Napo Pharmaceuticals, Inc. has in-licensed from the University of California Regents additional small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor technology including gastrointestinal (GI) and polycystic kidney disease (PKD) indications. PKD, a leading cause of end-stage renal disease and kidney transplants, affects approximately 600,000 people in the United States, and 12.5 million worldwide, according to the PKD Foundation.
Napo’s collaborator, Alan Verkman, M.D., Ph.D., of the University of California San Francisco (UCSF) Department of Medicine, was recently awarded a National Institutes of Health (NIH) challenge grant to further evaluate CFTR inhibitor technology targeting PKD. The goal of the NIH funded study is to evaluate a select group of CFTR inhibitors that, when orally administered, are effective in preventing renal cyst growth and renal function deterioration in mice.
Napo has exclusive rights to several classes of novel, proprietary, small-molecule CFTR inhibitors, which it is developing for a variety of indications, including PKD and secretory diarrheas, which may include diarrheas of infectious or other origins. To advance candidate molecules for both indications, Napo intends to leverage the knowledge of secretory biology and clinical development it has gained from its work with crofelemer, the company’s lead molecule and first-in-class CFTR inhibitor. Crofelemer, which is extracted and purified from a rain forest plant and cannot be synthesized, is too large to be significantly absorbed, making it a locally acting anti-diarrheal agent.
Napo’s licensee, Salix Pharmaceuticals, Inc., is evaluating crofelemer as a treatment for chronic diarrhea in people living with HIV/AIDS on anti-retroviral therapy in a final Phase 3 study called the ADVENT trial. Another Napo licensee, Glenmark Pharmaceuticals, Ltd., is testing crofelemer for use in late-stage adult acute infectious diarrhea (AAID) in India, and plans to expand its studies to severe diarrheal infection (including cholera) and pediatric diarrhea.
Earlier this year, Napo announced that SRI International had begun an early-stage discovery/pre-clinical drug development program using small molecules from Napo’s portfolio of CFTR inhibitor candidates. Special funding for this program was provided by the National Institute of Allergy and Infectious Diseases’ Division of Microbiology and Infectious Diseases (DMID) at the NIH in response to the dire need for novel drugs for additional treatment options for secretory diarrhea and GI disorders. SRI’s activities are focused on refining leads for further pre-clinical studies supporting the filing of an Investigational New Drug (IND) application for a small-molecule CFTR inhibitor.
“This is the second time this year that the CFTR technology has been recognized through NIH funding as an important mechanism in treatment of diarrheal diseases and PKD,” said Napo CEO Lisa Conte. “Two to three million children die each year from secretory diarrhea, and there are no therapeutic options for PKD, leading to dialysis and transplant options only for the patients.”