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 1, 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 |
|
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. ☐
Securities registered pursuant to Section 12(b) of the Exchange Act:
|
Title of each class |
Trading symbol(s) |
Name of each exchange on which registered |
|
|
Common stock, par value $0.001 per share |
BPMC |
Nasdaq Global Select Market |
|
Item 7.01 Regulation FD Disclosure.
On June 1, 2019, Blueprint Medicines Corporation (the “Company”) issued a press release announcing updated data from its Phase 1 NAVIGATOR clinical trial evaluating avapritinib for the treatment of patients with advanced gastrointestinal stromal tumors (“GIST”). The data were presented on Saturday, June 1, 2019 in a poster presentation at the American Society of Clinical Oncology 2019 Annual Meeting (“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 is furnished as Exhibit 99.2 to this Current Report on Form 8-K.
On June 3, 2019, the Company issued a press release announcing updated data from its Phase 1 ARROW clinical trial evaluating BLU-667 for the treatment of patients with RET-altered non-small cell cancer (“NSCLC”), medullary thyroid cancer (“MTC”) and other advanced solid tumors. The data for patients with RET-mutant MTC and other RET-altered cancers were presented on Saturday, June 1, 2019 in a poster presentation at the ASCO Annual Meeting. The data for patients with RET-fusion NSCLC will be presented on Monday, June 3, 2019 in an oral presentation at the ASCO Annual Meeting. A copy of the press release is furnished as Exhibit 99.3 to this Current Report on Form 8-K, a copy of the presentation for patients with RET-mutant MTC and other RET-altered cancers is furnished as Exhibit 99.4 to this Current Report on Form 8-K and a copy of the presentation for patients with RET-fusion NSCLC is furnished as Exhibit 99.5 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, 99.3, 99.4 and 99.5, 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 9.01 Financial Statements and Exhibits.
(d) Exhibits.
|
Exhibit No. |
|
Description |
|
99.1 |
|
Press release issued by Blueprint Medicines Corporation on June 1, 2019 |
|
99.2 |
|
|
|
99.3 |
|
Press release issued by Blueprint Medicines Corporation on June 3, 2019 |
|
99.4 |
|
|
|
99.5 |
|
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: June 3, 2019 |
By: |
/s/ Tracey L. McCain |
|
|
|
Tracey L. McCain |
|
|
|
Chief Legal Officer |
3
Exhibit 99.1
Blueprint Medicines Presents NAVIGATOR Trial Data in PDGFRA Exon 18 Mutant GIST and Fourth-Line GIST at ASCO 2019 Supporting Planned Marketing Applications for Avapritinib
-- 86% ORR and median DOR not reached in PDGFRA Exon 18 mutant GIST --
-- 22% ORR and 10.2 month median DOR in fourth-line GIST --
-- On track to submit NDA to FDA in June 2019 and MAA to EMA in third quarter of 2019 --
CAMBRIDGE, Mass., June 1, 2019 – Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced data from the registration-enabling NAVIGATOR trial of avapritinib in patients with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST) and fourth-line GIST. These results were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting and will form the basis for planned worldwide marketing applications for avapritinib, an investigational, highly selective KIT and PDGFRA inhibitor for patients with advanced GIST. The data demonstrate clinical activity and favorable tolerability in patients with PDGFRA Exon 18 mutant and fourth-line GIST, two populations with no effective therapies.
Data from the ongoing NAVIGATOR trial in patients with PDGFRA Exon 18 mutant GIST, which primarily includes the D842V mutation, and fourth-line GIST support Blueprint Medicines’ plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in June 2019 and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the third quarter of 2019. Avapritinib has received FDA Breakthrough Therapy Designation for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation.
In patients with PDGFRA Exon 18 mutant GIST, the objective response rate (ORR) was 86 percent and the median duration of response (DOR) was not reached. In patients with fourth-line GIST, the ORR was 22 percent and the median DOR was 10.2 months. ORR and DOR per central radiographic review will be the primary registrational endpoints. Avapritinib was well-tolerated with most adverse events (AEs) reported by investigators as Grade 1 or 2. These results were as of a data cutoff date of November 16, 2018.
“These data highlight the potential of avapritinib to shift the treatment paradigm for GIST toward a precision medicine approach based on the genomic driver of disease,” said Michael Heinrich, M.D., Professor of Medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial. “In the PDGFRα D842V population where we currently have no effective agents, avapritinib demonstrated remarkable activity regardless of line of therapy. I believe these results will further catalyze the use of mutational testing in GIST patients prior to starting therapy, which is currently recommended by treatment guidelines. Importantly, avapritinib has also demonstrated the potential to suppress complex and heterogenous mutational profiles associated with treatment-resistant fourth-line GIST. Combined with the well-tolerated safety profile of avapritinib, I believe these data show the broad potential of avapritinib to advance care across the GIST treatment landscape.”
“These results further demonstrate the activity and favorable tolerability of avapritinib, a potent and highly selective PDGFRA and KIT inhibitor, in two patient populations with tumor mutations resistant to currently available therapies,” said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. “Based on the strength of these data and the clear medical needs in PDGFRA Exon 18 mutant and fourth-line GIST, we look forward to working closely with global regulatory authorities to bring this important advance in treatment to patients as expeditiously as possible. In addition, the previously reported preliminary data in third-line and second-line GIST support our broad clinical development program and highlight the potential of avapritinib to become a foundational GIST treatment.”
Highlights from ASCO Presentation of NAVIGATOR Trial Data
As of the data cutoff date of November 16, 2018, 204 patients were treated with avapritinib at a starting dose of 300 or 400 mg once daily (QD). Patients with PDGFRA Exon 18 mutant GIST were treated across all lines of therapy. Patients with fourth-line or later GIST had a median of four prior lines of therapy (ranging from three to 11) prior to receiving avapritinib.
Clinical Activity Data
As of the data cutoff date, 43 patients with PDGFRA Exon 18 mutant GIST (including 38 patients with PDGFRα D842V-driven GIST) and 111 patients with fourth-line GIST were treated at a starting dose of 300 or 400 mg QD and evaluable for response assessments. Patients were evaluable if they had at least one centrally reviewed radiographic scan, and data are based on modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST 1.1 criteria) for GIST.
In evaluable patients with PDGFRA Exon 18 mutant GIST:
|
· |
The ORR was 86 percent, with three confirmed complete responses (CR) and 34 partial responses (PR; one pending confirmation). |
|
· |
The ORR was 100 percent (two CRs and three PRs; all responses were confirmed) in the first-line treatment setting. |
|
· |
The median DOR was not reached. |
|
· |
28 patients (78 percent) remained in response as of the data cutoff date. |
|
· |
Median follow-up was 10.9 months. |
In evaluable patients with fourth-line GIST:
|
· |
The ORR was 22 percent, with one confirmed CR and 23 PRs (one pending confirmation1). |
|
· |
The median DOR was 10.2 months. |
|
· |
Median follow-up was 10.8 months. |
Safety Data
Avapritinib had a favorable safety profile in patients treated at a starting dose of 300 or 400 mg QD, with most AEs determined by investigators to be Grade 1 or 2 as of the data cutoff date. Across all patients, 8 percent of patients discontinued treatment with avapritinib due to treatment-related AEs. A lower incidence of commonly reported AEs was reported at 300 mg QD dosing compared to 400 mg QD dosing.
Across all grades, the most common treatment-emergent AEs (regardless of relationship to avapritinib) reported by investigators (≥25 percent) were nausea, fatigue, anemia, cognitive effects, periorbital edema, vomiting, decreased appetite, diarrhea, increased lacrimation and peripheral edema. Investigator-reported Grade 3 or 4 treatment-related AEs (≥2 percent) included anemia, fatigue, cognitive effects, increased blood bilirubin, diarrhea, hypophosphatemia, decreased neutrophil count, neutropenia and lymphopenia.
These data on avapritinib were presented at the ASCO 2019 Annual Meeting in a poster presentation on Saturday, June 1 (Abstract Number: 11022). A copy of the poster is available in the “Science—Publications and Presentations” section of Blueprint Medicines’ website at www.BlueprintMedicines.com.
About the Avapritinib Clinical Development Program in GIST
Blueprint Medicines is pursuing a broad clinical development program for avapritinib across all lines of GIST. Avapritinib is currently being evaluated in two global registration-enabling clinical trials for GIST: the Phase 1 NAVIGATOR trial and the Phase 3 VOYAGER trial.
The NAVIGATOR trial is designed to evaluate the safety, tolerability and clinical activity of avapritinib in patients with unresectable or metastatic GIST. The trial consists of two parts, a dose escalation portion and an expansion portion. Trial objectives include assessing response using blinded central radiology review, as well as pharmacokinetics and pharmacodynamic measures. The expansion cohorts of the trial enrolled patients at multiple sites in the United States, European Union and Asia.
