Generative AI for Novel Therapies | Sean McClain, Absci

In this special panel episode recorded in Zurich, the founders of Apricot Bio, Michael Zering (CEO), Lucas Pelkmans (Scientific Founder), and Independent Professor Andreas Wicki from the University of Zurich explore the new field of functional precision oncology—an approach that goes beyond genomics to test how living cancer cells actually respond to treatment. The conversation covers the limits of genetic diagnostics, the promise of ex vivo drug testing, AI-driven decision-making, and how smarter trial design could transform cancer care. The panel also dives into Switzerland’s biotech ecosystem, venture capital realities, and what it takes to bring high-risk, high-impact science from the lab to the clinic.00:00 – 03:30 | Introduction & Panel SetupRecorded in Zurich, this special panel episode introduces functional precision oncology and why current diagnostic paradigms are reaching their limits.03:30 – 12:00 | The Limits of Genomics in Cancer CareWhy genetic screening alone can’t capture tumor complexity, molecular heterogeneity, and real-world treatment response.12:00 – 22:00 | What Is Functional Precision Oncology?Testing patient-derived cancer cells ex vivo to understand drug response, cellular context, and therapeutic combinations.22:00 – 32:00 | “The Google Maps of the Cell” AnalogyHow contextual, real-time cellular data improves decision-making compared to static genetic snapshots.32:00 – 43:00 | Clinical Trials ReimaginedWhy traditional drug-centric trials struggle—and how diagnostic-led, patient-specific trials could change oncology research.43:00 – 53:00 | AI, Data Science & Cellular ContextHow machine learning models integrate phenotypic, spatial, and functional data to predict treatment response.53:00 – 1:03:00 | Drug Combinations & RepurposingWhy single agents often fail—and how functional testing uncovers synergistic therapies missed by standard screens.1:03:00 – 1:12:00 | Beyond Oncology: What Comes Next?Potential applications in immunology, hematology, neurology, and other diseases driven by cellular dysfunction.1:12:00 – 1:20:00 | Switzerland’s Biotech EcosystemStrengths, gaps, venture capital realities, and how Swiss innovation compares globally.1:20:00 – 1:23:00 | Founder Advice, Books & Closing ThoughtsLessons for scientist-founders, navigating tough funding environments, and recommended reading. 

Time Stamps:01:22 First spark for science  05:09 Burnout with academia & turn to activism  10:18 Who should pursue a career in science  13:31 Leaving academia for industry & biotech  17:36 Rethinking drug development timelines  22:11 “Chief drug hunter” philosophy  24:39 What makes a good drug hunter  30:42 Third Rock Ventures 35:26 Curie Bio’s model & “freeing the founders”  42:52 Forward Therapeutics case study  49:18 Founding in a tough market: mindset & practical path  56:28 Communicating your idea as a founder  59:19 Two fundamental types of discoveries1:07:32 Advice for academic founders  1:13:00 The academia–industry gap & why Curie was built  1:17:07 The single biggest mistake founders make  1:18:19 Final recommendations 

Time Stamps[00:00] Titus’s ethos of doing hard things with good people[00:43] Introduction to the Nucleate Podcast and Alexander Titus[01:22] Titus discusses his post-college pivot and solo travel through Central America [04:47] How travel philosophy maps to Titus’s career [05:56] Titus discusses his experience living in a casino and learning risk management via blackjack[12:39] Resilience and irreversible mistakes [17:12] Titus discusses his non-linear career path [20:57] Tackling hard problems: humility, small wins and amplifying others [27:05] National Security Commission on Emerging Biotechnology (NSCEB) & $15B roadmap[30:53] Balancing policy and industry roles[34:42] The under-invested pillar of bio-literacy[37:50] Sci-fi novel Synthetic Eden and using fiction as a bio-ethics tool[46:36] AI, biotech risk and data-driven governance [49:04] Titus’s insights into AI in therapeutics, especially its current reality versus hype [59:39] Rapid-fire Q&A: name, favorite places, book recommendations 

Time Stamps[00:44] — Introduction to the Nucleate podcast and Mikael Dolsten.[02:42] — Mikael shares his upbringing and academic journey at Lund University, highlighting the influence of mentors.[05:46] — Transitioning from academia to the pharmaceutical industry, driven by curiosity and patient needs.[19:18] — Reflecting on the pressures and leadership style of managing thousands of scientists at Pfizer.[39:56] — Highlights of vaccine development, particularly Pfizer’s role in COVID-19 vaccines and global impact.[51:09] — Behind the scenes of developing Paxlovid during COVID-19 and Mikael’s personal connection to the pandemic.[1:05:15] — Traits Mikael looks for in founders: the value of humility, talent, and collaborative culture.[1:12:05] — How to support early-stage biotech companies while maintaining entrepreneurial spirit and adaptability.[1:13:41] — Mikael’s insights into the evolving role of AI in drug discovery and precision medicine.[1:23:32] — Rapid-fire Q&A: personal reflections, career advice, and influences outside of science.

