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Dr. Monty Pal and Dr. Jason Westin discuss the federal funding climate for cancer research and the persistent problem of drug shortages, two of the major concerns facing the oncology community in 2026. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I am your host, Dr. Monty Pal. I am a medical oncologist and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. There are always multiple challenges facing oncologists, and today, we discuss two of them that really stand out for 2026: threats to federal funding for cancer research and the persistent problem of drug shortages. I am thrilled to welcome Dr. Jason Westin, who believes that one way to meet these challenges is to get oncologists more involved in advocacy, and he will share some strategies to help us meet this moment in oncology. Dr. Westin is a professor in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center, but he actually wears a lot of hats within ASCO. He is a member of the Board of Directors and has also previously served as chair of ASCO's Government Relations Committee. And he is also one of the inaugural members of ASCO's Political Action Committee, or PAC. He has testified before Congress about drug shortages and many other issues. Dr. Westin, I am really excited to have you on the podcast today and dive into some of these elements that will really impact our community in 2026. Thanks so much for joining us today. Dr. Jason Westin: Thank you for having me. Dr. Monty Pal: You've had such a range of experience. I already alluded to you testifying before Congress. You've actually run for office before. You wear so many different hats. I'm used to checking my PubMed every other day and seeing a new paper out from you and your group, and you publish in the New England Journal [of Medicine] on practice-setting standards and the diseases that you treat. But you've also done all this work in the domain of advocacy. I can't imagine that balancing that is easy. What has sort of motivated you on the advocacy front? Dr. Jason Westin: Advocacy to me is another way to apply our skills and help more people than just those that you're sitting across from at the time. Clinical research, of course, is a tool to try and take what we know and apply it more broadly to people that you'll never meet. And advocacy, I think, can do the same thing, where you can have a conversation with a lawmaker, you can advocate for a position, and that hopefully will help thousands or maybe even more people down the road who you'd never get to directly interact with. And so, I think it's a force multiplier in the same way that research can be. And so, I think advocacy is a wonderful part of how doctors care for our patients. And it's something that is often difficult to know where to start, but once people get into advocacy, they can see that the power, the rewarding nature of it is attractive, and most people, once they get going, continue with that through the rest of their career. Dr. Monty Pal: So, I'll ask you to expand on that a little bit. We have a lot of our younger ASCO members listening to this podcast, folks that are just starting out their careers in clinical practice or academia. Where does that journey begin? How do you get to the point that you're testifying in front of Congress and taking on these bigger sort of stances for the oncology community? Dr. Jason Westin: Yeah, with anything in medicine and in our careers, you have to start somewhere. And often you start with baby steps before you get in front of a panel of senators or other high-profile engagement opportunities. But often the first setting for junior colleagues to be engaged is doing things – we call them "Hill Days" – but basically being involved in kind of low-stakes meetings where you're with a group of peers, some of whom have done this multiple times before, and can get engaged talking to members of representatives' offices, and doing so in a way where it's a natural conversation that you're telling a story about a patient in your clinic, or that you're telling a personal experience from a policy that impacted your ability to deliver optimal care. It sounds stressful, but once you're doing it, it's not stressful. It's actually kind of fun. And it's a way that you can get comfort and skill with a group of peers who are there and able to help you. And ASCO has a number of ways to do that, both at the federal level, there's the Hill Day where we each April have several hundred ASCO members travel to Capitol Hill. There's also state engagement that can be done, so-called visiting at home, when representatives from the U.S. Congress or from state legislators are back in district. You can meet with your own representatives on behalf of yourself, on behalf of your organization, and advocate for policies in a way that can be beneficial to your patients. But those initial meetings that are in the office often they're low stakes because you could be meeting not with the representative but with their staff. And that staff sometimes is as young or even younger than our junior colleagues. These sometimes can be people in their 20s, but they're often extremely knowledgeable, extremely approachable, and are used to dealing with people who are new to advocacy. But they actually help make decisions within the office. So it's not a waste of time. It's actually a super useful way to engage. So, it's that first step of anything in life. The activation energy is always high to do something new. But I'd encourage people who are listening to this podcast already having some level of interest about it to explore ways that they could engage more. Dr. Monty Pal: You know, I have to tell you, I'm going to riff on what you just said for a second. ASCO couldn't make it any easier, I think, for folks to participate and get involved. So, if you're listening to this and scratching your head and thinking, "Well, where do I begin? How do I actually sign on for that meeting with a local representative?" Go to the ASCO ACT Network website. And I'll actually talk to our producer, Geraldine, to make sure we've got a link to that somewhere associated with this podcast after it's published, Jason, but I actually keep that on my browser and it's super easy. I check in there every now and then and see if there's any new policy or legislation that ASCO, you know, is sort of taking a stance on, and it gives me some fodder for conversation with my local representatives too. I mean, it's just an awesome, awesome vehicle. I'm going to segue right from there right to the issues. So, you and I are both at academic centers. You know, I think this is something that really pervades academia and enters into implications for general clinical practice. There's been this, you know, massive sort of proposal for decreased funding to the NCI and to the NIH and so forth. Tell us what ASCO is doing in that regard, and tell us perhaps how our community can help. Dr. Jason Westin: We live in interesting times, and I think that may be an understatement x 100. But obviously investments in research are things that when you're at an academic center, you see and feel that as part of your daily life. Members of Congress need to be reminded of that because there's a lot of other competing interests out there besides investing in the future through research. And being an elected representative is a hard job. That is something where you have to make difficult choices to support this, and that may mean not supporting that. And there's lots of good things where our tax dollars could be spent. And so, I'm sympathetic to the idea that there's not unlimited resources. However, ASCO has done an excellent job, and ASCO members have led the charge on this, of stating what research does, what is the benefit of research, and therefore why should this matter to elected representatives, to their staff, and to those people that they're elected to serve. And ASCO has led with a targeted campaign to basically have that message be conveyed at every opportunity to elected representatives. And each year on Hill Day, one of the asks that we have is to continue to support research: the NCI, NIH, ARPA-H, these are things that are always in the asks to make sure that there's appropriate funding. But effectively playing offense by saying, "It's not just a number on a sheet of paper, this is what it means to patients. This is what it means to potentially your loved ones in the future if you are in the opposite situation where you're not on the legislative side, but you're in the office receiving a diagnosis or receiving a difficult piece of news." We only have the tools we have now because of research, and each breakthrough has been years in the making and countless hours spent funded through the engine of innovation: clinical research and translational research. And so ASCO continues to beat that drum. You mentioned earlier the ACT Network. Just to bring that back again is a very useful, very easy tool to communicate to your elected representatives. When you sign up on the ASCO ACT website, you get emails periodically, not too much, but periodically get emails of, "This is a way you can engage with your lawmakers to speak up for this." And as you said, Monty, they make it as easy as possible. You click the button, you type in your address so that it figures out who your elected representatives are, and then it will send a letter on your behalf after like five clicks to say, "I want you to support research. I want you to vote for this particular thing which is of interest to ASCO and by definition to members of ASCO." And so the ACT Network is a way that people listening can engage without having to spend hours and significant time, but just a few clicks can send that letter to a representative in Congress. And the question could be: does that matter? Does contacting your senator or your elected representative do anything? If all they're hearing is somebody else making a different argument and they're hearing over and over again from people that want investments in AI or investments in something else besides cancer research, whatever it is, they may think that there's a ground shift that people want dollars to be spent over here as opposed to at the NIH or NCI or in federally funded research. It is important to continue to express the need for federal funding for our research. And so, it really is important for folks to engage. Dr. Monty Pal: 100%. One of the things that I think is not often obvious to a lot of our listeners is where the support for clinical trials comes from. You know, you've obviously run the whole gamut of studies as have I. You know, we have our pharmaceutical company-sponsored studies, which are in a particular bucket. But I would say that there's a very important and critical subset of studies that are actually government funded, right? NCI-funded clinical trials. If you don't mind, just explain to our audience the critical nature of the work that's being done in those types of studies and if you can, maybe compare and contrast the studies that are done in that bucket versus perhaps the pharmaceutical bucket. Dr. Jason Westin: Both are critical, and we're privileged that we have pharma studies that are sponsored and federally funded clinical research. And I think that part of a healthy ecosystem for us to develop new breakthroughs has a need for both. The pharma sponsored studies are done through the lens of trying to get an approval for an agent that's of interest so that the pharma company can then turn around and use that outside of a clinical trial after an FDA approval. And so those studies are often done through the lens of getting over the finish line by showing some superiority over an existing treatment or in a new patient population. But they're done through that lens of kind of the broadest population and sometimes relatively narrow endpoints, but to get the approval so that then the drug can be widely utilized. Clinical trials done through cooperative groups are sometimes done to try and optimize that or to try and look at comparative things that may not be as attractive to pharma studies, not necessarily going for that initial approval, but the fine tuning or the looking at health outcomes or looking at ensuring that we do studies in representative populations that may not be as well identified on the pharma sponsored trials, but basically filling out the gaps in the knowledge that we didn't gain from the initial phase 3 trial that led to the approval. And so both are critical. But if we only do pharma sponsored trials, if we don't fund federally supported research and that dries up, the fear I have, and many others have, is that we're going to be lacking a lot of knowledge about the best ways to use these great new therapies, these new immune therapies, or in my team, we do a lot of clinical trials on CAR T-cell therapies. If we don't have federally funded research to do the important clinical studies, we'll be in the dark about the best ways to use these drugs, and that's going to be a terrible shame. And so we really do need to continue to support federal research. Dr. Monty Pal: Yeah, there are no softball questions on this podcast, but I think everybody would be hard pressed to think that you and I would come on here and say, "Well, no, we don't need as much money for clinical trials and NCI funding" and so forth. But I think a really challenging issue to tackle, and this is something we thought to ask you ahead of the podcast, is what to do about the general climate of, you know, whether it's academic research or clinical practice here that seems to be getting some of our colleagues thinking about moving elsewhere. I've actually talked to a couple of folks who are picking up and moving to Europe for a variety of considerations, other continents, frankly. The U.S. has always been a leader when it comes to oncology research and, one might argue, research in general. Some have the mindset these days that we're losing that footing a little bit. What's your perspective? Are you concerned about some of the trends that you're seeing? What does your crystal ball tell you? Dr. Jason Westin: I am highly concerned about this. I think as you said, the U.S. has been a leader for a long time, but it wasn't always. This is not something that's preordained that the world-leading clinical research and translational research will always be done in the United States. That is something that has been developed as an ecosystem, as an engine for innovation and for job development, new technology development, since World War II. That's something that through intentional investments in research was developed that the best and brightest around the world, if they could choose to go anywhere, you wanted them to come to work at universities and academic places within the United States. And I think, as you said, that's at risk if you begin to dry up the investment in research or if you begin to have less focus on being engaged in research in a way that is forward thinking, not just kind of maintaining what we do now or only looking at having private, for profit sponsored research. But if you don't have the investment in the basic science research and the translational research and the forward-thinking part of it, the fear is that we lose the advantage and that other countries will say, "Thank you very much," and be happy to invest in ways to their advantage. And I think as you mentioned, there are people that are beginning to look elsewhere. I don't think that it's likely that a significant population of researchers in the U.S. who are established and have careers and families – I don't think that we're going to see a mass exodus of folks. I think the real risk to me is that the younger, up-and-coming people in undergraduate or in graduate school or in medical school and are the future superstars, that they could either choose to go into a different field, so they decide not to go into what could be the latest breakthroughs for cancer patients but could be doing something in AI or something in a different field that could be attractive to them because of less uncertainty about funding streams, or they could take that job offer if it's in a different country. And I think that's the concern is it may not be a 2026 problem, but it could be a 2036 or a 2046 problem that we reap what we sow if we don't invest in the future. Dr. Monty Pal: Indeed, indeed. You know, I've had the pleasure of reviewing abstracts for some of our big international meetings, as I'm sure you've done in the past too. I see this trend where, as before, we would see the preponderance of large phase 3 clinical trials and practice setting studies being done here in the U.S., I'm seeing this emergence of China, of other countries outside of the U.S. really taking lead on these things. And it certainly concerns me. If I had to sort of gauge this particular issue, it's at the top of my list in terms of what I'm concerned about. But I also wanted to ask you, Jason, in terms of the issues that are looming over oncology from an advocacy perspective, what else really sort of keeps you up at night? Dr. Jason Westin: I'm quite concerned about the drug shortages. I think that's something that is a surprisingly evergreen problem. This is something that is on its face illogical that we're talking about the greatest engine for research in the world being the United States and the investment that we've made in drug development and the breakthroughs that have happened for patients all around the world, many of them happen in the United States, and yet we don't necessarily have access to drugs from the 1970s or 1980s that are cheap, generic, sterile, injectable drugs. This is the cisplatins and the vincristines and the fludarabine type medications which are not the sexy ones that you see the ads in the magazine or on TV at night. These are the backbone drugs for many of our curative intent regimens for pediatrics and for heme malignancies and many solid tumors. And the fact that that's continuing to be an issue is, in my opinion, a failure to address the root causes, and those are going to require legislative solutions. The root causes here are basically a race to the bottom where the economics to invest in quality manufacturing really haven't been prioritized. And so it's a race to the cheapest price, which often means you undercut your competitor, and when you don't have the money to invest in good manufacturing processes, the factory breaks down, there's no alternative, you go into shortage. And this has been going on for a couple of decades, and I don't think there's an end in sight until we get a serious solution proposed by our elected officials. That is something that bothers me in the ways where we know what we should be doing for our patients, but if we don't have the drugs, we're left to be creative in ways we shouldn't have to do to figure out a plan B when we've got curative intent therapies. And I think that's a real shame.  There's obviously a lot of other things that are concerning related to oncology, but something that I have personally had experience with when I wanted to give a patient a CAR T-cell, and we don't have a supply of fludarabine, which is a trivial drug from decades ago in terms of the technology investments in genetically modified T-cells, to not then have access to a drug that should be pennies on the dollar and available at any time you want it is almost like the Air Force investing in building the latest stealth bomber, but then forgetting to get the jet fuel in a way that they can't use it because they don't have the tools that they need. And so I think that's something that we do need to have comprehensive solutions from our elected officials. Dr. Monty Pal: Brilliantly stated. I like that analogy a lot. Let's get into the weeds for a second. What would that proposal to Congress look like? What are we trying to put in front of them to help alleviate the drug shortages? Dr. Jason Westin: We could spend a couple hours, and I know podcasts usually are not set up to do that. And so I won't go through every part. I will direct you that there have been a couple of recent publications from ASCO specifically detailing solutions, and there was a recent white paper from the Senate Finance Committee that went through some legislative solutions being explored. So Dr. Gralow, ASCO CMO, and I recently had a publication in JCO OP detailing some solutions, more in that white paper from the Senate Finance. And then there's a working group actually going through ASCO's Health Policy Committee putting together a more detailed proposal that will be published probably around the end of 2026. Very briefly, what needs to happen is for government contracts for purchasing these drugs, there needs to be an outlay for quality, meaning that if you have a manufacturing facility that is able to deliver product on time, reliably, you get a bonus in terms of your contract. And that changes the model to prioritize the quality component of manufacturing. Without that, there's no reason to invest in maintaining your machine or upgrading the technology you have in your manufacturing plant. And so you have bottlenecks emerge because these drugs are cheap, and there's not a profit margin. So you get one factory that makes this key drug, and if that factory hasn't had an upgrade in their machines in 20 years, and that machine conks out and it takes 6 months to repair or replacement, that is an opportunity for that drug to go into shortage and causes a mad dash for big hospitals to purchase the drug that's available, leaving disparities to get amplified. It's a nightmare when those things happen, and they happen all the time. There are usually dozens, if not hundreds, of drugs in shortage at any given time. And this has been going on for decades. This is something that we do need large, system-wide fixes and that investment in quality, I think, will be a key part. Dr. Monty Pal: Yeah, brilliantly said. And I'll make sure that we actually include those articles on the tagline for this podcast as well. I'll talk to our producer about that as well.  I'm really glad you mentioned the time in your last comment there because I felt like we just started, but in fact, I think we're right at our close here, Jason, unfortunately. So, I could have gone on for a couple more hours with you. I really want to thank you for these absolutely terrific insights and thank you for all your advocacy on behalf of ASCO and oncologists at large. Dr. Jason Westin: Thank you so much for having me. I have enjoyed it. Dr. Monty Pal: Thanks a lot. And many thanks to our listeners too. You can find more information about ASCO's advocacy agenda and activities at asco.org. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks so much. ASCO Advocacy Resources: Get involved in ASCO's Advocacy efforts: ASCO Advocacy Toolkit Crisis of Cancer Drug Shortages: Understanding the Causes and Proposing Sustainable Solutions, JCO Oncology Practice 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. Monty Pal   @montypal   Dr. Jason Westin @DrJasonWestin   Follow ASCO on social media:      @ASCO on X     ASCO on Bluesky    ASCO on Facebook      ASCO on LinkedIn      Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Jason Westin: Consulting or Advisory Role: Novartis, Kite/Gilead, Janssen Scientific Affairs, ADC Therapeutics, Bristol-Myers Squibb/Celgene/Juno, AstraZeneca, Genentech/Roche, Abbvie, MorphoSys/Incyte, Seattle Genetics, Abbvie, Chugai Pharma, Regeneron, Nurix, Genmab, Allogene Therapeutics, Lyell Immunopharma Research Funding: Janssen, Novartis, Bristol-Myers Squibb, AstraZeneca, MorphoSys/Incyte, Genentech/Roche, Allogene Therapeutics

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/WDQ865. CME/AAPA credit will be available until November 25, 2026.Fibrosis, Flares, and Forward Thinking in Inflammatory Bowel Disease Care: Unlocking the TL1A Axis In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Genentech, a member of the Roche Group and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/WDQ865. CME/AAPA credit will be available until November 25, 2026.Fibrosis, Flares, and Forward Thinking in Inflammatory Bowel Disease Care: Unlocking the TL1A Axis In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Genentech, a member of the Roche Group and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.

