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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) 

of the Securities Exchange Act of 1934

 

Date of Report (Date of Earliest Event Reported): September 22, 2020

Blueprint Medicines Corporation

(Exact name of registrant as specified in its charter)

Delaware

 

001-37359

 

26-3632015

(State or other jurisdiction

of incorporation)

 

(Commission File Number)

 

(I.R.S. Employer
Identification No.)

 45 Sidney Street

Cambridge, Massachusetts

 

02139

(Address of principal executive offices)

 

(Zip Code)

 Registrant’s telephone number, including area code: (617) 374-7580

 

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Securities registered pursuant to Section 12(b) of the Exchange Act:

Title of each class

Trading symbol(s)

Name of each exchange on which registered

Common stock, par value $0.001 per share

BPMC

Nasdaq Global Select Market

Item 7.01 Regulation FD Disclosure.

On September 22, 2020, Blueprint Medicines Corporation (the “Company”) is hosting an investor conference call and webcast to report top-line data from its Phase 1 EXPLORER and Phase 2 PATHFINDER clinical trials of AYVAKIT™ (avapritinib) in patients with advanced systemic mastocytosis. A copy of the presentation from the investor conference call and webcast is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

The information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01 Other Events. 

On September 22, 2020, the Company issued a press release announcing top-line data from its Phase 1 EXPLORER and Phase 2 PATHFINDER clinical trials of AYVAKIT in patients with advanced systemic mastocytosis. A copy of the press release is filed herewith as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No.

Description

99.1

Corporate slide presentation of Blueprint Medicines Corporation dated September 22, 2020

99.2

Press release issued by Blueprint Medicines Corporation on September 22, 2020

104

Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101)

2

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

 

 

 

BLUEPRINT MEDICINES CORPORATION

 

 

 

 

 Date: September 22, 2020

By:

/s/ Jeffrey W. Albers

 

 

Jeffrey W. Albers

 

 

Chief Executive Officer

3

Exhibit 99.1

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© 2020 Blueprint Medicines Corporation R.S., living with systemic mastocytosis Topline data for EXPLORER and PATHFINDER clinical trials in advanced systemic mastocytosis SEPTEMBER 22, 2020

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Forward-looking statements 2 This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions 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 limitation, statements regarding plans, timelines and expectations for interactions with the U.S. Food and Drug Administration (“FDA”) and other regulatory authorities; plans and timelines for submitting an supplemental New Drug Application to the FDA for AYVAKIT™ (avapritinib) for the treatment of advanced systemic mastocytosis (“SM”); expectations regarding the potential benefits of AYVAKIT in treating patients with SM; and the strategy, goals and anticipated milestones, business plans and focus of Blueprint Medicines Corporation (the “Company”). The Company has based these forward-looking statements on management’s current expectations, assumptions, estimates and projections. While the Company believes these expectations, assumptions, estimates and projections 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 the Company’s control and may cause actual results, performance or achievements to differ materially from those expressed or implied by any forward-looking statements. These risks and uncertainties include, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic to the Company’s’ business, operations, strategy, goals and anticipated milestones, including the Company’s ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; the Company’s ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT and GAVRETO™ (pralsetinib); the Company’s ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO in additional geographies in the future; the delay of any current or planned clinical trials or the development of the Company’s current or future drug candidates; the Company’s advancement of multiple early-stage efforts; the Company’s ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for the Company’s drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; 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 or licensing arrangements, including the Company’s global collaboration with Roche for the development and commercialization of GAVRETO. These and other risks and uncertainties are described in greater detail under “Risk Factors” in the Company’s filings with the Securities and Exchange Commission (“SEC”), including its most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings it has made or may make with the SEC in the future. The Company cannot guarantee future results, outcomes, levels of activity, performance, developments, or achievements, and there can be no assurance that its expectations, intentions, anticipations, beliefs, or projections will result or be achieved or accomplished. The forward-looking statements in this presentation are made only as of the date hereof, and except as required by law, the Company undertakes no obligation to update any forward-looking statements contained in this presentation as a result of new information, future events or otherwise. This presentation also contains estimates, projections and other statistical data made by independent parties and by the Company relating to market size and growth and other data about the Company’s industry. These 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 the Company’s future performance and the future performance of the markets in which the Company operates are necessarily subject to a high degree of uncertainty and risk.

