BeOne chooses degradation over inhibition

BeOne looked like it was taking a dual-pronged approach in CDK2 and pan-KRAS, but it has now streamlined its efforts. The company said in its first-quarter presentation that it had deprioritised its inhibitors, BG-68501 and BGB-53038 respectively. However, it still has degraders against these targets.

Meanwhile, the group has also ditched an EGFR degrader, BG-60366, which already looked to be in trouble, and a MAT2A inhibitor, BG-89894, in the latest blow for synthetic lethality mechanisms.

The sidelining of the latter, which BeOne licensed from China’s CSPC in 2024, could also raise questions about BeOne’s PRMT5 inhibitor BGB-58067, which in its phase 1 trial is being tested both alone, and in combination with the MAT2A blocker and other compounds. PRMT5 inhibition took a blow last week with Amgen’s discontinuation of its contender, AMG 193.

Still, BeOne also highlighted a PRMT5 inhibitor combo with its PD-1 blocker Tevimbra and chemo in first-line NSCLC; data are due in the second half of this year.

CDK2 choice

In CDK2 BeOne licensed the inhibitor BG-68501 from Ensem in November 2023 for an undisclosed up-front fee. The asset went into a phase 1 trial in early 2024, in which it was being tested as monotherapy in solid tumours, and in combination with Faslodex and BeOne’s CDK4 inhibitor BGB-43395 in breast cancer specifically.

However, early data were underwhelming, with just two partial responses, both in breast cancer and both unconfirmed, among 37 solid tumour patients.

BeOne’s CDK2 degrader, BG-75098, has “much improved selectivity” for CDK2 versus CDK1 than small-molecule inhibitors, the company has said. That project hit the clinic at the end of last year; it’s also being tested alone and in combo with Faslodex and BGB-43395.

Pan-KRAS plans

Meanwhile, pan-RAS and KRAS inhibition is hot, thanks to Revolution Medicine’s recent data with its pan-RAS contender daraxonrasib.

But here BeOne has moved away from the pan-KRAS inhibitor BGB-53038, apparently in favour of a preclinical and as yet unnamed KRAS degrader that’s expected to go into clinical development in the second half of this year.

BGB-53038 was in a phase 1 trial in KRAS-mutant solid tumours, in which it was being tested alone, as well as in combination with Tevimbra (in NSCLC) and Erbitux (in colorectal cancer).

Proof of concept data had once been expected in the second half of 2025; these were pushed back to the first half of 2026, before the latest development.

EGFR exit 

The situation with the EGFR degrader BG-60366 seems more clear cut. The phase 1 study of this project, in EGFR-mutated NSCLC, looked in trouble last month when its status was changed to “active, not recruiting” on clinicaltrials.gov, with enrolment halted at 33 patients, well short of the 93 originally planned. 

At the time, BeOne told ApexOnco that the study had been paused while the company evaluated the data – evidently, the group hasn't seen anything worth salvaging. Data had also been delayed from late 2025 to the start of 2026.

Four other EGFR degraders are in clinical trials, according to OncologyPipeline, but have also yet to yield data.

BeOne’s first-quarter deprioritisations

Source: OncologyPipeline & company presentation.