- 30% CR/CRh rate in efficacy evaluable
population; 27% CR/CRh rate observed in both mNPM1 and KMT2Ar
(MLLr) R/R acute leukemia patients treated at RP2D -
- 9 of 12 patients who underwent stem
cell transplant after achieving a response with revumenib remained
in remission, with four continuing beyond one year -
- Company to host conference call and webcast
on Sunday, December 11, 2022 at
8:00 a.m. CT/ 9:00 a.m. ET -
WALTHAM,
Mass., Dec. 10, 2022 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical-stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies, today presented updated positive data from the
Phase 1 portion of the ongoing Phase 1/2 AUGMENT-101 trial of
revumenib in patients with nucleophosmin mutant (mNPM1) and KMT2A
rearranged (KMT2r) relapsed/refractory (R/R) acute myeloid or acute
lymphoid leukemias (ALL or AML). Revumenib is the Company's highly
selective, oral menin inhibitor. The data were featured during two
oral sessions today at the 64th American Society of Hematology
(ASH) Annual Meeting.
"Both AUGMENT-101 data presentations featured today at the ASH
Annual Meeting highlight revumenib's compelling clinical profile
and continue to support the potential for revumenib to be a
first-in-class and best-in-class therapy for both KMT2Ar and NPM1
acute leukemias," said Michael A.
Metzger, Chief Executive Officer. "We previously announced
that revumenib received Breakthrough Therapy Designation for the
treatment of adult and pediatric patients with R/R acute leukemia
(AML or ALL) harboring KMT2A rearrangements, further emphasizing
the compelling data that we have generated in the Phase 1 portion
of the trial that included 46 R/R KMT2Ar acute leukemia patients as
well as the unmet need that exists in this population. We remain on
track to report top-line data from at least one of the cohorts from
the pivotal Phase 2 portion of the trial beginning in the third
quarter of 2023, followed by a potential New Drug Application
filing by the end of 2023."
"Patients with genetically-defined acute leukemias, including
those harboring NPM1 mutations and KMT2A-rearrangements, have a
limited number of effective treatment options and face a
particularly poor prognosis," said Ghayas
C. Issa, M.D., Assistant Professor, Department of Leukemia,
Division of Cancer Medicine, The University of
Texas MD Anderson Cancer Center. "The deep, durable
responses and manageable safety profile observed continue to
support the potential for revumenib to serve as a meaningful new
addition to the treatment armamentarium for this patient
population. I look forward to contributing to the continued
advancement of this promising therapeutic option."
The oral presentation titled "The Menin Inhibitor Revumenib
(SNDX-5613) Leads to Durable Responses in Patients with
KMT2A-Rearranged or NPM1 Mutant AML: Updated Results of a Phase 1
Study" featured updated results from the Phase 1 portion of the
AUGMENT-101 trial. As of the March
2022 data cutoff date, 60 patients with R/R mutant NPM1 or
KMT2Ar acute leukemia were efficacy evaluable. In the efficacy
evaluable population, the ORR was 53% (32/60) with a CR/CRh rate of
30% (18/60), and 78% (14/18) of patients with CR/CRh attaining
minimal residual disease (MRD) negativity. Additional analyses from
the trial indicate that at doses which met the protocol defined
criteria for a recommended Phase 2 dose (RP2D), the CR/CRh rate was
27% in both the KMT2Ar (10/37) and the mutant NPM1 (3/11) patient
populations. A total of 38% (12/32) of responders proceeded to
transplant. The median time to response in the trial was 1.9
months, and the median duration of CR/CRh response was 9.1 months
in the efficacy evaluable population as of data cutoff.
