PRECISION THAT MOVES™ Staying one step ahead of disease R.T ., living with GIST J.P. Morgan Healthcare JANUARY 13-16, 2020 Conference 1 © 2020 Blueprint Medicines Corporation

Forward-looking statements T his presentation contains forward -looking statements as defined in the Private Securities Litigation Reform Act of 1995, as ame nded. T he words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar ex pressions are intended to identify forward -looking statements, although not all forward-looking statements contain these identifying words. In this presentation, forward -looking statements include, without li mitation, statements regarding Blueprint Medicines’ 2020 key milestones; Blueprint Medicines’ plans, strategies, timelines and expectations for the preclinical and clinical development a nd commercialization of AYVAKIT ™ (avapritinib), pralsetinib, fisogatinib, and BLU-263; plans and timelines for submitting marketing applications for avapritinib and pralsetinib and, if approved, commercializing avapritinib for additional indications or pralsetinib; the potential benefits of Blueprint Medicines’ current and future drug candidates in treating patients; expectations regarding Bl ueprint Medicines’ existing cash, cash equivalents and investments; and Blueprint Medicines’ strategy, goals and anticipated milestones, business plans and focus. Blueprint Medicines has based thes e forward-looking statements on management’s current expectations, assumptions, estimates and projections. W hile Blueprint Medicines believes these expectations, assumptions, estimates and pro jections are reasonable, such forward -looking statements are only predictions and involve known and unknown risks, uncertainties and other important factors, many of which are beyond Blueprin t Medicines’ control and may cause actual results, performance or achievements to differ materially from those expressed or implied by any forward -looking statements. T hese risks and uncertainti es include, without limitation, risks and uncertainties related to the delay of any current or planned clinical trials or the development of Blueprint Medicines’ drug candidates, including avaprit inib, pralsetinib, fisogatinib and BLU-263, or the licensed products, including BLU-782; Blueprint Medicines’ advancement of multiple early-stage efforts; Blueprint Medicines’ ability to successfully demonstr ate the efficacy and safety of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines’ drug candidat es, which may not support further development of such drug candidates; actions or decisions of regulatory agencies or authorities, which may affect the initiation, timing and progress of clinical trials o r marketing applications; Blueprint Medicines’ ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing; Blueprint Medicines’ abil ity and plans for establishing a commercial infrastructure, and successfully launching, marketing and selling its current or future approved products; Blueprint Medicines’ ability to successfully expand the indications for AYVAKIT in the future; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines’ current and future collaborations, partnerships, and license, including its collaborations with F. Hoffmann -La Roche Ltd and Hoffmann-La Roche Inc. (collectively, “Roche”) and CStone Pharmaceuticals (“CStone”) and its license agreement with Clementia Pharmaceuticals Inc. (“ Clementia”). T hese and other risks and uncertainties are described in greater detail under “Risk Factors” in Blueprint Medicines’ filings with the Securities and Exchange Commission (“SEC”), including Blueprint Medicines’ most recent Quarterly Report on Form 10 -Q and any other filings Blueprint Medicines has made or may make with the SEC in the future. Blueprint Medicines cannot guarantee future results, outcomes, levels of activity, performance, developments, or achievements, and there can be no assurance that Bluepri nt Medicines’ expectations, intentions, anticipations, beliefs, or projections will result or be achieved or accomplished. T he forward -looking statements in this presentation are made only as of the date hereof, and except as required by law, Blueprint Medicines undertakes no obligation to update any forward -looking statements contained in this presentation as a result of new information, future events or otherwise. T his presentation also contains estimates, projections and other statistical data made by independent parties and by Blueprin t Medicines relating to market size and growth and other data about Blueprint Medicines’ industry. T hese data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of Blueprint Medicines’ future performance and the future performance of the markets in which Blueprint Medicin es operates are necessarily subject to a high degree of uncertainty and risk. 2

2020 Blueprint: three key themes Now approved in the U.S. R.S., living with SM Fully integrated commercial-stage company, with multiple planned global regulatory submissions for avapritinib and pralsetinib Expanded strategic focus on systemic mastocytosis and related mast cell disorders Continuous strengthening of pipeline, with plans to nominate up to 3 development candidates this year SM, systemic mastocytosis. Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) (CSTI). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. 3 Not for promotional use.

