On March 11, 2021 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a synthetic lethality-focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported publication of abstracts at the 2021 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Ideaya Biosciences, MAR 11, 2021, View Source [SID1234576550]). IDEAYA will present data for its potential first-in-class synthetic lethality programs IDE397, a Phase 1 methionine adenosyltransferase 2a (MAT2A) inhibitor, poly (ADP-ribose) glycohydrolase (PARG) for which a development candidate is targeted in 2021, and IDE196, a Phase 1/2 protein kinase C (PKC) inhibitor targeting GNAQ/11-mutation cancers.
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The IDEAYA abstracts were posted online by AACR (Free AACR Whitepaper) (View Source) in advance of the 2021 Annual Meeting of AACR (Free AACR Whitepaper), which will be held April 10-15, 2021:
"MAT2A inhibitor, IDE397, displays broad anti-tumor activity across a panel of MTAP-deleted patient-derived xenografts" (Marcus Fischer et al.)
"Genomic and metabolomic analysis of MAT2A inhibition reveals increased RNA splicing, lipid metabolism and cell cycle arrest in MTAP deleted tumor models" (Neil Bhola et al.)
"Synthetic lethality of PARG inhibition in tumors with homologous recombination deficiencies" (Monah Abed et al.)
"Preclinical evaluation of a PKC and MET inhibitor combination in metastatic uveal melanoma" (Marie-Claire Wagle et al.)
IDEAYA is evaluating IDE397, a potential first-in-class small molecule inhibitor targeting MAT2A, in a Phase 1 clinical trial for patients having tumors harboring MTAP deletion. IDEAYA plans to present preclinical data evaluating the efficacy of monotherapy IDE397 in over forty patient-derived xenograft (PDX) models with homozygous MTAP deletions across a range of solid tumor types. IDEAYA will also present preclinical data evaluating the genomic and metabolic effects of pharmacological inhibition of MAT2A in an isogenic cell pair and of proliferation effects in MTAP deleted and MTAP wild type cell lines.
IDEAYA is advancing its wholly-owned PARG synthetic lethality program for patients having tumors with a defined biomarker based on genetic mutations and/or molecular signatures. IDEAYA plans to present preclinical data evaluating the effects of pharmacological inhibition of PARG in a panel of HR-deficient cell lines and cell line derived xenografts (CDX).
"We have established a broad and potential first-in-class clinical stage pipeline in synthetic lethality – an emerging area of precision medicine oncology, and are excited to present our program data at AACR (Free AACR Whitepaper) 2021," said Dr. Michael Dillon, Ph.D., Senior Vice President, Chief Scientific Officer and Head of Research at IDEAYA Biosciences.
IDEAYA is evaluating IDE196, a potential first-in-class PKC inhibitor, in a Phase 1/2 clinical trial for the treatment of metastatic uveal melanoma (MUM) and GNAQ/11-mutation skin melanoma. In MUM, the IDE196 clinical program is focused on clinical combinations, including with binimetinib, a MEK inhibitor, and independently with crizotinib, a cMET inhibitor, pursuant to a clinical trial and supply agreement with Pfizer.
IDEAYA plans to present translational data at AACR (Free AACR Whitepaper) retrospectively evaluating cMET expression in clinical biopsies from MUM patients in an IDE196 Phase 1 clinical trial, as well as preclinical data evaluating synergy between IDE196 and crizotinib in relevant cell models of a liver tumor microenvironment, a site of approximately 90% of uveal melanoma metastases.
"We identified a cMET inhibitor as a potential combination agent through our translational research, and we believe these preclinical data provide a compelling biological rationale for the IDE196 and crizotinib combination to treat patients with metastatic uveal melanoma," said Matthew Maurer, M.D., Vice President, Head of Clinical Oncology and Medical Affairs at IDEAYA Biosciences.