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): June 5, 2017
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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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:
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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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.
On June 5, 2017, Blueprint Medicines Corporation (the “Company”) issued a press release announcing new data from its ongoing Phase 1 clinical trial evaluating BLU-285 for the treatment of advanced gastrointestinal stromal tumors (“GIST”). The press release also announced that the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to BLU-285 for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. The data were presented on Monday, June 5, 2017 in an oral presentation at the 2017 American Society of Clinical Oncology (“ASCO”) Annual Meeting in Chicago, Illinois. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K, and a copy of the presentation at the ASCO Annual Meeting is furnished as Exhibit 99.2 to this Current Report on Form 8-K.
In addition, on June 5, 2017, the Company hosted an investor event and live webcast to discuss the data presented at the ASCO Annual Meeting. A copy of the presentation from the investor event is furnished as Exhibit 99.3 to this Current Report on Form 8-K.
The information in Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1, 99.2 and 99.3, 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.
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Exhibit No. |
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Description |
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99.1 |
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Press release issued by Blueprint Medicines Corporation on June 5, 2017 |
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99.2 |
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Presentation by Blueprint Medicines Corporation at the ASCO Annual Meeting on June 5, 2017 |
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99.3 |
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Presentation by Blueprint Medicines Corporation at investor event on June 5, 2017 |
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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: June 6, 2017 |
By: |
/s/ Tracey L. McCain |
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Tracey L. McCain |
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Chief Legal 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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Press release issued by Blueprint Medicines Corporation on June 5, 2017 |
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99.2 |
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Presentation by Blueprint Medicines Corporation at the ASCO Annual Meeting on June 5, 2017 |
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99.3 |
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Presentation by Blueprint Medicines Corporation at investor event on June 5, 2017 |
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Exhibit 99.1
Blueprint Medicines Announces New Phase 1 Clinical Data for BLU-285 in Advanced Gastrointestinal Stromal Tumors and Plans to Pursue Expedited Development in Patients with a PDGFRα D842V Mutation
– BLU-285 receives Breakthrough Therapy Designation for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation –
– Encouraging clinical activity demonstrated in multiple GIST patient populations, including preliminary evidence of prolonged progression free survival –
– Blueprint Medicines to host investor event and webcast on Monday, June 5, 2017 –
CAMBRIDGE, Mass., June 5, 2017 /PRNewswire/ – Blueprint Medicines Corporation (NASDAQ:BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, today announced new Phase 1 clinical data and outlined registration plans for BLU-285, a potent and highly selective PDGFRα and KIT inhibitor in development as a potential treatment for patients with advanced gastrointestinal stromal tumors (GIST). In patients with PDGFRα-driven GIST harboring a D842 mutation, the data showed an objective response rate (ORR) of 60 percent and an estimated 9-month progression free survival (PFS) of 87 percent. Among patients with treatment-resistant KIT-driven GIST, tumor reduction was observed in eight of 14 evaluable patients treated at dose levels of at least 300 mg once daily (QD). BLU-285 was well tolerated, and most adverse events (AEs) reported by investigators were Grade 1 or 2. The data will be presented today in an oral presentation during the “GIST: Imatinib and Beyond” session from 1:15 to 2:45 p.m. CT (Abstract 11011) at the 2017 ASCO Annual Meeting in Chicago.
Blueprint Medicines also announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to BLU-285 for the treatment of patients with unresectable or metastatic PDGFRα D842V-driven GIST, and the Company plans to pursue expedited development of BLU-285 in this population. Based on feedback from the FDA at a recent End-of-Phase 1 meeting, additional data from the expansion portion of the ongoing Phase 1 clinical trial of BLU-285 may be sufficient to support a New Drug Application (NDA) for the treatment of patients with PDGFRα D842V-driven GIST. Blueprint Medicines currently estimates it will complete enrollment of the PDGFRα D842V expansion cohort, which is expected to include approximately 50 patients, by the middle of 2018. The Company also plans to initiate a global, pivotal Phase 3 clinical trial of BLU-285 in the first half of 2018, with the goal of supporting the registration of BLU-285 in a broader GIST patient population.
“Advanced GIST is a devastating disease marked by rapid disease progression, and patients with PDGFRα-driven GIST and treatment-resistant KIT-driven GIST have limited or no effective treatments,” said Michael Heinrich, M.D., Oregon Health & Science University, an investigator on the clinical trial. “The new data announced today reinforce the clinical potential of BLU-285 in these populations. High response rates and prolonged progression free survival suggest BLU-285 has the potential to transform the treatment of PDGFRα D842-driven GIST. In addition, BLU-285 showed very encouraging anti-tumor activity in the treatment-resistant KIT-driven GIST population with a complex mutational burden, for whom disease control is a major treatment goal. Together, these results support efforts to expand the clinical development of BLU-285, including into earlier lines of GIST treatment."
“Blueprint Medicines is committed to advancing BLU-285 as swiftly as possible with the goal of addressing the significant medical need in advanced GIST,” said Andy Boral, M.D., Chief Medical Officer at Blueprint Medicines. “Based on the updated BLU-285 clinical data and our recent interactions with the FDA, we believe we have paths forward in PDGFRα D842-driven GIST and treatment-resistant KIT-driven GIST. Importantly, the FDA is open to considering additional data from our ongoing Phase 1 clinical study as the basis for an NDA for BLU-285 in PDGFRα D842V-driven GIST. These developments bring us closer to achieving our vision of rapidly delivering targeted kinase medicines to patients with genomically defined diseases.”
New Data from the Ongoing Phase 1 Clinical Trial of BLU-285 in Advanced GIST
BLU-285 is currently being evaluated in a Phase 1 clinical trial in patients with unresectable PDGFRα-driven GIST and patients with treatment-resistant KIT-driven GIST. Following completion of the dose escalation portion of the trial and determination of the maximum tolerated dose (MTD), Blueprint Medicines initiated the expansion portion of the trial in the first quarter of 2017.