In our latest episode, we sit down with Dr. John Maraganore, the legendary founding CEO of Alnylam Pharmaceuticals and one of the most influential voices in modern therapeutics. Raised in a Greek immigrant family in Chicago, John’s journey is a rare blend of scientific obsession, business acumen, and relentless optimism. We cover his whole career journey. From his early days at Biogen, where he invented the anticoagulant bivalirudin (Angiomax), to taking a leap of faith on RNA interference when few believed it could work. He opens up about being “thrust” from the lab into the business battlefield, the serendipitous experiments that changed his career, and the near-misses that almost stopped him in his tracks. We dive into how he built Alnylam from a small startup into a company with multiple approved drugs for devastating rare diseases like TTR amyloidosis, and the leadership philosophies that kept him and his team moving forward. Along the way, John shares candid lessons for today’s founders. Whether you’re a scientist, entrepreneur, or just someone who loves stories of grit and discovery, this conversation will inspire you. Don’t miss out on this deep dive into innovation, failure, and the future of medicine. Time Stamps 00:32 Dr. John Maraganore is introduced as the featured guest and a leader in biotech. 00:50 Asked to explain his job to a five-year-old, his answer captures a lifetime of purpose in three words. 01:05 Growing up in a Greek immigrant family shaped more than his values—it built the mindset that would drive biotech breakthroughs. 02:44 His parents wanted a doctor. One college experiment changed everything. 04:14 Snake venom, of all things, sparked his obsession with discovery. 06:20 John shares how his biotech career began at Upjohn and Biogen, inventing bivalirudin (Angiomax), and other highlights. 10:31 He talks about property hurdles behind bivalirudin’s development. 12:57 A forced career pivot from the lab to business turned out to be the twist that defined his leadership path. 17:21 Seeing science from the business side unlocked something—an insight that later shaped how he built companies. 19:09 The genomics boom at Millennium tested his ability to turn data into real drugs—and nearly broke the field in the process. 22:25 Betting on RNA interference when almost no one believed it could work. 27:40 Ten years of trial and error later, the science finally caught up to the vision. 30:57 Behind every biotech success are make-or-break partnership calls—he shares how timing meant survival. 36:14 Balancing independence with pharma partnerships became a strategy that redefined how small biotechs grow. 39:06 John shares the criteria and reasoning behind choosing TTR amyloidosis as Alnylam’s lead rare disease program. 54:22 John shares practical advice for founders facing tough market conditions. 57:47 Talking about sleep, pizza preferences, memorable child moments, and music. 1:00:43 He recommends the best reading material on drug pricing and the biotech business. 1:01:30 Conclusion and final advice from Dr. John Maraganore.

