Blueprint Medicines was built to find the next Gleevec-style cancer drug. It ended up pivoting to allergic disease instead, and selling to Sanofi for $9B. This is the platform, the pivot, and who got paid. Blueprint Medicines set out to be the natural sequel to Gleevec: a company founded by two of the scientists behind that landmark cancer drug, built to order by Third Rock Ventures' "venture creation" model, with a proprietary kinase-inhibitor library designed to drug the 517 other broken molecular switches Gleevec couldn't touch. A decade later, Sanofi paid roughly $9 billion for the company... just not for a cancer drug. Blueprint's blockbuster asset, avapritinib (AYVAKIT), found its real market almost by accident: indolent systemic mastocytosis, a debilitating, often-undiagnosed mast-cell disease that took patients years to get diagnosed and had no approved treatment. In this episode, we trace two threads at once: the science of designing truly selective kinase inhibitors, and the venture capital philosophy -- company creation, not just company funding -- that built Blueprint from a whiteboard sketch into a platform biotech. We cover the near-death Series B, the accidental discovery that opened up mastocytosis, the GAVRETO partnership that fell apart against a faster competitor, the Sanofi negotiation (CVRs and all), and the wide gap between what the venture firm and hired executives made versus what the founding scientists -- like Gleevec's co-inventor Nick Lydon -- walked away with. We end covering the efforts of Blueprint diaspora to create a new model of seed investing: Curie Bio. Featuring interviews with: Alexis Borisy: Former Blueprint CEO/Chairman; founding chairman, Curie.BioChristoph Lengauer: Founding CSO, Blueprint Medicines; Chief Drug Hunter, Curie.BioErica Evans: Former VP Biology, Blueprint Medicines; SVP, Curie.BioTim Guzi: Former Head of Medicinal Chemistry, Blueprint MedicinesDr. Charles Sawyers, M.D. — Academic co-founder, Blueprint MedicinesDr. Mariana Castells, M.D., Ph.D — Director, Mastocytosis Center, Brigham and Women's HospitalCREDITS Co-hosted by Alex Kesin and Matthew Pech Written, edited, and produced by Alex Kesin Music: “Food” by nerowski * Special thanks to the team at NFX for the use of their recording studio. * This episode is presented by JLL. Featuring Grant Dettmer on biotech real estate strategy. Sources1. Books and case studies Vasella, Daniel, with Robert Slater. Magic Cancer Bullet: How a Tiny Orange Pill Is Rewriting Medical History. HarperBusiness, New York, 2003. ISBN 9780060010300 · OCLC 50859163.Hamermesh, Richard G., Kathy Giusti, and Susie L. Ma. "Breakthroughs at Blueprint Medicines." Harvard Business School Case 820-001, June 29, 2020.Levin, Mark. "Mastering the Value Chain: An Interview with Mark Levin of Millennium Pharmaceuticals." Harvard Business Review, June 2001.2. SEC filings Blueprint Medicines (CIK 1597264) Form S-1, March 23, 2015.Stockholders Agreement (Ex. 4.5), November 7, 2014.Investors' Rights Agreement (Ex. 4.4), November 7, 2014.Schedule 14D-9, June 17, 2025.Schedule 14D-9 Amendment No. 1, July 10, 2025.Schedule 14D-9 Amendment No. 3, July 18, 2025.Form 8-K — Roche immunokinase collaboration press release, March 18, 2016.Form 8-K — VOYAGER Phase 3 topline, April 28, 2020.Form 8-K — Roche pralsetinib collaboration press release, July 14, 2020.Roche Collaboration Agreement (Ex. 10.1 to Q2 2020 10-Q).Form 8-K — Royalty Pharma + Sixth Street financing, June 30, 2022.Form 10-K, FY2022.Form 8-K — Roche termination of Gavreto collaboration, February 23, 2023.Form 8-K — EGFR program discontinuation, January 8, 2024.Form 8-K — Gavreto handoff to Rigel, February 22, 2024.Form 8-K — BLU-222 deprioritization, January 13, 2025.CORRESP — response to SEC accounting comments, 2021.DEF 14A, 2018.DEF 14A, 2019.DEF 14A, 2021.DEF 14A, June 18, 2025.Sanofi Schedule TO-T (Offer to Purchase), June 17, 2025.Schedule TO-C — Hudson deal-call transcript, June 3, 2025.Schedule TO-T/A, July 17, 2025.Form 6-K, June 2, 2025.
