Podcasts about Gilead Sciences

From accidental quality professional to global quality leader - Valerie Brown's story is one of courage, curiosity, and conviction.In today's episode I was joined by Valerie Brown, Head of Global Quality Assurance and Compliance at Thermo Fisher Scientific's Clinical Research Group.I really wanted to speak to Valerie because she brings something different to the quality leadership conversation. Yes, she has held senior quality roles across innovator companies, CDMOs, and now one of the largest CROs in the world. But what makes her story compelling is how she got there - and what she learned along the way.Valerie didn't plan to work in quality. At 22, she was asked to be a scribe for an FDA inspection. The host fell ill on the day. She stepped in - no preparation, no safety net - and handled it.Someone told her she had a knack for it. She wasn't sure she agreed. She still wanted to be in the lab, in manufacturing, doing what she knew. But that moment planted a seed.What followed was a career that took her across CDMOs, innovator companies including Gilead Sciences, and now Thermo Fisher - where she leads global quality assurance and compliance for the clinical research group. She has sat on both sides of the table, as sponsor and as service provider, and that experience shapes everything about how she leads.We talk about the following:How Valerie accidentally became a quality professional, and why that unplanned start shaped everything that followedWhat it felt like to host an FDA inspection at 22, with no preparation and no safety netHer philosophy of servant leadership and what it really means to lead with empathy in a regulated environmentThe challenge of transforming a fragmented quality organisation into a connected, strategic function at Thermo FisherThe difference between working on the innovator side versus the CRO side - and the unique skill set the latter demandsWhy speed and quality are not in conflict, and how embedding quality by design from the outset actually accelerates deliveryHer approach to talent development - why she prefers to grow leaders from within and how she identifies that potential earlyThe growing importance of AI and digital governance in regulated environments, and why quality professionals need to engage with these tools nowWhat keeps her up at night heading into 2026 - from talent gaps to trial complexity to the pace of regulatory changeThe advice she would give her younger self, and what she believes every aspiring quality leader needs to understandValerie Brown is a highly accomplished global quality leader whose career is a masterclass in adaptability, influence, and patient-centric thinking. She leads with purpose, develops people with intention, and approaches every challenge with the mindset of a problem solver - exactly the kind of leader our industry needs more of.Thank you Valerie for sharing your incredible journey. Hope everyone enjoys the show!

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/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care 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 activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care 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 activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world.Today, we delve into the latest from an industry that continues to break new ground in both scientific innovation and regulatory landscapes. The pharmaceutical and biotech sectors are buzzing with activity as companies engage in bold strategies and face significant challenges in their quest for groundbreaking treatments.A recent event illustrating the high-stakes nature of this industry involves Novo Nordisk and its decision to conduct a head-to-head clinical trial for Cagrisema against Eli Lilly's Zepbound. This trial, which typically occurs post-approval, was conducted at the candidate stage. Novo Nordisk aimed to establish market dominance by proving superiority early on. However, the trial did not go as planned, with Cagrisema failing to outperform Zepbound. This outcome serves as a reminder of the competitive dynamics in early-stage testing and the strategic risks companies are willing to take in their bid for market leadership.Meanwhile, Gilead Sciences has made a bold move with a $7.8 billion investment in Arcellx, focusing on CAR T-cell therapy. This investment highlights Gilead's commitment to advanced cancer treatments, particularly Anito-cel for relapsed or refractory multiple myeloma. CAR T-cell therapies involve modifying a patient's T-cells to target cancer cells more effectively, representing a significant leap forward in oncological treatments. With an FDA decision anticipated by December 2026, Gilead's investment underscores its strategic focus on transformative therapies that could redefine cancer care.In legal news, Regenxbio has secured a notable victory against Sarepta Therapeutics regarding adeno-associated virus (AAV) technology patents. The appeals court ruling in favor of Regenxbio emphasizes the intricate nature of patent law in biotechnology, where innovations often intersect with naturally occurring biological processes. This decision not only solidifies Regenxbio's intellectual property but also sets a precedent for future patent disputes within the sector.On the regulatory front, Vanda Pharmaceuticals has rebounded from previous setbacks by securing FDA approval for drugs targeting bipolar disorder and schizophrenia. This achievement marks a promising shift for Vanda, demonstrating resilience and adaptability in redirecting focus towards neuropsychiatric conditions. The approval expands therapeutic options for these complex disorders, addressing long-standing unmet needs within mental health care.Despite these advancements, some areas continue to face hurdles. Gene therapies like Casgevy and Lyfgenia for sickle cell disease have struggled to gain traction two years post-launch. These therapies promise a one-time cure by correcting genetic defects but have encountered challenges in achieving widespread adoption. The difficulties reflect broader issues in transitioning from clinical success to market viability.Moreover, workforce reductions at major companies such as Bristol-Myers Squibb and Catalent signal structural changes within the industry. These layoffs may indicate shifts in strategic focus or responses to evolving market pressures as companies strive for efficiency and innovation.Regulatory practices are also undergoing scrutiny as the FDA considers defaulting to single clinical trial requirements for drug approvals. While this move could streamline development processes, it raises concerns about maintaining rigorous safety standards—a balance that remains crucial as companies push to bring innovative treatments to market swiftly yet safely.The dynamic nature of this industry is further highlighted by Candel Therapeutics' recent $100 million royalty deal aimed at launching its prostate cancer treatment. This strategic move underscores growing interest in innovative oncology solutions thaSupport the show

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/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care 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 activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care 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 activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Plus: Renault to take full control of Flexis electric-van. And Nvidia chips for laptop computers set to hit the market this year. Julie Chang hosts. Learn more about your ad choices. Visit megaphone.fm/adchoices

Další lék proti viru HIV má českou stopu. Zásadní podíl na něm má Tomáš Cihlář se svým kalifornským týmem. Na rozdíl od denně užívaných antivirotik lék stačí injekčně aplikovat dvakrát ročně a funguje i jako prevence. „Myslím, že naše látka může významně přispět k omezení počtu nových infekcí,“ říká v Leonardu Plus Tomáš Cihlář, viceprezident pro virologii společnosti Gilead Sciences, kterého časopis Time zařadil mezi sto nejvlivnějších lidí světa.

Další lék proti viru HIV má českou stopu. Zásadní podíl na něm má Tomáš Cihlář se svým kalifornským týmem. Na rozdíl od denně užívaných antivirotik lék stačí injekčně aplikovat dvakrát ročně a funguje i jako prevence. „Myslím, že naše látka může významně přispět k omezení počtu nových infekcí,“ říká v Leonardu Plus Tomáš Cihlář, viceprezident pro virologii společnosti Gilead Sciences, kterého časopis Time zařadil mezi sto nejvlivnějších lidí světa.Všechny díly podcastu Leonardo Plus můžete pohodlně poslouchat v mobilní aplikaci mujRozhlas pro Android a iOS nebo na webu mujRozhlas.cz.

Další lék proti viru HIV má českou stopu. Zásadní podíl na něm má Tomáš Cihlář se svým kalifornským týmem. Na rozdíl od denně užívaných antivirotik lék stačí injekčně aplikovat dvakrát ročně a funguje i jako prevence. „Myslím, že naše látka může významně přispět k omezení počtu nových infekcí,“ říká v Leonardu Plus Tomáš Cihlář, viceprezident pro virologii společnosti Gilead Sciences, kterého časopis Time zařadil mezi sto nejvlivnějších lidí světa.

Thrive Corporate: Success Guide Wise Mind In this episode of Tim Stating the Obvious, host Tim Staton sits down with Edward Bjurstrom, author of The Success Guide: How to Thrive in the Corporate Environment. Drawing from over 40 years leading in biopharma at companies like Amgen and Gilead Sciences, Edward shares a practical roadmap for how to survive in corporate America and how to thrive in the corporate world—whether you're navigating high-stakes regulated environments or aiming to get promoted faster in a large company.   Edward explains how to think and work holistically, balancing the rational mind (logic and facts) with the emotional mind (feelings and intuition) to reach the wise mind—that integrated state where decisions feel clear and effective. He dives into the rational mind vs emotional mind dynamic, why the wise mind rational mind emotional mind balance matters so much in leadership, and how understanding the psychological definition of a flow state can unlock peak individual and team performance.   You get actionable insights on avoiding common pitfalls, fostering trust and accountability, and applying concepts like design thinking understanding how designers think and work to solve complex corporate challenges. Whether you're dealing with burnout, mistrust, or just wanting sustained success, Edward's lessons from his book offer a no-nonsense guide to building excellence without sacrificing well-being.   Connect with Tim: Website: timstatingtheobvious.com Facebook: https://www.facebook.com/timstatingtheobvious YouTube: https://www.youtube.com/channel/UCHfDcITKUdniO8R3RP0lvdw Instagram: @TimStating TikTok: @timstatingtheobvious LinkedIn: https://www.linkedin.com/in/tim-staton-04b41a271/ SKOOL Community: https://www.skool.com/timstatingtheobvious-9537/about?ref=de9c7e65d8ba4eeabc1a8eea413c125b Enroll in the Leadership Course: https://themanyhatsofleadership.learnworlds.com/course/the-edge-mindset   Connect with Edward Bjurstrom Book: https://www.amazon.com/dp/B0G4RBL543 Website : www.mountaintopconsul.com LinkedIn: linkedin.com/in/edwardbjurstrom Facebook: https://www.facebook.com/edward.bjurstrom

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of breakthroughs and strategic maneuvers that are reshaping the landscape of this dynamic industry.Roche is making waves with its antibody Gazyva, initially recognized for cancer treatment. The company has successfully ventured into autoimmune diseases, targeting kidney conditions. Recent phase 3 trials have reinforced Gazyva's efficacy in treating immune-mediated kidney diseases, building on its prior approval for lupus nephritis. This marks a potential paradigm shift from oncology to autoimmune therapy applications, offering a promising new avenue for treating complex kidney disorders. Such advancements underscore the power of immune modulation in addressing severe health conditions.Turning to oncology, Eli Lilly is expanding the use of its cancer drug, Retevmo. Originally approved for specific lung and thyroid cancers with rare biomarkers, Lilly is now exploring its use in the adjuvant setting for non-small cell lung cancer. This effort reflects a broader trend in oncology: companies are increasingly looking to extend the application of targeted therapies beyond their initial indications. This expansion could significantly enhance treatment options and improve patient outcomes.In ophthalmology, Ocular Therapeutix is preparing for an FDA filing following positive phase 3 results for its wet age-related macular degeneration treatment. Their candidate, AXPAXLI, showed superior efficacy compared to Regeneron's Eylea in head-to-head trials. Despite investor skepticism, Ocular remains confident in its product's potential to impact retinal disease management positively. The competitive landscape in ophthalmology is fierce, and innovative treatments with substantial clinical benefits over existing therapies can redefine standards of care.Eli Lilly is also strategically stockpiling Orforglipron, its oral GLP-1 candidate, in anticipation of FDA approval for obesity treatment. This proactive measure aims to prevent supply chain issues seen during previous GLP-1 launches. It reflects an industry-wide focus on ensuring product availability at launch to meet growing market demand effectively.On the regulatory front, there are significant shifts as well. The Trump administration's renewed pilot of 340B rebates aims to optimize drug pricing frameworks. Novartis has secured a long-term supply agreement with Niowave for Actinium-225 (Ac-225), crucial for developing targeted cancer therapies. This highlights the sustained demand for radiopharmaceutical isotopes as part of precision medicine initiatives.Biopharma funding is expected to recover steadily by 2026, albeit with a cautious approach favoring de-risked assets over broader platform technologies. Venture capitalists prefer predictable returns amidst an evolving market landscape.Now, let's turn to Japan, where Innovacell is planning a $92 million IPO on the Tokyo Stock Exchange. This move signals a renewed interest in biotech within the region after a long drought in IPOs. Financial strategies like these are vital for advancing cell therapies that hold promise for treating conditions once deemed challenging.Gilead Sciences has acquired synthetic lethal therapy from Genhouse Bio through a $1.5 billion deal, further underscoring the growing interest in synthetic lethality as a novel cancer treatment approach. This strategy focuses on targeting tumors while sparing normal cells, offering more effective therapies with fewer side effects.In mental health innovations, Compass Pathways has reported positive results from its pivotal trial using psilocybin for treatment-resistant depression. The success of this phase 3 trial highlights the potential role of psychedelics in psychiatric care and could revolutionize mental health treatments by providing new options Support the show

