Ep12: David Schenkein

Episode Summary

Executive Summary: The episode traces Agios CEO David Shankin’s path from underdog physician-scientist to biotech builder, highlighting how his experiences at Millennium and Genentech shaped a company culture centered on science, patients, and speed. He explains Agios’ origin in cancer metabolism, the IDH mutation breakthrough, Celgene partnership, and the company’s push to bring precision medicines to AML patients while building a durable, independent biotech.

Main Topics: Shankin’s personal path from Queens to biotech CEO (Priority: 5/5): Shankin describes growing up in Forest Hills as a first-generation American, attending Stuyvesant, struggling to gain admission to medical school, and finding his calling through role models and hematology/oncology training at Tufts. The influence of Genentech and Millennium on his leadership style (Priority: 5/5): He credits Genentech and Millennium for showing him how industry can transform patient care at scale, and how visionary leaders and strong culture can enable major scientific advances. Agios’ founding thesis in cancer metabolism (Priority: 5/5): Agios was built around the idea that cancers hijack metabolic pathways, and the team sought to identify metabolic enzyme targets that could be exploited as cancer’s Achilles heel. Discovery of IDH as a gain-of-function cancer target (Priority: 5/5): A pivotal paper on IDH mutations prompted Agios to run biochemistry experiments that revealed the mutant enzyme produced a new metabolite at far higher levels, turning a presumed dead enzyme into a druggable target. Celgene partnership and building a durable company (Priority: 4/5): Agios used an early, strategic partnership with Celgene to secure funding and commercialization rights while preserving control of early research, enabling both rapid development and long-term independence. Precision medicine, AML, and the clinical impact of IDH inhibitors (Priority: 5/5): The discussion details how biomarker-driven trials in AML led to rapid approvals and dramatic patient benefit, including oral targeted therapies replacing toxic chemotherapy for mutation-positive patients. Culture, hiring, and the future of biotech innovation (Priority: 4/5): Shankin emphasizes no-jerk, no-hierarchy, anti-silo culture, decision-making speed, and scientific rigor as essential to sustaining innovation as Agios grows.

Key Arguments: Underrepresented, non-elite backgrounds can still produce top biotech leaders when paired with resilience, mentorship, and opportunity. Industry can have greater patient impact than academic medicine by developing therapies that change standards of care at scale. Genentech’s model showed that culture and science must be tightly linked to keep patients at the center of decisions. Cancer metabolism was a promising but uncertain field; Agios’ willingness to challenge dogma enabled the IDH breakthrough. Precision medicine improves efficiency by selecting the right patients up front, speeding trials and making development more capital efficient. Early strategic partnerships can fund breakthrough science without surrendering a company’s long-term independence. A strong company culture requires intentional design: no jerks, no silos, direct accountability, and freedom to fail on experiments. Agios aims to be judged not just on short-term financial metrics but on whether its science produces genuine clinical benefit and durable medicines.

Data Points: Years to first drug market: 10 years - Agios went from concept to a drug on the U.S. market in about a decade. Company size at founding: About 10 employees - Shankin describes Agios in its earliest days as a tiny startup with only a handful of people. Company size during IDH discovery period: About 15-16 employees - The team was very small when the IDH finding emerged from early biochemistry work. Company size at Nature publication time: About 25 employees - Agios had grown modestly by the time the IDH paper was published in Nature in 2009. Current company size: About 400 people - Shankin notes Agios had scaled substantially while preserving its research culture. Medical school applications: 31 applied, 29 rejected, 1 waitlist - Shankin uses this to illustrate his underdog story and resilience. Tufts residency duration: Close to 14 years - He practiced and taught at Tufts for nearly 14 years before moving into industry. Millennium tenure: About 5 years - He spent roughly five years at Millennium helping develop Velcade. Genentech tenure: About 4 years - He led hematology/oncology development at Genentech before Roche’s acquisition changed the organization. Celgene upfront payment: $130 million - Agios received this upfront in the 2010 partnership that funded IDH work and preserved key rights. AML incidence: ~50,000 new patients/year - Shankin cites U.S. and major European AML incidence as the market for IDH-targeted therapy. AML with IDH mutation: ~20% - He says about one-fifth of AML patients carry IDH1 or IDH2 mutations. IDH-mutated AML patients: ~10,000 per year - Derived from the cited AML incidence and mutation frequency, excluding Asia. IDFA launch date: August 1, 2017 - This was the launch date for the first approved IDH2 inhibitor, sold with Celgene. Time from trial start to approval: 3 years, 11 months - The first clinical trial began in September 2013 and led to approval in 2017. First clinical cohort response: 1 of first 3 patients achieved complete remission - An early dose-escalation patient with relapsed/refractory AML had a dramatic response. Primary efficacy dataset: ~125 patients - The pivotal safety/efficacy set for the approval was in relapsed/refractory AML. Complete remission rate: ~25%-30% - Approximately a quarter to a third of treated patients achieved complete remission. Broader safety database: 300-400 patients - The application included additional trial data beyond the primary dataset. Capital raised/spent by approval: ~$1.5 billion raised; ~half spent (~$700 million) by approval - Shankin emphasizes capital efficiency despite expensive drug development. Year NDA for IDH1 inhibitor submitted: December 2017 - Agios submitted the wholly owned IDH1 inhibitor NDA to the FDA in December. FDA action timing: By end of February 2018 - Shankin says the FDA would decide whether to file/accept the NDA and assign a PDUFA date. New target prevalence: 15% of all cancers - He mentions a new molecule heading into the clinic that targets a mutation found across many cancers.

Pivotal Quotes: "I want to build a true research organization that will discover novel targets, make medicine, that changed the field." — David Shankin: Describing his vision for Agios when negotiating with investors and choosing to leave Genentech. "research is the beating heart of Agios and always will be." — David Shankin: Explaining why the company must remain science-led even as it grows commercially. "we've had a no-asshole rule from the beginning" — David Shankin: Summarizing the cultural norm Agios uses to preserve rigorous but respectful scientific debate.

Implications: The episode underscores that durable biotech success depends on patient-centered science, disciplined culture, and biomarker-driven development. For industry, it’s a case study in how small teams can build transformative medicines without sacrificing long-term independence.