Bristol’s son of Revlimid goes pivotal

As part of its Celgene takeover Bristol Myers Squibb inherited a pipeline of “celmod” molecules designed to help weather Revlimid’s patent expiry, and the third of these, golcadomide, is now entering phase 3 development. The Golseek-1 study will enrol 850 front-line B-cell lymphoma patients and compare golcadomide plus R-Chop versus R-Chop alone, a new clinicaltrials.gov listing reveals. This follows the entry into phase 3 of two other Bristol celmods, iberdomide and mezigdomide, in various multiple myeloma settings. Celmods are small molecules that bind to the cereblon protein and lead to the degradation of certain substrates, for instance Ikaros and Aiolos, and it’s only relatively recently that imids like Revlimid and Pomalyst have been found to work this way too. The follow-on compounds have higher potency, however, acting in patients with lower cereblon expression levels, and each is apparently optimised for a different disease setting. Bristol has had a few false starts here: avadomide, an early iteration of golcadomide, was discontinued, as were CC-885 and eragidomide, which degrade the substrate GSPT1. Bristol's work on GSPT1 is now focused on ORM-6151, an anti-CD33 MAb-based asset acquired from Orum Therapeutics.

Bristol’s oral small-molecule cereblon E3 ligase modulator (celmod) agents

Note: *Aiolos (IKZF3) & Ikaros (IKZF1) are zinc finger protein lymphoid transcription factors essential for myeloma cell survival; ^CK1α=casein kinase 1α; ^^GSPT1 is a translation termination factor. Source: OncologyPipeline & company information.