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.Bio
Christoph Lengauer: Founding CSO, Blueprint Medicines; Chief Drug Hunter, Curie.Bio
Erica Evans: Former VP Biology, Blueprint Medicines; SVP, Curie.Bio
Tim Guzi: Former Head of Medicinal Chemistry, Blueprint Medicines
Dr. Charles Sawyers, M.D. — Academic co-founder, Blueprint Medicines
Dr. Mariana Castells, M.D., Ph.D — Director, Mastocytosis Center, Brigham and Women’s Hospital
Chapters
00:00:00 Introduction & Hook
00:03:21 Third Rock Ventures: The Venture Creation Model
00:16:07 Blueprint’s Science: Kinase Selectivity & Gleevec
00:23:45 Blueprint Is Born: Founding & Early Challenges
00:27:06 The Platform: Building the Kinase Library
00:34:33 Near-Death & Series B: Running on Fumes
00:42:49 IPO & Clinical Programs: The Platform Pays Off
00:50:19 The Pivot: From Cancer to Mastocytosis
01:00:20 Clinical Wins, Commercial Struggles & Kate Haviland
01:24:31 FDA Approval & Diagnosis Ecosystem
01:35:35 The Sanofi Deal: A $9B Acquisition
01:53:25 Competition: Cogent Biosciences & Bezuclastinib
01:57:45 Post-Acquisition & Curie Bio: The Next Generation
02:15:31 Blueprint vs. Bluebird: A Tale of Two Platforms
02:21:12 Scorecard: Patient, Financial & Academic Impact
Sources
1. 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 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.
Form 8-K — Royalty Pharma + Sixth Street financing, June 30, 2022.
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.
Sanofi
Schedule TO-C — Hudson deal-call transcript, June 3, 2025.
Third Rock Ventures and insider filings
Comparator and adjacent companies
Unum Therapeutics / Kiq LLC, Form 8-K (Ex. 2.1), July 6, 2020.
Day One Biopharmaceuticals, Form 424B4 (IPO prospectus), 2021.
3. FDA
NDA 212608 (Ayvakit) — Drugs@FDA supplement index.
NDA 212608/S-000 — Multi-Discipline Review, GIST approval, January 9, 2020.
NDA 212608/S-007 — Advanced SM / MCL approval letter, June 16, 2021.
NDA 212608/S-013 — Multi-Discipline Review, indolent SM, May 22, 2023.
NDA 212608/S-013 — approval letter.
NDA 212608/S-013 — approved label.
NDA 213721/S-014 — Gavreto thyroid indication withdrawal letter, July 20, 2023.
FDA, “FDA approves pralsetinib for lung cancer with RET gene fusions,” September 4, 2020.
FDA, “FDA approves pralsetinib for RET-altered thyroid cancers,” December 1, 2020.
4. Clinical trials
NCT02508532 — NAVIGATOR (avapritinib, GIST).
NCT02561988 — EXPLORER (avapritinib, advanced SM).
NCT03465722 — VOYAGER (avapritinib vs. regorafenib, GIST).
NCT03580655 — PATHFINDER (avapritinib, advanced SM).
NCT03731260 — PIONEER (avapritinib, indolent SM).
NCT04910685 — HARBOR (elenestinib, ISM).
NCT05609942 — elenestinib + azacitidine, advanced SM (terminated March 2025).
NCT06931405 — BLU-808, Phase 2 CSU/CIndU.
5. Patents
US 9,944,651 B2 — avapritinib (BLU-285) composition of matter.
US 10,030,005 B2 — pralsetinib (BLU-667) composition of matter.
Justia — Brian L. Hodous inventor index.
Justia — Joseph L. Kim inventor index.
6. Scientific literature
Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A. “Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand.” EMBO J 1987;6(11):3341–51.
Furitsu T, et al. “Identification of mutations in the coding sequence of the proto-oncogene c-kit.” J Clin Invest 1993;92:1736–1744.
Kim JL, et al. “Crystal structure of the hepatitis C virus NS3 protease domain.” Cell 1996;87:343–355.
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. “The protein kinase complement of the human genome.” Science 2002;298(5600):1912–34.
Kantarjian H, et al. (incl. Druker B). “The price of drugs for chronic myeloid leukemia (CML): a reflection of the unsustainable cancer drug prices.” Blood 2013;121(22):4439–4442.
“First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway.” Cancer Discovery 2015;5(4):424.
Evans EK, Gardino AK, Kim JL, Hodous BL, Shutes A, Davis A, et al. “A precision therapy against cancers driven by KIT/PDGFRA mutations.” Sci Transl Med 2017;9(414):eaao1690.
