bpmc_8K (corporate presentation) (January 2019)

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): January 7, 2019

 


 

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:

 

o

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

o

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

o

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

o

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. ☐

 

 


 

Item 7.01Regulation FD Disclosure.

 

Blueprint Medicines Corporation (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. The Company is posting to the “Investors” portion of its website at http://ir.blueprintmedicines.com/ a copy of its current corporate slide presentation. These slides are attached to this Current Report on Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.

 

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 9.01Financial Statements and Exhibits.

 

(d) Exhibits.

 

Exhibit No.

    

Description

99.1

 

Corporate slide presentation of Blueprint Medicines Corporation dated January 7, 2019

 

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: January 7, 2019

By:

/s/ Tracey L. McCain

 

 

Tracey L. McCain

 

 

Chief Legal Officer

 

 

3


bpmc_Ex99_1

Exhibit 99.1

 

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2020 Blueprint global business strategy January 7, 2019

 

 


 

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Forward-looking statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words “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 about plans and timelines for the development of avapritinib, BLU-554, BLU-667 and BLU-782 and the ability of Blueprint Medicines Corporation (the “Company”) to implement those development plans; the potential benefits of Blueprint Medicines’ current and future drug candidates in treating patients; Blueprint Medicines’ “2020 Blueprint” strategy, key goals and anticipated milestones through 2020; plans and timelines for marketed products and marketing applications in the United States and Europe, therapeutic candidates in clinical development and research programs; expectations regarding the Company’s existing cash, cash equivalents and investments and the future financial performance of the Company; and the Company’s strategy, business plans and focus. 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 delay of any current or planned clinical trials or the development of the Company's drug candidates, including avapritinib, BLU-554, BLU-667 and BLU-782; the Company's advancement of multiple early-stage efforts; the Company's ability to successfully demonstrate the efficacy and safety of its drug candidates; the preclinical and clinical results for the Company's drug candidates, 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; the Company’s ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing; the Company's ability to develop and commercialize companion diagnostic tests for its current and future drug candidates, including companion diagnostic tests for BLU-554 for FGFR4-driven hepatocellular carcinoma, avapritinib for PDGFRα D842V-driven GIST and BLU-667 for RET-driven non-small cell lung cancer (“NSCLC”); and the success of the Company’s current and future collaborations, including its cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. and its collaboration with CStone Pharmaceuticals. These and other risks and uncertainties are described in greater detail under “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, as filed with the Securities and Exchange Commission (“SEC”) on October 31, 2018, and any other filings the Company 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 the Company’s 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. 2

 

 


 

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Precision therapies for people with cancer and rare diseases 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 A new way of looking at kinase medicines With a focus on core areas of expertise GENOMICALLY DEFINED CANCERS CANCER IMMUNOTHERAPY SELECTIVE NON-SELECTIVE avapritinib Rydapt® (midostaurin) RARE DISEASES

 

 


 

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The promise of precision therapy throughout the development cycle HCP, healthcare professional 4 Rational drug design selectively targets genetic drivers of disease Efficient clinical development with small trials and focused investment Demonstrable value to patients, HCPs, payers and healthcare systems Dramatically improved outcomes in selected patients, even in early trials

 

 


 

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Our vision for a sustainable precision therapy company 5 Robust scientific platform reproducibly designing potent and selective kinase medicines Disciplined portfolio management focusing on therapeutic area leadership and novel targets Effective and nimble commercial organization delivering medicines to patients globally Rapid, reproducible product development Reinvestment of revenue to sustain constant innovation cycle

 

 


 

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Our “2020 Blueprint” strategy to make this vision a reality 6 2 marketed products in the US 4 pending marketing applications in the US and EU 6 therapeutic candidates in global clinical development 8 research programs Global commercial footprint, with 2 marketed products in the US and 1 marketed product in the EU ANTICIPATED ACHIEVEMENTS BY YEAR-END 2020

 

 


 