As of the data cutoff date of April 28, 2017, 72 patients had been treated with BLU-285 in the dose escalation and expansion portions of the Phase 1 clinical trial, at eight dose levels (ranging from 30 mg QD to 600 mg QD), including 32 patients with PDGFRα-driven GIST and 40 patients with KIT-driven GIST. The median number of prior tyrosine-kinase inhibitor (TKI) regimens was 1.5 for patients with PDGFRα-driven GIST (ranging from zero to six), and four for patients with KIT-driven GIST (ranging from two to 11). Among patients with KIT-driven GIST, 36 patients (90 percent) had been treated with at least three prior TKI regimens, including 34 patients (85 percent) who had been previously treated with regorafenib.
Pharmacokinetic (PK) data demonstrated a mean half-life of more than 24 hours, supporting a once-daily dosing regimen. Consistent with previously reported preclinical data, PK data from the ongoing clinical trial suggested that exposure at dose levels ranging from 300 to 400 mg QD confers activity against a broad spectrum of disease-driving mutations.
Safety Data
As of the data cutoff date, BLU-285 was observed to be well-tolerated. Most AEs reported by investigators were Grade 1 or 2. Across all grades, AEs reported by investigators most commonly included nausea (60 percent), fatigue (53 percent), vomiting (42 percent), periorbital edema (36 percent), diarrhea (33 percent), and peripheral edema (31 percent). Investigators reported treatment-related Grade ≥3 AEs in 18 patients (25 percent). Grade ≥3 AEs occurring in two or more patients included fatigue, hypophosphatemia, anemia, nausea, vomiting and hyperbilirubinemia. Two patients experienced dose-limiting toxicities at 600 mg QD (Grade 2 hyperbilirubinemia in one patient; Grade 2 rash, Grade 2 hypertension and Grade 2 memory impairment all in one patient), leading to the determination of 400 mg QD as the MTD. Only one patient discontinued treatment with BLU-285 due to a drug-related toxicity (Grade 3 hyperbilirubinemia). An additional 20 patients discontinued treatment, including 19 patients due to progressive disease and one patient due to the investigator’s decision. Among all 72 enrolled patients, 51 remained on the trial as of the data cutoff date.
Clinical Activity Data
As of the data cutoff date, 26 patients with PDGFRα-driven GIST were evaluable for response assessment, including 23 patients with a D842V mutation, two patients with other D842 mutations, and one patient
with an exon 14 mutation who was excluded from analyses of clinical activity. In addition, 25 patients with KIT-driven GIST were evaluable for response assessment. Patients were evaluable if they had at least one centrally reviewed radiographic scan, and all reported data are based on blinded central radiographic review as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Radiographic scans were also assessed by Choi criteria, a supportive method of response assessment in soft tissue sarcoma. An additional 21 enrolled patients had not been evaluated for response by the data cutoff date.
PDGFRα D842-driven GIST
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Radiographic tumor reductions were observed in 25 of 25 evaluable patients with PDGFRα D842-driven GIST. |
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By Choi criteria, 25 patients had a PR, representing an ORR of 100 percent. |
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Median PFS was not reached and 9-month PFS was estimated to be 87 percent. In contrast, historical data showed a zero percent ORR and median PFS of 2.8 months in patients with PDGFRα D842V–driven GIST treated with imatinib.1 |
Treatment-resistant KIT-driven GIST
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Radiographic tumor reductions were observed in 10 of 25 evaluable patients, including patients with complex genotypes involving primary and secondary KIT mutations (e.g., mutations in exons 8, 9, 11, 13, 17 and 18). |
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In patients treated at dose levels of at least 300 mg QD, eight of 14 patients had tumor reductions per RECIST, including one patient who achieved a PR. |
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By RECIST criteria, two patients had a PR (one confirmed, one pending confirmation), and 12 patients had SD, representing a preliminary ORR of eight percent and a DCR of 56 percent. |
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By Choi criteria, eight patients had a PR, and six patients had SD, representing a preliminary ORR of 32 percent and a DCR of 56 percent. |
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Median PFS among patients treated at dose levels of at least 300 mg QD was 9.3 months. In contrast, historical data showed a zero percent ORR and median PFS of 1.8 months in patients with TKI-resistant advanced GIST re-treated with imatinib in a third-line or later setting.2 |
Investor Event and Webcast Information
Blueprint Medicines will host an investor event on Monday, June 5, 2017 beginning at 6:00 p.m. CT (7:00 p.m. ET) in Chicago to review the updated clinical data for BLU-285 in GIST. Formal presentations and the live webcast will begin at 6:30 p.m. CT (7:30 p.m. ET). The event can be accessed by dialing 1-855-728-4793 (domestic) or 1-503-343-6666 (international) and providing the passcode 13676007. A live webcast will also be available under “Events & Presentations” in the Investors 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 event concludes and will be available for 30 days following the event.
Informational Webinar for the GIST Patient Community
Blueprint Medicines will host an informational webinar for the GIST patient community on Thursday, June 22, 2017 beginning at 12:00 p.m. ET. To participate in the webinar, please dial 1-855-880-1246 (domestic) or 1-408-638-0968 (international) and refer to webinar ID 855 846 509. A live webcast of the presentation will be available at www.blueprintmedicines.com in the “Patients” section of Blueprint Medicines’ website under “Patient Community Events.” The archived webcast will be available on Blueprint Medicines’ website approximately one day after the webinar and will be available for 30 days following the webinar.
