornerstone asset emraclidine failed in schizophrenia—while uniQure announced it has aligned with the FDA on “key elements” of the accelerated approval pathway for its investigational gene therapy for Huntington's, AMT-130.

BioSpace
Pfizer's Q3 Earnings Win, Deals Galore, Countdown to Election, More

BioSpace

Play Episode Listen Later Oct 30, 2024 17:43


Earnings heat up as Pfizer got a much-needed Q3 beat amidst criticism from activist investor Starboard Value. Novartis and Sanofi are among others that have outpaced Wall Street expectations this quarter, as Eli Lilly, Merck, AbbVie, Amgen, Biogen, GSK, Bristol Myers Squibb and Takeda are all reporting today and tomorrow. The past week has also seen a pack of deals, with AbbVie's $1.4 billion buy of Aliada Therapeutics, Roche's potential $1 billion deal with Dyno Therapeutics and Novartis' up to $2.1 billion commitment to Monte Rosa's molecular glue degraders. With less than a week until Election Day, we unpack what biopharma might expect under a Trump or Harris administration. We also take a look back at 10 years of BioSpace's NextGen list of top up-and-coming startups. A lot have been bought out by bigger companies—some for big money—while some, such as CRISPR Therapeutics, continue to operate independently. Finally, we took a close look at questions stemming from Sarepta's new data for Duchenne muscular dystrophy gene therapy Elevidys, and separately but not unrelatedly, at the FDA's accelerated approval pathway.

Chip Stock Investor Podcast
Episode 221: A Best Stock For 2025 and Beyond? Chip Stock Investors, Check This 1 Top Growth Stock Out Now

Chip Stock Investor Podcast

Play Episode Listen Later Oct 9, 2024 17:14


Check out the New Bond account with an initial APY of 6.9%, only at https://public.com/csi In this episode of Chip Stock Investor, the focus shifts to the biotech and big pharma sector, specifically examining Vertex Pharmaceuticals (VRTX). Following work on semiconductors' contribution to healthcare technology, Nick and Kasey discuss Vertex's current operations. Cystic fibrosis treatments and a partnership with CRISPR Therapeutics on a new treatment for blood diseases are the current moneymakers. But Vertex has a wide pipeline of other potential treatments, including those for type 1 diabetes and pain management, framing Vertex as an enduring growth business. Will VRTX be a top Chip Stock Investor non-chip stock for 2025? Join us on Discord with Semiconductor Insider: https://ko-fi.com/chipstockinvestor

BioSpace
Sickle Cell Gene Therapies Reach Patients, Moderna Cuts, Obesity Pill Race and ESMO 2024

BioSpace

Play Episode Listen Later Sep 18, 2024 17:56


After their groundbreaking approval last year, infusions of Vertex and CRISPR Therapeutics' and bluebird bio's sickle cell gene therapies have begun, bringing hope to patients and the companies closer to realizing revenue. Meanwhile, bispecifics and anti-TIGIT therapies were all the rage at ESMO 2024 as BioNTech, GSK and iTeos, BMS and more reported positive results across multiple cancers. Last week, Moderna announced it would slash its R&D budget by $4 billion as it targets 10 new approvals through 2027. Possibly boding well for this target, the biotech features prominently on our list of 5 late-stage mRNA vaccines to watch. Meanwhile, the oral obesity drug race continues to heat up, with Terns Pharmaceuticals, Roche and Novo Nordisk all reporting new data from their respective trials. And in the equally hot radiopharmaceuticals space, Sanofi inked a $110 million licensing deal with RadioMedix to develop a neuroendocrine tumor candidate. Finally, BioSpace takes a deep dive into the HEALEY ALS Platform Trial, which has so far seen quick failures and small victories as leaders and early participants remain hopeful.

Pharma and BioTech Daily
Biopharma Breakdown: The Latest in Pharma and Biotech News

Pharma and BioTech Daily

Play Episode Listen Later Sep 12, 2024 4:38


Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. This week's commercialization news includes Dupixent's success in a chronic hives study, Lilly's development of a weekly insulin shot, and BioMarin's plans for growth. The House backs a bill restricting China's role in US biotech, while Lykos CEO is set to depart after FDA rejection and layoffs. The newsletter also discusses key developments in cell therapy and offers insights on utilizing a direct-to-patient model in the healthcare industry. Various resources and upcoming events in the biopharma industry are also highlighted. Biopharma Dive provides in-depth journalism and insights into the latest news and trends shaping the biotech and pharma industries.BridgeBio has reduced its gene therapy budget after data from a trial on an adrenal gland medicine did not meet the company's investment threshold. GlaxoSmithKline has discontinued a herpes vaccine after it did not meet efficacy goals in a phase 2 study. Roivant has launched a new 'vant' focused on a hypertension drug. Centessa's sleepiness drug has shown promising results in early studies, leading to a rise in the company's shares. Additionally, Dupixent has succeeded in a chronic hives study, giving Sanofi and Regeneron a chance to resubmit their application for approval. Investors are also paying attention to Centessa's sleepiness drug. This news comes alongside updates on other pharmaceutical developments, such as Saxenda's effectiveness for children as young as 6 and Roche's expansion of R&D labs. Additionally, the newsletter covers upcoming events and resources for biopharma professionals. Biopharma Dive provides in-depth coverage of news and trends in the biotech and pharma industries, including clinical trials, FDA approvals, gene therapy, drug pricing, and research partnerships.Iowa has awarded Centene's subsidiary, Iowa Total Care, a Medicaid managed care contract worth $2.8 billion. Telehealth groups are urging Congress and the White House to extend controlled substance virtual prescribing before pandemic-era flexibilities expire. The Biden administration has finalized a rule raising mental health coverage standards for private plans. Steward Health Care received court approval to sell its three most valuable hospitals to Orlando Health for $439 million. The importance of data quality in realizing value from medical imaging data is emphasized by Enlitic. Payers are encouraged to optimize quality and grow revenue through key strategies in an upcoming webinar. Healthcare Dive provides in-depth journalism and insight into the most impactful news and trends shaping healthcare across various sectors like health IT, policy & regulation, insurance, digital health, payer-provider partnerships, and value-based care.Novo Nordisk showcased its investigational GLP-1 pill that resulted in a remarkable 13% weight loss. This comes after positive Phase I results for the pill, which analysts compared to weight loss pills being developed by Lilly and Pfizer. Expanded coverage for cardiovascular disease under Medicare could have significant implications for Novo's obesity drug, Wegovy. Analysts estimate that the expansion of Wegovy's label beyond obesity could lead to an annual Medicare spending of $145 billion. Meanwhile, GSK has abandoned the development of its herpes vaccine after disappointing Phase I/II results, and Crispr Therapeutics and Vertex Pharmaceuticals are facing challenges in making their sickle cell gene therapy profitable. Novo's other drug, Saxenda, was found to effectively and safely lower BMI in children, according to a study published in NEJM. Additionally, Lilly continues to make progress with its once-weekly insulin, while Bain has raised $3 billion for a fund supporting life sciences companies. The biopharmaceutical industry continues to see changes, with Biomarin facing challenges and Terns moving forward in the obesity spac

ASCO Daily News
GU Oncology Highlights from ASCO24

ASCO Daily News

Play Episode Listen Later Jun 27, 2024 34:54


Dr. Neeraj Agarwal and Dr. Rana McKay discuss promising studies in GU cancers featured at the 2024 ASCO Annual Meeting that highlighted improved outcomes in urothelial carcinoma, improved survival in renal cell carcinoma, and the role of ctDNA as a potential biomarker for predicting outcomes.   TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News.  I am delighted to welcome Dr. Rana McKay, a GU medical oncologist and associate professor at the University of California San Diego. Today, we'll be discussing some key GU abstracts featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Rana, we're thrilled to have you on the podcast today to share your insights on key advances in GU oncology from ASCO24. Dr. Rana McKay: Thank you so much, Neeraj; it's a pleasure to be here. Dr. Neeraj Agarwal: So, Rana, let's start with some bladder cancer abstracts. Could you tell us about Abstract 4503, titled “Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer”? Dr. Rana McKay: Of course, I would be delighted to. First, I would like to remind our listeners that enfortumab vedotin (EV) was approved as a monotherapy for the treatment of locally advanced or metastatic urothelial cancer based on the results of EV-201 and EV-301 trials. In these pivotal studies, EV was initiated at a dose of 1.25 mg/kg, and dose modifications, such as reductions and interruptions, were used to manage adverse events. In the abstract presented at ASCO 2024, Dr. Daniel Petrylak and colleagues conducted a post-hoc exploratory analysis to evaluate the association between EV plasma exposure and outcomes. They used multiple pharmacokinetic samples collected during the first two cycles and pre-dose samples from 3 EV monotherapy studies, namely EV-101, EV-201, and EV-301, that were conducted in patients with previously treated locally advanced or metastatic urothelial carcinoma. Dose reductions to 1 mg/kg were required in 42.1% and 35.1% of patients in the EV-201 and EV-301 trials, respectively, and reductions to 0.75 mg/kg were required in 13.6% and 11.1% in the EV-201 and EV-301 trials, respectively. Higher EV exposure during the first two cycles was associated with a higher objective response rate. The ORR was 21.4% for the dose of 0.75 mg/kg, while it was 18.5% for the dose of 1.0 mg/kg. Interestingly, increasing the dosage to 1.25 mg/kg improved the ORR, which ranged from 40 to 51.1% across various studies. In the EV-301 trial, when comparing the efficacy of EV to chemotherapy, EV improved PFS and OS across all dose quartiles, and there was no evidence that recommended dose modifications impacted long-term efficacy outcomes. Dr. Neeraj Agarwal: Thank you, Rana, for this great summary. I would like to add that the meticulously conducted pharmacokinetic studies demonstrated that serum levels of EV correlated with responses. Importantly, patients who had to decrease the dose did not experience compromised outcomes as EV improved PFS and OS outcomes vs chemotherapy in across all exposure quartiles in the EV-301 trial where EV was compared with chemotherapy. These findings highlight the need to start at the recommended dose of 1.25 mg/kg and reduce it, if necessary, however, clinicians should not start at a lower dose.  Dr. Rana McKay: I totally agree with you, Neeraj. Now, moving on to a different setting in bladder cancer, what can you tell us about LBA4517, titled “Perioperative sacituzumab govitecan alone or in combination with pembrolizumab for patients with muscle-invasive urothelial bladder cancer: SURE-01/02 interim results”? Dr. Neeraj Agarwal: Of course! So, SURE was a multicohort, open-label, phase 2 study in patients with muscle-invasive bladder cancer assessing sacituzumab govitecan as a neoadjuvant therapy either alone in SURE-01 or as a combination with pembrolizumab followed by adjuvant pembro in SURE-02 in a flexible design allowing a bladder-sparing approach. In the abstract presented at ASCO 2024, Dr. Antonio Cigliola and colleagues report interim results of the SURE-01 study. Patients with cT2-4N0M0 urothelial carcinoma who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy were planned to receive 4 cycles of neoadjuvant sacituzumab govitecan at a dose of 10 mg/kg followed by radical cystectomy.  An extensive assessment was performed at baseline and after the 4 cycles for response assessment. Patients with clinical complete response defined with negative MRI, cystoscopy and ctDNA assays refusing radical cystectomy were offered redo transurethral resection of the bladder tumor or repeat TURBT followed by observation in the absence of viable high-grade tumor in the bladder. The primary endpoint was pathological complete response rate, while secondary endpoints included pathological downstaging rate and safety. After the first 8 patients were enrolled, the protocol was amended due to the occurrence of grade 3 and 4 neutropenia and diarrhea in 75% and 50% of patients, respectively, and 2 deaths – one of which was deemed to be treatment-related due to sepsis. Key protocol changes included the reduction of the dose of sacituzumab govitecan to 7.5 mg/kg, the introduction of G-CSF as primary prophylaxis, and the exclusion of patients at high risk of febrile neutropenia per ASCO guidelines.  Among 21 patients who received at least one cycle of sacituzumab govitecan and included in the intention-to-treat population, 47.6% had a complete pathological response, and 52.4% had pathological downstaging. 11 patients underwent radical cystectomy, while 7 received repeat-TURBT due to complete clinical response or patient preference. Regarding the safety profile, grade 3 or more adverse events occurred in 42.5% of patients. Treatment-related adverse events leading to dose interruptions or discontinuations were more common before the protocol amendment. It is noteworthy that 3 patients died after treatment discontinuation, with one deemed treatment-related, as previously mentioned. Dr. Rana McKay: Thank you, Neeraj, for a great summary. The pathological complete responses observed show promising activity for sacituzumab govitecan as a neo-adjuvant therapy and a window for bladder-sparing approaches, which is definitely exciting news for our patients! However, although the 3 deaths encountered in a neo-adjuvant setting could be concerning, the improvement of the safety profile after protocol amendments is reassuring and supports the continuation of the study. Dr. Neeraj Agarwal: Before wrapping up the bladder cancer section, would you like to share your insights with our listeners on Abstract 4518, titled “Quantitative circulating tumor DNA (ctDNA) assessment in patients with advanced urothelial carcinoma treated with pembrolizumab or platinum-based chemotherapy from the phase 3 KEYNOTE-361 trial”?  Dr. Rana McKay: Sure. So, the KEYNOTE-361 trial was a randomized phase 3 study with 3 arms that included pembrolizumab plus chemotherapy, pembrolizumab monotherapy, or chemotherapy alone in patients with previously untreated advanced urothelial carcinoma. The results showed that neither the combination of pembrolizumab plus chemotherapy nor pembrolizumab monotherapy improved survival outcomes compared to the chemotherapy arm. So, in this exploratory analysis presented at ASCO24, Dr. Tom Powles and colleagues sought to assess the role of ctDNA as a potential biomarker between the pembrolizumab monotherapy arm and the chemotherapy arm. Tumor tissue mutations were evaluated using whole exome sequencing, and plasma ctDNA was assessed with the Guardant 360 assay. Changes in ctDNA from pre-treatment cycle 1 to on-treatment cycle 2, so 3 weeks post-baseline assessment, were quantified by the maximum variant allele frequency of tumor tissue-specific mutations.  Results showed that lower baseline ctDNA levels were associated with improved clinical outcomes of response in the pembrolizumab arm but not in the chemotherapy arm. This improvement in the pembrolizumab arm was also robust to adjustment for tumor mutational burden and PD-L1. Additionally, chemotherapy led to a ctDNA clearance rate of 41% compared to 11% in the pembrolizumab arm. Patients who had a large ctDNA reduction with pembrolizumab had significantly improved outcomes compared to those achieving a large reduction with chemotherapy with a hazard ratio of 0.25. However, this did not replicate in patients who did not achieve a large reduction, as these patients had similar outcomes across both arms. Let's switch gears to kidney cancer and start with Abstract 4508, reporting the final OS analysis from the JAVELIN Renal-101 trial. Neeraj, what would you like to tell us about this abstract? Dr. Neeraj Agarwal:  Well, as a quick reminder, the JAVELIN Renal-101 was a randomized phase 3 trial where patients with previously untreated advanced or metastatic clear cell renal cell carcinoma were randomized to receive either the combination of avelumab plus axitinib or sunitinib. In previous analyses, the combination of avelumab and axitinib significantly improved PFS compared to sunitinib and was subsequently approved by the FDA for the first-line treatment of patients with advanced RCC in 2019. This superiority in PFS was maintained across the different analyses; however, OS data remained immature. In the abstract presented at ASCO24 by Dr. Robert Motzer from Memorial Sloan Kettering Cancer Center and colleagues, the authors reported OS results at a median follow-up of around 73 months and a minimum of 68 months for all patients, which is the longest follow-up for any ICI-TKI combination in RCC. The final analysis in the overall population favored the combination of avelumab plus axitinib with a median OS of 44.8 months compared to 38.9 months with sunitinib, however, this did not reach statistical significance with a hazard ratio of 0.88. The PFS results and safety profile were consistent with previous analyses.  Dr. Rana McKay: Thank you, Neeraj, for such a nice overview of this abstract. These new data could make this regimen less optimal than other ICI-TKI combinations in the first-line mRCC setting.   Dr. Neeraj Agarwal: I concur, Rana. Moving on to perhaps one of the most exciting GU abstracts featured, Abstract 4506, titled “Circulating kidney injury molecule-1 biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection.” Rana, what are your thoughts on this abstract? Dr. Rana McKay: Well, first, I would like to take a step back and remind our audience that in the IMmotion010 trial, patients with resected intermediate to high-risk RCC with clear cell and/or sarcomatoid component were randomized in a 1:1 ratio to receive either atezolizumab or placebo. Investigator-assessed disease-free survival, which was the primary endpoint, favored the atezolizumab arm but did not reach statistical significance. In the abstract featured at ASCO24, Dr. Laurence Albiges and colleagues build on data previously reported in the ASSURE and CheckMate 914 trials and report provocative findings regarding a molecule known as kidney injury molecule 1 or KIM-1, which is a type 1 membrane glycoprotein that has been identified as a minimally invasive potential peripheral blood circulating biomarker. The KIM-1 level of 86 pg/ml was identified as the optimized threshold for defining post-nephrectomy KIM-1 high vs KIM-1 low subgroups in the IMmotion010 trial. KIM-1 levels were measured at baseline or pre-treatment, at cycle 4 day 1, and at disease recurrence or discontinuation without disease recurrence. Baseline characteristics were balanced between the KIM-1 high and KIM-1 low groups, except perhaps for a slightly higher pathological stage in the KIM-1 high subgroup.  I would like to highlight 3 key takeaways from this abstract. First, KIM-1 high level was associated with significantly worse DFS with a hazard ratio of 1.75. Second, patients in the KIM-1 high subgroup receiving atezolizumab had a 28% reduction in the risk of recurrence or death compared to those receiving placebo, while those in the KIM-1 low subgroup had comparable outcomes across both treatment arms. Third, patients in the KIM-1 high subgroup receiving atezolizumab were significantly less likely to experience an on-treatment increase in KIM-1 levels, which was associated with worse DFS in both high and low KIM-1 subgroups, regardless of treatment arm. Thus, these findings support the use of KIM-1 as both a predictive and prognostic biomarker in patients with RCC. Dr. Neeraj Agarwal: Yes, Rana, this is amazing data! I would like to add that these results warrant larger and, ideally, prospective studies to validate the utility of KIM-1 as a noninvasive biomarker for identifying minimal residual disease after nephrectomy and for predicting outcomes to immune checkpoint inhibitors. Dr. Rana McKay: Also, in the field of biomarkers, 2 abstracts interrogating different biomarkers in a different setting, so in patients with advanced or metastatic RCC were presented. Neeraj, could you tell us more about these abstracts? Dr. Neeraj Agarwal: Of course! I think you are referring to Abstracts 4504 and 4505. In abstract 4504, Dr. Toni Choueiri and colleagues sought to assess the clinical implications of different biomarkers in the CLEAR trial, which was a randomized phase 3 trial that led to the approval of the combination of pembrolizumab plus lenvatinib in the first-line mRCC setting. On the other hand, in abstract 4505, Dr. Brian Rini presented biomarker results in KEYNOTE-426, which was also a randomized phase 3 trial based on which the combination of pembrolizumab plus axitinib was approved in patients with mRCC. The authors in both trials sought to investigate the role of biomarkers in predicting treatment outcomes from 3 different angles. Starting with PD-L1 expression, the superiority of the combination arms over sunitinib was not impacted by PD-L1 status in both trials. Moving on to RCC driver gene mutations on whole exome sequencing, such as VHL, SETD2, PBRM1, and BAP1, ICI combination therapies improved outcomes regardless of mutation gene status, and this improvement was statistically significant with PBRM1 mutations in KEYNOTE-426 compared to wild-type PBRM1, but this did not replicate in the CLEAR trial. Finally, using transcriptomic signatures derived from RCC trials, especially the IMmotion 151 and JAVELIN Renal 101 trials, where 7 clusters or molecular subtypes were identified, the combination arms outperformed sunitinib in all clusters in both trials and the magnitude of this benefit differed across clusters.  Dr. Rana McKay: Thank you for this very interesting summary and comparison of the results of these 2 abstracts. These findings support the use of ICI-based combinations in all patients with mRCC as a first-line option. Although these abstracts could not identify specific biomarkers that could guide us clinicians in treatment selection, they provide very interesting biological insights on these molecular biomarkers that are, however, not yet clinically actionable. Dr. Neeraj Agarwal: Very interesting point, Rana. Moving on to prostate cancer, let's start with abstract LBA5000 titled, “Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: The CHAARTED2 trial of the ECOG-ACRIN Cancer Research Group (EA8153).” Rana, what is your takeaway on this abstract? Dr. Rana McKay: As a reminder to our audience, the CHAARTED2 trial was a randomized open-label phase 2 study that compared the combination of cabazitaxel and abiraterone to abiraterone alone in patients with mCRPC previously treated with ADT plus docetaxel in the hormone-sensitive setting. The primary endpoint was progression-free survival. After a median follow-up of 47.3 months, Dr. Christos Kyriakopoulos and colleagues reported in LBA5000 that patients receiving the combination of cabazitaxel plus abiraterone had a 27% reduction in the risk of progression or death. However, there was no significant difference in overall survival between the two arms, with a median OS of 25 months in the cabazitaxel+abiraterone arm and 26.9 months in the abiraterone arm, although the study was underpowered for this endpoint. Regarding the toxicity profile, the combination of cabazitaxel and abiraterone was overall well tolerated with more cytopenias, as expected.  Dr. Neeraj Agarwal: Very nice summary of this abstract, Rana. I would like to add that the treatment landscape of patients with mHSPC has evolved since the design of the study and now includes combination therapies of ADT + ARPI with or without docetaxel, and ADT + docetaxel is no longer a standard of care, which limits the applicability of these results in clinical practice today.  Dr. Rana McKay: Excellent point, Neeraj. Let's discuss Abstract 5001, titled “CYCLONE 2: A phase 3 study of abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer”. Dr. Neeraj Agarwal: Sure! In the abstract featured at ASCO24, Dr. Matthew Smith and colleagues report the primary results of the CYCLONE 2 trial, which was a randomized phase 2/3 study that investigated the combination of abemaciclib plus abiraterone versus abiraterone monotherapy in patients with mCRPC. Stratification factors included radiographic progression at study entry, presence of measurable disease, and prior docetaxel for mHSPC. Part 1 of the study established the recommended phase 2 dose of abemaciclib at 200 mg twice daily. In part 2, patients were randomized to placebo or abemaciclib, and an adaptive interim analysis using prespecified criteria was performed and recommended the expansion of the study to part 3. The primary endpoint was investigator-assessed radiographic progression-free survival by RECIST 1.1 and PCWG3 criteria in the intention-to-treat population. At the time of the primary analysis, adding abemaciclib to abiraterone did not improve rPFS, with a hazard ratio of 0.83. The median rPFS was 22 months for the combination arm and 20.3 months for the abiraterone arm. The combination was well tolerated, and the safety profile was consistent with the known adverse events. Dr. Rana McKay: So, the addition of abemaciclib to abiraterone did not improve outcomes in patients with mCRPC. These findings suggest that no further investigation is warranted for abemaciclib or CDK4/6 inhibitors in biomarker-unselected patients with prostate cancer.  Dr. Neeraj Agarwal: Rana, what's your take-home message on Abstract 5006, titled “Health-related quality of life results from PRESTO (AFT-19), a phase 3 randomized trial of intensification of androgen blockade in patients with high-risk biochemically relapsed castration sensitive prostate cancer”? Dr. Rana McKay: So, as a reminder to our audience, the PRESTO trial was a randomized phase 3 study that assessed the effects of intensified androgen receptor blockade in patients with biochemically recurrent prostate cancer following local therapies. Patients with a PSA doubling time of less than 9 months and no evidence of metastatic disease were randomized to receive either 52 weeks of ADT alone, ADT plus apalutamide, or ADT plus apalutamide plus abiraterone. In their paper published earlier this year in the Journal of Clinical Oncology, the authors showed that patients receiving ADT plus apalutamide with or without abiraterone had significantly longer PSA-progression-free survival than those receiving ADT alone. In the oral presentation featured at ASCO24, Dr. Ronald Chen and colleagues report health-related quality of life outcomes that were assessed using various questionnaires or scales at baseline, at cycle 7, which is around 6 months on treatment, and at the end of treatment. Results showed that this intensified approach with apalutamide did not significantly increase severe adverse events, did not lengthen the time to testosterone recovery, and did not meaningfully increase common treatment-related symptoms such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue. Importantly, additional intensification with abiraterone did not further improve PSA-PFS but did increase the rate of serious adverse events, lengthened the time to testosterone recovery, and increased hot flash interference.  Dr. Neeraj Agarwal: So, in conclusion, the PRESTO trial supports using intensified androgen blockade with apalutamide to improve PSA-PFS in patients with high-risk biochemically recurrent prostate cancer without compromising health-related quality of life. However, adding abiraterone did not offer additional benefits and increased side effects.  Dr. Rana McKay: Let's move on to LBA5002 titled, “A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.” Would you like to share your insights on this abstract with our listeners? Dr. Neeraj Agarwal: Absolutely. MAST was a randomized, double-blinded, placebo-controlled trial that investigated the impact of metformin on the progression of low-risk localized prostate cancer in patients choosing to undergo active surveillance. Eligible patients had biopsy-proven, low-risk, localized prostate cancer diagnosed within the past 6 months, characterized by a Gleason score of less than 6 observed in less than one-third of the total cores, less than 50% positivity in any one core, a PSA level of less than 10 ng/ml, and a clinical-stage between T1c and T2a. Patients were randomized in a 1:1 ratio to receive either metformin 850 mg twice daily or placebo for three years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint was time to progression, defined as the earliest occurrence of primary prostate cancer therapy, such as prostatectomy, radiation, hormonal therapy, or pathological progression on subsequent biopsies, which was defined as more than 1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher. The study included 407 patients, with 204 receiving metformin and 203 receiving a placebo. Results presented by Dr. Anthony Joshua showed no statistically significant difference in progression-free survival, including therapeutic and pathologic progression, with an unadjusted hazard ratio of 1.08.  Interestingly, there was a signal that patients with a BMI more than 30 had a detriment to taking metformin with a higher risk of progression compared to those receiving placebo with an unadjusted HR of 2.39 and a p-value of 0.01. Dr. Rana McKay: I would like to add that this study showed that metformin use does not prevent the progression of low-risk localized prostate cancer on active surveillance and could represent a potential detriment for patients with high BMI at study entry. Dr. Neeraj Agarwal: Yes, Rana, I concur. Any final remarks before we conclude today's podcast? Dr. Rana McKay:  Thank you, Neeraj; it's been wonderful being here with you today and you having me on the podcast to highlight these important advances and the amazing work that many investigators are conducting and the patients who were involved in the context of these trials. It's really excellent to see these updated results.   Dr. Neeraj Agarwal: Before we wrap up this podcast, I would like to say that we have reviewed a selection of abstracts addressing prostate, bladder, and kidney cancer, which are significantly impacting our medical practices now and in the near future. Rana, thank you for sharing your insights today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion. Many thanks. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Find out more about today's speakers:    Dr. Neeraj Agarwal   @neerajaiims   Dr. Rana McKay  @DrRanaMcKay     Follow ASCO on social media:      @ASCO on Twitter      ASCO on Facebook      ASCO on LinkedIn         Disclosures:        Dr. Neeraj Agarwal:         Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences     Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas      Dr. Rana McKay:   Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus

The Practical Islamic Finance Podcast
Has the time come for these stocks?

The Practical Islamic Finance Podcast

Play Episode Listen Later Jun 1, 2024 21:28 Transcription Available


► If you enjoyed the episode, please leave us a good review!► More from PIF: https://linktr.ee/practicalislamicfinanceHas the time come for these stocks?In this episode, we will cover:Introduction and revisiting a past investing idea. Identifying out-of-favor opportunities with potential. Gene editing technology and its investment prospects. Evolution of therapeutic strategies and benefits of CRISPR. Potential cures and advantages of gene editing. FDA-approved CRISPR therapy for sickle cell disease and beta-thalassemia.Major players: CRISPR Therapeutics, Intellia, and Beam. Comparing the financial health and pipelines of these companies. Analyst price targets and investment opportunities. Audience Q&A on biotech investing and real estate.CONTACT USsalam@practicalislamicfinance.comABOUT OUR PODCASTOur podcast is about helping people ethically build wealth. We cover a broad range of topics including stock and crypto investing, product reviews, and general financial well-being.DISCLAIMERAnything you hear in this video is an opinion. It is not personalized financial advice. Make sure you do your due diligence before making any investment decisions.

ASCO Daily News
Key Abstracts in GU Cancers at ASCO24

ASCO Daily News

Play Episode Listen Later May 25, 2024 26:04


Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode. Jeanny, it's great to have you on the podcast. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here. Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.”  Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma.  In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response.  Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone.  The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone. Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients.  In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, as quick reminder to our audience, this regimen was tested in the EV-302 phase 3 trial, where patients with previously untreated, locally advanced or metastatic urothelial carcinoma were randomized to receive enfortumab vedotin, plus pembrolizumab or gemcitabine plus either cisplatin or carboplatin. These data were also first presented at ESMO 2023 and subsequently published in the New England Journal of Medicine. They showed that this immune based combination significantly improved both progression free survival and overall survival, which were the primary endpoints compared to chemotherapy. In this abstract, Dr. Shilpa Gupta from the Cleveland Clinic and colleagues present the results of patient reported outcomes based on quality-of-life questionnaires in this trial.  Time to pain progression and time to confirm deterioration were numerically longer in patients treated with EV plus pembro, and patients with moderate to severe pain at baseline receiving this combination had a meaningful improvement in the Brief Pain Inventory Short-Form worst pain from week 3 through 26. Dr. Neeraj Agarwal: Thank you, Jeanny. This means that patients treated with EV plus pembro did not only have improved survival compared with platinum-based chemotherapy, but also improvement in their quality-of-life and functioning, further supporting the value of this combination for patients with locally advanced or metastatic urothelial carcinoma. This is terrific news for all of our patients.   Before we wrap up the bladder cancer section, would you like to tell our listeners about Abstract 4565, which provides the data on the efficacy of trastuzumab deruxtecan in patients with bladder cancer? Dr. Jeanny Aragon-Ching: Yes, Neeraj; this is timely given the recent FDA approval, which we will talk about. The abstract is titled, “Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2 Expressing Solid Tumors: Results from the Bladder Cohort of the DESTINY-PanTumor02 Study.” And as a quick reminder, the DESTINY-PanTumor02 was a phase 2 open-label study where trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 expression on cancer cells, was evaluated in patients with HER2-expressing locally advanced or metastatic disease who previously received systemic treatment or who had no other treatment options. The expression of HER2 was evaluated on immunohistochemistry by local or central testing.   The primary endpoint was confirmed objective response rate by investigator assessment. Secondary endpoints included duration of response, progression free survival, disease control rate, and safety. The primary analysis, which was published in the Journal of Clinical Oncology, showed an ORR of 37.1% and responses across all cohorts and the median duration of response was 11.3 months. Based on these results, fam-trastuzumab deruxtecan-nxki was just granted accelerated FDA approval for unresectable or metastatic HER2-positive solid tumors in April 2024.  So, back to this abstract; Dr. Wysocki and colleagues report the results of the bladder cancer cohort. This study included 41 patients with urothelial cancer and at a median follow up of around 12.6 months, the objective response rate among these patients was 39%, the median PFS was 7 months, and the duration of response median was 8.7 months. The disease control rate at 12 weeks was around 71%. Regarding the safety profile, 41.5% of patients experienced grade ≥3 drug related adverse events and interstitial lung disease or pneumonitis did occur in about 4 patients. Although there was no statistical comparison between different groups, the ORR was numerically highest among the HER2 3+ group with 56.3%.  Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data support consideration of trastuzumab deruxtecan as a salvage therapy option for pre-treated patients with HER2 expressing urothelial cancers and show that we are extending our treatment options to include therapies with novel mechanisms of action. This is definitely exciting news for patients with bladder cancer. Dr. Jeanny Aragon-Ching: Yes, absolutely, Neeraj. Now, let's switch gears a bit to prostate cancer. Could you tell us about Abstract 5005 which is titled, “EMBARK Post Hoc Analysis of Impact of Treatment Suspension on Health Quality-of-Life?” Dr. Neeraj Agarwal: Of course, I'd be happy to. So, enzalutamide was recently granted FDA approval for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk of metastasis, based on the results of the EMBARK trial, which was a phase 3 study where patients with high-risk biochemical recurrence were randomized to receive either enzalutamide with leuprolide, enzalutamide monotherapy, or placebo plus leuprolide. The primary endpoint was metastasis-free survival with secondary endpoints including overall survival and safety.  Results showed that patients receiving enzalutamide alone or enzalutamide plus leuprolide had significantly improved metastasis-free survival compared to those treated with leuprolide alone while preserving health-related quality-of-life.   One important aspect in the design of the trial was that patients who achieved undetectable PSA at week 37 underwent treatment suspension. The treatment was resumed if PSA rose to more than 2 ng/ml for patients who underwent radical proctectomy or when PSA rose to more than 5 ng/ml for those who did not undergo surgery.  In this abstract, Dr. Stephen Freedland and colleagues present a post-hoc analysis of health-related quality-of-life outcomes after treatment suspension between weeks 37 and 205. They found that treatment was suspended in 90.9% of patients receiving enzalutamide plus leuprolide, 85.9% of those receiving enzalutamide monotherapy, and 67.8% of those receiving leuprolide monotherapy. Among those patients who stayed on treatment suspension, a trend toward numerical improvement in health-related quality-of-life after week 37 was seen in all 3 arms and this reached clinically meaningful threshold at week 205 in pain questionnaires, physical well-being, urinary and bowel symptoms. For hormonal treatment side effects, all arms reached clinically meaningful improvement at the subsequent assessments of week 49 to week 97. However, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 in patients receiving the combination of enzalutamide and leuprolide and those treated with leuprolide.    Concerning sexual activity, a clinically meaningful improvement was reported only in patients receiving enzalutamide plus leuprolide, possibly because sexual function was better preserved prior to suspension in the enzalutamide monotherapy arm and thus there was less opportunity for “improvement” while on suspension.  Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for this great summary. This analysis confirms that treatment suspension in good responders might lead to a clinically meaningful improvements in health-related quality-of-life.   Now, moving on to patients with metastatic castration-resistant prostate cancer, what can you tell us, about Abstract 5008 titled, “Baseline ctDNA analyses and associations with outcomes in taxane-naive patients with mCRPC treated with 177Lu-PSMA-617 versus change of ARPI in PSMAfore”?  Dr. Neeraj Agarwal: Sure, Jeanny. The PSMAfore trial was a phase 3 study that compared the efficacy of 177Lu-PSMA-617 versus an ARPI switch in patients with mCRPC and prior progression on a first ARPI, and not previously exposed to docetaxel chemotherapy. The primary endpoint was rPFS and OS was an important secondary endpoint. The primary analysis presented at ESMO 2023 showed a significantly prolonged rPFS in patients receiving lutetium. In the abstract that will be featured at the 2024 ASCO Annual Meeting, Dr. Johann De Bono and colleagues present an exploratory analysis regarding the associations between baseline circulating tumor DNA and outcomes.  ctDNA fraction was evaluated in all samples as well as alterations in key prostate cancer drivers prevalent in more than 10% of participants.  The investigators sought to interrogate the association of ctDNA fraction or alterations with rPFS, PSA response, and RECIST response at data cutoff. They showed that median rPFS was significantly shorter in patients with a ctDNA fraction >1% compared to those with a fraction < 1% regardless of the treatment arm. Furthermore, ctDNA fraction >1% was also associated with worst RECIST response and PSA50 response. Regarding prostate cancer drivers, median rPFS was significantly shorter in patients with alterations in the AR, TP53 or PTEN in both treatment arms. There was no significant association between ctDNA alterations and PSA or objective responses. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that the presence of a ctDNA fraction >1% or alterations in AR, P53 and PTEN were all associated with worse outcomes regardless of treatment with lutetium or change in the ARPI. These data are definitely important for counseling and prognostication of patients in the clinic and may guide the design of future clinical trials. Let's move on to kidney cancer. Neeraj, do you have any updates for us?  Dr. Neeraj Agarwal:  Sure. In Abstract 4512 titled, “A Multi-institution Analysis of Outcomes with First-Line Therapy for 99 Patients with Metastatic Chromophobe Renal Cell Carcinoma,” Dr. Sahil Doshi and colleagues present a retrospective, multi-institutional study comparing survival outcomes, including time-to-treatment failure and overall survival, between different first-line treatment options in patients with metastatic chromophobe renal cell carcinoma, where limited clinical trial data exists to guide systemic therapy. They categorized patients into 4 treatment groups: and immune checkpoint inhibitors + targeted therapy doublets (such as ICI VEGF TKI); pure immune checkpoint inhibitor monotherapy and doublets (such as ipilimumab plus nivolumab); targeted therapy doublets (such as lenvatinib plus everolimus), and targeted monotherapy (such as sunitinib).  They identified 99 patients, of whom 54 patients received targeted monotherapy, 17 received ICI VEGF-TKI, 14 received targeted doublet, and 14 patients received only ICI therapies. So the patients treated with any doublet containing a targeted agent had a 52% decrease in the risk of treatment failure and a 44% decrease in the risk of death compared to those treated with targeted monotherapy. The median time to treatment failure was 15 months with IO-targeted doublet, and the median overall survival was 56 months. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that targeted doublet regimens resulted in a longer time to treatment failure and overall survival compared to any monotherapy in patients with chromophobe metastatic RCC and definitely provides valuable insights on treatment selection, albeit I would say there's still a small number of patients that were included in this retrospective analysis. Dr. Neeraj Agarwal: I completely agree this is a relatively small number of patients, but I decided to highlight the abstract given how rare the cancer is, and it is highly unlikely that we'll see large randomized clinical trials in patients with metastatic chromophobe renal cell carcinoma.  So, before we wrap up the podcast, what would you like to tell us about Abstract 5009 which is titled, “A Phase II Trial of Pembrolizumab Platinum Based Chemotherapy as First Line Systemic Therapy in Advanced Penile Cancer: HERCULES (LACOG 0218) Trial.” Dr. Jeanny Aragon-Ching: I'm glad you brought this up, Neeraj. As our listeners may know, advanced penile squamous cell carcinoma has a poor prognosis with limited treatment options. From this perspective, the results of the LACOG 0218 trial are very important. As you mentioned, this was a phase 2 single-arm study evaluating the addition of pembrolizumab to platinum-based chemotherapy as first-line treatment in patients with metastatic or locally advanced penile squamous cell carcinoma not amenable to curative therapy. Patients enrolled received chemotherapy, namely 5-Fluorouracil with cisplatin or carboplatin and pembrolizumab 200 mg IV every 3 weeks for 6 cycles, followed by pembrolizumab 200 mg IV every 3 weeks up to 34 cycles. The primary endpoint was confirmed overall response rate by investigator assessment.  In the 33 patients eligible for the efficacy analysis, the confirmed ORR by investigator assessment was 39.4% and included one complete response and 12 partial responses. The confirmed ORR was 75% in patients with high TMB and 55.6% in patients positive for HPV16, making TMB and HPV16 potential predictive biomarkers for efficacy in this study. Concerning the toxicity profile, any grade treatment-related adverse events were reported in around 92% of patients, and grade 3 or more treatment-related adverse events occurred in 51% of patients. 10.8% of patients discontinued treatment due to adverse events.  Dr. Neeraj Agarwal: Thank you, Jeanny. I would like to add that HERCULES is the first trial to demonstrate the efficacy of an immune checkpoint inhibitor in advanced penile squamous cell carcinoma with a manageable safety profile. Thus, the combination of ICI with platinum-based chemotherapy is a promising treatment for advanced penile squamous cell carcinoma and warrants further investigation.  Dr. Jeanny Aragon-Ching: I agree, Neeraj. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Jeanny, I really want to thank you for your participation and valuable insights. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. It was a pleasure.  Dr. Neeraj Agarwal:  As we bring this podcast to an end, I would like to acknowledge the significant advances happening in the treatment of patients with genitourinary cancers. During our upcoming 2024 ASCO Annual Meeting, there will be an array of different studies featuring practice-changing data presented by researchers and physicians from around the globe. I urge our listeners to not only participate in this event to celebrate these achievements, but to also play a role in sharing these cutting-edge data with healthcare professionals worldwide. Through our collective efforts, we can surely optimize the benefits of patients on a global scale.   And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you very much.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:  Dr. Neeraj Agarwal  @neerajaiims  Dr. Jeanny Aragon-Ching    Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:    Dr. Neeraj Agarwal:     Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas     Dr. Jeanny Aragon-Ching:  Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