This is one in a series about possible futures, which will be published in Booch News over the coming weeks. Episode 7 appeared last week. New episodes drop every Friday. Overview Peer-to-peer flavor-sharing platforms enabled home brewers to distribute taste profiles as digital files. Blockchain-verified SCOBY genetics allowed anyone to recreate award-winning kombucha flavors. Traditional beverage companies lost control as open-source fermentation recipes spread globally. This episode follows teenage hacker Luna Reyes as she reverse-engineers Heineken’s proprietary “A-yeast” strain and the century-old master strain used for Budweiser, releasing them under Creative Commons license, triggering a flavor renaissance that made corporate beverages taste like cardboard by comparison. Luna Reyes: The Seventeen-Year-Old Who Liberated Flavor Luna Reyes was brewing kombucha in her Oakland garage when she changed the course of human history. The daughter of Mexican immigrants, she had learned fermentation from her grandmother while teaching herself bioinformatics through YouTube tutorials and volunteering at the Counter Culture Labs Maker Space on Shattuck Avenue. By fifteen, she was running the Bay Area’s most sophisticated home laboratory, utilizing jury-rigged DNA sequencers and microscopes constructed from smartphone cameras. Her breakthrough came in February 2043 while investigating why her kombucha never tasted quite like expensive craft varieties and was different again from her grandmother’s home brew. Using Crispr techniques learned from online forums, Luna began reverse-engineering the microbial genetics of premium alcoholic beverages. Her target wasn’t kombucha—it was the closely guarded yeast strains that gave corporate beers their distinctive flavors. Luna hunched over her microscope, examining bacterial cultures from her latest kombucha batch. Around her, salvaged DNA sequencers hummed, fermentation vessels bubbled, and computer screens displayed multi-hued patterns of genetic sequences. Her grandmother, Rosa, entered carrying a tray with three glasses of homemade kombucha. “Mija, you’ve been working for six hours straight. Drink something.” Luna accepted the glass without looking up. “Abuela, your kombucha tastes better than anything I can buy in stores and the ones I’ve experimented with. Why? I’m using the same base ingredients—tea, sugar, water—but mine never has this complexity.” Her grandmother laughed. “Because I’ve been feeding this SCOBY for forty years. It knows what to do. You can’t rush relationships.” Luna’s sister Maya, lounging against a workbench, waved her phone. “Luna, people have noticed your forum post about Health-Ade’s fermentation process. Someone says you’re wasting your time trying to replicate commercial kombuchas.” “I’m not trying to replicate them,” Luna said, finally looking up. “I’m trying to understand why their kombucha tastes different than that I make at home. It’s not the ingredients. It’s not the process. It’s the microbial genetics.” Rosa sat down beside her granddaughter. “When I was young in Oaxaca, every family had their own kombucha culture, passed down generation to generation. Each tasted different because the bacteria adapted to their environment, their ingredients, their care. We had a saying, Hay tantas fermentaciones en el mundo como estrellas en el cielo nocturno – there are as many ferments in the world as stars in the night sky. The big companies want every bottle to be identical. That kills what makes fermentation special.” “Exactly!” Luna pulled up genetic sequences on her screen. “I’ve been reverse-engineering samples from different commercial kombuchas. Health-Ade, GT’s, Brew Dr—they all have consistent microbial profiles.” The Great Heist: Cracking Corporate DNA Luna’s first major hack targeted Heineken’s legendary “A-yeast” strain, developed in 1886 by Dr. Hartog Elion—a student of renowned chemist Louis Pasteur—in the company’s Amsterdam laboratory and protected by over 150 years of trade secret law. Using samples obtained from discarded brewery waste (technically legal under the “garbage doctrine”), she spent six months mapping the strain’s complete genetic sequence in her makeshift lab. The breakthrough required extraordinary ingenuity. Luna couldn’t afford professional gene sequencers, so she modified a broken Illumina iSeq100 purchased on eBay for $200. Her sequencing runs took weeks rather than hours; her results were identical to those produced by million-dollar laboratory equipment. Her detailed laboratory notebooks, later published as The Garage Genomics Manifesto, became essential reading for the biotech hacker movement. The Budweiser project proved even more challenging. Anheuser-Busch’s century-old master strain had been protected by layers of corporate secrecy rivaling classified military programs. The company maintained multiple backup cultures in cryogenic facilities across three continents, never allowing complete genetic mapping by outside researchers. Luna’s success required infiltrating the company’s waste-disposal systems at four breweries, collecting samples over 18 months while evading corporate security. The Decision The night before Luna was scheduled to meet her fellow bio-hackers at Oakland’s Counter Culture Labs, she sat at her workstation, hesitant, wondering if she was doing the right thing. Her sister Maya came in, looking worried. “Luna, I found something you need to see,” she says. “Remember Marcus Park? He tried releasing proprietary yeast information in 2039. Heineken buried him. He lost everything. His daughter dropped out of college. His wife left him. He’s working at a gas station now.” Luna spent the night researching what happened to Park. She found that almost everyone who challenged corporate IP ended up on the losing side of the law. It was not pretty. In the morning, Abuela Rosa finds her crying in her room. “Mija, what’s wrong?” she asks. “Oh, Abuela,” Luna says between sobs. “What am I doing? What if I’m wrong? What if I destroy our family? What if this ruins Mom and Dad? What if I’m just being selfish?” “That’s the fear talking.” Her grandmother reassured her. “Fear is wisdom warning you to be careful. But fear can also be a cage.” That evening at the Counter Culture Labs, Luna assembled a small group of advisors. She needed their guidance. She had the completed genetic sequences for Heineken A-yeast and Budweiser’s master strain on her laptop, ready for release. But is this the time and place to release them to the world? Dr. Marcus Webb, a bioinformatics researcher in his forties and Luna’s mentor, examined her sequencing data. “This is solid work, Luna. Your jury-rigged equipment is crude. The results are accurate. You’ve fully mapped both strains.” “The question isn’t whether I can do it,” Luna said. “It’s whether I should let the world know I did it.” On screen, Cory Doctorow, the author and digital rights activist, leaned forward. “Let’s be clear about what you’re proposing. You’d be releasing genetic information that corporations have protected as trade secrets for over a century. They’ll argue you stole their intellectual property. You’ll face lawsuits, possibly criminal charges.” “Is it their property?” Luna challenged. “These are naturally occurring organisms. They didn’t create that yeast. Evolution did. They just happened to be there when it appeared. That does not make it theirs any more than finding a wildflower means they own the species. Can you really own something that existed before you found it?” Doctorow, the Electronic Frontier Foundation representative spoke up. “There’s legal precedent both ways. Diamond v. Chakrabarty established that genetically modified organisms can be patented. But naturally occurring genetic sequences? That’s murky. The companies will argue that their decades of cultivation and protection created protectable trade secrets.” “Trade secrets require keeping information secret,” Luna argued. “They throw this yeast away constantly. If they’re not protecting it, how can they claim trade secret status?” Dr. Webb cautioned, “Luna, even if you’re legally in the right—which is debatable—you’re seventeen years old. You’ll be fighting multinational corporations with unlimited legal resources. They’ll bury you in litigation for years.” “That’s where we come in,” Doctorow said. “The EFF can provide legal defense. Creative Commons can help structure the license. You need to understand: this will consume your life. College, career plans, normal teenage experiences—all on hold while you fight this battle.” Luna was quiet for a moment, then pulled up a photo on her laptop: her grandmother Rosa, teaching her to ferment at age seven. “My abuela says fermentation is about sharing and passing living cultures between generations. Corporations have turned it into intellectual property to be protected and controlled. If I can break that control—even a little—isn’t that worth fighting for?” Maya spoke up from the back. “Luna, I love you, but you’re being naive. They won’t just sue you. They’ll make an example of you. Your face on every news channel, portrayed as a thief, a criminal. Our family harassed. Your future destroyed. For what? So people can brew beer with the same yeast as Heineken?” “Not just beer,” Luna responded passionately. “This is about whether living organisms can be owned. Whether genetic information—the code of life itself—can be locked behind intellectual property law. Yes, it starts with beer yeast. But what about beneficial bacteria? Life-saving microorganisms? Medicine-producing fungi? Where does it end?” Dr. Webb nodded slowly. “She’s right. This is bigger than beer. As biotech advances, genetic control becomes power over life itself. Do we want corporations owning that?” Doctorow sighed. “If you do this, Luna, do it right. Release everything simultaneously—BitTorrent, WikiLeaks, Creative Commons servers, distributed networks worldwide. Make it impossible to contain. Include complete cultivation protocols so anyone can reproduce your results. Make the data so damn widely available that suppressing it becomes futile.” “And write a manifesto,” he added. “Explain why you’re doing this. Frame the issue. Make it about principles, not piracy.” Luna nodded, fingers already typing. “When should I release?” “Pick a date with symbolic meaning,” Dr. Webb suggested. “Make it an event, not just a data dump.” Luna smiled. “December 15. The Bill of Rights Day. Appropriate for declaring biological rights, don’t you think?” Maya groaned. “You’re really doing this, aren’t you?” “Yes. I’m really doing this.” The Creative Commons Liberation On Tuesday, December 15, 2043—a date now celebrated as “Open Flavor Day”—Luna released the genetic sequences on multiple open-source networks. Her manifesto, titled Your Grandmother’s Yeast Is Your Birthright, argued that microbial genetics belonged to humanity’s shared heritage rather than corporate shareholders. It stated: Commercial companies have protected yeast strains for over a century. They’ve used intellectual property law to control flavor itself. But genetic information isn’t like a recipe or a formula—it’s biological code that evolved over millions of years before humans ever cultivated it. These strains are protected as trade secrets—the bacteria don’t belong to anyone. They existed before Heineken, before Budweiser, before trademark law. The companies just happened to isolate and cultivate them. Her data packages included DNA sequences and complete protocols for cultivating, modifying, and improving the strains. Luna’s releases came with user-friendly software that allowed amateur brewers to simulate genetic modifications before attempting them in real fermentations. Within 24 hours, over ten thousand people worldwide downloaded the files. The Creative Commons community erupted in celebration. Cory Doctorow’s blog post, The Teenager Who Stole Christmas (From Corporate Beer), went viral within hours. The Electronic Frontier Foundation immediately offered Luna legal protection, while the Free Software Foundation created the “Luna Defense Fund” to support her anticipated legal battles. The Legal Assault Heineken’s response was swift. The company filed emergency injunctions in 12 countries simultaneously, seeking to prevent the distribution of its “stolen intellectual property.” Their legal team, led by former U.S. Attorney General William Barr III, demanded Luna’s immediate arrest for “economic terrorism” and “theft of trade secrets valued at over $50 billion.” Anheuser-Busch’s reaction was even more extreme. CEO Marcel Telles IV appeared on CNBC, calling Luna “a bioterrorist who threatens the foundation of American capitalism.” The company hired private investigators to surveil Luna’s family and offered a $10 million reward for information leading to her prosecution. Their legal filing compared Luna’s actions to “stealing the formula for Coca-Cola and publishing it in the New York Times.” In Heineken’s Amsterdam headquarters, executives convened an emergency meeting. “Who is Luna Reyes?” the CEO demanded. The legal counsel pulled up information. “She’s a seventeen-year-old high school student in Oakland, California. No criminal record. Volunteers at a maker space. Has been posting about fermentation on various forums for years.” “A child released our proprietary yeast strain to the world, and we didn’t know she was even working on this?” The CEO’s face reddened. “How do we contain it?” “We can’t. It’s distributed across thousands of servers in dozens of countries with different IP laws. We can sue Reyes, but the information is out there permanently.” An executive interjected, “What about the other breweries? Will they join our lawsuit?” “Some are considering it. Others…” The counsel paused. “Others are quietly downloading the sequences themselves. They see an opportunity to break our market dominance.” “She obtained samples from our waste disposal,” another executive explained. “Technically legal under the garbage doctrine. The sequencing itself isn’t illegal. The release under Creative Commons…” “Is theft!” the CEO shouted. “File emergency injunctions. Twelve countries. Get her arrested for economic terrorism.” Similar scenes played out at Anheuser-Busch headquarters in St. Louis. CEO Telles addressed his team: “This is bioterrorism. She’s destroyed intellectual property worth billions. I want her prosecuted to the fullest extent of the law. Hire private investigators. Find everything about her and her family. Make her life hell!” By noon, both companies had filed lawsuits. By evening, Fox News was running stories about the “teenage bioterrorist” who “stole American corporate secrets.” Back in Oakland, Luna’s phone rang constantly. Her parents discovered what she’d done. Her mother cried. Her father was furious and terrified. Friends called with either congratulations or warnings. She was convinced that private investigators were photographing their house. Maya suspected she was followed to work. On Wednesday morning, Dr. Webb calls: “Luna, they’re offering me $2 million to testify against you. They’re going after everyone in your network.” Luna has a sickening feeling that she’s put everyone at risk. By Thursday, she is considering taking it all back somehow, sending an apology to the corporations, anything to protect her family. Luna turned off her phone and sat with her grandmother. “It’s started,” Luna said quietly. “Sí, mija. You’ve declared war. Now we see if you can survive it.” Maya burst in, laptop in hand. “Luna, you need to see this. The downloads aren’t slowing—they’re accelerating. Every time Heineken or Budweiser shuts down a website, ten mirror sites appear. People are treating this like a digital freedom fight. You’ve become a symbol.” Luna pulled up her own screen. The #FreeLuna hashtag was trending. Crowdfunding campaigns for her legal defense had raised $400,000 in twelve hours. Academic institutions were publicly endorsing her release, calling it “essential scientific information.” “They’re trying to destroy you,” Maya said, “but they’re making you famous instead.” Rosa handed Luna a fresh kombucha. “This is what happens when you fight for what’s right, mija. Sometimes the world surprises you by supporting you.” Luna’s Fame The corporations’ attempts to suppress Luna’s releases had the opposite effect. Every cease-and-desist letter generated thousands of new downloads. The genetic data became impossible to contain once the academic community embraced Luna’s work. Dr. Jennifer Doudna, the legendary Crispr pioneer now in her eighties, publicly endorsed Luna’s releases in a Science magazine editorial: Ms. Reyes has liberated essential scientific information that corporations held hostage for commercial gain. Genetic sequences from naturally occurring organisms should not be locked behind intellectual property law. They belong to humanity’s knowledge commons. While corporations claim Luna stole trade secrets, I argue she freed biological knowledge that was never theirs to own. There are no trade secrets in biology—only knowledge temporarily hidden from the commons. This is civil disobedience of the highest order—breaking unjust laws to advance human freedom. Ms. Reyes didn’t steal; she liberated. MIT’s biology department invited Luna to lecture, while Harvard offered her a full scholarship despite her lack of a high school diploma. The legal battles consumed corporate resources while generating negative publicity. Heineken’s stock price dropped 34% as consumers organized boycotts in support of Luna’s “yeast liberation.” Beer sales plummeted as customers waited for home-brewed alternatives using Luna’s open-source genetics. The Flavor Renaissance Luna’s releases triggered an explosion of creativity that corporate R&D departments had never imagined. Within six months, amateur brewers worldwide were producing thousands of flavor variations impossible under corporate constraints. The open-source model enabled rapid iteration and global collaboration, rendering traditional brewing companies obsolete. The world was engaged. In some of the most unlikely places. In Evanston, Illinois, a group of former seminary students who discovered fermentation during a silent retreat, transformed Gregorian chants into microbial devotionals. Tenor Marcus Webb (Dr. Webb’s nephew) realized symbiosis mirrored vocal harmony—multiple voices creating something greater than their parts. “In honoring the mystery of fermentation we express our love of the Creator,” he said. Here's ‘Consortium Vocalis' honoring the mother SCOBY. [Chorus]Our SCOBYIs pureOur SCOBYIs strongOur SCOBYKnows no boundariesOur SCOBYStrengthens as it fermentsOur SCOBYIs bacteria and yeast Our SCOBYTurns sucrose into glucose and fructoseIt ferments these simple sugars into ethanol and carbon dioxide,Acetic acid bacteria oxidize much of that ethanol into organic acidsSuch as acetic, gluconic, and other acids.This steadily lowers the pHMaking the tea taste sour-tangy instead of purely sweet. [Chorus] Our SCOBYThen helps microbes produce acids, enzymes, and small amounts of B‑vitaminsWhile probiotics grow in the liquid.The pH falls to help inhibit unwanted microbesOur SCOBY creates a self-preserving, acidic environment in the tea [Chorus] In Kingston, Jamaica, Rastafarian’s combined an award-winning kombucha sequenced in Humboldt County, California, with locally grown ganja into a sacramental beverage to help open their mind to reasoning and focus on Jah. Once fermented, it was consumed over the course of a three-day Nyabinghi ceremony. “Luna Reyes is truly blessed. She strengthened our unity as a people, and our Rastafari’ booch help us chant down Babylon,” a Rasta man smiled, blowing smoke from a spliff the size of his arm. The Groundation Collective’s reggae anthem ‘Oh Luna’ joyfully celebrated Luna Reyes’ pioneering discovery. Oh Luna, Oh Luna, Oh Luna ReyesI love the sound of your nameYou so deserve your fame Luna, Luna, Oh Luna ReyesShining brightYou warm my heart Luna, Luna, Oh Luna ReyesYou cracked the codeTeenage prophet, fermentation queenSymbiosis roadA genius at seventeen Oh Luna, Luna, Luna ReyesBeautiful moonMakes me swoon Oh Luna, Luna, Luna ReyesFreedom to fermentYou are heaven sentTo save us Luna, Luna, Oh Luna ReyesYou opened the doorTo so much moreKombucha tastes so goodLike it should Oh Luna, Oh Luna, Oh LunaI love you, love you, love youOh Luna, Luna, LunaLove you, love you,Love Luna, Luna love. In São Paulo, Brazil, MAPA-certified Brazilian kombucha brands combined Heineken and cacao-fermenting yeasts with cupuaçu from indigenous Amazonian peoples, to create the chocolate-flavored ‘booch that won Gold at the 20th World Kombucha Awards. A cervejeiro explained to reporters: “Luna Reyes gave us the foundation. We added local innovation. This is what happens when you democratize biology.” The Brazilian singer Dandara Sereia covered ‘Our Fermented Future’—The Hollow Pines tune destined to become a hit at the 2053 Washington DC Fermentation Festival. Baby sit a little closer, sip some ‘booch with meI brewed this batch with the SCOBY my grandma gave to me.On the back porch swing at twilight, watching fireflies danceYour hand in mine, kombucha fine, the sweetest sweet romance. They say that wine and roses are the way to win the heartBut your kombucha warmed me right up from the start.Fermentation makes the heart grow fonder, truer words they ain’t been saidYour SCOBY’s got a place forever — in my heart, and in my bed. Let’s share our SCOBYs, baby, merge our ferments into oneLike cultures in a crock jar dancing, underneath the sun.The tang of your Lactobacillus is exactly what I’m missingYour Brettanomyces bacteria got this country girl reminiscing. Oh yeah, let’s share those SCOBYs, baby, merge our ferments into oneYour yeasts and my bacteria working till the magic’s doneYou’ve got the acetic acid honey, I’ve got the patience and the timeLet’s bubble up together, let our cultures intertwine. I’ve got that symbiotic feeling, something wild and something trueYour SCOBY’s in my heart, right there next to youThe way your Acetobacter turns sugar into goldIs how you turned my lonely life into a hand to hold. We’ve got the acetic acid and the glucuronic tooWe’ve got that symbiotic feeling, so righteous and so trueOne sip of your sweet ‘booch, Lord, and you had me from the start,It’s our fermented future, that no-one can tear apart. It’s our fermented future…It’s our fermented future…It’s our fermented future… “Luna Variants”—strains derived from her releases—began winning international brewing competitions, embarrassing corporate entries with their complexity and innovation. Traditional beer flavors seemed flat and artificial compared to the genetic symphonies created by collaborative open-source development. Despite the outpouring of positive vibes, the corporations spared no expense to hold Luna to account in the courts. The Preliminary Hearing A preliminary hearing was held in the United States District Court for the Northern District of California on June 14, 2044. Luna sat at the defendant’s table, her hands folded so tightly her knuckles had gone white. She wore a borrowed blazer—too big in the shoulders—over a white button-down shirt Maya had ironed that morning. At seventeen, she looked even younger under the courtroom’s fluorescent lights. Across the aisle, Heineken’s legal team occupied three tables. Fifteen attorneys in matching navy suits shuffled documents and whispered into phones. Their lead counsel, William Barr III, wore gold cufflinks that caught the light when he gestured. Luna recognized him from the news—the former Attorney General, now commanding $2,000 an hour to destroy people like her. Her own legal representation consisted of two people: Rose Kennerson from the Electronic Frontier Foundation, a public interest lawyer who’d flown in from DC on a red-eye, and Dr. Marcus Webb, technically a witness but sitting beside Luna because she’d asked him to. Behind them, the gallery was packed. Luna’s parents sat in the second row, her father’s face gray, her mother clutching a rosary. Maya had taken the day off work. Abuela Rosa sat in the front row directly behind Luna, her ancient SCOBY wrapped in silk in her lap, as if its presence might protect her granddaughter. Judge Catherine Ironwood entered—sixty-ish, steel-gray hair pulled back severely, known for pro-corporate rulings. She’d been a pharmaceutical industry lawyer for twenty years before her appointment. “All rise,” the bailiff called. Judge Ironwood settled into her chair and surveyed the courtroom with the expression of someone who’d already decided the outcome and resented having to perform the formalities. “We’re here for a preliminary injunction hearing in Heineken International B.V. versus Luna Marie Reyes.” She looked directly at Luna. “Ms. Reyes, you’re seventeen years old?” Luna stood, hesitant. “Yes, your honor.” “Where are your parents?” “Here, your honor.” Luna’s mother half-rose, then sat back down. “Ms. Kennerson, your client is a minor. Are the parents aware they could be held liable for damages?” Rose Kennerson stood smoothly. “Yes, your honor. The Reyes family has been fully advised of the legal implications.” Luna glanced back. Her father’s jaw was clenched so tight she could see the muscles working. He wouldn’t meet her eyes. “Very well. Mr. Barr, you may proceed.” Barr rose like a battleship emerging from fog—massive, expensive, inevitable. He buttoned his suit jacket and approached the bench without notes. “Your honor, this is the simplest case I’ve argued in thirty years. The defendant admits to obtaining my client’s proprietary biological materials. She admits to sequencing their genetic information. She admits to distributing that information globally, in deliberate violation of trade secret protections that have existed for over 150 years. She did this knowingly, systematically, and with the explicit intent to destroy my client’s competitive advantage.” Luna felt Sarah’s hand on her arm—stay calm. Barr continued. “Heineken International has invested over $200 million in the development, cultivation, and protection of the A-yeast strain. Then this teenager”—he pointed at Luna—”obtained samples from our waste disposal systems, reverse-engineered our genetic sequences, and released them to the world via BitTorrent, deliberately placing them beyond retrieval.” He paced now, warming to his theme. “The damage is incalculable. We estimate lost market value at $50 billion. But it’s not just about money. The defendant has destroyed the possibility of competition in the brewing industry. When everyone has access to the same genetic materials, there’s no innovation, no differentiation, no reason for consumers to choose one product over another. She has, in effect, communized an entire industry.” Luna couldn’t help herself. “That’s not—” Sarah grabbed her wrist. “Don’t.” Judge Ironwood’s eyes narrowed. “Ms. Reyes, you will have your opportunity to speak. Until then, you will remain silent, or I will have you removed from this courtroom. Do you understand?” “Yes, your honor.” Luna’s voice came out smaller than she intended. Barr smiled slightly. “Your honor, the relief we seek is straightforward. We ask this court to order the defendant to provide us with a complete list of all servers, websites, and distribution networks where the stolen genetic data currently resides. We ask that she be ordered to cooperate fully in suppressing the data. We ask that she be enjoined from any further distribution. And we ask that she be ordered to pay compensatory damages of $5 billion, plus punitive damages to be determined at trial.” He returned to his seat. One of his associate attorneys handed him a bottle of Pellegrino. He took a sip and waited. Judge Ironwood looked at Sarah. “Ms. Kennerson?” Sarah stood. She looked tiny compared to Barr—five-foot-three, maybe 110 pounds, wearing a suit from Target. But when she spoke, her voice filled the courtroom. “Your honor, Mr. Barr has given you a compelling story about a corporation that’s been wronged. But it’s not the right story. The right story is about whether naturally occurring organisms—creatures that evolved over millions of years, long before humans ever existed—can be owned by a corporation simply because that corporation happened to isolate them.” She walked toward the bench. “Let’s be clear about what the A-yeast strain is. It’s not a genetically modified organism. It’s not a patented invention. It’s a naturally occurring yeast. Heineken didn’t create it. Evolution created it. Heineken merely found it. And for 158 years, they’ve claimed that finding something gives them the right to prevent anyone else from studying it, understanding it, or using it.” Barr was on his feet. “Objection, your honor. This is a preliminary hearing about injunctive relief, not a philosophical debate about intellectual property theory.” “Sustained. Ms. Kennerson, please focus on the specific legal issues before this court.” “Your honor, the specific legal issue is whether naturally occurring genetic sequences constitute protectable trade secrets. My client contends they do not. She obtained the yeast samples from Heineken’s waste disposal—materials they had discarded. Under the garbage doctrine, she had every right to analyze those materials. The genetic sequences she discovered are factual information about naturally occurring organisms. You cannot trade-secret facts about nature.” Luna watched Judge Ironwood’s face. Nothing. No reaction. Sarah pressed on. “Mr. Barr claims my client ‘stole’ genetic information worth $5 billion. But information cannot be stolen—it can only be shared. When I tell you a fact, I don’t lose possession of that fact. We both have it. That’s how knowledge works. Heineken hasn’t lost their yeast. They still have it. They can still brew with it. What they’ve lost is their monopoly on that knowledge. And monopolies on facts about nature should never have existed in the first place.” “Your honor—” Barr tried to interrupt. Judge Ironwood waved him down. “Continue, Ms. Kennerson.” “Your honor, Heineken wants this court to order a seventeen-year-old girl to somehow suppress information that has already been distributed to over 100,000 people in 147 countries. That’s impossible. You can’t unring a bell. You can’t put knowledge back in a bottle. Even if this court ordered my client to provide a list of servers—which she shouldn’t have to do—that list would be incomplete within hours as new mirror sites appeared. The information is out. The only question is whether we punish my client for sharing factual information about naturally occurring organisms.” She turned to face Luna’s family. “Ms. Reyes taught herself bioinformatics from YouTube videos. She works at home with equipment she bought on eBay. She has no criminal record. She’s never been in trouble. She saw a question that interested her—why do commercial beers taste like they do?—and she pursued that question with the tools available to her. When she discovered the answer, she shared it with the world, under a Creative Commons license that specifically protects sharing for educational and scientific purposes. If that’s terrorism, your honor, then every scientist who’s ever published a research paper is a terrorist.” Sarah sat down. Luna wanted to hug her. Judge Ironwood leaned back. “Ms. Reyes, stand up.” Luna rose, her legs shaking. “Do you understand the seriousness of these proceedings?” “Yes, your honor.” “Do you understand that Heineken International is asking me to hold you in contempt of court if you refuse to help them suppress the information you released?” “Yes, your honor.” “Do you understand that contempt of court could result in your detention in a juvenile facility until you reach the age of eighteen, and potentially longer if the contempt continues?” Luna’s mother gasped audibly. Her father put his arm around her. “Yes, your honor,” Luna said, though her voice wavered. “Then let me ask you directly: If I order you to provide Heineken with a complete list of all locations where the genetic data you released currently resides, will you comply?” The courtroom went silent. Luna could hear her own heartbeat. Sarah started to stand—”Your honor, I advise my client not to answer—” “Sit down, Ms. Kennerson. I’m asking your client a direct question. She can choose to answer or not.” Judge Ironwood’s eyes never left Luna. “Well, Ms. Reyes? Will you comply with a court order to help Heineken suppress the information you released?” Luna looked at her parents. Her mother was crying silently. Her father’s face was stone. She looked at Abuela Rosa. Her grandmother nodded once—tell the truth. Luna looked back at the judge. “No, your honor.” Barr shot to his feet. “Your honor, the defendant has just admitted she intends to defy a court order—” “I heard her, Mr. Barr.” Judge Ironwood’s voice was ice. “Ms. Reyes, do you understand you’ve just told a federal judge you will refuse a direct order?” “Yes, your honor.” “And you’re still refusing?” “Yes, your honor.” “Why?” Sarah stood quickly. “Your honor, my client doesn’t have to explain—” “I want to hear it.” Judge Ironwood leaned forward. “Ms. Reyes, tell me why you would risk jail rather than help undo what you’ve done.” Luna took a breath. Her whole body was shaking, but her voice was steady. “Because it would be wrong, your honor.” “Wrong how?” “The genetic sequences I released evolved over millions of years. Heineken didn’t create that yeast. They isolated one strain and claimed ownership of it. The code of life belongs to everyone. That’s humanity’s heritage. Even if you send me to jail, I can’t help suppress the truth.” Judge Ironwood stared at her for a long moment. “That’s a very pretty speech, Ms. Reyes. But this court operates under the law, not your personal philosophy about what should or shouldn’t be owned. Trade secret law exists. Heineken’s rights exist. And you violated those rights.” Luna did not hesitate. “With respect, your honor, I don’t think those rights should exist.” Barr exploded. “Your honor, this is outrageous! The defendant is openly stating she believes she has the right to violate any law she disagrees with—” “That’s not what I said.” Luna’s fear was transforming into something else—something harder. “I’m saying that some laws are unjust. And when laws are unjust, civil disobedience becomes necessary. People broke unjust laws during the civil rights movement. People broke unjust laws when they helped slaves escape. The constitution says members of the military do not have to obey illegal orders, despite what those in power might claim. Sometimes the law is wrong. And when the law says corporations can own genetic information about naturally occurring organisms, the law is wrong.” Judge Ironwood’s face flushed. “Ms. Reyes, you are not Rosa Parks. This is not the civil rights movement. This is a case about intellectual property theft.” “It’s a case about whether life can be property, your honor.” “Enough.” Judge Ironwood slammed her gavel. “Ms. Kennerson, control your client.” Sarah pulled Luna back into her chair. “Luna, stop talking,” she hissed. Judge Ironwood shuffled papers, visibly trying to compose herself. “I’m taking a fifteen-minute recess to consider the injunction request. We’ll reconvene at 11:30. Ms. Reyes, I strongly suggest you use this time to reconsider your position.” The gavel fell again, and Judge Ironwood swept out. The hallway outside the courtroom erupted. Reporters swarmed. Luna’s father grabbed her arm and pulled her into a witness room. Her mother followed, still crying. Maya slipped in before Sarah closed the door. “What were you thinking?” Luna’s father’s voice shook. “You just told a federal judge you’ll defy her orders. They’re going to put you in jail, Luna. Do you understand that? Jail!” “Ricardo, please—” Her mother tried to calm him. “No, Elena. Our daughter just committed contempt of court in front of fifty witnesses. They’re going to take her from us.” He turned to Luna, his eyes wet. “Why? Why couldn’t you just apologize? Say you made a mistake? We could have ended this.” “Because I didn’t make a mistake, Papa.” “You destroyed their property!” “It wasn’t their property. It was never their property.” “The law says it was!” “Then the law is wrong!” Her father stepped back as if she’d slapped him. “Do you know what your mother and I have sacrificed to keep you out of trouble? Do you know how hard we’ve worked since we came to this country to give you opportunities we never had? And you throw it away for yeast. Not for justice. Not for people. For yeast.” Luna’s eyes filled with tears. “It’s not about yeast, Papa. It’s about whether corporations get to own life. If Heineken can own yeast, why not bacteria? Why not human genes? Where does it stop?” “It stops when my daughter goes to jail!” He was shouting now. “I don’t care about Heineken. I don’t care about yeast. I care about you. And you just told that judge you’ll defy her. She’s going to put you in jail, and there’s nothing I can do to stop it.” “Ricardo, por favor—” Elena put her hand on his arm. He shook it off. “No. She needs to hear this. Luna, if you go to jail, your life is over. No college will accept you. No company will hire you. You’ll have a criminal record. You’ll be marked forever. Is that what you want?” “I want to do what’s right.” “What’s right is protecting your family! What’s right is not destroying your future for a principle!” he said. Luna responded, “What’s right is not letting corporations own the code of life!”They stared at each other. Maya spoke up quietly from the corner. “Papa, she can’t back down now. The whole world is watching.” “Let the world watch someone else!” Ricardo turned on Maya. “You encourage this. You film her, you post her manifestos online, you help her become famous. You’re her sister. You’re supposed to protect her, not help her destroy herself.” “I am protecting her,” Maya said. “I’m protecting her from becoming someone who backs down when the world tells her she’s wrong, even though she knows she’s right.” Ricardo looked between his daughters. “Ambos están locos! You’re both insane.” Abuela Rosa opened the door and entered. She’d been listening from the hallway. “Ricardo, enough.” “Mama, stay out of this.” “No.” Rosa moved between Ricardo and Luna. “You’re afraid. I understand. But fear makes you cruel, mijo. Your daughter is brave. She’s doing something important. And you’re making her choose between you and what’s right. Don’t do that.” “She’s seventeen years old! She’s a child!” “She’s old enough to know right from wrong.” Rosa put her hand on Ricardo’s cheek. “When I was sixteen, I left Oaxaca with nothing but the clothes on my back and this SCOBY. Everyone said I was crazy. Your father said I would fail. But I knew I had to go, even if it cost me everything. Sometimes our children have to do things that terrify us. That’s how the world changes.” Ricardo pulled away. “If they put her in jail, will that change the world, Mama? When she’s sitting in a cell while Heineken continues doing whatever they want, will that have been worth it?” “Yes,” Luna said quietly. “Even if I go to jail, yes. Because thousands of people now have the genetic sequences, Heineken can’t put that back. They can punish me, but they can’t undo what I did. The information is free. It’s going to stay free. And if the price of that is me going to jail, then that’s the price.” Her father looked at her as if seeing her for the first time. “I don’t know who you are anymore.” “I’m still your daughter, Papa. I’m just also someone who won’t let corporations own life.” A knock on the door. Sarah poked her head in. “They’re reconvening. Luna, we need to go.” Back in the courtroom, the atmosphere had shifted. The gallery was more crowded—word had spread during the recess. Luna recognized several people from online forums. Some held signs reading “FREE LUNA” and “GENETICS BELONG TO EVERYONE.” Judge Ironwood entered and sat without ceremony. “I’ve reviewed the submissions and heard the arguments. This is my ruling.” Luna’s hand found Maya’s in the row behind her. Squeezed tight. “The question before this court is whether to grant Heineken International’s motion for a preliminary injunction requiring Ms. Reyes to assist in suppressing the genetic information she released. To grant such an injunction, Heineken must demonstrate four things: likelihood of success on the merits, likelihood of irreparable harm without the injunction, balance of equities in their favor, and that an injunction serves the public interest.” Barr was nodding. These were his arguments. “Having considered the evidence and the applicable law, I find that Heineken has demonstrated likelihood of success on the merits. Trade secret law clearly protects proprietary business information, and the A-yeast strain appears to meet the legal definition of a trade secret.” Luna’s stomach dropped. “However, I also find that Heineken has failed to demonstrate that a preliminary injunction would effectively prevent the irreparable harm they claim. Ms. Kennerson is correct that the genetic information has already been distributed to over 100,000 people worldwide. Ordering one teenager to provide a list of servers would be, in technical terms, pointless. New copies would appear faster than they could be suppressed.” Barr’s face tightened. “Furthermore, I find that the balance of equities does not favor Heineken. They ask this court to potentially incarcerate a seventeen-year-old girl for refusing to suppress information that is, by her account, factual data about naturally occurring organisms. The potential harm to Ms. Reyes—including detention, criminal record, and foreclosure of educational and career opportunities—substantially outweighs any additional harm Heineken might suffer from continued distribution of information that is already widely distributed.” Luna felt Maya’s grip tighten. Was this good? This sounded good. “Finally, and most importantly, I find that granting this injunction would not serve the public interest. The court takes judicial notice that this case has generated substantial public debate about the scope of intellectual property protection in biotechnology. The questions raised by Ms. Reyes—whether naturally occurring genetic sequences should be ownable, whether facts about nature can be trade secrets, whether knowledge can be property—are questions that deserve answers from a higher authority than this court. These are questions for appellate courts, perhaps ultimately for the Supreme Court. And they are questions best answered in the context of a full trial on the merits, not in an emergency injunction hearing.” Barr was on his feet. “Your honor—” “Sit down, Mr. Barr. I’m not finished.” He sat, his face purple. “Therefore, Heineken International’s motion for preliminary injunction is denied. Ms. Reyes will not be required to assist in suppressing the genetic information she released. However,”—Judge Ironwood looked directly at Luna—”this ruling should not be construed as approval of Ms. Reyes’ actions. Heineken’s claims for damages and other relief remain viable and will proceed to trial. Ms. Reyes, you may have won this battle, but this war is far from over. Anything you want to say?” Luna stood slowly. “Your honor, I just want to say… thank you. For letting this go to trial. For letting these questions be answered properly. That’s all I ever wanted—for someone to seriously consider whether corporations should be allowed to own genetic information about naturally occurring organisms. So thank you.” Judge Ironwood’s expression softened slightly. “Ms. Reyes, I hope you’re prepared for what comes next. Heineken has unlimited resources. They will pursue this case for years if necessary. You’ll be in litigation until you’re twenty-five years old. Your entire young adulthood will be consumed by depositions, court appearances, and legal fees. Are you prepared for that?” “Yes, your honor.” “Why?” Luna glanced at her grandmother, who nodded. “Because some questions are worth answering, your honor. Even if it takes years. Even if it costs everything. The question of whether corporations can own life—that’s worth answering. And if I have to spend my twenties answering it, then that’s what I’ll do.” Judge Ironwood studied her for a long moment. “You remind me of someone I used to know. Someone who believed the law should serve justice, not just power.” She paused. “That person doesn’t exist anymore. The law ground her down. I hope it doesn’t do the same to you.” She raised her gavel. “This hearing is adjourned. The parties will be notified of the trial date once it’s scheduled. Ms. Reyes, good luck. I think you’re going to need it.” The gavel fell. Outside the courthouse, the scene was chaotic. News cameras surrounded Luna. Reporters shouted questions. But Luna barely heard them. She was looking at her father, who stood apart from the crowd, watching her. She walked over to him. “Papa, I’m sorry I yelled.” He didn’t speak for a moment. Then he pulled her into a hug so tight it hurt. “Don’t apologize for being brave,” he whispered into her hair. “I’m just afraid of losing you.” “You won’t lose me, Papa. I promise.” “You can’t promise that. Not anymore.” He pulled back, holding her shoulders. “But I’m proud of you. I’m terrified, but I’m proud.” Her mother joined them, tears streaming down her face. “No more court. Please, no more court.” “I can’t promise that either, Mama.” Elena touched Luna’s face. “Then promise me you’ll be careful. Promise me you’ll remember that you’re not just fighting for genetics. You’re fighting for your life.” Luna smiled. “I promise.” Abuela Rosa appeared, carrying her SCOBY. “Come, mija. We should go before the reporters follow us home.” As they pushed through the crowd toward Maya’s car, Luna's phone buzzed continuously. Text messages and emails pouring in. But what caught her attention was a text from Dr. Webb: You were right. I’m sorry I doubted. Check your email—Dr. Doudna wants to talk. Luna opened her email. The subject line made her stop walking: From: jennifer.doudna@berkeley.eduSubject: Civil Disobedience of the Highest Order She started to read: Dear Ms. Reyes, I watched your hearing this morning. What you did in that courtroom—refusing to back down even when threatened with jail—was one of the bravest things I’ve seen in forty years of science. You’re not just fighting for yeast genetics. You’re fighting for the principle that knowledge about nature belongs to humanity, not to corporations. I want to help… Luna looked up at her family—her father’s worried face, her mother’s tears, Maya’s proud smile, Abuela Rosa’s serene confidence. Behind them, the courthouse where she’d nearly been sent to jail. Around them, reporters and cameras and strangers who’d traveled across the country to support her. She thought about Judge Ironwood’s warning: This war is far from over. She thought about Barr’s face when the injunction was denied. She thought about the thousands who’d downloaded the genetic sequences and were, right now, brewing with genetics that had been locked away for 158 years. Worth it. All of it. Even the fear. Maya opened the car door. “Come on, little revolutionary. Let’s go home.” The Corporate Surrender By 2045, both Heineken and Anheuser-Busch quietly dropped their lawsuits against Luna. Their legal costs had exceeded $200 million while accomplishing nothing except generating bad publicity. More importantly, their “protected” strains had become worthless in a market flooded with superior alternatives. Heineken’s CEO attempted to salvage the company by embracing open-source brewing. His announcement that Heineken would “join the La Luna Revolution” was met with skepticism from the brewing community, which recalled the company’s aggressive legal tactics. The craft brewing community’s response was hostile. “They spent two years trying to destroy her,” a prominent brewmaster told The New Brewer Magazine. “Now they want credit for ’embracing’ the revolution she forced on them? Heineken didn’t join the Luna Revolution—they surrendered to it. There’s a difference.” The global brands never recovered their market share. Luna’s Transformation Luna’s success transformed her from a garage tinkerer into a global icon of the open knowledge movement. Her 2046 TED Talk, “Why Flavor Belongs to Everyone,” went viral. She argued that corporate control over living organisms represented “biological colonialism” that impoverished human culture by restricting natural diversity. Rather than commercializing her fame, Luna founded the Global Fermentation Commons, a nonprofit organization dedicated to preserving and sharing microbial genetics worldwide. Their laboratories operated as open-access research facilities where anyone could experiment with biological systems. The headquarters of the Global Fermentation Commons occupied a former Genentech facility donated by Dr. Webb. Six continents, forty researchers, one mission: preserve and share microbial genetics worldwide. Luna addressed a crowded auditorium at the organization’s third anniversary. “When I released Heineken and Budweiser’s yeast strains, some people called it theft. Others called it liberation. I called it returning biological knowledge to the commons, where it belongs. Three years later, so-called Luna Variants have created economic opportunities for thousands of small brewers, improved food security in developing regions, and demonstrated that genetic freedom drives innovation faster than corporate control.” She continued. “We’re not stopping with beer. The same principles apply to all fermentation: cheese cultures, yogurt bacteria, koji fungi, sourdough starters. Every traditionally fermented food relies on microorganisms that corporations increasingly claim to own. We’re systematically liberating them.” A World Health Organization representative raised a concern: “Ms. Reyes, while we support democratizing food fermentation, there are legitimate concerns about pharmaceutical applications. What prevents someone from using your open-source genetics to create dangerous organisms?” Luna nodded. “Fair question. First, the organisms we release are food-safe cultures with centuries of safe use. Second, dangerous genetic modifications require sophisticated laboratory equipment and expertise—far beyond what releasing genetic sequences enables. Third, determined bad actors already have access to dangerous biology, enabled by AI. We’re not creating new risks; we’re democratizing beneficial biology.” “Pharmaceutical companies argue you’re undermining their investments in beneficial organisms,” another representative pressed. “Pharmaceutical companies invest in modifying organisms,” Luna clarified. “Those modifications can be patented. What we oppose is claiming ownership over naturally occurring organisms or their baseline genetics. If you genetically engineer a bacterium to produce insulin, patent your engineering. Don’t claim ownership over the bacterial species itself.” A Monsanto representative stood. “Your organization recently cracked and released our proprietary seed genetics. That’s direct theft of our property.” Luna didn’t flinch. “Seeds that farmers cultivated for thousands of years before Monsanto existed? You didn’t invent corn, wheat, or soybeans. You modified them. Your modifications may be protectable; the baseline genetics are humanity’s heritage. We’re liberating what should never have been owned.” “The ‘Luna Legion’ has cost us hundreds of millions!” the representative protested. “Good,” Luna responded calmly. “You’ve cost farmers their sovereignty for decades. Consider it karma.” After the presentation, Dr. Doudna approached Luna privately. “You’ve accomplished something remarkable,” the elderly scientist said. “When I developed Crispr, I never imagined a teenager would use similar principles to challenge corporate biology. You’re forcing conversations about genetic ownership that we’ve avoided for decades.” “It needed forcing,” Luna replied. “Corporations were quietly owning life itself, one patent at a time. Someone had to say no.” “The pharmaceutical industry is terrified of you,” Doudna continued. “They see what happened to brewing and imagine the same for their carefully controlled bacterial strains. You’re going to face even more aggressive opposition.” “I know. Once people understand that biological knowledge can be liberated, they start questioning all biological ownership. We’re not stopping.” The New Economy of Taste Following Luna’s breakthrough, peer-to-peer flavor-sharing platforms emerged as the dominant force in food culture. The “FlavorChain” blockchain allowed brewers to track genetic lineages while ensuring proper attribution to original creators. SCOBY lineages were carefully sequenced, catalogued, and registered on global blockchain ledgers. Each award-winning kombucha strain carried a “genetic passport”—its microbial makeup, the unique balance of yeasts and bacteria that gave rise to particular mouthfeel, fizz, and flavor spectrum, was mapped, hashed, and permanently recorded. Brewers who created a new flavor could claim authorship, just as musicians once copyrighted songs. No matter how many times a SCOBY was divided, its fingerprint could be verified. Fermentation Guilds formed to share recipes through FlavorChain, enabling decentralized digital markets like SymbioTrdr, built on trust and transparency rather than speculation. They allowed people to interact and transact on a global, permissionless, self-executing platform. Within days, a SCOBY strain from the Himalayas could appear in a brew in Buenos Aires, its journey traced through open ledgers showing who tended, adapted, and shared it. Kombucha recipes were no longer jealously guarded secrets. They were open to anyone who wanted to brew. With a few clicks, a Guild member in Nairobi could download the blockchain-verified SCOBY genome that had won Gold at the Tokyo Fermentation Festival. Local biotech printers—as common in 2100 kitchens as microwave ovens had once been—could reconstitute the living culture cell by cell. Children began inheriting SCOBY lineages the way earlier generations inherited family names. Weddings combined SCOBY cultures as symbolic unions. (Let’s share our SCOBYs, baby, merge our ferments into one.) When someone died, their SCOBY was divided among friends and family—a continuation of essence through taste. Kombucha was no longer merely consumed; it was communed with. This transparency transformed kombucha from a minority regional curiosity into a universal language. A festival in Brazil might feature ten local interpretations of the same “Golden SCOBY” strain—one brewed with passionfruit, another with cupuaçu, a third with açaí berries. The core microbial signature remained intact, while the terroir of fruit and spice gave each version a unique accent. Brewers didn’t lose their craft—they gained a canvas. Award-winning SCOBYs were the foundations on which endless new flavor experiments flourished. Many people were now as prolific as William Esslinger, the founder of St Louis’s Confluence Kombucha, who was renowned for developing 800 flavors in the 2020s. Code of Symbiosis The Symbiosis Code, ratified at the first World Fermentation Gathering in Reykjavik (2063), bound Fermentation Guilds to three principles: Transparency — All microbial knowledge is to be shared freely. Reciprocity — No brew should be produced without acknowledging the source. Community — Every fermentation must nourish more than the brewer. This code replaced corporate law. It was enforced by reputation, not by governments. A Guild member who betrayed the code found their SCOBYs mysteriously refusing to thrive—a poetic justice the biologists never quite explained. Every Guild had elders—called Mothers of the Jar or Keepers of the Yeast. They carried living SCOBYs wrapped in silk pouches when traveling, exchanging fragments as blessings. These elders became moral anchors of the age, counselors and mediators trusted more than politicians. When disputes arose—over territory, resources, or ethics—brewers, not lawyers, met to share a round of Truth Brew, a ferment so balanced that it was said to reveal dishonesty through bitterness. The Fullness of Time The International Biotech Conference of 2052 invited Luna to give the closing keynote—a controversial decision that prompted several corporate sponsors to withdraw support. The auditorium was packed with supporters, critics, and the merely curious. “Nine years ago, I released genetic sequences for beer yeast strains protected as trade secrets. I was called a thief, a bioterrorist, worse. Today, I want to discuss what we’ve learned from those years of open-source biology.” She displayed a chart showing the explosion of brewing innovation since 2043. “In the traditional corporate model, a few companies control a few strains, producing a limited variety. With the open-source model, thousands of brewers using thousands of variants, producing infinite diversity. As Duff McDonald wrote “Anything that alive contains the universe, or infinite possibility. Kombucha is infinite possibility in a drink.” And the results speak for themselves—flavor innovation accelerated a thousand-fold when we removed corporate control.” A student activist approached the microphone. “Ms. Reyes, you’ve inspired movements to liberate seed genetics, soil bacteria, and traditional medicine cultures. The ‘Luna Legion’ is spreading globally. What’s your message to young people who want to continue this work?” Luna smiled. “First, understand the risks. I was sued by multinational corporations, received death threats, spent years fighting legal battles. This work has costs. Second, be strategic. Release information you’ve generated yourself through legal methods—no hacking, no theft. Third, build communities. I survived because people supported me—legally, financially, emotionally. You can’t fight corporations alone. Finally, remember why you’re doing it: to return biological knowledge to the commons where it belongs. That purpose will sustain you through the hard parts.” Teaching By twenty-eight, Luna was a MacArthur Fellow, teaching fermentation workshops in a converted Anheuser-Busch facility. As she watched her students—former corporate employees learning to think like ecosystems rather than factories—she reflected that her teenage hack had accomplished more than liberating yeast genetics. She had helped humanity remember that flavor, like knowledge, grows stronger when shared rather than hoarded. Luna’s garage had evolved into a sophisticated community biolab. The original jury-rigged equipment had been replaced with professional gear funded by her MacArthur Fellowship. Abuela Rosa still maintained her fermentation crocks in the corner—a reminder of where everything started. A group of five

