Akeso casts doubts on CD73 efforts
The company has ditched a trial of drebuxelimab plus ivonescimab.
The company has ditched a trial of drebuxelimab plus ivonescimab.
Akeso has various efforts ongoing in CD73 targeting, but these look on shaky ground following the discontinuation this month of a phase 1/2 study of drebuxelimab, an antibody against this protein. The Chinese trial, testing a combination with the anti-PD-1 x VEGF bispecific ivonescimab in second-line NSCLC, was halted owing to “strategic development reprioritisation”.
The move comes after another phase 1/2 study, evaluating drebuxelimab plus the PD-1 x CTLA-4-targeting cadonilimab, was ended for similar reasons last year. As well as looking bad for drebuxelimab, the developments could have a knock-on effect on Akeso’s bispecific CD73-targeting assets, which are at an earlier stage.
The company is also working on AK131, which additionally hits PD-1, and AK137, which also targets Lag3. Both are in Chinese phase 1 trials, which appear to be ongoing, at least for now.
Akeso declined to give more details on drebuxelimab’s future. However, another ivonescimab combo study in solid tumours, which had been set to complete in 2024, is listed as status “unknown” in clinicaltrials.gov.
The main hope for drebuxelimab now appears to be a colorectal cancer study, again with an invonescimab combo. This is expected to complete this May, so drebuxelimab’s fate could become clear fairly soon.
Akeso’s CD73-targeting projects
| Project | Description | Trial(s) |
|---|---|---|
| Drebuxelimab | Anti-CD73 MAb | China ph1/2 AK119-201 in 2nd-line NSCLC, + ivonescimab +/- chemo*; terminated Mar 2026 owing to “sponsor strategic development reprioritisation” |
| China ph1/2 AK119-104 in solid tumours, + cadonilimab; terminated Feb 2025 owing to “development strategy adjustment” | ||
| China ph1/2 AK119-105 in solid tumours, + ivonescimab, status unknown | ||
| China ph1/2 AK119-202 in 1st/3rd-line pMMR/MSS CRC, + ivonescimab +/- chemo*; completes May 2026 | ||
| AK131 | Anti-PD-1 x CD73 bispecific MAb | China ph1 in solid tumours; completes Aug 2026 |
| AK137 | Anti-Lag3 x CD73 bispecific MAb | China ph1 in solid tumours; completes May 2027 |
Note: *also includes ivonescimab monotherapy. Source: OncologyPipeline.
CD73 has had several setbacks, with Lilly discontinuing the small-molecule CD73 inhibitor LY3475070 in 2021, and Novartis walking away from Coherus’s MAb NVS930 in 2024.
Since then, Otsuka licensed Arcus’s small molecule quemliclustat in Japan, and Sanofi teamed up with I-Mab on Chinese development of uliledlimab; however, I-Mab, now known as NovaBridge Biosciences, suspended development last year to focus on givastomig. Uliledlimab could be resurrected if positive Loqtorzi combo data emerge.
One notable player still involved in CD73 is AstraZeneca, whose oleclumab is in the phase 3 Pacific-9 trial testing an Imfinzi combo in stage III unresectable NSCLC that hasn’t progressed following platinum-based chemoradiation.
That study also evaluates Imfinzi plus Innate Pharma’s Anti-NKG2A MAb monalizumab, with Imfinzi monotherapy as control. Data are due in the second half of this year, providing a big test for the class.
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