Ed Bjurstrom has decades of experience in management working in the pharmaceutical industry, including companies such as Amgen and Gilead Sciences. He owned Mountain Top Consulting and recently wrote a new book titled, "The Success Guide: How to Thrive in the Corporate Environment: A Focused Roadmap for Achieving Peak Performance, Leadership Excellence, and Building a Trust-Based Culture." Order your personal copy of his book at the link below! TIMESTAMPS 0:00 Introduction to Bjurstrom's Leadership Experience 2:55 How did your engineering brain aid you and challenge you in your leadership experience? 5:50 How difficult is it to change your thinking to encourage success? 8:40 How do you keep your emotions from hijacking your leadership when under stress? 12:50 What do you mean by being in a "zone of creative tension?" 17:13 How do you manage to get the rest and sleep you need while working in a demanding position? 20:50 What advice would you give a manager in trying to align people with their passions at work? 24:16 What is the "flow state?" 28:42 If you were building a team today, what characteristics would you look for in potential team members? 32:00 Closing Remarks "The Success Guide" Link: https://www.amazon.com/Success-Guide-Environment-Performance-Trust-Based-ebook/dp/B0G3YHKCDN/ref=sr_1_1?crid=27LN92PHV2VNS&dib=eyJ2IjoiMSJ9.tsXSY6Kn6S7ULsiMykokv5BwJrLUI2CpszYHxzUOgG97mMvLN9zJla7EA9y5JOPRgzB-mFPbL-40Ly0rXTv7qMzaJutCnWtrP8HA8WM0amSbTgNmk46QI6pl9zJJfHdVUwN4ezGpBVSIlD3Py-saEA.e8HgV-305B9a5o9UYfyq9zr6XyT_TSmnw2dgPvyQEpM&dib_tag=se&keywords=the+success+guide+how+to+thrive+in+the+corporate+environment&nsdOptOutParam=true&qid=1770905320&sprefix=how+to+thrive+in+a+corporate+e%2Caps%2C199&sr=8-1 Mountain Top Consulting: https://www.linkedin.com/company/mountain-top-consulting-llc/about/  Questions or comments? Email us at podcast@blackaby.org DONATE: If you have enjoyed this podcast and want to support our ministry into the next 20 years, click here: https://bit.ly/382Exi3 RESOURCES: Mark your calendars for May 18-20, 2026 when Richard will be presenting Experiencing God – Part 2 at the Cove in Asheville, NC. More info to come. Join Blackaby Ministries' next Spiritual Leadership Coaching Workshop here: https://www.blackabycoaching.org/workshop CONNECT: X: @richardblackaby Facebook: https://bit.ly/2WvZPzw Read Richard's latest blog posts at www.richardblackaby.com

Supplier due diligence is one of the most important and impactful activities that procurement leads. Managing risk and ensuring visibility into supplier commitments on sustainability-related business objectives requires constant involvement and careful oversight. These programs depend upon senior-level commitment, but they must also be flexible enough to work across complex, decentralized organizations, and to allow different stakeholder groups inside and outside of the organization to participate.  In this episode of The Sourcing Hero podcast, Host Kelly Barner welcomes Dru Krupinsky. Dru is a Senior Manager in procurement at Gilead Sciences. More specifically, he is focused on supplier risk and sustainability, initiatives that all companies are (or should be) increasingly focused on today. Dru shares his perspective on the conditions required for successful and sustainable supplier relationships: Recommendations for effective ownership and accountability structures  The importance of focusing on the quality and accessibility of data Partnership with key suppliers to manage risk and sustainability jointly   Links: Dru Krupinsky on LinkedIn

“Intrinsically, there is nothing wrong with using Chinese CDMOs. But because of geopolitical issues, some large pharma want to have redundancy of that supply chain in the US.”Dr. Reza Oliyai, President and CEO of Oliyai Consulting Corporation, spent 28 years at Gilead Sciences rising from research scientist to SVP overseeing 1,700 people across seven sites and multiple modalities including biologics, ADCs, small molecules, and sterile manufacturing.In this PharmaSource podcast episode, Reza shares his framework for helping biotechs de-risk their external manufacturing strategy, navigate geopolitical supply chain challenges, and make phase-appropriate decisions that balance speed with resource constraints.Read the full article

The leaders of this year’s list of the most anticipated drug launches will likely come as no surprise: Fierce’s annual report on the biggest potential launches of 2026 details how the next obesity meds from Novo Nordisk and Eli Lilly are expected to rake in a respective $17.2 billion and $11.8 billion in annual sales by 2032, so long as they score their expected approvals this year. Elsewhere in the report are candidates from the likes of Gilead Sciences, Johnson & Johnson, AstraZeneca and other biopharmas big and small, spanning a range of indications from breast cancer to essential tremor. All together, predicted 2032 sales for the year’s top 10 weigh in at nearly $46 billion. In this week’s episode of “The Top Line,” Fierce’s Andrea Park and Gabrielle Masson dive into the report, mapping out how it stacks up against last year’s edition and digging into the enormous sales potential of the top two drugs on the list. To learn more about the topics in this episode: Top 10 most anticipated drug launches of 2026 Novo Nordisk stock crashes after CagriSema misses phase 3 weight-loss goal Lilly's obesity pill largely maintains weight lost on injectable GLP-1s Top 10 most anticipated drug launches of 2025 See omnystudio.com/listener for privacy information.

This interview is highly valuable for anyone who wants to do more than merely survive in the corporate world and instead build a truly successful, resilient, and fulfilling career. In his conversation with Edward Bjurstrom, former Vice President of Operations at Gilead Sciences and author of The Success Guide: How to Thrive in the Corporate Environment, Niels Brabandt explores what sustainable success in large organisations really requires. The discussion moves far beyond generic career advice and focuses on the practical realities leaders and professionals face every day: pressure, politics, constant change, technological disruption, and the challenge of remaining effective and credible over long careers Listeners gain rare insights from four decades of senior leadership experience in a highly regulated, high-performance industry. Bjurstrom explains why self-awareness is a decisive leadership competence, how lack of it destroys trust, and why senior executives must actively build systems for honest feedback if they want to avoid living in an echo chamber. He shows how focus and productivity can be regained in an age of permanent distraction, how the psychological state of flow can be cultivated for deep work and strategic problem-solving, and why emotional regulation and asking the right questions are often more powerful than issuing directives. The interview also provides a realistic view on leadership development across cultures and hierarchies, including what it takes to build trust, credibility, and performance in complex international environments. Bjurstrom's reflections on purpose, learning, storytelling, and long-term career growth speak directly to decision makers who want to create impact rather than burn out in constant firefighting. For ambitious professionals, senior managers, and executives who want to understand how to thrive, not just cope, in demanding corporate systems, this conversation offers structured thinking, practical tools, and leadership wisdom grounded in real experience rather than theory. Host: Niels Brabandt / NB@NB-Networks.com Contact with Niels Brabandt: https://www.linkedin.com/in/nielsbrabandt/ Niels Brabandt's Leadership Letter: https://expert.nb-networks.com/ Niels Brabandt's Website: https://www.nb-networks.biz/ 

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a landscape marked by rapid transformations and strategic maneuvers that are reshaping the industry.Novo Nordisk is at a pivotal point under the leadership of CEO Maziar Mike Doustdar. The company is navigating a significant transition, focusing on reclaiming its leadership in the glucagon-like peptide-1 (GLP-1) market. This is crucial as GLP-1 receptor agonists are central to diabetes and obesity treatments, areas where Novo Nordisk aims to solidify its presence amidst fierce competition.AstraZeneca is setting ambitious targets, aiming for $80 billion in revenue by 2030. Their confidence is buoyed by strong Phase 3 clinical trial performances, particularly in oncology and rare diseases, underscoring the importance of a robust and successful pipeline. AstraZeneca's acquisition of Modella AI marks an integration of advanced AI models into oncology R&D operations, aligning with industry trends leveraging AI for drug discovery processes. By incorporating AI technologies, AstraZeneca aims to revolutionize precision medicine approaches within oncology treatments.Travere Therapeutics finds itself at a critical juncture with the FDA's delayed decision on Filspari (sparsentan) for focal segmental glomerulosclerosis (FSGS). This potential approval could tap into a significant market opportunity, but the delay highlights regulatory challenges that can impact timelines and revenue forecasts.Gilead Sciences continues to strengthen its position in HIV treatment with lenacapavir's approval for bi-annual dosing. This advancement not only enhances patient compliance but also positions Gilead advantageously for strategic partnerships. Their strategic positioning post-approval of lenacapavir for HIV prevention marks a milestone, emphasizing innovation's role in drug formulations.Leo Pharma's pursuit of partnerships in rare dermatological diseases reflects a broader trend towards specialization and diversification into niche markets. Meanwhile, Ionis Pharmaceuticals is gearing up to launch Tryngolza (olezarsen) for new indications, doubling their sales projections and demonstrating confidence in their RNA-targeted therapy.Caldera's emergence with significant funding points to ongoing investor interest in innovative biotech ventures, particularly those involving cross-border collaborations like their licensed drug from China for inflammatory bowel disease. Cross-border collaborations such as Caldera's venture into inflammatory bowel disease treatments are becoming more prevalent, integrating innovations from different regions to accelerate novel therapy availability for complex diseases.Illumina's efforts to navigate export challenges with China highlight geopolitical factors influencing biotech operations and global supply chains. They are actively working to stabilize their business environment while supporting academic research initiatives. Illumina's collaboration efforts with China amidst geopolitical tensions further demonstrate complexities within international trade relations affecting scientific collaborations.The American Medical Association's investment in "precision education" using data analytics exemplifies how technology is reshaping healthcare education and practice, aiming to enhance outcomes by tailoring learning experiences.AbbVie has committed $100 billion to U.S. research and development over the next decade, focusing on biologics and autoimmune disorders. This substantial investment underscores their commitment to innovation while seeking competitive edge enhancements through tariff exemptions.On clinical fronts, significant advancements are being made in therapies targeting rare diseases such as Sentynl Therapeutics' FDA approval for Zycubo—a novel protein therapy addressing Menkes disease—highlightSupport the show

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. 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. Follow today's speakers:        Dr. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

