BTX-10908 / BioTheryX - LARVOL DELTA

Identification of first-in-class, orally bioavailable SOS1 bifunctional degraders for the treatment of KRAS- and RTK-driven cancers (AACR 2024) - "Together, our SOS1 degraders alone and in combination with other targeted agents demonstrated anti-tumor activity in a variety of KRAS- and RTK-driven cancer cell lines and xenograft models. These results support the potential of orally bioavailable SOS1 degraders to help mitigate pathway reactivation for enhanced efficacy and prolonged response duration."

Oncology • Solid Tumor • ABL1 • BCR • CRBN • EGFR • KRAS

Cereblon-Based Bifunctional Degrader of SOS1, BTX-6654, Targets Multiple KRAS Mutations and Inhibits Tumor Growth. (PubMed, Mol Cancer Ther) - "In two KRAS G12C xenograft models, BTX-6654 degraded SOS1 in a dose-dependent manner correlating with tumor growth inhibition, additionally exhibiting synergy with KRAS and MEK inhibitors. Altogether, BTX-6654 provided preclinical proof of concept for single-agent and combination use of bifunctional SOS1 degraders in KRAS-driven cancers."

Journal • Oncology • CRBN • KRAS

Development of bifunctional CRBN-SOS1 degraders for treatment of mutant KRAS cancers. (ASCO 2023) - "Strong synergistic antiproliferative effects were observed when SOS1 degraders were co-treated with KRAS inhibitors AMG510 (G12C) and MRTX1133 (G12D) in respective KRAS-mutant cell lines as well as with MEK inhibition and EGFR inhibition. Together, these results highlight the potential of SOS1 degraders alone and in combination as therapeutic options for a variety of KRAS-driven cancers."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CRBN • HRAS • KRAS

Biotheryx to Present New Preclinical Data on Bifunctional Degraders for CDK4/6 and SOS1 at 2023 ASCO Annual Meeting (PRNewswire) - "Biotheryx...announced two poster presentations at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting....BTX-9341 demonstrated in vitro CDK4 and CDK6 degradation in multiple breast cancer cell lines and potent inhibition of cell proliferation....Biotheryx's SOS1 bifunctional degraders demonstrated antiproliferative effects across a range of KRAS-mutant cell lines. Treatment with SOS1 degraders in KRAS-mutant xenograft models resulted in greater than 90% degradation of SOS1 in tumors and subsequently led to significant tumor growth inhibition as a single agent."

Preclinical • Breast Cancer • Oncology • Solid Tumor

Novel Cereblon mediated bifunctional degraders of SOS1 for treatment of pan-KRAS mutant tumors (AACR 2023) - "SOS1 degradation was validated to be dependent on the proteasome and CRBN as cotreatment with proteasomal inhibitors (MG132 or MLN4924) or treatment in a CRBN KO cells abolished degradation. For example, combination treatment of AMG510 and SOS1 degraders resulted in strong synergistic effects in KRAS G12C H358 cells. Together, our data SOS1 degradation could be a valuable potential treatment option for a range of KRAS mutant cancers."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CRBN • KRAS