WALTHAM, Mass., April 20, 2021 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. ("Syndax," the "Company" or "we")
(Nasdaq:SNDX), a clinical stage biopharmaceutical company
developing an innovative pipeline of cancer therapies, today
announced updated positive data from the Phase 1 dose escalation
portion of the ongoing Phase 1/2 AUGMENT-101 trial of SNDX-5613 in
patients with mixed lineage leukemia rearranged (MLLr) and
nucleophosmin (NPM1c) mutant relapsed/refractory (R/R) acute
leukemias. SNDX-5613 is the Company's highly selective, oral menin
inhibitor. Information on how to access the live video webcast and
accompanying slide presentation can be found below.
"Data reported today further support the potential for SNDX-5613
to induce clinically meaningful responses in patients with
genetically-defined acute leukemias," said Briggs W. Morrison, M.D., Chief Executive
Officer of Syndax. "Notably, robust clinical activity, including
multiple complete responses with no evidence of minimal residual
disease (MRD-), were observed in heavily pretreated MLLr and NPM1c
patients. We have identified a candidate recommended Phase 2 dose
(RP2D) and expect to commence the pivotal Phase 2 portion of the
trial by the end of the second quarter."
"Genetically-defined acute leukemias, including those harboring
MLLr and NPM1c mutations, represent a disease area with a
particularly poor prognosis and few effective treatment options,"
said Eytan M. Stein, M.D., Assistant
Attending Physician and Director, Program for Drug Development in
Leukemia, Department of Medicine at Memorial Sloan Kettering Cancer
Center, and the trial's principal investigator. "With five-year
survival rates in MLLr and NPM1c mutant acute leukemias of 50% or
less, novel treatments that can offer clinically-meaningful benefit
are desperately needed. I am excited to present evidence that
underscores previous observations that SNDX-5613 has the potential
to disrupt the treatment paradigm for this disease."
As of a March 12, 2021 data cutoff
date, 43 patients with a median of three prior therapies, such as
prior stem cell transplant, venetoclax and chemotherapy, were dosed
in the Phase 1 portion of the AUGMENT-101 trial. A total of 31
patients were evaluable for efficacy at the time of the data cutoff
date, with the remaining patients either not yet at their initial
efficacy assessment (n=4) or not harboring either the MLLr or NPM1c
mutation (n=8). The overall response rate1 (ORR) among
evaluable patients was 48% (n=15), with 67% (n=10) of these
responders achieving MRD negative status, with four of
these patients proceeding to receive stem cell transplant. The
ORR in evaluable patients harboring an MLL-rearrangement (n=24),
was 54% (n=13), and in evaluable patients harboring an NPM1c
mutation (n=7), was 29% (n=2).
A candidate RP2D of 226 mg every 12 hours was identified for
patients who are not receiving a concomitant strong CYP3A4
inhibitor, and 113 mg every 12 hours for patients on a concomitant
strong CYP3A4 inhibitor treatment. Eighteen patients treated at the
RP2D were efficacy-evaluable and response results observed at the
RP2D were consistent with the overall population.
Across all patients enrolled in the trial as of the data cutoff
date (n=43), SNDX-5613 was generally well-tolerated, with no
discontinuations due to treatment-related adverse events observed
in heavily pretreated patients. The only grade 3 or greater related
adverse events occurring in at least 5% of patients were QT
prolongation, anemia, and differentiation syndrome. Among all
patients treated at the candidate RP2D (n=22) as of the data cutoff
date, 9% of patients (n=2) experienced grade 3 QT prolongation.
About AUGMENT-101
AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate
the safety, tolerability, pharmacokinetics, and efficacy of orally
administered SNDX-5613. The Phase 1 dose escalation portion of
AUGMENT-101 was separated into two cohorts based on concomitant
treatment with a strong CYP3A4 inhibitor. Arm A enrolled patients
not receiving a strong CYP3A4 inhibitor, while Arm B enrolled
patients receiving a strong CYP3A4 inhibitor. The pivotal Phase 2
portion of the trial will evaluate efficacy, as defined by complete
response rate (per International Working Group response criteria),
across three expansion cohorts: MLLr acute lymphoblastic leukemia
(ALL), MLLr acute myeloid leukemia (AML), and NPM1c mutant AML.
Conference Call and Webcast Details
The Company will host a conference call and webcast
today, Tuesday, April 20, 2021 at 8:00 a.m. ET. The
presentation will feature the trial's principal investigator,
Eytan M. Stein, M.D., Assistant
Attending Physician and Director, Program for Drug Development in
Leukemia, Department of Medicine at Memorial Sloan Kettering Cancer
Center.
