This SBIR Phase II project aims to develop a novel engineered microbiome as a potential therapeutic for a rare skin disease called Netherton syndrome. Netherton syndrome (NS) is a rare, severe skin disease with high mortality and few treatment options. This proposal aims to develop a new therapeutic for this disease, a microbe-based protein delivery system of LEKTI, the missing protein responsible for NS symptoms. At the end of this project, a candidate live biotherapeutic product candidate (LETKI-secreting strain of S. epidermidis) will be nominated and the Company will have sufficient data with which to proceed into formal preclinical studies and subsequent human testing. This proposed product will have the potential to address thousands of patients in the U.S., and the broader proof-of-principle of this microbe-based technology offers significant potential to treat millions of patients living with skin conditions. This offers significant advances in innovation in addition to broad commercial potential.
This project aims to develop a novel therapeutic candidate composed of an engineered strain of S. epidermidis that secretes LEKTI protein to the skin for the treatment of Netherton syndrome (NS). NS is a rare but severe autosomal recessive disease that affects the skin, hair, and immune system. NS is caused by mutations in in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI), which contains 15 serine protease inhibitory domains. The goal of this Phase II project is to demonstrate a proof-of-concept therapeutic for NS: an engineered commensal microbe that delivers discrete domains of LETKI to the skin. The proposed Phase II research plan will establish critical criteria for nominating a potential live biotherapeutic product (LBP) candidate composed LEKTI-secreting S. epidermidis. This research will perform key activities in preclinical development of an LBP: identify an optimal sequence of LEKTI; develop analytical methods for detecting LEKTI secreted from an engineered strain of S. epidermidis; and develop analytical methods for measuring biodistribution and adsorption of LEKTI secreted by S. epidermidis in a human in vitro model.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
