Foghorn gets an all-clear from Lilly

There seem to be two key elements of Foghorn’s FHD-909 that spurred Lilly to select it for an upcoming phase 1 trial: the molecule is oral, and it’s selective for SMARCA2. This is important in light of the relatively small pipeline of competing projects with this mechanism, some being intravenously delivered, and some hitting SMARCA2 as well as SMARCA4. Foghorn’s own pipeline lead is FHD-286, an oral SMARCA2/4 inhibitor that continues in phase 1 in AML despite suffering a clinical hold two years ago; its development in uveal melanoma is no longer being pursued. The clinical hold, subsequently lifted, was the result of deaths thought to have been due to differentiation syndrome, and sent Foghorn stock into a protracted slump. Though the shares surged 23% on Friday Foghorn still trades 63% below its 2020 IPO price. After Lilly’s buy-in the spotlight falls on Prelude Therapeutics, which has a SMARCA2-selective degrader in phase 1, though this is dosed IV; an unnamed oral molecule could enter the clinic at a similar time as FHD-909, Prelude reckons. While Ryvu was also working preclinically on oral SMARCA2-selective inhibition that project was axed back in 2021.

The SMARCA2 pipeline

Note: SMARCA2=BRM; SMARCA4=BRG1. Source: OncologyPipeline.