About the Phase 1 Clinical Trial for BLU-285 in PDGFRα-Driven and KIT-Driven GIST
The Phase 1 clinical trial of BLU-285 is designed to evaluate the safety and tolerability of BLU-285 in adults with advanced GIST. The trial consists of two parts, a dose-escalation portion and an expansion portion. The dose-escalation portion is complete, and the MTD has been determined to be 400 mg QD. The expansion portion is actively enrolling patients in two defined cohorts, including a cohort of patients with a PDGFRα D842V mutation, regardless of line of therapy, and a cohort of patients who have received imatinib and at least one other KIT-directed TKI. Trial objectives include assessing response, pharmacokinetics and pharmacodynamic measures. The two expansion cohorts of the trial are designed to enroll approximately 100 patients at multiple sites in the United States, United Kingdom and European Union. Please refer to www.clinicaltrials.gov for additional details related to this Phase 1 clinical trial (NCT02508532). Patients and physicians may contact the study director for more information about this Phase 1 clinical trial at studydirector@blueprintmedicines.com.
About GIST
GIST is the most common sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction. Approximately 80 percent of GIST patients have KIT-driven GIST, and Blueprint Medicines estimates that KIT exon 17 mutations occur in approximately 90 percent of GIST patients with KIT-driven GIST following treatment with at least two TKIs. Approximately five percent of all advanced GIST cases are driven by D842V mutant PDGFRα. Patients diagnosed with GIST at an early stage may undergo surgery. For patients with KIT-driven GIST, treatment with the currently approved frontline therapy typically leads to treatment resistance and disease progression. Treatment options for KIT-driven GIST patients whose disease progresses or develops resistance are currently limited, with approved therapies providing a progression free survival of up to six months and a response rate between five percent and seven percent. There are no effective treatment options for patients with PDGFRα D842V-driven GIST, and progression often occurs in as little as three months with available treatment options.
About BLU-285
BLU-285 is an orally available, potent and highly selective inhibitor of PDGFRα and KIT. Preclinical data have shown that BLU-285 is active across a broad spectrum of PDGFRα and KIT mutations, including PDGFRα D842V and KIT exon 17 mutations for which there are limited or no effective treatment options. Blueprint Medicines is initially developing BLU-285, an investigational medicine, for the treatment of patients with advanced GIST and advanced systemic mastocytosis. BLU-285 was discovered by Blueprint
Medicines’ research team leveraging its proprietary compound library, and the Company retains worldwide development and commercialization rights for BLU-285.
In June 2017, BLU-285 received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening disease or condition, when preliminary clinical evidence indicates that the drug candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Previously, the FDA granted orphan drug designation to BLU-285 for the treatment of GIST. The FDA also granted Fast Track designation to BLU-285 for the treatment of patients with unresectable or metastatic GIST that progressed following treatment with imatinib and a second TKI and for the treatment of patients with unresectable or metastatic GIST in patients with the PDGFRα D842V mutation regardless of prior therapy.
About Blueprint Medicines
Blueprint Medicines is developing a new generation of targeted and potent kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other diseases driven by the abnormal activation of kinases. Blueprint Medicines is advancing four programs in clinical development for subsets of patients with gastrointestinal stromal tumors, hepatocellular carcinoma, systemic mastocytosis, non-small cell lung cancer, medullary thyroid cancer and other advanced solid tumors, as well as multiple programs in research and preclinical development. For more information, please visit www.blueprintmedicines.com.
References
1 Cassier PA, Fumagalli E, Rutkowski P, et al. Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha–Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era. Clin Cancer Res. 2012;18(16):4458–64.
2 Kang YK, Ryu MH, Ryoo BY, et al. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1175–82.
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 and timelines for the clinical development of BLU-285, including plans and timelines for pursuing expedited development in patients with a PDGFRα D842V mutation and plans and timelines for the initiation of a global, pivotal Phase 3 clinical trial of BLU-285; Blueprint Medicines’ ability to implement its clinical development plans for BLU-285 in advanced GIST; Blueprint Medicines’ ability to enroll patients in its ongoing Phase 1 clinical trial for BLU-285 in advanced GIST and expectations regarding the completion of enrollment of the PDGFRα D842V expansion cohort; expectations regarding current and future interactions with the U.S. Food and Drug Administration (FDA) and the impact of Breakthrough Therapy Designation on the development of BLU-285; and Blueprint Medicines’ strategy, business plans and focus. 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 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 delay of any current or planned clinical trials or the development of Blueprint Medicines’ drug candidates, including BLU-285, BLU-554 and BLU-667; Blueprint Medicines’ advancement of multiple early-stage efforts; Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the preclinical and clinical results for Blueprint Medicines’ drug candidates, which may not support further development of such drug candidates; and actions of the FDA or other 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, including companion diagnostic tests for BLU-554 with Ventana Medical Systems, Inc. and for BLU-285 with QIAGEN Manchester Limited; and the success of Blueprint Medicines’ 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 Blueprint Medicines’ Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, as filed with the Securities and Exchange Commission (SEC) on May 3, 2017, and other filings that Blueprint Medicines 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. Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.
