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XMT-1592 is an investigational antibody-drug conjugate (ADC) developed using the Dolasynthen platform by Mersana Therapeutics. It targets sodium-dependent phosphate transport protein 2B (NaPi2b), which is highly expressed on certain tumor cells, including those in ovarian cancer and non-small cell lung cancer. The ADC consists of a proprietary NaPi2b-targeting antibody linked to an auristatin-based cytotoxic payload via the DolaLock mechanism, which allows for precise control of drug-to-antibody ratio and site-specific bioconjugation. Upon binding to NaPi2b-expressing tumor cells, XMT-1592 is internalized; the cytotoxic payload then inhibits tubulin polymerization, leading to mitotic arrest and apoptosis in targeted cancer cells. Preclinical studies demonstrated enhanced efficacy compared to earlier generation ADCs targeting the same antigen. Clinical development was discontinued during Phase 1 due to portfolio reprioritization.
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