News Releases

-- Breadth of pipeline featured in multiple early clinical data presentations, reflecting diversity of fundamental growth drivers across development programs --

CAMBRIDGE, Mass., June 3, 2023 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced clinical data for multiple programs across its precision therapy portfolio at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentations showcase the company's progress in developing precision therapies to address the needs of broad patient populations, including hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer and EGFR-mutant non-small cell lung cancer (NSCLC).

"At ASCO, we are reporting early clinical data for three therapeutic candidates highlighting the breadth of our pipeline, which lays the foundation for our next wave of precision therapy programs to tackle significant medical challenges," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Together, these presentations reflect how we are developing differentiated, highly selective therapies against promising disease targets, and demonstrate strong execution in advancing potential treatment options for large patient populations, including HR+/HER2- breast cancer and EGFR-mutant lung cancer. The datasets represent a diversity of fundamental value drivers in our clinical portfolio, which create opportunities to substantially expand our patient impact and highlight our ambition to deliver many more transformational medicines to patients in the future."

CDK2 Program

CDK2 is a cell cycle regulator and important cancer target across a broad range of malignancies, including HR+/HER2- breast cancer. Based on the underlying science on the role of CDK2 inhibition in cancer, and the potential for this mechanism to impact large populations of patients, BLU-222 represents one of the most important programs within Blueprint Medicines' early clinical development pipeline. The data reported at ASCO begin to demonstrate the clinical profile of BLU-222, a highly selective and potent oral CDK2 inhibitor.

VELA trial: BLU-222 in HR+/HER2- metastatic breast cancer and other advanced cancers
Abstract number: 3095
Presentation location and time: Hall A; Saturday, June 3 from 8:00 a.m. — 11:00 a.m. CT

Results from the ongoing dose escalation part of the VELA trial of BLU-222 (n=27) showed encouraging safety and evidence of cell cycle pathway modulation consistent with the treatment's best-in-class preclinical profile. Based on these data, Blueprint Medicines is continuing monotherapy dose escalation to identify a maximum tolerated dose, and has initiated dose escalation of BLU-222 in combination with the CDK4/6 inhibitor, ribociclib, and the estrogen receptor antagonist, fulvestrant, in patients with HR+/HER2- metastatic breast cancer.

• BLU-222 was generally well-tolerated with no discontinuations due to adverse events (AEs). Treatment-related hematologic AEs commonly seen with CDK4/6 inhibitors were generally mild and primarily reported in patients with a history of low blood cell counts. No cardiac AEs or QTc prolongation were observed.
• BLU-222 showed evidence of cell cycle pathway modulation as demonstrated by circulating and tumor tissue-based biomarker data. Increased BLU-222 doses led to robust reductions in thymidine kinase 1 (TK1) activity and phosphorylated retinoblastoma (pRB).
• In addition, the presentation highlighted a confirmed partial response in a BLU-222 monotherapy-treated patient with HR+/HER2- metastatic breast cancer who previously received five lines of therapy, including the CDK4/6 inhibitors palbociclib and abemaciclib.

EGFR Programs

EGFR represents one of the most common oncogenic drivers in NSCLC, and Blueprint Medicines is developing a portfolio of investigational precision therapies to inhibit the broad spectrum of EGFR activating and resistance mutations. With three novel EGFR inhibitors, the company seeks to transform treatment options for patients with EGFR-mutant NSCLC, including with highly active, well-tolerated combinations in the front-line setting. Data reported at ASCO feature two of the company's investigational EGFR inhibitors:

• BLU-451, a wildtype-EGFR-sparing, CNS-penetrant oral inhibitor of EGFR exon 20 insertions and atypical mutations with best-in-class potential
• BLU-945, a potent oral EGFR inhibitor designed to be highly selective over wildtype EGFR, supporting its potential as a differentiated combination partner

CONCERTO trial: BLU-451 in advanced NSCLC driven by EGFR exon 20 insertions or atypical mutations
Abstract number: 9064
Presentation location and time: Hall A; Sunday, June 4 from 8:00 a.m. — 11:00 a.m. CT

Results from the ongoing dose escalation part of the CONCERTO trial of BLU-451 in heavily pretreated patients with NSCLC driven by EGFR exon 20 insertions (n=48) or atypical mutations (n=9) showed evidence of safety and clinical benefits, including central nervous system (CNS) activity. The data support continued dose escalation to determine the recommended Phase 2 dose (RP2D), and further development in patients with EGFR exon 20 insertions as well as additional patients with atypical EGFR mutations. Collectively, these mutations represent approximately 20 percent of EGFR-mutant NSCLC cases.

