– Amends second-line trial design to stratify for
transfusion dependence based on positive preliminary data –
Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a
clinical-stage biopharmaceutical company using its expertise in
epigenetics to discover and develop novel therapeutics, today
announced several planned updates to the Phase 2 portion of its
ongoing MANIFEST study, an open-label Phase 1/2 clinical trial of
its BET inhibitor CPI-0610 in MF.
MANIFEST is evaluating CPI-0610, either as a
monotherapy or in combination with ruxolitinib, in patients with MF
who are refractory or intolerant or have relapsed or lost response
to the standard of care. Based on encouraging preliminary data in
this trial, Constellation is amending the design of each
second-line cohort to stratify all patients enrolled in the study
based on transfusion dependence status. In addition, the Company is
amending the design of MANIFEST to include a third cohort designed
to evaluate treatment with CPI-0610 in combination with ruxolitinib
as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients.
The Company made these updates based on the unmet
medical need for disease-modifying therapies in myelofibrosis,
especially among patients requiring red-blood-cell transfusions.
The changes are intended to enhance the clinical trial design by
providing additional measures of potential clinical benefit and to
expand the potential addressable patient population for
CPI-0610.
“We are encouraged by the preliminary data from
MANIFEST, which may indicate synergistic and disease-modifying
effects of CPI-0610 in myelofibrosis,” said Adrian Senderowicz,
Senior Vice President and Chief Medical Officer of Constellation
Pharmaceuticals. “We are enhancing the study’s design to better
measure these potential effects. Among the key goals of MANIFEST
are identifying the most appropriate endpoints and patient
populations for future pivotal studies. We continue to look forward
to determining proof of concept for CPI-0610 in MF by
mid-2019.”
MANIFEST Enhancements
The Phase 2 proof-of-concept portion of MANIFEST in
a second-line setting is designed to study the anti-tumor activity
and safety of the BET inhibitor CPI-0610 in treatment of patients
with MF as a monotherapy and in combination with the JAK-1/2
inhibitor ruxolitinib. This portion of the study had been expected
to enroll 70 patients (35 on monotherapy and 35 on combination
therapy) to evaluate safety, pharmacokinetics, reduction in spleen
volume, and patient-reported symptom improvement in all enrolled
patients, as well as improvements in red-blood-cell transfusion
independence rate in patients who were transfusion-dependent at
baseline. Preliminary data from this trial demonstrated spleen
volume reduction, symptom improvement, and positive hemoglobin
effects, which Constellation believes may be the result of improved
hematopoiesis. In addition, as Constellation reported previously,
one of four patients treated with CPI-0610 was
transfusion-dependent at baseline and later converted to
transfusion independence.
As a result of this positive preliminary
hematological data, all enrolled patients in both the combination
and monotherapy arms will now be stratified by transfusion
dependence status, with each cohort expected to enroll up to 16
transfusion-dependent patients and up to 25
non-transfusion-dependent patients. Proof of concept in these
cohorts will be based on conversion to transfusion independence and
other factors in transfusion-dependent patients; and by reduction
in spleen volume, patient-reported symptom improvement, and other
factors in non-transfusion-dependent patients.
In addition, Constellation is adding a third cohort
to this trial, which will evaluate treatment with CPI-0610 in
combination with ruxolitinib as first-line therapy in up to 43 JAK
1/2-inhibitor-naïve MF patients. This cohort will only enroll
anemic patients. Constellation’s current plan for a potential
pivotal trial of CPI-0610 as a first-line treatment would be to
enroll all-comers. Proof of concept for this cohort will be
measured by reduction in spleen volume, patient-reported symptom
improvement, and other factors.
The Company expects to update this protocol change
at https://clinicaltrials.gov under study
ID NCT02158858 in the near future.
Conference Call/Corporate Presentation
Constellation’s CEO Jigar Raythatha and CMO Adrian
Senderowicz will host a conference call to discuss this protocol
change in greater detail at 8:30 AM EDT on Thursday, October 11. To
participate in the conference call, please dial (877) 473-2077 (US)
or +1(661) 378-9662 (international) and refer to conference ID
4165317. A live webcast will be available in the investor section
of the company's website. The webcast will be archived for 60 days
following the call. Constellation has posted an updated version of
its corporate presentation in the investor section of the company’s
website.
About Constellation
Pharmaceuticals
Constellation Pharmaceuticals is a clinical-stage
biopharmaceutical company developing novel therapeutics that
selectively modulate gene expression to address serious unmet
medical needs in patients with cancer. The Company has a deep
understanding of how epigenetic and chromatin modifications in
cancer cells and in the tumor and immune microenvironment play a
fundamental role in driving disease progression and drug
resistance. Constellation is driving development of the EZH2
inhibitors CPI-1205 and CPI-0209 for the treatment of metastatic
castration-resistant prostate cancer and other cancers as well as
the BET inhibitor CPI-0610 for the treatment of myelofibrosis. The
Company is also applying its broad research and development
capabilities to explore other novel targets that directly and
indirectly impact gene expression to fuel a sustainable pipeline of
innovative small-molecule product candidates.
Forward-Looking Statements
This press release contains “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995 that involve substantial risks and
uncertainties, including statements regarding the development
status of the Company’s product candidates, the anticipated
benefits of the changes to its clinical trial protocols and its
anticipated achievement of milestones, including determination of
proof of concept. All statements, other than statements of
historical facts, contained in this press release, including
statements regarding the Company’s strategy, future operations,
future financial position, prospects, plans and objectives of
management, are forward-looking statements. The words “anticipate,”
“believe,” “continue,” “could,” “estimate,” “expect,” “intend,”
“may,” “plan,” “potential,” “predict,” “project,” “should,”
“target,” “will,” “would” and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements are based on management’s current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in, or implied by,
such forward-looking statements. These risks and uncertainties
include, but are not limited to, risks associated with
Constellation’s ability to: obtain and maintain necessary approvals
from the FDA and other regulatory authorities; continue to advance
its product candidates in clinical trials; replicate in later
clinical trials positive results found in preclinical studies and
early-stage clinical trials of CPI-1205, CPI-0610 and its other
product candidates; advance the development of its product
candidates under the timelines it anticipates, or at all, in
current and future clinical trials; obtain, maintain or protect
intellectual property rights related to its product candidates;
manage expenses; and raise the substantial additional capital
needed to achieve its business objectives. For a discussion of
other risks and uncertainties, any of which could cause the
Company’s actual results to differ from those contained in the
forward-looking statements, see the “Risk Factors” section, as well
as discussions of potential risks, uncertainties, and other
important factors, in the Company’s most recent filings with the
Securities and Exchange Commission. In addition, the
forward-looking statements included in this press release represent
the Company’s views as of the date hereof and should not be relied
upon as representing the Company’s views as of any date subsequent
to the date hereof. The Company anticipates that subsequent events
and developments will cause the Company’s views to change. However,
while the Company may elect to update these forward-looking
statements at some point in the future, the Company specifically
disclaims any obligation to do so. CPI-1205, CPI-0610, CPI-0209,
and other product candidates are investigational in nature and have
not yet been approved by the FDA or other regulatory
authorities.
Contact
Ronald Aldridge Investor RelationsConstellation
Pharmaceuticals+1
617-714-0539ron.aldridge@constellationpharma.com
Lauren ArnoldMedia RelationsMacDougall Biomedical
Communications+1 781-235-3060larnold@macbiocom.com
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