The rapid evolution of Blueprint Medicines IMAGINING A NEW PLATFORM 2011 – 2014 BUILDING THE PIPELINE 2015 – 2019 REALIZING THE VISION 2020 – FUTURE H I G H L Y S E L E C T I V E K I N AS E M E D I C I N E D I S C O V E R Y P L AT F O R M R AP I D C L I N I C AL P R O O F - OF - C O N C E P T AC R O S S M U L T I P L E P R O G R AM S Integrated commercialization Indication expansion Therapeutic area leadership Innovative kinase biology avapritinib Av apritinib in adv anced systemic mastocytosis: change in serum tryptase1 1 Data presented at the European Hematology Association Annual Meeting in June 2019. Data cutoff date: January 2, 2019. Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) (CSTI). The foregoing website is maintained by CSTI, and Blueprint 4 Medicines is not responsible for its content. Not for promotional use.

A powerful vision for delivering durable benefit with targeted therapy HIGHLY S E LE CT IV E INHIB ITO RS Potent inhibition of genetic drivers leads to rapid, deep and durable responses D E TE C T IN TE R P R E T PAT IE NT S E LE CT ION Understanding of disease heterogeneity enables responder hypotheses A DA P T IV E A B ILIT Y Research engine rapidly empowers solutions for acquired resistance AC T 5 Not for promotional use.

Expand applications to reach broader patient populations Address disease heterogeneity Address disease evolution Expand to new populations 3 4 Patient lection rategy 2 Fast expansion on PO sequential treatment approaches Change the paradigm Target single driver 5 Tumor agnostic treatment and preventative combinations Selective and pote inhibitor 1 Discrete Patient population Expanded POC, proof of concept 6 Not for promotional use.

Build therapeutic leadership by leveraging insights and efficiencies Next-generation inhibitors Combination strategies Enhanced patient selection C L I N I C A L A N D C O M M E R C I A L S C A L E T R A N S L A T I O N A L I N S I G H T S 7 Not for promotional use.

Seek to deliver a portfolio of new medicines to patients globally MU LT IP LE A N T IC IPAT E D C OMME R C IA L LA U N C H E S T H R OU GH 2021 20213 Q1 2020 Q2 2020 Q3 2020 Q4 2020 US - PDGFRA GIST1 US - 4L GIST EU - PDGFRA GIST2 US - 3L GIST GIST avapritinib US - Adv anced SM SM avapritinib US - NSCLC US - 2L MTC RET pralsetinib EU - NSCLC Launch underway Launch planned 1. Approved in the U.S. for unresectable or metastatic GIST harboring a PDGFRA exon 18 mutant, including PDGFRA D842V mutatio ns. 2. The proposed MAA indication is unresectable or metastatic GIST harboring a PDGFRA D842V mutation. 3. Represents planned NDA/MAA submissions. GIST, gastrointestinal stromal tumor; MAA, marketing authorization application; MTC, medullary thyroid cancer; NDA, 8 new drug application; NSCLC, non-small cell lung cancer; SM, systemic mastocytosis; 2L, second-line; 3L, third-line; 4L, fourth-line Not for promotional use.

Avapritinib: a precision therapy with broad potential U.S. REGULATORY SUBMISSION STATUS LATE CLINICAL DEVELOPMENT PDGFRA exon 18 mutant GIST APPROVED1 4L GIST SUBMITTED 2H 2020 3L GIST Advanced SM 2H 2020 Indolent and smoldering SM Avapritinib Potent and highly selective KIT and PDGFRA inhibitor 1. Approved in the U.S. for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) (CSTI). The foregoing website is mai ntained by CSTI, and Blueprint Medicines is not responsible for its content. 9 Not for promotional use.

