Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) today announced
that three posters relating to the MANIFEST clinical trial of
CPI-0610 in myelofibrosis (MF) were published online in association
with the European Hematology Association (EHA) annual meeting. The
data in these posters are based on a data cutoff of April 17, 2020,
and reflect an analysis of clinical activity in 51 first-line (1L)
and 73 second-line (2L) patients.
“I’m encouraged that the initial signals of activity with
CPI-0610, such as spleen and symptom responses, that were presented
last December at ASH continue to be observed in a larger dataset
presented in these EHA posters,” said Claire Harrison, D.M.
(Oxon.), Professor of Haematology and a MANIFEST investigator. “In
addition, we continue to see signals of disease modification, such
as increases in hemoglobin, conversions of transfusion-dependent
patients to transfusion independence, and bone marrow fibrosis
improvements. If corroborated in further testing, these data
suggest that CPI-0610 could potentially change the treatment
paradigm in MF.”
“We are excited about the emerging profile of CPI-0610,” said
Jigar Raythatha, Chief Executive Officer of Constellation
Pharmaceuticals. “Our goal is to drive CPI-0610 to registration and
to transform the standard of care in myelofibrosis and potentially
other hematologic diseases.”
Data Highlights
Arm 3 (1L) – CPI-0610 + ruxolitinib in JAK-inhibitor-naïve
patients
- 37 of 51 evaluable patients (73%) achieved a 35% reduction in
spleen volume (SVR35) at 12 weeks and had a median spleen volume
reduction of 51%
- 19 of 30 evaluable patients (63%) achieved SVR35 at 24 weeks
(the primary endpoint for Arm 3) and had a median spleen volume
reduction of 53%
- 17 of 29 evaluable patients (59%) achieved a 50% improvement in
Total Symptom Score (TSS50) at 24 weeks and had a median TSS
improvement of 64%
- No evidence of correlation between SVR35 response and baseline
risk status, platelet count, or spleen volume
Arm 1 (2L) – CPI-0610 monotherapy in JAK-inhibitor-experienced
or -ineligible patients
- 3 of 14 (21%) evaluable transfusion-dependent (TD) patients
converted to transfusion independence (TI), the primary endpoint
for cohort 1A
- 5 of 21 (24%) evaluable non-TD patients achieved SVR35 (the
primary endpoint for cohort 1B) and 9 of 19 (47%) evaluable non-TD
patients achieved TSS50 at 24 weeks
- 11 of 19 (58%) non-TD patients on treatment for at least 12
weeks without any transfusions achieved a ≥1.5 g/dL mean increase
in hemoglobin
Arm 2 (2L) – CPI-0610 + ruxolitinib in ruxolitinib-experienced
patients
- 11 of 32 (34%) evaluable TD patients converted to TI, the
primary endpoint for cohort 2A
- 4 of 18 (22%) evaluable non-TD patients achieved SVR35 (the
primary endpoint for cohort 2B) and 7 of 19 (37%) evaluable non-TD
patients achieved TSS50 at 24 weeks
Safety
CPI-0610 in MANIFEST, both as monotherapy and in combination
with ruxolitinib and in both JAK-inhibitor-naïve and
JAK-inhibitor-experienced and -ineligible patients, was generally
well tolerated.
Among the most common treatment-emergent adverse events (TEAEs)
for CPI-0610 monotherapy in 43 safety-evaluable patients in Arm 1,
those that were Grade 3 were thrombocytopenia (14.0%), anemia
(9.3%), diarrhea (4.7%), and respiratory tract infection (2.3%).
Six patients discontinued treatment because of TEAEs. There were no
Grade 4 or Grade 5 TEAEs.
Among the most common TEAEs in 70 safety-evaluable patients in
Arm 2, those that were Grade 3 were thrombocytopenia (22.9%),
anemia (7.1%), fatigue (5.7%), diarrhea (4.3%), respiratory tract
infections (4.3%), nausea (2.9%), and abdominal pain (1.4%). Grade
4 TEAEs included thrombocytopenia (1.4%) and anemia (1.4%). Seven
patients discontinued treatment due to TEAEs, including four Grade
5 TEAEs, which were acute kidney injury, traumatic subdural
hematoma, brain stem hemorrhage (no concomitant thrombocytopenia),
and disease progression.
Among the most common TEAEs in 64 safety-evaluable patients in
Arm 3, those that were Grade 3 were anemia (15.6%), respiratory
tract infections (3.1%), and thrombocytopenia (1.6%). Grade 4 TEAEs
included thrombocytopenia (3.1%), anemia (1.6%), and respiratory
tract infection (1.6%). Four patients discontinued treatment due to
TEAEs, including two Grade 5 TEAEs, each due to multi-organ failure
due to sepsis.
For further details, please see the EHA poster presentations
here.
