Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a
clinical-stage biopharmaceutical company using its expertise in
epigenetics to discover and develop novel therapeutics, today
announced the presentation of updated interim data from MANIFEST,
the Company’s Phase 2 clinical trial of CPI-0610 in MF. The interim
data, which highlight the tolerability and potentially
disease-modifying activity of CPI-0610, were presented in a poster
at the annual meeting of the American Society for Clinical Oncology
(ASCO) in Chicago.
“We are excited by these interim data from the MANIFEST trial,
which indicate that CPI-0610 is generally well-tolerated and showed
signs that it is an active therapeutic agent for the treatment of
myelofibrosis, both as a monotherapy and in combination with a
standard-of-care JAK inhibitor,” said Adrian Senderowicz, M.D.,
Chief Medical Officer at Constellation Pharmaceuticals. “Moreover,
as these data highlight improvements across key hallmarks of
myelofibrosis, we believe that CPI-0610 has the potential to
address a broad range of unmet needs in patients with this
difficult-to-treat cancer. We look forward to the continued
evaluation of CPI-0610 in this ongoing Phase 2 trial and to
providing additional data from MANIFEST later this year.”
The data were gathered from 44 patients enrolled as of April 17,
2019. Twelve patients received 24-week assessments and 16 patients
received 12-week assessments. Below is a summary of results from
the interim update across primary and secondary endpoints from the
trial:
- 14 of 16 evaluable patients demonstrated spleen volume
reductions. Overall, the median best on-trial spleen volume change
from baseline was -19.2%.
- Of these 16 evaluable patients, 11 were evaluable for
improvement in Total Symptom Score (TSS) according to the
Myelofibrosis Symptom Assessment Form, Version 4.0. Six of the 11
(55%) evaluable patients achieved greater than 50% TSS improvement
from baseline as a best response.
- All of these 16 patients were evaluable for Patient Global
Impression of Change (PGIC). Fifteen of 16 (94%) evaluable patients
reported improvements in PGIC, of which 10 reported feeling either
“much improved” or “very much improved” and no patients reported
feeling worse following treatment.
- Of 12 evaluable patients who received at least 24 weeks of
treatment, three were severely anemic and dependent on
red-blood-cell transfusions at baseline. Of these three patients,
two converted to transfusion independence. These two patients have
remained transfusion independent for more than 69 and 24 weeks,
respectively, as of April 17, 2019, and remain on trial.
- Ten patients were evaluable for bone marrow fibrosis, of which
six (60%) experienced improvement in bone marrow morphology of at
least one point on a scale of 0-3. Four of these six patients
exhibited improvements within six months of starting CPI-0610
therapy.
Based on the interim data, CPI-0610 was generally
well-tolerated, both as a monotherapy and in combination with
ruxolitinib. Overall, the most commonly reported side effects
(≥10%) were diarrhea, vomiting, upper respiratory tract infection,
headache, epistaxis, fatigue, dysgeusia, cough and pruritis. Grade
3 or greater treatment-emergent adverse events were only reported
in the combination arm, and those reported in more than one patient
included thrombocytopenia, anemia, and decreased platelet counts,
each of which was reported in two patients. There was one patient
death, which the Company assessed as unlikely to have been related
to CPI-0610. The combination therapy of CPI-0610 and ruxolitinib
showed a non-cumulative, manageable, and mostly reversible
asymptomatic thrombocytopenia.
Each of the first four patients enrolled in MANIFEST, of which
two received CPI-0610 as a monotherapy and two received CPI-0610 in
combination with ruxolitinib, remained on therapy and had been
treated for approximately 16 and 20 months, respectively, as of
April 17, 2019.
Please see the poster in the Investors & Media section of
Constellation’s website for additional details.
As previously announced in November 2018, Constellation expanded
the MANIFEST trial to include a third cohort, designed to evaluate
CPI-0610 in combination with ruxolitinib as a first-line therapy in
JAK-inhibitor-naïve patients with advanced MF. The Company has
begun treating patients in this arm of the trial and expects to
provide initial results from this cohort, as well as additional
data from the ruxolitinib-resistant and -refractory (second-line)
cohorts, in the fourth quarter of 2019.
Investor Event
Constellation will host an analyst/investor meeting, with an
accompanying conference call and webcast, to discuss this interim
update in the Jackson Park D room at Hyatt Regency McCormick Place
in Chicago at 8:00 AM EDT/7:00 AM CDT on June 4, 2019. The agenda
of the meeting will include:
- An overview of myelofibrosis (MF) and the potential impact of
Constellation’s BET inhibitor CPI-0610 in treating MF
- A review of the interim data from the MANIFEST clinical trial
presented in a poster at ASCO on June 3
- A panel discussion with two key opinion leaders in MF:
- Dr. Srdan Verstovsek, a medical oncologist at
the University of Texas MD Anderson Cancer Center and an
investigator in the MANIFEST trial; and
- Dr. Raajit Rampal, a hematologic oncologist at
Memorial Sloan Kettering Cancer Center
The event will be webcast live and can be accessed on the
Investor Relations section of Constellation’s website at
http://ir.constellationpharma.com/events-and-presentations/events.
Participants may also access the event and participate in the live
question-and-answer session by dialing (877) 473-2077 (domestic) or
(661) 378-9662 (international) and referring to conference ID
1295319.
Medical Presentation at EHA
Dr. Ronald Hoffman of Mt. Sinai Health System, an investigator
in the MANIFEST trial, will make an oral presentation on this
interim update of MANIFEST at the European Hematology Association
(EHA) annual meeting at 12:15 PM CEST/6:15 AM EDT on June 15, 2019.
Slides from the presentation will be posted to Constellation’s
website.
About MANIFEST
MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in
patients with myelofibrosis (MF), a rare cancer of the bone marrow
that disrupts the body’s normal production of blood cells.
Constellation is evaluating CPI-0610, either as a monotherapy or in
combination with ruxolitinib, in a second-line setting in patients
with MF who are refractory to or intolerant of or have relapsed or
lost response to ruxolitinib. Patients in the two second-line arms
are being stratified based on transfusion-dependent status. The
primary endpoint for the cohorts with transfusion-dependent
patients is conversion to transfusion independence for 12
consecutive weeks. The primary endpoint for the patients who were
not transfusion-dependent at baseline is spleen volume reduction.
In addition, the Company added a third arm designed to evaluate
treatment with CPI-0610 in combination with ruxolitinib as a
first-line therapy in JAK-1/2-inhibitor-naïve MF
patients.
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 implications of preliminary or interim
clinical data, the development status of the Company’s product
candidates, and the Company’s plans for future data presentations.
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;
whether preliminary or interim data from a clinical trial will be
predictive of the final results of the trial; 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 Senior Director, Investor RelationsConstellation
Pharmaceuticals+1
617-714-0539ron.aldridge@constellationpharma.com
Lauren ArnoldMedia RelationsMacDougall Biomedical
Communications+1 781-235-3060larnold@macbiocom.com
Constellation Pharmaceut... (NASDAQ:CNST)
Graphique Historique de l'Action
De Juin 2024 à Juil 2024
Constellation Pharmaceut... (NASDAQ:CNST)
Graphique Historique de l'Action
De Juil 2023 à Juil 2024