Alexion Pharmaceuticals presents data on first-of-a-kind injectable retroviral particles for human gene therapy; results to be published in Human Gene Therapy.

STEAMBOAT SPRINGS, Colo.--(BUSINESS WIRE)--March 30, 1995-- Alexion Pharmaceuticals presented research today on the successful preclinical development of immune-protected, injectable murine retroviral vector particles at the Keystone Symposia on Molecular and Cellular Biology. Alexion senior scientist, Russell Rother, Ph.D., presented the data during the Gene Therapy and Molecular Medicine Session. In addition, a report on Alexion's work in this area will be published in the April issue of the journal Human Gene Therapy.

Retroviral-mediated gene transfer is employed in the majority of the more than 100 approved gene therapy trials. Despite the recent advances in the use of retroviral vectors for gene transfer, nearly all human gene therapy trials involve ex vivo applications-- transduction of autologous cells outside the body and subsequent transplantation of these engineered cells into patients.

"Alexion's retroviral vector technology stems from its broader scientific focus on understanding and regulating the human immune system," said Stephen Squinto, Ph.D., Vice President of Research, Molecular Sciences for Alexion. "Alexion's technology substantially improves the ability to directly administer retroviral gene therapy vectors for in vivo human gene therapy by employing immunoprotective properties that, for the first time, allow the retroviral gene therapy vectors to survive in human blood."

Alexion discovered that naturally occurring anti-carbohydrate antibodies in humans work in conjunction with certain components of the complement system to clear and destroy murine retroviruses. The complement system is an important part of the human immune response made up of approximately 20 distinct proteins that normally help clear infectious agents and immune complexes from the body.

Two Methods to Protect Murine Retroviral Particles

When naturally occurring human antibodies bind to a carbohydrate molecule, called Galalpha1-3GalB1-4GlcNAc-R (alphaGal), that is present in abundance on the surface of retroviral particles, complement is activated to lyse the particles. Alexion has developed novel murine packaging cell lines genetically modified to down regulate the expression of the alphaGal epitope on the surface of the retroviral particle. As a result, retroviral particles produced from these cell lines are deficient in alphaGal and are therefore not eliminated by antibodies and complement.

Secondly, Alexion's research showed that human serum including the complement proteins inactivated murine retroviral particles. However, following incubation of Alexion's proprietary complement inhibitor compounds with retroviral particles in human sera, the particles maintained the ability to transduce target cells. These data demonstrate that the use of soluble complement inhibitors may enable retroviral particles to resist complement-mediated inactivation in vivo in humans.

"Alexion's discovery of the molecular mechanisms responsible for the clearance and destruction of murine retroviruses by the human immune system represents a potential breakthrough in the longstanding effort to develop a viable in vivo retroviral gene transfer technology," said Leonard Bell, M.D., President and Chief Executive Officer of Alexion. "Alexion will pursue this technology and also take a collaborative approach with gene therapy companies who are interested in fully utilizing these discoveries."

Alexion Pharmaceuticals, founded in 1992, is a private, research- based biopharmaceutical company headquartered in New Haven, Conn., focused on developing novel immunoregulatory biotherapeutics targeting severe autoimmune and cardiovascular disorders and organ transplantation.

CONTACT: Alexion Pharmaceuticals

Stephen Squinto, Ph.D.

David Keiser

203/776-1790

or

NCI Public Relations

Ken Wallace

609/452-0101