Pfizer drops its B7-H4 conjugate

A year ago, Pfizer discontinued a B7-H4-targeting bispecific in favour of a Seagen antibody-drug conjugate; now, that ADC, felmetatug vedotin, has also fallen by the wayside.

The only clue about the project’s demise was a line in Pfizer’s fourth-quarter earnings release, stating that the group had taken a $1bn impairment charge relating to the asset. When asked if the project was still in play, a spokesperson for Pfizer replied that it had been discontinued based on clinical data indicating that it was “unlikely to achieve a meaningful improvement over standard-of-care chemotherapy in patients with advanced solid tumours, including triple-negative breast cancer”.

The spokesperson added that there had been no new safety signals spurring what Pfizer called a “business decision”.

This looks like bad news for Mersana, which is particularly exposed to B7-H4: its lead project is emiltatug ledadotin, another ADC against this target. That group recently reported phase 1 solid tumour data, with a focus on TNBC, suggesting that a biomarker strategy might be needed to identify the patients most likely to benefit.

And a closer look at Pfizer’s data showed the benefit with felmeta-V to also have been driven by high B7-H4 expressers.

The omens around B7-H4 haven’t been great for some time, with AstraZeneca also underwhelming with its candidate, puxitatug samrotecan.

Others in the space include GSK, via a 2023 deal with Hansoh, BeiGene, via an agreement with DualityBio, and NextCure, which recently took its lead asset, LNCB74, into phase 1.

However, Pfizer might not be out of B7-H4 entirely: while felmetatug vedotin used an MMAE payload, the big pharma also is also developing a preclinical B7-H4-targeting ADC that employs a toposiomerase 1 inhibitor payload, SGN-B7H4C, it disclosed at its February 2024 R&D day.