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): December 1, 2016
Blueprint Medicines Corporation
(Exact name of registrant as specified in its charter)
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Delaware |
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001-37359 |
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26-3632015 |
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(State or other jurisdiction of incorporation) |
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(Commission File Number) |
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(I.R.S. Employer |
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38 Sidney Street, Suite 200 Cambridge, Massachusetts |
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02139 |
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(Address of principal executive offices) |
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(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))
Item 8.01 Other Items.
On December 1, 2016 in an oral presentation at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany (the “EORTC-NCI-AACR Symposium”), Blueprint Medicines Corporation (the “Company”) presented initial data from the dose escalation stage of its ongoing Phase 1 clinical trial evaluating BLU-285 for the treatment of advanced gastrointestinal stromal tumors (“GIST”). BLU-285 is an orally available, potent and highly selective inhibitor that targets D842V mutant PDGFRα and Exon 17 mutant KIT. A copy of the slide presentation is filed as Exhibit 99.1 to this Current Report on Form 8-K and incorporated herein by reference.
Cautionary Note Regarding Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans and timelines for the clinical development of BLU-285; and the Company’s ability to implement its clinical development plans for BLU-285 for the treatment of advanced GIST. 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. Any forward-looking statements in this Current Report on Form 8-K 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 Current Report on Form 8-K, including, without limitation, risks and uncertainties related to the delay of any current or planned clinical trials or the development of BLU-285; the Company’s advancement of multiple early-stage efforts; the Company’s ability to successfully demonstrate the efficacy and safety of its drug product candidates; the preclinical and clinical results for the Company’s drug product candidates, which may not support further development of such drug product candidates; and actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; the Company’s ability to develop and commercialize companion diagnostics for its current and future drug candidates, including companion diagnostics for BLU-285 with QIAGEN Manchester Limited; and the success of the Company’s rare genetic disease collaboration with Alexion Pharma Holding and its cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, as filed with the Securities and Exchange Commission (“SEC”) on November 10, 2016, and other filings that Blueprint Medicines may make with the SEC in the future. Any forward-looking statements contained in this Current Report on Form 8-K represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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Exhibit No. |
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Description |
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99.1 |
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Slide presentation by Blueprint Medicines Corporation on December 1, 2016 at the EORTC-NCI-AACR Symposium |
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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.
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BLUEPRINT MEDICINES CORPORATION |
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Date: December 1, 2016 |
By: |
/s/ Jeffrey W. Albers |
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Jeffrey W. Albers |
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Chief Executive Officer |
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EXHIBIT INDEX
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Exhibit No. |
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Description |
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99.1 |
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Slide presentation by Blueprint Medicines Corporation on December 1, 2016 at the EORTC-NCI-AACR Symposium |
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Exhibit 99.1
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Preliminary safety and activity in a first-in-human Phase 1 study of BLU-285, a potent, highly selective inhibitor of KIT and PDGFR activation loop mutants in advanced gastrointestinal stromal tumor (GIST) Michael Heinrich1, Robin Jones2, Patrick Schoffski3, Sebastian Bauer4, Margaret von Mehren5, Ferry Eskens6, Philippe Cassier7, Olivier Mir8, Hongliang Shi9, Terri Alvarez-Diez9, Mary Ellen Healy9, Beni Wolf9, Suzanne George10 1Oregon Health & Sciences University, Oregon, USA; 2Royal Marsden Hospital/Institute of Cancer Research, London, UK; 3Leuven Cancer Institute, Leuven, Belgium; 4University of Essen, Essen, Germany; 5Fox Chase Cancer Center, Pennsylvania, USA; 6Erasmus MC Cancer Institute, Rotterdam, Netherlands; 7Centre Leon Berard, Lyon, France; 8Institut Gustave Roussy, Paris, France; 9Blueprint Medicines Corporation, Massachusetts, USA; 10Dana-Farber Cancer Institute, Massachusetts, USA EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium, Munich, Germany, 01 Dec 2016 |
