Anvumetostat

iStock, Mininyx Doodle Amgen will continue to advance half of the combo, PRMT5 inhibitor AMG 193, for which it is running a mid-stage trial in MTAP-null advanced non-small cell lung cancer. Amgen and Ideaya will no longer push through with their cancer combo therapy and will wind down testing for the PRMT5 blocker AMG 193 with the MAT2A inhibitor IDE397. According to Ideaya, which disclosed the news in its fourth-quarter business report on Thursday, the companies have “mutually agreed” to discontinue the cancer program this month “and will not pursue dose expansion.” BioSpace has reached out to Amgen for comment and will update this space accordingly. Amgen and Ideaya inked their cancer collaboration in July 2022. The arrangement was a mutually non-exclusive clinical trial and supply partnership targeting solid tumors null for the MTAP marker. Amgen was responsible for running Phase I studies of the combo regimen, while the companies shared external costs and jointly managed clinical development. Commercial rights remained with their respective owners. Following the decision to discontinue testing for the combination therapy, Ideaya will instead study IDE397 with its own PRMT5 inhibitor IDE892 in non-small cell lung cancer, according to its Thursday press release. Similarly, Amgen is moving forward with its assessments of AMG 193. Last year, the pharma shared first-in-human data for AMG 193 monotherapy, demonstrating a 21.4% objective response rate in evaluable patients. Treatment responses were documented across eight different tumor types, including pancreatic adenocarcinoma and squamous/non-squamous non-small cell lung cancer (NSCLC). As for safety, the study found adverse events in around half of patients, the most common ones being nausea (48.8%), fatigue (31.3%) and vomiting (30%). Eight study participants encountered dose-limiting toxicities. In its fourth-quarter business report , Amgen announced that it had initiated a Phase II study of AMG 193 in MTAP-null patients with advanced NSCLC, for which enrollment is ongoing. The pharma is also running a Phase I/Ib/II study of AMG 193 in MTAP-null solid tumors, as well as two Phase Ib studies of the asset, alone or as part of a combo regimen, in MTAP-null thoracic malignancies and gastrointestinal, biliary tract and pancreatic cancers. Thursday’s news adds to Amgen’s recent pipeline woes . In its quarterly report, the pharma revealed that the FDA has put its early-stage obesity asset AMG 513 on clinical hold. Though details remain sparse, CEO Robert Bradway said during the investor call that the pause is likely unrelated to the drug candidate. Amgen at the time also announced that it will terminate the development of fipaxalparant in diffuse cutaneous systemic sclerosis following an underwhelming mid-stage readout.

Ideaya Biosciences is retaining an interest in MAT2A-PRMT5 combinations.\n Amgen and Ideaya Biosciences are winding down their cancer combination study, closing off one way the Big Biotech was looking to dial up the efficacy of its PRMT5 inhibitor AMG 193.The combination study was set in motion by a 2022 deal that positioned the partners to test AMG 193 with Ideaya’s MAT2A inhibitor IDE397. MAT2A inhibition is linked to PRMT5 activity, leading the biotechs to identify the combination as a way to improve outcomes in certain solid tumors. BeiGene bought itself a place in the MAT2A-PRMT5 combination race late last year.Thursday, Ideaya scratched the combination of IDE397 and AMG 193 off the list of drug cocktails that BeiGene is going up against. The biotech said it and Amgen mutually agreed to wind the current study down and drop plans to start dose expansion.While Ideaya is letting Amgen go, it is retaining an interest in MAT2A-PRMT5 combinations. Ideaya has a PRMT5 inhibitor, IDE892, that it plans to test with IDE397 in people with MTAP-deletion non-small cell lung cancer in the second half of the year. The biotech unveiled IDE892 at an R&D event in December. At the event, Ideaya CEO Yujiro Hata hailed the drug candidate as a potential best-in-class PRMT5 inhibitor that was “handpicked to be combined with IDE397.” Yet, while Ideaya trumpeted the merits of its combination, the biotech also professed its ongoing commitment to the Amgen pact.Back then, Hata said the “partnership with Amgen continues to be a significant priority for us,” adding that the plan at that time was “to push both opportunities forward.” Two months later, Ideaya has decided to focus squarely on pushing its in-house opportunity forward.The mutually agreed destruction of the collaboration leaves Amgen without a MAT2A inhibitor to pair with AMG 193. The PRMT5 inhibitor has underwhelmed as a monotherapy, racking up an 11% response rate in phase 1/2 data shared last year, but Amgen still moved the candidate into phase 2 late last year. If the trial shows lackluster efficacy, the biotech may still be able to salvage the asset using combinations.AMG 193 faces competition, though. IDE892 is the latest entrant to a field that includes candidates from AstraZeneca, BeiGene, Bristol Myers Squibb, Servier and Tango Therapeutics. BeiGene and Servier sit alongside Ideaya on the list of companies with inhibitors of PRMT5 and MAT2A.