On June 8, 2020 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics, reported that it has selected development candidate, IDE397, for its Methionine adenosyltransferase 2a (MAT2A) Synthetic Lethality program (Press release, Ideaya Biosciences, JUN 8, 2020, View Source [SID1234560913]). The MAT2A program targets patients with tumors having methylthioadenosine phosphorylase (MTAP) deletions. With the nomination of IDE397 as a development candidate for the MAT2A program, IDEAYA has initiated IND-enabling studies and is targeting filing the Investigational New Drug (IND) application in the fourth quarter 2020.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"With IDE397, we have achieved our preclinical target product profile of a differentiated compound, including potency, safety assessment, and physicochemical property characteristics. Based on the preclinical in vivo efficacy data we have generated, we believe IDE397 has the potential for evaluation in both monotherapy and combination studies in select solid tumor types with the genetic alteration of MTAP-deletion," said Michael Dillon, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.
IDE397 Product Profile and MAT2A Program Summary:
Monotherapy activity with robust tumor growth inhibition and pharmacodynamic (PD) modulation in multiple endogenous MTAP-/- in vivo models
Monotherapy activity and tumor regression in HCT116 MTAP-/- xenograft model
No changes in liver enzymes or increased unconjugated bilirubin levels observed in preclinical studies
Favorable physicochemical properties and pharmacokinetics observed across multiple species
MAT2A program enabled by structure-based drug design; over 17 high resolution co-crystal structures have been resolved to enable lead optimization
About MAT2A and MTAP-Deletion:
MTAP-null cells lack the ability to metabolize 5-methylthioadenosine, or MTA, which is an essential step in a biochemical pathway involved in salvaging metabolite S-adenosyl methionine, or SAM. Increased levels of MTA partially inhibit the methyltransferase PRMT5 for which SAM is the substrate. This partial inhibition renders MTAP-null cells more dependent on the activity of methionine adenosyltransferase II alpha or MAT2A, an enzyme that is responsible for the synthesis of SAM. Because of this dependence, loss of MTAP results in synthetic lethality when MAT2A is pharmacologically inhibited.
MTAP deletions are prevalent in approximately 15% of all human tumors across various tumor types. Genetic profiling tests for the deletion of MTAP or for the commonly co-deleted gene CDKN2A are commercially available.