VOYAGER clinical trial top-line results APRIL 28, 2020 CONFERENCE CALL © 2020 Blueprint Medicines Corporation

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VOYAGER trial top-line results conference call Introductory remarks Jeff Albers, Chief Executive Officer Summary of top-line VOYAGER trial data Andy Boral, MD, PhD, Chief Medical Officer Q&A 3

VOYAGER was a well-designed and well-conducted clinical trial 4 Avapritinib (n = ~230) 300 mg once daily Regorafenib (n = ~230) 160 mg once daily for 3 out of every 4 weeks 3L or 4L Advanced GIST Randomized, 1:1 N = ~460 Design • Randomized, phase 3 clinical trial Eligibility • Adults with metastatic and/or unresectable GIST • Previously treated with imatinib and 1 or 2 other TKIs Enrollment • 476 patients enrolled at 95 sites across 18 countries Primary endpoint: progression-free survival GIST, gastrointestinal stromal tumor; TKI, tyrosine kinase inhibitor; 3L, third-line; 4L, fourth-line.

VOYAGER did not meet the primary endpoint AE, adverse event; ORR, overall response rate; mPFS, median progression-free survival. 5 Avapritinib (n=240) Regorafenib (n=236) mPFS 4.2 months 5.6 months ORR 17% 7% TOP-LINE EFFICACY • Difference in mPFS between avapritinib and regorafenib was not statistically significant • Additional data analyses are ongoing with plans to present results at a future scientific meeting 3L AND 4L GIST (PRIMARY EFFICACY POPULATION) Not for promotional use. TOP-LINE SAFETY • Consistent with previously reported data for avapritinib • Avapritinib was generally well-tolerated and most AEs were grade 1 or 2 • 8% discontinued avapritinib due to treatment-related AEs • 26% rate of cognitive effects in the avapritinib group, compared to a 41% rate in the NAVIGATOR trial

Summary and next steps for the avapritinib program in advanced GIST • Avapritinib did not demonstrate an improvement in mPFS over regorafenib in 3L or 4L GIST – Efficacy results highlight the complexity of treatment-resistant advanced GIST • Top-line safety results for avapritinib were consistent with previously reported data • Planned next steps: – Continue to commercialize AYVAKIT™ (avapritinib) in the United States for PDGFRA exon 18 mutant GIST – Continue to seek marketing authorization in the European Union for PDGFRA D842V mutant GIST – Discontinue further development of avapritinib for all other GIST indications 6 Not for promotional use.

Portfolio opportunities in systemic mastocytosis and RET-altered cancers remain our priorities, with multiple planned regulatory submissions in 2020 1. Includes estimated net proceeds of $308.4M from January 2020 follow-on public offering and anticipated product revenues. Excludes any potential option fees, milestone payments or other payments under collaboration or license agreements. advSM, advanced systemic mastocytosis; EMA, European Medicines Agency; FDA, U.S. Food and Drug Administration; MAA, marketing authorization application; MTC, medullary thyroid cancer; NDA, new drug application; NSCLC, non-small cell lung cancer; sNDA, supplemental NDA. 7 • sNDA to FDA for advSM in 2H 2020 ✓NDA to FDA for RET+ NSCLC in Q1 2020 • MAA to EMA for RET+ NSCLC in Q2 2020 • NDA to FDA for RET+ MTC in Q2 2020 CONTINUE TO EXPECT EXISTING CASH BALANCE WILL FUND OPERATIONS INTO THE 2H OF 2022, BASED ON CURRENT OPERATING PLANS1 PRALSETINIB AVAPRITINIB Systemic mastocytosis Non-small cell lung cancer Medullary thyroid cancer

Q&A