Structure-Activity Relationship of CM101 Tumor antiangiogenic agent with its lect

DESCRIPTION (provided by applicant): CM101 is a polysaccharide tumor angiogenesis-targeting, complement activating, immune stimulating biological produced fermentatively from Group B Streptococcus. CM101 binds a capillary endothelium receptor, HP59, causing inflammatory cytokine cascades, recruiting CD69+ granulocytes to destroy neovasculature and surrounding tumor. This SBIR proposal is to determine Structure-Activity-Relationship (SAR) for CM101 to identify angiogenesis-specific HP59-targeting mechanismsand establish minimal active molecular structure (pharmacophore). CM101 is not an angiogenesis inhibitor like Avastin and related biologicals and drugs, but has a completely different mechanism of action, stimulating immune attack on HP59+ tumor neovasculature. CM101 is a promising active pharmaceutical ingredient (API) biological for cancer therapy in results from animal studies and a human Phase I safety trial published in 1997. More recent intellectual property for CM101 purification and the HP59 receptor now protects products through 2026-2028. CM101 development was interrupted by previous business failures, despite the promising technology. By establishing the pharmacophore, pinpointing biochemical binding interaction with the tumor capillary endothelium lectin receptor HP59 (See Wikipedia), we will discover mechanism of action details, new composition of matter intellectual property, and potential for development of small drug pipelines, to stimulate investors and major pharmaceutical companies' incentive to support planned Phase I/II clinical trials. In sum, CM101, the Group B Streptococcal Toxin (GBS-Toxin) is a 270Kda polysaccharide exhibits targeted binding to HP59, a specific tumor cell endothelial cell surface lectin, therefore a highly specific tumor vasculature targeting biological therapeutic, needing SAR for development. PUBLIC HEALTH RELEVANCE: This SBIR grant proposal seeks to determine the Structure-Activity-Relationship for CM101, a tumor neovasculature targeting Group B Streptococcal toxin that binds the lectin tumor angiogenesis marker HP59. HP59 binding by CM101 results in complement activation and subsequent inflammatory response against the tumor, which has been published in animal and human Phase I trials. We intend to molecularly identify the HP59 targeting mechanism, to define mechanism of action, to establish updated intellectual property, and provide potential drug pipelines by identification of a minimum pharmacophore for HP59 binding and for complement activation.