-- Early dose escalation data show
dose-dependent reductions in ctDNA and tumor burden --
-- Generally well-tolerated with most AEs
Grade 1 or 2, supporting continued dose escalation --
-- Initiating SYMPHONY trial cohort to
evaluate BLU-945 in combination with osimertinib --
-- Clinical trial supply agreement signed with
AstraZeneca to provide osimertinib for combination development in
ongoing BLU-945 and BLU-701 trials --
-- Blueprint Medicines to host investor
conference call and webcast on Friday, April
8 at 2:00 pm ET --
CAMBRIDGE, Mass., April 8,
2022 /PRNewswire/ -- Blueprint Medicines Corporation
(NASDAQ: BPMC) today announced proof-of-concept data from the Phase
1/2 SYMPHONY clinical trial of BLU-945, an investigational
precision therapy for advanced EGFR-mutant non-small cell lung
cancer (NSCLC). The trial results showed early evidence of safety
and clinical activity consistent with preclinical data, supporting
plans to expand development of BLU-945 in combination with multiple
agents including osimertinib, with the goal of preventing or
treating tumor resistance to prolong patient benefit. The data were
reported today at the American Association for Cancer Research
(AACR) Annual Meeting 2022 in New
Orleans.
Early data from the ongoing Phase 1 dose escalation part of the
SYMPHONY trial showed dose-dependent decreases in circulating tumor
DNA (EGFR variant allele fractions) and radiographic tumor
reductions, including a partial response (PR) in a patient treated
with 400 mg once daily (QD), the highest dose tested as of the data
cutoff date. Pharmacokinetic results showed BLU-945 exposures at
higher doses were associated with broad EGFR mutation coverage,
including the activating L858R mutation with or without the
osimertinib-resistant C797S mutation. BLU-945 was generally
well-tolerated, with no significant adverse events (AEs) associated
with wild-type EGFR inhibition. The maximum tolerated dose and
recommended Phase 2 dose have not yet been identified, and dose
escalation is continuing.
"Today, targeted therapies are the mainstay treatment for
EGFR-mutant lung cancer, but tumor resistance emerges in the
majority of patients, driving mutational heterogeneity and disease
progression. Innovative treatment strategies, including targeted
therapy combinations, are urgently needed to prevent or treat this
mutational heterogeneity and prolong patient benefit," said
Elaine Shum, M.D., assistant
professor in the Department of Medicine and a medical oncologist at
NYU Langone Health's Perlmutter Cancer Center, and an investigator
on the SYMPHONY trial. "The initial BLU-945 data reported today,
which highlight its potential to address resistance to current
standard of care therapies including osimertinib and enable
well-tolerated, broad-acting combinations, are an important step
forward toward improving outcomes for patients with EGFR-mutant
lung cancer."
"We believe BLU-945 is distinguished from other EGFR-directed
therapies, based on its ability to inhibit the most
difficult-to-target EGFR mutations while maintaining a wide
therapeutic index over wild-type EGFR, a known driver of toxicity.
As a result, BLU-945 has significant potential as a combination
partner with other targeted therapies and broad-acting agents,"
said Fouad Namouni, M.D., President, Research & Development at
Blueprint Medicines. "We are excited to see the preclinical profile
of BLU-945 translated in the clinic, with early dose escalation
data showing evidence of clinical activity, broad EGFR mutation
coverage and tolerability. Based on these promising data, we plan
to rapidly expand development of BLU-945 in combination with
osimertinib and other agents to address important medical needs
across all lines of therapy."
Blueprint Medicines is initiating a SYMPHONY trial cohort
assessing BLU-945 in combination with osimertinib in patients with
second-line or later EGFR-mutant NSCLC, following disease
progression on osimertinib. After the selection of a recommended
Phase 2 combination dose regimen, the company plans to initiate an
expansion cohort with registration potential in biomarker-selected
second-line patients, as well as an expansion cohort in front-line
patients, by the end of 2022. Additional combinations with BLU-701,
chemotherapy and antibody-drug conjugate therapy are planned across
multiple mutation profiles and lines of therapy.
