Podcasts about alnylam

This episode covers: Cardiology This Week: A concise summary of recent studies Colchicine for secondary prevention An algorithmic approach to the workup of syncope Milestones: CIBIS II Host: Rick Grobbee Guests: Carlos Aguiar, Sanjit Jolly, Michele Brignole Want to watch that episode? Go to: https://esc365.escardio.org/event/1805 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Michele Brignole, Diederick Grobbee and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Sanjit Jolly has declared to have potential conflicts of interest to report: grant support from Boston Scientific, honorarium from Boston Scientific, Shockwave, Abiomed, SIS, and Teleflex.  Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Rick Grobbee Guest: Michele Brignole Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1805?r  Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Michele Brignole, Diederick Grobbee and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

We love to hear from our listeners. Send us a message. On today's episode, Tolga Tanguler, EVP and Chief Commercial Officer at Alnylam Pharmaceuticals, talks about commercializing RNAi therapies, how they fit into health insurance reimbursement systems, the company's use of value-based contracts, and building therapeutic franchise "skyscrapers." Tangular also shares his thoughts on commercializing RNAi therapies for larger patient populations, compared with rare disease populations, and reflects on changes in the biopharmaceutical sales and promotion model.This episode is brought to you by Avantor. For more information, visit avantorsciences.comAccess this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.comFind Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

This episode covers: Cardiology This Week: A concise summary of recent studies Hypertension in the elderly The digital twin in cardiology Snapshots Host: Emer Joyce Guests: Carlos Aguiar, Gianfranco Parati, Nico Bruining, Joost Lumens Want to watch that episode? Go to: https://esc365.escardio.org/event/1804 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Nico Bruining, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Joost Lumens has declared to have potential conflicts of interest to report: research grants from Medtronic (all grants paid to institute, Maastricht University). Gianfranco Parati has declared to have potential conflicts of interest to report: honoraria for lectures by Omron, Merck, Viatris, Somnomedics. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guests: Joost Lumens and Nico Bruining Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1804?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.  Declarations of interests: Stephan Achenbach, Nico Bruining, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Joost Lumens has declared to have potential conflicts of interest to report: research grants from Medtronic (all grants paid to institute, Maastricht University). Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Lilly is currently involved in a legal battle with compounders over knockoff versions of tirzepatide, marketed as Zepbound for weight loss. The FDA has prohibited compounders from producing these knockoffs after confirming the end of the tirzepatide shortage in December 2024. On the other hand, BMS is facing disappointment with Cobenfy's late-stage failure in treating schizophrenia, marking their second high-profile setback in recent weeks. RFK is contemplating removing COVID-19 from the CDC's vaccine guidelines for children to align with other countries and the WHO. Biotech investors are navigating a turbulent period due to new tariffs and economic uncertainty, causing additional upheaval in an already fragile market. Trump is looking to reinstate international drug pricing policies, while Swiss ADC Biotech is opting for the SPAC route to Nasdaq.Summit's bispecific has outperformed another cancer medication, putting pressure on Keytruda's dominance. In the midst of this biotech downturn, Wacker Biotech is offering advanced therapy process development and production services. Moving on to the next news, executives in the pharmaceutical industry often receive substantial golden parachutes upon leaving a company. Pfizer is defending its cardiac blockbuster drug against competition from Alnylam and BridgeBio. The biotech sector was showing signs of a rebound until new tariffs and economic uncertainty introduced further instability.Lilly is pursuing legal action against compounders for producing counterfeit drugs, while Roche and Regeneron are committing billions to US manufacturing amidst tariff challenges. The industry is undergoing significant changes under the current administration, with opportunities to learn from global markets. Challenges such as investor pullback and market volatility are impacting the biotech sector.Janssen's departure from Galapagos and the promising future of all-American biotech companies are also discussed. Stay tuned for more updates on upcoming events and job opportunities in the field.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Roche and Regeneron are both investing heavily in US manufacturing, with Roche committing $50 billion and Regeneron signing a $3 billion deal with Fujifilm. This move comes as Trump's tariffs threaten the industry. Meanwhile, Pfizer, Alnylam, and BridgeBio are competing in the market for ATTR-CM treatment, with Alnylam and BridgeBio vying for patients switching from Pfizer's tafamidis drug and all three companies seeking new patients.Novo Nordisk has filed for FDA approval of an oral weight loss pill, AstraZeneca and Daiichi Sankyo are pushing their drug Enhertu for frontline breast cancer treatment, and Gilead's Trodelvy in combination with Keytruda has shown promise in slowing disease progression in triple-negative breast cancer. Wacker Biotech is offering services for advanced therapies, while Tempest has recently laid off 80% of its workforce.The industry is facing regulatory challenges and economic uncertainty, with Trump's tariffs potentially impacting pharma companies. Lilly has promised to manufacture a weight-loss pill in the US following a phase III win, and Makary discusses rare disease approvals and public distrust in a new interview. Biotech's future may be more focused on American companies according to PitchBook.

This episode covers: Cardiology This Week: A concise summary of recent studies Current indications for pulmonary vein isolation Conduction system pacing EHRA 2025 scientific highlights Host: Susanna Price Guests: Haran Burri, Isabel Deisenhofer, Helmut Puererfellner, Emma Svennberg Want to watch that episode? Go to: https://esc365.escardio.org/event/1803   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Haran Burri has declared to have potential conflicts of interest to report: institutional research and fellowship support or speaker honoraria from Abbott, Biotronik, Boston Scientific, Medtronic, Microport. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Isabel Deisenhofer has declared to have potential conflicts of interest to report: speaker honoraria and travel grants from Abbott Medical, Biosense-Webster, Boston Scientific, BMS, Volta Medical, and research grant (for the institution) from Abbott Medical and Daiichi Sankyo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Helmut Puererfellner has declared to have potential conflicts of interest to report: speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member, etc., including travel funding related to these activities for the following companies: Abbott, Biotronik, Biosense Webster, Boston Scientific, Daiichi Sankyo, Medtronic. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Sanofi and Alnylam have received FDA approval for the first RNAi treatment for hemophilia, with the drug, Qfitlia, indicated for both hemophilia A and B. This approval is significant as it can be given regardless of the presence of neutralizing antibodies against clotting factors VIII or IX. However, the sudden departure of FDA director Peter Marks has caused uncertainty in the biopharma industry. In other news, Vertex has cut a diabetes asset but analysts remain optimistic about their phase III option. Lilly's RNA silencer has shown promising results in lowering a key cardiovascular biomarker. Trilink is offering custom guide RNAs for CRISPR workflow to accelerate therapy discoveries. Despite market challenges, the cell and gene therapy sector has seen a 30% investment surge. Companies like Amgen, Aldeyra, and Argenx are among those with upcoming FDA actions. Arbutus has announced layoffs, while big pharmas are pushing boundaries in radiopharmaceuticals. Michelle Werner of AltoRNA is focused on making better drugs. Safety questions are looming in Duchenne as Dyne and Wave plan FDA filings. There are job opportunities available in data management and program leadership within the biopharma industry.Moving on to other news, several big pharmaceutical companies such as Novartis, Bayer, AstraZeneca, Bristol Myers Squibb, and Eli Lilly are competing in the radiopharmaceuticals market, which is projected to be worth over $13 billion by 2033. The FDA is expected to announce decisions on therapies for dry eye disease soon. Michelle Werner, CEO of AllTrna, is focused on developing trna-based treatments for various diseases.Safety concerns are emerging in the Duchenne muscular dystrophy space as companies like Dyne and Wave plan FDA filings. The EU rejected Lilly's Alzheimer's drug Kisunla, Biontech's bispecific showed promise in treating SCLC patients, and Wave's duchenne exon-skipper reversed muscle damage in a mid-stage trial. Job opportunities within the biopharma industry were also highlighted for those interested.Thank you for tuning in to Pharma and Biotech daily - keeping you updated on all the latest news in the world of pharmaceuticals and biotechnology.