BioSpace
BioSpace Heads to #ASGCT, Along with Thousands in Cell and Gene Therapy

BioSpace

Play Episode Listen Later May 3, 2024 12:20


In this special edition of The Weekly, we discuss the much-anticipated annual meeting of the American Society of Gene & Cell Therapy in Baltimore. It starts Tuesday and will hit on wide-ranging issues facing the cell and gene therapy (CGT) space, from new therapeutic advances to safety concerns and regulatory considerations to manufacturing and commercialization. Big hitters in the CGT space will be there. Sarepta, whose gene therapy for Duchenne muscular dystrophy Elevidys received accelerated approval in June 2023, will be presenting, as will CRISPR Therapeutics, which in the last few months brought to market Casgevy, its Vertex-partnered CRISPR-based therapy, for sickle-cell disease and beta thalassemia. There will also be plenty of big names, including Peter Marks, director of the FDA's Center for Biologics Evaluation and Research. Marks will be speaking in two sessions at ASGCT 2024, one on global regulatory convergence and the other on the regulation of CGTs, from IND to BLA. Stay tuned for this week's regular episode on Wednesday when we discuss what we're seeing and hearing in Baltimore.

Alles auf Aktien
KI-Stromgewinner und Cathie Woods schlechtes Deutschland-Timing

Alles auf Aktien

Play Episode Listen Later Apr 18, 2024 19:34


In der heutigen Folge von „Alles auf Aktien“ sprechen die Finanzjournalisten Laurin Meyer und Holger Zschäpitz über einen überraschenden Chip-Schocker, Luxusprobleme bei LVMH und doppelt jubelnde Fußballfans. Außerdem geht es um ASML, AMD, Nvidia, United Airlines, Boeing, American Airlines, Southwest Airlines, Delta, Alaska Air, First Solar, SolarEdge Technologies, Borussia Dortmund, Tesla, Goldman Sachs, GE Vernova, American Electric Power, Constellation Energy, Xcel Energy, Atkore, Comfort Systems USA, Emcor Group, Primoris Services, Meta, Microsoft, American Water Works, Xylem, Tesla, Coinbase, Roku, Block, UiPath, CRISPR Therapeutics, Roblox, Zoom, Robinhood, Unity Software, iShares Global Water ETF (WKN: A0MM0S), ARK Innovation ETF (WKN: A408AW), ARK Genomic Revolution ETF (WKN: A408AY), ARK Artificial Intelligence & Robotics ETF (WKN: A408AX), ARK Autonomous Technology & Robotics (WKN: A14RW2), ARK Next Generation Internet (WKN: A14Y8J), iShares Diversified Commodity Swap (WKN: A2DK6R), iShares Bloomberg Enhanced Roll Yield Commodity Swap (WKN: A2JQ2G) und L&G Multi Strategy Enhanced Commodities ETF (WKN: A409RZ). Wir freuen uns an Feedback über aaa@welt.de. Ab sofort gibt es noch mehr "Alles auf Aktien" bei WELTplus und Apple Podcasts – inklusive aller Artikel der Hosts und AAA-Newsletter.[ Hier bei WELT.](https://www.welt.de/podcasts/alles-auf-aktien/plus247399208/Boersen-Podcast-AAA-Bonus-Folgen-Jede-Woche-noch-mehr-Antworten-auf-Eure-Boersen-Fragen.html.) Disclaimer: Die im Podcast besprochenen Aktien und Fonds stellen keine spezifischen Kauf- oder Anlage-Empfehlungen dar. Die Moderatoren und der Verlag haften nicht für etwaige Verluste, die aufgrund der Umsetzung der Gedanken oder Ideen entstehen. Hörtipps: Für alle, die noch mehr wissen wollen: Holger Zschäpitz können Sie jede Woche im Finanz- und Wirtschaftspodcast "Deffner&Zschäpitz" hören. Außerdem bei WELT: Im werktäglichen Podcast „Das bringt der Tag“ geben wir Ihnen im Gespräch mit WELT-Experten die wichtigsten Hintergrundinformationen zu einem politischen Top-Thema des Tages. +++ Werbung +++ Du möchtest mehr über unsere Werbepartner erfahren? [**Hier findest du alle Infos & Rabatte!**](https://linktr.ee/alles_auf_aktien) Impressum: https://www.welt.de/services/article7893735/Impressum.html Datenschutz: https://www.welt.de/services/article157550705/Datenschutzerklaerung-WELT-DIGITAL.html

For our Love of Science
The CRISPR Cure for Sickle Cell Disease

For our Love of Science

Play Episode Listen Later Apr 8, 2024 34:40


In this fourth installment of the CRISPR Chronicles, show hosts Fatu and Shekerah give  a review of sickle cell anemia, the cause and symptoms of the disease, and discuss how the CRISPR gene therapy treatment works.Tune in to learn more about:The genetic basis of Sickle Cell DiseaseWhat Amazon delivery vans have in common with your Red Blood CellsThe effect of mutant hemoglobin on Red Blood CellsThe variety and severity of symptoms that SCD patients experienceThe disease burden of SCD throughout the worldThe clever strategy used to treat the disease with CRISPR gene therapyThe results of the CRISPR Therapeutics and Vertex Pharmaceuticals gene therapy clinical trialsFor more information on this topic, visit our website: welovesciencepodcast.comHear directly from Sickle Cell Disease patients who received the treatment during the clinical trial: Victoria Gray and Jimi OlaghereIf you enjoyed this episode, you will also enjoy:The first CRISPR Chronicles episode: How CRISPR gene therapy is bringing hope to the worldA foundational discussion explaining the secret behind CRISPR gene therapy A look into the ups and downs of how the CRISPR saga developed  Reach out to Fatu:www.linkedin.com/in/fatubmTwitter: @thee_fatu_band LoveSciencePodcast@gmail.com Reach out to Shekerah:www.linkedin.com/in/shekerah-primus and LoveSciencePodcast@gmail.com Music from Pixabay: Future Artificial Intelligence Technology 130 by TimMoorMusic from https://freemusicarchive.org/music/Scott_Holmes: Hotshot by ScottHolmesMusic

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 28, 2024 88:58


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Feb 28, 2024 89:00


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast

Play Episode Listen Later Feb 28, 2024 89:00


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 28, 2024 88:58


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 28, 2024 88:58


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Clinical Pharmacology CME/CNE/CPE Video
Sumanta Kumar Pal, MD, FASCO - Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies

PeerView Clinical Pharmacology CME/CNE/CPE Video

Play Episode Listen Later Feb 28, 2024 89:00


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 25, 2025.Advancing Personalized Care in RCC: Navigating Rapid Therapeutic Expansion and Sequencing Strategies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Kidney Cancer Research Alliance. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, Eisai Inc., Exelixis, Inc., and Merck & Co., Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerPedro C. Barata, MD, MSc, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AVEO Pharmaceuticals, Inc; Bristol Myers Squibb; Clovis Oncology; EMD Serono; Eisai Co., Ltd.; Exelixis, Inc.; Ipsen Biopharmaceuticals, Inc.; Pfizer; and Sanofi.Grant/Research Support from EMD Serono and Exelixis, Inc.Speakers Bureau participant with Bayer Corporation; Caris Life Sciences; Merck & Co., Inc.; and Sanofi.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Faculty/PlannerTian Zhang, MD, MHS, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Aravive; AstraZeneca; AVEO Pharmaceuticals, Inc.; Bayer Corporation; Bristol Myers Squibb; Caris Life Sciences; Eisai Co., Ltd.; EMD Serono; Exelixis, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Sanofi; and Seagen Inc.Grant/Research Support from ALX Oncology; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; and Tempus.Other Financial or Material Support for leadership or fiduciary role in Kidney Cancer Association (KCA) Medical Steering Committee; Kidney Cancer Research Alliance (KCCure) Scientific Advisory Board; and National Cancer Institute (NCI) Steering Renal Task Force.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Healthscape
Episode 24: The CRISPR Revolution: Exploring Gene Editing and Careers in Business Development with Dr. Alex Harding, Senior Vice President and Head of Business Development at CRISPR Therapeutics

Healthscape

Play Episode Listen Later Feb 12, 2024 31:46


In this episode, Dr. Alex Harding, Senior Vice President and Head of Business Development at CRISPR Therapeutics, sits down with Pam Divack to discuss his background and career path, what makes CRISPR "revolutionary," and how to succeed in biotech business development. The Healthcare Community at Kellogg is always looking to collaborate with industry leaders. To learn more about Healthscape or the Kellogg Healthcare Club, please contact Pam Divack

Science Friday
The FDA Approved The First CRISPR-Based Therapy. What's Next?

Science Friday

Play Episode Listen Later Feb 7, 2024 18:00


Last month the FDA approved a new treatment for sickle cell disease, the first medical therapy to use CRISPR gene editing technology. It works by identifying the gene or genes causing the disorder, modifying those genes and then returning them to the patient's body.There are now two gene therapies offered by pharmaceutical companies for sickle cell disease: Casgevy from Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia from BlueBird Bio. But prices for these one-time treatments are steep: Casgevy costs $2.2 million per patient and Lyfgenia $3.1 million.Both promise a full cure, which would be life-changing for patients with this debilitating condition. Over 100,000 Americans, mostly of African descent, have sickle cell disease.This milestone raises more questions: What will be the next disease that CRISPR can help cure? And is it possible to reduce the costs of gene therapy treatments?Ira talks with Dr. Fyodor Urnov, professor of molecular and cell biology and scientific director of technology and translation at the Innovative Genomics Institute, based at the University of California, Berkeley, about the future of CRISPR-based cures.Transcripts for this segment will be available the week after the show airs on sciencefriday.com. To stay updated on all things science, sign up for Science Friday's newsletters.

ASCO Daily News
Key Advances in Prostate, Kidney, and Bladder Cancers at GU24

ASCO Daily News

Play Episode Listen Later Feb 6, 2024 30:06


Drs. Neeraj Agarwal and Todd Morgan discuss CONTACT-02, KEYNOTE-564, CheckMate-67T, and other notable studies featured at the 2024 ASCO Genitourinary Cancers Symposium, as well as additional key abstracts in prostate, kidney, and bladder cancers that will significantly influence clinical practice. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-changing abstracts and other key advances in GU oncology featured at the 2024 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Todd Morgan, the chair of this year's ASCO GU. Dr. Morgan is a urologic surgeon, chief of urologic oncology at Michigan Medicine, and a professor of urology at the University of Michigan. Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found at asco.org/DNpod. Todd, thank you for joining us today. Dr. Todd Morgan: Thanks so much, Neeraj. It's an honor to be here and I'm just thrilled to be able to do this with you. Dr. Neeraj Agarwal: Thank you. So, the GU meeting showcased significant advancements across the spectrum of GU malignancies. Can you tell us about the hot topics that captured the headlines this year? What did you find exciting this year at the ASCO GU Symposium? Dr. Todd Morgan: The theme of this year's meeting was "20 Years of Advancing Science and Transforming Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the last 2 decades. We were thrilled to welcome over 5,200 attendees from over 70 countries, and, believe it or not, there were more than 875 abstract submissions, compared to more than 300 in the meeting's first year. Most of the participants were present in person and that was fantastic. It enabled great networking opportunities and opportunities for experts, trainees, and mentees to exchange knowledge and ideas. Without a doubt, ASCO GU remains the annual meeting in our field, and it's amazing to hear the breadth and depth of the state-of-the-art science that's presented at this meeting, and so much of it impacts patient care the second that you return home. Additionally, the meeting's focus on diversity and interactivity, networking, multidisciplinary collaboration, and evidence-based care were absolutely phenomenal from my standpoint. We had a lunch session for women's networking that was a huge success—the first time we've done that. The keynote lecture by Dr. Cheryl Lee that talked about ensuring adequate representation in clinical trials was a huge hit, and we had tremendous positive feedback from that lecture. There were also multiple featured sessions on different diagnostic and therapeutic challenges in localized, recurrent, and advanced GU cancers. And, Neeraj, my personal favorite during the symposium is always the Trainee and Early-Career Networking Luncheon on the first day and then the additional networking luncheons on the 2 following days. I had great conversations with a ton of trainees and junior faculty, and I feel so fortunate for the opportunity to get to know the future superstars in our field. So I'd like to kick it back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. A great example is Abstract 17, which was the second oral presentation delivered, and really congratulations to you, Neeraj, on sharing the exciting data from the CONTACT-02 trial which we were eagerly awaiting. And I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial? Dr. Neeraj Agarwal: Yes, Todd, I agree with you. It was such an exciting conference overall, and thank you for your leadership of this conference. So let's talk about the CONTACT-02 trial. It was a phase 3 randomized trial assessing the combination of cabozantinib and atezolizumab versus a second NHT in patients with metastatic castration-resistant prostate cancer after progression on one NHT. This patient population had to have extrapelvic soft tissue metastases, which could be liver metastases, lung metastases, or lymph nodal metastases, and about up to a quarter of patients had liver metastases. And overall, this was a high-risk patient population which was randomized to, as I said, cabozantinib plus atezolizumab versus a second line NHT. And these patients had received a prior NHT, mostly in the mCRPC setting.  The co- or dual primary endpoints were overall survival and progression-free survival (PFS). And a unique thing was that PFS was assessed only by RECIST 1.1 because, as per our discussions with regulatory authorities, the trial was focused on soft tissue metastases because of questions in the past that cabozantinib can affect bone lesions in an artifactual fashion, possibly concerns. That's why the PCWG 3 criteria were not used as the primary endpoint, but, of course, indeed used as another key endpoint, so we have information on both. Anyway, coming back to the endpoint 1:1 randomization. The randomization was stratified by presence or absence of liver metastases, prior docetaxel chemotherapy, and the setting in which NHT was given (mCSPC or CRPC). The PFS or primary endpoint was significantly improved with a 35% reduction in risk of progression or death with the cabozantinib-atezolizumab combination versus second NHT. And there was a trend for overall survival, with a hazard ratio of 0.79 favoring the cabozantinib-atezolizumab combination. Interestingly, all subgroups benefitted, regardless of age, region, site of metastases, but we decided to choose three clinical subgroups of interest such as patients with liver metastases, patients with prior docetaxel chemotherapy in the castration-sensitive setting, and bone metastases, and all these subgroups seemed to be benefitting with the strongest signal in the liver metastasis subgroup, with a 57% reduction in risk of progression or death, which I would argue we have never seen with any combination or any regimen in the metastatic prostate cancer setting yet, barring some targeted therapies in very selected patients. But overall, across the non-biomarker-selected patients, we have never seen this kind of signal. Toxicity — no discussion is complete without discussing toxicity, so I would like to highlight that. Safety signal — there were no new safety signals. The most common grade 3-4 adverse events were hypertension in 7%, anemia in 6%, which were similar in both arms, and, of course, diarrhea and fatigue in 4% each. And if we look at the secondary endpoints, such as time to chemotherapy and time to symptomatic skeletal events, they tended to favor the cabozantinib-atezolizumab. To sum it up, cabozantinib-atezolizumab showed a significant PFS benefit, with a 35% reduction in risk of progression or death, with a trend for overall survival in this patient population with an unmet need. So thank you so much, Todd, for allowing me to summarize the results of this trial. Dr. Todd Morgan: Yeah, wow. That's so impressive, and not surprising that you could so fluidly go right through all that data. Amazing. We heard some discussion of the NHT control arm in this trial. Could you discuss that for a bit? Because it obviously has implications on the similar control arm of other ongoing trials in this setting. Dr. Neeraj Agarwal: Absolutely. Pretty much all trials, every trial which has recently been reported or started in metastatic castrate-resistant prostate cancer have a similar second NHT arm. Whether there were multiple immunotherapy trials which we have just reported, or new trials which are starting or just started enrolling patients. And the reason for that is no randomized trial has ever shown superiority of docetaxel chemotherapy over a second NHT after failure of prior NHT in the mCRPC setting. That's number one. If you look at NHT as a control, it is accepted by health authorities globally with multiple recent trials which are just starting also having NHDR and it would not have been possible without the approval of global regulatory authorities across the world.  Then, if you look at the recently reported trial in the mCRPC setting with prior treatment with an NHT, there is an indication that chemotherapy may not be superior to NHT. For example, in the KEYNOTE-641 trial in patients with mCRPC with prior NHT, randomizing patients to enzalutamide plus pembrolizumab versus enzalutamide, the median PFS with enzalutamide was 9 months. This is very similar with docetaxel in patients randomized to docetaxel plus pembrolizumab versus docetaxel; the median PFS with docetaxel is 8 months or 8.3 months. And lastly, if you really want to have a comparison of chemotherapy with NHT which has been done after progression on NHT and docetaxel chemotherapy, so later line of mCRPC setting, that is the CARD trial, as you can imagine, cabazitaxel versus NHT, especially in patients with visceral metastasis, which was the point of discussion. For example, people may not feel comfortable randomizing patients to NHT compared to taxane. The hazard ratio for PFS supporting cabazitaxel was 0.79, so almost a 0.80 PFS hazard ratio, which we have never seen turning out to be a clinically significant benefit. So, if you combine all these data together, I think it was absolutely acceptable to us as investigators to have a second NHT as the control arm. And of course, when we are consenting the patient, we have to keep alternatives in mind, and we do talk about those alternatives with the patients. And if alternatives seem more applicable, we should not be talking to patients about those clinical trials or a given clinical trial in the clinic. I'm glad you brought this up, Todd, because this control NHT arm is not an issue with this trial, but all trials which should be presented in GU ASCO in the future meetings in the coming years. So, thank you. Dr. Todd Morgan: Yeah, thank you. It's such an important topic and controversy at some level, but it's a difficult problem to think about and obviously highly relevant to all the trials that we're looking at. Congrats again on that trial, that's tremendous. There was another important randomized phase 3 trial and it covers radiotherapy in patients with high-risk localized prostate cancer. Can you give us your insights on that one? Dr. Neeraj Agarwal: Yeah, Todd, I think you are referring to LBA259, titled "Long-term Results of Dose Escalation of Radiation Therapy from 70 Gy to 80 Gy Combined with Long-term Androgen Deprivation Therapy in High-risk Prostate Cancer: The GETUG-AFU 18 Randomized Trial." As you mentioned, in this randomized phase 3 trial, Dr. Christophe Hennequin and colleagues randomized patients with high-risk prostate cancer, which means they had to have either clinical stage T3 or T4 disease, or PSA ≥20 nanograms per milliliter, or a Gleason score between 8 and 10. These patients were randomized to receive ADT for 3 years combined with either dose-escalated intensity-modulated radiotherapy. So, I'd like to highlight, this was in the context of IMRT in the dose of 80 Gy or a conventional dose of 70 Gy. Now, you can argue that more people are using more than 70 Gy nowadays, but across the world, the conventional dose is still considered 70 Gy. So, 80 Gy versus 70 Gy were tested. Patients also had to have negative lymph node status on CT scans and MRI. The primary endpoint was biochemical progression-free survival or clinical progression-free survival at 5 years following the ASTRO Phoenix definition. Secondary endpoints – and these are quite important secondary endpoints – include overall survival, acute and late toxicity, and quality of life. The best part is that this trial met its primary endpoint with a 44% reduction in risk of biochemical or clinical progression or death in the dose-escalation radiotherapy arm compared with the conventional radiotherapy arm. Interestingly, a significant 52% improvement in prostate cancer-specific survival and a 39% improvement in overall survival was observed in the dose-escalated arm. So, 80 Gy continued to be superior to 70 Gy IMRT across the primary and secondary endpoints. Now, the best part is, regarding the toxicity profile, there was no significant difference between the 2 arms, with 78% of patients in the higher dose arm and 76% of patients in the conventional arm experiencing grade 2 or more toxicities. Dr. Todd Morgan: Great summary and really important, great news for our patients. Of course, it's a slightly different setting as it's high-risk localized prostate cancer. I checked in with our radiation oncologists at the University of Michigan after that [presentation] because I couldn't remember exactly where we are in terms of dose on these patients. And they were like, “Yeah, we've been doing 80 to 90 Gy for several years,” so it's great having this data to support that. And I think, as you said, the field at many centers has already moved that way. And again, the key takeaway from this abstract would be that IMRT, in combination with long-term androgen deprivation therapy, is effective and safe and increases not only the biochemical or clinical PFS rate, but also the cancer-specific survival and overall survival, again, in high-risk localized prostate cancer patients. And it does not appear to increase long-term toxicity. So really important. It'd be great to switch gears and discuss kidney cancer, if that's okay, and talk about some key abstracts in that field. What do you think? Dr. Neeraj Agarwal: There were so many exciting data in all cancers, which is amazing. So, Todd, could tell us about the LBA359, which I thought was one of the most impactful abstract presentations in the ASCO GU this year. It was titled, “Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab Versus Placebo for Treatment of Clear Cell Renal Cell Carcinoma (ccRCC)."   Dr. Todd Morgan: Yeah, this was a really big moment in our field, complete with a mid-presentation round of applause that was well deserved. And so this abstract was presented by Dr. Toni Choueiri from Dana-Farber Cancer Institute, and it included patients with clear cell renal cell carcinoma at intermediate high or high risk of recurrence, meaning that they had positive nodal disease or negative nodal disease with PT 2 and grade 4, or sarcomatoid features, or stage PT 3 or 4. These patients underwent nephrectomy with or without metastasectomy less than 12 weeks before randomization and had not received prior systemic therapy for clear cell RCC. Patients were randomized to receive either pembrolizumab 200 milligrams or placebo IV every three weeks for at least 17 cycles, or until disease recurrence, intolerable toxicity, or withdrawal of consent. Disease-free survival by investigator assessment was the primary endpoint, and overall survival was a key secondary endpoint. In this abstract, Dr. Choueiri and colleagues report results of the third prespecified interim analysis with a median follow-up of around 57 months in 496 patients receiving pembrolizumab and 498 patients receiving placebo. So, just as a reminder to the audience here, the first interim analysis reported at a median follow-up of 24 months and showed a significant reduction of 32% in the risk to recurrence or death in patients in the pembrolizumab arm. Then subsequently in November of 2021, the FDA approved pembrolizumab for the adjuvant treatment of patients with RCC who are at intermediate high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. At that time, though, overall survival data were still immature. So, at the third prespecified interim analysis with a median follow-up of around 57 months, pembrolizumab showed, for the first time in an adjuvant RCC setting, improved overall survival with a 38% reduction in the risk of death. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86% with placebo. Furthermore, the OS benefit was observed across key subgroups, including patients with non-metastatic disease, patients with metastatic but no evidence of disease, patients with PDL-1 combined positive score less than or greater than or equal to one, and patients with presence or absence of sarcomatoid features. In each of these subgroups, the forest plot looks really impressive. And the DFS benefit was similar to previously reported interim analyses with a hazard ratio of 0.72. Also, no new safety signals with pembrolizumab were observed so just tremendous data. Dr. Neeraj Agarwal: Thank you, Todd, for such a great summary of these very important results. So the key message from this abstract, as you said, is that after a median follow-up of around 57 months, which is a long follow-up, adjuvant pembrolizumab demonstrates a statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with RCC at high risk of disease recurrence after surgery. And this is, by the way, the first phase 3 study to show improved overall survival with any adjuvant therapy in RCC. Basically, this means we should continue to use adjuvant pembrolizumab or at least bring it up in our discussion with our patients who are in a similar situation with high-risk RCC after surgery. So this is great news overall. Todd, there was another kidney cancer abstract, LBA360, which compared, interestingly, subcutaneous nivolumab with intravenous nivolumab in patients with metastatic renal cell carcinoma. Could you please give us your insight about this abstract?   Dr. Todd Morgan: Sure. Really interesting study. Really interesting data that were presented. So as you mentioned, CheckMate 67T was a multicenter, randomized, open-label phase three study led by Dr. Saby George and colleagues that evaluated pharmacokinetics and objective response rate non-inferiority of subcutaneous nivolumab versus IV nivolumab in patients with locally advanced or metastatic clear cell RCC. So patients with measurable disease that progressed during or after 1 to 2 prior systemic regimens and who did not receive a prior immuno-oncology treatment were randomized 1-1 to receive either subcutaneous nivolumab 1200 milligrams every 4 weeks or IV nivolumab 3 milligrams per kilogram every two weeks until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death. The coprimary pharmacokinetics endpoints for non-inferiority testing were time-average serum concentration over the first 28 days and minimum serum concentration at steady state determined by a population pharmacokinetics analysis. A key secondary endpoint was objective response rate by independent review. So in 248 patients receiving subcutaneous nivolumab and 247 patients receiving IV nivolumab, non-inferiority for the coprimary pharmacokinetics and key-powered secondary objective response rate endpoints were met. The relative risk ratio for objective response rate was 1.33. The median PFS by independent review was 7.23 months in the subcutaneous group and 5.65 months in the IV group. Treatment-related serious adverse events occurred in 6.5% of patients in each group, and study drug toxicity led to 3 deaths in the subcutaneous group and 1 death in the IV group. These results could support using subcutaneous nivolumab as a new option to improve healthcare efficiency, especially since the average injection time with subcutaneous nivolumab was less than 5 minutes. I think we all know what issues are going on in infusion beds across the country, including, I'm sure, your center and mine. Dr. Neeraj Agarwal: Yes, absolutely. I think this is great news for our patients, Todd. Thank you. This shows that we are not only improving therapeutic options and diagnostic tools, but maybe we're also on the right track towards more practical administration routes, assisting in addressing the treatment burden and improving the efficiencies of healthcare systems. We love to have this option available for our patients, especially those who are pressed for time. So, Todd, would you like to move on to bladder cancer now?  Dr. Todd Morgan: Yeah, Neeraj, that'll be fantastic. I'm sure listeners would love to hear more about LBA530. Could you tell us more about this one, Neeraj? Dr. Neeraj Agarwal: Of course. I think this abstract is titled "Enfortumab Vedotin in Combination with Pembrolizumab Versus Chemotherapy in Previously Untreated, Locally Advanced or Metastatic Urothelial Carcinoma: Subgroup Analysis Results from EV-302," which was a global phase three study and was presented by Dr. Michiel Van Der Heijden. As our audience may recall, the EV-302 trial was presented at the ESMO 2023 meeting by Dr Tom Powles and the results were very exciting where, for the first time, a combination outperformed traditional gemcitabine-cisplatin chemotherapy. In this trial, patients with previously untreated with metastatic advanced urothelial carcinoma were randomized 1-1 to receive a 3-week cycle of a combination of enfortumab vedotin, which, as we know, is an antibody-drug conjugate targeting nectin-4 expressed on the cancer cells and pembrolizumab, which is a PD-1 inhibitor, versus gemcitabine and cisplatin or carboplatin, which were, until recently, the standard of care in this setting, and continue to be so in many countries in the world. The combination of enfortumab and pembrolizumab reduced the risk of progression or death by 55% and reduced the risk of death by 53% in the overall population. So consistent decrease in the hazard ratios for PFS and OS, and consistent improvement in overall survival and PFS in that previously reported presentation in the ESMO 2023. Now, based on these results, this combination was recently approved by the FDA in December 2023 for patients with advanced or metastatic urothelial carcinoma. So now the abstract, which was presented at the ASCO GU 2024 meeting, reported the results of a prespecified subgroup analysis. Select secondary endpoints included objective responses, duration of response, and safety. In 442 patients receiving the combination of enfortumab vedotin plus pembrolizumab, and a similar number of patients receiving chemotherapy both PFS and OS were higher for the combination of EV and pembro among prespecified subgroups such as race, platinum eligibility, PDL-1 expression, metastatic site, involvement of the liver or kidney function. Interestingly, the combination of EV and pembro reduced the risk of death by 53% in patients with visceral metastasis and 54% in patients with node-only metastasis. The improvement in PFS seems to be consistent regardless of the site of metastasis. In patients with moderate to severe renal function, the risk of death was reduced by 50% in patients receiving combination therapy. This is one of the best findings of these results because we always face challenges in treating patients with suboptimal kidney function and we cannot use cisplatin. Overall, EV plus pembro continues to show superior efficacy compared to platinum-based regimens across subgroups across the subgroups across the site of metastasis regardless of kidney function and so on. Dr. Todd Morgan: Yeah, just amazing data. I love hearing you spell it out like that. So, thank you again for the opportunity for me to sit here with you and listen to you talk about these data. It's impressive that we have been able to expand our therapeutic arsenal for urothelial carcinoma with an immune-targeting regimen that can spare our patients potential side effects of chemotherapy. What would your final takeaway on this abstract be? Dr. Neeraj Agarwal: I agree with you, Todd. I would add that the OS benefit was consistently observed across these select prespecified subgroups, including those historically associated with poor prognosis. The results of this new analysis support the finding of primary results, which indicate that EV plus pembro is a potentially new standard of care for patients with newly diagnosed, locally advanced, or metastatic urothelial carcinoma. Before we wrap up the bladder cancer session and the podcast, Todd, could you please give us insights about LBA531? Dr. Todd Morgan: Yeah, absolutely. I loved getting to hear this abstract presented. This one is titled “Ambassador,” known as the AMBASSADOR trial aligns A031501, a phase 3 randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma versus observation, that was presented by Dr. Andrea Apolo. It's an open-label, randomized, phase 3 trial that included patients with muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra. Eligible patients had pathologic tumor stage T2 or greater and/or positive pathologic nodal disease or positive margins at surgery following neoadjuvant chemotherapy, or patients with pathologic tumor stage T3 or greater and/or positive pathologic nodal disease or positive margins at surgery without prior neoadjuvant chemotherapy, and who were cisplatin ineligible or declined adjuvant cisplatin-based therapy. These patients were randomized one to one to either receive pembrolizumab 200 milligrams every 3 weeks for 1 year or observation. The dual primary endpoints were disease-free survival and overall survival. Secondary objectives included evaluation of DFS and OS in PDL-1 positive and negative patients and assessing safety. A total of 354 patients were enrolled to receive pembrolizumab and 348 to the observation arm, and 21% of the patients in the observation arm received a subsequent immune checkpoint inhibitor. At a median follow-up of 22.3 months for DFS, the median disease-free survival in the pembrolizumab arm was 29 months, while it was only 14 months in the observation arm with a hazard ratio of 0.69. At the interim analysis, OS data showed only a trend toward better outcomes in the pembrolizumab arm, which did not, however, reach statistical significance, with a median of 50.9 months in the pembrolizumab arm and 55.8 months in the observation arm with a hazard ratio of 0.98. These results could nevertheless have been impacted by the subsequent treatment of patients in the observation arm with an immune checkpoint inhibitor, especially after the FDA approval of nivolumab in 2021 for patients with muscle-invasive urothelial carcinoma, based on results of the CheckMate 274 trial. In terms of the safety profile, grade three or more adverse events occurred in 48.4% of patients in the pembrolizumab arm and 31.8% of patients in the observation arm. Dr. Neeraj Agarwal: That's great, Todd. This is such a great summary of this trial, and this is exciting news for our patients with muscle-invasive urothelial carcinoma. I'm hoping that pembrolizumab will be another option for our patients when we are discussing adjuvant immunotherapy in the clinic, moving forward very soon. With that, we have covered several abstracts addressing prostate, bladder, and kidney cancer, significantly influencing our medical practices, at least at the current moment or in the near future. Todd, thank you for sharing your insights today. These are undoubtedly exciting updates for all members of the GU oncology community, and we are grateful for your valuable contribution to the discussion. Many thanks. Dr. Todd Morgan: Thanks, for having me, Neeraj; this was really fun. I'm just really proud and excited to still be part of this field, to be part of the GU oncology field, and it continues to be exciting for all the folks who are coming up. Dr. Neeraj Agarwal: Indeed. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much.   Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:   Dr. Neeraj Agarwal @neerajaiims   Dr. Todd Morgan @wandering_gu   Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:    Dr. Neeraj Agarwal:    Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas   Dr. Todd Morgan: Consulting or Advisory Role: Myriad Genetics, MDxHealth, TerumoBCT Research Funding (Institution): Prostate Cancer Foundation, National Institutes of Health, Department of Defence, GenomeDX Biosciences, Myriad Genetics, MDxHealth  

Year Of The Opposite - Travis Stoliker's Substack Podcast
New FDA Approved Sickle Cell Disease Treatments cost $2 - $3 Million.

