Edasalonexent is a novel investigational drug for the treatment of Duchenne muscular dystrophy (DMD) that we designed to potentially benefit all boys suffering from DMD regardless of mutation type. Edasalonexent inhibits NF-κB. This approach is different from investigational methods that are mutation-specific that have the potential to treat small sub-sets of those affected by DMD.
NF-κB inhibition is a potentially important mechanism for DMD treatment 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. 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. In Part B of the MoveDMD® trial, the primary efficacy end point of magnetic resonance imaging (MRI) T2 was not met. The edasalonexent 100 mg/kg/day treatment group consistently showed numerical improvement versus placebo across multiple timed function tests and the North Star Ambulatory Assessment, although as expected the changes were not statistically significant. The 67 mg/kg/day treatment group had mixed results compared with both the 100 mg/kg/day treatment group and placebo, which in each case were not statistically significant. Edasalonexent was well-tolerated with no safety signals observed.
Edasalonexent is currently being studied in Part C of the MoveDMD trial. The full analysis of data from Part B of the trial and from Part C of the MoveDMD trial is continuing and we plan to submit the data for presentation at upcoming scientific conferences.
The 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.
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.
We are developing CAT-5571 as a potential oral treatment for cystic fibrosis (CF) with potential effects on both cystic fibrosis transmembrane conductance regulator (CFTR) and on the clearance of Pseudomonas aeruginosa. CAT-5571 is a small molecule that activates autophagy, a process that maintains cellular homeostasis and host defense mechanisms, which is known to be impaired in CF. We have shown in preclinical studies that CAT-5571, in combination with lumacaftor/ivacaftor, enhances cell-surface trafficking and function of CFTR with the F508del mutation. We have also shown that CAT-5571 enhances the clearance of P. aeruginosa infection in preclinical models of CF, irrespective of CFTR mutation status.
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.