Arvinas, Inc. (Nasdaq: ARVN) announced today that it will present new preclinical combination data for its investigational PROTAC BCL6 degrader, ARV-393, at the upcoming American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois, from April 25-30, 2025.
The presentation will highlight preclinical studies demonstrating ARV-393's potential when combined with various standard of care lymphoma treatments. The data shows that the combination induces tumor regressions in diffuse large B-cell lymphoma (DLBCL) models.
ARV-393 is part of Arvinas' innovative PROteolysis TArgeting Chimera (PROTAC) platform, designed to harness the body's natural protein disposal system to selectively degrade disease-causing proteins. This particular compound targets B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas.
Mechanism of Action and Significance
BCL6 has long been recognized as a critical factor in lymphoma development but has proven difficult to target with conventional approaches. Dr. Ian Taylor, Chief Scientific Officer at Arvinas, explained the significance of their approach.
"BCL6 is considered 'undruggable' by traditional small molecule inhibitors due to its complex protein-protein interactions," said Taylor. "Our PROTAC technology allows us to address this challenge by tagging BCL6 for degradation by the cell's own protein disposal machinery, rather than simply inhibiting its function."
The BCL6 protein facilitates B-cell tolerance of rapid proliferation and somatic gene recombination by repressing cell cycle checkpoints, terminal differentiation, apoptosis, and DNA damage response. By degrading BCL6, ARV-393 aims to restore these natural cellular safeguards in malignant B-cells.
Study Details and Findings
The poster presentation, titled "ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, Combined With Biologics or Small-Molecule Inhibitors Induces Tumor Regressions in Diffuse Large B-Cell Lymphoma Models," will be presented on Monday, April 28, 2025, from 9:00 a.m. to 12:00 p.m. CT in Poster Section 18.
The study investigated ARV-393 in combination with both biologic therapies and small-molecule inhibitors currently used in lymphoma treatment. While specific efficacy data will be revealed at the conference, the abstract indicates that these combinations demonstrated synergistic effects in preclinical models, resulting in tumor regression.
"These findings suggest that ARV-393 could potentially enhance the effectiveness of existing lymphoma treatments," noted Dr. John Houston, President and CEO of Arvinas. "This aligns with our goal of developing therapies that can be integrated into current treatment regimens to improve outcomes for patients with limited options."
Clinical Development Status
ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma. The trial is designed to assess safety, tolerability, pharmacokinetics, and preliminary efficacy.
Non-Hodgkin lymphoma represents a significant unmet medical need, particularly for patients who have relapsed or become refractory to standard treatments. According to the American Cancer Society, approximately 80,000 new cases of non-Hodgkin lymphoma are diagnosed annually in the United States, with diffuse large B-cell lymphoma being the most common subtype.
Arvinas' PROTAC Platform
The ARV-393 program is part of Arvinas' broader portfolio of PROTAC protein degraders. The company is currently advancing multiple investigational drugs through clinical development, including:
- Vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer
- ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma
- ARV-102, targeting LRRK2 for neurodegenerative disorders
The PROTAC technology represents a paradigm shift in drug development, offering a potential solution for targeting proteins previously considered undruggable. Unlike traditional inhibitors that block protein function, PROTAC degraders facilitate the complete removal of disease-causing proteins from cells.
Industry Perspective
The development of protein degradation therapies has attracted significant attention in the pharmaceutical industry, with several companies now exploring this approach for various disease targets.
"Protein degradation has emerged as one of the most promising new modalities in drug development," said Dr. Houston. "Arvinas was the first company to bring PROTAC degraders into clinical trials, and we continue to lead the field with multiple clinical-stage programs."
The full abstract for the ARV-393 presentation can be accessed via the AACR 2025 online interactive program. Detailed results from the study will be available following the presentation at the conference.
