Lilly jumps ahead of Tyra

At the 2024 Triple meeting Tyra Biosciences presented the first clinical results suggesting that its lead pipeline project, dabogratinib, was an impressive FGFR3-selective inhibitor, but just one year later it’s already been overtaken. The challenge has come from Lilly, which fresh from presenting mid-stage data with its own FGFR3 inhibitor vepugratinib at ESMO has moved this project into phase 3. The pivotal Forager-2 study is to test vepugratinib plus Padcev and Keytruda, against Padcev/Keytruda alone, in 450 first-line, FGFR3-altered urothelial bladder cancer patients, and is to begin next month, according to a just unveiled clinicaltrials.gov listing. At ESMO the phase 1 Forager-1 study yielded a 32% ORR in 102 FGFR inhibitor-naive FGFR3m urothelial patients given vepugratinib monotherapy. Meanwhile, Tyra has a slightly different focus, recently embarking on a phase 2 trial of dabogratinib in the less advanced bladder cancer setting of non-muscle invasive disease. The rationale behind targeting FGFR3 specifically is that Johnson & Johnson’s Balversa, an approved pan-FGFR inhibitor, is associated with toxicities thought to result from activity at FGFR1 and 2. Last weekend’s Triple (EORTC-NCI-AACR) symposium included presentations from two preclinical FGFR3 challengers, Onco3R and BridGene.

Small-molecule FGFR3-selective inhibitors in development

Source: OncologyPipeline.