When board turns, but mission stays | Armon Sharei, Founder & CEO at Portal on Resilience in Biotech

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

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