AYVAKIT™ (avapritinib) is now approved in the United States INDICATION AYVAKIT is indicated for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations AVAILABLE DOSE STRENGTHS 100, 200 and 300 mg tablets First precision therapy for GIST • Approved regardless of line of therapy Only highly effective treatment for PDGFRA exon 18 mutant GIST 10 Full prescribing information is available at www.AYVAKIT.com. Not for promotional use.

Full approval of AYVAKIT based on Phase 1 NAVIGATOR trial 11 Full prescribing information is available at www.AYVAKIT.com. CI, confidence interval. Not for promotional use. EFFICACY PARAMETER PDGFRA EXON 18 (N=43) PDGFRA D842V (N=38) Overall response rate (95% CI) 84% (69%, 93%) 89% (75%, 97%) Complete response, n (%) 3 (7%) 3 (8%) Partial response, n (%) 33 (77%) 31 (82%) Duration of response n=36 N=34 Median in months (range) Not reached (1.9+, 20.3+) Not reached (1.9+, 20.3+)

Safety highlights from AYVAKIT prescribing information MOST COMMON ADVERSE REACTIONS (≥20%; ANY GRADE):1 • Edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness WARNINGS AND PRECAUTIONS: • Intracranial hemorrhage –Occurred in 1% of 267 patients with GIST who received AYVAKIT CNS adverse reactions –Occurred in 58% of 335 patients who received AYVAKIT • • Cognitive impairment: 41% (3.6% Grade 3 or 4) –Overall, 3.9% of patients required treatment discontinuation due to a CNS adverse reaction Embryo-fetal toxicity • Important safety information and full prescribing information are available at www.AYVAKIT.com. 1. Adverse reactions in 204 patients with unresectable or metastatic GIST who received 300-400 mg once daily of AYVAKIT. CNS, central nervous system. Not for promotional use. 12

Strategic imperatives for the AYVAKIT launch Be recognized as the leader in precision medicine by hematology/oncology centers of excellence Drive positive first experiences with AYVAKIT among GIST prescribers Provide best-in-class patient support to optimize patient access and adherence Catalyze patient identification in GIST and across J.D., living w ith GIST portfolio therapeutic areas Focused portfolio field footprint with ~40 area business managers 13 Not for promotional use.

Systemic mastocytosis is one disease with a common genetic driver ~95% of patients have KIT D816V mutation Life-threatening impact Requirement for long-term therapy Requirement for high treatment intensity 75,000 prevalent patients in major markets1 14 Major markets include US, EU5 and Japan. 1. Cohen S et al Br J Haematol (2014) 166(4):521-8 and W orld Bank Population estimates. Not for promotional use. Debilitating symptoms Indolent SM Advanced SM

Comprehensive systemic mastocytosis clinical trial program Advanced SM Phase 1 dose-escalation trial with open-label expansion Advanced SM Phase 2 single-arm trial Indolent SM Phase 2 randomized, double-blind, placebo-controlled trial 15 Not for promotional use.

EXPLORER trial data for patients with advanced SM: Profound activity on all measures of mast burden in nearly all patients B O N E MA R R O W MA S T C E L L S S E R U M T RY P TA S E K I T D 8 1 6 V MU TA N T S P L E E N V O L U ME A L L E L E F R A C T I O N 16 EXPLORER trial data reported on December 8, 2019. Data cutoff: August 30, 2019. Not for promotional use. Maximum Percent Change from Baseline Maximum Percent Change from Baseline Maximum Percent Change from Baseline Maximum Percent Change from Baseline