The live video webcast and accompanying slides may be accessed
through the Events & Presentations page in the Investors
section of the Company's website at www.syndax.com.
Alternatively, the conference call may be accessed through the
following:
Conference ID: 3129568
Domestic Dial-in Number: (877) 474-0326
International Dial-in Number: (918) 922-6881
Live webcast:
https://onlinexperiences.com/Launch/QReg/ShowUUID=E0296F2E-256E-494B-A4F6-FD7220BACE26
For those unable to participate in the live event, a replay will
be available on the Investors section of the Company's
website, www.syndax.com.
About SNDX-5613
SNDX-5613 is a potent, selective, small molecule inhibitor of
the menin-MLL binding interaction that is being developed for the
treatment of mixed lineage leukemia rearranged (MLLr) acute
leukemias including acute lymphoblastic leukemia (ALL) and acute
myeloid leukemia (AML), and NPM1c mutant AML. In preclinical models
of MLLr acute leukemias, SNDX-5613 demonstrated robust,
dose-dependent inhibition of tumor growth, resulting in a marked
survival benefit. Menin-MLL interaction inhibitors have also
demonstrated robust treatment benefit in multiple preclinical
models of NPM1c mutant AML, which represents the most frequent
genetic abnormality in adult AML. SNDX-5613 is currently being
evaluated in the Company's AUGMENT-101 Phase 1/2 open-label
clinical trial for the treatment of relapsed/refractory (R/R) acute
leukemias. SNDX-5613 was granted Orphan Drug Designation by the
U.S. Food and Drug Administration for the treatment of patients
with AML.
About Mixed Lineage Leukemia Rearranged Acute
Leukemias
Rearrangements of the MLL gene give rise to mixed lineage
leukemia rearranged (MLLr) acute leukemias known to have a poor
prognosis, with less than 25% of adult patients surviving past five
years. MLL rearrangements produce fusion proteins that require
interaction with the protein called menin to drive leukemic cancer
growth. Disruption of the menin-MLLr interaction has been shown to
halt the growth of MLLr leukemic cells. MLLr leukemias, which are
routinely diagnosed through currently available cytogenetic or
molecular diagnostic techniques, occur in approximately 80% of
infant acute leukemias and up to 10% of all acute leukemias. There
are currently no approved therapies indicated for MLLr
leukemias.
About NPM1c Mutant Acute Myeloid Leukemia
NPM1c mutant acute myeloid leukemia (AML), which is
distinguished by point mutations in the NPM1c gene that drive the
leukemic phenotype, is the most common type of cytogenetically
normal adult AML and represents approximately 30% of all adult AML
cases. This subtype of AML has a five year overall survival rate of
approximately 50%. Similar to mixed lineage leukemia rearranged
(MLLr) leukemias, NPM1c mutant AML is highly dependent on the
expression of specific developmental genes shown to be negatively
impacted by inhibitors of the menin-MLL interaction. NPM1c mutant
AML is routinely diagnosed through currently available screening
techniques. There are currently no approved therapies indicated for
NPM1c mutant AML.
About Syndax Pharmaceuticals, Inc.
Syndax Pharmaceuticals is a clinical stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies. The Company's pipeline includes SNDX-5613, a
highly selective inhibitor of the Menin–MLL binding interaction,
axatilimab, a monoclonal antibody that blocks the colony
stimulating factor 1 (CSF-1) receptor, and entinostat, a class I
HDAC inhibitor.
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
design, progress, timing, clinical development and scope of
clinical trials, plans for initiating future clinical trials,
reporting of clinical data for Syndax's product candidates, the
association of data with treatment outcomes 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 trials, clinical trial site
activation or enrollment rates that are lower than expected,
changes in expected or existing competition, changes in the
regulatory environment, the COVID-19 pandemic may disrupt our
business and that of the third parties on which we depend,
including delaying or otherwise disrupting our clinical trials and
preclinical studies, manufacturing and supply chain, or impairing
employee productivity, 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.
Reference
1. Overall Response Rate = CR + CRh + CRi +
CRp + MLFS
Syndax Contacts
Investor Contact
Melissa Forst
Argot Partners
melissa@argotpartners.com
Tel 212.600.1902
Media Contact
Benjamin Kolinski
GCI Health
Benjamin.Kolinski@gcihealth.com
Tel 862.368.4464
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.