On this week's episode, Sam Fazeli, Eric Schmidt, and Brian Skorney are joined by Roivant's Matthew Gline to discuss data, deals and the latest policy updates. The episode kicks off with concerns over potential U.S. Department of Health and Human Services (HHS) funding cuts for domestic HIV programs, with the group analyzing the impact on companies like Gilead and GSK, whose HIV prevention drugs have driven significant investor enthusiasm. They then discuss the uncertainty surrounding the new administration's commitment to public health initiates, considering Robert F. Kennedy Jr.'s appointment as HHS Secretary and his past controversial views on vaccines and HIV prevention. The conversation then shifts to data, including positive results from Immunovant and Roivant's Phase 3 study of batoclimab for myasthenia gravis. The group also examines the surprising absence of short sellers engaging with Roivant post-data release, highlighting shifts in biotech trading strategies. In the muscular dystrophy space, new exon-skipping therapies from Avidity and Dyne show unprecedented dystrophin restoration, suggesting potential functional benefits. However, the tragic death of a patient treated with Sarepta's gene therapy, Elevidys, reignites concerns about accelerated approvals and the FDA's risk-benefit calculus in rare disease research. On the deal-making front, AstraZeneca's $425M acquisition of stealth-mode cell therapy startup EsoBiotec and Sanofi's $600M deal with Dren Bio underscore biotech's valuation disconnect, where early-stage private assets command premium prices while public biotechs struggle. The episode closes with insights into Alnylam's broad label win for Amvuttra in ATTR cardiomyopathy and AstraZeneca's $2.5B investment in biotech agreements and manufacturing in China, reflecting its long-term strategic vision despite ongoing geopolitical tensions. *This episode aired on March 21, 2025

Host: Susanna Price  Guest: Thomas Deneke  Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1802?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Thomas Deneke, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Relevance and management of ventricular ectopic beats  Lp(a) in cardiovascular risk management Mythbusters: A vegetarian diet lowers cardiovascular risk Host: Susanna Price Guests: Carlos Aguiar, Thomas Deneke, Kausik Ray Want to watch that episode? Go to: https://esc365.escardio.org/event/1802 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Thomas Deneke, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Kausik Ray declared to have potential conflicts of interest to report: research grants from Amarin, Amgen, Daiichi Sankyo, Merck Sharp & Dohme, Pfizer, Regeneron, and Sanofi, consultant for Abbott, Amarin, Amgen, AstraZeneca, Bayer, Biologix, Boehringer Ingelheim, Cargene Therapeutics, CRISPR, CSL Behring, Eli Lilly and Company, Esperion, Kowa Pharmaceuticals, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Scribe Therapeutics, Silence Therapeutics, Vaxxinity, and Viatris, honoraria for lectures from Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi, Amgen, Esperion, Daiichi Sankyo, Macleod and stock options New Amsterdam Pharma, Pemi 31, SCRIBE Therapeutics. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

President Donald Trump doubled down on tariff threats targeting pharma, saying additional levies on pharmaceuticals will come “at some point,” per CNBC. Meanwhile, Johnson & Johnson became the latest big pharma to respond to Trump's warning of potential tariffs if companies don't reshore their manufacturing, announcing a massive $55 billion U.S. manufacturing and R&D investment. Not all companies are on board, however: AstraZeneca is looking eastward, pumping $2.5 billion into a new research facility in Beijing.    Also on the policy front, Trump nominated acting CDC director Susan Monarez for the top job after pulling his first nominee, Dave Weldon, days before his senate hearing was expected to begin. If confirmed, Monarez would be the first CDC director since 1953 to not have a medical degree; she holds a Ph.D. in microbiology and immunology from the University of Wisconsin.   In weight loss news, Novo Nordisk is paying China-based United Laboratories $200 million upfront to license a triple agonist of the GLP-1, GIP and glucagon receptors that could one day compete with Eli Lilly's retatrutide. And BioSpace examines the next great challenge for GLP-1s: oral formulation manufacturing.    Two more therapeutic spaces in focus last week are Duchenne muscular dystrophy and spinal muscular atrophy, where companies including Dyne Therapeutics, REGENXBIO and Novartis presented new data on their respective candidates. And the Duchenne community continued to react to news of the death of a patient taking Sarepta's approved gene therapy Elevidys.  In cardiovascular news, Alnylam won a much-anticipated approval for Amvuttra as the first RNAi silencer for transthyretin amyloid cardiomyopathy, setting up a three-way race with Pfizer's tafamidis—marketed as Vyndaqel and Vyndama—and BridgeBio's Attruby. Next up is Milestone Therapeutics' CARDAMYST in paroxysmal supraventricular tachycardia, which has a PDUFA date of March 27.   Finally, the saga of Cassava Sciences' Alzheimer's hopeful simufilam is over, as the company announced it has ended development of the controversial candidate.   

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.The CDC has rescheduled a vaccine meeting for April, while President Trump is considering Texas Republican Michael Burgess as the new director of the agency. J&J's Tremfya has won approval for expansion in treating Crohn's disease, while Adaptimmune is facing financial uncertainty despite sales of its T cell therapy. Alnylam's Amvuttra has been approved as the first RNAi silencer for a rare type of cardiomyopathy, setting up competition with Pfizer and BridgeBio. Sino Biological has developed reagents for the 2025-2026 influenza vaccine strains. In other news, J&J plans to boost US manufacturing following tariff threats, Novartis' Fabhata has been approved as the first therapy for a rare kidney disease, and Sanofi commits up to $1.9 billion for Dren Bio's bispecific antibody for autoimmune diseases. Paratek has acquired Optinose for up to $330 million, Purdue Pharma has filed for bankruptcy again to support an opioid settlement, and Novartis' Zolgensma has been found effective in older children.The FDA has approved Alnylam's Amvuttra as the first RNAi silencer for a rare type of cardiovascular disease called ATTR-CM, following the approval of BridgeBio's Attruzy for the same condition. This approval has sparked a three-way race in the rapidly expanding space, with Pfizer's Tafamidis also in the competition. Alnylam is optimistic about Amvuttra's unique mechanism of action, which targets the disease at its source by rapidly reducing the disease-causing TTR protein. This approval comes after Attruzy was also approved for polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in June 2022. This development has brought cardiovascular disease back into the spotlight, with other companies launching new drugs and treatments for various heart conditions.