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7 registration-enabling trials to build on first potential avapritinib approval 2L, second-line; 3L, third-line; 4L, fourth-line; GIST, gastrointestinal stromal tumors; MTC, medullary thyroid cancer; NSCLC, non-small cell lung cancer; SM, systemic mastocytosis. 7 Program Trial NAME Target indications ONGOING Avapritinib NAVIGATOR PDGFRA Exon 18 mutant / 4L GIST PDGFRA Exon 18 mutant GIST and 4L GIST VOYAGER 3L GIST 3L GIST PATHFINDER Advanced SM Advanced systemic mastocytosis PIONEER Indolent and smoldering SM Indolent systemic mastocytosis BLU-667 ARROW 2L RET-fusion NSCLC / 2L RET-mutant MTC 2L RET-fusion NSCLC and 2L RET-mutant MTC PLANNED INITIATION IN 2H 2019 Avapritinib COMPASS-2L 2L GIST BLU-667 --- 1L RET-fusion NSCLC

 

 


 

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Research areas of focus leverage robust scientific platform, clinical expertise and planned commercial profile 8 Leadership in therapeutic areas of focus Cancer immunotherapy under Roche collaboration Novel genetic drivers Plan to disclose up to 2 new targets at R&D day in 2019 Systemic mastocytosis Lung cancer GIST

 

 


 

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DRUG CANDIDATE (TARGET) DISCOVERY EARLY CLINICAL DEVELOPMENT LATE CLINICAL DEVELOPMENT REGULATORY SUBMISSION APPROVED COMMERCIAL RIGHTS Avapritinib (KIT & PDGFRA) BLU-667 (RET) BLU-554 (FGFR4) BLU-782 (ALK2) 4 undisclosed targets Immunokinase targets Rapidly advancing pipeline of investigational precision therapies EGFR-m, EGFR mutant; FOP, fibrodysplasia ossificans progressiva; HCC, hepatocellular carcinoma. 1 Unresectable or metastatic disease. 2 Phase 1 trial in healthy volunteers. * CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritinib, BLU-554 and BLU-667 in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains all rights in the rest of the world. ** Blueprint Medicines has U.S. commercial rights for up to two programs. Roche has worldwide commercialization rights for up to three programs and ex-U.S. commercialization rights for up to two programs. 9 ** * PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST) 1 4L GIST 1 3L GIST 1 2L GIST 1 Advanced systemic mastocytosis (SM) 1 Indolent and smoldering SM 1 Hepatocellular carcinoma (HCC) 1 2L RET-fusion non-small cell lung cancer (NSCLC) 1 2L RET-mutant medullary thyroid cancer 1 1L RET-fusion NSCLC 1 – trial planned 2H 2019 Other RET-altered solid tumors 1 FOP 2 – trial planned Q1 2019 Up to 5 cancer immunotherapy programs; development stage undisclosed EGFR-mut NSCLC (+osimertinib)1 – trial planned 2H 2019 HCC (+CS-1001) 1 – trial planned 2H 2019 trial planned 2H 2019 NDA planned 1H 2019 NDA planned 1H 2019 NDA planned 2020 NDA planned 1H 2020 NDA planned 1H 2020 PDGFRA Exon 18 mutant GIST 1 4L GIST 1 3L GIST 1 2L GIST 1 Advanced SM Indolent and smoldering SM Advanced HCC 2L RET-fusion NSCLC 1 2L RET-mutant MTC 1 1L RET-fusion NSCLC 1 – trial planned 2H 2019 Other RET-altered solid tumors 1 EGFR-m NSCLC (+osimertinib) 1 – trial planned 2H 2019 Advanced HCC (+CS-1001) – trial planned 2H 2019 trial planned 2H 2019 NDA planned 1H 2019 NDA planned 1H 2019 NDA planned 2020 NDA planned 1H 2020 NDA planned 1H 2020 NDA planned 2020

 

 


 

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Avapritinib: an investigational precision therapy with broad commercial potential *CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritinib in Mainland China, Hong Kong, Macau and Taiwan. **Represents estimated number of patients with PDGFRA-driven GIST; 2L, 3L, 4L KIT-driven GIST; and advanced, smoldering and indolent SM in major markets (US, France, Germany, Italy, Spain, the United Kingdom and Japan). DOR, duration of response; NDA, new drug application; ORR, overall response rate. 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. 10 Avapritinib KIT and PDGFRA inhibitor Plan to submit NDA for PDGFRA Exon 18 mutant GIST and 4L GIST in 1H 2019 ORR and DOR per central radiology are primary endpoints for registration 5 ongoing or planned registration-enabling studies for avapritinib in multiple GIST and SM populations DEVELOPMENT STATUS POTENTIAL COMMERCIAL PROFILE Blueprint Medicines retains global commercial rights, excluding Greater China* ~30,000 patients across relevant GIST and SM populations in major markets** Scalable commercial footprint initially focused on driving patient identification and treatment through engagement with recognized centers of excellence

