Quinazoline Program Makes Progress Toward Drug Treatment for Spinal Muscular Atrophy -- Families of SMA 2010 Program Update

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Late last year, Families of Spinal Muscular Atrophy (FSMA) announced that it had entered into a groundbreaking exclusive license agreement with Repligen Corporation for the development of a potential treatment for Spinal Muscular Atrophy (SMA). FSMA is dedicated to creating a treatment and cure for SMA by funding and advancing comprehensive research and drug discovery programs.

Late last year, Families of Spinal Muscular Atrophy (FSMA) announced that it had entered into a groundbreaking exclusive license agreement with Repligen Corporation for the development of a potential treatment for Spinal Muscular Atrophy (SMA). FSMA is dedicated to creating a treatment and cure for SMA by funding and advancing comprehensive research and drug discovery programs.

The FSMA funded Quinazoline Program has had several significant milestones - the first ever pre-IND (Investigational New Drug) meeting for SMA with the FDA took place in 2009, and FSMA then obtained Orphan Drug Designation for the drug. In the next step of the process toward finding a viable treatment for SMA, the well-established biopharmaceutical company Repligen Corporation, with extensive experience in clinical development in neurological indications, now takes on responsibility and funding for clinical development of a new SMA drug.

SMA, the leading genetic killer of children under the age of two, is typically marked by the degeneration of muscle movement including the muscles that control crawling, walking, swallowing and breathing. There are no approved therapies for the treatment of SMA to date, which affects one in every 6,000 babies. One in every 40 people carry the gene that causes SMA, indicating approximately 7.5 million carriers in the United States.

“Families of SMA has made remarkable progress in defining a series of highly potent compounds which may be clinical candidates for SMA,” stated Walter C. Herlihy, President and Chief Executive Officer of Repligen Corporation. “We look forward to working with FSMA and their collaborators in the development of what we hope will be an important new treatment for SMA.”

Importance of the Quinazoline Program
Through FSMA’s leadership, ten years of research has resulted in a drug candidate that is targeted to treat the underlying cause of SMA. The licensed Quinazoline compounds increase the amount of SMN protein made from the back-up gene in SMA called SMN2. In preclinical studies, the drug has been shown to efficiently cross the blood brain barrier - a critical feature for a neurological drug - and prolong survival significantly in two different mouse models of SMA.

Quinazoline Program Update - Repligen Corporation
The “clinical candidate” identified by FSMA is at a pre-clinical research phase in which detailed studies of safety, pharmacology, and toxicology are being conducted. In parallel, mouse models of SMA disease are being used to document efficacy of the drug and examine what dose and dose schedule might give the best treatment result. These two lines of research will culminate in designing and seeking approval to test the drug first in healthy volunteers and then in patients. Early phase clinical trials will be conducted in adult volunteers and then patients to establish the safety and pharmacology of the drug.

“While always difficult to predict progress milestones accurately, the preclinical work and early clinical safety and pharmacology studies in healthy humans will be the focus of the program for the next 1-2 years. If successful in establishing a safe dose which is also thought to be efficacious, future studies can examine the efficacy of the drug treatment in SMA patients”, according to James Rusche, PhD, Senior Vice President, Research and Development of Repligen Corporation.

Progress Made
FSMA’s first venture into drug discovery began in 2000 as a collaboration with Aurora Biosciences, since acquired by Vertex Pharmaceuticals. The initial goal of the collaboration was to develop screening tools to search for chemical compounds that could increase SMN levels from the SMN2 gene. Several compounds with the capability of doing this were discovered and one of these compound classes called Quinazolines were chemically modified at deCODE Chemistry with full funding by FSMA to optimize and generate drug-like properties. In late 2007 a clinical candidate was selected.

In August of 2009, FSMA received FDA Orphan Drug Designation for Quinazoline495, our clinical candidate in this program, for the treatment of SMA.

FSMA then conducted the first ever SMA pre-IND meeting with the FDA.

In October of 2009, Families of SMA licensed this series of compounds to Repligen Corporation for development as a potential treatment for Spinal Muscular Atrophy.

Under the guidance of drug discovery and development experts, FSMA has made investments of $13 million during the last decade to bring this groundbreaking program to the cusp of clinical development.

Importantly, the Quinazoline program also shows that SMA drug discovery is feasible! This has encouraged many others in the government and industry to invest in SMA research.

FSMA Funds Key Drug Discovery Programs
One of FSMA’s primary and critical goals is to help build the size of it’s SMA drug pipeline, which simply means increasing the number of viable SMA candidate therapies in pre-clinical or clinical drug development. To date FSMA has been involved in five such ventures, including the groundbreaking Quinazoline Program.

Traditionally it has been difficult to attract major pharmaceutical companies to conduct research for orphan diseases like SMA, which have small patient populations with small potential for profit. Therefore FSMA has taken the strategy of providing seed funding to encourage biotech and pharmaceutical partners to engage in SMA drug research. The objective is to reduce the risk for industrial partners by simultaneously providing funding, research tools, scientific expertise, and established clinical networks. This strategy effectively lowers the barriers for embarking in SMA drug discovery bringing us closer to discovering new therapies and ultimately, a cure for SMA.

About Families of Spinal Muscular Atrophy
FSMA is dedicated to creating a treatment and cure for SMA by: Funding and advancing a comprehensive research program; Supporting SMA families through networking, information and services; Improving care for all SMA patients; Educating health professionals and the public about SMA; Enlisting government support a; Embracing all touched by SMA in a caring community. http://www.curesma.org

About Repligen Corporation
Repligen Corporation is a biopharmaceutical company in Waltham, Massachusetts that focuses on the development of innovative therapeutic drugs for unmet medical needs especially in the field of neurodegenerative disease. Repligen has licensed the compounds developed by FSMA that hold promise as a treatment for SMA.

Contact Information
Families of SMA
925 Busse Road
Elk Grove Village, IL 60007
Phone (800) 886-1762
Fax (847) 367-7623
Email info(at)fsma(dot)org
http://www.curesma.org

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Laura Franzen

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