Contact
Investor Relations:
Kristin Hodous
Blueprint Medicines Corporation
617-714-6674
KHodous@blueprintmedicines.com
Media Relations:
Rachel Hutman
W20 Group
301-801-5540
rhutman@wcgworld.com
Exhibit 99.2
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GIST: imatinib and beyond Clinical activity of BLU-285 in advanced gastrointestinal stromal tumor (GIST) Michael Heinrich1, Robin Jones2, Margaret von Mehren3, Patrick Schoffski4, Sebastian Bauer5, Olivier Mir6, Philippe Cassier7, Ferry Eskens8, Hongliang Shi9, Terri Alvarez-Diez9, Oleg Schmidt-Kittler9, Mary Ellen Healy9, Beni Wolf9, Suzanne George10 1Oregon Health & Sciences University, Oregon, USA; 2Royal Marsden Hospital/Institute of Cancer Research, London, UK; 3Fox Chase Cancer Center, Pennsylvania, USA; 4Leuven Cancer Institute, Leuven, Belgium; 5University of Essen, Essen, Germany; 6Institut Gustave Roussy, Paris, France; 7Centre Leon Berard, Lyon, France; 8 Erasmus MC Cancer Institute, Rotterdam, Netherlands; 9Blueprint Medicines Corporation, Massachusetts, USA; 10Dana-Farber Cancer Institute, Massachusetts, USA Abstract no: 11011 Presented by: Dr. Michael Heinrich |
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Disclosures 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 studies 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 2 |
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Imatinib revolutionized Gastrointestinal Stromal Tumor (GIST) treatment Imatinib binds the inactive kinase conformation and inhibits many primary mutants Imatinib is a highly effective first-line GIST therapy A-loop imatinib A-loop imatinib Inactive conformation Active conformation KIT KIT mutations drive ~75–80% of GIST PDGFR mutations drive ~5–10% of GIST KIT PDGFR Extracellular Juxtamembrane Kinase-1 Kinase-2 (activation loop) Transmembrane Exons 12 18 9 11 17/18 13 Domains Primary Resistance Mutational hotspots 3 |
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Beyond imatinib, there are no highly effective therapies1–6 Primary resistance Secondary resistance 3L regorafenib 1L imatinib 2L sunitinib ORR ~60% PFS 19 mo ORR ~7% PFS 6 mo 4L no approved therapy ORR ~5% PFS 4.8 mo ORR ~0% PFS ≤1.8 mo* 4 Prevalence7,8 Resistance mutation Primary Secondary PDGFRα D842V ~5–6% Rare KIT exon 17/18 ~1% 2L ~23% ≥3L ~90% KIT exon 13 N/A 2L ~40% Primary and secondary mutations cause therapeutic resistance Approved agents are ineffective against PDGFRα D842V *Imatinib re-challenged |
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BLU-285: highly potent and selective targeting of KIT/PDGFR GIST mutants 5 High kinome selectivity* Binds active conformation BLU-285 *Image reproduced courtesy of CSTI (www.cellsignal.com) |
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KIT exon 11/17 mutant KIT exon 11/13 mutant BLU-285: highly active against imatinib-resistant GIST patient derived xenografts Tumor regression at 10 and 30 mg/kg QD Tumor regression at 30 mg/kg QD 6 |
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BLU-285 Phase 1 study Advanced GIST MTD Part 2 Dose expansion enrolling Unresectable GIST after imatinib and ≥1 other TKI (n=50) PDGFR D842V-mutant GIST (n=50) Part 1 Dose escalation completed Key objectives Part 1: MTD, safety, pharmacokinetics, ctDNA analyses, anti-tumor activity Part 2: response rate, duration of response, safety 3+3 design with enrichment Dose levels: 30, 60, 90, 135, 200, 300, 400 and 600 mg QD MTD determined to be 400 mg PO QD 7 |
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Demography and baseline patient characteristics Parameter All patients, N=72 Age (years), median (range) 61 (25–85) n (%) GIST subtype KIT mutant PDGFR mutant 40 (56) 32 (44) Metastatic disease 69 (96) Largest target lesion size (cm) ≤5 >5–≤10 >10 18 (25) 25 (35) 29 (40) No. prior kinase inhibitors Median (range) ≥3 Prior regorafenib PDGFR 1.5 (0–6) 10 (31) 8 (25) KIT 4 (2–11) 36 (90) 34 (85) Data are preliminary and based on a cut off date of 28 April 2017 8 |
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BLU-285 pharmacokinetics support QD dosing and broad mutational coverage Relatively rapid absorption Tmax ~2–8 hours and long half-life >24 hours Exposure at the 300 and 400 (MTD) mg provides broad coverage of primary and secondary KIT/PDGFR mutations based on patient derived xenografts (PDX) 9 *includes escalation and expansion data |
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Radiographic response per RECIST 1.1 in PDGFR D842V-mutant GIST Ongoing at cycle 5 Prior imatinib and sunitinib Confirmed PR, -63% target sum Ongoing at cycle 3 Prior imatinib PR (pending confirmation), -85% target sum Target lesion resolution Baseline After 4 months BLU-285 300 mg (dose escalation) BLU-285 400 mg (dose expansion) 10 Baseline After 2 months Target lesion resolution |
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Tumor regression across all dose levels in PDGFR D842-mutant GIST (central radiology review) 11 |
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High response rate and prolonged PFS in PDGFR D842-mutant GIST Best response (N=25) Choi Criteria n (%) RECIST 1.1 n (%) PR 25 (100%) 15* (60%) SD 0 10 (40%) DCR (PR + SD) 25 (100%) 25 (100%) PD 0 0 Central radiographic review Approved agents are ineffective1,2 ORR ~0% * 12 confirmed, 3 pending confirmation 12 |
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Radiographic response in heavily pre-treated KIT-mutant GIST Ongoing at cycle 12 6 prior TKIs; exon 11, 13, and 18 mutations CHOI PR (density -53%); RECIST SD (-21%) Screening Cycle 3 Cycle 5 Cycle 7 Ongoing at cycle 4 5 prior TKIs; 1 exon 11 mutation; ctDNA pending CHOI PR (density -76%); RECIST PR (-41%) BLU-285 300 mg (dose escalation) BLU-285 400 mg (dose expansion) 13 Screening Cycle 3 |
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Dose-dependent tumor reduction across multiple KIT genotypes (central radiographic review) 14 *ctDNA results pending **per archival tumor and ctDNA |