The VOYAGER trial is a global, open-label, randomized, Phase 3 trial designed to evaluate the safety and efficacy of avapritinib versus regorafenib in patients with third- or fourth-line GIST. The trial is designed to enroll approximately 460 patients randomized 1:1 to receive either avapritinib or regorafenib at multiple sites in the United States, Canada, European Union, Australia and Asia.
In the second half of 2019, Blueprint Medicines plans to initiate COMPASS-2L, a global, randomized, Phase 3 precision medicine trial. The trial will evaluate the safety and efficacy of avapritinib versus sunitinib in second-line GIST patients with pre-specified disease genotypes.
Patients and physicians interested in the Phase 3 VOYAGER trial can contact the Blueprint Medicines study director at VOYAGER@blueprintmedicines.com or 1-617-714-6707. For more information about the VOYAGER trial, please visit www.BlueprintClinicalTrials.com/VOYAGER. Additional details are available on www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03465722).
About GIST
GIST is a 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 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.
Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. Because currently available therapies primarily bind to
the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.
Treatment options for KIT-driven GIST patients who progress beyond imatinib are currently limited. There are no effective treatment options for patients with metastatic PDGFRα D842V-driven GIST, and progression occurs in a median of approximately three to four months with available therapy. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Mutational testing is critical to tailor therapy to the underlying disease driver and is recommended in expert guidelines.
About Avapritinib
Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies. In contrast to approved multi-kinase inhibitors, avapritinib has shown marked selectivity for KIT and PDGFRA over other kinases. In addition, avapritinib is uniquely designed to selectively bind and inhibit D816V mutant KIT, the common driver of disease in approximately 95 percent of all systemic mastocytosis (SM) patients. Preclinical studies have shown avapritinib potently inhibited KIT D816V at sub-nanomolar potencies with minimal off-target activity.
Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced SM, and indolent and smoldering SM. The FDA has granted avapritinib two Breakthrough Therapy Designations, one for the treatment of unresectable or metastatic GIST harboring the PDGFRα D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.
Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.
Blueprint Medicines is a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We are currently advancing four investigational medicines in clinical development, along with multiple research programs. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans and timelines for the clinical development of avapritinib; expectations regarding the potential benefits of avapritinib in treating patients with GIST; plans and timelines for submitting an NDA to the FDA for avapritinib for the treatment of PDGFRA Exon 18 mutant GIST and fourth-line GIST; plans and timelines for submitting an MAA to the EMA for avapritinib for the treatment of PDGFRα D842V mutant GIST and fourth-line GIST; expectations regarding clinical data for avapritinib in third-line and second-line GIST; plans, timelines and expectations for interactions with global regulatory authorities; and Blueprint Medicines’ strategy, goals and anticipated milestones, 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 avapritinib, BLU-667, BLU-554 and BLU-782; Blueprint Medicines’ advancement of multiple early-stage efforts; Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines’ drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines’ current and future collaborations, 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 in the section entitled “Risk Factors” in Blueprint Medicines’ Quarterly Report on Form 10-Q for the period ended March 31, 2019, as filed with the Securities and Exchange Commission (SEC) on May 9, 2019, and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.
Investor Relations Contact
Kristin Hodous
617-714-6674
ir@blueprintmedicines.com
Media Relations Contact
Andrew Law
617-844-8205
media@blueprintmedicines.com
Exhibit 99.2
| Clinical Activity of Avapritinib in ≥4th Line (4L+) and PDGFRA Exon 18 Gastrointestinal Stromal Tumors (GIST) Michael Heinrich,1 Robin L. Jones,2 Margaret von Mehren,3 Sebastian Bauer,4 Yoon-Koo Kang,5 Patrick Schöffski,6 Ferry Eskens,7 Olivier Mir,8 Philippe Cassier,9 Cesar Serrano,10 William D. Tap,11 Jonathan Trent,12 Piotr Rutkowski,13 Shreyaskumar Patel,14 Sant P. Chawla,15 Eyal Meiri,16 Teresa Zhou,17 Khalid Mamlouk,17 Maria Roche,17 Suzanne George18 1OHSU Knight Cancer Institute, Portland, OR, USA; 2Royal Marsden Hospital and Institute of Cancer Research, London, UK; 3Fox Chase Cancer Center, Philadelphia, PA, USA; 4University of Duisburg-Essen, Essen, Germany; 5Asan Medical Centre, Seoul, South Korea; 6University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; 7Erasmus MC Cancer Institute, Rotterdam, The Netherlands; 8Institut Gustave Roussy, Villejuif, France; 9Centre Léon Bérard, Lyon, France; 10Vall d’ Hebron Institute of Oncology, Barcelona, Spain; 11Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; 13Maria Sklodowska-Curie Institute–Oncology Center, Warsaw, Poland; 14MD Anderson Cancer Center, Houston, TX, USA; 15Sarcoma Oncology Center, Santa Monica, CA, USA; 16Cancer Treatment Center of America, Atlanta, GA, USA; 17Blueprint Medicines Corporation, Cambridge, MA, USA; 18Dana Farber Cancer Institute, Boston, MA, USA BACKGROUND • The current standard of care for metastatic GIST post-imatinib involves sequential use of multikinase inhibitors, which are associated with low ORR and off-target effects. As secondary resistance mutations accumulate, multikinase inhibitors do not substantially address the underlying molecular basis of the disease and have limited efficacy1-4 • Currently, no therapies are approved and available for relapsed GIST after failure of imatinib, sunitinib, and regorafenib. Retreatment with imatinib has a 0% ORR1–7 • Avapritinib is an investigational precision therapy designed to be a highly selective and potent inhibitor of KIT and PDGFRA mutant kinases1,2 • Avapritinib has received breakthrough therapy designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRA D842V mutation OBJECTIVE • The objective of this analysis of the NAVIGATOR study (ClinicalTrials.gov Identifier: NCT02508532) was to determine the clinical activity of avapritinib at the RP2D (300 mg QD) and MTD (400 mg QD) in patients with GIST with mutations in PDGFRA Exon 18 or in 4L+ METHODS • NAVIGATOR is an open-label, dose escalation/dose expansion phase 1 study of avapritinib Study design and objectives. 4L+ GISTa n = 121 PDGFRA Exon 18 GIST n = 43 Pivotal analyses Populations with no available therapy Avapritinib QD at the RP2D of 300 mg or MTD of 400 mg Advanced GIST (N = 46) RP2D Avapritinib PO QD Key eligibility: • Metastatic GIST following at least 2 prior lines of TKI therapy • Mutation in KIT or PDGFRA Key objectives • ORR • DOR • Safety • Enrollment for the 2L cohort complete and analysis is pending. aWhile enrollment criteria in the study protocol specified that patients in expansion group 1 were required to have received only at least 2 prior lines of TKI therapy, equating to an analysis population of 3L+, the observed enrollment reflected a population more heavily pretreated. RESULTS • Data are based on a data cut-off date of November 16, 2018. Avapritinib is an investigational agent discovered and currently in development by Blueprint Medicines Corporation • Most AEs were grade 1 or 2, with a higher incidence of commonly reported AEs in the 400 mg QD dose group compared with the 300 mg QD dose group • No treatment-related grade 5 AEs were reported • Most patients were able to remain on treatment with dose modifications when needed; relative dose intensity was 86% at 300 mg QD and 73% at 400 mg QD • 8.3% of patients discontinued avapritinib for a treatment-related toxicity in the starting dose 300/400 mg QD group – – 2.0% discontinued treatment for cognitive effects References 1. Sutent® [package insert]. New York, NY: Pfizer Laboratories; 2017. 2. Stivarga® [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2017. 3. Demetri GD, et al. Lancet. 2006;368(9544):1329-1338. 4. Demetri GD, et al. Lancet. 2013;381(9863):295-302. 5. Nishida T, et al. Gastric Cancer. 2016;19(1):3-14. 6. Serrano C, George S. Ther Adv Med Onc. 2014;6(3):115-127. 