• BLU-451 was generally well-tolerated in patients, with no grade 3 or higher AEs associated with wildtype EGFR inhibition, no dose-limiting toxicities and no discontinuations due to treatment-related AEs.
• In patients with EGFR exon 20 insertion-positive NSCLC, BLU-451 demonstrated evidence of clinical activity including circulating tumor DNA (ctDNA) clearance, tumor reductions including confirmed partial responses, and CNS activity. Multiple patients showed CNS benefits including one who had a partial CNS response per RECIST version 1.1 criteria and one who had a CNS complete response with resolution of multiple non-target brain lesions, as highlighted by patient vignettes in the presentation.
• In patients with NSCLC driven by atypical EGFR mutations, BLU-451 showed emerging dose-dependent ctDNA clearance and tumor shrinkage, reflecting an expanded development opportunity.

SYMPHONY trial: BLU-945 monotherapy and in combination with osimertinib in late-line, EGFR-mutant NSCLC
Abstract number: 9011
Presentation location and time: S406; Monday, June 5 from 11:30 a.m. — 12:30 p.m. CT

Updated results from the dose escalation part of the SYMPHONY trial showed the safety and clinical activity of BLU-945 as a monotherapy (n=112) and in combination with osimertinib (n=55) in patients with late-line, osimertinib-refractory, EGFR-mutant NSCLC. Based on the unprecedented and favorable safety profile for the combination of BLU-945 and osimertinib observed to-date, dose escalation is continuing which impacts the timeframe to establish the RP2D and begin the randomized, first-line treatment portion of the study. Consequently, the company no longer anticipates presenting initial dose expansion data for BLU-945 in combination with osimertinib in first-line, EGFR L858R-positive NSCLC by the end of 2023.

• BLU-945, as a monotherapy and in combination with osimertinib, was generally well-tolerated, and AEs associated with wildtype EGFR inhibition were infrequent, with the majority reported as Grade 1. For the combination, the discontinuation rate due to treatment-related AEs was 3.6 percent.
• BLU-945 monotherapy and the combination showed evidence of clinical activity, with ctDNA clearance and tumor reductions including confirmed partial responses observed in patients whose tumors had progressed following treatment with osimertinib. For combination regimens with a total BLU-945 daily dose of 300 mg or higher, tumor shrinkage was observed in 51 percent of patients with molecularly heterogenous, osimertinib-refractory, late-line EGFR-mutant NSCLC, with multiple confirmed responses.

Copies of Blueprint Medicines data presentations from the ASCO Annual Meeting are available in the "Science—Publications and Presentations" section of the company's website at www.blueprintmedicines.com.

About Blueprint Medicines

Blueprint Medicines is a global precision therapy company that invents life-changing therapies for people with cancer and blood disorders. Applying an approach that is both precise and agile, we create medicines that selectively target genetic drivers, with the goal of staying one step ahead across stages of disease. Since 2011, we have leveraged our research platform, including expertise in molecular targeting and world-class drug design capabilities, to rapidly and reproducibly translate science into a broad pipeline of precision therapies. Today, we are delivering our approved medicines to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer, breast cancer and other genomically defined cancers, and cancer immunotherapy. 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 Blueprint Medicines' views with respect to its ability to expand its patient impact and deliver more transformational medicines to patients; the potential benefits of Blueprint Medicines' current and future approved drugs or drug candidates in treating patients; and Blueprint Medicines' strategy, goals and anticipated milestones, business plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to our ability and plans in continuing to expand Blueprint Medicines' commercial infrastructure, and successfully launching, marketing and selling current or future approved products; Blueprint Medicines' ability to successfully expand the approved indications for AYVAKIT/AYVAKYT or obtain marketing approval for AYVAKIT/AYVAKYT in additional geographies in the future; the delay of any current or planned clinical trials or the development of our current or future drug candidates; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for its products or any drug candidates it is developing; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its products or any of its current and future drug candidates; Blueprint Medicines' ability to successfully expand its research platform and the costs thereof; and the success of Blueprint Medicines' current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the SEC on February 16, 2023, 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 assumes no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

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SOURCE Blueprint Medicines Corporation