EXPLORER trial data for patients with advanced SM: Remarkable response rate and prolonged duration of response BEST RESPONSE PER IWG -MRT -ECNM CRIT ERIA ALL DOSES (N=48)1 • • • FDA breakthrough therapy designation3 Robust activity across all disease subtypes Median follow up of 21 months with 77% Confirmed ORR2 Median DOR and OS not reached up to ~3.5 years1 ongoing treatment • • Avapritinib was generally well-tolerated, and most AEs were grade 1 or 2 4 Most common treatment-emergent AEs were periorbital edema, anemia, diarrhea, fatigue, peripheral edema, nausea, thrombocytopenia, vomiting and cognitive effects Across all doses, 6 patients discontinued treatment due to treatment -related AEs S AF E T Y AL L D O S E S ( N = 8 0 ) 1 • 1. EXPLORER trial data reported on December 8, 2019. Data cutoff: August 30, 2019. 2. ORR defined as complete remission with full or partial recovery of peripheral blood counts, partial remission or clinical improvement. 3. Avapritinib granted Breakthrough Therapy Designation for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia. 4. After the data cutoff date, one patient with SM and an associated hematologic neoplasm (SM-AHN) of myelodysplastic syndrome had a Grade 5 intracranial bleed. At the time of the bleeding event, the patient had severe throm bocytopenia and experienced a serious injury 17 involving head trauma. AE, adverse events. DOR, duration of response; ORR, overall response rate; OS, overall survival. Not for promotional use.

Adjustment of NDA submission timing for avapritinib for advanced SM enhances dataset at 200 mg QD dose and increases probability of success C O MB IN E D E X P L O R E R AN D PAT H F IN D E R T R IAL D ATAS E T Q 1 2 0 2 0 2 H 2 0 2 0 * • Based on ongoing discussions with FDA, now plan to submit supplemental NDA for avapritinib for advanced SM in 2H 2020 Safety Population N= 101 Safety Population N= ~135 • Plan to include additional patients treated with a starting dose of 200 mg QD, the proposed indicated dose • Target enrollment for efficacy in PATHFINDER trial is complete and follow-up is ongoing Patients with starting dose of 200 mg QD and IWG evaluable Patients with all other starting doses or not IWG evaluable * Estimated based on Blueprint Medicines’ clinical trial plan. QD, once daily. 18 Not for promotional use. n= 15 n= ~50

EXPLORER trial data for patients with indolent SM: Robust reductions on measures of mast cell burden Serum tryptase Marrow mast cells Spleen volume Marrow KIT D816V Data presented at the European Hematology Association Annual Meeting in June 2019. Data cutoff date: January 2, 2019. 19 Not for promotional use.

EXPLORER trial data for patients with indolent SM: Improvement in disease symptoms and PRO survey total symptom score Total Symptom Score Total Symptom Score 00 Total Symptom Score 00. ota Sy pto Sco e 70 70 Fatigue Vomit Fatigue Vomit 60 60 08 Vomit 01 Fatigue 08.Vomit 01.Fatigue 50 50 40 40 30 30 20 20 Itching g Spots Flushing Spots 10 10 Flushinushging 0N3 Naa usea Itching Nausea tching 03.Spo Diarrhea Abdominal Diarrhea Abdominal 20 EXPLORER trial data analysis. Data cutoff date: August 30, 2019. PRO, patient reported outcomes. Not for promotional use. Mean baseline score Best score reduction ALL PATI E N TS ( N = 3 9 ) I NDO L E NT S M PAT I E NT S ( N= 5 )

EXPLORER trial data for patients with indolent SM: Prolonged durations of therapy at low doses • • 14 of 15 (93%) remained on treatment up to nearly 3 years (cycle 36) Average dose was 126 mg with 73% treated at 100 mg QD EXPLORER trial data analysis. Data cutoff date: January 2, 2019. ISM, indolent SM; SSM, smoldering SM. 21 Not for promotional use.

PIONEER trial data for patients with indolent SM: All avapritinib doses showed rapid and robust reductions in serum tryptase M E AN P E R C E N T C H AN GE IN S E R U M TRYP TAS E BAS E LINE CHARACTE R IS T ICS • Significant symptom burden in every patient enrolled • 84% of screened patients met minimum symptom burden eligibility requirement • Baseline median Total Symptom Score was 52 (range: 19–100) • Most reported AEs were grade 1 or 2 • No intracranial bleeding, thrombocytopenia or anemia reported • No patients discontinued treatment due to an AE S AF E T Y ( N = 3 0 ) AL L D O S E S 22 PIONEER data presented at ASH 2019 Annual Meeting. Data cutoff: November 12, 2019. Not for promotional use.