7. Cassier PA, et al. Clin Cancer Res. 2012;18(16):4458-4464. Acknowledgments The authors would like to thank the participating patients, their families, all study co-investigators, and research coordinators. Third-party medical writing assistance was provided by Ashfield Healthcare Communications. QR Code Disclaimer Copies of this poster obtained through QR (Quick Response) code are for personal use only and may not be reproduced without written permission of the authors. Abbreviations 1L, 1st treatment line; 2L, 2nd treatment line; 3L, 3rd treatment line; 4L, 4th treatment line; AE, adverse event; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; FDA, Federal Drug Administration; GIST, gastrointestinal stromal tumor; KIT, KIT receptor tyrosine kinase; mDOR, median duration of response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; MTD, maximum tolerated dose; NE, not evaluable; ORR, overall response rate; PD, progressive disease; PDGFR, platelet-derived growth factor receptor; PO, orally; PR, partial response; QD, once daily; RP2D, recommended phase 2 dose; SD, stable disease; TKI, tyrosine kinase inhibitor; RECIST, Response Evaluation Criteria in Solid Tumors. Presented at the 2019 American Society of Clinical Oncology Annual Meeting, May 31–June 4, 2019, Chicago, IL Most Common AEs Occurring in ≥ 15% of Patients % (n) 300/400 mg QD Starting Dose (N = 204) All AEs Treatment-related AEs All Gradesb Grade ≥3c All Gradesb Grade ≥3c Nausea 64.2 (131) 2.5 (5) 59.3 (121) - Fatigue 55.4 (113) 7.4 (15) 47.1 (96) 6.4 (13) Anemia 50.0 (102) 28.4 (58) 36.3 (74) 16.2 (33) Cognitive effectsa 41.2 (84) 3.9 (8) 41.2 (84) 3.9 (8) Periorbital edema 40.7 (83) - 40.2 (82) - Vomiting 38.2 (78) 2.0 (4) 31.9 (65) - Decreased appetite 37.7 (77) 2.9 (6) 28.4 (58) - Diarrhea 37.3 (76) 4.9 (10) 31.9 (65) 2.9 (6) Increased lacrimation 32.8 (67) - 30.4 (62) - Peripheral edema 30.9 (63) - 27.0 (55) - Face edema 24.5 (50) - 24.0 (49) - Constipation 22.5 (46) - - - Dizziness 22.1 (45) - - - Hair color changes 21.1 (43) - 20.6 (42) - Blood bilirubin increased 21.1 (43) 4.4 (9) 18.6 (38) 3.9 (8) Abdominal pain 20.1 (41) 5.4 (11) - - Headache 16.7 (34) - - - Dyspnea 16.7 (34) 2.5 (5) - - Dyspepsia 15.7 (32) - - - Hypokalemia 15.7 (32) 2.9 (6) - - Dysgeusia 15.2 (31) - 15.2 (31) - aCognitive effects include pooled terms of memory impairment (29.4%), cognitive disorder (10.8%), confusional state (7.4%), and encephalopathy (1.5%). Blueprint Medicines considered all cognitive effect AEs as treatment-related in this analysis. Note: 3 events of intracranial hemorrhage occurred, 2 were grade 3, 1 was grade 1. bAll grade AEs occuring in ≥15% of patients. cGrade ≥3 AEs occuring in ≥2% of patients. Characteristic PDGFRA Exon 18 (n = 43) 4L+ (n = 121) Age, median (min–max) 64 (29–90) 59 (33–80) Sex, % (n) Male 67.4 (29) 57.9 (70) Race, % (n) White 67.4 (29) 71.1 (86) GIST mutational subtype, % (n) KIT 0 90.9 (110) PDGFRA D842V 88.4 (38) 6.6 (8) PDGFRA Exon 18 non-D842Va 11.6 (5) 2.5 (3) Number of prior lines of TKIs, median (range) 1 (0–5) 4 (3–11) Metastatic disease, % (n) 97.7 (42) 98.3 (119) Largest target lesion (central radiology review), % (n) ≤5 cm 46.5 (20) 33.1 (40) >5 to ≤10 cm 32.6 (14) 47.1 (57) >10 cm 20.9 (9) 18.2 (22) Prior surgical resection, % (n) Yes 86.0 (37) 88.4 (107) ECOG PS, % (n) 0 32.6 (14) 32.2 (39) 1 60.5 (26) 64.5 (78) 2 7.0 (3) 3.3 (4) aPDGFRA Exon 18 non-D842V mutations including D842Y, DI 842-845V, I843_D846del, I843_D846del, and D842-H845. Antitumor activity (central radiology review) and duration of response: PDGFRA Exon 18 avapritinib 300/400 mg QD starting dose Antitumor activity (central radiology review) and duration of response: 4L+ avapritinib 300/400 mg QD starting dose CONCLUSIONS • Pivotal data analyses from the NAVIGATOR trial demonstrate important clinical activity and favorable tolerability in advanced Exon 18 mutant PDGFRA and 4L+ GIST, highlighting the potential of avapritinib to change the treatment paradigm for patients with advanced GIST – – Avapritinib shows remarkable activity in both D842V, a previously undruggable target, and other Exon 18 mutant PDGFRA GIST – – In the fourth line setting, patients with advanced GIST have no effective therapies; avapritinib has activity with durable responses, and response rates exceeding that reported with other kinase inhibitors – – The safety profile of avapritinib is predictable and manageable, thus allowing for prolonged treatment in patients benefiting from avapritinib – – Based on its overall safety profile and antitumor activity, 300 mg QD is the recommended dose for patients with unresectable or metastatic GIST • These data support evaluating avapritinib in earlier lines of therapy; plan to initiate COMPASS-2L trial in 2H 2019 and the VOYAGER-3L trial is ongoing Best response, % (n) 300/400 mg QD Starting Dose 1L n = 5 2L+ n = 38 Total n = 43 CR 40.0 (2) 2.6 (1) 7.0 (3) PR 60.0 (3) 78.9 (30) 76.7 (33) SD 0 15.8 (6) 14.0 (6) PD 0 2.6 (1) 2.3 (1) 11022 Best confirmed response: PDGFRA Exon 18 by line of therapy. • Avapritinib demonstrated clinical activity in first line and subsequent lines of therapy in the PDGFRA Exon 18 population Maximum percent reduction from baseline in target lesion diameter (%) -100 -75 -50 -25 0 25 Patients 86% ORRc 95% with tumor reduction Best Response,b n PDGFRA Exon 18 n=43 CR 3 PRb 34 (1 pending) SD 5 PD 1 ORR (CR+PR),c % (95% CI) 86.0 (72.1–94.7) CBR,d % (95% CI) 95.3 (84.2–99.4) DOR,e months (95% CI) NE (11.5–NE) PFS, months (95% CI) NE (13.4–NE) aAssessed by mRECIST 1.1. Patients who have had ≥1 post-baseline radiographic assessment. Response evaluable at 300/400 mg QD.b1 response pending confirmation. cORR defined as the proportion of patients with a confirmed best response of CR or PR. dCBR defined as CR/PR+SD lasting ≥16 weeks from first dose. eDOR defined as the time from first documented response (CR/PR) to the date of first documented disease progression or death due to any cause, whichever came first. Duration of response (%) Months from first documented response (CR/PR) Number at risk 300/400 mg QD:* 0 20 40 60 80 100 0 3 6 12 18 24 36 33 22 8 2 0 300/400 mg QD Censored mDOR NE (95% CI: 11.3–NE) • 78% (28/36) of PDGFRA Exon 18 patients were still in response as of the November 16, 2018, data cutoff • Median follow-up was 10.9 months *Patients with confirmed response. Best Response,c n 4L+ n=111 CR 1 PR (confirmed) 23 (1 pending) SD 52 PD 35 ORR (CR+PR), % (95% CI) 22 (14.4–30.4) CBR, % (95% CI) 41 (32.2–51.2) DOR, months (95% CI) 10.2 (7.2–NE) PFS, months (95% CI) 3.7 (3.4–5.6) Maximum percent reduction from baseline in target lesion diameter -100 0 100 Patientsa * 22% ORRb *One patient had an outlier value for percent change from baseline of >200% increase in target lesion diameter. aTwo patients who had best response assessment are not included in the waterfall plot because they did not have measurable target lesions at baseline and thus, no percent change could be calculated. bThere were 8 patients with PDGFRA D842V mutations and when these patients were removed from analysis, the ORR is 17% and DOR remains unchanged. cAssessed by mRECIST 1.1. Patients who have had ≥1 post-baseline radiographic assessment. Response evaluable at 300/400 mg QD. Duration of response (%) Months from first documented response (CR/PR) Number at risk 300/400 mg QD:* 0 20 40 60 80 100 0 3 6 12 18 24 23 21 13 2 1 0 300/400 mg QD Censored mDOR 10.2 months (95% CI: 7.2–NE) • Median follow-up was 10.8 months across all 4L+ patients *Patients with confirmed response. |
Exhibit 99.3
Blueprint Medicines’ Highly Selective RET Inhibitor BLU-667 Shows Durable Anti-Tumor Activity in Patients with RET-Altered Cancers in Updated ARROW Trial Data Presented at ASCO 2019
-- 60% ORR in post-platinum RET-fusion NSCLC and 63% ORR in RET-mutant MTC patients previously treated with multi-kinase inhibitors; median durations of response not reached --
-- Responses observed across treatment-naïve and previously treated patients,
and regardless of RET alteration or tumor type --
-- Strong activity against brain metastases in NSCLC patients --
-- Plan to submit initial NDA to FDA for BLU-667 in RET-fusion NSCLC in first quarter of 2020 --
-- Blueprint Medicines to host investor event and webcast on Monday, June 3, 2019 at 6:30 p.m. CT --
CAMBRIDGE, Mass., June 3, 2019 – Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced updated data from the ongoing registration-enabling ARROW trial of BLU-667 in patients with RET-altered cancers. The data presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting show durable clinical activity in patients with RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other cancers. Designed by Blueprint Medicines, BLU-667 is a potent and highly selective oral inhibitor of RET fusions and mutations, including predicted resistance mutations.