In addition, Blueprint Medicines announced today a clinical
trial supply agreement with AstraZeneca (LSE/STO/Nasdaq: AZN).
Under the terms of the agreement, Blueprint Medicines will evaluate
BLU-945 and BLU-701 in combination with osimertinib in the ongoing
SYMPHONY and HARMONY trials, respectively.
BLU-945: Data from the Phase 1/2 SYMPHONY Trial
As of a data cutoff date of March 9,
2022, 33 patients with EGFR-mutant NSCLC have been treated
with BLU-945 across five dose escalation cohorts (range: 25-400 mg
QD). The majority of patients (79 percent) previously received at
least three lines of systemic therapy, including osimertinib (97
percent). Patient eligibility criteria require the presence of an
EGFR mutation based on local assessment of tumor biopsy or
circulating tumor DNA (ctDNA).
BLU-945 was generally well-tolerated at all doses tested. The
most common AEs (regardless of relationship to BLU-945; ≥10
percent) were nausea, headache, fatigue, cough, dyspnea, vomiting,
hyponatremia, dry mouth and anemia. Reported AEs associated with
wild-type EGFR inhibition were infrequent and low grade, including
rash (one patient; Grade 1) and diarrhea (three patients; all Grade
1). One dose-limiting toxicity (Grade 3 transaminitis) occurred in
the 400 mg QD cohort, which improved with dose interruption. There
were no treatment discontinuations due to AEs.
Pharmacokinetic data showed dose-proportional plasma
concentrations, with exposures at increasing doses consistent with
broad EGFR mutation coverage, based on preclinical activity
thresholds. Mean plasma exposures at doses of 100 mg QD or higher
exceeded the IC90 for mutants harboring the T790M and
C797S resistance mutations, regardless of activating mutation. In
addition, mean plasma exposure at 400 mg QD exceeded the
IC90 for mutants harboring the activating L858R mutation
with or without the C797S mutation.
The SYMPHONY trial is one of the first oncology studies to
analyze plasma ctDNA via real-time next-generation sequencing to
assess tumor biology and early drug activity. Results for patients
with detectable T790M and C797S allele fractions at baseline and
available post-baseline assessments showed dose-dependent
reductions in both variant allele fractions. In patients treated
with 400 mg QD, all detectable T790M and C797S allele fractions
declined, including three that fell below the limit of detection
(clearance).
Patients with measurable target lesions at baseline and at least
one post-baseline scan were evaluable per Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. In a heavily
pre-treated population, higher BLU-945 doses led to increased
antitumor activity. Tumor shrinkage was observed in patients
treated with 200-400 mg QD, including an unconfirmed PR1
in a patient treated with 400 mg QD. This patient had NSCLC
harboring exon 19 deletion, T790M and C797S mutations, and
previously received platinum-based chemotherapy, erlotinib and
osimertinib with a best response of stable disease.
Copies of Blueprint Medicines data presentations from the AACR
annual meeting, including the SYMPHONY trial presentation, are
available in the "Science--Publications and Presentations" section
of the company's website at www.blueprintmedicines.com.
Investor Conference Call Information
Blueprint Medicines will host a live webcast today, April 8, 2022 beginning at 2:00 p.m. ET, to discuss the data reported at
AACR. To access the live call, please dial 844-200-6205 (domestic)
or 929-526-1599 (international), and refer to conference ID 084402.
A webcast of the conference call will be available in the Investors
& Media section of Blueprint Medicines' website at
http://ir.blueprintmedicines.com/. The archived webcast will be
available on Blueprint Medicines' website approximately two
hours after the conference call and will be available for 30 days
following the call.
About Blueprint Medicines' Clinical Development Programs in
EGFR-Mutant NSCLC
Blueprint Medicines is developing three investigational agents,
BLU-701, BLU-945 and BLU-451, with the goal of addressing nearly
all activating mutations (>90 percent) in EGFR-mutant NSCLC. The
introduction of EGFR-targeted therapies, including osimertinib, has
transformed the care of patients with EGFR-mutant NSCLC; however,
there is a significant need for new treatment options designed to
prevent or treat a broad range of resistance mechanisms before they
emerge, with the goal of prolonging patient benefit. There are no
approved targeted therapies for patients with disease progression
following osimertinib, and limited treatment options for patients
with EGFR exon 20 insertion-positive NSCLC.