Starpharma CEO Cheryl Maley joined Steve Darling from Proactive to discuss the company's recent momentum in oncology development and strategic partnerships, underscoring growing commercial and clinical interest in its proprietary dendrimer-based drug delivery platform. Maley explained that Starpharma's technology enables more efficient and targeted drug delivery and has demonstrated significant benefits in oncology. The dendrimer platform is designed to improve the therapeutic performance of medicines while reducing side effects and toxicity, and can be applied across a wide range of molecules, from small-molecule drugs to complex antibodies. She confirmed that Starpharma signed two major agreements in 2025. The first was an exclusive licensing deal with Genentech, valued at up to 860 million Australian dollars plus royalties, focused on a specific and undisclosed area of oncology. The second was a research collaboration with Radiopharm Theranostics that includes an option for exclusivity. In parallel with its partnering activity, Starpharma continues to advance its internal development programs, particularly in radiotherapy. Maley said the company is targeting the entry of these assets into clinical trials in 2026. Starpharma also maintains a strategic relationship with private equity group Medicxi through a joint venture structure. On the commercial front, Maley highlighted the company's plans to grow revenue from its two registered products, VIRALEZE and VivaGel, which are now available in approximately 35 countries. She added that Starpharma currently has three Phase 2 assets in development, with two of those programs actively targeted for licensing. #proaxctiveinvestors #starpharma #asx #spl #otc #sphry #OncologyInnovation #DrugDeliveryTech #BiotechNews #CherylMaley #GenentechPartnership #Radiopharm #VIRALEZE #VivaGel #DendrimerTechnology #PharmaPartnerships #ASXBiotech #ClinicalTrials #BiopharmaUpdates #Medicxi

In this episode of JCO Article Insights, host Dr. Ece Cali Daylan interviews author Dr. Jeffrey Bradley about the article, "Simultaneous Durvalumab and Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer" by Bradley, et al published October 13, 2025. TRANSCRIPT Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO Editorial Fellow. Today I'm joined by Dr. Jeffrey Bradley, Professor of Radiation Oncology at the University of Pennsylvania, to discuss the manuscript, "Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non-Small-Cell Lung Cancer: The Phase III PACIFIC-2 Study." The PACIFIC-2 study was a phase III, double-blind, randomized trial comparing the efficacy and safety of simultaneous durvalumab with concurrent chemoradiation followed by consolidation durvalumab to the concurrent chemoradiation followed by placebo in patients with unresectable stage III non-small cell lung cancer. The primary endpoint was progression-free survival by blinded independent central review. The secondary endpoints were overall response rate, overall survival, and safety. Three hundred twenty-eight patients were randomized 2:1 to durvalumab and placebo, respectively. Unfortunately, this trial did not meet its primary endpoint. There were no statistically significant differences in PFS or OS. The frequency of adverse events was similar between the two arms. Grade 3 or higher adverse events were observed in 53% of the patients in the durvalumab arm compared to 59% of the patients in the placebo arm. Of note, the frequency of pneumonitis was similar in the two arms. Approximately 28% of patients in each arm developed pneumonitis, and about 5% of the pneumonitis observed in each arm was grade 3 or higher in severity. Treatment discontinuation rates secondary to the adverse events were higher in the durvalumab arm, 25% compared to 12%. Adverse events leading to treatment discontinuation and death were more frequently seen in the durvalumab arm during the first four months of the treatment, which corresponds to the simultaneous administration of chemoradiation and durvalumab. Dr. Bradley, before we delve into the results, can you please explain the rationale for this study design and how this concept fits into the current treatment landscape? Dr. Jeffrey Bradley: Yeah, this trial came on the heels of PACIFIC after there was a progression-free survival benefit showed in PACIFIC that in the locally advanced unresectable population that consolidation immunotherapy, in this case durvalumab, had a progression-free survival benefit. A number of us in the clinical trial space thought to add concurrent immunotherapy in addition to consolidation immunotherapy that that would also improve outcomes for patients. So a number of trials were launched to follow up of PACIFIC. In this case, this is a phase III trial where the control arm was placebo. There was no overall survival results yet from PACIFIC, just a PFS benefit, and a number of countries across the world had not approved maintenance durvalumab in this space. So this trial looked at the experimental arm, which was concurrent immunotherapy, durvalumab, and chemoradiation followed by consolidation durvalumab versus placebo. Dr. Ece Cali: And if we were to focus on the safety profile first, an increased pneumonitis risk was a theoretical concern when immunotherapy is given concurrently with radiation. Do we see any major differences in the safety profile between the two arms in this trial? Dr. Jeffrey Bradley: No, and we were concerned about the addition of concurrent immunotherapy and chemoradiation, like you said, towards concern about increased pneumonitis rate, but we did not see increased pneumonitis in the experimental arm over placebo. And the grade 3 or higher, as you said, it was roughly 5%, more or less, in both arms, so we didn't see increase in pneumonitis toxicity with concurrent IO and chemoradiation. Dr. Ece Cali: But interestingly though, despite the lack of significantly increased toxicity with durvalumab, unfortunately, administering immunotherapy simultaneously with chemoradiation therapy did not improve survival. Lack of superiority of this treatment regimen, as you mentioned, is further confirmed across multiple similar negative trial readouts such as ECOG-ACRIN 5181 and CheckMate 73L. Dr. Bradley, in your view, what are some potential explanations for why this strategy did not pan out in clinical trials? Dr. Jeffrey Bradley: Regarding toxicity, let me go back and point out that we did see an increased number of immune-mediated adverse events. It was 34.7% in the concurrent immunotherapy arm versus 15.7% in the placebo arm. So that led to a higher number of discontinuations of immunotherapy which I think probably had an effect. So we didn't... there was an increased pneumonitis toxicity, but there were expected immune-mediated toxicities that caused people to stop giving immunotherapy. You can see that in the PFS curves. They were, you know, they crossed over after like a month, but initially there was lower PFS for the experimental arm, and then the experimental arm got better after we divided into four months, before four months and after four months. Dr. Ece Cali: For one reason or another, it looks like the simultaneous administration did not really improve outcomes. We now know that simultaneously giving them another concurrent radiation should really no longer be pursued in clinical trials for this patient population. Can you share with our audience what strategies are being studied in this setting and what trials to watch out for in the future? Dr. Jeffrey Bradley: Sure, I think when you add concurrent radiation to immunotherapy, there were more central tumors in this trial, I think you're killing lymphocytes and negating the effect of immunotherapy. So I think that's the smoking gun for this trial, for the ECOG trial, for the small cell trial that NRG reported, LU005, and other trials. So correct, I don't think there's any need to continue to pursue concurrent immunotherapy in this space of lung cancer. But that's not to say there aren't many other trials that are either ongoing, have accrued and awaiting results, or being planned for the next phase of clinical trials. We have a trial within NRG Oncology called NRG-LU008. It's a randomized phase III trial that is using an SBRT boost to a peripheral primary and chemoradiation to the nodes, because the primary tumor is the one that fails more often than the lymph nodes, and that's compared to PACIFIC in the control arm. PACIFIC-9 is another trial in the same line as the other PACIFIC trials. That one is using dual checkpoint inhibition versus the control arm being PACIFIC. So there are three arms in that trial, durva and oleclumab, durva and monalizumab versus the PACIFIC arm. And that trial is completed accrual, but we have no results from that study yet. Johnson & Johnson has a trial open looking at a nanoparticle. That's a radiosensitizer where bronchoscopy is used to inject the primary tumor and the lymph nodes with a radiosensitizer. That's a randomized phase ll trial that's ongoing. It's got three arms, two different doses of this radiosensitizing drug and then a control arm without injection at all. The control arm is again the PACIFIC arm. And then those of us within the NCI-based clinical trials evaluation program, CTEP, are proposing an intergroup trial that would compare induction chemo-immunotherapy followed by chemoradiation followed by maintenance immunotherapy versus PACIFIC in a phase III study. So I think there's other trials that are either completed, ongoing completed, or on the horizon to assess in this patient population. Dr. Ece Cali: Yeah, we definitely have an unmet need to improve survival outcomes for stage III patients, and it's great to hear that there are so many efforts looking at different strategies to improve outcomes for these patients.  Thank you so much, Dr. Bradley, for this informative discussion and for sharing your insights. Any last thoughts? Dr. Jeffrey Bradley: Yeah, we need something, you know. PACIFIC was first reported in 2017, and we really haven't made progress in terms of changing that standard of care control for the last eight years. So we need progress in this area. Dr. Ece Cali: Yep, definitely. Thank you so much for joining, Dr. Bradley.  And thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. DISCLOSURES Dr. Bradley Honoria: Mevion Medical Systems, Inc. Consulting or Advisory Role: Varian, Inc, Genentech, Inc. Research Funding: Varian Medical Systems Dr. Cali Research Funding Company: BeiGene, Nuvalent, Inc., Astra Zeneca 

