Repligen Corporation (NASDAQ:RGEN) today announced positive results from a Phase 1 study to evaluate the pharmacokinetic (PK) and safety profile of RG3039, a novel small molecule drug candidate for the potential treatment of spinal muscular atrophy (SMA). SMA is a inherited neurodegenerative disease in which symptoms of progressive damage to motor neurons including loss of muscle function typically appear very early in life and often progress to severe physical disability and early loss of life. The Phase 1 trial was a blinded, ascending, single dose study of RG3039 administered to 32 healthy volunteers. The study results demonstrate that RG3039 was well tolerated at all doses administered, with no serious adverse events reported. The data also showed evidence of a dose-related drug response resulting in 90% inhibition of the target enzyme. These outcomes may help to establish appropriate RG3039 dosing regimens for future studies, including potential efficacy studies in SMA patients. “The safety and PK outcomes from our Phase 1 study of RG3039 are encouraging, and we look forward to initiating the next steps for this drug candidate in alignment with guidance from the U.S. Food and Drug Administration,” said Walter C. Herlihy, President and Chief Executive Officer of Repligen. “The agency has previously granted Orphan Drug and Fast Track designations to RG3039, in recognition of the unmet medical need that exists for patients with SMA and the urgency to advance a treatment for this devastating disease.” Repligen licensed RG3039 in 2009 from Families of Spinal Muscular Atrophy (FSMA), a patient advocacy organization that funded and directed the preclinical development of RG3039 with an investment of more than $13 million. This was the first drug discovery program ever conducted specifically for SMA. Repligen's research efforts including this Phase 1 study have been partially supported by a grant from the Muscular Dystrophy Association (MDA).
RG3039 is the first clinical-stage drug candidate to target the core genetic deficit in SMA in order to treat the biochemical deficits caused by decreased levels of the survival motor neuron (SMN) protein. This key protein is necessary for normal neuromuscular function but is insufficiently produced in SMA patients. RG3039 is an orally bioavailable small molecule inhibitor of an RNA processing enzyme called DcpS. RG3039 has been shown to increase production of the SMN protein in cells derived from patients. In addition, RG3039 has been shown to improve motor neuron pathology, mobility and lifespan in animal models of SMA.Top-line results from this Phase 1 study of RG3039 are scheduled to be presented as part of a special neuroscience program at the 64 th Annual Meeting of the American Academy of Neurology (AAN). The AAN meeting is being held April 21-28, 2012 at the New Orleans Ernest N. Morial Convention Center. James P. Van Meerbeke, Research Assistant from the lab of Charlotte J. Sumner, M.D., Associate Professor of Neurology and Neuroscience, Johns Hopkins University School of Medicine, will present the abstract titled “ The Therapeutics Effects of RG3039 in Severe Spinal Muscular Atrophy – Mice and Normal Human Volunteers,” during “The Future of Neuroscience Conference: Neurologists and Neuroscientists Defining the Next Generation of CNS Therapies,” taking place on April 27. In addition to the Phase 1 clinical trial outcomes, the AAN presentation highlights the results of earlier mouse model studies conducted with RG3039 at Johns Hopkins University and in the lab of Dr. Chien-Ping Ko at University of Southern California. In these preclinical studies, which provided proof of principle for conducting human clinical studies, administration of RG3039 resulted in a significant improvement in survival, increased maximum body weight and improved motor behavior in severe SMA mice. The effects were associated with increased SMN2 transcript levels and improved neuromuscular junction morphology and physiology. At therapeutic levels of RG3039 in mice, the target enzyme DcpS was inhibited greater than 90%. This appears to parallel outcomes from the Phase 1 human study, which achieved greater than 90% inhibition of DcpS in peripheral blood cells for 48 hours with a single dose of RG3039 and in absence of any toxicity.
In addition to the presentation at AAN, Dr. David Jacoby, Medical Director at Repligen Corporation, will present the RG3039 Phase 1 study outcomes during the 2012 International SMA Research Group Meeting. This FSMA organized meeting is being held in Minneapolis from June 21-23, 2012. Dr. Jacoby’s presentation titled, “A Phase I Study in Healthy Volunteers to Assess the Safety, Pharmacokinetics and Pharmacodynamics of the DcpS inhibitor RG3039,” is scheduled for Friday, June 22, 2012 at 3:40 p.m.About Spinal Muscular Atrophy Spinal muscular atrophy is an autosomal recessive neuromuscular 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. It is the leading cause of infant mortality and the second most common inherited neuromuscular disease, with symptoms that typically emerge before the age of two. SMA is characterized by progressive muscle weakness leading to severe physical disability and often, loss of life due to respiratory insufficiency. The prevalence of SMA in the U.S. and EU is approximately 20,000 patients. Orphan Drug and Fast Track Designations Repligen has previously received U.S. Orphan Drug and Fast Track designations for RG3039 for the treatment of SMA, as well as Orphan Medicinal Product designation in the EU. Fast Track is a process designed to facilitate the development and expedite the review of drugs that have the potential to treat serious disease and fill an unmet medical need. The orphan programs provide incentives for the research, development and marketing of products intended to diagnose, prevent or treat rare conditions and/or serious or debilitating diseases with unmet medical needs. Orphan designation grants the sponsor exclusive marketing rights for seven years in the U.S. and ten years in the EU following regulatory approval of the designated product. In the U.S., rare diseases are defined as those affecting fewer than 200,000 Americans. In the U.S., rare diseases are defined as those affecting fewer than 200,000 Americans. In the EU, rare diseases are considered those that affect no more than five per ten thousand persons in the community.