BLU-701 and BLU-945 were designed to provide broad coverage of
common activating and on-target resistance mutations, spare
wild-type EGFR and other kinases to help limit off-target
toxicities, and prevent or treat central nervous system (CNS)
metastases. These preclinical profiles may enable BLU-701 and
BLU-945 to become the backbones of a range of combination
strategies across lines of therapy. The Phase 1/2 SYMPHONY trial
(NCT04862780) of BLU-945 and the Phase 1/2 HARMONY trial
(NCT05153408) of BLU-701 are currently ongoing for patients with
EGFR-mutant NSCLC.
BLU-451 is a selective and potent inhibitor of EGFR exon 20
insertion-positive NSCLC. Based on preclinical data, BLU-451
potently inhibited all common EGFR exon 20 insertion variants with
marked selectivity over wild-type EGFR and off-target kinases, and
has shown CNS penetration. Blueprint Medicines has initiated a
Phase 1/2 trial of BLU-451 (NCT05241873) in EGFR exon 20
insertion-positive NSCLC.
To learn about ongoing or planned clinical trials,
contact Blueprint Medicines at
medinfo@blueprintmedicines.com or 1-888-BLU-PRNT
(1-888-258-7768). Additional information is available
at blueprintclinicaltrials.com or clinicaltrials.gov.
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' plans, strategies, timelines and
expectations for clinical trials, trial cohorts and indications;
the anticipated benefits of the preclinical profiles of BLU-945,
BLU-701 and BLU-451; Blueprint Medicines' plans, strategies and
timelines for the development of BLU-945 and BLU-701 as
monotherapies and in combination with other agents; the potential
benefits of Blueprint Medicines' current or 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 the impact of the
COVID-19 pandemic to Blueprint Medicines' business, operations,
strategy, goals and anticipated milestones, including Blueprint
Medicines' ongoing and planned research and discovery activities,
ability to conduct ongoing and planned clinical trials, clinical
supply of current or future drug candidates, commercial supply of
current or future approved products, and launching, marketing and
selling current or future approved products; Blueprint Medicines'
ability and plans in establishing a commercial infrastructure, and
successfully launching, marketing and selling current or future
approved products, including AYVAKIT® (avapritinib) and GAVRETO®
(pralsetinib); Blueprint Medicines' ability to successfully expand
the approved indications for AYVAKIT and GAVRETO or obtain
marketing and reimbursement approvals for AYVAKIT and GAVRETO in
additional geographies in the future; the delay of any current or
planned clinical trials or the development of Blueprint Medicines'
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; the timing of the
initiation of clinical trials and trial cohorts at clinical trial
sites and patient enrollment rates; actions of regulatory agencies,
which may affect the initiation, timing and progress of clinical
trials and marketing applications; Blueprint Medicines' ability to
develop and commercialize companion diagnostic tests for its
current and future drug candidates; Blueprint Medicines' ability to
successfully expand its operations, research platform and portfolio
of therapeutic candidates, and the timing and costs thereof;
Blueprint Medicines' ability to realize the anticipated benefits of
its executive leadership transition plan; and the success of
Blueprint Medicines' current and future acquisitions,
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
Blueprint Medicines' most recent Annual Report on Form 10-K, as
supplemented by its most recent Quarterly Report on Form 10-Q 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.
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
approved medicines directly to patients in the United
States and Europe, and we are globally advancing multiple
programs for systemic mastocytosis, lung cancer and other
genomically defined cancers, and cancer immunotherapy. For more
information, visit www.BlueprintMedicines.com and follow us on
Twitter (@BlueprintMeds) and LinkedIn.
Trademarks
Blueprint Medicines, AYVAKIT, GAVRETO and associated logos are
trademarks of Blueprint Medicines Corporation.
1 An unconfirmed PR is a PR in which tumor reduction
≥30% has occurred, but has not yet been confirmed via a subsequent
scan.
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