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RG3039: An Innovative Approach to Treating Spinal Muscular Atrophy

Repligen is developing RG3039, a DcpS inhibitor for treatment of patients with spinal muscular atrophy (SMA). RG3039 has the potential to be the first in its class for the treatment of SMA. SMA is an inherited neurodegenerative disease in which a defect in the SMN1 ("survival motor neuron") gene results in low levels of the protein SMN and leads to progressive damage to motor neurons and loss of muscle function.

Clinical Development Program

Patients lacking a functional SMN1 gene survive only because humans carry a second gene, known as SMN2, which produces an identical protein, but at much lower levels. Genetic analysis of SMA patients has shown a striking correlation between disease severity and the number of copies of the SMN2 gene carried by the patient. Patients with two copies of the SMN2 gene develop severe disease while patients with four copies develop few symptoms before adulthood. The average life expectancy of a patient carrying twos copies of the SMN2 gene is approximately two years, while the average life expectancy of patients carrying four copies of the gene is approximately fifty years. Doubling the gene copy number dramatically alters disease course, suggesting that a therapy that increases the level of SMN protein in motor neurons may provide a clinical benefit to patients fighting this debilitating disease. Repligen's lead compound, RG3039, increased the production of SMN in preclinical studies of cells derived from patients.

In May, Repligen received approval from the Food and Drug Administration to initiate a Phase 1 clinical trial of RG3039. This is a double-blind study to evaluate the pharmacokinetic and safety profile of escalating doses RG3039 in up to 40 healthy volunteers. This will be the first clinical trial of a novel drug specifically designed to treat SMA and the first treatment approach which seeks to increase levels of the protein SMN. This program was licensed in 2009 from Families of Spinal Muscular Atrophy. Families of SMA fully funded and directed the preclinical development work with an investment of more than $13 million. It was the very first drug development program done for SMA. Repligen's ongoing research efforts have been partially funded with grants from the Muscular Dystrophy Association.

About Spinal Muscular Atrophy:

Spinal Muscular Atrophy is the second most common inherited neuromuscular disease. The disease is characterized by loss of motor neurons that result in the loss of muscle function, and, in many patients, early death. Symptoms of SMA typically emerge before the age of two and often progress to severe physical disability or loss of life. SMA is diagnosed in approximately one in every 6,000 births in the United States and Europe, where the estimated prevalence is approximately 20,000 patients. There is currently no treatment or cure for SMA.