Company: ARVN
Filing Date: 2025-11-05
Form Type: 10-Q
Source: 0001628280-25-049527
Chunk: 9

Company: ARVINAS, INC.
Filing Date: 2025-11-05
Form: 10-Q
Item: Part I, Item 2
Chunk 9
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 and has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and non-small cell lung cancer.

In the preclinical setting, ARV-806 demonstrated high potency and selectivity, with robust antitumor activity through dose-responsive degradation of KRAS G12D in KRAS G12D mutated cancers, including pancreatic and colorectal cancers. ARV-806 bound to both the active and inactive forms of KRAS G12D, achieving potent and durable elimination rather than inhibition of the target in all models tested. In addition, as shown below, in preclinical studies, ARV-806 achieved in vitro potency approximately 25 times greater than KRAS inhibitors and 40 times greater than the leading clinical-stage degrader.

In the fourth quarter of 2025, we presented preclinical data for ARV-806 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, or the 2025 Triple Meeting, in Boston, Massachusetts. Key highlights from the presentation at the 2025 Triple Meeting include the following:

•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 rat sarcoma, or RAS, isoforms.

•ARV-806 is differentiated from other KRAS G12D targeting agents in development and we believe has potential to be a best-in-class therapy for KRAS G12D mutated cancers due to:

◦Catalytic activity, which allows it to overcome upregulation, a common mechanism of resistance to inhibitor treatment.

◦Compared with clinical-stage KRAS G12D ON and OFF inhibitors and another clinical-stage G12D degrader, ARV-806 demonstrated:

▪more than 25-fold greater potency in reducing cancer cell proliferation;

▪more than 40-fold higher potency in degrading KRAS G12D protein (versus the comparable clinical-stage G12D degrader); and

▪more than 10-fold lower concentrations required to induce pro-apoptotic BIM (Bcl-2-interacting mediator of cell death, a pro-apoptotic factor) expression.

•Following a single intravenous dose in a colorectal tumor xenograft model, ARV-806 degraded greater than 90% of KRAS G12D for seven days, with parallel suppression of c-MYC (a key driver of cancer