A patient with Duchenne muscular dystrophy taking Sarepta's gene therapy Elevidys has died of acute liver failure, possibly related to a recent viral infection. Sarepta, which said it will update Elevidys' label to reflect the new safety signal, saw its shares drop 22% on the news but analysts still seem positive on the drug, as treatment options for Duchenne remain limited.Meanwhile, both AstraZeneca and Taiho Pharmaceuticals announced acquisitions worth up to $1 billion or more in two sizzling therapeutic spaces, cell therapy and antibody-drug conjugates, respectively.Despite canceling a vaccine advisory committee late last month, the FDA on Thursday selected flu strains to be targeted in the upcoming 2025-2026 flu season. And at another federal agency, the Centers for Disease Control and Prevention, employees will have to wait a bit longer to see who will take the helm under Donald Trump, as the president's nominee, Dave Weldon, was pulled hours before he was set to appear before a Senate committee on Thursday. Like HHS Secretary Robert F. Kennedy Jr., Weldon has expressed anti-vaccine views in the past, particularly his continued suggestion of the link between vaccines and autism. Guggenheim Partners called the move to revoke Weldon's nomination “a positive sign for reigning in vaccine criticism.”In the weight loss arena, BioSpace takes deep dives into the tendency for biopharma to develop fast-followers, or me-too drugs—following a pattern seen with PD-1 checkpoint inhibitors after the approvals of Merck's Keytruda and Bristol Myers Squibb's Opdivo. One key difference between these two markets, however, is that when it comes to GLP-1s for weight loss, patients are not staying on these medicines. Drug developers are trying several approaches to improve treatment persistence, including titration, combinations and even secondary drugs that address side effects. They're also making other moves to differentiate themselves, including focusing on overall health outcomes—in areas like cardiovascular, sleep apnea and kidney disease.Following on BioSpace's coverage of the major patent cliffs that many Big Pharma companies are facing in coming years, we also take a look back at some of the companies that have already weathered such loss of exclusivity. It's rarely a straightforward story of sales crashing off patent, as companies take various tacks to extend their blockbuster sales.Finally, the cardiovascular space is expecting some movement this week. First, Alnylam is anticipating a decision on its RNAi silencer Amvuttra in ATTR-CM. An approval—which is widely expected—would make three companies on the market in this rapidly expanding space after Pfizer's tafamidis was approved in May of 2019, and BridgeBio's Attruby got the greenlight in November last year. And second, Milestone Pharmaceutical has a PDUFA coming up for etripamil in paroxysmal supraventricular tachycardia.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.AstraZeneca has recently made a significant investment of up to $1 billion in cell therapy through the acquisition of esobiotec. This move is part of AstraZeneca's larger strategy to expand in the cell therapy space, positioning itself to be a major player in the market. Dyne is also looking to file for accelerated approval for its Duchenne exon skipping oligomer, while Taiho Pharmaceutical has acquired ADC partner Araris for up to $1.1 billion. Alnylam is expected to enter the transthyretin amyloid cardiomyopathy market, which is projected to reach $11.2 billion by 2030.Sino Biological has developed reagents for the 2025-2026 influenza vaccine strains, offering a range of recombinant proteins for vaccine development. The pharmaceutical industry is seeing significant activity in various therapy areas, with companies making strategic investments and advancements in research and development.Alnylam is awaiting approval for their drug Amvuttra in the transthyretin amyloid cardiomyopathy market, which is currently dominated by Pfizer and BridgeBio. The obesity drug market is becoming increasingly competitive, with companies focusing on overall health benefits rather than just weight loss. Biopharma companies are now exploring the use of CAR T cell therapies for autoimmune disorders, with several readouts expected this year. Ionis and Ultragenyx are competing to develop treatments for Angelman syndrome, while Neuren is trying to catch up.Overall health outcomes are becoming more important in the obesity drug market, with successful studies in therapeutic areas like cardiovascular and sleep apnea providing a market advantage. Other news includes flu vaccine recommendations from the FDA and updates on drugs for alcohol use disorder, plaque psoriasis, breast cancer, and weight loss. The biopharma industry continues to evolve, with readers encouraged to provide suggestions for future coverage topics.