Founded in 1979, Transgene has transformed itself into a leading personalized cancer vaccine player. Alessandro talks about the transformation, his history in cell therapy and how Europe's biotech space can rival those of the US and China.---Learn more about Transgene: https://bit.ly/tg_flotbio---⭐️ ABOUT THE SPEAKERAlessandro became Transgene's CEO in 2023 after joining in 2022 as Chairman of the Board of Directors. He also played a key role in Gilead Sciences' acquisition of Kite Pharma and the regulatory approval of the CAR-T therapy Yescarta.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world.The industry continues to navigate a dynamic landscape marked by significant scientific advancements, regulatory changes, and strategic shifts. Eli Lilly's acquisition of Ventyx Biosciences for $1.2 billion underscores Lilly's commitment to expanding its portfolio in inflammation-related therapeutics, particularly following promising readouts in Parkinson's and cardiovascular conditions. This acquisition exemplifies big pharma's strategy to bolster pipelines with promising biotechs, reflecting an industry-wide focus on innovation-driven growth. Concurrently, Lilly has partnered with InduPro in a potential $950 million deal to develop next-generation cancer treatments, highlighting the ongoing trend of leveraging innovative biotech approaches to address complex oncological challenges.In regulatory news, the FDA issued an untitled letter to Esperion Therapeutics concerning misleading claims in a commercial for its cholesterol-lowering drug, Nexlizet. This action highlights the FDA's continued vigilance over direct-to-consumer advertising practices, ensuring that pharmaceutical promotions remain accurate and evidence-based. Meanwhile, the FDA has also eased regulations on AI-enabled consumer wearables, allowing more devices to enter the market under the wellness category without full regulatory review. This shift may accelerate the adoption of digital health technologies, fostering innovation and potentially enhancing patient care through more personalized and accessible health monitoring solutions.Clinical trial and study findings continue to shape therapeutic strategies across various domains. Gilead Sciences reported that while HIV can develop resistance to its antiviral drug lenacapavir, this adaptation compromises the virus's replication capabilities. This finding underscores the ongoing challenges in antiviral therapy development and the need for continued research into resistance mechanisms. In obesity management, Viking Therapeutics is ramping up commercialization efforts to compete with major players like Amgen and Eli Lilly, while Novo Nordisk is engaging in public discourse to address weight stigma, emphasizing the multifaceted nature of obesity.The biosimilar sector is at a pivotal juncture as it confronts what some term a 'biosimilar void.' With key patents set to expire and evolving global policies, stakeholders are urged to reassess strategies to maintain momentum in this cost-reduction avenue for biologic therapies. This period presents opportunities for innovation in biosimilar development and commercialization strategies.In organizational updates, AstraZeneca appointed Rick Suarez as head of its U.S. biopharma unit, leading a $50 billion investment surge aimed at strengthening its foothold in the American market. Such strategic leadership appointments are crucial as companies navigate competitive landscapes and pursue ambitious growth targets.The industry's response to COVID-19 continues to evolve, with Inflarx adjusting its business strategy by reducing its workforce by 30% and reallocating resources from COVID-related projects to focus on its promising candidate for inflammatory conditions. This strategic pivot reflects broader industry trends where companies re-evaluate their portfolios post-pandemic to align with core strengths and emerging opportunities.Furthermore, partnerships remain integral to advancing therapeutic innovations. Lexeo Therapeutics has teamed up with Johnson & Johnson's Abiomed unit to explore heart pump technology as a delivery system for cardiac gene therapies. Such collaborations are instrumental in driving forward cutting-edge treatment modalities that could significantly impact patient outcomes in cardiology.The pharmaceutical and biotech sectors are witnessing significant financiSupport the show

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode.  Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind.  The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain.  So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival.  The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer.  Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer.  Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please 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 opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Monty Pal @montypal Dr. Hope Rugo   @hoperugo Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world.In a dynamic landscape marked by both advancements and challenges, the pharmaceutical and biotech sectors continue to evolve with notable scientific, regulatory, and strategic updates. Ipsen's recent $1 billion acquisition of Simcere's preclinical LRRC15-targeting asset underscores a growing focus on antibody-drug conjugates (ADCs). These conjugates leverage the targeted action of antibodies combined with the cytotoxic effects of drugs, representing a promising approach to cancer treatment by potentially minimizing systemic toxicity. Ipsen's strategic move reflects its commitment to expanding its oncology portfolio and staying competitive within the rapidly advancing ADC landscape.AstraZeneca has been active in its pursuit of innovative cancer treatments. The company has invested $100 million in Jacobio's clinical-stage pan-KRAS inhibitor, a promising development targeting KRAS mutations prevalent in various cancers. This investment aligns with AstraZeneca's strategy to tackle challenging oncogenic targets. However, their efforts faced a setback as their Phase 3 trial for ceralasertib, an ATR inhibitor for lung cancer, failed to meet its primary endpoint. Despite this setback, AstraZeneca maintains confidence by investing significantly in promising areas like KRAS inhibitors, highlighting the inherent risks involved in pioneering novel therapeutic strategies, particularly those aiming to overcome resistance mechanisms in immuno-oncology.BioMarin has quietly discontinued its liver disease candidate amid a $4.8 billion deal with Amicus. This decision points to the complex nature of pipeline prioritization and resource allocation within high-stakes financial environments. The company's strategic shifts reflect ongoing evaluations of their development priorities in light of evolving market demands.Boehringer Ingelheim has demonstrated a commitment to renal therapeutics with a $448 million investment in Rectify Pharmaceuticals for a preclinical chronic kidney disease program. This partnership seeks to address significant unmet medical needs within kidney disease treatment. Meanwhile, Gilead Sciences has entered into a $35 million licensing agreement with Assembly Biosciences for herpes simplex virus (HSV) assets, diversifying its infectious disease portfolio and expanding its reach within antiviral therapies.Novo Holdings-backed Windward Bio's acquisition of rights to Qyun's clinical-stage immunology bispecifics for $700 million highlights robust activity in the immunology space. Bispecific antibodies are gaining traction due to their ability to target two antigens simultaneously, offering enhanced therapeutic efficacy. This acquisition illustrates ongoing interest in this area as companies seek innovative solutions to complex immunological challenges.The broader industry is also witnessing strategic partnerships such as Aditum Bio's launch of a new biotech venture with Fosun Pharma. This collaboration aims to foster novel therapies through a synergistic blend of biotechnology innovation and pharmaceutical expertise. These alliances reflect an industry trend towards collaborative efforts that leverage diverse strengths to advance therapeutic development.In regulatory news, nine major pharmaceutical companies have reached agreements with the U.S. government to lower certain drug prices in exchange for tariff relief. This development signals ongoing negotiations aimed at balancing drug affordability with industry sustainability amid growing scrutiny over pricing practices.In December 2025, significant developments emerged, impacting scientific innovation, regulatory approvals, mergers, and strategic partnerships across the industry. Notably, the U.S. Food and Drug Administration (FDA) granted early approval to Cytokinetics' MyqorzSupport the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of significant updates that are shaping the future of healthcare, patient care, and drug development.The U.S. Food and Drug Administration has been particularly active recently, granting Johnson & Johnson a National Priority Review Voucher for its multiple myeloma drug combination. This move highlights the importance of J&J's treatment in addressing unmet needs within oncology, a field continuously striving for innovative solutions. These vouchers expedite the review process, reflecting a broader commitment to accelerating the availability of critical therapies for patients who need them most.Continuing with regulatory advancements, AstraZeneca and Daiichi Sankyo's Enhertu, in combination with Roche's Perjeta, has gained FDA approval as a first-line treatment for unresectable or metastatic HER2-positive breast cancer. This breakthrough is supported by late-stage study results demonstrating a 44% reduction in disease progression or death compared to standard care. The approval signifies not only progress in breast cancer therapeutics but also underscores the potential benefits of strategic collaborations in drug development. Such partnerships are increasingly vital as they aim to optimize therapeutic efficacy through shared expertise and resources.In contrast to these advancements, Pfizer is facing financial recalibrations with projected revenues for 2026 estimated to decline due to diminishing COVID-19 vaccine sales and patent expirations. This situation reflects broader industry challenges as companies navigate post-pandemic market dynamics and patent cliffs, forcing reevaluations of long-term strategies.On another front, Gilead Sciences continues to push boundaries in HIV treatment with a promising single-tablet regimen combining bictegravir and lenacapavir. This innovation targets underserved segments within the HIV market, offering streamlined treatment options that could enhance patient adherence and outcomes significantly.Shifting focus to obesity management, Novo Nordisk's oral semaglutide is emerging as a highly anticipated medication among primary care providers. This trend highlights a growing preference for oral GLP-1 therapies as convenient alternatives to injectable formulations, marking a shift in how obesity—a major public health concern—is managed.The importance of regulatory compliance remains evident as Novo Nordisk received an FDA warning letter concerning manufacturing issues at an Indiana site previously owned by Catalent. This incident underscores the necessity for rigorous quality control in pharmaceutical manufacturing, which can have far-reaching implications on operational dynamics and supply chains.The FDA is also pioneering efforts to incorporate real-world evidence into medical device submissions by opening pathways for extensive deidentified datasets from sources like national cancer registries and electronic health records. This policy shift aims to integrate diverse data sources into the evidentiary foundation for medical device evaluations, potentially fostering innovation within this sector.In line with collaborative efforts, Genentech has partnered with Caris Life Sciences in a multi-year agreement valued at up to $1.1 billion, emphasizing the strategic importance of integrating diagnostic advancements with therapeutic developments to achieve precision medicine goals.Meanwhile, Yarrow Bioscience has acquired an autoimmune thyroid disease drug from China's Gensci, exemplifying a growing trend of cross-border collaborations aimed at leveraging global innovation ecosystems to address diverse therapeutic areas. This acquisition is part of a $1.37 billion deal, reinforcing the globalization of biotech partnerships as companies seek access to novel therapeutics andSupport the show

In this episode, Stephen Sukumaran, Director of the Long Acting Injectable (LAI) Program at Callen-Lorde Community Health Center, explains how his team streamlined insurance navigation, documentation, and care coordination by optimizing Electronic Health Record (EHR) workflows, leading to major improvements in patient access, efficiency, and long acting injectable HIV Pre-exposure Prophylaxis (PrEP) uptake.This episode is sponsored by Gilead Sciences.