“Precision targeted therapy with BLU-667 for RET-driven cancers.” Cancer Discovery 2018;8(7):836.
“First-in-human Phase I study of fisogatinib (BLU-554) validates aberrant FGF19 signaling as a driver event in hepatocellular carcinoma.” Cancer Discovery 2019;9(12):1696.
Heinrich, et al. “Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR).” Lancet Oncology 2020.
“Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial.” Nature Medicine 2021.
Mesa, et al. “TouchStone SM patient survey.” Cancer 2022.
Slaff, et al. “TouchStone SM healthcare-provider survey.” Cancer 2022.
Castells M, et al. “Avapritinib versus placebo in indolent systemic mastocytosis (PIONEER).” NEJM Evidence, May 23, 2023.
Duncan CN, et al. “Hematologic malignancies after elivaldogene autotemcel for cerebral adrenoleukodystrophy.” NEJM, October 9, 2024. DOI 10.1056/NEJMoa2400442 (companion: 10.1056/NEJMoa2405541)
“[MASTering SM](https://www.jaci-global.org/article/S2772-8293(24).” JACI Global 2024.
“Avapritinib for Systemic Mastocytosis“ (review), PMC.
Cogent Biosciences, SUMMIT primary analysis abstract. Blood 2025;146(Suppl 1):80.
Blueprint Medicines, elenestinib HARBOR Part 1 abstract. Blood 2023;142(Suppl 1):76.
STK17B / kinase-selectivity context. Frontiers in Immunology 2024.
7. Journalism
Blueprint Medicines
C&EN — “Blueprint Medicines Is Oncology Start-Up,” October 26, 2011.
Boston Globe — “Fidelity Biosciences invests in Blueprint Medicines,” May 24, 2012.
Fierce Biotech — “Third Rock’s Blueprint Medicines scores $147M windfall in another hot IPO,” April 2015.
Boston Globe — “Blueprint shares up after raising $147 million in IPO,” April 30, 2015.
Fierce Biotech — “Blueprint Medicines Announces Worldwide Cancer-Immunotherapy Collaboration,” March 2016.
BioPharma Dive — “Blueprint posts ‘impressive’ data for lead candidate, but investor response tepid,” 2018.
STAT — “Blueprint gains approval for its first drug, a treatment for a rare GI cancer,” January 9, 2020.
OncLive — “Avapritinib Falls Short in VOYAGER Phase 3 GIST Trial,” 2020.
Fierce Biotech — “Roche to pay Blueprint $775M for pralsetinib rights, setting up showdown with Lilly,” July 2020.
BioPharma Dive — “Blueprint’s Gavreto wins FDA approval,” September 2020.
Boston Globe — “Blueprint Medicines wins FDA approval for drug to treat rare blood disorder,” June 16, 2021.
STAT — “Blueprint Medicines seeks ‘continuity, not change’ in CEO transition,” January 6, 2022.
Fierce Pharma — “Blueprint’s Albers hands CEO baton to deal mastermind Haviland,” January 2022.
BioPharma Dive — “Blueprint secures access to more than $1B in funding through two new deals,” June/July 2022.
STAT — “Blueprint drug reduces mastocytosis symptoms in a new study,” August 17, 2022.
BioPharma Dive — “Roche takes $2.8B in impairments, writing down Spark and Gavreto,” February 3, 2023.
Fierce Pharma — “After splashing $1B, Roche returns lagging cancer drug Gavreto to Blueprint,” February 2023.
Fierce Pharma — “Blueprint CEO touts Ayvakit’s rare disease win, but analysts flag looming ‘commercial debate’,” 2023.
Fierce Pharma — “Roche pulls Gavreto’s accelerated approval as Blueprint severance and confirmatory trial turns,” July 2023.
pharmaphorum — “After Roche’s exit, Blueprint passes Gavreto on to Rigel,” 2024.
Fierce Pharma — “Blueprint boosts Ayvakit peak sales estimate to $2B,” 2024.
Fierce Biotech — “Blueprint ends work on clinical-stage CDK2 inhibitor,” January 2025.
ApexOnco — “Blueprint clears house: EGFR.”
pharmaphorum — “Ipsen adds Blueprint’s FOP rare disease drug to pipeline for $535M,” September 2019.
Drug Hunter — avapritinib molecule case study.
The Sanofi acquisition
BioPharma Dive — “Sanofi to acquire Blueprint for up to $9.5B,” June 2, 2025.
STAT — “Sanofi to buy Blueprint Medicines in deal worth more than $9 billion,” June 2, 2025.
