Sanofi switches to another CEACAM5 asset

Sanofi today threw in the towel on the anti-CEACAM5 ADC tusamitamab ravtansine, after a delay and setbacks to competitor projects. While this doesn’t look great for the handful of other companies pursuing this antigen, Sanofi isn’t giving up entirely, saying it would continue investigating anti-CEACAM5 ADCs, referring presumably to the Pfizer-partnered SGN-CEACAM5C, which remains in the clinic. Sanofi said the phase 3 Carmen-LC03 study, in second-line non-squamous NSCLC, failed to show a PFS benefit for tusamitamab ravtansine over docetaxel. This second-line space is tough, with Daiichi Sankyo/AstraZeneca’s TROP2-directed ADC datopotamab deruxtecan yielding somewhat underwhelming results Tropion-Lung01, for instance. But Carmen-LC03 was notable for preselecting for CEACAM5-positive cancers, and the fact this enrichment hasn’t worked out seems especially disappointing. Tusamitamab ravtansine was initially to have been filed in 2022, but that got pushed back to this year, and in the event all clinical work is now being stopped. Bolt Biotherapeutics earlier discontinued a preclinical CEACAM5-targeting immune-stimulating antibody conjugate, BDC-2034, after deaths in non-human primate studies, blaming this on BDC-2034’s binding to other CEACAM family members. When Gilead bought Immmunomedics the next most advanced ADC after Trodelvy was the CEACAM5-directed labetuzumab govitecan, which no longer appears in its pipeline.

Selected MAb-based approaches in CEACAM5 targeting

Source: OncologyPipeline.