This episode covers: Cardiology This Week: A concise summary of recent studies AI and the future of the Electrocardiogram The heart in rheumatic disorders and autoimmune diseases Statistics Made Easy: Bayesian analysis Host: Susanna Price Guests: Carlos Aguiar, Paul Friedman, Maya Buch  Want to watch that episode? Go to: https://esc365.escardio.org/event/1801 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Antonio Greco, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Maya Buch has declared to have potential conflicts of interest to report: grant/research support paid to University of Manchester from Gilead and Galapagos; consultant and/or speaker with funds paid to University of Manchester for AbbVie, Boehringer Ingelheim, CESAS Medical, Eli Lilly, Galapagos, Gilead Sciences, Medistream and Pfizer Inc; member of the Speakers' Bureau for AbbVie with funds paid to University of Manchester. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Paul Friedman has declared to have potential conflicts of interest to report: co-inventor of AI ECG algorithms. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Susanna Price Guest: Maya Buch Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1801?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Maya Buch has declared to have potential conflicts of interest to report: grant/research support paid to University of Manchester from Gilead and Galapagos; consultant and/or speaker with funds paid to University of Manchester for AbbVie, Boehringer Ingelheim, CESAS Medical, Eli Lilly, Galapagos, Gilead Sciences, Medistream and Pfizer Inc; member of the Speakers' Bureau for AbbVie with funds paid to University of Manchester. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Non-bacterial thrombotic endocarditis Managing cardiovascular risk in transgender people Milestones: RAVEL Host: Perry Elliott Guests: Kyle Klarich, Christian Delles Want to watch that episode? Go to: https://esc365.escardio.org/event/1800 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor.  This programme is intended for health care professionals only and is to be used for educational purposes.  The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Christian Delles, Kyle Klarich and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Perry Elliott Guest: Christian Delles Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1800?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Christian Delles and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Atrial fibrillation in athletes 'Work and life' of a medical journalist Mythbusters: Female doctors with better outcomes Host: Perry Elliott Guests: Carlos Aguiar, Isabelle van Gelder, Shelley Wood Want to watch that episode? Go to: https://esc365.escardio.org/event/1799   Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests  Stephan Achenbach, Nicolle Kraenkel, Isabelle van Gelder and Shelley Wood have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Perry Elliott Guest: Isabelle van Gelder Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1799?resource=interview   Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Nicolle Kraenkel and Isabelle van Gelder have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guest: Gilles Montalescot Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1798?resource=interview   Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Gilles Montalescot has declared to have potential conflicts of interest to report: research funds for Action Groupe or honoraria from Abbott, Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Celecor, CSL Behring, Hexacath, Idorsia, Lilly, Novo Nordisk, Pfizer, SMT, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Dual antiplatelet therapy in 2025 Optimal communication with patients Snapshots Host: Emer Joyce  Guests: Carlos Aguiar, Michelle Kittleson, Gilles Montalescot Want to watch that episode? Go to: https://esc365.escardio.org/event/1798   Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Emer Joyce, Michelle Kittleson and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Gilles Montalescot has declared to have potential conflicts of interest to report: research funds for Action Groupe or honoraria from Abbott, Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Celecor, CSL Behring, Hexacath, Idorsia, Lilly, Novo Nordisk, Pfizer, SMT, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Coronary spasm management Sex differences in heart failure Milestones: London Bus Driver Host: Emer Joyce Guests: Filippo Crea, Lynne Stevenson Want to watch that episode? Go to: https://esc365.escardio.org/event/1797 Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Filippo Crea, Emer Joyce, Nicolle Kraenkel and Lynne Stevenson have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guest: Filippo Crea Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1797?resource=interview Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Filippo Crea, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Hypertensive disorders during pregnancy Depression and heart disease Mythbusters: "The French Paradox" Host: Perry Elliott Guests: Carlos Aguiar, Martha Gulati, Hector Bueno Want to watch that episode? Go to: https://esc365.escardio.org/event/1796 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Martha Gulati, Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Hector Bueno has declared to have potential conflicts of interest to report: research funding from the European Union (EU4H-2022-JA-03), Instituto de Salud Carlos III, Spain (FORTALECE program, PI21/01572), Sociedad Española de Cardiología, AstraZeneca, Boehringer Ingelheim, Janssen, and Novartis; and has received in the past consulting/speaking fees from Astra-Zeneca, Novartis, Novo Nordisk and Organon. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Biopharma had its collective deal-making hat on heading into the Thanksgiving holiday, with Roche buying Poseida for up to $1.5 billion, and Sarepta and Arrowhead tying up in a collaboration potentially worth up to $10 billion. These announcements followed last week's news from Novartis, which snatched up Kate Therapeutics for a little over $1 billion while promising more acquisitions below $5 billion. On the regulatory front, the FDA gave BridgeBio—and transthyretin amyloid cardiomyopathy (ATTR-CM) patients—something to be thankful for late last week with the approval of Attruby for the rare, cardiovascular disease. The nod sets up a potential three-way race with Pfizer's tafamidis and Alnylam's Amvuttra, the latter of which was accepted for FDA review in ATTR-CM on Monday.   On the opposite end of the clinical development spectrum, Cassava Sciences' controversial Alzheimer's drug failed to reduce cognitive or functional decline in a Phase III trial. And investors were unimpressed by the 20% weight loss generated by Amgen's MariTide in a much-anticipated Phase II trial, as the company's stock tumbled 11% Tuesday. Drawing much attention from the biopharma industry, President-elect Donald Trump continued with his nominees for top healthcare posts, announcing COVID-19 critic Marty Makary to lead the FDA and well-known vaccine skeptic Dave Weldon for CDC director. Meanwhile, the FDA is grappling with the loss of Chevron Deference pertaining to a legal challenge over Eli Lilly's GLP-1 shortages. Finally, the next generation of antibody-drug conjugates remains hot, with Danish biotech Adcendo reeling in $135M in a Series B financing round.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly.  This episode covers: Cardiology This Week: A concise summary of recent studies Aortic aneurysms Return to elite sports after a severe cardiac event Milestones: CAST Host: Emer Joyce Guests: Carlos Aguiar, Jose Rodriguez Palomares, Harald Jorstad Want to watch that episode? Go to: https://esc365.escardio.org/event/1795 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Emer Joyce, Nicolle Kraenkel and Jose Rodriguez Palomares have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Harald Jorstad has declared to have potential conflicts of interest to report: unrestricted research grants to institution: Dutch Olympic Committee, Dutch Heart Foundation, Zon-Mw, Heart to Handle. Unrestricted, unrelated research grants to institution: Novartis, Amarin, Novo Nordisk, Sanofi. Unrelated advisory fees to institution: Amarin, Amgen. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly.  This episode covers: Cardiology This Week: A concise summary of recent studies Heart disease in dialysis patients Substance abuse and heart disease Snapshots: Pneumopericardium Host: Emer Joyce Guests: Carlos Aguiar, Patrick Mark, Theo Pezel, Stephan Achenbach Want to watch that episode? Go to: https://esc365.escardio.org/event/1794 Disclaimer: ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests: Stephan Achenbach, Emer Joyce, Nicolle Kraenkel and Theo Pezel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Patrick Mark has declared to have potential conflicts of interest to report: lecture/advisory board honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Pharmacosmos, Astellas, GSK, Vifor. Grants from Boehringer Ingelheim, AstraZeneca. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Dr. Ryan Augustin and Dr. Jason Luke discuss neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, promising new TIL therapy for advanced melanoma, and the emerging role of CD3 engagers in treatment strategies. TRANSCRIPT Dr. Ryan Augustin: Hello, I'm Dr. Ryan Augustin, your guest host of the ASCO Daily News Podcast today. I'm a medical oncology fellow at Mayo Clinic in Rochester, Minnesota. Joining me today is Dr. Jason Luke, an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. I had the privilege of working as a postdoc in Jason's translational bioinformatics lab, where we investigated mechanisms of resistance to immunotherapy in melanoma and other cancers.  Today, we'll be discussing 3 important topics, including neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, the impact and practical considerations for incorporating TIL therapy into melanoma, and the current and future use of CD3 engagers in both uveal and cutaneous melanoma.  You'll find our full disclosures in the transcript of this episode.  Jason, it's great to have this opportunity to speak with you today. Dr. Jason Luke: Absolutely. Thanks, Ryan. It's great to see you. Dr. Ryan Augustin: So, to kick things off, Jason, we, of course, have seen tremendous advances in cancer immunotherapy, not only in metastatic disease but also the perioperative setting. Recent data have shown that the use of neoadjuvant therapy can provide not only critical prognostic information but can also help individualize post-resection treatment strategies and potentially even eliminate adjuvant therapy altogether in patients who achieve a pathologic, complete response. This signifies a conceptual shift in oncology with the goal of curing patients with immunotherapy. In triple-negative breast cancer, the KEYNOTE-522 regimen with pembrolizumab is standard of care. In non-small cell lung cancer, there are now four FDA approved chemo-IO regimens in both the neoadjuvant and perioperative settings. And, of course, in melanoma, starting with SWOG S1801 utilizing pembro mono therapy, and now with combined CTLA-4 PD-1 blockade based on results from the NADINA trial, neoadjuvant IO is the new standard of care in high-risk, resectable melanoma. It's important to highlight this because whereas other tumor types have more mature multidisciplinary care, for example, patients with breast cancer are reviewed by the whole team in every center, and every patient with lung cancer certainly benefits from multidisciplinary care conferences, that's not always the case with melanoma, given the relative frequency of cases compared to other tumor types.  Jason, would you say that we have now moved into an era where the integration of a multidisciplinary team and melanoma needs to be prioritized. And why is it important to have multidisciplinary team coordination from the onset of a patient's diagnosis? Dr. Jason Luke: Well, I think those are great questions, Ryan, and I think they really speak to the movement in our field and the great success that we've had integrating systemic therapy, particularly immunotherapy, into our treatment paradigms. And so, before answering your question directly, I would add even a little bit more color, which is to note that over the last few years, we've additionally seen the development of adjuvant therapy into stages of melanoma that, historically speaking, were considered low-risk, and medical oncologists might not even see the patient. To that, I'm speaking specifically about the stage 2B and 2C approvals for adjuvant anti-PD-1 with pembrolizumab or nivolumab. So this has been an emerging complication.  Classically, patients are diagnosed with melanoma by either their primary care doctor or a dermatologist. Again, classically, the next step was referral to a surgeon who had removed the primary lesion, with discussion around nodal evaluation as well. And that paradigm has really changed now, where I think integration of medical oncology input early on in the evaluation of the appropriate treatment plan for patients with melanoma is quite a pressing issue now, both because we have FDA approvals for therapeutics that can reduce risk of recurrence, and whether or not to pursue those makes a big difference to the patient for discussion early on.  And, moreover, the use of systemic therapies now, prior to surgery, of course, then, of course, requires the involvement of medical oncology. And just for an emphasis point on this, it's classically the case, for good reason, that surgeons complete their surgery and then feel confident to tell the patient, “Well, we got it all, and you're just in really good shape.” And while I understand where that's coming from, that often leaves aside the risk of recurrence. So you can have the most perfect surgery in the world and yet still be at very high risk of recurrence. And so it's commonly the case that we get patients referred to us after surgery who think they're just in totally good shape, quite surprised to find out that, in fact, they might have a 20% to 50% risk of recurrence. And so that's where this multidisciplinary integration for patient management really does make a big difference.  And so I would really emphasize the point you were making before, which is that we need multidisciplinary teams of med onc with derm, with surgery early on, to discuss “What are the treatment plans going to be for patients?” And that's true for neoadjuvant therapy, so, for palpable stage 3, where we might give checkpoint inhibitors or combinations before surgery. But it's true even in any reasonably high-risk melanoma, and I would argue in that state, anything more than stage 1 should be discussed as a group, because that communication strategy with the patient is so important from first principles, so that they have an expectation of what it's going to look like as they are followed out over time. And so we're emphasizing this point because I think it's mostly the case at most hospitals that there isn't a cutaneous oncology disease management meeting, and I think there needs to be.  It's important to point out that usually the surgeons that do this kind of surgery are actually either the GI surgeons who do colon cancer or the breast surgeons. And so, given that melanoma, it's not the most common kind of cancer, it could easily be integrated into the existing disease review groups to review these cases. And I think that's the point we really want to emphasize now. I think we're not going to belabor the data so much, but there are enormous advantages to either perioperative or adjuvant systemic therapy in melanoma. We're talking about risk reduction of more than 50%, 50-75% risk reduction. It's essential that we make sure we optimally offer that to patients. And, of course, patients will choose what they think is best for their care. But we need to message to them in a way that they can understand what the risks and benefits of those treatments are and then are well set up to understand what that treatment might look like and what their expectations would be out over time.  So I think this is a great art of medicine place to start. Instead of belaboring just the details of the trial to say, let's think about how we take care of our patients and how we communicate with them on first principles so that we can make the most out of the treatments that we do have available. Dr. Ryan Augustin: That's great, Jason. Very insightful points. Thank you.  