Nature Biotechnology — “Mast cells drive Blueprint mega-deal,” July 2025.
Endpoints News — “Sanofi’s new CEO faces a reckoning on immunology-focused R&D strategy.”
BioSpace — “Biopharma’s continued staff cuts in 2025,” November 2025.
Cogent Biosciences and the competitive landscape
STAT — “Cogent Biosciences–Blueprint Medicines tiff turns spicy on eve of immune drug study readout“ (Adam Feuerstein), June 19, 2025.
BioSpace — “Cogent Jumps on Positive Mid-Stage Mastocytosis Data and NDA Plans,” July 7, 2025.
Drug Hunter — bezuclastinib (CGT9486) molecule page.
Third Rock Ventures and the company-creation model
VentureBeat — “Life sciences briefing: Friday, Sept. 14, 2007.”
Xconomy Boston — “Third Rock Ventures Heads ‘Back to the Basics’,” September 23, 2008.
Xconomy Boston — “Agios Lands Genentech Cancer Drug Leader as New CEO,” May 27, 2009.
MIT Technology Review — “Co-opting a Cancer Treatment to Spur Fat Loss,” July 15, 2009.
Global Venturing — “Third Rock incubates new venture capital model,” October 4, 2010.
Boston Globe — “Boston’s Third Rock Ventures closes $516m fund,” March 25, 2013.
Boston Globe — “Foundation Medicine files to go public,” July 30, 2013.
VentureBeat — “Foundation Medicine shares pop 89 percent after $106M IPO,” September 2013.
MIT Technology Review — “Biotech’s Top VCs“ (Antonio Regalado), February 18, 2014.
Nature — “Biotechnology: The start-up engine,” 2014.
Boston Globe — “Third Rock Ventures has emerged as a key Boston-area engine for forming biotech startups“ (Robert Weisman), June 14, 2014.
Boston Globe — “Third Rock’s IPO class of 2013 remain stock market favorites,” February 3, 2015.
Fortune — “Third Rock Ventures: Giving birth to a new generation of biotechs“ (Erika Fry), February 19, 2015.
BioSpace — Mark Levin, MassBio Innovative Leadership (Termeer) Award, March 2015.
Boston Globe — “Third Rock hunting for Cambridge lab space,” May 14, 2015.
Boston Globe — “Pharma gives drug development the Hollywood treatment“ (Robert Weisman), September 27, 2015.
Boston Globe — “Third Rock launches cancer-fighting startup“ (Neon), October 1, 2015.
GeekWire — “Editas Medicine raises $94M in first gene-editing IPO,” February 2016.
Fierce Biotech — “Third Rock raises $616m for fourth biotech venture fund,” October 31, 2016.
Boston Globe — “Five things you should know about Abbie Celniker,” February 17, 2017.
Boston Globe — “With $55 million, Third Rock launches cancer drug startup Tango Therapeutics,” March 31, 2017.
Endpoints News — “Protein degradation 2.0? Third Rock sinks $56M into Cedilla’s unusual approach,” April 2018.
Fierce Biotech — “Celsius bags $65M to develop precision meds for cancer, autoimmune disease,” 2018.
STAT — “Third Rock raises $770 million in new funding round“ (Damian Garde), June 6, 2019.
Fierce Biotech — “Third Rock raises $770M to build and grow more biotechs,” June 2019.
Endpoints News — “Maze Therapeutics launches with $191M led by Arch, Third Rock,” February 2019.
BioCentury — “Solving for the medical and business case in pediatric cancer: Day One,” 2020.
Fierce Biotech — “Daphne Koller, A-list backers unite to create machine-learning drug R&D startup,” 2020.
BioSpace — “Precision oncology startup Flare Therapeutics launches with $82M Series A,” May 2021.
C&EN — “MOMA Therapeutics launches,” 2021.
STAT — “Third Rock Ventures plots next chapter after raising $1.1 billion fund“ (Allison DeAngelis), June 15, 2022.
STAT — “American Cancer Society’s BrightEdge and Third Rock to collaborate on oncology,” July 2022.
STAT — “Faze Medicines is shutting down,” November 8, 2022.
Fierce Biotech — “Third Rock, J&J spinout Rapport arrives with $100M,” March 7, 2023.
Fierce Biotech — “Clasp Tx hooks $150M Series A for next-gen cancer treatments,” March 20, 2024.
Fierce Biotech — “Third Rock’s Rapport reveals upsized $154M IPO,” June 2024.
Fierce Biotech — “Third Rock-backed Trace uses $101M Series A to go after same ALS target as Lilly,” November 2024.