Year Of The Opposite - Travis Stoliker's Substack Podcast

Play Episode Listen Later Feb 5, 2024 4:07


Sickle Cell Disease impacts about 100,000 people in the US every year. It's an incredibly painful disease where the cells become misshapen like a crescent moon or a sickle. This shape causes the cells to get trapped and restrict the blood flood which causes chronic pain, organ damage, strokes, and shortened life expectancy. Bone marrow transplant has been the best treatment for patients, but it was very challenging to find a potential donor. Only 15% of siblings are a suitable match to be a donor and the chances of finding a match in the general population is about 10%. This means that only about 25% of patients suffering with Sickle Cell Disease had an option for treatment. Year Of The Opposite - Travis Stoliker's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The FDA has now approved two new treatments, Casgevy and Lyfgenia. “Both products are made from the patients' own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. Prior to treatment, a patients' own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia. Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product's safety and effectiveness.” (Link to FDA release)“bone marrow transplant was the first potential cure for sickle cell disease, but trying to find a good match for a transplant is a big barrier. This new technology uses gene therapy to allow patients to be their own match.” - Cece Calhoun, MD, MBA, a Yale Medicine hematologist-oncologist.This is a huge advancement and this same type of gene therapy could be offering hope for other diseases in the near future. But what about the cost? Casgevy, the first CRISPR therapy approved by the FDA, will cost $2.2 million. Lyfgenia the competing genetic medicine is priced at $3.1 million.Those price points are hard to imagine. But let's put some context around them.. Lets compare the cost of the new treatments versus the current standard of care. Insurance companies and the industry estimates the cost of managing sickle cell over a lifetime for someone with recurrent pain is between $4 - $6 million. So $4-6 million for the current treatment vs $2-$3million for the new treatment. How much did it cost to develop Casgevy? That has been a bit hard for me to track down exactly. Vertex (the maker of Casgevy) and CRISPR Therapeutics have an interesting development agreement where they split the cost and profits 60:40. Vertex made a $200,000,000 payment to CRISPR Therapeutics to cover some of the R&D expense as they crossed the milestone of getting FDA approval. However, this doesn't really represent the entire cost of creating Casgevy, because it relies upon the technology created with CRISPR itself. CRISPR alone has had more than $1billion in R&D expense in the past 3-4 years. So how much did it cost to develop Casgevy? It's hard to know exactly, but well into the billions of dollars for sure. So should Casgevy cost $2.2million per treatment? I don't know. But it's something we are going to have to think about as a society. On one hand, we want to be able to fund research and development that invents new technologies that could help hundreds of thousands of people every year. But we also don't want a health care system that is so large that the budget eats into the entire US economy. It's going to be interesting to see how this plays out over the coming years. This isn't the last drug that is going to cost millions of dollars to get. Thank you for reading Year Of The Opposite - Travis Stoliker's Substack. This post is public so feel free to share it. Get full access to Year Of The Opposite - Travis Stoliker's Substack at www.yearoftheopposite.com/subscribe

Xtalks Life Science Podcast
Life Science Trends for 2024

Xtalks Life Science Podcast

Play Episode Listen Later Jan 24, 2024 43:03


In this episode, Ayesha talked about some of the trends in the life sciences to watch out for in 2024. From the increasing integration of artificial intelligence (AI) and machine learning (ML) tools in drug development to medically accurate health wearables, hear about the trends and innovations that will be shaping the life sciences this year.Ayesha spoke to industry experts and innovators in the pharmaceutical, biotechnology and medical device spaces to learn more about these trends and more. Hear about the latest technologies and approaches that will help drive innovations in drug discovery, clinical research and medical device design this year. Read the full article here:Life Science Trends to Look Out for in 2024For more life science and medical device content, visit the Xtalks Vitals homepage.Follow Us on Social MediaTwitter: @Xtalks Instagram: @Xtalks Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

ASCO Daily News
What's New in Prostate Cancer, RCC, and mUC at GU24

ASCO Daily News

Play Episode Listen Later Jan 22, 2024 25:10


Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year.  You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod.  Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj?  Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression.   Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting.  The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits.  Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj?  Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods.   Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny?  Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma.  Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib.  Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma.   Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment.  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy.  Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review.  I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting.  So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers.  Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist.  So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer.  Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts.  So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today.   As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world.  And thank you to our listeners for joining us today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much.  Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:     Dr. Neeraj Agarwal  @neerajaiims  Dr. Jeanny Aragon-Ching    Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:      Dr. Neeraj Agarwal:       Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas     Dr. Jeanny Aragon-Ching:    Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

New FDA Approvals
Erdafitinib for Urothelial Carcinoma, TTFields in NSCLC, AI-Powered Device to Detect Skin Cancer, Casgevy for Beta Thalassemia, HyQvia for CIDP, Physicians' Understanding of FDA Approval Process

New FDA Approvals

Play Episode Listen Later Jan 22, 2024 9:42


For the free course "ChatGPT4 for Medical Writers and Editors," go to learnAMAstyle.com Visit Nascentmc.com/podcast for detailed show notes and links.         Erdafitinib for Urothelial Carcinoma: The FDA has fully approved erdafitinib (Balversa) for advanced or metastatic urothelial carcinoma with FGFR3 genetic alterations in adults. This follows its initial accelerated approval and is based on the phase 3 THOR trial results, showing improved survival rates and manageable side effects. Erdafitinib reduced death risk by 36% and had a lower treatment discontinuation rate compared to chemotherapy.        TTFields in NSCLC: The FDA is reviewing a premarket approval application for tumor treating fields (TTFields) combined with standard therapies for platinum-resistant non–small cell lung cancer. TTFields, first approved in 2011, disrupt cancer cell division and showed enhanced survival in NSCLC patients when combined with immune checkpoint inhibitors or docetaxel, without increasing systemic toxicities. The FDA's decision is expected in the second half of 2024.        AI-Powered Device to Detect Skin Cancer: The FDA has approved the first AI-powered handheld device by DermaSensor for assisting in skin cancer detection. It uses AI-driven spectroscopy for analyzing skin lesions and is based on a study involving over 1000 patients. While not a primary screening tool, it aids in detecting melanoma and other skin cancers, especially in patients over 40, and requires further validation testing.        Casgevy for Transfusion-Dependent Beta Thalassemia: The FDA has approved Casgevy (exa-cel), developed by Vertex Pharmaceuticals and CRISPR Therapeutics, for treating transfusion-dependent beta-thalassemia. This follows its approval for sickle cell disease and marks the first CRISPR gene-editing technology application for this condition. The approval came ahead of the anticipated date and follows Bluebird Bio's 2022 approval for a similar gene therapy.        HyQvia for CIDP: HyQvia, an immune globulin infusion 10%, has been approved by the FDA for chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. Initially approved for primary immunodeficiency, HyQvia is the only product combining immunoglobulin with hyaluronidase, allowing for monthly subcutaneous infusions. The approval is based on its demonstrated efficacy in preventing neuromuscular disability relapse.        Physicians' Understanding of FDA Approval Process: A national survey reveals that many physicians have limited understanding of the FDA's drug and medical device approval processes. Only 41% of the surveyed physicians reported moderate or better comprehension of the drug approval process. Despite believing in the adequacy of FDA standards, there's a call for more rigorous post-marketing studies and enhanced education on FDA processes to avoid misconceptions and inaccurate patient advice.

Medication Talk
First-Line Meds for Hypertension

Medication Talk

Play Episode Listen Later Jan 1, 2024 31:15


Special guest Luke Laffin, MD, FACC, the Co-Director, Center for Blood Pressure Disorders with the Department of Cardiovascular Medicine at the Cleveland Clinic joins us to talkabout first-line meds for hypertension.Listen in as they discuss nuances regarding selection of a first-line medication for the treatment of hypertension.You'll also hear practical advice from panelists on TRC's Editorial Advisory Board:Andrea Darby Stewart, MD, Associate Director, Honor Health Family Medicine Residency Program and Clinical Professor of Family, Community & Occupational Medicine at the University of Arizona College of Medicine - PhoenixDouglas S. Paauw, MD, MACP, Professor of Medicine at the University of Washington School of MedicineFor the purposes of disclosure, Dr. Luke Laffin reports relevant financial relationships with CRISPR Therapeutics [hyperlipidemia], Eli Lilly [obesity], Medtronic [hypertension] (honorarium); Arrowhead [hyperlipidemia], AstraZeneca [hyperlipidemia], Mineralys Therapeutics [hypertension] (grants/research support).The other speakers have nothing to disclose. All relevant financial relationships have been mitigated.TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist's Letter or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.The clinical resources mentioned during the podcast are part of a subscription to Pharmacist's Letter and Prescriber Insights: Chart: Treatment of HypertensionChart: Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme InhibitorsChart: Comparison of Calcium Channel BlockersChart: Comparison of Commonly Used DiureticsIf you're not yet a Pharmacist's Letter or Prescriber Insights subscriber, find out more about our product offerings at trchealthcare.com. Follow or subscribe, rate, and review this show in your favorite podcast app. You can also reach out to provide feedback or make suggestions by emailing us at ContactUs@trchealthcare.com.

The MM+M Podcast
Kathy Delaney calls for creative ‘sea change' to find, fix inequities

The MM+M Podcast

Play Episode Listen Later Dec 20, 2023 41:44


Jack O'Brien interviews Kathy Delaney about the creative “sea change” needed to find and fix health inequities, especially tapping diverse voices. Lecia Bushak explains a bipartisan bill targeting the opioid epidemic that passed in the House last week. And SNL's “Yankee swap” sketch involving CRISPR Therapeutics' recently approved gene therapy tops our Trends segment, along with Oprah's weight-loss Rx. Plus, editors offer their reflections and 2024 outlook. Music by Sixième Son.Follow us: @mmmnewsTo read more of the most timely, balanced and original reporting in medical marketing, subscribe here.

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 14, 2023 58:26


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 14, 2023 58:19


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 14, 2023 58:19


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Pharma and BioTech Daily
The Pharma and Biotech Roundup: Key News from the Industry in One Episode

Pharma and BioTech Daily

Play Episode Listen Later Dec 14, 2023 4:01


Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Today we have a packed episode with news from the healthcare industry. Let's dive in.Integra is set to acquire J&J's Acclarent for $275 million, making them a market leader in ENT procedures. Illumina is divesting its acquisition, Grail, following orders from regulators. Zimvie has received clearance for its spinal fixation system through a collaboration with Brainlab. Crispr Therapeutics and Vertex Pharmaceuticals have developed a sickle cell disease therapy using Crispr technology. Heart device makers are investing in left atrial appendage closure as a potential $6 billion market by 2030. Activist investor Engaged Capital has taken a stake in Nevro.Pfizer is planning to deepen its cost cuts after sales forecasts missed expectations. Vertex Pharmaceuticals is building a case for a non-opioid pain drug. Doctors at the ASH meeting have praised new sickle cell gene therapies. Biotech mergers and acquisitions are picking back up, with Astrazeneca's acquisition of Icosavax being the first large buyout of a vaccine developer since GSK's purchase of Affinivax. Tome Biosciences has debuted with $213 million in funding.Centene attempted to ease concerns about the potential overhaul of the ACA. KKR is reportedly in talks to buy a stake in Cotiviti. Google has revealed new generative AI models for healthcare called MedLM. Cerner is expected to be a growth story for Oracle after this fiscal year. There have been reports of hackers having access to patient information in a cyberattack on a New York hospital.Pfizer's stock price dropped after providing its full-year 2024 guidance. Johnson & Johnson and Genmab released data from a phase III study of their darzalex faspro-based quadruplet therapy. The FDA has created the Genetic Metabolic Diseases Advisory Committee. Biopharma companies are shifting their advertising budgets away from Xplus. South Africa is moving towards greater local biopharmaceutical production.AstraZeneca is set to acquire vaccine maker Icosavax. The FTC has led Sanofi to terminate a drug research deal with Maze Therapeutics. Editas presented its gene therapy for sickle cell disease at the ASH23 conference. Tome Biosciences has debuted with $213 million in funding. Bristol Myers Squibb has paid SystImmune $800 million in a deal involving ADCs. AbbVie's Humira leads ICER's list of "unsupported" price hikes. Pfizer presented new data at the ASH conference.Bristol Myers Squibb has acquired the rights to develop SystImmune's bi-specific ADC. Pfizer's acquisition of Seagen has cleared regulatory hurdles. Sanofi has dropped its acquisition of Maze Therapeutics' Pompe disease drug. AstraZeneca has entered the RSV vaccine market with its purchase of Icosavax. Sino Biological has developed three HEK293 expression-based platforms.The Daily Dive newsletter from Marketing Dive highlights several key stories. Oscar Mayer and Mint Mobile are teaming up for a national campaign called "A Side of Bacon." Frito-Lay is reaffirming its commitment to diverse creators with a new campaign called "My Joy." IPG Mediabrands has struck a deal with Amazon for ad-supported streaming. The newsletter also includes an opinion piece on retail media networks and an upcoming virtual event on generative AI in marketing.The pharmaceutical industry is preparing for upcoming changes and challenges. The cost of medicine is expected to be a major debate point in the 2024 presidential election. Bristol Myers Squibb's Chief Commercial Officer discusses the industry's shifting approach. The article includes sponsored content from AstraZeneca, highlighting their expansion in blood cancer care. The text concludes with links to other resources and press releases.And that's all for today's episode. Stay tuned for more important news from the Pharma and Biotech world. Goodbye!

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 14, 2023 58:26


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 14, 2023 58:26


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Clinical Pharmacology CME/CNE/CPE Video
Sumanta Kumar Pal, MD, FASCO - Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings

PeerView Clinical Pharmacology CME/CNE/CPE Video

Play Episode Listen Later Dec 14, 2023 58:19


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/DJA865. CME/MOC/AAPA credit will be available until December 10, 2024.Leveling Up Our RCC Care Strategy: Real-World Translation of Key Evidence Across Treatment Settings In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through medical education grants from AVEO Pharmaceuticals, Inc., Bristol Myers Squibb, and Exelixis, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerSumanta Kumar Pal, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Allogene Therapeutics; CRISPR Therapeutics; Eisai Co., Ltd.; Exelixis, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; and Pfizer all paid to institution.Faculty/PlannerProf. Laurence Albiges, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; Bristol Myers Squibb; Eisai Co., Ltd.; F. Hoffmann-La Roche AG; Ipsen Pharma.; Janssen Global Services, LLC.; Merck & Co., Inc.; Merck Sharp & Dohme; Novartis AG; and Pfizer all paid to institution.Faculty/PlannerDavid F. McDermott, MD, has no financial interests/relationships or affiliations in relation to this activity.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

BioSpace
Major FDA approvals for Vertex/CRISPR; bluebird gets black box warning and price scrutiny

BioSpace

Play Episode Listen Later Dec 13, 2023 16:55


That was Week with a capital W. Two major FDA approvals for sickle cell came through on Friday - Casgevy, the first-ever CRISPR-based gene editing therapy from Vertex and CRISPR Therapeutics, and bluebird bio's Lyfgenia, which comes with a hefty price tag and a black box warning.  Axcella announced its closure; what does the future of long-covid treatments look like, especially as attention shifts to different markets like ADCs and neurological treatments?  Also discussed - Vanda drops $100m on rights to MS drug Ponvory, AI regulatory developments in Europe.  BioSpace's Lori Ellis, Greg Slabodkin and Tyler Patchen discuss.

Pharma and BioTech Daily
The Pharma and Biotech Daily Digest: Mergers, Profits, Cyberattacks, and Breakthroughs

Pharma and BioTech Daily

Play Episode Listen Later Dec 12, 2023 3:20


Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. In recent news, Cigna and Humana have reportedly abandoned their merger discussions due to a less-than-positive market reaction. Moving on, Boston-based operator Mass General Brigham posted a profit of $432 million in FY 2023, boosted by federal funds. On the other hand, Veradgim, a health IT company, has seen its CEO and CFO step down amid a financial reporting investigation. The company has failed to meet financial reporting requirements that could lead to its delisting. In more positive news, CommonSpirit has named Terika Richardson as its new COO. Richardson is an industry veteran and will assume the post on Monday. Shifting gears, the HHS has settled its first phishing cyberattack investigation with Louisiana medical group Lafourche Medical Group. The agency found that the group failed to conduct a risk analysis or regularly review its information system activity. The breach in 2021 may have exposed the data of nearly 35,000 patients. Ransomware attacks in the healthcare sector are also on the rise, with Norton Healthcare experiencing an attack that exposed the data of 2.5 million people. According to the HHS, ransomware attacks have impacted more than 88 million people in the first 10 months of 2023.In the world of oncology, Gilead Sciences is aiming to become a major player while still focusing on infectious diseases like HIV. Their drug Sunleca, approved for multidrug-resistant HIV treatment, is also being tested as a twice-yearly injection for prevention. Gilead's commercial chief believes that Sunleca could help end the spread of HIV. Additionally, the FDA is urging oncology drugmakers to find the optimal dose early in development to minimize harm and balance efficacy and tolerability.In the field of gene therapies, the FDA has granted approval to two treatments for sickle cell disease, including the first CRISPR-based medicine. The therapies aim to provide a curative treatment for the genetic disorder. However, the FDA is also considering the potential risks and side effects of gene-editing treatments as more therapies move forward in development. Merck has reported a phase III failure for its PD-1 inhibitor Keytruda in a late-stage endometrial carcinoma study, marking the second phase III failure for Keytruda in as many days.Moving on, the FDA is expected to make a historic decision on the approval of a gene editing treatment developed by CRISPR Therapeutics and Vertex Pharmaceuticals. If approved, launching the therapy successfully will be a challenge, considering the low uptake and financial difficulties faced by previous gene therapies. However, companies can learn from past launches to build a foundation for success.Lastly, healthcare industry updates include the White House investigating private equity investment in healthcare, hospital lobbies opposing a bill for equalized payments for drugs administered in outpatient clinics, and Kroger launching a benefits program to expand access to affordable food. Healthcare executives are also looking to implement generative artificial intelligence (AI) tools next year.That's all for today's episode of Pharma and Biotech Daily. Stay tuned for more important updates in the world of Pharma and Biotech.

Closing Bell
Closing Bell: Overtime: CRISPR Therapeutics CEO On Milestone FDA Approval; Rick Caruso On Potential Macy's Sale 12/11/23

Closing Bell

Play Episode Listen Later Dec 11, 2023 44:41


Major averages notched their third straight positive session. Wells Fargo's Scott Wren and CFRA's Sam Stovall break down the market action. Jefferies analyst Brent Thill breaks down Oracle's revenue miss. Caruso Founder Rick Caruso talks rumors of a Macy's sale and the broader state of commercial real estate. CRISPR Therapeutics CEO Sam Kulkarni on his company's partnership with Vertex Pharma leading to breakthrough FDA approval for a sickle cell treatment, the first in US to be approved that uses CRISPR gene-editing technology. 

Pharma and BioTech Daily
Pharma and Biotech Daily: The Latest in Oncology, Gene Therapies, and Healthcare News

Pharma and BioTech Daily

Play Episode Listen Later Dec 11, 2023 3:21


Good morning from Pharma and Biotech Daily: the podcast focusing on essential news in the Pharma and Biotech world. Today, we'll cover multiple stories.Gilead Sciences aims to be a key oncology player while maintaining its focus on infectious diseases, particularly HIV. Its drug, Sunleca, approved in 2022 for treating multidrug-resistant HIV, is also being explored as a biannual preventive injection. Gilead is dedicated to tackling HIV's global health challenges.The FDA advises oncology drugmakers to establish optimal doses early in development. Astrazeneca is advancing in blood cancer care with novel scientific developments. Cell therapies are transforming healthcare, offering solutions to various diseases. Biopharma Dive explores the journey of the first CRISPR medicine, including its challenges and milestones. Moderna and Merck have begun a late-stage mRNA cancer therapy study. Experts at ASH respond cautiously to the approval of sickle cell gene therapies. There's also a call to increase RSV vaccination rates among older adults.The FDA has greenlit two gene therapies for sickle cell disease (SCD), including a pioneering CRISPR-based treatment. These mark a significant progress in SCD treatments, offering hope beyond bone marrow transplants. However, long-term safety and efficacy of gene-editing treatments remain under scrutiny. The FDA plans to continue evaluating these therapies' outcomes.Gene therapies are being researched for various genetic disorders, promising targeted treatments. Yet, these therapies require further study to ensure their safety and effectiveness.The FDA has approved a new CRISPR therapy, Casgevy, for SCD developed by Vertex Pharmaceuticals and CRISPR Therapeutics. This marks a significant step in gene editing, though there are hurdles for its broad adoption.Merck faces challenges as trials involving Keytruda, a major revenue source, fail. Meanwhile, Spyre Therapeutics raised $180 million for its anti-inflammatory drug pipeline. Biotech venture firms experienced increased funding interest.In healthcare, the White House investigates private equity's role. The AHA and FAH oppose a bill affecting outpatient drug payments. Ardent Health Services recovers from a ransomware attack. Kroger introduces a benefits program for Medicare Advantage, Medicaid, and employer benefits recipients. A KLAS Research survey shows growing interest in generative AI among healthcare executives.Lastly, the FDA is poised to approve the first CRISPR gene editing treatment. This could be a milestone in gene editing, setting a precedent for treating genetic diseases. The therapy's launch will be crucial for its long-term success. Companies in gene therapy have learned from past experiences and are now better positioned to navigate the healthcare system.

Stock Market Today With IBD
S&P 500 Hits 2023 High; Arm Holdings, Microsoft, Crispr Therapeutics In Focus

Stock Market Today With IBD

Play Episode Listen Later Dec 8, 2023 16:45


Friday's jobs report and tumbling inflation expectations helped push the S&P 500 to a 2023 high, with the Nasdaq almost there, suggesting the market rally may be on the cusp of another leg higher. Arm Holdings blasted out of an IPO base as chip stocks heat up. Microsoft has held a buy point and a key level. Crispr Therapeutics won a historic FDA approval, but CRSP suffered a classic “sell the news” reversal.

Pharma and BioTech Daily
Pharma and Biotech Daily: The Latest News and Developments in the Industry

Pharma and BioTech Daily

Play Episode Listen Later Nov 23, 2023 4:38


Good morning from Pharma and Biotech Daily, the podcast that gives you only what's important to hear in the Pharma and Biotech world. Today's episode covers a range of news and developments in the industry. Let's get started.## Evelo Biosciences shuts down after clinical setbackFlagship-backed microbiome biotech company Evelo Biosciences is shutting down after facing a clinical setback and laying off staff. The company, which focused on developing microbiome-based therapies, was unable to find a viable alternative to its closure. This news comes as several biotech M&A deals are being announced, although fewer oncology deals have been made this year compared to previous years.## Freeline agrees to take-private deal with SynconaGene therapy company Freeline has agreed to a take-private deal with Syncona after making cuts. This acquisition adds to the string of bargain buyouts and reverse mergers in the gene therapy sector. Meanwhile, fewer biotech companies are going public this year, with only three IPOs taking place in the third quarter. However, there are still many startups waiting in the queue.## Medtronic CEO downplays impact of obesity drugs The CEO of Medtronic, Geoff Martha, downplays the impact of obesity drugs on procedures and devices. Despite the surging demand for GLP-1 agonists, Martha argues that the hit to medtech firms like Medtronic will be minimal.## Index Pharmaceuticals discontinues trial for cobitolimodIndex Pharmaceuticals has decided to discontinue a Phase 3 trial for cobitolimod in ulcerative colitis following a negative review by an independent data monitoring committee. The drug did not meet the primary endpoint of clinical remission compared to placebo.## Moderna's mRNA patent declared invalidThe European Patent Office has declared one of Moderna's mRNA patents invalid, marking a win for Pfizer and BioNTech in ongoing patent disputes between COVID-19 vaccine developers.## CRISPR gene therapy receives approval in the UKCRISPR gene therapy has received its first-ever approval in the UK for the treatment of beta thalassemia. Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, this approval raises questions about whether the US FDA will follow suit in approving CRISPR gene therapies.## Digital tools support patients in search for specialistsOver 25% of rare disease patients have to visit multiple hospitals before receiving a diagnosis, and almost half of them wait a year for that diagnosis. Digital tools can play a crucial role in supporting patients in their search for specialists and care. These tools can narrow down the initial search, identify healthcare professionals with the required expertise, and empower patients through tailored resources.## Google and NBCU offer behind-the-scenes look at Macy's Thanksgiving Day ParadeGoogle and NBCU have partnered to offer a behind-the-scenes look at the Macy's Thanksgiving Day Parade through custom ads. The ads feature the Radio City Rockettes and showcase the AI-powered features of Google's Pixel 8 smartphone. Disney and Verizon have also collaborated on an AR experience to support children through donations to Toys for Tots.## Advertising industry falls short of net-zero goalsA report finds that the advertising industry is "not even close" to realizing its net-zero goals in terms of reducing carbon emissions. The slow adoption of sustainability standards among agencies and production companies is having a negative impact on the entire marketing communications supply chain.## Gene editing, mRNA, and cell therapies promise new medicinesThe text discusses the progress in gene editing, mRNA, and cell therapies, highlighting their potential to revolutionize medicine. Funding challenges and an IPO dry spell are acknowledged, but recent investments indicate continued interest and support for biotech innovation.## Merck acquires Caraway TherapeuticsMerck plans to acquire Caraway Therapeutics in a deal worth up to

BioCentury This Week
Ep. 204 - First CRISPR Approval & IRA's Lost Orphans

BioCentury This Week

Play Episode Listen Later Nov 20, 2023 29:40


The world's first approval of a CRISPR-based gene editing therapy, granted by the U.K.'s MHRA, was a milestone for the technology that was just discovered about 12 years ago. On the latest BioCentury This Week podcast, BioCentury's editors discuss the implications of the landmark and the challenges that still face partners Vertex Pharmaceuticals and CRISPR Therapeutics in launching and scaling the rollout of Casgevy exagamglogene autotemcel (exa-cel) in the U.K. and beyond. The editors also discuss the unintended consequences of the Inflation Reduction Act (IRA) on the development of orphan drugs and new legislation that aims to address the problem by providing an exemption to price negotiations for therapies that are approved only for orphan indications, regardless of how many. The team also reflects on the legacy of FDA's Janet Woodcock ahead of her planned retirement next year; the sentiment coming out of last week's Jefferies Healthcare Conference in London; and the aftermarket performance of two market debuts last week from antibody-drug conjugate CMO WuXi XDC Cayman and Mural Oncology.Music for the 24th Bio€quity Europe promo produced by:Thomas de Paula Eby, Andreas Unge, Epidemic Sound via Getty Images

Pharma and BioTech Daily
Healthcare Evolution: Gene Therapy, Next-Gen Solutions, Influencer Marketing, and Macro-Trends

Pharma and BioTech Daily

Play Episode Listen Later Nov 17, 2023 4:34


Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. ## The world's first CRISPR medicine, Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, has been approved in the UK for the treatment of sickle cell disease and beta thalassemia. However, a gene editing therapy like CRISPR may not be as simple as it seems. While Casgevy can mute the damaging symptoms of sickle cell disease, treatment may not be straightforward. Red Tree Venture Capital plans to expand into San Diego's biotech pipeline and build a competitor to Boston-area investors. The FDA has approved Augtyro, a new drug developed by Bristol Myers, for the treatment of lung cancer. Astellas has published a paper detailing a gene therapy study that led to patient deaths. The company is working with regulators to lift a clinical hold on the treatment.## The Biden administration has finalized a rule requiring nursing homes to disclose their ownership. CommonSpirit, a nonprofit operator, has started its 2024 fiscal year with a $738 million loss. CMS has proposed stricter network adequacy standards for plans sold in state-run ACA exchanges. Centene, a health insurer, has named Susan Smith as its new Chief Operating Executive. UnitedHealth is being sued for using an algorithm to deny care for Medicare Advantage members. There is an increasing trend of electronic health record (EHR) adoption, which has facilitated the rise of big data in healthcare.## The UK's Medicines and Healthcare Products Regulatory Agency (MHRA) has granted conditional marketing authorization for gene-edited therapy ExA-Cel, developed by Vertex Pharmaceuticals and CRISPR Therapeutics. This marks the world's first approval for a CRISPR-edited therapy. Bristol Myers Squibb's (BMS) drug Augtyro has received FDA approval to treat ROS1-positive non-small cell lung cancer (NSCLC). Astellas sees a path forward for its gene therapy AT132 despite four patient deaths in a clinical trial.## The traditional approach to health marketing is becoming inadequate and less effective compared to biotech and pharmaceutical marketers' expectations. Quad offers next-generation solutions that aim to deliver superior results at a lower cost. The text mentions that Quad has a downloadable resource called "next-gen solutions for health marketing" that covers various topics. Quad also offers advertising opportunities to reach over 96,000 biopharma industry executives.## Influencer marketing is growing at a faster rate than traditional paid social media and is projected to reach $21.2 billion worldwide by 2023. Top retailers are taking note of this trend and using it to shape their strategies for the future. The trendline highlights several examples of how brands are leveraging influencer marketing.## Cognizant's Life Sciences Manufacturing Practice offers resources such as web content, whitepapers, videos, and thought leadership articles on their website. They specialize in creating connected GMP manufacturing and lab systems using digital technology adoption and support.## An infographic discusses the factors and macro-trends that different types of medical device companies need to consider when developing a location strategy. The infographic highlights several macro-trends that companies should take into account when developing their manufacturing strategies.## Finance and procurement professionals in the healthcare industry are encouraged to stay ahead by embracing change and utilizing automation. There is an e-book available that provides tools for success and offers a custom demo for transforming operations management in healthcare organizations.## Novo Nordisk plans to invest $6 billion in expanding its manufacturing capabilities in Denmark. Valneva has received regulatory approval from the FDA for its chikungunya vaccine. The American Medical Association (AMA) has called for broader health insurance coverage f

Pharma and BioTech Daily
Pharma and Biotech Daily: Your Essential Dose of Marketing and Biotech Buzz

Pharma and BioTech Daily

Play Episode Listen Later Nov 15, 2023 2:16


Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. Today, we have a packed episode with news from the marketing and biotech sectors.In the marketing world, Chili's is making a nostalgic move by remixing its famous jingle with Boyz II Men. The campaign plays on the misconception that the group was behind the jingle when it first became popular in the 90s. Meanwhile, Lego is using augmented reality (AR) to host a snowball throwing contest at its flagship stores in New York and London. Shoppers will compete to see which city can throw the most digitized snowballs. Lay's and former "The Bachelor" star Matt James are getting in on a viral cooking hack of turning chips into mashed potatoes. They are running a social media sweepstakes to promote their cookbook kit. Trade Desk, an advertising technology company, has reported strong Q3 earnings as its Unified ID 2.0 (UID2) gains momentum. However, the company's shares dropped due to lower Q4 guidance based on advertiser caution. Lastly, alcohol e-commerce platform Drizly is launching a game show campaign and gift registry to meet evolving consumer habits.Now, moving on to biotech news. Ajinomoto, a Japanese food and biotechnology company, has partnered with Forge Biologics in the gene therapy space. Cargo Therapeutics, a CAR-T biotech company, has priced its IPO at $281 million. However, there are concerns about the viability of using CRISPR as a cure for genetic diseases like sickle cell disease. While a therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics has shown promise in muting the symptoms of sickle cell disease, there are complexities and challenges that need to be addressed. In an interview, 23andMe CEO Anne Wojcicki discusses how the company is expanding into drug research and development. Finally, there has been a decline in the number of biotech companies going public, with fewer IPOs in recent years. This trend is seen as oncology-focused drugmakers dominate new biotech stock offerings.That wraps up today's episode of Pharma and Biotech Daily. Stay tuned for more important news and updates in the world of Pharma and Biotech. Have a great day!