Join us for a December program and celebration featuring youth speakers from San Francisco's LYRIC Center for LGBTQQ+ Youth. These young people will speak about today's important social issues affecting their lives. After the program, stick around for an appreciation reception with food and beverages. The Commonwealth Club thanks Gilead Sciences, Inc. for its generous support of The Michelle Meow Show.  See more  Michelle Meow Show programs at Commonwealth Club World Affairs of California.   This program contains EXPLICIT language.  Learn more about your ad choices. Visit megaphone.fm/adchoices

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/UAD865. CME/MOC/AAPA credit will be available until November 20, 2026.Harnessing the Power of ADCs in Gynecologic Cancers: Expert Insights for Practice Integration 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 activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Authors Drs. Jessica Ross and Alissa Cooper share insights into their JCO PO article, "Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas"  Host Dr. Rafeh Naqash and Drs. Ross and Cooper discuss the landscape of Delta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) across NECs from eight different primary sites. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO PO and an Associate Professor at the OU Health Stephenson Cancer Center. Today, I'm excited to be joined by Dr. Jessica Ross, third-year medical oncology fellow at the Memorial Sloan Kettering Cancer Center, as well as Dr. Alissa Cooper, thoracic medical oncologist at the Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School. Both are first and last authors of the JCO Precision Oncology article entitled "Clinical and Pathologic Landscapes of Delta-like Ligand 3 and Seizure-Related Homolog Protein 6 or SEZ6 Protein Expression in Neuroendocrine Carcinomas." At the time of this recording, our guest disclosures will be linked in the transcript. Jessica and Alissa, welcome to our podcast, and thank you for joining us today. Dr. Jessica Ross: Thanks very much for having us. Dr. Alissa Cooper: Thank you. Excited to be here. Dr. Rafeh Naqash: It's interesting, a couple of days before I decided to choose this article, one of my GI oncology colleagues actually asked me two questions. He said, "Rafeh, do you know how you define DLL3 positivity? And what is the status of DLL3 positivity in GI cancers, GI neuroendocrine carcinomas?" The first thing I looked up was this JCO article from Martin Wermke. You might have seen it as well, on obrixtamig, a phase 1 study, a DLL3 bi-specific T-cell engager. And they had some definitions there, and then this article came along, and I was really excited that it kind of fell right in place of trying to understand the IHC landscape of two very interesting targets. Since we have a very broad and diverse audience, especially community oncologists, trainees, and of course academic clinicians and some people who are very interested in genomics, we'll try to make things easy to understand. So my first question for you, Jessica, is: what is DLL3 and SEZ6 and why are they important in neuroendocrine carcinomas? Dr. Jessica Ross: Yeah, good question. So, DLL3, or delta-like ligand 3, is a protein that is expressed preferentially on the tumor cell surface of neuroendocrine carcinomas as opposed to normal tissue. It is a downstream target of ASCL1, and it's involved in neuroendocrine differentiation, and it's an appealing drug target because it is preferentially expressed on tumor cell surfaces. And so, it's a protein, and there are several drugs in development targeting this protein, and then Tarlatamab is an approved bi-specific T-cell engager for the treatment of extensive-stage small cell lung cancer in the second line. SEZ6, or seizure-like homolog protein 6, is a protein also expressed on neuroendocrine carcinoma cell surface. Interestingly, so it's expressed on neuronal cells, but its exact role in neuroendocrine carcinomas and oncogenesis is actually pretty poorly understood, but it was identified as an appealing drug target because, similarly to DLL3, it's preferentially expressed on the tumor cell surface. And so this has also emerged as an appealing drug target, and there are drugs in development, including antibody-drug conjugates, targeting this protein for that reason. Dr. Alissa Cooper: Over the last 10 to 15 years or so, there's been an increasing focus on precision oncology, finding specific targets that actually drive the cancer to grow, not just within lung cancer but in multiple other primary cancers. But specifically, at least speaking from a thoracic oncology perspective, the field of non-small cell lung cancer has completely exploded over the past 15 years with the discovery of driver oncogenes and then matched targeted therapies. Within the field of neuroendocrine carcinomas, including small cell lung cancer but also other high-grade neuroendocrine carcinomas, there has not been the same sort of progress in terms of identifying targets with matched therapies. And up until recently, we've sort of been treating these neuroendocrine malignancies kind of as a monolithic disease process. And so recently, there's been sort of an explosion of research across the country and multiple laboratories, multiple people converging on the same open questions about why might patients with specific tumor biologies have different kind of responses to different therapies. And so first this came from, you know, why some patients might have a good response to chemo and immunotherapy, which is the first-line approved therapy for small cell lung cancer, and we also sort of extrapolate that to other high-grade neuroendocrine carcinomas. What's the characteristic of that tumor biology? And at the same time, what are other targets that might be identifiable? Just as Jesse was saying, they're expressed on the cell surface, they're not necessarily expressed in normal tissue. Might this be a strategy to sort of move forward and create smarter therapies for our patients and therefore move really into a personalized era for treatment for each patient? And that's really driving, I think, a lot of the synthesis of this work of not only the development of multiple new therapies, but really understanding which tumor might be the best fit for which therapy. Dr. Rafeh Naqash: Thank you for that explanation, Alissa. And as you mentioned, these are emerging targets, some more further along in the process with approved drugs, especially Tarlatamab. And obviously, DLL3 was something identified several years back, but drug development does take time, and readout for clinical trials takes time. Could you, for the sake of our audience, try to talk briefly about the excitement around Tarlatamab in small cell lung cancer, especially data that has led to the FDA approval in the last year, year and a half? Dr. Alissa Cooper: Sure. Yeah, it's really been an explosion of excitement over, as you're saying, the last couple of years, and work really led by our mentor, Charlie Rudin, had identified DLL3 as an exciting target for small cell lung cancer specifically but also potentially other high-grade neuroendocrine malignancies. Tarlatamab is a DLL3-targeting bi-specific T-cell engager, which targets DLL3 on the small cell lung cancer cells as well as CD3 on T cells. And the idea is to sort of introduce the cancer to the immune system, circumventing the need for MHC class antigen presentation, which that machinery is typically not functional in small cell lung cancer, and so really allowing for an immunomodulatory response, which had not really been possible for most patients with small cell lung cancer prior to this. Tarlatamab was tested in a phase 2 registrational trial of about 100 patients and demonstrated a response rate of 40%, which was very exciting, especially compared with other standard therapies which were available for small cell lung cancer, which are typically cytotoxic therapies. But most excitingly, more than even the response rate, I think, in our minds was the durability of response. So patients whose disease did have a response to Tarlatamab could potentially have a durable response lasting a number of months or even over a year, which had previously not ever been seen in this in the relapsed/refractory setting for these patients. I think the challenge with small cell lung cancer and other high-grade neuroendocrine malignancies is that a response to therapy might be a bit easier to achieve, but it's that durability. The patient's tumors really come roaring back quite aggressively pretty quickly. And so this was sort of the most exciting prospect is that durability of response, that long potential overall survival tail of the curve really being lifted up. And then most recently at ASCO this year, Dr. Rudin presented the phase 3 randomized controlled trial which compared Tarlatamab to physician's choice of chemotherapy in a global study. And the choice of chemotherapy did vary depending on the part of the world that the patients were enrolled in, but in general, it was a really markedly positive study for response rate, for progression-free survival, and for overall survival. Really exciting results which really cemented Tarlatamab's place as the standard second-line therapy for patients with small cell lung cancer whose disease has progressed on first-line chemo-immunotherapy. So that has been very exciting. This drug was FDA approved in May of 2024, and so has been used extensively since then. I think the adoption has been pretty widespread, at least in the US, but now in this global trial that was just presented, and there was a corresponding New England Journal paper, I think really confirms that this is something we really hopefully can offer to most of our patients. And I think, as we all know, that this therapy or other therapies like it are also being tested potentially in the first-line setting. So there was data presented with Tarlatamab incorporated into the maintenance setting, which also showed exciting results, albeit in a phase 1 trial, but longer overall survival than we're used to seeing in this patient population. And we await results of the study that is incorporating Tarlatamab into the induction phase with chemotherapy as well. So all of this is extraordinarily exciting for our patients to sort of move the needle of how many patients we can keep alive, feeling functional, feeling well, for as long as possible. Dr. Rafeh Naqash: Very exciting session at ASCO. I was luckily one of the co-chairs for the session that Dr. Rudin presented it, and I remember somebody mentioning there was more progress seen in that session for small cell lung cancer than the last 30, 35 years for small cell, very exciting space and time to be in as far as small cell lung cancer. Now going to this project, Jessica, since you're the first author and Alissa's the last, I'm assuming there was a background conversation that you had with Alissa before you embarked on this project as an idea. So could you, again, for other trainees who are interested in doing research, and it's never easy to do research as a resident and a fellow when you have certain added responsibilities. Could you give us a little bit of a background on how this started and why you wanted to look at this question? Dr. Jessica Ross: Yeah, sure. So, as with many exciting research concepts, I think a lot of them are derived from the clinic. And so I think Alissa and I both see a good number of patients with small cell, large cell lung cancer, and then high-grade neuroendocrine carcinomas. And so I think this was really born out of a basic conversation of we have these drugs in development targeting these two proteins, DLL3 and SEZ6, but really what is the landscape of cancers that express these proteins and who are the patients that really might benefit from these exciting new therapies. And of course, there was some data out there, but sort of less than one would imagine in terms of, you know, neuroendocrine carcinomas can really come from anywhere in the body. And so when you're seeing a patient with small cell of the cervix, for example, like what are the chances that their cancer expresses DLL3 or expresses SEZ6? So it was really derived from this pragmatic, clinically oriented question that we had both found ourselves thinking about, and we were lucky enough at MSK, we had started systematically staining patients' tumors for DLL3, tumors that are high-grade neuroendocrine carcinomas, and then we had also more recently started staining for SEZ6 as well. And so we had this nice prospectively collected dataset with which to answer this question. Dr. Rafeh Naqash: Excellent. And Alissa, could you try to go into some of the details around which patients you chose, how many patients, what was the approach that you selected to collect the data for this project? Dr. Alissa Cooper: This is perhaps a strength but also maybe a limitation of this dataset is, as Jesse alluded to, our pathology colleagues are really the stars of this paper here because we were lucky enough at MSK that they were really forethinking. They are absolute experts in the field and really forward-thinking people in terms of what information might be needed in the future to drive treatment decision-making. And so, as Jesse had said, small cell lung cancer tumor samples reflexively are stained for DLL3 and SEZ6 at MSK if there's enough tumor tissue. The other high-grade neuroendocrine carcinomas, those stains are performed upon physician request. And so that is a bit of a mixed bag in terms of the tumor samples we were able to include in this dataset because, you know, upon physician request depends on a number of factors, but actually at MSK, a number of physicians were requesting these stains to be done on their patients with high-grade neuroendocrine cancers of of other histologies. So we looked at all tumor samples with a diagnosis of high-grade neuroendocrine carcinoma of any histology that were stained for these two stains of interest. You know, I can let Jesse talk a bit more about the methodology. She was really the driver of this project. Dr. Jessica Ross: Yeah, sure. So we had 124 tumor samples total. All of those were stained for DLL3, and then a little less than half, 53, were stained for SEZ6. As Alissa said, they were from any primary site. So about half of them were of lung origin, that was the most common primary site, but we included GI tract, head and neck, GU, GYN, even a few tumors of unknown origin. And again, that's because I think a lot of these trials are basket trials that are including different high-grade neuroendocrine carcinomas no matter the primary site. And so we really felt like it was important to be more comprehensive and inclusive in this study. And then, methodologically, we also defined positivity in terms of staining of these two proteins as anything greater than or equal to 1% staining. There's really not a defined consensus of positivity when it comes to these two novel targets and staining for these two proteins. But in the Tarlatamab trials, for some of the correlative work that's been done, they use that 1% cutoff, and we just felt like being consistent with that and also using a sort of more pragmatic yes/no cutoff would be more helpful for this analysis. Dr. Alissa Cooper: And that was a point of discussion, actually. We had contemplated multiple different schemas, actually, for how to define thresholds of positivity. And I know you brought up that question before, what does it mean to be DLL3 positive or DLL3 high? I think you were alluding to prior that there was a presentation of obrixtamig looking at extra-pulmonary neuroendocrine carcinomas, and they actually divvied up the results between DLL3 50% or greater versus DLL3 low under 50%. And they actually did demonstrate differential efficacy certainly, but also some differential safety as well, which is very provocative and that kind of analysis has not been presented for other novel therapies as far as I'm aware. I could be wrong, but as far as I'm aware, that was sort of the first time that we saw a systematic presentation of considering patients to be, quote unquote, "high" or "low" in these sort of novel targets. I think it is important because the label for Tarlatamab does not require any DLL3 expression at all, actually. So it's not hinging upon DLL3 expression. They depend on the fact that the vast majority of small cell lung cancer tumors do express DLL3, 85% to 90% is what's been demonstrated in a few studies. And so, there's not prerequisite testing needed in that regard, but maybe for these extra-pulmonary, other histology neuroendocrine carcinomas, maybe it does matter to some degree. Dr. Rafeh Naqash: Definitely agree that this evolving landscape of trying to understand whether an expression for something actually really does correlate with, whether it's an immune cell engager or an antibody-drug conjugate is a very evolving and dynamically moving space. And one of the questions that I was discussing with one of my friends was whether IHC positivity and the level of IHC positivity, as you've shown in one of those plots where you have double positive here on the right upper corner, you have the double negative towards the left lower, whether that somehow determines mRNA expression for DLL3. Obviously, that was not the question here that you were looking at, but it does kind of bring into question certain other aspects of correlations, expression versus IHC. Now going to the figures in this manuscript, very nicely done figures, very easy to understand because I've done the podcast for quite a bit now, and usually what I try to do first is go through the figures before I read the text, and and a lot of times it's hard to understand the figures without reading the text, but in your case, specifically the figures were very, very well done. Could you give us an overview, a quick overview of some of the important results, Jessica, as far as what you've highlighted in the manuscript? Dr. Jessica Ross: Sure. So I think the key takeaway is that, of the tumors in our cohort, the majority were positive for DLL3 and positive for SEZ6. So about 80% of them were positive for DLL3 and 80% were positive for SEZ6. About half of the tumors were stained for both proteins, and about 65% of those were positive as well. So I think if there's sort of one major takeaway, it's that when you're seeing a patient with a high-grade neuroendocrine carcinoma, the odds are that their tumor will express both of these proteins. And so that can sort of get your head thinking about what therapies they might be eligible for. And then we also did an analysis of some populations of interest. So for example, we know that non-neuroendocrine pathologies can transform into neuroendocrine tumors. And so we specifically looked at that subset of patients with transformed tumors, and those were also- the majority of them were positive, about three-quarters of them were positive for both of these two proteins. We looked at patients with brain met samples, again, about 70% were positive. And then I'd say the last sort of population of interest was we had a subset of 10 patients who had serial biopsies stained for either DLL3 or SEZ6 or both. In between the two samples, these patients were treated with chemotherapy. They were not treated with targeted therapy, but interestingly, in the majority of cases, the testing results were concordant, meaning if it was DLL3 positive to begin with, it tended to remain DLL3 positive after treatment. And so I think that's important as well as we think about, you know, a patient who maybe had DLL3 testing done before they received their induction chemo-IO, we can somewhat confidently say that they're probably still DLL3 positive after that treatment. And then finally, we did do a survival analysis among specifically the patients with lung neuroendocrine carcinomas. We looked at whether DLL3 expression affected progression-free survival on first-line platinum-etoposide, and then we looked at did it affect overall survival. And we found that it did not have an impact or the median progression-free survival was similar whether you were DLL3 positive or negative. But interestingly, with overall survival, we found that DLL3 positivity actually correlated with slightly improved overall survival. These were small numbers, and so, you know, I think we have to interpret this with caution, for sure, but it is interesting. I think there may be something to the fact that five of the patients who were DLL3 positive were treated with DLL3-targeting treatments. And so this made me think of, like in the breast cancer world, for example, if you have a patient with HER2-positive disease, it initially portended worse prognosis, more aggressive disease biology, but on the other hand, it opens the door for targeted treatments that actually now, at least with HER2-positive breast cancer, are associated with improved outcomes. And so I think that's one finding of interest as well. Dr. Rafeh Naqash: Definitely proof-of-concept findings here that you guys have in the manuscript. Alissa, if I may ask you, what is the next important step for a project like this in your mind? Dr. Alissa Cooper: Jesse has highlighted a couple of key findings that we hope to move forward with future investigative studies, not necessarily in a real-world setting, but maybe even in clinical trial settings or in collaboration with sponsors. Are these biomarkers predictive? Are they prognostic? You know, those are still- we have some nascent data, data has been brewing, but I think that we we still don't have the answers to those open questions, which I think are critically important for determining not only clinical treatment decision-making, but also our ability to understand sequencing of therapies, prioritization of therapies. I think a prospective, forward-looking project, piggybacking on that paired biopsy, you know, we had a very small subset of patients with paired biopsies, but a larger subset or cohort looking at paired biopsies where we can see is there evolution of these IHC expression, even mRNA expression, as you're saying, is there differential there? Are there selection pressures to targeted therapies? Is there upregulation or downregulation of targets in response not just to chemotherapy, but for example, for other sort of ADCs or bi-specific T-cell engagers? I think those are going to be critically important future studies which are going to be a bit challenging to do, but really important to figure out this key clinical question of sequencing, which we're all contemplating in our clinics day in and day out. If you have a patient, and these patients often can be sick quite quickly, they might have one shot of what's the next treatment that you're going to pick. We can't guarantee that every patient is going to get to see every therapy. How can you help to sort of answer the question of like what should you offer? So I think that's the key question sort of underlying any future work is how predictive or prognostic are these biomarkers? What translational or correlative studies can we do on the tissue to understand clinical treatment decision-making? I think those are the key things that will unfold in the next couple of years. Dr. Rafeh Naqash: The last question for you, Alissa, that I have is, you are fairly early in your career, and you've accomplished quite a lot. One of the most important things that comes out from this manuscript is your mentorship for somebody who is a fellow and who led this project. For other junior investigators, early-career investigators, how did you do this? How did you manage to do this, and how did you mentor Jessica on this project with some of the lessons that you learned along the way, the good and other things that would perhaps help other listeners as they try to mentor residents, trainees, which is one of the important things of what we do in our daily routine? Dr. Alissa Cooper: I appreciate you calling me accomplished. Um, I'm not sure how true that is, but I appreciate that. I didn't have to do a whole lot with this project because Jesse is an extraordinarily smart, driven, talented fellow who came up with a lot of the clinical questions and a lot of the research questions as well. And so this project was definitely a collaborative project on both of our ends. But I think what was helpful from both of our perspectives is from my perspective, I could kind of see that this was a gap in the literature that really, I think, from my work leading clinical trials and from treating patients with these kinds of cancers that I really hoped to answer. And so when I came to Jessica with this idea as sort of a project to complete, she was very eager to take it and run with it and also make it her own. You know, in terms of early mentorship, I have to admit this was the first project that I mentored, so it was a great learning experience for me as well because as an early-career clinician and researcher, you're used to having someone else looking over your shoulder to tell you, "Yes, this is a good journal target, here's what we can anticipate reviewers are going to say, here are other key collaborators we should include." Those kind of things about a project that don't always occur to you as you're sort of first starting out. And so all of that experience for me to be identifying those more upper-level management sort of questions was a really good learning experience for me. And of course, I was fantastically lucky to have a partner in Jesse, who is just a rising star. Dr. Jessica Ross: Thank you. Dr. Rafeh Naqash: Well, excellent. It sounds like the first of many other mentorship opportunities to come for you, Alissa. And Jessica, congratulations on your next step of joining and being faculty, hopefully, where you're training. Thank you again, both of you. This was very insightful. I definitely learned a lot after I reviewed the manuscript and read the manuscript. Hopefully, our listeners will feel the same. Perhaps we'll have more of your work being published in JCO PO subsequently. Dr. Alissa Cooper: Hope so. Thank you very much for the opportunity to chat today. Dr. Jessica Ross: Yes, thank you. This was great. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so as you never miss an episode. You can find all ASCO shows at asco.org/podcasts. 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. Disclosures: Dr. Alissa Jamie Cooper Honoraria Company: MJH Life Scienes, Ideology Health, Intellisphere LLC, MedStar Health, Physician's Education Resource, LLC,  Gilead Sciences, Regeneron, Daiichi Sankyo/Astra Zeneca, Novartis,  Research Funding: Merck, Roche, Monte Rosa Therapeutics, Abbvie, Amgen, Daiichi Sankyo/Astra Zeneca Travel, Accommodations, Expenses: Gilead Sciences

