SOT-102: A Comprehensive Analysis of a Discontinued CLDN18.2-Targeted Antibody-Drug Conjugate and its Strategic Implications

Executive Summary

This report provides a comprehensive analysis of SOT-102, an investigational antibody-drug conjugate (ADC) developed by SOTIO Biotech for the treatment of CLDN18.2-positive solid tumors, primarily gastric and pancreatic adenocarcinoma. SOT-102 was engineered with a distinct molecular architecture, combining a proprietary, high-affinity monoclonal antibody targeting the tumor-associated antigen Claudin 18.2 (CLDN18.2) with a highly potent topoisomerase II inhibitor payload, PNU-159682. The construct utilized a site-specific, non-cleavable linker technology, reflecting a design philosophy heavily focused on maximizing stability and tolerability.

The preclinical data for SOT-102 were exceptionally promising, demonstrating complete tumor responses in all tested patient-derived xenograft models, including those with low target expression, suggesting a potentially wide therapeutic window and broad patient applicability. This compelling preclinical package supported the initiation of the Phase 1/2 CLAUDIO-01 clinical trial in April 2022. The trial was designed to efficiently evaluate SOT-102 as both a monotherapy and in combination with standard-of-care regimens in patients with advanced gastric and pancreatic cancer.