Next steps for the PIONEER trial of avapritinib in indolent SM Safety PIONEER Dose-finding Part 1 PIONEER Registration-enabling Part 2 Select RP2D Serum tryptase ISM-SAF TSS Complete enrollment of dose-finding Part 1 Report initial safety and serum tryptase data at ASH 2019 Annual Meeting Plan to report additional Part 1 data in late-breaking oral abstract at AAAAI 2020 on March 14, 2020 Complete enrollment of the registration-enabling Part 2 by the end of 2020 AAAAI, American Academy of Allergy, Asthma & Immunology; RP2D, recommended part 2 dose. 23 Not for promotional use.

BLU-263 was advanced based on insights from avapritinib POTENT Sub-nanomolar potency against KIT D816V SELECTIVE Highly selective for KIT, with low off-target activity CNS PROFILE Designed to not cross blood-brain barrier P LA N TO IN IT IAT E P H A S E 1 T R IA L IN H E A LT H Y V OLU N T E E R S IN 1H 2020 24 Not for promotional use.

Pralsetinib: an investigational precision therapy for RET-altered cancers LATE CLINICAL DEVELOPMENT U.S. REGULATORY SUBMISSION STATUS RET fusion NSCLC Q1 2020 2L MTC Q2 2020 RET-altered tumors Pralsetinib Potent and highly selective RET inhibitor IN IT IAT E D R OLLIN G N D A S U B MIS S IO N TO FD A FOR R E T FU S ION N S C LC IN JA N U A RY 2020 Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) (CSTI). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. Not for promotional use. 25

RET alterations: oncogenic drivers lacking a targeted therapeutic approach <1% RET-altered, including:5,6 colorectal 1 Lipson, et al. Nat Med 2012. 2 Takeuchi, et al. Nat Med 2012. 3 Romei, et al. Oncotarget 2018. 4 Santoro, et al. J Clin Invest 1992. 5 Kato, et al. Clin Cancer Res 2017. 6 Ballerini, et al. Leukemia 2012. Not for promotional use. 26 Multiple other tumor types esophageal pancreatic breast melanoma leukemia Non-small cell lung cancer: ~1-2% RET fusions1,2 Advanced medullary thyroid cancer: ~90% RET mutations3 Papillary thyroid cancer: ~20% RET fusions4

Pralsetinib is a potential best-in-class selective RET inhibitor and the cornerstone of our lung cancer portfolio EQUIPOTENT INHIBITION of RET fusions and mutations, including predicted gatekeeper resistance mutations CLINICAL RESPONSES in 2 of 4 patients previously treated with selpercatinib 2 HIGH RESPONSE RATES AND DURABLE ACTIVITY in RET+ NSCLC1 and MTC2 patients FDA BREAKTHROUGH THERAPY DESIGNATIONS for RET+ NSCLC and MTC3 STRONG ACTIVITY AGAINST BRAIN METASTASES in patients with RET+ NSCLC2 WELL-TOLERATED WITH LOW DISCONTINUATION RATES in advanced cancer populations1,2 1. Top-line NSCLC data reported on January 8, 2020. Data cutoff date: November 18, 2020. 2. Data presented at ASCO Annual Meeting in June 2019. Data cutoff date: April 28, 2019. 3. FDA has granted breakthrough therapy designations to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and RET-mutant MTC that requires systemic treatment and for which there are no acceptable alternative treatments. Not for promotional use. 27

NSCLC patients with RET fusions have no highly effective treatment options 1 Mazieres, et al. JCO 2018. 2 Drillon, et al. Lancet 2017. 3 Yoh, et al. Lancet Respir Med 2017. 28 Not for promotional use. • Chemotherapy: nonspecific, low response rates, significant toxicity • Checkpoint inhibition: Preliminary evidence for lack of benefit in RET-altered NSCLC1 • Multi-kinase inhibitors: ↓ activity, ↑ off-target toxicity2,3 • Growing understanding of RET-driven resistance • No selective RET inhibitors are approved