 

 


 

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Avapritinib is a potentially transformative selective KIT/PDGFRA inhibitor 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. All compounds were screened at 3 uM concentration against a panel of 392 wild type kinase constructs using the KINOMEscan assay platform at DiscoveRx Corporation. The size of the circle indicates binding potency. The bigger the circle, the more potently the compound binds to the particular kinase. 11 Precision therapies Multi-kinase therapies imatinib avapritinib sunitinib regorafenib DCC-2618 Approved Investigational midostaurin

 

 


 

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Beyond imatinib, there are no highly effective therapies for advanced GIST PFS, progression free survival. * Imatinib re-challenged. 12 1L 2L 3L 4L imatinib ORR ~60% PFS 19 months sunitinib ORR ~7% PFS 6 months regorafenib ORR ~5% PFS 4.8 months No approved therapy ORR ~0% PFS 1.8 months* - All approved agents are ineffective against PDGFRα D842V GIST - Genetic drivers PDGFRA D842V ~5-6% KIT ~80%

 

 


 

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Maximum reduction: sum of diameter change from baseline (%) High response and clinical benefit rates in PDGFRα D842V-mutant GIST 1 Data previously presented in November 2018 at the CTOS Annual Meeting. Data cutoff: October 15, 2018. 2 Top-line data will be used to support planned NDA submission in 1H 2019. Data cutoff: November 16, 2018. Median PFS not reached. * 4 PR pending confirmation. Patients who have had ≥1 post-baseline radiographic assessment. Response evaluable includes all doses. † PR + SD lasting ≥4 months. CBR, clinical benefit rate; CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; PD, progressive disease; PR, partial response; QD, once daily; SD, stable disease. 13 Best response, % (n) per central radiology mRECIST 1.1 ORR 84% (47) CR/PR* 9% (5) / 75% (42) SD 16% (9) CBR† 96% (54) TOP-LINE DATA2 PDGFRA Exon 18 mutant GIST (n=43; 300-400 mg) 86% ORR (1 response pending confirmation) Median DOR not reached Median DOR not reached 76.3% 12-month DOR rate CTOS 2018 Annual Meeting1

 

 


 

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~20% ORR in ≥4L KIT-driven GIST patients 1 Data previously presented in November 2018 at the CTOS Annual Meeting. Data cutoff: October 15, 2018. 2 Top-line data will be used to support planned NDA submission in 1H 2019. Data cutoff: November 16, 2018. Median PFS (central radiology) same as reported at CTOS 2018 Annual Meeting. Population included 8 (7%) patients harboring PDGFRα D842V mutation, consistent with expected real-world ≥4L GIST population. * 1 PR pending confirmation. Patients who have had ≥1 post-baseline radiographic assessment. Response evaluable includes 300 mg QD and 400 mg QD. † PR + SD lasting ≥4 months 14 TOP-LINE DATA2 ≥4L GIST (n=111; 300-400 mg) 7.2 months median DOR CTOS 2018 Annual Meeting1 22% ORR (1 response pending confirmation) 10.2 months median DOR Best response, % (n) per central radiology mRECIST 1.1 ORR 20% (22) CR/PR* 1% (1) / 19% (21) SD 46% (50) CBR† 40% (44)

 

 


 