So, shifting gears now, I'd also like to ask you a little bit about TIL therapy in melanoma. So our listeners will be aware that TIL is a promising new approach for treating advanced melanoma and leverages the power of a patient's cytotoxic T cells to attack cancer cells. While we've known about the potential of this therapy for some time, based on pioneering work at the NCI, this therapy is now FDA approved under the brand AMTAGVI (Lifileucel) from Iovance Biotherapeutics, making it the first cellular therapy to be approved for a solid tumor. Now, I know TIL therapy has been administered at your institution, Jason, for several years now, under trial status primarily for uveal melanoma using an in-house processing. But for many cancer centers, the only experience with cellular therapy has come under the domain of malignant hematology with CAR T administration. At our institution, for example, we have only recently started administering TIL therapy for melanoma, which has required a tremendous multidisciplinary effort among outpatient oncology, critical care, and an inpatient hematology service that has expertise in cytokine release syndrome.  Jason, where do you see TIL therapy fitting into the metastatic space? Which patients do you think are truly candidates for this intensive therapy? And what other practical or logistical considerations do you think we should keep in mind moving forward? Dr. Jason Luke: Well, thanks for raising this. I think the approval of lifileucel, which is the scientific name for the TIL product that's on the market now. It really is a shift, a landscape shift in oncology, and we're starting in melanoma again, as seems to be commonly the case in drug development. But it's really important to understand that this is a conceptually different kind of treatment, and therefore, it does require different considerations. Starting first with data and then actualization, maybe secondarily, when we see across the accelerated approval package that led to this being available, we quote patients that the response rate is likely in the range of 30%, maybe slightly lower than that, but a meaningful 25% to 30% response rate, and that most of those patients that do have response, it seems to be quite durable, meaning patients have been followed up to four years, and almost all the responders are still in response. And that's a really powerful thing to be able to tell a patient, particularly if the patient has already proceeded through multiple lines of prior standard therapy. So this is a very, very promising therapy.  Now, it is a complicated therapy as well. And so you highlighted that to do this, you have to have a tumor that's amenable for resection, a multidisciplinary team that has done a surgery to remove the tumor, sent it off to the company. They then need to process the TIL out of the tumor and then build them up into a personalized cell product, bring it back, you have to lympho-deplete the patient, re-introduce this TIL. So this is a process that, in the standard of care setting under best circumstances, takes roughly six weeks. So how to get that done in a timely fashion, I think, is evolving within our paradigms. But I think it is very important for people who practice in settings where this isn't already available to realize that referring patients for this should be a strong consideration. And thinking about how you could build your multidisciplinary team in a way to be able to facilitate this process, I think is going to be important, because this concept of TIL is relevant to other solid tumors as well. It's not approved yet in others, but we kind of assume eventually it probably will be. And so I think, thinking through this, how could it work, how do you refer patients is very important.  Now, coming back to the science, who should we treat with this? Well, of course, it's now an air quotes “standard of care option”, so really it ought to be available to anybody. I will note that currently, the capacity across the country to make these products is not really adequate to treat all the patients that we'd want. But who would we optimally want to treat, of course, would be people who have retained a good performance status after first line therapy, people who have tumors that are easily removable and who have not manifested a really rapid disease progression course, because then, of course, that six-week timeline probably doesn't make sense. The other really interesting data point out of the clinical trials so far is it has looked like the patients who got the least amount of benefit from anti-PD-1 immunotherapy, in other words, who progressed immediately without any kind of sustained response, those patients seem to have the best response to TILs, and that's actually sort of a great biomarker. So, this drug works the best for the population of patients where checkpoint inhibitors were not effective. And so as you think about who those patients might be in your practice, as you're listening, I think prioritizing it for primary progression on anti PD-1, again and giving it ahead thought about how would you get the patient through this process or referred to this process very quickly is really important because that lag time is a problem. Patients who have melanoma tend to progress reasonably quickly, and six weeks can be a long time in melanoma land. So, thinking ahead and building those processes is going to be important moving into the future Dr. Ryan Augustin: Definitely appreciate those practical considerations. Jason, thank you.  Moving on to our final topic, I was hoping to discuss the use of immune cell engagers in melanoma. So, similar to CAR T therapy, bispecific T-cell engagers, or BiTEs, as they're commonly known, are standard of care in refractory myeloma and lymphoma. But these antibodies engaging CD-3 on T cells and a tumor specific antigen on cancer cells are relatively new in the solid tumor space. Tarlatamab, which is a DLL-3 and CD-3 bispecific antibody, was recently approved in refractory small cell lung cancer, and, of course, tebentafusp, an HLA-directed CD-3 T cell engager was approved in uveal melanoma in 2022. Both T and NK cell engaging therapies are now offering hope in cancers where there has historically been little to offer. However, similar to our discussion with TIL therapy, bispecifics can lead to CRS and neurotoxicity, which require considerable logistical support and care coordination.  Jason, I was wondering if you could briefly discuss the current landscape of immune cell engagers in melanoma and how soon we may see these therapies enter the treatment paradigm for cutaneous disease. Dr. Jason Luke: I think it is an exciting, novel treatment strategy that I think we will only see emerge more and more. You alluded to the approval of tebentafusp in uveal melanoma, and those trials were, over the course of a decade, where those of us in solid tumor land learned how to manage cytokine release syndrome or the impact of these C3 bispecifics, in a way that we weren't used to. And what I'll caution people is that CRS, as this term, it sounds very scary because people have heard of patients that, of course, had difficult outcomes and hematological malignancies, but it's a spectrum of side effects. And so, when we think about tebentafusp, which is the approved molecule, really what we see is a lot of rash because GP100, the other tumor antigen target, is in the skin. So, patients get a rash, and then people do get fevers, but it's pretty rare to get more than that. So really what you have to have is the capacity to monitor patients for 12 hours, but it's really not more scary than that. So it really just requires treating a few people to kind of get used to these kinds of symptoms, because they're not the full-on ICU level CRS that we see with, say, CAR T-cells.  But where is the field going? Well, there's a second CD3 bispecific called brenetafusp that targets the molecule PRAME, that's in a phase 3 clinical trial now for frontline cutaneous melanoma. And tebentafusp is also being evaluated in cutaneous melanoma for refractory disease. So, it's very possible that these could be very commonly used for cutaneous melanoma, moving into, say, a two-to-four-year time horizon. And so therefore, getting used to what are these side effects, how do you manage them in an ambulatory practice for solid tumor, etc., is going to be something everyone's going to have to learn how to deal with, but I don't think it should be something that people should be afraid of.  One thing that we've seen with these molecules so far is that their kinetics of treatment effect do look slightly different than what we see with more classic oncology therapies. These drugs have a long-term benefit but doesn't always manifest as disease regression. So, we commonly see patients will have stable disease, meaning their tumor stops growing, but we don't see that it shrank a lot, but that can turn into a very meaningful long-term benefit. So that's something that we're also, as a community, going to have to get used to. It may not be the case we see tumors shrink dramatically upfront, but rather we can actually follow people with good quality- of-life over a longer period of time.  Where is the field going? You mentioned tarlatamab in small cell lung cancer, and I think we're only going to see more of these as appropriate tumor antigens are identified in different tumors. And then the other piece is these CD3 engagers generally rely upon some kind of engagement with a T cell, whether CD3 engagers, and so they can be TCR or T-cell receptor-based therapies, although they can be also SCFV-based. But that then requires new biomarkers, because TCR therapy requires HLA restriction. So, understanding that now we're going to need to profile patients based on their germline in addition to the genomics of the tumor. And those two things are separate. But I would argue at this point, basically everybody with cutaneous melanoma should be being profiled for HLA-A(*)0201, which is the major T-cell receptor HLA haplotype that we would be looking for, because whether or not you can get access immediately to tebentafusp, but therefore clinical trials will become more and more important.  Finally, in that T-cell receptor vein, there are also T cell receptor-transduced T cells, which are also becoming of relevance in the oncology community and people listening will be aware in synovial sarcoma of the first approval for a TCR-transduced T cell with afamitresgene autoleucel. And in melanoma, we similarly have TCR-transduced T cells that are coming forward in clinical trials into phase 3, the IMA203 PRAME-directed molecule particularly. And leveraging our prior conversation about TILs, we're going to have more and more cellular based therapies coming forward, which is going to make it important to understand what are the biomarkers that go with those, what are the side effect profiles of these, and how do you build your practice in a way that you can optimally get your patients access to all of these different treatments, because it will become more logistically complicated, kind of as more of these therapies come online over the next, like we said, two to four years kind of time horizon. So, it's very exciting, but there is more to do, both logistically and scientifically. Dr. Ryan Augustin: That's excellent. Thanks, Jason, and thank you so much for sharing your great insight with us today on the ASCO Daily News Podcast. Dr. Jason Luke: Thanks so much for the opportunity. Dr. Ryan Augustin: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode, and you can follow Dr. Luke on X, formerly known as Twitter, @jasonlukemd. And you can find me, @RyanAugustinMD. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers: @ryanaugustinmd Dr. Jason Luke @jasonlukemd   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Ryan Augustin: No relationships to disclose Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Optimal management of angina Artificial sweeteners and cardiovascular risk Statistics Made Easy: Network meta-analyses Host: Perry Elliott Guests: Carlos Aguiar, Christiaan Vrints, Marco Witkowski Want to watch that episode? Go to: https://esc365.escardio.org/event/1793 Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Antonio Greco, Nicolle Kraenkel, Christiaan Vrints and Marco Witkowski have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Which MRA to use in which heart failure patient Managing electrical storm Mythbusters: garlic protects from the heart Host: Perry Elliott Guests: Carlos Aguiar, Sana Al-Khatib, Rudolf de Boer Want to watch that episode? Go to: https://esc365.escardio.org/event/1792 Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Sana Al-Khatib and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Rudolf de Boer has declared to have potential conflicts of interest to report: direct research funding from European Research Council (ERC), Netherlands Heart Foundation, Fondation leDucq, Netherlands Organization for Scientific Research. Research funding to department or institution: AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, NovoNordisk. Direct fees from Abbott, AstraZeneca, Cardior Pharmaceuticals GmbH, NovoNordisk, Roche Diagnostics. Fees to department or institution: NovoNordisk. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.This week's commercialization news includes updates on Zepbound supply, Enjaymo's new home, and expanding access to HIV drugs. Medicare has tweaked rules for drug price talks, while GSK reports that its RSV vaccine protects against disease over three seasons. GSK's Viiv plans to expand the supply of HIV drugs in Africa, and Sanofi's rare disease drug finds a new home at Recordati. Other news includes a protein prediction winning the Chemistry Nobel and Alnylam submitting an important drug application. Trends suggest that biosimilars may make a mark in 2025, with incentives favoring them in the Medicare market. Protein prediction wins the Chemistry Nobel Prize, Alnylam submits a crucial drug application, Lilly partners with AI specialist Insitro to develop metabolic medicines, and Purespring raises $105 million for gene therapy for kidney disease. AI startup Basecamp allies with The Broad Institute to create 'programmable' genetic medicines. Additionally, Lilly appoints Mount Sinai scientist Thomas Fuchs as its first Chief AI Officer to lead AI initiatives in drug discovery and clinical trials. Other news includes J&J closing a cancer study, Alnylam seeking approval for a potential blockbuster drug, and Propharma receiving a regulatory and compliance award at CPhI.The Supreme Court declined to review a Texas abortion case related to emergency care, a blow to the Biden administration's efforts. A survey found that nearly 70% of healthcare organizations affected by cyberattacks experienced disruptions in patient care. Steward Health Care is auctioning off assets, including closing Norwood Hospital in Massachusetts. Baxter reported no structural damage at their North Carolina site affected by Hurricane Helene. The payer-provider relationship in healthcare is becoming more complex with consolidation and value-based care, leading to tensions over reimbursement and access.Kezar's lupus trial has been put on hold after four patient deaths, making it a potential buyout target. Investor Kevin Tang is interested in acquisition. Big pharma is also investing in cell and gene therapies, with companies like Lilly and Sanofi making moves in the industry. The Genscript Biotech Global Forum 2025 is coming up on January 15, offering a platform to discuss innovations and challenges in gene and cell therapy. Additionally, Lilly's obesity clinical program faces challenges, while Stealth's ultrarare disease candidate may not meet approval standards.Eli Lilly's obesity program is highlighted as a key factor in the company's dominance in the industry, with CEO David Ricks confident in their position. Wuxi Biologics faces uncertainty in the U.S. after setbacks, while big pharma companies show growing interest in cell and gene therapy. Five radiopharma biotechs are identified as potential buyout targets, and Trilink Biotechnologies introduces custom sets of mRNA for screening studies. Other news includes increased investment in cell and gene therapy, activist investor Starboard's stake in Pfizer, and Merck's success with Keytruda in head and neck cancer. AstraZeneca puts $2 billion towards heart disease drugs, Sanofi offloads a rare autoimmune drug, and AbbVie trims earnings guidance.

