ACE-2494, our newest product candidate within our neuromuscular therapeutic program, is intended to have a systemic effect on muscle mass and strength for diseases that cause muscle weakness throughout the body. ACE-2494 utilizes the “Myostatin +” approach believed to inhibit multiple negative regulators of muscle growth.
We have an ongoing Phase 1 trial with ACE-2494 in healthy volunteers which was supported by strong preclinical data that demonstrated systemic increases in skeletal muscle mass and strength. The randomized, double-blind, placebo-controlled, dose-ranging trial will enroll multiple single-ascending dose cohorts to evaluate safety, tolerability and pharmacodynamics. We expect to enroll up to 48 healthy volunteers for this Phase 1 trial and anticipate reporting preliminary results during the first half of 2019.
ACE-2494 is an investigational therapy that is not approved for any use in any country.
Possible Planned Neuromuscular Indications
Pending the outcome of Phase 1 results, we will conduct a Phase 2 trial with ACE-2494. There are four indications we could choose from when designing the Phase 2 trial, including:
Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that involve the nerve cells responsible for controlling voluntary muscle movement, including chewing, walking, and talking. ALS affects about 12,000 people in the U.S., and there is currently no cure or effective treatment to halt or reverse the progression of the disease.
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness, caused by an absence of dystrophin— a protein that helps keep muscle cells intact. DMD affects about 14,000 patients in the U.S., primarily boys, and symptoms include muscle weakness beginning with the hips, pelvic area, thighs and shoulders, and moving to the skeletal (voluntary) muscles in the arms, legs and trunk. By the early teens, the heart and respiratory muscles are often affected. Although there is currently no cure, based on recent medical advances, the life expectancy has increased from early teens to the early 30s.
Facioscapulohumeral muscular dystrophy (FSHD) is 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.
Spinal muscular atrophy (SMA) is a genetic disease which involves the loss of nerve cells called motor neurons in the spinal cord. This affects voluntary muscle movement and leads to muscle wasting which impacts activities such as crawling, walking, sitting up, and controlling head movement. In severe cases, the muscles used for breathing and swallowing are affected as well. There are many types of spinal muscular atrophy, but the most common form of SMA affects muscles closest to the center of the body, including the shoulders, hips, thighs and upper back. It is estimated that about 10,000 people in the U.S. have SMA, and treatment options for the progressive disease are limited.