Time is running out for the NRF2 mechanism

The quiet discontinuation of a phase 1 study of Novartis’s MGY825 leaves Bayer’s BAY 3605349 as the last molecule with activity on NRF2 still in clinical development. And even that asset, derived from Bayer’s $1.5bn acquisition of Vividion in 2021, looks to be on uncertain ground; a phase 1 trial of BAY 3605349 dosed its first patient two years ago, but since then there’s been silence as to any data, though as of 30 October the project was still listed as active in Bayer’s R&D pipeline. As for Novartis, that group’s phase 1 trial of MGY825 in non-small cell lung cancer was marked “terminated” on clinicaltrials.gov a few days ago, with “business decision” stated as the reason. Novartis has told ApexOnco that the discontinuation followed a strategic review. MGY825’s targets included NFE2L2 and KEAP1 (both are involved in NRF2 expression and regulation), while BAY 3605349 is described as a KEAP1 activator and NRF2 inhibitor; some cancers are thought to be NRF2-driven. While the latter is still in play, Bayer on Wednesday separately revealed the discontinuation of another Vividion-originated asset – the STAT3 inhibitor VVD-130850/BAY 3630914 – as well as the anti-CCR8 MAb lanerkitug/BAY 3375968.

Selected projects with activity on NRF2

Source: OncologyPipeline.