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Blueprint Medicines call participants Introduction Kristin Hodous, Sr. Manager, Investor Relations Opening remarks Jeff Albers, Chief Executive Officer Review of topline EXPLORER and PATHFINDER data Andy Boral, MD, PhD, Chief Medical Officer Opportunity to deliver therapeutic value to patients with SM Christy Rossi, Chief Commercial Officer Q&A All 3

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Top-line advanced SM data adds to increasing portfolio strength 1. Full prescribing information is available at www.GAVRETO.com. advSM, advanced systemic mastocytosis; ESMO, European Society of Medical Oncology; FDA, U.S. Food and Drug Administration; GIST, gastrointestinal stromal tumors; ISM, indolent system mastocytosis; NDA, new drug application; NSCLC, non-small cell lung cancer; SM, systemic mastocytosis; sNDA, supplemental NDA. 4 STRENGTHEN PIPELINE WITH NEW PROGRAMS ADVANCE REGISTRATION PROGRAMS FOR SM ✓Report Part 1 PIONEER data in ISM and select recommended Part 2 dose ✓Initiate registration-enabling Part 2 of PIONEER trial of avapritinib in ISM ✓Report top-line data for avapritinib in advSM • Submit sNDA to FDA for avapritinib for advSM in Q4 2020 ✓Present preclinical data for BLU-945 at ESMO 2020 Congress • Nominate up to two additional development candidates in Q4 2020 • Complete Phase 1 healthy volunteer trial of BLU-263 in Q4 2020 Not for promotional use. NOW APPROVED For adults with RET fusion-positive metastatic NSCLC1 BUILD COMMERCIAL MOMENTUM ✓Enter global collaboration with Roche to develop and commercialize GAVRETO ✓Obtain U.S. approval of GAVRETO for RET+ NSCLC • Obtain EU approval for avapritinib for PDGFRA D842V GIST in Q3 2020 • Obtain U.S. approval of GAVRETO for RET+ thyroid cancers in Q1 2021

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Top-line EXPLORER and PATHFINDER data Andy Boral, MD, PhD, Chief Medical Officer

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Driven by KIT D816V, systemic mastocytosis is characterized by severely debilitating symptoms and organ damage Mild symptoms Non-Advanced SM Severe symptoms Indolent SM (ISM) • Some progression to advanced disease (4%)2 • Long-term morbidity, including life- threatening anaphylaxis, frequent GI upset, and debilitating fatigue3 Smoldering SM (SSM) • Increased organ infiltration1,4 • Increased progression to advanced disease (9%)2 AML, acute myeloid leukemia; ASM, aggressive systemic mastocytosis; GI, gastrointestinal; MCL, mast cell leukemia; SM-AHN, systemic mastocytosis with associated hematologic neoplasm. 1. Pardanani A. Am J Hematol. 2016;91(11):1146-1159. 2. Sperr WR et al. Lancet Haematol. 2019;6(12):e638-e649. 3. Jennings SV et al. Immunol Allergy Clin North Am. 2018;38(3):505-525. 4. Swerdlow SH et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Lyon, France: International Agency for Research on Cancer; 2017. 5. Shomali W, Gotlib J. Hematology Am Soc Hematol Educ Program. 2018;2018(1):127-136. 6. Desmond DH, Carmichael MG. Hawaii J Med Public Health. 2018;77(2):27-29. Minimal organ damage4 Advanced SM (ASM, SM-AHN, MCL) • Extensive organ infiltration and damage1 • Historical overall survival (OS) <6 mo to <5 years1,5,6 Organ damage4 6 Not for promotional use.