This is one in a series about possible futures, which will be published in Booch News over the coming weeks. Episode 6 appeared last week. New episodes drop every Friday. Introduction Legacy beverage corporations attempting hostile takeovers of kombucha startups failed to understand the living systems involved. Their sterile production methods eliminated beneficial microorganisms, while regulatory capture backfired as health authorities mandated probiotic content. Mega-Cola’s final CEO, James Morrison, desperately tried fermenting cola using SCOBYs, creating undrinkable disasters. This episode chronicles the corporation’s transformation from global giant to urban composting service, with former executives becoming mushroom farmers in Detroit’s abandoned factories. The $49 Billion Graveyard: When Giants Couldn’t Learn to Dance Harvard Business School’s legendary case study “The Mega-Cola Kombucha Catastrophe” became required reading for understanding how industrial thinking proved fatal in the biological economy. Between 2035 and 2042, legacy beverage corporations spent $48.7 billion attempting to acquire kombucha startups, only to discover that living systems couldn’t be purchased—they could only be cultivated. Mega-Cola’s acquisition spree began aggressively in 2035 under CEO James Morrison, a chemical engineer before ascending to the C-suite. He’d once loved the alchemy of bubbles and sweetness. His father had worked at a bottling plant; he’d grown up thinking carbonation was progress. He viewed kombucha as merely another “disruption” to be absorbed and had become a champion of “hydration portfolios”—a polite euphemism for diversifying out of soda into teas, waters, and ferments. The company spent $12.7 billion acquiring 47 kombucha brands, from market leader Health-Ade to smaller artisanal producers like Portland’s Brew Dr Kombucha. Morrison’s strategy seemed logical: leverage Mega-Cola’s distribution network and manufacturing scale to dominate the emerging probiotic market. The Sterilization Disaster The first catastrophic failure occurred when Mega-Cola attempted to scale Humm Kombucha production at its Oregon facility. Morrison stood before a 10,000-gallon fermentation tank—ten times the size of any used by the acquired kombucha companies. Chief Science Officer Dr. Hiram Walsh explained the modifications they’d made. “We’ve adapted our quality control protocols from our soft drink lines,” Walsh said proudly. “Every input is filtered, pasteurized, and chemically treated. We’ve eliminated 99.9% of microbial contamination risk.” Walsh pulled up charts showing their testing results. “Batch consistency is perfect. Zero deviation. Every bottle identical.” Morrison smiled. “Exactly what we wanted. When do we start distribution?” “Next week,” Walsh confirmed. “We’re calling it MegaBucha. Focus groups love the name.” One week later, Morrison sat in an emergency meeting. The first consumer feedback was catastrophic. Walsh read from report after report: “‘Tastes like carbonated vinegar.’ ‘Chemical aftertaste.’ ‘Nothing like real kombucha.’ ‘Dead and flat.’ Return rates are 87%.” Walsh looked confused. “I don't understand it. The bacteria counts are perfect. We followed their recipes exactly.” On the teleconference screen, Health-Ade founder Vanessa Dew shook her head. “You killed it. Your ‘quality control’ eliminated every living organism. Kombucha isn’t about sterility—it’s about controlled biological diversity. You can’t pasteurize and filter kombucha and expect it to remain the same. You’ve simply made acidic sugar water.” Morrison spluttered, “We spent $2.1 billion acquiring your company. We’re not walking away because of ‘quality control’ issues.” “It’s not quality control—it’s biology,” Vanessa explained. “Kombucha cultures need biodiversity to thrive. Your system is built to prevent exactly that.” Morrison’s jaw tightened. “Then we’ll adjust the process. Keep some bacteria alive.” Vanessa sighed. “Your entire facility is designed to kill microbes. Your pipes, your tanks, your air filtration, your worker protocols—everything optimized for sterility. You’d have to rebuild from scratch. And even then, you’d need to fundamentally rethink how you approach production. Living systems don’t work like machines.” The company had overlooked the success of the UK’s ROBOT Kombucha, the “A.I. Cola” replicated cola’s taste in a fermented drink, becoming the beverage of choice for adults who had first tasted it as teenagers when it was introduced in 2025. Founder Pascal du Bois had selected his ingredients from a range of different organic botanicals from which the flavor was extracted. He then created a complex blend of more than a dozen types of bacteria and four strains of organic yeast. After fermenting for seven weeks they add a teaspoon of 100% organic honey, sourced from France, to each can. This mimics the familiar cola taste without added sugars or aspartame. The result was a healthy alternative designed to appeal to cola lovers, not a standardized Frankenbooch. Dr. Kenji Nakamura—the former Genentech researcher who later founded the Eastridge Mall Kollective—was hired as a $5 million consultant to solve the Mega-Cola problem. His report sat on Morrison’s desk—200 pages detailing why Mega-Cola’s approach couldn’t work. “I’ll cut to the conclusion,” Nakamura said. “Your industrial infrastructure is fundamentally incompatible with living beverages. Your entire supply chain is designed to kill exactly what makes kombucha valuable.” Morrison leaned forward. “We paid you to find solutions, not problems.” “The solution is accepting that some things can’t be industrialized,” Nakamura replied calmly. “Kombucha succeeds because of microbial relationships that develop over time through careful cultivation. You’re trying to force-manufacture relationships. It’s like trying to raise children in a morgue—the environment is hostile to life. Your kombucha tastes bad because you’ve optimized the life out of it. You can’t ‘optimize’ life—you can only cultivate it.” Mega-Cola CFO Samantha Chen pulled up financial projections. “We’ve now spent $14.8 billion on kombucha acquisitions and infrastructure. We need to either make this work or write off the entire investment.” Nakamura shook his head. “Every dollar you spend trying to industrialize kombucha is wasted. The companies you acquired succeeded because they were small—they could maintain microbial diversity, respond to batch variation, cultivate living systems. Scale destroys those advantages.” Morrison’s face reddened. “Are you telling me that a bunch of hippies in Portland can do something Mega-Cola, with our resources and expertise, cannot?” “Yes,” Nakamura said simply. “Because they’re not trying to dominate biology. They’re partnering with it. Your entire corporate culture is about control, optimization, standardization. Living systems require adaptation, diversity, patience. Those are fundamentally incompatible approaches.” Morrison stood. “We’ll find someone else. Someone who can make this work.” Nakamura gathered his materials. “You’ll spend millions more reaching the same conclusion. Biology doesn’t care about your quarterly earnings or your market cap. You can’t buy your way out of this.” After Nakamura left, Morrison and Chen sat in silence. Chen finally spoke. “He’s right, you know.” Morrison didn’t respond. The Regulatory Trap: When Capture Became Captivity Legacy corporations had initially celebrated the FDA’s Probiotic Verification Act of 2038, which they had lobbied for extensively. The law required all “live beverage” products to contain minimum concentrations of beneficial bacteria, verified through independent testing. Mega-Cola’s legal team believed this would create barriers for small producers while giving large corporations with deep pockets competitive advantages through regulatory compliance costs. The strategy backfired catastrophically. While artisanal kombucha producers thrived under the new standards—their naturally diverse microbial ecosystems easily exceeded requirements—corporate products consistently failed testing. Mega-Cola spent $20 million on fermentation consultants and biotechnology acquisitions, but its sterile facilities couldn’t maintain the mandated bacterial diversity. Meanwhile, in the company boardroom, a tense meeting took place. Chen read the headline from a Wall Street Journal article: “Mega-Cola’s ‘Kombucha’ Contains Fewer Probiotics Than Yogurt, FDA Testing Reveals.“ Morrison stared at the headline. “How did this happen?” “Our sterilization processes,” Walsh admitted. “We can’t maintain bacterial counts through our production and distribution systems. The small producers can because they’re working with robust, diverse cultures in small batches. We’re working with weakened, standardized cultures in massive volumes. The bacteria die.” The legal counsel shifted uncomfortably. “The regulation we pushed for is now our biggest problem. We can’t legally call our product kombucha. We could petition the FDA to lower the standards—” Morrison’s voice was quiet. “How much have we spent trying to fix this?” Chen checked her tablet. “$20.3 million on fermentation consultants and biotechnology acquisitions. None of it worked.” The Medical Tsunami: Soda as Poison By 2040, the medical evidence against sugar-laden sodas had become overwhelming. The American Heart Association officially classified high-fructose corn syrup as a “Class II toxin,” requiring warning labels similar to tobacco. The crisis came to a head when the Journal of the American Heart Association published “The Corporate Diabetes Epidemic: A Century of Metabolic Warfare” in 2041. The paper demonstrated that diabetes and obesity rates directly correlated with Mega-Cola’s market penetration across 147 countries. Areas with higher Cola consumption showed disease patterns resembling chemical contamination rather than natural illness. Dr. Harold Lustig presented twenty years of longitudinal research to a packed auditorium. The screen behind him showed stark data: “Regular soda consumption increases diabetes risk by 340%. It shortens lifespan by an average of 7.4 years. We’re officially classifying high-fructose corn syrup as a Class II toxin, requiring warning labels similar to tobacco.” Mega-Cola CEO Morrison watched from the back. His phone buzzed constantly—board members, investors, media requesting comment. Lustig continued: “Children who drink one soda daily show measurable delays in brain development compared to peers consuming fermented beverages. Brain imaging reveals high-fructose corn syrup literally shrinks the prefrontal cortex.” A reporter raised his hand. “Are you saying soda causes brain damage?” “I’m saying the evidence strongly suggests regular soda consumption impairs cognitive development,” Lustig responded. “Meanwhile, children consuming diverse fermented foods show superior health outcomes across every metric we measured.” Morrison left before the Q&A. In the hallway, CFO Chen was waiting. “The stock dropped 12% during the presentation,” she said quietly. “Investors are calling soda ‘the new tobacco.'” Morrison stared out the window at the Washington Monument. “We knew sugar was problematic. We’ve been reformulating—” “It’s not just sugar,” Chen interrupted. “It’s the entire category. Industrial beverages versus living fermentation. We’re on the wrong side.” “We’re a $300 billion company,” Morrison said. “We can’t just pivot to kombucha. We tried that. It failed.” Chen’s voice was gentle but firm. “Then maybe we need to accept that some companies don’t survive paradigm shifts.” The Educational Exodus: Schools Declare War on Soda The Los Angeles Unified School District’s vote to ban all non-fermented beverages in schools attracted phalanxes of Mega-Cola lobbyists and lawyers. A Mega-Cola representative presented their case: “Banning our beverages punishes students from low-income families who can’t afford expensive alternatives. We’re prepared to offer healthier formulations—” A parent cut him off. “You’ve been promising ‘healthier formulations’ for thirty years while marketing addictive sugar-water to our children.” Dr. Rebecca Scharf's groundbreaking research demonstrated that children who were given an alternative to sugar-sweetened soda were healthier. The school district called her as an expert witness. She summarized her findings: “Two years after schools switched to kombucha dispensaries with on-campus fermentation labs, we see 67% reduction in behavioral problems, 45% improvement in test scores, 89% decrease in childhood obesity.” A high school student approached the microphone. “I’m sixteen. I grew up drinking your soda. I was diagnosed with pre-diabetes at fourteen. Since switching to fermented beverages, my health has improved. But my little brother is eight—he’s never had soda, only fermentation. He’s healthier than I ever was. You took my health. Don’t take his.” By 2052, 43 states had implemented similar bans. The “Fermentation Generation”—children who grew up drinking school-provided kombucha—showed dramatically superior health outcomes compared to predecessors who consumed soda. These children literally rejected Mega-Cola on a physiological level; their optimized gut microbiomes found industrial beverages repulsive. Medical Prescriptions Against Corporate Beverages The American Academy of Pediatrics’ 2044 guidelines required doctors to “prescribe against” soda consumption, treating it as seriously as smoking cessation recommendations. Insurance companies began covering kombucha prescriptions while penalizing patients who tested positive for high-fructose corn syrup consumption. Dr. Chen’s research (detailed in Episode 2) provided the scientific foundation for these medical interventions. Her studies proved that even occasional soda consumption disrupted the personalized gut microbiomes that enabled optimal cognitive function. Doctors began prescribing specific kombucha strains to repair metabolic damage caused by years of consuming industrial beverages. Morrison’s Tower Disaster: Industrial Control Meets Living Systems Following his 2050 visit to Aberdeen’s agricultural tower, Morrison commissioned twelve “MegaTower” facilities across North America, investing $8.4 billion in what he called “industrial-scale fermentation infrastructure.” His engineers replicated the physical structure perfectly—1,200-meter climate-controlled spires with alternating tea cultivation and kombucha production floors. The catastrophe unfolded within months. Morrison’s towers, designed for efficiency optimization, automated every process that Aberdeen’s workers performed intuitively. Computer algorithms regulated temperature, humidity, and nutrient delivery with microsecond precision, eliminating “human inefficiency.” The tea plants withered. The SCOBYs died. Dr. MacLeod’s warnings proved prophetic: Morrison had copied the machinery while killing the ecosystem. His sterile protocols eliminated the beneficial fungi, bacteria, and insects that made Aberdeen’s floors function as living environments. His “optimized” nutrient solutions lacked the complexity of naturally composting tea waste. His automated systems couldn’t respond to the subtle biological cues that experienced cultivators recognized instinctively. By 2053, all twelve MegaTowers stood empty—$8.4 billion monuments to the fundamental incompatibility between industrial control and biological partnership. The failure accelerated Mega-Cola’s eventual bankruptcy, proving that living systems cannot be purchased; they can only be cultivated. Morrison’s Desperate Gambit: Fermented Cola Stung by his failed “MegaTower” experiments, Morrison staked Mega-Cola’s survival on developing fermented cola using modified SCOBYs. The “New Cola Kombucha” project consumed $67 million over three years, employing thousands of microbiologists and fermentation specialists. The results were universally catastrophic. Dr. Park, a fermentation specialist hired from Korea, led Morrison through the lab. Rows of fermentation vessels bubbled with dark liquid. Scientists monitored bacterial counts, pH levels, sugar content. “We’ve engineered SCOBY cultures that can ferment in the presence of cola flavorings,” Park explained. “It’s taken three years, but we have a stable culture.” Morrison looked hopeful for the first time in years. “And it tastes good?” Park hesitated. “It tastes… interesting.” They entered a tasting room where twenty focus group participants sat with cups of dark, fizzy liquid. Morrison watched through one-way glass as participants tasted the fermented cola. The reactions were immediate and universal: grimacing, coughing, one person actually gagged. “Fizzy coffee grounds mixed with cleaning products,” one person said. “Like someone fermented tire rubber,” another offered. “I think I can taste failure,” a third concluded. Park pulled Morrison aside. “The SCOBY cultures are stressed by the chemical additives in cola formulation. They’re producing unusual compounds—not toxic, exactly, but profoundly unpleasant. They’re causing gastrointestinal distress in 89% of test subjects.” Morrison stared at the focus group, then turned to Park. “Give me options. Can we adjust the flavor profile? Different additives?” “We’ve tried 47 formulations,” Park explained. “The problem isn’t the recipe—it’s the fundamental incompatibility between cola chemistry and healthy fermentation at this scale. The bacteria are literally stressed by the environment we’re asking them to live in.” “So what you’re telling me is that fermented cola is impossible?” Park hesitated. “I’m telling you that your version of fermented cola—one that tastes like Mega-Cola but contains living bacteria—is impossible. If you were willing to let go of the cola formula entirely and create something new…” “Then it wouldn’t be Mega-Cola,” Morrison insisted. “That’s what I’m trying to save.” Morrison sank into a chair. “How much have we spent on this?” “$67 million,” Park confirmed. “And it’s undrinkable.” “Yes.” Morrison laughed bitterly. “We can put a man on Mars, but we can’t ferment cola.” Park’s voice was kind. “We can’t ferment cola because we’re trying to put it on Mars. Fermentation requires accepting biology on its own terms. We keep trying to force it into our industrial model. Biology keeps refusing.” The FDA’s emergency recall of Morrison’s prototype batches in 2059 triggered the final collapse of investor confidence. The Bankruptcy Cascade: Industrial Liquidation Mega-Cola declared bankruptcy on November 1, 2060—the Mexican Day of the Dead seemed grimly appropriate for the death of an American institution. The company’s $284 billion in debts exceeded its assets by a factor of three, as brand value evaporated alongside consumer demand. The company was not alone. BigSoda collapsed six months later, then Dr Gipper —the third-ranking cola in the world —creating a cascade of corporate failures worth over $1.2 trillion. Morrison sat alone in his office as the board meeting proceeded via video conference. The board chair spoke: “The FDA has issued an emergency recall of all New Cola Kombucha prototypes after test subjects required hospitalization. Our stock price has fallen 89% from its peak. Our debt exceeds assets. We have no choice.” Morrison knew what he must announce. “Mega-Cola Corporation is filing for Chapter 11 bankruptcy protection, effective immediately.” On screens across America, news anchors delivered the story. Morrison watched employees leave the building carrying boxes. Fifty thousand jobs ending. A century-old brand dying. Chen entered his office quietly. “I’m sorry, James.” Morrison didn’t turn from the window. “You tried to warn me. Back in 2035. You asked if we could industrialize biology without killing what made it valuable.” “I did.” “The answer was no.” “I guess I just didn't listen.” Morrison was quiet for a long moment. “I spent my whole career optimizing systems, maximizing efficiency, scaling operations. I was good at it. But biology doesn’t care about efficiency. It cares about diversity, resilience, relationships. Everything I knew how to do was wrong for this.” Chen sat beside him. “What will you do now?” Morrison laughed without humor. “I’m 62 years old. My entire career has been corporate optimization. I don’t know how to do anything else.” “You could learn,” Chen suggested. “Learn what?” Morrison asked. “How to brew kombucha in my garage? I destroyed people’s livelihoods trying to industrialize something that shouldn’t be industrialized. I don’t deserve to be part of what comes next.” “Maybe that’s exactly why you should be,” Chen said softly. “You understand what doesn’t work. That’s valuable knowledge.” The liquidation auctions became symbols of industrial obsolescence. Mega-Cola’s Detroit headquarters sold for $47 million to the Georgia Fermentation Kollective, which converted the building into vertical kombucha gardens. The iconic “Land of Cola” museum became the “Museum of Metabolic Harm,” displaying artifacts from humanity’s sugar-addiction era alongside warnings about corporate food manipulation. Urban Composting: From Soda to Soil Morrison’s personal transformation paralleled that of his company. After Mega-Cola’s bankruptcy, he founded “Regenerative Detroit,” converting abandoned bottling plants into urban composting facilities that produced soil for vertical tea gardens. His memoir, From Syrup to SCOBY: A CEO’s Redemption, became a bestseller, chronicling his journey from corporate predator to ecological steward. Nakamura, the consultant who told Morrison his approach would fail, visited the facility. “You were right,” Morrison said without preamble. “Everything you said in that meeting. I spent five more years and hundreds of millions trying to prove you wrong, only to end up proving you right.” Nakamura watched Morrison teach a teenage girl how to inoculate a growing medium with mushroom spores. “This is unexpected. I thought you’d retire to a beach somewhere, try to forget.” Morrison laughed. “I tried that for six months. I was miserable. Spent forty years destroying things. Figured I should spend whatever time I have left trying to build something.” “Why composting?” “Because it’s the opposite of what I did at Mega-Cola,” Morrison explained. “There, we tried to force sterility, eliminate variability, control every process. Here, we cultivate diversity, encourage complexity, work with biological systems rather than against them. We take waste and transform it into something useful. It’s… healing, I guess.” A teenager approached. “Mr. Morrison, my mushrooms are growing!” Morrison’s face lit up. “Let me see!” He examined her cultivation tray with genuine excitement. “Beautiful! You maintained perfect humidity. These will be ready to harvest in two weeks.” After the children left for lunch, Nakamura and Morrison walked through the facility. “How many people work here?” Nakamura asked. “Forty-seven,” Morrison responded. “Thirty-two are former Mega-Cola employees. When the company collapsed, they lost everything. I felt responsible. So I used what was left of my savings to buy this facility and train them in regenerative agriculture.” “And the composting is profitable?” Morrison shrugged. “We break even. Barely. But that’s not really the point. The point is transforming industrial waste into living soil. The point is teaching the next generation that decay isn’t the enemy—it’s the beginning of new life. The point is learning to think like an ecosystem instead of a corporation.” They stopped before a wall displaying Morrison’s memoir: From Syrup to SCOBY: A CEO’s Redemption. “I read your book,” Nakamura said. “Brutal self-assessment.” “Had to be,” Morrison replied. “I spent decades helping build a system that made billions by making people sick. If I’m going to do anything meaningful with the rest of my life, I need to be honest about what I did wrong.” Nakamura gave him a piercing look. “What’s the hardest lesson, James?” Morrison thought for a moment. “That you can’t buy relationships. Mega-Cola tried to purchase kombucha companies and force them into our industrial model. But the reason those companies succeeded was because they maintained living relationships—between bacteria, between brewers and their cultures, between producers and customers. We thought we could commodify those relationships. We were wrong.” Nakamura looked into the other man’s eyes. “Do you regret your career at Mega-Cola?” “Every day,” Morrison said. “But regret without action is just self-pity. I can’t undo the harm I caused. I can only try to spend whatever time I have left doing things differently.” The two men stood silent. “And now?” Nakamura eventually asked. “Now I’m learning that the same principle applies to everything. Healthy soil requires relationships between millions of organisms. Healthy communities require relationships between people. You can’t manufacture relationships. You can only cultivate them.” A former Mega-Cola executive, now managing the composting operation, approached. “James, the new batch is ready. Want to check it?” They walked to a massive composting area where industrial waste had been transformed into rich, dark soil. Morrison picked up a handful, letting it sift through his fingers. “Five years ago, I couldn’t have told you what healthy soil looked like. Now I can diagnose it by touch, smell, and sight. I know the difference between soil that’s alive and soil that’s dead. I wish I’d learned that forty years ago.” Business School Autopsies: Failed Integration Studies Mega-Cola’s failed acquisitions became business school case studies teaching a fundamental lesson about the new economy: you couldn’t buy biological relationships, only nurture them. Companies that thrived in the fermentation future were those that learned to think like ecosystems rather than machines, valuing symbiosis over extraction and cooperation over control. The old extraction-based capitalism of brands, advertisements, and artificial scarcity had dissolved in the acid of transparency. In its place rose a commerce of connection, a network of exchange based on trust, craft, and living value. No one “sold” kombucha anymore. They shared it—encoded with local identity, story, and microbial lineage. Each brew was a living signature, traceable back to the brewer’s SCOBY ancestry through transparent bio-ledgers—open microbial blockchains that recorded not profits, but relationships. Harvard Business School’s legendary case study “The Mega-Cola Kombucha Catastrophe” had become required reading for understanding how industrial thinking fails when confronting biological complexity. Professor George Santos—a reformed fraudster turned champion of ethical business studies at Harvard—projected key figures on his classroom screen summarizing the Mega-Cola meltdown: $48.7 billion spent on kombucha acquisitions and infrastructure Zero successful products launched 94% loss of beneficial bacteria in acquired brands Complete corporate collapse within 15 years Morrison sat in the audience, invited as a guest speaker. The students didn’t know he was there yet. Santos lectured: “Mega-Cola’s failure wasn’t about lack of resources or expertise. They had the best food scientists, unlimited capital, and a dominant market position. They failed because they tried to apply industrial logic to biological relationships. It’s a category error—treating living systems like machines.” A student raised her hand. “But couldn’t they have just left the kombucha companies independent? Kept them small-scale?” “Good question,” Santos responded. “But that would have defeated the purpose of the acquisition. Morrison wanted to leverage industrial efficiency to dominate the market. He couldn’t accept that efficiency itself was the problem.” “Sounds arrogant,” another student said. “It was,” Morrison spoke from the audience. “Unforgivably arrogant.” The room went silent as students realized who he was. Santos smiled. “Class, we have a special guest. Mr. Morrison has agreed to discuss his decisions and their consequences.” Morrison walked to the front slowly. At 72, he looked older than his years. “I’m here because Professor Santos asked me to help you understand how intelligent, well-intentioned people can make catastrophic mistakes,” Morrison began. “In 2035, I was confident, even cocky, firmly believing we could apply our industrial processes to kombucha. I have degrees from Wharton and McKinsey experience. I’d successfully optimized dozens of operations. I didn’t see kombucha as a challenge—I saw it as an opportunity.” “What changed?” a student asked. “Repeated failure,” Morrison said simply. “We acquired kombucha brands. We killed them by trying to scale them. We hired consultants. They told us what we were doing wrong. We didn’t listen. We tried to ferment cola using SCOBYs. We created undrinkable disasters. Eventually, even I couldn’t ignore reality: you can’t industrialize living relationships.” “Why not?” another student challenged. “We industrialize lots of biological processes. Agriculture, pharmaceuticals—” “Different scale, different complexity,” Morrison explained. “Kombucha requires dozens of organisms in complex relationships. You can’t standardize that without destroying what makes it work. And more fundamentally, I didn’t respect what I was trying to control. I saw bacteria as inputs to be optimized, not as living partners to be cultivated. That disrespect guaranteed failure.” Samantha Chen, sitting in the back, spoke up. “I was Mega-Cola’s CFO. I warned James from the beginning that we were trying to commodify relationships. He didn’t listen until we’d burned through billions and destroyed the brands we’d acquired. The lesson isn’t just about fermentation—it’s about recognizing when your core competencies are incompatible with what you’re attempting.” A student asked the obvious question: “Mr. Morrison, you lost billions of dollars and collapsed a century-old company. Why should we listen to you?” Morrison smiled sadly. “Because I failed spectacularly at something many of you will attempt: forcing biological systems into industrial models. Climate change, environmental restoration, and sustainable agriculture—you’ll all face situations where industrial thinking fails. If hearing about my failures helps even one of you recognize that trap earlier, then bankrupting Mega-Cola will have served some purpose.” Cola Coda The demise of Mega-Cola and Morrison's redemption was celebrated in song by a young group of Baltimore kombucha brewers whose anthem ‘It's an Unreal Thing' was played on college radio stations by retro-70's leather-jacketed DJ's with pierced ears. Here’s Hexotronix: Go now, take what you think will lastBut whatever you wish to keep, you better grab it fastAll your failed investments, they’re all going homeYour fermentation formula had the wrong biomeYour scientists who just walked out the doorHave taken all their SCOBYs from the brewery floorThe towers too have failed to come throughAnd now it's time to go find something new. [Chorus]You sold your soda to a worldThat you thought you'd taught to singIn perfect harmonyBut it's an unreal thing, an unreal thing. You bought up all our breweries, didn't you?Your fake fermented drinks just didn't come through .You killed what made kombucha realSo how does it feelTo be completely unreal?How does it feelTo be a joker?How does it feelTo be a bankrupt, down at heel?With the whole world laughingAt your soda? [Chorus] Your beverage was a bustYour dreams all turned to dustThe missing partWas our SCOBY heartRight there at the startBut you didn't seeWhat we sawDidn't feelWhat we feltDidn't knowWhat we knewDidn't loveWhat we loved. [Chorus] Leave your corporate life behind, something calls for youThe dream that you once had is clearly through.Forget the drinks you've served, they will not follow youGo tell another story start anewThe compost and mushrooms, they now call to you. [Chorus] Epilogue: The Next Discovery Morrison’s transformation from CEO to mushroom farmer illustrates that recognizing failure honestly opens paths to genuine learning. His redemption isn’t about success—it’s about accepting that some approaches are fundamentally wrong and committing to something different. However, one man’s transformation was only the beginning. While corporate executives struggled to understand living systems, a brilliant citizen scientist was making discoveries that would prove the human brain itself required biological partnerships to reach its full potential. Check back next Friday as the gripping tale of ‘Our Fermented Future’ continues. Disclaimer This is a work of speculative fiction. Names, characters, businesses, events, and incidents are the product of the author's imagination, assisted by generative A.I. References to real brands and organizations are used in a wholly imaginative context and are not intended to reflect any actual facts or opinions related to them. No assertions or statements in this post should be interpreted as true or factual. Audio Listen to an audio version of this Episode and all future ones via the Booch News channel on Spotify, Apple Podcasts, or wherever you get your podcasts. If you just want to listen to the music (classic 80’s punk!) tune in as follows: Hexotronix, It’s an Unreal Thing, 36:17 Lyrics ©2025 Booch News, music generated with the assistance of Suno. The post Our Fermented Future, Episode 7: Corporate Death Spiral—How Cola Became Compost appeared first on 'Booch News.

Sandra Walker is CEO, Viacern Group, and Venture Partner at Hard Climate, a seasoned and inspirational pharma and biotech executive leading Commercial, Medical Operations and Excellence, Government Affairs, Global Strategy and Product Planning at companies such as Genentech, Roche, Eli Lilly and Abbvie. She delivered a state-of-the-art, candid, and intriguing keynote presentation that forces you to reflect on the language and process you use to make decisions in medicine, healthcare, and how you can challenge your current approaches and biases using neuroscience-based practical, real-world solutions to make bolder decisions with evidence to drive innovation forward.3:10 Speaker Introduction4:12 Turning Innovation into OutcomesThree Common recurring Decision PatternsExplaining Biases in Decision-makingPractical Solutions to Transform DecisionsThe Bolder WayDecision Audit5:56 Three Invisible Decision Patterns6:37 Status Quo Bias8:51 Countermoves You Can Use vs Status Quo Bias9:29 Confirmation Bias11:54 10-Minute Challenge Round To use Vs. Confirmation Bias 13:09 Completion Bias - Relief of Feeling Done16:30 Explaining the Brain under Pressure with Neuroscience 18:50 How to Quiet the Noise in BiasLabel the state – identify the bias, problem, riskExternalize thinking – move ideas onto paper to createpublic reasoningTeach the cheerleader to celebrate learning not justfinishing.Train for Learning not Finishing21:01 The Bolder Way - 6 steps to turn Awareness into ActionB - Bias and Blind Spots visualization (see the invisible)O - Observe: Disciplined CuriosityL - Learn: Broadened PerspectivesD - Decide with clarity and transparencyE - Empower: Trust with ContextR - Recalibrate: Boldness into Learning27:11 Bolder Way Framework Aligned to the Scientific Method 28:02 Language You Use is Key to Decision Outcome28:38 The Decision Audit to Deliver Clarity in 5 Minutes31:09 How Speed of Decision Impacts the Outcome

On this episode Gil Bashe and Gregg Masters engage Dennis Purcell, founding partner of Aisling Capital and architect of the original H&Q Life Sciences Conference that became the go to industry standard J.P. Morgan Healthcare Investor Conference. Purcell reflects on four decades of biotech investing—from Genentech's 1980 IPO to today's GLP-1 metabolic revolution. He unpacks capital cycles, the role of purpose-based investors, and the moral call to redirect innovation toward chronic disease and global health equity. To stream our Station live 24/7 visit www.HealthcareNOWRadio.com or ask your Smart Device to “….Play Healthcare NOW Radio”. Find all of our network podcasts on your favorite podcast platforms and be sure to subscribe and like us. Learn more at www.healthcarenowradio.com/listen

Two venture capitalists dissect why biotech burns billions while China runs trials in weeks—and why the next Genentech won't look anything like the last one. Elliot Hershberg reveals the "three horsemen" strangling drug development as costs explode to $2.5 billion per approval, while Lada Nuzhna exposes how investigator-initiated trials in Shanghai are rewriting the competitive playbook faster than American founders can file INDs. When the infrastructure that built monoclonal antibodies becomes the commodity threatening to hollow out an entire industry, the only path forward demands inventing medicines that are literally impossible to make without tools that don't exist yet—and they're betting everything on which approach survives. Resources:Follow Jorge on X: https://x.com/JorgeCondeBioFollow Lada on X: https://x.com/ladanuzhnaFollow Elliot on X: https://x.com/ElliotHershbergFollow Erik on X: https://x.com/eriktorenberg Stay Updated: If you enjoyed this episode, be sure to like, subscribe, and share with your friends!Find a16z on X: https://x.com/a16zFind a16z on LinkedIn: https://www.linkedin.com/company/a16zListen to the a16z Podcast on Spotify: https://open.spotify.com/show/5bC65RDvs3oxnLyqqvkUYXListen to the a16z Podcast on Apple Podcasts: https://podcasts.apple.com/us/podcast/a16z-podcast/id842818711Follow our host: https://x.com/eriktorenbergPlease note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.   Stay Updated:Find a16z on XFind a16z on LinkedInListen to the a16z Podcast on SpotifyListen to the a16z Podcast on Apple PodcastsFollow our host: https://twitter.com/eriktorenberg Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Avoidance has long been the standard for managing food allergies. But new options, such as oral immunotherapy (OIT) and biologic medications like Xolair (omalizumab), are changing the landscape. With more choices available, many patients and parents are wondering how to start the conversation with their allergist and what questions to ask. Kortney and Dr. Payel Gupta talk with Dr. Shahzad Mustafa, a board-certified allergist and immunologist, about how patients can navigate today's food allergy treatments with confidence. Together, they explore what to consider before starting OIT or Xolair, how to set realistic expectations, and why strict avoidance is still the right choice for many families. What we cover about food allergy treatment options: Food Allergy Avoidance: Why it remains an effective and valid approach for many, and how to make it work in daily life, including the nuances that make every case unique. Oral Immunotherapy (OIT): What it involves, who it's best suited for, and what families should know about time, cost, and safety. Xolair (omalizumab): How this injection therapy works to reduce reactions from accidental exposures and what it doesn't do. Setting expectations: How to talk with your allergist about your goals, quality of life, and what “success” really looks like. More episodes about food allergies Ep. 129: Omalizumab for Multiple Food Allergies – The OUtMATCH Trial Ep. 98: Food Allergy Treatment and Management More resources about food allergies Food Allergy Treatment & Management ___ Made in partnership with The Allergy & Asthma Network. Thanks to Genentech for sponsoring today's episode.  This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.  

Synopsis: Nimbus Therapeutics CEO Abbas Kazimi walks Alok Tayi through the company's evolving pipeline and playbook for choosing the right risks in a noisy biotech environment. From Werner helicase for MSI-high cancers to a highly selective SIK2 program and GLP-1–adjacent strategies focused on body composition, Abbas details how Nimbus balances rigor, speed, and capital efficiency. He shares candid lessons from pausing and later resurrecting AMPK beta in partnership with Eli Lilly, the decision to remain modality-agnostic but small-molecule-centric, and the importance of knowing when not to chase the latest fad. Throughout, Abbas returns to a consistent theme: success at Nimbus comes from disciplined target selection, deep collaboration, and a culture that empowers teams to make hard calls in service of patients rather than headlines. Biography: Abbas Kazimi is the Chief Executive Officer of Nimbus Therapeutics. Previously, he served as Chief Business Officer, leading the company's strategic and corporate development efforts while overseeing business operations. Since joining Nimbus in 2014, he has helped raise over $630 million in equity financing and led transactions totaling more than $8 billion. Notably, Mr. Kazimi spearheaded the $6 billion sale of Nimbus's TYK2 program to Takeda, the $1.2 billion sale of its NASH (ACC) program to Gilead, and multiple licensing deals exceeding $1.5 billion with partners such as Genentech, Celgene/Roche, and Eli Lilly. Under his leadership, Nimbus has advanced four programs into the clinic, returned over $4 billion to investors, and continues to expand its computational drug discovery and clinical development capabilities. In 2025, Mr. Kazimi joined the board of Unnatural Products (UNP), a biotech company pioneering orally delivered macrocyclic peptides to tackle previously undruggable targets. He also serves on the Editorial Advisory Board for In Vivo magazine, a leading publication offering strategic insights and analysis of the pharmaceutical, biotechnology, medtech, and consumer health industries. Along with his family, he established the Kazimi Family Endowment for Data Science in Oncology at MD Anderson Cancer Center. This endowment reflects their personal commitment to philanthropy and their vision for revolutionizing cancer treatment through data-driven innovation. At the core of Mr. Kazimi's leadership is a deep sense of purpose—one that seeks to change the trajectory of medical diagnoses where options are limited. The ability to give patients, prescribers, and families a new outlook on life is a powerful responsibility—and one he knows the biopharmaceutical sector has the ability to fulfill. Before Nimbus, he was at Extera Partners, LLC (formerly PureTech Development, LLC), where he provided strategic advisory, supported fundraising, and executed numerous business development transactions. Earlier in his career, he was with JSB-Partners, LP, a specialized investment banking and advisory firm serving biotech and pharmaceutical companies. Mr. Kazimi holds a B.A. from the University of Texas at Austin and an M.S. from Harvard University.

When it comes to keeping kids with food allergies safe at school, school nurses are often the quiet heroes behind the scenes. From managing allergy action plans and emergency responses to training teachers and organizing care for hundreds of students, their role is essential, but often misunderstood. Kortney and Dr. Payel Gupta sit down with Elizabeth Elliott, a school nurse and President of the Maryland Association of School Health Nurses. Liz shares what really happens inside the health room and how school nurses coordinate care for students with food allergies and asthma. Plus, why communication between families and school staff is key to keeping kids safe. After this episode, you'll have a whole new appreciation for your school nurse and a better understanding of how to partner with them to make every school day safer for kids with allergies. What we cover about food allergy management at school: The school nurse's role: How nurses bridge communication between families, teachers, and doctors to keep children with food allergies safe and included during the school day. Coordinating care: How school nurses use action plans and 504s to ensure everyone, from teachers to cafeteria staff, knows how to keep kids safe. Training and emergency preparedness: How school nurses teach staff to recognize anaphylaxis, use epinephrine, and stay calm during an emergency. Field trips, cafeterias, and bus safety: What goes into planning safe experiences beyond the classroom, and why “no-food on the bus” rules really matter. Advocating for resources: How families can support their school nurses and advocate for better funding, staffing, and allergy awareness in schools. ___ Made in partnership with The Allergy & Asthma Network. Thanks to Genentech for sponsoring today's episode.  This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.

