Podcasts about Celgene

This Day in Legal History: Patent Act of 1790On April 10, 1790, the United States passed its first patent law, the Patent Act of 1790, laying the groundwork for a legal framework that would protect inventors and promote innovation. This early legislation granted inventors the exclusive right to their discoveries for a period of 14 years, provided the invention was deemed "useful and important." It was signed into law by President George Washington and represented one of the earliest legal efforts by the new republic to encourage economic growth through technological advancement. The law established a board composed of the Secretary of State, the Secretary of War, and the Attorney General, who were tasked with reviewing patent applications and deciding whether to approve them.Notably, the law gave the federal government broad discretion over what could be patented and required that a patent be granted only if the invention was new and useful. The first U.S. patent under this act was issued on July 31, 1790, to Samuel Hopkins for a process of making potash, a key industrial chemical. Although modest in scope, the law was revolutionary in its recognition of intellectual property as a public good worth safeguarding. It helped move the United States toward a more structured innovation economy, setting a precedent that influenced global norms on patent protection.The 1790 law was replaced just three years later by the Patent Act of 1793, which shifted the review process to a more administrative function, but the foundational principle—that inventors should have exclusive rights to their creations—remained intact. This early commitment to fostering invention through legal means helped spur the rapid technological growth that would define American industry in the 19th century and beyond. The act exemplified how the law could be used to incentivize creativity and economic development at a national scale.Bristol Myers Squibb successfully got a proposed class action lawsuit dismissed that had accused it of using fraudulent tactics to maintain a monopoly over its cancer drug, Pomalyst. The suit, led by Blue Cross Blue Shield of Louisiana, claimed that Bristol Myers and its subsidiary Celgene illegally secured patents and filed sham lawsuits to delay the entry of generic versions of Pomalyst, which is used to treat multiple myeloma. However, U.S. District Judge Edgardo Ramos ruled that the plaintiffs failed to prove that any of the six patents were obtained through fraud. He also found no evidence that the nine lawsuits Celgene filed between 2017 and 2020 against generic manufacturers like Teva and Mylan were baseless or intended to secure fraudulent settlements.The plaintiffs alleged that they had been overpaying for the drug since October 2020, the point at which generics could have entered the market if not for the alleged conduct. Pomalyst brought in $3.55 billion in sales in 2024, accounting for more than 7% of Bristol Myers' revenue. Celgene originally developed the drug, and Bristol Myers acquired the company in 2019. The case was heard in the U.S. District Court for the Southern District of New York.Bristol Myers wins dismissal of lawsuit alleging Pomalyst monopoly | ReutersThe Trump administration has frozen over $1 billion in federal funding for Cornell University and $790 million for Northwestern University amid investigations into alleged civil rights violations. The freeze affects grants and contracts from several federal agencies, including health, education, agriculture, and defense. This move is part of a broader crackdown targeting universities over pro-Palestinian campus protests, diversity programs, and transgender policies. The administration previously warned 60 universities, including Cornell and Northwestern, about potential enforcement if they failed to address what it labeled as antisemitism.Cornell confirmed it received “stop work” orders from the defense department affecting research projects but said it hasn't been formally notified of the total funding freeze. Northwestern similarly acknowledged awareness of media reports but stated it hadn't received official notice. The university emphasized the freeze could endanger critical research, including projects on cybersecurity, pacemakers, and Alzheimer's treatment.This action follows similar measures taken against Harvard, Princeton, Columbia, and the University of Pennsylvania. Columbia, which lost $400 million in funding, later agreed to administrative changes in exchange for potential reinstatement. Federal agents have also begun detaining and deporting some foreign student protesters, revoking visas in the process. Critics, including human rights groups, have voiced concerns over free speech, academic freedom, Islamophobia, and anti-Arab discrimination amid the escalating response to pro-Palestinian activism on campuses.US freezes funding for Cornell, Northwestern University in latest crackdownPresident Trump has issued a new executive order aimed at blocking state-level climate policies that seek to reduce fossil fuel use and limit carbon emissions. The directive instructs the U.S. attorney general to identify and challenge state laws related to climate change, environmental justice, ESG (environmental, social, and governance) standards, and carbon regulation. The move aligns with Trump's broader agenda to boost domestic fossil fuel production and roll back Democratic-led environmental initiatives.The order specifically targets policies in states like New York, Vermont, and California, including financial penalties on fossil fuel companies, California's cap-and-trade system, and climate-related lawsuits brought by state governments. Trump described these measures as ideologically driven and harmful to national energy and economic security.Governors Kathy Hochul (NY) and Michelle Lujan Grisham (NM), co-chairs of the U.S. Climate Alliance, condemned the order, asserting states' rights to enact environmental protections. They reaffirmed their commitment to clean energy and climate resilience. The American Petroleum Institute supported Trump's move, framing it as a defense against unconstitutional state actions that burden oil and gas companies.Trump issues order to block state climate change policies | Reuters This is a public episode. 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With Susanne Biro, a coach to C-suite and executive-level leaders. She is also a senior facilitator, executive development program designer, author, Forbes and CEO Magazine contributing writer, and a TEDx and keynote speaker. For over two decades, Susanne has worked internationally with senior-level leaders in some of the world's best companies. Whether coaching one-on-one or authoring, designing, and delivering leadership programs, her passion is the same: to help leaders reach their next level. She is the Founder of Inner Life Leadership, an app for business professionals who want to reach an unprecedented level of personal understanding and corresponding leadership (and life) success. She is also the author of the “I Want You To Win!” Coaching Skills for Creative Leadership, co-author of “Together” Executive Team Development, and the book Unleashed! Leader as Coach, adopted by organizations like General Electric, American Express, St. Jude Medical, Celgene, Mayo Clinic, salesforce.com, and numerous othersJoin us in our conversation as Susanne shares powerful insights on leadership, self-awareness, and the mindset shifts that drive success. She discusses why even top executives struggle with self-doubt, how character and integrity can be your greatest advantage in business, and the simple yet transformative habits that can elevate your performance. Tune in to learn how to lead with confidence, cultivate a mindset that serves you, and build a business—and life—you truly love.To listen to the podcast and access the show notes and any other resources mentioned in this episode, visit us at www.legalwebsitewarrior.com/podcast.

In this episode, Bob and Peter discuss Stem Cells 101, why it's not available in America, and the importance of stem cell treatment for humanity.  Recorded on Nov 21st, 2024 Views are my own thoughts; not Financial, Medical, or Legal Advice. Dr. Robert Hariri is the Chairman, Founder, and CEO of Celularity, Inc., a leader in human cellular therapeutics developing placental stem cell-based therapies for cancer, autoimmune diseases, and other conditions. A distinguished surgeon, scientist, and entrepreneur, Dr. Hariri is known for discovering pluripotent stem cells from the human placenta and holds over 170 patents in the field. He founded Anthogenesis Corporation, later acquired by Celgene, and co-founded Human Longevity, Inc. Dr. Hariri, an MD and PhD graduate from Cornell University, serves as an Adjunct Professor of Neurosurgery at Weill Cornell Medical College and has earned prestigious honors, including the Pontifical Medal for Innovation and two Thomas Alva Edison Awards. His groundbreaking work continues to shape regenerative medicine and immuno-oncology. He's also a founding partner of Fountain Life. Learn more about Celularity: https://celularity.com/  Lifebank USA: https://www.lifebankusa.com/  Get my Longevity Guidebook here: https://qr.diamandis.com/book-audiopodcast ____________ I only endorse products and services I personally use. To see what they are, please support this podcast by checking out our sponsors:  Get started with Fountain Life and become the CEO of your health: https://fountainlife.com/peter/ AI-powered precision diagnosis you NEED for a healthy gut: https://www.viome.com/peter  Get 15% off OneSkin with the code PETER at  https://www.oneskin.co/ #oneskinpod _____________ I send weekly emails with the latest insights and trends on today's and tomorrow's exponential technologies. Stay ahead of the curve, and sign up now: Tech Blog _____________ Connect With Peter: Twitter Instagram Youtube Moonshots

Quels sont les progrès les plus marquants dans le diagnostic et le traitement des spondyloarthrites ? Quelles perspectives de recherche prometteuses pourraient transformer la prise en charge des spondyloarthrites ? Comment ces avancées et perspectives impactent-elles la pratique clinique et la qualité de vie des patients ?   Le Professeur Daniel Wendling, rhumatologue au CHU de Besançon, nous éclaire à ce sujet. Notre invité déclare avoir des liens d'intérêts avec AbbVie, BMS, MSD, Pfizer, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Celgene, Lilly, Sandoz, et Alfa Sigma.   L'équipe :   Comité scientifique : Pr Jérémie Sellam, Pr Thao Pham, Dr Catherine Beauvais, Dr Véronique Gaud-Listrat, Dr Céline Vidal, Dr Sophie Hecquet Animation : Marguerite de Rodellec Production : MedShake Studio Soutien institutionnel : Pfizer  

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Robert F. Kennedy Jr., known for his anti-vaccine views, has been chosen by President Trump to lead the Department of Health and Human Services. Kennedy has expressed plans to overhaul the FDA and reduce the NIH's headcount, raising concerns about the future of healthcare regulation. In other news, Celgene shareholders are suing Bristol-Myers Squibb for allegedly avoiding contingent value right payments related to their acquisition deal, while Eyenovia's stock plummets after dropping their lead program due to lack of efficacy. Bluebird Bio is facing a cash shortage with only two quarters of funding left, prompting executives to seek financing to reach breakeven point by 2025. Overall, the pharmaceutical industry had a tumultuous third quarter, with companies like Gilead and Kite cutting employees and closing sites. The industry is in a state of uncertainty as it navigates through these challenges.

Synopsis: Rob Williamson, CEO of Triumvira, joins Biotech 2050 host, Rahul Chaturvedi, to discuss his dynamic career from economics to biotech, tackling the volatile capital markets, and navigating high-stakes decisions in cell therapy. He shares insights on therapeutic developments in cell therapy, the pressures of solid tumor research, and the evolving biotech ecosystem. A deep dive into biotech board dynamics, funding strategies, and the potential of AI in healthcare, Rob offers invaluable lessons and forward-thinking perspectives on life sciences and patient care innovation. Biography: Robert F. Williamson, III has been active in building biotechnology companies and shareholder value for over two decades. He currently is the President and COO of Triumvira Immunologics. Previously, he was the CBO of OncoMyx, an oncolytic virus company, and CEO of BioTheryX, a protein degradation therapeutics company, raising a $100M crossover round and preparing the company for an IPO. Prior to BioTheryX, Mr. Williamson served as CEO of both PharmAkea and ATXCo, oncology and fibrosis companies financed through a partnership with Celgene, until PharmAkea's acquisition by Galecto and ATXCo's acquisition by Blade Therapeutics. Prior, Mr. Williamson was CEO of Arriva Pharmaceuticals, President and COO of Eos Biotechnology, which he sold to Protein Design Labs, and COO of DoubleTwist, Inc. through its acquisition by Merck and Hitachi. Mr. Williamson also serves as a director and adviser for foundations, private, and public companies. Notably, Mr. Williamson served as an early Director of Pharmasset, Inc., where he helped finance, grow, and advance the company into the public markets and through its acquisition by Gilead in 2011 for $11 billion. Earlier, Mr. Williamson was a Partner with The Boston Consulting Group and a Research Assistant for the Federal Reserve Board. He received a BA in economics from Pomona College and an MBA from Stanford.

In this episode of Life Science Success, we welcome Ani Sinha, the Vice President of Commercial Operations at Shionogi Inc. Ani brings nearly 15 years of deep commercial expertise in the pharmaceutical and biotech industries. She shares her inspiring journey from studying microbiology and biochemistry at Yale and Columbia to holding strategic leadership roles at companies like Pfizer, Bayer, and Celgene. We delve into her current role at Shionogi, exploring how she leads functions like Analytics and Insights, Market Research, and Field Operations. Ani discusses the innovative projects she's excited about and how they're contributing to Shionogi's mission. She also shares the greatest piece of leadership advice she's ever received and opens up about what inspires, concerns, and excites her in the world of life sciences. Tune in to gain valuable career insights and explore the dynamic future of pharmaceutical advancements.   00:00 Introduction to Life Science Success Podcast 00:42 Sponsor Message: D3 Digital Media Marketing 01:25 Interview with Ani Sinha Begins 02:08 Ani Sinha's Career Journey 05:18 Transition from Lab to Consulting 07:58 Skills Gained from Management Consulting 11:25 Joining Shinogi and Role in Commercial Operations 20:13 Future of Commercial Operations 22:21 Building a Team: The Land of Misfit Toys 23:02 Navigating Different Companies and Roles 24:05 The Evolving Role of Analytics and Insights 25:41 Challenges in Market Research and Operations 29:32 Addressing Trends in Biotech and Pharma 32:13 Greatest Leadership Advice Received 34:44 Inspiration and Concerns in the Pharma Industry 40:52 Final Thoughts and Farewell

Join us for this special revisited episode of the Treasury Career Corner Podcast, as we reconnect with Sandra Ramos Alves the Senior Vice President and Treasurer at Bristol Myers Squibb about her journey in finance and treasury and what she's been up to since she was last on the show.Sandra Ramos Alves is the Senior Vice President and Treasurer at Bristol Myers Squibb, a global biopharmaceutical company. She has extensive experience in finance and treasury and has successfully led her team through a period of transformation. Her expertise and insights make her a valuable guest to listen to.In this episode, Sandra discusses her career journey, starting from her early days in accounting to her current role in treasury. She shares how she discovered treasury by chance and how she quickly adapted to the role. Sandra also talks about her experience at Celgene, where she helped build a best-in-class treasury organization. She emphasizes the importance of supporting the business and making a difference in people's lives through treasury. Sandra highlights the growth and development of the treasury function at Celgene and the challenges and successes she encountered along the way. She also shares her thoughts on the future of treasury, including the importance of technology and innovation.On the podcast we discussed…Sandra's journey from accounting to treasury The growth and development of the treasury function The importance of supporting the business and making a difference in people's lives through treasury.The future of treasury and the role of technology and innovation.Sandra's advice for treasury professionals, including taking risks, speaking up, and owning your career.You can connect with Sandra Ramos Alves on LinkedIn. Are you interested in pursuing a career within Treasury?Whether you've recently graduated, or you want to search for new job opportunities to help develop your treasury career, The Treasury Recruitment Company can help you in your search for the perfect job. Find out more here. Or, send us your CV and let us help you in your next career move!If you're enjoying the show please rate and review us on whatever podcast app you listen to us on, for Apple Podcasts click here!To subscribe to the Treasury Career Corner podcast via:Apple

Eylem Demir Sentürk, Founder of Women on Stage, shared the story behind her title with us on September 25, 2024.⭐⭐⭐⭐⭐Rating: 5 out of 5.Of the interview, our founder and host, Sue Rocco, says: "Listen in as I sit down with Eylem this week to talk about Eylem's family having to flee Turkey as Kurdish members, the challenge of integrating into a new culture in Switzerland, her experience with workplace bullying by her manager in a large Pharma company that led to a mental and physical breakdown, and the founding of her new venture to help working women thrive."ABOUT EYLEM: Beginning her career in the banking world, Eylem swiftly transitioned into the Pharma Industry, leaving an indelible mark at renowned companies such as Actelion, Celgene, Vifor Pharma, Novartis, and Bayer. Over a span of 22 years, she not only led international teams but also collaborated with professionals from 40 different nationalities. Eylem's commitment to excellence extended beyond corporate boundaries as she coached, and trained over 1000 individuals.Support this podcast at — https://redcircle.com/women-to-watch-r/donationsAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with Chris Garabedian, CEO at Xontogeny and Venture Fund Manager at Perceptive Advisors. Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with Chris, covering: How he utilized his pharma experience to become a CEO and revitalize a biotech company, positioning it for a $15bn market cap Why the biotech space had such a market downturn, and how the uptake in the industry will be data-driven Demystifying the role of a biotech CEO and understanding what it takes to drive successful drug development Why relying on outsourcing is critical for biotechs today The emerging, secondary-tier biotech clusters in the US... but why does Boston remain unrivalled? Chris Garabedian founded Xontogeny in June of 2016 to support multiple promising technologies from early development through clinical proof of concept. In 2017, Chris joined Perceptive Advisors to develop their Venture Fund strategy and is Portfolio Manager of the Perceptive Xontogeny Ventures Fund, which supports early-stage companies with Series A investments across biotech, medtech and healthtech. Chris has a broad base of experience and a track record of success over his decades-long experience in the biopharma industry. Chris served as the President and CEO of Sarepta Therapeutics from 2011 to 2015, overseeing the turnaround of a company that is now a commercial-stage leader in the genetic technology space. He also led Corporate Strategy for Celgene from 2007 to 2010 and served in several global commercial and corporate development leadership roles at Gilead from 1997 to 2005. He serves on the boards of several life sciences companies and speaks at industry conferences on a wide range of important issues. He is a member of the Corporate Relations Board for the Keck Graduate Institute. He has previously served on the Board of Directors of MassBio and is a Senior Advisor for the Boston Consulting Group. ----- Join Molecule to Market and ramarketing for an exclusive panel discussion series at this year's CPHI Milan - across 3 power-packed sessions, our industry experts will be sharing insights into driving brand growth with strategic marketing. Find out more and pre-register here ----- Please subscribe, tell your industry colleagues and join us in celebrating and promoting the value and importance of the global life science outsourcing space. We'd also appreciate a positive rating! Molecule to Market is sponsored and funded by ramarketing, an international marketing, design, digital and content agency helping companies differentiate, get noticed and grow in life sciences.

In this exclusive interview, Chadi welcomes Dr. Patrick Soon-Shiong, a Chinese immigrant who grew up under apartheid in South Africa and rose to become one of the world's most successful physician executives. Now the CEO of ImmunityBio, Dr. Soon-Shiong opens up about his remarkable journey. He shares what inspired him to pursue medicine, his entrepreneurial ventures, his move to the United States, and the story of his first investment. He discusses creating the groundbreaking chemotherapy drug Abraxane, which led to the formation of Abraxis, later acquired by Celgene, now part of BMS. He also expounds on his most recent FDA-approved drug, Anktiva, for bladder cancer. With complete candidness, Dr. Soon-Shiong reflects on his challenging upbringing, the discrimination he faced, and how he overcame these obstacles to achieve great success. He and Chadi explore life lessons, leadership styles, and a range of topics including Kobe Bryant, Gavin Newsom, COVID-19, the first pancreatic transplant, the acquisition of the Los Angeles Times, and his public feud with his brother. This 2024 podcast episode offers an unparalleled glimpse into the life of a highly public and inspiring figure and is one you'll want to listen to more than once and share with everyone you know. Read more about Dr. Soon-Shiong. https://immunitybio.com/our-founder/ Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Dr Linda Stein Gold and Dr Jonathan Silverberg discuss the epidemiology, clinical presentation, and classification of atopic dermatitis of the hand and feet as well the as quantifying the multidimensional burden it has on patients' quality of life in clinical practice. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: Dr Jonathan Silverberg: Honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena Therapeutics, Amgen, AOBiome, Apollo Pharma, Arcutis, Arena Pharmaceuticals, Asana, ASLAN Pharmaceuticals, Attovia, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, FIDE, Galderma, GSK, Incyte, Invea, Kiniksa, LEO Pharma, Lilly, Merck, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, Target RWE, Teva, UNION, and UpToDate. Speaker for AbbVie, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi-Genzyme. Institution received grants from Galderma, Incyte, and Pfizer. Dr Linda Stein Gold: Investigator/advisor and/or speaker for AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi. © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2400314 - 1.0 - 06/2024  MAT-US-2405589 v1.0 - P Exp Date: 06/04/2026

Dr Linda Stein Gold and Dr Jonathan Silverberg discuss the challenges associated with diagnosis of atopic dermatitis of the hands and feet and how disease severity can be assessed in clinical practice. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: Dr Jonathan Silverberg: Honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena Therapeutics, Amgen, AOBiome, Apollo Pharma, Arcutis, Arena Pharmaceuticals, Asana, ASLAN Pharmaceuticals, Attovia, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, FIDE, Galderma, GSK, Incyte, Invea, Kiniksa, LEO Pharma, Lilly, Merck, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, Target RWE, Teva, UNION, and UpToDate. Speaker for AbbVie, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi-Genzyme. Institution received grants from Galderma, Incyte, and Pfizer. Dr Linda Stein Gold: Investigator/advisor and/or speaker for AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi. © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2402602- 1.0 - 05/2024 MAT-US-2405594 v1.0 - P Exp Date: 06/04/2026

On this episode of Investor Connect, Hall welcomes Brian Cain, President Keiretsu, Philadelphia Chapter. Based in Philadelphia and Jacksonville, Keiretsu Forum is a global network of angel investors, venture capitalists, and business leaders focused on fostering strategic partnerships and accessing promising investment opportunities worldwide.   Brian Cain brings a wealth of experience to his role as President of Keiretsu Forum Mid-Atlantic's Philadelphia chapter. With a background in Market Research, Business Intelligence, and Commercial Analytics at major pharmaceutical companies such as J & J, BMS, Celgene, Merck, and smaller biotechs like Ironwood, Brian possesses a comprehensive understanding of the pharmaceutical landscape and strategic decision-making processes. His involvement as a board member for various early-stage life science companies further enhances his value to Keiretsu members and portfolio companies.   Brian shares his journey from the pharmaceutical sector to the early-stage investment community, highlighting the appeal of working with small biotech startups. He discusses the evolution of Keiretsu Forum's Philadelphia chapter under his leadership, emphasizing the importance of due diligence and collaboration among members.   Brian elaborates on the rigorous company vetting process at Keiretsu Forum, emphasizing the objective assessment of opportunities and risks. He also reflects on emerging trends in the early-stage investment landscape, particularly in AI, and offers advice for both investors and entrepreneurs to leverage networks and expertise. Finally, Brian encourages listeners to get involved with Keiretsu Forum and engage in discussions to enhance their understanding and portfolio strategies.   For more information about Brian Cain and Keiretsu Forum, visit their website at . You can connect with Brian on LinkedIn at and follow Keiretsu Forum on LinkedIn at . For inquiries, reach out to Brian via email at _________________________________________________________ For more episodes from Investor Connect, please visit the site at:    Check out our other podcasts here:   For Investors check out:   For Startups check out:   For eGuides check out:   For upcoming Events, check out    For Feedback please contact info@tencapital.group    Please , share, and leave a review. Music courtesy of .

