Generative AI for Novel Therapies | Sean McClain, Absci

From science to startup: real talk on biotech founding paths. For many early-stage biotech founders, that’s where the real challenge begins—and that’s where Persephoni Bio Partners comes in. In this episode of the Nucleate Podcast, Hillary Schultz and Dr. William Heath share how their unique journeys from clinical medicine and pharmaceutical R&D to early-stage investing led them to co-found Persephoni Bio, a venture studio focused on transforming breakthrough science into scalable biotech companies. Hillary and William reveal the most overlooked reasons biotech startups struggle, highlighting that success often hinges more on the team than the technology. They offer candid insights into IP strategy, founder dynamics, and patient-centered development, while also emphasizing the importance of resilience, adaptability, and a growth mindset.For anyone navigating the next step after Nucleate, this episode offers practical guidance and inspiration for building biotech that lasts! Time StampsPersonal Background and Motivation: 0:03:40 - Hillary discusses her early passion for heathcare and impact0:07:07 - William explains his journey into science, starting from childhoodNucleate Experience: 0:14:12 - Hillary's advice on making the most of Nucleate0:16:45 - William's perspective on Nucleate's valuePersephoni Bio Partners:0:26:09 - Hillary explains the founding of Persephoni0:28:56 - William discusses the mission of supporting early-stage biotechIP and Technical Challenges:0:47:48 - Discussion on IP strategies for startups0:57:11 - Technical challenges in biotech development0:58:39 - Importance of understanding patient needsEntrepreneurship Advice:1:02:11 - Advice for Nucleate Activator program graduates1:05:00 - Discussing entrepreneurial mindset and resilience1:07:24 - Embracing failure as a learning opportunityPersonal Balance: 1:10:47 - Hillary and William discuss work-life balance1:13:47 - Importance of team dynamics in success

Follow us at https://signal.nucleate.xyz0:03:41 - Dr. Pao discusses losing his father to colon cancer at age 13, which motivated his career in medicine0:05:30 - Describes his early academic training, including his PhD work on Gamma Delta T cells0:09:54 - Begins discussing the EGFR mutation discovery in lung cancer research 0:13:16 - Shares the story of being "scooped" by other researchers when publishing his EGFR mutation findings0:32:44 - Starts discussing his book "Breakthrough: The Quest for Life-Changing Medicines"0:42:35 - Tells the serendipitous story of Tylenol's discovery0:58:38 - Begins discussing entrepreneurship and decision-making in drug development1:04:29 - Talks about starting his own company, Revelio Therapeutics1:11:28 - Discusses future trends in medical research and potential breakthrough areas1:15:52 - Offers final advice about resilience for aspiring entrepreneurs and scientists These timestamps highlight key moments in the conversation about Dr. Pao's career, research, book, and insights into medical innovation.

Follow us at https://signal.nucleate.xyz/[0:00] Peter begins by discussing his upbringing in a New Zealand university town.[2:39] He realizes he is not suited for bench work during his PhD and discovers a passion for computational analysis.[4:30] Campbell joins the Sanger Institute and participates in one of the first cancer genome sequencing projects using new technology.[8:00] He describes the revolutionary period of cancer genomics from 2008 to 2015, systematically exploring genetic changes in cancers.[12:32] Campbell shifts research focus to studying mutations in normal tissues across different organ systems.[13:44] Flagship Pioneering reaches out to discuss the potential clinical relevance of their research.[14:56] He co-founds Quotient Therapeutics with Flagship Pioneering to explore therapeutic applications of somatic mutation research.[20:39] Campbell explains the evolutionary process of mutations in cells, comparing it to natural selection.[26:49] He discusses the incredible genetic diversity within a single individual's cell populations.[35:12] The conversation explores the potential for personalized medicine based on genetic mutation analysis.[39:55] Campbell explains how cells adapt to environmental changes and potentially revert mutations when pressures are removed.[49:29] He describes Quotient's approach to identifying and potentially targeting specific mutations.[58:47] Campbell discusses the partnership with Pfizer in cardiovascular and renal disease research.[1:08:01] He compares the differences between academic and startup research environments.[1:15:39] Campbell offers final advice for entrepreneurs transitioning from academia to startups.

