Arvinas Advances Multiple PROTAC Programs While Navigating Pivotal Transition

Arvinas (Nasdaq: ARVN) delivered a landmark moment for its protein degradation platform this quarter, marking a significant inflection point for the clinical-stage biotech firm. The company’s portfolio of PROTAC degraders is progressing across multiple therapeutic areas, underpinned by both regulatory achievements and compelling early-stage clinical readouts.

Vepdegestrant: First-of-Class PROTAC to Reach Regulatory Milestone

The most consequential development came with the filing of a New Drug Application to the FDA for vepdegestrant, representing the first PROTAC degrader ever submitted for regulatory approval. This oral estrogen receptor (ER) degrader, developed in collaboration with Pfizer, demonstrated a 2.9-month improvement in median progression-free survival compared to fulvestrant in the VERITAC-2 Phase 3 trial for previously treated patients with ESR1-mutated, ER+/HER2- breast cancer.

While the trial missed statistical significance in the broader intent-to-treat population, the drug exhibited a favorable safety profile with minimal discontinuation rates and low gastrointestinal-related adverse events. The companies are preparing for the FDA’s PDUFA action date and planning to present additional data on patient-reported outcomes at the European Society for Medical Oncology Congress in October 2025.

Notably, Arvinas and Pfizer are reworking their collaboration agreement to maximize vepdegestrant’s commercial potential. The partnership is also exploring a combination cohort pairing the PROTAC with Pfizer’s investigational KAT6 inhibitor in an ongoing Phase 1 trial.

ARV-102 Delivers Brain Penetration Evidence in Parkinson’s Program

Data from the Phase 1 trial of ARV-102, a LRRK2-targeting degrader, showed the compound achieved substantial central nervous system engagement. At single oral doses of 60 mg or higher, the drug achieved greater than 50% LRRK2 reduction in cerebrospinal fluid, while peripheral blood mononuclear cells demonstrated reductions exceeding 90%.

The compound also demonstrated bioavailability, dose-dependent CSF exposure, and engagement of downstream LRRK2 pathway biomarkers including Rab10 phosphorylation inhibition. Safety data revealed no serious adverse events across dosing cohorts. Having completed enrollment in the healthy volunteer single ascending dose phase, Arvinas is now preparing sites for dosing initiation in Parkinson’s disease patients.

BCL6 Degrader Shows Combination Potential Across Lymphoma Models

ARV-393, the company’s BCL6-targeting PROTAC for non-Hodgkin lymphoma, demonstrated broad combinability with standard-of-care treatments at recent medical conferences. Preclinical data unveiled significant single-agent activity in nodal T-cell lymphoma and transformed follicular lymphoma models, alongside enhanced tumor growth inhibition when paired with small molecule inhibitors in aggressive diffuse large B-cell lymphoma settings.

The Phase 1 trial in relapsed/refractory NHL continues recruiting, with early indications suggesting ARV-393 could serve as an attractive backbone for chemo-free or all-oral combination regimens.

KRAS G12D Program Enters Clinical Testing

Enrollment has initiated in the Phase 1 trial of ARV-806, targeting the KRAS G12D mutation prevalent in solid tumors including pancreatic and colorectal cancers. Preclinical evidence demonstrated potent, selective degradation of mutant KRAS with sustained MAPK pathway suppression and robust anti-tumor activity.

Financial Performance and Cash Position

Arvinas reported revenue of $22.4 million for Q2 2025, compared to $76.5 million in the year-ago period. The decline primarily reflects completion of technology transfers under previous Novartis collaboration agreements, which generated $45.6 million of the prior-year revenue. The Pfizer vepdegestrant collaboration accounted for the bulk of current revenue, though it declined by $6.8 million due to removal of certain combination trial cohorts from the development plan.

Research and development expenses totaled $68.6 million for the quarter, down from $93.7 million in Q2 2024. The reduction stemmed from decreased external program spending on vepdegestrant and luxdegalutamide programs, partially offset by increased ARV-102 and ARV-806 investments.

General and administrative expenses fell to $25.3 million from $31.3 million year-over-year, reflecting streamlined personnel and infrastructure costs.

As of June 30, 2025, Arvinas held $861.2 million in cash, cash equivalents, and marketable securities, down from $1.04 billion at year-end 2024. The company projects this balance is sufficient to fund operations through the second half of 2028.

Leadership Transition Underway

John Houston, Ph.D., who has served as CEO and President, informed the board of his intention to retire from these executive roles following identification of a successor. Houston will transition to the position of Board Chairperson, while the board has initiated a CEO search.

What Lies Ahead

The company faces a calendar packed with potential catalysts. Near-term expectations include final data from ARV-102’s healthy volunteer cohorts, initial readouts from Parkinson’s disease patients, and preliminary Phase 1 data for ARV-393 in NHL. The ARV-806 program will continue enrollment, with preclinical data sharing planned for the second half of 2025.

The vepdegestrant approval pathway remains central to investor attention, with FDA decision timing representing the most material near-term event. Simultaneously, the company’s emerging programs in neurodegenerative disease and hematologic malignancy suggest a diversified pipeline capable of generating multiple inflection points over the next 12 months.