This week I had a great conversation with Iva Toudjarska, founder and CEO of Zeal Therapeutics. From earning a PhD in molecular biology to a solid scientific career at Alnylam, to working in venture capital, to selling a successful SaaS company, Iva's career that's set her up well to enjoy this new challenge – founding a baby biotech. Her expertise marries business development, venture capital, and company-building. Iva shared valuable advice for biotech founders on securing funding, making strategic decisions, and building effective partnerships. Tune in to hear her experiences, lessons learned, and her current work leading Zeal Therapeutics, a precision kidney RNA therapeutics company.Get Iva's favorite book! The AlchemistLink In with Iva!Connect with us!Link In with CarinaSubscribe here:AppleSpotifyGoogle PodcastRSS feedLearn more about Recruitomics ConsultingCheck out our reading listDownload our free startup resources guide to grow your biotech efficientlyIf you're on the job market, visit the Collaboratory Career Hub 00:00 - Intro to Iva Toudjarska's Career00:48 - Career overview, Iva Toudjarska, Zeal Therapeutics04:26 - Successful biotech strategies, industry insights07:02 - Building successful partnerships, collaboration tips12:15 - Angel investing, funding strategies, biotech financing20:20 - Leveraging background, skills for biotech success24:38 - Setbacks in biotech, lessons learned, resilience27:20 - Bootstrapping a company, startup funding, entrepreneurship28:23 - Support for Eva, mentorship, biotech advice29:18 - Future goals, biotech vision, 10-year plan30:45 - Current reading, professional development, industry literature24:24 Lessons Learned and Future Goals28:08 Conclusion and Final Thoughts