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Important clinical activity in heavily pre-treated KIT-mutant GIST Beyond third-line regorafenib there are no approved therapies Imatinib re-treatment in ≥third-line GIST3 ORR ~0% Central radiographic review * 1 confirmed, 1 pending confirmation ↑ PFS with BLU-285 ≥300 mg Best response (N=25) Choi Criteria n (%) RECIST 1.1 n (%) PR 8 (32) 2* (8) SD 6 (24) 12 (48) DCR (PR + SD) 14 (56) 14 (56) PD 11 (44) 11 (44) 15 |
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Adverse events (AE) associated with BLU-285 18 (25%) patients had Grade (G) ≥3 treatment-related (Fatigue [8%], hypophosphatemia [6%], anemia [4%], nausea, vomiting, hyperbilirubinemia [3% each]) DLT in 2 patients at 600 mg: 1 G2 hyperbilirubinemia; 1 G2 rash, hypertension, memory impairment BLU-285 discontinuations: disease progression n=19, treatment-related toxicity (G3 hyperbilirubinemia) n=1, and investigator’s decision n=1 Safety population, N=72 Severity, n (%) AEs in ≥20% of patients n (%) Grade 1 Grade 2 Grade 3 Grade 4/5 Nausea 43 (60) 31 (43) 9 (13) 3 (4) 0 Fatigue 38 (53) 16 (22) 16 (22) 6 (8) 0 Vomiting 30 (42) 21 (29) 6 (8) 3 (4) 0 Periorbital edema 26 (36) 22 (31) 4 (6) 0 0 Diarrhea 24 (33) 19 (26) 4 (6) 1 (1) 0 Edema peripheral 22 (31) 18 (25) 4 (6) 0 0 Decreased appetite 20 (28) 15 (21) 4 (6) 1 (1) 0 Anemia 18 (25) 4 ( 6) 8 (11) 6 (8) 0 Lacrimation increased 17 (24) 12 (17) 5 (7) 0 0 Dizziness 16 (22) 13 (18) 3 (4) 0 0 16 |
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Conclusions BLU-285 is well tolerated on a QD schedule at doses up to the MTD of 400 mg Exposure at 300–400 mg QD provides broad coverage of primary and secondary KIT / PDGFR mutants BLU-285 has strong clinical activity in PDGFR D842-mutant GIST with an ORR of 60% per central review and median PFS not reached Potential expedited paths for approval are being evaluated BLU-285 demonstrates important anti-tumor activity including radiographic response and prolonged PFS in heavily pre-treated, KIT-mutant GIST at doses of 300–400 mg QD Based on these encouraging data, planning is underway for a Phase 3 randomized study of BLU-285 in third-line GIST 17 |
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Acknowledgments 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 We also thank Sarah Jackson, PhD, of iMed Comms, an Ashfield company, who provided editorial writing support funded by Blueprint Medicines 18 |
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References Cassier et al. Clin Cancer Res. 2012;18(16):4458–64 Yoo et al. Cancer Res Treat. 2016;48(2):546–52 Kang et al. Lancet Oncol. 2013;14(12):1175–82 National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors. 2016 Demetri et al. Lancet. 2006;368:1329 Demetri et al. Lancet. 2013;381:295-302 Corless et al. J Clin Oncol. 2005;23:5357 Barnett and Heinrich. Am Soc Clin Onc Ed Book. 2012;663 19 |
Exhibit 99.3
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2017 ASCO Annual Meeting Monday, June 5, 2017 Advances in GIST |
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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 “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 clinical development of BLU-285, BLU-554 and BLU-667 and the ability of Blueprint Medicines Corporation (the “Company”) to implement those clinical development plans; the potential benefits of the Company’s current and future drug candidates in treating patients; plans and timelines for regulatory submissions, filings or discussions; plans and timelines for the development and commercialization of companion diagnostics for the Company’s current or future drug candidates; plans and timelines for current or future discovery programs; plans and timelines for future collaborations, if any, with strategic partners; the future financial performance of the Company; expectations regarding potential milestones in 2017; 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 future clinical trials or the development of the Company’s drug candidates, including BLU-285, BLU-554 and BLU-667; 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 current or future 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 diagnostics for its current and future drug candidates, including a companion diagnostic for BLU-554 with Vantaa Medical Systems, Inc. and a companion diagnostic 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 under “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, as filed with the Securities and Exchange Commission (“SEC”) on May 3, 2017, and any other filings the Company 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. |
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Agenda Welcome Jeff Albers, Chief Executive Officer, Blueprint Medicines Overview of BLU-285 in GIST Andy Boral, MD, Chief Medical Officer, Blueprint Medicines Phase 1 clinical trial results Michael Heinrich, MD, Professor, Oregon Health and Science University Proposed registration path Andy Boral, MD, Chief Medical Officer, Blueprint Medicines Question and answer session Michael C. Heinrich, MD, Professor, Oregon Health and Science University Jeff Albers, Chief Executive Officer, Blueprint Medicines Andy Boral, MD, Chief Medical Officer, Blueprint Medicines Closing remarks Jeff Albers, Chief Executive Officer, Blueprint Medicines 3 |
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Medicinal chemistry Proprietary compound library Genomic targeting A blueprint for a healthier tomorrow 4 Targeted kinase medicines for genomically defined diseases Discovery platform for exquisitely selective kinase inhibitors, matched to specific molecular drivers of disease, with rapid path to clinical proof-of-concept |