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Comprehensive development program designed to support avapritinib registration in advanced systemic mastocytosis 7 mIWG, modified International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) response criteria. QD, once daily. Not for promotional use. AdvSM Open-label N= ~80 AdvSM Open-label N= ~100 30-400 mg QD 300 mg QD 200 mg QD 200 mg QD DOSE ESCALATION EXPANSION PHASE 1 TRIAL PHASE 2 TRIAL PRIMARY ENDPOINT FOR APPROVAL: OVERALL RESPONSE RATE PER mIWG

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Planned avapritinib sNDA submission for advanced SM to include pooled data from the EXPLORER and PATHFINDER trials All topline data in this presentation are as of a data cutoff of May 27, 2020 for EXPLORER and a data cutoff of June 23, 2020 for PATHFINDER, with response assessments per central review completed in September 2020. 8 Enrolled 86 patients 62 patients 200 mg QD mIWG evaluable 13 patients 31 patients All doses mIWG evaluable 53 patients 32 patients Prior midostaurin 32% 53% 81 patients 44 patients 2 0 0 M G Q D POOLED GROUP Not for promotional use.

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Consistently high ORRs and prolonged duration of response across trials CR, complete remission; CRh, CR with partial hematologic recovery; CI, clinical improvement; mDOR, median duration of response; mOS, median overall survival; NE, not estimable; ORR, overall response rate; PR, partial remission. 9 ORR (CR+CRh+PR+CI) 75.5% (61.7- 86.2) 75.0 (56.6 – 88.5) CR+CRh 35.8% 18.8% mDOR (months) 38.3 (21.7 - NE) NE (NE - NE) mOS (months) NE (46.9 - NE) NE 68.2% 18.2% PATHFINDER interim analysis was positive (p-value=0.0000000016) Not for promotional use. Median follow up: 27.3 months Median follow up: 10.4 months Median follow up: 10.4 months 2 0 0 M G Q D POOLED GROUP

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EXPLORER and PATHFINDER response kinetics are similar, with deepening responses over time with longer-term follow up PD, progressive disease; SD, stable disease. 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 0 10 20 30 40 50 60 70 80 90 100 P a t i e n t s ( % ) NE PD SD CI PR CRh CR 32 n = Cycle 31 30 28 28 27 27 23 22 16 14 13 9 8 7 7 6 5 3 2 MEDIAN FOLLOW UP: 27.3 MONTHS MEDIAN FOLLOW UP: 10.4 MONTHS 1 53 5 52 10 39 15 33 20 28 25 21 30 16 35 10 40 6 45 3 50 2 54 1 Cycle Patients 1 32 5 28 10 16 15 7 20 2 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% Patients (%) CR/CRh PR CI SD PD NE Not for promotional use.

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Consistent impact on objective measures of mast cell burden across trials 11 -100 -80 -60 -40 -20 0 20 M a x i m u m P e r c e n t C h a n g e f r o m B a s e l i n e BLU-285-2202 BLU-285-2101 Study SERUM TRYPTASE -100 -80 -60 -40 -20 0 20 40 60 M a x i m u m P e r c e n t C h a n g e f r o m B a s e l i n e BLU-285-2202 BLU-285-2101 Study BONE MARROW MAST CELLS -100 -80 -60 -40 -20 0 20 M a x i m u m P e r c e n t C h a n g e f r o m B a s e l i n e BLU-285-2202 BLU-285-2101 Study KIT D816V ALLELE FRACTION -100 -80 -60 -40 -20 0 20 40 60 80 M a x i m u m P e r c e n t C h a n g e f r o m B a s e l i n e BLU-285-2202 BLU-285-2101 Study SPLEEN VOLUME Explorer Pathfinder Not for promotional use.

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Avapritinib demonstrated improved tolerability at 200 mg QD 12 Treatment Emergent AEs ≥ 20%, All Grades* 200 mg n=81 (%) All doses N=148 (%) Peripheral Edema 39 ( 48.1) 65 ( 43.9) Periorbital Edema 32 ( 39.5) 81 ( 54.7) Thrombocytopenia 28 ( 34.6) 55 ( 37.2) Anemia 26 ( 32.1) 65 ( 43.9) Diarrhea 23 ( 28.4) 53 ( 35.8) Nausea 20 ( 24.7) 49 ( 33.1) Fatigue 15 ( 18.5) 44 ( 29.7) Vomiting 15 ( 18.5) 42 ( 28.4) • Overall, 8.1% of patients discontinued treatment due to treatment-related AEs • ICB risk mitigations implemented o Starting dose of 200 mg QD o Exclusion criteria for pre-existing severe thrombocytopenia o Increased platelet monitoring o Mandatory dose interruption for severe thrombocytopenia • ICB events in patients without pre-existing severe thrombocytopenia o Pooled 200 mg group (n=76): 2 (2.6%)† o PATHFINDER (n=57): 0‡ Cognitive effects 10 ( 12.3) 37 ( 25.0) ≥Grade 2 2 (2.5) 13 (8.8) Not for promotional use. † Both ICB events in EXPLORER patients were Grade 1 and asymptomatic. ‡ 1 ICB event occurred in a PATHFINDER patient with pre-existing severe thrombocytopenia prior to exclusion of such patients for 1/62 (1.6%) overall. AE, adverse event; ICB, intracranial bleed. * Most common AEs in patients treated at 200mg in EXPLORER and PATHFINDER

