Preclinical Development of a Novel Therapeutic Agent for Idiopathic Pulmonary Fibrosis

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Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a median survival of only 3 - 5 years from diagnosis. Although two FDA-approved drugs, pirfenidone and nintedanib, may slow the rate of decline of lung function in some IPF patients, neither drug significantly alters the course of this lethal disease. There is a great need for new drugs with greater efficacy and less toxicity for the treatment of patients with IPF. This STTR application addresses the unmet need for new therapeutic approaches to IPF 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 IPF. In Specific Aim 1, we will determine antifibrotic activity of M10 in primary lung fibroblasts isolated from IPF patients and evaluate an inhibitory effect of M10 on fibrogenic characteristics of IPF lung fibroblasts. In Specific Aim 2, we will define the efficacious dosing of M10 in two different animal models of pulmonary fibrosis: 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 IPF therapeutic and will justify further studies focusing on gaining FDA clearance, scaling production, and a human clinical trial.