Preclinical Development of M10 as a Therapeutic Agent for Scleroderma

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Abstract Scleroderma (systemic sclerosis, SSc) is an autoimmune fibrotic disorder that affects multiple systems including the skin and visceral organs of the body. The leading cause of death in scleroderma patients is pulmonary dysfunction resulting from progressive interstitial lung fibrosis. Although immunosuppressive agents and other drugs such as nintedanib may stabilize lung function, long-term treatment is required, significant toxicity may occur, and many patients fail to respond to such therapies. Around 40% of scleroderma-associated interstitial lung disease (SSc-ILD) patients will die within 10 years of diagnosis; therefore, there is an urgent need for new therapeutic approaches that would be more effective and less toxic than current treatments. 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 SSc-ILD. In Specific Aim 1, we will determine basic PK parameters, metabolism, biodistribution, and toxicity of M10 after subcutaneous administration in mice. In Specific Aim 2, we will define the efficacious dosing of M10 in two different animal models of SSc-ILD: bleomycin-induced therapeutic 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 antifibrotic therapeutic and will justify further studies focusing on gaining FDA clearance, scaling production, and a human clinical trial.