营养不良型大疱性表皮松解症（DEB）系统性蛋白替代疗法.PDF

Systemic Protein Replacement Therapy for Dystrophic Epidermolysis Bullosa (DEB) Mark P. de Souza, PhD EB-CLINET Conference Salzburg October 6, 2012 Company Overview • Founded in 2010 to develop recombinant Collagen Type VII (rC7) as protein therapy for Dystrophic Epidermolysis Bullosa (DEB) • Exclusive license to USC and Stanford intellectual property on rC7 • Compelling data in mouse and dog models demonstrates intravenous rC7 reverses the DEB phenotype • Clear path to regulatory approval - longitudinal severity study in 2012, Phase 1 human clinical trial in 2013 and regulatory approval in DEB in 4-5 years • Scientific leaders in C7 protein therapy and experienced management team • Secured significant financing in June 2011 2 Intradermal rC7 Reverses DEB Phenotype • Drs. Woodley and Chen – pioneers of protein therapy for DEB • Recombinant collagen type VII (rC7) purified from a human fibroblast cell line using methods described for a HEK 293 cell line1 • Intradermal rC7 injected into two mouse models of DEB: • DEB skin equivalents transplanted onto athymic nude mice2 • C7 knock out mice3 • Intradermal injections restored C7 and anchoring fibrils at the basement membrane zone and reversed RDEB disease phenotype in both mouse models Athymic Nude Mouse Model C7 Knock Out Model Untreated rC7 Treated Untreated rC7 Treated Reverses separation of dermal-epidermal junction (DEJ) Corrects skin blister formation in C7 knock-out mice of RDEB skin equivalents grafted on nude mice 1. Chen, M., et al., 2002. J. Bio