AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today the commencement of an investigator initiated Phase 2 study at UC San Francisco (UCSF) for its novel inhaled form of sirolimus, LAM-001, for the treatment of bronchiolitis obliterans syndrome (BOS) in patients post-lung transplant. BOS remains the leading cause of death after transplantation and affects approximately 50% of all lung transplant recipients by 5 years. Worldwide, 4,600 lung transplantations are performed each year.
“BOS is a major complication in lung transplant patients for which there are no approved therapies. BOS pathology is driven by inflammation of the small airways, fibroproliferation and abnormal regeneration of the epithelium. Progressive narrowing of these airways leads to difficulty breathing and the ultimate need for re-transplantation or death,” said Steven Hays, MD, medical director of the UCSF Lung Transplant Program, and Principal Investigator of the trial. “While retrospective analyses have shown that oral sirolimus can improve survival in BOS patients, systemic toxicities have limited its widespread adoption. An inhaled version of sirolimus has the promise of delivering drug directly to the lung tissue where it is needed while potentially reducing systemic exposures and concomitant toxicities.”
The 48-week, randomized, double blind, placebo-controlled study is designed to evaluate the safety, tolerability and efficacy of LAM-001 in 30 adults with newly diagnosed BOS (Grade 1-2). The primary endpoints of the trial are safety, tolerability and progression free survival (defined as the earliest to occur of >10% decline in FEV1 from baseline or death from respiratory failure). Secondary endpoints include change in FEV1 and FEV1/FVC at 48 weeks from baseline or time to progression free survival (as defined by the earliest of a change in FEV1 from baseline of >20% or death from respiratory failure). Further assessments will include change in quality of life as measured by SGRQ-C over 48 weeks, change in 6-minute walk distance (6MWD) from baseline at 48 weeks, blood and BAL levels of sirolimus and various exploratory measures.
LAM-001 is a proprietary, investigational, inhaled formulation of sirolimus, also known as rapamycin. Sirolimus’s potential in BOS is supported by both human and animal data. Limited retrospective data in humans administered oral sirolimus post lung transplant has demonstrated improved survival in both the prevention and treatment settings of BOS. These data are further bolstered by data in a mouse model of BOS which demonstrated that sirolimus prevented occlusion of airways via several mechanisms, including reduction in recruitment of fibrocytes, protection against airway epithelial loss and increased infiltration of immune inhibitory Treg and Breg cells.