Additional results included:
Best
Response
|
Efficacy
Population
(N=60)
|
Efficacy
Population
Doses Meeting
Criteria for
RP2D
(n=48)
|
Response
|
|
|
Overall response
rate1, n, (%)
|
32
(53 %)
|
25
(52 %)
|
CR/CRh
|
18
(30 %)
|
13
(27 %)
|
CR
|
12
(20 %)
|
8
(17 %)
|
CRh
|
6
(10 %)
|
5
(10 %)
|
CRp
|
5 (8 %)
|
5
(10 %)
|
MLFS
|
9
(15 %)
|
7
(15 %)
|
|
|
|
MRDneg
rate2
|
18/32 (56%)
|
14/25 (56%)
|
within
CR/CRh MRDneg, n, (%)
|
14/18 (78%)
|
10/13 (77%)
|
within
CR/CRh/CRp MRDneg, n, (%)
|
18/23 (78%)
|
14/18 (78%)
|
KMT2Ar
(MLLr)
|
|
|
Overall response
rate1, n, (%)
|
27/46 (59%)
|
20/37 (54%)
|
CR/CRh
|
15/46 (33%)
|
10/37 (27%)
|
mNPM1
|
|
|
Overall response
rate1, n, (%)
|
5/14 (36%)
|
5/11 (46%)
|
CR/CRh
|
3/14 (21%)
|
3/11 (27%)
|
1. Overall Response
Rate = CR+CRh+CRp+MLFS; 2. MRD status assessed locally by PCR or
MCF
|
Revumenib was well-tolerated, and no new safety signals were
identified in the trial, including in patients who proceeded to
stem cell transplant. There were no discontinuations due to
treatment-related adverse events. The only dose limiting toxicity
was asymptomatic Grade 3 QT prolongation, observed in 10% of
patients treated at the RP2D and 13% of patients treated at all
doses tested. No ventricular arrythmias or other clinical sequelae
related to QTc prolongation were reported. Differentiation syndrome
occurred in 16% of patients, and all cases of differentiation
syndrome were Grade 2, and responded to standard management of
steroids with or without hydroxyurea.
The oral presentation titled "Outcomes After Transplant in
Relapsed/Refractory KMT2Ar (MLLr) and mNPM1 (NPM1c) Leukemia
Patients Achieving Remissions After Menin Inhibition: Revumenib
(SNDX-5613) Ph1 Experience" describes outcomes after transplant in
patients achieving remissions in the Phase 1 portion of the
AUGMENT-101 trial. Across evaluable patients with mNPM1 (n=14) or
MLLr (n=46) acute leukemia who received revumenib, 12 (20%)
patients proceeded to stem cell transplant, 11 (92%) of whom were
MRD negative prior to transplant. Nine of the 12 patients (75%) who
received a stem cell transplant remained in remission as of the
data cutoff date, with a median follow-up of 12.3 months, and four
patients experienced remission for longer than one year without
additional maintenance therapy.
A copy of today's presentations will be available in the
Publications and Meeting Presentations section of Syndax's
website.
Conference Call and Webcast
The Company will host a conference call and webcast to discuss
the ASH data update tomorrow, Sunday,
December 11, 2022 at 8:00 a.m.
CT/ 9:00 a.m. ET. Joining
the call will be members of the Syndax management team as well as
two of the Primary Investigators on the AUGMENT-101 trial
[Eytan M. Stein, M.D., Assistant
Attending Physician and Director, Program for Drug Development in
Leukemia, Department of Medicine at Memorial Sloan
Kettering Cancer and Ghayas C. Issa,
M.D., Assistant Professor, Department of Leukemia, Division of
Cancer Medicine, The University of
Texas MD Anderson Cancer Center].
The live audio webcast and accompanying slides may be accessed
through the Events & Presentations page in the
Investors section of the Company's website. Alternatively, the
conference call may be accessed through the following:
Conference ID: SYNDAX12
Domestic Dial-in Number: 800-225-9448
International Dial-in Number: 203-518-9708
Live
webcast: https://www.veracast.com/webcasts/OpenEx/General/p08Np3.cfm
For those unable to participate in the conference call or
webcast, a replay will be available on the Investors section of the
Company's website at www.syndax.com approximately 24
hours after the conference call and will be available for a limited
time.
