30 January 2020
- Results support ongoing Phase 1/2 AUGMENT-101 trial of Syndax Pharmaceuticals' lead Menin-MLL inhibitor, SNDX-5613, for the treatment of adults with relapsed/refractory acute leukemias, including NPM1 mutant AML -
This study examined the activity of VTP-50469, an orally-available inhibitor of MLL1-Menin interaction and close analog of the Company's lead Menin inhibitor, SNDX-5613, for the treatment of established NPM1 AML and the possible prevention of the disease in high-risk populations. Using preclinical models of NPM1 AML, the authors established that the presence of an NPM1 mutation is a clear indicator of pre-leukemic activity and represents a critical step in the development of AML. VTP-50469 was shown to eradicate NPM1 mutant cells at various stages of disease development, suggesting that Menin-MLL inhibition could potentially serve either as a targeted preventive therapy or as a treatment of established disease.
"These unprecedented findings highlight the potential for single agent Menin-MLL inhibition to rapidly eradicate fully developed NPM1 mutant leukemia, even in the case of aggressive relapsed AML," said
"NPM1 mutant AML represents the most common type of cytogenetically normal AML," said
SNDX-5613 is a potent, selective, small molecule inhibitor of the Menin-MLL binding interaction that is being developed for the treatment of MLL-rearranged (MLL-r) acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML); VTP-50469 is a close analog of SNDX-5613. MLL rearrangements occur in approximately 80% of acute leukemia cases in infants and up to 10% of all leukemias. In preclinical models of MLL-r 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 NPM1 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.
AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate the efficacy, safety, tolerability and pharmacokinetics of orally administered SNDX-5613. The Phase 1 dose escalation portion of AUGMENT-101 will enroll adults with R/R acute leukemias and establish a recommended Phase 2 dose. The Phase 2 portion will evaluate efficacy, as defined by Complete Response rate (per
About NPM1 Mutant Acute Myeloid Leukemia
NPM1 mutant AML, which is distinguished by point 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 5-year overall survival rate of approximately 50%. Similar to MLL-r 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.
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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 and the reporting of clinical data for Syndax's product candidates, 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
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