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SYNB011128 is a novel bispecific peptide-drug conjugate (PDC) designed to target both Epidermal Growth Factor Receptor (EGFR) and Carbonic Anhydrase IX (CAIX). Developed by Syneron Tech, this 4 kDa molecule consists of a bispecific peptide ligand conjugated to the potent tubulin inhibitor monomethyl auristatin E (MMAE) via a tumor-specific protease-cleavable linker. SYNB011128 exerts its anti-tumor activity through three distinct mechanisms: competitive inhibition of the EGFR pathway, inhibition of CAIX enzyme function (critical for survival in hypoxic/acidic tumor environments), and targeted delivery of the cytotoxic payload. Preclinical data demonstrate complete tumor regression in pancreatic and colon cancer models, as well as efficacy in osimertinib-resistant non-small cell lung cancer (NSCLC). Its small size facilitates deep tumor penetration and rapid blood clearance, potentially improving the safety profile compared to traditional antibody-drug conjugates (ADCs).
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