Company: ARVN
Filing Date: 2025-08-06
Form Type: 10-Q
Source: 0001655759-25-000139
Chunk: 172

Company: ARVINAS, INC.
Filing Date: 2025-08-06
Form: 10-Q
Item: Part I, Item 8
Chunk 172
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 observed.

•ARV-102 at single doses of greater than or equal to 30 mg induced greater than 50% decreases in peripheral phospho-Rab10T73, a LRRK2 substrate and biomarker for downstream LRRK2 activity; data for this endpoint in the MAD cohort is pending.

•ARV-102 at single doses of greater than or equal to 30 mg resulted in greater than 90% decrease of bis(monoacylglycerol)phosphate in urine, a biomarker of lysosomal function; data for this endpoint in the MAD cohort is pending.

•In CSF, ARV-102 induced dose-dependent LRRK2 reduction, with greater than 50% LRRK2 reduction at single doses of greater than or equal to 60 mg and repeated doses of greater than or equal to 20 mg.

ARV-806

KRAS, is one of the most frequently mutated human oncogenes and G12D is the most common mutation of the KRAS protein. KRAS G12D is a well-characterized oncogenic driver associated with poor prognosis and resistance to standard treatments across several major tumor types, including pancreatic, colorectal, and lung cancers.

ARV-806, our PROTAC KRAS G12D degrader, is a potent small molecule degrader of KRAS G12D and is designed to eliminate, rather than inhibit, KRAS G12D. 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, 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.

We filed an investigational new drug application with the FDA for ARV-806 in the first quarter of 2025 and received a safe-to-proceed letter from the FDA in the second quarter of 2025. We initiated enrollment in a first-in-human Phase 1 clinical trial of ARV-806 in patients with solid tumors harboring KRAS G12D mutations in the second quarter of 2025. We anticipate sharing preclinical data from ARV-