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Avapritinib is well-tolerated in patients with GIST Treatment-Emergent Adverse Events (Safety Population; N = 231) Adverse event (AE), % (n) Any Grade Grade 1 Grade 2 Grade 3 Grade 4 Nausea 61% (142) 46% (106) 13% (30) 3% (6) 0 Fatigue 55% (127) 21% (48) 28% (64) 6% (15) 0 Anemia 46% (107) 5% (11) 15% (35) 25% (58) 1% (3) Periorbital edema 40% (93) 34% (79) 6% (13) <1% (1) 0 Diarrhea 39% (90) 22% (50) 13% (30) 4% (10) 0 Vomiting 38% (88) 30% (69) 6% (14) 2% (5) 0 Decreased appetite 35% (82) 23% (54) 9% (20) 3% (8) 0 Peripheral edema 33% (77) 23% (53) 10% (22) <1% (2) 0 Increased lacrimation 31% (72) 28% (64) 3% (8) 0 0 Memory impairment* 26% (60) 19% (45) 6% (15) 0 0 Constipation 23% (53) 14% (32) 8% (18) <1% (2) <1% (1) Face edema 23% (53) 19% (43) 4% (9) <1% (1) 0 Hair color changes 21% (49) 20% (46) <1% (2) <1% (1) 0 Dizziness 20% (47) 16% (38) 3% (8) <1% (1) 0 Most AEs were Grade 1 or 2 No treatment-related Grade 5 AEs 8.7% (20) of patients discontinued due to related AEs Grade 3-4 treatment-related AEs ≥2%: anemia, fatigue, hypophosphatemia, increased bilirubin, decreased white blood count/neutropenia, and diarrhea 1 Data previously presented in November 2018 at the CTOS Annual Meeting. Data cutoff: October 15, 2018. 2 Top-line data will be used to support planned NDA submission in 1H 2019. Data cutoff: November 16, 2018. * The most commonly reported cognitive AE. Top-line safety results consistent with data previously reported at CTOS 2018 Annual Meeting2 15 CTOS 2018 Annual Meeting1

 

 


 

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Preliminary 26% ORR for avapritinib1 versus 5% ORR for regorafenib2 Preliminary Phase 1 data in 3L/4L regorafenib-naïve GIST de-risk ongoing Phase 3 VOYAGER trial 1 Data previously presented in November 2018 at the CTOS Annual Meeting. Data cutoff: October 15, 2018. 2 Regorafenib data in FDA-approved product insert. R, randomized. 16 Anticipate completion of VOYAGER trial enrollment in 2H 2019 Primary endpoint: PFS 3L/4L GIST R, 1:1 avapritinib regorafenib Maimum reduction – sum of diameter change from baseline, % 50 0 -50 -100 PDGFR D842V patients, n=10, and ORR 80% are not included here PD SD PR CR KIT Other PDGFRA n = 23 patients 300/400 mg

 

 


 

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Preliminary Phase 1 data support design of Phase 3 COMPASS-2L trial in genotype-selected 2L GIST population ctDNA, circulating tumor DNA. 1 Data previously presented in November 2018 at the CTOS Annual Meeting. Data cutoff: October 15, 2018. ctDNA analysis in ≥4L population. 17 V654A and T670I negative V654A or T670I positive Increased avapritinib activity in KIT V654A/T670I negative patients (~75-80% of population)1 Phase 1 ctDNA analysis In 2L GIST, sunitinib has shown activity against KIT V654A and T670I mutations Primary endpoint: PFS Plan to initiate COMPASS-2L trial in 2H 2019 R 1:1 ctDNA selected KIT V654A/T670I negative patients avapritinib sunitinib

 

 


 

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SM with Associated Hematologic Neoplasm (SM-AHN) Aggressive SM (ASM) Mast Cell Leukemia (MCL) Advanced SM Spectrum Patient impact Indolent SM (ISM) Smoldering SM (SSM) ~90-95% of patients have KIT D816V mutation1 Avapritinib is the only highly selective KIT D816V inhibitor in development for systemic mastocytosis 18 Debilitating symptoms Increasing organ dysfunction and damage Decreased overall survival2 1 Garcia-Montero AC et al, 2006. 2 Based on published natural history data. Indolent SM

 

 


 

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47% normalization 66% <20ng/mL 6% molecular clearance Best percentage change from baseline (%) *prior midostaurin # prior DCC-2618 + S/A/R mutation positive Spleen Volume (central review) Serum Tryptase (central assay) Blood KIT D816V ddPCR (central assay) Bone marrow mast cells Clinical activity in all evaluable patients: decline in mast cell burden across all disease subtypes, regardless of prior therapy or co-mutation status Data previously presented in December 2018 at the ASH Annual Meeting. Data cutoff: September 30, 2018. 19 Bone marrow mast cells serum tryptase (central assay) Spleen Volume (central review) Blood KIT D816V ddPCR (central assay) 66% <20ng/mL 47% normalization 6% molecular clearance 0 -20 -40 -60 -80 -100

 

 


 

