Development of a Novel Therapeutic Agent for Skin Fibrosis

Systemic sclerosis or scleroderma is an autoimmune rheumatic disease characterized by fibrosis
of the skin and internal organs that has the highest case fatality among rheumatic diseases. The
increased deposition of collagen and other extracellular matrix proteins in the tissues leads to
impaired function of visceral organs and early death. Although several drugs such as recently
approved nintedanib and tocilizumab may stabilize lung function in some scleroderma patients,
none of those have a significant effect on skin fibrosis as measured by the modified Rodnan skin
score, underscoring the need to develop new therapies for this potentially lethal disease.
Small peptides are widely involved in multiple cellular events and play very important roles in
various cell functions. Interest in peptides as potential drug candidates remains high. With
advances in such fields as chemical synthesis and peptide formulation, peptide drugs - especially
short synthetic and long-acting peptides - are quickly increasing in the global market. The
advantages of small peptides as drugs include their high biological activity, high specificity, and
low toxicity.
FibroBiologics, LLC proposes to develop the novel peptide M10 as an efficacious antifibrotic
therapeutic agent, with a lead indication for the treatment of patients who suffer from skin fibrosis
associated with scleroderma. In Specific Aim 1, we will determine antifibrotic activity of M10 in
primary skin fibroblasts isolated from scleroderma patients and evaluate an inhibitory effect of
M10 on fibrogenic characteristics of scleroderma skin fibroblasts. In Specific Aim 2, we will define
the efficacious dosing of M10 in two different animal models of dermal fibrosis: bleomycin-induced
mouse model and FSP-driven TβR1CA mouse model. The successful completion of these two
specific aims will provide important information about the feasibility of developing M10 as a novel
therapeutic for skin fibrosis and will justify further studies focusing on gaining FDA clearance,
scaling production, and a human clinical trial.

Grant Number: 1R41AR084935-01
NIH Institute/Center: NIH
Principal Investigator: GALINA BOGATKEVICH