Discover how innovative drip irrigation technologies are transforming water management and boosting efficiency in farming. Mike Hemman, Netafim Senior Vice President of North America, shares his journey from crop protection to leading irrigation solutions, highlighting the challenges and opportunities in modern agriculture. Tune in to explore the future of precision farming and the vital role of water conservation across the globe. *** Show Notes: Ag Solutions Network Socials: https://www.agsolutionsnetwork.com/agemergepodcast https://www.facebook.com/ASN.farm https://www.linkedin.com/company/agsolutionsnetwork https://twitter.com/POWER2GRO https://www.instagram.com/agsolutionsnetwork/ Ag Solutions Network website: https://www.agsolutionsnetwork.com/ Click to watch or listen and as always, let us know if you have any questions or guest ideas by emailing ​contactus@agsolutionsnetwork.com​. Chapters: 00:00:00 - Introduction to Drip Irrigation 00:06:00 - Mike Hemman's Journey 00:12:00 - Innovative Irrigation Solutions 00:18:00 - Water Conservation and Efficiency 00:24:00 - Future of Precision Farming 00:30:00 - Challenges in Water Management 00:36:00 - The Role of Technology in Agriculture 00:42:00 - Sustainable Farming Practices 00:48:00 - Netafim's Global Impact 00:54:00 - Closing Thoughts and Future Outlook *** *** Introducing the Ag Modernization Fund Water basins are strained across the nation, and while modern irrigation remains one of the fastest and most proven ways to improve water use efficiency, many farmers still face barriers to accessing the financing for installing the latest systems. To address this challenge, Orbia, Netafim USA along with California Water Resilience Initiative (CWRI), launched the Ag Modernization Fund, a first-of-its-kind investment vehicle that pools private-sector capital to directly fund irrigation upgrades for growers. Backed by Keurig Dr Pepper, Gilead Sciences, and General Mills, the fund closed in 2025 with $300,000, already supporting five farms spanning 200 acres. These projects, to be completed within the year, are projected to reduce water use by 491 acre-feet — nearly 159 million gallons annually, enough to fill 241 Olympic-sized pools. This fund is also listed on the UN-backed CEO Water Mandate's Water Action Hub, aligning with global sustainability goals to address water stress across 100 priority basins worldwide — 8 of which are in the United States. About Our Guest: Mike Hemman - SVP, Netafim North America Division Mike joined Netafim, Orbia Precision Agriculture business, in 2019 as the President of Netafim USA and was promoted to Senior Vice President of North America in 2024. He has been instrumental in driving strategic growth and expanding profit margins through innovative market strategies, customer segmentation, product lifecycle management, and improvements in supply chain and manufacturing efficiencies. With multiple decades of experience in the crop protection and seed industry, Mike has held key commercial leadership positions at DuPont, Corteva, and Pioneer Seed. His extensive background in biologicals, fertility, crop protection, seed, and irrigation give him a unique cross-sector perspective on the agricultural industry. Mike holds a Bachelor of Science degree in Plant Science from California State University, Fresno, where he also pursued Master of Science coursework in agronomy. He is currently a member of the Executive Board of the Irrigation Association and has previously served on the boards of the Agricultural Retailers Association, Western Plant Health Association, and California Association of Pest Control Advisers.

