Abstract 414: QED-203, a dual TRPV6 and AR small molecule preclinical candidate for advanced prostate cancer resistant to standard of care.

Abstract TRPV6, a calcium channel, is an oncochannel that is overexpressed in epithelial cancers, especially prostate cancer. We have observed that concomitant TRPV6 and AR inhibition is synergistic in prostate cancer cells resulting in a strong anti-proliferative effect. Our preclinical candidate QED-203 inhibits TRPV6-mediated calcium influx (FLIPR and electrophysiology) and NFAT activity (NFAT luciferase reporter) with low nM potency and potently inhibits AR (AR ligand displacement, AR luciferase reporter and translocation assay). QED-203 maintains effectiveness in prostate cancer cell lines that are resistant to next generation AR inhibitors including enzalutamide with multiple resistance mechanisms. QED-203 has high oral bioavailability with a pharmacokinetic profile amenable to once-a-day dosing. QED-203 is well tolerated in rodents with excellent in vivo efficacy in castrated mouse models of prostate cancers, including a PDX model with resistance to first and second-generation AR inhibitors (HID-28). TRPV6 target engagement has been demonstrated for QED-203 in rodents through changes in urine calcium levels, and via gene expression changes consistent with TRPV6 and AR inhibition in xenograft tumours. QED-203 thus targets a novel dual axis pathway (AR/TRPV6) to supress prostate cancer growth. QED-203 may offer a new opportunity to treat prostate cancer patients who have developed resistance to next generation AR therapies, where there is a clear clinical need for new therapeutic approaches Citation Format: Kimberley Beaumont, Rebecca Pouwer, Mei Yeh, Rebecca Farrow, Matthew McLachlan, Therese Johnson, Akanksha Upadhyaya, Aaron Gregson, Raphael Rahmani, Claire Levrier, Hasanthi Wijesekera, Malika Kumasiri, Grant Stuchbury, Terrie-Anne Cock, Andrew Harvey, Gregory Monteith, Brian Dymock. QED-203, a dual TRPV6 and AR small molecule preclinical candidate for advanced prostate cancer resistant to standard of care [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 414.