Hydrogel-based Serine Protease Inhibitor Drug for topical treatment of dermatitis

• Grant number: 22/14187-4
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Aquiles Melchior Sant Ana
• Grantee: Aquiles Melchior Sant Ana
• Company: Krabs Desenvolvimento em Biotecnologia Ltda
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: Santo André
• Associated researchers: Jair Ribeiro Chagas
• Associated scholarship(s): 24/17421-3 - Hydrogel-based serine protease inhibitor drug for topical treatment of dermatitis., BP.TT; 23/08442-4 - Hydrogel-based Serine Protease Inhibitor Drug for topical treatment of dermatitis, BP.TT; 23/07197-6 - Hydrogel-based serine protease inhibitor drug for topical treatment of dermatitis, BP.PIPE

Abstract

KRABS Biotechnology is a startup that works with the development of new chimeric monoclonal antibodies (qmAb) for therapeutic applications and diagnoses. These compounds, when properly selected, are identical to monoclonal antibodies in terms of affinity, selectivity, and specificity. Our first product is related to the inhibition of a protease from the kallikrein family, crucial in the desquamation process, and, consequently, involved in the development of some skin diseases such as atopical dermatitis and psoriasis. It uses an antibody fragment capable of recognizing and inhibiting the human tissue kallikrein 7 (hKLK7). The human tissue kallikrein forms a family of 15 proteolytic enzymes (hKLK1-hKLK15) widely distributed and differentially expressed in several tissues. The hKLK7 acts cleaving the corneodesmosomes, structures responsible for maintaining the cellular cohesion in the stratum corneum of the skin. Therefore, hKLK7 is crucial for the skin desquamation process. However, when this enzyme malfunctions, it can cause an uncontrolled desquamation process, as previously described in patients with psoriasis, atopical dermatitis, and Netherton Syndrome. Thus, molecules capable of controlling the activity of the hKLK7 are pointed out as new therapeutic approaches for these dermatological diseases. The molecule LUP37C11, obtained for the fusion of an anti-hKLK7 scFv with a human Fc sequence, is part of a patent application on INPI (BR 10 2020 009679 6) and the PCT process PCT/BR2021/050201, by the Universidade Federal do ABC and the Technische Universität Braunschweig. Currently, the technology is exclusively licensed to KRABS Biotechnology for drug development with applications for skin diseases. Recently, the LUP37C11 was part of a "PIPE Fase I" project conducted by KRABS Biotechnology in which it developed a topical hydrogel formulation and used in the first animal tests done in dogs to determine the compound safety. The LUP37C11 hydrogel-based formulation proposes a treatment easy to apply, besides having as a target the control of the enzymatic activity and not molecules related to the immunological response, as other treatments. Besides, KRABS Biotechnology has invested in an innovative technology aiming the development of new biding and specifics fusion proteins based on the variables regions of antibodies, generating new qmAb, which will also serve as a service platform for the company, securing revenue and cash flow until the first product reaches the market. This platform will utilize human antibody fragments phage display library with modifications from our most recent studies. We are certain that at the end of this proposal, we will have a new drug closer to the market and a platform ready to serve our clients. (AU)