The new results support Blueprint Medicines’ plans to submit an initial New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for BLU-667 for the treatment of patients with RET-fusion NSCLC previously treated with platinum-based chemotherapy in the first quarter of 2020, and an NDA to the FDA for the treatment of patients with RET-mutant MTC previously treated with an approved multi-kinase inhibitor (MKI) in the first half of 2020.
“Targeted therapies have transformed the management of multiple oncogenic subsets of lung cancer, but RET-fusion positive lung cancers have not derived similar benefit from current therapeutic approaches. To date, no selective RET inhibitors are approved,” said Justin Gainor, M.D., director of Targeted Immunotherapy at Massachusetts General Hospital Cancer Center and an investigator on the ARROW trial. “In the data presented at ASCO, BLU-667 demonstrated high response rates across multiple populations of RET-altered cancer patients, including patients with untreated brain metastases.”
“This growing body of evidence supports our plans to rapidly advance BLU-667, a highly selective RET inhibitor, for the treatment of patients with RET-altered cancers,” said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. “We remain on track to submit our first New Drug Application to the FDA for BLU-667 for previously treated RET-fusion non-small cell lung cancer patients in the first quarter of 2020. Based on the encouraging data to date and FDA feedback, we are now working to expand ARROW trial enrollment for treatment-naive patients with RET-fusion positive non-small cell lung cancer, with the goal of supporting an accelerated path to registration in first-line patients. In
addition, based on the strong data for BLU-667 across RET alteration and tumor types, we plan to continue to work with investigators and global regulatory authorities to bring BLU-667 to the broader population of patients with RET-altered cancers who could potentially benefit from this treatment.”
Highlights from ASCO Presentations of ARROW Trial Data
The presented data include 120 patients with RET-fusion NSCLC, 64 patients with RET-mutant MTC and 12 patients with other RET-altered cancers (nine papillary thyroid cancer (PTC), two pancreatic cancer and one intrahepatic bile duct carcinoma) enrolled in the ARROW trial as of a data cutoff date of April 28, 2019. The patients with RET-fusion NSCLC and RET-mutant MTC received a starting dose of 400 mg once daily (QD), which is the recommended Phase 2 dose (RP2D). Patients with other RET-altered cancers were included regardless of starting dose.
At baseline, 40 percent of the RET-fusion NSCLC patients had brain metastases. Brain metastases commonly occur in NSCLC patients, and the prognosis in these patients is typically poor. Regardless of starting dose and including the dose-escalation portion of the ARROW trial, the RET-fusion NSCLC patients have been on treatment up to 24 months.
For clinical activity data, NSCLC and MTC patients were evaluable if they were enrolled as of November 14, 2018 with follow-up through the data cutoff date, which enabled them to have at least two radiographic scans. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Clinical Activity Data — RET-Fusion NSCLC
As of the data cutoff date, 48 patients with RET-fusion NSCLC were evaluable for response assessment, including 35 patients previously treated with platinum-based chemotherapy.
|
· |
Nearly all patients (90 percent) had radiographic tumor reductions. |
|
· |
The objective response rate (ORR) was 60 percent (one complete response and 20 partial responses (PR); all responses were confirmed), and the disease control rate (DCR) was 100 percent in the patients previously treated with platinum-based chemotherapy. |
|
· |
The ORR was 71 percent (five confirmed PRs) in seven patients naïve to prior systemic treatment. |
|
· |
Across all patients, the median duration of response (DOR) was not reached, and 82 percent of responders remained on treatment as of the data cutoff date. |
|
· |
In nine patients with measurable brain metastases, 78 percent had shrinkage of brain metastases. |
|
· |
No patients starting at the 400 mg QD dose had disease progression due to new brain involvement. |
|
· |
BLU-667 was highly active regardless of RET fusion partner, including RET-KIF5B and RET-CCDC6. |
Clinical Activity Data — RET-Mutant MTC and Other RET-Altered Cancers
As of the data cutoff date, 32 patients with RET-mutant MTC were evaluable for response assessment, including 16 patients previously treated with the MKIs cabozantinib or vandetanib.
|
· |
The ORR was 63 percent (nine confirmed PRs, one PR pending confirmation) and the DCR was 94 percent in RET-mutant MTC patients previously treated with cabozantinib or vandetanib. |
|
· |
Across all RET-mutant MTC patients, the median DOR was not reached and all responders remained on treatment as of the data cutoff date, with treatment durations up to 15.6 months for patients receiving a starting dose of 400 mg QD. |
As of the data cutoff date, clinical activity data were reported in patients with other RET-altered cancers:
|
· |
Six patients with PTC were evaluable for response assessment by RECIST version 1.1. In these patients, the ORR was 83 percent (three confirmed PRs, two PRs pending confirmation). |
|
· |
Five patients with PTC have remained on treatment for one year or longer, and eight patients with PTC remained on treatment as of the data cutoff date. |
|
· |
Additional responses were observed in patients with other RET-fusion cancers, including pancreatic cancer (one confirmed PR, one PR pending confirmation) and intrahepatic bile duct carcinoma (one confirmed PR). |
Four patients (two with RET-fusion NSCLC, two with RET-mutant MTC) enrolled in the ARROW trial were previously treated with LOXO-292. Among them:
|
· |
Two patients had a PR, one of which was confirmed as of the data cutoff date, and one of which was pending as of the data cutoff date and subsequently confirmed prior to the presentation. |
|
· |
One patient had stable disease with radiographic tumor reductions and remained on treatment as of the data cutoff date. |
Safety Data
As of the data cutoff date, 226 patients received a starting dose of 400 mg QD and were evaluable for safety. Across all patients, BLU-667 was well-tolerated and most adverse events (AEs) reported by investigators were Grade 1 or 2. Across all grades, the most common treatment-emergent AEs (regardless of relationship to BLU-667) reported by investigators (≥15 percent) were constipation, hypertension, increased aspartate aminotransferase, neutropenia, diarrhea, fatigue, anemia, increased alanine aminotransferase and increased blood creatinine. Investigator-reported Grade 3 or 4 treatment-related AEs (≥2 percent) included neutropenia, hypertension, anemia, increased blood creatine phosphokinase and leukopenia.
Across all patients, only 4 percent of patients discontinued treatment with BLU-667 due to treatment-related AEs. Seven percent of patients with RET-fusion NSCLC discontinued treatment with BLU-667 due to treatment-related AEs, and no patients with RET-mutant MTC discontinued treatment with BLU-667 due to treatment-related AEs.
These updated data for BLU-667 were reported in two presentations at the ASCO 2019 Annual Meeting, including a poster presentation on trial results in thyroid cancer on Saturday, June 1 (Abstract Number: 6018) and an oral presentation on trial results in NSCLC on Monday, June 3 (Abstract Number: 9008). Copies of the data presentations are available in the “Science—Publications and Presentations” section of Blueprint Medicines’ website at www.BlueprintMedicines.com.
BLU-667 Clinical Development Update
Based on encouraging clinical activity in patients with NSCLC naïve to prior systemic therapy and feedback from the FDA, Blueprint Medicines today announced plans to expand the enrollment target of the ongoing ARROW trial cohort for treatment-naïve patients with RET-fusion NSCLC, with the goal of supporting expedited development in first-line RET-fusion NSCLC.
Investor Event and Webcast Information
Blueprint Medicines will host an investor event on Monday, June 3, 2019 beginning at 6:00 p.m. CT (7:00 p.m. ET) in Chicago to provide a portfolio update, including a review of updated clinical data from the ongoing ARROW trial of BLU-667 in patients with RET-altered cancers and the ongoing registration-enabling NAVIGATOR trial in patients with PDGFRA Exon 18 mutant and fourth-line gastrointestinal stromal tumors (GIST). Formal presentations and the live webcast will begin at 6:30 p.m. CT (7:30 p.m. ET). The event will be webcast live and can be accessed under the “Investors & Media—Events & Presentations” section of Blueprint Medicines’ website at www.BlueprintMedicines.com. A replay of the webcast will be available approximately two hours after the event and will be available for 30 days following the event.