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Best response* n (%) All doses (n=29) ORR (CR + CRh + PR + CI) 24 (83%) Complete response (CR) 3 (10%) CR, partial hematologic recovery2 (CRh) 4 (14%) Partial response (PR) 14 (48%) Clinical improvement (CI) 3 (10%) Stable disease (SD) 5 (17%) Progressive disease (PD) 0 ≤200mg1 QD (n=10) 9 (90%) 3 (30%) 2 (20%) 3 (30%) 1 (10%) 1 (10%) 0 Ongoing treatment durations of up to 31 months (range 1+ to 31+ months) Median duration of response (DOR) not reached (median follow up 14 months) 76% 12-month DOR rate Median time to response is 2 months Median time to CR/CRh is 9 months Responses per IWG criteria are durable and deepen over time Data previously presented in December 2018 at the ASH Annual Meeting. Data cutoff: September 30, 2018. 1 Started at ≤200mg QD. 90% have not dose escalated above 200mg as of the data cutoff date. 2 CRh: Requires all criteria for CR be met and response duration must be ≥12 weeks (to be confirmed); however, patient may have residual cytopenias. The following are required for CRh: ANC > 0.5 × 109/L with normal differential (absence of neoplastic MCs and blasts < 1%) and Platelet count > 50 × 109/L and Hgb level > 8.0 g/dL. *Pending confirmation: 3 transitioning from confirmed response to a deeper response, 3 transitioning from SD to first response. IWG criteria have regulatory precedent, with comparable 28% ORR for midostaurin 20

 

 


 

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Avapritinib is well-tolerated in patients with systemic mastocytosis 21 Treatment-Emergent Adverse Events (Safety Population; N = 67) Non-hematologic AEs >15%, % (n) Any Grade Grade 3/4 Periorbital edema 45 (67) 3 ( 4) Fatigue 25 (37) 5 ( 7) Nausea 24 (36) 3 ( 4) Diarrhea 23 (34) 1 ( 1) Peripheral Edema 23 (34) 0 Vomiting 19 (28) 2 ( 2) Cognitive effects 19 (28) 1 ( 1) Hair color changes 17 (25) 1 ( 1) Arthralgia 13 (19) 1 ( 1) Dizziness 13 (19) 1 ( 1) Abdominal pain 12 (18) 1 ( 1) Hematologic AEs >10%, % (n) Any Grade Grade 3/4 Anemia 35 (52) 18 (26) Thrombocytopenia 21 (31) 12 (17) Neutropenia 8 (12) 7 (10) Most AEs were grade 1 or 2 No treatment-related grade 5 AEs 4% (3/67) of patients discontinued due to treatment-related AEs Refractory ascites, encephalopathy and intracranial bleed 66% (44/67) of patients had ≥grade 3 treatment-related AEs and dose reduced Most commonly hematologic AEs, typically in patients with prior cytopenias Most dose reductions occurred at ≥300mg QD 78% (52/67) remain on treatment as of data cutoff Data previously presented in December 2018 at the ASH Annual Meeting. Data cutoff: September 30, 2018.

 

 


 

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Evaluable ISM/SSM patients in Phase 1 EXPLORER trial Preliminary Phase 1 data highlight the potential of avapritinib in ISM/SSM Data previously presented in December 2018 at the ASH Annual Meeting. Data cutoff: September 30, 2018. BM, bone marrow; ISM, indolent systemic mastocytosis; RP2D, recommended Phase 2 dose; SSM, smoldering systemic mastocytosis. 22 RP2D R, 1:1 Part 1: Dose-finding Part 2: Efficacy Part 3: Extension 25 mg QD 50 mg QD 100 mg QD Open-label extension avapritinib placebo First PIONEER trial site is open, with initiation of patient screening anticipated in January 2019 BM Mast Cells Serum Tryptase KIT D816V ddPCR (blood) Best Percentage Change from Baseline * prior midostaurin 10 -20 -40 -60 -80 -100 Cr

 

 


 

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Growing portfolio of highly selective investigational kinase medicines 23 Non-small cell lung cancer Medullary thyroid cancer Other RET-altered solid tumors BLU-667 RET inhibitor Hepatocellular carcinoma BLU-554 FGFR4 inhibitor Fibrodysplasia ossificans progressiva BLU-782 ALK2 inhibitor 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.