Drs. John Sweetenham and Lawrence Shulman discuss the challenges that oncologists will be confronting in 2024 and share insights on how to build clinician resilience and optimize the oncology workforce to provide better, safer care for patients with cancer. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. I'm thrilled to welcome my friend and colleague, Dr. Larry Shulman, to the podcast today. Dr. Shulman is a professor of medicine, associate director of special projects, and the director of the Center for Global Medicine at the University of Pennsylvania Abramson Cancer Center. Dr. Shulman is also the immediate past chair of the Commission on Cancer, and also serves on the National Cancer Policy Forum of the National Academies of Science, Engineering, and Medicine. His acclaimed research has led to the development of models of clinical care to improve the patient experience and quality of care in the United States and internationally. His activities have also included innovations in health information technology, cancer survivorship care, and some other related areas. Today, Dr. Shulman will be sharing his valuable insights on some of the growing complexities and challenges that we'll be grappling with in oncology in 2024 and beyond, and potential solutions to address these issues. You'll find our four disclosures in the transcript of this episode, and disclosures of all guests on the podcasts are available at asco.org/DNpod. Larry, it's great to have you on the podcast today. Dr. Lawrence Shulman: Thank you so much, John. Dr. John Sweetenham: To start with Larry, as you know, the growth in the number of patients with cancer and cancer survivors in the U.S. is greatly outpacing the number of clinicians available to care for them. The American Association for Cancer Research, for example, estimates that there will be nearly 2 million new cancer cases in the U.S. alone this year and that the number will increase significantly in the years to come. The number of cancer survivors in total in the U.S. is predicted to grow to around 20.3 million by 2026. So, the question our community has been grappling with for some time now is: “How do we confront these realities and provide optimal care for patients, while at the same time building the resilience of the clinicians who need to care for them?” This is an area I know that you've focused on for a long time and you've published several papers in recent years as well as the great work that you've done as co-chair of the National Cancer Policy Forum workshop on the oncology workforce. Can you share your insights into some of these challenges? Dr. Lawrence Shulman: Sure, John. Thank you very much. As you mentioned, the number of oncologists in this country is pretty stable. There's consistent but relatively low number entering the workforce and those of us who were really in the first wave of oncologists in the 1970s are beginning to retire. A number of years ago we thought, well, we need to figure out ways to recruit more medical students and trainees into the field of oncology, but that's clearly not going to happen. And as you also mentioned, the number of cancer patients is rapidly increasing in this country, partly because of the aging population and partly because frankly we're better at treating them. The cure rates are better, and the number of survivors is going up. So, the math is pretty straightforward. We have a relatively stable number of oncology providers trying to care for a rapidly increasing number of patients and that's just not going to change. So, we need to have plan B; we need to figure out how we can better meet the needs in this country. And I think all of us who practice are feeling the strain of trying to take care of these increasing number of patients. I think there are a few things that are contributing to this as well. One—the good news is we have lots of new therapies, we have lots of genomics, which are leading us to better tailor therapies for our patients. But this is all complicated and it's a lot for us all to learn and keep abreast of and to manage on a day-to-day basis in the middle of a busy clinic. But the other thing is that I believe our care has become progressively more inefficient, making it harder every day that we go to clinic to care for the number of patients we need to. And that really has to change. For those of us who've been doing this for a long time, and I know you have as well, this has been a trend really over decades. It's gone in the wrong direction. It was a lot easier to practice a number of decades ago. Now, the requirements for documentation and pre-authorization and many other administrative tasks has just grown progressively over these years. And we need to figure out how to change that. And in addition, our electronic health records, which is where we live in clinic, have been remarkable and wonderful in many ways, but are also inefficient to use and we need to do a better job in optimizing their functionality. Dr. John Sweetenham: Great, thanks Larry. I do agree with you there and I think that in addition to the challenges of running the electronic health record and using that at the point of care, of course the other thing that many of our clinicians face now is an increasingly complex treatment landscape and a greater need for clinical decision support tools, which of course are not always at the moment quite as facile as we would like them to be. And I think partly because of that, many oncologists are feeling overburdened partly with these various administrative tasks they have, partly with frankly keeping up with their own specialty areas or if they're community-based general oncologists, just keeping up in general with the new information that's coming at them. And then add on top of all of that the emotional toll of caring for patients with cancer. And not surprisingly, perhaps I think we have started to see, certainly we have experienced an exodus of some oncologists in recent years who've decided to pursue careers outside of direct patient care and oncology. And those included some moving into other areas of academia, some going into industry, some going into various tech companies and so on. Are you concerned that we all struggle in the effort of building and support a resilient oncology workforce to meet the needs of this growing population that you mentioned? Dr. Lawrence Shulman: Yeah, I'm very concerned about that, John. And I think one way to think about this is that as you say, the practice of oncology inherently is a stressful and difficult, though quite rewarding way to spend your professional career. But we layer on top of that a lot of frustration and difficulties that really don't need to exist. And when I think about this, I think about really two buckets. There's a bucket of factors that are within our control in an individual institution or an individual practice, and I'll come back to that in a minute. The other bucket are external forces, things that are required by the government regulators, by the payers that need to be done in routine practice. We have less direct influence over those, though I think it's a profession, we need to think hard about how to influence the external factors as well. At the practice level, there are a lot of things that we can do. One has to do with optimizing our electronic health record, which does have, in most cases, the ability to have it customized by institution in a way that would make it optimal. And some of that again, is external because we're dealing with a vendor product that has some limited ability to be customized, but we need to do a better job of the technology that underlies our practice every day when we go to clinic. The other major factor in support, whether it's advanced practice providers, nurses, medical assistants, navigators, and other personnel who can in fact help to support the patients, help to support their families, and help to support the clinicians who are on the front line trying to care for these patients. And we all use the term, practicing at the top of your license and aspire to that. But I think frankly we don't do a great job in that regard, and we need to really think harder about how we do have the appropriate team around us. In addition, I would say that there are a lot of other things at the practice level that we need to think about, including the facility of ordering radiologic studies and consultations and so on, all of which are often more cumbersome than they should be. We really need to not put these obstacles in the way of our clinicians. Externally, I think we need to get the payers and to get the government CMS to understand that the current state, it's just not going to be viable going forward and they need to make some big changes. And I think one of the ways to think about this is that rather than doing something differently, you want to do a different thing. I mean, they really need to make some paradigm changes and what's required day in and day out from our clinicians. Dr. John Sweetenham: Absolutely. So, I want to pick up on something that you mentioned there, which is the role of navigators and the benefits that navigation, patient navigation, can have in several domains, but certainly it can help to reduce the burden on oncologists and strain in the system in general. But to take that a little bit further, I wonder if we could talk a little bit about how navigation can help in reducing care disparities. You were saying before we came on the podcast today, the concept of using patient navigators to reduce disparities in care is not new. It's been around for many, many years, but it seems like we almost have to keep relearning that they really help in terms of reducing various disparities which may be rural disparities, racial and ethnic and so on. There are plenty of data out there, as you've mentioned, just to quote a couple of studies, there was the ACCURE trial published a couple of years ago now, which was really a multi-pronged intervention to help Black patients overcome obstacles to completion of treatment. And it included navigation along with a number of other interventions, electronic health record flags to alert caregivers to missed appointments, providers to missed appointments, I should say. It also included physician champions to help engage the health care teams and some educational interventions as well with a significant impact on the access to care from Black patients. The Levine Cancer Institute in the Carolinas conducted a study in my own world, in aggressive large B-cell lymphoma a number of years ago, where they showed that they were able to navigate all of their patients into guideline-concordant care, which essentially eliminated the disparity in outcome between Black and White patients in their population. And then more recently, a study from the University of Maryland looked at Black men with prostate cancer and demonstrated that with the intervention from a navigator, the number of those patients who had their appropriate genetic testing was increased enormously to levels which were comparable with the White patients in their community. No clear evidence yet that that's impacted outcome, although intuitively, I think it would, but nevertheless, as you've already pointed out, there is a ton of evidence that navigation can help us to eliminate disparities. Could you talk a little bit about your own insights into that area and the work that you've done? Dr. Lawrence Shulman: Sure. A few years ago, the National Cancer Policy Forum held a workshop on navigation in cancer and we spent a couple of days in Washington going over many of the studies you've mentioned. And one of our speakers was Harold Freeman, who was a surgeon in Harlem. About 60 years ago, he showed that patient navigation could reduce disparities in cancer care in his setting. And I think the surprising and somewhat disappointing aspect of this is, well, we have a new therapy, whether it's immunotherapy or whatever that is shown to improve overall survival and outcomes. We adopt that, and we start using it. And yet here something that's relatively straightforward, patient navigation, which has been shown as you say, to improve access to care, to improve guideline-concordant diagnostics, guideline-concordant treatment, patient satisfaction, and ultimately improve outcomes and reduce disparities, but has not been embraced in the same way that new therapies have been embraced. And from my point of view, these factors are equally important. They translate in the patient outcomes ultimately just like the therapies that we choose to. And we need to really buy into that. We need to understand that this really affects our patient outcomes as much as our therapies do. So, a couple of things. One is that you've already mentioned the different ways that navigation might improve outcomes, and that's clearly the case. But there are other aspects which are really critical to a lot of conversations we've been having, and that is that navigators fill vital roles that when they're not present are often filled by the treating physician, trying to make sure that the diagnostic tests, the genomics are all done, trying to make sure that the patient is getting their radiologic studies on time, trying to make sure that the appropriate appointments are being set up. Navigators are very, very good at doing this. They're very good at bonding to the patients and helping the patients feel secure through this cancer journey. But if they're not there, either those things don't get done or the clinician, the treating physician or the advanced practice provider is doing that. And so, it has the dual effect of both burdening clinicians who really have another role in the care of the patients doing these other scheduling and navigation functions as well as improving the overall care. I will say that in my own experience, it's important to have navigators who are skilled in their areas, that understand the diseases that we're treating, that understand the patient's needs in relation to those diseases and the treatments and diagnostics that we have to offer. So, there is a real skill to navigation, but a skilled navigator really makes a huge difference to the patient. And again, not only in the very tangible ways that you mentioned, but also frankly in the psychological security of the patient. And patients will tell you this and there are surveys out there that show this, that patients who are undergoing a new diagnosis of cancer are terrified, do much better psychologically when they have a navigator at their side through this journey. But it has tremendous benefit to the clinicians as well. And why haven't we embraced navigators? I can only speculate, but one of the comments that I get from health system administrators is, “Well, they cost a lot of money, and their work is not reimbursed as part of health care reimbursement.” But there is, again, overwhelming evidence to show that the return on investment for navigators is substantial. And it's substantial because it keeps patients in your practice, it provides more efficient care at all levels. And we published out of the National Cancer Policy Forum work, an article that basically shows from a variety of different centers, including mine at Penn, that there is a tremendous ROI for having navigators. So yeah, it's a little bit of money upfront to hire them, but ultimately, it's a good thing financially as well as clinically. Dr. John Sweetenham: Yeah. So often with these kind of wraparound services that are so important to our patients showing and being able to clearly demonstrate the kind of downstream revenue from those services is difficult, but is I think probably evident to those of us who are in the clinic and see what happens. So, maybe we need some more sophisticated financial models to be able to highlight that to our leaders in the health systems, I think that the evidence is really quite clear. So, Larry, one of the disparities that you've mentioned, and perhaps we haven't focused on quite so much in this discussion, has been the issue of cancer care for rural versus urban communities. And I think it's important that we highlight the challenges that oncologists are facing in rural communities across the country in caring for patients who live many miles away from a hospital or clinical practice and where the oncologists do not have the kind of support system that you'd find in an academic center in a major city. Can you comment a little on that? Lawrence Shulman: Sure, John. This is a real problem. I and others have published on cancer survival statistics in rural settings and in small community hospitals and they are in fact inferior to larger academic cancer centers, probably for a multitude of reasons. And one of our colleagues, Dr. Otis Brawley, made the comment a number of years ago and still repeats it, that your likelihood of surviving cancer in the U.S. is more tightly linked to your ZIP code than your genetic code. And there is some truth to that. Now, there are tremendous challenges for providing cancer care in a small, rural hospital. We practice in academic medical centers; I'm a breast cancer doctor and I spend all of my time trying to stay current in breast cancer. And it's a field that's changing rapidly. It's hard for me to imagine how my colleagues who are generalists in the community are keeping up with the advances in so many different diseases. And I think frankly, it's really, really hard to do that. In addition, all of us at academic centers have weekly tumor boards. We get to ask our colleagues what their thoughts are about our difficult cases. We get a lot of input from pathologists, radiologists, and other colleagues. And frequently clinicians, physicians, oncologists, practicing in rural hospitals don't have that constituency around them for them to bounce difficult patients off of to try to figure out what the best approach might be for a patient. So, the differences are terrific, and the support is just not there. This is something that our country has not really confronted. We have a very big country geographically. Some of the areas of the country are quite rural. A patient can't be expected to travel four hours in each direction to an academic cancer center. We need to figure out how to better partner between our academic cancer centers and our community colleagues to support their care in ways that we've not done routinely up to this point. I know that the National Cancer Institute is very interested in this and trying to figure it out. But again, I think we have to feel a collective responsibility to support our colleagues in the community. They try really hard, they're working really hard, they're doing the best they can, but they just don't have the support that we have in academic cancer centers. Dr. John Sweetenham: Yeah, sure. Before we wrap up the podcast today, I'd like to circle back a little to something that you said earlier and a topic that I know that you've published about quite extensively in the past and that's the issue of health care technology. And I think we probably all agree that health care's been a little bit slow to capitalize on technology to improve our care processes and outcomes. And your research has highlighted that technology can facilitate patient-clinician interactions in a number of ways through augmented intelligence, texting, chatbots, among other things. Can you tell us a little bit about this, how you think that AI might be able to help us in the future to streamline the management of some of these medical and administrative issues that we've been talking about today? Dr. Lawrence Shulman: Sure, John. It's hard to turn the TV on or read a newspaper without an article on artificial intelligence. But the word you used is the word that I use, which is augmented intelligence. I don't think we're looking to replace clinicians with technology, but we're looking to in fact make their jobs easier, to remove some of the tasks that they don't need to do themselves as really an assistant, if you will, another assistant. We have used technology extremely poorly in the medical profession overall. I'm not quite sure why that is. But if you look at the banking industry or other industries, they've used technology tremendously well with great benefit, benefit not only for the people who are using the services, in our case, the patients, but also those who are providing the services, in our case, the clinicians. So, I think we need to do a better job. We need to have electronic health records that are in fact helping rather than sometimes hindering or making frustrating the care of the patients. We need to use artificial intelligence or augmented intelligence to interact with patients and help to manage them. We're using augmented intelligence chatbots to manage patients who are on oral chemotherapy able to do a lot of the tasks that normally the clinicians would be doing without in any way jeopardizing the safety or the well-being of the patients. The patients actually tell us that they like this, that it's just another way to feel connected to their practice in a way that's efficient and easy for them through texting rather than sometimes trying to call the practice, which can be frustrating. But there are lots of other things as well in analyzing data, bringing data forward that will help us to make the appropriate decisions. And one of the things that I often use as an example is the airline industry. And they have a remarkable safety record as we all know, thank goodness. But if you sit in the cockpit of an airplane and you look at the instruments, all the critical data is right in front of them, unencumbered and very clearly presented because they need those data to fly the plane, and they need those data to be rapidly and easily accessible. They can get all the data they need; you look at the cockpit ceiling, it's got a thousand switches on, everything they need is there, but the critical data is never hidden and always presented. I don't think that that in fact is the way our electronic health records are set up. In fact, quite the contrary. And all of us spend a fair amount of time looking for data and so on because the records are complicated, and they're used by a lot of different specialists. But we can use augmented intelligence to bring all the critical data up, just like the cockpit in an airplane, to make sure that we have what we need rapidly accessible, and we don't miss anything. We don't go looking for the genomic test and can't find them and then assume they weren't done and make a decision without critical data when in fact they were done, but the data is hidden. So, I think we have a lot of options to use technology to improve our daily lives. I think it will take away some of the frustrations that lead to burnout, and we'll also make practice not only more efficient, but frankly also much safer. I think we have to work hard on this. We could partner with that technology colleagues. We at Penn are trying to do that. I know others are trying to do it as well. And I think the patients will benefit, will all benefit. Practice will be better, safer, less frustrating, and the outcomes of the patients will be better. Dr. John Sweetenham: Yeah, thanks Larry. I think your analogy with an aircraft cockpit is so perceptive and I think that that's something if we could unclutter our electronic health records and what we're seeing in front of us in at the points of care in the clinic, I agree 100% that will be such a step forward. So, thanks for sharing that. Thanks also, Larry, for discussing some of these challenges that we're going to be confronting in the next year and beyond, as well as the potential solutions. I think one thing that is really important to remember despite these challenges is something that I mentioned in the introduction to the podcast today. So, when we are all feeling a little bit disheartened because of the challenges ahead of us, it's important to remember that in 2026 there will be an estimated 20.3 million cancer survivors in the United States, which really does underline how far we've come, certainly in the time that you and I have been practicing oncology, and really important not to lose sight of that. We had a lot of challenges, but really the achievements of the last 50 years or so are pretty remarkable. It's been a real pleasure to have you on the podcast today, so thank you again for joining us and for sharing your thoughts with us. Dr. Lawrence Shulman: Thanks so much for having me, John. Dr. John Sweetenham: And thank you to our listeners for your time today. 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. For more information on Dr. Shulman's research discussed in this episode, please see the articles below: The Future of Cancer Care in the United States—Overcoming Workforce Capacity Limitations | Health Care Workforce | JAMA Oncology | JAMA Network Developing and Sustaining an Effective and Resilient Oncology Careforce: Opportunities for Action - PubMed (nih.gov) Re-envisioning the Paradigm for Oncology Electronic Health Record Documentation by Paying for What Matters for Patients, Quality, and Research | Health Care Reform | JAMA Oncology | JAMA Network Survival As a Quality Metric of Cancer Care: Use of the National Cancer Data Base to Assess Hospital Performance - PubMed (nih.gov) Establishing effective patient navigation programs in oncology - PubMed (nih.gov) Patient Navigation in Cancer: The Business Case to Support Clinical Needs Cancer Care and Cancer Survivorship Care in the United States: Will We Be Able to Care for These Patients in the Future? - PMC (nih.gov) Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:      Dr. John Sweetenham  Dr. Lawrence Shulman     Follow ASCO on social media:       @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn       Disclosures:      Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness     Dr. Lawrence Shulman: Consulting or Advisory Role: Genetech Research Funding (Inst.): Celgene, Independence Blue Cross

Drs. John Sweetenham and Fred Locke discuss the FDA investigation on the risk of cancer from CAR T-cell therapy and share insights on the known number of cases and the potential implications on clinical research and patient care. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. CAR T-cell therapies have been game changers for treating certain cancers including lymphomas and leukemias, as well as multiple myeloma, since the vast majority of patients who have received CAR-T do not have other curative options with conventional non-cellular, anti-cancer therapies. But on November 28, the U.S. Food and Drug Administration announced that it is investigating whether CAR T-cell therapy can, in rare cases, cause secondary cancers. The FDA launched the probe after receiving reports from clinical trials and other data sources of T-cell malignancies in patients who received CAR T-cell immunotherapies. Joining me to discuss the investigation and its implications for the field is Dr. Fred Locke, a medical oncologist and translational researcher and a senior member and chair in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at the Moffitt Cancer Center in Tampa, Florida. Dr. Locke is an internationally renowned clinical research leader in the field of CAR T-cell therapy. You'll find our disclosures in the transcript of this episode, and disclosures of all guests on podcasts are available at asco.org/DNpod. Fred, it's great to have you on the podcast today. Dr. Fred Locke: Thanks, John, I'm really glad to be here. Dr. John Sweetenham: So, T-cells are the backbone of CAR T-cell therapies, and there are currently 6 CAR-T products approved by the FDA. As our listeners will know, CAR T-cell therapies manipulate a patient's T-cells, enabling them to recognize and attack antigens on cancer cells and induce potential long-standing changes in the immune system. In its statement on November 28, the FDA said it determined that the risk of T-cell malignancies is applicable to all of the currently approved BCMA- and CD19-directed, genetically modified, autologous CAR T-cell immunotherapies. Fred, could you comment for us on the investigation: How many patients are reported to have developed second malignancies from CAR T-cell therapy, and whether there are likely to be more secondary cancers reported? Dr. Fred Locke: Yes, so the FDA and the reports are coming out that there are 19 cases of T-cell malignancy that we're aware of that have occurred after the current FDA-approved CAR T-cell therapies were administered for the treatment of leukemia, lymphoma, or multiple myeloma. The majority of those cases were reported through the FDA Adverse Event Reporting System. And we don't know a lot of details of those 19 cases. We think that there's probably about 13,000 to 14,000 patients who've been treated with the commercial CAR T-cell therapies. So if you kind of do some crude math, you can come up with 19 out of say, 13,500; we're at about 0.1% of patients who could have developed T-cell lymphoma after treatment with these CAR T-cell therapies. It's not entirely out of the realm of possibility that T-cell lymphoma could develop from gene-modified T-cells, and these are all the patient's own T-cells that have been modified outside of the body. But I would still posit that this is a really low incidence of T-cell lymphomas in these patients who really are without other great treatment options. Dr. John Sweetenham: Yeah, and I think that's a point that we'll return to a little bit later on in the conversation around the fact that you know, clearly, there are major benefits that have been associated with CAR T-cell therapy and hematologic malignancies so far. And of course over the years, I think that many of us have become familiar with and learned a great deal about how to manage some of the more serious side effects of CAR T-cell therapy. And you, of course, have led several pivotal national trials of anti-CD19 CAR-Ts for lymphoma. Can you comment at all on whether you've seen previous data from your own practice or others on the risk of second malignancy from CAR T-cell therapy? And can you share your insights on the data and any new emerging data that warrants our attention for the concern or risk of second malignancy? And I guess to round up that series of questions, is there anything currently in yours or others research into CAR-T to explain what's happening and why this is going on? Dr. Fred Locke: I think what may have prompted the FDA's announcement of this is that on the same date that they came out with announcing their investigation, there was the release of the abstracts for the American Society of Hematology Annual Meeting. And within those abstracts, and unfortunately it was not selected for poster or oral abstract presentation, but discovered within those abstracts was one on a CAR+ T-cell lymphoma after ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma. And what these investigators and the company were reporting is that a patient with refractory multiple myeloma received the cilta-cel BCMA-directed CAR T-cell therapy and developed a stringent complete response, and about 5 months later developed a nasal facial plaque and PET+ cervical lymph nodes. And both the lymph nodes and the plaque were biopsied and showed a T-cell lymphoma in which 90% to 100% of the cells were positive by qPCR for the CAR construct and immunohistochemistry for the CAR protein. So this was a T-cell lymphoma growth where the cells were expressing the inserted protein, the chimeric antigen receptor protein, which is obviously not natural. And when they looked a little bit deeper at these patients, 91% of the cells have the same T-cell receptor sequence. So this was really a clonal sort of process. They did CAR integration analysis to see how the insertion of the CAR, the chimeric antigen receptor gene, could have potentially disrupted a gene within the T-cells. And what they found is that there were some dominant sort of insertions within certain genes suggesting monoclonality, but it wasn't within any sort of obvious activating genes that would be expected to lead to the T-cell lymphoma. They went on and did some additional analysis, and they showed that there was some existing TET2 mutations in the T-cells of this patient, prior to probably prior to the CAR T-cell manufacturer, and they weren't associated with clonal insertion. And I think, you know, it's possible that this patient who had a pre-existing mutation may have been susceptible to the development of a T-cell lymphoma prior to the CAR T-cell treatment. And TET2 was previously shown a number of years ago in a CLL patient treated with CD19 CAR T-cell therapy; it was shown that there was insertional mutagenesis, silencing the TET2 gene, and that associated with clonal expansion of the CAR T-cells in that patient and corresponded with remission of the CLL. However, the difference here is that that patient's T-cell clone went back down and contracted, and the patient remained in remission 5 years later with their T-cells still in the blood, but the minority of those T-cells had that that TET2 mutational insertional mutagenesis. All this is something we thought was theoretically possible, that T-cell lymphoma could develop after car T-cell therapy. And in fact, a prior trial using a different method of delivery of a CAR gene; instead of using a virus to insert the car into the into the T-cells, a transposon system called piggyBac was used. And in that trial, again, CD19 CAR trial, but in this case, it was allogeneic donor cells for patients who had relapsed after an allogeneic transplant. So it's sort of an autologous, you know, analogy, but it's using the donor cells. And in that trial, 2 out of like 10 patients developed clonal T-cell lymphoma, which was CAR+, but they weren't able to identify a clear insertional mutagenesis event in those cases. So, we've known this is possible, and it would have been great if this poster or if this abstract at ASH was presented as an oral or a poster so we could get more detail, but it's possible that that's the likely reason for the FDA's announcement. Dr. John Sweetenham: Thanks. The bottom line, I guess, is that for now, the jury's still out on exactly what's underlying these observations, but something which I'm sure is going to be the subject of a lot of discussion during the ASH meeting this year and moving forward. I'd like to inform our listeners that ASCO released a statement on the FDA investigation, stating that the risk of T-cell malignancies due to CAR T-cell therapy appears to be very low. And we've just heard from Dr. Locke that, of the several thousand patients who've received CAR Ts, there are 19 cases so far, it's been reported, which puts us into some type of proportion. The ASCO statement goes on to say that based on available data, and while such malignancies have occurred in patients who have received CAR T-cell therapy, the causal relationship, whether these cases are spontaneous or are caused by the therapy, needs to be investigated further, and we've just heard a little about the detail of that. ASCO added that by issuing a warning but not revoking approval of these therapies, the FDA clearly believes that the current available evidence suggests the overall benefits of these products, used within their approved label, continue to outweigh the potential risks. So Fred, the risk of secondary malignancies is already included as a class warning in the U.S. prescribing information for these CAR T-cell therapies. But do you think that the CAR-T products could eventually be taken off the market, and how would your research be impacted if this were to happen? And maybe finally, how long will patients on CAR T-cell therapy need to be monitored moving forward? Dr. Fred Locke: I don't believe that CAR T-cell therapy will be taken off the market. As we've already talked about, the incidence is extraordinarily low and the causality is unclear. It would certainly impact my research, as I'm doing clinical trials with CAR T-cell therapies, but it would more importantly impact the way we treat patients. We did over 300 CAR T-cell therapy treatments last year here at Moffitt Cancer Center. We're one of the busiest programs in the world giving CAR T-cell therapy, and it is truly a transformative therapy for all the diseases that we administer these FDA-approved therapies for. For example, in diffuse large B-cell lymphoma, we participated in the ZUMA-7 clinical trial and recently reported that patients randomized to CAR T-cell therapy had improved overall survival. They were living longer than patients randomized in the second-line setting to get conventional chemotherapy and autologous transplant. This is clearly a therapy that can work. I would also add that the risk of secondary malignancies is real, but that's a risk for all cancer patients, particularly patients with hematologic malignancies, and for example, lymphoma patients who've gotten an autologous stem cell transplant are at a relatively high lifetime risk of developing a secondary myeloid malignancy, most commonly, treatment-related MDS or AML. And that risk is also present after CAR T-cell therapy. The degree of attribution of CAR-T versus the condition of chemotherapy for CAR-T versus the previous chemotherapy is all unclear, and more analysis needs to be done. But the risk of developing treatment-related MDS or leukemia is certainly higher than the small number of T-cell lymphomas reported. The other thing I want to point out is that there was an analysis of the SEER database that patients with B-cell lymphomas are at about a 5-fold higher risk of developing a T-cell lymphoma than the otherwise healthy population; and vice versa, by the way, T-cell lymphoma patients are at risk for developing B cell lymphoma. And in fact, in that SEER database, it's not a wildly different percentage chance of developing a T-cell lymphoma after a B-cell lymphoma. And this data came out before the advent of CAR T-cell therapy. So I really think we need more science to be done to understand what's happening for these patients. Will this impact the field? Well, certainly, there are treatments that are not CAR T-cell therapy that compete with CAR T-cell therapy or could; I'm a strong believer that they don't offer the same outcomes for patients, but we will certainly see people talking about this for some time. Then the other place where this could be relevant, I think, is as we look at CAR T-cell therapy for autoimmune disorders, and we're starting to see studies of that for lupus and other diseases, the risk to benefit ratio could be different in those cases. So this is something we really need to consider as we move forward with CAR T- cell therapy. Dr. John Sweetenham: Yeah, thanks, Fred. And as a major clinical investigator in the field of CAR-T at the moment, do you see any potential concerns about difficulties in getting patients onto the trials of CAR T-cell in the light of this information? Dr. Fred Locke: No, I really don't. We're not seeing hesitancy, at least in the patients who are referred in for CAR T-cell therapy. Again, it may give ammunition for those who are already predisposed to not refer patients in for CAR T-cell therapy, but I don't think it should. I think that these are low risks, and these therapies clearly have benefits to patients. And we should give their patients an opportunity to get these therapies, and I don't see it impacting our clinical trials at this point. Dr. John Sweetenham: Yeah, and your comments address what was going to be my final question to you and that is, as a referring oncologist, how would you advise a referring oncologist to talk with their patients about these data and their implications moving forward? Dr. Fred Locke: If the patient brings it up, I think the response should be that these are very few cases of very low incidence and very low risk. There are other risks to CAR T-cell therapy that are greater, and really speaking with a cell therapist who administers the treatment is probably the best way to give the patient the option to get CAR T-cell therapy if they want to, knowing all the risks and benefits. So, I would leave it up to the CAR-T treatment center to discuss those risks with the patient.   Dr. John Sweetenham: Well, thanks, Fred, for sharing your insights with us on these concerning developments in CAR T-cell therapy, and I think also for putting them into context in terms of the sort of magnitude of this problem in the context of the overall number of patients who are benefiting from this therapy right now. We truly appreciate your time, and thanks for sharing your thoughts with our listeners. Dr. Fred Locke: Thanks, John, my pleasure. Dr. John Sweetenham: And thank you to our listeners for your time today. If you value the insights you hear on ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.    Find out more about today's speakers:      Dr. John Sweetenham Dr. Fred Locke @DrFredLocke     Follow ASCO on social media:         @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn         Disclosures:        Dr. John Sweetenham:    Consulting or Advisory Role: EMA Wellness     Dr. Fred Locke: Consulting or Advisory Role: Novartis, Celgene, Calibr, Allogene, Gerson Lehrman Group, EcoR1, Amgen, Bluebird Bio, Bristol Myers Squibb, Iovance Biotherapeutics, Legend Biotech, Cowen, Kite (Gilean), Umoja Biopharma, Takeda, Sana Biotechnology, Daiichi Sankyo/UCB Japan, Bristol-Myers Squibb/Celgene, Janssen, A2 Biotherapeutics, Mittenyi Biotec, Caribou Biosciences, Takeda, Umoja Biopharma Research Funding: Kite Pharma, Allogene, Novartis, Bluebird Bio, Bristol-Myers Squibb/Calgene Patients, Royalties, Other Intellectual Property: Double Mutant Survivin Vaccine. US010414810B2 CAR T Cells with Enhanced Metabolic Fitness; Serial Number: 62/939,727 Methods of Enhancing CAR T Cell Therapies. Serial Number: 62/892,292. Evolutionary Dynamics of Non-Hodgkin Lymphoma CAR-T cell therapy.  Serial Number: 62/879,534. Travel, Accommodations, Expenses: Kite Pharma, A2 Biotherapeutics

Recorded on 11/10/23 TD Cowen analyst Yaron Werber speaks with Chris Garabedian, co-founder, chairman, and CEO of Xontogeny and Portfolio Manager of the Perceptive Advisors Ventures Fund. Chris shares his insights about 1) what makes or breaks a successful biotech from his time at Gilead, Celgene, and Sarepta, 2) how investing has changed now that interest rates are high and capital is expensive, and 3) his investment philosophy at Xontogeny and advice to other early-stage investors. For Disclosures, click here bit.ly/3cPHkNW

In this episode of Meeting Mic, we bring you Healio's top headlines from ACG 2023. Paul Feuerstadt, MD, FACG, AGAF, discusses data that link health-related quality of life and microbiome composition among patients with recurrent Clostridioides difficile infection. :38 Edward V. Loftus Jr., MD, FACG, discusses results from the INSPIRE trial for ulcerative colitis. 7:52 Jan Wehkamp, MD, PhD, discusses results from the QUASAR study, in which Tremfya outperformed placebo in clinical response patients with ulcerative colitis. 12:08 Paul Feuerstadt also discusses the evolution of treatment for Clostridioides difficile infection, from antimicrobials to recently FDA-approved live biotherapeutics. 15:32 Thomas F. Imperiale, MD, discusses the results of the BLUE-C study, which evaluated the clinical performance of Cologuard, a next-generation, multitarget stool DNA test. 21:08 Read the full coverage here: https://www.healio.com/news/gastroenterology/20231023/video-rebyota-not-only-shuts-down-recurrence-also-affects-quality-of-life-in-c-diff https://www.healio.com/news/gastroenterology/20231025/video-risankizumab-a-great-option-for-patients-induces-clinical-remission-in-uc https://www.healio.com/news/gastroenterology/20231024/video-more-than-75-of-uc-patients-achieve-clinical-response-at-24-weeks-with-tremfya https://www.healio.com/news/gastroenterology/20231025/video-future-is-now-here-for-recurrent-c-difficile-thanks-to-live-biotherapeutics https://www.healio.com/news/gastroenterology/20231025/sensitivity-of-nextgeneration-cologuard-in-precancer-detection-numerically-exceeded-fit Disclosures: Feuerstadt reports financial relationships with Ferring Pharmaceuticals, Regeneron Pharmaceuticals, Seres Therapeutics and Takeda Pharmaceuticals. Imperiale reports grant and research support from Exact Sciences. Loftus reports financial relationships with AbbVie, Alvotech, Amgen, Arena, Avalo Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Exact Sciences, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Scopes, Janssen, KSL Diagnostics, Lilly, Morphic, Ono Pharma, Pfizer, Protagonist, Receptos, Robarts Clinical Trials, Scipher Medicine, Sun Pharma, Surrozen, Takeda, Theravance and UCB. Wehkamp reports no relevant financial disclosures.