EHA Poster Presentations
TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein
(BET) Inhibitor, in Combination with Ruxolitinib, in JAK Inhibitor
Treatment Naive Myelofibrosis Patients: Update of MANIFEST Phase 2
Study (Presentation Code: EP1084)
TITLE: CPI-0610, A Bromodomain and
Extraterminal Domain Protein (BET) Inhibitor, as Monotherapy in
Advanced Myelofibrosis Patients Refractory / Intolerant to JAK
Inhibitor: Update from Phase 2 MANIFEST Study (Presentation Code:
EP1091)
TITLE: CPI-0610, Bromodomain and Extraterminal Domain Protein
(BET) Inhibitor, as “Add-on” to Ruxolitinib (Rux), in Advanced
Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST
Phase 2 Study (Presentation Code: EP1083)
Session: Myeloproliferative Neoplasms—Clinical
Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT
Investor Event
Constellation will host a virtual analyst/investor event and
conference call on June 12 at 8:00 AM EDT to discuss the data from
these three posters relating to the MANIFEST clinical trial for
CPI-0610 being presented at the European Hematology Association
meeting. The agenda of the event 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 data from the MANIFEST clinical trial presented
in the EHA posters
- A live question-and-answer session
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. To
participate in the live question-and-answer session, please dial
(877) 473-2077 (domestic) or (661) 378-9662 (international) and
refer to conference ID 6275774.
EZH2 Program Prioritization
Constellation today announced that it plans to prioritize
further clinical development of its next-generation EZH2 inhibitor
CPI-0209. The decision is based on a recent data cut and
review of ProSTAR, the ongoing Phase 1b/2 clinical study evaluating
CPI-1205, a small-molecule inhibitor of EZH2, combined with
enzalutamide or abiraterone in patients with metastatic
castration-resistant prostate cancer (mCRPC). The data did not
demonstrate the definitive signal of activity necessary to advance
the program into pivotal studies in mCRPC. A full data set from
ProSTAR will be presented at a future medical meeting.
“We thank the patients and investigators who participated in
ProSTAR,” said Jigar Raythatha. “While we are disappointed with the
outcome of this study, we remain committed to EZH2 as an important
cancer target and will apply the learnings from ProSTAR to our
second-generation EZH2 inhibitor, CPI-0209. We believe the deeper
and more durable target engagement as well as the improved
metabolic properties that CPI-0209 demonstrated in preclinical
studies give it the potential to be a best-in-class EZH2 inhibitor
for use in a broad range of cancer types. CPI-0209 is progressing
through the dose escalation portion of a phase 1/2 clinical trial,
and we expect to determine a recommended Phase 2 dose later in the
year.”
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 in combination with
ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a
primary endpoint of the proportion of patients with a ≥35% spleen
volume reduction from baseline (SVR35) after 24 weeks of treatment.
Constellation is also evaluating CPI-0610, either as a monotherapy
in patients who are resistant to, intolerant of, or ineligible for
ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy
in combination with ruxolitinib in patients with a sub-optimal
response to ruxolitinib or MF progression (Arm 2). Patients in Arms
1 and 2 are being stratified based on TD status. The primary
endpoint for the patients in cohorts 1A and 2A, who were TD at
baseline, is conversion to TI for 12 consecutive weeks. The primary
endpoint for the patients in cohorts 1B and 2B, who were not TD at
baseline, is the proportion of patients with a ≥35% spleen volume
reduction from baseline after 24 weeks of treatment.
About ProSTAR
ProSTAR is an open-label Phase 1b/2 clinical trial of CPI-1205,
a potent and highly selective small-molecule EZH2 inhibitor, in
patients with metastatic castration-resistant prostate cancer
(mCRPC) in the second-line setting. The ProSTAR study is evaluating
CPI-1205 in combination with either enzalutamide or
abiraterone/prednisone (“abiraterone”), which are androgen receptor
signaling (ARS) inhibitors, in mCRPC patients who experienced
disease progression while receiving the other ARS inhibitor.
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 BET inhibitor CPI-0610 for the treatment of
myelofibrosis as well as the EZH2 inhibitors CPI-1205 and CPI-0209
for the treatment of metastatic castration-resistant prostate
cancer and other cancers. 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, Company’s plans, strategies and prospects for its
business and statements regarding the development status of the
Company’s product candidates. 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 the Company’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-0610, CPI-1205 and CPI-0209;
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; raise the
substantial additional capital needed to achieve its business
objectives; the COVID-19 pandemic and general economic and market
conditions. CPI-0610, CPI-1205 and CPI-0209 are investigational
therapies and have not been approved by the FDA (or any other
regulatory authority). 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, including the Company’s Quarterly Report on Form 10-Q
for the quarter ended March 31, 2020. 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.
Contacts Kia Khaleghpour, Ph.D.Vice President,
Investor Relations and CommunicationsConstellation
Pharmaceuticals+1
617-844-6859kia.khaleghpour@constellationpharma.com
Ronald AldridgeSenior 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