Amsterdam Molecular Therapeutics (AMT), a leader in human gene therapy, announced that it has entered into an agreement with Institut Pasteur, Paris, France, and a group of French research institutes (together the "Consortium") to support clinical development of a novel gene therapy to treat Sanfilippo B. This rare genetic disease affecting new-born children leads to progressive neuronal degeneration and death. There is no approved therapy currently available.

On behalf of the Consortium, Institut Pasteur will lead the development programme and will also sponsor the initial phase I/II clinical study of a gene therapy to replace an enzyme (alpha-N-acetylglucosaminidase) that is missing in brain cells of Sanfilippo B patients. This enzyme is specifically required for the degradation of heparan sulfate glycosaminoglycans (GAGs), essential carbohydrate molecules used to build tissue. The accumulation of incompletely degraded GAG molecules triggers a cascade of pathological events leading to neuronal dysfunction and death.

AMT will manufacture and supply the Adeno-Associated Viral 5 (AAV5) gene therapy product to the Consortium. Thanks to donations collected during the French Telethon, the French Muscular Dystrophy Association (AFM), a Consortium member, will fully fund the development program through to completion of the Phase I/II clinical study, including all AMT manufacturing costs. The overall manufacturing contract entails payments to AMT of EUR1.8 million. If the Consortium successfully demonstrates proof of concept in the phase I/II study, AMT will have an option to acquire full commercial rights for the programme. The phase I/II clinical study is scheduled to begin before 2013.

“This partnership leverage's AMT's proven expertise in cGMP manufacturing of gene therapy products and our experience in progressing these products through clinical development and the regulatory processes needed for successful commercialization,” said Jorn Aldag, CEO of AMT. “In addition, we will have an option to acquire full commercial rights for the program on completion of the phase I/II study, which supports our strategy to build a pipeline of orphan and ultra-orphan indications.”

Muriel Eliaszewicz, medical director of Institut Pasteur, said: “AMT is one of the only companies in the world that has a proven ability in manufacturing cGMP quality gene therapy products, not only in batches sufficient for clinical development but also in support of a potential regulatory approval. We are delighted that we now have the ability to commence the difficult process of developing a cure for patients with this very challenging disease.”

AMT has a cGMP-licensed, 375 m2 manufacturing facility to produce its AAV vectors for gene therapy products. This highly specialized facility is fully validated for commercial production and has a capacity capable of producing enough material to supply its European and North American target markets with AMT's lead product Glybera, currently under review at the European Medicines Agency (EMA) for treatment of Lipoprotein Lipase Deficiency (LPLD) and for the next phases of clinical development of all other programs currently in the pipeline.

In December 2010, Consortium researchers published preclinical data on the Sanfilippo B gene therapy in Molecular Therapy, the official publication of the American Society of Gene and Cell Therapy. This data demonstrated safety and efficient spreading of the AAV5 gene vector particles throughout the brain in models of the disease. The gene vectors also exhibited long-term viability within the cells and an improvement of histological and biochemical markers.

Sanfilippo B is a rare autosomal recessive lysosomal storage disease, which manifests in young children. Initial symptoms include a slowing of development and/or behavioural problems, followed by progressive intellectual decline resulting in severe dementia and progressive motor disease. In the final phase of the illness, children become increasingly immobile and unresponsive, often require wheelchairs, and develop swallowing difficulties and seizures. The life-span of an affected child does not usually extend beyond late teens to early twenties. Currently there is no approved therapy for this disease. The estimated number of new cases of SanFilippo B syndrome in the European Union is 14 per year.

AMT is a world leader in the development of human gene based therapies. The company's lead product Glybera, a gene therapy for the treatment of Lipoprotein Lipase Deficiency (LPLD), is currently under review by the European Medicines Agency (EMA). If approved, Glybera will be the first gene therapy product to be marketed in Europe. AMT also has a product pipeline of several gene therapy products in development for haemophilia B, Duchenne muscular dystrophy, acute intermittent porphyria, and Parkinson's disease. Using Adeno-Associated Viral (AAV) derived vectors as the delivery vehicle of choice for therapeutic genes, the company has been able to design and validate probably the world's first stable and scalable AAV manufacturing platform. This proprietary platform can be applied to a large number of rare (orphan) diseases caused by one faulty gene and allows AMT to pursue its strategy of focusing on this sector of the industry. AMT was founded in 1998 and is based in Amsterdam.

Louis Pasteur created the Institut Pasteur in 1887 as a private non-profit foundation that rapidly became world-renowned for its biomedical research. The main aim of the Institut Pasteur is understanding and preventing diseases throughout the world through excellent scientific and public health research, teaching and other activities. Together with its major contribution to a deeper understanding of fundamental aspects of life, the Institut Pasteur continues to devote a large part of its efforts to infectious diseases, inherited disorders, neurodegenerative diseases and certain cancers. Close to 2,600 people work on its main campus in Paris, this is at the heart of an international network of 32 research institutes on 5 continents. Over the years, 10 Institut Pasteur researchers have received the Nobel Prize.

AFM, a Consortium member, has become a major player in biomedical research on rare diseases in France and around the world. Thanks to donations from France's annual Telethon, the AFM is currently funding 36 clinical trials on 30 different genetic diseases: neuromuscular or neurological diseases, and diseases of the blood, eyes, skin and immune system.