ASP-1002: A Novel Bispecific Antibody Targeting CLDN4 and CD137 for Solid Tumor Immunotherapy

I. Executive Summary

ASP-1002 is an investigational, first-in-human bispecific antibody currently under development by Astellas Pharma Inc..[1] It is engineered as a tetravalent IgG-scFv antibody designed to concurrently target Claudin 4 (CLDN4), a protein often overexpressed on the surface of various tumor cells, and CD137 (also known as 4-1BB), a potent co-stimulatory receptor found on T cells.[1] The primary therapeutic goal of ASP-1002 is to augment the host's anti-tumor immune response. This is achieved by creating a bridge between CLDN4-expressing cancer cells and CD137-bearing T cells, thereby triggering CD137-mediated co-stimulation, which in turn promotes T-cell activation, proliferation, and cytotoxic capabilities directed against the tumor.[1] A significant design characteristic of ASP-1002 is its "silent" Fc region, which is intended to minimize Fc/FcγR-mediated systemic toxicities that have been a concern with previous CD137-targeting agonistic antibodies.[2]

Preclinical investigations have yielded promising results, demonstrating that ASP-1002 can induce CLDN4-dependent activation of CD137, leading to enhanced interferon-gamma (IFNγ) production by T cells. Moreover, these studies have shown substantial anti-tumor efficacy, including instances of complete tumor regression in various murine cancer models.[2]