Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 111

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 111
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ug interaction at the 2024 SABCS.

Hematology Program: ARV-393

ARV-393 is an investigational, orally bioavailable PROTAC designed to 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. Prior to the advent of PROTAC technology, the BCL6 protein was considered "undruggable." We believe that ARV-393 PROTAC-mediated degradation of BCL6 may provide an important novel therapeutic option for patients with NHL.

Patient Population and Market Opportunity

There are approximately 80,000 new cases and 20,000 deaths in the U.S. related to NHL annually. NHL is a heterogeneous group of diseases, with large B-cell lymphoma, or LBCL, and follicular lymphoma, or FL, being the most common subtypes. Each subtype has a distinct biologic and clinical characteristics and requires different approaches to treatment. Unmet medical needs include managing aggressive subtypes, treatment resistance, and improving outcomes for older patients.

In particular, we believe our PROTAC BCL6 degrader could be a potential therapy for diffuse large B-cell lymphoma, or DLBCL, a sub-set of NHL, often associated with deregulated BCL6 expression and/or functions. More than 25,000 patients are diagnosed with DLBCL each year in the U.S. Treatment for DLBCL is largely devoid of oral options and there are currently no approved BCL6-targeted therapies on the market or in the clinic. NHL originates from B cells, T cells, and/or natural killer cells, with those of B-cell origin constituting approximately 80%–85% of all NHL cases. We believe additional opportunities for a BCL6 degrader exist in FL 

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and Angioimmunoblastic T-cell lymphoma. BCL6 may also be a clinically relevant therapeutic target in other hematologic malignancies, some solid tumors and B-cell driven autoimmune diseases.

Preclinical and Clinical Development

Based on our preclinical models, complete tumor stasis, which correlates with 95%-100% degradation of measurable BCL6, was achieved when our oral, BCL6-targeting PROTAC clinical candidate was taken at low, oral daily doses. We saw similar activity in multiple DLBCL models, including for activated B-cell and