Pharma and BioTech Daily
The Pharma and Biotech Daily Podcast: Stay Informed with Only the Essential News

Pharma and BioTech Daily

Play Episode Listen Later Nov 10, 2023 3:03


Good morning from Pharma and Biotech Daily, the podcast that gives you only what's important to hear in the Pharma and Biotech world. ## AstraZeneca's New Deal with EccogeneAstraZeneca has entered into a new deal with China-based biotech company Eccogene. This deal allows AstraZeneca to gain access to an experimental glp-1 drug, which is used to treat diabetes and obesity. The deal involves an upfront payment of $185 million. This move keeps AstraZeneca in the race for developing glp-1 drugs.## Eli Lilly's FDA Approval for Weight Loss DrugEli Lilly has won approval from the FDA for its weight loss drug called Zepbound. This drug is a glp-1 drug and will be sold at a list price about 20% lower than Novo Nordisk's competing therapy. This approval provides another treatment option for individuals struggling with obesity and related health issues.## Atara Biotherapeutics' Shares Tumble After Phase 2 Trial ResultsAtara Biotherapeutics saw its shares tumble by 75% after the results of a phase 2 trial for its cell therapy approach to multiple sclerosis (MS) fell short. Participants given a placebo showed more improvement than those given the experimental treatment.## Takeda's FDA Approval for Colon Cancer DrugTakeda has secured FDA approval for its colon cancer drug. The pharmaceutical company paid $400 million earlier this year to license the drug from Hutchmed in an effort to strengthen its oncology business.## Promising Gene Editing Therapy for Sickle Cell DiseaseA gene editing therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics has shown promise in muting sickle cell disease symptoms. However, treatment may not be as simple as it seems, and there may be challenges and complexities involved.## Coca-Cola's Use of Artificial Intelligence in Las Vegas SphereCoca-Cola has used artificial intelligence (AI) to transform the Las Vegas Sphere, creating an attention-grabbing venue that showcases the future. This initiative builds on the launch of Coca-Cola Y3000 Zero Sugar, a beverage co-created with AI.## Uber's Successful TikTok Creator StrategyUber has successfully built its TikTok creator strategy by looking beyond vanity metrics. Leveraging creators has helped Uber grow its following to over 750,000 within a year.## Unilever's Partnership with TikTokUnilever has partnered with TikTok to create a content series called #CleanTok. The series features animated versions of home care products and aims to attract Gen Z viewers who have driven cleaning trends.## AI's Impact on the Agency LandscapeForrester predicts that AI will permanently disrupt the agency landscape by 2024. Concerns over AI misuse will lead to a 10% increase in agency reviews, and digital agencies may disappear as the technology becomes more widespread.## Under Armour's Revamping of Marketing ApproachUnder Armour is revamping its marketing approach as its outlook worsens. The company plans to focus more on

New FDA Approvals
Pembrolizumab, Secukinumab, Ustekinumab biosimilar, Vonoprazan, Abatacept, Exa-cel

New FDA Approvals

Play Episode Listen Later Nov 6, 2023 8:26


Summary: Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast   Here are the highlights: Pembrolizumab (Keytruda) has received FDA approval for the treatment of metastatic biliary tract cancer, both in combination with chemotherapy and as a monotherapy. The approval is based on the positive outcomes of the KEYNOTE-966 trial, where patients receiving pembrolizumab plus chemotherapy demonstrated a statistically significant improvement in overall survival compared to those receiving a placebo with chemotherapy. Common adverse reactions included hematologic abnormalities, pyrexia, fatigue, cholangitis, and hepatic enzyme elevations. Approval was granted to Merck. Secukinumab (Cosentyx) has gained FDA approval for the treatment of moderate-to-severe hidradenitis suppurativa (HS), making it the first FDA-approved IL-17A inhibitor for this condition. Approval is based on results from the SUNSHINE and SUNRISE trials, showing significant improvements in response rates in HS patients treated with secukinumab compared to placebo. Ustekinumab-auub (Wezlana) has been granted FDA approval as an interchangeable biosimilar for Stelara, offering treatment options for multiple inflammatory diseases. It is indicated for moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis in adult patients, as well as pediatric patients with plaque psoriasis and psoriatic arthritis. Vonoprazan (Voquezna) has received FDA approval for the treatment of erosive esophagitis (GERD). As a potent potassium-competitive acid blocker (PCAB), it offers an alternative to proton pump inhibitors (PPIs). Approval is based on the PHALCON-EE study, where vonoprazan demonstrated noninferiority to lansoprazole in healing GERD. Abatacept (Orencia) has been expanded for use in pediatric patients aged 2 years and older to treat psoriatic arthritis. Originally approved for rheumatoid arthritis in adults in 2005, abatacept was also approved for adult psoriatic arthritis in 2017. Exa-cel, a CRISPR-based therapy developed by CRISPR Therapeutics and Vertex, is under FDA review for sickle cell disease. The advisory panel has found it safe for clinical use, with potential approval expected in December. Exa-cel aims to alleviate sickle cell symptoms through gene editing technology Intro and outro music Garden Of Love by Pk jazz Collective  

Pharma and BioTech Daily
Pharma and Biotech Daily: Your Essential Dose of Industry Updates

Pharma and BioTech Daily

Play Episode Listen Later Nov 2, 2023 2:15


Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. ## Health AI startup Olive is shutting down. The company, once valued at $4 billion, has struggled due to high costs and the failure to secure new funding. This news is a blow to the digital health industry, which has seen a boom in funding recently. ## On another note, Doctors' Management Services has settled claims with the US Department of Health and Human Services (HHS) regarding a ransomware attack that exposed patient information. This settlement marks the first time HHS has taken action against a company for failing to comply with breach notification rules under HIPAA. ## President Joe Biden has issued an executive order for HHS to collect reports on the safety of healthcare AI. This move is part of a larger effort to ensure "safe, secure, and trustworthy" artificial intelligence in healthcare. ## Lastly, Kaiser Permanente has reached a tentative contract deal with a labor union in Washington, preventing a strike by 3,000 workers scheduled for November 1.## In other news, British biopharmaceutical company GSK has reported a 10% increase in sales in the third quarter. This growth can be attributed to strong sales of their respiratory syncytial virus shot Arexvy and shingles vaccine Shingrix. As a result, GSK has raised its outlook for the year.## The US Food and Drug Administration's advisory committee has determined that the off-target analysis for Vertex Pharmaceuticals and CRISPR Therapeutics' sickle cell disease candidate, ExA-Cel, is sufficient.## Astrazeneca has invested $245 million in French biotech firm Cellectis as part of their ongoing efforts to advance cell and gene therapy development. This investment caused Cellectis shares to increase by over 180% in premarket trading.## And finally, a webinar will be held to discuss the optimization of biomarker assays to bridge the gap in clinical trial participation. The use of multiplexed patient-centric assays could help reduce the burden on patients.That's all for today's episode. Stay tuned for more important news in the Pharma and Biotech world.

Pharma and BioTech Daily
Pharma and Biotech Daily: AI Revolutionizes Regulatory Approval, Abzena's Biologics Success, Sarepta's Setback, Eli Lilly's Gene Therapy Move, Pfizer's RSV Vaccine Sales, Novartis' Kidney Disease Drug Success, Neuroscience Advancements

Pharma and BioTech Daily

Play Episode Listen Later Nov 1, 2023 3:42


Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world. Today, we have some interesting news to share with you. Let's get started.## Artificial Intelligence Revolutionizing Regulatory Approval ProcessesArtificial intelligence (AI) is making advancements in regulatory approval processes in the life sciences industry. It has the potential to revolutionize these processes by accelerating and improving consistency and confidence. AI can significantly speed up the regulatory approval process, which currently takes an average of 10 years for drug development. Embracing new technologies like AI is crucial for the industry to move forward.## Abzena: A Leader in Biologics and BioconjugatesAbzena, a contract development and manufacturing organization (CDMO), specializes in biologics and bioconjugates. They have a proven track record of helping clients discover lead candidates, create production cell lines, and deliver programs for investigational new drug (IND) applications. Their effectiveness at getting things done has led to 85% of clients returning to work with them again.## Sarepta Therapeutics Shares Drop After Failed StudySarepta Therapeutics' shares dropped by more than 40% after the results of the Embark study failed to meet its main goal. The study aimed to confirm the approval of its gene therapy Elevidys for treating Duchenne muscular dystrophy. However, there is still hope for gene editing technology as the FDA reviews Vertex Pharmaceuticals and CRISPR Therapeutics' case for approval of a sickle cell therapy.## Eli Lilly Acquires Beam TherapeuticsEli Lilly has acquired Beam Therapeutics in a deal worth $200 million upfront and an additional $50 million investment. This acquisition gives Lilly option rights to several gene editing programs. It is an exciting move that showcases the company's commitment to advancements in gene therapy.## Pfizer's RSV Vaccine Sees Strong SalesPfizer's respiratory syncytial virus (RSV) vaccine, Abrysvo, has seen over $300 million in sales during its first few months on the market. This success is expected to help offset declining sales of COVID-19 vaccines. It is a positive development in the fight against respiratory diseases.## Promising Results for Novartis' Kidney Disease DrugNovartis' bet on a kidney disease drug has yielded positive results in a phase 3 trial. The therapy, acquired through the acquisition of Chinook Therapeutics, met its goals in the trial. This success highlights the potential for advancements in treating kidney diseases.## Neuroscience Drug Development Shows PromiseIn the field of neuroscience drug development, there are promising new drugs for conditions such as Alzheimer's, ALS, and depression. These developments show that neuroscience is becoming a priority again in the biopharmaceutical industry. It is an exciting time for advancements in treating neurological disorders.## Philips Recalls Sleep Apnea Devices, GE Healthcare Remains ResilientPhilips has issued multiple recalls of its sleep apnea devices and ventilators due to problems with soundproofing foam. Despite these recalls, GE Healthcare's sales have remained resilient. The company has raised its earnings forecast for 2023 and plans to expand margins. They are navigating challenges such as China's anti-corruption campaign.## Amgen Takes Write-down, Sarepta Fails Phase III TrialAmgen has announced a $650 million write-down after discontinuing its prostate cancer drug candidate. Sarepta Therapeutics has also failed to meet the primary endpoint in a Phase III trial of its gene therapy for Duchenne

Faster, Please! — The Podcast

On Faster, Please! — The Podcast, I've interviewed guests on exciting new technologies like artificial intelligence, fusion energy, and reusable rockets. But today's episode explores another Next Big Thing: biotechnology. To discuss recent advances in CRISPR gene editing and their applications for medicine, I'm sitting down with Kevin Davies.Kevin is executive editor of The CRISPR Journal and author of the excellent 2020 book, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing.In This Episode* CRISPR advances over the past decade (1:13)* What CRISPR therapies will come next? (8:46)* Non-medical applications of gene editing (13:11)* Bioweapons and the ethics of CRISPR (18:43)* Longevity and genetic enhancements (25:48)Faster, Please! is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Below is an edited transcript of our conversationCRISPR advances over the past decadeWhen people talk about AI, for instance, they might be talking about different versions or applications of AI—machine learning being one. So when we talk about CRISPR, are we just talking about one technique, the one they figured out back in 2012? Are there different ones? Are there improvements? So it's really a different technique. So how has that progressed?You're right. CRISPR has become shorthand for genome editing. But the version of CRISPR that was recognized with the Nobel Prize three years ago in 2020 to Jennifer Doudna and Emmanuelle Charpentier was for one, we can call it the traditional form of CRISPR. And if I refer to it again, I'll call it CRISPR-Cas9. Cas9 is the shorthand name for the enzyme that actually does the cutting of the DNA. But we are seeing extraordinary progress in developing new and even more precise and more nuanced forms of genome editing. They still kind of have a CRISPR backbone. They still utilize some of the same molecular components as the Nobel Prize–winning form of CRISPR. But in particular, I'm thinking of techniques called base editing and prime editing, both of which have commercial, publicly funded biotech companies pushing these technologies into the clinic. And I think over the next five to 10 years, increasingly what we refer to as “CRISPR genome editing” will be in the form of these sort of CRISPR 2.0 technologies, because they give us a much broader portfolio of DNA substitutions and changes and edits, and give the investigators and the clinicians much more precision and much more subtlety and hopefully even more safety and more guarantees of clinical efficiency.Right. That's what I was going to ask. One advantage is the precision, because you don't want to do it wrong. You don't want mutations. Do no harm first. A big advantage is maybe limiting some of the potential downsides.In the ideal gene-editing scenario, you would have a patient with, say, a genetic disease that you can pinpoint to a single letter of the genetic code. And we want to fix that. We want to zero in on that one letter—A, C, T, or G is the four-letter alphabet of DNA, as I hope most of your listeners know—and we want to revert that back to whatever most normal, healthy people have in their genetic code at that specific position. CRISPR-Cas9, which won the Nobel Prize, is not the technology to do that sort of single base edit. It can do many other things, and the success in the clinic is unquestionable already in just a few years. But base editing and, in particular, prime editing are the two furthest developed technologies that allow investigators to pinpoint exactly where in the genome we want to make the edit. And then without completely cutting or slicing the double helix of DNA, we can lay up the section of DNA that we want to replace and go in and just perform chemistry on that one specific letter of DNA. Now, this hasn't been proven in the clinic just yet. But the early signs are very, very promising that this is going to be the breakthrough genome-editing technology over the next 10 to 20 years.Is CRISPR in the wild yet, or are we still in the lab?No, we're in the clinic. We are in human patients. There are at least 200 patients who have already been in or are currently enrolled in clinical trials. And so far, the early results—there are a few caveats and exceptions—but so far the overwhelming mood of the field is one of bullish enthusiasm. I don't want to complete this interview without singling out this one particular story, which is the clinical trial that has been sponsored by CRISPR Therapeutics and Vertex Pharmaceuticals for sickle cell disease. These are primarily African-American patients in this country because the sickle cell mutation arose in Africa some 7,000 years ago.We're talking about a pretty big share of the African-American population.This is about 100,000 patients just in America, in the US alone. And it's been a neglected disease for all kinds of reasons, probably beyond the scope of our discussion. But the early results in the first few dozen patients who have been enrolled in this clinical trial called the exa-cel clinical trial, they've all been cured. Pretty much all cured, meaning no more blood transfusions, no more pain crises, no more emergency hospitalizations. It is a pretty miraculous story. This therapy is now in the hands of the FDA and is speeding towards—barring some unforeseen complication or the FDA setting the bar so high that they need the investigators to go back and do some further checks—this should be approved before the end of this year.There's a catch, though. This will be a therapy that, in principle, will become—once approved by the FDA and the EMA in Europe, of course—will become available to any sickle cell patient. The catch will, of course, be the cost or the price that the companies set, because they're going to look for a return on their investment. It's a fascinating discussion and there's no easy answer. The companies need to reward their shareholders, their investors, their employees, their staff, and of course build a war chest to invest in the next wave, the next generation of CRISPR therapies. But the result of that means that probably we're going to be looking at a price tag of, I mean, I'm seeing figures like $1.9 million per patient. So how do you balance that? Is a lifetime cure for sickle cell disease worth $2, maybe $3 million? Will this patient population be able to afford that? In many cases, the answer to that will be simply, no. Do you have to remortgage your house and go bankrupt because you had a genetic quirk at birth? I don't know quite how we get around this.Different countries will have different answers with different health systems. Do you have a sense of what that debate is going to be like in Washington, DC?It's already happening in other contexts. Other gene therapies have been approved over the last few years, and they come with eye-watering price tags. The highest therapy price that I've seen now is $3.5 million. Yes, there are discounts and waiver programs and all this sort of stuff. But it's still a little obscene. Now, when those companies come to negotiate, say, with the UK National Health Service, they'll probably come to an agreement that is much lower, because the Brits are not going to say that they're going to be able to afford that for their significant sickle cell population.Is it your best guess that this will be a treatment the government pays for?What's interesting and what may potentially shift the calculus here is that this particular therapy is the disease affects primarily African-Americans in the United States. That may change the political calculus, and it may indeed change the corporate calculus in the boardrooms of Vertex and CRISPR Therapeutics, who may not want the backlash that they're going to get when they say, “Oh, by the way, guys, it's $2 million or you're out of luck.”There are companies that are studying using CRISPR to potentially correct the mutations that cause genetic forms of blindness, genetic forms of liver disease.What CRISPR therapies will come next?And after this CRISPR treatment for sickle cell disease is available, what therapies will come next?Probably a bunch of diseases that most people, unless they are unfortunate enough to have it in their family, won't have heard of. There are companies that are studying using CRISPR to potentially correct the mutations that cause genetic forms of blindness, genetic forms of liver disease. It turns out the liver is an organ that is very amenable to taking up medicines that we can inject in the blood. The other big clinical success story has come from another company in the Boston area called Intellia Therapeutics. Also publicly traded. They've developed CRISPR therapies that you can inject literally into the body, rather than taking cells out and doing it in the lab and then putting those cells back in, as in the case of sickle cell.I'm not sure that was actually even clear: that you can do it more than one way.Yes.And obviously it sounds like it would be better if they could just inject you.Exactly. That's why people are really excited about this, because this now opens up the doors for treating a host of diseases. And I think over the next few years we will see a growing number of diseases, and it won't just be these rare sort of genetic diseases with often unpronounceable names. It may be things like heart disease. There's another company—they're all in Boston, it seems—Verve Therapeutics, which is taking one of these more recent gene-editing technologies that we talked about a minute ago, base editing, and saying that there's a gene that they're going to target that has been clearly linked with cholesterol levels. And if we can squash production of this gene, we can tap down cholesterol levels. That will be useful, in the first instance, for patients with genetic forms of high cholesterol. Fair enough. But if it works in them, then the plan is to roll this out for potentially thousands if not millions of adults in this country who maybe don't feel that they have a clearly defined genetic form of high cholesterol, but this method may still be an alternative that they will consider versus taking Atorvastatin for the rest of your life, for example.Where are the CRISPR cancer treatments?They're also making progress, too. Those are in clinical trials. A little more complicated. Of course, cancer is a whole slew of different diseases, so it's a little hard to say, “Yeah, we're making progress here, less so there.” But I think one of the most heartwarming stories—this is an n of one, so it's an anecdotal story—but there was a teenager in the UK treated at one of the premier London medical schools who had a base editing form of CAR T therapy. A lot of people have heard of CAR T therapy for various cancers. And she is now in remission. So again, early days, but we're seeing very positive signs in these early clinical tests.It sounds like we went from a period where it was all in the lab and that we might be in a period over the next five years where it sounds like a wave of potential treatments.I think so, yeah.And for as much as we've seen articles about “The Age of AI,” it really sounds like this could be the age of biotechnology and the age of CRISPR…I think CRISPR, as with most new technologies, you get these sort of hype cycles, right? Two and a half years ago, CRISPR, all the stocks were at peak valuations. And I went on a podcast to say, why are the CRISPR stocks so high? I wasn't really sure, but I was enjoying it at the time. And then, of course, we entered the pandemic. And the biotech sector, perversely, ironically, has really been hit hard by the economy and certainly by the market valuations. So all of the CRISPR gene-editing companies—and there are probably at least eight or 10 now that are publicly traded and many more poised to join them—their valuations are a fraction of what they were a couple of years ago. But I suspect as these first FDA approvals and more scientific peer review papers, of course, but more news of the clinical success to back up and extend what has already been clearly proven as a breakthrough technology in the lab with the Nobel Prize—doesn't get much better than that, does it?—then I think we're going to start to see that biotech sector soar once again.Certainly, there are a lot of computational aspects to CRISPR in terms of designing the particular stretches of nucleic acid that you're going to use to target a specific gene. And AI can help you in that quest to make those ever more precise.Non-medical applications of gene editingThere are also non-medical applications. Can you just give me a little state of play on how that's looking?I think one of the—when CRISPR…And agriculture.Feeding the planet, you could say.That's certainly a big application.It's a human health application—arguably the biggest application.I think one of the fun ones is the work of George Church at Harvard Medical School, who's been on 60 Minutes and Stephen Colbert and many other primetime shows, talking about his work using CRISPR to potentially resurrect the woolly mammoth, which sort of sounds like, “That's Jurassic Park on steroids. That's crazy.” But his view is that, no, if we had herds—if that's the technical term—of woolly mammoths—roaming Siberia and the frozen tundra, they'll keep the ground, the surface packed down and stop the gigatons of methane from leaching out into the atmosphere. We have just seen a week, I've been reading on social media, of the hottest temperatures in the world since records began. And that's nothing compared to what we're potentially going to see if all these greenhouse gases that are just under the surface in places like Siberia further leach into the atmosphere. So that's the sort of environmental cause that Church is on. I think many people think this is a rather foolish notion, but he's launched a company to get this off the ground called Colossal Biosciences, and they're raising a lot of money, it appears. I'm curious to see how it goes. I wish him well.Also, speaking of climate change, making crops more resilient to the heat. That's another I've heard…One of the journals I'm involved in, called GEN Biotechnology, just published a paper in which investigators in Korea have used CRISPR to modify a particular gene in the tomato genome to make it a higher source of vitamin D. And that may not seem to be the most urgent need, but the point is, we can now engineer the DNA of all kinds of plants and crops, many of which are under threat, whether it's from drought or other types of climate change or pests, bacteria, parasites, viruses, fungi, you name it. And in my book Editing Humanity, which came out a couple of years ago, there was a whole chapter listing a whole variety of threats to our favorite glass of orange juice in the morning. That's not going to exist. If we want that all-natural Florida orange juice, we're not going to have that option. We've either got to embrace what technology will allow us to do to make these orange crops more resistant to the existential threat that they're facing, or we're going to have to go drink something else.I started out talking about AI and machine learning. Does that play a role in CRISPR, either helping the precision of the technology or in some way refining the technology?Yeah, hopefully you'll invite me back in a year and I'll be able to give you a more concrete answer. I think the short answer is, yes. Certainly, there are a lot of computational aspects to CRISPR in terms of designing the particular stretches of nucleic acid that you're going to use to target a specific gene. And AI can help you in that quest to make those ever more precise. When you do the targeting in a CRISPR experiment, the one thing you don't want to have happen is for the little stretch of DNA that you've synthesized to go after the gene in question, you don't want that to accidentally latch onto or identify another stretch of DNA that just by statistical chance has the same stretch of 20 As, Cs, Ts, and Gs. AI can help give us more confidence that we're only honing in on the specific gene that we want to edit, and we're not potentially going to see some unforeseen, off-target editing event.Do you think when we look back at this technology in 10 years, not only will we see a wider portfolio of potential treatments, but we'll look at the actual technique and think, “Boy, back in 2012, it was a butchery compared to what we're doing; we were using meat cleavers, and now we're using lasers”?I think, yeah. That's a slightly harsh analogy. With this original form of CRISPR, published in 2012, Nobel Prize in 2020, one of the potential caveats or downsides of the technology is that it involves a complete snip of the double helix, the two strands of DNA, in order to make the edit. Base editing and prime editing don't involve that double-stranded severance. It's just a nick of one strand or the other. So it's a much more genetically friendly form of gene editing, as well as other aspects of the chemistry. We look forward to seeing how base and prime editing perform in the clinic. Maybe they'll run into some unforeseen hurdles and people will say, “You know what? There was nothing wrong with CRISPR. Let's keep using the originally developed system.” But I'm pretty bullish on what base and prime editing can do based on all of the early results have been published in the last few years on mice and monkeys. And now we're on the brink of going into the clinic.One medical scenario that they laid out would be, what if two people with a deadly recessive disease like sickle cell disease, or perhaps a form of cystic fibrosis, wanted to have a healthy biological child?Bioweapons and the ethics of CRISPRThis podcast is usually very optimistic. So we're going to leave all the negative stuff for this part of the podcast. We're going to rush through all the downsides very quickly.First question: Especially after the pandemic, a lot more conversation about bioweapons. Is this an issue that's discussed in this community, about using this technology to create a particularly lethal or virulent or targeted biological weapon?Not much. If a rogue actor or nation wanted to develop some sort of incredibly virulent bioweapon, there's a whole wealth of genetic techniques, and they could probably do it without involving CRISPR. CRISPR is, in a way, sort of the corollary of another field called synthetic biology or synthetic genomics that you may have talked about on your show. We've got now the facility, not just to edit DNA, but to synthesize custom bits of DNA with so much ease and affordability compared to five or 10 years ago. And we've just seen a global pandemic. When I get that question, I've had it before, I say, “Yeah, did we just not live through a global pandemic? Do we really need to be engineering organisms?” Whether you buy the lab leak hypothesis or the bioengineering hypothesis, or it was just a natural transfer from some other organism, nature can do a pretty good job of hurting human beings. I don't know that we need to really worry too much about bioweapons at this point.In 2018, there was a big controversy over a Chinese researcher who created some genome-edited babies. Yeah. Is there more to know about that story? Has that become a hotter topic of discussion as CRISPR has advanced?The Chinese scientist, He Jiankui, who performed those pretty abominable experiments was jailed for the better part of three years. He got early release in China and slowly but surely he's being rehabilitated. He's literally now moved his operation from Shenzhen to Beijing. He's got his own lab again, and he's doing genome editing experiments again. I saw again on social media recently, he's got a petition of muscular dystrophy families petitioning Jack Ma, the well-known Chinese billionaire, to fund his operation to devise a new gene editing therapy for patients with Duchenne muscular dystrophy and other forms of muscular dystrophy. I wouldn't want He Jiankui let within a thousand miles of my kids, because I just wouldn't trust him. And he's now more recently put out a manifesto stating he thinks we should start editing embryos again. So I don't know quite what is going on.It seems the Chinese threw the book at him. Three years is not a trivial prison sentence. He was fined about half a million dollars. But somebody in the government there seems to be okay with him back at the bench, back in the lab, and dabbling in CRISPR. And I don't know that he's been asked, does he have any regrets over the editing of Lulu and Nana. There was a third child born a few months later as well. All he will say is, “We moved too fast.” That is the only caveat that he has allowed himself to express publicly.We know nothing more about the children. They're close to five years old now. There's one particular gene that was being edited was pretty messed up. But we know it's not an essential gene in our bodies, because there are many people walking around who don't have a functional copy of this CCR5 receptor gene, and they're HIV resistant. That was the premise for He Jiankui's experiment. But he has said, “No, they are off limits. The authorities are not going to reveal their identities. We are monitoring them, and we will take care of them if anything goes wrong.” But I think a lot of people in the West would really like to help, to study them, to offer any medical assistance. Obviously, we have to respect their privacy. The twin girls and the third child who was born a bit later, maybe they're being protected for their own good. How would you like it if you grew up through childhood and into your teenage years, to walk around knowing that you were this human experiment? That may be a very difficult thing to live with. So more to come on that.There's no legitimate discussion about changing that in the West or anywhere else?Obviously, in the wake of what He Jiankui did, there were numerous blue ribbon panels, including one just organized by the National Academy of Sciences, just a stone's throw from where we're talking today. And I thought that report was very good. It did two things. This was published a couple of years ago. Two important things came out of it. One is this all-star group of geneticists and other scientists said, “We don't think that human embryo editing should be banned completely. There may be scenarios down the road where we actually would want to reserve this technology because nothing else would help bring about a particular medical outcome that we would like.” And the one medical scenario that they laid out would be, what if two people with a deadly recessive disease like sickle cell disease, or perhaps a form of cystic fibrosis, wanted to have a healthy biological child?There are clinics around the country and around the world now doing something called pre-implantation genetic diagnosis. If you have a family history of a genetic disease, you can encourage the couple to do IVF. We form an embryo or bunch of embryos in the test tube or on the Petri dish. And then we can do a little biopsy of each embryo, take a quick sneak peek at the DNA, look to see if it's got the bad gene or perhaps the healthy gene, and then sort of tag the embryos and only implant the embryos that we think are healthy. This is happening around the country as we speak for hundreds, if not thousands, of different genetic diseases. But it won't work if mom and dad have a recessive, meaning two copies of a bad gene, because there's no healthy gene that you can select in any of those embryos. It would be very rare, but in those scenarios, maybe embryo editing is a way we would want to go. But I don't see a big clamor for this right now. And the early results have been published using CRISPR on embryos in the wake of He Jiankui did have said, “It's a messy technique. It is not safe to use. We don't fully understand how DNA editing and DNA repair works in the human embryo, so we really need to do a whole lot more basic science, as we did in the original incarnation of CRISPR, before we even dare to revisit editing human embryos.” Longevity is interesting because, of course, in the last 18 months there's a company in Silicon Valley called Altos, funded by Yuri Milner, employing now two dozen of the top aging researchers who've been lured away from academia into this transnational company to find hopefully cures or insights into how to postpone aging. Longevity and genetic enhancementsAnother area is using these treatments not to fix things, but to enhance people, whether it's for intelligence or some other trait. A lot of money pouring into longevity treatments from Silicon Valley. Do we know more about the potential of CRISPR for either extending lifespans or selecting for certain desirable traits in people?This sort of scenario is never going to go away. When it comes up, if I hear someone say, “Could we use CRISPR or any gene editing technology to boost intelligence or mathematical ability or music musical ability, or anything that we might want…”Or speed in the hundred meters.“…or speed in the hundred meters, to enhance our perfect newborn?” I would say, what gene are you going to enhance? Intelligence—are you kidding me? Half of the 10,000 genes are expressed in the human brain. You want to start meddling with those? You wouldn't have a prayer of having a positive outcome. I think we can pretty much rule that out. Longevity is interesting because, of course, in the last 18 months there's a company in Silicon Valley called Altos, funded by Yuri Milner, employing now two dozen of the top aging researchers who've been lured away from academia into this transnational company to find hopefully cures or insights into how to postpone aging. That's going to be a long, multi-decade quest to go from that to potentially, “Oh, let's edit a little embryo, our newborn son or daughter so they have the gift of 120 years on this decaying, overheating planet…” Yes, there's a lot to wade through on that.And you have another book coming out. Can you give us a preview of that?I'm writing a book called Curved Air, which is about the story of sickle cell disease. It was first described in a paper from physicians in Chicago in 1910 who were studying the curious anemia of a dental student who walked into their hospital one day. That gentleman, Walter Noel, is now buried back in his homeland, the island of Grenada. But in the 1940s, it was described and characterized as the first molecular disease. We know more about sickle cell disease than almost any other genetic disease. And yet, as we touched on earlier, patients with this who have not had the wealth, the money, the influence, they've been discriminated against in many walks of life, including the medical arena.We're still seeing terribly, tragically, videos and stories and reports of sickle cell patients who are being turned away from hospital rooms, emergency rooms, because the medical establishment just looks at a person of color in absolute agony with one of these pain crises and just assumed, “Oh, they want another opioid hit. Sickle cell? What is that?” There's a lot of fascinating science. There's all this hope in the gene editing and now in the clinic. And there's all this socioeconomic and other history. So I'm going to try to weave all this together in a format that hopefully everyone will enjoy reading.Hopefully a book with a happy ending. Not every book about a disease has a wonderful…I think a positive note to end on is the first American patient treated in this CRISPR clinical trial for sickle cell disease four years ago,Victoria Gray, has become something of a poster child now. She's been featured on National Public Radio on awhole series of interviews and just took her first overseas flight earlier this year to London to speak at a CRISPR gene editing conference. She gave a lovely 15-minute personal talk, shaking with nerves, about her personal voyage, her faith in God, and what's brought her here now, pain-free, traveling the world, and got a standing ovation. You don't see many standing ovations at medical conferences or genetics conferences. And if ever anybody deserved it, somebody like Victoria Gray did. Early days, but a very positive journey that we're on. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit fasterplease.substack.com/subscribe

I AM BIO
The New Age of CRISPR (Redux)

I AM BIO

Play Episode Listen Later Jul 18, 2023 27:40


CRISPR has emerged as a powerful tool for altering DNA sequences with incredible precision, opening up new avenues of research into the treatment of disease. In this episode, we explore the science behind CRISPR, as well as its potential. From curing genetic disorders to creating new crop varieties, the possibilities seem endless. Our four guests today are scientists working to push these gene editing tools to the next frontier.

Canary Cry News Talk
BASIL BACK BETTER

Canary Cry News Talk

Play Episode Listen Later Jun 15, 2023 140:40


The Best Christian Podcast in the Metaverse Canary Cry News Talk #633 - 06.14.2023 - Recorded Live to Tape BASIL BACK BETTER | Billy Xi, Trumpers, Commercial CRISPR, 33 Immortals Deconstructing Corporate Mainstream Media News from a Biblical Worldview We Operate Value 4 Value: http://CanaryCry.Support Join Supply Drop: http://CanaryCrySupplyDrop.com Submit Articles: http://CanaryCry.Report Join the Tee Shirt Council: http://CanaryCryTShirtCouncil.com Resource: Index of MSM Ownership (Harvard.edu) Resource: Aliens Demons Doc (feat. Dr. Heiser, Unseen Realm) All the links: http://CanaryCry.Party   This Episode was Produced By: Executive Producers Caroline F*** Juan E*** Sir Kevin M*** Tracy S***   Producers Sir Marti K Knight of the Wrong Timeline Christine S Heather M Sir LX Protocol V2, Knight of the Berrean Protocol Morgan E Jacob B Sir Morv Knight of the Burning Chariots Sir Casey the Shield Knight Dame Gail Canary Whisperer and Lady of X's and O's Veronica D Sir Scott Knight of Truth   CanaryCry.ART Submissions LittleOwen Sir Dove Knight of Rusbeltia   Microfiction Runksmash - The dastardly coyote slinks silently towards the coop, but tonight his meal will meet him with resistance he didn't expect. As he nears the coop a heroic tuft of feathers darts out and starts pecking and scratching, but the ordeal is over too soon.   CLIP PRODUCER Emsworth, FaeLivrin, Joelms, Laura   TIMESTAPERS Jade Bouncerson, Christine C, Pocojo, Morgan E   CanaryCry.Report Submissions JAM, Sir Ike   REMINDERS Clankoniphius   SHOW NOTES T - 3:31 on D-Live HELLO, RUN DOWN 7:20 V / 3:49 P CATCHING UP with BASIL 9:51 V / 6:20 P Clip: No Agenda talking about VR podcasting (52:00)   DAY JINGLE/V4V/EXEC./TREASURE    FLIPPY This Insane Robotic Chef Could Soon Be Cooking Up Meals on Your Flight (Robb Report)   CRISPR First for the FDA. Could It Signal Big Turning Point for CRISPR Therapeutics? (Motley Fool) → CRISPR Therapeutics to Participate in Goldman Sachs Global Healthcare Conference    TRUMP Trump faces a max of 400 years in prison and a $9M fine over federal indictment (NY Post)    NEW WORLD ORDER → San Francisco's secretive Bohemian Grove sued by valets (SF Gate)   BILL GATES Bill Gates-backed solar company raises $103 million for US wafer factory (Deccan Herald) → Exclusive-Bill Gates to Meet President Xi on Friday During China Visit - Sources (US News)   TAIWAN US preparing 'evacuation plans' for American citizens in Taiwan (FirstPost)   COVID → J&J's COVID vaccine is dead in the US; FDA revokes authorization (ars Technica) → Japan, ppl who got used to masks during COVID attending smiling lessons (Sky News)    33 '33 Immortals' first look: Defying a god is more fun with friends (Engadget)   V4V/SPEAKPIPE/TALENT/TIME END

ASCO Daily News
ASCO23: Key Abstracts from Precision Oncology to Cancer Disparities

