Syndax Announces Updated Data Supporting Impressive Clinical Profile of Revumenib in Genetically-Defined Acute Leukemias to Be Presented at the 65th ASH Annual Meeting

– Additional data from pivotal AUGMENT-101 trial in R/R KMT2Ar acute leukemia further highlight revumenib's potential best-in-class profile –

– 100% ORR (n=7) and manageable safety profile observed in Phase 1 results of SAVE trial, an all-oral combination regimen of revumenib plus venetoclax-decitabine/cedazuridine in R/R AML –

– Patients re-started on treatment with revumenib in post-transplant maintenance exhibit durable MRD negative responses –

WALTHAM, Mass., Nov. 2, 2023 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that updated data from multiple trials across its clinical program for revumenib, the Company's highly selective, oral menin inhibitor, will be featured in three poster presentations at the 65^th American Society of Hematology (ASH) Annual Meeting being held December 9-12, 2023, in San Diego, California. Copies of the abstracts are now available online via the ASH website at www.hematology.org.

"We look forward to sharing updated data, which we believe continue to underscore revumenib's potential to serve as a first- and best-in-class treatment option for patients with KMT2Ar and mNPM1 acute leukemia across a variety of settings as monotherapy and in combination with standard of care agents," said Michael A. Metzger, Chief Executive Officer. "Following recently reported positive topline data from our pivotal AUGMENT-101 trial, and with an NDA filing on track for year-end, we are excited to finish what has thus far been a transformational year with several key data updates at ASH."

Phase 1/2 AUGMENT-101 Trial

Pivotal Phase 2 Portion

The Company previously announced positive topline data from the protocol-defined pooled analysis of the pivotal Phase 2 portion of the AUGMENT-101 trial. The trial met its primary endpoint with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% at the interim analysis of the pooled KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cohorts (p-value = 0.0036). Based on the Independent Data Monitoring Committee (IDMC) recommendation, the Company stopped the trial to further accrual in the KMT2Ar cohorts. Syndax continues to expect to submit a New Drug Application (NDA) for revumenib for the treatment of relapsed/refractory (R/R) KMT2Ar acute leukemia to the U.S. Food and Drug Administration by year-end under the Real-Time Oncology Review (RTOR) program. Full data from the pivotal portion of the study will be reported at the meeting.

Abstract Number: 2907
Title: Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemias: Efficacy and Safety Results from the Augment-101 Phase 1/2 Study
Presenter: Ibrahim Aldoss, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 – 8:00 p.m. PT

Phase 1/2 SAVE Study

The Phase 1/2 SAVE study is an investigator-sponsored trial of the all-oral regimen of revumenib, venetoclax, and ASTX727 (fixed-dose combination of decitabine and cedazuridine) in children and adults with R/R AML and mixed phenotype acute leukemias. As of a data cutoff date of July 20, 2023, eight patients were enrolled, with 2.5 median prior lines of therapy.

Seven of eight patients were response-evaluable, and all seven attained a morphologic remission (overall response rate of 100%). Three patients transitioned to hematopoietic stem-cell transplantation (HSCT) following response. Two patients are in continued remission and have started maintenance treatment with revumenib. Enrollment in the study is ongoing, and updated data will be presented at the meeting.

The combination was well tolerated in this relapsed and refractory population.  Grade ≥3 treatment related adverse events (TRAEs) were febrile neutropenia (63%), decreased platelets count (25%), and decreased neutrophil count (25%). There was one dose-limiting toxicity (DLT), Grade 4 prolonged thrombocytopenia and neutropenia. There were no deaths due to TRAEs and no Grade 3 or higher QTc prolongation occurred.

Abstract Number: 58
Title: Early Results of the Phase I/II Study Investigating the All-Oral Combination of the Menin Inhibitor Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE)
Presenter: Ghayas Issa, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Upcoming Therapies in Newly Diagnosed and Relapsed/Refractory AML
Session Date: Saturday, December 9, 2023
Session Time: 9:30 – 11:00 a.m. PT
Presentation Time: 10:15 a.m. PT

Revumenib Maintenance Therapy Post-HSCT

The ASH abstract #4950 describes data from AUGMENT-101 Phase 1 patients who received revumenib maintenance therapy, including some ongoing for more than one year after HSCT. Revumenib duration of treatment in the maintenance setting at the time of this analysis ranged from 23 to 588 days, with treatment ongoing for five of the nine patients. CRc (CR + CRh + CRp + CRi + MLFS) was maintained in six of nine patients after HSCT and maintenance revumenib. One patient with reported minimal residual disease (MRD) after HSCT converted to MRD negative status following initiation of revumenib maintenance therapy. MRD negative remissions were maintained in five patients as of the data cutoff. Three patients remain on revumenib maintenance therapy for more than one-year post-transplant. The presentation will include longer follow-up of these patients and data from the patients in the pivotal portion of the AUGMENT-101 trial. 

Abstract Number: 4950
Title: Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant
Presenter: Andrius Žučenka, M.D.
Session Name: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster III
Session Date: Monday, December 11, 2023
Presentation Time: 6:00 – 8:00 p.m. PT

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Revumenib was granted Orphan Drug Designation by the 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 granted BTD by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. Syndax expects to complete an NDA submission for KMT2Ar acute leukemia under the Oncology Center of Excellence Review RTOR Program by year-end 2023.

About the AUGMENT-101 trial

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 included 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 has enrolled R/R patients across the following trial populations: patients with mNPM1 AML, patients with KMT2Ar AML, and patients with KMT2Ar ALL.  Following the receipt of Breakthrough Therapy designation from the FDA for revumenib for the treatment of R/R acute leukemia harboring a KMT2A rearrangement, regardless of age or tumor type, and based on discussions with the FDA, the Company decided to pool data from the AUGMENT-101 cohorts enrolling R/R KMT2Ar AML and R/R KMT2Ar ALL.  Based on the Independent Data Monitoring Committee (IDMC) recommendation at the protocol pre-specified interim analysis, the Company stopped the trial to further accrual in the KMT2A cohorts. The trial continues to enroll R/R patients with mNPM1 AML and expects to complete enrollment of this cohort by year-end. The primary endpoint for each of the cohorts is efficacy as measured by complete remission rate (CR + CRh) per protocol, with 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 that is 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 one year and the majority of patients suffer relapse within five 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 three months. There are currently no approved therapies indicated for KMT2A-rearranged acute leukemia.

About NPM1-Mutant Acute Myeloid Leukemia

NPM1-mutant 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 KMT2A-rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A 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

Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective inhibitor of the menin–KMT2A binding interaction, and axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. 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," "could," "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 potential submission of an NDA by year-end as well as the potential impact of RTOR on the Company's submission timeline, 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; 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.
[email protected]
Tel 781.684.9827

SNDX-G

SOURCE Syndax Pharmaceuticals, Inc.