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Summary of top-line EXPLORER and PATHFINDER trial results 13 Consistently high IWG response rates across trials and at the proposed labeled 200 mg QD dose, with prolonged overall survival in EXPLORER Avapritinib was generally well-tolerated, with improved safety at 200 mg QD and with platelet management Detailed results expected to be presented at a future scientific congress Plan to submit sNDA to FDA for avapritinib for advanced SM in Q4 2020 1 2 3 4 Not for promotional use.

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Opportunity to deliver therapeutic value to patients with SM Christy Rossi, Chief Commercial Officer

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Systemic mastocytosis is one disease driven by KIT D816V 15 Advanced SM Non-advanced SM (Indolent and smoldering) Requirement for life-long chronic treatment Debilitating symptoms Significant organ damage Importance of time to response ~75,000 patients in major markets Patient numbers in major markets based on estimated prevalence for advanced, indolent and smoldering systemic mastocytosis in the US, EU5 and Japan. Not for promotional use.

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Significant initial target patient population with additional growth potential Major markets include US, EU5 and Japan. 1. Cohen S et al Br J Haematol (2014) 166(4):521-8 and World Bank Population estimates. 16 ~75,000 Patients in major markets ~1/3 Diagnosed Initial opportunity Growth opportunity Estimated addressable patients (extrapolated from U.S. claims data and market research analyses) Not for promotional use. Estimated prevalence1 • ~5% advanced SM • ~95% non-advanced SM ~1/3 Cutaneous SM ~1/3 Undiagnosed Non-advanced

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Avapritinib is the only clinically validated, highly potent inhibitor of KIT D816V, the genetic driver of SM 1. Topline EXPLORER and PATHFINDER data reported in September 2020. 2. Data reported at AAAAI Annual Meeting in March 2020. Data cutoff: December 27, 2019. 17 REDUCE MAST CELL BURDEN IMPROVE DISEASE SYMPTOMS INDUCE DEEP AND DURABLE RESPONSES -100 -80 -60 -40 -20 0 20 M a x i m u m P e r c e n t C h a n g e f r o m B a s e l i n e BLU-285-2202 BLU-285-2101 Study -5 0 -4 0 -3 0 -2 0 -1 0 0 1 0 W e e k s I S M - S A F T o t a l S y m p t o m S c o r e m e a n % c h a n g e f r o m b a s e l i n e 0 4 8 12 16 a v a p ritin ib 2 5 m g (n = 1 0 ) p la c e b o (n = 9 ) NON-ADVANCED SM2 ADVANCED SM1 Safety profile enables tailored dosing based on patient need Not for promotional use. ADVANCED SM1 NON-ADVANCED SM2

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Thank you Blueprint Medicines, AYVAKIT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.

Exhibit 99.2

Blueprint Medicines Announces Positive Top-line Results from EXPLORER and PATHFINDER Trials

of AYVAKIT™ (avapritinib) in Patients with Advanced Systemic Mastocytosis

-- 76% confirmed ORR in EXPLORER, with a median duration of response of 38.3 months --

-- 75% confirmed ORR in PATHFINDER, with a median duration of response not reached --

-- AYVAKIT safety profile reinforced at 200 mg QD dose in advanced SM --

-- Plan to submit supplemental new drug application to FDA for advanced SM in fourth quarter of 2020 --

-- Blueprint Medicines to host investor conference call today at 8:30 a.m. ET --

CAMBRIDGE, Mass., September 22, 2020 – Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced positive top-line results from the Phase 1 EXPLORER and Phase 2 PATHFINDER clinical trials of AYVAKIT™ (avapritinib) in patients with advanced systemic mastocytosis (SM). Consistent with previously reported EXPLORER trial results, the registrational data for AYVAKIT showed profound reductions in mast cell burden, high overall response and complete remission rates, and durable clinical benefit, including prolonged median overall survival (OS). AYVAKIT was generally well-tolerated, with an improved safety profile at the 200 mg once daily (QD) dose. Based on these data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT for the treatment of advanced SM in the fourth quarter of 2020.