Dr. Monty Pal and Dr. Pauline Funchain discuss the latest efforts to diagnose, prevent, and treat the series of immune-related adverse events that have emerged in the era of immunotherapy. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I am Monty Pal, a medical oncologist, professor and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles, California. Now, it is probably no surprise to this audience that immunotherapy has transformed the treatment landscape for multiple cancer types. It remains a pillar of modern oncology. Having said that, I think we have all been baffled by certain toxicities that we run into in the clinic. Today, I am delighted to be joined by Dr Pauline Funchain to discuss some of the checkpoint inhibitor toxicities that people struggle with most. And we will also touch on some side effects of immunotherapy beyond checkpoint inhibitors: CAR-T cells, bispecifics, so on and so forth. Dr Funchain is a dear friend, and she is an associate professor and associate director of cancer research training and education at the Stanford Cancer Institute. She is co-director of the Immunotherapy Toxicity Program and the Skin Cancer Genomics Program at Stanford, where she also serves as associate program director of hematology and oncology fellowship. Dr. Funchain is also the co-founder of ASPIRE, and we are going to talk about that a little bit today, the Alliance for the Support and Prevention of Immune-Related Events. FYI for listeners, if you are interested in our disclosures, they are available at the transcript of this episode. Pauline, thanks so much for joining us today. Dr. Pauline Funchain: Monty, thank you for this invitation. It is always great to talk. Dr. Monty Pal: So, for the audience, Pauline and I know each other from my days as a fellow at City of Hope. She was a resident at Harbor UCLA and a stellar resident at that. It has just been amazing to sort of see your career grow and blossom and to witness all the cool things that you are doing. ASPIRE, in particular, sort of caught my eye. So again, for listeners, this is the Alliance for the Support and Prevention of Immune-Related Events. Can you tell us a little bit briefly about the genesis of that, how that came about? Dr. Pauline Funchain: So, there was a bunch of us who were really struggling, I mean, all of us have struggled with these immune-related adverse events, these irAEs. You know, they are new disease states, and even though they look like autoimmune diseases, they tend to need a whole lot more steroid than autoimmune diseases do and they do not totally present in the same way. And in fact, you know, Triple-M, or Triple-M overlap syndrome, is a completely new irAE, a new immune state that we have never had before the advent of checkpoint inhibitor. And so a Triple-M, for those of you who are not as familiar, that is the constellation of myocarditis, myositis, and myasthenia gravis, something that never occurs as a natural autoimmune disease. So we were starting to realize that there were some major differences with these irAEs and autoimmune diseases. We could not treat them the right way. We really needed to learn more about them. And a bunch of us who had interest in this said, "Look, we really need to be all in one space to talk about what we are doing," because all of our treatments were our own little homegrown brews, and we needed to really get together and understand how to treat these things, how to diagnose them, and then learn more about them. So, Dr. Alexa Meara from Ohio State, Dr. Kerry Reynolds from Mass Gen, we put together this research consortium, brought together all of our irAE friends, got our best subspecialists together in a research consortium, which is now only about a year and a half old. And we made this research consortium, the Alliance for Support of Prevention of Immune-Related Events, and we reached out to ASCO, and ASCO was so kind to grant us a [Alliance for Support and Prevention of Immune-Related adverse Events (ASPIRE)] Community of Practice. So we met for the first time as a Community of Practice at the ASCO Annual Meeting just this past June and really got an ASCO community together to really think about how to again, diagnose, prevent, treat irAEs. Dr Monty Pal: This is interesting to me. The ASCO Community of Practice phenomenon is something that I was not super familiar with. Can you explain to our listenership what is the ASCO Community of Practice model? If you have particular interests, how do you sort of get one started? Dr Pauline Funchain: Yeah, so ASCO has an entire page on their Community of Practice. There are multiple Community of Practice groups or COPs. There are ones for Supportive Oncology and Survivorship. There is Women in Oncology. There is a group for International Medical Graduates. And there is about, I think 10 or 12 now that have a physical presence at ASCO but also a virtual presence on the ASCO Community of Practice site. So, if you were interested in any one of these, and you can see them on the ASCO Communities of Practice sites, you would ask to become a member. Once granted membership, then there is a whole webpage of postings and conversations that people can have. You can get email digests of conversations that happen on the website, and then you can anchor it with in-person participation at the Annual Meeting. Dr Monty Pal: That is awesome, and I can think of so many different foci within oncology that really sort of deserve a Community of Practice. This definitely being one of them. You know, it strikes me as being so interesting. I mean, the checkpoint inhibitors have been around for a while now. I think when you and I were in training, gosh, back then, these were just a little bit of a pipe dream, right? But having said that, I would probably say that more than half of my kidney cancer practice is either on checkpoint inhibitors, and the vast majority have been on one at some point in their past, right? With that in mind, you know, we have all treated a lot of patients with these drugs. Why is it that we still struggle to manage the toxicities? And just to take that one step further, what are some of the toxicities that, perhaps through ASPIRE or through your experience, people struggle with the most? Dr Pauline Funchain: So, I think we are still struggling with these because again, they are new disease states, right? This is what we all experienced with COVID, a brand-new virus and a brand-new syndrome. We now have 20-plus of these as irAEs. And what we have realized about them is the immune activation that happens with these is so much more than what we have seen with autoimmune diseases. So for instance, if you have a Crohn's or ulcerative colitis, you will top out at 40 to 60 milligrams of prednisone if a Crohn's flare or ulcerative colitis flare happens. But for our severe IR colitises, you know, it is at least 1 mg per kg, often goes up to 2 mg per kg. We, in some cases, have done 1 gram pulses if we are worried that somebody is going to perforate. So that was sort of like the first 5 years of treating irAE, and then now in the sort of second 5 years of treating irAE, we have realized that that is a lot of immunosuppression, and we might be able to get away with less with the newer biologics that are on board. So, we are struggling to try to get the data for some of these irAEs that we knew, we have known for a while, but to try to get newer treatments that may immunosuppress less so that you may still be able to retain that tumor response. And in fact, some of the preclinical studies suggest that some of these biologics may actually synergize with the immunotherapy and actually make the immunotherapy more effective from a tumor perspective and calm down the irAE as sort of the bystander effect. So we are still trying to optimize those. Getting up trials in the space has been very difficult. That is one of the reasons for the genesis of ASPIRE because we realized we needed to band together to have a bigger voice in that realm. Then there are other things that are brand new. So we talked about Triple-M. So Triple-M, again, with Triple-M or any myocarditis or myasthenia, I mean, there is about a 50% chance of death from irAE based on the literature. I think we are getting better at recognizing this, and so at Stanford we have some data to say that if you serially follow troponin, that maybe your outcomes are better. You can potentially lower the percentage of cases that are fatal because you can catch them early. I mean, this is all preliminary data, but again, these are all things that are evolving, and we do not all have the right answer. I mean, even the serial troponin thing, I think, is pretty controversial. And in fact, at one of our quarterly Zoom meetings that we are doing in ASPIRE in December is going to sort of flush out that controversy about serial troponin measuring and what is the best thing to use? Would you use something like abatacept or would you use ruxolitinib? Which one is better? I think there is a lot of controversy still about these things. Dr Monty Pal: You have really piqued my curiosity here because you think about the cons of treating irAEs, right? And I worry exactly about what you had mentioned, right, which is, "Gosh, what is going on with this tumor in terms of immunosuppression?" But you think about some of the newer agents, you mentioned ruxolitinib, I have heard of dasatinib, for instance, in this setting. Frankly speaking, a lot of these, as you point out, are really thought of as being also anticancer drugs. So you have really got me thinking about the potential synergy between perhaps suppressing an irAE and augmenting antitumor activity, which I think is very interesting. Am I on the right track with that? Dr Pauline Funchain: I think so, but you will find that a lot of people will not even go there because they are worried about how much immunosuppression you are going to cause. I am at heart a geneticist, but I think an immunologist will happily tell you that the immune system is very complex. There are multiple pathways, and these drugs do not all target the same immune pathways. So if we understand a little bit more about the pathways we are targeting and pick apart the pathways that are really, really tumor relevant and the other pathways that are not tumor relevant, you may be able to piece together a better marriage of tumor response and irAE control. Dr Monty Pal: Kind of on this topic, and again, leaning on your background in genetics, where are we in terms of predicting these irAEs? I mean, you would think the holy grail would be picking out a snip or something of this for it, right, that could potentially identify that patient who is going to get Triple-M or, you know, at the very least a significant high-grade irAE event. Are we anywhere closer to that in 2025? Dr Pauline Funchain: There have been data published. There have been some big GWAS studies. All of the effect sizes are pretty small. So there are some prediction algorithms, but none of them are clinically useful. And I think when you look at the odds ratios, they will increase risk by maybe 20%. I think one of the things that we found in a very small series and supported anecdotally is something as easy as family history of autoimmune disease is probably more predictive at this point than any of those types of markers. I think we will get there, but we are not anywhere near where we would like to be. Things like TMB also, actually, there is some good data about higher TMB, higher risk of irAE too. Dr Monty Pal: Interesting. I see all this data coming through, IL-8 polymorphisms, etc. And I just wondered if any of that was ready for prime time. But I mean, this is a good message for the practicing clinician. Sounds like we are not quite there yet. And I could probably keep you on for another entire podcast to talk about this topic, but let us see if we can at least skim the surface. I never thought I would see the day when BiTEs and CAR-Ts were entering into my kidney cancer practice, but in fact, it is really become central to a lot of our clinical trials in RCC these days. I would be lying if I did not say that I was not struggling with the toxicities and so forth associated with these drugs. Can you give us a quick primer, maybe just good resources that people can go to for managing toxicity with BiTEs and with CAR and with some of these novel therapeutic modalities that we are using in the oncology clinics? Dr Pauline Funchain: I know there is a recently published toxicity manual for BiTEs in hematologic malignancies, I think it was in Blood. CAR-T is covered in many irAE guidelines. So ASCO guidelines actually has a CAR-T [cell therapy guideline], and I would be remiss not to point out that actually ASCO has a, I am a little biased, but a wonderful guideline on irAE that is actually being updated as we speak. We are hoping for publication next year. I find the format of that, there are many guidelines out there, actually. There is ASCO, SITC, ESMO has a guideline for irAE, but I find the formatting of the ASCO guideline to be much easier to flip through during clinic, just because of the visual format of the tables. But that is going to be updated next year. And with CAR-T, there is now multiple publications also in terms of guidelines. But what I will say about bispecifics and CAR-T, so they have very similar toxicities in terms of the cytokine release and also with the ICANS, so the neurotoxicity. But what we have been finding that is really interesting with BiTEs and CAR-T, and actually even with TIL, cytokine release is very similar to some of the IL-2 toxicities but not identical that we see with TIL treatment. But now we are starting to see overlap. So patients who have been treated with immunotherapy and then go on to get a bispecific or then go on to get TIL, so I have seen some colitises that have occurred after the fact. Some of the newer CAR-Ts without checkpoint have been causing some really interesting, probably not in a good way, but interesting biologically, colitises that are really refractory. So we are starting to see some overlap, and again, I think this field is just evolving constantly. Dr Monty Pal: Yeah, no, I almost think I need to go back to that fellowship that you and I did together 20 years ago and, you know, and see if I could repeat some coursework on CAR-T management.  You know, Pauline, I could probably keep you on the horn for hours, but this has just been terrific. Thank you so much for sharing all of your insights with us today on the ASCO Daily News Podcast. Dr Pauline Funchain: Thank you for the invitation. It was wonderful to talk about this, and it was wonderful to catch up a little bit, Monty. Dr Monty Pal: Same here, same here. And thanks to our listeners too. If you value the insights you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the 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. Monty Pal    @montypal   Dr. Pauline Funchain @FunchainMD Follow ASCO on social media:       @ASCO on Twitter      ASCO on Bluesky     ASCO on Facebook       ASCO on LinkedIn     Disclosures: Dr. Monty Pal:     Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview    Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical    Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis    Dr. Pauline Funchain: Consulting or Advisory Role: Merck, Replimune, Sanofi/Regeneron, Immunocore, Tempus Research Funding (Inst.): Pfizer, Bristol-Myers Squibb, IDEAYA Biosciences, Linnaeus Therapeutics Travel, Accommodations, Expenses: Merck

Episode 472 features Dr. Sheila Gujrathi, a biotech entrepreneur, executive, and champion for under represented leaders. Her new book, "The Mirror Effect: A Transformative Approach To Growth For The Next Generation Of Female Leaders" is out now.Chapters:00:00 Introduction and Book Announcement02:15 The Unmet Need: Writing for My Younger Self05:30 Overcoming Challenges: A Personal Journey09:45 The Power of Mentorship and Sponsorship14:00 Spiritual Growth and Finding Purpose18:20 Building a Personal Board of Directors23:10 The Inner Critic and Self-Compassion28:45 The Importance of Storytelling in Leadership33:00 Navigating Negative Work Environments37:15 Conclusion: Embracing Vulnerability and ConnectionFind Sheila Online:Website: ​​https://sheilagujrathimd.com/ TEDxTalk: https://www.youtube.com/watch?v=2DpDx6T3-X4 LinkedIn: https://www.linkedin.com/in/sheila-gujrathi-md/ Instagram: https://www.instagram.com/sheilagujrathimd/ Book: https://sheilagujrathimd.com/book/ About Sheila:Sheila is a biotech entrepreneur, executive, and champion for under represented leaders. Over the past 25 years, she's had the privilege of developing life-changing medicines for patients with serious diseases while building and running private and public biotech companies—including some exciting exits. Today she's a founder, chairwoman, board director, strategic advisor, and consultant to start-up companies and investment funds. Dr. Gujrathi was the co-founder and former CEO of Gossamer Bio and former Chief Medical Officer of Receptos. Her journey started at Northwestern University, where she earned both her M.D. and biomedical engineering degree, and took her from the halls of Harvard, UCSF, and Stanford to the corporate offices of Fortune 500 companies like McKinsey, Genentech, and Bristol-Myers Squibb.Dr. Gujrathi has earned multiple leadership awards, including AIMBE Fellow, BLOC100 Luminary, Healthcare Technology Report Top 25 Women Leaders in Biotechnology, Corporate Directors Forum Director of the Year, and Fiercest Women in Life Sciences. But what really lights her up is creating the inclusive environments she wished she'd had throughout her career. That's why she co-founded the Biotech CEO Sisterhood, a group of trailblazing female CEOs—because we're all better when we support each other.

AI is transforming biotechnology from the inside out. What was once a world of petri dishes and pipettes is now increasingly powered by algorithms, models, and digital twins. But as machine learning accelerates drug discovery and reshapes clinical trials, how far can we go before biology itself becomes the follower, not the leader?In this episode of Tech Tomorrow, David Elliman speaks with Bibi Ephraim, Head of Digital Sciences at Genentech, about how artificial intelligence is redefining the biotech landscape. They explore how data-driven approaches are rapidly compressing timelines in drug discovery, enabling precision medicine, and even simulating virtual clinical trials.They also tackle the cultural and organisational transformations needed to make digital biotech work; from breaking down data silos and fostering collaboration across competitors, to treating data as a product and investing in strong governance. Drawing parallels with digital transformation in other industries, they ask what it will take for biotech to move from project-based to product-based innovation, and why pre-competitive collaboration could unlock the next generation of cures.Episode Highlights:01:40 – What do AI, data science, and digital governance in the biotech landscape look like today?03:06 – Biotech and the data foundations needed for transformation.04:52 – Examples of successful data-driven approaches in biotech.08:10 – Will parts of the medical process be completely handed over to AI?09:39 – David's thoughts: The importance of sustained, iterative innovation.11:49 – The biggest mistake Bibi sees executives make in relation to data.13:08 – The huge issue of low-quality data.14:59 – Data sharing is critical in this field.19:03 – David's thoughts: How pre-competitive collaboration benefits everyone.21:17 – Is biotech reaching a standardisation tipping point?24:11 – Can biotech scale digitally and effectively?26:30 – Will the next biotech breakthrough be digital before it's biological?28:33 – If digitalisation expands, will researchers miss the “happy accidents” of drug discovery?About Zühlke:Zühlke is a global transformation partner, with engineering and innovation at its core. We help clients envision and build their businesses for the future – running smarter today while adapting for tomorrow's markets, customers, and communities.Our multidisciplinary teams specialise in technology strategy and business innovation, digital solutions and applications, and device and systems engineering. We thrive in complex, regulated sectors such as healthcare and finance, connecting strategy, implementation, and operations to help clients build more effective and resilient businesses.Links:Zühlke WebsiteZühlke on LinkedInDavid Elliman on LinkedInBibi Ephraim on LinkedInGenentech Website

Your process works perfectly at two-liter bench scale. Then you hit fifty liters and titer drops 20%. By two hundred liters, aggregation appears and charge variants shift. Your management team asks: "How long to fix this?" The honest answer? Three to twelve month, because you're flying blind.In Part 2 of this Quality by Design Master Class, David Brühlmann reveals why scale-up chaos isn't inevitable. It's a solvable engineering problem. Drawing on experience leading bioprocess innovation at Merck and guiding biotech companies through CMC development, David delivers the process control framework that transforms reactive troubleshooting into predictive manufacturing.The core truth: eighty percent of quality problems stem from twenty percent of your process variables. David shows how to identify Critical Process Parameters, implement intelligent control strategies, and leverage hybrid modeling that reduces experiments by 60-80%. With case studies from Genentech and Amgen, you'll gain the blueprint that turns QbD requirements into competitive advantage.Part 1 taught you what to build and measure. Part 2 shows you how to control your process to consistently deliver commercial-scale quality.Topics Discussed:The common pitfalls of scaling up manufacturing from bench to production, and why process control must go beyond end-product testing (02:10)Overview of the QbD framework: Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), and the focus of this episode - Control Strategies for manufacturing (05:00)Identifying and monitoring Critical Process Parameters (CPPs) and their impact on quality, with real-world examples from Genentech's monoclonal antibody platform (08:20)Structure of an effective manufacturing control strategy: Input, process, and output controls - including practical details on real-time monitoring and release testing (11:00)The role of hybrid modeling and machine learning in accelerating process optimization, and how this approach can dramatically reduce the experimental burden (13:30)Real examples of improved outcomes and efficiency through model-based control strategies, and why training and process understanding are essential for team success (16:10)A quick, actionable exercise biotech teams can use to map process risks and identify critical control points (16:55)Whether you're part of a start-up or a large biotech firm, this episode offers clear, strategic steps for implementing QbD and improving process reliability. Don't forget to listen to Part 1 for more on QTPP and CQA, and visit www.bruehlmann-consulting.com for additional resources.Next step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We're building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105

Navigating food allergies is tough enough, but adding family dynamics to the mix can make things even more complicated. When loved ones don't understand you or your child's allergies or dismiss the rules meant to keep them safe, it can lead to conflict, hurt feelings, and stress for everyone involved. Kortney and Dr. Payel Gupta sit down with psychologist Dr. Amanda Whitehouse to talk about how families can find common ground when emotions run high. Together, they unpack what it means to stay regulated in difficult conversations, how to set healthy boundaries with family members, and why understanding different coping styles can help prevent conflict before it starts. What we cover about communication and boundary-setting for food allergy families: Coping styles and conflict: Learn how different stress responses, such as “fight” versus “flight,” shape how partners, parents, and relatives react to food allergy challenges. Staying calm and regulated: Understand how your body reacts to stress and how recognizing those signals can help you stay grounded during tough conversations. Setting and holding boundaries: Get practical tips for explaining what feels safe, keeping communication clear, and responding calmly when others push back. Working together as a team: Whether it's with your partner, kids, or extended family, learn how to support each other and stay united when emotions rise. Bridging family differences: Explore ways to include children and siblings in allergy safety, and approach older relatives with patience and compassion when views or communication styles differ. ___ Made in partnership with The Allergy & Asthma Network. Thanks to Genentech for sponsoring today's episode.  This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.

Dr. Monty Pal and Dr. Fumiko Chino discuss several of the top abstracts presented at the 2025 ASCO Quality Care Symposium, including research on federally funded clinical trials and financial reimbursement for trial participation. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I am your host, Dr. Monty Pal. I am a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, we are highlighting key abstracts that were presented at the 2025 ASCO Quality Care Symposium. I am delighted to be joined today by the chair of this year's meeting, Dr. Fumiko Chino. Dr. Chino is an associate professor in radiation oncology at MD Anderson Cancer Center with a research focus on access, affordability, and equity. She is also a consultant editor of JCO Oncology Practice and the host of the Put into Practice podcast. I have got to listen to that.  Dr. Chino, welcome, and thanks so much for being on the podcast today. Dr. Fumiko Chino: I am overjoyed to be here, and absolutely, you should take a listen. Dr. Monty Pal: Definitely. And FYI for listeners, our full disclosures are all available in the transcript of this episode, so do have a look if you are inclined. Now, we have really seen some fantastic advances in health services and quality and supportive care, digital health, and beyond. There are some great abstracts that were presented at this year's meeting. I have actually picked a couple that I am particularly interested in and that I believe you share my interest in as well.  So, the first is an abstract actually from my friends at SWOG (Abstract 94). So, this was a terrific abstract from Joe Unger and Michael LeBlanc and Dawn Hershman. And this, I think, really hits on a very, very key issue right now, which is the benefit of federally funded trials. Do you mind just kind of spelling out some of the observations from what I think is a really brilliant piece of work? Dr. Fumiko Chino: Absolutely, and I think Dr. Unger's work is really important for our current funding environment. I think that this research is really essential to do to show the role of federal sponsorship in the design and conduct of clinical trials. Because what they did was really look at a landscape analysis over the last 20 years looking at funding and were able to show quite clearly that federal funding really matters for advancing the science in cancer care. So what they showed was that the federal funding was more commonly essential for early-stage clinical trials, so those phase 1, phase 2 trials that really help advance the science. And that federal funding was really essential for multimodality drug combinations, combinations with drug and surgery, combinations with drug and radiation. Those trials were much more likely to be federal funded. And then the last thing is that they showed that the patients that are, I think, the largest at risk for gaps in care who really need the advancements in science that keep U.S. health care amazing and wonderful and world-leading, so the kids, the pediatric patients, the patients with rare cancers, and the patients actually that could benefit from de-escalation or right-sizing of treatment, they were also all more likely to have federal funding. So I think this research that was presented really shows that if, unfortunately, current status of restricted federal funding continues, that we are going to lose out in terms of the next generation of cancer cures, cancer de-escalations, and the type of combination treatments that make advancements in science. Dr. Monty Pal: Indeed. You know, I always point to Joe Unger's paper, and I think it is in JAMA Oncology, right, that showed life-years gained from NCI trials. It is such an important piece of work. I think this is a really nice complement to that, isn't it, to show the specific areas that otherwise would be, am I right in saying, kind of largely untouched? Dr. Fumiko Chino: I think you are right in that what we know from what industry will sponsor versus what the federal government will sponsor, that the federal government really helps make up the gap to really make those advancements that save lives, that lead to more birthdays, that advance our knowledge and our capacity for providing more cures and more successful futures for our patients. I always like pointing to the de-escalation research, which is, and this is not to dig pharma, but no pharmaceutical company is going to run a trial that says you can give less of their drug, right? It just does not make sense for the business end of the science. And so, thinking about how to right-size treatments, how to do more with less, that really is the purview of the federal government. Dr. Monty Pal: Absolutely. Absolutely.  I am going to shift gears here and bring up another abstract that I found to be quite intriguing, and this relates to reimbursement of expenses, et cetera, for clinical trials. This is an abstract from Courtney Williams and team. It brings to mind the importance, I think, of recognizing the hardships that patients take on by clinical trials, but I also would love for you to comment on that sort of fine line between reimbursement for expenses and then, you know, sort of undue enticement. It is a challenging balance there. But give me your reflections on this abstract. Dr. Fumiko Chino: Absolutely. You are speaking about Dr. Williams' Abstract 93 from the Alabama group, and Alabama actually has this incredible group of health services researchers which is, are doing really important work in this space. What this trial shows is that, you know, it is a small pilot study, it is 30-something patients that received some support primarily for their travel and additional expenses related to their clinical trial participation for breast cancer. It showed that the money helps, and I think what we all know is that it is expensive to participate in clinical trials. It requires additional visits. It often requires some significant travel burden for our patients, and I do not feel that money reimbursement for clinical trial expenses is an inducement. Nobody participates in a clinical trial to get the money for their gas, right? We know that our patients are making some pretty significant sacrifices in order to participate in clinical trials, and what this type of program does is just actually reimburse them for their outlaying of funds.  And I loved this trial because the patients were actually given $1,000 a month for the first 4 months of their trial participation, and what the study showed is that the patients were using it for things like travel-related food, for things like transportation, caregiver expenses, or even some of their out-of-pocket medical expenses like cost sharing or prescriptions. And that they said that overall, the reimbursement really made a difference in terms of their capacity for staying on the clinical trial. Because we know our clinical trials really are not able to enroll the full diversity of patients that often have a disease, and that the patients that are at biggest risk for a health care disparity or a gap in care are also the least likely to enroll in a clinical trial.  Programs like this are an essential part of showing how financial toxicity can be overcome with pretty straightforward assistance to patients to help reimburse them for the things that they are already taking out of their pocket, for parking costs, for that $10 soup that they buy at the cancer center, for those additional expenses that we are, unfortunately, putting on them. Dr. Monty Pal: Very well said. And you know, I have started to dabble in clinical trials looking at CAR T-cell therapies for kidney cancer, and I have to tell you, it is just insane the amount of cost that a patient would have to take on to comply with the stipulations for some of these novel therapies. We require that they stay within 30 minutes of the facility for 28 days, and unless we are compensating for some of that, I mean, how can one afford a hotel stay that is that long? I mean, it is just, it is unprecedented, and it would certainly provide a huge barrier to many patients who would otherwise enroll. Really well said. I also wanted to bring up another financially driven topic, and treating renal cell, again, I would say the vast majority, 90% plus of my patients in clinic are on oral drug therapies. And I cannot tell you how often a patient will show up in my practice and say, "Doc, I have got 15 days out of this 30-day prescription left. What do I do with it?" You know, or some come with pill bottles from a deceased loved one. And it is so frustrating to say, "Take it to the pharmacy and they will just get rid of it for you." But sounds like there is an abstract from Dr. Mackler, Abstract 102, that seems to address this topic quite well. Am I right? Dr. Fumiko Chino: Absolutely. This presentation, I was the most excited about seeing because this group, which helps run a cancer drug repository, theirs is called YesRx, presented their data from the last approximately two years of running this repository, and they were able to show incredible benefit for their patients in Michigan. And it is a really straightforward program. It is run by pharmacists. It has support from the legislation in Michigan. And what they were able to show is that they repurposed medications that would otherwise have been discarded. They delivered them directly to the oncologist, which then actually dispersed them to the patients. They helped 1,000 patients in less than two years. They saved them millions of dollars, over $15 million presented in the abstract. And it is just a win-win-win because I know that patients actually, and sometimes patient caregivers, they feel very sad to have spent a lot of money out of pocket for their medication, and then if they have a dose reduction or, obviously, you know, if the surviving spouse then has to get rid of their medication, just dispose of them, it is very disheartening. And this is a way of kind of reclaiming power for patients. So they were able to accept donations from all over the state of Michigan and then also help over 1,000 patients. And so, it is a phenomenal program. Dr. Monty Pal: Just wild when I came across the dollar amounts, right, that they were saving. It just, it seems like a place that, you know, we just have to look, as cancer centers, right, and really take this on. Just brilliant. On that same theme of cost savings and so forth, you know, I think there has been a lot of focus on what recent policies have done in the context of us having access to therapies and so forth. And one of the topics that has come up is the Inflation Reduction Act and how changes pertaining to the IRA have really played a role in one's ability to take on some of these expensive prescriptions. And I believe John Lin and colleagues tackled that issue in Abstract 97. Could you comment on that, Fumiko? Dr. Fumiko Chino: Absolutely. Dr. Lin is one of my colleagues here at MD Anderson, so I know him very well, and he has been doing really phenomenal work over the last several years with looking at drug affordability and access. And what his analysis shows is that for patients, after the Inflation Reduction Act's cap on out-of-pocket expenses, is that it really did show that out-of-pocket expenses decreased. So what the Inflation Reduction Act did is that it eliminated the 5% co-insurance and placed this $2,000 cap on out-of-pocket expenses. And what that led to for these patients that were not able to have the low-income subsidy is that there were lower costs, and that there was a lower rate of drug abandonment, meaning that the prescription was not refilled. There was also a lower rate of unfilled prescriptions as well. And I think that it shows that health policy really can improve access to care. I think the flip side of the fact that the IRA, this policy, really did seem to help people is that what his research showed is that actually, even with the benefits of this cap, is that actually it is still really high in terms of the rate of people who are not able to fill their prescriptions or that completely abandon them over time. And that unfortunately, even with this change, that over half of people without the low-income subsidy were potentially not getting the full benefit of their medications because they were not able to afford them. And so I think it really kind of highlights that we still need to do more work about making drugs affordable. Dr. Monty Pal: Indeed, indeed. And I mean, in a setting like this, I mean, I think it is important to recognize that $2,000 is a lot, it is a big chunk of change, right, for a lot of families in the U.S. What do you think of the prospect of, like, decreasing that cap? Is that something that from a policy standpoint you would be supportive of? Dr. Fumiko Chino: Well, so something that is a real option for patients on Medicare is there is something called the Medicare Prescription Payment Plan, and what it allows you to do is actually prorate the $2,000 over the whole year. And so instead of having to pay $2,000 as soon as you fill your prescription, because you are going to have, if you have an expensive medication, it is essentially you have to pay the $2,000 in January, right? It allows you to prorate it, so essentially $170 a month, and that comes to you as like a regular bill. And I think that as rolled out as part of the IRA is a really lovely way of thinking about how do we make these payments more stable over time, so it is not a huge hit sort of at the beginning of the year. And I think that alone actually can make a difference in terms of trying to help make sure that people can actually get their medications. Dr. Monty Pal: That is an excellent tip. Excellent tip.  We are going to shift gears entirely. We have been talking a lot about the dollars and cents of things and talk about an abstract from Sophia Smith and colleagues. So this is Abstract 550 at your meeting. And this hinged on a program of sorts to deal with post-traumatic stress disorder. We do not often think about PTSD in the vernacular for oncology patients, but indeed, I mean, it is something that they must face, especially in the context of long-term survivorship. Can you talk a little bit about Dr. Smith's abstract? Dr. Fumiko Chino: Absolutely. I love this work from Dr. Smith, who is at Duke. She worked with Dr. Applebaum, who was my old colleague at Memorial Sloan Kettering. And this group of researchers really is trying to figure out how to best support people into survivorship so that they can actually thrive. And their patient population for this work was actually people who received stem cell transplant, and they focused on people who had PTSD symptoms. And what they were able to show through this SMART design, which is essentially this serial, multiple randomized trial, so everyone got randomized upfront to either usual care or this app, so this digital app that actually helped coach people through cancer distress. And then for the people who were non-responders, they were then additionally randomized to either the app plus coaching or a therapist versus the cognitive behavioral therapy or CBT.  And what they were able to show is that, number one, anyone who had the app seemed like they did better than those who did not start the path with the app. But then the additional help of either the therapist or the coach or the CBT made additional benefit over time. And so, I think this shows a really nice stepped care, which is you can potentially have some right-sizing of treatments cost saving, if we sort of give everyone the app, which is, I think, overall pretty low cost. And that for the people who do not get the full benefit from the app, then you can think about these maybe more tailored approaches, the therapist, the coach, the CBT, but that some people actually just respond to the app. And I think it allows us to, again, right-size the care for our patients. And I think it is really innovative to think about how technology can help improve access to care in the setting of something like PTSD. Dr. Monty Pal: Brilliant summary. Brilliant summary.  Gosh, it looks like such an exciting meeting this year. Congratulations on a terrific program for the ASCO Quality Care Symposium. I know you played a huge role in developing it, and thanks for sharing your insights on the ASCO Daily News Podcast. Dr. Fumiko Chino: No, I really appreciate you having me. ASCO Quality is my favorite meeting of the year. You know, it is really a phenomenal meeting, and I am so excited for next year in Boston in 2026. Dr. Monty Pal: Awesome. And thanks to our listeners too. You are going to find links to all the abstracts that we discussed today in the transcript of this episode. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. 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. More on today's speakers: Dr. Sumanta (Monty) Pal  @montypal Dr. Fumiko Chino @fumikochino Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures of Potential Conflicts of Interest: Dr. Monty Pal:     Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis Dr. Fumiko Chino:  Consulting or Advisory Role: Institute for Value Based Medicine Research Funding: Merck

Join host David Wild as he speaks with Stacie Bell, chief clinical research officer at Lupus Therapeutics, about the dramatic transformation happening in lupus drug development. From a field once avoided by pharma companies to one generating unprecedented excitement, Bell discusses how her organization's 62-center network is revolutionizing clinical trials through patient engagement and scientific innovation. Learn about promising oral therapies, Genentech's cancer drug Gazyva under FDA review for lupus nephritis, cell therapy approaches offering potential long-term remission and how combination treatments may become the new standard. Bell shares insights on overcoming clinical trial barriers, advancing biomarker research and ensuring representative participation from lupus communities. A must-listen for anyone interested in autoimmune disease research, clinical development innovation, and patient-centered drug development.

