Edasalonexent is a novel investigational drug being evaluated as a potential treatment of Duchenne muscular dystrophy (DMD) that we designed to benefit all boys affected by DMD regardless of mutation type.
Edasalonexent inhibits NF-κB, an important mechanism in DMD because NF-κB regulation plays a key role in skeletal muscle health and activated NF-κB is seen in boys affected with DMD prior to the clinical manifestations of their disease. In the placebo-controlled Phase 2 and open-label extension of the MoveDMD trial investigating the safety and efficacy of edasalonexent in boys enrolled at ages 4 to 7 affected with DMD (any confirmed mutation), edasalonexent substantially slowed DMD disease progression through 36 weeks of treatment. Across all key assessments of muscle function, consistent improvements were observed in the rate of decline after 24 and 36 weeks of oral 100 mg/kg/day edasalonexent treatment compared to the rate of change in the control period for boys prior to receiving edasalonexent treatment. Improvements were also seen across additional measures of muscle health. Edasalonexent has been well tolerated with no safety signals observed in the trial.
Favorable safety, tolerability, pharmacokinetics and positive biological marker results were observed in Phase 1 trials with healthy adults and boys affected by DMD who received edasalonexent. In animal models of DMD, edasalonexent inhibited NF-κB, reduced muscle degeneration and improved muscle regeneration and function, and beneficial effects were observed in skeletal muscle, diaphragm and heart.
FDA has granted edasalonexent Orphan Drug, Fast Track and Rare Pediatric Disease designations for the treatment of DMD. The European Commission has granted Orphan Medicinal Product designation for edasalonexent for the treatment of DMD.
CAT-5571 is an oral small molecule designed to restore host defense by activating autophagy being developed for the treatment of cystic fibrosis (CF). Autophagy is a mechanism for recycling cellular components and digesting pathogens, which is depressed in CF. People with CF suffer from persistent lung infections with opportunistic pathogens such as P. aeruginosa and B. cenocepacia, causing chronic infections that are difficult to eradicate and ultimately lead to respiratory failure. CAT-5571 has been shown to restore autophagy, reestablish host defense and enhance the clearance of pathogens, including P. aeruginosa and B. cenocepacia, in preclinical models of CF.
We expect to initiate a Phase 1 trial for CAT-5571 in the second half of 2018.
We are initially developing CAT-4001 for the potential treatment of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Friedreich's ataxia. CAT-4001 activates the Nrf2 pathway and inhibits the NF-κB pathway, both of which have been implicated in ALS and Friedreich's ataxia. We are conducting preclinical evaluation of CAT-4001 in ALS and Friedreich's ataxia.
The CAT-2000 series are small molecules for the potential treatment of nonalcoholic steatohepatitis (NASH). NASH is a severe form of non-alcoholic fatty-liver disease which can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).
The CAT-2000 molecules inhibit Sterol Regulatory Element-Binding Protein (SREBP), a master regulator of lipid and cholesterol metabolism. SREBP is implicated in the progression of fatty liver disease to NASH, fibrosis and HCC. We have seen positive pre-clinical results for CAT-2003 in a model of NASH with significant improvements in steatosis, inflammation, fibrosis and pre-neoplastic lesions.
We see the CAT-2000 series as a potential partnership opportunity in NASH.