GenSci143: A Dual-Target ADC Emerging for Metastatic Prostate Cancer

GenSci143 (aka GenSci-143) is a bispecific antibody-drug conjugate under development for metastatic castration-resistant prostate cancer (mCRPC) and other solid tumors.

The construct targets B7-H3 (CD276) and PSMA simultaneously with a bispecific antibody, coupled via a stable, cleavable linker to a topoisomerase I inhibitor payload, aiming to improve tumor cell killing and bystander effects across heterogeneous antigen expression landscapes in prostate cancer. This dual-targeting strategy is intended to overcome limitations seen with single-target ADCs where variable expression or spatial heterogeneity can constrain efficacy in mCRPC.​

Preclinical data presented across conference forums and company communications report robust anti-tumor activity in human cell-derived xenograft (CDX) prostate cancer models, including tumor regression across a range of B7-H3 and PSMA expression levels and superior efficacy versus analogs of single-target comparators DS-7300 (anti–B7-H3) and ARX517 (anti-PSMA). In patient-derived xenograft (PDX) models, combination testing with enzalutamide showed potential synergy, and pharmacokinetic and tolerability profiles were described as favorable in preclinical evaluations.​

The scientific rationale is supported by pathology data indicating high co-expression of B7-H3 and PSMA in prostate cancer tissues, including a cohort analysis of 102 samples cited in the abstract record, reinforcing the case for simultaneous targeting in mCRPC. By engaging both antigens in a single construct, GenSci143 is positioned to expand patient coverage and mitigate resistance mechanisms that arise from antigen heterogeneity and clonal evolution.​

Regulatory momentum accelerated in October 2025, with acceptance of an investigational new drug (IND) application by the U.S. FDA reported in mid-October, followed by Chinese National Medical Products Administration (NMPA) clinical trial approval later in the month, enabling initiation of first-in-human studies in advanced solid tumors that include prostate cancer. These clearances mark the transition from IND-enabling work into Phase I safety, dose-escalation, and preliminary activity assessment in patients, a critical inflection point for any ADC platform.​

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