About the ARROW Trial
ARROW is a Phase 1 clinical trial designed to evaluate the safety, tolerability and efficacy of BLU-667 in multiple ascending doses in adults with RET-altered NSCLC, MTC and other advanced solid tumors. The trial consists of two parts: a dose escalation portion, which is now complete, and an expansion portion, in which enrollment is ongoing. The expansion portion consists of seven defined cohorts of patients treated with BLU-667 at the RP2D of 400 mg QD: (1) RET-fusion NSCLC patients previously treated with a platinum-based chemotherapy, (2) RET-fusion NSCLC patients who have not previously received a platinum-based chemotherapy, (3) RET-mutant MTC patients previously treated with cabozantinib or vandetanib, (4) RET-mutant MTC patients who have not previously received cabozantinib or vandetanib, (5) patients with other RET-fusion tumors, (6) patients with other RET-mutant tumors and (7) RET-altered solid tumor patients previously treated with a selective RET inhibitor. Trial objectives include assessing response, pharmacokinetics, pharmacodynamics and safety. The trial is enrolling patients at multiple sites in the United States, European Union and Asia.
Patients and physicians interested in the ARROW clinical trial can contact the Blueprint Medicines study director at arrow@blueprintmedicines.com or 1-617-714-6707. Additional details are available at www.BlueprintClinicalTrials.com/ARROW or www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03037385).
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with PTC, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant, EGFR-mutant NSCLC.
Currently, there are no approved therapies that selectively target RET-driven cancers, although there are several approved MKIs with RET activity being evaluated in clinical trials. To date, clinical activity attributable to RET inhibition has been uncertain for these approved MKIs, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and anticipated resistance mutations.
About BLU-667
BLU-667 is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing BLU-667 for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. The FDA has granted Breakthrough Therapy Designation to BLU-667 for the treatment of RET-fusion positive NSCLC that has progressed following platinum-based chemotherapy, and RET-mutation positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.
BLU-667 was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, BLU-667 consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, BLU-667 demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 90-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, BLU-667 has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.
Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of BLU-667 and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for BLU-667 in the rest of the world.
About Blueprint Medicines
Blueprint Medicines is a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We are currently advancing four investigational medicines in clinical development, along with multiple research programs. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans and timelines for the clinical development of BLU-667; expectations regarding the potential benefits of BLU-667 in treating patients with RET-fusion NSCLC, RET-mutant MTC and other RET-altered cancers; plans and timelines for submitting an NDA to the FDA for BLU-667 for the treatment of RET-fusion NSCLC and RET-mutant MTC; plans, timelines and expectations for interactions with global regulatory
authorities; plans to expand the enrollment target of the ongoing ARROW trial cohort for treatment-naïve RET-fusion NSCLC patients; expectations regarding the expedited development of BLU-667 in first-line RET-fusion NSCLC; plans to initiate a Phase 3 trial of BLU-667 in first-line RET-fusion NSCLC; and Blueprint Medicines’ strategy, goals and anticipated milestones, 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 avapritinib, BLU-667, BLU-554 and BLU-782; Blueprint Medicines’ advancement of multiple early-stage efforts; Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines’ drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines’ current and future collaborations, 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 in the section entitled “Risk Factors” in Blueprint Medicines’ Quarterly Report on Form 10-Q for the period ended March 31, 2019, as filed with the Securities and Exchange Commission (SEC) on May 9, 2019, and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.
Investor Relations Contact
Kristin Hodous
617-714-6674
ir@blueprintmedicines.com
Media Relations Contact
Andrew Law
617-844-8205
media@blueprintmedicines.com
Exhibit 99.4
| 0 2 4 6 8 10 12 14 16 Study Month aData for response-evaluable patients enrolled by 14 Nov 2018. Response-evaluable population includes patients with measurable disease and ≥1 evaluable post-treatment disease assessment. Treatment and Response Duration RET-mutated MTC (400 mg QD starting dose)a -100 -80 -60 -40 -20 0 20 Maximum % Reduction from Baseline Sum of Diameters of Target Lesions Cabo or Vand-naïve Prior Cabo or Vand Cabo and Vand-naïve ORR, overall response rate, DCR, disease control rate (best response of SD or better). aData for response-evaluable patients enrolled by 14 Nov 2018. Response-evaluable population includes patients with measurable disease and ≥1 evaluable post-treatment disease assessment. bTwo patients (one previously received vand, one cabo/vand-naïve) are pending confirmation of response. CEA, carcinoembryonic antigen; ctDNA, circulating tumor deoxyribonucleic acid. Reduction of RET Mutant ctDNA, Calcitonin, and CEA RET-mutated MTC (400 mg QD Starting Dose) BLU-667 vs. pharmacologically relevant kinases: • BLU-667 is 90-fold more selective for RET than VEGFR2 • BLU-667 is 20-fold more selective for RET than JAK1 Tumor Response RET-mutated MTC (400 mg QD starting dose)a RESULTS: ADVANCED RET-MUTATED MTC METHODS Activity and Tolerability of BLU-667, a Highly Potent and Selective RET Inhibitor, in Patients with Advanced RET-altered Thyroid Cancers Matthew H. Taylor1, Justin F. Gainor2, Mimi I-Nan Hu3, Viola Weijia Zhu4, Gilberto Lopes5, Sophie Leboulleux6, Marcia S. Brose7, Martin H. Schuler8, Daniel W. Bowles9, Dong-Wan Kim10, Christina S. Baik11, Elena Garralda12, Chia-Chi Lin13, Douglas Adkins14, Debashis Sarker15, Giuseppe Curigliano16, Hui Zhang17, Corinne Clifford17, Michael R. Palmer17, Christopher D. Turner17, Vivek Subbiah3 1Oregon Health & Science University, Portland, OR; 2Massachusetts General Hospital, Boston, MA; 3The University of Texas MD Anderson Cancer Center, Houston, TX; 4Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA; 5Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; 6Institut Gustave Roussy, Villejuif, France; 7Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; 8West German Cancer Center, University Hospital Essen, Essen, Germany; 9University of Colorado, Aurora, CO; 10Seoul National University Hospital, Seoul, Korea, Republic of (South); 11Fred Hutchinson Cancer Research Center, Seattle, WA; 12Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 13Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 14Washington University School of Medicine, St. Louis, MO; 15King's College Hospital, Institute of Liver Studies, London, United Kingdom; 16University of Milano, European Institute of Oncology, Division of Early Drug Development, Milan, Italy; 17Blueprint Medicines Inc, Cambridge, MA BACKGROUND • RET alterations are targetable oncogenic drivers in multiple tumor types, including ~90% of advanced medullary thyroid cancer (MTC)1 and 20% of papillary thyroid cancer (PTC)2,3 • No selective RET inhibitors are approved BLU-667: High kinome selectivity for RETa BLU-667: Designed to Treat RET-Altered Cancers • BLU-667 was approximately 90-fold more selective for RET than VEGFR2 • BLU-667 was 20-fold more selective for RET than JAK1 Table presents IC50, half maximal inhibitory concentration Part 1: Dose-Escalation (Complete; N=62) RET-altered advanced solid tumors BLU-667 30-600 mg PO daily (QD or BID) Phase 2 dose determined (400 mg QD) BLU-667 400 mg QD • Unresectable, advanced solid tumor • RET alteration status by local tumor testing • No additional driver mutation • ECOG PS 0-1 • Progressive disease or intolerant to SOC therapy, or not a candidate Primary objectives: • Overall response rate (RECIST 1.1) • Safety Part 2: Expansion Cohorts (Ongoing) RET fusion+ NSCLC, prior platinum (n=80) RET fusion+ NSCLC, platinum naïve (n=40) MTC, prior cabozantinib or vandetanib (n=60) MTC, no prior cabozantinib or vandetanib (n=40) RET fusion+ tumors, including PTC (n=40) RET-altered, prior selective RET inhibitor (n=20) Other RET-mutated tumors (n=20) Antitumor Activity Characteristic RET fusion+ PTC (All Starting Doses; N=9a) Age (years), median (range) 66 (23–70) Male, n (%) 5 (56) ECOG PS, n (%) 0 1-2 4 (44) 5 (56) Metastatic disease, n (%) 9 (100) Prior systemic regimens, median (range) 2 (0–8) Any prior anticancer treatment Sorafenib or lenvatinib, n (%) Radioactive iodine, n (%) 8 (89) 3 (33) 8 (89) RET fusion partner CCDC6 NCOA4 Other (SNRNP70) 4 (44) 4 (44) 1 (11) aIncludes 2 patients with starting doses of 200 mg and 300 mg QD in dose-escalation. CONCLUSIONS • BLU-667 demonstrates broad and durable antitumor activity in patients with advanced, RET-altered MTC and PTC - 63% ORR and 94% DCR in RET-mutated MTC previously treated with cabozantinib or vandetanib; 83% ORR in PTC - Reponses observed regardless of treatment history or RET mutation genotype (including gatekeeper mutation V804M) - Well-tolerated at 400 mg QD; all responding patients with MTC remain on treatment • Breakthrough therapy designation granted for RET-mutated MTC requiring systemic treatment and for which there are no acceptable alternative treatments • Additional cohorts continue to assess benefit of BLU-667 in multiple other RET- mutated and RET fusion+ solid tumors BLU-667 IC50 Cabozantinib IC50 Vandetanib IC50 Wild-type RET 0.4 11 4 RET V804L Gatekeeper resistance 0.3 45 3597 RET V804M Gatekeeper resistance 0.4 162 726 RET M918T Mutation 0.4 8 7 CCDC6-RET Fusion 0.4 34 20 VEGFR2 Anti-target 35 2 4 BLU-667 potently and selectively inhibits RET alterations, including those that confer resistance to MKI, while sparing VEGFR.4 Patient Baseline Characteristics RESULTS: ADVANCED RET FUSION+ PTC Patient Baseline Characteristics Tolerability Among 9 patients with RET fusion+ PTC (regardless of starting dose): • Safety profile similar to MTC • No patients discontinued BLU-667 due to treatment-related toxicity Adverse Event Term RET-mutated MTC (400 mg QD Starting Dose; N=64) Treatment-Emergent (≥15% overall) n (%) Treatment-Related n (%) All Grade ≥3 All Grade ≥3 Hypertension 26 (41) 15 (23) 19 (30) 10 (16) Constipation 21 (33) 1 (2) 12 (19) 1 (2) Neutropeniaa 17 (27) 7 (11) 15 (23) 7 (11) Anemia 14 (22) 3 (5) 6 (9) 1 (2) Aspartate aminotransferase increased 14 (22) - 9 (14) - Leukopeniab 14 (22) 1 (2) 11 (17) - Alanine aminotransferase increased 13 (20) - 8 (13) - Diarrhea 13 (20) 3 (5) 6 (9) 1 (2) Headache 12 (19) - 5 (8) - Blood creatinine increased 11 (17) - 7 (11) - Fatigue 11 (17) - 6 (9) - Hypocalcemia 11 (17) 4 (6) 4 (6) 1 (2) Additional grade ≥3 treatment related AEs (≥2%): blood creatine phosphokinase increased (5%). aCombined term including decreased neutrophil count. bCombined term including decreased white blood cell count. Characteristic RET-mutated MTC (400 mg QD Starting Dose) All (N=64) Prior Cabo or Vand (N=43) Age (years), median (range) 59 (19–81) 57 (25–81) Male, n (%) 42 (66) 27 (63) ECOG PS, n (%) 0 1-2 21 (33) 43 (66) 9 (21) 33 (79) Metastatic disease, n (%) 64 (100) 43 (100) Prior systemic regimens, median (range) 1 (0–10) 2 (1–10) Any prior anticancer treatment Cabozantinib or vandetanib, n (%) Cabozantinib and vandetanib, n (%) 50 (78) 43 (67) 13 (20) 43 (100) 43 (100) 13 (30) RET mutation, n (%) M918T C634R/S/W V804M Other 36 (56) 10 (16) 3 (5) 15 (23) 26 (61) 7 (16) 2 (5) 8 (19) Cabo, cabozantinib; vand, vandetanib. 6018 IC50, half maximal inhibitory concentration, MKI, multikinase inhibitor. aKinome 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. ARROW: BLU-667 Dose-Escalation/Expansion Study Acknowledgments We thank the participating patients, their families, all study co-investigators, research coordinators and data managers who contributed to this study. Third- party writing assistance was provided by Ashfield Healthcare and funded by Blueprint Medicines. References 1. Romei, et al. Oncotarget, 2018;9:9875-9884. 2. Santoro, et al. J Clin Invest. 1992;89(5):1517-1522. 3. Song, et al. Endocrinol Metab. 2015;30:252-262. 4. Subbiah, et al. Cancer Discov. 2018;8(7):836-849. QR Code Disclaimer Copies of this poster obtained through QR (Quick Response) code are for personal use only and may not be reproduced without written permission of the authors. BID, twice daily dosing; ECOG PS, Eastern Cooperative Oncology Group performance status; PO, orally; QD, once daily dosing; RECIST, response evaluation criteria in solid tumors; SOC, standard of care. • ORR: 83% (5/6)a • 5 pts have received treatment for ≥1 year • 8 of 9 pts continue treatment aConfirmation of response is pending for two patients. Three patients are not response evaluable due to absence of measurable disease at baseline (n=1) and pending response assessments (n=2). Antitumor Activity RET fusion+ PTC (All starting doses) Tolerability Among 64 patients with RET-mutated MTC receiving BLU-667 starting dose of 400 mg QD: • Treatment-related toxicity is generally low-grade and reversible • No patients discontinued BLU-667 due to treatment-related toxicity (4% across the entire study) All MTC (n=32) Prior Cabo or Vand (n=16) ORR (95% CI) 56% (38–74) 63% (35–85) Best response: CR PRb SD PD 1 17 13 1 - 10 5 1 DCR (95% CI) 97% (84–100) 94% (70–100) Tumor shrinkage 94% 100% Treatment ongoing Cabo and Vand-naïve Prior Cabo or Vand CR PR PD Presented at the Annual Congress of the American Society of Clinical Oncology Annual Meeting, June 1, 2019, Chicago, IL 0 2 4 6 8 10 12 14 -100 -80 -60 -40 -20 0 20 Study Month % C h a n g e i n S u m o f T a r g e t L e s i o n D i a m e t e r s * SD PR PD • Patients remain on treatment up to 15.6 months, with treatment ongoing • Responses accumulate over time • All 18 patients with tumor response remain on treatment • Median duration of response not yet reached * Data are preliminary and based on a data cut-off date of April 28, 2019. BLU-667 is an investigational agent discovered and currently in development by Blueprint Medicines Corporation (Blueprint Medicines). ARROW is registered with clinicaltrials.gov (NCT03037385) * RET Mutant ctDNA Calcitonin CEA -100 -50 0 50 100 % R e d u c t i o n f r o m B a s e l i n e C y c l e 2 D a y 1 RET Mutant ctDNA -100 -50 0 50 % R e d u c t i o n f r o m B a s e l i n e C y c l e 2 D a y 1 Calcitonin -100 -50 0 50 % R e d u c t i o n f r o m B a s e l i n e C y c l e 2 D a y 1 CEA |
Exhibit 99.5
