CELDARA MEDICAL, LLC — Department of Health and Human Services SBIR Phase I: NHLBI

Description

DESCRIPTION provided by applicant Idiopathic pulmonary fibrosis IPF kills about persons in the United States each year There are currently around Americans afflicted with this fatal disease that typically results in death within years This year alone another approximately Americans will receive this devastating diagnosis While two recently approved drugs reduce the time to decline in certain lung parameters and the risk for acute exacerbations there is no currently available approach beyond lung transplantation that has been proven to extend the lives of IPF patients Our ultimate goal is to improve the lives of patients faced with this grim prognosis by developing a safe and effective inhalable therapeutic to halt and possibly reverse the fibrotic process underlying IPF pathogenesis We have identified the redox regulating enzyme glutaredoxin Grx as a promising therapeutic candidate Our studies using the well established bleomycin and TGF lung fibrosis models in mice have demonstrated that Grx knockout mice develop markedly more severe lung damage than control mice mice that overexpress Grx in epithelial cells are protected from fibrosis and aerosol delivery of recombinant Grx reverses multiple parameters of lung pathology even in aged mice and even when administered after establishment of fibrotic alterations As Grx is highly conserved in all mammals we anticipate that human recombinant Grx will have similar effects Our development plan includes a collaboration with Pulmatrix Inc a company with a proven track record for incorporating large molecules into their proprietary iSPERSE dry powder formulation and advancing clinical development of such for serious respiratory conditions like cystic fibrosis In Phase I of this application we propose to produce a murine recombinant Grx iSPERSE proprietary dry powder formulation iSPERSE Pulmatrix Inc and optimize both process conditions and excipients We will then perform in vitro and in vivo testing to confirm equivalence and determine the maximum tolerated dose MTD in mice In Phase II we will complete murine efficacy studies and then identify develop and characterize a lead formulation for the clinical grade product a human Grx iSPERSE dry powder formulation and conduct nonclinical safety and toxicity studies with this product in rats and monkeys Upon successful completion of non clinical safety and toxicity studies we will submit an IND to pursue clinical studies with our novel inhalable product The successful development of inhalable human Grx iSPERSE would result in an entirely new approach to treat IPF This application describes the work necessary to complete preclinical development and will position Grx iSPERSE for initial clinical trials PUBLIC HEALTH RELEVANCE Idiopathic pulmonary fibrosis IPF is a uniformly lethal disease that kills about persons in the United States each year Two recently approved drugs reduce the time to decline in certain lung parameters but there is no currently available therapy that impacts the overall survival of IPF patients We have identified a promising therapeutic candidate based upon a redox modifying enzyme and are developing an inhalable treatment for clinical trials