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BLU-285 is an investigational agent currently in development by Blueprint Medicines Corporation (Blueprint Medicines) Dr. Michael Heinrich is an investigator for Blueprint Medicines’ ongoing Phase 1 study in unresectable gastrointestinal stromal tumor Dr. Michael Heinrich has the following disclosures: Consultant: Blueprint Medicines, Novartis, MolecularMD Equity interest: MolecularMD Research funding: Blueprint Medicines, Deciphera, Ariad Expert testimony: Novartis Patents: four patents on diagnosis and treatment of PDGFR-mutant GIST Disclosures |
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Cancer of the interstitial cells of Cajal Primary tumor usually presents as a stomach or intestinal mass Metastatic recurrences spread to liver, peritoneum, and other distant sites Chemotherapy has no impact Gastrointestinal Stromal Tumor (GIST) Most common GI sarcoma Primary mutational hotspots KIT Exons 9 or 11 PDGFR D842V Exons 12 and 18 Resistance mutations KIT Exons 13 and 17 PDGFR D842V Exon 18 Activating RTK mutations drive metastatic GIST KIT ~ 80% PDGFR ~ 8% GI, gastrointestinal; JM, juxtamembrane; KIT, receptor tyrosine kinase protein; PDGFR, platelet-derived growth factor receptor; RTK, receptor tyrosine kinase; TM, transmembrane Barnett & Heinrich (2012) Am Soc Clin Oncol Educ Book;663; Nowain et al (2005) J Gastroen Heptol;20:818; Dematteo et al (2000) Ann Surg;231:51; Plumb et al (2013) Clin Radiol;68:770; Joensuu (2006) 17 Suppl 10:x280 Extracellular Domain JM Domain Kinase Domain-1 Kinase Domain-2 (activation loop) TM Domain Exons 9 11 17 12 18 13 Colon and rectum 5% Small intestine 30% Stomach 60% Duodenum 5% |
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Advanced GIST has high medical need Activation loop mutations are associated with resistance to therapy Approved agents are ineffective against PDGFR D842V ORR ~ 0% mPFS ~ 3 months Primary resistance Secondary resistance Prevalence Resistance mutation Primary Secondary KIT Exon 17 ~ 1% 2L ~ 20% 3L ~ 90% PDGFR D842V ~ 5-6% rare 4L BSC or trial 1L imatinib 2L sunitinib 3L regorafenib mPFS, median progression-free survival; ORR, objective response rate; PFS, progression-free survival Cassier (2012) CCR;18:4458; Yoo (2016) Can Res Treat;48:546; Corless (2005) JCO;23:5357; Barnett and Heinrich (2012) Am Soc Clin Onc Ed Book: 663; Demetri (2006) Lancet;368:1329; Demetri (2013) Lancet;381:295-302 |
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BLU-285 imatinib sunitinib regorafenib BLU-285 is a highly potent and selective inhibitor of KIT and PDGFR activation loop mutants Tumor regression in KIT exon 11/17* mutant GIST PDX Biochemical profiles Compound PDGFR D842V IC50 nM KIT D816V IC50 nM KIT V560G/D816V IC50 nM BLU-285 0.24 0.27 0.10 imatinib 759 8150 6145 sunitinib 120 207 97.2 regorafenib 810 3640 1685 Exon 17 Exon 11/17 Activation loop Exon 18 JM domain/ activation loop BID, twice daily; IC50, half maximal inhibitory concentration; PDX, patient derived xenograft; QD, once daily Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) *del556-558/Y823D Tumour volume (mm3) Days after the start of treatment 0 10 20 30 0 200 400 600 800 1000 Vehicle QD Imatinib 50 mg/kg BID BLU-285 3 mg/kg QD BLU-285 10 mg/kg QD BLU-285 30 mg/kg QD |
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BLU-285 Phase 1 study Advanced GIST MTD Dose expansion Unresectable GIST after imatinib and ≥ 1 other TKI PDGFR D842-mutant GIST BLU-285 continuous once daily oral dosing Dose escalation Primary objectives – determine the MTD and RP2D, and assess safety and tolerability Secondary objectives – PK, mutational status, anti-tumor activity Enrolling First patient enrolled October 2015 Anticipated initiation first half 2017 MTD, maximum tolerated dose; PK, pharmacokinetics; RP2D, recommended Phase 2 dose; TKI, tyrosine-kinase inhibitor NCT02508532 |
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Parameter All patients, N = 36 Age (years), median (range) 61 (41 – 77) n (%) GIST subtype KIT mutant PDGFR mutant 18 (50) 18 (50) Metastatic Disease 35 (97) Largest target lesion size (cm) ≤ 5 > 5 – ≤ 10 > 10 pending 8 (22) 12 (33) 14 (39) 2 (6) #Prior TKI, median (range) ≤ 2 > 2 3.5 (0 – 12) 12 (33) 24 (67) Demography and baseline patient characteristics Data are preliminary and based on a cut off date of 1 November 2016 |
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Patients with unresectable GIST Prior imatinib and ≥ 1 TKI PDGFR D842 mutation regardless of prior therapy 3 + 3 dose escalation with additional accrual to dose levels declared safe at a dose escalation meeting 36 patients enrolled over 12 months MTD has not been reached Initial dose escalation results 75% (n=27) of patients remain on treatment, range 0.8 – 12.3 months All PDGFR patients remain on treatment 9 patients off treatment (all due to progressive disease) BLU-285 mg/day Patients treated by dose N = 36 30 3 + 2 enrichment 60 3 + 3 enrichment 90 3 + 3 enrichment 135 3 + 3 enrichment 200 3 + 2 enrichment 300 3 + 1 enrichment 400 4 |