Centrally reviewed top-line ARROW trial data showed robust and durable clinical activity for pralsetinib in RET fusion NSCLC A L L N S C L C PAT I E N T S ( 4 0 0 MG Q D ) P E R C E N T R A L R A D I O L O G Y RET-fusion NSCLC with prior platinum chemotherapy 400 mg QD, N=80 61% O R R 1 RET-fusion NSCLC with no prior systemic therapy 400 mg QD, N=26 73% O R R 2 • Median DOR not reached (95% CI: 11.3 months, NE) in patients treated with 400 mg QD • Safety results (N=354; 400 mg QD) were consistent with prior data; most reported AEs were grade 1 or 2 • Overall, 4% of patients discontinued treatment due a treatment-related AE Top-line data from the Phase 1/2 ARROW trial in patients with RET fusion NSCLC. Data cutoff date: November 18, 2019. 1. Two responses pending confirmation. 2. All responses confirmed. CR, complete response; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease. 29 Not for promotional use.

RET-altered thyroid cancer patients may benefit from highly targeted therapy 1 Drillon, et al. Nature Reviews Clinical Oncology, 2017. 30 Not for promotional use. • Multi-kinase inhibitors are approved for MTC, but have important limitations:1 • 25-44% ORR • Off-target toxicity often requiring dose modification or discontinuation • Emergence of resistance • No selective RET inhibitors are approved

ARROW trial data presented at ASCO 2019 showed robust and durable clinical activity for pralsetinib in MTC and other RET-altered cancers A L L MT C PAT I E N T S ( 4 0 0 MG Q D ) 20 0 RET-mutant MTC previously treated with an MKI 63% ORR1 -20 -40 400 mg QD, n=16 -60 Cabo oarndVaVnadn-dn-anïaveive -80 -100 ADDITIONAL RESULTS • • • • Across all MTC patients, 97% disease control rate Median duration of response not reached; all responders remain on treatment with durations up to 15.6 months 83% ORR in papillary thyroid cancer3 Additional clinical responses observed in pancreatic cancer and intrahepatic bile duct carcinoma Data presented at ASCO Annual Meeting in June 2019. Includes MTC patients treated at the recommended Phase 2 dose of 400 mg QD and enrolled as of November 14, 2018 with follow-up through a data cutoff date of April 28, 2019. All responses were investigator assessed. 1 Two responses pending confirmation. 3 Six patients were evaluable for 31 response assessment (3 confirmed PRs, 2 PRs pending confirmation). Cabo, cabozantinib; Vand, vandetininb. Not for promotional use. Prior Cabo or Vand

A powerful scientific platform with a focused research strategy Difficult-to-drug Kinase targets that are difficult to drug with existing technologies Treatment-resistant Kinase targets characterized by alterations promoting resistance to existing therapies Novel biology New kinase targets identified via computational and cell biology Nominated potential first-in-class development candidate for resistant EGFR+ triple mutant NSCLC Plan to nominate up to 2 additional development candidates in 2020 32 Not for promotional use.

EAR LY-ST AG E D EVELO PMEN T LAT E-ST AG E D EVELO PMEN T R EG U LAT O R Y SU BMISS IO N D ISC O VER Y APPR O VED Avapritinib (KIT & PDGFRA) PDGFRA GIST1,2, 3 4L GIST1,2 3L GIST1,2 2L GIST1,2 Advanced SM2 Indolent SM2 U.S. Pralsetinib, formerly BLU-667 (RET) 2L RET+ NSCLC1,2 1L RET+ NSCLC1,2 EGFR+ NSCLC (+osimertinib)1,2 2L MTC1,2 Other RET-altered solid tumors1,2 Fisogatinib, formerly BLU-554 (FGFR4) Advanced HCC2 Advanced HCC (+CS-1001)2 BLU-263 (KIT) Indolent SM (EGFR+ C797S double mutant) EGFR+ NSCLC1 1. Unresectable or metastatic disease. 2. CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritini b, pralsetinib and fisogatinib in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains all rights in the rest of the world. 3. Approved in the U.S. for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The proposed MAA indication is unresectable or metastatic GIST harboring a PDGFRA D842V mutation. 4. Expect to complete rolling NDA in Q1 202 0. 5. In collaboration with Roche. Blueprint Medicines has U.S. commercial rights for up to two programs. Roche has worldwide commercialization rights for up to two programs and ex-U.S. commercialization rights for up to two programs. 1L, first-line; HCC, hepatocellular carcinoma. 33 Not for promotional use. (3 undisclosed immunokinase targets)5 (MAP4K1)5 (EGFR+ T790M/C797S triple mutant)EGFR+ NSCLC1 o ng o ing o r c o mp le te d p lanne d (2 undisclosed targets) NDA4 / MAA NDA MAA NDA NDA NDA