| Clinical Activity and Tolerability of BLU-667, a Highly Potent and Selective RET Inhibitor, in Patients with Advanced RET-Fusion+ Non-small Cell Lung Cancer Justin F. Gainor1, Dae Ho Lee2, Giuseppe Curigliano3, Robert C. Doebele4, Dong-Wan Kim5, Christina S. Baik6, Daniel Shao-Weng Tan7, Gilberto Lopes8, Shirish M. Gadgeel9, Philippe Alexandre Cassier10, Matthew H. Taylor11, Stephen V. Liu12, Benjamin Besse13, Michael Thomas14, Viola Weijia Zhu15, Hui Zhang16, Corinne Clifford16, Michael R. Palmer16, Christopher D. Turner16, Vivek Subbiah17 1Massachusetts General Hospital, Boston, MA; 2University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South); 3University of Milano, European Institute of Oncology, Division of Early Drug Development, Milan, Italy; 4University of Colorado Cancer Center, Aurora, CO; 5Seoul National University Hospital, Seoul, Korea, Republic of (South); 6Fred Hutchinson Cancer Research Center, Seattle, WA; 7National Cancer Center, Singapore, Singapore; 8Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; 9University of Michigan/Rogel Cancer Center, Ann Arbor, MI; 10Centre Léon-Bérard, Lyon, France; 11Oregon Health & Science University, Portland, OR; 12Georgetown University Medical Center, Washington, DC; 13Paris-Sud University, Orsay and Gustave Roussy, Villejuif, France; 14Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany; 15Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA; 16Blueprint Medicines Inc, Cambridge, MA; 17The University of Texas MD Anderson Cancer Center, Houston, TX Justin F. Gainor 1 PRESENTATION DATE: June 3, 2019 |
| Disclosures 2 Justin F. Gainor, MD • Honoraria: Pfizer, Novartis, Theravance, Merck, Incyte, Roche • Consulting or advisory role: Bristol-Myers Squibb, Ariad/Takeda, Genentech/Roche, Loxo, Blueprint Medicines, Amgen, Agios, Regeneron, Oncorus • Research funding: Novartis, Genentech, Takeda • Institutional Research funding: Tesaro, Moderna, Blueprint Medicines, Bristol-Myers Squibb, Jounce, Array Biopharma, Adaptimmune, Novartis, Alexo, Merck • Travel: Novartis, Pfizer, Takeda, Genentech/Roche • Employment: Ironwood Pharmaceuticals (Spouse) BLU-667 is an investigational agent discovered by and currently in development by Blueprint Medicines Corporation (Blueprint Medicines) Justin F. Gainor |
| RET Alterations: Diverse Oncogenic Drivers Lacking Targeted Therapeutic Approach Justin F. Gainor 3 • Chemotherapy: nonspecific, low response rates, significant toxicity NSCLC patients with RET fusions have not significantly benefited from existing therapy Non-small cell lung cancer: ~1-2% RET fusions1,2 Advanced medullary thyroid cancer: ~90% RET mutations3 Papillary thyroid cancer: ~20% RET fusions4 Multiple other tumor types including esophageal, breast, melanoma, colorectal, and leukemia: <1% RET-altered5,6 NSCLC, non-small cell lung cancer; ORR, overall response rate; PFS, progression-free survival. 1. Lipson, et al. Nat Med 2012; 2. Takeuchi, et al. Nat Med 2012; 3. Romei, et al. Oncotarget 2018; 4. Santoro, et al. J Clin Invest 1992; 5. Kato, et al. Clin Cancer Res 2017; 6. Ballerini, et al. Leukemia 2012; 7. Mazieres, et al. JCO 2018; 8. Drillon, et al. Lancet 2017; 9. Yoh, et al. Lancet Respir Med 2017 • Checkpoint inhibition: Preliminary evidence for lack of benefit in RET-altered NSCLC7 • Multikinase inhibitors: ↓ activity, ↑ off-target toxicity8,9 No selective RET inhibitors are approved |
| BLU-667 Potently and Selectively Inhibits RET Alterations and Resistance Mutants Justin F. Gainor 4 aKinome 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. BLU-667 is an investigational agent discovered and currently in development by Blueprint Medicines Corporation (Blueprint Medicines). 1. Subbiah, et al. Cancer Discovery 2018; 2. Blueprint internal data BLU-667: High kinome selectivity for RETa BLU-667 vs. pharmacologically relevant kinases: • 90-fold more selective for RET than VEGFR2 • 20-fold more selective for RET than JAK1 BLU-667 Cellular activity in KIF5B-RET2 KIF5B-RET KIF5B-RET V804L KIF5B-RET V804M KIF5B-RET V804E BLU-667 10.1 nM (1x) 8.1 nM (0.8x) 14.1 nM (1.4x) 8.1 nM (0.8x) KIF5B-RET Cabozantinib-resistant KIF5B-RET(V804L) In vivo models of implanted, engineered Ba/F3 cells1 Vehicle QD Cabozantinib 60 mg/kg QD BLU-667 3 mg/kg BID BLU-667 10 mg/kg BID BLU-667 30 mg/kg BID |
| ARROW: BLU-667 Dose-Escalation and Expansion Study ARROW is registered with clinicaltrials.gov (NCT03037385) Part 1: Dose-Escalation (N=62; Complete)1 Phase 2 dose determined (400 mg QD) Justin F. Gainor 5 BID, twice daily dosing; ECOG PS, Eastern Cooperative Oncology Group performance status; MTC, medullary thyroid cancer; QD, once daily dosing; RECIST, response evaluation criteria in solid tumors; SOC, standard of care. 1. Subbiah, et al. Cancer Res 2018. RET-altered advanced solid tumors BLU-667: 30-600 mg by daily oral administration (QD or BID) RET fusion+ NSCLC, prior platinum (n=80) RET fusion+ NSCLC, platinum naïve (n=40) MTC, prior cabozantinib or vandetanib (n=60) MTC, no prior cabozantinib or vandetanib (n=40) Other RET fusion+ tumors (n=40) RET-altered, prior selective RET inhibitor (n=20) Other RET-mutated tumors (n=20) Part 2: Expansion Cohorts (Ongoing) BLU-667 400 mg QD • Unresectable, advanced solid tumor • RET alteration status by local tumor testing • No additional driver mutation • ECOG PS 0-1 • Asymptomatic brain metastases allowed • Progressive disease or intolerant to SOC therapy, or not a candidate Primary objectives: Overall response rate (RECIST 1.1) Safety |
| Baseline Characteristics RET Fusion+ Advanced NSCLC Patients ECOG PS, Eastern Cooperative Oncology Group Performance Status. aSmoking history is unknown for one patient. bIncludes RET fusion+ by fluorescence in situ hybridization (FISH); RET fusion partner to be determined via central analysis. Data cut-off date: 28 Apr 2019. Justin F. Gainor 6 RET Fusion Partner KIF5B 66% CCDC6 13% Other (DOCK1, EML4) 2% Fusion partner unknownb 19% RET-Fusion+ Advanced NSCLC 400 mg QD Starting Dose Characteristic All (N=120) Prior Platinum (N=91) Age (years), median (range) 60 (28-87) 60 (28-85) Male, n (%) 59 (49) 45 (49) ECOG PS, n (%) 0 46 (38) 33 (36) 1-2 74 (62) 58 (64) Brain metastases, n (%) 48 (40) 36 (40) Prior systemic regimens, median (range) 2 (0-11) 2 (1-11) Any prior anticancer treatment 101 (84) 91 (100) Chemotherapy, n (%) 92 (77) 91(100) PD-1 or PD-L1 inhibitor, n (%) 47 (39) 41 (45) Chemotherapy + PD-(L)1 combination, n (%) 41 (34) 41 (45) Multikinase inhibitor, n (%) 21 (18) 20 (22) Smoking historya Current/Prior 41 (34) 33 (36) Never 78 (65) 57 (63) Histology Adenocarcinoma 114 (95) 87 (96) Other 6 (5) 4 (4) |
| BLU-667 is Well Tolerated by Patients with RET Fusion+ Advanced NSCLC RET Fusion+ Advanced NSCLC 400 mg QD Starting Dose (N=120) Adverse Events Treatment-Emergent (≥15% overall) Treatment-Related All Grade ≥3 All Grade ≥3 Constipation 30% 2% 17% 2% Neutropeniaa 26% 13% 26% 13% AST increased 24% 5% 20% 2% Fatigue 21% 3% 13% 3% Hypertension 20% 13% 13% 10% Anemia 18% 7% 11% 4% Diarrhea 18% 2% 9% - Pyrexia 18% - 2% - ALT increased 17% 3% 13% 2% Cough 17% - 3% - Dry mouth 17% - 12% - Justin F. Gainor Among 120 pts with advanced NSCLC receiving BLU-667 starting dose of 400 mg QD: • Treatment-related toxicity is generally low-grade and reversible • 7% discontinued BLU-667 due to treatment-related toxicity* - Pneumonitis, respiratory distress/ hypoxemia, mucositis/colitis, myelosuppression, gait disturbance, anemia Additional grade ≥3 treatment related AEs (≥2%): increased CPK (3%), leukopeniab (3%). 7 aCombined term including decreased neutrophils and neutropenia. bCombined term including leukopenia and white blood cell count decreased. AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase. Data cut-off date: 28 Apr 2019. * Across the entire study (n=276), rate of discontinuation due to treatment-related toxicity is 4%. |
| BLU-667 Demonstrates Substantial Antitumor Activity in RET Fusion+ Advanced NSCLC 8 CI, confidence interval; CR, complete response; DCR, disease control rate (best response of SD or better); ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease. Patients enrolled by 14 Nov 18, data cut-off 28 Apr 19. Response-evaluable population includes patients with measurable disease at baseline and ≥1 evaluable post-treatment disease assessment, and excludes 4 patients who previously received >1 cycle of a selective RET inhibitor. -100 -80 -60 -40 -20 0 20 40 Maximum % Reduction from Baseline Sum of Diameters of Target Lesions BLU-667 Starting Dose 400 mg QD Platinum-naive Prior Platinum Justin F. Gainor * All responses are confirmed on two consecutive assessments as per RECIST 1.1. ● 5/7 (71%) treatment-naïve patients had confirmed PR Best Response All (N=48) Prior Platinum (N=35) ORR (95% CI) 58% (43–72) 60% (42–76) CR* PR* SD PD 1 27 18 2 1 20 14 - DCR (95% CI) 96% (86–99) 100% (90–100) |
