- 30% CR/CRh rate and 53% ORR in R/R acute leukemia patients with NPM1
or MLLr (KMT2Ar) mutations; no discontinuations due to
treatment-related adverse events -
- Median duration of CR/CRh response of
9.1 months -
- 9 of 12 patients who underwent stem
cell transplant after achieving a response with revumenib remained
in remission, with 4 continuing beyond one year -
- Data will be featured in two oral
presentations at the 64th ASH Annual Meeting -
- 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., Nov. 3, 2022 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical-stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies, today announced updated positive data from the
Phase 1 portion of the ongoing Phase 1/2 AUGMENT-101 trial of
revumenib in patients with nucleophosmin (NPM1) mutant and mixed
lineage leukemia rearranged (MLLr) relapsed/refractory (R/R) acute
leukemias. Revumenib is the Company's highly selective, oral
menin inhibitor. Updated data from the Phase 1 portion of the trial
will be featured during two oral sessions at the 64th American
Society of Hematology (ASH) Annual Meeting on Saturday, December 10, 2022 at 10:00 a.m. CT and 4:45
p.m. CT. Copies of the abstracts are available on the ASH
website at www.hematology.org.
"These data continue to showcase revumenib's potential as a
best-in-class treatment option for patients with mNPM1 or MLLr
acute leukemia. We are highly encouraged by the updated data
including the percentage of patients achieving a CR/CRh, which
improved to 30%," said Michael A.
Metzger, Chief Executive Officer. "We expect to report
top-line data for at least one of the cohorts from the pivotal
Phase 2 portion of the AUGMENT-101 trial beginning in the third
quarter of 2023, followed by an expected New Drug Application
filing by the end of 2023. In addition to the R/R setting, we are
committed to unlocking the full potential of revumenib by testing
combinations to enable the expansion into newly diagnosed and
maintenance settings in mNPM1 and MLLr acute leukemias, as well as
into colorectal cancer, our first assessment of revumenib in solid
tumors."
The ASH abstract #63 describes updated results from the Phase 1
portion of the AUGMENT-101 trial. As of the March 2022 data cutoff date, sixty patients with
R/R mutant NPM1 or MLLr (KMT2Ar) acute leukemia were efficacy
evaluable, an increase of nine patients from the 51 evaluable for
efficacy at the 2021 ASH Annual Meeting. The overall response rate
(ORR) was 53% (32/60) with a
CR/CRh rate of 30% (18/60). There were no discontinuations due to
treatment-related adverse events, and the median duration of
response in the trial was 9.1 months as of data cutoff.
Additional results included:
Best
Response
|
Efficacy Population
(N=60)
|
Response
|
|
Overall response
rate1, n, (%)
|
32
(53 %)
|
CR/CRh
|
18
(30 %)
|
CR
|
12
(20 %)
|
CRh
|
6
(10 %)
|
CRp
|
5 (8 %)
|
MLFS
|
9
(15 %)
|
MRDneg
|
|
CRc MRDneg
rate2
|
18/60 (30%)
|
within
CR/CRh MRDneg, n, (%)
|
14/18 (78%)
|
within
CR/CRh/CRp MRDneg, n, (%)
|
18/23 (78%)
|
MLLr
(KMT2Ar)
|
|
Overall response
rate1, n, (%)
|
27/46 (59%)
|
CR/CRh
|
15/46 (33%)
|
mNPM1
|
|
Overall response
rate1, n, (%)
|
5/14 (36%)
|
CR/CRh
|
3/14 (21%)
|
1. Overall Response
Rate = CR+CRh+CRp+MLFS; 2. CR+CRh+CRp; 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. The only dose limiting toxicity observed was
asymptomatic Grade 3 QT prolongation. No ventricular arrythmias or
other clinical sequelae related to QTc prolongation were reported.
All cases of differentiation syndrome were Grade 2, and readily
managed with standard therapies.
The ASH abstract #376 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, ten (83%) of whom were
minimal residual disease-negative. 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. Three
patients were treated in the compassionate use setting with
revumenib maintenance following stem cell transplant or
non-myeloablative stem cell boost, two (67%) of whom remained in
remission as of the data cutoff date for over one year.
Details for the presentations are as follows:
- Abstract Number: 63
- Title: The Menin Inhibitor SNDX-5613 (revumenib) Leads
to Durable Responses in Patients (Pts) with KMT2A-Rearranged or
NPM1 Mutant AML: Updated Results of a Phase (Ph) 1 Study
- Presenter: Ghayas Issa,
M.D.
- Session Name: 616. Acute Myeloid Leukemias:
Investigational Therapies, Excluding Transplantation and Cellular
Immunotherapies: Relapsed/Refractory AML
- Session Date: Saturday, December
10, 2022
- Session Time: 9:30 a.m. - 11:00
a.m. CT
- Presentation Time: 10:00 a.m.
CT
- Abstract Number: 376
- Title: Outcomes after Transplant in Relapsed/Refractory
KMT2Ar (MLLr) and mNPM1 (NPM1c) leukemia Patients Achieving
Remissions after Menin Inhibition: SNDX-5613 (revumenib) Ph1
Experience
- Presenter: Ghayas Issa,
M.D.
- Session Name: 723. Allogeneic Transplantation: Long-term
Follow-up and Disease Recurrence II
- Session Date: Saturday, December
10, 2022
- Session Time: 4:00 p.m. - 5:30
p.m. CT
- Presentation Time: 4:45 p.m.
CT
Conference Call and
Webcast
The Company also announced today that it will host a conference
call and webcast to discuss the ASH data update on 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 principal investigators in the
AUGMENT-101 trial.
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 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 portion
of AUGMENT-101 is currently underway. A total of 64 adult and up to
ten pediatric patients will be enrolled across each of the
following three distinct trial populations: patients with NPM1
mutant AML, patients with MLLr (KMT2A) AML, and patients with MLLr
(KMT2A) ALL. Discussions with the FDA have confirmed that
AUGMENT-101 may potentially serve as the basis for regulatory
filings in each of the three distinct trials. The primary endpoint
for each of the three trials will be efficacy as measured by
complete remission rate (CR + CRh), with key secondary endpoints
including DOR and overall survival.
About Mixed Lineage Leukemia (MLL
a.k.a. KMT2A) Rearranged Acute Leukemias
Rearrangements of the MLL (KMT2A) 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 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 Revumenib
Revumenib 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 NPM1 mutant AML. Revumenib 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. 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 U.S. FDA for
the treatment of adult and pediatric patients with R/R acute
leukemias harboring a mixed lineage leukemia rearranged MLLr or
NPM1 mutation.
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, and the potential use of our 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 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.
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.