OnKure is no longer the only game in town

As OnKure awaits a key catalyst in release of the first substantial human data for its lead project, OKI-219, it might take heart that this is no longer the industry’s only clinical-stage PI3Kα inhibitor specific for the H1047R mutation. That was the case until this month, when Cogent started a phase 1 study with its contender, CGT6297, a new listing on clinicaltrials.gov reveals.

Disclosures of new first-in-human studies also feature an anti-integrin beta-6 ADC that was the subject of a curious recent deal between Kelun and Crescent Biopharma, as well as another ADC originated by Zai Lab. The latter targets a relatively novel protein, but its main claim to fame could be its use of MediLink’s very popular linker-payload technology, Tmalin.

Last month Roche gave Tmalin its latest endorsement when it picked up rights to MediLink’s tambotatug pelitecan. At the time MediLink boasted that Tmalin lay behind 13 clinical-stage ADCs, but in March that number will go up to 14, when Zai Lab’s LRRC15-targeting ADC ZL-6201 starts a just-disclosed phase 1 trial.

LRRC15 has to its name relatively little industry competition, as well as a notable clinical failure in AbbVie’s samrotamab vedotin. And Zai already has one clinical-stage project that uses Tmalin and was licensed from MediLink: the DLL3-targeted zocilurtatug pelitecan.

PI3Kα

Meanwhile, PI3Kα inhibition is seeing renewed enthusiasm, with Lilly advancing several shots on goal, most recently through the acquisition of Scorpion Therapeutics and its mutant-selective (wild-type sparing) lead asset, tersolisib.

The latest to enter the fray is Cogent, with a molecule coded CGT6297, which starts a phase 1 trial in PIK3CA-mutated solid tumours this month. This move is highly relevant for OnKure, a distressed biotech that in the current quarter expects to reveal key data with its lead pipeline project, OKI-219.

CGT6297 and OKI-219 are now the only clinical-stage inhibitors of PI3Kα that are specific for the H1047R mutation. That’s notable because of Lilly’s work in this area: the US big pharma group had earlier tried to develop an H1047R mutation-specific molecule, LY3849524, but abandoned this in favour of a broader, wild-type sparing approach, of which the Scorpion acquisition is its latest example.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 30 Jan and 4 Feb 2026.

Last December saw a curious cross-licensing deal, in which Crescent licensed right to Kelun’s anti-integrin beta-6 ADC SKB105, and Kelun gained rights to Crescent’s anti-PD-1 x VEGF MAb CR-001. One goal was to look at combinations of these two molecules, and the transaction involved two separate deals, whose respective up-front fees netted off at $60m payable by Crescent.

Now SKB105 is starting its first clinical trial, though this appears to be nothing to do with Crescent, a Nasadaq-listed entity resulting from a reverse merger into Glycomimetics. The study is sponsored by Kelun, and is to be carried out at hospitals in China, suggesting that the first-in-human trial Crescent promised to begin, presumably in the US, early this year has yet to materialise.

New first-in-human study initiations also include two mystery Genmab antibodies, GEN3018 and GEN1079. Nothing is disclosed about their mechanisms of action, and the trials are starting after Genmab discontinued another secretive project, the T-cell engager GEN1078, last year.