ASCO Daily News

Play Episode Listen Later May 25, 2023 20:54


Dr. John Sweetenham and Dr. Neeraj Agarwal discuss advances across the spectrum of malignancies, including key studies in precision oncology and disparities in cancer care in advance of the 2023 ASCO Annual Meeting.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, now the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast. I'm delighted to welcome Dr. Neeraj Agarwal, director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, who is editor-in-chief of the ASCO Daily News.  Today we'll be discussing some key advances across the spectrum of malignancies, as well as novel approaches in precision medicine and cancer disparities that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/DNpod.  Neeraj, it's great to have you back on the podcast today. Dr. Neeraj Agarwal: Thank you so much, John, for having me. Dr. John Sweetenham: Neeraj, let's begin by discussing some practice-changing phase 3 trials, starting with Abstract 5500, the KEYNOTE-826 study. This study reports the final overall survival results from a randomized, double-blind, phase 3 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer, which will be presented by Dr. Bradley Monk.  Dr. Neeraj Agarwal: I'd be happy to. The initial analysis of the KEYNOTE-826 study revealed that first-line pembrolizumab plus chemotherapy provided significant improvements in the overall survival and progression-free survival compared to placebo plus chemotherapy in patients with metastatic, persistent, or recurrent cervical cancer who had not previously received systemic chemotherapy and were not candidates for curative treatments such as surgery or radiation. In this study, patients were randomly assigned in a 1:1 ratio to receive pembrolizumab or placebo at 200 milligrams every three weeks for up to 35 cycles, along with chemotherapy with paclitaxel, plus a platinum therapy with or without bevacizumab.   From November 2018 to January 2020, 617 patients were enrolled with 308 receiving pembrolizumab plus chemotherapy and 309 patients receiving placebo plus chemotherapy. At the data cutoff of October 3, 2022, the median follow-up was 39 months. At this protocol-specified final overall survival analysis, pembrolizumab plus chemotherapy treatment continues to show a significant improvement in overall survival and progression-free survival, regardless of whether patients receive bevacizumab or not. The incidence of grade 3 or more adverse events was higher in the pembrolizumab plus chemotherapy arm than the placebo plus chemotherapy arm, with the most common adverse event being anemia, neutropenia, and hypertension. Dr. John Sweetenham: These are exciting data, Neeraj. So the main message from this trial is that pembrolizumab plus chemotherapy, with or without bevacizumab, can now be considered as standard of care for first-line treatment of persistent, recurrent, or metastatic cervical cancer. Dr. Neeraj Agarwal: Yes, I agree, John. Now, moving on to a different common type of cancer, let's discuss Abstract 1001, titled “Second-Line Endocrine Therapy with or without Palbociclib Maintenance in Patients with Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer: Results from the PALMIRA Trial,” which will be discussed by Dr. Antonio Llombart-Cussac. So, John, based on this abstract, can you please tell us about the role of palbociclib after prior progression on this drug? Dr. John Sweetenham: Yes. In this study, the authors aimed to determine if palbociclib maintenance with an alternative endocrine therapy improves the anti-tumor activity of second-line treatment in patients with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer who had disease progression to first-line treatment with palbociclib in combination with endocrine therapy. After including 198 patients in the trial with a 2:1 randomization, 136 patients received palbociclib with endocrine therapy and 62 patients received endocrine therapy alone. And at a median follow-up of 8.7 months, the primary endpoint of progression-free survival was not met with a median progression-free survival of 4.2 months in the palbociclib-containing combination versus 3.6 months in the control arm. Also, higher grade 3 to 4 adverse events were reported in patients treated in the palbociclib arm. Dr. Neeraj Agarwal: Thanks, John. So you are saying that continuing the CDK4/6 inhibitor palbociclib after prior disease progression on palbociclib, even when the primary endocrine therapy has been changed, doesn't seem to be beneficial, therefore, this practice may be discouraged in the clinical setting? Dr. John Sweetenham: Yes, that's correct. Neeraj, I think that's the conclusion from this study. Dr. Neeraj Agarwal: So, John, now let's switch gears and highlight some precision oncology studies.  Dr. John Sweetenham: Well, Abstract 3602, titled “Real World Rates of FDA-Approved Targeted Therapy and Immunotherapy Prescriptions for Metastatic Colorectal Cancer Patients in the VA's National Precision Oncology Program” will be presented by Dr. Alice Nono Djosta. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Well, comprehensive genomic profiling has the potential to guide the administration of FDA-approved biomarker-directed therapies and improve outcomes among patients with metastatic colorectal cancer. So, in this study, Abstract 3602, investigators sought to determine the rates of actionable biomarkers and prescription of associated FDA-approved therapies among veterans in the National Precision Oncology Program. Patients with metastatic colorectal cancer who had undergone comprehensive genomic profiling via tissue or liquid biopsy were included between 2019 and 2022 and had 1 of the following 5 actionable biomarker profiles including: NRAS, KRAS, BRAF wild-type, BRAF V600E mutation, MSI-high, TMB-high, NTRK fusion or rearrangements.  Prescription data for seven FDA-approved biomarker-directed therapies were extracted and rates of comprehensive genomic profiling (CGP)-directed therapy prescriptions were assessed by the investigators. A total of 908 patients with metastatic colorectal cancer underwent comprehensive genomic profiling, with 80% patients having colon adenocarcinoma and 20% with rectal adenocarcinoma. The combined rates of any actionable variants were 47% in patients with colon adenocarcinoma and 45% in patients with rectal adenocarcinoma. After including 424 eligible patients for FDA-approved biomarker therapy, only 70% patients with MSI-high, 48% patients with TMB-high, 38% patients with NRAS, KRAS, and BRAF wild-type, and only 17% of patients with BRAF V600E mutation received FDA-approved CGP-directed therapies.  Dr. John Sweetenham: Very important data, Neeraj. What's the main conclusion of this study? Dr. Neeraj Agarwal: So, in conclusion, this study found that almost 30% of patients with MSI-high metastatic colorectal cancer did not receive effective immune checkpoint inhibitors. And overall, a significant number of eligible patients did not receive FDA-approved biomarker-directed therapies. So, it is crucial that we evaluate the barriers to prescribing comprehensive genomic profiling-directed therapies in our patients with metastatic colorectal cancers.  So, John, let's move on to lung cancer, where the use of single-gene testing is still common in the community practice. Can you please tell us about Abstract 6506, titled “The Impact of Single-Gene Testing on Subsequent Comprehensive Genomic Profiling Success in Community Oncology Practice for Advanced Non–small Cell Lung Cancer”? These are results from a prospective observational reference laboratory testing program and these results will be presented by Dr. Mary Nesline. Dr. John Sweetenham: Yes, definitely. In this study, researchers aim to investigate the impact of prior single-gene testing on comprehensive genomic profiling success and therapeutic opportunities for patients with non–small cell lung cancer in community settings. They included patients who underwent at least 1 single gene testing for guideline recommending genomic variants in non–small cell lung cancer such as BRAF, EGFR, KRAS, MET exon 14 skipping mutations, ALK, RET, and ROS1 rearrangements as well as PD-L1 immunohistochemistry.  And they offered comprehensive genomic profiling either before or after receipt of a negative single gene test. Of 580 patients with non–small cell lung cancer with the comprehensive genomic profiling ordered between 2021 and 2022, around 30% of the patients had at least 1 single-gene testing ordered prior to the comprehensive testing, with a median of 5 prior single-gene tests. Compared to CGP-only cases. CGP per cases with prior negative single gene testing was canceled twice as often at tissue review, had a higher DNA extraction failure, and a lower DNA sequencing success. CGP also identified guideline-recommended variants in genes with no single-gene testing offered during the study period, such as ERBB2 mutations, or NTRK2/3 fusions, as well as variants targeted in ongoing clinical trials in 28% of patients. Dr. Neeraj Agarwal: Very interesting. So John, what is your key takeaway message from this? Dr. John Sweetenham: The main message is that in a community oncology setting, the practice of ordering single gene testing prior to comprehensive genomic profiling for patients with non–small cell lung cancer is common. Prior negative single-gene testing led to a higher rate of CGP test cancellation due to tissue insufficiency and increased CGP DNA extraction failures. The practice of single-gene testing does not align with practice guideline recommendations and may negatively impact the potential benefits of CGP testing for patients with non–small cell lung cancer.  Now, let's move on to another important abstract that our fellow clinicians should hear about. This is Abstract 1534 titled “Real-World Experience of an In-House Dihydropyrimidine Dehydrogenase Genotype Test to Guide Fluoropyrimidine Dosing at a Multi-Site Cancer Hospital” that will be presented by Dr. Jai Patel. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. Fluoropyrimidines, such as 5-fluorouracil and capecitabine, are commonly used to treat solid tumor cancers such as gastrointestinal and breast cancers. We know that severe toxicity occurs in one-third of patients, which delays the timely completion of treatments and result in prolonged hospitalization of these patients. These toxicities may be due in part to genetic variation in the DPYD gene. Five variants are known to have moderate to strong evidence according to the Clinical Pharmacogenetics Implementation Consortium. So, in this observational study, the authors describe the implementation of an in-house DPYD test and its impact on the dosing of these fluoropyrimidines, which include capecitabine and 5-fluorouracil.  From March 2020 to December 2022, 491 patients received DPYD genotyping testing, and 90% of them had gastrointestinal cancers. The median lab turnaround time was only 3 days. Pre-treatment testing was ordered in 80% of patients, and 93% of patients had results before starting cycle 1. Overall, 6% of patients were heterozygous carriers. Fluoropyrimidine dose was reduced, avoided, or discontinued in 90% of these patients. Moreover, in pre-treatment carriers, 90% of patients received an upfront dose reduction, avoidance, or they even declined chemotherapy. Dr. John Sweetenham: Thanks, Neeraj. So what do you think is the key takeaway message here? Dr. Neeraj Agarwal: So, DPYD genotype-guided dosing of fluoropyrimidine, including 5-fluorouracil and capecitabine, is logistically feasible with a rapid turnaround time and can result in treatment dose modifications for most carriers, potentially avoiding or mitigating severe toxicities, especially in those patients who received pre-treatment testing. Dr. John Sweetenham: Thanks again. Now let's transition to studies that focus on disparities in cancer care. Dr. Neeraj Agarwal: Definitely. Let's discuss Abstract 6530, titled “Impact of Free Hospital-Provided Rideshare Service on Radiation Therapy Completion Rates: A Matched Cohort Analysis.” In this study, Dr. Eric Chen and colleagues assess the potential of rideshare services in facilitating timely radiation therapy for patients facing barriers, such as limited transportation, financial constraints, and lack of adequate social support. So the authors analyzed data from about 2,900 patients who underwent radiation therapy and found that 58 of them utilized a free hospital-provided rideshare service.  These free hospital-provided rideshare service utilizers had a lower median age and were more likely to identify as Black or African American compared to those who did not utilize these services. They also had higher socioeconomic disadvantages and traveled shorter distances for treatment. Interestingly, more rideshare utilizers underwent radiation therapy with curative intent, had longer treatment course duration, and a higher number of fractions prescribed. In the matched-cohort analysis, the study found that radiation therapy completion rates were significantly higher for rideshare utilizers compared to non-rideshare utilizers, especially for patients who were undergoing radiation therapy with curative intent.  Dr. John Sweetenham: So what's the key take-home message from this abstract? Dr. Neeraj Agarwal: This study highlights the potential benefit of utilizing hospital-provided free ride-share services, particularly for patients facing barriers to timely treatment. So, using these services were associated with higher radiation therapy completion rates, especially in the curative setting.  So, John, there is another study, Abstract 1606, titled “Trends and Disparities in Oncology Telehealth after the Initial Pandemic Era” that will be presented by Dr. Michael Lee and colleagues. They evaluated whether telehealth utilization continued after the pandemic and if demographic differences in its users persist. So John, please tell us more about this abstract. Dr. John Sweetenham: Yes, the authors conducted a retrospective cohort study in 22 Kaiser Permanente Northern California hematology and oncology clinics between October 1, 2020, and June 1, 2022. The study investigated the use of office, video, and telephone visits, analyzing more than 340,000 hematology oncology visits with MD or DO providers. Of these visits, 25% were in-office, 37% were video visits, and 39% were telephone visits. Monthly telehealth visits peaked in January 2021, representing around 86% of total visits, and decreased to 69% of the total visits by June 2022. Video visits were more common for new appointments, whereas telephone visits were more common for return appointments. Moving to the post-pandemic period, telehealth visits remained popular, with video visits being the most commonly utilized. However, telehealth use varied among demographic populations. Video visits were a significantly higher proportion of all visits among individuals less than 45 years old, primary English speakers, patients with commercial insurance, non-Hispanic Whites and Asians, compared with Hispanic, Whites, and Blacks, and patients living in the deprived neighborhoods. Dr. Neeraj Agarwal: Interesting data, John. So what is the key takeaway message from this abstract? Dr. John Sweetenham: Well, overall, it's encouraging to see that even after the pandemic, telehealth continued to be widely used. However, the concerning issue is that telehealth is less utilized in patients who may need it most. The next step, in my view, will be to work on barriers to access telehealth by underprivileged populations.   And that brings our discussion to a close today. Before we wrap up the podcast, Neeraj, do you have any final thoughts to share? Dr. Neeraj Agarwal: Yes, thanks, John. I would urge our listeners to come and join us at the ASCO Annual Meeting, not only to celebrate these successes but also to help disseminate these cutting-edge data to practitioners and patients across the world. Dr. John Sweetenham: Absolutely. I'd like to thank our listeners for joining us today, and thank you, Neeraj, for sharing your insights with us as well.  You will find links to the abstracts discussed today on the transcripts of this episode. Finally, if you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers: Dr. John Sweetenham Dr. Neeraj Agarwal @neerajaiims Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Neeraj Agarwal:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas

ASCO Daily News
ASCO23: Novel Approaches in RCC, mUC, and Prostate Cancer

ASCO Daily News

Play Episode Listen Later May 25, 2023 24:49


Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss the CLEAR study in renal cell carcinoma, a new exploratory analysis combining the TheraP and VISION trials in metastatic urothelial cancer, and compelling advances in prostate cancer and across GU oncology in advance of the 2023 ASCO Annual Meeting.  TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host for the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia.   Today, we'll be discussing some key abstracts in GU oncology that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcript at asco.orgDNpod.   Jeanny, it's great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4502 regarding long-term updated results on the CLEAR study. The abstract reports the final, prespecified overall survival analysis of the CLEAR trial, a four-year follow-up of lenvatinib plus pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yes, I would be happy to. So, just as a reminder, the combination of lenvatinib and pembrolizumab was initially approved by the FDA in August 2021 for first-line treatment of adult patients with advanced renal cell carcinoma. So, this was based on significant benefits that were seen in progression-free survival, which was a primary endpoint, but also showed improvement in the overall response rates compared with sunitinib in first-line advanced renal cell carcinoma.   So this abstract reports on longer-term follow-up now at a median of 49.8 months, and PFS favored the combination lenvatinib and pembrolizumab compared to sunitinib across all MSKCC risk groups, and PFS benefit versus lenvatinib and pembro compared to sunitinib was maintained with a hazard ratio of 0.47. And even overall survival was also maintained with the combination with a hazard ratio of 0.79, and the overall survival favored the combination across all risk groups. If we look at the CR rate, it was 18.3% for the combination compared to 4.8% with sunitinib, unless patients in the combination arm received subsequent anticancer therapies, and that's intuitive. And the PFS2 was also longer with the combination at 43 months compared to 26 months. Now, it is important to note that grade III or more treatment-related adverse events did occur in about 74% of the patients in the combination of lenvatinib and pembro, compared to 60.3% in patients with sunitinib. Dr. Neeraj Agarwal: Jeanny, this is good news. So the main message from the abstract is that sustained results from this combination of lenvatinib plus pembrolizumab are being seen even after a longer follow-up of more than four years.  Dr. Jeanny Aragon-Ching: Yes, I agree. So now, moving on, Neeraj, to a different setting in the RCC space, let's look at Abstract 4519, which is titled “Efficacy of First-line Immunotherapy-based Regimens in Patients with Sarcomatoid and/or Rhabdoid Metastatic Non-Clear Cell RCC: Results from the IMDC,” which will be discussed by Dr. Chris Labaki. So, Neeraj, based on this abstract, can you tell us a little bit more about the impact of these adverse pathologic risk features in non-clear cell RCC?  Dr. Neeraj Agarwal: Of course. So, using real-world patient data, the IMDC investigators compared the outcomes of patients with metastatic non-clear cell RCC who were treated with immunotherapy-based combination regimens versus those who were treated with VEGF-TKIs alone. They also assessed the impact of sarcomatoid and rhabdoid features on response to IO-based combinations versus VEGF-TKIs. Of 103 patients with metastatic non-clear cell RCC who had rhabdoid or sarcomatoid features, 32% of patients were treated with immunotherapy-based combinations.   After adjusting for confounding factors, the authors show that those treated with a combination of two immune checkpoint inhibitors or an immune checkpoint inhibitor with a VEGF-TKI combination had significantly improved overall survival, which was not reached in the immunotherapy combination group versus seven months within the VEGF-TKI group. Time to treatment failure and objective responses were also prolonged, significantly higher, and better in the immunotherapy groups compared with patients who were treated with VEGF-TKIs alone. Interestingly, if you look at those 430 patients with metastatic non-clear cell RCC who did not have sarcomatoid or rhabdoid features, they didn't seem to benefit with immunotherapy-based combinations.  Dr. Jeanny Aragon-Ching: This is an exciting update, Neeraj. What are the key takeaways from this abstract? Dr. Neeraj Agarwal: So the main takeaway is if you see a patient with advanced non-clear cell RCC who has sarcomatoid and rhabdoid features, there appears to be a rather substantial and selective benefit with IO-based combinations. And in this context, I would like to highlight the ongoing SWOG 2200 trial also known as PAPMET2 trial, which is comparing the combination of cabozantinib plus atezolizumab. So immuno-therapy-based combinations versus cabozantinib alone in advanced papillary renal cell carcinoma setting. So this trial is being led by Dr. Benjamin Maughan and Dr. Monty Pal. And I like to encourage our listeners to consider referring their patients for involvement in this federally funded trial so that we can validate the data from this retrospective study in a prospective way. So, Jeanny, let's now move on to another important disease type which is urothelial carcinoma. There is a very recent accelerated FDA approval of the drug combination of enfortumab vedotin and pembrolizumab for cisplatin-ineligible metastatic urothelial carcinoma patients. This is Abstract 4505, which is being presented by Dr. Shilpa Gupta and colleagues. Can you please tell us more about this update? Dr. Jeanny Aragon-Ching: Yeah, absolutely. So, as you mentioned, Neeraj, the FDA just granted accelerated approval in April 2023 for this combination of enfortumab vedotin or EV, which is and ADC, antibody drug conjugate against nectin-4 and the PD-1 inhibitor pembroluzimab. So it's a combination for patients with locally advanced or metastatic urothelial carcinoma who are considered cisplatin ineligible. So this is nearly a four-year follow-up.   So as a reminder, this was a phase 1b/2 trial that included 45 patients and it had a primary endpoint of safety and tolerability although the key secondary endpoints included confirmed overall responses, duration of response, progression-free survival, and the resist criteria was investigated via investigator and BICRs which is in a blinded independent central review. Even overall survival was a key secondary endpoint.  So, the bottom line was the confirmed overall response by BICR was 73.3%, the disease control rate was about 84%, and the CR rate was 15.6% with a PFS of close to 13 months, and a 12-month overall survival rate of 83%. However, it is important to cite that there were treatment-related adverse events including skin reactions in 66%, neuropathy occurred in 62%, and ocular disorders in 40%. And there was a little bit of pneumonitis in close to 9%, colitis, and hypothyroidism, so there are side effects to watch out for.  Dr. Neeraj Agarwal: So, Jeanny this is great. What is the key takeaway from this trial?  Dr. Jeanny Aragon-Ching: So I think the most important thing is we now have a new combination of EV and pembro which shows very promising responses and survival in part which led to the FDA accelerated approval in the cisplatin-ineligible population of patients. However, we must note that the phase 3 trial of EV302 will ultimately establish which approach is really beneficial for all of our cisplatin-ineligible patients, either a carboplatin-based chemotherapy regimen or a non-platinum-based regimen such as EV and pembro. Dr. Neeraj Agarwal: Thanks Jeanny, would you like to discuss any other study in the bladder cancer space? Dr. Jeanny Aragon-Ching: Absolutely. I think Abstract 4508 from Dr. Seth Lerner and colleagues will be very relevant to our colleagues. This abstract is SWOG S1011, which is a phase 3 surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at the time of radical cystectomy for muscle-invasive bladder cancer.  Dr. Neeraj Agarwal: Yes. So this trial, as you said, is an important trial which randomized in a one-on-one fashion 618 patients with muscle-invasive bladder cancer undergoing radical cystectomy, and these patients were randomized to either standard lymph node dissection or an extended lymph node dissection. And standard lymph node dissection included, as we know, external and internal iliac and operative lymph node. The extended lymph node dissection included lymph nodes up to aortic bifurcation which included common iliac, presciatic, and presacral lymph nodes. At a median follow-up of approximately 6 years, there was no disease-free survival or overall survival benefit in patients undergoing an extended lymph node dissection compared to standard lymph node dissection. And extended lymph node dissection was also associated with greater morbidity and preoperative mortality. Dr. Jeanny Aragon-Ching: Very interesting data, Neeraj. So these results, I think, will be very useful for a lot of our surgical colleagues in both academia and the community who may still be inclined to perform extended lymphadenectomy during cystectomy. This study shows that it's actually not necessary. Dr. Neeraj Agarwal: Absolutely. So now let's move on to another disease type, which is very important - prostate cancer. There are several practice-informing abstracts that are worthwhile discussing. The first of these involves Abstract 5002, which looks at the impact of the PSA nadir as a prognostic factor after radiation therapy for localized prostate cancer, which will be presented by Dr. Praful Ravi and  colleagues. Jeannie, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, definitely. So this abstract, as you mentioned, Neeraj, is a prognostic impact of PSA nadir of more than or equal to 0.1 nanogram per ml within six months after completion of radiotherapy for localized prostate cancer - an individual patient data analysis of randomized trials from the ICECaP Collaborative. Basically, it refers to an attempt to evaluate early surrogate measures to predict for long term outcomes such as prostate cancer-specific survival, metastases-free survival, and overall survival. So they looked at a big registry from the ICECaP collaboration that included 10,415 patients across 16 randomized controlled trials. And those men underwent treatment for intermediate risk and high risk prostate cancer treated with either radiation therapy alone in about a quarter of patients, or they got RT with short-term ADT in about 58% of patients, and 17% of them got RT with long-term ADT.  So, after a median follow-up of ten years, what they found was, if you had a PSA nadir that is over or equal to 0.1 nanogram per ml within six months after completion of radiation therapy, it was associated with worse prostate cancer-specific survival, metastases-free survival, and overall survival. For instance, the five-year metastases-free survival for those who achieved a PSA nadir of less than 0.1 was 91% compared to those who did not, which was 79%. Therefore, they concluded that if you achieve a bad PSA of 0.1 or above within six months after you completed radiation, you had worse outcomes.  Dr. Neeraj Agarwal: Jeanny, what is the key takeaway message from this study? Dr. Jeanny Aragon-Ching: The key takeaway from this ICECaP analysis is that this information would be very important to augment a signal-seeking endpoint, especially for clinical trial development, so that we can develop further strategies to de-escalate for those who don't need systemic intensification or therapy intensification versus escalation for those who really do. Dr. Neeraj Agarwal: So, my radiation oncology colleagues need to watch out for those patients who do not achieve a PSA of less than 0.1 nanogram per ml within the first six months of finishing radiation therapy. Very interesting data.  Dr. Jeanny Aragon-Ching: Yes, absolutely. So. Neeraj another important abstract for our fellow clinicians, switching gears a little bit now, is Abstract 5011, which is titled “Do Bone Scans Overstage Disease Compared to PSMA PET?” This was an international, multicenter retrospective study with blinded, independent readers. Can you tell us more about this abstract? Dr. Neeraj Agarwal: Yes, a relatively small retrospective study, but still pertinent to our practice. So I'll summarize it. This study by Dr. Wolfgang Fendler and colleagues evaluated the ability of bone scans to detect osseous metastasis using PSMA PET scan as a reference standard. So in this multicenter retrospective study, 167 patients were included, of which 77 patients were at the initial staging of prostate cancer, 60 had biochemical recurrence after definitive therapy, and 30 patients had CRPC or castor-resistant disease.  These patients had been imaged with a bone scan and a PSMA PET scan within 100 days. And in all patients, the positive predictive value, negative predictive value and specificity for bone scan were evaluated at different time points. They had bone scan and PSMA PET scan and both were compared. And what they found was interesting. All these three values - positive predictive value, negative predictive value, and specificity for bone scan were 0.73, 0.82 and 0.82 in all patients, and in initial staging, it was even lower at 0.43 and 0.94 and 0.80.  So, without getting into too much detail regarding these numbers, I want to highlight the most important part of the study, that at the initial staging, 57% patients who had a positive bone scan had false positive bone scans. The interreader agreement for bone disease was actually moderate for bone scans and quite substantial for the PSMA PET scan.  Dr. Jeanny Aragon-Ching: So, Neeraj, what do you think is the key takeaway message here for our audience?   Dr. Neeraj Agarwal: The key takeaway message is that positive predictive value of bone scan was low in prostate cancer patients at initial staging, with the majority of positive bone scans being false positive. This suggests that a large proportion of patients which we consider to have low-volume metastatic disease by bone scan actually have localized disease. So in the newly diagnosed patients with prostate cancer, patients should ideally have a PSMA PET scan to rule out metastatic disease.   So, let's move on to another abstract I would like to discuss, which has important implications in treatment, especially now that lutetium 177 is approved, but frankly not available widely. Dr. Jeanny Aragon-Ching: Yeah, that's actually very timely. So the abstract you're referring to is 5045, which is being presented by Dr. Yu Yang Sun and colleagues entitled “Effects of Lutetium PSMA 617 on Overall Survival in TheraP Versus VISION Randomized Trials: An Exploratory Analysis.” So, Neeraj, can you tell us more about the relevance of this exploratory analysis? Dr. Neeraj Agarwal: Definitely. In this abstract, Dr. Yang Sun and colleagues assess the effect of lutetium PSMA on overall survival in two different trials, TheraP and VISION trials. So, just for our listeners' recollection, the phase 2 TheraP trial compared lutetium PSMA and cabazitaxel in patients with mCRPC who had progression on docetaxel and had significant PSMA avidity on gallium PSMA pet scan, which was defined as a minimum uptake of SUV max of 20 at least one site of disease and SUV max of more than 10 at all sites of measurable disease.  In this trial, 20 of 101 patients in the cabazitaxel arm crossed over to lutetium PSMA, and 32 of 99 patients in the lutetium PSMA arm crossed over to cabazitaxel. In the VISION trial, patients with mCRPC who previously progressed on at least one ARPI and one taxane-based therapy and had a positive gallium PSMA scan, and here, positivity was not stringently pre-specified as it was done in the context of TheraP trial. So, positive gallium pet scans were randomly assigned in two to one fashion to receive either lutetium PSMA plus best supportive care or standard of care versus standard of care.  And I'd like to highlight that the standard of care comprised ARPIs and bone protecting agents and these patients were not allowed to have cytotoxic chemotherapy such as cabazitaxel in the standard of care arm. Now, overall survival was similar in the lutetium PSMA group regardless of whether they got lutetium PSMA in the VISION trial or TheraP trial. There was no difference in overall survival with lutetium in the lutetium arms of VISION and TheraP trial with a hazard ratio of 0.92. And there was no difference in the overall survival between the lutetium PSMA and the cabazitaxel group in the TheraP trial if you use counterfactual analysis, assuming crossover had not occurred. So, quite interesting in my view. Dr. Jeanny Aragon-Ching: Yeah, thanks Neeraj for that wonderful synopsis and discussion. So, what is the key take home message then? Dr. Neeraj Agarwal: The main message in this new exploratory analysis, which combined both the TheraP and VISION trials, is that lutetium PSMA and cabazitaxel seem to be associated with similar overall survival benefit in these highly selected patients with PSMA positivity. Additionally, the difference in the observed effect of lutetium PSMA and overall survival in the TheraP and VISION trials may be actually better explained by the use of different treatments in the respective control arms of these trials. And these results, in my view, are quite pertinent for those patients and providers who do not have access to lutetium-177 therapy.  Let's go to another abstract that is currently relevant to our practice, given many patients with advanced prostate cancer who have concurrent diabetes; I'm talking about Abstract 5066. Jeanny, can you please tell us more about this abstract?  Dr. Jeanny Aragon-Ching: Certainly, Neeraj. So this abstract will be presented by Dr. Amy Shaver and colleagues. So it's also very relevant, since many men who are diagnosed with prostate cancer frequently also have a concomitant diagnosis of type 2 diabetes mellitus. So, this was a SEER-Medicare population database analysis that looked at men who were treated with either abiraterone or enzalutamide and also had concomitant diagnosis of type 2 diabetes mellitus (DM). And they were identified using ICD-9 and ICD-10 codes and they were all tied in to acute care utilization. So they looked at CMS research data codes and ER hospitalization visits six months after treatment initiation was recorded. So all in all, they took a sample of 11,163 men, of whom close to 62% were treated with abiraterone and about 38% were treated with enzalutamide.  So, of these, about 27% of them had type 2 DM, of whom 59% received abiraterone and about 41% had enzalutamide. So, the bottom line is, compared to those without diabetes mellitus, those who had type 2 diabetes had worse acute care utilization, which was 43% higher than those who got abiraterone compared to enzalutamide, and also had higher overall mortality. Therefore, the bottom line is, having type 2 diabetes mellitus, unfortunately, portends worse outcomes in men with prostate cancer, so careful attention needs to be paid to those who are starting out already with such comorbidities. So Neeraj, any final thoughts you have regarding this abstract and overall before we wrap up on the podcast today?  Dr. Neeraj Agarwal: Absolutely. So it looks like, based on this very important pertinent Abstract 5066, which talks about the impact of diabetes on our patients, I think we need to be very watchful regarding the impact of diabetes on our patients who are being treated with abiraterone or enzalutamide, especially drugs which are known to make the metabolic syndrome and diabetes worse. I think close monitoring and close attention to control of diabetes is very important. So with that, I would urge the listeners to come and join us at the Annual Meeting, not only to celebrate these successes but also to help disseminate this cutting-edge data to practitioners and maximize the benefit to our patients across the globe.   And thank you to our listeners for joining us today. You will find links to the abstracts we discussed today on the transcript of this episode. Finally, if you value the insights that you hear on our ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant,  Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.

I AM BIO
The New Age of CRISPR

I AM BIO

Play Episode Listen Later Apr 11, 2023 27:40


CRISPR has emerged as a powerful tool for altering DNA sequences with incredible precision, opening up new avenues of research into the treatment of disease. In this episode, we explore the science behind CRISPR, as well as its potential. From curing genetic disorders to creating new crop varieties, the possibilities seem endless. Our four guests today are scientists working to push these gene editing tools to the next frontier.

Treating Blood Cancers
CAR T-cell Therapy in Review 2022: Updates in Treatment

Treating Blood Cancers

Play Episode Listen Later Dec 21, 2022 32:46


Sattva S. Neelapu, MD, M.D. Anderson Cancer Center, Houston, TX Recorded on December 16, 2022 Chimeric antigen receptor (CAR) T-cell therapy has generated impressive results in hematologic malignancies, with many drugs still in clinical trials. In this episode, Dr. Sattva S. Neelapu from MD Anderson Cancer Center, joins us to discuss updates on CAR T-cell therapy from the 2022 American Society of Hematology (ASH) Annual Meeting. Dr. Neelapu also provides a high-level overview of how CAR T-cell therapy works, including the manufacturing process, and discusses the risk of recurrence following therapy, risk for patients in the era of COVID-19, secondary cancers, associated costs, roadblocks to therapy, and why early referral matters. Tune in to this informative podcast episode to learn more! This podcast episode is supported by Allogene Therapeutics, Bristol Myers Squibb, CRISPR Therapeutics, Janssen Oncology & Legend Biotech, Kite, A Gilead Company and Novartis Oncology.

Cancer.Net Podcasts
Research Highlights from ESMO Congress 2022, with David Ilson, MD, PhD, FASCO, Sumanta Pal, MD, FASCO, and Tian Zhang, MD