Brian Whitlock, Vice President of Global R&D Procurement at Bristol Myers Squibb shares his experience in building a high-performance operating model to support the business objectives of biopharmaceutical research. In the latest episode of the PharmaSource podcast Brian explains how the procurement operating model had to change following 2019, when BMS announced the acquisition of Celgene. “The acquisition was a sea change for how we think about procurement, and how to support a much larger critical R&D business unit with 9,000 scientists worldwide.” he says. Procurement had to align with the priorities for the wider Bristol Myers Squibb business: building a world class pipeline, improving productivity and reducing development cycle times while also delivering high quality medicines to our patients. In order for procurement to support this, Brian explains that “There has been a lot of process reengineering, both internally and with our partners, but also tapping capabilities that exist within the supplier market, that perhaps we have not made a direct investment in.” Brian worked with leaders within R&D function to design an operating model that “not only focuses on driving the high volume, high risk and high visibility opportunities but also have individuals with unique skill sets that can drive an innovation portfolio.” “Procurement played a very important role sitting at the table with our stakeholders to bring those new capabilities to our enterprise.” “One of the things I absolutely love about R&D is we have very creative scientists that come up with challenging opportunities. Every day is different. Every challenge is a little bit unique. It's that variation, and the complexity of these challenges that really motivate us day to day.” The conversation covers the follows: Strategic procurement helps navigate challenging times Cultivate an innovation mindset to increase speed to market Re-designing procurement for speed Deep accountability for your category Innovation comes from smaller transactions One team, serving Patients BMS Prime: Enabling self service The growing importance of Computer Aided Research How important is having a scientific background? Full article here

Qu'est-ce que l'infection à HPV ? Le risque du cancer du col de l'utérus augmente-il en cas de polyarthrite rhumatoïde ? Comment prévenir le cancer du col de l'utérus ? Comment s'effectue le dépistage du cancer du col de l'utérus en France ? Le dépistage au cours de la polyarthrite rhumatoïde diffère-t-il de la population générale ? Le Dr Fabienne Coury-Lucas, rhumatologue à l'hôpital Lyon Sud des Hospices Civils de Lyon, répond à vos questions.   Invitée : Dr Fabienne Coury-Lucas – Hôpital Lyon Sud – HCL Lyon https://www.chu-lyon.fr/service-rhumatologie-lyon-sud  Le Dr Coury-Lucas déclare des liens d'intérêts avec les laboratoires Abbvie, Biogen, Celgene, Chugai, Novartis, Pfizer, UCB.   L'équipe :
 Comité scientifique : Pr Jérémie Sellam, Pr Thao Pham, Dr Catherine Beauvais, Dr Véronique Gaud-Listrat, Dr Céline Vidal, Dr Sophie Hecquet Animation :  Pyramidale Communication Production : Pyramidale Communication Soutien institutionnel : Pfizer   Crédits : Pyramidale Communication, Sonacom

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with J.D. Mowery, President and Chief Executive Officer at KBI Biopharma. Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with J.D., covering: The experience of bringing a product to market... and then many years later seeing that product used on his wife to help bring his sons into the world How bringing a commercial facility online for Genentech to impact thousands of patients compares to the ‘vain to vain', hospital-based, one-off patient CAR-T product for Juno Why the ethos of taking care of the person on your left and the person on your right helps with the scale-up of a multi-national global CDMO The emergence of a partnership-based, absorption business model between innovators and CDMOs in the wake of the shift in capital markets What the next generation CDMO will look like… J.D. is an accomplished leader with a distinguished reputation in the biopharma industry and proven expertise in guiding global innovators and contract development and manufacturing organizations (CDMOs) for nearly 25 years. Throughout his diverse career, J.D. has demonstrated strategic vision and the ability to drive all aspects of an organization, including operations, R&D, manufacturing, tech transfer, facility construction, business development, employee growth, and investor relations. He is an expert in diverse modalities, including small molecules, biologics, and cell and gene therapy. J.D. has held executive leadership positions as  Head of Operations at Lonza and Executive Vice President of U.S. Operations at AGC Biologics. He has also held influential roles at innovators, including Genentech, Celgene, and Juno, and most recently served as Chief Operating Officer at Treadwell Therapeutics. J.D. holds a Bachelor of Science from George Fox University and an MBA from Marylhurst University. Please subscribe, tell your industry colleagues, and join us in celebrating and promoting the value and importance of the global life science outsourcing space. We'd also appreciate a positive rating! Molecule to Market is sponsored and funded by ramarketing, an international marketing, design, digital, and content agency helping companies differentiate, get noticed, and grow in life sciences.

Orca Bio's Dan Kirby has played a hand in prepping more than a few approved biologic therapeutic candidates for commercialization. Equally important, he knows firsthand what makes or breaks post-approval commercial efforts, having played virtually every role there is to play in drug sales and marketing. He "carried the bag" for GSK in his early days, directed oncology marketing efforts at Amgen, and led marketing and U.S. commercial efforts at Juno, then Celgene after it acquired the former. Kirby joined Orca Bio in timely fashion back in 2020, as today the company ushers its first cell therapy into phase 3 clinical trials, with strategically-dispersed follow-up candidates spanning all phases back to R&D. On this week's episode of the Business of Biotech, we get a one-on-one commercialization preparation discussion with one of the best in the business, and the straight-talking veteran doesn't disappoint in the strategy and insight departments. Subscribe to the NEW #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!

Drs. Vamsi Velcheti, Taofeek Owonikoko, and Janakiraman Subramanian discuss their experiences navigating the cancer drug shortage in the United States, the impact on patients and clinical trial enrollment, lessons learned, and proactive strategies to mitigate future crises. TRANSCRIPT  Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone. On today's episode, we'll be discussing the impact of the shortage of cancer chemotherapy drugs across the United States. This has been affecting several thousands of patients with adult and pediatric cancers and hampering enrollment in clinical trials. Among the shortages are very commonly used drugs like cisplatin, carboplatin, methotrexate, and fludarabine. Some of these shortages have persisted since the time of the pandemic in 2020.   So today, to discuss this really troubling scenario, I have two outstanding colleagues, Dr. Janakiraman Subramanian, the director of thoracic oncology at Inova Schar Cancer Institute in Virginia, and Dr. Taofeek Owonikoko, a professor of medicine and the chief of the Division of Hematology and Oncology at the University of Pittsburgh Hillman Cancer Center in Pittsburgh.   Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod.  So, a recent survey by the NCCN found that 90% of the nation's largest cancer centers have experienced a shortage in carboplatin, and 70% of the centers have reported a shortage in cisplatin. These are platinum-based chemotherapies we use frequently in patients with cancer, and these are often curative intent treatments for several cancers, and these are used in several tumor types, both solid tumors and hematologic malignancies. So, the scale of the problem is immense.   Dr. Owonikoko, I'd like to hear your take on this situation and how are you dealing with this at the UPMC Cancer Center.  Dr. Taofeek Owonikoko: Yeah, thank you, Dr. Velcheti, and happy to be part of this panel. As you rightly surmised, the chemotherapy drug shortage is what we've all experienced across the length and breadth of the United States. Our cancer center here in Pittsburgh is not an exception. We've had to be proactive as well as think outside the box to be able to manage the challenge. Just like every other cancer center across the country, maybe to varying degrees, we've had to look at patients in need of chemotherapy with these standard-of-care agents such as cisplatin or carboplatin, and to some degree docetaxel, during this past episode of drug shortage that we all went through. And while we did not have to, fortunately, cancel any patient treatment, we all went through it with bated breath; not sure of where the next batch of chemotherapy drugs will come through, but I would say in the past couple of weeks, we've actually seen some improvement in drug availability.   But before then, we've had to have contingency plans where, on a weekly basis, we review our patient list and the drug regimens that they're going to need, and must make sure that we have enough drug on hand for those patients. And in situations where we thought we might not have enough drug; we also had a plan to use alternative regimens. We were proactive in having guiding principles that are consistent with ASCO's recommendations in terms of quality care delivery for cancer patients. So, I'm sure that this is more or less the same approach adopted by other leading cancer centers across the country.   Dr. Vamsi Velcheti: Thank you, Dr. Owonikoko. And Dr. Subramanian, you're in a community setting, a large cancer center that serves a lot of patients in the state of Virginia. So, what is the scale of the problem at your institution and how are you handling it?   Dr. Janakiraman Subramanian: First of all, Dr. Velcheti, thanks for having me here on this panel. And as you rightly said, this is a significant problem, and it is across the country like Dr. Owonikoko said. And as medical oncologists, we are not always thinking of drug shortages. Our focus is on taking care of our patients. So, this is one more issue that we need to keep in mind now as we manage our patients with cancer. When this shortage started, the biggest problem, as you know, was when we became aware of this was primarily in cisplatin and we had some of our patients who were getting curative treatment and we had to make a decision - can they get cisplatin or can they get carboplatin. And one of the things we did was to have an ethics committee that will review each patient that is being planned to receive cisplatin-based chemotherapy and come to a decision on how best we can support them.   The template for some of this was based upon some of the triage mechanisms we used during COVID, as well as the ASCO guideline document for managing this chemotherapy shortage, which was one of the blueprints we used. And they have reviewed all cases, all patients that are being planned for cisplatin or carboplatin for that matter, and we come to a decision based on that. And we also have another committee that constantly monitors drug availability on a weekly basis and tries to forecast where the next problem would be as we take care of our patients.   And particularly as a lung cancer doctor, we've had situations where we had to use carboplatin instead of cisplatin and even we also have carboplatin shortage. And so, the committee usually approves two cycles at a time, but thankfully so far we have not had a situation where we could not offer our patients the chemotherapy treatment. But we are very carefully monitoring the situation, hoping that this will improve.   The other aspect of the shortage has been in 5FU. A lot of our GI colleagues; I treat esophageal cancer patients as well, where we've had to forego the bolus 5FU and have a 10% reduction on all 5FU infusions. And we've been using some of that dose reduction to ensure that we can have 5FU available for all our patients. And that's how we've been trying to manage this shortage situation here at Inova Schar.   Dr. Vamsi Velcheti: Dr. Subramanian and Dr. Owonikoko, we are oncologists, we are treating patients, and the toughest part really is telling a patient that we don't have access to certain drugs and we have to switch treatments to perhaps another treatment regimen that may be suboptimal. And it's always a very anxiety-provoking discussion, and especially for patients with metastatic cancer, they're already under a lot of stress and it's a really difficult conversation. How do you handle that, Dr. Owonikoko?  Dr. Taofeek Owonikoko: That's a conversation we all hope we don't have to have. And fortunately, with this current crisis, I've actually not had such misfortune of having to inform a patient that we don't have drugs to treat them or that we have to switch to something inferior. But conceptually, it's possible that could have happened and that would have been very difficult. But the one thing that we did, though, as part of our mitigation strategy was actually to inform the patient ahead of time because the way we handled this was to look at our inventory on a week-by-week basis. And if there are patients where we felt maybe they will be coming in towards the end of the week and we may not have enough drugs for them, to let them know the possibility exists that we might have to switch them to something different. While we did not have to do that for any patient, yes, there are patients that we had to give that heads up to, to say, “We're having this shortage. We're doing everything we can to make sure it's available. But just in case it's not available…” I think what is most important for most patients is to be aware of that decision ahead of time, to be able to process it, and to be transparent.   The other challenge that we face was, if you have to choose between patients, what should be your guiding principles as to who gets the drug and who doesn't get it? I think it's very easy for all of us to say, “Oh, if it's curative intent, we do it. If it's not curative intent, we don't do it.” It's a little more complicated than that because if we put the equity hat on, curative intent doesn't actually mean that that life is more valuable than somebody who cannot be cured. And this is where really, I think having people with expertise in ethics of care delivery and disaster management will be very important for us to proactively anticipate that, should this become a recurrent problem in the future that we actually have a well-vetted approach, just like we did during COVID where you have to ration resources that we have those people with expertise to help us as oncologists because not all of us, at least personally I can speak for myself, that is not my area of expertise and comfort.  Dr. Vamsi Velcheti: Excellent points. Dr. Subramanian, anything to add?  Dr. Janakiraman Subramanian: Oh, absolutely. I echo what Dr. Owonikoko said. These are conversations that we would like to hopefully never have with our patients. But this is a crisis that we are facing now. And personally, I can tell you two situations where we ran into this problem. But overall, though, we never had to stop a treatment or cancel a treatment for our patient. In the first situation, we had a young man with a rare germ cell tumor in the hospital for whom cisplatin was key. He was already in the ICU and sometimes the treatment start dates are not perfect, unlike what we do in the outpatient setting, depending on how well he's doing or the treatment start dates might move by a day or so. So we basically had to hold a certain dose of cisplatin for him.   This brings the next question, which is how do we decide who gets cisplatin versus who can go for an alternative option? And I think Dr. Owonikoko made a great point where, just because it is a curative disease does not mean their life is more valuable. This is where I think trying to make that decision at an individual level, as an individual treating physician can be extremely hard. And that's why at our institution we have this ethics committee where we have oncologists, pharmacists, and ethicists that review these chemotherapy orders, particularly for cisplatin, and try to use some guiding principles that we learned from COVID as well as ASCO's guidance to decide how we assign our resources. That's one option, one way we have done it.    And then in another situation that was faced by one of my GI oncology colleagues was a patient that was originally planned to go on a clinical trial where the chemotherapy backbone was FOLFOX and because we had the 5FU shortage, we could not offer that patient clinical trial enrollment. And that was a tough conversation where they had to tell them that they could not go on a clinical trial that they were looking forward to. And this then brings the next question, which is by foregoing the bolus 5FU and by the 10% reduction in the infusional 5FU, are we providing them inferior treatment? And it's a conversation that's had at a very individual level. I don't envy my colleague who had to have that conversation. It's a challenge and we try to do our best to communicate to our patients that we are trying to provide care without trying to compromise the effectiveness of treatment for them.  Dr. Vamsi Velcheti: Thank you so much both of you. And we had the same issues here at NYU in New York City as well. It appears, you know, the degree of shortage and the drugs that are in shortage has been somewhat different at different locations across the United States. But the theme has been that we are having to ration treatments for our patients. And of course, there are some tumor types where there's really no adequate substitution, for example, GU cancers. I mean, you can't really not give them cisplatin. A lot of these are situations which have curative intent and young patients. So, it's really troubling.   And I think one of the things that really came out of this is there's been a lot of push from professional societies that actually ASCO has been spearheading and some intense discussions with CMS and legislators to kind of provide more long-term fix for these things. And I think all of us have to be more engaged in those discussions with our professional societies like ASCO to kind of help promote awareness. So if you kind of think about it, these drugs are not that expensive. These are generic drugs that we've all been using for such a long time. And the fact that we can't provide these drugs for various reasons is kind of really concerning. We spend so much money on research and more expensive drugs and not being able to manufacture these drugs within the country and kind of having to rely on complex supply chains is troubling, and I hope the situation improves very soon.    So, I know both of you are at large cancer centers that enroll patients on clinical trials. Of course, these drugs, especially carboplatin, for lung cancer, especially, are like core treatments that are used in managing cancer patients with lung cancer. So how is this affecting your clinical trial accrual? Are you prioritizing patients on clinical trials for these drugs? Have you had to make any decisions to hold clinical trial accrual for certain trials? Kind of curious to hear.  Dr. Taofeek Owonikoko: Yeah, so I can maybe weigh in a little bit on that in terms of what we've had to do for patients receiving treatment as standard of care versus those going on clinical trials. As we all recognize that when a patient goes on a clinical trial, even if they are going to receive a standard-of-care regimen as part of that trial, it still has to be administered in line with the protocol. So, during the extreme period of shortage anxiety, we actually had consideration for perhaps not putting patients on trial if we're not sure that they will be able to continue to receive the protocol-mandated treatment, whether it's a control intervention or the experimental intervention.   The good thing to come out of this is at least here at UPMC, we actually did not have any instance where we had to deny a patient clinical trial participation. But there were anxious periods when we already had patients enrolled and they were scheduled to receive a platinum-containing regimen and we were not sure whether or not we were going to have adequate supply of the drug for them while on trial. I think this really raises an important consideration going forward as we come out of this current shortage. I don't by any stretch of the imagination assume that this is going to be the last one we experience, but I think the lessons learned here, we have to also carry that forward both in the design of the trial as well as in the regulatory environment surrounding clinical trial conduct, to say, should another incidence of drug shortage are to happen, how do we actually operationalize that with respect to patients on trial, whether starting or already on trial?   I think it's much more challenging when the patient is already on the trial, they've already started. It's less challenging if you just have to make a decision about somebody starting newly on the trial. But equally important is that by not allowing new patients to go on trial is denying something that potentially could be of benefit to them, albeit it is still a trial, it's not an established treatment option yet.  Dr. Janakiraman Subramanian : I completely agree with Dr. Owonikoko. Those were very key points and issues that we face as well. In terms of my patients with lung cancer, we haven't had a problem in getting them on clinical trials. Even though we have had carboplatin shortage patients who are already on treatment, they were able to get the carboplatin. For new patients, we were still able to provide them carboplatin as well. The biggest problem for clinical trials has been primarily with my GI colleagues who have to use 5FU. And there, as I said before, we are unable to give bolus 5FU and there is a 10% reduction of the infusional 5FU. So, we can't have any of these patients go on clinical trials.    And as a result, anything that has to do with 5FU has come to a screeching halt in terms of clinical trials for our patients. And I think I echo the point of Dr. Owonikoko that by no means this is the last drug shortage we're going to be dealing with and we are here today discussing this, also because this shortage has not ended. It's been ongoing. It's one of the longest drug shortages in my memory as a medical oncologist, and that's concerning. We still see that there is some improvement, but we haven't gotten past it yet.     And therefore, as we develop clinical trials and we need to have methods to address drug shortages and how we manage patient enrollment as well as how do we manage existing patients who are already on a clinical trial and, if possible, what might be their options in that situation. We may not have all the answers, but it is definitely an issue that we need to think about in the future as we develop and implement newer clinical trials for our patients.  Dr. Vamsi Velcheti: I completely agree and great points, both of you. And we've had the same issues with clinical trials at NYU Langone as well due to the shortage. It's been a challenge, and I think this is a problem that's so complex because of supply chain issues and the way the drugs are priced and incentives for manufacturing these drugs in the United States are not lucrative enough to actually onshore a lot of the production of these drugs.   I think at the end of the day, I think we have to come up with some creative, innovative, reimbursement structures for these generic chemotherapy drugs. I think this would require a very complex economic solution that perhaps ASCO and other organizations should kind of really foster an environment of innovation to kind of help facilitate onshoring some of the manufacturing of these key drugs within the United States. I think ASCO is already trying to do that, trying to collaborate with all the stakeholders to kind of address this problem is very critical, and I think all of us have to be engaged in some of the advocacy efforts that are ongoing to kind of address these drug shortages. And this is not a short-term problem.  So, Dr. Owonikoko and Dr. Subramanian, any final thoughts before we wrap up the podcast today?  Dr. Janakiraman Subramanian: So, Vamsi, you mentioned the whole complex supply chain and the fact that we rely primarily on overseas manufacturers to get these drugs that are off-patent but still a key backbone of our cancer treatment. I think those are all key issues that policymakers and leaders in the field have to keep in mind. As an institution at Inova, one of the key mechanisms that have helped us to sort of stay ahead of the shortage was to have this inventory management team that monitors the inventory out there. And in fact, the inventory management team does have access to what the inventory is in some of their main suppliers in terms of the drugs. And they also have an idea of how many patients are going through treatment, what is the weekly usage of a specific drug like carboplatin. And they try to forecast what is coming down the road and try to prepare for it.   And as we try to look for solutions, maybe a forecasting mechanism in a larger scale like either spearheaded by ASCO or by policymakers level that can, for the overall country, try to see where some of the inventory is for some of these critical drugs and try to prepare for it ahead of time, rather than wait till we hit the shortage and then try to find alternative suppliers to get the drug, which obviously doesn't happen quick enough. It takes months or even longer to catch up and get the inventory back to the level where we can comfortably take care of our patients.  I think that is something we should be advocating for that as well as the professional societies should take a handle on that and see if they can support something like that as well as letting the institutions know ahead of time what's coming might be very helpful.  Dr. Vamsi Velcheti: Yeah, very good point, Janakiraman, and I think that's a key takeaway here. I think we have to learn from other industries and try to– I mean this is not unique to healthcare by any means. I mean these chronic shortages due to supply chain issues, inventory management, there might be some learnings from other industries here that we probably should also focus on inventory management and improve supply chain logistics.   Dr. Owonikoko, any closing thoughts?   Dr. Taofeek Owonikoko: Yeah, I agree as well with all the points made by Dr. Subramanian and yourself. This is a chronic problem that requires a long-term strategy. I think it's both an economic problem as well as a regulatory problem. As we all know, part of the reason why we went through this current crisis is the regulatory decision by the FDA regarding safety of one of the manufacturers. So being proactive in terms of how these audits are conducted and giving people lead time I think will help avoid similar situations in the future.    It's an economic problem. There's a reason why a lot of the big pharma companies are not producing these drugs. And if the cost of production is such that the amount of money you get paid is enough to cover your price, I think there is an economic issue there to be addressed. That is unfortunately not within the scope of what any one of us can do individually, but as advocates in terms of the structure of incentivizing new drug versus old drug, some of these newer drugs are quite expensive, but oftentimes they are used along with standard drugs that are not as expensive. So, where do we strike that balance where we do not stifle innovation but at the same time, we don't create a perverse incentive system where everybody just wants to come up with the newest, most expensive drug and nobody is interested in really producing the backbone chemotherapy and other agents that will make those new drugs work well.   So, I think we have to pay attention. We have to advocate for our patients through our different institutions and organizations, and I hope that society as a whole that we've learned a lot of lessons from this crisis and that will help us craft some long-term strategies.   Dr. Vamsi Velcheti: Thank you both Dr. Owonikoko and Dr. Subramanian for your time today to speak with me and our listeners and for sharing your insights with us on the ASCO Daily News podcast.   Dr. Taofeek Owonikoko: Thank you.   Dr. Janakiraman Subramanian: Thank you.  Dr. Vamsi Velcheti: And thank you to our listeners for your time today. If you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  ASCO Resources Related to Drug Shortages are available here.     Follow today's speakers:    Dr. Vamsidhar Velcheti    @VamsiVelcheti    Dr. Janakiraman Subramanian  @RamSubraMD  Dr. Taofeek Owonikoko  @teekayowo    Follow ASCO on social media:     @ASCO on X (formerly Twitter)    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Vamsidhar Velcheti:     Honoraria: ITeos Therapeutics    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus    Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline      Dr. Janakiraman Subramanian:  Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Daichi, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology, Lilly, Blueprint Medicines, Axcess, BeiGene, Cardinal Health, Takeda, OncoCyte  Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology  Research Funding (Inst.): G1 Therapeutics, Tesaro/GSK, Novartis, Genentech, Novocure, Merck   Dr. Taofeek Owonikoko:  Stocks and Other Ownership Interests: Cambium Oncology, GenCart, Coherus Biosciences  Consulting or Advisory Role: Novartis, Celgene, Abbvie, Eisai, GI Therapeutics, Takeda, Bristol-Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Merck, Jazz Pharmaceuticals, Zentalis, Wells Fargo, Ipsen, Roche/Genentech, Janssen, Exelixis, BeiGene, Triptych Health Partners, Daichi, Coherus Biosciences  Speakers Bureau: Abbvie  Research Funding (Inst.): Novartis, Astellas Pharma, Bayer, Regeneron, AstraZenece/MedImmune, Abbvie, G1Therapeutics, Bristol-Myers Squibb, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Oncorus, Ispen, GlaxoSmithKline, Calithera Biosciences, Eisai, WindMIL, Turning Point Therapeutics, Roche/Genentech, Mersana, Meryx, Boehringer Ingelheim  Patents, Royalties, Other Intellectual Property (Inst.):   Overcoming Acquired Resistance to Chemotherapy Treatments Through Suppression of STAT3  Selective Chemotherapy Treatments and Diagnostic Methods Related Thereto  DR4 Modulation and Its Implications in EGFR-Target Cancer Therapy Ref: 18089 PROV (CSP) United States Patent Application No. 62/670,210 June 26, 2018 (Co-Inventor)  Soluble FAS ligand as a biomarker of recurrence in thyroid cancer; provisional patent 61/727,519 (Inventor)  Other Relationship: Roche/Genentech, EMD Serono, Novartis  Uncompensated Relationships: Reflexion Medical           

In this CME episode, Dr. Andrew Cutler interviews Dr. Stephen Stahl and Dr. Sarah Vinson about the ethicality and morality of involuntary treatment for serious mental illness (SMI), the relationship between SMI and the criminal justice system, and community-based changes that are being pursued to improve treatment and reduce the criminalization of SMI. Optional CME/CE Credits and Certificate Instructions: After listening to the podcast, to take the optional posttest and receive CME/CE credit, click: https://nei.global/POD23-SMI Learning Objectives: After completing this educational activity, you should be better able to: Recognize the neuroethics involved in involuntary treatment of serious mental illness Identify methods to prevent patients with serious mental illness from entering the criminal justice system, including the utility of diversion programs Institute community-based changes that have the potential to reduce the criminalization of serious mental illness, both on the individual and the policy level Accreditation: In support of improving patient care, Neuroscience Education Institute (NEI) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NEI designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit ™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity was planned by and for the healthcare team, and learners will receive 1.0 Interprofessional Continuing Education (IPCE) credit for learning and change. A posttest score of 70% or higher is required to receive CME/CE credit. The content in this activity does not pertain to pharmacology and is worth 0.0 continuing education hour of pharmacotherapeutics. Credit Types: The following are being offered for this activity: Nurse Practitioner: ANCC contact hours Pharmacy: ACPE application-based contact hours Physician: ACCME AMA PRA Category 1 Credits ™ Physician Associate: AAPA Category 1 CME credits Psychology: APA CE credits Social Work: ASWB-ACE CE credits Non-Physician Member of the Healthcare Team: Certificate of Participation stating the program is designated for AMA PRA Category 1 Credits™ Interprofessional Continuing Education: IPCE credit for learning and change Peer Review: The content was peer-reviewed by an MD specializing in forensic psychiatry to ensure the scientific accuracy and medical relevance of information presented and its independence from commercial bias. NEI takes responsibility for the content, quality, and scientific integrity of this CME/CE activity. Disclosures: All individuals in a position to influence or control content are required to disclose any relevant financial relationships. Potential conflicts of interest are identified and mitigated prior to the activity being planned, developed, or presented. Interviewer Andrew J. Cutler, MD Clinical Associate Professor, Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY Chief Medical Officer, Neuroscience Education Institute, Carlsbad, CA Consultant/Advisor: AbbVie, Acadia, Alfasigma, Alkermes, Axsome, Biogen, BioXcel, Boehringer Ingelheim, Cerevel, Corium, Intra-Cellular, Ironshore, Janssen, Jazz, Karuna, Neumora, Neurocrine, Noven, Otsuka, Relmada, Sage Therapeutics, Sunovion, Supernus, Teva, Tris Pharma, VistaGen Therapeutics Speakers Bureau: AbbVie, Acadia, Alkermes, Axsome, BioXcel, Corium, Intra-Cellular, Ironshore, Janssen, Jazz, Lundbeck, Neurocrine, Noven, Otsuka, Sunovion, Supernus, Takeda, Teva, Tris Pharma Interviewees Stephen M. Stahl, MD, PhD, DSc (Hon.) Clinical Professor, Department of Psychiatry and Neuroscience, University of California, Riverside School of Medicine, Riverside, CA Adjunct Professor, Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA Honorary Visiting Senior Fellow, University of Cambridge, Cambridge, UK Editor-in-Chief, CNS Spectrums Director of Psychopharmacology Services, California Department of State Hospitals Grant/Research: Acadia, Alkermes, Allergan/AbbVie, Arbor, AssureX, AstraZeneca, Avanir, Axovant, Biogen, Boehringer Ingelheim Braeburn, BristolMyer Squibb, Celgene, CeNeRex, Cephalon, Daiichi Sankyo-Brazil, Dey, Eisai, Forest, Genomind, Glaxo Smith Kline, Harmony Biosciences, Indivior, Intra-Cellular, Ironshore, Janssen, JayMac, Jazz, Lilly, Lundbeck, Merck, Neurocrine, Neuronetics, Novartis, Otsuka, Pear, Pfizer, Reviva, Roche, Sage, Servier, Shire, Sprout, Sunovion, Supernus, Takeda, Teva, Tonix, Torrent, Vanda Consultant/Advisor: Acadia, Adamas, Alkermes, Allergan/AbbVie, Altus, Arbor, AstraZeneca, Avanir, Axovant, Axsome, Biogen, Biomarin, Biopharma, Celgene, Cerevel, ClearView, Clexio, Concert, DepotMed, Done, EMD Serono, Eisai, Enveric, Eurolink, Fabre-Kramer, Ferring, Forest, Gedeon Richter, Genetica, Genomind, Innovative Science Solutions, Impel, Intra-Cellular, Ironshore, Janssen, Jazz, Karuna, Libbs, Lilly, Lipidio, Longboard, Lundbeck, Merck, Neos, NeuraWell, Neurocrine, NeuroPharma, Novartis, Noveida, Otsuka, Perrigo, Pfizer, Pierre Fabre, Proxymm, Recordati, Relmada, Reviva, Sage, Saniona, Servier, Shire, Sprout, Sunovion, Supernus, Takeda, Taliaz, Teva, Tonix, Tris, Trius, Vanda, Vertex, Viforpharma Speakers Bureau: Acadia, Allergan/AbbVie, Genentech, Janssen, Lundbeck, Merck, Neurocrine, Otsuka, Servier, Sunovion, Takeda, Teva Options Holdings: Delix, Genomind, Lipidio, NeuraWell Sarah Y. Vinson, MD, FAPA Interim Department Chair; Clinical Associate Professor; Director, Child and Adolescent Psychiatry Fellowship Program; Department of Psychiatry and Behavioral Sciences, Morehouse School of Medicine, Atlanta, GA Medical Director, Substance Abuse and Mental Health Services Administration (SAMHSA) African American Behavioral Health Center of Excellence, Atlanta, GA No financial relationships to disclose. Pre-Interview Author Sabrina K. Bradbury-Segal, PhD Senior Medical Writer, Neuroscience Education Institute, Carlsbad, CA No financial relationships to disclose. The Planning Committee, Content Editor, and Peer Reviewer have no financial relationships to disclose. Disclosure of Off-Label Use: This educational activity may include discussion of unlabeled and/or investigational uses of agents that are not currently labeled for such use by the FDA. Please consult the product prescribing information for full disclosure of labeled uses. Cultural Linguistic Competencies and Implicit Bias: A variety of resources addressing cultural and linguistic competencies and strategies for understanding and reducing implicit bias can be found in this handout—download me. Support: This activity is supported by an unrestricted educational grant from Alkermes. Released: July 25, 2023      CME/CE credit expires: July 24, 2026

Synopsis: Gregory Verdine, Ph.D., is the Co-Founder, President and CEO of LifeMine Therapeutics and FogPharma. LifeMine Therapeutics is reinventing drug discovery by mining genetically-encoded small molecules (GEMs) from the biosphere. FogPharma is developing a new class of drugs to address the limitations of today's precision medicines and achieve universal druggability. In this episode, Greg discusses his unique journey from starting as an academic scientist to transitioning to an investor, and how that exposure to the venture world rounds out his approach to how he now runs biotechs. He talks about what it's been like running two companies for six years and how he structures his time so he can successfully operate between the two. He also discusses fundraising in a challenging environment and the importance of being part of a team in biotech. Biography: Greg Verdine is a leader in the discovery, development and commercialization of new drug modalities. A passionate and accomplished inventor of novel approaches and drug classes to engage targets widely believed intractable, Greg coined the phrase “drugging the undruggable” to describe his life's mission. Greg is the co-founder of FogPharma, which has its roots in the scientific work of Greg and his academic team at Harvard University and Harvard Medical School, a hotbed of innovation and invention in the new modality therapeutics space. Greg is also the co-founder and CEO of LifeMine Therapeutics, a biopharmaceutical company refashioning drug discovery by mining genetically-encoded small molecules from the biosphere. Together with co-founder WeiQing Zhou, he developed the scientific and business concept for FogPharma and LifeMine and co-led the companys' initial capitalization and operationalization in mid-2016 and 2017, respectively. Greg is highly regarded for having moved seamlessly between roles as an academic scientist, biotech entrepreneur, investor and company executive. As Erving Professor at Harvard University and Harvard Medical School, he founded the burgeoning field of hyperstabilized alpha-helical peptides, starting with the first-generation all-hydrocarbon stapled peptide technology, and invented not only the modality but also the direct precursor to the Phase 2 stapled peptide ALRN 6924. The greatly improved second-generation Helicon technology was developed in the Verdine Lab at Harvard and licensed exclusively to FogPharma, and subsequently developed by FogPharma into the third-generation approach that is so impactful today. The Verdine Lab at Harvard also made seminal contributions to understanding fundamental mechanisms of DNA repair and epigenetic DNA methylation. As an entrepreneur, Dr. Verdine has founded multiple public biotech companies including Variagenics, Enanta Pharmaceuticals, Eleven Bio, Tokai Pharmaceuticals, Wave Life Sciences and Aileron Therapeutics, and a private company, Gloucester Pharmaceuticals, which was acquired by Celgene. These companies have succeeded in achieving FDA approval for three marketed drugs. Greg has served on the board of directors of Enanta Pharmaceuticals, Wave Life Sciences, Warp Drive Bio and LifeMine Therapeutics. Having led the formation and financing of Wave Life Sciences, Warp Drive Bio and LifeMine Therapeutics, Greg took a role in managing these companies as their president, chief executive officer and chief scientific officer. Greg also conceived of, co-founded and served as the founding president and chairman of the tandem non-profits Gloucester Biotechnology Academy, which trains high school graduates for technical careers in biotech, and Gloucester Marine Genomics Institute, which is supporting fisheries science and economic development on Cape Ann. Greg earned his Ph.D. in chemistry from Columbia University and served as an NIH postdoctoral fellow in molecular biology at MIT and Harvard Medical School. He also holds an honorary Ph.D. degree from Clarkson University.