Is the future of biotech innovation at risk because of workforce shortages? In this episode, host Elaine Hamm, PhD, talks with Van Ton-Quinlivan, MBA, CEO of Futuro Health and host of the WorkforceRx podcast, about how the biotech and healthcare industries can overcome the growing workforce crisis. Together, they explore how intentional workforce development, stackable credentials, and stronger partnerships between industry and education can help close the talent gap and create a more diverse, sustainable pipeline of healthcare professionals. In this episode, you'll discover: Why workforce shortages—not funding—may be the biggest threat to healthcare innovation. How stackable credentials and education partnerships can expand access to biotech and allied health careers. Strategies for building a diverse and future-ready workforce that keeps innovation moving forward. Tune in to hear how biotech and healthcare leaders can tackle the talent crisis head-on and build a stronger, more resilient future for innovation. Links: Connect with Van Ton-Quinlivan, MBA, and check out Futuro Health and the WorkforceRx podcast. Connect with Elaine Hamm, PhD, and learn about Tulane Medicine Business Development and the School of Medicine. Check out the California Health Workforce Education and Training Council, Genentech, Kaiser Permanente, and NextFlex. Connect with Ian McLachlan, BIO from the BAYOU producer. Check out BIO on the BAYOU and make plans to attend October 28 & 29, 2025. Learn more about BIO from the BAYOU - the podcast. Bio from the Bayou is a podcast that explores biotech innovation, business development, and healthcare outcomes in New Orleans & The Gulf South, connecting biotech companies, investors, and key opinion leaders to advance medicine, technology, and startup opportunities in the region.

How do you operationalize scientific truth in regulated environments? Top Global Startups features Dr. Lieza Danan, PhD—Founder & CEO of LiVeritas Biosciences—on agentic AI execution systems that elevate data integrity from method design to audit‑ready results. A mass spectrometrist and cancer survivor, Lieza has contributed to 20+ IND/BLA filings (Genentech, Sutro, Stemcentrx) and built analytical labs across the U.S. and Southeast Asia. Recently honored with the 2025 PhilDev Award for Innovation, she shares how “Built from Truth” became her Ikigai—and a blueprint for better biotech.What you'll learn:Agentic AI for regulated science: compliant execution, traceability, and auditabilityData quality systems that withstand IND/BLA scrutinyLessons from 20+ submissions across leading biopharma teamsBuilding and scaling labs in the U.S. and Southeast AsiaFounder story: survivorship, mass spectrometry, and mission‑driven leadershipIkigai in action: turning values into operating DNACall to action:Subscribe for more global founder conversations from GSD Venture Studios:GSD Venture Studios: https://gsdvs.com#AgenticAI #RegulatedScience #ScientificIntegrity #DataIntegrity #GxP #IND #BLA #Biotech #Pharma #MassSpectrometry #LiVeritas #Ikigai #PhilDevAward #TopGlobalStartups #PodcastLive

Seeing your allergist on a screen instead of in the office might feel strange at first, but for many people with allergies, telehealth isn't just convenient.  it's effective. In this episode, we sit down with telemedicine pioneer Dr. Jay Portnoy to explore how virtual allergy care works, what it can and can't do, and how it's helping patients get the care they need without the wait or the long drive. Dr. Portnoy shares over two decades of experience leading allergy telemedicine programs in rural areas and explains how remote care has grown from a fringe idea into a standard part of allergy care. He and Dr. G also discuss the benefits for both patients and clinicians. So how do you know when telehealth is enough and when it's not? What we cover in our episode about virtual allergy care and telemedicine: How does telemedicine work for allergy patients? Learn how video visits and asynchronous tools are making care faster and easier, especially in rural or underserved areas. Telemendine limitations. We break down when in-person care is still needed, like for food challenges, skin tests, or urgent symptoms. Privacy and safety in virtual care. From HIPAA-compliant platforms to quiet spaces at home or in schools, we talk about how to keep your virtual visit just as private as a clinic one. How testing works with telemedicine. Telehealth doesn't mean skipping tests. Many can be ordered remotely and done at a local lab or clinic near you. The future of allergy care. Hear how virtual care is shifting toward patient choice, whether you want to video call, send a message, or still come in. ___ Made in partnership with The Allergy & Asthma Network. Thanks to Genentech for sponsoring today's episode.  This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.

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

In July 2024, Chris Bombardier leads a team of climbers with bleeding disorders on an attempt to summit Mont Blanc, the tallest peak in the Alps. Chris is older and wiser than he was when he climbed the Seven Summits–but now he has new responsibilities, like fatherhood.     This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film.   Guests:  Dr. Ryan Warner, clinical psychologist and speaker, founder of RC Warner Consulting    Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”    Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)  Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life” 

Multiple food allergies are a daily stressor for millions of families. From avoiding social events to fearing accidental exposures, it can feel like living in a constant state of alert. Until recently, there were no FDA-approved treatments that targeted more than one allergen at a time. In this episode, we break down the study: “Omalizumab for the Treatment of Multiple Food Allergies,” published in 2024 in the New England Journal of Medicine. Known as the OUtMATCH trial, it's the first large-scale study to show that omalizumab (Xolair), a biologic already used for asthma and hives, may help people with multiple food allergies by raising the threshold for reactions. We explain how omalizumab works by blocking IgE, the antibody that triggers allergic reactions, and how the study measured changes in reaction thresholds (the amount of an allergen a person can ingest before reacting). We also explore the trial design, results, safety profile, and what all of this means for the day-to-day management of food allergies. What we cover in our episode about OUtMATCH trial How omalizumab works to prevent allergic reactions: Learn how blocking IgE increases the amount of allergen needed to trigger symptoms, offering protection from small, accidental exposures. Who qualified for the OUtMATCH trial and why: Find out which patients were included and how eligibility impacted outcomes. What success looked like in this study: Understand how researchers defined protection across multiple allergens. Why not everyone responded the same to omalizumab: Explore the variability in results and what it means for clinical care. What else the study found beyond food challenges: Hear about safety findings, quality of life data, and the open-label extension.

After climbing the Seven Summits, Chris becomes executive director of Save One Life. It's a chance to help people with bleeding disorders. But it's also his first time in a leadership role.  This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film. Guests:  Amy Board, MNM, Believe Limited Senior Vice President of Engagement and Programs    Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)     Dr. Ryan Warner, clinical psychologist and speaker, founder of RC Warner Consulting    Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”    The Final Summit is produced by BloodStream Media. To get in touch, email mailbag@bloodstreammedia.com Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter  BloodStream on Instagram BloodStream on LinkedIn BloodStream on TikTok  

Dr. Monty Pal and Dr. Mina Sedrak discuss the science behind cancer treatment-induced accelerated aging and the development of drug therapies and technologies aimed at helping older patients and cancer survivors. TRANSCRIPT Transcript: Cancer and Aging: Researching the Path to Longer, More Vibrant Lives Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Monty Pal. I am a medical oncologist and professor and vice chair of medical oncology here at the City of Hope Comprehensive Cancer Center. I am also host of this podcast. Today, we are going to be talking to somebody that I consider to be my little brother, if you will, in oncology, Mina Sedrak. Mina is an expert in the area of cancer and aging, which really includes the development of drug therapies and technologies that help enable older adults and survivors to live longer, healthier, and more vibrant lives. I am really excited to chat with him. He is an expert not just in cancer and aging but also breast cancer. He was my former colleague here at City of Hope before he moved over to the UCLA Jonsson Comprehensive Cancer Center, where he is an associate professor and director there of the Cancer and Aging Program. Dr. Sedrak's research involves mechanisms behind cancer treatment-induced accelerated aging and really aims to take this science into more of a therapeutic direction, which I am super, super excited about.  Mina, thanks so much for joining us today, and just FYI for our listeners, we have all of our disclosures in the transcript of this episode. Dr. Mina Sedrak: Thank you, Monty. Thank you, Dr. Pal, for having me. I am really excited to be here. Dr. Monty Pal: I feel like we have to go on a first-name basis here with how well we know each other. So Mina, you and I together have witnessed this evolution in cancer and aging. I mean, both of us worked together here with just a legendary figure in the field of geriatric oncology, I will call it, Dr. Arti Hurria, mentor to me, mentor to you, mentor to so many. Can you give us a sense of where cancer and aging has gone since the time that you and I started here together at City of Hope? Dr. Mina Sedrak: Dr. Hurria and her collaborators, Dr. [Willliam] Dale and Dr. [Supriya] Mohile, they were like huge pioneers in the field. They were one of the very first people to highlight the importance of looking at older adults beyond just their chronological age and their comorbidities and moving us beyond just seeing patients and making decisions using what we call the eyeball test. "Oh, this person looks fit or not fit, frail or robust," to really using objective measures to assess our patient's health status and incorporate that assessment into our evaluation of the treatment, prognostication, and discussions with our patients throughout the cancer continuum. And so that is what geriatric oncology has and continues to be, and it is a huge, important part. And their work has laid the foundation to show that when we look at our patients beyond just their chronological age and we look at their functional age, and we do these objective assessments, we can gain much more deeper information to tailor the treatment for our patient that is sitting in front of us, rather than do a prescriptive treatment or over- or undertreatment in that population. So that is sort of where the field is growing, and a lot of the work now is, how do we implement that? How do we put that into clinical practice? Dr. Monty Pal: Well, let me kind of spearhead that discussion, right? I have these moments when I go to the ASCO Annual Meeting – I remember this happened to me a while ago when Dr. Jennifer Temel presented that terrific work around early palliative care interventions, right? Or it even happened to me this year, right, when Dr. Christopher Booth presented the CHALLENGE trial around exercise and colon cancer. You know, these amazing, I am going to say simple, they are not simple, but they are simple interventions relative to, you know, some of the complex drugs and mechanisms that we are using nowadays that really help outcomes for our cancer patients. The big question becomes, how do you implement, right? But my understanding is that there are easy ways for us to take tools in cancer and aging and sort of plug them into our daily practice. Am I right about that? Dr. Mina Sedrak: Yes, and that is something that they are – the Cancer and Aging Research Group, which was founded by Dr. Hurria and now is co-led by Dr. Dale, Dr. Mohile, and Dr. [Heidi] Klepin, they have been incredible at really trying to develop practical tools, like the Practical Geriatric Assessment, which is now endorsed by the ASCO and other NCCN guidelines. And so, there are tools that are becoming more and more practical to help incorporate that into clinic.  Now, what might be practical in a resource-intensive setting may not be practical in some of the limited resources, whether it is rural and/or other countries where the resources may be more limited. So that is why Cristiane Bergerot, Enrique Soto, and others have been really working hard. There was actually a really beautiful paper that was just published in the Journal of Global Oncology, where they have shown that there are guidelines [ASCO Geriatric Assessment Global Guideline] about how to implement these tests, these tools, these assessments in clinical practice, even in different resource settings. So I think we are going to get to the future where this is much more – it is definitely important, but it is much more easily ‘incorporatable' into our practice. Dr. Monty Pal: Yeah, you know how close I am to Cris, and I was so proud when I saw that paper come out. That was really exciting. You know, I skimmed it. I have to tell you, I did not get into the weeds, but it was apparent to me that, you know, some of these geriatric oncology tools are things that, you know, I could probably plug and play into my practice where I am double- and triple-booked over, you know, most slots, right? I mean, I could still probably afford a little bit of time or maybe have, like, a nurse or an extender kind of help participate in the evaluation process. I thought that was, yeah, really, really interesting. Dr. Mina Sedrak: I will just say that at UCLA, we are working with Dr. Arash Naeim, who is a geriatric oncologist, and he has developed an AI platform where the assessments can be done by an AI computer. So it is like talking to your ChatGPT. They can talk to you, and for a few minutes, they will ask you the questions. So you do not even have to fill it out on a piece of paper. You could give the patient a little iPad, put them in a private room while they are waiting for their doctor, and get the results, and it is right there for you. And so, we have been trying to think about how can technology help with the completion of the assessment, at least doing that? And I think it is actually, it has been very cool. We did a pilot study. He is writing that up, and we are going to continue to do some of this exciting work. How do we think about AI in the context of this? And, you know, older adults, they are not like what they used to be. A lot of older adults are very familiar with and comfortable with phones and computers and iPads, much more so today than they were even at the time when Dr. Hurria was alive. Dr. Monty Pal: That is so interesting. You mentioned this, the AI approach is something I have been thinking about in this context because what if, for instance, you know, we have got video monitors all over our hospital, right? What if you are actually just taking a look at that patient as they make their way towards your clinic? Capture that video, use an AI algorithm to say, "Hey, you know, the timed get-up-and-go test in this patient is not particularly good based on what I am seeing here," right? There are so many ways that you could, you know, stir the pot and come up with creative ways to get these tests done. Dr. Mina Sedrak: That's right. And Arash is looking at also sensors. So he has some studies where he is putting sensors inside people's homes, where they would put them, like, on top of an Alexa app or the equivalent. A lot of people have these apps, and basically, they can sense how you are moving around and what you are doing, just movement-wise. And then they can collect that information to gain information about your life beyond just what we are seeing in the 20-minute visit in the clinic. Even when I do a walk test where I get gait speed or physical performance, short physical performance battery, the chair sit-up, those are oftentimes a single, cross-sectional, static measure. But what about the dynamic ability of capturing what has been happening for the last 7 days? What has been happening for the last 25 days between the visits, between the cycles of chemotherapy? And could that inform how I make decisions when I see patients and who do I need to target and identify? And so, we are very excited because really at UCLA, Arash is leading the technology efforts and thinking about implementation of these important measures and these important tools but leveraging new technology. And we do not want to be behind; we want to be ahead of the game. Dr. Monty Pal: I love that idea because there is a Hawthorne effect, isn't there, where you observe a process, and it naturally gets better. I mean, when you ask that patient to get up in the clinic and move, they are probably functioning to the best of their abilities, but we could probably learn a lot from just watching how fast that patient picks up a remote control at home. Some simple movement like that that is volitional would probably help out a ton. And I got to tell you, it is so funny when you mention Arash Naeim's name. I distinctly remember him serving as an attending on the wards when he was brand new at UCLA on faculty when I was a resident there. And his dad is a legendary hematopathologist, right? Dr. Mina Sedrak: I did not know that. Dr. Monty Pal: Yeah, yeah. Faramarz Naeim wrote the book on a lot of heme-path malignancies. Incredible guy. Very, very storied hematopathologist at UCLA.  I could probably go on this topic forever, but in the interest of time, I am going to shift to something that again, I could probably talk about forever, which is this area of senescence that you are involved in. You know, you had mentioned this to me, I am going to say during your outro from City of Hope and towards your transition to UCLA, it is such an exciting area. I mean, understanding the actual biologic process of aging and using those underpinnings to really sort of tailor therapy. So tell us where the state of the science is there with this body of work that you are doing. Dr. Mina Sedrak: As I said before, we have tools now to assess patients and to then do something about the deficits. So if a patient is falling, what we do is we refer them to physical therapy where they can do fall precautions and strength training to give them the information. But all of these supportive care interventions are very important. They are great. But they oftentimes are not targeting the root cause of why they are happening. And so that is really where I have been very interested in, how can we understand why is it that something like chemotherapy or immunotherapy is causing a decline in cognitive function or a decline in physical function? And so that has really led us to think about geriatric oncology rather than a discipline of older adults, but to think about aging as a physiologic process. We are all aging. As every day goes by, we are aging. And what that means is that our bodies are accumulating damage, the cells are being exposed to various stressors, and the repair mechanisms are declining. And as we get older, it is really more damage and less repair mechanism at the cellular molecular level. And it turns out that these processes of how our cells repair and respond to damage are fundamental processes of biological aging. And there has been a large amount of preclinical and now really exciting clinical work to show that there are hallmarks that could be used to assess the rate of which we age by looking at these processes. And that includes things like epigenetics, telomeres, inflammation, and something called ‘cellular senescence.' And we have been interested in my lab in senescence because it is a unique process that has an important role in aging, but it also has a really important role in cancer. Senescence is a cell state. Cells, when they are stressed, they respond to entering this state of senescence. The stress could come from anything. It could come from an oncogene activation. It could come from a reactive oxygen species. It could come from a direct damage to the cell. But it is a cell state, just like apoptosis, necrosis. Senescence is a state in which the cell, in response to that stressor, undergoes an arrest from the G to the S phase. And that arrest is oftentimes associated with a resistance to apoptosis. So then the cell does not die, but it is alive, and it remains metabolically active. And in fact, downstream pathways of these cell cycle inhibition of this G-to-S phase lead to the increase of these transcription factors in the chromatin and lead to the development of these pro-inflammatory factors. So these cells, which can occur in various tissues in the body, can continue to live despite having developed these changes, and then they secrete these proinflammatory molecules like cytokines, chemokines, metalloproteinases, all of these, which are called the senescence-associated secretory phenotype, or SASP. And as we age, we accumulate more and more of these cells, and our bodies are no longer able – our immune system, like macrophages and T cells – are no longer able to remove them effectively. And as we accumulate them in various organs, these organs release a lot of inflammatory cytokines, and the chronic inflammation in that tissue leads to the tissue being damaged, and it does not work as well, and then it starts to decline in function. And that is believed to be how senescence plays a role in aging. It is the accumulation of senescent cells that occurs with increased damage and then the repair mechanism of clearing these cells effectively, which then leads to build up of inflammation and chronic inflammation leads up to damage in multiple tissues. Dr. Monty Pal: This concept to me is fascinating. And I guess the big question is – senescence is bad, right – is it not reasonable to think that this body of research, I mean, if you are able to sort of have a meaningful impact on senescence, it could have implications well beyond oncology. Is that fair? You really could extend lifespan all around. Is that reasonable to think, all-cause mortality? Dr. Mina Sedrak: One hundred percent. And that is what they have been shown in animal models. And the reason senescence is exciting is because it turns out that you can target these cells and you can induce apoptosis of these cells, but it requires active targeting of various pathways, but it can occur. And when it does, and it is done either genetically or pharmacologically in mice, we see that the mice can reverse damage. So if you take an old mouse and you genetically engineer it to remove senescent cells, that mouse will go from being frail to fit. And if you take a young mouse and you induce senescent cells at a high rate and you accumulate them in that mouse, that mouse, even though it is young, will become frail.  So that has really led to this exciting opportunity of, can we translate this finding that we are seeing in animals and in in vivo cells, cell cultures, into humans? And could that have a benefit beyond just one disease? Could it have a benefit in multiple diseases? And not just really longevity, which I think it would be great, but what people are really looking for is, how do we live healthy as we get older? How do we move the curve so that people are not developing chronic diseases in their 60s, but they are developing them in their 80s towards shortening the period of their life with disability rather than what we have currently, which is people are living to 70s, the average life expectancy is in the mid-70s, but they are spending 10 or 11 years in disability of that life. And so, how could we reduce that time frame? Dr. Monty Pal: This is brilliant, Mina. And for our audience, this compelling dialogue that we have had here thankfully is translating to funding for Mina's work. He just scored in the second percentile for his NIH R01 based on this topic. We are so, so proud of you. I mean, it is just remarkable work. It is not easy in the current climate to get funding, and a second percentile score is just absolutely wonderful. You know, Mina, I could probably go on with you for a couple more hours here talking about your work in cancer and aging. I think I am going to have to have you back on the podcast here. But a million thanks for sharing your thoughts here today on the ASCO Daily News Podcast.  And thanks to our listeners too. If you value the insights that you heard today on the ASCO Daily News Podcast, please do not forget to rate, review, and subscribe wherever you get your podcasts. Thanks, Mina. Dr. Mina Sedrak: 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. Find out more about today's speakers:     Dr. Sumanta (Monty) Pal   @montypal  Dr. Mina Sedrak @minasedrakmd   Follow ASCO on social media:      @ASCO on Twitter     ASCO on Bluesky    ASCO on Facebook      ASCO on LinkedIn      Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Mina Sedrak: Patents, Royalties, Other Intellectual Property: Up-to-Date

Chris looks back on his journey to climb the Seven Summits through a new lens: what it was like to become a role model in the international bleeding disorder community, and how it affected him.    This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film.   Guests:  Dr. Ryan Warner, clinical psychologist and speaker, founder of RC Warner Consulting    Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)     Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”  The Final Summit is produced by BloodStream Media. To get in touch, email mailbag@bloodstreammedia.com Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter  BloodStream on Instagram BloodStream on LinkedIn BloodStream on TikTok  

The high cost associated with cancer diagnosis, treatment, and survivorship makes the burden of financial toxicity an unavoidable reality for many patients—and makes financial navigators central to the delivery of high-quality cancer care. In this vodcast episode, CANCER BUZZ speaks with Heather Simpson, BCPA, patient financial navigator lead, who shares her experience using the ACCC Financial Advocacy Network's financial advocacy services guidelines assessment tool to pinpoint financial navigation challenges within her cancer program. Heather Simpson, BCPA Patient Financial Navigator Lead              Allina Health Cancer Institute   River Falls, WI “When [ACCC] came out with a gap assessment tool in 2024...it allowed us to see where we had hit the mark with our program and where we had some gaps we could take care of to really be in line with the [Financial Advocacy Network's] guidelines.” Resources: Financial Advocacy Guidelines Financial Advocacy Services Assessment Tool Financial Advocacy Services Guidelines Assessment Tool User Guide In the Field: Practical Financial Advocacy Strategies for Supporting Cancer Patients Oncology Reimbursement Meetings This podcast is made possible by funding and support provided by Genentech, Eisai, Pfizer, and Regeneron and in partnership with AONN+, NPAF, Triage Cancer, and CancerCare.  