Follow us at signal.nucleate.xyz2:23 Raj describes growing up in India as a land of hustlers and the importance of being aggressive to advance oneself.6:37 Discusses the challenges of the current biotech funding environment and the importance of being capital efficient.11:17 Explains his career transition from large pharma to biotech, highlighting his ability to translate breakthrough science into products.21:11 Describes founding Rectify Pharmaceuticals and building a platform for positive functional modulators targeting membrane proteins.25:08 Explains the company's pivot to focusing on hepatobiliary diseases, particularly primary sclerosing cholangitis (PSC).33:00 Emphasizes the importance of relationships, mentorship, and getting feedback from various stakeholders in building a successful biotech company.56:46 Discusses how they initially vetted the Rectify platform by extensively researching ABC transporters and developing screening assays. 1:05:21 Highlights the courage to explore broader applications of their platform beyond rare monogenic diseases.1:12:44 Provides final advice for entrepreneurs, stressing the importance of having a detailed plan, being realistic, and building a strong founding team.

In this episode of the Nucleate Podcast, Aikium co-founder and CEO Eswar Iyer joins host Anastasia Janas to explore how drug discovery can move beyond structured targets to engage the disordered proteome. Aikium is developing SeqRs, programmable, sequence-specific binders that can selectively target intrinsically disordered regions of proteins, unlocking new therapeutic possibilities in cancer, neuroinflammation, and autoimmune diseases. Built using generative AI and screened with a proprietary trillion-scale mRNA display system, Aikium’s platform challenges the traditional assumptions of druggability and expands the therapeutic landscape into areas once considered inaccessible.Beyond the science, Eswar reflects on the emotional realities of building a company at the frontier of biology, sharing lessons on believing in an idea before the world is ready, navigating failure and doubt, and sustaining conviction when there is no established path forward. If you are interested in the future of therapeutics, the evolution of protein engineering, or the personal journey behind pioneering biotech startups, this conversation offers a rare and honest perspective.

In this episode, Anastasia Janas and Paula Lengerke Diaz sit down with Dr. Uli Stilz, Head of the Bio Innovation Hub (BIH) at Novo Nordisk, to explore how strategic partnerships and emerging technologies are redefining the future of drug discovery. Uli reflects on his journey from chemistry and molecular biology to biopharma leadership, and shares how the BIH is accelerating breakthroughs in cardiometabolic diseases using emerging modalities like RNA editing, AI-guided drug discovery, and partnership-first science.Whether you’re an aspiring innovator, translational researcher, or healthcare entrepreneur, this episode offers a candid masterclass in how bold ideas get translated into impact — especially in the space of chronic diseases like diabetes and obesity.Show Notes0:00 - 02:20: Uli’s early fascination with science (and a chemistry set mishap at home)02:20 - 05:15: Transitioning from chemistry to biology to biophysics — and why it mattered05:15 - 09:45: The value of speaking multiple “scientific languages”09:45 - 13:00: Why Uli left academia for pharma, and what drove that leap13:00 - 17:30: Founding the Bio Innovation Hub (BIH) at Novo Nordisk17:30 - 20:00: Three big questions BIH is trying to solve in cardiometabolic disease20:00 - 24:30: How programmable RNA editing is being applied to drug discovery24:30 - 28:00: Why BIH funds early science without contracts — the Greenhouse model28:00 - 33:00: How AI, human biology, and subtyping diabetes open new possibilities33:00 - 36:30: What makes small biotechs a “superpower” in R&D36:30 - 41:00: The role of trust, creativity, and iteration in building partnerships41:00 - 45:20: Advice for young scientists: embrace discomfort, follow curiosity45:20 - 49:30: What excites Uli most? The unknown. “I’m most excited about the things I don’t know today.”

