Pre-release summary
Selective βIII-tubulin inhibition by CCI-001: preclinical and Phase 1 evidence in bladder cancer with translational signal in breast cancer
PharmaMatrix Inc. with collaborators at the University of Alberta and partner institutions.
Abstract (preview)
CCI-001 is a novel colchicine derivative engineered to selectively bind βIII-tubulin, an isotype enriched in cancer cells but largely absent from healthy somatic tissue. In a series of in vitro assays against human bladder and breast cancer cell lines, CCI-001 demonstrated greater potency than several licensed tubulin-binding agents while sparing matched non-malignant controls. Animal models confirmed tumor regression at doses well below those associated with systemic toxicity. CCI-001 does not appreciably cross the blood–brain barrier, addressing one of the principal limitations of conventional colchicine. Phase 1 clinical evaluation is ongoing under NCT04823897.
Key findings
- • Selective βIII-tubulin binding confirmed by computational and biochemical assay
- • Sub-nanomolar potency in bladder cancer cell lines
- • Activity retained in MDR-expressing tumor models
- • Strong signal in triple-negative breast cancer cell lines
- • Wide therapeutic window in murine xenograft studies
Implications
- • Potential for earlier-line use vs. existing tubulin inhibitors
- • Combination potential with checkpoint inhibitors and platinum agents
- • Pipeline expansion into additional βIII-enriched tumors
- • Reduced neurotoxicity vs. taxanes and vinca alkaloids