In this episode, Benjamin Levy, MD, FASCO, and Alex Spira, MD, PhD, FASCO, discuss the latest developments in targeting TROP2 and TIGIT for the treatment of lung cancer, including:TROP2-targeting ADCs: datopotamab deruxtecan, sacituzumab govitecan, sacituzumab tirumotecan TROP2 ADCS for patients with EGFR-mutated NSCLCTIGIT-targeting agents: domvanalimab, rilvegostomigPresenters:Benjamin Levy, MD, FASCOAssociate ProfessorJohns Hopkins School of MedicineClinical DirectorJohns Hopkins Kimmel Cancer Center, National Capitol Region (NCR)Washington, DCAlex Spira, MD, PhD, FASCODirector Clinical ResearchVirginia Cancer SpecialistsCEO NEXT Oncology VirginiaFairfax, VirginiaContent based on an online CME program supported by an independent educational grant from Gilead Sciences, Inc.Link to full program:https://bit.ly/4qZLR6B Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into several groundbreaking advancements and strategic shifts in the industry that promise to reshape the landscape of patient care and therapeutic innovations.The U.S. Food and Drug Administration has introduced a novel regulatory pathway aimed at expediting the approval process for custom gene-editing therapies. Articulated by FDA officials Vinay Prasad, M.D., and Martin Makary, M.D., this new approach is set to revolutionize personalized medicine, particularly for genetic disorders where tailored interventions are crucial. Gene editing technologies, like CRISPR-Cas9, have opened unprecedented avenues for addressing genetic conditions directly at their source. However, the regulatory framework has struggled to keep pace with these advances, often hampering innovation with lengthy and complex approval processes.This proposed pathway seeks to streamline these requirements by adopting a risk-based assessment model that considers the unique properties of gene-editing therapies. Unlike traditional drugs, which follow a uniform clinical trial path, gene-editing treatments require a more nuanced regulatory approach due to their precision and potential off-target effects. The framework emphasizes adaptive trial designs—allowing for modifications based on interim results—and integrates real-world data to create a dynamic regulatory process. This not only promises faster development times but also fosters innovation by making it easier for companies to bring cutting-edge therapies to market.The implications are far-reaching. For researchers and biotech firms, this represents a chance to reduce time-to-market significantly while maintaining high safety standards. It also sets a precedent for future regulatory models that prioritize patient-centric approaches, acknowledging the diverse genetic landscapes of individuals with rare diseases. On a broader scale, this shift underscores the increasing recognition of personalized medicine's potential to transform healthcare delivery.In parallel developments, Gilead Sciences has achieved positive phase 3 results for its single-tablet regimen combining bictegravir and lenacapavir for HIV treatment. This milestone offers hope for simplifying treatment protocols for patients currently on multi-tablet regimens, potentially enhancing adherence and improving health outcomes. Gilead's preparation for regulatory filings marks an essential step forward in their therapeutic portfolio.Turning to cancer treatment advancements, Kyowa Kirin's collaboration with Kura Oncology has led to FDA approval for an oral medication targeting a subset of acute myeloid leukemia patients. This approval highlights the power of strategic partnerships in expediting the development of targeted cancer therapies and brings new hope to patients with limited treatment options.Meanwhile, several pharmaceutical companies, including Fresenius, Sun Pharma, and Teva, have been involved in product recalls ranging from hospital drugs to antibiotics and ADHD medications. These recalls underscore ongoing challenges in maintaining drug safety standards and emphasize the need for rigorous quality control measures across the industry.Zealand Pharma has opted to pause development of its dual GLP-1/GLP-2 agonist, dapiglutide, due to an increasingly crowded metabolic disorder treatment landscape. By reallocating resources towards programs with greater clinical differentiation potential, Zealand reflects broader industry trends prioritizing investments in areas with clearer paths to market success.In malaria treatment advances, Novartis has achieved significant progress with its next-generation drug 'Ganlum,Support the show

Overview: In this episode, Dr Melissa Jones and Dr Christian Ramers discuss the importance of pan-viral screening for HIV and hepatitis. They emphasize the need for integrated testing and prevention strategies and the current barriers to implementation. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Christian B Ramers, MD, MPH, FIDSA, AAHIVS; Melissa Jones, DNP, APRN-BC   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AASLD/IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2025. Available from: https://www.hcvguidelines.org/ (Accessed June 10, 2025). Arora DR et al. ISRN AIDS 2013;2013:287269 Alter MJ. J Hepatol 2006;44:S6–9. Bazargan M, Cobb BMS, Assari S. Ann Fam Med 2021;19:4–15. Beard N, Hill A. Open Forum Infect Dis 2024;11:ofad666. Bottero J, Boyd A, Gozlan J et al. Open Forum Infect Dis 2015;2:ofv162. Brunetto, Maurizia Rossana et al. J Hepatol 2023;79:433–60. Calabrese SK, Krakower DS, Mayer KH. Am J Public Health 2017;107:1883–89. CDC. Status neutral HIV care and service delivery eliminating stigma and reducing health disparities. 2022. Available from: https://stacks.cdc.gov/view/cdc/129024 (Accessed June 10, 2025). CDC. Clinical guidance for PrEP. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/prep/index.html (Accessed June 10, 2025). CDC. Clinical screening and diagnosis for hepatitis C. 2025. Available from: https://www.cdc.gov/hepatitis-c/hcp/diagnosis-testing (Accessed June 10, 2025). CDC. Clinical testing and diagnosis for hepatitis B. 2025. Available from: https://www.cdc.gov/hepatitis-b/hcp/diagnosis-testing/  (Accessed June 10, 2025). CDC. Clinical testing guidance for HIV. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/index.html (Accessed June 10, 2025). CDC. Getting tested for HIV. 2025. Available from: https://www.cdc.gov/hiv/testing/ (Accessed June 10, 2025). CDC. Hepatitis A vaccine. 2025. Available from: https://www.cdc.gov/hepatitis-a/vaccination/index.html (Accessed June 10, 2025). CDC. Hepatitis B vaccine. 2025. Available from: https://www.cdc.gov/hepatitis-b/vaccination/index.html (Accessed June 10, 2025). CDC. HIV infection among heterosexuals at increased risk--United States, 2010. MMWR Morb Mortal Wkly Rep 2013;62:183-8. CDC. Viral hepatitis among people with HIV. 2025. Available from: https://www.cdc.gov/hepatitis/hcp/populations-settings/hiv.html (Accessed June 10, 2025. Clinical info HIV.gov. 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Overview: In this episode, Toyin Nwafor, MD, and Christian B Ramers, MD, draw on their experience in primary care, HIV and HIV prevention to highlight missed opportunities for HIV prevention and discuss strategies to help address gaps in the HIV care continuum. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Toyin Nwafor, MD; Christian B Ramers, MD, MPH, FIDSA, AAHIVS   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AIDSVu.org. Prevalence in the United States. 2022. Available from: https://map.aidsvu.org/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. Baeten J et al. Curr HIV/AIDS Rep 2013;10:142–51. CDC. Clinical testing guidance for HIV. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/index.html (Accessed June 25, 2025). CDC. Discussing sexual health with your patients. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/sexual-history/index.html (Accessed June 25, 2025). CDC.gov. HIV diagnoses, deaths, and prevalence. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/hiv-diagnoses-deaths-prevalence.html (Accessed June 25, 2025). CDC. National HIV prevention and care objectives: 2025 update. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/national-hiv-prevention-and-care-objectives-2025.html (Accessed June 25, 2025). CDC. Preexposure prophylaxis for the prevention of HIV infection in the United States – 2021 update: a clinical practice guideline. 2021. Available from: https://stacks.cdc.gov/view/cdc/112360 (Accessed June 25, 2025). Doblecki-Lewis S et al. J Int Assoc Provid AIDS Care 2019;18:2325958219848848. DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 2, 2025). HIV.gov. HIV treatment as prevention. 2023. Available from: https://www.hiv.gov/tasp (Accessed June 25, 2025). HIV.gov. US statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics (Accessed May 21, 2025). HIV.gov. Viral suppression and undetectable viral load. 2025. Available from: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-treatment/viral-suppression (Accessed July 18, 2025). HIV.gov. Who is at risk for HIV. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/who-is-at-risk-for-hiv (Accessed June 25, 2025). Johns Hopkins Bloomberg School of Public Health. What to know about PrEP. 2025. Available from: https://publichealth.jhu.edu/2025/who-needs-prep-for-hiv-prevention (Accessed June 25, 2025). Kamis KF et al. Open Forum Infect Dis 2019;6:ofz310. KFF. HIV testing in the United States. 2024. Available from: https://www.kff.org/hiv-aids/hiv-testing-in-the-united-states/ting in the United States | KFF (Accessed August 26, 2025). NIH. HIV and sexually transmitted infections (STIs). 2021. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-sexually-transmitted-infections-stis (Accessed June 25, 2025). Ramchandani MS et al. Curr HIV/AIDS Rep 2019;16:244–56. Saag MS et al. JAMA 2018;320:379–96. Sweeney P et al. J Acquir Immune Defic Syndr 2019;82(Suppl 1):S1–5. The White House. National HIV/AIDS strategy for the United States 2022–2025. 2021. Available from: https://files.hiv.gov/s3fs-public/NHAS-2022-2025.pdf (Accessed June 25, 2025). UNAIDS.org. Recommended 2030 targets for HIV. 2025. Available from: https://www.unaids.org/en/recommended-2030-targets-for-hiv (Accessed August 26, 2025). United States Census Bureau. National population by characteristics: 2020-2024. 2024. Available from: https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html (Accessed June 25, 2025). United States Census Bureau. United States Population Growth by Region. 2025. Available from: https://www.census.gov/popclock/ (Accessed June 25, 2025). Yumori C et al. Sex Transm Dis 2021;48:32–6.