SM is a rare, debilitating disease driven by the KIT D816V mutation in nearly all patients. Uncontrolled mast cell proliferation and activation may lead to life-threatening complications across the SM patient population. In advanced SM subtypes, the median OS is approximately 3.5 years in aggressive SM (ASM), approximately two years in SM with an associated hematologic neoplasm (SM-AHN) and less than six months in mast cell leukemia (MCL). AYVAKIT, an investigational precision therapy for the treatment of SM, is the only highly potent KIT D816V inhibitor that has been clinically validated in SM.

“New treatment options are urgently needed to address mast cell infiltration associated with advanced systemic mastocytosis, which often leads to extensive organ damage and poor survival despite existing therapeutic interventions,” said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. “These top-line data underscore the transformative impact shown by AYVAKIT, with patients achieving profound reductions in mast cell burden, durable responses that deepen over time and prolonged overall survival relative to historical outcomes. Based on these positive results, we aim to rapidly bring this promising treatment to patients, with the goal of improving and extending their lives beyond what is possible with currently available therapy.”

Top-line EXPLORER and PATHFINDER Trial Data

Across both trials, 85 patients were evaluable for response per the modified IWG-MRT-ECNM criteria (IWG criteria), including 44 patients treated with a starting dose of 200 mg QD. Top-line results are being reported as of a data cutoff date of May 27, 2020 in the EXPLORER trial and a data cutoff date of June 23, 2020 in the PATHFINDER trial,

with response assessments per central review completed in September 2020. Registrational endpoints are overall response rate (ORR) and duration of response (DOR), based on central review. ORR was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. All reported clinical responses were confirmed.

In the EXPLORER trial, 53 patients were response evaluable, with a median follow-up of 27.3 months. In EXPLORER, the ORR was 76 percent (95% CI: 62%, 86%), and 36 percent of patients had a CR/CRh. The median DOR was 38.3 months (95% CI: 21.7 months, not estimable). The median OS was not estimable (95% CI: 46.9 months, not estimable).

In a pre-specified interim analysis from the PATHFINDER trial, 32 patients were response evaluable, with a median follow-up of 10.4 months. The ORR was 75 percent (95% CI: 57%, 89%), and 19 percent of patients had a CR/CRh. In addition, the data showed that responses are continuing to deepen over time, at a rate consistent with the


EXPLORER trial. The median DOR was not estimable (95% CI: not estimable, not estimable), and OS was not assessed due to the length of time patients have been enrolled in PATHFINDER. The top-line PATHFINDER results were based on a pre-planned analysis designed to assess the superiority of AYVAKIT versus the ORR per IWG criteria previously reported for the multi-kinase inhibitor midostaurin. The interim analysis achieved its primary endpoint with a p-value of p=0.0000000016.

In a pooled efficacy analysis from the 200 mg QD dose group, 44 patients were response evaluable, with a median follow-up of 10.4 months. In this group, the ORR was 68 percent, and 18 percent of patients had a CR/CRh.

Safety data were consistent with previously reported results, and no new signals were observed. AYVAKIT was generally well-tolerated with most adverse events (AEs) reported as Grade 1 or 2. In the EXPLORER and PATHFINDER trials, AYVAKIT demonstrated improved tolerability at a starting dose of 200 mg QD, compared to all doses. Across both trials, 8.1 percent of patients discontinued AYVAKIT due to treatment-related AEs.