 

 


 

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BLU-667 is designed to treat RET-altered cancers 24 High kinome selectivity for RET1,2 More potent and selective than multi-kinase inhibitors1,2 IC50, half maximal inhibitory concentration. Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (CSTI) (www.cellsignal.com). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. 1 Data previously presented in April 2018 at AACR Annual Meeting. Data cutoff: April 6, 2018. 2 Subbiah V et al. Cancer Discov. 2018;8(7):836-849. 3 Epidemiology based on estimated incidence for NSCLC (across treatment lines) and estimated prevalence for MTC in major markets (US, France, Germany, Italy, Spain, the United Kingdom and Japan). Wild-type RET RET V804L Gatekeeper resistance RET V804M Gatekeeper resistance RET M918T Mutation CCDC6-RET Fusion VEGFR2 Anti-target BLU-667 0.4 0.3 0.4 0.4 0.4 35 Cabozantinib 11 45 162 8 34 2 Vandetinib 4 3597 726 7 20 4 BLU-667 is 88-fold more selective for RET than VEGFR2 BLU-667 is 20-fold more selective for RET than JAK1 RET opportunity in major markets ~10,000 NSCLC patients3 ~800 MTC patients3 Low variable frequency across multiple solid tumors

 

 


 

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Plan to submit NDA for 2L RET-fusion NSCLC and 2L RET-mutant MTC in 1H 2020 25 Dose escalation RET-altered solid tumors RET-fusion NSCLC, prior platinum Part 1 complete MTC, prior MKI Part 2 enrolling RET-fusion solid tumors, prior standard of care RET-mutated tumors, prior standard of care RET-altered solid tumors, prior selective RET TKI Endpoints: ORR, duration of response, safety MKI, multi-kinase inhibitor; TKI, tyrosine kinase inhibitor Plan to complete enrollment of 2L RET-fusion NSCLC and 2L RET-mutant MTC patient cohorts in 1H 2019 Plan to initiate Phase 3 trial in 1L RET-fusion NSCLC in 2H 2019 RET-fusion NSCLC, no prior platinum MTC, no prior MKI RP2D 400 mg QD

 

 


 

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Data have strengthened as patients treated at RP2D 26 AACR April 20181 ATA October 20182 84% of patients with tumor shrinkage (NSCLC, MTC and PTC) 53% ORR in RET-fusion NSCLC and PTC patients 40% ORR in RET-mutant MTC patients 90% of patients with tumor shrinkage (MTC and PTC) 62% response rate in RET-mutant MTC patients at 300/400 mg QD for ≥24 weeks All responders and all patients treated at 400 mg QD remain on therapy as of data cutoff AACR, American Association for Cancer Research Annual Meeting; ATA, American Thyroid Association Annual Meeting; PTC, papillary thyroid cancer. 1 Data previously presented at AACR Annual Meeting in April 2018. Data cutoff: April 6, 2018. 2 Data previously presented at ATA Annual Meeting in October 2018. Patients enrolled as of May 9, 2018 with follow-up as of Sep 14, 2018. Safety population includes patients with NSCLC, MTC and PTC. Safety population (N=69)2 Most AEs reported by investigators were Grade 1 Treatment-related Grade ≥3 AEs in ≥2 patients included anemia, hypertension, decreased white blood cell count, diarrhea and neutropenia Only 2 discontinuations due to a treatment-related AE PD SD PR 1 confirmed CR; 10 confirmed PR, 7 pending confirmation PR 20 10 0 –20 –30 –10 –40 –50 –60 –70 –90 –80 –100 20 10 0 –20 –30 –10 –40 –50 –60 –70 –90 –80 –100 PD SD PR Medullary thyroid cancer Papillary thyroid cancer 1 confirmed CR; 14 confirmed PR, 2 pending confirmation PR

 

 


 

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BLU-782 is designed to target mutant ALK2, the underlying cause of fibrodysplasia ossificans progressiva 27 MALFORMED BIG TOES TUMOR-LIKE SWELLINGS EXTRASKELETAL BONE PROGRESSIVE INCAPACITATION Causes abnormal transformation of skeletal muscle, ligaments and tendons into bone Beginning in childhood, disease manifestations include painful disease flare-ups, locking of joints, progressive loss of mobility and respiratory dysfunction Premature death typically occurs in middle age due to cardiorespiratory complications There are no approved therapies IND application cleared by FDA; plan to initiate Phase 1 healthy volunteer trial in Q1 2019