Overview: In this episode, Dr Gina Brown and Dr Sahar Khalili draw on their expertise in HIV prevention to provide an overview of the current PrEP landscape in the United States. They highlight advancements in HIV prevention and emphasize the importance of targeted programs to address disparities in access and uptake across population groups and geographic regions. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Gina Brown, MD; Sahar Khalili, PharmD   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References ACOG. Preexposure prophylaxis for the prevention of human immunodeficiency virus. 2024. Available from: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/06/preexposure-prophylaxis-for-the-prevention-of-human-immunodeficiency-virus (Accessed June 25, 2025). ADAP Directory. About. 2024. Available from: https://adap.directory/about (Accessed June 25, 2025). Aidsmap. Condoms. 2023. Available from: https://www.aidsmap.com/about-hiv/condoms#toc-how-effective-are-condoms (Accessed June 25, 2025). AIDSVu. AIDSVu releases new PrEP data and launches PrEPVu.org, a new PrEP equity platform. 2024. Available from: https://aidsvu.org/news-updates/aidsvu-releases-new-prep-data-and-launches-prepvu-org-a-new-prep-equity-platform/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. AIDSVu releases 2024 PrEP use data showing growing use across the U.S. 2025. Available from: https://aidsvu.org/news-updates/aidsvu-releases-2024-prep-use-data-showing-growing-use-across-the-u-s/ (Accessed July 18, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. Location profiles: South. 2025. Available from: https://map.aidsvu.org/profiles/region/south/prevention-and-testing#1-2-PnR (Accessed July 31, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. PrEP use significantly associated with decreasing new HIV diagnoses across U.S. states. 2025. Available from: https://aidsvu.org/news-updates/prep-use-significantly-associated-with-decreasing-new-hiv-diagnoses-across-u-s-states/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. Baeten J et al. Curr HIV/AIDS Rep 2013;10:142–51. Bekker LG et al. N Engl J Med 2024;391:1179–92. CDC. About ending the HIV epidemic in the US. 2024. Available from: https://www.cdc.gov/ehe/php/about/index.html (Accessed June 2, 2025). CDC. Clinical Guidance for PrEP. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/prep/index.html (Accessed June 25, 2025). CDC. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2021 update. 2021. Available from: https://stacks.cdc.gov/view/cdc/112360 (Accessed June 25, 2025). Coates TJ et al. Lancet 2008;372:669–84. DHHS. Pre-exposure (PrEP) to prevent HIV during periconception, antepartum, ad postpartum. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/perinatal-hiv/pre-exposure-prophylaxis-prep-prevent-hiv-perinatal.pdf (Accessed June 25, 2025). Gandhi RT et al. JAMA 2023;329:63–84. HIV.gov. HIV treatment as prevention. 2023. Available from: https://www.hiv.gov/tasp (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 2, 2025). HIV.gov. Pre-exposure prophylaxis. 2025. Available from: https://www.hiv.gov/hiv-basics/hiv-prevention/using-hiv-medication-to-reduce-risk/pre-exposure-prophylaxis (Accessed June 25, 2025). Kelley CF et al. N Engl J Med 2025;392:1261–76. Kourtis AP et al. Ann Epidemiol 2025:106:48-54. Landers S et al. Am J Public Health 2017;107:1534–35. Landovitz RJ et al. N Engl J Med 2021;385:595–608. NIH. HIV and sexually transmitted infections (STIs). 2021. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-sexually-transmitted-diseases-stds (Accessed June 25, 2025). NIH. HIV medicines during pregnancy and childbirth. 2025. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-medicines-during-pregnancy-and-childbirth (Accessed July 31, 2025) NIH. Post-exposure prophylaxis (PEP). 2025. 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Overview: In this episode, Dr Joel Gallant gives a history of antiretroviral therapy and HIV drug resistance, drawing on his personal and professional experience beginning in the early 1980s. The views expressed are those of the panelist and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2023 and the content reflects the information available at that time. Guest: Joel Gallant, MD, MPH    For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus    References AIDSVu.org. New HIV diagnoses. 2023. 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Overview: In this episode, Dr Toyin Nwafor and Dr Andrew Zolopa provide an overview of the HIV treatment landscape both globally and in the United States. They highlight the current gaps in the HIV care continuum, emphasize the importance of rapid start and viral suppression in reducing HIV transmission through sex and describe initiatives and strategies aimed at closing these gaps to help end the HIV epidemic in the United States. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Toyin Nwafor, MD; Andrew Zolopa, MD   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AETC. Rapid (immediate) ART initiation and restart: guide for clinicians. 2023. Available from: https://aidsetc.org/resource/rapid-immediate-art-initiation-restart-guide-clinicians (Accessed June 25, 2025). Baxter A et al. J Acquir Immune Defic Syndr 2025;99:47–54. CDC. About ending the HIV epidemic in the US. 2024. Available from: https://www.cdc.gov/ehe/php/about/index.html (Accessed June 25, 2025). CDC. Clinical testing guidance for HIV. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/index.html (Accessed June 25, 2025). CDC. Getting tested for HIV. 2025. Available from: https://www.cdc.gov/hiv/testing/index.html#cdc_testing_why_get_tested-why-get-tested (Accessed June 25, 2025). CDC. Laboratory testing for the diagnosis of HIV infection. 2014. Available from: https://stacks.cdc.gov/view/cdc/23446 (Accessed June 25, 2025). CDC. National HIV prevention and care objectives: 2025 update. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/national-hiv-prevention-and-care-objectives-2025.html (Accessed June 25, 2025). Delaney KP et al. Am J Prev Med 2021;61(5 Suppl 1):S6–S15. DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (Accessed June 25, 2025). HIV.gov. EHE overview. 2025. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview (Accessed June 25, 2025). HIV.gov. Global statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics (Accessed June 25, 2025). HIV.gov. HIV Care Continuum. 2025. Available from: https://www.hiv.gov/federal-response/other-topics/hiv-aids-care-continuum (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 25, 2025). HIV.gov. US statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics (Accessed June 25, 2025). HIV.gov. Viral suppression and undetectable viral load. 2025. Available from: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-treatment/viral-suppression (Accessed June 25, 2025). Mirzazadeh A et al. PLoS Med 2022;19:e1003940. NIH. HIV testing. 2025. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-testing (Accessed June 25, 2025). Palacio-Vieira J et al. BMC Public Health 2021;21:1596. Saag MS et al. JAMA 2018;320:379–96. The White House. National HIV/AIDS strategy for the United States 2022–2025. 2021. Available from: https://files.hiv.gov/s3fs-public/NHAS-2022-2025.pdf (Accessed June 25, 2025). WHO. Supporting re-engagement in HIV treatment services: policy brief. 2024. Available from: https://www.who.int/publications/i/item/9789240097339 (Accessed June 25, 2025).

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of groundbreaking developments that are reshaping the landscape of drug development and patient care. These stories highlight the dynamic nature of the pharmaceutical and biotechnology industries, where scientific advancements and regulatory changes are driving significant shifts.We begin with a crucial milestone in oncology treatment. The FDA has granted approval to Johnson & Johnson's Darzalex Faspro for patients with high-risk smoldering multiple myeloma. This approval is particularly significant as it provides a new therapeutic pathway for individuals with this precursor condition to active multiple myeloma, which previously had few treatment options. The drug works by targeting CD38 proteins on myeloma cells, representing a leap forward in monoclonal antibody treatments for cancer. This decision underscores the FDA's ongoing commitment to expanding treatment options for conditions with high unmet needs, potentially setting a precedent for future approvals in early-stage malignancies.Meanwhile, Gilead Sciences encountered challenges with its oncology pipeline as Trodelvy failed to meet its primary endpoint in a Phase 3 trial for first-line HR+/HER2-negative metastatic breast cancer. This outcome highlights the complexities of oncology drug development, despite previous successes in other indications. Such setbacks remind us of the inherent risks involved in bringing innovative therapies to market.In contrast, Akeso has announced positive data for ivonescimab, a PD-(L)1xVEGF bispecific antibody. The drug demonstrated significant overall survival benefits in patients with previously treated EGFR-mutated non-small cell lung cancer. This advancement underscores the therapeutic potential of bispecific antibodies in cancer immunotherapy, which continue to gain traction as they target multiple pathways involved in tumor growth and immune evasion.Regulatory incentives have also been making waves. The FDA's rollout of the second round of "national priority" voucher winners aims to accelerate drug development timelines, particularly in critical areas such as obesity. Companies like Lilly and Novo Nordisk have been recognized for their efforts, highlighting a broader strategy to bring transformative therapies to market more swiftly.On the corporate front, Bayer's proposed private equity buyout fell through due to insufficient shareholder support, reflecting ongoing financial volatility and strategic recalibrations within biotech firms. Meanwhile, CMS's introduction of a new Medicaid pricing model aims to implement "most-favored nation" pricing strategies to control drug costs, signaling potential shifts in how pharmaceutical companies approach pricing negotiations and reimbursement strategies.Technological advancements are also at the forefront of innovation. Eli Lilly has expanded its AI-driven drug discovery partnership with XtalPi, focusing on antibody development. This collaboration exemplifies how AI is increasingly being integrated into pharmaceutical research to enhance drug discovery processes.Furthermore, China's decision to lift its ban on Illumina's DNA sequencers is expected to facilitate greater access to advanced genomic technologies within the region, fostering innovation in precision medicine.Leadership changes continue to shape industry dynamics. For instance, Recursion Pharmaceuticals is undergoing executive restructuring to better align with evolving market needs and innovation strategies. These changes are crucial for maintaining competitiveness and fostering an environment conducive to scientific breakthroughs.The industry is also witnessing strategic realignmenSupport the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of fascinating advancements and strategic movements that are shaping the landscape of drug development and patient care.Starting with a significant milestone in precision oncology, China has approved its first EGFR-targeted antibody-drug conjugate. This approval marks a pivotal moment in the industry's shift towards targeted therapies, which promise more precise treatment options with potentially fewer side effects than traditional chemotherapy. Targeted therapies are at the forefront of personalized medicine, where treatments are tailored to individual genetic profiles, offering hope for more effective cancer care.In the realm of HIV prevention, Gilead Sciences has reported impressive sales for its new long-acting pre-exposure prophylaxis medication, Yetztugo. Since its launch in June 2025, Yetztugo has generated $54 million in U.S. sales, underscoring the demand for long-term HIV prevention solutions. This development is part of Gilead's broader strategy to strengthen its HIV franchise as it advances its pipeline with promising candidates like GS-3242 alongside lenacapavir. The aim is to develop treatments that require less frequent dosing, which could significantly improve patient adherence and outcomes. Despite challenges within its HIV portfolio and declining Veklury sales, Gilead Sciences is actively seeking growth opportunities through strategic partnerships and pipeline advancements—an essential approach for navigating patent cliffs while sustaining long-term growth.On the financial front, AbbVie has increased its revenue forecast by $400 million to a staggering $60.9 billion, driven by robust sales from its immunology drugs Skyrizi and Rinvoq. These treatments address chronic inflammatory conditions like psoriasis and rheumatoid arthritis, reflecting AbbVie's strong positioning in this therapeutic area despite competitive pressures. AbbVie continues to report strong earnings from Skyrizi and Rinvoq, reinforcing its dominance in the immunology market and highlighting the profitable nature of successful biologics in treating chronic inflammatory diseases.Biogen continues to bolster its multiple sclerosis franchise by focusing on both legacy treatments and new product launches. This strategy highlights the importance of balancing innovation with lifecycle management to maintain market strength against generic competition—a common challenge in the industry.Meanwhile, the American Academy of Pediatrics has taken a cautious stance by not endorsing leucovorin for autism treatment due to insufficient evidence. This decision emphasizes the critical need for rigorous, evidence-based practices in developing clinical guidelines for complex disorders like autism.Internationally, CSL Seqirus has partnered with Saudi Arabia to supply cell-based influenza vaccines and support local production capabilities. This move aligns with global efforts to enhance pandemic preparedness and healthcare resilience through local manufacturing initiatives.The volatile nature of the biotech sector is evident with reports of 16 companies ceasing operations in 2025 due to high R&D costs and regulatory challenges. Despite these closures, such volatility opens doors for new innovations that could address unmet medical needs.Turning our attention to obesity treatment, Eli Lilly stands at a crucial juncture with its novel obesity medication, orforglipron. The company aims to make this weight loss pill accessible while maintaining financial viability for future R&D—a balancing act faced by many pharmaceutical companies as they strive to deliver affordable yet innovative treatments amid growing global health concerns. However, not all R&D efforts reach fruition. Eli Lilly has decided to discontinue its mid-stage program Support the show

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management 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 program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management 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 program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management 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 program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management 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 program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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. Follow today's speakers:       Dr. Hope Rugo  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