Cancer.Net Podcasts

Play Episode Listen Later Nov 10, 2022 28:34


ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Cancer.Net Editorial Board members discuss new research in gastrointestinal and genitourinary cancers presented at this year's ESMO Congress, held September 9-13 in Paris, France. First, Dr. David Ilson discusses treatment advances in liver, colorectal, and gastric, or stomach, cancers. Dr. Ilson is an attending physician and member at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College. You can view Dr. Ilson's disclosures at Cancer.Net. Dr. Ilson: Hi, I'm Dr. David Ilson from Memorial Sloan Kettering Cancer Center in New York. I'm a GI medical oncologist, and it's my pleasure today to review some important presentations in GI cancers from the recent ESMO meeting in Paris from 2022. I have no relevant relationships to disclose for this discussion. So, important presentations were made in hepatocellular cancer, in colorectal cancer, and gastric and other cancers, and I'm going to highlight some of the key presentations from the meeting.  One of the most anxiously awaited presentations was one in hepatocellular or liver cancer. For patients that have advanced disease who are not candidates for surgery or local treatments, standard therapy now, it used to be lenvatinib and sorafenib, and that's now been replaced by the combination of an immunotherapy drug, atezolizumab combined with the drug bevacizumab. That's the new standard of care. And recently, we had a promising data for another immunotherapy combination using the drug durvalumab combined with tremelimumab. So what we saw this year was another important global study looking at the first-line use of immunotherapy in hepatocellular cancer. This trial took 794 patients with advanced hepatocellular cancer and assigned them to a standard treatment with a drug called lenvatinib. Lenvatinib and sorafenib were the old standard treatments for hepatocellular cancer. And lenvatinib alone was compared to a combination of lenvatinib and pembrolizumab, an immunotherapy drug. The primary endpoint was to see whether adding immunotherapy to lenvatinib improved survival. And this was a negative trial. It did not show an improvement in survival for adding pembrolizumab to lenvatinib over lenvatinib alone, and there was really no significant difference in the time that patients were on treatment. The response was slightly higher with the addition of pembrolizumab to lenvatinib, but again there was no survival difference. So this combination will not move forward. And again, as I said earlier, the new standard first-line treatment is atezolizumab plus bevacizumab. In colorectal cancer, probably one of the most exciting presentations was the use of immunotherapy treatments in locally advanced colon cancer. There is an important subset of colorectal cancer that has what's called an MSI-high status. MSI-high colon cancers are very responsive to immunotherapy drugs, and there has been a lot of interest in patients with localized colorectal cancer using immunotherapy drugs prior to surgery rather than conventional chemotherapy or radiation. So this important trial looked at 112 patients with localized colorectal cancer. Most of the patients were stage 3, and they all were documented to have this MSI-high status, which indicated a higher chance of response to immunotherapy. And patients received a brief course of immunotherapy, 2 doses of the drug nivolumab combined with 1 dose of ipilimumab over only 6 weeks followed by surgery. What they showed in these 112 patients who went to surgery, there was almost 100% response to this treatment. In fact, almost two-thirds of patients had no cancer found at surgery, even only after several weeks of immunotherapy. And in the 112 patients treated, there have been no recurrences in any of these patients. So it's quite remarkable that immunotherapy could induce a complete remission in two-thirds of patients, and that was only after a few weeks of exposure of the drug. So I think we're going to see more interest in using immunotherapy treatments as a potential pre-surgical treatment for colon cancer. And we could argue with such a high rate of complete remission, if we gave immunotherapy longer, maybe we could consider nonsurgical management, to just keep treating the patients with immunotherapy. This is actually the case that's now been seen in rectal cancer, a recent study presented from my institution where they treated patients with rectal cancer with immunotherapy, and we also achieved 100% remission, and none of the patients in this small study required surgery. So I think this important study, which is called the NICHE-2 trial, indicates a high degree of effectiveness of immunotherapy in MSI-high colon cancers. And certainly, it raises interest in using this as a preoperative treatment and potentially could lead to some patients getting treatment with immunotherapy alone without surgery. Then I'm going to comment a little bit about advanced metastatic colon cancer. Another important presentation was studying a new drug called fruquintinib. Fruquintinib is an oral drug that targets the VEGF pathway, which is an angiogenesis pathway in colon cancer. Standard treatment for colon cancer when it's stage 4 disease is now use of chemotherapy, like FOLFOX and FOLFIRI, drugs like bevacizumab, cetuximab, and panitumumab. And in more chemotherapy-resistant cancers, we use drugs like regorafenib and TAS-102. So this trial looked at a large group of patients, over 690 patients who had received all conventional treatments. They had progressive disease on all conventional treatments, including the late-line drugs regorafenib and TAS-102. And this was a placebo-controlled trial in which patients either received the drug fruquintinib or they received placebo plus supportive care. It was reasonable to offer a placebo in this trial because there really was no other standard treatment option for these patients. The primary endpoint of overall survival was improved with fruquintinib. Survival was improved with a reduction in the risk of death by about 30% and improvement in time on treatment. Very few patients responded to fruquintinib, so this was largely a drug that stabilized the cancer, but it did lead to modest improvements in time on treatment and modest improvements in survival. So this drug may potentially be evaluated as a new treatment option in very chemotherapy-resistant colorectal cancer. I just want to mention briefly another new class of agents for which we had data presented at the ESMO meeting. These are drugs that inhibit a mutation in their cancer called KRAS G12C. There are promising drugs that target this pathway. And there were 2 drugs that were followed up on at ESMO, one was a drug called sotorasib and another drug was adagrasib. These are drugs that target KRAS G12C mutations in colon cancer. And both of the trials that were presented used these drugs combined with drugs that target the EGFR pathways, so either panitumumab or cetuximab, and very encouraging responses were seen on these trials. The trial that looked at the combination of adagrasib plus cetuximab achieved a response in about 46% of patients, which is very encouraging. The trial that studied sotorasib, combined sotorasib with panitumumab, and they observed a 30% response, and some of these responses were durable. So the take-home message is that these drugs, adagrasib and sotorasib, are promising new agents to target KRAS G12C mutations in patients with advanced colon cancer and indicate that we may get even a higher degree of activity when we add EGFR-targeted drugs including panitumumab or cetuximab to these agents. So the other area that I want to comment on is gastric cancer. Recently, in the United States, we had a regulatory approval for the drug trastuzumab deruxtecan in patients who have HER2-positive gastric cancer that's advanced and is being treated with chemotherapy alone, HER-2-positive patients who had received previous trastuzumab or Herceptin. So trastuzumab deruxtecan is a promising drug used in patients that develop resistance to trastuzumab. So there was an update of the trial called Gastric-DESTINY02, which was a phase 2 trial of trastuzumab deruxtecan in Wwestern patients as a second-line treatment for patients with HER2-positive gastric cancer, and the updated analysis again showed a promising response in 40% of patients. The response duration was about 8 months, and patients achieved a survival of a year or more. So this updated presentation really reinforced that this is an active drug for patients with HER2-positive gastric cancer whose disease progresses on previous treatment with trastuzumab. So this was a very exciting ESMO meeting. There were a lot of other studies and important presentations, but I've tried to highlight today what I think are the most important as we move forward in trying to identify new treatments for patients. ASCO: Thank you, Dr. Ilson. Next, Dr. Sumanta (Monty) Pal and Dr. Tian Zhang discuss new research in kidney, bladder, and prostate cancers. Dr. Pal is the co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. You can view disclosures for Dr. Pal and Dr. Zhang at Cancer.Net. Dr. Pal: Welcome to this Cancer.Net podcast. My name is Monty Pal. I'm a medical oncologist in the City of Hope in Los Angeles. I'm thrilled to be here today with my dear friend and colleague, Dr. Tian Zhang from UT Southwestern. Tian, mind giving us a quick intro? Dr. Zhang: Hi, Monty. Great to be here with you today. Tian Zhang at UT Southwestern in Dallas, Texas, where I'm a GU medical oncologist. I'm really excited to talk through the ESMO trials with you today. Dr. Pal: A little bit of housekeeping first. Let's go ahead and get some of our disclosures out of the way. I get travel support from CRISPR Therapeutics and from Ipsen. Tian, how about you? Dr. Zhang: Sure. I've received honoraria from Exelixis, BMS, Genentech, AstraZeneca, and Janssen, all relevant to our discussion today. Dr. Pal: Very good, very good. Well, thank you so much for joining us today. We've got a lot to talk about in about 15 minutes. The first thing that I wanted to chat about is adjuvant therapy. First of all, before we dive into the weeds here, can you just kind of tell our audience what adjuvant therapy is in broad strokes? Dr. Zhang: In kidney cancer, we think a lot about how we might prevent disease recurrence after surgery. So adjuvant treatment refers to systemic treatment that's given after a big surgery. And so in kidney cancer, that's usually after nephrectomy or removal of the kidney. Dr. Pal: Excellent, excellent. You beat me to the punchline. We are going to focus on kidney cancer, no doubt. This year at the European Society of Medical Oncology, or ESMO, meeting, which was held in early September, we actually had some really key studies presented in this space, one of which I'll disclose that I led. Studies I would say were maybe a little bit disheartening there, but nonetheless, I do think we can learn a lot from them. One of these trials was called PROSPER. This was a really interesting study that actually didn't just look at adjuvant therapy but actually looked at treatment before surgery, which we called neoadjuvant therapy. Tian, can you kind of walk us through the design of that trial really quickly? Dr. Zhang: This was a trial done in the ECOG Cooperative Group, and patients were randomized to receiving either nivolumab, which is an immune checkpoint inhibitor, before surgery, followed by a year of nivolumab after surgery, or to surgery and observation with ongoing scans. So it was really trying to look at a perioperative approach of using nivolumab. Dr. Pal: So how about this? Maybe we'll kind of discuss some of these results in amalgam, but maybe let's go through these trial designs first. The second trial that was highlighted this year at ESMO was called IMmotion010. That's one thing that I just love about these studies. They all have very clever names. I don't know what an IMmotion is, but tell us about IMmotion010 and what that trial design looked like. Dr. Zhang: Sure. So IMmotion010, again, also was an adjuvant trial for resected intermediate- and high-risk kidney cancers, randomized folks to either atezolizumab for a year or placebo for a year. And so this is in the context of having had resected kidney cancers and following folks for the treatment results, and the primary endpoint there was disease-free survival. Dr. Pal: Okay. So we've got an immune therapy called nivolumab and the PROSPER trial that was looked at before and after surgery. We've got atezolizumab, a different checkpoint inhibitor that was looked at following surgery. Tell us about the third trial. This is the last study in the space called CheckMate 914. What did that trial look at? Dr. Zhang: That one, again, also a phase 3 adjuvant trial, enrolling folks after surgery that had high-risk kidney cancer and randomized to either the combination of nivolumab with ipilimumab, both checkpoint inhibitors versus placebo. And again, this treated patients for about 6 months and also primary endpoint of disease-free survival. Dr. Pal: Now, whenever we do these studies, we always define them as being positive or negative, and that's really not meant to sort of cast any aspersions on how well the study was done or any really sentiments around the trial itself. It's really objective, and it's based on whether or not a study hits what we define ahead of the trial as being called a primary endpoint. So we actually, in these studies, looked at a primary endpoint of something called recurrence-free survival. And so that's really the proportion of patients who actually are living on without any sort of recurrence of their kidney cancer. I think it might be easy enough to sort of describe whether or not these trials hit that endpoint were positive or negative. What was the final report here on these trials, Tian? Dr. Zhang: Well, Monty, I think all 3 of these trials were, quote-unquote, "negative," and we all had high hopes for all 3 of these trials. And certainly, many, many patients participated, and we will learn eventually a lot from these trials. But none of these 3 met their prespecified primary endpoint of recurrence-free survival endpoint. Dr. Pal: So this is a little bit tricky because we did have these 3 negative studies presented at ESMO this year, but there was 1 positive trial that's adjuvant or postoperative space presented previously and then now published, actually, in the New England Journal of Medicine with an FDA approval to boot. Can you tell us about that, Tian? Dr. Zhang: Well, that one was called KEYNOTE-564 and randomized patients to either a year of pembrolizumab or placebo. And so you're absolutely right. It did show an improvement in disease-free survival comparing pembrolizumab with placebo. And so pembrolizumab is approved in this adjuvant setting after nephrectomy. Dr. Pal: And so this can be kind of a tough space because I can imagine our listeners are hearing this saying, "OK. Well, at ESMO, we've got 3 negative trials looking at postoperative therapy, and we've got 1 positive trial looking at pembrolizumab in the space." So what's one to do in this setting? What are you telling patients these days about whether or not to use adjuvant treatment for kidney cancer? Dr. Zhang: Yeah. I think it's a conversation that patients have with their oncologist after surgery, and it really depends on their own risk factors, their clinical and pathologic features at the time of resection. It depends a lot on patient preferences and their own priorities and things such as their tolerance for toxicity or how often they're coming into the treatment center. And I do think this is a time point where they have a shared decision-making that we can help our patients understand the totality of the data and then decide if a year of pembrolizumab is worthwhile or if they'd rather continue with surveillance after surgery. Dr. Pal: I totally agree with you, and I love that term “shared decision-making,” because it's never one of those situations where I walk into the clinic room and say, "Here's what you're going to do." And it's also never the situation where the patient walks into the clinic room and says, "Here's what I want." It's always this really sort of mutual process, isn't it, where you sort of look at a patient's clinical state. You look at some of the features under the microscope, but then it comes down to really, really lengthy and personal discussions around what that patient wants to get out of treatment. So I think that's very well said, Tian.  I'm going to move to actually a different setting, which is termed “metastatic disease.” So we've talked about localized kidney cancer, where the disease is sort of confined to the kidney for the most part. We talked about what we do after we remove visible evidence of disease. But there is, unfortunately, a number of patients where we can't necessarily remove all the disease burden. So we lean more heavily on what we call systemic treatments. These are treatments that enter into the bloodstream either by mouth or through the veins. And in kidney cancer, just to give you a really, really brief synopsis, there's been this huge evolution over time. When I started in the field, it was really the advent of using a single oral therapy for kidney cancer. And over the next five 5 years, we sort of saw this evolution towards using doublet therapies, which is a mix of pills and IVs or maybe IVs alone. And more recently, there's been a lot of excitement. You can probably see where this is going, right? We've looked at 1 drug, and it works. We've looked at 2 drugs, and they seem to work. Logic would perhaps suggest that maybe you could get away with using 3 drugs in concert. So, Tian, this year at ESMO, there was a really important trial called COSMIC-313 that looked at 3 drugs versus 2 drugs. Can you tell us a little bit more about the design of the study? Dr. Zhang: COSMIC-313, the large phase 3 study, which randomized more than 850 patients to either the triplet, as you're speaking of, the cabozantinib, nivolumab, and ipilimumab versus nivolumab and ipilimumab with placebo standing in for cabozantinib. And so this was a very large trial, looking particularly at progression-free survival, comparing the triplet versus the immunotherapy doublet. Dr. Pal: And then tell us about the results of this because I have to tell you. I mean, I spent a lot of time looking over this, and I struggled with the end results a little bit. We talked about the primary endpoint of studies when we were discussing adjuvant therapy. And one of the things we'd mentioned is that you decide on this beforehand. And the primary endpoint in this trial was actually the delay in cancer growth. And as you pointed out, the study met that endpoint. But how do you interpret the results overall? How are you incorporating triplet therapy now? Dr. Zhang: Sure. I think it did certainly meet the progression-free survival primary endpoint. The median was not reached for the triplet versus 11.3 months for the doublet. And so importantly, I think it was a, quote-unquote, "positive trial." But how are we using this? Well, we have not seen the overall survival data of these patients. And so when you're thinking about combining all 3 drugs in the frontline setting, I think it's really important to think about what might come after and whether these folks truly live longer with using all 3 upfront versus a sequential approach. So I think the jury is still out. It certainly met its primary endpoint, and it's quite promising. But I'm still waiting for the overall survival data to really inform or change my practice. Dr. Pal: I've got to agree with you there. One of the things that we always discussed in clinic is whether or not a particular treatment strategy is going to increase longevity. It comes up in every conversation, I would say, whenever we're thinking about approaching a new line of treatment. And I wish I could say definitively that this triplet strategy improves longevity, but to be totally fair, that data just doesn't exist yet. So it's a really difficult conversation. I agree with you. Maybe a little pause before we start incorporating triplets. So I've got to say, it was certainly a big year for kidney cancer, one of my fellows put this table together, and it really showed that this year amongst the past maybe 10 years in kidney cancer, we had more big phase 3 trials being reported as more than any year previously. But there are also some pretty key developments in other diseases that you and I treat, Tian, and one of those is bladder cancer. And a trial that I think was really quite important has the name EV-103. Tough name to remember, but it actually looked at a disease space that I think can be a bit of a challenge for us, and that's the patient who is presenting in the clinic has actually advanced bladder cancers spread to other parts of the body and is quite ill and perhaps can't receive conventional aggressive chemotherapy with a drug called cisplatin. So what did this proportion of EV-103 that was presented show us? Dr. Zhang: Well, people hear about Cohort K thrown around, and so this trial actually has had multiple cohorts. And this particular cohort came out of some really exciting data from their dose escalation studies, and also Cohort A, where patients were treated with an antibody drug conjugate, this enfortumab vedotin, or EV, with an immune checkpoint inhibitor called pembrolizumab. And in the early cohort of 40 patients, they saw a pretty high objective response rate. That means the rate of patients where tumors were shrinking. And so that was about 70% of those 40 patients had objective responses. And so they designed this Cohort K to randomize patients to either enfortumab vedotin with pembrolizumab or enfortumab vedotin on its own, which has been approved in refractory metastatic urothelial cancer but particularly for first-line cisplatin-ineligible patient population. And so they randomized about 150 patients in the setting and looked at objective responses, and I agree with you. Certainly, very promising in terms of having objective response rate of about 65% and compared with enfortumab vedotin on its own, which came in around 45%. It does seem that this combination has more activity than the monotherapy. Dr. Pal: Yeah. That's a great summary. And to the patients out there listening, when we talk about responses, we're talking about pretty deep responses here, meaning 30% or more reductions in the size of tumors. And Tian mentions that you've got 65% to 70% of patients with these responses. It really does entail a sizable reduction, not just a small decrease in the volume of tumors. And I'm telling you, just from having been in the scene for 15 years now, I mean, it's just remarkable sort of progress that we're making.  We're going to wrap up by talking about prostate cancer, and just to really describe some overarching results. So there's a setting in prostate cancer that I always find to be a bit of a challenge, and these are patients who have had surgery for their prostate cancer. So extensively no visible spread of their disease, but they start having their PSA creep up afterwards. And there was a trial that sort of addressed that. Tian, can you give us the sort of quick and dirty summary of the study? Dr. Zhang: Sure. So we call this PSA recurrence or biochemical recurrence setting. And this trial was led by Dr. Rahul Aggarwal in the Alliance Cooperative Group. But everyone who had biochemical recurrence were randomized to receiving androgen deprivation therapy alone, which is usually our standard of care; a combination of that androgen deprivation therapy with apalutamide, which is an androgen receptor blocker; or the combination of a triplet of the androgen deprivation therapy, the apalutamide, and then an abiraterone acetate, which is a blocker of steroid synthesis in the adrenal glands. And so this trial enrolled ultimately about 500 patients and randomized them 1 to 1 to 1 to these 3 cohorts. And interestingly, the combinations of either the androgen receptor, androgen deprivation therapy with apalutamide or the triplet with combined abiraterone acetate all prolonged PSA progression-free survival compared to androgen deprivation therapy alone. So I think it was a really well-done study in the cooperative groups and helps answer some questions around intensifying treatment in that biochemical recurrent space. Dr. Pal: Yeah. These cooperative groups studies, each one of them are so critical. These are just funded by our federal government, and they really offer us a chance to really ask pure questions, so really, really important study design. And maybe in 30 seconds, let's go over this last study over here. I don't want to keep our listeners on for too long, but there was a study called PROpel. Again, you got to love these study names. So this PROpel study looked at advanced prostate cancer. So again, this is prostate cancer where the disease has spread from the prostate to other organ systems. This is potentially a new paradigm for the disease. Before, we used to just basically give everybody hormone therapy in this setting. We've doubled down and given patients more advanced hormonal therapy with drugs like abiraterone that you alluded to, but now there's this potential to use targeted treatments. And maybe you can tell us a little bit about how that's been incorporated in PROpel, Tian. Dr. Zhang: Sure. Well, PROpel randomized patients to a combination of abiraterone with olaparib, which is what we call PARP inhibitor, and it blocks DNA damage repair, basically, in cancer cells. And olaparib has been approved as a single agent in more refractory, metastatic, castration-resistant prostate cancer. And so this trial randomized folks with a combination in sort of earlier lines of castration-resistant disease to either that combination or abiraterone with placebo. We saw earlier this year, actually, that the primary endpoint was improved for all comers, but I don't know if we saw some more subgroup analysis of patients with BRCA alterations and also with homologous recombination repair alterations. And I think that's very important, the fact that we saw more of an improvement in those subpopulations than those patients without the BRCA alterations or the homologous recombination repair mutations. Dr. Pal: Excellent. Excellent summary. I think that's about all that we've got time for today. New paradigms in prostate cancer and bladder cancer potentially and a massive amount of new data in kidney cancer to things going forward with clinical practice from ESMO 2022. Tian, thanks so much for joining me today, and I hope everyone listening enjoyed this as well. Dr. Zhang: Thanks, Monty. Take care. ASCO: Thank you, Dr. Pal and Dr. Zhang. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Between the Biotech Waves
Episode 15: A Between the Biotech Waves Conversation with Rodger Novak and Shaun Foy, co-founders with Emmanuelle Charpentier of CRISPR Therapeutics

Between the Biotech Waves

Play Episode Listen Later Sep 13, 2022 67:22


Discussing the formation of CRISPR Tx, the positives, negatives and everything in between. This is the first time all three of us reconnected since our respective departures from our founding roles and features some candid moments from our respective journeys. Enjoy.

Die besten wikifolio-Trader im Börsenradio Interview
Trend & Fundamental Kais Wikifolio mit: Energiekontor, Nvidia, Secunet Security, Funkwerk, GFT Technologies

Die besten wikifolio-Trader im Börsenradio Interview

Play Episode Listen Later Aug 5, 2022 16:13


"Halbprofi87", Kai Knobloch gehört mit seinem wikifolio.com zu den alten Hasen unter den Tradern. Kai vereint mit seinem Wikifolio Trends & Fundamental-Analyse zusammen. Seit 2014 hat er eine Performance von über +190 % --> https://go.brn-ag.de/205 Unter seinen besten Werten sind: Energiekontor +356 %, Nvidia +292 %, Secunet Security +210 %, Funkwerk +158 %, Alphabet (C) +152 % GFT Technologies +143 %, CRISPR Therapeutics +141 %, aber leider auch eine Westwing Group mit -78,3 %. Kai ist derzeit voll investiert und hat 72 Aktien und rund 30 ETFs in seinem wikifolio-Depot.

KeyStone Stock Talk Podcast
Stock Talk Podcast Episode 172

KeyStone Stock Talk Podcast

Play Episode Listen Later Aug 3, 2022 56:03


We are back this week after rave reviews, a few crying babies, and further shock and awe at our faces-for-radio now revealed on our YouTube platform. We kick off this week's show with a brief discussion on the strong stock market gains to end July following the worst first half in U.S. markets in 52 years. In our Your Stock, Our Take segment Ryan will take a look at a TV streaming platform Roku Inc. (ROKU:NASDAQ). The Pandemic stay at home star is down 72% year to-date and 86% from its 2021 highs. A listener asks if the stock finally offers value. Aaron is going to take you to school by looking into “Three things to never do when valuing a stock on a PE or price-to-earnings basis.” Brett is going to launch our legendary or famous investors series with a look into recent market darling Cathie Wood. Wood is an American active investment manager who is the current CEO and CIO of Ark invest, which was founded it in 2014. Incidentally, Roku is one of the top holdings in her flagship fund alongside well-known names such as Tesla, Zoom, Crispr Therapeutics, and Block. Brennan will handle our Star and Dog of the week. The Dog of the week is Datametrex AI Ltd. (DM:CSE) a Canadian-based IT company focused on, Machine Learning and Artificial Intelligence which collects and analyzes data – that is a bunch of buzz words. The micro cap is down 35% year-to-date and 61% since its 52-week high. The Star of the week is Enphase Energy Inc. (ENPH:NASDAQ), an energy technology company and the world's leading supplier of microinverter-based solar and battery systems. The stock has jumped 25% in the last 5 trading sessions and is up 61% year to date and was the top-performing stock in the S&P 500 in the last quarter powered by strong quarterly growth.

Biotech Bros
More Issues for CRISPR Therapeutics: Another CAR-T Failure in Solid Tumors

Biotech Bros

Play Episode Listen Later Jul 5, 2022 44:20


This week on the podcast Agustin discusses the recent data release from CRISPR Therapeutics, Galapagos' CAR-T cell therapy acquisition, and the over-saturation of SCD therapies entering the market. If you are a fan of this show make sure to like, comment, subscribe and follow me on Twitter @biotech_bros. If you have any questions regarding the product offerings feel free to explore my website biotechbros.com

BioCentury This Week
Ep. 124 - CRISPR's High Bar, Private Equity Inroads and the Distillery

BioCentury This Week

Play Episode Listen Later Jun 13, 2022 27:21


Stellar data for Vertex Pharmaceuticals and CRISPR Therapeutics could set a high bar for the next generation of gene editing players to beat in β thalassemia and sickle cell disease, indications that had previously been considered as the best disease to show proof-of-concept for the modality, said Executive Director of Biopharma Intelligence Lauren Martz on the latest edition of BioCentury This Week. The BioCentury podcast team also reviews Associate Editor Stephen Hansen's analysis of how the trend of private equity firms acquiring or partnering life sciences VCs will impact the financing environment, and Washington Editor Steve Usdin's take on the one big difference between the PDUFA user fee bills making their way through the House and Senate. Senior Editor and Head of Discovery & Preclinical Development Karen Tkach Tuzman also reviews the latest highlights from BioCentury's Distillery

Treating Blood Cancers
CAR T-cell Therapy in 2022: What You Need to Know Part II

Treating Blood Cancers

Play Episode Listen Later Apr 26, 2022 38:48


Rayne H. Rouce, MD, BS, Texas Children's Cancer Center for Cell and Gene Therapy, Houston, TX Recorded on April 8, 2022 As CAR T-cell therapy continues to evolve in new and exciting ways, new indications are approved and treatment toxicities reduced. In this episode, Dr. Rayne Rouce, from the Texas Children's Cancer Center for Cell and Gene Therapy at Baylor College in Houston, joins us to discuss hot topics in CAR T-cell therapy, including how CAR-T has evolved over the past few years, understanding why some patients do better than others, access to treatment and overcoming logistics, shared care models with the referring physician, CAR-T in pediatric patients, communicating with patients, and so much more! This podcast episode is supported by Bristol Myers Squibb, CRISPR Therapeutics, Kite, a Gilead Company, Janssen Oncology & Legend Biotech, and Novartis Pharmaceuticals Corporation.

Healthcare Unfiltered
CRISPR: The Healthcare Technology of the Future

Healthcare Unfiltered

Play Episode Listen Later Apr 12, 2022 60:16


Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics, joins the show to chronicle his journey to CRISPR Therapeutics and to break down the ins-and-outs of the technology. He begins by sharing the evolution of CRISPR as a “molecular barcode” and its first viable indication; how he “bets” the technology will have a major footprint in the cancer, diabetes, and cardiovascular disease treatment landscape; shares strategies for shortening the potential time to market for some of the therapies; explains how AI is used in his line of work; and a variety of other topics. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on Youtube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

LifeSci Beat
Dr. Ali Behbahani, Partner at NEA, on evaluating and investing in cutting-edge life sciences

LifeSci Beat

Play Episode Listen Later Feb 13, 2022 33:06


In this episode, we sat down with Dr. Ali Behbahani, General Partner at New Enterprise Associates. Dr. Behbahani has been with NEA since 2007, spearheading over 40 biotech and medtech investments such as CRISPR Therapeutics, Adaptimmune, and Nevro. We discussed his views on breaking into VC, his approach to assessing early-stage life science innovations, the current trends in the biotech investing landscape, and much more.NEA is a global VC firm with $25B in AUM and over 300 active investments across both technology and healthcare sectors. Founded in 1977, NEA has made transformational investments such as Robinhood, Salesforce, Bright Health, and CRISPR Therapeutics. NEA has offices in Menlo Park, San Francisco, New York, and the Washington, D.C. metro area, and is widely considered one of the largest leading VCs in the world.

The 7investing Podcast
The Next Generation of Health Care with Kelly ETFs Founder Kevin Kelly

The 7investing Podcast

Play Episode Listen Later Feb 8, 2022 24:43


The disruptive potential of gene editing could have huge implications for health care. Suddenly, several chronic diseases -- which may have required patients to be treated for decades -- have a potential to be fundamentally cured at the genomic level. This is unlocking publicly-tradable investment opportunities. Companies are utilizing the power of CRISPR gene editing, base editing, and prime editing to directly modify patient DNA. Larger pharmaceutical companies are partnering with these smaller drug developers and are building commercial programs that could be worth billions of dollars. Genetic sequencing companies are reducing costs and unlocking broader market adoption, which is rewarding them with greater volumes and higher profits. These opportunities are what has led Kelly ETFs to launch its newest investment product, the CRISPR & Gene Editing Technology ETF (Nasdaq: XDNA). In this exclusive conversation with 7investing CEO Simon Erickson, Kelly ETFs founder Kevin Kelly describes why he brought the ETF to market and how it is less-correlated with other health care funds that are available. He describes his allocation approach and why he isn't afraid to take large stakes in smaller companies. The two also dig into several of the ETF's largest positions, including Beam Therapeutics (Nasdaq: BEAM), Intellia Therapeutics (Nasdaq: NTLA), and Illumina (Nasdaq: ILMN). Publicly-traded companies mentioned in this interview include Abbott Laboratories, Beam Therapeutics, CRISPR Therapeutics, Editas Medicine, Illumina, Intellia Therapeutics, Regeneron, and Thermo Fisher. 7investing's advisors or its guests may have positions in the companies mentioned. Welcome to 7investing. We are here to empower you to invest in your future! We publish our 7 best ideas in the stock market to our subscribers for just $49 per month or $399 per year. Start your journey toward's financial independence: https://www.7investing.com/subscribe Stop by our website to level-up your investing education: https://www.7investing.com Join the 7investing Community Forum: https://discord.gg/6YvazDf9sw Follow us: ► https://www.facebook.com/7investing ► https://twitter.com/7investing ► https://instagram.com/7investing --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

The 7investing Podcast
7investing Team Podcast: Our Reckless Predictions for 2022

The 7investing Podcast

Play Episode Listen Later Jan 27, 2022 18:33


We're only four weeks in, and 2022 is already proving to be an eventful year. Between the S&P 500 and the Nasdaq's recent corrections, concerns about a war between Russia and Ukraine, and the Fed's promises of an upcoming rate hike, the new year has brought more than a few interesting financial media headlines. While the upcoming Year of the Tiger is still a young cub, we figured now was the time to make a few reckless predictions. Our 7investing advisors gathered together to have some fun, and we came up with five “hey it could happen” prognostications that could have significant impacts for investors in 2022. Steve Symington believes a small & mid cap rally is inevitable, while Maxx Chatsko believes CRISPR and gene editing are prone to come back down to earth. Anirban Mahanti thinks Peloton (Nasdaq: PTON) might soon be acquired, and Dana Abramovitz believes Facebook/Meta Platforms (Nasdaq: FB) is destined to enter health care. And 7investing founder and CEO Simon Erickson believes this is the year that the US will finally put a ban on Payments for Order Flow. While we're not guaranteeing a 1.000 success rate (these are “reckless”, after all!), we do enjoy thinking out loud about what innovation in the markets could mean for stock investors. If you'd like to join the fun and discuss any of our predictions in greater detail, please bring your thoughts to our newly-launched 7investing Community Forum. Publicly-traded companies mentioned in this interview include Crispr Therapeutics, Meta Platforms, Peloton, and Robinhood. 7investing's advisors or its guests may have positions in the companies mentioned. Welcome to 7investing. We are here to empower you to invest in your future! We publish our 7 best ideas in the stock market to our subscribers for just $49 per month or $399 per year. Start your journey toward's financial independence: https://www.7investing.com/subscribe Stop by our website to level-up your investing education: https://www.7investing.com Join the 7investing Community Forum: https://discord.gg/6YvazDf9sw Follow us: ► https://www.facebook.com/7investing ► https://twitter.com/7investing ► https://instagram.com/7investing --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

Treating Blood Cancers
CAR T-cell Therapy in 2022: What You Need to Know

Treating Blood Cancers

Play Episode Listen Later Jan 25, 2022 41:55


Caron Jacobson, MD, Dana-Farber Cancer Institute, Boston, MA Recorded on January 4, 2022 As we move into 2022, chimeric antigen receptor (CAR) T-cell therapy continues to be a very exciting and effective treatment option for some blood cancer patients. In this episode, Dr. Caron Jacobson, Assistant Professor of Medicine, Harvard Medical School, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute in Boston, MA, discusses updates in CAR T-cell therapy, including progress in managing toxicities, barriers to treatment, CAR T structure and manufacturing, other practical issues such as determining the best treatment option for patients facing serious disease, and future directions. Tune in to learn more! This podcast episode is supported by Bristol Myers Squibb; CRISPR Therapeutics; Kite, a Gilead Company and Novartis Pharmaceuticals Corporation.

FYI - For Your Innovation
An Outlook on Biotechnology with Sam Kulkarni, CEO CRISPR Therapeutics

FYI - For Your Innovation

Play Episode Listen Later Jan 17, 2022 56:28


Today, 20 years after we sequenced the first human genome, we're starting to see the fruits of genomics. Instead of treating symptoms, researchers are focused on finding cures for once chronic and fatal diseases. We're starting to reimagine medicine in ways previously thought impossible. This week on the For Your Innovation Podcast, we're joined by Dr. Samarth Kulkarni, Chief Executive Officer of CRISPR Therapeutics. Sam joined CRISPR in early 2015 as Chief Business Officer. Two years later, in 2017, he was appointed to CEO. In addition to his expertise in biotech strategy and operations, Sam has spearheaded initiatives in personalized medicine, immunotherapy, and other therapeutic technologies. In today's episode, we're also joined by ARK's CEO/ CIO, Cathie Wood, who helps provides her insights on macrotrends currently affecting the biotech industry as we come out of last week's J.P. Morgan Health Care conference. Tune in to hear more on costs of genomic therapies, AI integration, and why Sam believes the “roaring twenties” of biotech may be on the horizon. “Every pharma company will have to have a cell gene therapy unit otherwise you risk being left behind” – @CrisprSam Key Points From This Episode: Why today is an exciting time for biotech Why Cathie believes macro factors, such as fears of inflation and valuations, are determining the present course of genomics companies Innovations and Improvements emerging in the biomedical innovation space The importance of former iterations of patented CRISPR-Cas9 for future treatments Will the timeline for advancing drugs to market shrink with time? Potential gene-editing developments in the near future – including the balance of ex vivo and in vivo The possibilities of what it will take to expand human life, while also treating rare diseases Sam on why having a capital base for sustainable funding could lead to better long term effects Moonshot Ideas and the next 10 years

FYI - For Your Innovation
An Outlook on Biotechnology with Sam Kulkarni, CEO CRISPR Therapeutics

FYI - For Your Innovation

Play Episode Listen Later Jan 17, 2022 56:28


The 7investing Podcast
5 Big Reveals from the 2022 JP Morgan Healthcare Conference

The 7investing Podcast

Play Episode Listen Later Jan 13, 2022 23:46


There aren't many single events that bring together a Who's Who list of the leading private and public companies in biotech and synthetic biology. The JP Morgan Healthcare Conference is one of the rare exceptions. The annual event, held every January, is one of the biggest stages for companies to reveal innovative new products in development, announce acquisitions, and form landscape-shifting collaborations. Investors were left wanting more after the 2021 meeting, which was relatively subdued due to the coronavirus pandemic. The first few days of the 2022 event seemed to live up to historical expectations, with a handful of companies making splashy announcements so far. In this episode of the podcast, 7investing Lead Advisors Simon Erickson and Maxx Chatsko sit down to provide quick takeaways on some of the biggest reveals from the beginning of the 2022 JP Morgan Healthcare Conference. These include: The unveiling of a long-read DNA sequencing technology from Illumina (NASDAQ: ILMN) and an enzymatic DNA synthesis technology from Twist Bioscience (NASDAQ: TWST). Molecular testing leader Exact Sciences (NASDAQ: EXAS) used the stage to reveal that it comfortably beat full-year 2021 guidance and jump into hereditary cancer testing. Meanwhile, Beam Therapeutics (NASDAQ: BEAM) announced a research collaboration with Pfizer (NYSE: PFE) that had an unusual structure. Simon and Maxx also share their thoughts on the slow pace of merger and acquisitions (M&A) in drug development in the last two years — and why record cash balances and a constant need for innovation at the largest companies suggest that could change in 2022. Publicly-traded companies mentioned or alluded to in this podcast include Beam Therapeutics, CRISPR Therapeutics, Eli Lilly, Exact Sciences, Illumina, Intellia Therapeutics, Novo Nordisk, Pacific Biosciences, and Twist Bioscience. 7investing's advisors may own positions in the companies that are mentioned. Welcome to 7investing. We are here to empower you to invest in your future! We publish our 7 best ideas in the stock market to our subscribers for just $49 per month or $399 per year. Start your journey toward's financial independence: https://www.7investing.com/subscribe Stop by our website to level-up your investing education: https://www.7investing.com Follow us: ► https://www.facebook.com/7investing ► https://twitter.com/7investing ► https://instagram.com/7investing --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

Investor Audio
Crispr Therapeutics: CRSP (2020) - Transformative Gene-Based Medicine!

Investor Audio

Play Episode Listen Later Nov 15, 2021 16:01


Let's understand the business of the company that is transforming the lives of patients with serious diseases.Industry: Biotechnology

Sales vs. Marketing
How to Pivot In Your Career With Bob Richards, Executive Vice Chairman at Cushman Wakefield

Sales vs. Marketing

Play Episode Listen Later Sep 9, 2021 55:58


➡️ Like The Show? Leave A Rating: https://ratethispodcast.com/successstory ➡️ About The Guest Bob Richards is the Executive Vice Chairman and member of the Global Advisory Board at Cushman Wakefield. Locally, Bob leads the Cambridge/Urban team and also heads the Life Science and Healthcare Practice Groups. He also serves on the Boston Office Steering Committee. Bob has represented numerous corporate clients in transactions nationally and internationally. He has successfully completed complex assignments in India, China, Singapore, Australia, The United Kingdom, The Netherlands and Denmark, as well as all major cities in The United States. He counsels tenant clients such as Dana-Farber Cancer Institute, Harvard Medical School, Bristol-Myers Squibb, Raytheon, Forrester Research, CRISPR Therapeutics, Acceleron, and The Wyss Institute. Prior to joining Cushman & Wakefield, Bob was a founding partner and president of Richards Barry Joyce & Partners, which was acquired by Transwestern in 2013. Prior to co-founding RBJ, he was a Principal at Trammell Crow Company. Beflore entering commercial real estate, Bob spent five years working as a sportscaster for CNN and WTBS in Atlanta. ➡️ Talking Points 00:00 - Intro 09:13 - Being comfortable speaking to anyone. 10:54 - How to manage a career pivot. 22:31 - Moving to Cushman Wakefield 30:26 - Remote work & real estate. 41:06 - Bet on yourself. 43:01 - Your clients are a reflection of you. 48:05 - Always have clarity of purpose. ➡️ Show Links https://www.linkedin.com/in/bob-richards-03a28221/ https://www.cushmanwakefield.com/en/united-states/people/robert-richards ➡️ Podcast Sponsors 1. Hubspot Podcast Network https://hubspot.com/podcastnetwork 2. Ladder - Life Insurance Solutions https://ladderlife.com/successstory

Talking Stocks
Talking Stocks: The Pros and Cons Every Investor Ought to Know About Gene Editing

Talking Stocks

Play Episode Listen Later Sep 7, 2021 53:06


Editing genes to fix genetic mutations could revolutionize how we treat disease, but gene editing research is only in early stages, and plenty still needs to learned before we know it's safe for widespread use. In this episode of Limelight Alpha's Talking Stocks, 7Investing Lead Advisor, Maxx Chatsko, joins Todd Campbell to explains the pros and cons of gene editing. The duo discuss: How gene editing, including CRISPR Cas, compares to RNAi therapies; What gene editing companies are furthest along in their research; What data is on tap from leading gene editing stocks, including Crispr Therapeutics, Editas Medicine, Caribou Biosciences, and Intellia Therapeutics, and What could go wrong in gene editing drug development, including risks associated with double-strand breaks. You can learn more about 7Investing here: https://7investing.com/subscribe/?referred_by_id=747 You can learn more about Limelight Alpha here: https://seekingalpha.com/author/limelight-alpha-management-partners/research Follow Limelight Alpha on Twitter: @AlphaLimelight Follow Maxx Chatsko on Twitter: @7MaxxChatsko --- Support this podcast: https://anchor.fm/limelight-alpha/support

25 minuter
#166: Investeringstaktik (Aktiespecial)

25 minuter

Play Episode Listen Later Sep 6, 2021 42:58


Huvudämnena är: Investeringsramverk, Entry vs Exit, Varför GAV är irrelevant, Ska man köpa i uppgång eller nedgång? Conviction och toptrading, RANGEr - årlig snittavkastning vs riktkurs, När ska man omvikta portföljen? Den omnämnda videon: Introduktion till Värdeinvesteringar. Bolag som nämns: Twitter, Azelio, Addvise, Stockwik, Oscar Properties, CRISPR Therapeutics, Moderna. Och Uransektorns uppgång sista veckorna. Gör en Tidig Ansökan på www.Finanskursen.se innan 25 september om du vill bli garanterad en plats.

