MAT2A and PRMT5 have emerged as critical cancer targets, with about 15% of all tumors showing MTAP depletion—a number that can increase to 30% after chemotherapy. Despite their promise, developing MAT2A inhibitors has proven challenging for many companies, with several discontinuing efforts due to toxicity observed in animal models with higher levels of MTAP depletion than humans.
However, groups with advanced toxicology expertise have successfully advanced MAT2A inhibitors to human clinical trials, demonstrating both safety and efficacy. One notable example is IDEAYA, whose molecule showed a 39% overall response rate (ORR) in Phase II trials, surpassing PRMT5 inhibitors in performance.
For companies with PRMT5 inhibitors and strong toxicology capabilities, targeting MAT2A represents a key opportunity for future cancer therapies.
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