Strong financial position entering 2020 Based on current operating plans, expect existing cash balance will fund operations into 2H 2021** * Unaudited ** Includes $25.0 million upfront cash payment from Clementia and $8.0 million research milestone achieved in the fourth quarter of 2019 under the Roche collaboration but excludes any additional potential option fees, milestone payments or other payments from Roche, CStone or Clementia. 34 Three Months Ended September 30, 2019* 2018* $9.1M $1.1M $81.5M $64.6M $25.6M $12.0M $(94.3)M $(72.7)M Statement of Operations Collaboration Revenue Research & Development Expenses General & Administrative Expenses Net Loss September 30, 2019* December 31, 2018 $594.5M $494.0M Balance Sheet Cash, Cash Equivalents and Investments

Anticipated 2020 milestones R E G U L AT O RY AP P R O VAL S Avapritinib in fourth-line GIST in the U.S. in Q2 2020 Avapritinib in PDGFRA D842V GIST in the EU in Q3 2020 Pralsetinib in RET+ NSCLC in the U.S. by the end of 2020 ME D IC AL ME E T IN G P R E S E N TAT IO N S Avapritinib PIONEER trial Part 1 in ISM in Q1 2020 Pralsetinib ARROW trial in RET+ NSCLC in 2020 Pralsetinib ARROW trial in RET+ MTC in 2020 Avapritinib VOYAGER trial in 3L GIST in 2020 Avapritinib EXPLORER and PATHFINDER trials in advSM in 2H 2020 R E G U L AT O RY S U B MIS S IO N S Pralsetinib NDA to FDA for RET+ NSCLC in Q1 2020 Pralsetinib NDA to FDA for 2L RET+ MTC in Q2 2020 Avapritinib sNDA to FDA for advSM in 2H 2020 Avapritinib sNDA to FDA for 3L GIST in 2H 2020 Pralsetinib MAA to EMA for RET+ NSCLC in Q2 2020 C O MP L E T E T R IAL E N R O L L ME N T Avapritinib PIONEER trial Part 2 in ISM by the end of 2020 T R IAL IN IT IAT IO N S BLU-263 Phase 1 trial in healthy volunteers in 1H 2020 Pralsetinib Phase 3 trial in 1L MTC in 2H 2020 T O P - L IN E R E G IS T R AT IO N D ATA Avapritinib VOYAGER trial in 3L GIST in Q2 2020 R E S E AR C H P IP E L IN E Nominate up to 3 development candidates in 2020 advSM, advanced systemic mastocytosis; sNDA, supplemental new drug application. 35 Not for promotional use.

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In January 2020, announced the U.S. Food and Drug Administration (FDA) granted a full approval to AYVAKIT for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. Read the press release here and visit www.AYVAKIT.com for full Prescribing Information.

