WALTHAM, Mass., Nov. 11, 2017 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq:
SNDX), a clinical stage biopharmaceutical company developing
entinostat and SNDX-6352 in multiple cancer indications, today
announced results from the non-small cell lung cancer (NSCLC) and
melanoma cohorts of ENCORE 601, an open-label, Phase 1b/2 clinical
trial employing a Simon two-stage design to evaluate the
combination of entinostat, the Company's class I selective HDAC
inhibitor, plus Merck's (also known as MSD outside of the United States and Canada) anti-PD-1 (programmed death
receptor-1) therapy, KEYTRUDA®. In addition, data from
the single ascending dose (SAD) trial of SNDX-6352, the Company's
anti-CSF-1R monoclonal antibody, in healthy volunteers were
presented at the Society of Immunotherapy of Cancer (SITC) Annual
Scientific Meeting being held November 8-12,
2017 in National Harbor, Maryland.
ENCORE 601 Updates
In an oral presentation titled, "ENCORE-601: Phase 1b/2 study of
entinostat (ENT) in combination with pembrolizumab in patients with
non-small cell lung cancer (NSCLC)," Leena
Gandhi, M.D., Ph.D., director of the Thoracic Medical
Oncology Program at NYU Langone's Perlmutter Cancer Center, shared
data from the first stage of both NSCLC cohorts of ENCORE 601,
including patients with PD-(L)1 refractory disease, as well as
PD-(L)1 naïve patients. The observed overall response rate was 10%
(95% CI: 2%-26%) in patients who had progressed on prior anti-PD-1
or PD-(L)1 therapy and 24% (95% CI: 7%-50%) in patients naïve to
PD-1 or PD-(L)1 therapy. Across both NSCLC cohorts, the responders
with known PD-(L)1 expression levels were all observed to be low
(1-49%) or negative expressors (< 1%). Three patients from each
cohort remain on therapy, and two of the six have been on the
combination for over one year.
"The responses observed in patients receiving entinostat with
pembrolizumab who had previously progressed on prior checkpoint
blockade are encouraging, particularly in those who did not achieve
responses on their prior PD-1 therapy. While the numbers of
patients treated to date are small, these initial results support
further exploring this combination to potentially address an unmet
medical need for these patients," noted Dr. Gandhi.
In addition to the NSCLC data, the poster, "Analysis of
biomarkers from a cohort of advanced melanoma patients previously
exposed to immune checkpoint inhibition treated with entinostat
(ENT) and pembrolizumab" containing updated data highlighting the
clinical activity and novel translational research findings from
the ENCORE 601 cohort of melanoma patients whose disease had
progressed on prior PD-1 therapy was presented today. As of early
September, four of 13 patients in this PD-1 refractory cohort
remained on study, two of whom have received more than a year of
the combination treatment. Pre-treatment tumor biopsies were
obtained for all patients and matched post-treatment biopsies were
available from nine patients. Gene expression, PD-1 and
immunofluorescence analysis of tissue samples demonstrate that
entinostat combined with KEYTRUDA may generate immune
responsiveness in tumors previously resistant to immune checkpoint
inhibition.
"Data presented at SITC continue to support our hypothesis that
entinostat has the potential to enhance immune checkpoint blockade
mediated anti-tumor responses in a broad range of tumors," said
Briggs Morrison, M.D., Chief
Executive Officer of Syndax. "Of note, in the melanoma cohort of
ENCORE 601, we are encouraged to see conversion of a non-inflamed
to inflamed tumor microenvironment after treatment with entinostat
and KEYTRUDA in two of the three responders for whom we had both
pre- and post-treatment tumor biopsies. We are also excited by the
rapid accrual into the second stage of the PD-(L)1 refractory NSCLC
cohort, which we believe speaks to the interest in, and need for,
novel approaches to address such unmet needs. We look forward to
sharing full Phase 2 data from the NSCLC and melanoma cohorts in
the first half of 2018, and in the same time frame, we expect to
share a registration plan for entinostat in combination with a PD-1
inhibitor for patients with PD-1 refractory melanoma."
SNDX-6352 Updates
The poster, "First in human, single ascending dose study in
healthy volunteers of SNDX-6352, a humanized IgG4 monoclonal
antibody targeting colony stimulating factor-1 receptor (CSF-1R),"
containing safety, pharmacokinetic and pharmacodynamic data from
the first in human, SAD trial of SNDX-6352, was also presented
during the SITC annual meeting. Three dose levels of 0.15 mg/kg, 1
mg/kg, and 3 mg/kg were administered during the SAD trial, and
increases in CSF-1 and IL-34, and transient reduction of
circulating non-classical monocytes were observed, consistent with
binding of SNDX-6352 to CSF-1R. The safety profile of SNDX-6352 was
as expected, with mild to moderate adverse effects observed
consistent with other agents in this class.
