Generative AI for Novel Therapies | Sean McClain, Absci

Time Stamps [00:00] Laurence explains biotech to a five-year-old  [01:55] Early life in the UK and first steps toward biotech  [02:47] How The Double Helix and Celltech shaped his path  [07:15] Moving from bench science to Cell and a wider view of research  [13:04] Learning business development at Millennium [15:30] Why relationships matter in biotech deals  [17:43] How Millennium changed from platform company to drug developer  [28:01] Joining Alnylam and building around RNAi  [39:19] Becoming a CEO at Warp Drive Bio  [44:36] Novel antibiotics, molecular glues, and the RevMed merger [52:07] What founders should know about building to make a lasting impact [54:50] Joining Decibel during restructuring and COVID  [58:55] Rebuilding culture and sharpening strategy  [1:09:49] Why Decibel focused on gene therapy for the inner ear [1:25:05] Advice for founders raising money in a hard market

Time Stamps (0:55) Introduction to Michal’s background and her professional journey  (7:58) How Michal leveraged tech skills to break into computational biology  (13:15) Her experience at Compugen working on early AI-enabled drug discovery   (19:52) Challenges startup founders face and strategies to overcome them (25:19) Michal’s personal experience as a founder at Anima Biotech (32:52) Resources available at academic institutions to support startups  (40:15) How to successfully negotiate as a scientific founder (46:51) Michal’s role at Johnson & Johnson (53:13) Introduction to MassBio and their purpose (58:35) Advice on networking and how to form meaningful partnerships

Time Stamps 1:37 Introduction to Szabi’s journey from economics to healthcare  3:23 Szabi’s early startup experience at Tresorit  5:27 Key takeaways from his first venture 11:46 What led Szabi to pivot into healthcare and how he managed that transition 14:37 Introduction to Turbine 17:10 Example of running large-scale experiments in collaboration with Merck  19:17 Explanation of the main phases of application of the model  22:32 What fundamental tenets were used to build Turbine’s model  29:16 How to form successful partnerships 38:53 Szabi’s experience with raising funds in a tight capital market  40:00 Advice for founders navigating this challenging market 49:20 How to find the right mentor and form a meaningful connection  51:07 Final words of wisdom

Time Stamps1:58 Merrick Smela's Early Influence03:36 Ovelle's Founding:  Travis Potter and Merrick Smela05:07 Travis Potter's Motivation After Facing Fertility Struggles06:44 Underfunding of IVG07:48 Finance/Biotech Commonalities09:15 Scientific Co-founder Role: Merrick Smela09:56 Using Statistics in Design12:25 Definition of IVG12:54 Ovelle's Mission to Revolutionize Infertility Treatment13:33 IVG vs. IVF15:49 Ovelle's Unique Scientific Approach16:39 Direct Activation vs. Natural Signaling: 18:17 Meiosis Paper Innovation: Identifying Regulatory Factors that can Activate Meiosis from Stem Cells21:23 Team Building: Finding Dedicated Scientists24:20 Culture Difference (Meaning vs. Money)28:35 IVG Process Overview: 29:36 IVM is Achieved in Humans: 30:35 Quality Control and Safety of Eggs32:35 Prioritization using Critical Path Analysis:35:02 Investor Funding for IVG as a New Fertility Approach41:21 Rapid Fire Questions

In this episode of the podcast we sit down with Claire Smith, Partner at SpringTide. She reflects on her journey from a biological engineering student at MIT to her current role in venture capital, and the key lessons she’s learned along the way. Claire explains SpringTide’s investment scope, introduces companies from her portfolio, and shares what drives her investment decisions. The conversation also explores the current landscape of TechBio and AI, including how to distinguish genuine innovation from hype, how pharma is realistically adopting AI, and differences in East Coast and West Coast perspectives on the technology. Claire provides guidance for early-stage founders navigating today’s ever-changing environment. She discusses the importance of planning realistic timelines, how and when to launch a company, and what qualities investors are looking for. She advises on what makes a great pitch, arguing that the goal of the initial meeting is not to secure funding, but to earn a second conversation. Trust is built through preparation, authenticity, and intellectual honesty, never by faking it in biotech. Books mentioned: The Pyramid Principle by Barbara MintoWhy Genius Failed: The Rise and Fall of Long-Term Capital Management by Roger LowensteinTime Stamps:0:01:20 Introduction to Claire’s  journey from MIT biological engineering to SpringTide0:05:44 There’s “no overnight successes” in biotech0:06:47 Claire’s experience as a start up operator at Crestovo and the key lessons she learned0:09:35  Explanation of the investment  scope of Springtide 0:12:31 How Claire assesses risk when building an investment portfolio 0:14:47 Things to consider when evaluating technical founders0:15:55 Introduction to Paterna Biosciences and their impact within the fertility space  0:19:27 Platforms vs assets in tough capital markets and why Springtide has a countercyclical platform focus0:22:50 Meaning of “look boring today, but will be infrastructure tomorrow”0:24:24 Advancements in Palantir‑style business models for pharma0:28:42 What does the term “TechBio” means to Claire0:30:39 How the pharma industry is currently leveraging AI 0:33:55 Markers of AI success to keep an eye out for0:35:29 How to identify companies that are driving genuine AI innovation0:37:50 Example of Niche Bio and how they’re generating data for machine learning0:39:22 Differences in opinions between East Coast and West Coast investors on AI0:42:16 Advice for companies navigating the current capital market0:44:16 Why proactive buffer planning is critical when setting a timeline0:45:36 Advice for early stage founders on how and when to launch their company 0:50:59 What sets a great pitch apart 0:55:00 Explanation of the Pyramid Principle by Barbara Minto0:55:44 3 main points about SpringTide as an investment firm0:58:28 Importance of forming authentic connections but don’t “fake it ‘til you make it” 1:01:22 Quick-fire questions

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.