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Report top-line data from the Phase 3 VOYAGER trial of avapritinib in third-line GIST in the second quarter of 2020

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Gain regulatory approval and launch avapritinib in fourth-line GIST in the U.S. in the second quarter of 2020

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Gain regulatory approval and launch avapritinib in PDGFRA D842V GIST in Europe in the third quarter of 2020

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Present the registration dataset from the VOYAGER trial of avapritinib in third-line GIST in 2020

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Submit a  supplemental new drug application (NDA) to the FDA for third-line GIST in the second half of 2020

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Today announced an update on the planned submission of a supplemental NDA to the FDA for avapritinib for advanced SM. Based on ongoing discussions with the FDA,  the company plans to focus its supplemental

NDA on data from patients in the Phase 1 EXPLORER and Phase 2 PATHFINDER trials who started at the proposed indicated dose of 200 mg once daily (QD), supported by pooled data from all doses. To allow for a sufficient number of patients and follow-up, Blueprint Medicines now plans to submit the supplemental NDA to the FDA in the second half of 2020.

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In December 2019, reported initial data from Part 1 of the PIONEER trial of avapritinib in patients with indolent SM. The data showed rapid and robust reductions in serum tryptase, a measure of mast cell burden, in patients treated with 25, 50 or 100 mg QD of avapritinib. All dose levels of avapritinib tested were well-tolerated, and no patients discontinued treatment due to an adverse event (AE). Read the press release here.

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Today announced updated data from Part 1 of the PIONEER trial have been accepted for presentation as a late-breaking oral abstract at the American Academy of Allergy, Asthma & Immunology 2020 Annual Meeting in Philadelphia on March 14, 2020.

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Present updated data from Part 1 of the PIONEER trial of avapritinib in indolent SM in the first quarter of 2020

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Initiate a Phase 1 trial of BLU-263 in healthy volunteers in the first half of 2020

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Submit a supplemental NDA to FDA for avapritinib for advanced SM in the second half of 2020

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Present updated data from the EXPLORER and PATHFINDER trials of avapritinib in advanced SM in the second half of 2020

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Complete enrollment of Part 2 of the PIONEER trial of avapritinib in indolent SM by the end of 2020

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In January 2020, reported top-line data from the Phase 1/2 ARROW trial of pralsetinib in RET fusion-positive non-small cell lung cancer (NSCLC) as of a data cutoff date of November 18, 2019 in patients treated with the proposed indicated dose of 400 mg QD. In patients with previously treated RET fusion-positive NSCLC, the overall response rate (ORR) was 61 percent (95% CI: 50-72%) per central review (two responses pending confirmation), and the median duration of response was not reached. In patients with treatment-naïve RET fusion-positive NSCLC, the ORR was 73 percent (95% CI: 52-88%) per central review (all responses confirmed), with 12 percent of patients achieving a complete response. Pralsetinib was well-tolerated, and most reported AEs were Grade 1 or 2 with only four percent of patients discontinuing treatment with pralsetinib due to treatment-related AEs. In addition, the company announced it had initiated a rolling NDA submission to the FDA for pralsetinib for the treatment of RET fusion-positive NSCLC. Read the press release here.

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Today announced the activation of the first trial site for the company’s Phase 3 AcceleRET Lung trial of pralsetinib in patients with first-line RET fusion-positive NSCLC. More information about the trial is available at www.clinicaltrials.gov (NCT04222972).

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Complete the submission of a rolling NDA to the FDA for pralsetinib for RET fusion-positive NSCLC in the first quarter of 2020

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Submit an NDA to the FDA for pralsetinib for previously treated RET-mutant medullary thyroid cancer  (MTC) in the second quarter of 2020

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Submit an MAA to EMA for pralsetinib for RET fusion-positive NSCLC in the second quarter of 2020

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Present registration datasets from the Phase 1/2 ARROW trial of pralsetinib in RET fusion-positive NSCLC and RET-mutant MTC in 2020

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Initiate a  Phase 3 trial of pralsetinib in first-line RET-mutant MTC in the second half of 2020

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Gain regulatory approval and launch pralsetinib in RET fusion-positive NSCLC in the U.S. by the end of 2020

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In November 2019, at Blueprint Medicines’ first R&D Day, announced four new research programs enabled by the company’s integrated precision medicine platform. Read the press release here.

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Today announced the nomination of a potential first-in-class development candidate for the treatment of resistant EGFR-positive triple mutant NSCLC.

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Nominate up to two additional development candidates by the end of 2020