Dr. Sheila Gujrathi is a physician-executive with a deep track record in translational science and drug development. She currently sits on the board for Ventyx Biosciences, IMMPACT Bio, ADARx Pharmaceuticals, and Janux Therapeutics and is prior Venture Advisor at OrbiMed and prior chair of Turning Point Therapeutics. She is co-founder and former CEO of Gossamer Bio, a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology. Prior to Gossamer Bio, Dr. Gujrathi served as Chief Medical Officer of Receptos, which was acquired by Celgene in 2015. Prior to Receptos, Dr. Gujrathi was Vice President of the Global Clinical Development Group in Immunology at Bristol-Myers Squibb, where she led clinical development and supported numerous global regulatory filings and approvals for Orencia® and Nulojix®. Prior to Bristol-Myers Squibb, Dr. Gujrathi held roles in the immunology, tissue growth and repair clinical development groups at Genentech. --- Support this podcast: https://podcasters.spotify.com/pod/show/theia-hc/support

Brian Feretic is the Founder of Blossm, a community marketplace to buy, sell, and trade plants. Victoria talks to Brian about how coming up with the concept happened, getting started in a very scrappy way and then filling in gaps, and opening up the app to have full marketplace functionality with buying, selling, and trading capabilities. Blossm (https://blossm.garden/) Follow Blossm on LinkedIn (https://www.linkedin.com/company/blossm-plant-marketplace/), Twitter (https://twitter.com/blossmllc), Instagram (https://www.instagram.com/blossmplantswap/), Facebook (https://www.facebook.com/blossmplantswap) or TikTok (https://www.tiktok.com/@blossmplantswap). Follow Brian Feretic on LinkedIn (https://www.linkedin.com/in/brian-feretic-3b2b337a/). Follow thoughtbot on Twitter (https://twitter.com/thoughtbot) or LinkedIn (https://www.linkedin.com/company/150727/). Become a Sponsor (https://thoughtbot.com/sponsorship) of Giant Robots! Transcript: VICTORIA: This is the Giant Robots Smashing Into Other Giant Robots Podcast, where we explore the design, development, and business of great products. I'm your host, Victoria Guido or Tori. And with me today is Brian Feretic, Founder of Blossm, a community marketplace to buy, sell, and trade plants. Brian, thank you for joining us. BRIAN: Hey, it's great to be here, Tori. VICTORIA: Great. I'm excited to hear more about Blossm. Why don't you just tell me a little bit more about the concept? BRIAN: The concept actually happened at the end of 2019, and I'd already been a plant enthusiast for a couple of years. I was actually just going on my way to surf in my town of Ocean Beach, San Diego, and I stopped by this garage sale. And when I came back to pay my neighbor, I brought this rubber plant that are propagated just as a neighborly gift. She flipped out. She was ecstatic. She's like, "Oh my God, I'm such a huge plant person. Thank you so much. Why don't you come into my backyard, and I'll give you a plant tour, and you can pick something out." And what was cool about this was it wasn't just like a simple exchange. It was like this hour-long interaction with someone that lived four blocks from me that happened to be this big plant nerd like me. And I got her whole story. She went through all these different species I didn't know about. And then, she helped me pick one out, which I still have to this day. It's this crassula succulent. When I was walking home with my new plant, I was like, oh wow, I got to go download the app for this. I would have never known this person that lives four houses away was a big plant person like me. And when I got home, I searched the App Store. I did a Google search. I just couldn't find what I was looking for, which was basically this plant-swapping plant-connecting platform where I could find fellow plant nerds in my neighborhood. And so that kind of set me off on this path. I did some more research and decided...I was like, you know what? I'm going to commit to this and make this happen for myself and for my community. VICTORIA: Well, what do you think makes someone a plant person [laughs] or like a...how did you describe yourself? A plant nerd? What sets that user apart? BRIAN: We'll say it's like on a spectrum where people can shift along the spectrum. But I'd say when people start treating their plants more than objects and more what they are. They are these living things. They're beautiful. They bring people joy. I find it therapeutic to take care of them. And then the beautiful thing about it is that these plants grow, and you can propagate them and share them with your friends. And I think that is a critical aspect of this whole plant person thing. VICTORIA: So the plants have become a little more like pets, and you can grow them in a way that creates a community around your friendship and your local area. BRIAN: Yeah, exactly. That was actually the early signal about this whole plant world is that I saw people creating plant-dedicated Instagram accounts as if it was your dog or cat. And that was something that I realized this is a different type of person. This is a very passionate person willing to, like, they're so proud of their plant babies, we call them. [laughter] VICTORIA: Right. And it's funny, you say, plant babies. When I think of people I know who I would consider plant people, they do talk to their plants like their babies. They're like, "Oh, it's so cute." [laughs] Or they're like, "Oh, he's not feeling so well." So I think that's great. And so you started to do some research into this community, into this group. What surprised you about your early findings? BRIAN: This was actually something that I didn't realize until I dug deeper was that I thought that it was only going to be a local thing. People wanted to experience what I did with Sondra, who's the neighbor I swapped with, this in-person connection, swapping, checking each other's gardens out and houseplants. But I learned very quickly that people ship plants to each other not only within your own state but across the country, and this is global. And I was just like, how do people ship plants? Turns out I do it all the time, almost weekly now, for years. That aspect was critical to realize, all right; this plant community doesn't necessarily have to be bound by physical in-person distance. It can connect online, and people share all over via shipping. VICTORIA: That's really cool. So you decided that there's a whole international community. So is that when you decided to really start building something like an application to help people? BRIAN: I remember just throwing this idea out to a lot of different friends, like, various backgrounds. And I was like, "Hey, what do you think of this idea about connecting people through this shared love?" And there is not one person who thought it was a terrible idea. And then I remember talking about it with a roommate at the time, and basically the same thing. I was like, "Hey, man, imagine people connecting through the shared passion. Who knows? Maybe even love can blossom." And he was like, "Dude, that's what you should call it." I was like, oh, that's a great name. It's about three and a half years now, and it's stuck ever since. VICTORIA: I love that, [laughter] about sharing love, and how the name came about, and just starting with your friends and people you knew and bouncing ideas off of them. But your background is not specifically in technology. So what about your background applied? And what did you have to learn new to take along this journey? BRIAN: So my whole career, I've been involved within the science sector. I actually moved to San Diego to pursue graduate school in neuroscience. I was very curious about kind of full neural networks and how those contribute to behavior. Actually, the Ph.D. program I wanted to get into at UCSD, there's a specific lab doing this really cool research with this new innovative imaging technique. And I applied twice, and I didn't get in. And so I went into biotech. But I would say probably two things helped me. I realize now going through this entrepreneur path, things that helped train me for this, was definitely a graduate school where you're pretty much broke the whole time. My lab didn't have too much funding, so you had to be really resourceful and creative to figure stuff out with minimal resources. And that's perfectly summed up the last couple of years, just like figuring stuff out. We have no money. How do we get awareness of our product when we can't spend, you know, we don't have ad spend or marketing budget? And it just kind of requires you to get creative and think outside the box and just really think, all right, what do I do here? And I came up with some hacky-type strategies that have been very effective. [laughs] VICTORIA: Well, very cool. It sounds like you found your team now to start working with you on this in a very scrappy way. So how did you fill in those gaps, maybe in your knowledge or your background on how to get this done by the people that you grew around you? BRIAN: For me, it wasn't too difficult. Well, one, my background. I was very naive with tech at the time and just programming in general. So my first task, I laid out three options. It was like, one, I can learn how to code. I dabbled in it for a week, and I was like, man, there's no way. [laughter] Two, I was like, I can outsource it, maybe somewhat cheaply, but I don't want to spend all my savings on it. But more, I knew that, you know, say you come out of MVP product, the product always is growing, adapting, evolving, or you encounter bugs. And I could just see how full of friction the process would be if I had to, like, all right, we have found a bug, send the contract out. They have to accept the contract. And I just knew progress would be too slow to operate in that fashion. And the third option was, like, find a technical co-founder and pursue this dream with, you know, a buddy. I was like, all right, who do I know that is in the computer stuff? And that was my thought. And my first guy I pitched it to was a friend I went to college with at Bucknell University. And he was like, I think, "This is a good idea." But he's like, "I'm going to retire probably in five years, and this is going to be a very lengthy thing." He's like, "I'm not interested." The second guy was extremely down for it, but it turns out he didn't know how to do any mobile app development. He uses a consultant. [laughs] And so the third and who I ended up working with was my surfing and climbing buddy Nick Mitchell. I just knew he did computer-type stuff. I pitched him the idea, and he was like, "What's up with this plant thing?" VICTORIA: [laughs] BRIAN: And I was like, "Oh, dude, this is a rapidly growing market. I know the ins and outs really well. I know this audience. I'm one of them." He wasn't sold until he heard an NPR piece talking about the houseplant boom. And then his father sent him an article from the New York Times saying how millennials are embracing houseplants and driving this new houseplant market. And so I think this was maybe end of December, now in 2019. And he hit me up, and of course, he's like, "Oh, dude, I want in. Let's do it." But I also wanted to make sure I knew he could actually do what was the task at hand. [laughter] So I had my other first friend vet his GitHub and stuff just to make sure. [laughs] VICTORIA: Oh, cool. [laughs] BRIAN: And he was like, "Yeah, you know, he looks good. Worth a shot." And it turns out Nick is excellent. He did all the front end, back end. He built this whole app basically from scratch. It's pretty amazing what he's capable of. So I got it right on the third try. [laughs] VICTORIA: That's funny. And I'm not surprised it came from networking in the climbing community, either. BRIAN: Right. There's a lot of smart...definitely a lot of smart people in the climbing community. And those are like my closest friends now. So it was kind of cool to find someone in that place. VICTORIA: And I've been climbing with friends before, and you're talking about work or whatever. And they're like, "Oh, yeah, I'm also like an Azure architect," [laughs] like some specific skill that's related to what you need. And I think it's a similar cultural mindset of people you want to be working with too. Maybe that's just me. So, okay, so you found your partner. You had someone who had all the skills that you needed to make this happen. How long did it take until you really had something you were proud of? BRIAN: So, for me, I was laid off in August of 2019. I was working at Celgene, and they got acquired by Bristol Myers Squibb for like 72 billion, so massive merger. And I was kind of getting over the field. And so I was already basically unemployed. Nick, when we started actually working together in...we'll just call it January 2020. We started working on it casually, and then the pandemic happened. And then he got laid off. And he did about a three-month stint before he got another job at ServiceNow. But within those three months, he really cranked out like a full MVP. And then I had about probably at least 60 or 70 people I knew beta test the product for feedback and just initial thoughts. And so that was like a very critical time where we were all locked down. We have this cool idea. Let's just crank this out. So we had an MVP pretty quick. And then we actually launched it in June 2020. And I was already very stoked about the product. As long as it did its core thing, which is connecting people through this shared love, I knew it was like a proper test, a good enough test to see if this is a worthy endeavor. VICTORIA: That's really cool. So was there any surprising feedback that you got from that initial beta testing? BRIAN: Yeah. [laughs] So the initial concept was essentially like a Tinder for plants. [laughter] And I was just thinking about this idea, like, if people could just swipe on plants they've uploaded, and then if both people liked a particular plant and they swiped on each other, and they matched, it would open up a chat that would connect them. And it took the...one of the issues with bartering, in general, is people are like, "Oh, I'd love to swap that with you." And they're like, "Oh, what do you want to swap? What do you have?" And a lot of times, people don't align with what they have and what they want to swap. So I figured that would get this kind of friction out of there, but still, the core was connecting people. And then, very quickly, people found it fun. And this is still a feature right now on Blossm, which we've moved to the homepage. And it got a lot of engagement and interactions on it. But one of the simple changes was like, all right, maybe this is not the optimal way to present these plants people are uploading. Nick actually drew a lot of inspiration from OfferUp. And he was like, "Oh, this is very simple. This is a very clean way to present these things." So we started getting inspiration from OfferUp, and we changed that kind of swipe card functionality just to a scrollable grid. And that was a great insight on his part, and some of that has been core to the product from that point on. VICTORIA: That's so cool. So I can just go in the app and see a whole list of plants that people are willing to trade. BRIAN: Right. Actually, I would say another thing that happened very early on, too, was, once again, bartering is not the most efficient way to exchange things with each other. And within weeks, we're seeing people being like, "Oh, well, what do you want to swap?" And then people are like, "Oh, well, I don't want to swap for that. I already have that." And then other people are like, "Hey, I don't want to swap anything. I just want to buy it." And then other people are like, "Hey, I don't have anything. but how do I get stuff for you?" So right away, we opened it up to full marketplace kind of functionality with buying, selling, and trading. And we didn't have necessarily any payment system to facilitate that. We would just connect people. And then they would use Venmo, or Paypal, or Cash App, or things like that. VICTORIA: That makes sense. MID-ROLL AD: Now that you have funding, it's time to design, build, and ship the most impactful MVP that wows customers now and can scale in the future. thoughtbot Liftoff brings you the most reliable cross-functional team of product experts to mitigate risk and set you up for long-term success. As your trusted, experienced technical partner, we'll help launch your new product and guide you into a future-forward business that takes advantage of today's new technologies and agile best practices. Make the right decisions for tomorrow today. Get in touch at thoughtbot.com/liftoff. VICTORIA: Now you kind of got your core features figured out, and you see people engaging with the app. What are you the most excited about on the horizon in your roadmap? BRIAN: We're about to actually finish the TechStars accelerator next week. Next week is our demo day. It's been such a great experience, and I feel blessed. But during this time, we're really figuring out, like, what's our big vision with Blossm? And we kind of went back to really harp on, like, we're more than just an e-commerce or marketplace. We're like this special passionate community where people can do this buying, and selling, and trading. One of the things that's been the trend for years now is instead of just photos; we're about to integrate some video functionality. This is a lead in to the bigger goal. And the idea is creating this...we're calling this full plant experience focused around live video where people can engage with each other on this totally different intimate level and can really showcase their plant collection and give each other a plant tour. How do you take care of this plant? Is another big topic that always comes up. It's just hard to really decipher what's wrong with something just from ecstatic images. And we imagine we could have live plant help. And then people can just show their plant up to the camera and showing a really holistic view of what's going on. And so this vision of live with video and creating a more complete plant experience centered around really using the community as this way to promote that and really build that even further. VICTORIA: That's very cool. I think I've talked to you a little bit before about this giant fiddle fig I have in my office. [laughs] It's going to the ceiling. And I got it from Home Depot, so it may not be the highest quality. And I've asked you about, like, is it alive? It keeps dropping leaves. So if I had a video and I could just show you around and show you where the leaves are browning a little bit and where it's not growing, I could see the value in having that interaction like that. BRIAN: Yeah, exactly. No one's doing that. And definitely, we want to keep innovating the space. We were first to market many years ago. And then, actually, we have some direct competitors that are blatantly just copying us, like copying email templates, features. And on one hand, it's flattering, but also we realize we have to be careful about positioning and making sure we stay ahead of the curve. And we think this is going to be the future and something that delivers really extreme value to this demographic. VICTORIA: Absolutely. And you mentioned you're a part of a tech accelerator. Could you tell me a little bit more about choosing which program you went to and how that's affected your overall approach to your app? BRIAN: Yeah. So last year, we added two more team members, so actually Nick's younger brother, Calvin, we poached from Amazon, which felt really good. [laughter] And then we had another friend, Ari Olmos, who we knew had experience in the startup world. He started, or I think he was, co-founder or CEO of a few other social mission startups. So he understood just the fundraising process was probably the most critical trait we're looking for, just someone that can help refine our systems, our processes, things like that. So now we're a team of four. And we were like, all right; we need money if we want to keep this alive. And I've been full-time since the idea conception. Ari joined full-time. Nick and Calvin both had jobs. But we just knew it's critical for a high-potential startup like ours to really grow; we needed some sort of fundraising. And it seemed logical. We gave our shot at proper fundraising with some angels and VCs last year. There were very encouraging signs, but didn't necessarily translate to any checks being written for us. And then we applied to a bunch of accelerators; Y Combinator and TechStars were our top two. We got a few rounds of interviews from TechStars, and the director, Ryan Kuder, who's great; he's actually based in San Diego. And I credit him to definitely being a key component here because I knew he really liked us. He saw the really good complementary team we built. We had a pretty mature product with traction and an active user base. And we accepted, and it did a lot of things for us. It was our first proper fundraising beyond a Kickstarter. So Nick and Calvin became full-time once we got in. And then we just had this, like, you have access to this massive network and get this really detailed one on one mentorship. We had almost six or seven mentors that we met with weekly. They're always available to help. And probably the coolest thing about it is they're just there to help you. There's no two-sided, like, I'll help you if you can help me. We are here to help you build, grow, accelerate your business. And they gave us really good insights on direction, really formalizing how to build in systems that will last much longer than the three month-program that essentially just mimicked a lot of stuff we've done on the program within our own team, like hosting little daily stand-ups every day. We've always done weekly meetings but using that time more efficiently, knowing how to test and measure more effectively. They've really just refined our company to be a proper business instead of four dudes trying to make this cool plant app. VICTORIA: That's really cool. And I wonder now, like, after you've had this experience, what advice would you give yourself if you could go back in time to when this all started? BRIAN: First thing that popped in my head was...and I kind of knew this going into it, like, this is a big project that needs time. Things that prevent startups usually is, one, you don't execute, or you just don't start it at all, or you give up too soon. And I guess I would tell myself, hey, things are going to be all right. Like, just keep sticking with it. And you're getting all the signals; this is something substantial and worthwhile. Just be patient, stick with it. Survive those valleys, and there are peaks on the way. And getting into TechStars was the ultimate validation. Yeah, I feel extremely blessed to be in it. And I think we're poised to do big things this year. VICTORIA: That's very cool. So you've mentioned those peaks and valleys and how much time you have to spend on this type of starting a company [laughs] and building an app. How do you balance that with also having a regular life and going surfing and climbing? BRIAN: It's tough to find your specific balance and especially during the accelerator where I didn't want to waste any opportunity. So there were a lot of times...I think January was a month straight no days off. And actually, I was injured so I couldn't surf, climb, or even play piano, so all my outlets. But just be okay with setting aside time to where you don't think about work at all. And it took me a few months to reach that point. And I found that as long as I have one activity or some exercise per day, either I surf or climb, I'm good. I don't mind working 12-plus hour days if I do one of those. And then just to allocate one day of the week where I am like, I do a couple of hours in the morning. But one mostly day of don't think about work, just enjoy life. And that has been enough for me to feel refreshed going into next week. And so I think I got a good rhythm, and I got a good formula for what works for me. It might be different for other people, but it's important to set aside time where you don't think about it. VICTORIA: Right. Yeah, just to turn off your brain. Sometimes I find, like, you know, you mentioned surfing and climbing helps you do that because you really just can't be on your phone [laughs] when you're out there sometimes. BRIAN: Right. It's kind of funny because I'll almost say it's a catch-22. But sometimes, those things can be distracting, but they're also necessary for you to be focused if that makes sense. [laughs] VICTORIA: Yeah, totally. Let me bring it back to plants. What is your favorite house plant that you have right now? BRIAN: Man, it's changed over the years, but I do have one. It's like the most popular high-in-demand one; it's the Monstera albo. Its common counterpart is the Monstera deliciosa, which is all green. This one has white variegation on the leaves. They're just inherently beautiful plants. And anyone that sees it can be like, "Wow, that is gorgeous." But I have one specific one, and why it's my favorite is that years ago, I was telling a climbing friend about the app, and I guess the app is out by now, but telling her about it. And she's like, "Oh, my grandmother was a huge plant person. My mom now takes care of them. I think she has one of those Monstera plants with the white on it. It was my grandma's though." And I was like, no way. I have to see this. And when I get there, she has this massive one, incredibly mature and old. I think she said it was almost 50 years old. I can't even believe this. VICTORIA: Wow. BRIAN: And then I asked her. I was like, "Hey," [laughs] I was like, "Can I have a little bit of that?" [laughs] And she was like, "Oh yeah, just go ahead. This is a plant. I'll grow it back." And I felt a little bad because I took a nice big cutting like multiple leave cutting. And she absolutely did not care and just was so happy. Turns out she had three of these like big mother plants. There's one cutting that had very low variegation, so it showed barely any white on it. Over time, I grew it out. Every subsequent leaf kept showing more and more white. And now it's just so beautiful. I check up on it every day, and every new leaf is just more beautiful than the next. And it's a special one. And it was gifted to me by my friend's mother. It started off like you can say a lowly variegated plant, and now it's just thriving and beautiful. So it has some history, and it came from a friend. So without a doubt, that's my favorite one. [laughs] VICTORIA: That's very cool. Yeah, I know those Monsteras that you're talking about. They're really interesting-looking plants. I kept one alive for a short time, and I'm very proud of myself for it. [laughs] So I'm interested in using Blossm to keep my plants alive possibly. But that's awesome. Thank you so much for sharing that. What else can I ask you? Is there anything that I should ask you that I haven't yet? BRIAN: Well, we could actually segue from what you just said. This is an interesting thing. So I think everybody who's been through this has gone through this exact process. So they have a couple of plants. They're like, what's wrong with my plant? How do I take care of this? And they go down the Google rabbit hole, or they happen to buy one of these plant ID plant care apps. Usually, they're like freemium. You get a couple of free tries, and then you have to buy a subscription or whatever. I also did this. And I was like, you know what? These apps suck. They just don't work, or they're too general. The best plant advice you can get is from other plant people because there are so many variables. Like, which growing zone are you in? What kind of light do you have? What's your ambient humidity, temperature? All these factors come into play on how to properly care for your plant and what could be wrong. And the best advice I've gotten was from other plant people. And so we have, like, beyond the marketplace grid, we have this fully functioning community forum essentially like a Facebook group in a way where people can post questions about what's wrong with my plant, or what plant is this? Or share memes and just nerd out. And it's been such a critical component I think of Blossm to cultivate this community. But it's also just very functional and effective because really the only way to get that advice and care information is by interacting with other people. That's something we want to build upon in the future too with that whole live and video capabilities. VICTORIA: Yeah, that makes sense. Just a funny story, sometimes I'll call my mom who's a big plant person, and ask her questions, and she's like, "Well, you should go check that book I got you." [laughter] It's like, it's not helpful at all. [laughs] But yeah, no, I think that's right. I think people get excited about AI and image recognition. But sometimes it's still easier to get a real effective answer from a human. BRIAN: Yeah, I'd be curious with the whole AI getting its spotlight right now. And without a doubt, I could see applications there for it. Right now, I don't think that exists, but I'm very curious and excited to see what happens with all of it. It's going to be cool. VICTORIA: Yeah. Well, that's awesome. And I am excited that what Blossm does is really create this community around plants and learning about them and with the people around you. Do you have any final takeaways for our listeners? BRIAN: Hmm, final takeaways, you know, shameless self-promotion; if you love plants or you're getting into plants, Blossm is tailored for the plant person, which is what I think makes it special. And more general, I never intended to be the entrepreneur. I never intended for Blossm to be like, oh, this big tech company. I just had something I was super passionate about and wanted to see come alive for myself and for other people. Without a doubt, that passion paired with perseverance, I think, are critical attributes to follow any idea to the end or to some level of success. So don't be afraid to take that leap. By no means has it been easy. It's been the most difficult thing I've ever done but also the most rewarding. It's been really fun too. So if you got a cool idea, maybe try to build it out, find a good co-founder, a good team. Give it a go and create something for everyone. VICTORIA: Well, I really loved your story, Brian. I think you've found your niche. You built something. You took advantage of the time you had when you had it, and look where you are now. [laughs] I'm very excited to see what comes next. BRIAN: Cool. Yeah, thank you so much for having me. This has been lovely, and yeah, stoked to listen to the next episodes too. VICTORIA: Excellent. You can subscribe to the show and find notes along with a complete transcript for this episode at giantrobots.fm. If you have questions or comments, you can email us at hosts@giantrobots.fm. And you can find me on Twitter @victori_ousg. This podcast is brought to you by thoughtbot and produced and edited by Mandy Moore. ANNOUNCER: This podcast is brought to you by thoughtbot, your expert strategy, design, development, and product management partner. We bring digital products from idea to success and teach you how because we care. Learn more at thoughtbot.com. Special Guest: Brian Feretic.

In episode 18, Emma and Rebekah are joined by Patrick Gay, a Partner in Herbert Smith Freehills' Competition, Regulation & Trade team. Together they unpack the ACCC's 2022 draft determination which proposed to deny authorisation of a settlement and licence agreement that was intended to resolve an ongoing patent dispute in the Federal Court between Celgene and generic drug companies Juno and Natco. With Patrick's insights, Emma and Rebekah touch on the potential impacts of the draft determination on parties looking to settle IP disputes in the future.

