Shire plc,  the global specialty biopharmaceutical company, and Sangamo BioSciences, Inc., a leader in genome-editing technology, have entered into a collaboration and license agreement to develop therapeutics for haemophilia and other monogenic diseases based on Sangamo's zinc finger DNA-binding protein (ZFP) technology.

Shire will receive exclusive world-wide rights to ZFP Therapeutics designed to target four genes (for blood clotting Factors VII, VIII, IX and X) which will be used to investigate curative therapies for haemophilia A and B.  Shire also receives the right to designate three additional gene targets.  Sangamo is responsible for all activities through submission of Investigational New Drug (IND) Applications and European Clinical Trial Applications (CTA) for each product and Shire will reimburse Sangamo for its internal and external research programme-related costs. Shire is responsible for clinical development and commercialization of products arising from the alliance.  Shire will pay Sangamo $13 million upfront followed by research, regulatory, development and commercial milestone payments, and royalties on product sales.

"Sangamo's ground-breaking ZFP gene-editing technology will enable us to expand our therapeutic pipeline into therapies for other genetic disorders such as haemophilia," said Sylvie Gregoire, president of Shire's Human Genetic Therapies business. "While still early in the clinical development process, this DNA-binding protein technology is aligned with our focus of developing new treatments that can add value for physicians, patients and their families, and the healthcare community overall."

"We are delighted to be partnering the first of our monogenic disease programs with Shire, a company known for its development of innovative medicines for genetic diseases," said Edward Lanphier, Sangamo's president and chief executive officer. "This alliance is further validation of our ZFP platform as a transformative technology for the development of novel therapeutics, which have the potential to revolutionize the treatment of a wide range of genetic diseases."

Sangamo's ZFP Therapeutic approach utilizes its proprietary ZFP nuclease (ZFN) and ZFP transcription factor (ZFP TF) technology. ZFPs can be engineered to recognize any specific DNA sequence within a gene, and may be applicable to certain Shire therapeutic areas, including hematology and lysosomal storage disorders.

Haemophilia, a rare bleeding disorder, is an example of a monogenic disease. There are several types of haemophilia caused by mutations in genes that encode factors which help the blood clot and stop bleeding when blood vessels are injured.  The most prevalent form of the disease, haemophilia A, is caused by a defect in clotting Factor VIII while defects in clotting Factor IX lead to haemophilia B. The most severe forms of haemophilia affect males. According to the National Haemophilia Foundation, haemophilia A occurs in about one in every 5,000 male births in the US, and haemophilia B in about 1 in every 25,000. The standard treatment for individuals with haemophilia is replacement of the defective clotting factor with regular infusion of concentrates or recombinant factors, which are expensive, carry the risk of transmission of blood-borne diseases and sometimes stimulate the body to produce antibodies against the factors that inhibit the benefits of treatment.  In these situations, other clotting factors such as Factor VII and X may be used to treat patients.

Using a mouse model of haemophilia B, Sangamo scientists and its collaborators have already established proof of concept that ZFN-mediated genome editing can be accomplished in vivo and is curative in the animal.  They have demonstrated the production of stable levels of corrected human clotting Factor IX that are clinically meaningful, restoring clotting times to normal, after a single, systemic administration of ZFNs specific for the Factor IX gene.  The data were published in the scientific journal Nature in June 2011.