ARVINAS, INC. 8-K

What Happened

• On March 18, 2026 ARVINAS (ARVN) filed an 8‑K and issued a press release reporting positive Phase 1 data for ARV‑102, an oral PROTAC intended to cross the blood‑brain barrier and degrade LRRK2 (a protein implicated in Parkinson’s disease). Data from the randomized, double‑blind, placebo‑controlled multiple‑dose cohort were presented at AD/PD™ 2026 in Copenhagen.
• In the trial, patients received once‑daily oral ARV‑102 at 20 mg, 40 mg, or 80 mg for 28 days (with follow‑up to day 42). ARV‑102 produced dose‑dependent CSF exposure and achieved peripheral and central (CSF) LRRK2 degradation of approximately 50% or greater by day 14 that was maintained through day 28. The drug had a mean terminal plasma half‑life of 68 hours.

Key Details

• Doses tested: 20 mg, 40 mg, 80 mg once daily for 28 days; follow‑up to day 42.
• LRRK2 pharmacodynamics: ~50%+ LRRK2 degradation in CSF by day 14, maintained through day 28.
• Safety: Multiple doses were well tolerated; all treatment‑emergent and treatment‑related adverse events were mild; no serious adverse events, discontinuations, or deaths reported; no significant lung function changes observed.
• Biomarkers/PK: CSF levels increased dose‑dependently; AUC0‑24 and Cmax rose with dose; reductions observed in endolysosomal and neuroinflammatory proteins (e.g., CD68, GPNMB).

Why It Matters

• These results show target engagement in the brain (LRRK2 degradation in CSF) and a favorable short‑term safety and PK profile, supporting continued development of ARV‑102 for LRRK2‑associated neurodegenerative diseases.
• ARVINAS plans to continue investigation and, pending regulatory feedback, intends to start a Phase 1b trial in progressive supranuclear palsy in Q2 2026 with the potential to begin a registrational trial in late 2026, while evaluating options for Parkinson’s disease.
• For investors: this is early clinical (biomarker) data — encouraging for development progress and potential near‑term clinical milestones, but not proof of clinical benefit; the company’s plans are subject to regulatory feedback and typical clinical and development risks noted in the filing.