STAT — “Third Rock Ventures tops STAT’s annual biotech VC rankings“ (Allison DeAngelis), August 27, 2025.
Fierce Biotech — “Third Rock-backed Merida launches with $121M Series A,” 2025.
STAT — “Servier to acquire Day One Biopharmaceuticals,” March 6, 2026.
Axial Observations — “Eight lessons from Mark Levin, Third Rock.”
Curie.Bio and “freeing the founders”
STAT — “A new biotech investment firm, headed by a pair of noteworthy VCs, seeks to ‘free the founders’,” May 11, 2022.
STAT — “With $520 million in hand, two entrepreneurs try to upend the biotech funding model,” February 14, 2023.
Fast Company — “Why Curie.Bio believes it can change how new drugs get discovered,” February 2023.
STAT — “Biotech incubator Curie.Bio graduates its first startup,” November 8, 2023.
STAT — “Biotech accelerator Curie.Bio extends its reach with new $380 million fund,” June 26, 2024.
C&EN — “Cashing in on founder-led biotech,” November 2024 (102/i36).
BioWorld — “Alkira Bio exits stealth via seed round to develop GPCR-targeting antibodies,” 2024.
STAT — “Biotech accelerator Curie.Bio raises $340 million for a new seed fund,” January 29, 2025.
Drug Hunter — “From AZ to VC: Tracing Our Industry’s Recent Evolution Through A Career“ (Chris De Savi), 2025.
STAT — “For its first two medicines, EQRx abandons its bold strategy to lower drug prices,” November 10, 2022.
STAT — “EQRx, failed developer of low-priced cancer drugs, is sold for cash,” August 1, 2023.
bluebird bio and the comparator TRV/2015 IPO cohort
Xconomy Boston — “bluebird bio (Third Rock, Genzyme’s Gene-Therapy Bet) Shows Promise for Blood Disorder,” September 15, 2010.
Boston Globe — “Bluebird shares soar after gene therapy shows promise treating inherited blood disease,” December 9, 2014.
STAT — “Axovant’s intepirdine fails in Alzheimer’s trial,” September 26, 2017.
PharmiWeb — “Merck to complete acquisition of Cidara Therapeutics in $9.2 billion deal.”
DCAT Value Chain Insights — “Roche completes $4.3 billion acquisition of Spark Therapeutics.”
BioPharma Dive — “Josh Bilenker, Loxo: Executive of the Year.”
Fierce Pharma — “Array CEO Squarer, other execs to take home tens of millions in Pfizer sale.”
Fierce Biotech — “Bayer bags Algeta’s cancer drug portfolio for $2.9B.”
Genzyme, Henri Termeer, and the Sanofi cultural lineage
Boston Globe — “Genzyme family tree: how Henri Termeer spawned a network of Genzyme alums leading dozens of biotechs,” July 11, 2015.
Boston Globe — Henri Termeer obituary, May 13, 2017.
Boston Globe — “Family, friends recall contributions of former Genzyme executive Henri Termeer,” May 20, 2017.
BioCentury — “Henri: N of 1.”
Boston Globe — “Eleven years after buying Genzyme, Sanofi officially ditches subsidiary’s storied name,” February 3, 2022.
BioPharma Dive — “Sanofi to pay $315 million to settle Lemtrada ‘go-slow’ claims.”
Glenn Chan — “Genzyme contingent value rights (GCVRZ) post-mortem,” November 9, 2013.
Fast Company — “The Trials of ImClone,” September 2004.
CFO.com — “Onetime CFO Resigns as ImClone CEO,” November 14, 2005.
STAT — “The Survivors“ (Gleevec patients, 25 years on), April 25, 2017.
8. Venture-model analysis (Bruce Booth / LifeSciVC)
“The Biotech Venture Capital Math Problem,” March 2012.
“Two Really Big Fish That Got Away,” March 2018.
“2018’s Biotech IPO Bonanza: View From the After Market,” October 2018.
“Generations: Talent Dispersion in Biotechnology“ (Tariq Kassum, guest), November 2018.
“The Creation of Biotech Startups: Evolution Not Revolution,” August 2019.
“Biotech Risk Cycles: Assets and Platforms,” October 2024.
“Atlas XIV And Reflections On The VC Math Problem,” December 2024.
“Twenty Years In Early Stage Biotech VC — Part 1: Science,” October 14, 2025.
“Twenty Years In Early Stage Biotech VC — Part 2: People,” October 15, 2025.
“Twenty Years In Early Stage Biotech VC — Part 3: Business,” October 16, 2025.
9. Patient accounts
10. Web archives