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10000 1000 100 10 1 0 30 mg 60 mg 90 mg 135 mg 200 mg 300 mg Time (hour) 0 10 20 30 10000 1000 100 10 1 0 Plasma concentration (ng/mL) Time (hour) Half-life > 24 hour, supporting QD dosing Relatively rapid absorption: Tmax ~ 2 – 8 hr Accumulation in plasma: 2.5 – 4.7 -fold after 15 days Exposure at 300 mg is at low end of predicted therapeutic range based on KIT Exon 17 mutant xenograft studies BLU-285 pharmacokinetics support once daily dosing C1D15 steady state C1D1 C1D1, Cycle 1 Day 1; C1D15, Cycle 1 Day 15; Tmax, time at which Cmax is observed; QD, once daily 0 20 40 60 80 |
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65 yo female, Primary Gastric GIST, PDGFR D842V Previous surgical de-bulking: stomach; peritoneal metastases x 2; colon Prior response to crenolanib followed by progression Progression on prior dasatinib (no response) Ongoing at Cycle 13 with confirmed partial response (-52% per RECIST 1.1) Radiographic response per RECIST 1.1 in PDGFR D842V GIST (dose level 1, 30 mg) Baseline After 8 weeks, partial response (-42%) Rapid PDGFR D842V ct-DNA decline CT, computerized tomography; ct-DNA, circulating tumor DNA; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors PDGFRα D842V [%] Days on study Tumor [mm] |
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Strong clinical activity against PDGFR D842-mutant GIST at all dose levels Maximum reduction – sum of diameter change from Baseline (%) 30 PDGFRα Exon 14 PDGFRα D842 20 10 0 –10 –20 –30 –40 –50 –60 200 60 60 60 60 135 200 90 90 135 200 135 90 135 30 PR SD PD 14 out of 14 D842-mutant patients with tumor reductions All PDGFR patients remain on treatment The values above/below the bars denote the dose level (mg) QD received by each patient SD, stable disease; PD, progressive disease; PR, partial response |
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57 year old male, KIT Exon 11 (delWK557-8)/Exon 17 (D816V) mutations Prior imatinib, sunitinib, nilotinib, sorafenib, imatinib + BKM120 Ongoing at Cycle 8 with confirmed partial response per RECIST 1.1 Radiographic response per RECIST 1.1 in heavily pretreated KIT Exon 11/17 GIST (dose level 4, 135 mg) Baseline After 24 weeks, partial response (-62%) |
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KIT GIST - early dose-response relationship Maximum reduction – sum of diameter change from baseline (%) 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 Off treatment # BLU-285 30 – 90 mg BLU-285 135 – 300 mg 90 60 30 30 90 30 60 300 135 200 300 300 135 PD SD PR # # # # # # Patient # NB: The values above/below the bars denote the dose level (mg) QD received by each patient 4 of 6 patients with tumor reduction 5 of 6 patients remain on treatment ≥ 5 cycles |
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Best radiographic response with BLU-285 per RECIST 1.1 Of 7 partial responses, 6 confirmed; 1 pending (still on treatment) DCR, disease control rate Best response (per investigator) PDGFR N=15 n (%) KIT N=13 n (%) Total N=28 n (%) PR 6 (40) 1 (8) 7 (25) SD 9 (60) 6 (46) 15 (54) DCR (PR +SD) 15 (100) 7 (54) 22 (79) PD 0 6 (46) 6 (21) |
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No DLTs or treatment-related Grade 4 – 5 AEs No patient discontinued BLU-285 due to treatment-related toxicity 11 (31%) patients had Grade 3 or higher AEs; of these, 3 were considered treatment-related: 1 patient with Grade 3 nausea and vomiting 1 patient with Grade 3 anemia and intratumoral hemorrhage 1 patient with Grade 3 hypophosphatemia AEs occurring in ≥ 20% of patients Nausea (42%) Vomiting (33%) Peripheral edema (31%) Fatigue (28%) Constipation (22%) Adverse events associated with BLU-285 AE, adverse event; DLT, dose limiting toxicity |
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BLU-285 has been well tolerated on a QD schedule at doses of 30 – 400 mg Half-life > 24 hours, supports QD dosing BLU-285 demonstrates strong clinical activity in PDGFR D842-mutant GIST at all dose levels Significant anti-tumor activity in TKI-resistant, KIT-mutant GIST observed at doses ≥ 135 mg with tumor reduction in 4 of 6 patients, including 1 PR Dose escalation continues with the goal of maximizing clinical activity in KIT-mutant GIST and to define the MTD and RP2D Anticipate initiation of expansion cohorts in first half of 2017 Summary |
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We thank the participating patients, their families, all study co-investigators, and research coordinators at the following institutions: Oregon Health & Sciences University Royal Marsden Hospital/Institute for Cancer Research Leuven Cancer Institute University of Essen Fox Chase Cancer Center Erasmus MC Cancer Institute Centre Leon Berard Institut Gustave Roussy Dana-Farber Cancer Institute Acknowledgments |