The availability and quality of cancer care varies in different parts of the globe. Some locations find it difficult to have proper equipment, access to medications or even trained staff on hand. In this ASCO Education podcast we look how a group of doctors are sharing their skills and experience to set up training programs to help improve outcomes for patients with cancer in Kenya. Our guests will explore the creation of a pediatric oncology fellowship program in Kenya (11:48), how a young doctor found herself interested in improving global health (14:30), and discuss lessons learned that are applicable to health care in the United States (21:07).  Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Terry Vik: Research Funding Takeda, Bristol Myers Squibb Foundation Dr. Jennifer Morgan: None Resources: Podcast: Oncology, Etc. - Dr. Miriam Mutebi on Improving Cancer Care in Africa Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan (Part 1) Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan Part 2 If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Disclosures for this podcast are listed in the podcast page. Dave Johnson: Welcome, everyone, to a special edition of Oncology, Etc., an oncology educational podcast designed to introduce our listeners to interesting people and topics in and outside the world of Oncology. Today's guest is my co-host, Dr. Pat Loehrer, who is the Joseph and Jackie Cusick Professor of Oncology and Distinguished Professor of Medicine at Indiana University, where he serves as the Director of Global Health and Health Equity. Pat is the Director Emeritus of the Indiana University Simon Comprehensive Cancer Center. Pat has many different accomplishments, and I could spend the next hour listing all of those, but I just want to point out, as many of you know, he is the founder of what formerly was known as the Hoosier Oncology Group, one of the prototypes of community-academic partnerships which have been hugely successful over the years.  He's also the founding director of the Academic Model for Providing Access to Healthcare Oncology Program, which has grown rather dramatically over the last 17 years. This includes the establishment of fellowship programs in GYN oncology, pediatric oncology, and medical oncology through the Moi University School of Medicine in Kenya. Through its partnership with the Moi Teaching and Referral Hospital, over 8000 cancer patients a year are seen, and over 120,000 women from western Kenya have been screened for breast and cervical cancer in the past five years. Pat is also the co-PI of the U-54 grant that focuses on longitudinal HPV screening of women in East Africa. He currently serves as a Senior Consultant of the NCI Cancer for Global Health.  So, Pat, welcome. We have with us today two special guests as well that I will ask Pat to introduce to you. Pat Loehrer: Dave, thanks for the very kind introduction. I'm so pleased today to have my colleagues who are working diligently with us in Kenya. The first is Terry Vik, who is Professor of Pediatrics here at Indiana University and at Riley Hospital. He's been the Director of the Fellowship Program and the Pediatric Hematology-Oncology Program and Director of the Childhood Cancer Survivor Program. He got his medical degree at Johns Hopkins and did his residency at UCLA and his fellowship at Dana-Farber. And he's been, for the last 10 to 15 years, been one of my co-partners in terms of developing our work in Kenya, focusing on the pediatric population, where he helps spearhead the first pediatric oncology fellowship in the country.  And then joining us also is Dr. Jennifer Morgan. Jenny is a new faculty member with us at Indiana University as an Assistant Professor. She, I think, has 16 state championship medals for track and field in high school. I've never met an athlete like that in the past. She ended up going to Northwestern Medical School. She spent time in Rwanda with Partners in Health, and through that, eventually got interested in oncology, where she completed her fellowship at University of North Carolina and has spent a lot of her time in Malawi doing breast cancer research. I don't know of anyone who has spent as much time at such a young age in global oncology.  Dave Johnson: So Pat, obviously, you and I have talked a lot over the years about your work in Kenya, but our listeners may not know about Eldoret. Maybe you can tell us a little bit about the history of the relationship between your institution and that in Kenya. Pat Loehrer: It's really a remarkable story. About 30 some odd years ago, Joe Mamlin and Bob Einterz, and Charlie Kelly decided they wanted to do a partnership in Global Health. And they looked around the world and looked at Nepal and looked at Mexico, and they fell upon Eldoret, which was in Western Kenya. They had the birth of a brand new medical school there, and this partnership developed. In the midst of this came the HIV/AIDS pandemic. And these gentlemen worked with their colleagues in Kenya to develop one of the most impressive programs in the world focused on population health and dealing with the AIDS pandemic. They called it the Academic Model for Prevention and Treatment of HIV/AIDS or AMPATH, and their success has been modeled in many other places. They have many different institutions from North America and Europe that have gone there to serve Western Kenya, which has a catchment area of about 25 million people.  About 15 to 20 years ago, I visited AMPATH, and what they had done with HIV/AIDS was extraordinary. But what we were seeing there in cancer was heartbreaking. It reminded us, Dave, as you remember back in the ‘60s and ‘70s with people coming in with advanced cancers of the head and neck and breast cancers that were untreated. And in addition, we saw these young kids with Burkitt's Lymphomas with huge masses out of their jaws. And seeing that and knowing what was possible, what we saw in the States and what seemed to be impossible in Kenya, spurred me on, as well as a number of other people, to get involved. And so, we have built up this program over the last 15 and 20 years, and I think it's one of the most successful models of global oncology that's in existence.  Dave Johnson: That's awesome. Terry, tell us a little bit about your involvement with the program at Moi University.  Terry Vik: Sure. So, I took an unusual path to get to Eldoret because I started off in work in signal transduction and protein kinases, then morphed into phase I studies of kinase inhibitors that was happening in the early 2000s. But by the end of the decade, Pat was beginning to establish oncology programs in Kenya. And because half the population is children and there were lots of childhood cancers, and many of them can be curable, he mildly twisted my arm to go with him to set up pediatric oncology in Kenya. And through his help and Matt Strother, who is a faculty member on the ground, establishing that, I first went in 2010 just to see how things were running and to see all the things that Pat had recognized as far as things that needed to be done to make Eldoret a center for cancer care.   And so, the last 13 years now, I've been working, going anywhere from one to four times a year to Kenya, mainly helping the Kenyans to develop their medical care system. Not so much seeing patients or taking care of patients, other than talking about best practices and how we do things in the US that can be readily translated to what's going on in Kenya. And so, we've been able to establish a database, keep track of our patients in pediatric oncology, recognize that lots of kids are not coming into care, not being diagnosed. There's a huge gap between numbers who you would expect to have childhood cancer versus the numbers actually coming to the hospital. As the only pediatric treatment center for a catchment area of 25 million, half of whom are under the age of 20, we should be seeing a lot of kids with cancer, but we are probably only seeing 10% of what we would expect.  So, myself, many of my colleagues from Indiana University, as well as colleagues from the Netherlands Princess Maxima Hospital for Pediatric Cancer, we've been partnering for these past 13 years to train Kenyans to recognize cancer, to have treatment protocols that are adapted for the capabilities in Kenya, and now finally starting to show real progress in survival for childhood cancer in Kenya, both in leukemias, lymphomas, and solid tumors, with a fair number of publications in Wilms tumor and Burkitt lymphoma and acute lymphoblastic leukemia. So, it's been really heartening, I think.  I tell people that the reason I go to Kenya studying signal transduction and protein kinase inhibitors in pediatric cancer, I can maybe save a couple of kids over a career by that kind of work. But going to Kenya to show people how to find and treat kids with leukemia, I'm literally seeing the impact of hundreds of kids who are alive today that wouldn't be alive otherwise. So, that's really been the success of pediatric oncology there. Dave Johnson: Is the spectrum of childhood cancer in Kenya reflective of what we see in the States, or are there some differences? Pat Loehrer: It really is surprisingly similar. I think the only thing that– Well, two things that are more common in Kenya because of the so-called ‘malaria belt' and the association with Burkitt Lymphoma, there's a fair number of kids with Burkitt's Lymphoma there. Although, as mosquito control and malaria control has improved, actually, the numbers of cases of Burkitt's have been dropping, and a lot of cancers were sort of hidden, not recognized as leukemia or not recognized as other lymphomas. Just because if Burkitt's is endemic, then every swelling is Burkitt's. And I think that's been shown by looking at pathology retrospectively to say a lot of what they thought was Burkitt's was maybe not necessarily Burkitt's. And then nasopharyngeal carcinoma with Epstein-Barr virus prevalence also is a little bit more common than I'm used to seeing, but otherwise, the spectrum of cancers are pretty similar. So, it's heartening to know that we've been treating childhood cancers with simple medicines, generic medicines, for 50 years in the US. And so I like to tell people, I just want to get us up to the ‘90s, maybe the 2000s in Kenya, and that will really improve the survival quite a bit. Dave Johnson: You mentioned that there were adjustments that you were making in the therapies. Could you give us some examples of what you're talking about? Terry Vik: The biggest adjustments are that the ability to give blood product support, transfusions of platelets is somewhat limited. So, for instance, our ability to treat acute myeloid leukemia, which is heavily dependent on intensive myelosuppressive chemotherapy, we're not so good at that yet because we don't have the support for blood products. Similarly, the recognition and treatment of infections in patients is somewhat limited. Yet, just the cost of doing blood cultures, getting results, we actually have the antibiotics to treat them, but figuring out that there actually is an infection, and we're just beginning to look at resistance patterns in bacteria in Kenya because I think that's an indiscriminate use of antibiotics. In Kenya, there are a lot of resistant organisms that are being identified, and so figuring out how best to manage those are the two biggest things. But now, in Eldoret, we have two linear accelerators that can give contemporary radiation therapy to kids who need it. We have pediatric surgeons who can resect large abdominal tumors. We have orthopedic surgeons and neurosurgeons to assist. All those things are in place in the last three to five years. So, really, the ability to support patients through intensive chemotherapy is still one of the last things that we're working diligently on improving. Dave Johnson: So one thing that I've read that you've done is you're involved heavily in the creation of a pediatric oncology fellowship program. If I read it correctly, it's a faculty of one; is that correct? Terry Vik: Well, now that two have just graduated, it's a faculty of three, plus some guest lecturers. So I feel quite good about that.  Dave Johnson: So tell us about that. That must have been quite the challenge. I mean, that's remarkable. Terry Vik: That goes back to one of my longtime colleagues in Kenya, Festus Njuguna, who is Kenyan. He did his medical school training at Moi University and then did pediatric residency there. They call it a registrar program there. And then he was, since 2009, 2010, he's been the primary pediatric oncologist. Although he always felt he did not have the formal training. He'd spent time in the US and in Amsterdam to get some added training for caring for kids. But it was his vision to create this fellowship program. So Jodi Skiles, one of my colleagues who had spent some time in Kenya and myself and he worked on creating the fellowship document that needs to go through the university to get approved. That finally got approved in 2019. And so the first two fellows…I was on a Fulbright Scholar Award to start that fellowship program for a year right in the middle of the pandemic, but we were able to get it started, and I was able to continue to go back and forth to Kenya quite a bit in the last two years to get through all of the training that was laid out in our curriculum. And two fellows, Festus and another long-standing colleague of mine, Gilbert Olbara, both completed the fellowship and then sat for their final exams at the end of last year and graduated in December. So it really was heartwarming for me to see these guys want to build up the workforce capacity from within Kenya, and being able to support them to do that was a good thing. Pat Loehrer: Parenthetically, Dave, we had the first Gynecology Oncology program in the country, too, led by Barry Rosen from Princess Margaret, and they have 14 graduates, and two of them now are department chairs in Kenya. Jenny's spearheading a medical oncology curriculum now so that we have that opened up this year for the first time. Dave Johnson: It's uncommon to find a junior faculty as accomplished as Jenny. Jenny, tell us a little about your background and how you got interested in global health, and your previous work before moving to IU.  Jennifer Morgan: I was an anthropology major at undergrad at Michigan, and I think I really always liked studying other cultures, understanding different points of view. And so I think part of that spirit when you study anthropology, it really sticks with you, and you become a pretty good observer of people and situations, I think, or the goal is that you become good at it. I think my interest in medicine and science, combined with that desire to learn about different cultures really fueled a lot of my interests, even from undergrad and medical school. I really felt strongly that access to health is a human right, and I wanted to work for Partners in Health when I graduated from residency. I had heard a lot about that organization and really believed in the mission around it.   And so I went to work in Butaro in Rwanda, and I really didn't have any plans to do cancer care, but then I just kind of got thrown into cancer care, and I really loved it. It was a task-shifting model that really where you use internists to deliver oncology care under the supervision of oncologists from North America. So, most of them were from Dana-Farber or a variety of different universities. And so it made me feel like this high-resource field of Oncology was feasible, even when resources and health systems are strained. Because I think a lot of people who are interested in Oncology but also kind of this field of global health or working in underserved settings really struggle to find the way that the two fit sometimes because it can feel impossible with the hyper-expensive drugs, the small PFS benefits that drive the field sometimes. And so I think, Butaro for me, and Partners in Health, and DFCI, that whole group of people and the team there, I think, really showed me that it's feasible, it's possible, and that you can cure people of cancer even in small rural settings. And so that drove me to go to fellowship, to work with Satish Gopal and UNC. And because of COVID, my time in Malawi was a bit limited, but I still went and did mainly projects focused on breast cancer care and implementation science, and they just really have a really nice group of people. And I worked with Tamiwe Tomoka, Shakinah Elmore, Matthew Painschab, really just some great people there, and I learned a lot.  And so, when I was looking for a job after fellowship, I really wanted to focus on building health systems. And to me, that was really congruent with the mission of AMPATH, which is the tripartite mission of advancing education and research and clinical care. And I knew from Pat that the fellowship program would be starting off, and I think to me, having been in Rwanda and Malawi and realizing how essential building an oncology workforce is, being a part of helping build a fellowship as part of an academic partnership was really exciting. And then also doing very necessary clinical outcomes research and trying to do trials and trying to bring access to care in many systems that are very resource constrained. So that's kind of how I ended up here.  Pat Loehrer: That's awesome. So tell us a little bit about your breast cancer work. What exactly are you doing at the moment? Jennifer Morgan: In Malawi, during my fellowship, we looked at the outcomes of women with breast cancer and really looking at late-stage presentations and the fact that in Malawi, we were only equipped with surgery, chemotherapy, and hormone therapy, but not radiation. You see a lot of stage four disease, but you also see a lot of stage three disease that you actually have trouble curing because it's so locally advanced, really bulky disease. And so that first study showed us the challenge of trying to cure patients– They may not have metastatic disease, but it can be really hard to locally even treat the disease, especially without radiation. And so that's kind of what we learned.   And then, using an implementation science framework, we were looking at what are the barriers to accessing care. And I think it was really interesting some of the things that we found. In Malawi, that has a high HIV rate, is that the stigma around cancer can be far more powerful than the stigma around HIV. And so, we are seeing a lot of women who are ostracized by their communities when they were diagnosed with cancer. And really, they had been on, many HIV-positive women, on ARVs for a long time living in their communities with no problem, and so HIV had kind of been destigmatized, but we're seeing the stigma of cancer and the idea that kids are as a death sentence was a really prominent theme that we saw in Malawi.  So some of these themes, not all of them, but some of them are very similar in Kenya, and so what I'm helping work on now is there's been this huge effort with AMPATH called the Breast and Cervical Cancer Screening Program, where around 180,000 women have been screened for breast cancer in a decentralized setting which is so important - so in counties and in communities. We're looking at who showed up to this screening and why did women only get breast cancer screening and why did some of them only get cervical, and why did some get what was intended - both. Because I think many people on the continent and then other LMICs are trying to do breast and cervical cancer co-screening to really reduce the mortality of both of those cancers. And the question is, I think: is mammography a viable screening mechanism in this setting or not? That's a real question in Kenya right now. And so we're going to be looking to do some studies around mammography use and training as well.  Dave Johnson: So, I have a question for all three of you. What lessons have you learned in your work in Kenya or Malawi that you've brought back to the States to improve care in the United States? Pat Loehrer: One is that the cost of care is ever present there. And so one of the things that we need to think about here is how can we deliver care more cheaply and more efficiently. It goes against the drug trials that are going on by industry where they want to use therapy for as long as they can and for greater times. And there are a lot of common things like access to care is a big issue there, and it's a big issue in our country. So we have used in IU some community healthcare workers in rural parts of our state as well as in the urban centers so that they can go to people's houses to deliver care.  Terry was involved with a wonderful project. It was a supplement from the NCI, which looked at barriers to care and abandonment of therapy. And just by giving patients and their families a small stipend that would cover for their travel and their food, the abandonment rate went down substantially, and they were able to improve the cure rate of Burkitt's Lymphoma. It's probably about 60% now. And so those are issues that I think we see here in our state, where people can't come to IU because of the cost of parking, that's $20 a visit. The lesson there is that we really need to get down to the patients and to their families and find out what their obstacles are.  Terry Vik: My favorite example, since I deal with kids and parents, is how striking parents are the same worldwide. They all want the best for their child. They all want anything that can be done to potentially cure them, treatment, they do anything they could. And I think the hardest thing, as Pat said, is the financial burden of that care. And the other thing that I bring back to my fellows in the US is that you don't have to do Q4-hour or Q6-hour labs to follow somebody when they start their therapy. Once a day, every 3 days, works quite well also. And just the realization that things can be done with a lot less stress in the US if you only decide to do it. Dave Johnson: Jenny, any thoughts from you on that? Jennifer Morgan: I think for me, decentralized cancer care is so important. Even being back on the oncology wards in Indiana in December, I saw a couple of really advanced patients who were really unfortunate, and they had tried to go through the system of referrals and getting to cancer care. And unfortunately, I think there are disparities in the US health system, just like in Kenya, and maybe on different scales. But cancer care that's accessible is so important, and accessible versus available, I think we a lot of time talk about therapies that may be available, but they're not accessible to patients. And that's really what we see in Kenya, what we see in rural Indiana. There are a number of grants that talk about reciprocal innovation because some of these things that we do in Kenya to minimize burden on the system are things that can be done in rural Indiana as well. And so, partnership on these issues of trying to improve decentralized care is important everywhere.  Pat Loehrer: And again, from the perspective as a medical oncologist, we see patients with late-stage diseases. We could eradicate the number one cause of cancer in Sub-Saharan Africa, cervical cancer, from the face of the earth just by doing prevention. We don't do enough in our country about prevention. The other dimension I guess I wanted to bring up as far as multidisciplinary care - when we think about that in our country, it's radiation therapy, surgery, medical oncology, but one of the lessons learned there is that the fourth pillar is policy. It's really about cancer policy and working with the government, Ministry of Health to affect better insurance cover and better care and to work with a different discipline in terms of primary care, much more strongly than we do in our country.  Dave Johnson: Are you encountering similar levels of vaccine hesitancy in Kenya as you might see in the States, or is that something that's less of an issue? Pat Loehrer: I'll let Terry and Jenny answer that. Terry Vik: I think there is some degree of vaccine hesitancy, and not so much that it's fear of the vaccine, but it's fear of the people pushing the vaccine. If it's coming from the government or if it's coming from outside drug companies or outside physician recommendations, it's less likely to be taken up. And if it's coming from within their own community or if it's their chiefs and their community leaders they respected, then I think there is less vaccine hesitancy certainly in a lot of things we do in pediatrics. So I think there is hesitancy, but it's coming from a different source than what we see in the US.   Jennifer Morgan: I would agree, and I think also COVID has changed the game on vaccine perceptions everywhere, and I don't think Kenya is spared from that either. So it may take a few years to see really what's going on with that.   Pat Loehrer: Jenny and I were at this conference, it's a Cancer Summit in Nairobi a couple of weeks ago, and we saw this little documentary there. And this notion of misinformation, as we've seen in our country, is also common over there. They were interviewing a number of men and women from Northern Kenya about prostate cancer, which is a very serious problem in Kenya. The notion was that even doing PSA screening caused infertility, and so the men and women didn't want their husbands to get screened for prostate cancer because they would become less fertile by doing that. So, again, there are lessons that we– as Jenny mentioned from the top about anthropology, I think we're all connected, we all have different ways of viewing communications in health, but I do think that we can learn from each other substantially. Dave Johnson: I mean, it's remarkable work. How is it funded?  Pat Loehrer: Well, I've been fortunate to be able to work with some friends who are philanthropists. We've had strong support as we've told our story with various different foundations. And we've been very grateful to Pfizer, who are very helpful to us in the early stages of this - Lilly Foundation, Takeda, Celgene. And I think as we basically share our vision of what we're trying to accomplish, we've been very humbled by the support that we have gotten for us. The U54 helps support some of the research. We have D43 we're doing through Brown University. So we plan to increase our research funding as best as we can. But this is active generosity by some wonderful people. We have a $5.5 million cancer and chronic care building in which a large sum of it came from Indiana University and the Department of Radiation Oncology. Dr. Peter Johnstone helped lead that. There was a Lilly heir that gave us quite a bit of money. An Indian Kenyan named Chandaria also donated money. So it's a matter of presenting the vision and then looking for people that want to invest in this vision.  Well, I just want to say, from my perspective, I am more of a cheerleader than on the field. But Terry, I know you spent a tremendous amount of time on the ground in Kenya, and Jenny, you're living there. I just wanted to say publicly that you guys are my heroes. Dave Johnson: Yeah. I think all of our listeners will be impressed by what they heard today, and we very much appreciate you both taking time to chat with us.  So at this point, I want to thank our listeners of Oncology, Etc., an ASCO Educational Podcast. This is where we'll talk about oncology medicine and beyond. So if you have an idea for a topic or a guest you'd like us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org.  Pat, before we go, I have an important question to ask you. Pat Loehrer: I can't wait. Dave Johnson: Do you know how snails travel by ship?  Pat Loehrer: As cargo! Dave Johnson: Awesome. You got it. All right. Well, Terry and Jenny, thank you so much for taking time to chat with us. It's been great. I'm very impressed with the work you guys are doing. Really appreciate your efforts. Terry Vik: Great. Thank you. Jennifer Morgan: Thank you. 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.  

Sandra Ramos-Alves was an assistant treasurer at Celgene when Bristol Myers Squibb bought it in 2019. By June of 2021, she was acting treasurer of BMS. And in October of that year she was named senior vice president and treasurer of the pharmaceutical giant that had acquired the company where she had worked for more than 14 years. In a Strategic Finance Lab podcast episode you can hear by heading to Apple or Spotify, Ms. Ramos-Alves says she may not have her current position if she hadn't taken the advice of an insistent mentor and mustered up the courage to set up a meeting with the CFO. At that meeting, she told him she was interested in being BMS treasurer “when the time is right.” That experience taught her the importance of advocating for yourself and telling people what you want. Because someday, when an opportunity arises, they may deliver for you. “We all do own our careers,” she says. She also tells NeuGroup's Nilly Essaides that mutual trust and integrity are the foundation of her leadership style. Trust in her team allows Ms. Ramos-Alves to empower people to make decisions and only bring her in when needed. By not wading too deep into the details of every issue, she avoids being an impediment, she says. Even better, the trust allows her to step away and spend time with her family—her top priority. That includes taking vacations and leaving her laptop at home. But she never completely disconnects, she admits. Her iPhone is always on.

Synopsis: Tariq Kassum, M.D. is the CEO of Celsius Therapeutics, a company pioneering new precision medicines in inflammatory disease by harnessing the power of single-cell RNA sequencing and human biology at scale. Tariq shares his unique journey from med school, to working in Wall Street as a biotech investment banker and stock analyst, to the corporate side working at Millennium Pharmaceuticals and Takeda, and finally the innovative biotech world. He discusses the importance of learning to adapt to each environment in order to remain productive and successful, and building meaningful relationships with coworkers and mentors. He also talks about what it will take for the biopharma executive of the future to be successful. Biography: Tariq Kassum brings 20 years of experience in corporate development, strategy and business leadership to Celsius. He joined the company in 2019 from Obsidian Therapeutics, where he was a co-founder and served as chief operating officer and head of corporate development. During this time, Tariq helped build Obsidian into a leading platform technology company and played a central role in the company's strategic partnership with Celgene. Prior to Obsidian, Tariq spent seven years with Millennium Pharmaceuticals and Takeda, most recently as vice president, business development and strategy for Takeda Oncology, responsible for transactions, collaborations, alliance management and strategic planning. Before that, he led Takeda's global corporate development efforts, where he managed multiple acquisitions and divestitures in the U.S. and internationally. He was also part of the business development team at Millennium Pharmaceuticals. Prior to Takeda, Tariq was an analyst covering healthcare equities for institutional investment firms, where he led scientific due diligence and investment decisions on numerous companies and pharmaceutical compounds across multiple therapeutic areas. He began his career as an investment banker with CIBC World Markets, serving clients in the biotechnology and specialty pharmaceuticals industries.

Synopsis: Andrew Allen is the Co-Founder, President and CEO of Gritstone bio, a clinical-stage biotech company developing groundbreaking immunotherapies for cancers and infectious diseases such as COVID-19 and HIV. Gristone seeks to generate a therapeutic immune response by leveraging insights into the immune system's ability to recognize and destroy diseased cells by targeting select antigens. Andrew joins host Rahul Chaturvedi for a conversation about his entrepreneurial journey founding a biotech, the state of biotech right now and how he manages his team during times of volatility. He also discusses the exciting science they're pursuing at Gritstone and the role T cells play in engaging the immune system against cancer and infectious diseases. Biography: Andrew Allen, M.D., Ph.D. co-founded Gritstone bio, Inc. and has served as President, CEO and a board member since 2015. In 2009, Dr. Allen co-founded Clovis Oncology and served as Chief Medical Officer until 2015, driving development of Rucaparib, a PARP inhibitor. Prior he was Chief Medical Officer at Pharmion Corporation, developing Vidaza, the first approved DNA methylation inhibitor, until acquisition by Celgene in 2008. Dr. Allen also served in clinical development leadership roles at Chiron Corporation and Abbott Laboratories, and worked at McKinsey & Company. He currently serves on the board of directors of TCR2 Therapeutics and Sierra Oncology (both public biopharma companies) and Revitope Oncology and Verge Genomics (both private biopharma companies). He previously served on the board of directors of Epizyme (developers of the first approved histone methylation transferase inhibitor) and Cell Design Labs (acquired by Gilead Sciences in 2017). Dr. Allen qualified in medicine at Oxford University and received a Ph.D. in immunology from Imperial College of Science, Technology and Medicine in London.