About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of
the menin-MLL binding interaction that is being developed for the
treatment of KMT2A rearranged, also known as mixed lineage leukemia
rearranged or MLLr, acute leukemias including acute lymphoblastic
leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant
AML. Revumenib is currently being evaluated in several clinical
trials, including the Company's pivotal AUGMENT-101 Phase 1/2
open-label clinical trial for the treatment of relapsed/refractory
(R/R) acute leukemias. Robust clinical activity with durable
responses have been reported in the Phase 1 portion of
AUGMENT-101. Revumenib was granted Orphan Drug
Designation by the U.S. Food and Drug
Administration (FDA) and European Commission for the
treatment of patients with AML, and Fast Track designation by
the FDA for the treatment of adult and pediatric patients with
R/R acute leukemias harboring a KMT2A rearrangement or NPM1
mutation. Revumenib was also granted Breakthrough Therapy
Designation by the FDA for the treatment of adult and pediatric
patients with R/R acute leukemia harboring a KMT2A
rearrangement.
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 revumenib. 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 Phase 2 pivotal
portion of AUGMENT-101 is currently underway. Patients will be
enrolled across each of the following trial populations: patients
with NPM1 mutant AML, patients with KMT2Ar (MLLr) AML, and patients
with KMT2Ar (MLLr) ALL. Discussions with the FDA have confirmed
that AUGMENT-101 may potentially serve as the basis for regulatory
filings in each patient population. The primary endpoint for each
of the trials will be efficacy as measured by complete remission
rate (CR + CRh), with key secondary endpoints including duration of
response (DOR) and overall survival (OS).
About KMT2A (MLL) Rearranged Acute Leukemia
Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene
give rise to KMT2Ar acute leukemia known to have a poor prognosis,
with less than 25% of adult patients surviving past five years.
KMT2A genes produce fusion proteins that require interaction with
the protein called menin to drive leukemic cancer growth.
Disruption of the menin-KMT2Ar interaction has been shown to halt
the growth of KMT2Ar leukemic cells.
KMT2Ar acute leukemia can phenotypically appear as AML,
ALL, or mixed phenotype acute leukemia (MPAL) and is routinely
diagnosed through currently available cytogenetic or molecular
diagnostic techniques. The median overall survival (OS) after
standard of care first-line treatment, including intensive
chemotherapy and transplant, is less than 1 year and the majority
of patients suffer relapse within 5 years. Most R/R patients
treated with second-line therapy relapse within the first year.
With third line treatment or beyond, only a small percentage of
patients achieve complete remission (CR), and the median OS is less
than 3 months.
About NPM1 Mutant Acute Myeloid Leukemia
NPM1 mutant acute myeloid leukemia (AML), which is distinguished
by mutations in the NPM1 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, NPM1
mutant AML is highly dependent on the expression of specific
developmental genes shown to be negatively impacted by inhibitors
of the menin-MLL interaction. NPM1 mutant AML is routinely
diagnosed through currently available screening techniques. There
are currently no approved therapies indicated for NPM1 mutant
AML.
About Syndax Pharmaceuticals, Inc.
Syndax Pharmaceuticals is a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies.
Highlights of the Company's pipeline include revumenib (SNDX-5613),
a highly selective inhibitor of the menin–MLL binding interaction,
and axatilimab, a monoclonal antibody that blocks the colony
stimulating factor 1 (CSF-1) receptor, both currently in pivotal
trials. For more information, please visit www.syndax.com or follow
the Company on Twitter and LinkedIn.
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, the reporting of clinical data for Syndax's product
candidates, the progress of regulatory submissions and approvals,
including the potential use of Syndax's product candidates to treat
various cancer indications and fibrotic diseases. 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
impact of macroeconomic conditions (such as COVID-19 pandemic, the
Russia-Ukraine war, inflation, among others) on
Syndax's business and that of the third parties on which Syndax
depends, including delaying or otherwise disrupting Syndax's
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.
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.