Dr. Monty Pal and Dr. Matteo Lambertini discuss a compelling global study on the clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers, the association of pre-diagnostic awareness of BRCA status with prognosis, and the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants. TRANSCRIPT Dr. Monty Pal: Well, hello everyone, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. Now, when we think about genetic testing, whether for patients diagnosed with breast cancer or for other family members of them, it seems to be widely underutilized. Today, we're going to be discussing a recently published study in the Journal of Clinical Oncology that reported on the clinical behavior of breast cancer and specifically young BRCA1 and BRCA2 carriers, and the association of pre-diagnostic awareness of BRCA status with prognosis. I thought this was just a fascinating piece, and I honestly couldn't wait to have this conversation. It's a really compelling paper that highlights the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants, and really the need for genetic counseling and testing to inform people about early detection that could lead to a better prognosis. I'm really delighted to welcome the study's lead author, Dr. Matteo Lambertini. He really needs no introduction. He's very well known in the breast cancer world for his amazing contributions to fertility in the context of breast cancer, to pregnancy in the context of breast cancer, and genetic testing. He's an associate professor at the University of Genova, and a breast cancer medical oncologist at the San Martino Polyclinic Hospital in Genova, Italy.  Dr. Lambertini, thank you so much for joining us today. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a great pleasure. Dr. Monty Pal: Oh, thanks. And just FYI, if you're listening in and you want to hear our disclosures, they're all listed at the transcript of this podcast.  So, I poured through this paper [Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status] yesterday, Dr. Lambertini, and first of all, congratulations on this study. This was a huge international multicenter effort, 4,752 patients. How did you pool all these patients with young breast cancer? Dr. Matteo Lambertini: Thanks a lot for the question. Yes, this was an effort made by several centers all over the world. The main idea behind the creation of this network that we have named as BRCA BCY Collaboration, was to get as many data as possible in a sort of niche patient population in the breast cancer field, meaning women diagnosed with breast cancer at the age of 40 years or younger, and all of them being BRCA carriers. We know that around, in the Western world, around 5% of breast cancer cases are being diagnosed under the age of 40 years, and among them around 10-15% are BRCA carriers. So, I would say it's a relatively rare patient population where we did not have a lot of evidence to support our choices in terms of counseling on treatment, prevention, and oncofertility as well. That was the idea behind the creation of this network that includes many centers. Dr. Monty Pal: Yeah. You know, what's so interesting about this is that you sort of draw this line between patients who have BRCA testing at the time of diagnosis and then BRCA testing earlier in their course and then leading to a diagnosis perhaps. And I think that's where really sort of the dichotomy in outcome sits. Can you maybe elaborate on this and tell us about timing of genetic testing in this study and what that meant ultimately in terms of prognosis? Dr. Matteo Lambertini: In this specific analysis from this large network, including almost 5,000 women with breast cancer diagnosed at the age of 40 years or younger and being a BRCA carrier, we looked specifically into the timing of genetic testing because this is a retrospective study and the criteria for inclusion are those that I have just mentioned, so diagnosis at a young age plus carrying germline BRCA pathogenic or likely pathogenic variant. In this analysis, we have looked into the time the patient has got the genetic testing and particular we focused on two populations: those that were diagnosed, knowing already to be a BRCA carrier, and those that got tested after being diagnosed with breast cancer. And the main findings from this analysis have been that knowing to be a BRCA carrier was associated with a lower stage at the time of diagnosis, meaning more T1 tumors, so a tumor less than 2 cm, more node-negative disease, and this translated into less aggressive treatment, so less often axillary dissection, less often use of chemotherapy and anthracycline-based chemotherapy. And even more importantly, we have seen a better overall survival for those patients that were diagnosed already knowing to be BRCA carriers as compared to those tested after breast cancer diagnosis. These results after adjusting for all the confounding, stage, treatment and so on, there was not significant anymore, meaning that it's not the timing of test per se that is probably leading to a better survival, but it is the fact that knowing to be a BRCA carrier would likely translate into having access to all the preventive measures that we have in this setting and this will translate into an overall survival benefit, so in terms of saving more lives in young BRCA carriers. Dr. Monty Pal: I think it's such an important point, and it's one that I think might sound implicit, right, but it needs to be proven, I think, through a study like this. You know, the fact that finding this early, identifying the mutation, doing enhanced screening, and so forth, is really going to lead to superior clinical outcomes. One of the things that I think many people puzzle over, including myself, is what to do? I personally occasionally will see BRCA altered patients in the context of prostate cancer. But that's a very different population of individuals, right? Typically older men. In young females with BRCA mutation, I guess there's a specific set of considerations around reproductive health. You'd already highlighted preventive strategies, but what sorts of things should we be talking about in the clinics once a patient's diagnosed and once perhaps their breast cancer diagnosis is established? Dr. Matteo Lambertini: Yes, exactly. Knowing to be a BRCA carrier has a lot of implications from prevention to treatment to survivorship issues including reproductive counseling. And this is important not only for the patient that has been diagnosed with breast cancer but also for all the family members that will get tested and maybe identify with this sort of genetic alteration before diagnosis of cancer. Why this is important is because we have access to very effective preventive measures, a few examples: MRI screening, which starts at a very young age and normally young women don't have an effective screening strategy outside the BRCA field. Also, primary preventive measures, for example, risk-reducing surgery. These women are known to have a high risk of breast cancer and high risk of ovarian cancer. So the guidelines are suggesting to undergo risk-reducing salpingo-oophorectomy at a young age, so 35 to 40 years in BRCA1 carrier, 40 to 45 years in BRCA2 carrier. And also risk-reducing mastectomy should be discussed because it is a very effective way to prevent the occurrence of breast cancer. And in some situations, including the setting that we are talking about, so young women with breast cancer, BRCA carrier, also risk-reducing mastectomy has shown to improve overall survival.  On the other side, once diagnosed with breast cancer, nowadays knowing to be or not a BRCA carrier can make a difference in terms of treatment. We have PARP inhibitors in the early setting, in the adjuvant setting as well as in the metastatic setting. And in terms of survivorship implication, one of the critical aspects for young women is the oncofertility care which is even more complicated when we talk about BRCA carriers that are women candidates for gynecological surgery at a very young age. So this sort of counseling is even more complicated. Dr. Monty Pal: One of the other things, and this is subtle in your paper and I hope you don't mind me bringing it up, is the difference between BRCA1 and BRCA2. It really got me thinking about that because there are differences in phenotype and manifestation. Do you mind just expanding on that a little bit for the audience because I think that's a really important reminder that you brought up in the discussion? Dr. Matteo Lambertini: The difference between BRCA1 and BRCA2 carriers has been known that there are different phenotypes of breast cancer that are more often diagnosed in these two different populations. Normally BRCA1 carriers have a higher likelihood to develop a triple negative breast cancer as compared to BRCA2 carriers, more likely to develop a hormone receptor-positive HER2-negative disease. In this study, again, a specific population of young women with breast cancer, we have seen the same findings, mostly triple negative disease in BRCA1 carrier, mostly luminal-like disease in BRCA2 carrier. But what's novel or interesting from this study is to look also at the age at the time of diagnosis of this disease. And particularly in BRCA1 carriers, we should be sort of more careful about diagnosis of breast cancer and also other primary tumors including ovarian cancer because the risk of developing these malignancies is higher even at a younger age as compared to BRCA2 carriers. And this has implications also in the primary and secondary prevention that we were talking about earlier. Dr. Monty Pal: Oh, interesting. I guess the fundamental question then from your paper becomes, how do we get at the right patients for screening for BRCA1 and BRCA2? And I realize our audience here is largely oncologists who are going to be listening to this podcast, oncology providers, MDs, nurses, etc. But maybe speak for a moment to the general practitioner. Are there things that, for instance, a general practitioner should be looking for to say, “Wait a minute, this patient's high risk, we should consider BRCA1, BRCA2 testing or germline screening”? Dr. Matteo Lambertini: Yes, it's a very important question for the breast cancer community. After the updated ASCO guideline, the counseling is way easier because right now the age cutoff goes up to 65 years, meaning that all the patients diagnosed with breast cancer below the age of 65 years should be tested these days. And then above the age of 65, there are different criteria like triple-negative disease or family history. From a general practitioner standpoint, it's of course a bit more difficult, but knowing particularly the family history of the person that they have in front will be crucial to know if there are cases of breast cancer diagnosed at a young age, maybe triple-negative cases, knowing cases of ovarian cancer in first-degree relatives or pancreatic cancer in first-degree relatives, and of course cases of prostate cancer as well. So, I would say probably mostly the family side will be important from a general practitioner perspective.  From an oncology one, the other point that I think is important to stress also based on the data that we have shown in this publication is that having a case of breast cancer known to carry a BRCA pathogenic or likely pathogenic variant. It means that all the people around this case should get tested and if found to be BRCA carrier and healthy carrier, these people should also undergo the primary and secondary prevention strategies because this is very critical also to improve their outcomes and try to avoid the developing of breast or ovarian cancer, but also in the case of diagnosis of this disease, a diagnosis at an earlier stage, as we have seen in this paper. Dr. Monty Pal: Brilliant. I'm going to diverge from our list of questions here and close by asking a question that I have at the top of my mind. You're very young. I know our podcast listeners can't see you, but you're very, very young. Dr. Matteo Lambertini: Thank you. Thank you for that. Not so young but yeah. Dr. Monty Pal: You have nearly 300 papers. Your H-index is 67. You've already made these seminal contributions, as I outlined it from the outset, regarding fertility, regarding use of GnRH analogs, regarding pregnancy and breast cancer. What are you studying now? What are you really excited about right now that you're doing that you think might potentially be practice changing? Give us a little teaser. Dr. Matteo Lambertini: Yeah. Thanks a lot, Dr. Pal. Receiving this compliment from you is fantastic. So, thanks a lot for that. From my side, in terms of my research, I've been interested in the field of breast cancer in young women since the start of my training. I've had very good mentors from Italy, from Europe, from the U.S. I'm still interested in this field, so I think we still have a lot to learn to try to improve the care of young women with breast cancer. For example, the oncofertility care, which is something I worked a lot over the past years. Now with all the new treatment options, there's a sort of new chapter of oncofertility counseling. So, what's the impact of immunotherapy? What's the impact of the new targeted agents?  More on the genetic aspects, now we know that there's not only BRCA1 or BRCA2. There are a lot of other different genes that may increase the risk of breast cancer and other malignancies. And also for these genes, we really don't have a lot of evidence to counsel women on prognosis, treatment, prevention strategy. So we need to learn way more for this special patient population that are quite rare, and so we really need a multicenter academic effort to try to give some evidence in this field. Dr. Monty Pal: Yeah. It's tough because these are rare circumstances, but, you know, I think that you've done really well to sort of define some collective experiences that I think really define therapy. I mean, I just remember when I was in training 25 years ago, just reading through textbooks where all the experience around breast cancer and pregnancy was really just very sort of anecdotal almost, you know? And so it's great to see that the state of the science has moved forward.  Well, gosh, I really enjoyed our conversation today. I think your study really reminds us how powerful genetic information is in terms of improving outcomes. And, you know, hopefully this will lead some individuals to perhaps test more broadly in appropriate settings. So, thank you so much, Matteo, for joining us today with your fantastic insights on the ASCO Daily News Podcast. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a real pleasure. Dr. Monty Pal: And thanks to our listeners too. You'll find a link to Dr. Lambertini's study in the transcript of this episode. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks a ton. 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. Sumanta (Monty) Pal  @montypal  Dr. Matteo Lambertini @matteolambe   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Monty Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Matteo Lambertini: Consulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seagen, Menarini, Nordic Pharma Speakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, Libbs, Daiichi Sankyo, Gilead Sciences, AstraZeneca, Menarini, AstraZeneca, Menarini Research Funding (Inst.): Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Daiichi Sankyo Europe GmbH, Roche

HIV isn’t over — it’s just been ignored. Black women account for a disproportionate number of new cases, the South is ground zero, and the stigma is still killing us. Roland Martin, Dr. Toyin Nwafor, Raheem DeVaughn, and frontline organizers break the silence on a public health crisis America refuses to face. In response to this staggering trend, Gilead Sciences has launched the Setting the P.A.C.E. initiative. The Prevention, Arts and Advocacy, Community, and Education program is a three-year, $12.6 million commitment aimed at expanding HIV prevention efforts in underserved communities. Dr. Toyin Nwafor, Executive Director of Gilead U.S. HIV Medical Affairs, and Raheem DeVaughn, an award-winning musician and partner in the Gilead Setting the P.A.C.E. initiative.