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A new way of looking at kinase medicines Kinome illustration reproduced courtesy of CSTI (cellsignal.com). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content; IO, immuno-oncology 5 BLU-554 Nexavar Sutent BLU-285 We aim to design and develop highly targeted kinase medicines with improved potency, less off-target activity, and a high probability of clinical success |
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Three major areas of focus 6 Genomically defined cancers Rare diseases Cancer immunotherapy Oncogenic kinases resulting from tumor genetic alterations BLU-285 gastrointestinal stromal tumors BLU-554 hepatocellular carcinoma BLU-667 RET-altered cancers Abnormally activated kinases due to rare genetic alterations BLU-285 systemic mastocytosis Alexion collaboration (1 target) Intracellular immunokinases involved in tumor immunity Roche collaboration (up to 5 targets) |
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Drug candidate Discovery Preclinical Clinical Commercial rights BLU-285 Inhibitor of KIT, including exon 17 mutations, and PDGFRα, including the D842V mutation BLU-554 Inhibitor of FGFR4 BLU-667 Inhibitor of RET fusions, mutations and resistant mutants PRKACA Inhibitor of PRKACA fusions Cancer immunotherapy Immunokinases Rare genetic disease Robust pipeline of diverse clinical stage assets PHASE 1 - PDGFR-DRIVEN GIST PHASE 1 - KIT-DRIVEN GIST PHASE 1 – SYSTEMIC MASTOCYTOSIS PHASE 1 – HEPATOCELLULAR CARCINOMA PHASE 1 – NSCLC & THYROID* FLC Up to 5 programs, STAGE UNDISCLOSED** Target and development stage undisclosed FLC, Fibrolamellar carcinoma; GIST, advanced gastrointestinal stromal tumors; NSCLC, non-small cell lung cancer. All Phase 1 clinical trials are in advanced disease. *Phase 1 trial includes a basket cohort that consists of other advanced solid tumors with RET alterations. **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. 7 |
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BLU-285 Drug Discovery Overview Andy Boral, M.D. Chief Medical Officer |
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Gastrointestinal stromal tumors (GIST) Colon and rectum 5% Small intestine 30% Stomach 60% Duodenum 5% Primary tumor sites 9 Typically presents as stomach or intestinal mass Metastases in liver, peritoneum and other distant sites Mutant receptor tyrosine kinases are key disease drivers PDGFRα ~5-10% KIT ~75-80% Beyond imatinib, no highly effective treatments |
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PDGFRα and KIT activation loop mutations stabilize the kinase active conformation, blocking binding of type 2 inhibitors Imatinib is a type 2 multikinase inhibitor that cannot bind the kinase active conformation due to a steric clash BLU-285 is a type 1 selective PDGFRα/KIT inhibitor that binds to the kinase active conformation BLU-285 Kinase in active conformation 10 Imatinib |
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Currently available therapies do not effectively address activation loop mutations *Estimated incidence for GIST patients in major markets (US, EU5 and Japan). **Estimated frequency of Exon 17 activation loop mutations. 11 PDGFRα D842V ALL GIST 1L imatinib PFS ~3 months ORR ~0% ~500 patients* 1L imatinib 2L sunitinib ORR ~60% PFS ~19 months ORR ~7% PFS ~6 months ORR ~5% PFS ~4.8 months 3L regorafenib ~8.7k patients* ~7.7k patients* ~5.0k patients* ~1% KIT exon 17** ~23% KIT exon 17** >90% KIT exon 17** |
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Promising preclinical data supported initiation of a Phase 1 clinical trial of BLU-285 in advanced GIST Most potent biochemical activity against activation loop mutants Biochemical activity across a broad PDGFRα and KIT mutational spectrum 12 Biochemical IC50 (nM) Data previously presented in April 2017 at the AACR Annual Meeting |
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Updated Phase 1 clinical trial results Michael C. Heinrich, M.D. Oregon Health & Sciences University (OHSU) |
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GIST: imatinib and beyond Clinical activity of BLU-285 in advanced gastrointestinal stromal tumor (GIST) Michael Heinrich1, Robin Jones2, Margaret von Mehren3, Patrick Schoffski4, Sebastian Bauer5, Olivier Mir6, Philippe Cassier7, Ferry Eskens8, Hongliang Shi9, Terri Alvarez-Diez9, Oleg Schmidt-Kittler9, Mary Ellen Healy9, Beni Wolf9, Suzanne George10 1Oregon Health & Sciences University, Oregon, USA; 2Royal Marsden Hospital/Institute of Cancer Research, London, UK; 3Fox Chase Cancer Center, Pennsylvania, USA; 4Leuven Cancer Institute, Leuven, Belgium; 5University of Essen, Essen, Germany; 6Institut Gustave Roussy, Paris, France; 7Centre Leon Berard, Lyon, France; 8 Erasmus MC Cancer Institute, Rotterdam, Netherlands; 9Blueprint Medicines Corporation, Massachusetts, USA; 10Dana-Farber Cancer Institute, Massachusetts, USA Abstract no: 11011 Presented by: Dr. Michael Heinrich |
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Disclosures 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 studies 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 15 |
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Imatinib revolutionized Gastrointestinal Stromal Tumor (GIST) treatment Imatinib binds the inactive kinase conformation and inhibits many primary mutants Imatinib is a highly effective first-line GIST therapy A-loop imatinib A-loop imatinib Inactive conformation Active conformation KIT KIT mutations drive ~75–80% of GIST PDGFR mutations drive ~5–10% of GIST KIT PDGFR Extracellular Juxtamembrane Kinase-1 Kinase-2 (activation loop) Transmembrane Exons 12 18 9 11 17/18 13 Domains Primary Resistance Mutational hotspots 16 |
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Beyond imatinib, there are no highly effective therapies1–6 Primary resistance Secondary resistance 3L regorafenib 1L imatinib 2L sunitinib ORR ~60% PFS 19 mo ORR ~7% PFS 6 mo 4L no approved therapy ORR ~5% PFS 4.8 mo ORR ~0% PFS ≤1.8 mo* 17 Prevalence7,8 Resistance mutation Primary Secondary PDGFRα D842V ~5–6% Rare KIT exon 17/18 ~1% 2L ~23% ≥3L ~90% KIT exon 13 N/A 2L ~40% Primary and secondary mutations cause therapeutic resistance Approved agents are ineffective against PDGFRα D842V *Imatinib re-challenged |
