Amsterdam Molecular Therapeutics, a leader in the field of human gene therapy, has signed an agreement with Digna Biotech/CIMA for the development of AAV-mediated insulin-like growth factor I (IGF-I) to treat late stage liver cirrhosis.

Earlier Digna Biotech had given exclusive license to Amsterdam Molecular Therapeutics (AMT) to commercialise all gene therapy products resulting from the R&D activities performed at the Center for the Study of Applied Medicine (CIMA) at the University of Navarra, Spain. Employing more than 400 researchers, CIMA is one of the leading gene therapy research centres in Europe. The IGF-1 program is the first initiated under that agreement.

Liver cirrhosis is the seventh-leading cause of death in the world and represents a late stage of progressive liver fibrosis. Today, no available treatment can stop or reverse the disease. The only option may be liver transplantation, which still carries a high-risk and, due to the lack of sufficient donors, is not available to many of these patients. More than 27,000 patients die of cirrhosis and chronic liver disease each year in the US alone.

The group of Professor Prieto at CIMA has established in relevant animal models an extensive Proof of Concept demonstrating that expression of low levels of IGF-I in fibrotic and cirrhotic liver is associated with a favourable outcome of the disease and that gene-therapy-mediated IGF-I expression has promising effects on the progression of the disease as well as its systemic complications. Prieto and his collaborators have demonstrated that even low doses of AAV engineered to carry IGF-1 were sufficient to interfere with, or even reverse fibrosis and achieve a long term effect. AAV vectors constitute the gene therapy platform of choice of Amsterdam Molecular Therapeutics.

A pilot clinical trial conducted by investigators in Pamplona, Spain and Groningen, The Netherlands in a small number of cirrhotic patients supports the importance of IGF-1 in treating cirrhosis - both an increased serum albumin and improved energy metabolism were achieved as a result of (subcutaneous) IGF-I protein administration. Because of the short half-life of IGF-1, a treatment based on the subcutaneous administration of recombinant IGF-I would require almost constant infusion and is not considered practical. The gene-therapy-mediated induction of IGF-I expression bypasses this disadvantage and shows long-term effect, as the animal studies at CIMA have shown. Clinical studies will need to confirm the long-term safety and efficacy in men.

Ronald Lorijn, CEO, AMT, said, "We are very pleased with our agreement with CIMA, which gives us access to programs that are already well-advanced and that have tremendous potential. Our technology platform seems ideally suited to develop IGF-I for the treatment of liver cirrhosis, a very serious disorder, which not only causes great human suffering, but also comes at a very high cost for society. AMT is fully dedicated and equipped to add this new program to its product pipeline and plans to start the necessary pre-clinical studies including a full toxicology program next year. We are confident to continue to leverage our close relationship with Digna and CIMA to fill our pipeline with promising products that address unmet medical needs."

The clinical development of AMT's lead product AMT-011 for the treatment of Lipoprotein Lipase Deficiency is proceeding according to plan. All patients have been recruited in the Canadian study. A total of 6 patients have been injected with AMT-011, completing the first 2 dose cohorts. The remaining 8 patients will be injected before the end of February, allowing the Company to file for registration with the EMEA, FDA and Health Canada before the end of the first half of 2008.

AMT has a unique gene therapy platform that to date appears to circumvent many if not all of the obstacles that have prevented gene therapy from becoming a mainstay of clinical medicine. Using adeno-associated viral (AAV) vectors as the delivery vehicle of choice for therapeutic genes, the company has been able to design and validate what is probably the first stable and scalable AAV production platform. As such, AMT's proprietary platform holds tremendous promise for thousands of rare (orphan) diseases that are caused by one faulty gene. AMT currently has a product pipeline with six products at different stages of development.