Exelixis abandons a synthetic lethality shot

Exelixis only took its PKMYT1 inhibitor XL495 into phase 1 last October, but has already thrown in the towel: in last week’s first-quarter release the company revealed that it had discontinued the project based on early clinical data. The group isn’t the only one to have fallen short here: Repare has disappointed with its contender lunresertib, for which it’s now seeking a partner. This leaves the most advanced active PKMYT1-targeting assets as Acrivon’s ACR-2316 and Schrödinger’s SGR-3515; both additionally hit Wee1, another mechanism that’s seen its fair share of failure. Both companies are due to report phase 1 data in the second half, setting up a showdown. However, the groups’ market caps are very different, with Schrödinger worth $1.7bn versus Acrivon’s $37m. As for Exelixis, that company is attempting to diversify away from its blockbuster Cabometyx, and recently took a PD-L1 x NKG2A MAb into the clinic. Its biggest hope is the next-gen kinase inhibitor zanzalintinib, but it’s unclear whether this is any better than Cabometyx, based on colorectal cancer data Stellar-001. Renal cancer results from Stellar-002 will feature at ASCO, while data from the phase 3 Stellar-303 (colorectal) and 304 (renal) studies are due in the second half.

PKMYT1 inhibitors in clinical development

Source: OncologyPipeline.