Syndax Announces Positive Interim Data Demonstrating Robust Clinical Activity in Phase 1 Portion of the AUGMENT-101 Trial of SNDX-5613 in Patients with Genetically-Defined Acute Leukemias

Rhea-AI Summary

Syndax Pharmaceuticals (SNDX) reported promising results from the Phase 1 portion of the AUGMENT-101 trial for SNDX-5613, an oral menin inhibitor targeting MLLr and NPM1c mutant acute leukemias. With a 48% overall response rate among 31 evaluable patients, 67% achieved minimal residual disease negative status. The company identified a recommended Phase 2 dose of 226 mg every 12 hours. The drug was well-tolerated, with no discontinuations due to treatment-related adverse events. The pivotal Phase 2 trial is anticipated to start by Q2 2021.

Positive

• 48% overall response rate in evaluable patients with SNDX-5613.
• 67% of responders achieved minimal residual disease negative status.
• Identified a recommended Phase 2 dose of 226 mg every 12 hours.
• Well-tolerated with no discontinuations due to treatment-related side effects.

Negative

• The trial population consisted of heavily pretreated patients, indicating a challenging treatment landscape.

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.

FAQ

What are the results of the Phase 1 AUGMENT-101 trial for SNDX-5613?

The trial reported a 48% overall response rate, with 67% of responders achieving minimal residual disease negative status.

When is the pivotal Phase 2 portion of the AUGMENT-101 trial expected to begin?

The pivotal Phase 2 trial is expected to commence by the end of Q2 2021.

What is the recommended Phase 2 dose for SNDX-5613?

The recommended Phase 2 dose is 226 mg every 12 hours for patients not on a strong CYP3A4 inhibitor.

How well was SNDX-5613 tolerated in the trial?

SNDX-5613 was generally well-tolerated, with no discontinuations due to treatment-related adverse events reported.

Who were the participants in the AUGMENT-101 trial?

The trial included 43 heavily pretreated patients with mixed lineage leukemia rearranged and nucleophosmin mutant acute leukemias.