217. LASER DOPÉS AU THULIUM : AVANTAGES ET PERSPECTIVES DANS LA PRISE EN CHARGE DE CALCULS URINAIRES - DR PANTHIERQu'est-ce qu'un laser thulium ?Quels sont les avantages du laser thulium fibré par rapport au laser holmium-YAG ?Quels sont les lasers recommandés en 2024 pour traiter les calculs urinaires ?Le laser thulium-YAG pulsé est-il adapté pour le traitement des calculs urinaires ?Cet épisode a été réalisé avec le soutien institutionnel des laboratoires Alnylam.L'orateur n'a pas reçu de rémunération pour la réalisation de cet épisode.Docteur Frédéric Pentier, chirurgien urologue à l'hôpital Tenon à Paris.Certaines données publiées peuvent ne pas avoir été validées par les autorités de santé françaises. La publication de ce contenu est effectuée sous la seule responsabilité de l'éditeur et de son comité scientifique.Musique du générique : Via AudioNetworkResponsable projet AFUF : Dr Fayek TahaProduction : La Toile Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology this Week: A concise summary of recent studies Strategic decisions in atrial fibrillation Critical evaluation of clinical trials Snapshots Host: Perry Elliott Guests: Stephan Achenbach, Carlos Aguiar, Jane Armitage, Isabel Deisenhofer Want to watch that episode? Go to: https://esc365.escardio.org/event/1720 Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Jane Armitage and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Isabel Deisenhofer has declared to have potential conflicts of interest to report: speaker honoraria and travel grants from Abbott Medical, Biosense-Webster, Boston Scientific, BMS, Volta Medical, and research grant (for the institution) from Abbott Medical and Daiichi Sankyo. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging, Inc., Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Medtronic's chief medical officer of acute care and monitoring has departed for a new role. The FDA has finalized voluntary malfunction summary reporting guidance. Penumbra is laying off 71 people after axing its virtual reality division. Qiagen and AstraZeneca have expanded their companion diagnostic pact. The Association for Molecular Pathology is suing to block an FDA lab test rule. Layoffs in the medical device industry continue to be a trend. Industry news includes the launch of the first over-the-counter glucose monitor, unexpected partnerships in diabetes tech, and pushback on FDA regulation of lab-developed tests.The text discusses various updates in the biopharma industry, including Alnylam's heart drug data sparking debate, Novo building a heart failure case for semaglutide, and a slump in cell and gene therapy investment. The industry is shifting towards more patient-centric commercialization strategies, with companies like Pfizer and Lilly breaking into the direct-to-consumer market. The summer has been a mixed bag for biotech, with market fluctuations and limited IPOs and acquisitions. Alnylam's full study data on its heart drug vutrisiran showed benefits but also raised skepticism. Novo's analysis showed semaglutide's effectiveness in reducing heart failure risk. Additionally, PBM executives are facing fines for alleged perjury in a house hearing defending their business practices.The text discusses the pricing and sales of gene therapies, particularly focusing on Novartis' Zolgensma, which has been the only gene therapy to cross the blockbuster threshold with sales of $1.2 billion in 2021 and $1.4 billion in 2022. While high price tags have not always resulted in significant returns for pharmaceutical companies with gene therapies, Zolgensma has been an exception. Other companies have faced challenges with new gene therapies, such as Biomarin Pharmaceuticals, which recently announced layoffs due to dismal sales of its hemophilia A gene therapy Roctavian.Alnylam Pharmaceuticals has released detailed data on their drug Vutrisiran, showing its benefits in treating a progressive and fatal heart condition known as ATTR cardiomyopathy. The results were published in the New England Journal of Medicine. While the data confirms the therapy's benefit, there are still questions about how exactly Vutrisiran should be used in treating the disease. The study is expected to continue to fuel debate among doctors.The text discusses the recent slump in investment in cell and gene therapy, with fewer venture funding rounds closed by developers in the first six months of 2024. Two companies, Biomarin and Tome Biosciences, are cutting jobs, with over 200 and over 100 layoffs respectively. Biomarin has made changes to its executive team and drug pipeline to refocus resources. Additionally, Bayer has partnered with RNA drugmaker Nextrna Therapeutics to develop new cancer therapies. The text also highlights the challenges faced in clinical trials, with nearly 80% failing to meet enrollment goals and schedules. The importance of understanding social determinants of health for research is emphasized.Biopharma Dive's Gene Therapy Weekly provides news and insights on gene therapy for biopharma leaders.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies What is new in lipid management – therapeutic options beyond statins Cardiac papillary fibroelastomas Snapshots Host: Rick Grobbee Guests: Stephan Achenbach, Carlos Aguiar, Kyle Klarich, Konstantinos Koskinas Want to watch that episode? Go to: https://esc365.escardio.org/event/1157 Disclaimer ESC TV Today and ESC 365, the cardiology knowledge hub are supported by Bristol Myers Squibb. The scientific content and opinions expressed in this programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Rick Grobbee, Kyle Klarich and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi, Novo Nordisk, Terumo, Medtronic. Konstantinos Koskinas has declared to have potential conflicts of interest to report: speaker fees / honoraria from Amgen, Daiichi-Sankyo, Sanofi.  Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Drug treatment of hypertrophic cardiomyopathy Humour in medicine Statistics Made Easy: Regression analysis Host: Susanna Price Guests: Carlos Aguiar, Milind Desai, Rohin Francis Want to watch that episode? Go to: https://esc365.escardio.org/event/1156   Disclaimer: ESC TV Today and ESC 365, the cardiology knowledge hub are supported by Bristol Myers Squibb. The scientific content and opinions expressed in this programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Rohin Francis, Antonio Greco, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report.  Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Milind Desai has declared to have potential conflicts of interest to report: consultant and research agreements with Bristol Myers Squibb, Tenaya, Edgewise, Cytokinetics and VIZ AI. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology this Week: A concise summary of recent studies   Lifetime management of aortic valve stenosis   Spirituality and cardiovascular health  Statistics Made Easy: Statistical Analyses using Chat GPT  Host: Perry Elliott Guests: Carlos Aguiar, Kavitha Chinnaiyan, Francesco Maisano Want to watch that episode? Go to: https://esc365.escardio.org/event/1155   Disclaimer ESC TV Today and ESC 365, the cardiology knowledge hub are supported by Bristol Myers Squibb. The scientific content and opinions expressed in this programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Kavitha Chinnaiyan and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Giuseppe Biondi-Zoccai has declared to have potential conflicts of interest to report : Aleph, Amarin, Balmed, Cardionovum, Crannmedical, Endocore Lab, Eukon, Guidotti, Innovheart, Meditrial, Menarini, Microport, Opsens Medical, Terumo, and Translumina. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi, Terumo, Medtronic. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics. Francesco Maisano has declared to have potential conflicts of interest to report : Grant Institute, Edwards, Abbott, NVT, Medtronic, Jenavalve and Boston Scientifics. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.      

