Elevation goes down on Claudin disaster

Claudin18.2 has been one of the most crowded oncology targets of late, but the wheels seem to be coming off, with the latest setback seeing the discontinuation of Elevation’s ADC EO-3021 on Thursday. The move comes not long after Bristol Myers Squibb and Merck & Co handed back Claudin18.2 ADCs to LaNova and Kelun respectively.

Elevation’s discontinuation came as it released a disappointing clinical update that has heaped more doubt on this target, and could also be bad news for Corbus, whose Nectin-4-targeting ADC CRB-701, like EO-3021, was licensed from CSPC Pharmaceutical. Elevation’s hopes, meanwhile, are now on its preclinical anti-HER3 ADC, EO-1022. 

A 70% workforce reduction should keep the company going into the second half of 2026, but investors aren’t hanging around; the group’s stock plunged 47% on Thursday morning.

22% in ≥20% expressers

EO-3021 has been on shaky ground since August, when a US-focused phase 1 trial failed to live up to results from an earlier Chinese study. Elevation reported a confirmed ORR of just 20% among 15 gastric cancer patients, but focused on seven Claudin18.2-high patients (meaning ≥20% at IHC 2+/3+), where it highlighted an ORR of 43%.

However, hope has now faded even for this patient subgroup. On Thursday, Elevation said that among 36 evaluable Claudin18.2-high gastric/gastroesophageal junction patients the confirmed ORR was just 22%. The company concluded that EO-1022 was uncompetitive versus other Claudin18.2-targeting ADCs.

One reason for EO-1022’s underperformance might be its monomethyl auristatin E payload; the ADC field is increasingly moving towards topoisomerase inhibitors.

However, Kelun’s SKB315 uses a topoisomerase inhibitor, and this didn’t stop it being ditched by Merck & Co last year. Meanwhile, Bristol pulled out of the space in October, handing the auristatin-based tecotabart vedotin back to LaNova.

The only big pharma still active here, according to OncologyPipeline, is AstraZeneca, with the Keymed-originated sonesitatug vedotin; that asset also employs an auristatin payload. Data are due next year from a global phase 3 trial in second-line plus, Claudin18.2-expressing gastric and GEJ cancers.

If the problem is more specific to CSPC’s construct this could be a bad omen for Corbus and CRB-701, although that group recently reported western data backing that asset. As for Elevation, it will now have to hope to make its mark in another crowded space, HER3.

Clinical-stage Claudin18.2-targeting ADCs

Source: OncologyPipeline & clinicaltrials.gov.