Dark clouds for Daiichi in Claudin6

After BioNTech’s quiet step back from work in Claudin6 last year, Daiichi Sankyo has decided that it sees no future for its first clinical attempt to target this antigen. The latest revelation came in the Japanese company’s fiscal third-quarter report, disclosing the discontinuation of the anti-Claudin6 antibody-drug conjugate DS-9606, which had been in phase 1. This appears to be the first discontinuation of an anti-Claudin6 project that uses the ADC modality, BioNTech having terminated one trial of the Car-T therapy BNT211, and reported disappointing results with the mRNA-encoded T-cell engager BNT142. The Daiichi move, first reported by Fierce Biotech, leaves Torl Therapeutics’ ixotatug vedotin as the industry’s most advanced anti-Claudin6 ADC. That has shown a 33% ORR in mostly Claudin6-positive tumours, while DS-9606’s 15% ORR looked uncompetitive, though the latter’s study didn’t require Claudin6-positivity. Discontinuation of DS-9606 also marks an inauspicious beginning for Daiichi’s development of ADC warheads beyond the high-profile deruxtecan used in drugs like Enhertu and Datroway; DS-9606 used a payload based on a prodrug of pyrrolobenzodiazepine, which doesn't appear to lie behind any other Daiichi ADCs.

Clinical-stage anti-Claudin6 ADCs

Source: OncologyPipeline.