The SITC presentations are available in the Publications section
of the Company's website, linked here.
About ENCORE 601
ENCORE 601 is an open-label, Phase 1b/2 clinical trial employing
a Simon two-stage design to evaluate the combination of entinostat,
the Company's class I selective HDAC inhibitor, plus Merck's
anti-PD-1 (programmed death receptor-1) blocking therapy,
KEYTRUDA®. The trial is evaluating four patient
populations: Patients with non-small cell lung cancer (NSCLC) who
have not previously received a PD-1 antagonist (cohort 1); patients
with NSCLC who have progressed on a PD-1 antagonist (cohort 2);
patients with advanced melanoma who have progressed on a PD-1
antagonist (cohort 3); and microsatellite stable colorectal cancer
who have not previously been treated with a PD-1 antagonist (cohort
4). The Company previously announced that cohorts 1, 2 and 3 have
met the pre-specified objective response threshold to advance into
the second stage of the Phase 2 trial, and cohorts 2 and 3 have
completed enrollment of the second stage of the trial. A decision
on the advancement of cohort 4 is expected in the first half of
2018.
About Syndax Pharmaceuticals, Inc.
Syndax is a clinical stage biopharmaceutical company developing
an innovative pipeline of cancer therapies. Our lead product
candidate, entinostat, which was granted Breakthrough Therapy
designation by the FDA following positive results from our Phase 2b
clinical trial, ENCORE 301, is currently being evaluated in a Phase
3 clinical trial in combination with exemestane for advanced
hormone receptor positive, human epidermal growth factor receptor 2
negative breast cancer. Given its potential ability to block the
function of immune suppressive cells in the tumor microenvironment,
entinostat is also being evaluated in combination with approved
PD-1 antagonists. Ongoing Phase 1b/2 clinical trials combine
entinostat with KEYTRUDA from Merck & Co., Inc. for non-small
cell lung cancer, melanoma and colorectal cancer; with
TECENTRIQ® from Genentech, Inc. for triple negative
breast cancer; and with BAVENCIO® from Pfizer Inc. and
Merck KGaA, Darmstadt, Germany,
for ovarian cancer. Our second clinical stage product candidate,
SNDX-6352, is a monoclonal antibody that blocks the colony
stimulating factor 1 (CSF-1) receptor and may also block the
function of immune suppressive cells in the tumor microenvironment.
SNDX-6352 is being evaluated in a Phase 1 clinical trial and is
expected to be developed to treat a variety of cancers.
Syndax's Cautionary Note on Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as "may," "will," "expect," "plan," "anticipate,"
"estimate," "intend," "believe" and similar expressions (as well as
other words or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements.
These forward-looking statements are based on Syndax's expectations
and assumptions as of the date of this press release. Each of these
forward-looking statements involves risks and uncertainties. Actual
results may differ materially from these forward-looking
statements. Forward-looking statements contained in this press
release include, but are not limited to, statements about the
progress, timing, clinical development and scope of clinical trials
and the reporting of clinical data for Syndax's product candidates,
and the potential use of our product candidates to treat various
cancer indications. Many factors may cause differences between
current expectations and actual results including unexpected safety
or efficacy data observed during preclinical or clinical studies,
clinical trial site activation or enrollment rates that are lower
than expected, changes in expected or existing competition, changes
in the regulatory environment, failure of Syndax's collaborators to
support or advance collaborations or product candidates and
unexpected litigation or other disputes. Other factors that may
cause Syndax's actual results to differ from those expressed or
implied in the forward-looking statements in this press release are
discussed in Syndax's filings with the U.S. Securities and Exchange
Commission, including the "Risk Factors" sections contained
therein. Except as required by law, Syndax assumes no obligation to
update any forward-looking statements contained herein to reflect
any change in expectations, even as new information becomes
available.
Investor Contact
Melissa Forst
Argot Partners
melissa@argotpartners.com
Tel 212.600.1902
Media Contact
Eliza Schleifstein
Argot Partners
eliza@argotpartners.com
Tel 973.361.1546
SNDX-G
View original
content:http://www.prnewswire.com/news-releases/syndax-pharmaceuticals-announces-presentation-of-data-from-immuno-oncology-clinical-trials-at-the-society-for-immunotherapy-of-cancer-32nd-annual-scientific-meeting-300554117.html
SOURCE Syndax Pharmaceuticals, Inc.