On December 9, 2019 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the publication of a preclinical report demonstrating that selective inhibition of the Menin-MLL interaction, provides consistent anti-proliferative and anti-leukemic activity across multiple mixed lineage leukemia rearranged (MLLr) samples (Press release, Syndax, DEC 9, 2019, View Source [SID1234552129]). The article, "A Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia," was published in the December 9 issue of Cancer Cell; the article is also available online.
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This study, which was led by researchers at Dana-Farber Cancer Institute and Children’s Cancer Institute, Sydney, Australia, examined the activity of VTP-50469, a close analog of the clinical lead SNDX-5613, against a range of MLLr harboring cell lines and patient-derived xenograft (PDX) models. Cell lines carrying MLL rearrangements were selectively responsive to VTP-50469, triggering disruption of menin containing transcription complexes and causing changes to gene expression that induced terminal differentiation and cell death. In PDX models, of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) subtypes of MLLr, single agent treatment with the Menin-MLL interaction inhibitor significantly reduced leukemia burden and led to profound survival benefit, with many mice remaining disease free more than one year after treatment.
"The newly developed Menin-MLL inhibitor demonstrated remarkable single-agent activity in PDX models of human MLL-rearranged leukemia including disease eradication," said Scott A. Armstrong, M.D., Ph.D., President, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and Chairman, Department of Pediatric Oncology, Dana-Farber Cancer Institute and senior author of the study. "This level of activity is unusual for single agent treatments in leukemia models."
"For patients with genetically-defined acute leukemias, there exists a dire unmet need for novel and effective therapeutic options," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "We are encouraged by these preclinical data, which continue to support our belief that SNDX-5613, our lead Menin inhibitor, has the potential to overcome the limitations of currently approved regimens, many of which do not yield a durable benefit. We are hopeful that these findings will translate positively in our ongoing Phase 1/2 AUGMENT-101 trial, for which we continue to expect initial data in 2020."
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 MLL-rearranged (MLL-r) acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). 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 acute leukemias.
About Mixed Lineage Leukemia Rearranged (MLL-r)
Rearrangements of the MLL gene give rise to MLL-r acute leukemias, known to have a poor prognosis, with less than 55% of patients surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with the protein called Menin to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r 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 MLL-r leukemias.