Betta joins Revolution in pan-RAS inhibition

With Revolution Medicines playing up the importance of pan-RAS inhibition through its lead project, daraxonrasib, it’s worth noting that there’s a new player in town: Betta’s pan-RAS contender BPI-572270 just entered its first-in-human study, recent clinicaltrials.gov listings reveal.

New entries also show a number of undisclosed molecules, from AstraZeneca, Incyte, Pfizer and Torl, going into the clinic, and no doubt any data coming out of these studies will be watched for clues as to their mechanisms of action. For Betta a move into pan-RAS was perhaps logical given that it’s also working on KRAS, with inhibitors as well as a degrader in its pipeline.

However, Betta’s previous clinical KRAS work fell on stony ground, with the discontinuation in 2024 of the G12C-specific inhibitor BPI-421286, which was in phase 1 but was dropped for lack of obvious clinical advantage.

The company also has BPI-501836 (G12D inhibitor), RD0255359 (degrader of G12C/D/V), BPI-585725 and BPI-585771 (pan-KRAS degraders), but these are at the preclinical stage. As such the advancement into the clinic of the broader-acting pan-RAS molecule BPI-572270 should be of interest.

While the industry pipeline is now full of molecules with anti-KRAS activity, pan-RAS inhibitors are rarer. Here daraxonrasib is the clear leader, in three phase 3 trials, but beyond the Revolution asset the clinical competition is limited to GenFleet with GFH276, Erasca/Joyo (ERAS-0015, a degrader), Adlai Nortye (AN9025), Jiangsu HengRui (HRS-2329) and 280Bio (YL-17231).

Still, it’s not entirely clear whether pan-RAS blockade will turn out to be better than pan-KRAS, and Revolution’s daraxonrasib studies include combinations with subtype-specific KRAS inhibition.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 20 Feb and 3 Mar 2026.

As for other clinical trial entrants, mystery surrounds Astra’s AZD4956, Incyte’s INCA036978, Pfizer’s PF-07994525 and Torl’s TORL-5-700.

These molecules’ clinicaltrials.gov listings give nothing away as to their mechanisms, though AZD4956 is said to be a small molecule, and as Torl is an ADC specialist it might be assumed that TORL-5-700 is a conjugate – however, this seems an unusual modality in a blood cancer.

Incyte is studying INCA036978 in myeloproliferative neoplasms including myelofibrosis and polycythemia vera, presumably aiming to build on its established Jakafi franchise. Notably, Incyte halted development of its BET inhibitor INCB57643 in this setting (while Novartis perseveres with the MorphoSys-originated pelabresib), so it’s possible that INCB57643 is a variation on this theme.

And ADCs newly into the clinic include Whitehawk’s HWK-007 and IntoCell’s ITC-6146RO, which both hit targets with a huge amount of industry competition: B7-H3 and PTK7 respectively. Investors in Whitehawk, a biotech formerly known as Aadi, will note the recent discontinuation of Genmab’s GEN1107; Day One, the group just bought out by Servier, does have an anti-PTK7 ADC in its pipeline, DAY301, but this is likely not the key attraction for its buyer.