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BLU-285: highly potent and selective targeting of KIT/PDGFR GIST mutants 18 High kinome selectivity* Binds active conformation BLU-285 *Image reproduced courtesy of CSTI (www.cellsignal.com) |
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KIT exon 11/17 mutant KIT exon 11/13 mutant BLU-285: highly active against imatinib-resistant GIST patient derived xenografts Tumor regression at 10 and 30 mg/kg QD Tumor regression at 30 mg/kg QD 19 |
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BLU-285 Phase 1 study Advanced GIST MTD Part 2 Dose expansion enrolling Unresectable GIST after imatinib and ≥1 other TKI (n=50) PDGFR D842V-mutant GIST (n=50) Part 1 Dose escalation completed Key objectives Part 1: MTD, safety, pharmacokinetics, ctDNA analyses, anti-tumor activity Part 2: response rate, duration of response, safety 3+3 design with enrichment Dose levels: 30, 60, 90, 135, 200, 300, 400 and 600 mg QD MTD determined to be 400 mg PO QD 20 |
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Demography and baseline patient characteristics Parameter All patients, N=72 Age (years), median (range) 61 (25–85) n (%) GIST subtype KIT mutant PDGFR mutant 40 (56) 32 (44) Metastatic disease 69 (96) Largest target lesion size (cm) ≤5 >5–≤10 >10 18 (25) 25 (35) 29 (40) No. prior kinase inhibitors Median (range) ≥3 Prior regorafenib PDGFR 1.5 (0–6) 10 (31) 8 (25) KIT 4 (2–11) 36 (90) 34 (85) Data are preliminary and based on a cut off date of 28 April 2017 21 |
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BLU-285 pharmacokinetics support QD dosing and broad mutational coverage Relatively rapid absorption Tmax ~2–8 hours and long half-life >24 hours Exposure at the 300 and 400 (MTD) mg provides broad coverage of primary and secondary KIT/PDGFR mutations based on patient derived xenografts (PDX) 22 *includes escalation and expansion data |
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Radiographic response per RECIST 1.1 in PDGFR D842V-mutant GIST Ongoing at cycle 5 Prior imatinib and sunitinib Confirmed PR, -63% target sum Ongoing at cycle 3 Prior imatinib PR (pending confirmation), -85% target sum Target lesion resolution Baseline After 4 months BLU-285 300 mg (dose escalation) BLU-285 400 mg (dose expansion) 23 Baseline After 2 months Target lesion resolution |
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Tumor regression across all dose levels in PDGFR D842-mutant GIST (central radiology review) 24 |
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High response rate and prolonged PFS in PDGFR D842-mutant GIST Best response (N=25) Choi Criteria n (%) RECIST 1.1 n (%) PR 25 (100%) 15* (60%) SD 0 10 (40%) DCR (PR + SD) 25 (100%) 25 (100%) PD 0 0 Central radiographic review Approved agents are ineffective1,2 ORR ~0% * 12 confirmed, 3 pending confirmation 25 |
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Radiographic response in heavily pre-treated KIT-mutant GIST Ongoing at cycle 12 6 prior TKIs; exon 11, 13, and 18 mutations CHOI PR (density -53%); RECIST SD (-21%) Screening Cycle 3 Cycle 5 Cycle 7 Ongoing at cycle 4 5 prior TKIs; 1 exon 11 mutation; ctDNA pending CHOI PR (density -76%); RECIST PR (-41%) BLU-285 300 mg (dose escalation) BLU-285 400 mg (dose expansion) 26 Screening Cycle 3 |
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Dose-dependent tumor reduction across multiple KIT genotypes (central radiographic review) 27 *ctDNA results pending **per archival tumor and ctDNA |
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Important clinical activity in heavily pre-treated KIT-mutant GIST Beyond third-line regorafenib there are no approved therapies Imatinib re-treatment in ≥third-line GIST3 ORR ~0% Central radiographic review * 1 confirmed, 1 pending confirmation ↑ PFS with BLU-285 ≥300 mg Best response (N=25) Choi Criteria n (%) RECIST 1.1 n (%) PR 8 (32) 2* (8) SD 6 (24) 12 (48) DCR (PR + SD) 14 (56) 14 (56) PD 11 (44) 11 (44) 28 |
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Adverse events (AE) associated with BLU-285 18 (25%) patients had Grade (G) ≥3 treatment-related (Fatigue [8%], hypophosphatemia [6%], anemia [4%], nausea, vomiting, hyperbilirubinemia [3% each]) DLT in 2 patients at 600 mg: 1 G2 hyperbilirubinemia; 1 G2 rash, hypertension, memory impairment BLU-285 discontinuations: disease progression n=19, treatment-related toxicity (G3 hyperbilirubinemia) n=1, and investigator’s decision n=1 Safety population, N=72 Severity, n (%) AEs in ≥20% of patients n (%) Grade 1 Grade 2 Grade 3 Grade 4/5 Nausea 43 (60) 31 (43) 9 (13) 3 (4) 0 Fatigue 38 (53) 16 (22) 16 (22) 6 (8) 0 Vomiting 30 (42) 21 (29) 6 (8) 3 (4) 0 Periorbital edema 26 (36) 22 (31) 4 (6) 0 0 Diarrhea 24 (33) 19 (26) 4 (6) 1 (1) 0 Edema peripheral 22 (31) 18 (25) 4 (6) 0 0 Decreased appetite 20 (28) 15 (21) 4 (6) 1 (1) 0 Anemia 18 (25) 4 ( 6) 8 (11) 6 (8) 0 Lacrimation increased 17 (24) 12 (17) 5 (7) 0 0 Dizziness 16 (22) 13 (18) 3 (4) 0 0 29 |
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Conclusions BLU-285 is well tolerated on a QD schedule at doses up to the MTD of 400 mg Exposure at 300–400 mg QD provides broad coverage of primary and secondary KIT / PDGFR mutants BLU-285 has strong clinical activity in PDGFR D842-mutant GIST with an ORR of 60% per central review and median PFS not reached Potential expedited paths for approval are being evaluated BLU-285 demonstrates important anti-tumor activity including radiographic response and prolonged PFS in heavily pre-treated, KIT-mutant GIST at doses of 300–400 mg QD Based on these encouraging data, planning is underway for a Phase 3 randomized study of BLU-285 in third-line GIST 30 |
