Corbus Pharmaceuticals Holdings, Inc. (Corbus), a clinical stage drug development company targeting rare, chronic, serious inflammatory and fibrotic diseases, announced that it has completed its phase 2 study evaluating JBT-101 (Resunab) for the treatment of cystic fibrosis (CF). JBT-101, the company's novel synthetic oral endocannabinoid-mimetic drug, is designed to resolve chronic inflammation and halt fibrosis. Corbus expects to report topline data from this study in the first quarter of 2017.
"We are pleased to announce the on-schedule completion of our phase 2 trial evaluating JBT-101 for the treatment of cystic fibrosis. We would like to express our sincere gratitude to all the individuals, their clinicians and the clinical staff who participated in this trial," stated Yuval Cohen, Ph.D., chief executive officer of the company.
The international, multi-center, double-blinded, randomized, placebo-controlled phase 2 study is supported by a $5 million Development Award from Cystic Fibrosis Foundation Therapeutics, Inc. The primary objective of the study was to test safety and tolerability of JBT-101 in adults with CF who had forced expiratory volume in 1 second (FEV1) percent predicted at least 40%, without regard to their CFTR mutation, infecting pathogen, or baseline treatment. Secondary objectives were to evaluate changes in pro-inflammatory and pro-resolving lipid mediators as a marker of mechanism of action of JBT-101 and to evaluate efficacy with FEV1 and Cystic Fibrosis Questionnaire Revised -- Respiratory Symptom Score. Exploratory outcomes included effects of JBT-101 on biomarkers of inflammation and the sputum microbiome. Eighty-five subjects on stable standard-of-care medications were dosed with study product at 21 CF centers in the US and Europe and treated with study product daily for a period of 84 days, with a follow-up period of 28 days.
"We look forward to having our first safety data on JBT-101 in CF. Because excessive inflammation is a key driver of airway obstruction and lung damage over time in CF, resolving inflammation has the potential to provide significant clinical benefit to CF patients, importantly without immunosuppression," said Barbara White, MD, chief medical officer of the company. "We believe that showing that JBT-101 has an acceptable safety profile in CF is a gate-keeping event for its further clinical development in CF, and we anticipate announcing top-line results before the end of the first quarter of 2017."
JBT-101 was granted Orphan Drug designation and Fast Track status for the treatment of CF from the US Food and Drug Administration (FDA) in 2015 and was granted Orphan Drug designation by the European Union for the treatment of CF in October 2016. The company recently reported positive topline data results from its phase 2 study in diffuse cutaneous systemic sclerosis (systemic sclerosis), showing clear signal of clinical benefit with JBT-101. Additionally, JBT-101 is being evaluated in a phase 2, 12-month open label extension study in systemic sclerosis, a phase 2 study in skin-predominant dermatomyositis, with a 12-month open label extension study in dermatomyositis and a another phase 2 study in systemic lupus erythematosus (SLE) planned to commence in the first quarter of 2017.
CF is a chronic, life-threatening, genetic disease caused by inheriting two dysfunctional CFTR genes that normally regulate salt and water movement across cells in the respiratory and digestive systems. CF affects approximately 30,000 patients in the U.S and 75,000 patients worldwide. People with CF have thick, sticky mucus that clogs their airways, with recurrent bacterial infections and chronic inflammation in their lungs. In the gastrointestinal tract, they also have mucus accumulation, bacterial overgrowth, and inflammation. The dysfunctional CFTR genes cause an exaggerated inflammatory response that compounds the damage from a coexisting infection in the lungs and gut. CF results in destruction of lung tissue, lung fibrosis, pancreatic insufficiency, CF-related diabetes, malabsorption, malnutrition, growth retardation, and liver disease, including cirrhosis. The harmful inflammation and accompanying fibrosis in CF damages multiple organs, impairs organ function, reduces health-related quality of life, and can lead to death.
JBT-101 is a novel synthetic oral endocannabinoid-mimetic drug that preferentially binds to the CB2 receptor expressed on activated immune cells and fibroblasts. CB2 activation triggers endogenous pathways that resolve inflammation and halt fibrosis. Preclinical and phase 1 studies have shown JBT-101 to have a favorable safety, tolerability and pharmacokinetic profile. It has also demonstrated promising potency in preclinical models of inflammation and fibrosis. JBT-101 is designed to trigger the production of "Specialized Pro-resolving Lipid Mediators" that activate an endogenous cascade responsible for the resolution of inflammation and fibrosis, while reducing production of multiple inflammatory mediators. JBT-101 has direct effects on fibroblasts to halt tissue scarring. In effect, JBT-101 triggers endogenous pathways to turn "off" chronic inflammation and fibrotic processes, without causing immunosuppression.