Dermadis develops selective inhibitors to target dysregulated proteases linked to inflammatory skin diseases. For this purpose Dermadis will exploit Med Discovery’s proprietary technologies and as well as additional new technologies to develop a family of protein and peptide inhibitors with the potential to block skin related kallikreins and other proteases.
The use of small chemical molecules as inhibitors of proteases has failed in many cases due to inacceptable toxicity caused by insufficient target selectivity. Biologics, recombinant proteins and peptides, combining high biologic activity with generally very favorable safety profiles are considered a very promising alternative.
Serpin (serine protease inhibitor) proteins inhibit a specific protease or class of proteases by formation of a stable, covalent complex with their target. The antiprotease technology is based on the modification of natural, serpin-type protease inhibitors to improve or change their specificity. As the inhibitor scaffold is natural, the technology allows the generation of leads which are generally very well tolerated.
Conversion of a natural inhibitor into a selective lead for inhibiting a therapeutic target
Peptides are being developed as an alternative to recombinant serpin type protease inhibitors. Recent improvements in synthesis and formulation technology are now allowing for the efficient and cost-effective production of these drugs. If required they can be further engineered for modification of activity, stability or pharmacokinetics. Furthermore, due to their small size, peptides are not immunogenic and show faster tissue penetration than larger proteins. Whereas the use of therapeutic peptides is often limited through their low half-life in circulation, this is expected to be not a concern in local, topical formulation.
Screening of proprietary distinct random peptide libraries is used as basis for the development of novel types of protease inhibitor leads. Identified peptide inhibitor lead sequences are further optimized through chemical modification to increase antiproteolytic activity and selectivity and decrease specific or non-specific degradation of the peptides in vivo.