After pursuing medical school, Chris finds his true passion: helping people with bleeding disorders. And a live-changing trip to Kenya inspire Chris to climb Mt. Kilimanjaro.    This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film.   Guests: Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)     Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”    Amy Board, MNM, Believe Limited Senior Vice President of Engagement and Programs  The Final Summit is produced by BloodStream Media. To get in touch, email mailbag@bloodstreammedia.com Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter  BloodStream on Instagram BloodStream on LinkedIn BloodStream on TikTok  

Dr. Sumanta (Monty) Pal and Dr. Petros Grivas discuss innovative new intravesical therapies and other recent advances in the treatment of non-muscle invasive bladder cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello and welcome. I'm Dr. Monty Pal here at the ASCO Daily News Podcast. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. And I'm really delighted to be your new host here. Today's episode is going to really sort of focus on an area near and dear to my heart, something I actually see in the clinics, and that's bladder cancer. We're specifically going to be discussing non-muscle invasive bladder cancer, which actually comprises about 75% of new cases. Now, in recent years, there's been a huge shift towards personalized bladder-preserving strategies, including innovative therapies and new agents that really are reducing reliance on more primitive techniques like radical cystectomy and radiation therapy. And I'm really excited about this new trend. And really at the forefront of this is one of my dear friends and colleagues, Dr. Petros Grivas. He's a professor in the Department of Medicine and Division of Hematology Oncology at the University of Washington. It's going to take a while to get through all these titles. He's taken on a bunch of new roles. He is medical director of the International Program, medical director of the Local and Regional Outreach Program, and also professor in the Clinical Research Division at the Fred Hutch Cancer Center. Petros, welcome to the program. Dr. Petros Grivas: Thank you so much, Monty. It's exciting for me to be here. Dr. Sumanta (Monty) Pal: Just FYI for our audience, our disclosures are available in the transcript of this episode.  We're going to get right into it, Petros. Non-muscle invasive bladder cancer, this is a really, really challenging space. We see a lot of recurrence and progression of the disease over time, about 50% to 70% of patients do have some recurrence after initial treatment, and about 30% are ultimately going to progress on to muscle-invasive or metastatic disease. Now, I will say that when you and I were in training, non-muscle invasive bladder cancer was something that was almost relegated to the domain of the urologist, right? They would use treatments such as BCG (Bacillus Calmette-Guérin) in a serial fashion. It was rare, I think, for you and I to really enter into this clinical space, but that's all changing, isn't it? I mean, can you maybe tell us about some of the new therapies, two or three that you're really excited about in this space? Dr. Petros Grivas: Monty, you're correct. Traditionally and conventionally, our dear friends and colleagues in urology have been managing patients with non-muscle invasive bladder cancer. The previous term was superficial bladder cancer. Now, it has changed, to your point, to non-muscle invasive bladder cancer. And this has to do with the staging of this entity. These tumors in superficial layers of bladder cancer, not invading the muscularis propria, the muscle layer, which makes the bladder contract for urine to be expelled. As you said, these patients have been treated traditionally with intravesical BCG, one of the oldest forms of immunotherapy that was developed back in the 1970s, and this is a big milestone of immunotherapy development. However, over the years, in the last 50 years, there were not many options for patients in whom the cancers had progression or recurrence, came back after this intravesical BCG. Many of those patients were undergoing, and many of them still may be undergoing, what we call radical cystectomy, meaning removal of the bladder and the lymph nodes around the bladder. The development of newer agents over the last several years has given the patients the option of having other intravesical therapies, intravesical meaning the delivery of drugs, medications inside the bladder, aiming to preserve the bladder, keep the bladder in place. And there are many examples of those agents. Just to give you some examples, intravesical chemotherapy, chemotherapy drugs that you and me may be giving intravenously, some of them can be given inside the bladder, intravesical installation. One example of that is a combination of gemcitabine and docetaxel. These drugs are given in sequence one after the other inside the bladder, and they have seen significant efficacy, good results, again, helping patients keeping the bladder when they can for patients with what we call BCG unresponsive non-muscle invasive bladder cancer. And again, there's criteria that the International Bladder Cancer Group and the FDA developed, how to define when BCG fails, when we have BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: And we're actually going to get into some of the FDA requirements and development pathways and so forth. What I'm really interested in hearing, and I'm sure our audience is too, are maybe some of the new intravesical treatments that are coming around. I do think it's exciting that the gemcitabine and docetaxel go into the bladder indeed, but what are some of the top new therapies? Pick two or three that you're excited about that people should be looking out for in this intravesical space. Dr. Petros Grivas: For sure, for sure. In terms of the new up-and-coming therapies, there are a couple that come to mind. One of them is called TAR-200, T-A-R 200. This agent is actually a very interesting system. It's an intravesical delivery of a chemotherapy called gemcitabine, the one that I just mentioned a few minutes ago, that is actually being delivered through what we call a pretzel, which is like a rounded [pretzel-shaped] structure working like an osmotic pump, and that is being delivered inside the bladder intravesically by urologists. And this drug is releasing, through the osmotic release mechanism, this chemotherapeutic drug, gemcitabine, inside the bladder. And this can be replaced once every 3 weeks in the beginning. And the data so far from early-phase trials are really, really promising, showing that this agent may be potentially regulatory approved down the road. So TAR-200 is something to keep in mind. And similarly, in the same context, there is a different drug that also uses the same mechanism, and this osmotic release, this pretzel, it's just encoded with a different agent. The different agent is an FGFR inhibitor, a target therapy called erdafitinib, a drug that you and me may give in patients with metastatic urothelial carcinoma if they have an FGFR3 mutation or fusion. And that drug is called TAR-210. Dr. Sumanta (Monty) Pal: And can I ask you, in that setting, do you have to have an FGFR3 mutation to receive it? Or what is the context there? Dr. Petros Grivas: So for TAR-210, TAR-2-1-0, usually there is a checking to see if there is an FGFR3 mutation or fusion. And the big question, Monty, is do we have adequate tissue, right? From a limited tissue on what we call the TURBT, right, that urologists do. And now there is a lot of development in technology, for example, urine circulating tumor DNA to try to detect these mutations in the urine to see whether the patient may be eligible for this TAR-210. Both of those agents are not FDA approved, but there are significant promising clinical trials. Dr. Sumanta (Monty) Pal: So now let's go to a rapid-fire round. Give us two more agents that you're excited about in this intravesical space. What do you think? Dr. Petros Grivas: There is another one called cretostimogene. It's a long name. Dr. Sumanta (Monty) Pal: They really make these names very easy for us, don't they? Dr. Petros Grivas: They are not Greek names, Monty, I can tell you, you know. Even my Greek language is having trouble pronouncing them. The cretostimogene, it's actually almost what we call a growth factor, a GM-CSF. The actual name of this agent is CG0070. This is a replicating mechanism where GM-CSF is replicating in cells. And this agent has shown significant results again, like the TAR-200, in BCG unresponsive non-muscle invasive bladder cancer. I would say very quickly, two agents that actually were recently approved and they're already available in clinical practice, is nadofaragene firadenovec, another long name. That's a non-replicating vector that has the gene of interferon alfa-2b that stimulates the immune system in the bladder. It's given once every 3 months. And the last one that was, as I mentioned, already FDA approved, it's an interleukin-15 superagonist. It's another long name, which is hard to pronounce, but I will give it a try. It's a drug that was recently actually approved also in the UK. The previous name was N-803. It's given together with BCG as a combination for BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: This is a huge dilemma, I think, right? Because if you're a practicing, I'm going to say urologist for the moment, I guess the challenge is how do you decide between an IL-15 superagonist? How do you decide between a pretzel-eluting agent? How do you decide between that and maybe something that's ostensibly, I'm going to guess, cheaper, like gemcitabine and docetaxel? What's sort of the current thinking amongst urologists? Dr. Petros Grivas: Multiple factors play into our account when the decision is being made. I discuss with urologists all the time. It's not an easy decision because we do not have head-to-head comparisons between those agents. As you mentioned, intravesical chemotherapy with gemcitabine and docetaxel has been used over the years and this is the lowest cost, I would say, the cheapest option with good efficacy results. Obviously, the nadofaragene firadenovec every 3 months and the interleukin-15 superagonist, N-803, plus BCG have also been approved. The question is availability of those agents, are they available? Are they reimbursed? Cost of those agents can come into play. Frequency of administration, you know, once every 3 months versus more frequent. And of course, the individual efficacy and toxicity data, preference of the patients; sometimes the provider, the urologist, may have something that they may be more familiar with. But we lack this head-to-head comparison. Of course, I want to make sure I mention that radical cystectomy may still be the option for appropriate patients. So that complicates also the decision making and has to be individualized, customized, and personalized, taking into account all those factors. And there is not one size fitting all. Dr. Sumanta (Monty) Pal: So I think we discussed five intravesical therapies. As you point out, and you know, I'm going to get some calls about this: I think I referred to radical cystectomy as being a more primitive procedure. Not true at all. I think it's something that still is, you know, a mainstay of management in this disease space. But I guess it gets even more complicated, am I right, Petros? Because now we have systemic therapies that we can actually apply in this non-muscle invasive setting for at this point, refractory disease. Can you maybe just give us a quick two-minute primer on that? Dr. Petros Grivas: Absolutely, and systemic therapies now come into play, as you said. And a classical example of that, Monty, came from the KEYNOTE-057 trial that we published about 6 years ago. This is intravenous pembrolizumab, given intravascularly, intravenously, as opposed to the previously discussed intravesical administration of agents. Pembrolizumab was tested in that KEYNOTE-057 trial and showed efficacy about, I would say, one out of five patients, about 20%, had a complete response of the tumor in the bladder in a year after starting the treatment. Again, it's hard to compare across different agents, but obviously when we give something intravenously, there is a risk of toxicity, side effects systemically, what we call immune-related adverse events. And this can also play in the decision making, right? When you have intravesical agents versus intravascular agents, there is different toxicity profiles in terms of systemic toxicity. But intravenous pembrolizumab has been an option, FDA approved, since, if I remember, it was early 2020 when this became FDA approved. There are other agents being tested in this disease, but like atezolizumab through the SWOG study that Dr. Black and Dr. Singh led, but atezolizumab is not FDA approved for this indication. Again, this is for BCG unresponsive, high-risk, non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: So maybe teach us how it works, for instance, at an expert center like the Fred Hutch. When you see a patient with non-muscle invasive bladder cancer, there's obviously the option of surgery, there's the intravesical therapies, which I imagine the urology team is still really at the helm of. But then, I guess there has to be consideration of all options. So you've got to bring up systemic therapy with agents like pembrolizumab. In that context, are you involved that early on in the conversation? Dr. Petros Grivas: That's a great discussion, Monty. Paradigm is shifting as we mentioned together. The urologists have been treating these patients and still they are the mainstay of the treaters, the managers in this disease. But medical oncologists come to play more and more, especially with the FDA approval of intravenous pembrolizumab about 5 years ago [GC1]  [KM2] . We have the concept of multidisciplinary bladder cancer clinic here at Fred Hutch and University of Washington. This happens every Tuesday morning, and we're very excited because it's a one-stop shop for the patients. We have the urologist, a medical oncologist, radiation oncologist, and experts from radiology and pathology, and we all review cases specifically with muscle-invasive bladder cancer. But every now and then, we see patients with BCG unresponsive non-muscle invasive bladder cancer. And this is where we discuss and we talk to the patient about pros and cons of all those options. And that's a classic example where medical oncologists may start to see those patients and offer their input and expertise. In addition to that, sometimes we have clinical trials, we may see these patients because there are systemic agents that may be administered in this setting. We have the SunRISe trial program that includes also a systemically administered checkpoint inhibitor. So that's another example where we see patients either in the context of multi-clinic or in individual solo clinics to counsel the patients about the pros and cons of the systemically administered agents in the context of clinical trials. Usually checkpoint inhibitors are the class of agents that are being tested in this particular scenario. Dr. Sumanta (Monty) Pal: I can see a scenario where it's really going to require this sort of deep dive, much in the way that we do for prostate cancer, for instance, where the medical oncologist is involved very early on and planning out any sort of systemic therapy component of treatment or at the very least, at least spelling out those options. I think it's going to be really interesting to see what this space looks like 5 or 10 years down the road. In closing, I wanted to go through something that I think is so different in this space, at least for the time being, and that is the paradigm for FDA approval. When you and I have our fellows in the clinics, we always say, “Look, you know, the paradigm in this disease and that disease and the other disease needs to be phase 3 randomized trials, right? Big thousand patient experiences where you're testing clinical endpoints.” That's tough in non-muscle invasive bladder cancer, right? Because thankfully, outcomes can actually be quite good, you know, in this setting, right? It's tough to actually estimate overall survival in some of these early-stage populations. Tell me what the current regulatory bar is, and this is a tough thing to do in 2 minutes or less but tell me where you see it headed. Dr. Petros Grivas: You alluded to that before, Monty, when I was giving the background and we talked about the regulatory approval. And I have to very quickly go back in time about 10 years ago because it's important for context that can help us in other disease types too. We had workshops with the FDA and the NCI with the help of the International Bladder Cancer Group and other colleagues. And we try to define a framework, what endpoints are meaningful for those patients in this disease. It was a multidisciplinary, multiple stakeholders meeting, where we tried to define what is important for patients. What are the available agents? What are the trial designs we can accept? And what are the meaningful endpoints that the regulatory agencies can accept for regulatory approval? And that was critical in that mission because it allowed us to design clinical trials, for example, single-arm trials in a disease where there was no standard of care. There was intravesical valrubicin and chemotherapy anthracycline that was approved for many years, but was not practically used in clinical practice, despite being approved, the valrubicin. And because of that, the FDA allowed these single-arm trials to happen. And obviously the endpoint was also discussed in that meeting. For example, for carcinoma in situ, complete response, clinical complete response, because the bladder remains intact in many patients, clinical complete response was a meaningful primary endpoint, also duration of response is also very important. So what is the durable clinical complete response in 1 year or 18 months is relevant. And when you have papillary tumors like Ta or T1 with CIS, for papillary tumors, event-free survival becomes one of the key endpoints and you look at it over time, for example, at 12 or 18 months, what is the event-free survival? So clinical complete response, duration of response, event-free survival, depending on the CIS presence or papillary tumors, I think these are endpoints that have allowed us to design those trials, get those agents approved.  Now, the question going forward, Monty, and we can close with that is, since now we have the embarrassment of riches, many more options available compared to where we were 6 and 7 years ago, is now the time to do randomized trials? And if we do randomized trials, which can be the control group? Which of those agents should be allowed to be part of the control group? These are ongoing discussions right now with the NCI, with other agencies, cooperative groups, trying to design those trials and move forward from here.[GC3]  Dr. Sumanta (Monty) Pal: Well, it's awesome to have you here on the program so we can get some early looks into some of these conversations. I mean, clearly, you're at the table at a lot of these discussions, Petros. So I want to thank you for sharing your insights with us today. This was just tremendous. Dr. Petros Grivas: Thank you, Monty. You know, patients in the center, I just came back from the Bladder Cancer Advocacy Network meeting in Washington, D.C., and we discussed all those questions, the topics you very eloquently mentioned and asked me today, and patients gave us great feedback and patients guide us in that effort. Thank you so, so much for having me and congratulations for the amazing podcast you're doing. Dr. Sumanta (Monty) Pal: Oh, cheers, Petros, thanks so much.  And thank you to the listeners who joined us today. If you really like the insights that you heard on this ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:      Dr. Sumanta (Monty) Pal  @montypal  Dr. Petros Grivas @PGrivasMDPhD   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Petros Grivas: Consulting or Advisory Role: Merck, Bristol-Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology, Abbvie, Bicycle Therapeutics Replimune, Daiichi Sankyo, Foundation Medicine, Bicycle Therapeutics, Eli Lilly, Urogen Pharma, Tyra Biosciences Research Funding (Inst.): Bristol-Myers Squibb, Merck, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, ALX Oncology, Genentech Travel, Accommodations, Expenses: Gilead Sciences

Addressing Swallowing Difficulties and Nutritional Deficiencies in MS - Episode 190 Swallowing issues and nutrition changes are common in MS but often overlooked. Host Stephanie Buxhoeveden is joined by speech-language pathologist Dr. Corinne Jones and dietitian Carla Cos to explore how MS affects eating—and what you can do about it. Learn practical strategies to stay safe, eat well, and adapt to changing symptoms without giving up the joy of food. Thank you to the generous support of our sponsors of this podcast episode, including Kathleen C Moore Foundation, Genentech, and Novartis. Disclaimer: This podcast provides general educational information. Can Do MS does not endorse, promote, or recommend any product or service associated with the content of this program.   Additional Resources: National Foundation of Swallowing Disorders IDDSI - International Dysphagia Diet Standardization Initiative

Chris takes us back to his days as a college baseball player with a bleeding disorder dreaming of the pros. How do you face your limitations? And how do you accept it when a dream doesn't work out?    This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film.   Guests:  Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”    Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)   Amy Board, MNM, Believe Limited Senior Vice President of Engagement and Programs The Final Summit is produced by BloodStream Media. To get in touch, email mailbag@bloodstreammedia.com Connect with BloodStream Media: BloodStreamMedia.com BloodStream on Facebook  BloodStream on X/Twitter  BloodStream on Instagram BloodStream on LinkedIn BloodStream on TikTok

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with Stephen Dilly, Chairman, President and Chief Executive Officer at Codexis. Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with Stephen, covering: His journey of almost 40 years in the industry, including 20 years as a CEO. Leading two therapeutic companies to two, successful, $billion+ exits... Not making snap judgements and instant opinions early on in your role as a senior leader. Why he took on the challenge of leading Codexis at this phase of his career. The importance of values as guiding principles, and spending in-person time with your team. As President & CEO of Codexis since August 2022, Stephen brings more than three decades of executive management experience in the biopharmaceutical industry. Most recently, he served as President and CEO of Sierra Oncology (NASDAQ: SRRA) through its recent sale to GlaxoSmithKline for $1.9 billion.  Previously, Dr. Dilly served as CEO of Aimmune Therapeutics, acquired by Nestle Health Science for $2.6 billion. Dr. Dilly has served in executive roles at Genentech, Chiron and SmithKline Beecham and has been associated with the development, approval and launch of more than twenty marketed drugs across multiple therapeutic areas. He holds both an MBBS and a PhD in Cardiac Physiology from the University of London.   Molecule to Market is also sponsored by Bora Pharma (boracdmo.com) and Charles River (www.criver.com), and supported by ramarketing.    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!

You have a problem. Your software subscriptions are seeing record signups but you're also losing people at an alarming rate. You've got investors breathing down your neck to grow your 2 year old SaaS company. Somethings missing, you just can't put your finger on it. You end up hiring a CX/UX Consultant, like our friend Nick Cawthon, Founder of Gauge, who joins us on this episode of The Longer Game. You find out you don't have the right feedback loops in place. Because of this, nobody is telling you your software functionality isn't quite what you thought it was. People like it but they're having to do manual work that should be intuitive in your design and your next new feature? They just don't need it. Listen in to hear how Nick handles these kinds of situations and why you always need to know where the closest coffee shop is. Grab your coffee, close your eyes, and enjoy the view.The Longer Game is a podcast focused on leaning into the trends and advancements in retail so brands see a clearer path to success across ALL channels. We're looking at retail in a whole new way, looking to better understand the future of retail. It's Retail Reimagined. Sharing hope about the future. No one channel can a business sustain. Go omni-channel.Like what you're hearing? Subscribe to our channel and make sure to click or tap the bell so you get notified whenever new episodes drop.Want to learn more about The Longer Game? Head over to https://thelongergame.com to read show notes, watch more episodes, or contact us.Follow us on LinkedIn: https://linkedin.com/company/thelongergameFollow us on Instagram: https://instagram.com/thelongergameFollow us on Facebook: https://facebook.com/thelongergameOur guest's Name is Nick Cawthon. Nick helps design teams stay ahead of the curve with their AI transformation. He has been curating self-assessments for UX & Design Teams at retrain.gauge.io, helping analyze industry trends and removing barriers to adoption. Nick founded Gauge in 2001 in the San Francisco Bay Area to help organizations with evidence-based strategy and product decisions. Clients have grown to include Electronic Arts, Genentech, Airbnb, Adobe, and many others. Nick is a professor in Data Literacy and Visualization in the Design Strategy MBA program at his alma mater, California College of the Arts. You can find them at...Website: https://gauge.io/Find them on LinkedIn: https://www.linkedin.com/in/nickcawthon-ux-digital-agency-product-design-leadership/Michael Maher, the host, would love to connect with you. Reach out to him at…Email: michael@thinkcartology.comLinkedIn: https://linkedin.com/in/immichaelmaherThis podcast is sponsored by Cartology and Podcastify Me.Cartology is a customized done-for-you service agency that helps brands accelerate growth and get profitable on the Amazon marketplace. They work directly with brands to create strategy and then go right out and execute it. Want to find out more?Website: https://thinkcartology.comFind Cartology on LinkedIn: https://linkedin.com/company/cartologyFind Cartology on Instagram: https://instagram.com/thinkcartologyFind Cartology on Facebook: https://facebook.com/thinkcartologyPodcastify Me is designed to help coaches of all kinds enter the podcasting space with minimal lift for them. And, inviting past, current and future clients to your show as part of your marketing and sales process sets you apart from your competition, in a time where podcasting is really gaining popularity.Website: https://podcastify.meFind Podcastify Me on LinkedIn: https://www.linkedin.com/company/podcastify-me/Find Podcastify Me on Instagram: https://www.instagram.com/podcastify.me/Find Podcastify Me on YouTube: https://www.youtube.com/channel/UCf2biqOTN2UbZ5aaM4Sx6NQ

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VFP865. CME/NCPD/CPE/AAPA/IPCE credit will be available until August 18, 2026.Raising Frontline Expectations in DLBCL: Principles for Refining Upfront Treatment and Addressing Unmet Needs With Modern Antibody-Based Combinations In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VFP865. CME/NCPD/CPE/AAPA/IPCE credit will be available until August 18, 2026.Raising Frontline Expectations in DLBCL: Principles for Refining Upfront Treatment and Addressing Unmet Needs With Modern Antibody-Based Combinations In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VFP865. CME/NCPD/CPE/AAPA/IPCE credit will be available until August 18, 2026.Raising Frontline Expectations in DLBCL: Principles for Refining Upfront Treatment and Addressing Unmet Needs With Modern Antibody-Based Combinations In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VFP865. CME/NCPD/CPE/AAPA/IPCE credit will be available until August 18, 2026.Raising Frontline Expectations in DLBCL: Principles for Refining Upfront Treatment and Addressing Unmet Needs With Modern Antibody-Based Combinations In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VFP865. CME/NCPD/CPE/AAPA/IPCE credit will be available until August 18, 2026.Raising Frontline Expectations in DLBCL: Principles for Refining Upfront Treatment and Addressing Unmet Needs With Modern Antibody-Based Combinations In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

Biotechnology company Genentech broke ground on its first east coast facility on Monday. It plans to hire 420 people in Holly Springs as it works on developing obesity drugs. WRAL's Shaun Gallagher explains what the company's plans are over the next five years.

Mehek Mohan is a Stanford Graduate School of Business student and the co-founder of Kahani, a personalized recovery platform for individuals navigating eating disorders. Prior to Stanford, Mehek led AI and automation initiatives at Genentech within the Early Clinical Development team. She earned her undergraduate degree in Molecular and Cell Biology from UC Berkeley and has experience in early-stage venture capital. Mehek is passionate about making mental health care tools more accessible by leveraging cutting-edge advances in technology. We will take a deep dive into this recovery platform to learn and understand how technology has the potential to improve outcomes. This platform is new, an 8-week pilot program was launched in April of this year just as we were recording this podcast.  Kahani is a digital recovery companion designed to help individuals navigating eating disorder recovery by providing structured, evidence-based activities in a game-like format.Think Inside Out meets Duolingo meets Farmville!   Email:  mmehek@stanford.edu  Linkedin:  https://www.linkedin.com/in/mehekmohan/ Our Hosts:   ·         Linda and John(Jack) Mazur founded a nonprofit 501(c)3 organization in 2022 in memory of their daughter, Emilee which provides peer support, social connection, and education for adults with eating disorders and for their family members. For more information or to contact them go to: www.theemileeconnection.com  Linda and John (Jack) Mazur wrote, Emilee: The Story of a Girl and Her Family Hijacked by Anorexia, to honor their daughter's wish, to raise awareness, evoke compassion, and foster change in how eating disorders are viewed and treated. Paperback: and Kindle:https://www.amazon.com/Emilee-Story-Family-Hijacked-Anorexia/dp/170092012X        Audiobook :https://www.amazon.com/Emilee-Story-Family-Hijacked-Anorexia/dp/B08R6LRPDS        Linda and Jack can also be reached through the book website:   https://emileethestoryofagirl.com or at Linda.john.mazur@gmail.com  Ellen Bennett is the director of KMB for Answers, a non-profit charity providing educational and financial support for mental health professionals as well as assistance for families in search of resources. For more information about Ellen Bennett and the foundation founded in memory of her daughter Katlyn, go to: www.Kmbforanswers.com