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Acknowledgments 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 We also thank Sarah Jackson, PhD, of iMed Comms, an Ashfield company, who provided editorial writing support funded by Blueprint Medicines 31 |
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References Cassier et al. Clin Cancer Res. 2012;18(16):4458–64 Yoo et al. Cancer Res Treat. 2016;48(2):546–52 Kang et al. Lancet Oncol. 2013;14(12):1175–82 National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors. 2016 Demetri et al. Lancet. 2006;368:1329 Demetri et al. Lancet. 2013;381:295-302 Corless et al. J Clin Oncol. 2005;23:5357 Barnett and Heinrich. Am Soc Clin Onc Ed Book. 2012;663 32 |
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Proposed registration path Andy Boral, M.D. Chief Medical Officer |
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BLU-285 clinical development program in advanced GIST 34 Dose escalation (N=36) PDGFRα D842V expansion cohort (N=50) ≥3L KIT expansion cohort (N=50) Ongoing Phase 1 clinical trial 3L GIST Breakthrough Therapy Designation granted for treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation Planned Phase 3 clinical trial |
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Strong clinical activity in PDGFRα D842V-driven GIST supports expedited approach to clinical development Best Response Choi Criteria (N = 25) mRECIST 1.1 (N = 25) PR 25 (100%) 15* (60%) SD 0 10 (40%) DCR (PR + SD) 25 (100%) 25 (100%) PD 0 0 Central Radiographic Review Approved agents are ineffective** ORR ~ 0% * 12 confirmed, 3 pending confirmation **Cassier CCR (2012); Yoo Can Res Treat (2015). 35 9-month PFS is estimated at 87% |
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Preliminary FDA feedback supports potentially expedited approval path for BLU-285 in PDGFRα D842V-driven GIST Breakthrough Therapy Designation granted for treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation FDA is open to considering additional data from ongoing Phase 1 trial as basis for New Drug Application in PDGFRα D842V-driven GIST Phase 1 trial accrual continues with 32 PDGFRα-driven GIST patients enrolled as of April 28, 2017 including 12 at 300-400 mg QD dose levels Estimate expansion cohort enrollment complete by mid-year 2018 36 |
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Prolonged progression free survival demonstrated in 5L KIT-driven GIST ↑PFS with BLU-285 ≥ 300 mg Prior kinase inhibitor treatment Median of 4 therapies 90% had ≥3 therapies 85% had regorafenib Regorafenib PFS in 3L ~4.8 months 37 Stable disease is clinically important to patients and physicians |
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Encouraging clinical activity supports advancing clinical development of BLU-285 into earlier lines of treatment Potential Phase 3 trial design: Population: 3L GIST Comparator: regorafenib, with option to cross-over to BLU-285 Primary endpoint: PFS Trial sites: global Investigators and expert advisors are enthusiastic for 3L approach Interactions with global regulatory authorities planned Trial initiation planned in 1H 2018 38 |
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Progress in advanced GIST represents a foundation for a broader vision 39 BLU-285 PDGFRα-driven advanced GIST 3L advanced GIST 2L advanced GIST Advanced systemic mastocytosis Indolent systemic mastocytosis KIT- and PDGFRα-driven diseases |
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Question & Answer Session |
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Closing Remarks Jeff Albers Chief Executive Officer 41 |
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Drug candidate Discovery Preclinical Clinical Commercial rights BLU-285 Inhibitor of KIT, including exon 17 mutations, and PDGFRα, including the D842V mutation BLU-554 Inhibitor of FGFR4 BLU-667 Inhibitor of RET fusions, mutations and resistant mutants PRKACA Inhibitor of PRKACA fusions Cancer immunotherapy Immunokinases Rare genetic disease Robust pipeline of diverse clinical stage assets PHASE 1 - PDGFR-DRIVEN GIST PHASE 1 - KIT-DRIVEN GIST PHASE 1 – SYSTEMIC MASTOCYTOSIS PHASE 1 – HEPATOCELLULAR CARCINOMA PHASE 1 – NSCLC & THYROID* FLC Up to 5 programs, STAGE UNDISCLOSED** Target and development stage undisclosed FLC, Fibrolamellar carcinoma; GIST, advanced gastrointestinal stromal tumors; NSCLC, non-small cell lung cancer. All Phase 1 clinical trials are in advanced disease. *Phase 1 trial includes a basket cohort that consists of other advanced solid tumors with RET alterations. **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. 42 |
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With maturing datasets, additional clinical data updates for BLU-285 and BLU-554 are expected in 2H 2017 Opportunity Previously presented Phase 1 data** BLU-285 in systemic mastocytosis BLU-554 in hepatocellular carcinoma Poor prognosis and limited effective treatments KIT D816V mutation is a key driver in 90-95% ~4.1k advanced SM patients with KIT D816V mutation in major markets* Encouraging clinical activity, including at lower dose levels Marked decreases in mast cell burden and improved patient symptoms Well tolerated to date; dose escalation ongoing 700k new cases and 600k deaths annually Abnormally activated FGFR4 pathway in ~30% of HCC patients ~26.9k FGFR4+ HCC patients in major markets* Evidence of increased clinical activity in biomarker-selected population Well tolerated at doses up to 600 mg QD; dose expansion ongoing 43 *Estimated prevalence for advanced SM in major markets (US, EU5 and Japan). Estimated incidence for 1L and 2L FGFR4+ HCC in major markets. **SM data previously presented in December 2016 at the American Society of Hematology Annual Meeting. HCC data previously presented in December 2016 at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium. |
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Thank you |