Previously reported results from the EXPLORER trial showed that pre-existing severe thrombocytopenia, which occurs in approximately 10 to 15 percent of advanced SM patients based on Blueprint Medicines estimates, and starting doses of 300 mg QD or higher were risk factors for intracranial bleeding (ICB). Based on these data, Blueprint Medicines implemented treatment management guidelines in the EXPLORER and PATHFINDER trials, including exclusion criteria for pre-existing severe thrombocytopenia, routine platelet monitoring and dose interruption guidelines for emergent severe thrombocytopenia. In 76 EXPLORER and PATHFINDER trial patients without pre-existing severe thrombocytopenia treated at the 200 mg QD dose, two patients (2.6 percent) had ICB events. Both AEs were Grade 1 and asymptomatic. These safety data validate the clinical impact of the treatment management guidelines.

Blueprint Medicines plans to present detailed results from the EXPLORER and PATHFINDER trials at a future medical meeting.

Conference Call Information

Blueprint Medicines will host a live webcast today beginning at 8:30 a.m. ET to discuss the top-line results of AYVAKIT in advanced SM. To access the live call, please dial (855) 728-4793 (domestic) or (503) 343-6666 (international) and refer to conference ID 5338896. A webcast of the conference call will be available under “Events and Presentations” in the Investors & Media section of Blueprint Medicines’ website at http://ir.blueprintmedicines.com. The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.

About SM

SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor OS.

Debilitating symptoms associated with SM, including anaphylaxis, maculopapular rash, pruritis, brain fog, fatigue and bone pain, often persist despite treatment with a number of symptomatic therapies. Patients often live in fear of attacks, have limited ability to work or perform daily activities, or isolate themselves to protect against unpredictable triggers.

Currently, there are no approved therapies that selectively inhibit D816V mutant KIT. A multi-kinase inhibitor, midostaurin, is approved for the treatment of advanced SM and has shown an ORR of 28 percent per IWG criteria, with ORR defined as complete remission, partial remission or clinical improvement.


About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit www.AYVAKIT.com.

AYVAKIT is not approved for the treatment of any other indication, including SM, in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and indolent SM. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of ASM, SM-AHN and MCL.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

About the Clinical Development Program for AYVAKIT in Advanced SM

AYVAKIT is currently being evaluated in two ongoing, registrational clinical trials for advanced SM: the EXPLORER trial (ClinicalTrials.gov Identifier: NCT02561988) and the PATHFINDER trial (ClinicalTrials.gov Identifier: NCT03580655).

The EXPLORER trial is an open-label, single-arm trial designed to identify the recommended Phase 2 dose and demonstrate proof-of-concept in patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. The EXPLORER trial has completed patient enrollment.

The PATHFINDER trial is an open-label, single-arm registration-enabling trial designed to confirm the clinical activity of AYVAKIT in patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. Patient enrollment is ongoing in the PATHFINDER trial.

Patients and physicians interested in SM clinical trials can contact the Blueprint Medicines study director at medinfo@blueprintmedicines.com or 1-888-BLU-PRNT (1-888-258-7768) in the U.S., or medinfoeurope@blueprintmedicines.com or +31 85 064 4001 in Europe. Additional information is available at www.BlueprintClinicalTrials.com and www.clinicaltrials.gov.

About Blueprint Medicines

Blueprint Medicines is a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We have two FDA-approved precision therapies and are currently advancing multiple investigational medicines in clinical development, along with a number of research programs. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, timelines and expectations for interactions with the FDA and other regulatory authorities; plans and timelines for submitting an


sNDA to the FDA for AYVAKIT for the treatment of advanced SM; expectations regarding the potential benefits of AYVAKIT in treating patients with SM; and Blueprint Medicines’ strategy, goals and anticipated milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic to Blueprint Medicines’ business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines’ ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines’ ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT and GAVRETO™ (pralsetinib); Blueprint Medicines’ ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO in additional geographies in the future; the delay of any current or planned clinical trials or the development of Blueprint Medicines’ current or future drug candidates; Blueprint Medicines’ advancement of multiple early-stage efforts; Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy 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 candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; 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 or licensing arrangements, including Blueprint Medicines’ global collaboration with Roche for the development and commercialization of GAVRETO. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Blueprint Medicines’ filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines’ most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.

Trademarks

Blueprint Medicines, AYVAKIT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.

Investor Relations Contact

Kristin Hodous

617-714-6674

ir@blueprintmedicines.com

Media Relations Contact

Andrew Law

617-844-8205

media@blueprintmedicines.com