Syndax Pharmaceuticals, Inc. Announces that Science Magazine Publishes Results from Preclinical Study on the Activity of Menin-Mll Inhibition for the Treatment of Npm1 Acute Myeloid Leukemia
January 31, 2020 at 12:41 am IST
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Syndax Pharmaceuticals, Inc. announced that Science magazine has published a preclinical report supporting the potential role of MLL1-Menin inhibition in the management of nucleophosmin (NPM1) mutant acute myeloid leukemia (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. 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 International Working Group response criteria), across three expansion cohorts: MLL-r ALL, MLL-r AML and NPM1 mutant AML.
Syndax Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company. It is focused on developing pipeline of cancer therapies. Its product candidates include revumenib, and axatilimab. It is developing revumenib, a potent, selective, small molecule inhibitor of the menin-MLL binding interaction for the treatment of KMT2A rearranged also known as mixed lineage leukemia rearranged, acute leukemias including acute lymphoblastic leukemia and acute myeloid leukemia (AML), and necleophosmin 1, also known as NPM1, mutant A. It is also exploring the use of revumenib as a treatment in solid tumors, specifically its activity in metastatic colorectal cancer. It is also developing axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 receptor (CSF-1R) in chronic graft-versus-host disease (cGVHD), as well as idiopathic pulmonary fibrosis. Entinostat is its oral, small molecule product candidate that has direct effects on both cancer cells and immune regulatory cells.
Syndax Pharmaceuticals, Inc. Announces that Science Magazine Publishes Results from Preclinical Study on the Activity of Menin-Mll Inhibition for the Treatment of Npm1 Acute Myeloid Leukemia