Diffuse Large B-Cell Lymphoma or DLBCL is the most common type of lymphoma. Much progress has been made in treatment of the disease lately, particularly with emergence of CAR T-cell therapy, but not all patients are benefiting from it. This episode of Cancer Topics features Drs. Loretta Nastoupil and Chijioke Nze exploring treatment approaches for two cases of refractory DLBCL: a 60-year-old man with no comorbidities (1:30) and a 39-year-old woman with HIV (18:35). The guests also discuss improving patient access to CAR T-cell therapy and managing its toxicities (10:35), as well as emerging therapies for DLBCL (14:30). To learn more about management of refractory DLBCL, check out the ASCO course linked bellow. Guest Disclosures:Loretta Nastoupil, MD: Honoraria – Gilead Sciences, Novartis, Bayer, Janssen Oncology, TG Therapeutics, Bristol-Myers Squibb, ADC Therapeuitcs, Morphosys, Epizyme, Genmab, Takeda, Genentech/Roche; Research Funding – Janssen Biotech, Celgene, Genentech/Roche, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Chijioke Nze, MD, MPH: No Relationships to Disclose Resources: ASCO Course: Second-line Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma (Free to Full and Allied ASCO Members) ASCO Podcast: Cancer Topics - New Therapies for Lymphoma (Part 1) ASCO Guideline: Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor (CAR) T-Cell Therapy ASCO Article: Navigating the Evolving Treatment Landscape of Diffuse Large B-Cell Lymphoma If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org.  TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Loretta Nastoupil: So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing a refractory disease, and potentially succumbing to the lymphoma. Hello, my name is Dr. Loretta Nastoupil, I'm an Associate Professor and Deputy Chair of the Department of Lymphoma and Myeloma, at the University of Texas MD Anderson Cancer Center. Welcome to this ASCO Education podcast episode. It's my pleasure to welcome Dr. Chijioke Nze. Dr. Chijioke Nze: Hello, everyone. I'm Dr. Chijioke Nze, a Hematology/Oncology fellow at MD Anderson, I'll be co-hosting this episode with Dr. Nastoupil. Dr. Loretta Nastoupil: We've seen notable advances in diffuse large B-cell lymphoma research lately, with novel treatments including CAR T-cell therapy, offering the prospect of long-term remission for some patients, yet many patients are not even receiving second-line or later therapy, and even fewer are treated beyond the second line. How do you approach a patient with refractory diffuse large B-cell lymphoma? In today's episode, we'll explore strategies for management of refractory diffuse large B-cell lymphoma through two patient cases. So, Dr. Nze, walk us through our first case. Dr. Chijioke Nze: Our first case is Frank. Frank is 60 years old and has no comorbidities. He presented with severe back pain in September 2021, and was evaluated locally. He had a CT scan that showed retroperitoneal mass, prompting further evaluation. He had a biopsy of the left retroperitoneal mass in November 2021, which was consistent with diffuse large B-cell, germinal center B-cell of phenotype Ki-67 of 90%. He had a subsequent PET-CT scan, which showed a large conglomerate, and invasive left retroperitoneal hypermetabolic mass with satellite nodularity and contiguous bulky retroperitoneal adenopathy. He had bulky, FDG-avid metastatic retrocrural and intrathoracic adenopathy as well. He was treated with R-CHOP for six cycles, and at the end, achieved complete remission. He had a PET-CT a year later that showed new and worsening intensely FDG-avid abdominal adenopathy. This was new from a PET scan he'd had in January 2022 of the same year. He had a biopsy of this retroperitoneal adenopathy, which was consistent with relapsed diffuse large B-cell germinal center phenotype, also Ki-67 of 90%. Locally, he was treated with ICE, times five cycles, and had a follow-up CT scan at the end, which showed persistent bulky nodal disease with periaortic regional nodes with double 5, consistent with persistent disease. He also was found to have new and more conspicuous nodes in other areas as well. He presented for his first visit at MD Anderson in September 2022. Dr. Nastoupil, when you see a patient like this coming into your clinic, what's your typical approach? Dr. Loretta Nastoupil: For a diffuse large B-cell lymphoma, we are always hoping for cure with frontline rituximab, containing anthracycline-based chemotherapy. And so, it's always a gross disappointment when patients experience relapse. The timing of that relapse right now informs our current approach. And the reason I mention that, is because there have been three large randomized studies conducted and reported out just in the last year demonstrating that CAR T-cell therapy is the preferred option for patients who experience either primary refractory disease, or relapse within 12 months. And that is because they resulted in better outcomes than standard salvage-based chemotherapy and high-dose therapy autotransplant in the setting of chemosensitive disease. I have to acknowledge, of the three studies that were done, two were positive trials, so that's why currently, we have axi-cel or Axicabtagene ciloleucel, or Lisocabtagene maraleucel, and not tisa-cel or Tisagenlecleucel, as CAR T-cell therapy options. And again, that's because two of the three studies were positive trials. Now, the challenge is why would we have two positive studies in one negative trial? There are a lot of caveats to how those studies were conducted, but I think one of the biggest important lessons to be gained is that if you're going to consider CAR T for these high-risk patients, you want to do it as soon as possible, because that delay from identifying CAR T as a preferred option to actually infusing cells in a disease-- in a case particularly like this, where patients may have bulky, aggressively-behaving disease - that prolonged time may actually have an impact on outcomes. Dr. Chijioke Nze: Excellent. Thank you. So, you've mentioned he had an early relapse. How would you define early relapse in this patient population? Dr. Loretta Nastoupil: Thinking back to how we've been approaching diffuse large B-cell lymphoma over the last two decades, the PARMA study, which was done prior to Rituximab, suggested that for patients who had chemosensitive disease to a platinum-based salvage chemotherapy, which generally, was at least a partial response on CT, if they went on to high-dose therapy autologous stem cell transplant, 50-60% of those patients could anticipate cure. Whereas for the folks who continued on salvage chemotherapy, 10-20% of those patients had favorable outcome. So, we generally do try salvage-based chemotherapy, and for patients with chemosensitive disease, go on to high-dose therapy autotransplant. However, in the modern era where we've approached patients who've had rituximab as part of their frontline therapy, at least two studies - the ORCHARD study, and the CORAL study suggested that only 20% of patients who relapse in the post-rituximab era, particularly within 12 months, were successfully salvaged with platinum-based chemotherapy and high-dose therapy autologous stem cell transplant. Now, fortunately for patients who fail salvage, we have had CAR T-cell therapy as an option based off of three pivotal phase II studies, demonstrating about 40% of patients could anticipate a cure with CAR T-cell therapy. So, it only made sense to try and move that therapy up into second line, and the preferred population was those that had progressed within 12 months of frontline rituximab and anthracycline-based chemo. Now, to qualify for those studies, patients had to be considered fit for the control arm, which was salvage and auto transplant. Nonetheless, I do think for a patient like this, who's 60, without any other significant comorbidities, whose biggest challenge to longevity of life is his aggressive lymphoma, CAR T-cell therapy should be considered as soon as possible for this patient. Dr. Chijioke Nze: Is there still a role for high-dose therapy and autologous transplant in the new era, given the efficacy shown with CAR T-cell therapy? Dr. Loretta Nastoupil: I think there is. And the reason why I say that is, the trials that were done really did focus on the highest-risk patients, which were those with primary refractory disease or those who progress within 12 months of frontline. Now, there are patients that will have later relapse. And so, I do think for those patients, particularly those who are young and otherwise fit, should be approached first with a platinum-based salvage chemotherapy, in the setting of chemosensitive disease, proceed onto high-dose therapy and autologous stem cell transplant. Now, what do we do for those patients who have a late relapse but are otherwise older, or who have comorbidities that would make them suboptimal candidates for the high-dose therapy preceding stem cell transplant? I have a couple other options for those patients - so, there was a trial done with liso-cel for patients who were otherwise older, or not fit for intensive therapy. It's a single-arm phase II without a randomized comparison, but also demonstrated that liso-cel in second-line, later relapsed patients who are not fit for intensive therapy, resulted in comparable outcomes to what we would anticipate on that third-line or later setting. We also have other non-CAR T-cell therapy options, such as tafasitamab, which is a naked CD19 antibody, which has been combined with lenalidomide in the L-MIND study, again, for patients without primary refractory disease and who would not be appropriate candidates for intensive therapy. So, I do think we have alternative options, it's just when we look at the totality of the data right now, my conclusion is that CAR T-cell therapy, particularly for high-risk patients, is the most likely chance to result in cure. Dr. Chijioke Nze: Excellent. In a patient who we are considering CAR T-cell therapy, what are some of the short-term and long-term consequences, or toxicities that we should worry about? Dr. Loretta Nastoupil: One of the challenges right now with CAR T, and why it's still only available in specialized centers, is the acute toxicity, which is really a derivative of its mechanism of action. We take patients' own T-cells, we use a viral vector to introduce extracellular receptor, but also a co-stimulatory molecule. So, once these cells engage their antigen, sort of prime to react to that, and that can lead to pretty rapid T-cell expansion, release of cytokines, recruitment of other inflammatory cells to that tumor bed, and as a result, a large portion of patients can anticipate to experience cytokine release syndrome, which again, is the result of the activation of these T-cells, the expansion and the recruitment of other inflammatory cells. Fortunately, for most patients, this results in fever alone that can be managed with supportive measures. Occasionally, they'll have concomitant hypoxia or hypotension, and unfortunately, few patients will have significant or severe toxicity. The other toxicity that's less easily manageable or less predictable is the neurotoxicity that can vary according to patient-specific characteristics, such as age, and the amount of tumor burden, their performance status going into CAR, but even more importantly, the construct that's utilized, with highest rates of neurotoxicity associated with axi-cel. Again, likely speaking to its construct and the CD28 costimulatory domain that is unique to axi-cel. As a result of these acute toxicities, patients are required to stay within two hours of their treating center for the first four weeks, and they're also discouraged from operating heavy machinery, such as driving, for the first eight weeks following CAR T. So, I do you think this creates some barriers to access to this therapy, particularly the patients that are treated in community settings that may reside long distances from these certified CAR centers. Dr. Chijioke Nze: So, you mentioned that obviously, given the specialized care needed for the CAR T therapy, that they're kind of localized in certain sites. What are some of these issues with access that you're noticing both in the logistics of giving CAR T, and also in patient access? Dr. Loretta Nastoupil: I'm hoping we're going to address one of those issues right now, which is, education and awareness, because we've had these three randomized studies, and two being positive readouts just in the last year. It's important to get the message out that CAR T-cell therapy for high-risk early relapsed refractory large cell lymphoma patients can result in a significant improvement in event-free survival and progression-free survival over the standard of care. And so, being aware that this therapy can result in more favorable outcomes is step one. Step two is, we have to ensure that there are minimal barriers to getting those patients into these treating centers as quickly as possible. So, recognizing who delivers the care - is it your traditional stem cell transplant physician? Is it a lymphoma doctor? What centers are certified? Some of these issues can be addressed with quick internet searches. So, for instance, in our center, we have a 1-800 number for anyone who's interested in CAR T-cell therapy that connects them directly to a CAR T coordinator who can help them understand do they meet the FDA-approved indication? Would they be interested in seeking consult? And we try and prioritize getting those patients in the door as soon as possible since time likely does have an impact on outcomes. And then, partnering with our community oncologist - you're going to be the primary oncologist for these patients leading up to CAR, and then after that four-week window, when we're keeping the patients in close proximity to our centers, we often send them back. And so, making sure that they're comfortable knowing what potential late toxicities to be on the lookout for, which include B-cell aplasia and risk for infection, or prolonged cytopenias, beyond just lymphopenia. And so again, there's a need for education and partnering with our community sites to make sure that there is successful handoff of these patients back after they've completed the monitoring for the acute toxicity. And then, really trying to explore opportunities to utilize some of the better tolerated CAR T, such as liso-cel, in your non-traditional academic centers. Those that are equipped to handle phase I studies or stem cell transplant, for instance, may not be affiliated with the university. So, I think those are all types of strategies that could be employed to try and improve access for patients. Dr. Chijioke Nze: And then, you mentioned the liso-cel, but in some of the toxicities, are there ways of predicting which patients will do better or worse? Are there ways to reduce toxicities? And is there any hope for things such as outpatient administration of CAR T? Dr. Loretta Nastoupil: So, my answer today may improve over time as we get larger numbers and more experience, but what we currently understand is that the patient performance status, their degree of tumor, how quickly that tumor is increasing, LDH and some inflammatory markers such as CRP or ferritin pretreatment can provide some insight into a higher risk of toxicity. And then obviously, the construct that's utilized. Again, axi-cel has higher rates of neurotoxicity. All will have some form of cytokine release syndrome, generally speaking, but rates of grade three or higher are quite infrequent, particularly with liso-cel and tisa-cel. So, it's multifactorial. That then raises the question, can we do anything to alter those modifiable risk factors? Can we reduce the disease burden? Can we improve the performance status? Can we do anything to reduce the inflammatory markers pre-treatment? And so, those are strategies that are being discussed, and I think in general, as we get more effective therapies that enter into the treatment landscape, it's probably some of the best ways to try and reduce some of those risk factors. Dr. Chijioke Nze: Rounding that up, are there any exciting developments or things to look out for, for exciting therapies in the relapse setting? Dr. Loretta Nastoupil: A couple of things beyond CAR T that I think we should all be aware of and anticipate to be in our toolkit relatively soon; probably, one of the most exciting, is the development of the bispecific antibodies. So, another challenge with CAR T is the requirement to collect these patients' own T-cells and send them off to a central manufacturing site, and the turnaround time can be anywhere from 3-4 weeks. And again, in a situation where you have an aggressive disease, that can be a long time to wait. And so, is there any treatments that are more readily available, that again, will be effective at reducing disease burden? And so, by specifics kind of fit those unmet needs to some extent - you have essentially two heads; one head is going to bind the endogenous T-cells that eliminates the need to leukapherese these patients and manufacture, and then the other head is going to generally engage CD20, which we know is an effective targeted antigen, particularly in B-cell lymphomas. And there are a number that are under development. We saw preliminary phase II data with glofitamab, epcoritamab, as well as combination strategies with mosunetuzumab. So, I do have optimism that the bispecific antibodies will potentially enter into the treatment landscape. I anticipate they'll probably be used first post-CAR T, but will likely move their way into earlier lines of therapy. I've already mentioned tafasitamab in combination with lenalidomide, which is an effective non-chemotherapy option. We have antibody-drug conjugates, such as Loncastuximab, which is a CD19 antibody-drug conjugate. It's essentially targeted delivery of chemotherapy, and it looks to have a pretty promising activity as a single agent in that third-line or later space, and then polatuzumab, which is a CD79b antibody drug conjugate, in the relapse setting has been combined with bendamustine and rituximab, but also demonstrated significant improvement in the frontline setting in the POLARIS study where vincristine was replaced with polatuzumab. So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing refractory disease, and potentially succumbing to the lymphoma. Dr. Chijioke Nze: And then, one additional question: How do you approach a patient who is not quite as fit, in thinking about what their options are for later-line therapies? You already mentioned some of these, but which of those would you prioritize in this setting? Dr. Loretta Nastoupil: Again, as we get more experience, we develop skills that help us sort of navigate all these different options. In my practice, if I'm even considering CAR T, I'm going to delay bendamustine until after I've collected those cells. I think that's one caveat that-- we do get nervous about the quality of those autologous CAR Ts if they're generated in someone who's had recent exposure to bendamustine. So, that may help me sequence that later on. We have questions right now about what's the optimal sequencing of CD19-directed therapy because we have several options beyond just CAR T-- As I mentioned, we have Lonca, we've got tafasitamab and lenalidomide. Currently, we don't have prospective data that really informs that question, and there's a number of research studies underway to try and help us understand if there is a preferred sequence, or even if it matters how we handle CD19 targeting. For my older, frailer patients where I'm really worried, they're not going to be able to tolerate something like liso-cel, or they're not going to be able to have that caregiver, and they're uncomfortable relocating to an area where CAR T might be available, my general approach right now is to consider tafasitamab and lenalidomide first in that relapse setting, followed by either Lonca or Pola-BR. Selinexor is another option. It's an oral agent, though again, in my opinion, if we look at the totality of the data, may be less effective than the other options. So, I might reserve that as a last option for someone, again, with relapsed/refractory large cell. Dr. Chijioke Nze: Excellent. Thank you. This has been very helpful. Dr. Loretta Nastoupil: All right. So, Dr. Nze, now I'm going to turn the table and ask you some questions. I'm going to change this up a little bit - she's now a 39-year-old female. She has significant comorbidities. She has HIV, and again, large cell lymphoma. So, let me walk you through her case, and then we'll discuss some of the challenges, again, in a very different scenario, albeit a similar disease. So, our female is, I mentioned 39, pre-existing HIV, she's treated frontline with six cycles of R-CHOP and intrathecal methotrexate for CNS prophylaxis. Because of her comorbidities, again, not well controlled HIV, she also has a poor functional status at the time of relapse. This was a couple years ago, and CAR T was not an option in second line, though she is someone who had a relapse that was beyond 12 months. So, for her second-line approach, because of her comorbidities, she actually receives rituximab in combination with high-dose cytarabine, dexamethasone, and oxaliplatin for three cycles, and actually achieves a chemosensitive disease and is referred to our stem cell transplant colleagues. Unfortunately, at that time, due to comorbidities, she was deemed not to be an appropriate candidate for high-dose therapy, and she's been monitored for signs of relapse. Despite being in the minority, she actually does not have a recurrence of her lymphoma but has a number of other, again, challenges in regards to her comorbidity, including multiple infections, resulting in recurrent hospitalizations. And so, it's always been a challenge for me in being intimately involved in her case, deciding when she's presenting, how alarmed to be about recurrent lymphoma versus infection, and how I might approach her in the setting of relapsed large cell lymphoma. So, what role does prior type and response to therapy play in treatment selection at your next line of treatment? Dr. Chijioke Nze: I think in this patient, it sounds like she got one adequate therapy on and the initial presentation with R-CHOP, and then with IT chemotherapy as well. She looked like she had a good response. I think the fact that she achieved a complete response and the duration of her response, lets me know that she likely has chemosensitive disease. This, in turn, helps me to pick what to do next. As you mentioned previously, we know how efficacious the CAR T therapy is, but in someone like her who had a long duration, trying salvage therapy and proceeding to autologous transplant might make sense. I'd be interested in your thoughts. Dr. Loretta Nastoupil: Yeah, I agree. And I think part of the challenge, particularly when we're facing patients with HIV, they're often excluded from prospective studies. And so, we're often in a scenario where we may not have the wealth of data to inform our treatment decision. But I do think in general, comorbidities play a major role-- we're navigating treatment options. Because again, traditionally, we've used intensive chemotherapy as our mainstay of treatment, and there are clear criteria that patients generally should meet that help us predict how likely they are to have significant or severe toxicity from high-dose therapy. And this is a prime example of even though she was young, her comorbidity made her a poor candidate for intensive therapy. I think the other sort of non-clinical factors that we sometimes take into consideration, because CAR T was approved off of single-arm phase II studies, again, none of which would've included someone like her, because of her HIV status, how do we extrapolate-- for instance, if she had relapsed in that third-line space, and suggesting that she did not have significant infection or other significant comorbidities, do we have experience to proceed with an autologous CAR in that setting? So, again, there've been a few cases where we have case reports where people have reported on their standard of care outcomes, particularly with CAR T in patients with active HIV disease, but one of the concerns I have in these scenarios is very selected. If you have active infection, that can make the acute toxicity with CAR significantly worse. And so again, we're trying to navigate a sort of limited data zone to try and help her and choose the right therapy. Again, you've met this patient with me, you helped care for her for some time, and you have a unique experience of also practicing in a county hospital where comorbidities, particularly, like HIV, can be much more common. What is your perception regarding barriers to accessing CAR T as it pertains to social factors, clinical factors, and again, this is a case that highlights some of those issues. Dr. Chijioke Nze: You mentioned at first that she had uncontrolled HIV. So, I think which, one, speaks to her treatment reference of her non-malignancy-related diseases, and trying to get that under control would be one of the first things I could think about. Thinking about how her care is managed and what kind of support she has are very important for us to think about as well. The other thing that's very important is, a lot of patients who we're seeing in the community may not have access to such specialized centers such as MD Anderson, where patients do have access to clinical trials and CAR T therapy. So, patients who are unlike her, who might qualify, may not actually be able to get these therapies as well. Part of the reason is, it can be insurance status, which is what we see in a lot of our patients. So, a barrier to get into the door. And then too barriers, lack of social support can be a big issue as well. And then there's also a big push in the community to improve the trust and awareness of these novel therapies, as you've mentioned. So, in a lot of the community practice, some of the community practitioners may not be comfortable with these, and a lot of the patients may not have heard of these new technologies, and also want to defer trying new therapies before having other people try new therapies before they consider them themselves. I think all these things present specific significant barriers to patients in the community. One, their ability to adhere to care, two, their insurance and their ability to get care and the financial toxicities associated with that. And then third, really understanding the options that are available. Dr. Loretta Nastoupil: And again, just to try and illustrate a couple other points. You know, we use a case here, which is a real case, with significant comorbidities such as HIV, which again, is something that is not frequently encountered, and will have a large impact on treatment selection. What if I just told you this patient has comorbidities, but she has moderate type-2 diabetes, and as a result, she has mild renal insufficiency, ejection fraction is actually adequate, would you have done anything different in this case? Dr. Chijioke Nze: No. I think in this particular case, I do think the fact that she did have a good response for a long duration of time, and did seem to have chemosensitive disease, I would probably still have tried a salvage therapy and autologous transplant in this patient. In the event that she was refractory, or had early relapse, and in that case, I would consider her to not be chemosensitive and would definitely have sought some more active therapies such as CAR T cell therapy through available products. Dr. Loretta Nastoupil: And then one last question for you: What if we just changed her age and we made her 79, but no other significant comorbidities, how would that have impacted your approach? Dr. Chijioke Nze: I'm going to turn that one over to you, I'm not exactly sure how I would treat with older patient with the same disease. Dr. Loretta Nastoupil: That's fair. So, if you have an older patient who has a late relapse, but not necessarily someone you would consider appropriate for salvage chemotherapy and high-dose therapy, then I think tafasitamab and lenalidomide would be probably my first choice in that setting, just based off of the L-MIND study. Dr. Chijioke Nze: Thank you, Dr. Nastoupil, for a great discussion of the management of diffuse large B-cell lymphoma. And thank you to all our listeners. We appreciate you tuning in to this episode of the ASCO Educational podcast.   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.

In this episode of Meeting Mic, we bring you expert insights from the ASH Annual Meeting and Exhibition. Mikkael A. Sekeres, MD, MS, chief of the division of hematology and professor of medicine at Sylvester Comprehensive Cancer Center and University of Miami Health System and chair of the ASH committee on communications, discusses some key take-home points from the Long COVID presentation. :00 Shakira J. Grant, MBBS, discusses multilevel interventions required to increase the rate at which Black individuals participate in hematology research studies. 3:44 Arushi Khurana, MBBS, reviews criteria used to disqualify patients from participating in front-line clinical trials, the acceptable ranges of which often prohibited Black and Hispanic patients from enrollment. 6:35 Tatyana Feldman, MD, discusses how the addition of brentuximab vedotin and nivolumab to doxorubicin and dacarbazine appeared active among patients with advanced-stage classical Hodgkin lymphoma. 9:32 Warren B. Fingrut, MD, reviews how hematopoietic stem cell transplant recipients of non-European ancestry had a significantly higher likelihood of receiving allogeneic grafts from HLA-mismatched donors than individuals of European ancestry. 12:02 Read the full coverage here: Restrictive diet an 'unnecessary burden' for patients undergoing HSCT Multilevel interventions needed to reduce racial disparities in clinical trial enrollment Eligibility criteria more likely to exclude minorities from lymphoma clinical trials Combination ‘promising' for advanced classical Hodgkin lymphoma Non-European HSCT recipients undergo more complex procedures with fewer resources Disclosures: Feldman reports consulting/advisory roles with, speakers bureau roles with or other financial relationships with AbbVie, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Genmab, Genomic Testing Cooperative, Janssen, Karyopharm Therapeutics, Kite Pharma, MorphoSys, Pharmacyclics, Secura Bio, Seagen and Takeda. Please see the abstract for all other researchers' relevant financial disclosures. Fingrut reports no relevant financial disclosures. Please see the abstract for all other researchers' relevant financial disclosures. Grant reports no relevant financial disclosures. Please see the abstract for all other researchers' relevant financial disclosures. Khurana reports no relevant financial disclosures.

Synopsis: Dennis Zaller is the Chief Scientific Officer of ROME Therapeutics, a company developing novel therapies for cancer and autoimmune diseases by harnessing the power of the dark genome, defined as vast stretches of uncharted genetic material that have long been dismissed as “junk DNA.” Dennis joins host Rahul Chaturverdi for a conversation about ROME's unique path to conquering disease and the multiple drug discovery programs they have underway. They also discuss Dennis' transition to biotech after having worked in big pharma for 30 years, the application of data science and drug development at ROME tx, what the company's pipeline and company building looks like over the next several years, and how the dynamic between biotech and big pharma has changed over the last 10-20 years, and where it's headed. Biography: Dennis is Chief Scientific Officer at ROME Therapeutics. He has more than 30 years of experience in the biopharma industry. Most recently, he spent five years as executive director, integrative sciences at Celgene (later Bristol Myers Squibb). In this role, he provided scientific leadership across a large portfolio of external collaborations with early stage biotechs that helped bring six novel molecules to the clinic. During his time at Celgene, Dennis participated in more than 20 joint steering research committees with biotechs and academic collaborators and helped bring six novel molecules to the clinic. Prior to Celgene, he spent 25 years at Merck Research Laboratories in a series of roles with increasing responsibility leading large drug discovery teams at Merck's New Jersey and Boston sites. While at Merck, Dennis helped to advance 28 molecules into the clinic resulting in eight marketed drugs, including aprepitant, sitagliptin and vibegron. Before joining industry, he conducted academic research at the California Institute of Technology. Dennis has a B.S. from the State University of New York at Albany, and an M.A., M.Phil. & Ph.D. from Columbia University. He is an author of more than 60 manuscripts in leading journals covering a variety of scientific discoveries and is an inventor on seven patents.

Host Dr. John Sweetenham, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and Dr. Eduardo Sotomayor, director of the cancer institute at Tampa General Hospital, discuss the impact of Hurricane Ian on cancer care in Florida, and the importance of disaster preparedness to protect patients and clinicians in regions prone to natural disasters.   TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News podcast. Hurricane Ian, a large and destructive Category 4 hurricane, has caused fatalities and widespread damage in Florida after causing huge destruction in Cuba. Communities in the hardest-hit areas have been destroyed, and hospitals across the state have been forced to evacuate patients. Today, I will be speaking with Dr. Eduardo Sotomayor, the director of the Cancer Institute at Tampa General Hospital, about the impact of the hurricane on cancer care. Our full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the ASCO Daily News podcast are available on our transcripts at asco.org/podcasts. Dr. Sotomayor, thanks for being on the podcast today. Dr. Eduardo Sotomayor: Thank you, John, and the ASCO Daily News Podcast, for having me. Dr. John Sweetenham: To begin with, Dr. Sotomayor, could you tell us a little about how Hurricane Ian impacted cancer care at your institution, and how soon do you think you'll have all of your cancer services restored? Dr. Eduardo Sotomayor: Thank you for the opportunity to talk to you about the effect of Hurricane Ian on the state of Florida. But before we start, I would like to say that our thoughts and our prayers are for those Florida citizens who were severely affected by this hurricane, in particular, our cancer patients and their caregivers. So, Tampa General Hospital is located on Davis Islands. So, we were at high risk for having inundation, major destruction, and disruptions in cancer care if the hurricane hit us directly. We were blessed that at the last minute, the hurricane changed its path. But it's important to emphasize all of the preparation that took place, starting seven days before the potential landfall of the hurricane in the state of Florida. This started at the highest levels of the hospital, with the senior leaders getting together as well as the leaders of the cancer institute. We have different scenarios that we call scenario A, B, and C. So, scenario A was the worst-case scenario that we would have a direct hit, then one or two floors of the cancer institute and the hospital would be under water. So, for that scenario, we knew that we needed to be ready to move cancer care to other facilities that Tampa General has inland in areas called Riverview and Brandon. So, scenario C is the scenario that fortunately for us, was the scenario that we dealt with during the storm. We didn't have a direct hit; we had only minimal damage, and we were able to reopen our doors 48 hours after the storm hit Florida. Important to mention also is that during those 48 hours, there was significant disruption in cancer care. In the inpatient service, we had to decrease the number of inpatients to keep those patients that really needed to be in the hospital. We closed all our outpatient facilities and therefore needed to call every patient to let them know about the cancellation of appointments, but also re-scheduling those appointments for the days after the storm has passed. As I said, again, we were among the lucky cancer centers in the state of Florida, but south of us, there were hospitals and community oncology practices that were severely affected by Hurricane Ian. Dr. John Sweetenham: So, it sounds to some extent, Dr. Sotomayor, as if your institution kind of dodged a bullet, although clearly people south of you were very badly affected. But I'm assuming that there had been some disruptions to care for your patients. Can you comment a little on that, and what you're doing to address the disruptions to care, assuming that you experienced some, even though you didn't take a direct hit. Dr. Eduardo Sotomayor: What we have learned from this experience is that preparation is extremely important. Within 24 hours, we created a command center, an operations team, our logistics team, safety team, and we started canceling those appointments that were not critical. When we knew that the hurricane was coming in our direction, then we had to cancel all of our operations. But then we had meetings twice a day with different members of our team to start making phone calls also regarding cancellation of appointments. And then, as the days passed, we started to adapt our plans and starting calling back patients. What is important, I think a silver lining of the COVID-19 pandemic, has been the availability of telehealth, of easy communication with patients. I think that patients are now savvier with managing telehealth. So, the days after the hurricane hit us, we had some patients that had to come back to receive chemotherapy infusions or radiation, but the large priority of patients were able to manage via telehealth. Dr. John Sweetenham: Yes. Thank you. I know one of the questions that I was going to ask you a little later on was whether the telehealth infrastructure that was developed during the COVID-19 pandemic was helpful in response to the hurricane, and clearly from your comments, it has made it easier in terms of patients' familiarity with the platform and so on. So, that's good to know. Dr. Eduardo Sotomayor: Right. And also, just to add to that is that technology before the COVID-19 pandemic, when we were facing a similar situation. Basically, all our call centers would be closed. So, these days we have technology in which employees or members of our team that were receiving or making phone calls, now can do through through special apps in case the internet goes down or electricity goes down. Still, now there are systems that can allow temporary communication with patients in a timelier way. Dr. John Sweetenham: Yeah, that's very reassuring. The Florida Hospital Association has said that many hospitals are feeling capacity pressure. Can you comment on what the Tampa General Hospital is able to help by perhaps offloading other institutions that were badly damaged in the storm, particularly those in the Southwest of Florida? Dr. Eduardo Sotomayor: Yeah, that's a very important question. I think that when we knew that we would be okay and there would not be a significant impact of the hurricane on our facilities, we changed our course and started calling our partners in the oncology community, private practice groups, Florida Cancer Specialists that have offices and provide cancer care in those areas that were severely affected by the hurricane. We are working together. One of the things that I have learned is that a significant percentage of cancer care is performed in the community. Communities were affected by this hurricane and therefore I think it is important to keep that open communication between academic centers and oncology practice in the community. With reference to your question, Tampa General has six helicopters; it has a command center and as soon as it was safe for our helicopters to travel, they went to these affected areas. There were hospitals near our region that didn't have electricity or water. I am proud of the service provided by Tampa General Hospital to other hospitals and cancer care communities that were severely affected by the hurricane. I think so far, we were able to transfer between 50 to 70 patients who were in critical condition and needed to be removed from those areas that were significantly affected by the hurricane. And I have to say, Tampa General Hospital is just one of the hospitals that responded; all of the hospitals in the state of Florida joined a forces to help our patients in general during these difficult times. Dr. John Sweetenham: Yeah, it's certainly great to hear of the oncology community and healthcare community in general coming together to overcome the challenges for so many of these patients. You know, one of the challenges that occurs to me, which might be an issue for you because of your increased patient volumes, as well as for those centers that are more directly affected by the hurricane, and that's the issue of supply chain and availability of medicines, and particularly chemotherapy and other antineoplastic drugs. Can you comment on whether you are experiencing any supply chain issues with medicines, or whether you're aware of other organizations in the southern part of Florida who are having those challenges at the moment? Dr. Eduardo Sotomayor: So, there are two answers to your question; if we are lucky to be in urban communities, I think that the supply chain was not significantly affected, but the problem has been in the rural communities in Florida. And unfortunately, in addition to the areas near the ocean, including Fort Myers, Naples, and Port Charlotte, the track of the hurricane through Florida affected the rural communities. And in those rural communities the problem was flooding, several trees went down, access in those areas was problematic, and they are still dealing with significant issues in the supply chain. What we are doing as are all the other big centers, is  trying to do our best to either provide those supplies to these affected areas or to transfer some of the patients from those areas to, I would say, urban hospitals that have more capacity. Dr. John Sweetenham: So, this raises, I think, a really important issue. We know that very typically underserved communities are disproportionately impacted when there are natural disasters. And to your point, it's clear that you've seen the potential for significant disruption to rural versus urban communities as a result of the hurricane. Do you have any other thoughts or maybe any other examples of how disproportionate care may have arisen because of the effects on underserved communities? Dr. Eduardo Sotomayor: Even before any natural disasters, rural communities-- and I want to focus on rural communities in the state of Florida because there is a significant number of Floridians that live in rural communities. And if you look at the incidence of cancer and mortality associated with cancer in those rural communities, it is greater than the mortality that occurs in urban areas or big cities. So, number one. And there are several issues; there is transportation, access to care, very few oncology providers in those areas. So, even before the natural disaster that just happened, those communities were significantly disadvantaged. And unfortunately, not only the hurricane affected those rural areas, but now I would say the few organizational capabilities that they have have been further impacted. So therefore, when we think about the impact of the hurricane in the state of Florida, we should also be thinking about our rural communities. They are the ones that are going to take longer, perhaps months, or even a year, to recover from the significant damage that Hurricane Ian has imposed upon those communities. Dr. John Sweetenham: Thanks. Switching gears a little, are you concerned about the disruption of research and clinical trials in parts of Florida in the months ahead? I'm just thinking with issues such as-- you know, initially it will be scheduling of treatments, perhaps the transportation disruption, and so on. Do you see these as being potential threats to clinical trial activity in the state for the coming months, and possibly years? Dr. Eduardo Sotomayor: So again, I think that clinical trials in big centers, in urban areas are going to be able to recover relatively quickly. I mean, for instance, our clinical trials operation is back to normal, and was not affected. So, there is a big community oncology practice in the state of Florida, Florida Cancer Specialists, especially if they have active clinical trials, but they have locations in several of the areas that were significantly affected by the hurricane. So, I think in those areas, it is going to take time to recover. But in my early conversations with our colleagues, Florida Cancer Specialists especially, they're going to be moving some clinical trials operations from those affected areas to areas that are fully functional. But definitely, there is going to be a disruption, yes. And unfortunately, that disruption is going to affect those patients enrolled in clinical trials that live in underserved areas, and in particular, those who live in rural areas because access to transportation is going to be a significant problem for them. Dr. John Sweetenham: Yeah, absolutely. I think is one of the consequences of what the emerging climate changes that we've been seeing over many years now, and certainly, there has been a significant interest in the literature, and indeed, on previous ASCO Daily News podcasts regarding the impact of climate change on cancer care. And perhaps, the most immediate example of that is in terms of disaster preparedness of cancer centers. Certainly, that has been tested for you and for other centers in Florida in the last couple of weeks. How would you assess the readiness of your cancer centers to respond to disasters of this scale? Do you think there are areas of care that you've now learned need more attention, just as a direct consequence of this most recent hurricane? Dr. Eduardo Sotomayor: So, I think it's going to be location-dependent. You know, Florida is a big state. For us and other centers that are in the islands, the surge was probably the major threat for us. I mean, there is a technology now called AquaFence. So basically, there are panels that will help you, to be able to give you time to evacuate or to protect the lower floors of the cancer center of the TGH hospital as a whole. It's called AquaFence. So, we install those panels around the whole hospital, and I think that's one of the technologies. And we are going to see more and more of those technologies to try to protect or minimize the potential damage that a hurricane can cause. I mean, my prediction is that it's going to be able to support a hurricane category two, three, or even four, but you know, five - time will tell. So, we need to start thinking more about technology, that's in our case. So, there are other cancer centers that are inland in which the problem for them is going to be flooding. So, one lesson that we have learned is, there has been constant communication between all the cancer centers in this region. In the academic institutions, the University of Miami, Florida, us, Moffitt Cancer Center, but also in the community - Florida Cancer Specialists, especially, community oncology practices. And I think that if you ask me, "What would be the next step?" It will be to foster stronger communication, a stronger collaboration that involves also our community oncology practices because as you know, John, most of the cancer care now is happening close to home. Dr. John Sweetenham: Well, thanks for that. I think that's such an important message, and I should add for our listeners that you can find information about disaster resources for care providers and patients on the ASCO website, at: asco.org. Dr. Sotomayor, I just want to thank you again for giving us your time today at what must be a really busy time for you all and would like to wish you and our many colleagues in the region, especially those in the hardest hit areas of southwest Florida, all the best during difficult and uncertain times as they try to recover from the hurricane. Dr. Eduardo Sotomayor: There are so many heroes here - talking about cancer care, you know, oncologists, nurses, APPs, MAs - they left their families at home and they went and they stayed with patients. So, I am proud to say that most of them, they offered to go there. We didn't need to say you, and you, and you. And I want to thank all of those, you know, our colleagues, providers, all the team members in all the hospitals, big, medium size, also small, in the state of Florida, that they left their loved ones to be support and take care of our patients. Dr. John Sweetenham: Certainly heartwarming to hear about that kind of response. And thanks again to you, Dr. Sotomayor. And thank you to our listeners for your time today. If you value the insights that you hear on ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy, should not be construed as an ASCO endorsement. Follow today's speakers: Dr. John Sweetenham @JSweetenhamMD Dr. Eduardo Sotomayor Tampa General Cancer Institute   Want more related content? Listen to our podcast on climate change and cancer: Climate Change and Cancer   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Eduardo Sotomayor: Consulting or Advisory Role: Seattle Genetics, Genentech/Roche, Celgene, Kite Pharma, Bayer, AstraZeneca, Pharmacyclics Speakers' Bureau: Seattle Genetics, Pharmacyclics