 

 


 

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Highly selective for mutant ALK2 Prevents surgery-induced HO* Prevents injury-induced HO* Foundational preclinical data support plans for clinical development of BLU-782 in FOP Cellular assay Micro CT at Day 17 28 Data previously presented at ASBMR Annual Meeting in September 2018. * Injury- and surgery-induced HO studies conducted in an ALK2 R2016H mouse model. CT, computed tomography; HO, heterotopic ossification. >100-fold difference BLU-782 Control 0 12 29 50 Day Control BLU-782 0 50 100 M e a n H O v o l u m e ± S E M (  m  m 3 ) ALK6 ALK3 ALK1 ALK2 ALK2 R206H CELLULAR IC20 (Nm) 10000 1000 100 10 1 Mean HO volume +SEM (mm3) Control Blu-782

 

 

 


 

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Leader in targeted kinase medicines Three clinical programs with demonstrated proof-of-concept Retain all rights in the rest of the world Deep development experience and network in China Growing oncology portfolio including immunotherapies Exclusive rights in Greater China1 1 Greater China consists of Mainland China, Hong Kong, Macau and Taiwan. Strategic collaboration accelerates BLU-554 clinical development program Plan to initiate BLU-554 monotherapy and combination trials in China by mid-2019 and in 2H 2019, respectively 29

 

 


 

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Strong financial position entering 2019 30 Balance Sheet (unaudited) 9/30/2018 12/31/2017 Cash, Cash Equivalents and Investments $559.6M $673.4M Three Months Ended Statement of Operations (unaudited) 9/30/2018 9/30/2017 Collaboration Revenue $1.1M $8.1M Research & Development Expenses $64.6M $39.3M General & Administrative Expenses $12.0M $7.4M Net Loss $(72.7)M $(37.7)M Based on current operating plans, expect existing cash balance will fund operations into the 2H of 2020* *Excludes any potential option fees and milestone payments under the Roche and CStone collaborations **Shares outstanding as of 9/30/2018: 43.9 million (basic) and 48.4 million (fully diluted).

 

 


 

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Program Milestone Anticipated Timing Avapritinib – GIST Submit NDA for PDGFRA Exon 18 mutant GIST and 4L GIST 1H 2019 Present data from Phase 1 NAVIGATOR trial supporting planned NDA for PDGFRA Exon 18 mutant GIST and 4L GIST 1H 2019 Complete enrollment of Phase 3 VOYAGER trial in 3L GIST 2H 2019 Initiate Phase 3 COMPASS-2L precision medicine trial in 2L GIST 2H 2019 Submit NDA for 3L GIST 2020 Avapritinib – SM Present updated data from Phase 1 EXPLORER trial in advanced SM 1H 2019 Present initial data from Phase 2 PIONEER trial in indolent and smoldering SM 2H 2019 Complete enrollment of Phase 2 PATHFINDER trial in advanced SM 2H 2019 Submit NDA for advanced SM 2020 BLU-667 – RET Present updated data from Phase 1 ARROW trial in RET-altered NSCLC, MTC and other advanced solid tumors 1H 2019 Complete enrollment of previously treated RET-altered NSCLC and MTC cohorts in Phase 1 ARROW trial 1H 2019 Initiate Phase 3 trial in 1L RET-fusion NSCLC 2H 2019 Initiate Phase 2 trial of BLU-667 and osimertinib in EGFR-mutant NSCLC harboring an acquired RET alteration 2H 2019 Submit NDA for 2L RET-fusion NSCLC and 2L RET-mutant MTC 1H 2020 BLU-554 – HCC Initiate enrollment in China in ongoing global Phase 1 trial of BLU-554 under collaboration with CStone Pharmaceuticals Mid-2019 Initiate Phase 1 combination trial of BLU-554 and CS-1001, CStone Pharmaceuticals’ anti-PD-L1 inhibitor, in China 2H 2019 BLU-782 – FOP Initiate Phase 1 trial in healthy volunteers Q1 2019 Initiate Phase 2 trial in patients with FOP 1H 2020 Research portfolio Provide a research portfolio update, including disclosure of up to 2 new targets, at an R&D day 2019 Nominate at least one new wholly-owned discovery program 2019 Summary of anticipated corporate milestones for 2019-2020

 

 


 

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Thank you