Arvinas presents preclinical data from studies of ARV-393

Arvinas (ARVN) presented data from preclinical studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera B-cell lymphoma 6 protein degrader. BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. ARV-393 demonstrated significant single-agent activity in a patient derived xenograft model of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type and PDX models of transformed follicular lymphoma. In combination with oral small molecule inhibitors, ARV-393 demonstrated enhanced antitumor activity, including tumor regressions, in cell line-derived xenograft models of high-grade B-cell lymphoma and aggressive diffuse large B-cell lymphoma. The results from these preclinical studies were shared at the European Hematology Association 2025 Congress in Milan, Italy. Key findings from the preclinical studies included: Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived from a patient who relapsed post chemotherapy. This is potentially the first preclinical evidence of anti-tumor activity with an efficacious BCL6-targeted small-molecule degrader in a human nTFHL-AI model. ARV-393 monotherapy treatment resulted in robust tumor growth inhibition in two PDX models of tFL. ARV-393 in combination with 5 classes of SMIs targeting potentially cooperative oncogenic drivers demonstrated increased TGI in CDX models of HGBCL and aggressive DLBCL compared with the respective monotherapy treatments. Tumor regressions were observed when ARV-393 was combined with tazemetostat, palbociclib, acalabrutinib, or venetoclax. RNA sequencing studies carried out to further characterize downstream mechanism of action suggested that ARV-393 inhibits tumor cell cycle progression and promotes differentiation, driving antitumor activity and broad combinability in preclinical models.