Monopolies! Competition law hates them, intellectual property law creates them. It's not that simple, but the two areas of law often find themselves in conflict, and in Australia they've been unleashed on each other after the repeal of a key exemption. Competition partner Susan Jones and IP partner John Lee dissect the issues after pharma competitors Celgene and Juno failed to get their patent settlement agreement authorised by the ACCC. Plus punishing (or at least deterring) penalties proposed, good news and bad news for Google in location tracking and defamation cases, and myths and legends from Olympus to the Olympics while the AEMO fiddles with the national energy objectives. All this and more with co-hosts Moya Dodd and Matt Rubinstein on The Competitive Edge with Gilbert + Tobin.   G+T's update on the proposed penalty increases Celgene/Juno on the ACCC's authorisation register More from John and Susan with special guests at the G+T/Legal 500 webinar in May Google pays in the Federal Court but wins in the High Court Check out the new National Energy Transformation Partnership Meet the Gilbert + Tobin Competition + Regulation team Email us at edge@gtlaw.com.au See omnystudio.com/listener for privacy information.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in multiple myeloma, breast cancer, and cancer in adults 60 and over that was presented at the 2022 ASCO Annual Meeting, held June 3-7. First, Dr. Sagar Lonial discusses a study on treatment for newly-diagnosed multiple myeloma in people under 65.   Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the Cancer.Net Associate Editor for Myeloma. View Dr. Lonial's disclosures at Cancer.Net. Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Winship Cancer Institute of Emory University in Atlanta, Georgia. And today I'm going to discuss one of the Plenary abstracts at ASCO 2022, which was the DETERMINATION study, again, presented at the ASCO Annual Meeting. For the sake of disclosure, I just want to make sure I list that I was an investigator on this study. I also have consulting relationships with Takeda, Celgene, BMS, Janssen, and other companies that have agents in the context of multiple myeloma. So the reason I want to talk about this study today is I think it's a really important study that was designed over a decade ago to really ask the question, with a really powerful induction regimen that uses what we now call the RVd regimen, lenalidomide with bortezomib and dexamethasone, do you really still need to have high-dose therapy and autologous transplant as part of the treatment approach? And so the trial was a very simple randomized trial that everybody received RVd induction. And then there was a randomization between early transplant and then going on to consolidation and continuous lenalidomide maintenance versus no transplant going on to consolidation and lenalidomide maintenance. So both arms actually received continuous lenalidomide maintenance, which is really one of the important endpoints of this study overall. And the reason I say that is there was a smaller study done in France a few years previous to this where patients only received 1 to 2 years of lenalidomide maintenance. And in that trial, clearly the use of transplant was better. And the remission duration for the group that received the transplant was about 48 months. So the question was, with continuous lenalidomide maintenance, can you make that longer? So randomized trial, over 600 patients were randomized between these 2 arms. And the follow-up now is somewhere around 7 years in total. And what was demonstrated both in the ASCO Annual Meeting as well as in the paper that came out at the same time in the New England Journal of Medicine was that the remission duration was clearly longer in the group that had the transplant than the group that did not, even with both arms receiving continuous lenalidomide maintenance. And it was almost 66 months in the group that received the transplant, 21 months longer, almost 2 years longer than the group that did not receive the transplant. And so I think this is really important because what it says is that even in an era of really good induction therapy, transplant continues to offer significant benefit in terms of progression-free survival. Now, the reason progression-free survival is so important in this study is that we know that no time is more sensitive for treatment of myeloma than that first time we treat the patient. And so prolonging that first remission is really important because the disease is at its most sensitive at that time point. Now, there were questions about overall survival. Should we see an overall survival benefit? And I'll tell you, A, this trial was never designed to measure an overall survival benefit. And, B, the median survival for myeloma patients is now between 10 and 15 years on average. And so with only 7 year follow-up, it seems to me unrealistic to expect this to have a survival benefit at this early time point. So rather than saying there's no difference in overall survival, I think it's a fair statement to say at the short follow-up we have, there is no difference in survival. But I actually don't think survival is the right endpoint for newly diagnosed myeloma trials in fit patients because we do have so many important treatments to discuss. Now, there was also discussion about adverse events. Obviously, the quality of life during the transplant dropped a little bit. Not a big surprise. That lasted about 2 to 3 weeks, and then quickly, by 3 months out, returned back to baseline for almost every patient in the study. Additionally, there was a concern about second primary malignancies. If you look at this data, it's really no different than what we saw in the French study. There was a slightly higher risk of second primary malignancy, but we know that this is the case not only in myeloma, but in patients who receive alkylate-based therapy. And despite that, the progression-free survival was 2 years longer in the group that received the transplant than the group that did not. So I think, in summary, this is really an important trial because there are many groups that are making the case that perhaps we don't need transplant in this modern era of myeloma therapy. And I think that it's important to recognize that what we're looking at are not short-term endpoints. We're not looking at early MRD (minimal residual disease) negativity. What we're looking at is really ultimate measurement of clinical benefit, which to me is prolonging that first remission as long as you can. And so this trial clearly demonstrates that for young, fit patients, transplant continues to offer significant benefit, almost 2 years of benefit with continuous lenalidomide maintenance. And while there's a push to say perhaps we can think about which patients may or may not need a transplant, honestly, as clinicians, we're not good enough to make that prediction. And what I think is really important is that we not lose sight of trying to prolong that first remission with the best tools that we have. And I think even in this modern era of 2022, high-dose therapy and autologous transplant continues to be one of those tools, and we want to use it to maximize the duration of that first remission. So thank you again for listening to this brief summary of the DETERMINATION trial presented at the 2022 ASCO Annual Meeting and published in the New England Journal of Medicine. ASCO: Next, Dr. Norah Lynn Henry discusses new treatment advances for people with metastatic breast cancer, as well as 2 studies in early-stage breast cancer. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer. View Dr. Henry's disclosures at Cancer.Net. Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2022 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We typically treat those cancers first with antiestrogen treatments, which block estrogen or lower estrogen levels. Other breast cancers are called “HER2 positive.” These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or very much HER2. These are called triple-negative breast cancer and are also often aggressive cancers. One of the biggest stories from the ASCO Annual Meeting was the results of the DESTINY-Breast04 trial. In this trial, researchers studied a type of medication called trastuzumab deruxtecan, which is also called Enhertu. This drug is a combination of the anti-HER2 antibody, trastuzumab, plus a chemotherapy drug, and the antibody targets the drug to the cancer sort of like a guided missile. Trastuzumab deruxtecan is currently routinely used to treat patients with metastatic HER2-positive breast cancer. Now, the interesting thing is there was already data from studies that suggested that this drug might also work against breast cancers that have some HER2 receptors on the surface of their cells, but not so many that they meet the true definition of being HER2 positive. For the DESTINY-04 study, patients' tumors had to have either 1+ or 2+ HER2, which some people called “HER2 low,” and could be either estrogen receptor positive or negative. Two thirds of the patients were treated with trastuzumab deruxtecan, and the other one-third were treated with 1 of 4 different standard chemo regimens that their physician thought was the best treatment option for them. Treatment with trastuzumab deruxtecan was shown to lengthen the time people were able to remain on treatment. Importantly, it was also shown to increase the overall survival of patients compared to standard chemotherapy by more than 6 months for patients with estrogen receptor-positive cancer and by more than 10 months for patients with estrogen receptor-negative cancer. Since this is a drug that we currently use to treat patients with other types of cancer, we actually know a lot about its side effects. One key toxicity is it can cause a very severe inflammation of the lungs in a very small subset of patients. So this is something that we have to watch for very carefully. Otherwise, it is a relatively well-tolerated drug, especially compared to standard chemotherapy. The main side effects are nausea and fatigue. Another clinical trial presented at ASCO called TROPiCS-02 also studied a drug that is currently used to treat a different type of breast cancer. In this case, the drug is sacituzumab govitecan, also called Trodelvy. It is also a combination of an antibody that is targeted against cancer cells plus a chemotherapy drug. Sacituzumab govitecan is currently approved to treat metastatic triple-negative breast cancer. In the TROPiCS-02 trial, however, it was tested to see how effective it is for treating hormone receptor-positive, HER2-negative metastatic breast cancer. All of the patients enrolled in this trial had already been treated with antihormone therapy medications as well as at least 2 chemotherapy regimens. Half of the patients were randomized to treatment with sacituzumab govitecan, and the other half were treated with 1 of 4 standard chemotherapy drugs that their physician thought was the best for them. Those patients who were treated with sacituzumab govitecan had a longer time on average that the treatment worked compared to those who received standard chemo. They also had improved quality of life based on responses that the participants themselves provided on questionnaires. Although the overall benefit was rather modest, this drug may represent a new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, although at this time it isn't yet approved for treatment of this type of breast cancer. Both of these are examples of being able to take drugs that have been shown to treat 1 type of cancer and potentially expand it so that they can be used to benefit more patients with breast cancer. These drugs are also being tested to see if they are beneficial for treating early-stage breast cancer. So we await more hopefully very exciting results in the future. To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of early-stage breast cancer. So typically, radiation therapy is recommended after lumpectomy since it reduces the likelihood of cancer returning in the breast. However, questions have arisen about how much benefit radiation is actually providing for some patients whose risk of having cancer return in the breast is really low to start with. Therefore, these patients may be at risk of the side effects of radiation as well as other risks, such as financial problems, without actually getting much benefit from the treatment. Therefore, this trial, called LUMINA, evaluated whether radiation therapy was beneficial after lumpectomy for patients who have small, low-risk breast cancers and no lymph node involvement. The trial included 500 women who were at least 55 years of age with invasive ductal cancers that were no more than 2 centimeters in size. They had to be estrogen receptor-positive, HER2-negative, either grade 1 or 2, and Ki-67 low. Everyone had to be planning to take antihormone therapy for at least 5 years. During the 5-year follow-up period, a total of 10 patients out of 500, about 2.3% of all patients, had their cancer return in the breast. The researchers therefore concluded that for patients with this type of very low-risk breast cancer, it is reasonable to omit radiation therapy and just take endocrine therapy. Similar results have previously been shown for patients over the age of 70 with small lymph node-negative low-risk cancers, but this trial expands that option to patients who are as young as 55. Finally, I will touch briefly on the updated results from the ABCSG-18 clinical trial. So this trial enrolled postmenopausal women with early-stage estrogen receptor-positive breast cancer who are being treated with aromatase inhibitor therapy. Aromatase inhibitors are known to cause reductions in bone density. This trial therefore evaluated a medication called denosumab, also called Prolia, which is used to treat osteoporosis. Participants were randomized to treatment every 6 months with either denosumab or a placebo. They found that the patients who were treated with denosumab were half as likely to have a bone fracture. Importantly, patients treated with denosumab also had an improvement in bone density despite taking the aromatase inhibitor medicine, whereas those who received placebo had a decrease in their bone density over time. The other very interesting thing from this study is that patients who received treatment with denosumab were less likely to have their breast cancer return or to develop a new cancer during the 8-year follow-up period. So it's actually already recommended that postmenopausal patients with all types of early-stage breast cancer consider treatment with a different type of bone strengthening medicine called a bisphosphonate as part of their breast cancer treatment. The goal is to further reduce their risk of cancer returning. These new results will now lead experts to debate whether to also include denosumab as a potential additional breast cancer treatment option, not just to help protect people's bone density. There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, and we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. Finally, Dr. Shakira Grant discusses 3 studies that looked at cancer in people 60 or older. This field is also known as geriatric oncology. Dr. Grant is an Assistant Professor in the Divisions of Hematology and Geriatric Medicine at the University of North Carolina at Chapel Hill and a board-certified Geriatric Hematologist/Oncologist. View Dr. Grant's disclosures at Cancer.Net. Dr. Grant: Hi, everyone. I am Dr. Shakira Grant. And I'm an assistant professor at the University of North Carolina at Chapel Hill. I'm also a clinician scientist with a focus on social disparities and how they influence the health and aging of older adults with cancer, primarily multiple myeloma. And for today's talk, I have no relevant conflicts of interest to disclose. It's such a pleasure to be able to talk today about the ASCO 2022 geriatric oncology and presenting key studies, which I believe were really practice-changing or really set up the foundation for informing future research directions. And to start us off, I wanted to start us with abstract 12012 by Dr. Mackenzie Fowler. And this was presented based on the University of Alabama at Birmingham's actual research group. And the title of their presentation was “Rural-Urban Disparities in Geriatric Assessment Impairments and Mortality Among Older Adults with Cancer.” And this was the result of a large registry study, predominantly patients with gastrointestinal cancer-- so cancers such as liver cancer, colon cancer. And what the authors really wanted to do here was to explore if whether or not living in a rural location, for example, is associated with having an impairment based on what people report in their ability to function at home, their quality of life. And they also wanted to see whether or not where you live, meaning a rural location, whether that can be associated with how long you are expected to live or your overall survival. So this was really a study that took patients who were truly older. There were patients who were above the age of 60. As I mentioned, these were patients predominantly with cancers of the liver, the colon, and the pancreas. And patients completed a baseline, what we call a geriatric assessment, to try to assess their overall or global health. And on these assessments, patients are asked questions about how they would rate their physical function and their quality of life. And what the authors found here is that in general, when patients lived in rural areas, this was associated with patients self-reporting more functional deficits, meaning that they reported that they had impairments in the ability to function at home from a physical perspective. They also had impairments in quality of life—so how you rate your general life and how you're doing from a day-to-day basis. And this was impaired if you lived in a rural residence. And then, importantly, this study also showed that living in a rural location—and, again, this study was centered in Alabama—that that was also associated with a reduced overall survival, meaning that people were found in rural areas to live a shorter life with these cancers compared to those who live in non-rural places or, as we call it, urban. And I think why I chose this particular study is because it's one of the first studies using a large data set of almost 1,000 patients that they have enrolled and really looking at the idea of the physical environment, so where a person lives, and how that really interacts with everything else to influence the health of an individual. And this study, I believe, really lays the foundation for an area of work in geriatric oncology where we are moving away from just thinking about the older adult, but we're also thinking about the older adult and the other identities. So we're really considering the sociocultural influence. So we think about race. We think about socioeconomic status, income. But now, we're also including the physical environment. And that is where people are living and spending the majority of their time. And that is in this study classified as rural-urban residency. So for this study, overall, I would say that this is really moving the field forward in a direction where we're moving away from just looking at just older adults, but we're thinking about older adults and all of the other stressors that they face, especially when they live in the community and how that impacts their health. The next study that I wanted to highlight was a study that was performed by Dr. Heidi Klepin at Atrium Health, Wake Forest Baptist. And this was a study that looked at evaluating the association between an electronic health record-embedded frailty measure and survival among patients with cancer. Again, this was an older adult population. It was just over 500 patients involved, and patients were over the age of 65. They had a new diagnosis of the most common cancers, which are lung cancer, colon cancer, and breast cancer. And the good thing about this particular study is that it sought to use data that is readily captured in the electronic health record to characterize a patient as fit, prefrail, and frail. So why is that important for the geriatric oncology community and even beyond is when we're dealing with older adults, we're always thinking about ways in which we can actually characterize their fitness and their ability to hence tolerate their therapies, being chemotherapy, and how likely they are to die if they're having these functional impairments. And so importantly, what this study showed was that in their sample, they found that up to 17% of people were characterized as frail using this index. And the significance of this finding is that when they looked at how long people were likely to live with these cancers, breaking it down according to if you were fit, prefrail, or frail, those who were frail had the shortest overall survival. So it means the time from which they were diagnosed until they die was much shorter than any of the other categories. And that equated to a difference between those who were fit and those who were prefrail of 10 months for those who were frail for overall survival and more than 54 months for those who were actually considered to be fit. So this is really, really important because what we are seeing is that if you are really fit, you are living on average with these cancers—the overall survival, at least for their institution, was more than 54 months. But then as you move across that spectrum of fitness, we're actually seeing that your survival decreases significantly. And so why is this important? So this is important because it's one of the first studies that is actually looking to operationalize the frailty measure for us to be able to potentially use and adapt into other health systems using data that we already collect. So it's no longer burdensome on patients to try to fill out additional forms or for other staff to be involved and collect this data. And this data is showing us that there is an association with this particular frailty index and the ability to predict overall survival-- so, again, a critical study in the geriatric oncology population looking at patients with the 3 most common types of cancer, which are lung cancer, colon cancer, and breast cancer, and really showing us that there is a way potentially to operationalize how we characterize the fitness level of an older adult and then using that data not just to say, "Yes, this person is frail," but for us in real-time to see results where we can see that there is a significant difference in terms of overall survival. Importantly, this is going to be a study where we continue to watch closely the developments over the next few years, especially as the authors and the research team note that their next steps involve looking at how to study how these frailty measures, or the frailty scores that people get when they come in and they're at baseline, how this changes throughout the course of treatment. And that has a lot of implications because now, we have the potential to start thinking about using a frailty-adapted approach to caring for older adults with cancer. What that means is when you're getting your treatment and we are following these scores, as we see things changing, this may be an indicator to us that, "Hey, we need to make some modifications in response to these frailty measures to make sure that our older adult population is able to tolerate their chemotherapies and have maximum benefit while also enjoying a good quality of life." So finally, I want to highlight this third study. And this was a study that was presented by Dr. Etienne Brain. And. Dr. Etienne Brain was also this year's B.J. Kennedy Award recipient. And each year ASCO recognizes the B.J. Kennedy Award recipient as an outstanding investigator who has made significant contributions in the area of research and clinical care of older adults with cancer. In this particular study, Dr. Etienne presented on behalf of his team the final results from a study that was looking at using endocrine therapy with or without chemotherapy for older adult women, so characterized as those who were over the age of 70, with a diagnosis of estrogen receptor-positive, HER2-negative breast cancer. And the importance for this study is that the question they sought to examine was whether or not patients who are in this age range still derive a benefit from receiving chemotherapy in addition to endocrine therapy. And what this study really showed is that there was no survival difference. Meaning when they looked at the data for 4 years, those who got chemotherapy plus endocrine therapy lived just as long as those who also just got endocrine therapy alone. And why this is important is because when you think about giving chemotherapy to an older adult population, as oncologists, we are always weighing the risks and the benefits associated with treatment. So we're always thinking about how tolerable is this drug likely to be? We want to minimize side effects because, at the end of the day, our goal is to treat the cancer, but we also want to focus in on the outcomes that matter most to the older adult population. And in general, these are things like maintaining your mobility, maintaining your mentation, maintaining good quality of life. And so we really want to make sure that we're balancing those risks. And this is why this particular study showing that with chemotherapy or without chemotherapy added to endocrine therapy, there seems to be no survival difference. This could be a way in which we move the field forward in thinking about a select group of patients with breast cancer and whether or not those patients truly need that extra toxicity or burden associated with using chemotherapy or whether endocrine therapy is enough. So with that, I will say across these 3 studies, even though they study different things-- we saw 1 study that looked at the intersectionality between older adults in terms of their chronological age but now starting to examine the influence of physical or social context and how that influences the health and outcomes for individuals with primarily gastrointestinal cancer. We also looked at the development of an electronic frailty index in patients with 3 most common solid tumors - lung cancer, colon, and breast cancer - and found that by using this frailty index collecting readily available data, that there was an association with predicting overall survival. And we saw that those who were characterized as frail had one of the shortest overall survivals. And then finally, in this study, looking at endocrine therapy alone versus chemotherapy and endocrine therapy, we saw that there was no survival difference again in an older adult population. And so what we are seeing here is a theme emerging as the importance of comprehensive evaluations of older adults and the importance also of these measures, when integrated across the research continuum, that they are useful in terms of predictive prognostic abilities and really lay the foundation for future research. So with that, I want to thank you for your time and thank you for listening. ASCO: Thank you, Dr. Grant. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Chris Garabedian is the Chairman & CEO of Xontogeny where he supports companies with cutting-edge technologies from early development through clinical proof of concept. Chris has decades of leadership experience in the biopharmaceutical industry. From 2011 to 2015, Chris led the turnaround of Sarepta Therapeutics as CEO. Prior to that, Chris served as VP of Corporate Strategy at Celgene and has held multiple executive roles at Gilead across corporate development, marketing, and medical affairs. Chris started his career in the biopharmaceutical industry as a consultant and holds a BS in Marketing from the University of Maryland.Thank you for listening!BIOS (@BIOS_Community) unites a community of Life Science innovators dedicated to driving patient impact. Alix Ventures (@AlixVentures) is a San Francisco based venture capital firm supporting early stage Life Science startups engineering biology to create radical advances in human health.Music: Danger Storm by Kevin MacLeod (link & license)

Dr. Sonali Smith, of University of Chicago Medicine, highlights dynamic sessions and hot topics that will be featured in the 2022 ASCO Annual Meeting Scientific Program, including practice-changing advances in breast cancer, colorectal cancer, sarcoma, and myeloma.     Transcript  ASCO Daily News: Hello and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. I'm delighted to welcome Dr. Sonali Smith, professor and chief of the hematology-oncology section at University of Chicago Medicine.  Dr. Smith is also the Chair of the 2022 ASCO Annual Meeting Scientific Program and joins me to discuss the hot topics and must-see sessions that will be featured at the meeting.  Her full disclosures are available in the show notes and disclosures relating to all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Dr. Smith, it's great to have you on the podcast today.  Dr. Sonali Smith: Thank you, Geraldine. It's a pleasure to be here.  ASCO Daily News: Well, thousands of abstracts were submitted for consideration this year and more than 2,900 were selected for presentation. We'll talk about some of the must-see sessions. First, can you tell us about the areas that have shown tremendous advances this year—the practice-changing abstracts that will make the headlines?  Dr. Sonali Smith: Yes, that's right. There were over 6,000 abstracts submitted for consideration this year and more than 2,900 abstracts were selected for presentation with over 250 oral presentations. We had 2,200 that were online publication only. And given the hybrid nature of ASCO [Annual Meeting] this year, we will have 86 sessions that will be livestreamed, including all of our abstracts that are oral.  I'm really excited about the Plenary. In particular, there are going to be some practice-changing abstracts involving breast cancer, colon cancer, sarcoma, and myeloma. We are really thrilled with the quality and the excitement around the data and I do think this is going to be very important for people who are in practice.  When we think about the different abstracts that have been submitted for the Plenary, they will focus on front-line colon cancer, the approach to Ewing sarcoma in pediatric patients, and the use of antibody-drug conjugates for breast cancer in a very specific subset. And then also some discussion about, or presentation about, the use of maintenance therapy in patients with myeloma.  ASCO Daily News: Excellent. Well, the Clinical Science Symposia are quite popular among participants. Can you tell us about some of the topics that will be featured this year?  Dr. Sonali Smith: Yes. So, the Clinical Science Symposia (CSS) were really a lot of fun to pull together. As this audience knows well, this is an opportunity for us to take a look at all of the abstracts submitted and look for cross-cutting themes between all of the different cancers that we take care of. They can focus on new technology. They can focus on new approaches to therapy. And after looking at all of the submitted data, we have 3 really outstanding special Clinical Science Symposia for which I'm really excited.  One is going to focus on circulating tumor DNA, “ctDNA: Dawn of a New Era,” and I really do believe in that title and encourage everybody to come and hear how this could be applied in practice.  The second special CSS will be on Bispecifics. Really asking the investigators as well as the discussants. “Bispecifics: Are Two Better Than One?” And then the third special Clinical Science Symposium will be called, “Is There a Ghost in the Machine? Putting Artificial Intelligence to Work.” And as many of us know, machine learning is finally finding its way into oncology. And I'm just thrilled at the abstracts that have been submitted.  I also just wanted to say that we've had a really outstanding speaker lineup and it's incredibly diverse with international perspectives brought to the table.  ASCO Daily News: Absolutely. And so, what are some of the other sessions that will be on your own list this year?  Dr. Sonali Smith: Well, I'm really excited about the opening session, which will be at 9:30 in the morning on Saturday, June 4th. We will have our president, Dr. Everett Vokes, speaking on his theme, Advancing Equitable Cancer Care Through Innovation.  We also have our FASCO presentations, and we have 2 special speakers. One will be Ned Sharpless, who is the head of the National Cancer Institute. And then we will also have Dr. Andre Ilbawi, who is the lead of cancer programs at the World Health Organization. He has had an incredible impact on improving access for children with cancer on a global level. And I think this series of speakers really fits with our theme this year.  Another session I'm really looking forward to is the [David A.] Karnofsky [Award and] lecture by this year's widely respected speaker, Dr. Jedd Wolchock. This is anticipated to be an incredibly thought-provoking and clinically relevant presentation, and I hope all of you will join us.  ASCO Daily News: In following up then on the theme of the meeting this year, it is, of course, Advancing Equitable Cancer Care Through Innovation, can you comment on how important it is that this theme is represented in as many of these programs, as many of these sessions as possible at meetings such as the [2022] ASCO Annual Meeting and other symposia?  Dr. Sonali Smith: A global approach and a global mentality when we are developing therapies, preventive approaches, are really incredibly important. In the United States, at least, the survival for patients with cancer has doubled, and I think it is really important to remember that we are a global organization and there are many people around the world who can benefit. And if we can put innovation into this, hopefully, it can be done better and faster.  ASCO Daily News: Absolutely! Well, thank you so much, Dr. Smith, for taking the time to be on the podcast today and for sharing some of these highlights. And a big thank you for your efforts to create a really robust scientific program for the 2022 ASCO Annual Meeting.  Dr. Sonali Smith: Thank you so much. It's been a real pleasure.  ASCO Daily News: And thank you to our listeners for your time today. If you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.      Disclosures:   Dr. Sonali Smith has been paid for any consulting or advisory role by ADC Therapeutics , Adaptive Biotechnologies , Gilead Sciences, Bristol Myers Squibb, MorphoSys, Janssen, Bantam Pharmaceutical, and Karyopharm Therapeutics, currently or during the past 2 years. Dr. Smith has received research funding from Portola Pharmaceuticals, Genentech, Acerta Pharma, Pharmacyclics, Celgene, Curis, Bristol Myers Squibb, TGTX, Merck, Forty Seven, and Novartis, currently or within the past 2 years.   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.   

