CytomX shifts towards EpCAM
The fate of the group’s previous lead project, the Amgen-partnered CX-904, looks uncertain.
The fate of the group’s previous lead project, the Amgen-partnered CX-904, looks uncertain.
CytomX has struggled to convince investors of the merits of its conditionally acting anti-EGFR T-cell engaging probody CX-904, and this Amgen-partnered project now looks to be on the back burner as part of a reshuffle announced after hours on Monday.
The new focus is the wholly owned EpCAM-targeting ADC CX-2051, which is set to yield phase 1 data in advanced colorectal cancer in the first half of this year. A look at the respective EGFR and EpCAM pipelines shows much less competition in the latter than the former.
Indeed, according to OncologyPipeline, CX-2051 is the only EpCAM ADC in development. The most prominent rival asset is Genmab and BioNTech’s BNT314, a bispecific antibody designed also to activate the co-stimulatory domain 4-1BB – an approach that, broadly speaking, hasn’t produced great results so far.
Meanwhile, others are pinning their hopes on T-cell engagers.
EpCAM-targeting projects in clinical development by industry
| Project | Company/ies | Description | Status |
|---|---|---|---|
| M701 | Wuhan YZY Biopharma | Anti-EpCAM T-cell engager | Ph3 China trial in malignant ascites caused by epithelial solid tumours; completes Aug 2025 |
| BNT314 (GEN1059) | Genmab/BioNTech | Anti-EpCAM x 4-1BB bispecific antibody | Ph1/2 +/- Keytruda in solid tumours; completes Jul 2027 |
| Catumaxomab | LINDIS Biotech | Anti-EpCAM T-cell engager | Ph1/2 China trial in BCG-unresponsive NMIBC; had been due to complete Nov 2024 |
| CX-2051 | Cytomx | Anti-EpCAM ADC probody | Ph1 in solid tumours; data in CRC due H1 2025 |
| BA3182 | BioAtla | Anti-EpCAM T-cell engager | Ph1 in adenocarcinoma; dose-escalation data due Q2 2025 |
| A-337 | ItabMed | Anti-EpCAM T-cell engager | Ph1 China trial in solid tumours; completes Jun 2026 |
| AM-928 | AcadeMab Biomedical | Anti-EpCAM MAb | Ph1 Taiwan trial in solid tumours; completes Jun 2026 |
| KK2269 | Kyowa Kirin | Anti-EpCAM x CD40 bispecific MAb | Ph1 Japan trial in solid tumours; completes Dec 2027 |
| ABO2202 | Abogen Biotechnology | Anti-EpCAM T-cell engager | Ph1 China trial in gastric cancer |
Source: OncologyPipeline & clinicaltrials.gov.
Although a lack of competition might be good for CytomX, it also suggests that many aren’t convinced by EpCAM as a target, making the group’s refocus look risky. The company's stock fell 5% on Tuesday morning.
Until Monday, its lead project had been the EGFR-targeting CX-904, which last May yielded data from a phase 1 basket trial in solid tumours. There were two partial remissions among six pancreatic cancer patients, but no activity in other cancer types, and CytomX’s share price went back into the doldrums after a brief spike.
One question that still hasn’t been answered is whether Amgen will want to take the asset forward; the big biotech would be responsible for late-stage development. On Monday CytomX said discussions with its partner were ongoing; CX-904 is still listed on Amgen’s pipeline, as AMG 651.
However, CytomX also described CX-904’s potential move into phase 1b as “pending”, given its “current capital constraints”. The company has just slashed its headcount by 40%, extending its cash runway from year-end 2025 into the second quarter of 2026.
This echoes I-Mab’s recent scaling back of clinical development despite having two years of cash in the bank, raising more doubts about biotech’s fund-raising prospects.
CytomX also has an interferon-alpha 2b project, CX-801, with early data due later this year – although all eyes will now be on EpCAM.
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