A new challenger in target degradation

Until now BTK degradation has been a two-horse race, with BeOne and Nurix putting up near-identical datasets for their two clinical contenders. China’s Ascentage Pharma will hope to change this status quo, starting a first-in-human study of its BTK degrader APG-3288 this month.

Ascentage has been playing up this asset, announcing the clearance of its IND last month; now this study, to be carried out in the US as well as in China, is to start, according to its just revealed clinicaltrials.gov listing. With just a handful of BTK degraders in clinical trials any moves here are of note, especially given AbbVie’s apparent discontinuation of its contender ABBV-101.

The precise status of ABBV-101 is unclear, with the company keeping it in its R&D pipeline despite reportedly telling analysts it had ended its development in non-Hodgkin’s lymphoma last month. But it’s chronic lymphoblastic leukaemia where BTK degraders have battled, and this indication is included in the phase 1 study of APG-3288, alongside diffuse large B-cell and other lymphomas.

In CLL Ascentage will have a high bar to meet. BeOne’s BGB-16673 and Nurix’s bexobrutideg have shown response rates above 80% in their respective Cadance-101 and NX-5948-301 trials, and BeOne has already begun the pivotal Cadance-302, 303 and 304 studies in various CLL settings.

Though BTK as a whole is a highly competitive setting there are still only a few degraders in development. The clinical-stage pipeline includes HealZen’s HZ-Q1070, Chia Tai’s TQB3019, Ubix’s UBX-303061 and a back-up from Nurix, zelebrudomide, which is said to be cereblon-recruiting but which spent time on clinical hold.

Recently disclosed first-in-human studies*

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

Other first-in-human study entrants include Boomray’s anti-Nectin-4 radiotherapeutic BRP-020063, after Aktis took a similarly acting project, AKY-1189, into phase 1 last July.

However, while the Aktis study is in Nectin-4-positive patients, Boomray’s doesn’t appear to mandate any level of Nectin-4 expression. BRP-020063 uses lutetium-177 as its radioisotope, while Aktis is developing two forms of AKY-1189, one using lutetium-177 and the other actinium-225.

As ever, conjugates remain a popular modality, and intrigue surrounds the target of GSK’s GSK5533524, which for now remains under wraps. Meanwhile, Chong Kun Dang is advancing the cMet-directed ADC CKD-703 into a phase 1 trial in cMet-positive solid tumours including lung cancer, and Met-amplified NSCLC specifically.

The cMet ADC space saw the approval of AbbVie’s Emrelis last year, though another asset that appeared to have a promising and slightly different approach, Mythic Therapeutics’ MYTX-011, ended in failure when that private biotech found it impossible to raise additional cash.