ARV-393: A PROTAC BCL6 Degrader for Non-Hodgkin Lymphoma – Preclinical Profile and Phase 1 Clinical Development

I. Introduction to ARV-393

A. Nomenclature, Class, and Developer

ARV-393 is an investigational, orally bioavailable small-molecule therapeutic agent classified as a PROteolysis TArgeting Chimera (PROTAC) specifically engineered to induce the degradation of the B-cell lymphoma 6 protein (BCL6).[1] The oral bioavailability of ARV-393 is a significant attribute, offering potential for patient convenience and outpatient administration regimens, which can be advantageous compared to intravenously administered therapies. The PROTAC modality itself represents a novel therapeutic strategy, aiming to eliminate target proteins rather than merely inhibiting their function, which may offer distinct advantages in overcoming resistance mechanisms and achieving more profound biological effects.

The development of ARV-393 is being spearheaded by Arvinas Inc., a clinical-stage biotechnology company that has established a prominent position in the field of targeted protein degradation.[2] Arvinas's core technological expertise lies in the design and optimization of PROTAC molecules for various therapeutic targets.

For clarity and comprehensive literature tracking, ARV-393 is also referred to by several alternative designations, including ARV 393, ARV393, PROTAC BCL6 degrader ARV-393, and proteolysis-targeting chimera protein degrader ARV-393.[8]

B. Investigational Status and Therapeutic Intent