Dr. John Sweetenham, of the UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and Dr. Marc Braunstein, of NYU Langone Health, discuss key data from the CAPTIVATE and GRIFFIN trials and other compelling studies in hematologic malignancies featured at the 2022 ASCO Annual Meeting.  Dr. John Sweetenham: Hello. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News podcast.  For my guest today, I'm pleased to introduce Dr. Marc Braunstein, a hematologist, and oncologist at NYU Perlmutter Cancer Center. We'll be discussing key posters on advances in hematologic malignancies that will be featured at the 2022 ASCO Annual Meeting.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Marc, it's great to have you on the podcast today.  Dr. Marc Braunstein: Thank you, John. It's a pleasure to be here.  Dr. John Sweetenham: So, Marc, there are going to be some very interesting abstracts with some provocative results presented at the ASCO Annual Meeting this year. I know we've selected a number of these to speak about today, beginning with Abstract 8027 on the subject of multiple myeloma. And this I think is a long-term follow-up study for long-term survivors of multiple myeloma more than 12 years out now. Can you comment on this and let us know what you believe the key takehomes from this study are?  Dr. Marc Braunstein: Sure. Absolutely, John. So, this was a prospective registry that has been in place since 2009, and it's composed of various practice settings, but primarily community practices where most patients get their myeloma care. And what they did was they looked at about 1,400 patients with newly diagnosed multiple myeloma across 250 sites in the U.S. between 2009 and 2011 who were included in the registry. The participants also filled out the quality-of-life surveys, and they compared a group of long-term survivors who had more than 8 years of follow-up to patients who were not long-term survivors below that 8-year threshold.  So, about 20% were in the long-term survival group and 80% in the non-long term survival group. And they basically characterized those 2 groups. What they found was that the individuals who did have long-term survival were generally younger—median age of 62 versus 68, and had better performance status, were more likely to receive stem cell transplants, about 66 versus 60%.  And therefore, the implication of this is that patients who fit those criteria may have a better prognosis in addition to the other cytogenetics and other factors we use as prognostic indicators. And what was also interesting was that the 8-year overall survival of the overall group was about 36%.  So, we still have room to go in terms of bringing new therapies to extend survival in this condition. And only 20% of the total population were long-term survivors at that 8-year threshold. So, those were the general findings of the abstract.  Dr. John Sweetenham: Do you think it gives us new information on patient selection for more intensive therapies upfront?  Dr. Marc Braunstein: Well, I think it certainly tells us which patients are more likely to have longer-term survival. I think we know in multiple myeloma that it's essential to really use the patient's presenting features, their disease features, their comorbidities, and their degree of fitness or frailty to guide how intensive a therapy or regimen we can devise for that individual patient. But I think it certainly says that if you have a patient who is on the younger side of the spectrum, who is eligible for stem cell transplant, who has a better performance status, those are the patients that are more likely to have the long-term survival. It doesn't necessarily say that if you're not in that category, you won't have long-term survival, but on average, those were the patients who fared better in the long term.  Dr. John Sweetenham: Okay. So, staying for a little while on the subject of multiple myeloma, Abstract 8037 is really addressing a very different question. It's the application of circulating tumor DNA analysis and its association with relapse in patients with refractory myeloma. Would you comment a little on this and maybe let us know what you think the significance of this will be for the future?  Dr. Marc Braunstein: Sure. My colleagues in the solid tumor space are using circulating tumor DNA regularly and in the myeloma field, we're a little bit jealous of them.  So, it's helpful to have a study like this that's looking at circulating peripheral blood markers, in this case circulating tumor DNA, to help guide various prognostic or predictive indices that will help us guide therapeutic decisions.  So, this was a study where they looked at patients who were enrolled in a phase 2 study of a free-drug regimen of carfilzomib-thalidomide-dexamethasone the MM17 study, and they took 50 transplant eligible multiple myeloma patients who were refractory to their first line of therapy, and they collected bone marrow samples and peripheral blood at 3 time points at the third cycle of treatment and at the end of the study or at the point of refractoriness to that regimen.  They collected about 187 samples in total. They used a sequencing technique to determine the variance of 22 gene signatures known to be mutated in multiple myeloma. And what they found was a particular gene signature that was associated with shorter progression-free and overall survival in that phase 2 study. And those genes included known oncogenic drivers, including BRAF genes, ATM, and P53.  What was particularly interesting among the circulating tumor DNA mutations was that they were found in about 88% of patients at the start of the study. So, what that tells us is, number 1, circulating tumor DNA offers a wealth of information that can be highly valuable in multiple myeloma, which is a disease where we typically rely on the bone marrow to assess the status of the plasma cells and status of the mutation profile.  And number 2, that many of these mutations may be present earlier on in a disease that we know evolves in a clonal way that leads to disease progression. So, I think there's still a lot of information we have to learn about the utility of circulating tumor DNA in myeloma, but this study certainly shows that there's a lot to be explored in terms of the mutational profile and peripheral blood in myeloma.  Dr. John Sweetenham: A couple of questions that arise for me out of this study. First of all, do you think this is going to have any implications for future study design and patient selection?  Dr. Marc Braunstein: Definitely. I think the whole field in multiple myeloma is progressing quickly in terms of how we assess response, how we use minimal residual disease, and moving more towards using novel markers in peripheral blood, including mass spectrometry, and now perhaps circulating tumor DNA to look at surrogate markers for survival.  And so, what this abstract is showing is that we could potentially use circulating tumor DNA both as prognostic markers, potentially as disease response markers, and prognostic markers to guide which patients may be more likely to have shorter survival. So, I think this has a lot of implications for how we design future studies.  Dr. John Sweetenham: Yeah. And the second question, do you think this is the beginning of the end of bone marrow analysis in multiple myeloma?  Dr. Marc Braunstein: So, I can tell you if it is, patients I think will be very happy and so will clinicians because we really want to know at the core what the degree of residual disease is in a patient. And right now, the only way to do that is through a bone marrow biopsy.  And so, I think that this is the beginning of the use of peripheral blood studies with higher resolution to allow us to gain more information on patients that hopefully will allow us to obviate the need for more invasive testing like bone marrow biopsies.  Dr. John Sweetenham: Yeah, absolutely. Thanks. Just changing gears now, moving on to Abstract 7050. This is an abstract that addresses what I think we'd all agree is becoming an increasingly important question in the management of chronic myeloid leukemia (CML), and that is number 1, is it safe to discontinue therapy in responding patients? And number 2, when is it safe to discontinue that therapy?  Dr. Marc Braunstein: So, this is an abstract that is looking primarily at CML. You know that we're making a lot of progress when we can begin to talk about discontinuation and de-escalation of therapy.  And so, in the field of CML, the use of tyrosine kinase inhibitors (TKIs) and the targeting of the BCR-ABL mutation has brought about tremendous progress in patients in the chronic phase.  So, there have been several retrospective studies that have looked at the role of discontinuing one of the TKIs. Most of the studies have focused on imatinib since that was the first one that was discovered, but they've looked at others in the class as well.  What struck me the most is that there's a remarkable consistency between these studies. So, when you discontinue one of these TKIs, the percentage of patients who remain in remission is somewhere between 40 to 50%. And what this abstract looked at was a single institution retrospective assessment of 284 patients with CML, between 1999 and 2017, who were treated with a TKI for their CML and then subsequently discontinued the therapy.  Now, what's worth noting in the various studies that have looked at discontinuation therapy is that patients who were taken off of the TKI generally were in a good molecular remission, MR 4 or 4.5, for at least 2 or 3 years. And in this study, about 70% of patients had electively discontinued and 24% of patients stopped due to adverse events.  So, it wasn't necessarily guided by their response to treatment at the time of discontinuation. What they found actually was fairly consistent with the literature that at a median follow-up of 36 months after TKI discontinuation, about 19% lost their molecular remission and 88% had achieved a molecular remission after resuming therapy. And that is consistent with the literature that fortunately, even if a patient loses their molecular remission off of the TKI therapy, the majority of patients will go back into molecular remission when you re-challenge them.  Dr. John Sweetenham: Important data, indeed. And you know, on something of a similar theme, the next abstract that we're going to look at is the Abstract 7519. In this case, in chronic lymphocytic leukemia (CLL), and certainly, those of us who remember when ibrutinib was initially introduced into the second-line treatment of CLL, didn't really know whether discontinuation or fixed duration treatment with agents like this was going to be something that we could pursue or whether treatment with these drugs was going to be indefinite. This abstract certainly addresses that specific question, and again, I'm interested in your insights into this.  Dr. Marc Braunstein: Sure. So, this is an abstract looking at CLL, where we've really begun to move away from chemotherapy, and we have a variety of targeted oral therapies that target the underlying pathology of this leukemia.  And so, as you mentioned, ibrutinib is approved both in the relapsed and more recently in the frontline setting, wherein the RESONATE-2 study that was published in the New England Journal of Medicine in 2015, there was actually an overall survival benefit of ibrutinib even in higher-risk patients.  So, the CAPTIVATE study is an ongoing phase 2 study that is looking at whether we can improve the efficacy of single-agent ibrutinib in the first-line setting when combined with venetoclax.  Ibrutinib targets protein tyrosine kinase and venetoclax targets Bcl-2, and that combination is hypothesized to further weaken the resistance of CLL and lead to better outcomes.  So, this was a multicenter phase 2 study. And in this abstract, they looked at the 3-year follow-up of patients who were actually able to discontinue therapy on this regimen. So, just as a bit of background, ibrutinib is typically continued until progression, and venetoclax as it's been studied in the first-line setting with obinutuzumab is given for about 12 months.  So, in this study, at 3-year follow-up, they looked at the patients in the cohort who were off therapy and looked at the percentage of patients who maintained a complete remission at 3 years. And that complete remission rate was about 57%.  The majority of patients, greater than 95% of patients, were alive at 3 years even in the high-risk cohort. So, I think the implications of the study is that upfront or oral targeted therapies when you combine ibrutinib and venetoclax really produce tremendous responses that are durable, and it's found even in the high-risk patients who are expected not to do quite as well at 3 years.  Dr. John Sweetenham: Yeah, I agree. I think it's very reassuring actually to see these durable responses with this fixed duration regimen. And to conclude, Abstract 8011 was an abstract which addressed treatment in the first-line setting for multiple myeloma. And again, I wonder if you could comment on this study.  Dr. Marc Braunstein: Sure! So, this is a study looking at the GRIFFIN regimen, which was a phase 2 randomized study of daratumumab (DARA), plus lenalidomide, bortezomib, and dexamethasone.  So, DARA RVd versus RVd alone. In that study, the primary endpoint was stringent, complete remission, and it has been previously presented and published that the stringent complete remission (CR) rate was significantly improved, 42% versus 32%, when you include daratumumab upfront.  In this abstract, they looked at the sustained rate of minimal residual disease negativity, which is basically the deepest possible remission you can achieve in upfront therapy and in myeloma.  What they found was that, again, when you looked at the quadruplet regimen versus the triplet regimen, the rates of minimum residual disease (MRD) negativity were just improved with the quad regimen.  So, at a median follow-up of 38.6 months, there were about 54 versus 20% of patients who were MRD negative at 12 months amongst the patients who had achieved a CR, and 59 versus 17% MRD negative among the patients who achieved a stringent CR favoring the daratumumab arm.  So, I think this abstract shows the benefit of including a monoclonal antibody upfront in newly diagnosed patients with myeloma combined with stem cell transplant and maintenance, allowing for sustained MRD negativity.  Dr. John Sweetenham: Do you think this represents a new standard of care?  Dr. Marc Braunstein: I do. At our institution, we've adopted this regimen for most newly diagnosed transplant-eligible patients. I think the data clearly show an improved depth of response and MRD negativity rates, and I think that there are a number of ongoing studies looking at the role of monoclonal antibodies in the maintenance phase as well.  I'm especially excited this year, at ASCO Annual Meeting there's a plenary session involving myeloma looking at patients who received RVd upfront and then went for transplant. But I think we can improve on that regimen by including monoclonal antibodies and immunotherapies upfront, and I do think it represents a new era of immunotherapies in multiple myeloma.  Dr. John Sweetenham: Well, thanks, Marc. I mean, to your last point, it sounds as if there is a lot, including these abstracts, to look forward to at the upcoming ASCO meeting. So, we really appreciate you sharing your insights into these abstracts with us today.  Dr. Marc Braunstein: Sure. My pleasure. Thank you for having me, John.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.      Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Celgene, Janssen, AstraZeneca, Amgen, Takeda, Verastem, Celgene, Janssen, Karyopharm Therapeutics, Epizyme, Morphosys, Takeda, Pfizer  Research Funding (Inst): Janssen, Celgene/BMS  Travel, Accommodations, Expenses: Takeda  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. 

Please note: as of 12/31/21, ARK's clients own greater than 1% of the shares outstanding of Beam Therapeutics. Base editing, and gene editing as a broader industry, are a major focus of our research at ARK, and a major piece of DNA Sequencing, one of our 5 technology platforms. To dive deeper into the world of base editing, Analyst Ali Urman sits down with industry expert, Beam Therapeutics CEO John Evans. Evans was previously a Venture Partner with ARCH Venture Partners and an early employee and member of the leadership team at Agios Pharmaceuticals. At Agios, he helped develop IDHIFA and TIBSOVO, two IDH inhibitors for the treatment of acute myeloid leukemia (AML), helped initiate and lead Agios' landmark alliance with Celgene, and co-led Agios's expansion into rare genetic diseases. On this episode, Ali and John discuss the falling costs of medicine, the convergence of 3D Printing and Base Editing, Base Editing's applications for chronic illness, the total opportunity of the gene editing space and much more! “Every base in the genome can be toggled, and, so, every base that has function, we can change that function” – @john_evans3 Key Points From This Episode: John's favorite poet, Wallace Stevens Medicine's cost declines and what that means for patients The efficiency of of Multiplex Gene Editing (MGE) The convergence between and potential of 3D Printing and Gene Editing The many colors of CRISPR Gene Editing Base editing applications for chronic illnesses The intersection between Base Editing and Prime Editing Beam Therapeutic's partnerships with Pfizer and Verve Measuring the opportunity in the Base Editing space The potential total market opportunity in the gene editing space The CRISPR patent ruling and its impact on the genomics field What John finds interesting about Twitter and why he is so active on the platform

In this episode, I'm bringing my friend, Dr. Dawn DiPeri back to chat about her new book, Graphic Design for Course Creators! Her book is CC-BY, which means you can print, copy, paste, and re-use the content however you like as long as you give her credit. This also means that the web version is FREE!! You can find it here: https://graphicdesignforcoursecreators.pressbooks.com/front-matter/dedication/Dr. Dawn DiPeri is a learning designer and graphic designer with over 15 years of experience working in the corporate sector in various capacities serving ad agencies, publishing firms, and as the owner of a certified minority women-owned business. Additionally, Dawn spent many years as a college professor teaching online, face to face, and in hybrid environments for both public and private universities. She has taught courses that range from new media literacies, educational technology, graphic design, animation, interpersonal communication, public speaking, and branding.  Dr. Dawn DiPeri has also published scholarly research on the topics of online pedagogy and also on the topics of gender and race disparity in the workforce. Dr. Dawn DiPeri has been lucky to work with some of best organizations and brands in the world including UNICEF, Harvard Graduate School of Education, United Way, Celgene, The Vanderbilt Museum, ONEHE, and many more. Additionally, Dr. Dawn DiPeri has also presented at conferences all over the world including the E-Learning Summit and the Q10 Conference.To contact Dawn Lee DiPeri for speaking, training or design opportunities email dawn.diperi@eastendadvertising.com or find her on Linkedin at https://www.linkedin.com/in/dawnleediperiDawn suggests finding an accountability partner if you want to write you own book, by joining communities or book coaching programs. 

In Hatch-Waxman cases, where is the act of infringement committed, and who commits it? Allison Schmitt (BCLT) and Seth Lloyd (MoFo) discuss the Celgene v. Mylan decision (17 F.4th 1111 (Fed. Cir. 2021)). Featuring Seth Lloyd. SPEAKERS Seth Lloyd, Allison Schmitt Allison Schmitt 00:00 Hello all and welcome to the Berkeley Center for Law and Technology's Expert Series podcast. My name is Allison Schmitt and I'm the director of the Life Sciences Program at BCLT. So today Seth Lloyd from Morrison and Foerster is joining us for our podcast series Beyond the Holding a nuanced look at the Federal Circuit's patents decisions. Thanks so much for joining us, Seth. Happy to have you back. Seth Lloyd 00:20 Yeah, thanks. Awesome. Allison Schmitt 00:22 So today we're going to discuss the November 5th Celgene v. Mylan decision that came down from the Federal Circuit. There's a number of issues to unpack here related to venue and pleading standards. And Seth is going to walk us through all of it. But before we dig into the substance of the decision itself, Celgene discusses a type of case that's different from most of the other cases that we've previously discussed on the podcast. So Celgene arose under the Hatch Waxman Act, which is a complex statutory framework created by Congress, with the goal of streamlining approval of generic drug products in the United States, and creating a framework for the patent challenges to the brand side company's patents prior to marketing the generic drug. So Seth, can you walk us through the background of how these Hatch Waxman cases work so that our listeners can get a sense of how these might be different from the typical patent cases that they're thinking about? Seth Lloyd 01:10 Yeah, I'll give it my best shot. You weren't exaggerating when you said complex, it is a complex statutory framework. But I think there are a few key points to understand for today's case. So in general, as you said, when a completely new drug is coming to market, the party files a new drug application or an NDA, with the Food and Drug Administration. And to get an NDA approved, there's a long process. The parties have to go through clinical studies and and go through several rounds, usually with the FDA to get approval, that tends to be a very lengthy and costly process. And so the Hatch Waxman Act was designed to allow quicker approval for kind of the follow on, so parties who want to market a generic form. So basically the same pharmaceutical formula. But without going through that lengthy process. And what the Hatch Waxman Act allows them to do is to submit an abbreviated new drug application, or an ANDA, as people in the industry call it. And with the ANDA they don't have to submit all the do new clinical trials and submit new data from clinical studies. Instead, they can simply show prove to the FDA that their drug is bio equivalent to an approved drug, it's the same formula, and they can get approval much quicker and with less cost. The part that's going to be relevant to our case today is how does this all work with patents because often, if somebody's come up with a new drug, they've patented the formula or they've patented a new method for using that drug. And so the new drug applicant, that NDA filer will also tell the FDA about any of those patents that covered the drug, or methods of using it, and they'll list those patents in what's called the orange book. Now, later, the company that wants to market the generic version comes along, they have to tell the FDA, what they intend to do with regard to any patents listed in the orange book. They have

The Elizabeth Holmes trial entered week 5 this week. This likely marks the midpoint of this trial and the prosecution focused heavily on Adam Rosendorff, the former Theranos lab director.The only other witness to take the stand this week was Victoria Sung, a scientist who interacted with Theranos while working at biopharma company Celgene.There are more unsealed documents to talk about this week, including some interesting diary entries written by Ms. Holmes herself including one that read “I want to be Steve Jobs” and other notes related to Steve Jobs. It was another interesting week and attorney Pete Sartes is here to break it all down for you.Join us to unpack week 5 of the Elizabeth Holmes/ Theranos Trial.#ElizabethHolmes #Theranos #lawyeryouknow

We discussed a number of things including:1. Best practices in times of crisis for IT leaders 2. Managing up, across and down during time of uncertainty 3. Communications with enterprise, vendors and customers JP Saini is CIO at SOS Security. He is a C-Level Business Leader and Technologist with the passion and leadership talents necessary to transform technology into a strategic business partner. For more than 24 years, JP has been successfully fostering and managing IT business and strategy. He has been leveraging technology to digitally transform business, support profitable growth & minimize risk. Developed from his portfolio of business, technology and operations experience is his ability to advance the overall strategic direction of information technology in alignment with strategic business plans and identify Commercialization opportunities. His sharp focus on excellence is driven by his knowledge of client service and performance-based metrics. ----- Ray Lipps is Executive Director, Cybersecurity & Risk at EY. Ray previously served in multiple executive leadership roles at JPMorgan Chase & Co., Citi, and most recently as CISO at Celgene. Ray has over 20 years of Global Information Security leadership experience with respect to the developing of people and Managing Risk in the fields of Information Technology, Information Security, Data Privacy, Business Resiliency, Business Continuity, Change Management, Technical Training, Project Management, Risk related Metrics Programs, Vendor Management, Corporate Outsourcing, Right Placement, and Audit / Compliance. He has held Global Information Security and IT related roles at Celgene, Citigroup, JPMorgan Chase, Roche, Prudential Healthcare, Prudential Financial.SHOW LESS 

In this podcast, Contributing Editor Dr. Saad Usmani has a conversation with Dr. Nikhil Munshi. They discuss Dr. Usmani's Mini Review article from the July/August 2021 issue of The Hematologist, titled, "Immune Therapies for Myeloma: The CARs Are Here but What's Next?" They discuss the latest approvals of chimeric antigen receptor T-cell therapies to treat multiple myeloma. You can access his Mini Review article online at https://ashpublications.org/thehematologist/article/doi/10.1182/hem.V18.4.2021413/476193/Immune-Therapies-for-Myeloma-The-CARs-Are-Here-but?utm_source=sfmc&utm_medium=email&utm_campaign=TheHem+July+2021&utm_term=Link+Text+%c2%bb&utm_id=102625&sfmc_id=32555314. Additional ASH affiliation and COI information: Dr. Usmani has received research funding from Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; consulting fees from Amgen, BMS, Celgene, EdoPharma, GSK, Janssen, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, and TeneoBio; speaker fees from Amgen, BMS, Janssen, and Sanofi. Music: “Jellyfish in Space” Kevin MacLeod (incompetech.com). Licensed under Creative Commons: By Attribution 3.0 creativecommons.org/licenses/by/3.0/

Like clockwork every Wednesday morning through chemo and during his three-week hospital stay where he underwent CAR T Cell therapy, he fired off a group text that I was fortunate enough to be a part of. It featured a message from Rich as well as a song of the day. On April 14th at 6:37am, on his 13th day in the hospital, he sent off the following message: “I look out my window and see Children's Hospital and two flight for life helipads. I wonder about everyone's stories and the randomness of it all. We all have a clock, but it's not until you experience a life changing event that you become more acutely aware of how you spend your time. My hope for everyone is that we all take time to appreciate that each day is a gift and we make the most of life, because none of us truly know how much time is left on our clock.” On the podcast, I asked him to elaborate on this message and how he has chosen to remain positive through his journey with cancer, while the rest of us continue to get stressed out and anxious about minute details and events of day-to-day life that really have no meaningful impact. He responded to my question by saying, “I'm thankful. Not that I got the disease, but that I've got time. It changes the way you react to certain things. Something changes where you appreciate everything, and you appreciate the little things more. I feel fortunate, I don't know how much time I have, but I do have time. Some people get (life) taken away from them in an instant or in a few months. None of us know when it's going to be over, so we should really all have that attitude. Sometimes you look at life, and you're like ‘where did that time go' most of the time, we just go through the day and don't appreciate the day."Luckily for Rich, along with his positive attitude, he is in great hands with Dr. Parmeswarn Hari at the Medical College of Wisconsin. Dr. Hari is rated one of the top doctors in America and started the Celgene bb2121 Car T Cell Clinical Trial right here in Milwaukee. Rich is only the sixth person in the world to get it. Essentially the treatment takes patient's T cells that are ineffective to treat myeloma and reprograms them genetically to convert the cells into supercharged, highly efficient T cells that can target and destroy every last myeloma cell. Approximately 450M cells were pumped into Rich's body. It's living cell therapy, and Dr. Hari is optimistic that many cancers will be cured this way in the next 20-25 years; right now, only three cancers can get treated like this. Dr. Hari and Rich both advise that if you think something is wrong with you, see a doctor as soon as possible as many of us procrastinate and wait until later stages to get looked at, and our health is the most important thing we have. 

Here are the links for everything discussed in Episode 57. Times are also below so feel free to skip around and get to the drugs that interest you. (0:47) Approval of Abecma for multiple myeloma CDC updates on COVID-19 & influenza reporting Connect with The Rx Daily Dose:Twitter      Instagram      YouTube      Linkedin       WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter       Instagram       Linkedin  ★ Support this podcast on Patreon ★

Carisma Therapeutics, Inc. announced (March 2021) that the first patient has been dosed in the Phase 1 multi-center clinical trial for CT-0508, studying the potential of chimeric antigen receptor macrophages (CAR-Ms) for cancer immunotherapy, specifically in solid tumors. Dr. Debora Barton, MD, Chief Medical Officer at Carisma is here to talk about this novel approach in gene-based therapy development, as it is the first time CAR--engineered macrophages are being studied in humans. CAR-T cell therapy has revolutionized how cancer is treated and revealed the power of gene-based therapies, and it has met challenges with solid tumors. Carisma's novel approach to immunotherapy may uncover potential treatment options that aim to address the unmet needs of patients, who are battling hard-to-treat cancers. Debora Barton joined Carisma Therapeutics in November 2019. She brings 18 years of oncology experience, both in academia as a practicing physician and in the biotechnology/pharmaceutical industry. In her role as CMO, Dr. Barton brings extensive clinical and oncology experience, having practiced for nine years while assuming integral roles in medical affairs, and clinical development for more than 13 years within the biotech and pharmaceutical industries. Most recently, she served as Senior Vice President, Clinical and Safety at Iovance Biotherapeutics, a late-stage cellular therapy biotech. In her previous positions, she built clinical development and drug safety teams, established an infrastructure for the orchestration of clinical studies, and played an instrumental role in obtaining FDA Breakthrough Designation for a cell therapy product and gaining the approval of a radiopharmaceutical agent by both the FDA and EMA. Dr. Barton also spent a combined 10 years at Celgene and Novartis, always focused on improving the lives of cancer patients. She completed her medical training at Pontifícia Universidade Católica de São Paulo, and her Oncology Fellowship at Federal University of São Paulo, in Brazil. #CarismaTherapeutics #GeneBasedTherapy #CARTCellTherapy