MoneyBall Medicine
Kevin Davies on the CRISPR Revolution and Genome Editing

MoneyBall Medicine

Play Episode Listen Later Aug 31, 2021 66:51


This week Harry is joined by Kevin Davies, author of the 2020 book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. CRISPR—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—consists of DNA sequences that evolved to help bacteria recognize and defend against viral invaders, as a kind of primitive immune system. Thanks to its ability to precisely detect and cut other DNA sequences, CRISPR has spread to labs across the world in the nine years since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking 2012 Science paper describing how the process works. The Nobel Prize committee recognized the two scientists for the achievement in 2020, one day after Davies' book came out. The book explains how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused. Today's interview covers all of that ground and more.Davies is a PhD geneticist who has spent most of his career in life sciences publishing. After his postdoc with Harvey Lodish at the Whitehead Institute, Davies worked as an assistant editor at Nature, the founding editor of Nature Genetics (Nature's first spinoff journal), editor-in-chief at Cell Press, founding editor-in-chief of the Boston-based publication Bio-IT World, and publisher of Chemical & Engineering News. In 2018 he helped to launch The CRISPR Journal, where he is the executive editor. Davies' previous books include Breakthrough (1995) about the race to understand the BRCA1 breast cancer gene, Cracking the Genome (2001) about the Human Genome Project, The $1,000 Genome (2010) about next-generation sequencing companies, and DNA (2017), an updated version of James Watson's 2004 book, co-authored with Watson and Andrew Berry.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3.Scroll down to find the subhead titled "Ratings & Reviews."4.Under one of the highlighted reviews, select "Write a Review."5.Next, select a star rating at the top — you have the option of choosing between one and five stars. 6.Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7.Once you've finished, select "Send" or "Save" in the top-right corner. 8.If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9.After selecting a nickname, tap OK. Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: We talk a lot on the show about how computation and data are changing the way we develop new medicines and the way we deliver healthcare. Some executives in the drug discovery business speak of the computing and software side of the business as the “dry lab” —to set it apart from the “wet labs” where scientists get their hands dirty working with actual cells, tissues, and reagents.But the thing is, recent progress on the wet lab side of biotech has been just as amazing as progress in areas like machine learning. And this week, my friend Kevin Davies is here to talk about the most powerful tool to come along in the last decade, namely, precise gene editing using CRISPR.Of course, CRISPR-based gene editing has been all over the news since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking Science paper in 2012 describing how the process works in the lab. That work earned them a Nobel Prize in medicine just eight years later, in 2020.But what's not as well-known is the story of how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused.Kevin put that whole fascinating story together in his 2020 book Editing Humanity. And as the executive editor of The CRISPR Journal, the former editor-in-chief of Bio-IT World, the founding editor at Nature Genetics, and the author of several other important books about genomics, Kevin is one of the best-placed people in the world to tell that story. Here's our conversation.Harry Glorikian: Kevin, welcome to the show. Kevin Davies: Great to see you again, Harry. Thanks for having me on.Harry Glorikian: Yeah, no, I mean, I seem to be saying this a lot lately, it's been such a long time since, because of this whole pandemic, nobody's really seeing anybody on a regular basis. I want to give everybody a chance to hear about, you had written this book called Editing Humanity, which is, you know, beautifully placed behind you for, for product placement here. But I want to hear, can you give everybody sort of an overview of the book and why you feel that this fairly technical laboratory tool called CRISPR is so important that you needed to write a book about it?Kevin Davies: Thank you. Yes. As you may know, from some of my previous “bestsellers” or not, I've written about big stories in genetics because that's the only thing I'm remotely qualified to write about. I trained as a human geneticist in London and came over to do actually a pair of post-docs in the Boston area before realizing my talents, whatever they might be, certainly weren't as a bench researcher. So I had to find another way to stay in science but get away from the bench and hang up the lab coats.So moving into science publishing and getting a job with Nature and then launching Nature Genetics was the route for me. And over the last 30 years, I've written four or five books that have all been about, a) something big happening in genomics, b) something really big that will have both medical and societal significance, like the mapping and discovery of the BRCA1 breast cancer gene in the mid-90s, the Human Genome Project at the turn of the century, and then the birth and the dawn of consumer genetics and personalized medicine with The $1,000 Genome. And the third ingredient I really look for if I'm trying to reach a moderately, significantly large audience is for the human elements. Who are they, the heroes and the anti heroes to propel the story? Where is the human drama? Because, you know, we all love a good juicy, gossipy piece of story and rating the good guys and the bad guys. And CRISPR, when it first really took off in 2012, 2013 as a gene editing tool a lot of scientists knew about this. I mean, these papers are being published in Science in particular, not exactly a specialized journal, but I was off doing other things and really missed the initial excitement, I'm embarrassed to say. It was only a couple of years later, working on a sequel to Jim Watson's DNA, where I was tasked with trying to find and summarize the big advances in genomic technology over the previous decade or whatever, that I thought, well, this CRISPR thing seems to be taking off and the Doudnas and the Charpentiers are, you know, winning Breakthrough Prizes and being feted by celebrities. And it's going on 60 Minutes. They're going to make a film with the Rock, Dwayne Johnson. What the heck is going on. And it took very little time after that, for me to think, you know, this is such an exciting, game-changing disruptive technology that I've got to do two things. I've gotta, a) write a book and b) launch a journal, and that's what I did. And started planning at any rate in sort of 2016 and 17. We launched the CRISPR Journal at the beginning of 2018. And the book Editing Humanity came out towards the end of 2020. So 2020, literally one day before the Nobel Prize—how about that for timing?—for Doudna and Charpentier for chemistry last year. Harry Glorikian: When I think about it, I remember working with different companies that had different types of gene editing technology you know, working with some particularly in the sort of agriculture space, cause it a little bit easier to run faster than in the human space. And you could see what was happening, but CRISPR now is still very new. But from the news and different advances that are happening, especially here in the Boston area, you know, it's having some real world impacts. If you had to point to the best or the most exciting example of CRISPR technology helping an actual patient, would you say, and I've heard you say it, Victoria Gray, I think, would be the person that comes to mind. I've even, I think in one of your last interviews, you said something about her being, you know, her name will go down in history. Can you explain the technology that is helping her and what some of the similar uses of CRISPR might be?Kevin Davies: So the first half of Editing Humanity is about the heroes of CRISPR, how we, how scientists turned it from this bizarre under-appreciated bacterial antiviral defense system and leveraged it and got to grips with it, and then figured out ways to turn it into a programmable gene editing technology. And within a year or two of that happening that the classic Doudna-Charpentier paper came out in the summer of 2012. Of course the first wave of biotech companies were launched by some of the big names, indeed most of the big names in CRISPR gene editing hierarchies. So Emmanuel Charpentier, Nobel Laureate, launched CRISPR Therapeutics, Jennifer Doudna co-founded Editas Medicine with several other luminaries. That didn't go well for, for reasons of intellectual property. So she withdrew from Editas and became a co-founder of Intellia Therapeutics as well as her own company, Caribou, which just went public, and Feng Zhang and others launched Editas Medicine. So we had this sort of three-way race, if you will, by three CRISPR empowered gene editing companies who all went public within the next two or three years and all set their sights on various different genetic Mendelian disorders with a view to trying to produce clinical success for this very powerful gene editing tool. And so, yes, Victoria Gray is the first patient, the first American patient with sickle cell anemia in a trial that is being run by CRISPR Therapeutics in close association with Vertex Pharmaceuticals. And that breakthrough paper, as I think many of your listeners will know, came out right at the end of 2020 published in the New England Journal of Medicine. Doesn't get much more prestigious than that. And in the first handful of patients that CRISPR Therapeutics have edited with a view to raising the levels of fetal hemoglobin, fetal globin, to compensate for the defective beta globin that these patients have inherited, the results were truly spectacular.And if we fast forward now to about two years after the initial administration, the initial procedures for Victoria Gray and some of her other volunteer patients, the results still look as spectacular. Earlier this year CRISPR Therapeutics put out of sort of an update where they are saying that the first 20 or 24 patients that they have dosed with sickle cell and beta thallasemia are all doing well. There've been little or no adverse events. And the idea of this being a once and done therapy appears very well founded. Now it's not a trivial therapy. This is ex-vivo gene editing as obviously rounds of chemotherapy to provide the room for the gene edited stem cells to be reimplanted into the patient. So this is not an easily scalable or affordable or ideal system, but when did we, when will we ever able to say we've pretty much got a cure for sickle cell disease? This is an absolutely spectacular moment, not just for CRISPR, but for medicine, I think, overall. And Victoria Gray, who's been brilliantly profiled in a long running series on National Public Radio, led by the science broadcaster Rob Stein, she is, you know, we, we can call her Queen Victoria, we can call it many things, but I really hope that ,it's not just my idea, that she will be one of those names like Louise Brown and other heroes of modern medicine, that we look and celebrate for decades to come.So the sickle cell results have been great, and then much more recently, also in the New England Journal, we have work led by Intellia Therapeutics, one of the other three companies that I named, where they've been also using CRISPR gene editing, but they've been looking at a rare liver disease, a form of amyloidosis where a toxic protein builds up and looking to find ways to knock out the production of that abnormal gene.And so they've been doing in vivo gene editing, really using CRISPR for the first time. It's been attempted using other gene editing platforms like zinc fingers, but this is the first time that I think we can really say and the New England Journal results prove it. In the first six patients that have been reported remarkable reductions in the level of this toxic protein far, not far better, but certainly better than any approved drugs that are currently on the market. So again, this is a very, very exciting proof of principle for in vivo gene editing, which is important, not just for patients with this rare liver disorder, but it really gives I think the whole field and the whole industry enormous confidence that CRISPR is safe and can be used for a growing list of Mendelian disorders, it's 6,000 or 7,000 diseases about which we know the root genetic cause, and we're not going to tackle all of them anytime soon, but there's a list of ones that now are within reach. And more and more companies are being launched all the time to try and get at some of these diseases.So as we stand here in the summer of 2021, it's a really exciting time. The future looks very bright, but there's so much more to be done. Harry Glorikian: No, we're just at the beginning. I mean, I remember when I first saw this, my first question was off target effects, right? How are we going to manage that? How are they going to get it to that place that they need to get it to, to have it to that cell at that time, in the right way to get it to do what it needs to do. And you know, all these sorts of technical questions, but at the same time, I remember I'm going to, trying to explain this to my friends. I'm like, “You don't understand, this can change everything.” And now a high school student, I say this to people and they look at me strangely, a high school student can order it and it shows up at your house.Kevin Davies: Yeah, well, this is why I think, and this is why one reason why CRISPR has become such an exciting story and receives the Nobel Prize eight years after the sort of launch publication or the first demonstration of it as a gene editing tool. It is so relatively easy to get to work. It's truly become a democratized or democratizing technology. You don't need a million-dollar Illumina sequencer or anything. And so labs literally all around the world can do basic CRISPR experiments. Not everyone is going to be able to launch a clinical trial. But the technology is so universally used, and that means that advances in our understanding of the mechanisms, new tools for the CRISPR toolbox new pathways, new targets, new oftware, new programs, they're all coming from all corners of the globe to help not just medicine, but many other applications of CRISPR as well.Harry Glorikian: Yeah. I always joke about like, there, there are things going on in high school biology classes now that weren't, available, when I was in college and even when we were in industry and now what used to take an entire room, you can do on a corner of a lab bench.Kevin Davies: Yeah. Yeah. As far as the industry goes we mentioned three companies. But you know, today there's probably a dozen or more CRISPR based or gene editing based biotech companies. More undoubtedly are going to be launched before the end of this year. I'm sure we'll spend a bit of time talking about CRISPR 2.0, it seems too soon to be even thinking about a new and improved version of CRISPR, but I think there's a lot of excitement around also two other Boston-based companies, Beam Therapeutics in Cambridge and Verve Therapeutics both of which are launching or commercializing base editing. So base editing is a tool developed from the lab of David Lu of the Broad Institute [of MIT and Harvard]. And the early signs, again, this technology is only five or six years old, but the early signs of this are incredibly promising. David's team, academic team, had a paper in Nature earlier this year, really reporting successful base editing treatment of sickle cell disease in an animal model, not by raising the fetal globin levels, which was sort of a more indirect method that is working very well in the clinic, but by going right at the point mutation that results in sickle cell disease and using given the chemical repertoire of base editing.Base editing is able to make specific single base changes. It can't do the full repertoire of single base changes. So there are some limitations on researchers' flexibility. So they were unable to flip the sickle cell variant back to the quote unquote wild type variants, but the change they were able to make is one that they can live with, we can live with because it's a known benign variant, a very rare variant that has been observed in other, in rare people around the world. So that's completely fine. It's the next best thing. And so that looks very promising. Beam Therapeutics, which is the company that David founded or co-founded is trying a related approach, also going right at the sickle cell mutation. And there are other companies, including one that Matthew Porteus has recently founded and has gone public called Graphite Bio.So this is an exciting time for a disease sickle cell disease that has been woefully neglected, I think you would agree, both in terms of basic research, funding, medical prioritization, and medical education. Now we have many, many shots on goal and it doesn't really, it's not a matter of one's going to win and the others are going to fall by the wayside. Just like we have many COVID vaccines. We'll hopefully have many strategies for tackling sickle cell disease, but they are going to be expensive. And I think you know the economics better than I do. But I think that is the worry, that by analogy with gene therapies that have been recently approved, it's all, it's really exciting that we can now see the first quote, unquote cures in the clinic. That's amazingly exciting. But if the price tag is going to be $1 million or $2 million when these things are finally approved, if and when, that's going to be a rather deflating moment. But given the extraordinary research resources that the CRISPRs and Intellias and Beams and Graphites are pouring into this research, obviously they've got to get some return back on their investment so that they can plow it back into the company to develop the next wave of of gene editing therapies. So you know, it's a predicament Harry Glorikian: One of these days maybe I have to have a show based on the financial parts of it. Because there's a number of different ways to look at it. But just for the benefit of the listeners, right, who may not be experts, how would you explain CRISPR is different from say traditional gene therapies. And is CRISPR going to replace older methods of, of gene therapy or, or will they both have their place? Kevin Davies: No, I think they'll both have their place. CRISPR and, and these newer gene editing tools, base editing and another one called prime editing, which has a company behind it now called Prime Medicine, are able to affect specific DNA changes in the human genome.So if you can target CRISPR, which is an enzyme that cuts DNA together with a little program, the GPS signal is provided in the form of a short RNA molecule that tells the enzyme where to go, where to go in the genome. And then you have a couple of strategies. You can either cut the DNA at the appropriate target site, because you want to inactivate that gene, or you just want to scramble the sequence because you want to completely squash the expression of that gene. Or particularly using the newer forms of gene editing, like base editing, you can make a specific, a more nuanced, specific precision edit without, with one big potential advantage in the safety profile, which is, you're not completely cutting the DNA, you're just making a nick and then coaxing the cell's natural repair systems to make the change that you sort of you're able to prime.So there are many diseases where this is the way you want to go, but that does not in any way invalidate the great progress that we're making in traditional gene therapy. So for example today earlier today I was recording an interview or for one of my own programs with Laurence Reid, the CEO of Decibel Therapeutics, which is looking at therapies for hearing loss both genetic and other, other types of hearing disorders.And I pushed him on this. Aren't you actually joinomg with the gene editing wave? And he was very circumspect and said, no, we're very pleased, very happy with the results that we're getting using old fashioned gene replacement therapy. These are recessive loss of function disorders. And all we need to do is get the expression of some of the gene back. So you don't necessarily need the fancy gene editing tools. If you can just use a an AAV vector and put the healthy gene back into the key cells in the inner ear. So they're complimentary approaches which is great.Harry Glorikian: So, you know, in, in this podcast, I try to have a central theme when I'm talking to people. The relationships of big data, computation, advances in new drugs, and other ways to keep people healthy. So, you know, like question-wise, there's no question in my mind that the whole genomics revolution that started in the ‘90s, and I was happy to be at Applied Biosystems when we were doing that, would have been impossible in the absence of the advances in computing speed and storage in the last three decades. I think computing was the thing that held up the whole human genome, which gave us the book of life that CRISPR is now allowing us to really edit. But I wonder if you could bring us sort of up-to-date and talk about the way CRISPR and computation are intertwined. What happens when you combine precision of an editing tool like CRISPR with the power of machine learning and AI tools to find meaning and patterns in that huge genetic ball? Kevin Davies: Yeah. Well, yeah. I'm got to tread carefully here, but I think we are seeing papers from some really brilliant labs that are using some of the tools that you mentioned. AI and machine learning with a view to better understanding and characterizing some of the properties and selection criteria of some of these gene editing tools. So you mentioned earlier Harry, the need to look out for safety and minimize the concern of off-target effects. So I think by using some of these some algorithms and AI tools, researchers have made enormous strides in being able to design the programmable parts of the gene editing constructs in such a way that you increase the chances that they're going to go to the site that you want them to go to, and nnot get hung up latching onto a very similar sequence that's just randomly cropped up on the dark side of the genome, across the nucleus over there. You don't want that to happen. And I don't know that anybody would claim that they have a failsafe way to guarantee that that could never happen. But the you know, the clinical results that we've seen and all the preclinical results are showing in more and more diseases that we've got the tools and learned enough now to almost completely minimize these safety concerns. But I think everyone, I think while they're excited and they're moving as fast as they can, they're also doing this responsibly. I mean, they, they have to because no field, gene therapy or gene editing really wants to revisit the Jesse Gelsinger tragedy in 1999, when a teenage volunteer died in volunteering for a gene therapy trial at Penn of, with somebody with a rare liver disease. And of course that, that setback set back the, entire field of gene therapy for a decade. And it's really remarkable that you know, many of the sort of pioneers in the field refuse to throw in the towel, they realized that they had to kind of go back to the drawing board, look at the vectors again, and throw it out. Not completely but most, a lot of the work with adenoviruses has now gone by the wayside. AAV is the new virus that we hear about. It's got a much better safety profile. It's got a smaller cargo hold, so that's one drawback, but there are ways around that. And the, the explosion of gene therapy trials that we're seeing now largely on the back of AAV and now increasingly with, with non-viral delivery systems as well is, is very, very gratifying. And it's really delivery. I think that is now the pain point. Digressing from your question a little bit, but delivery, I think is now the big challenge. It's one thing to contemplate a gene therapy for the eye for rare hereditary form of blindness or the ear. Indeed those are very attractive sites and targets for some of these early trials because of the quantities that you need to produce. And the localization, the, the physical localization, those are good things. Those help you hit the target that you want to. But if you're contemplating trying something for Duchenne muscular dystrophy or spinal muscular atrophy, or some of the diseases of the brain, then you're going to need much higher quantities particularly for muscular disorders where, you run into now other challenges, including, production and manufacturing, challenges, and potentially safeguarding and making sure that there isn't an immune response as well. That's another, another issue that is always percolating in the background.But given where we were a few years ago and the clinical progress that we've talked about earlier on in the show it, I think you can safely assume that we've collectively made enormous progress in, in negating most, if not all of these potential safety issues.Harry Glorikian: No, you know, it's funny, I know that people will say like, you know, there was a problem in this and that. And I look at like, we're going into uncharted territories and it has to be expected that you just…you've got people that knew what they were doing. All of these people are new at what they are doing. And so you have to expect that along the way everything's not going to go perfectly. But I don't look at it as a negative. I look at it as, they're the new graduating class that's going to go on and understand what they did right. Or wrong, and then be able to modify it and make an improvement. And, you know, that's what we do in science. Kevin Davies: Well, and forget gene editing—in any area of drug development and, and pharmaceutical delivery, things don't always go according to plan. I'm sure many guests on Moneyball Medicine who have had to deal with clinical trial failures and withdrawing drugs that they had all kinds of high hopes for because we didn't understand the biology or there was some other reaction within, we didn't understand the dosing. You can't just extrapolate from an animal model to humans and on and on and on. And so gene editing, I don't think, necessarily, should be held to any higher standard. I think the CRISPR field has already in terms of the sort of market performance, some of the companies that we've mentioned, oh my God, it's been a real roller coaster surprisingly, because every time there's been a paper published in a prominent journal that says, oh my God, there's, there's a deletion pattern that we're seeing that we didn't anticipate, or we're seeing some immune responses or we're seeing unusual off target effects, or we're seeing P53 activation and you know, those are at least four off the top of my head. I'm sure there've been others. And all had big transient impact on the financial health of these companies. But I think that was to be expected. And the companies knew that this was just an overreaction. They've worked and demonstrated through peer review publications and preclinical and other reports that these challenges have been identified, when known about, pretty much completely have been overcome or are in the process of being overcome.So, you know, and we're still seeing in just traditional gene therapy technologies that have been around for 15, 20 years. We're still seeing reports of adverse events on some of those trials. So for gene editing to have come as far as it's common, to be able to look at these two big New England Journal success stories in sickle cell and ATTR amyloidosis, I don't think any very few, except the most ardent evangelists would have predicted we'd be where we are just a few years ago. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian:One of your previous books was called The $1,000 Genome. And when you published that back in 2010, it was still pretty much science fiction that it might be possible to sequence someone's entire genome for $1,000. But companies like Illumina blew past that barrier pretty quickly, and now people are talking about sequencing individual genome for just a few hundred dollars or less. My question is, how did computing contribute to the exponential trends here. And do you wish you'd called your book The $100 Genome?Kevin Davies: I've thought about putting out a sequel to the book, scratching out the 0's and hoping nobody would notice. Computing was yes, of course, a massive [deal] for the very first human genome. Remember the struggle to put that first assembly together. It's not just about the wet lab and pulling the DNA sequences off the machines, but then you know, the rapid growth of the data exposure and the ability to store and share and send across to collaborators and put the assemblies together has been critical, absolutely critical to the development of genomics.I remember people were expressing shock at the $1,000 genome. I called the book that because I heard Craig Venter use that phrase in public for the first time in 2002. And I had just recently published Cracking the Genome. And we were all still recoiling at the billions of dollars it took to put that first reference genome sequence together. And then here's Craig Venter, chairing a scientific conference in Boston saying what we need is the $1,000 genome. And I almost fell off my chair. “what are you? What are you must you're in, you're on Fantasy Island. This is, there's no way we're going to get, we're still doing automated Sanger sequencing. God bless Fred Sanger. But how on earth are you going to take that technology and go from billions of dollars to a couple of thousand dollars. This is insanity.” And that session we had in 2002 in Boston. He had a local, a little episode of America's Got Talent and he invited half a dozen scientists to come up and show what they had. And George Church was one of them. I think Applied Biosystems may have given some sort of talk during that session. And then a guy, a young British guy from a company we'd never heard of called Celexa showed up and showed a couple of pretty PowerPoint slides with colored beads, representing the budding DNA sequence on some sort of chip. I don't know that he showed any data. It was all very pretty and all very fanciful. Well guess what? They had the last laugh. Illumina bought that company in 2006. And as you said, Harry you know, I think when, when they first professed to have cracked the $1,000 dollar genome barrier, a few people felt they needed a pinch of salt to go along with that. But I think now, yeah, we're, we're, we're well past that. And there are definitely outfits like BGI, the Beijing Genomics Institute being one of them, that are touting new technologies that can get us down to a couple of hundred. And those were such fun times because for a while there Illumina had enormous competition from companies like 454 and Helicose and PacBio. And those were fun heady times with lots and lots of competition. And in a way, Illumina's had it a little easy, I think over the last few years, but with PacBio and Oxford Nanopore gaining maturity both, both in terms of the technology platforms and their business strategy and growth, I think Illumina' gonna start to feel a little bit more competition in the long read sequence space. And one is always hearing whispers of new companies that may potentially disrupt next-gen sequencing. And that would be exciting because then we'd have an excuse to write another book. Harry Glorikian: Well, Kevin, start writing because I actually think we're there. I think there are a number of things there and you're right, I think Illumina has not had to bring the price down as quickly because there hasn't been competition. And you know, when I think about the space is, if you could do a $60 genome, right, it starts to become a rounding error. Like what other business models and opportunities now come alive? And those are the things that excite me. All right. But so, but you have a unique position as editor of the journal of CRISPR and the former editor of a lot of prominent, you know, publications, Nature Genetics, Bio-IT World, Chemical & Engineering News. Do you think that there's adequate coverage of the biological versus the computing side of it? Because I, I have this feeling that the computing side still gets a little overlooked and underappreciated. Kevin Davies: I think you're right. I mean I think at my own company Genetic Engineering News, we still have such deep roots in the wet lab vision and version of biotechnology that it takes a conscious effort to look and say, you know, that's not where all the innovation is happening. Bio-IT World, which you mentioned is interesting because we launched that in 2002. It was launched by the publisher IDG, best-known from MacWorld and ComputerWorld and this, this whole family of high-tech publications.And we launched in 2002 was a very thick glossy print magazine. And ironically, you know, we just couldn't find the advertising to sustain that effort, at least in the way that we'd envisioned it. And in 2006 and 2007, your friend and mine Phillips Kuhl, the proprietor of Cambridge Healthtech Institute, kind of put us out of our misery and said, you know what I'll, take the franchise because IDG just didn't know what to do with it anymore. But what he really wanted was the trade show, the production. And even though at the magazine eventually we fell on our sword and eventually put it out of its misery, the trade show went from strength to strength and it'll be back in Boston very soon because he had the vision to realize there is a big need here as sort of supercomputing for life sciences.And it's not just about the raw high-performance computing, but it's about the software, the software tools and data sharing and management. And it's great to go back to that show and see the, you know, the Googles and Amazons and yeah, all the big household names. They're all looking at this because genome technology, as we've discussed earlier has been one of the big growth boom areas for, for their services and their products.Harry Glorikian: Right. I mean, well, if you look at companies like Tempus, right. When I talked to Joel Dudley over there on the show it's, they want to be the Amazon AWS piping for all things genomic analysis. Right. So instead of creating it on your own and building a, just use their platform, basically, so it's definitely a growth area. And at some point, if you have certain disease states, I don't see how you don't get you know, genomic sequencing done, how a physician even today in oncology, how anybody can truly prescribe with all the drugs that are being approved that have, you know, genomic biomarkers associated with them and not use that data.Kevin Davies: On a much lower, lo-fi scale, as I've been doing a lot of reading about sickle cell disease lately, it's clear that a lot of patients who are, of course, as you, as you know, as your listeners know, are mostly African-American because the disease arose in Africa and the carrier status gives carriers a huge health advantage in warding off malaria. So the gene continues to stay, stay high in in frequency. Many African-American patients would benefit from some generic drugs that are available in this country that provide some relief, but aren't aware of it and maybe their physicians aren't completely aware of it either. Which is very sad. And we've neglected the funding of this disease over many decades, whereas a disease like cystic fibrosis, which affects primarily white people of Northern European descent that receives far more funding per capita, per head, than than a disease like sickle cell does. But hopefully that will begin to change as we see the, the potential of some of these more advanced therapies.I think as far as your previous comment. I think one of the big challenges now is how we tackle common diseases. I think we're making so much progress in treating rare Mendelian diseases and we know thousands of them. But it's mental illness and asthma and diabetes you know, diseases that affect millions of people, which have a much more complicated genetic and in part environmental basis.And what can we learn, to your point about having a full genome sequence, what can we glean from that that will help the medical establishment diagnose and treat much more common diseases, not quite as simple as just treating a rare Mendelian version of those diseases? So that's, I think going to be an important frontier over the next decade.Harry Glorikian: Yeah. It's complicated. I think you're going to see as we get more real-world data that's organized and managed well, along with genomic data, I think you'll be able to make more sense of it. But some of these diseases are quite complicated. It's not going to be find one gene, and it's going to give you that answer.But I want to go back to, you can't really talk about CRISPR without talking about this specter of germline editing. And a big part of your book is about this firestorm of criticism and condemnation around, you know, the 2018 when the Chinese researcher He Jankui, I think I said it correctly.Yep.Kevin Davies: He Jankui is how I say it. Close. Harry Glorikian: He announced that he had created twin baby girls with edits to their genomes that were intended to make them immune to HIV, which sort of like—that already made me go, what? But the experiment was, it seems, unauthorized. It seems that, from what I remember, the edits were sloppy and the case spurred a huge global discussion about the ethics of using CRISPR to make edits that would be inherited by future generations. Now, where are we in that debate now? I mean, I know the National Academy of Sciences published a list of criteria, which said, don't do that. Kevin Davies: It was a little more nuanced than that. It wasn't don't do that. It was, there is a very small window through which we could move through if a whole raft of criteria are met. So they, they refuse to say hereditary genome editing should be banned or there should be a moratorium. But they said it should not proceed until we do many things. One was to make sure it is safe. We can't run before we can walk. And by that, I mean, we've got to first demonstrate—because shockingly, this hasn't been done yet—that genome editing can be done safely in human embryos. And in the last 18 months there've been at least three groups, arguably the three leading groups in terms of looking at genetic changes in early human embryos, Kathy Niakan in London, Shoukhrat Mitalipov in Oregon, and Dieter Egli in New York, who all at roughly the same time published and reports that said, or posted preprints at least that said, when we attempt to do CRISPR editing experiments in very early human embryos, we're seeing a mess. We're seeing a slew of off-target and even on-target undesirable edits.And I think that says to me, we don't completely understand the molecular biology of DNA repair in the early human embryo. It may be that there are other factors that are used in embryogenesis that are not used after we're born. That's speculation on my part. I may be wrong. But the point is we still have a lot to do to understand, even if we wanted to.And even if everybody said, “Here's a good case where we should pursue germline editing,” we've gotta be convinced that we can do it safely. And at the moment, I don't think anybody can say that. So that's a huge red flag.But let's assume, because I believe in the power of research, let's assume that we're going to figure out ways to do this safely, or maybe we say CRISPR isn't the right tool for human embryos, but other tools such as those that we've touched on earlier in the show base editing or prime editing, or maybe CRISPR 3.0 or whatever that is right now to be published somewhere. [Let's say ] those are more safe, more precise tools. Then we've got to figure out well, under what circumstances would we even want to go down this road? And the pushback was quite rightly that, well, we already have technologies that can safeguard against families having children with genetic diseases. It's called IVF and pre-implantation genetic diagnosis. So we can select from a pool of IVF embryos. The embryos that we can see by biopsy are safe and can therefore be transplanted back into the mother, taken to term and you know, a healthy baby will emerge.So why talk about gene editing when we have that proven technology? And I think that's a very strong case, but there are a small number of circumstances in which pre-implantation genetic diagnosis will simply not work. And those are those rare instances where a couple who want to have a biological child, but have both of them have a serious recessive genetic disease. Sickle cell would be an obvious case in point. So two sickle cell patients who by definition carry two copies of the sickle cell gene, once I have a healthy biological child preimplantation genetic diagnosis, it's not going to help them because there are no healthy embryos from whatever pool that they produce that they can select. So gene editing would be their only hope in that circumstance. Now the National Academy's report that you cited, Harry, did say for serious diseases, such as sickle cell and maybe a few others they could down the road potentially see and condone the use of germline gene editing in those rare cases.But they're going to be very rare, I think. It's not impossible that in an authorized approved setting that we will see the return of genome editing, but that's okay. Of course you can can issue no end of blue ribbon reports from all the world's experts, and that's not going to necessarily prevent some entrepreneur whose ethical values don't align with yours or mine to say, “You know what, there's big money to be made here. I'm going offshore and I'm going to launch a CRISPR clinic and you know, who's going to stop me because I'll be out of the clutches of the authorities.” And I think a lot of people are potentially worried that that scenario might happen. Although if anyone did try to do that, the scientific establishment would come down on them like a ton of bricks. And there'll be a lot of pressure brought to bear, I think, to make sure that they didn't cause any harm.Harry Glorikian: Yeah. It's funny. I would like to not call them entrepreneurs. I like entrepreneurs. I'd like to call them a rogue scientist. Kevin Davies: So as you say, there's the third section of four in Editing Humanity was all about the He Jankui debacle or saga. I had flown to Hong Kong. It's a funny story. I had a little bit of money left in my travel budget and there were two conferences, one in Hong Kong and one in China coming up in the last quarter of 2018. So I thought, well, okay, I'll go to one of them. And I just narrowed, almost a flip of a coin, I think. Okay, let's go to the Hong Kong meeting.It's a bioethics conference since I don't expect it to be wildly exciting, but there are some big speakers and this is an important field for the CRISPR Journal to monitor. So I flew there literally, you know, trying to get some sleep on the long flights from New York and then on landing, turn on the phone, wait for the new wireless signal provider to kick in. And then Twitter just explode on my feed as this very, very astute journalists at MIT Technology Review, Antonio Regalado, had really got the scoop of the century by identifying a registration on a Chinese clinical trial website that he and only he had the foresight and intelligence to sort of see. He had met He Jankui in an off the record meeting, as I described in the book, about a month earlier. A spider sense was tingling. He knew something was up and this was the final clue. He didn't know at that time that the Lulu and Nana, the CRISPR babies that you mentioned, had actually been born, but he knew that there was a pregnancy, at least one pregnancy, from some of the records that he'd seen attached to this registration document. So it was a brilliant piece of sleuthing. And what he didn't know is that the Asociated Press chief medical writer Marilynm Marchion had confidentially been alerted to the potential upcoming birth of these twins by an American PR professional who was working with He Jankui in Shenzhen. So she had been working on an embargoed big feature story that He Jankui and his associates hoped would be the definitive story that would tell the world, we did this quote unquote, “responsibly and accurately, and this is the story that you can believe.” So that story was posted within hours.And of course the famous YouTube videos that He Jankui had recorded announcing with some paternal pride that he had ushered into the world these two gene edited, children, screaming and crying into the world as beautiful babies I think was [the phrase]. And he thought that he was going to become famous and celebrated and lauded by not just the Chinese scientific community, but by the world community for having the ability and the bravery to go ahead and do this work after Chinese researchers spent the previous few years editing human embryos. And he was persuaded that he had to present his work in Hong Kong, because he'd set off such a such an extraordinary firestorm. And I think you've all seen now you're the clips of the videos of him nervously walking onto stage the muffled, the silence, or the only sound in the front row, the only sound in the big auditorium at Hong Kong university—[which] was absolutely packed to the rim, one side of the auditorium was packed with press photographers, hundreds of journalists and cameras clicking—and the shutters clattering was the only, that was the applause that he got as he walked on stage.And to his credit, he tried to answer the questions directly in the face of great skepticism from the audience. The first question, which was posed by David Liu, who had traveled all the way there, who just asked him simply, “What was the unmet medical need that you are trying to solve with this reckless experiment? There are medical steps that you can do, even if the couple that you're trying to help has HIV and you're trying to prevent this from being passed on. There are techniques that you can use sperm washing being one of them. That is a key element of the IVF process to ensure that the no HIV is transmitted.”But he was unable to answer the question in terms of I'm trying to help a family. He'd already moved out and was thinking far, far bigger. Right? And his naiveté was shown in the manuscript that he'd written up and by that point submitted to Nature, excerpts of which were leaked out sometime later.So he went back to Shenzhen and he was put under house arrest after he gave that talk in Hong Kong. And about a year later was sentenced to three years in jail. And so he's, to the best of my knowledge that's where he is. But I often get asked what about the children? As far as we know, there was a third child born about six months later, also gene-edited. We don't even know a name for that child, let alone anything about their health. So one hopes that somebody in the Chinese medical establishment is looking after these kids and monitoring them and doing appropriate tests. The editing, as you said, was very shoddily performed. He knocked out the gene in question, but he did not mimic the natural 32-base deletion in this gene CCR5 that exists in many members of the population that confers, essentially, HIV resistance. So Lulu and Nana on the third child are walking human experiments, sad to say. This should never have been done. Never should have been attempted. And so we hope that he hasn't condemned them to a life of, you know, cancer checkups and that there were no off-target effects. They'll be able to live, hopefully, with this inactivated CCR5 gene, but it's been inactivated in a way that I don't think any, no other humans have ever been recorded with such modifications. So we, we really hope and pray that no other damage has been done. Harry Glorikian: So before we end, I'd love to give you the chance to speculate on the future of medicine in light of CRISPR. Easy, fast, inexpensive genome sequencing, give us access to everybody's genetic code, if they so choose. Machine learning and other forms of AI are helping understand the code and trace interactions between our 20,000 genes. And now CRISPR gives us a way to modify it. So, you know, it feels like [we have] almost everything we need to create, you know, precise, targeted, custom cures for people with genetic conditions. What might be possible soon, in your view? What remaining problems need to be solved to get to this new area of medicine? Kevin Davies: If you know the sequence that has been mutated to give rise to a particular disease then in principle, we can devise a, some sort of gene edit to repair that sequence. It may be flipping the actual base or bases directly, or maybe as we saw with the first sickle cell trial, it's because we understand the bigger genetic pathway. We don't have to necessarily go after the gene mutation directly, but there may be other ways that we can compensate boost the level of a compensating gene.But I think we, we should be careful not to get too carried away. As excited as I am—and hopefully my excitement comes through in Editing Humanity—but for every company that we've just mentioned, you know, you can go on their website and look at their pipeline. And so Editas might have maybe 10 diseases in its cross hairs. And CRISPR [Therapeutics] might have 12 diseases. And Intellia might have 14 diseases and Graphite has got maybe a couple. And Beam Therapeutics has got maybe 10 or 12. And Prime Medicine will hasn't listed any yet, but we'll hopefully have a few announced soon. And so I just reeled off 50, 60, less than a hundred. And some of these are gonna work really, really well. And some are going to be either proven, ineffective or unviable economically because the patient pool is too small. And we've got, how many did we say, 6,000 known genetic diseases. So one of the companies that is particularly interesting, although they would admit they're in very early days yet, is Verve Therapeutics. I touched on them earlier because they're looking at to modify a gene called PCSK9 that is relevant to heart disease and could be a gene modification that many people might undergo because the PCSK9 gene may be perfectly fine and the sequence could be perfectly normal, but we know that if we re remove this gene, levels of the bad cholesterol plummet, and that's usually a good thing as far as heart management goes. So that's an interesting, very interesting study case study, I think, to monitor over the coming years, because there's a company looking at a much larger patient pool potentially than just some of these rare syndromes with unpronounceable names. So the future of CRISPR and gene editing is very bright. I think one of the lessons I took away from CRISPR in Editing Humanity is, looking at the full story, is how this technology, this game-changing gene-editing technology, developed because 25 years ago, a handful of European microbiologists got really interested in why certain microbes were thriving in a salt lake in Southeastern Spain. This is not exactly high-profile, NIH-must-fund-this research. There was a biological question that they wanted to answer. And the CRISPR repeats and the function of those repeats fell out of that pure curiosity, just science for science's sake. And so it's the value of basic investigator-driven, hypothesis-driven research that led to CRISPR being described and then the function of the repeats.And then the story shifted to a yogurt company in Europe that was able to experimentally show how having the right sequence within the CRISPR array could safeguard their cultures against viral infection. And then five years of work people in various groups started to see, were drawn to this like moths to a flame. Jennifer Doudna was intrigued by this from a tip-off from a coffee morning discussion with a Berkeley faculty colleagues, Jill Banfield, a brilliant microbiologist in her own. And then she met meets Emmanuelle Charpentier in Puerto Rico at a conference, and they struck up a friendship and collaboration over the course of an afternoon. And that, why should that have worked? Well, it did, because a year later they're publishing in Science. So it's serendipity and basic research. And if that can work for CRISPR, then I know that there's another technology beginning to emerge from somewhere that may, yet trump CRISPR.And I think the beauty of CRISPR is its universal appeal. And the fact is, it's drawn in so many people, it could be in Japan or China or South Korea or parts of Europe or Canada or the U.S. or South America. Somebody is taking the elements of CRISPR and thinking well, how can we improve it? How can we tweak it?And so this CRISPR toolbox is being expanded and modified and updated all the time. So there's a hugely exciting future for genome medicine. And you know, whether it's a new form of sequencing or a new form of synthetic biology, you know, hopefully your show is going to be filled for many years to come with cool, talented, young energetic entrepreneurs who've developed more cool gadgets to work with our genome and other genomes as well. We haven't even had time to talk about what this could do for rescuing the wooly mammoth from extinction. So fun things, but maybe, maybe another time. Harry Glorikian: Excellent. Well, great to have you on the show. Really appreciate the time. I hope everybody got a flavor for the enormous impact this technology can have. Like you said, we talked about human genome, but there's so many other genomic applications of CRISPR that we didn't even touch. Kevin Davies: Yup. Yup. So you have to read the book. Harry Glorikian: Yeah. I will look forward to the next book. So, great. Thank you so much. Kevin Davies: Thanks for having me on the show, Harry. All the best.Harry Glorikian: Take care.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