In this episode of the Nucleate Podcast, Anastasia Janas sits down with Shelby Newsad, Partner at Compound VC, shares her journey from a small town in Appalachia to investing in some of the most transformative technologies shaping biotech and beyond. Starting as a first-generation college student with a pre-med background, she realized that commercialization is key to translating scientific research into real-world impact.Shelby discusses her work at Compound, a thesis-driven, research-centric venture firm investing across AI, robotics, crypto, and biotech. She explains how Compound builds deep expertise in emerging fields — developing theses, connecting with researchers, and creating ecosystems around transformational areas — to become the highest-context investors for early-stage companies. When critical gaps in the market appear, Compound even incubates companies themselves, such as in plant engineering for high-value, lower-regulation products.The conversation dives into emerging trends like autonomous science, science-driven consumer products, biohacking, and proactive healthcare. Shelby highlights the importance of individual health data ownership, the potential for brain modulation technologies, and why bold, contrarian founders are key to the future of biotech. She shares her optimism for the future, from conservation tech to cancer prevention, and invites listeners to think bigger, move earlier, and reach out with innovative ideas — and to get involved with Compound’s upcoming Research Days in San Francisco.Time Stamps00:04 - 00:27: Introduction about research days in San Francisco00:27 - 01:11: Intro about Shelby 01:11 - 03:06: Shelby’s background and fascination for science 03:06 - 10:54: Discussion about translation from academia to real-world products0:10:54 - 21:12: Compound's investment approach & what makes a good thesis 21:12 - 24:15: Compound’s incubation model 24:15 - 30:06: What Shelby looks for when meeting founders30:06 -37:06: Conversation about biohacking and medical perspectives37:06 - 40:09: Discussion about potential future technologies40:09 - 41:32: Contact information and upcoming research days41:32 - 45:32: Closing thoughts about scientific optimismFInd more about the Podcast at the Signal Website

Follow us here https://signal.nucleate.xyz/02:16 - Dave discusses his early career path and how he got into science 04:41 - Dave’s work on the Human Genome Project 13:38 - Founding Cofactor Genomics16:42 - Discussing Pioneer Fund and its investment approach 48:58 - Thoughts on AI in health and biology 58:27 - Advice for founders in the current challenging funding environment 1:09:04 - How Pioneer Fund makes investment decisions 1:14:16 - Most difficult advice for entrepreneurs 1:16:47 - Final advice for founders: "Just go do it"

Follow us https://signal.nucleate.xyz/Apply to the Entrepreneurial Fellows Program in Chicago with the CBC open from March 20-May 2,2025! https://chicagobiomedicalconsortium.org/awards/entrepreneurial-fellows/In our latest podcast, hosted by Sam Kessel, Dr. Michelle Hoffmann discusses her unique journey from a PhD in molecular neuroscience PhD to a biotech consultant, and how her experiences shaped her passion for developing future leaders in the biotech industry in Chicago.Dr. Hoffmann’s career path took her from academia to consulting, including a decade at Back Bay Life Science Advisors, where she used her scientific expertise to help biotech companies optimize their product strategies, secure funding, and build the biotech ecosystem via the Chicago Biomedical Consortium. She also discussed the Entrepreneurial Fellows program to train aspiring biomedical entrepreneurs in due diligence and company building within the Chicago ecosystem

Follow us on https://signal.nucleate.xyz/04:14 - Dr. Stehman-Breen discusses her decision to pursue a career in medicine.05:49 - Dr. Stehman-Breen explains her specialty choice in internal medicine and nephrology.08:09 - Skills and mindset that prepared Catherine for a career in industry.13:53 - The critical impact that physicians can have in biotech19:03 - Overview of epigenetic editing and Chroma Medicine's approach.0:28:22 - Early days of building Chroma Medicine from the ground up.0:38:22 - Merger with NVelop Therapeutics and future directions.0:44:22 - Dr. Stehman-Breen offers advice for entrepreneurs and the value of an Entrepreneur in Residence role.0:49:22 - Balancing her demanding career with personal hobbies and interests.