ABBV-969, a novel bispecific antibody drug conjugate (ADC), is being developed to address this unmet need by targeting prostate tumor antigens STEAP1 (six transmembrane epithelial antigen of the prostate-1) and PSMA (prostate-specific membrane antigen), which are highly expressed in prostate tumors.

STEAP1 is minimally expressed in normal tissues but is significantly upregulated in over 85% of prostate tumors, where it drives tumor proliferation and invasion. Similarly, PSMA, a prostate lineage marker, is expressed at levels up to 100-fold higher in tumor tissue compared to healthy prostate tissue, with its expression correlating with tumor stage, aggressiveness, and recurrence. The high prevalence and expression of these antigens make them ideal targets for ADCs.

However, heterogeneous expression of these antigens within and across tumors can limit the effectiveness of single-target ADCs. To overcome this, ABBV-969 employs a dual variable domain immunoglobulin (DVD-Ig) format, enabling bivalent engagement of both STEAP1 and PSMA. This bispecific approach enhances tumor cell coverage and potentially improves the durability of the therapeutic effect.

ABBV-969 is designed to deliver a potent cytotoxin to tumor cells via a proprietary topoisomerase-1 (Top1) inhibitor linker-drug. The conjugate binds with high affinity to cells expressing either STEAP1, PSMA, or both, demonstrating cytotoxicity across a range of prostate cancer cells. Preclinical studies have shown that ABBV-969 exhibits favorable drug-like properties, including promising pharmacokinetics and superior efficacy compared to standard ADCs targeting only STEAP1 or PSMA.
ABBV-969 is currently under investigation in a Phase 1 clinical trial (NCT06318273), which is focused on dose escalation to evaluate its safety, tolerability, and preliminary efficacy in patients with advanced prostate cancer.

Source.

Clinical trial.