Dr. Sumanta (Monty) Pal and Dr. Arielle Elkrief discuss the clinical relevance of the gut microbiome in cancer immunotherapy and the importance of antibiotic stewardship, as well as interventions currently being explored to treat gut dysbiosis and optimize immunotherapy response. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hi everyone, I'm Dr. Monty Pal, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist. I'm a professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles.  Today we're here to discuss one of my favorite topics, which is the gut microbiome. It's almost hard to avoid the gut microbiome nowadays if you look at medical literature within oncology. It's an emerging phenomenon, but there are a couple of individuals that I would really define as pioneers in the field. And one of them is actually with me today, Dr. Arielle Elkrief, to discuss the clinical relevance of the gut microbiome, particularly amongst patients receiving immunotherapy, although I imagine our conversation today will take many twists and turns. Arielle is an assistant professor and clinician scientist in the Department of Oncology at the University of Montreal, and she is co-director of the CHUM Microbiome Center there.  FYI for the listeners, we have our full disclosures in the transcript of this episode.  Arielle, thank you so much for joining us today. Dr. Arielle Elkrief: Thanks so much, Monty. This is going to be amazing. Dr. Sumanta (Monty) Pal: Well, I have to tell you what sort of inspired me to bring you on as a guest. It was one of many things, but it was this really terrific ASCO Educational [Book] article that you wrote. Now, I have to tell you, I've read all the articles sort of cover to cover in the book, and they're always a wonderful primer, so if our audience is studying for board research or something of that sort, it's a terrific resource to go through. I have to tell you, this piece on the gut microbiome that you wrote is nothing short of a masterpiece. If you read this cover to cover, it's actually going to give you, I think, a sense of the current state and future state of the field. I wanted to start by just sort of beginning with sort of the origin story for a lot of this, which is this association between the gut microbiome and immunotherapy response. This takes us back several years to this pivotal series of papers in Science. Maybe you could walk our audience through that. Dr. Arielle Elkrief: Absolutely. Well, thank you so much for your kind words about the ASCO [Educational] Book. It was a team effort with a lot of key opinion leaders in the field, so I'm really glad to learn that you've liked it.  Moving backwards in terms of how we came to understand that the gut microbiome is essential to priming a response to cancer immunotherapy actually goes back to 2015 and seminal papers that looked at what happens when we take mice that are germ-free mice that have never been exposed to a microbiome. These are mice that are born by cesarean section and essentially live in a bubble. And when we give those mice tumors and treat them, in the first papers with anti-CTLA-4 treatment, we realized that these antibodies don't work at all. And that was the first observation that the presence of a gut microbiome was essential to mounting an anti-cancer immune response. When we supplemented those same mice with beneficial bacteria or feces from responder patients, we were able to restore the response to immunotherapy. And so those were really the first preclinical observations that made us understand the critical role of the microbiome in immunotherapy response. Moving a little bit in the future, we examined the fecal microbiome composition using shotgun metagenomic sequencing in different cohorts of patients with solid tumors, namely lung cancers, kidney cancers, and also skin tumors like melanoma, and found that patients who responded to immunotherapy had a distinct microbiome that was characterized by beneficial bacteria compared to patients who experienced resistance to immunotherapy that had a dysbiotic or diseased microbiome. Dr. Sumanta (Monty) Pal: So, you know, it's interesting, these techniques that we're using to sequence the gut, they're a little bit different. So I wonder if you can give the audience a quick primer on these techniques that you're so well versed in, shotgun metagenomic sequencing, 16S rRNA sequencing. If you had to describe this in 30 seconds, which is a tall task, how would you do that? Dr. Arielle Elkrief: That's a tall task. Much of what we know about the microbiome initially came from a technique called 16S rRNA sequencing. This is a technique that amplifies the 16S region and basically tells you at the genus level what's going on at the level of bacterial composition. This technique is fast, relatively cheap, and can be performed on a laptop computer, which is excellent. The problem is that it's prone to a lot of technical variations. Different primers might give you different results, and you're really limited at the genus resolution. You can't get a good resolution in terms of species, and we're learning that different species from the same genus might have different physiological properties, and the same thing goes at the strain level. So when we really zone in and look at inter-species changes, we're seeing that these actually have specific functions in the host. So that brings us to metagenomic sequencing, which is a whole genome sequencing, next-generation sequencing based method that looks at the whole composition and gives you information not only on bacteria, but you might also get fungal and viral properties. You can zoom in on the strain level. You can also get functional output, so we can examine what the metabolic properties of specific species or strains might look like. The negative aspects of shotgun metagenomic sequencing is that it takes a lot of computational power in order to analyze the results and it might take a little bit longer. And certainly, within the clinical setting, not something that's feasible yet.  And that brings us to more novel point-of-care biomarker tools that we've collaborated in developing along with Dr. Laurence Zitvogel and Dr. Lisa Derosa at Gustave Roussy, that learning from the shotgun metagenomics results designed a probe using quantitative PCR which looks for this specific bacteria we know to be important and developed a ratio of harmful bacteria to beneficial bacteria. This is called the TOPOSCORE, and it actually is able to predict quite nicely the response to immunotherapy using a stool sample and a really good turnaround time of almost 72 hours. Dr. Sumanta (Monty) Pal: That was a perfect overview and a lot of information in a short amount of time. It also makes you take out your high school biology textbooks, doesn't it, to understand that the bacterial ribosome, right, is a different size and shape, and that's what we're sequencing here. But these techniques I think are incredibly important, and I'm glad you actually discussed this, this RT-PCR based strategy of calculating the TOPOSCORE. It lends itself to this phenomenon of dysbiosis, and I think for our audience, that's going to be an important term to understand as time goes on. There's the normal healthy gut and then there's this phenomenon of dysbiosis, which is, I guess, simply put, an unhealthy gut. But tell us about, you know, how often you see dysbiosis in a cancer patient, maybe versus a normal healthy adult. Dr. Arielle Elkrief: So, I think we can split up your question into two parts. One is we know from cohort studies and population level-based studies that the microbiome of patients with cancer is distinct from healthy patients or healthy people. And we know that because of the global composition. We also think that there are diversity metrics that lend themselves to being described as dysbiotic. But we do know that the microbiome of people with cancer is distinct from healthy volunteers. That's the first point.  In terms of how frequently dysbiosis occurs in patients with cancer, it's not very well defined. We know that even among healthy people, there is a certain level of dysbiosis. Laurence in her talk mentioned that to be about 10% to 20%. And the other fascinating component is that when we're thinking about dysbiosis and the cancer associated microbiome, in terms of the species that are enriched, it's quite striking that a lot of these dysbiotic or negative bacteria are also found to be enriched in patients with metabolic disease, like cardiovascular disease, for example. And so it's unclear if dysbiosis is the cause or consequence, but there definitely seems to be a general pattern of disease when looking at the microbiome compared to healthy people. Dr. Sumanta (Monty) Pal: That's interesting. So, I'll tell you, my second favorite portion of your article, and I'll tell you my favorite portion as well in the context of this podcast, but my second favorite part was the section around antibiotic stewardship. You know, the utilization of antibiotics in a very pragmatic fashion amongst our patients. Can you describe why that's so critical in the context of the microbiome? Dr. Arielle Elkrief: Antibiotics can disrupt the gut microbiome composition. We know this from mouse studies, but also cohort studies of patients that are exposed to antibiotics. And most importantly, we know that patients who are exposed to antibiotics, either before or during the immunotherapy period, have significantly worse progression-free survival and overall survival to immunotherapy. And this is true for immunotherapy in the monotherapy setting, but also when combined with chemotherapy. What's striking is that when we look at patients who are just treated with chemotherapy, we don't see the negative outcome of antibiotics on outcome and progression-free survival and overall survival, suggesting that the negative impact of antibiotics on outcomes is really specific to immunotherapy backbones. The other important point is that this negative signal is maintained even after adjusting for standard prognostic variables in the specific malignancies that we're looking at. And then most importantly, at the mechanistic level, we were able to actually pinpoint the mechanism behind this antibiotic related dysbiosis. And we see this with a bloom of negative bacteria which induces a loss of MAd-CAM, which is an endothelial gut checkpoint immune marker, and that causes an efflux of immunosuppressive T cells, which are usually in the gut, to go straight into the tumor where they make the tumor unamenable to an immunotherapy response. And so now we finally have the mechanism as to why antibiotics are harmful and why we need to practice antibiotic stewardship. Dr. Sumanta (Monty) Pal: And just to be clear for the audience, I mean, if a patient needs antibiotics, they need antibiotics. But perhaps it just suggests that, and we have, I suppose, this predilection as oncologists, just for the minor cold or cough or what have you, we maybe should be a little bit more cognizant of whether or not antibiotics are truly necessary. Is that fair? Dr. Arielle Elkrief: Absolutely. So what we're advocating for is antibiotic stewardship, and this is the clear recommendation that we can make. So that means confirming a bacterial infection. If it's there and antibiotics are indicated, to choose the most narrow spectrum for the shortest course and constantly re-evaluate the indication of antibiotics. And of course, we need to work with our colleagues in infectious diseases who've done incredible work in antibiotic stewardship. And all along this process we also need to be mindful of other medications and polypharmacy, such as proton pump inhibitors or narcotics, for example, we think that these other medications which are frequently prescribed in our cancer population can also potentially have negative impacts on the microbiome and immunotherapy response. Dr. Sumanta (Monty) Pal: I think that's a terrific summary and big guidance for the audience.  I promised you I'd tell you my favorite part of your article, and this is this huge table. I think the table is two and a half pages long, if I remember correctly, but it's an awesome table, and I highly recommend our audience to check this out. It lists literally every therapeutic trial for the microbiome under the sun. And so it begins with the approach of fecal microbiota transplant, which I'm going to ask you to tell us about in a second, but it also hinges on a lot of really cool sort of novel therapies, live bacterial products, mixes of different microbial products. Maybe take us through this whole approach of FMT (fecal microbiota transplantation). I actually wasn't aware of the dozens of trials that you listed there in this space. It seems like it's a very active area of research. Dr. Arielle Elkrief: Definitely. So, as you alluded to, FMT or fecal microbiota transplantation is the most well studied and direct way to modify the patient's microbiome. This technique aims to replace the patient's dysbiotic microbiome with that of a healthy microbiome, either from a healthy donor volunteer that's been heavily screened, or from a patient who experienced response to immunotherapy. And, as three landmark studies so far that have been published demonstrated the potential of FMT to reduce primary resistance or secondary resistance to immunotherapy, and this has been in melanoma.  We also recently reported on the results of our FMT-LUMINate trial, which looked at patients with lung cancer and melanoma. Once again, FMT, when combined with immunotherapy was safe and led to a higher proportion of responses than we would normally expect.  We're now also looking at randomized trials that have come out. So the first being the TACITO trial in kidney cancer, which compared FMT plus pembrolizumab and axitinib to placebo in patients with RCC, and again, FMT was safe and feasible and also led to an increased progression-free survival at one year, meeting the study's primary endpoint.  And so, so far, there's a wealth of data really showing the promise of FMT when combined with immunotherapy, and we're now in the process of conducting larger randomized trials, including in melanoma with the CCTG (Canada Cancer Trials Group) in our ME17 or Canbiome2 trial, where we're going to be enrolling 128 patients with metastatic melanoma to receive FMT and standard of care immunotherapy compared to standard of care immunotherapy alone. Dr. Sumanta (Monty) Pal: You're very humble, so I've got to highlight for our audience. This was a mega grant that Arielle received to fund really the largest prospective exploration of FMT that will exist to date. So I'm really excited about that. I wish this was something we could participate in stateside.  Before we jump into the other approach, which is live bacterial products and mixes thereof, where do you see FMT going? I think that one of the perceived challenges with FMT is that it's hard to implement, right? You need to have a really robust framework when it comes to gastroenterology, the preparation's challenging. Is there a way to envision FMT use being more generalized? Dr. Arielle Elkrief: Those are great questions. So we're lucky in Canada to work with pioneers in FMT, Michael Silverman, Saman Maleki, and John Lenehan in London, Ontario, who had this really robust FMT healthy donor screening program, which literally screens for every pathogen under the sun, and we haven't had any problems with feasibility or implementing FMT in Canada. But I think that once we're going to hopefully start doing larger scale, randomized phase three studies, that we might run into problems with scalability. And I think also with regards to reproducibility, and that's the feedback that we're getting from some regulatory authorities, especially at the level of the FDA, where there are some concerns around inter- and intra-donor variability because, of course, we can't guarantee that every fecal sample is going to be the same. So that has really pushed the field to think about other strategies, such as live biotherapeutic products which take modified FMT or bacteria from stools from either healthy donors or from responder patients and basically turn them into drugs that are regulated as drugs and can then be studied in the context of investigational new drugs or products. Dr. Sumanta (Monty) Pal: I like this and, you know, I do think that there's a future for it. We just have to kind of put our heads together and figure out how to get over all of these logistical hurdles, but, you know, I agree, I think your group and others have demonstrated, especially with this trial that you're fanning out all throughout Canada, that it can potentially be done.  This is a topic that could probably go on for another couple of hours, right, especially based on the size of the table that you put together in this brilliant article, but tell us about live bacterial products or LBPs, as we call them these days. What's the current status, what's the future there? And maybe I'll give you less than two minutes here, although again, I realize it's a two-hour topic. Dr. Arielle Elkrief: You're probably better suited to speak about that because you've been one of the pioneers in terms of this. So we can think about LBPs in terms of single strain organisms, like CBM588 for an example, which your group did some amazing work in showing that, in a randomized setting, that this led to better responses than we would expect compared to just work with controls. We also know that LBPs can have multiple strains, up to 30. We're collaborating with a company called Cannabis Bioscience that is actually working on much larger communities of consortia. And so we're really excited about the direction that that's taking in terms of taking these LBPs and developing them from the drug perspective. In addition to LBPs, we know that there are other ways that we can change the microbiome, notably prebiotics, which are compounds which can have a beneficial impact on the microbiome. And one of these is camu camu, which I know your group is leading a clinical trial looking at camu camu and kidney cancer, and we're excited to see how that compares to FMT or LBPs, because that might be a potentially scalable alternative. Dr. Sumanta (Monty) Pal: That's awesome. What a terrific overview, and that was less than two minutes. I don't know how you did it. That's terrific.  Arielle, this has been such an insightful conversation. I just want to thank you for, again, a terrific article in the ASCO Educational Book. I highly recommend all of our listeners to go there and check it out, and also for sharing all these terrific insights on the podcast today. Dr. Arielle Elkrief: Thank you so much, Monty. Dr. Sumanta (Monty) Pal: And thanks to our listeners, too. If you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Sumanta (Monty) Pal  @montypal Dr. Arielle Elkrief Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Arielle Elkrief: Honoraria: AstraZenica, Bristol-Myers Squibb, Merck, EMD Serono Consulting or Advisory Role: Bristol-Myers Squibb Research Funding (Inst.): Kanvas Bioscience, AstraZeneca, Merck Other Relationship: Royal College of Surgeons and Physicians of Canada, Cedar's Cancer Center (Henry R. Shibata Fellowship), Canadian Institutes of Health Research (CIHR)

Billions are being poured into healthcare AI, yet most innovations never make it past pilot projects. Why? And more importantly—how do we fix it? In this episode of Med Tech Gurus, we sit down with Marco Smit, serial entrepreneur, life sciences executive, and AI commercialization expert. With leadership experience at Roche, Genentech, Gesund.ai, CareSyntax, and now Domelabs.ai, Marco has seen the full spectrum of healthcare AI—from hype to hard-earned success. He shares why so many organizations fall victim to “pilotitis”, the critical role of AI governance, and how startups and health systems can build scalable, evidence-driven solutions that actually deliver ROI. From navigating the complex regulatory landscape to choosing the right investors and partners, Marco offers a pragmatic playbook for moving AI from the lab to real clinical impact. Whether you're a startup founder, health system innovator, or medtech investor, this episode is packed with actionable insights on avoiding hype, accelerating adoption, and building AI solutions that last.

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.## Viking Therapeutics' oral obesity pill, VK2735, achieved over 12% weight loss in a clinical trial, causing their stock to plummet due to safety concerns. The pending approval of oral Wegovy has also brought attention to high-dose peptides.## Meanwhile, leaked information reveals a proposed overhaul of vaccine strategies and access to novel therapies. The FDA rejected PTC Therapeutics' drug for Friedreich's ataxia, and Novo Nordisk reassured investors of their capacity to supply oral semaglutide. Fedegari now offers customized solutions for the pharmaceutical industry, and Vantai is in talks with Halda for a potential proteomics partnership. ## Other news includes conflicts of interest in vaccine committees declining, RegenxBio facing a delay in their gene therapy approval, and Genentech ending a partnership with Adaptive Biotechnologies. Kriya raises $313 million for gene therapy, Merck KGaA invests in RNA-targeting technology, and Novo Nordisk receives approval for Wegovy.

What happens when a veteran mountain climber with hemophilia returns to mountaineering after a six-year layoff? In 2018, Chris Bombardier became the first hemophiliac to climb the Seven Summits, including Mt. Everest. In 2024, Chris leads a group of climbers with bleeding disorders on a daring attempt to summit Mont Blanc, the highest peak in the French Alps. But is being older and wiser necessarily better? In Season 4 of The Final Summit, Chris and his guests re-tell his entire life story from a new perspective. They'll talk about finding your path, defining yourself as a role model and a leader, what it means to be a success, and how to change your definition of success.    This episode is brought to you by Genentech. Visit http://www.hemashort.com/ to watch the short film.   Guests:  Patrick James Lynch, Founder and CEO of Believe Limited, (Instagram)     Amy Board, MNM, Believe Limited Senior Vice President of Engagement and Programs    Joana Baquero, business strategist and resilience expert, author, Driven by Hope; Ted Talk: “Resilience: A Mindset for Everyday Life”  Dr. Ryan Warner, clinical psychologist and speaker, founder of RC Warner Consulting

Dr. Sumanta (Monty) Pal and Dr. Kimmie Ng discuss the disturbing rise of early-onset gastrointestinal cancers, the unique challenges faced by younger patients, and key research that is shedding light on potential drivers of early diagnoses in colorectal cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello, everyone. I'm Dr. Monty Pal, and I'm a medical oncologist and professor and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. I'm really delighted to welcome you all to the ASCO Daily News Podcast as the show's new host. I'll be bringing you discussions with leaders in the oncology space on a variety of topics. I've been working hard with the ASCO team on picking the ideal topics to bring to you, and I'm really delighted to introduce my first guest, a dear friend, Dr. Kimmie Ng, to discuss this huge problem that we're seeing nowadays of early-onset GI cancers. Dr. Ng is the associate chief of the Division of Gastrointestinal Oncology at the Dana-Farber Cancer Institute, and she's an associate professor of medicine at Harvard Medical School in Boston. She serves as co-director of the Colon and Rectal Cancer Program. She's also the founding director of the Young-Onset Colorectal Cancer Center at Dana-Farber. I'm sure we'll talk a little bit about that today.  Just to note, our full disclosures are available in the transcript of this episode.  Dr Ng, it's so great to have you on the podcast. Thanks so much for joining us. Dr. Kimmie Ng: Thank you so much for having me. It's great to be here. Dr. Sumanta (Monty) Pal: I'm going to refer to you as Kimmie, if you don't mind, for the rest of the podcast here. Please, we'll go by first names, if you don't mind.  Your research has really done so much to help improve our understanding of early-onset GI cancers. You've done a lot of work to increase awareness in this space. I don't think there's a couple of months that passes by when I don't see you on television on Good Morning America or other shows really broadcasting this really critical message. I think there's a certain sensitivity that we all have to this issue, right? I mean, because receiving a cancer diagnosis at any age is very challenging, but I'm sure that young patients who face a colorectal cancer diagnosis have some very unique challenges. Could you give us a sense of some of those? Dr. Kimmie Ng: I think the other reason why so many people are interested in this and feel touched by this is that it's not just gastrointestinal cancers that are increasing in young people, but actually a multitude of different cancers have been rising in young individuals. And while it is difficult at any age to receive a cancer diagnosis, we do all know that young people getting a diagnosis like this do face unique challenges. Studies have shown that over 80% have children under the age of 18 when they are diagnosed with colorectal cancer, for example, under the age of 50. And many experience career and education disruptions. They are in what we call the ‘sandwich generation,' where they're not only taking care of young families or starting to think about starting a young family, but they're also taking care of elderly parents. So it's just a very busy stage of life, and to then be facing a usually terminal cancer diagnosis, it is extremely challenging. The other factors that we've seen that seem to be unique or more prevalent in young patients is that there are higher levels of psychosocial distress, depression, and anxiety, and a majority of patients do need medical attention and treatment for those things, whether it's medication treatment or whether it's counseling or support from psychosocial oncologists. And so the other big issue is fertility. We know that so many of the treatments that these young patients receive do permanently and negatively impact fertility. And for a person who is young, who may still be trying to expand their family or again start a family, it is very important that these young patients do receive counseling about fertility preservation prior to starting treatment. Dr. Sumanta (Monty) Pal: You know, it's so interesting you bring this up, and I think about a patient who's in their 40s diagnosed with this disease. They're in the same demographic as I am, as you are. You know, I'm 44 years old, and you know, I'm thinking about my 11- and 12-year-old and my aging parents, right? I mean, the dilemmas that you highlighted are precisely what I'm facing in life, and it's so true, right? If I had to take my day-to-day and superimpose on that a colorectal cancer diagnosis, it would just be problematic in so many spheres, so many spheres. Dr. Kimmie Ng: Absolutely. And because we did think going into this, starting our Young-Onset Colorectal Cancer Center, that these patients will need unique supports, we did conduct a qualitative study and held some focus groups of young-onset colorectal cancer patients as well as their caregivers. And we really identified four primary themes that I think reflect a lot of the experience of patients with cancer, no matter what type of cancer when they're diagnosed young. And the first is the need, feeling overwhelmed by the healthcare system, and the need for patient navigation. As we know, a lot of these patients are previously healthy before they're facing this very serious diagnosis. The second is the need for peer-to-peer support, where they really value connecting with other young patients going through a similar experience. The third, we talked about already, the need for kind of formal psychosocial support in the form of psychosocial oncologists or psychiatrists or social workers. And the last is an interest in research. They are really very invested in getting germline genetic testing as well as somatic genomic profiling to help guide their therapy. Dr. Sumanta (Monty) Pal: That's really encouraging to hear that they themselves are interested in participating in research. I mean, obviously, that's a great way to move the field forward. I view your area of work here as being such a vexing problem because no matter what way you slice it, young-onset colorectal cancer still remains a relatively small proportion of all diagnoses. So how do you go about studying this phenomenon? I mean, it must be challenging to really sort of investigate underlying causes when ostensibly this is still a small piece of the pie. Dr. Kimmie Ng: That is such a great question and is one of the challenges me and my research team think about every single day. As you mentioned, one of the major barriers is that although these cancers are rising in young people, the absolute number of patients being diagnosed is still relatively small, and if it's going to take large scale epidemiologic studies to really understand, for example, what the dietary and lifestyle risk factors are, you need a considerable number of patients in order to have enough power to reach definitive conclusions.  And so this is where it is so important to collaborate. Any single institution is not going to see enough young-onset patients with colorectal cancer to be able to do this work on their own. And so I have really been intent on establishing an international prospective cohort study of patients with young-onset colorectal cancer so that we can increase the numbers of patients we partner with to try to answer these questions, but also so that we can study this on a global scale, because unfortunately this is not something that's just plaguing the United States. It is actually happening in multiple countries around the world. So that is one barrier.  The second, I would say, is that we think it's early life exposures to whatever environmental factor it is that's causing the rise that is likely contributing the most. And so if you imagine how difficult it would be to start studying individuals from when they're children through adolescence, through adulthood, and then all the way until a cancer diagnosis is obtained, a study like that would take too long, would cost too much, and really wouldn't be feasible. So we need to think of alternative ways to really try and answer this question of what is driving this rise in young-onset colorectal cancer. Dr. Sumanta (Monty) Pal: Honestly, Kimmie, this seems like almost an unfair question in the context of what you just mentioned, the challenges in terms of ascertaining causality, right? I'll tell you, I cheated a little bit ahead of this podcast. Kimmie and I had dinner together in Los Angeles a couple months ago. She came out to deliver a Presidential Lectureship at City of Hope. We were delighted to have her. And we did have a couple of thoughts exchanged over potential drivers of these early diagnoses, leaning on perhaps one of the things that you and I are both interested in, the microbiome. But amongst all these things, vitamin D, microbiome, etc., and I won't hold you to this, do you have at least a general sense of what might be contributing to this early-onset phenomenon? Dr. Kimmie Ng: Yeah, as we talked about during my visit there to City of Hope, we do hypothesize that it is a complex interaction between our exposome, which is everything we are exposed to in our environment, which does include diet and lifestyle factors, interacting with host immunity and antitumor immunity, and as well as the microbiome and shaping the composition and diversity of the gut microbiome that are likely interacting to increase susceptibility to colorectal cancer at a younger age. And I will say one of the biggest discoveries, if you will, about what might be driving young-onset colorectal cancer was published a few months ago in Nature. And that paper identified a specific mutational signature caused by the genotoxin colibactin, which is often produced by an organism called pks+ E. coli, as being much more prevalent in younger patients with colorectal cancer than older patients. And so while it doesn't explain necessarily all of young-onset colorectal cancer and why it's rising, it does give us a clue that the microbiome is likely very important in perhaps why this is rising in young people. Dr. Sumanta (Monty) Pal: After you mentioned it, I went back and dove deep into that paper. I was fascinated, fascinated by the content there. And this is just a massive exploration across thousands of patients worldwide. So, I mean, if there is a way to get at least some hint of what's driving this phenomenon, I suppose that's it. So thank you for pointing me in the direction of that manuscript. Now that we've addressed the issue of diagnosis, if we could just, you know, verge on the topic of treatment, right? And this is something that I struggle with. When I have my young patients with kidney cancer, I don't know necessarily that my treatment paradigm changes a whole heck of a lot. I guess what I will say is I might be a little bit more aggressive about concepts like definitive management with surgery. I suppose perhaps their treatment tolerance is a little bit higher. But tell us about the setting of young-onset colorectal cancer. Is the philosophy any different in terms of the actual sort of management of these patients? Dr. Kimmie Ng: That's a great question, and actually I was honored to participate in the first international consensus guidelines group to try to come up with uniform recommendations for how to treat young patients with colorectal cancer. And you know, the overall consensus is just as you said, the medical care of these young patients right now is really not that much different than that of an older patient with colorectal cancer. There are a couple of distinctions. One is that all young patients should get germline genetic testing, given that there is a higher prevalence of pathogenic germline variants when you are diagnosed at a young age. And the second is what we've already talked about, which is that all young patients should be referred for counseling about fertility preservation prior to starting treatment. But otherwise, the chemotherapy regimens recommended, you know, surgery, radiation, all of that seems very similar to older patients. I will say that because most of our young patients with colorectal cancer are diagnosed with left-sided cancers, including rectal cancers, where some of the treatment may be morbid and result in lifelong complications, we do consider de-escalation of therapy and try to consider the long-term implications when it's safe to do so and won't compromise outcomes. The other concerning thing is that younger patients don't necessarily have a better prognosis than older patients. And multiple studies have shown this, that even though we both often treat younger patients more aggressively – they more often receive multi-agent chemotherapy, and more often undergo surgery and radiation – their survival is not necessarily correspondingly better than an older patient with colorectal cancer. So that suggests to us that maybe these cancers are indeed biologically different and perhaps more aggressive or perhaps less responsive to treatment. And so that is some of the focus of our research too, to understand what is actually different about these cancers and how they respond to treatment. Dr. Sumanta (Monty) Pal: It's such a paradox, isn't it, right? Because you just brought this to my mind. I guess on the one hand, our younger patients may be able to tolerate perhaps a greater amount of chemotherapy, targeted therapy, etc. But you're absolutely right. I mean, they do sort of have these lingering issues with side effects that may persist for much longer than the 80- or 90-year-old that we're treating in the clinic. I mean, these tend to be sort of lifelong consequences and sequelae that they're dealing with. So that really does evolve to be a challenge. You've kind of changed my mindset there a little bit. Dr. Kimmie Ng: Yeah, I do think survivorship issues and long-term complications of therapy do need to be considered, especially for a young person who we hope will live a very, very long time. And so part of the work that our Young-Onset Colorectal Cancer Center is doing, we are participating in a pilot navigation study where we navigate patients to survivorship earlier than we typically would, perhaps, for an older patient. And that's so we can get a head start on addressing some of those potential complications of therapy and hopefully mitigate them so that they don't become an issue long term. Dr. Sumanta (Monty) Pal: Do you think there's a role for de-escalation studies formally in these young populations of patients? Dr. Kimmie Ng: I think de-escalation studies are important overall, and specifically for locally advanced rectal cancer, which again is one of the most common types of colorectal cancer diagnosed in our young patients, there are certain populations that may be able to forgo the radiation treatment to the pelvis, for example, and there's more and more patients who now may become candidates for non-operative management where they may not necessarily need to have their rectal cancer surgically removed. And elimination potentially of both of those modalities of treatment can really avoid some of the most serious and morbid complications that often occur with these treatments. Dr. Sumanta (Monty) Pal: Really interesting. Now, this is not and will never be a political podcast, but you know, obviously we're dealing with the consequences of changes on funding and so forth that have evolved over time. And I think it's worth sort of speculating how the landscape of research may change on account of that. Could you comment perhaps a little bit on how some of the funding cuts that we've seen recently at the NIH might affect the body of work that you're so integrally involved in? Dr. Kimmie Ng: I am honestly very worried about the current funding environment. Colorectal cancer is the third most commonly diagnosed cancer among men and women in the United States and globally, and when you combine men and women together, the second leading cause of cancer death. But proportionally, we receive much less funding for colorectal cancer compared to other cancer types. And my thoughts have always been that perhaps this is because there is this stigma around colorectal cancer and maybe some of the symptoms associated with colorectal cancer. And so on top of that, to have additional challenges in obtaining funding, I worry what it will do to the pace of progress for especially young patients with this disease. Also, because of some new stipulations that perhaps international collaborations are being discouraged, I also worry about that aspect of it because young-onset colorectal cancer and gastrointestinal cancers in general is a global phenomenon happening in multiple countries around the world. And if we are to understand what the environmental factors are affecting the different rates of rise in these different countries, we do so much need that international collaboration. So yes, I am worried, and I do hope that conversations like this will spark an awareness of the need for more funding and continued funding into this disease. Dr. Sumanta (Monty) Pal: I will say that, and the audience can't see this because this is an audio program, but I'm wearing my Southwest Oncology shirt here, a SWOG, and it's one of the National Cancer Institute-funded cooperative groups. And you know, I was recently dismayed to find that, you know, funding got cut for international collaborations and enrollment in South America and Latin America. And this was traditionally actually a mainstay of our enrollment for many trials, including trials in rare cancers that present themselves in younger patients in the GU space. So, I completely agree with you. We've got to do something to address this funding issue to make sure that this body of work, both yours and mine, continues, without a doubt. Kimmie, this has been a delightful conversation. I really want to thank you for, you know, leading the charge in the young-onset colorectal cancer space, and you've done so much tremendous work here. Dr. Kimmie Ng: Thank you for having me. Dr. Sumanta (Monty) Pal: If you value the insights that you hear on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. And again, thank you for joining us today. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:   Dr. Sumanta (Monty) Pal @montypal Dr. Kimmie Ng @KimmieNgMD Follow ASCO on social media:    @ASCO on Twitter   ASCO on Bluesky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Sumanta (Monty) Pal: Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis Dr. Kimmie Ng: Honoraria: Seagen, GlaxoSmithKline Consulting or Advisory Role: CytomX Therapeutics, Jazz Pharmaceuticals, Revolution Medicines, Abbvie, Bayer, Pfizer, Agenus, Johnson & Johnson/Janssen, Etiome, AstraZeneca Research Funding (Inst.): Pharmavite, Janssen Other Relationship: JAMA

Synopsis: Amy Burroughs, CEO of Terns Pharmaceuticals, joins Alok Tayi to share how she's leading bold innovation in CML and obesity treatment, driving two high-stakes data readouts in 2025. From a non-linear path through tech, brand management, and Genentech to building resilient biotech teams, Amy reveals why product positioning, tolerability, and mentorship matter just as much as the science. She also shares her take on CEO loneliness, the value of a “personal board of directors,” and what it takes to lead with clarity, grit, and purpose in today's biotech landscape. Biography: Amy Burroughs joined as our Chief Executive Officer and a member of our Board of Directors in February 2024, bringing more than 25 years of leadership experience. Most recently, she served as CEO at Cleave Therapeutics, where she led the company through financings, spearheaded licensing and collaboration deals, and oversaw the clinical development of its investigational therapy, CB-5339, for the treatment of acute myeloid leukemia. Previously, she served as executive in residence at 5AM Ventures and, in parallel, as senior advisor to one of its portfolio companies, Crinetics Pharmaceuticals, during its initial public offering. Earlier in her career, Ms. Burroughs held roles of increasing responsibility in commercial and strategy at Genentech, commercial and business development at other high growth therapeutics companies, talent and governance at Egon Zehnder International, and brand management at Procter & Gamble. Ms. Burroughs earned her M.B.A. from Harvard Business School, where she graduated as a Baker Scholar, and her B.A. in computer science with a minor in economics from Dartmouth College. She is currently a member of the board and audit committees at Tenaya Therapeutics.

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Susan Desmond-Hellmann is a physician and scientist whose remarkable career has spanned clinical medicine, oncology, biotech innovation, and global health leadership. In this episode, Susan shares insights from her journey training in internal medicine during the early AIDS crisis, treating HIV-related cancers in Uganda, and developing groundbreaking cancer therapies like Herceptin and Avastin. She reflects on her leadership roles at UCSF and the Bill and Melinda Gates Foundation, offering lessons on guiding large-scale health initiatives, navigating uncertainty, and fostering scientific innovation. The conversation explores the promise of precision medicine, the integration of patient care and policy, and the evolving role of artificial intelligence in transforming diagnostics, drug development, and global access to care. We discuss: Susan's medical training, the start of the AIDS epidemic, and the transformative experiences that shaped her career [3:00]; Susan's experience working on the frontlines of the HIV/AIDS crisis in Uganda [12:30]; Susan's time working in general oncology and her transition to biotech where she helped develop taxol—a top-selling cancer drug [26:30]; Genentech's origins, and its groundbreaking use of recombinant DNA to develop biologic drugs [33:45]; Susan's move to Genentech, and her pivotal role in the development and success of Herceptin as a groundbreaking therapy in targeted oncology [44:00]; The rise of antibody-based cancer therapies: the development of Rituxan and Avastin [52:15]; The step-by-step drug development process and the scientific and strategic challenges involved [1:01:30]; The ethical and economic controversy surrounding Avastin's high cost and limited survival benefit [1:12:30]; Susan's tenure as chancellor at UCSF: leading during a financially strained period, and her strategic approach to fundraising and institutional development [1:14:45]; What Susan learned as CEO of the Bill and Melinda Gates Foundation: strategic processes and decision-making frameworks [1:26:00]; Susan's philosophy of leadership and how she sought to build an empowering, values-driven culture at the Gates Foundation [1:35:15]; The erosion of public trust in science during COVID, the communication failures around controversial treatments like ivermectin, and the need for better public health engagement and transparency [1:39:30]; The role of AI in transforming medicine: from drug development to cancer detection and beyond [1:53:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube