Company: ARVN
Filing Date: 2025-11-05
Form Type: 10-Q
Source: 0001628280-25-049527
Chunk: 191

Company: ARVINAS, INC.
Filing Date: 2025-11-05
Form: 10-Q
Item: Part I, Item 8
Chunk 191
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AD Data from the Phase 1 Clinical Trial in Patients with PD and CSF Proteomic Data from the Phase 1 Trial in Healthy Volunteers

•Safety: The Phase 1 clinical trial in patients with PD included 15 patients treated with ARV-102 and 4 patients treated with placebo. In the trial, single doses of ARV-102 (50 mg or 200 mg) were well tolerated with only mild treatment-related AEs including headache, diarrhea, and nausea; no SAEs occurred.

•Pharmacokinetics: In patients with PD, ARV-102 exposure increased in a dose-dependent manner in both plasma and CSF, the latter indicating brain penetration.

•Pharmacodynamics: In patients with PD, treatment with ARV-102 resulted in median PBMC LRRK2 protein reductions of 86% with the 50 mg dose and 97% with the 200 mg dose.

•CSF Proteomics: In healthy volunteers treated with ARV-102 at 80 mg once daily for 14 days, unbiased proteomic analyses of CSF showed significant decreases in lysosomal pathway markers and neuroinflammatory microglial markers previously shown to be elevated in patients with PD harboring LRRK2 variants.

We believe these data presented at MDS highlight the potential PROTAC-mediated LRRK2 degradation, which supports the development of ARV-102 in ongoing studies of patients with PD, and potential future studies of patients with PSP. 

We plan to present initial data from the multiple dose cohort of the Phase 1 clinical trial of ARV-102 in patients with PD in 2026. Pending regulatory feedback, we plan to initiate a Phase 1b clinical trial of ARV-102 in patients with PSP in the first half of 2026.

ARV-393: Oral PROTAC BCL6 degrader

ARV-393 is an investigational, orally bioavailable PROTAC designed to specifically target and degrade BCL6, a transcriptional repressor and a key regulator of normal B-cell maturation and differentiation processes. Deregulation of BCL6 function (e.g., via chromosomal translocation, mutations) may lead to malignant transformation and development of NHL. During B-cell development, tightly controlled BCL6 protein expression regulates more than 600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation