ACE-083 is the lead product candidate in our neuromuscular therapeutic program. It is a locally active agent that may be useful for diseases of focal muscle loss such as muscular dystrophies, with a first indication in facioscapulohumeral muscular dystrophy (FSHD), for which it received Fast Track and Orphan Drug designations from the U.S. FDA. ACE-083 is designed to increase strength and function in specific target muscles for improved patient function and quality of life.
ACE-083 works by binding to and inhibiting select proteins in the TGF-beta protein superfamily that negatively regulate (reduce) muscle growth, such as activins and myostatin (GDF8). This “Myostatin +” approach, is believed to increase muscle mass and strength in the muscle where the drug is administered. Untreated muscles or other organs are not affected, reducing the potential for systemic side effects. Our approach is unique from that of competitors who have attempted to engage the superfamily’s targets selectively, only to receive marginal results. In contrast, we have achieved meaningful clinical results by engaging multiple TGF-beta targets.
Based on encouraging Phase 1 results, we initiated a two-part Phase 2 trial in FSHD patients with muscle weakness in the tibialis anterior or biceps, and recently announced positive preliminary results for the first two dose cohorts in Part 1 of the trial, and have initiated Part 2 of the Phase 2 FSHD trial. We are also conducting a Phase 2 trial in Charcot-Marie-Tooth disease, in which ACE-083 may benefit patients who suffer from muscle weakness causing foot drop and reduced mobility.
There are no FDA approved therapies for FSHD, one of the most common muscular dystrophies, a progressive, degenerative and often debilitating disorder that affects about 20,000 people in the U.S. Many of these patients have trouble walking and running, and develop upper arm muscle weakness, ultimately limiting their ability to perform daily tasks, such as eating or getting dressed. It is estimated that 20 percent of people with FSHD require the use of a wheelchair at least some of the time. Current management for the disease is primarily limited to physical and occupational therapy and certain surgical interventions.
We are conducting a trial of ACE-083 as a potential treatment for Charcot-Marie-Tooth (CMT) disease, the most common inherited neurological disorder for which we received Fast Track designation from the U.S. FDA. CMT, for which there is currently no FDA-approved treatment, affects approximately 1 in 2,500—or over 100,000—people in the U.S.
CMT is a group of disorders that impact certain peripheral nerves, resulting in muscle atrophy and weakness. Symptoms can begin in adolescence or early adulthood with initial signs of weakness in the lower leg muscles, affecting the patient’s ability to walk and causing frequent falls. As the disease progresses, muscle atrophy may occur in the feet and hands. CMT is currently managed with physical and occupational therapy, leg braces, and foot surgery.