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Alles auf Aktien

Play Episode Listen Later Aug 16, 2021 12:59


In der heutigen Folge „Alles auf Aktien“ berichten die Finanzjournalisten Nando Sommerfeldt und Holger Zschäpitz über haussierende AAA-Aktien, einen Dax, der zwar bei rekordhohen 16.000 Punkten steht. Sie erklären, wer nach dem großen Aufräumen bei den Autozulieferern, übrig bleibt. Außerdem geht es um Merck, Deutsche Telekom, Zooplus, Schaltbau, Delivery Hero, Varta, Upstart, Sonos, Google, Osram, Akasol, Deutsche Wohnen, Faurecia, Vonovia, Adva Optical, Aixtron, Elmos, Evotec, Exasol, Home24, K+S, Morphosys, New Work, Pfeiffer Vacuum, Pro7, SMA Solar, Software AG, Suess Microtech, Teamviewer, Vossloh, HVB-Zertfikat Solactive German Mergers & Acquisitions (WKN: HU5JPC), TomTom, Scor, Zur Rose, Clariant. AMS oder Asos. HVB Index Zertifikat Solactive European Mergers & Acquisitions Index (WKN: HZ0H11), Splunk, Yelp, Nutanix, Take Two Interactive, Zynga, Groupon, Trimble, Juniper Networks, Arista Networks, aber auch Biotech-Firmen wie Crispr Therapeutics, Allogene Therapeutics, Hella, Plastic Omnium, Schaeffler, Continental, Vitesco, Aptiv, Magna International, Veoneer. "Alles auf Aktien" ist der tägliche Börsen-Shot aus der WELT-Wirtschaftsredaktion. Die Wirtschafts- und Finanzjournalisten Holger Zschäpitz, Anja Ettel, Philipp Vetter, Daniel Eckert und Nando Sommerfeld diskutieren im Wechsel über die wichtigsten News an den Märkten und das Finanzthema des Tages. Außerdem gibt es jeden Tag eine Inspiration, die das Leben leichter machen soll. In nur zehn Minuten geht es um alles, was man aktuell über Aktien, ETFs, Fonds und erfolgreiche Geldanlage wissen sollte. Für erfahrene Anleger und Neueinsteiger. Montag bis Freitag, ab 6 Uhr morgens. Wir freuen uns an Feedback über aaa@welt.de. Disclaimer: Die im Podcast besprochenen Aktien und Fonds stellen keine spezifischen Kauf- oder Anlage-Empfehlungen dar. Die Moderatoren und der Verlag haften nicht für etwaige Verluste, die aufgrund der Umsetzung der Gedanken oder Ideen entstehen. Für alle, die noch mehr wissen wollen: Holger Zschäpitz können Sie jede Woche im Finanz- und Wirtschaftspodcast "Deffner&Zschäpitz" hören.

The 7investing Podcast
The 3 Frameworks for Evaluating Gene Editing Stocks

The 7investing Podcast

Play Episode Listen Later Aug 3, 2021 46:27


When Caribou Biosciences (NASDAQ: CRBU) became the seventh publicly-traded CRISPR stock in July 2021, I saw an exchange on social media. One person asked why the company sported a market valuation of $900 million when another newly-public CRISPR stock, Verve Therapeutics (NASDAQ: VERV), was valued near $2.3 billion. "Is there any reason for this other than the timing of the IPOs?", asked the individual. The thread received multiple responses confirming the seemingly large valuation difference between the two companies, with others "agreeing" or responding that they were buying Caribou Biosciences because of it. That was 100% the wrong take. I've observed similar arguments among individual investors within the gene editing space. However, it's important to acknowledge that there are significant differences between gene editing approaches and technology platforms. Caribou Biosciences and Verve Therapeutics might both be using CRISPR systems, but that's where the overlap ends. They're developing completely different tools that have almost nothing in common. Individual investors don't necessarily need to have a deep technical understanding of gene editing tools, but I would argue that there's a minimum level of information required to responsibly invest in the field. Unfortunately, the way the internet works means most investors aren't provided with the information they need. Let's fix that. In this episode of the podcast, 7investing Lead Advisors Maxx Chatsko (me) and Dan Kline introduce simple frameworks for evaluating opportunities and challenges in gene editing. These can be summarized as follows: The Emerging Approaches: There's first-generation tools (gene editing), second-generation tools (base editing), and third-generation tools (prime editing). These approaches are not limited to any specific system. For example, there are CRISPR, TALEN, ARCUS, and other tools capable of performing base editing. The Major Applications: There are knock outs, insertions, activations, precise corrections, knock ins, and other uses of gene editing tools. Each has advantages and disadvantages. The Major Administration Routes: This primarily comes down to in vivo (inside the body) and ex vivo (outside the body). Each has advantages and disadvantages. In addition to this podcast introducing the three frameworks, 7investing Lead Advisor Maxx Chatsko has written an in-depth article explaining these frameworks and how each gene editing stock fits into each -- and it's free to read! Publicly-traded companies mentioned in this podcast include Alnylam Pharmaceuticals, Beam Therapeutics, Caribou Biosciences, Cellectis, CRISPR Therapeutics, Editas Medicine, Graphite Bio, Intellia Therapeutics, Precision BioSciences, Sana Biotechnology, and Verve Therapeutics. 7investing Lead Advisors may have positions in the companies that are mentioned. This interview was originally recorded on August 2nd, 2021 and was first published on August 3rd, 2021. --- Send in a voice message: https://anchor.fm/7investing/message Support this podcast: https://anchor.fm/7investing/support

The daily tech stock news briefing
06/28/2021, Intellia Therapeutics (NTLA) stock jumped more than 50%

The daily tech stock news briefing

Play Episode Listen Later Jun 28, 2021 0:45


Intellia Therapeutics (NTLA) stock jumped more than 50% after the biotech, along with Regeneron Pharmaceuticals (REGN), reported positive results from its first clinical trial using a new, Nobel Prize-winning Crispr technology to treat Transthyretin Amyloidosis, a rare condition characterized by an abnormal buildup of a protein called amyloid in the body's organs and tissues. Other Crispr-related companies saw gains on Monday as well. Crispr Therapeutics has increased by 6.39 percent, while Beam Therapeutics has increased by 15.98 percent.

Best of US Investors's Podcast
CRISPR Therapeutics: Pullback Created Multi-Bagger Stock Opportunity

Best of US Investors's Podcast

Play Episode Listen Later May 28, 2021 13:56


The race is on for the winners in the Medical Revolution.  Now is the buying opportunity.Welcome back tribe members! Today I'm discussing "CRISPR Therapeutics: Pullback Created Multi-Bagger Stock Opportunity". If you enjoy this video feel free to SUBSCRIBE! Make sure to follow me on social media for even more coverage of the stock market.Link to our Discord: https://discord.io/bestofusGet Surfshark VPN at  https://surfshark.deals/INVESTORS and enter promo code INVESTORS for 83% off and 3 extra months for free!  Follow Me: Facebook: https://www.facebook.com/BestofUSLLC/Instagram: https://www.instagram.com/bestofusinv...Twitter: https://twitter.com/BestOfUsInvestSubscribe:https://www.youtube.com/channel/UC-hq...Help Kerry and Nita win the race against Childhood Cancer and keep their daughter Shay's memory alive. Your support makes a direct impact in the fight against Pediatric Cancer at Children's of Alabama by helping advance research in finding a cure for cancer. http://give.childrensal.org/bestofusWe have Up-Graded Our Discord: Kerry's Portfolio, Trades and InsightsThis is the new link: https://discord.io/bestofus. It is now organized by topics and will be easier to navigate and communicate.

Blood & Cancer
Gene therapies in hemophilia with Dr. Glenn Pierce

Blood & Cancer

Play Episode Listen Later May 13, 2021 24:10


A “very basic” type of gene therapy could potentially cure hemophilia, but a major hurdle has been the lack of an effective mode of delivery. Recent strides in using adeno-associated virus (AAV) vectors are changing that, and Glenn Pierce, MD, World Federation of Hemophilia Vice President, Medical, predicts approvals in the next 12-18 months. Dr. Pierce shared his personal experience with hemophilia and discussed his and others’ ongoing research on the use of AAV-mediated gene therapy with host David Henry, MD, in this episode. Hemophilia and AAV gene therapy key points: Hemophilia is caused by a monogenic defect and could, theoretically, be cured by gene replacement or augmentation, says Dr. Pierce, who notes that “it sounds disarmingly simple, but behind that simplicity is a very complex procedure.” The approach uses “gene addition,” which is a basic gene therapy involving the addition of a normal gene to the variant in an individual. This ultimately corrects the clotting factor deficiency. The complexity is in getting the normal gene into the body where it can have the intended therapeutic effect. After more than 20 years of working to overcome that barrier, Dr. Pierce and others are finding success with using AAVs. The approach has some similarities to that used in developing the mRNA COVID-19 vaccines but requires the use of DNA established within the virus (rather than mRNA) to provide a more stable effect. Questions about how long it will last are currently being investigated. Multiple phase 3 trials are underway or completed. Data from two of those have been released in recent months, and the results are very encouraging: “It’s a remarkable achievement – many patients are doing well and, for all intents and purposes, could be considered free of [hemophilia],” Dr. Pierce says, adding that he would “potentially … use the ‘C word’ – cured – for at least a period of time.” The therapy is generally well tolerated. Efforts are ongoing to identify the best ways to proactively and reactively use prednisone to manage side effects such as mild increases in transaminase levels. To date, the risk-benefit profile appears reasonable for patients with clotting factor IX deficiency, and it is likely that the therapy in that setting “will march toward the regulatory process to determine if it’s safe and effective for approval,” he said. Responses in those with clotting factor VIII deficiency have been more variable, with some patients requiring long-term prednisone use, which is problematic. More information is needed about this, but investigation is ongoing, he said. Registries are available and many companies are involved in clinical trials. Clinicians and patients can look for information at clinicaltrials.gov, wfh.org (which publishes trial results and conducts workshops and meetings), and at the US National Hemophilia Foundation (Hemophilia.org) and the Society of Thrombosis and Hemostasis (ISTH.org). Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Pierce disclosed relationships with Ambys Medicines, BioMarin, BridgeBio, CRISPR Therapeutics, Decibel Therapeutics, Frontera, Geneception, Generation Bio, Novo Nordisk, Pfizer, Regeneron, Third Rock Ventures, Voyager Therapeutics, Global Blood Therapeutics, VarmX SAB, the National Hemophilia Foundation Medical and Scientific Advisory Council, and the World Federation of Hemophilia. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd  

FirstTake on Pharma - Pharma News and Analysis Podcast
The FirstTake Podcast – Bluebird Bio and Vertex provide contrasting gene therapy updates

FirstTake on Pharma - Pharma News and Analysis Podcast

Play Episode Listen Later Apr 22, 2021 21:36


FirstWord Pharma PLUS editors Michael Flanagan, Simon King and Becky Simon discuss the implications of two noteworthy news events in the field of gene therapy this week – bluebird bio's decision to walk away from Zynteglo reimbursement negotiations in Germany and Vertex's investment of $900m to increase its share of the economics in CTX001, a gene-editing sickle cell disease therapy being co-developed with CRISPR Therapeutics. They also discuss feedback from a key opinion leader who thinks Bristol Myers Squibb could be poised to lead the neoadjuvant non-small cell lung cancer market with its immunotherapy Opdivo and run the rule over Roche and Biogen's first-quarter results.

The Bid
Moderna and CRISPR Therapeutics on fighting Covid-19

The Bid

Play Episode Listen Later Mar 24, 2021 45:13


The Covid-19 pandemic has put genomics and immunology front and center. In the first episode of a five-part mini-series on megatrends, CEO of Moderna Stéphane Bancel and CEO of CRISPR Therapeutics Dr. Samarth Kulkarni share their perspectives as companies on the frontlines.First, Stéphane shares how Moderna innovated to produce a Covid-19 vaccine in record time and the potential of mRNA technology. Then, Samarth discusses how the medical breakthroughs of CRISPR technology will impact other medical crises like cancer and sickle cell disease in years to come.This material is for informational purposes and is prepared by BlackRock, is not intended to be relied upon as a forecast, research or investment advice, and is not a recommendation, offer or solicitation to buy or sell any securities or to adopt any investment strategy. The opinions expressed are as of date of publication and are subject to change. The information and opinions contained in this material are derived from proprietary and nonproprietary sources deemed by BlackRock to be reliable and are not guaranteed as to accuracy or completeness. This material may contain ’forward looking’ information that is not purely historical in nature. There is no guarantee that any forecasts made will come to pass. Reliance upon information in this material is at the sole discretion of the reader. Past performance is not indicative of current or future results. This information provided is neither tax nor legal advice and investors should consult with their own advisors before making investment decisions. The value of investments and the income from them can go down as well as up and you may not get back the amount invested.In the U.S. and Canada, this material is intended for public distribution.In the UK this is issued by BlackRock Investment Management (UK) Limited, authorised and regulated by the Financial Conduct Authority. Registered office: 12 Throgmorton Avenue, London, EC2N 2DL. Tel: + 44 (0)20 7743 3000. Registered in England and Wales No. 2020394. For your protection telephone calls are usually recorded. BlackRock is a trading name of BlackRock Investment Management (UK) Limited. Please refer to the Financial Conduct Authority website for a list of authorised activities conducted by BlackRock. In Singapore, this is issued by BlackRock (Singapore) Limited (Co. registration no. 200010143N). This advertisement or publication has not been reviewed by the Monetary Authority of Singapore. In Hong Kong, this material is issued by BlackRock Asset Management North Asia Limited and has not been reviewed by the Securities and Futures Commission of Hong Kong. In Australia, issued by BlackRock Investment Management (Australia) Limited ABN 13 006 165 975 AFSL 230 523 (BIMAL). The material provides general information only and does not take into account your individual objectives, financial situation, needs or circumstances.In Latin America: this material is for educational purposes only and does not constitute investment advice nor an offer or solicitation to sell or a solicitation of an offer to buy any shares of any Fund. No securities regulators in Latin America have confirmed the accuracy of any information contained herein. The provision of investment management and investment advisory services is a regulated activity in Mexico thus is subject to strict rules. For more information on the Investment Advisory Services offered by BlackRock Mexico please refer to the Investment Services Guide available at www.blackrock.com/mx.IN MEXICO, FOR INSTITUTIONAL AND QUALIFIED INVESTORS USE ONLY. INVESTING INVOLVES RISK, INCLUDING POSSIBLE LOSS OF PRINCIPAL. THIS MATERIAL IS PROVIDED FOR EDUCATIONAL AND INFORMATIONAL PURPOSES ONLY AND DOES NOT CONSTITUTE AN OFFER OR SOLICITATION TO SELL OR A SOLICITATION OF AN OFFER TO BUY ANY SHARES OF ANY FUND OR SECURITY. This information does not consider the investment objectives, risk tolerance or the financial circumstances of any specific investor. This information does not replace the obligation of financial advisor to apply his/her best judgment in making investment decisions or investment recommendations. It is your responsibility to inform yourself of, and to observe, all applicable laws and regulations of Mexico. If any funds, securities or investment strategies are mentioned or inferred in this material, such funds, securities or strategies have not been registered with the Mexican National Banking and Securities Commission (Comisión Nacional Bancaria y de Valores, the “CNBV”) and thus, may not be publicly offered in Mexico. The CNBV has not confirmed the accuracy of any information contained herein. The provision of investment management and investment advisory services (“Investment Services”) is a regulated activity in Mexico, subject to strict rules, and performed under the supervision of the CNBV. The materials that may be shared in this forum are for information purposes only, do not constitute investment advice, and are being shared in the understanding that the addressee is an Institutional or Qualified investor as defined under Mexican Law. BlackRock México Operadora, S.A. de C.V., Sociedad Operadora de Fondos de Inversión (“BlackRock México Operadora”) is a Mexican subsidiary of BlackRock, Inc., authorized by the CNBV as a Mutual Fund Manager (Operadora de Fondos), and as such, authorized to manage Mexican mutual funds, ETFs and provide Investment Advisory Services. For more information on the Investment Services offered by BlackRock Mexico, please review our Investment Services Guide available in www.blackrock.com/mx . This material represents an assessment at a specific time and its information should not be relied upon by the you as research or investment advice regarding the funds, any security or investment strategy in particular. Reliance upon information in this material is at your sole discretion. BlackRock México is not authorized to receive deposits, carry out intermediation activities, or act as a broker dealer, or bank in Mexico. For more information on BlackRock México, please visit:www.BlackRock.com/mx. BlackRock receives revenue in the form of advisory fees for our advisory services and management fees for our mutual funds, exchange traded funds and collective investment trusts. Any modification, change, distribution or inadequate use of information of this document is not responsibility of BlackRock or any of its affiliates. Pursuant to the Mexican Data Privacy Law (Ley Federal de Protección de Datos Personales en Posesión de Particulares), to register your personal data you must confirm that you have read and understood the Privacy Notice of BlackRock México Operadora. For the full disclosure, please visit www.BlackRock.com/mx and accept that your personal information will be managed according with the terms and conditions set forth therein. BlackRock® is a registered trademark of BlackRock, Inc. All other trademarks are the property of their respective owners.©2021 BlackRock, Inc. All Rights Reserved. BLACKROCK is a registered trademark of BlackRock, Inc. All other trademarks are those of their respective owners.

The Doctor is Out
S1E07: Venture Capital - Simeon George

The Doctor is Out

Play Episode Listen Later Feb 16, 2021 36:24


SR One Capital Management CEO Dr. Simeon George provides insights into the path of becoming a venture capitalist. An investor with a storied track record serving on the boards of companies including CRISPR Therapeutics, Nkarta, Progeny and Turning Point Therapeutics, Simeon discusses challenges and opportunities he faces spinning out the 36-year old firm from GSK recently launching SR One's first independent $500M fund. Join for a very special discussion around breaking into venture capital, the values of residency and an MBA in the field, and what it means to be a VC. --- Send in a voice message: https://anchor.fm/tdio/message

Best of US Investors's Podcast
The Golden Age of Biotechnology CRISPR Therapeutics

Best of US Investors's Podcast

Play Episode Listen Later Dec 8, 2020 9:48


The Coronavirus will be the most important event of the 2020's and the most important change as a result of the Coronavirus will be Biotech and Crispr Therapeutics will lead that change.Welcome back, tribe members! Today I'm discussing "The Golden Age of Biotechnology CRISPR Therapeutics". If you enjoy this video feel free to SUBSCRIBE! Make sure to follow me on social media for even more coverage of the stock market.Follow Me: Facebook: https://www.facebook.com/BestofUSLLC/Instagram: https://www.instagram.com/bestofusinv...Twitter: https://twitter.com/BestOfUsInvestSubscribe:https://www.youtube.com/channel/UC-hq...We have Up-Graded Our DiscordThis is the new link: https://discord.io/bestofus. It is now organized by topics and will be easier to navigate and communicate.

Researchat.fm
79. Connecting Dots

Researchat.fm

Play Episode Listen Later Nov 9, 2020 78:48


pomeさんをゲストに迎え、ボストン界隈を中心としたCRISPR関連のバイオスタートアップについて話を伺いました。Show notes Top CRISPR Startup Companies Changing the Future of Biotech and Medicine … CRISPR関連スタートアップまとめ Researchat.fm, ep76 … ゲノム編集特集回 Researchat.fm, ep77 … ゲノム編集特集回 Researchat.fm, ep2 … CRISPR特集回 Researchat.fm, ep77 Researchat.fm, ep47 … SHERLOCKについて話しました。 Boston MIT … マサチューセッツ工科大学。Kendall Station近くに位置する。厳密にはボストン市ではなく、ケンブリッジ市である。 Harvard University … ハーバード大学。こちらもメインキャンパスはケンブリッジ市。Oxford Stに位置する建物もあるため、Oxford St., Cambridgeと住所的には何が何だかわからないところもある。 Boston University … BU University of Massachusetts … UMass Tufts University Berklee College of Music … いつもバークリーなのかバークレーなのかわからなくなる。有名な音楽学校。 NOVARTIS Takeda Biogen Bayer Cell Press … いわゆるCell誌。MIT,ハーバードの目と鼻の先にある。 カリフォルニア州 マサチューセッツ州 ニューヨーク州 ニュージャージー州 Akamai Feng Zhang David Liu Researchat.fm, Ep60 … 培養肉などについて話しました。 GMO …Genetically modified organism Plantedit FAD2 Solive … by Plantedit spCas9 Cas12 Cas13 Inscripta mad7 nuclease Unreal Engine Unity C4U BioPallete Cas3 モダリス Beam Therapeutics Researchat.fm, ep22 … Base editorやTarget AIDについて話しました。 in vivo ex vivo 鎌状赤血球 CRISPR Therapeutics 造血幹細胞 CD34+ ヘモグロビン BCL11A eGenesis Bio George Church 胚盤胞置換法 Living cell technologies (LCT) Diatranz Otsuka CAR-T レンチウイルス AAV HIV ゾルゲンスマ TLO … Technology License Organizationの略 Wyss Institute Wyss Instituteのポッドキャスト … めちゃくちゃ良い。tadasuはリピートしまくって聞いている時期が度々ある。 Peng Yin Researchat.fm, ep74 … DNA Origamiについて話しました。 Cambridge Innovation Center (CiC) Venture Cafe Venture Cafe Tokyo … 虎ノ門ヒルズ内にある。木曜日にイベントをやっているようです。 CiC Tokyo … 虎ノ門ヒルズ内にある。 Cambridge City, MA … ケンブリッジ市 スタンフォード大学のパテントに関する資料 … Stanford UniversityのOTLによる資料。 lab central Johnson & Johnson Roche Job Description 四行教授 … とあるブログ様を引用させていただきました。当時修士のtadasuに四行教授や「履歴書を汚せ」と説いた人物は黒川清先生です。 Researchat.fm, ep75 … I’m not sure though. Editorial notes とっても楽しいおしゃべりでした。仕事と関係ないマニアックな話をできる場はあんまりないので貴重です。またやりましょう。(pome) 後編もお楽しみに〜 (soh) 同じ地区に住んでいるのに何にも活かせていません…(tadasu) (coela)

Motley Fool Money
Netflix, Tesla, and the State of the Movie Business

Motley Fool Money

Play Episode Listen Later Oct 23, 2020 38:37


Intel falls on a big drop in its data center business. Netflix reports its weakest subscriber growth in 4 years. Tesla reports its 5th consecutive quarter of profitability. Southwest Airlines rises despite reporting its biggest loss ever. Chipotle falls despite a surge in digital sales. Procter & Gamble hits an all-time high. Boston Beer gets a big boost from hard seltzer and Twisted Tea. Coca-Cola reports better-than-expected profits. Quibi calls it quits. And Jack in the Box serves up chicken-scented face masks. Motley Fool analysts Ron Gross and Jason Moser discuss those stories, weigh in on some recent dividend hikes, and share two stocks on their radar: Ameris Bancorp and CRISPR Therapeutics. Plus, corporate governance expert and film critic Nell Minow shares some surprising insights on the state of the movie business.

Motley Fool Money
Rising Unemployment, Rising Investor Optimism

Motley Fool Money

Play Episode Listen Later Apr 17, 2020 38:41


More than 5 million more Americans file for unemployment as the monthly total surpasses 22 million. Abbott Labs gets a boost on optimism over its coronavirus testing. Gilead Sciences gets a boost on optimism over its coronavirus treatment. Procter & Gamble reports its biggest U.S. sales gain in decades. Amazon hits an all-time high. Comcast launches a preview of its Peacock streaming service. And Verizon buys BlueJeans Network, a videoconferencing company. Motley Fool analysts Jason Moser and Ron Gross discuss those stories, take stock in the banking and airline industries, and weigh in on some dividend hikes. Plus, the guys share a few stocks on their radar: Spotify and CRISPR Therapeutics. And Okta co-founder and COO Frederic Kerrest talks cloud-based security software, password protection, and misconceptions about entrepreneurs.

Matt McCall's Moneyline
Major Breakthrough in Biotech, Cannabis Stocks Rally, and Recapping the Web Summit

Matt McCall's Moneyline

Play Episode Listen Later Nov 22, 2019 17:51


This week was monumental in the future of biotech. CRISPR Therapeutics reported the results of its gene editing study on humans and the results are better than expected. The Nasdaq Biotech Index is breaking out and setting up for a big 2020. Matt recaps his favorite themes he came across at the world’s largest tech conference in Portugal. The show wraps up with an update on cannabis stocks as they start to rally from a multi-year low.

Industry Focus
Healthcare: Is Amarin's Fish Oil Pill On Track To Become a Blockbuster? Plus, How Gene Editing Company CRISPR Therapeutics Just Took A Big Step Forward

Industry Focus

Play Episode Listen Later Nov 20, 2019 24:24


Amarin's shares rocketed higher after a key FDA committee recommended expanding the label of its triglycerides lowering drug, Vascepa, to include data showing it can reduce the risk of heart attack and stroke. Meanwhile, shares in CRISPR Therapeutics and partner Vertex Pharmaceuticals are also soaring following the release of interim, early-stage results for its gene-editing therapy for beta thalassemia and sickle cell disease therapy. Stocks: AMRN, CRSP, VRTX Check out more of our content here: TMF's podcast portal YouTube Twitter Join Our Motley Fool Podcast Facebook Group LinkedIn StockUp, The Motley Fool's weekly email newsletter

Rare Disease, Cell & Gene Therapy Weekly RoundUp
Weekly Roundup: June 12, 2019

Rare Disease, Cell & Gene Therapy Weekly RoundUp

Play Episode Listen Later Jun 12, 2019 10:10


This week, the team discuss Vertex's acquisition of Exonics and expansion of its collaboration with CRISPR Therapeutics. Also, we take an indepth look at the European Medicines Agency's approval of Bluebirdbio's gene therapy Zynteglo as a treatment for beta-thalassemia . Presenter: Aparna Krishnan Contributor: Jack Rawson Producer: Aparna Krishnan

WIRED Science: Space, Health, Biotech, and More
Gene Editing Is Trickier Than Expected—but Fixes Are in Sight

WIRED Science: Space, Health, Biotech, and More

Play Episode Listen Later Mar 1, 2019 9:17


Of all the big, world-remaking bets on the genome-editing tool known as Crispr, perhaps none is more tantalizing than its potential to edit some of humanity's worst diseases right out of the history books. Just this week, Crispr Therapeutics announced it had begun treating patients with an inherited blood disorder called beta thalassemia, in the Western drug industry's first test of the technology for genetic disease.

FirstWord Pharmaceutical News
FirstWord Pharmaceutical News for Thursday, October 11 2018

FirstWord Pharmaceutical News

Play Episode Listen Later Oct 11, 2018 4:49


FirstWord Pharmaceutical News
FirstWord Pharmaceutical News for Thursday, May 31 2018

FirstWord Pharmaceutical News

Play Episode Listen Later May 31, 2018 2:26


El Viajero de la Ciencia - Carlos Alameda
Ep. 67 | Facebook y Zuckerberg no pasan el examen de la privacidad, ¿qué es la comunicación máquina a máquina?

El Viajero de la Ciencia - Carlos Alameda

Play Episode Listen Later Apr 24, 2018 59:59


Hoy en El Viajero de la Ciencia… Hablamos sobre todo de tecnología. Analizamos el escándalo de Facebook y nos sumergimos en el mundo de las líneas móviles entre máquinas, nos preguntamos ¿qué son? ¿cómo funcionan? ¿por qué han crecido tanto? Twitter: @ViajeroCiencia Facebook: El Viajero de la Ciencia www.capitalradio.es TITULAR 1. Un lunar artificial detecta de forma precoz el cáncer Colocado sobre la piel, el tatuaje detecta la elevación del calcio que lleva aparejado el desarrollo de un tumor e induce la liberación de melanina para crear un ‘lunar de alarma'. TITULAR 2. Neandertales y 'Homo sapiens' coexistieron menos de 1.000 años en la Región Cantábrica. El Centro Nacional para la Interpretación de la Evolución Huama participa en la datación por radiocarbono de trece yacimientos cuyos resultados publicados en PLOS ONE precisan la cohabitación de ambas especies en esta región del suroeste de Europa durante un lapso de tiempo que reduce sus posibilidades de interacción y reforzaría la hipótesis de una causa de extinción intrínseca. TITULAR 3: La NASA lanza con éxito la misión TESS para buscar nuevos exoplanetas Pasadas las 22:51 de ayer, la NASA logró enviar al espacio su nueva misión para buscar mundos fuera del sistema solar, después de retrasar su puesta en órbita por problemas técnicos el pasado lunes. A bordo de un cohete Falcon 9, la agencia norteamericana ha conseguido el despegue exitoso de TESS desde el complejo de lanzamiento 40 de Cabo Cañaveral, situado en Florida. TITULAR 4: Primer ensayo clínico en Europa para probar CRISPR en humanos La compañía CRISPR Therapeutics recibe luz verde para realizar el primer ensayo clínico en Europa con CRISPR-Cas para probar su seguridad y eficacia contra la beta talasemia, una enfermedad rara que provoca que los pacientes produzcan menos hemoglobina de lo normal. TITULAR 5: Una terapia génica evita la enfermedad que obliga a recibir transfusiones sanguíneas de por vida El nuevo tratamiento consiste en extraer células madre hematopoyéticas de la médula ósea de los pacientes e inyectarles LentiGlobin, un fármaco basado en una variante desactivada del VIH que contiene una pequeña secuencia de ADN. TITULAR 6: Primeros pasos hacia la construcción del Big Falcon Rocket de SpaceX Elon Musk ha mostrado el molde en el que se construiría el Big Falcon Rocket o, simplemente, BFR. El llamado a ir a Marte. El gigantesco cohete ha dejado de ser una mera prueba de concepto teórico y que los planes del fundador de SpaceX van en serio. Según explicó el año pasado, el BFR superará los cien metros de longitud y alcanzará nada menos que nueve metros de diámetro.

WIRED Science: Space, Health, Biotech, and More
A Flawed Study Shows How Little We Understand Crispr's Effects

WIRED Science: Space, Health, Biotech, and More

Play Episode Listen Later Apr 4, 2018 5:08


Biotech has been betting big on Crispr, the gene-editing technique that promises to snip away some of humanity's worst diseases. But last May, a small case study suggested the much-hyped technology might actually be quite dangerous—and pop went the Crispr bubble, briefly tanking shares of Crispr companies like Editas Medicine, Intellia Therapeutics, and Crispr Therapeutics.

Behind The Idea
Behind The Idea #5: Gilead's Hunt And The Crispr Crapshoot

Behind The Idea

Play Episode Listen Later Feb 26, 2018 40:52


Mergers & Acquisitions (M&A) garner headlines and lead to big returns for the right investors, but they can often be a bit of a crapshoot, especially in the Pharmaceutical industry. SA author Biosci Capital Partners makes the case in two articles that Crispr Therapeutics, a pioneer of gene editing technologies, might be a target for Gilead Sciences. Behind The Idea breaks down the case and discusses how to deal with the hope of a big payout and the risk that it won't happen. Learn more about your ad choices. Visit megaphone.fm/adchoices

WIRED Science: Space, Health, Biotech, and More
Crispr Therapeutics Plans Its First Clinical Trial for Genetic Disease

WIRED Science: Space, Health, Biotech, and More

Play Episode Listen Later Dec 14, 2017 8:14


In late 2012, French microbiologist Emmanuelle Charpentier approached a handful of American scientists about starting a company, a Crispr company. They included UC Berkeley's Jennifer Doudna, George Church at Harvard University, and his former postdoc Feng Zhang of the Broad Institute—the brightest stars in the then-tiny field of Crispr research. Back then barely 100 papers had been published on the little-known guided DNA-cutting system. It certainly hadn't attracted any money.

FirstWord Pharmaceutical News
FirstWord Pharmaceutical News for Monday, Dec 21, 2015

FirstWord Pharmaceutical News

Play Episode Listen Later Dec 21, 2015 1:36