Nucleate Podcast

John Maraganore, the founding CEO of Alnylam Pharmaceuticals, shares his inspiring journey from a Greek immigrant family to a biotech legend. He reveals how a serendipitous lab experience led him to create bivalirudin and pivot into business. John discusses challenges in advancing RNAi therapies, targeting TTR amyloidosis, and maintaining team morale during tough times. His insights offer valuable lessons for entrepreneurs and scientists alike, emphasizing resilience, optimism, and a patient-focused approach to innovation.

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 this engaging conversation, Joe Horsman, an investor at Madrona Ventures, shares his fascinating journey from academia to venture capital. Growing up in Seattle ignited his scientific passion, leading to a PhD in biochemistry. Joe discusses key lessons from his roles at NanoString and Stratos Genomics, including the significant cultural shifts post-Roche acquisition. He delves into how AI is transforming drug development and what it takes to succeed in biotech today, emphasizing the importance of differentiation and building relationships.

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

Join Prof. Dr. Dominik Ruettinger, an oncological surgeon and Global Head of Research & Early Development Oncology at Bayer Pharmaceuticals, as he shares insights from his journey in cancer treatment innovation. He discusses the challenging 10% success rate in drug development and the importance of questioning traditional norms in biotech. Dominik explores the impact of AI in drug discovery and the delicate balance between quality of life and longevity for patients. His vision for future cancer prevention emphasizes early detection and personalized medicine.

Armand Cognetta, CEO and founder of General Proximity, shares his transformative journey from a struggling student to a pioneering figure in biotech. He discusses the resilience required to navigate startup life and the unique challenges of fundraising, including imposter syndrome. Armand highlights the innovative concept of proximity in drug discovery and explores its potential to tackle previously undruggable diseases. His insights emphasize the importance of working on ambitious ideas and staying focused in the complex biotech landscape.

Hilary Schulz, Co-founder and CEO of Persephoni BioPartners, and Dr. William Heath, Chief Scientific Officer, share their journeys from healthcare to biotech entrepreneurship. They discuss how co-founder dynamics can overshadow technology in startup success. The duo reveals critical insights on IP strategies, patient-centered approaches, and the importance of resilience in entrepreneurship. With real-world advice for navigating the biotech landscape, they emphasize the value of collaboration and a strong team to overcome challenges and drive lasting innovation.

Dr. William Pao, CEO and co-founder of Revelio Therapeutics, shares his compelling journey from losing his father to colon cancer at 13 to spearheading breakthroughs in lung cancer research. He discusses the discovery of EGFR mutations and the fierce competition in publishing this pivotal finding. Dr. Pao highlights the serendipitous origins of Tylenol and delves into drug development challenges in the biotech world. He offers valuable insights on resilience for aspiring entrepreneurs and the future of medical innovation.

Peter Campbell, CSO of Quotient Therapeutics, discusses his journey from a traditional medical background in New Zealand to becoming a pioneer in cancer genomics. He shares insights from his time at the Sanger Institute, highlighting groundbreaking cancer sequencing projects and the evolution of genomic research. Campbell emphasizes the importance of understanding genetic mutations for personalized medicine, collaborations with Pfizer for innovative therapies, and how adaptive mutations impact cell regeneration. His passion for translating genomic insights into real-world applications is truly inspiring.

Raj Devraj, CEO of Rectify Pharmaceuticals and a seasoned venture partner, shares his insights on the ever-evolving biotech landscape. He reflects on his journey from India to pharmaceutical success, emphasizing the need for determination and aggressive advancement. The conversation dives into the challenges of securing funding in a risk-averse market and the importance of strategic team-building. Raj also discusses the pivot to hepatobiliary diseases, advocating for innovative, broad applications of biotechnology while stressing mentorship and solid planning for aspiring entrepreneurs.