BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- breast cancer (~70% have acquired resistance to CDK4/6 inhibitors). BTX-9341 began a Phase 1 clinical trial in the third quarter of 2024.

BTX-10908 is a first-in-class, oral degrader of SOS1, an important upstream target in the KRAS pathway. KRAS is the most frequently mutated cancer-causing oncogene and is mutated in over 20% of all human cancers, including an estimated 90% of pancreatic tumors, 45% of colorectal tumors, and 30% of lung tumors. In preclinical models, our development candidate, BTX-10908, has demonstrated rapid and potent degradation of SOS1 across pan-KRAS mutant cancer cell lines and tumor growth inhibition in in vivo KRAS-driven models. Furthermore, BTX-10908 has significant combination potential, demonstrating synergies with inhibitors of the RTK-RAS-MAPK pathway, including sotorasib, osimertinib, quizartinib, and dasatinib.

We are exploring collaboration opportunities for our first-in-class degraders of Phosphodiesterase 4 (PDE4), a highly validated target for auto-immune and inflammatory diseases. Our PDE4 degraders are highly selective picomolar degraders of the PDE4D isoform that have shown up to 4,000-fold superior potency compared to PDE4 and JAK1/JAK2 inhibitors in inhibition of key inflammatory cytokines such as TNF-α, IFN-γ and IL-1β in preclinical models. We also believe the design of our PDE4 degraders has the potential to avoid several of the key gastrointestinal tolerability issues experienced by patients taking PDE4 inhibitors, enabling an overall favorable tolerability profile relative to other oral agents used for inflammatory diseases.

We are leveraging our PRODEGY platform to develop bifunctional degraders and molecular glues to pursue targets that may benefit from degradation.

Biotheryx has entered into a research collaboration and license agreement with Incyte to discover and develop molecular glue degraders for multiple historically undruggable novel oncology targets.