Arvinas presents preclinical data for ARV-806

Arvinas (ARVN) announced preclinical data for ARV-806, a PROTAC KRAS G12D degrader, at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts. The ARV-806 data presented show a differentiated profile based on degradation potency, antiproliferative activity, and induction of cancer cell death. ARV-806 is designed to target both the ON and OFF forms of KRAS G12D, which is the most common mutation of the KRAS protein. ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and non-small cell lung cancer. “These data suggest the potential of targeted protein degradation to overcome historical limitations in addressing undruggable KRAS mutations,” said Angela Cacace, Ph.D., Chief Scientific Officer of Arvinas. “ARV-806’s ability to eliminate both ON and OFF forms of KRAS G12D, combined with its potency and durability shown in preclinical models, supports our confidence in its clinical potential to deliver meaningful benefit for patients with KRAS G12D-mutated cancers.” In vitro, ARV-806 degraded KRAS G12D with picomolar potency across pancreatic, colorectal, and lung cancer cell lines but did not induce degradation of wild-type and other mutant RAS isoforms. ARV-806 is differentiated from other KRAS G12D targeting agents in development and has potential to be a best-in-class therapy for KRAS G12D mutated cancers. Following a single intravenous dose in a colorectal tumor xenograft model, ARV-806 degraded greater than90% of KRAS G12D for seven days, with parallel suppression of c-MYC for greater than or equal to5 days. ARV-806 demonstrated robust efficacy responses at low doses in tumor models including: greater than or equal to30% tumor volume reductions in pancreatic and colorectal cell line-derived xenograft models and a patient-derived xenograft model of lung cancer. These data demonstrate sustained pharmacodynamic activity consistent with long-lasting target degradation, which we believe supports intermittent clinical dosing. Arvinas is currently evaluating ARV-806 in a Phase 1 clinical trial in patients with KRAS G12D-mutated advanced solid tumors.