Ideaya exits Werner and Pol theta

In December GSK walked away from two Ideaya assets, and the latter company just confirmed during its first-quarter results that it’s discontinuing the projects itself. The assets are IDE275, a Werner helicase inhibitor, and IDE705, a DNA Pol theta (polymerase θ) inhibitor.

Ideaya said it was “currently evaluating strategic options” for the compounds, but it seems unlikely to drum up much licensing interest, given several broad setbacks with both synthetic lethality approaches.

The Werner inhibitor field has suffered various blows, including Roche handing RO7589831 back to Vividion (Bayer), and Novartis presenting underwhelming data with HRO761 at ESMO last year. Other groups still active here include Eikon and Nimbus, whose EIK1005 and NDI-219216 respectively are in phase 1/2.

In Pol theta inhibition Artios is the only company to have reported clinical results to date, but its contender ART6043 has only produced responses in its phase 1/2 trial when combined with Lynparza. Another player here is AstraZeneca, whose AZD4956 recently went into the phase 1/2 Parthenon trial, and was in an AACR poster revealed to have this mechanism.

MAT2A mishaps

Ideaya still has plenty of other irons in the fire, including IDE397, a MAT2A inhibitor also once partnered with GSK; the big pharma decided in 2022 not to opt in to that asset, which has since shown early promise. However, Ideaya now looks to be focused on a testing that project alongside its PRMT5 inhibitor IDE892, with a combination cohort of its phase 1 trial set to start mid-year.

A recent disappointment in PRMT5 inhibition saw one of the leaders, Amgen, discontinue its contender, AMG 193.

Meanwhile, in MAT2A, Ideaya disclosed  in March that it was abandoning a combo of IDE397 and Gilead’s TROP2-targeting ADC Trodelvy in MTAP-deleted urothelial and lung cancers. The first hints that Gilead was cooling on IDE397 emerged in February, when the big biotech paid $80m up front for Genhouse's much earlier-stage MAT2A inhibitor, GH31.

At least Gilead still sees promise in this mechanism: on Wednesday BeOne slipped out the deprioritisation of its MAT2A inhibitor, BG-89894, among other assets.