| 0 2 4 6 8 10 12 14 16 Treatment Duration (Months) BLU-667 Induces Rapid and Durable Responses in RET Fusion+ Advanced NSCLC 9 Justin F. Gainor Patients enrolled by 14 Nov 18, data cut-off 28 Apr 19. Treatment ongoing Treatment after PD Post-treatment follow-up CR PR PD - Most responses occur at the first scan (week 8) - 82% of responding patients remain on treatment as of the data cut-off - Median duration of response not yet reached - Patients have been on treatment up to 24 months (including dose-escalation and regardless of starting dose) Duration of Treatment and Response: BLU-667 Starting Dose 400 mg QD |
| BLU-667 is Active Regardless of Prior Checkpoint Treatment Justin F. Gainor -100 -80 -60 -40 -20 0 20 40 Maximum Reduction - Sum of Diameter Change from Baseline, % BLU-667 Starting Dose 400 mg QD 10 Patients enrolled by 14 Nov 18, data cut-off 28 Apr 19. -100 -80 -60 -40 -20 0 20 40 Maximum % Reduction from Baseline Sum of Diameters of Target Lesions BLU-667 Starting Dose 400 mg QD Prior PD-1 or PD-L1 inhibitor PD-1 and PD-L1 inhibitor naïve |
| BLU-667 is Active Across RET Fusion Genotypes Justin F. Gainor -100 -80 -60 -40 -20 0 20 40 Maximum % Reduction from Baseline Sum of Diameters of Target Lesions BLU-667 Starting Dose 400 mg QD CCDC6 KIF5B Other/unknown 11 Patients enrolled by 14 Nov 18, data cut-off 28 Apr 19. |
| BLU-667 is Active Regardless of CNS Involvement Justin F. Gainor -100 -80 -60 -40 -20 0 20 40 Maximum % Reduction from Baseline Sum of Diameters of Target Lesions BLU-667 Starting Dose 400 mg QD CNS involvement No CNS involvement 12 CNS, central nervous system Patients enrolled by 14 Nov 18, data cut-off 28 Apr 19. |
| BLU-667 is Active Against Intracranial Metastases • 7 of 9 (78%) patients had shrinkage of measurable brain metastases • No patients at 400 mg QD starting dose had progression due to new CNS involvement Justin F. Gainor 13 aData shown for 9 patients with brain lesion(s) identified as RECIST 1.1 target lesions at baseline. Data cut-off date: 28 Apr 2019. 0 2 4 6 8 -100 -75 -50 -25 0 25 50 Months on Study C h a n g e i n S u m o f D i a m e t e r o f T a r g e t B r a i n L e s i o n s , % Shrinkage of Brain Metastasesa RET fusion partner: Unknown CCDC6 KIF5B |
| • 52-year-old woman, RET fusion+ NSCLC, prior platinum and checkpoint inhibitor • Near-complete resolution of previously untreated target brain metastasis after two months of BLU-667 400 mg QD • Continues to receive treatment with ongoing confirmed PR (70% shrinkage) at 6 months • 59-year-old man, RET fusion+ NSCLC, prior platinum and checkpoint inhibitor • Complete resolution of previously untreated nontarget brain metastasis after two months of BLU-667 400 mg QD • Continues to receive treatment with ongoing confirmed PR (67% shrinkage) at 6 months BLU-667 is Active Against Intracranial Metastases Images courtesy Dr. P Cassier Centre Leon Berard, Lyon, FR Images courtesy of Dr. Stephen Liu, Georgetown University, Washington, D.C. Justin F. Gainor 14 Data cut-off 28 Apr 19. Baseline Cycle 3, Day 1 Baseline Cycle 3, Day 1 |
| Rapid and Robust Clearance of RET Variant ctDNA with BLU-667 Among patients receiving a BLU-667 starting dose of 400 mg QD: • 18/20 (90%) with detectable RET fusion ctDNA at baseline had complete clearance within the first cycle • Clearance of genomic driver variants ctDNA has been associated with improved cancer outcomes1–3 -100 -50 0 % c t D N A R e d u c t i o n ( C 2 D 1 f r o m B a s e l i n e ) Best response PD SD PR RET Fusion+ Advanced NSCLC, BLU-667 starting dose 400 mg QD Justin F. Gainor 15 ctDNA: circulating tumor DNA. Data cut-off date: 28 Apr 2019. 1. Cabel, et al. Ann Oncol 2017; 2. Mok, et al. Clin Cancer Res 2015; 3. Drilon, et al. Nat Rev Clin Oncol 2018; Awad, et al. J Thorac Oncol 2018. |
| BLU-667 has Activity in Other RET Fusion+ Malignancies • PR in 2/2 patients with metastatic pancreatic cancer - 67 yo male, CCDC6-RET fusion, continues with confirmed PR (53% shrinkage) at 6 months – 31 yo male, TRIM33-RET and JMJD1C-RET fusions, continues treatment after PR (41% shrinkage) at first response assessment • PR in a patient with intrahepatic bile duct carcinoma – 51 yo female, NCOA4-RET fusion, continues with confirmed PR (67% shrinkage) at 15 months • ORR 83% (5/6)* in RET-fusion PTC (Abstract 6018 presented June 1, 2019) • Safety profile similar to what was seen in RET fusion+ NSCLC 16 Justin F. Gainor * Confirmation of response is pending for two patients. Data cut-off date: 28 Apr 2019. |
| Conclusions • BLU-667 demonstrates broad and durable antitumor activity in patients with RET fusion+ advanced NSCLC - 60% ORR and 100% DCR in patients previously treated with platinum chemotherapy, and 58% ORR in all RET fusion+ patients - Responses observed regardless of treatment history, RET fusion partner or CNS involvement - Active against intracranial metastases - Well tolerated at 400 mg QD with most AEs grade 1/2 • BLU-667 has FDA breakthrough therapy designation in RET fusion+ NSCLC that progressed following platinum based chemotherapy • Data support expansion of ARROW trial in treatment-naïve NSCLC patients and continued enrollment of other RET-altered solid tumor groups 17 Justin F. Gainor RP2D, recommended phase 2 dose. Data are preliminary and based on a data cut-off date of April 28, 2019. |
| Acknowledgments • Participating patients and families • BLU-667-1101 Investigators and research coordinators • Colleagues at Blueprint Medicines Corporation 18 Justin F. Gainor - The University of Texas MD Anderson Cancer Center, Houston, TX, United States - Oregon Health & Science University, Portland, OR, United States - Massachusetts General Hospital Cancer Center, Boston, MA, United States - University of Pennsylvania, Philadelphia, PA, United States - University of California Irvine Medical Center, Irvine, CA, United States - University of Miami, Miami, FL, United States - Georgetown University Medical Center, Washington, District of Columbia, United States - University of Washington, Seattle, WA, United States - University of Michigan, Ann Arbor, MI, United States - Cornell University, New York, NY, United States - University of Colorado, Aurora, CO, United States - Washington University School of Medicine, St. Louis, MO, United States - Mayo Clinic, Rochester, MN, United States - Mayo Clinic, Jacksonville, FL, United States - Mayo Clinic, Phoenix, AZ, United States - Texas Oncology, Dallas, TX, United States - Thoraxklinik Heidelberg, Heidelberg, Germany - Universitatsklinikum Essen, Essen, Germany - Pius-Hospital Oldenberg, Oldenberg, Germany - Vall d’Hebron University Hospital, Barcelona, Spain - Hospital Universitario 12 de Octubre, Madrid, Spain - Hospital Universitario Ramon y Cajal, Madrid, Spain - Hospital Clinic Barcelona, Barcelona, Spain - Hospital Duran I Reynals, Barcelona, Spain - Centre Leon Berard, Lyon, France - Gustave Roussy, Villejuif, France - Institut Claudius Regaud, Toulouse, France - CHU de Rennes, Rennes, France - CHRU de Lille, Lille, France - Institut Bergonie, Bordeaux, France - University College of London NHS Foundation Trust, London, UK - Guy’s Hospital St. Thomas NHS Foundation Trust, London, UK - The Christie NHS Foundation Trust, Manchester, UK - University of Milano, Istituto Europeo di Oncologia, Milan, Italy - Grande Ospedale Metropolitano Niguarda, Milan, Italy - University Medical Center Gronigen, Gronigen, Netherlands - National Cancer Centre Singapore, Singapore, Singapore - Seoul National University Hospital, Seoul, Republic of Korea - Asan Medical Center, Seoul, Republic of Korea - Severance Hospital, Seoul, Republic of Korea - National Taiwan University Hospital, Taipei, Taiwan |
