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IDE892 + IDE397
- Development stage
- Unknown
- Lead developer
- IDEAYA Biosciences
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
IDE892 + IDE397 (tuvutromstat) is an investigational, orally administered combination therapy being developed by IDEAYA Biosciences for the treatment of solid tumors harboring methylthioadenosine phosphorylase (MTAP) deletion. The combination consists of IDE892, a potential best-in-class, methylthioadenosine (MTA)-cooperative inhibitor of protein arginine methyltransferase 5 (PRMT5), and tuvutromstat (IDE397), a potential first-in-class, allosteric inhibitor of methionine adenosyltransferase 2A (MAT2A). In MTAP-deleted tumor cells, the loss of MTAP leads to the accumulation of MTA, creating a synthetic lethal vulnerability that increases cellular dependence on both PRMT5 and MAT2A. By simultaneously inhibiting MAT2A (which depletes the PRMT5 methyl donor S-adenosylmethionine) and cooperatively blocking PRMT5, the combination aims to deliver synergistic antitumor activity. The combination is currently being evaluated in a Phase 1 clinical trial (NCT07277413) for patients with MTAP-deleted advanced solid tumors, with a primary focus on non-small cell lung cancer (NSCLC) and pancreatic cancer.
- Other names
- GSK-4362676 + IDE892GSK4362676 + IDE892IDE397 + IDE892IDE892 + GSK-4362676IDE892 + GSK4362676IDE892 + IDE397IDE892 + tuvutromstatIDE892/IDE397tuvutromstat + IDE892
02
Targets
MAT2A (Methionine adenosyltransferase 2A)MAT2B (Methionine adenosyltransferase 2 subunit beta)pMHC-I (Peptide–MHC class I complex)PRMT5 (Protein arginine N-methyltransferase 5)spliceosome (NineTeen Complex)
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