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Coronary artery calcium scoring Checklists in aviation and in medicine Mythbusters: Being married reduces cardiovascular mortality Host: Susanna Price Guests: Thomas Achenbach, Carlos Aguiar, Michael Blaha, Edward Nicol Want to watch that episode? Go to: https://esc365.escardio.org/event/1154 Disclaimer ESC TV Today and ESC 365, the cardiology knowledge hub are supported by Bristol Myers Squibb. The scientific content and opinions expressed in this programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Thomas Achenbach, Michael Blaha, Edward Nicol, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme. 

Ohne Aktien-Zugang ist's schwer? Starte jetzt bei unserem Partner Scalable Capital. Alle weiteren Infos gibt's hier: scalable.capital/oaws. Aktien + Whatsapp = Hier anmelden.  Lieber als Newsletter? Geht auch.  Das Buch zum Podcast? Jetzt lesen.  China pusht Auto-Aktien, die Arabische Halbinsel pusht Covestro und Siemens. Wachstumsphantasien pushen Deutz, nix pusht NVIDIA oder den Bitcoin. Außerdem hat Apple ein EU-Problem, RXO kauft Konkurrenz und Alnylam hat gute Studien. Wer bohrt das Öl? Die Kollegen bei Baker Hughes (WKN: A2DUAY). Wer hebt die Container? Die Kräne von Konecranes (WKN: 899827). Diesen Podcast vom 25.06.2024, 3:00 Uhr stellt dir die Podstars GmbH (Noah Leidinger) zur Verfügung.

Nvidia notching another day of losses, but the broader markets aren't taking it too hard. How investors are handling the semi slide. Plus A big jump for one biopharma stock as Alnylam delivers promising new heart drug results. What the CEO had to say about the data, and the impact it could have on the space. Fast Money Disclaimer

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Genetic testing in dilated cardiomyopathy Gut microbiome and heart disease Mythbusters: Sitting is the new smoking Host: Rick Grobbee Guests: Carlos Aguiar, Arash Haghikia and Juan Pablo Kaski Want to watch that episode? Go to: https://esc365.escardio.org/event/1153 Disclaimer This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Rick Grobbee, Arash Haghikia, Juan Pablo Kaski and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, 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. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly.   This episode covers: Cardiology This Week: A concise summary of recent studies State-of-affairs in hypertension treatment Anticoagulation in pregnancy Statistics Made Easy : Accuracy and AUC    Host: Perry Elliott Guests: Carlos Aguiar, Gianfranco Parati, Julie De Backer Want to watch that episode? Go to: https://esc365.escardio.org/event/1152   Disclaimer This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Julie De Backer and Nicolle Kraenkel have declared to have no potential conflicts of interest to report.  Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics. Gianfranco Parati has declared to have potential conflicts of interest to report: honoraria for lectures by Omron, Viatris, Merck, Recor, Somnomedics. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond.  TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center.  You will find our full disclosures in the transcript of this episode.  Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work.  Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO.  Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time?  Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo.  The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen.   Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi?   We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this?  Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma.  By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data.  And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab?  At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that.  So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression.   The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival.   So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy.  You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm.  Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment.   So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform.  Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME.  So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector.   So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma.  Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response.   At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that.  Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors.  In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data.  It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches?  Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up.   So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations.  We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies.  I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent.  So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll see you soon.   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. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio      

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Long-term beta blockers after myocardial infarction Pros and Cons of the microaxial pump in cardiogenic shock Snapshots Host: Perry Elliott Guests: Stephan Achenbach, Carlos Aguiar, Michael Boehm, Lene Holmvang Want to watch that episode? Go to: https://esc365.escardio.org/event/1151   Disclaimer This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Michael Boehm, Lene Holmvang and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies All you need to know about omega-3 fatty acids Lead induced tricuspid regurgitation MythBusters: Pomegranates are heart-healthy Host: Rick Grobbee Guests: Carlos Aguiar, Martin Andreas, Deepak Bhatt Want to watch that episode? Go to: https://esc365.escardio.org/event/1150 Disclaimer This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Rick Grobbee and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Martin Andreas has declared to have potential conflicts of interest to report: proctor/speaker/consultant (Edwards, Abbott, Medtronic, Boston, Braun, Zoll) and institutional Research Grants (Edwards, Abbott, Medtronic, LSI). Deepak Bhatt has declared to have potential conflicts of interest to report: research funding from Amarin paid to Brigham and Women's Hospital and the Icahn School of Medicine at Mount Sinai for my role as Principal Investigator of REDUCE-IT. Davide Capodanno has declared to have potential conflicts of interest to report: Abbott Vascular, Novo Nordisk, Sanofi. Terumo, Medtronic. Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.