In this episode, Allyson Berent, Chief Science Officer, Foundation For Angelman Syndrome Therapeutics (FAST), shares her remarkable journey from a career in veterinary medicine to becoming a leading advocate and innovator in the field of rare disease drug development, inspired by her daughter’s diagnosis with Angelman syndrome. She recounts the challenges of obtaining an early diagnosis, the emotional impact on her family, and her determination to find solutions where none existed. Allison describes how she immersed herself in scientific research, connected with experts, and joined the Foundation for Angelman Syndrome Therapeutics, eventually helping to launch and lead multiple initiatives aimed at accelerating the development of transformative therapies for Angelman syndrome and similar neurodevelopmental disorders.Throughout the conversation, Allison emphasizes the importance of true patient-focused drug development, sharing how her personal experience shaped her approach to building companies, running clinical trials, and fostering collaboration across the biotech ecosystem. She offers practical advice for entrepreneurs and executives, urging them to listen to patients and families, remain humble, and surround themselves with experts to address knowledge gaps. This episode highlights the profound impact that new therapies are having on patients’ lives and underscores the value of mission-driven innovation in advancing treatments for rare diseases.Time Stamps00:02 – Introduction and Allison’s upbringing and early interest in veterinary medicine.00:15 – Allison shares the story of how she decided to become a vet and her educational journey.01:34 – She discusses her career as a vet, starting a family, and her daughter’s diagnosis with Angelman syndrome.04:36 – Allison describes the early signs, medical consultations, and the process of getting a diagnosis for her daughter.11:22 – Sam and Allison discuss the challenges of delayed diagnosis and the importance of proactive care.13:01 – She shares stories from the community and changes in genetic testing practices.0:14:35 – Allison explains how she and her family responded to the diagnosis and her drive to find solutions.18:18 – She describes connecting with the foundation, joining the board, and developing a roadmap for a cure.26:15 – The process of moving from mouse model research to human clinical trials, raising funds, and starting a company.31:12 – Discussion on what true patient-driven development means and how it shaped Allison’s approach.39:07 – Allison details the journey of the company, partnership with Ultragenyx, and the impact of the acquisition.45:49 – Explanation of the accelerator model, portfolio companies, and collaborative approach to drug development.51:20 – How the accelerator shares resources and knowledge across programs and with other companies.52:24 – Quincy’s Progress and the Impact of New Therapies,participation in clinical trials, and the real-world impact on families.56:05 – Sam and Allison discuss the life-changing effects of new treatments for Angelman syndrome.58:56 – Allison offers advice on keeping the patient at the center of drug development and listening to families.1:06:13 – She shares suggestions for integrating patient stories and perspectives into company culture and meetings.1:09:14 – Final Words of Wisdom for Entrepreneurs: Allison emphasizes humility, gap analysis, teamwork, and resilience for those starting companies.1:11:53 – Conclusion and Thanks

 In our latest episode of the Nucleate Podcast, we sit down with Joe Horsman, Investor at Madrona VC, to explore his unique path from academic researcher to biotech operator and ultimately to venture capital. Joe shares how growing up in Seattle shaped his passion for science, why he pursued a PhD in biochemistry, and what it took to stand out when transitioning into industry. From early roles at NanoString and Stratos Genomics to the Roche acquisition, he reflects on lessons learned across startups and large companies alike. We talk about:🔹 His transition from academia to industry and the importance of differentiating a PhD resume🔹 Lessons from NanoString, Stratos Genomics, and the Roche acquisition🔹 Navigating culture shifts from startup to big pharma🔹 Madrona’s investment thesis at the life sciences–tech intersection🔹 How AI and data science are reshaping the drug development lifecycle This one’s for anyone curious about where biotech meets computer science, and what it takes to build companies that endure 

In this episode of the Nucleate Podcast, Armon Sharei shares his journey from early life experiences in California, Iran, and Dubai to pursuing higher education at Stanford and MIT, ultimately leading to a career at the intersection of science and entrepreneurship. The conversation explores his motivations to make a positive impact on the world, the transition from academia to founding his first company Squeeze: a company based on innovative cell engineering technology and the challenges of navigating the biotech industry. Armon discusses the evolution of Squeeze from a platform to a therapeutics company, the difficulties of convincing investors and industry veterans, and the high-stakes decisions that shaped the company’s fate, including a major strategic pivot and the eventual fallout with the board. The episode also delves into personal and professional lessons learned, including the impact of a cancer diagnosis, the importance of safety and quality of life in drug development, and the value of mentorship and betting on talent. After Squeeze's liquidation, Armon founded Portal Biotechnologies, applying hard-earned lessons to focus on enabling broad innovation in cell therapy through platform technology. The discussion highlights the realities of biotech entrepreneurship, the significance of resilience, and the ongoing mission to empower others in the field, all while balancing personal passions and family life. Episode Notes: 00:00- Kicking off the episode and setting the stage 02:25- Armon shares a quick overview of his journey 03:24- He reflects on growing up in California, Iran, Dubai, and the US and how it shaped his worldview 05:13- Armon talks about his early love for science and how he chose his career path 06:26- Diving into Armon’s first big ideas and research interests 08:14- Armon discusses the shift from scientist to entrepreneur 10:47- How Squeeze was born. Armon shares the story behind the tech and his PhD research 13:58- Mapping the journey: PhD, founding Squeeze, and postdoc life 18:45- Armon opens up about the challenges of being a young biotech founder and raising early funding 22:53- He explains the strategic pivot from platform tech to therapeutics 26:40- Highlighting key wins: investor interest and the Roche partnership 20:01- Armon shares the tough moments — going public, market shifts, and internal debates 34:34- Navigating board decisions, layoffs, and the fallout with Roche 36:34- Armon reflects on leaving Squeeze and the emotional toll it took 40:27- Starting Portal: Armon shares what motivated him to begin again 44:27- Armon opens up about his cancer diagnosis and how it changed his perspective 49:03- Lessons from being a patient, Armon talks about safety and quality of life in drug development 51:11- He shares broader insights on industry incentives, pricing, and systemic challenges 54:10- What makes Portal’s tech unique? Armon breaks down its competitive edge 56:57- Real-world use cases and early adopters of Portal’s platform 1:00:21- Armon discusses the long-term vision: platform-first vs. therapeutics 1:03:49- Armon highlights the importance of mentorship and betting on talent 1:09:33- He talks about balancing work, life, and personal passions