RG3039 is a new chemical entity that is the subject of worldwide composition of matter patents which, if allowed, will remain in force until 2028 prior to any patent term extensions.About Families of Spinal Muscular Atrophy Families of SMA funds and directs the leading SMA research programs to develop a treatment and cure for the disease. The successful results and progress that the organization has delivered, from basic research to drug discovery to clinical trials, provide real hope for families and patients impacted by the disease. The charity has invested over $50 million in research and been involved in funding half of all the ongoing novel drug programs for SMA. Families of SMA is a nonprofit 501(c)3 organization, with 31 Chapters and 85,000 members and supporters throughout the United States, and is dedicated to creating a treatment and cure by: funding and advancing a comprehensive research program; supporting SMA families through networking, information and services; improving care for all SMA patients; educating healthcare professionals and the public about SMA; enlisting government support for SMA; embracing all touched by SMA in a caring community. For more information: www.curesma.org. About the Muscular Dystrophy Association The Muscular Dystrophy Association (MDA) is the leading nonprofit health agency dedicated to curing muscular dystrophy, ALS, SMA and related diseases by funding worldwide research. The Association also provides comprehensive healthcare and support services, advocacy and education. In addition to funding more than 300 research projects worldwide, MDA maintains a national network of some 200 hospital-affiliated clinics; orchestrates hundreds of support groups for families affected by neuromuscular diseases; facilitates extraordinary local summer camp opportunities for thousands of youngsters fighting progressive muscle diseases. Known globally for the MDA Labor Day Telethon, the Association is the first nonprofit organization to receive a Lifetime Achievement Award from the American Medical Association “for significant and lasting contributions to the health and welfare of humanity.”
About Repligen CorporationRepligen Corporation is a leading supplier of critical biologic products used to manufacture biologic drugs. Repligen also applies its expertise in biologic product development to SecreFlo™, a synthetic hormone being developed as a novel imaging agent for the diagnosis of a variety of pancreatic diseases. In addition, the Company has two central nervous system (CNS) rare disease programs in Phase 1 clinical trials. Repligen’s corporate headquarters are located at 41 Seyon Street, Building #1, Suite 100, Waltham, MA 02453. Additional information may be requested at www.repligen.com. This press release contains forward-looking statements, which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Investors are cautioned that statements in this press release which are not strictly historical statements, including, without limitation, express or implied statements regarding the potential utility of RG3039 for the treatment of SMA, the clinical success of RG3039 and its further clinical development, plans and objectives for future operations, plans and objectives for product development, plans and objectives for regulatory approval, product development, our market share and product sales and other statements identified by words like “believe,” “expect,” “may,” “will,” “should,” “seek,” or “could” and similar expressions, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, risks associated with: the success of our clinical trials, including our Phase 1 clinical trial of RG3039 of in healthy volunteers, our ability to develop and commercialize products and the market acceptance of our products; reduced demand for our products that adversely impacts our future revenues, cash flows, results of operations and financial condition; the ability to obtain, and the timing and receipt of, FDA approval for our NDA; our ability to obtain other required regulatory approvals; the success of current and future collaborative or supply relationships; our ability to compete with larger, better financed bioprocessing, pharmaceutical and biotechnology companies; new approaches to the treatment of our targeted diseases; our compliance with all Food and Drug Administration and EMEA regulations; our ability to obtain, maintain and protect intellectual property rights for our products; the risk of litigation regarding our intellectual property rights; our limited sales capabilities; our volatile stock price; and other risks detailed in Repligen’s report on Form 10-K on file with the Securities and Exchange Commission and the other reports that Repligen periodically files with the Securities and Exchange Commission. Actual results may differ materially from those Repligen contemplated by these forward-looking statements. These forward looking statements reflect management’s current views and Repligen does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date hereof except as required by law.