In this episode of the Nucleate Podcast, we are joined by Prof. Dr. Dominik Rüttinger — oncological surgeon, MD/PhD, and Global Head of Research & Early Development Oncology at Bayer Pharmaceuticals. We talk about his journey from the operating room to biotech startups and global pharma leadership, navigating a 10% success rate in oncology drug development, building unbiased decision frameworks for high-stakes calls, the realistic role of AI in drug discovery and clinical trials, balancing quality of life versus longevity in cancer treatment, and his vision for the future of prevention, early detection, and personalized medicine. Whether you’re a scientist, innovator, or leader, this conversation will challenge how you think about risk, decision-making, and impact in healthcare.  Episode Chapters: 00:00 Intro 02:30 Dominik talks about his childhood, family background, and early influences that led him toward science 04:45 Dominik explains his decision to pursue both medicine and science, describing how his medical school and PhD experiences overlapped 07:30 Offering early career advice, Dominik talks about the importance of aiming high, questioning the status quo, and embracing a bit of naivete 11:06 Dominik discusses why he chose oncology and how interdisciplinary training shaped his career 16:45 Dominik describes his transition from academia to industry, sharing his motivations and the decision-making process behind the move 20:02 Reflecting on his adjustment to industry, Dominik highlights the differences in work environment and expectations compared to academia 23:33 Dominik provides practical tips for others transitioning from academia to industry, emphasizing humility and the value of building a diverse “toolbox” of skills 28:01 Dominik talks about moving from a startup to a large company, and how his responsibilities shifted to managing a broader portfolio 33:28 Dominik describes what his daily life looks like as a portfolio leader in oncology R&D and the types of decisions he makes regularly 37:24 Dominik delves into the challenges of decision-making in drug development, discussing success rates and the importance of a “10% mindset.” 39:27 Dominik explains the impact of biases in drug development and how organizations use frameworks to make more objective decisions 42:46 Dominik shares his perspective on the role of AI in drug development and how it can support better decision-making 47:02 Dominik discusses the use of AI in clinical trials and considers whether it can make development faster and less expensive 51:46 Drawing on his clinical experience, Dominik talks about patient care and patient perspectives, especially the balance between quality of life and longevity in cancer treatment 55:38 Dominik looks to the future of cancer prevention, early detection, and prediction, and how these areas might evolve

In this episode of the Nucleate Podcast, Armand Cognetta, founder and CEO of General Proximity, shares his compelling journey from a directionless college student to a biotech entrepreneur. Drawing from personal experiences of academic struggles and scientific curiosity, Armand discusses how his passion for chemical biology and small molecule drug discovery led him to create a groundbreaking proximity therapeutics platform. He candidly explores the challenges of startup life, including early fundraising difficulties, imposter syndrome, and the critical importance of persistence, grit, and maintaining a high bar for talent. Throughout the conversation, Armand emphasizes the value of working on ambitious, world-changing ideas, the power of proximity in biological systems, and the need for founders to stay focused, resilient, and mission-driven. His story is a testament to the transformative potential of scientific innovation and entrepreneurial spirit, offering inspiration for young scientists and aspiring founders navigating the complex landscape of biotech startups.Time Stamps00:00 – Intro 03:12 – Growing up in northern Florida 06:44 – Taking a year off college due to poor grades 07:05 – A transformative internship experience 08:33 – Paul Graham’s blog & early obsession with tech 11:25 – Learning persistence through failure 20:06 – How to generate and evaluate startup ideas 36:02 – What is General Proximity? 53:15 – Impostor syndrome & early founder struggles 1:02:00 – How past failures prepared him 1:05:53 – Recruiting and retaining talent in startups 1:09:57 – Biotech vs. tech: hiring challenges 1:16:28 – Building an effective advisory board 1:19:46 – Advice for aspiring founder-scientists 1:22:00 – Final thoughts on entrepreneurship & ambition