Alexion receives second SBIR for its in vivo gene therapy program.

NEW HAVEN, Conn.--(BUSINESS WIRE)--Aug. 14, 1995--Alexion Pharmaceuticals Inc. announced today that it has received its second Phase I Small Business Innovation Research Grant for its in vivo gene therapy program. The amount of the grant is $100,000. Alexion senior scientist Russell Rother, Ph.D., is the principle investigator for the grant to further develop Alexion's proprietary immune-protected retroviral vector particles, and producer cells, which are designed to be directly administered to patients for in vivo human gene therapy. A report on Alexion's work in this area was 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 are limited to cumbersome ex vivo applications - transduction of autologous cells outside the body and subsequent administration of these engineered cells back to patients.

"Alexion's in vivo gene transfer 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 technologies employ proprietary immunoprotective properties that, for the first time, allow retroviral gene transfer particles and producer cells to survive in human blood. These proprietary technologies substantially improve the ability to directly administer retroviral gene therapy particles as a direct gene therapeutic and to implant producer cells as a source for the prolonged delivery of a gene therapeutic for in vivo human gene therapy."

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

Three Methods to Protect Retroviral Particles and Producer Cells

When naturally occurring human antibodies bind to a carbohydrate molecule, called Gal(alpha)1-3Gal(beta)1-4GlcNAc-R ((alpha)Gal), that is present in abundance on the surface of retroviral particles and producer cells, complement is activated to lyse the particles and cells, respectively. Alexion has developed novel packaging cell lines that have been genetically modified to down regulate the expression of the (alpha)Gal epitope on the surface of the producer cells and the resultant retroviral particles. As a result, these producer cells and the retroviral particles produced from these cell lines are deficient in (alpha)Gal and are therefore not eliminated by antibodies and complement in in vitro studies.

Secondly, Alexion scientists have developed novel packaging cell lines and retroviral particles that have been genetically modified to express high levels of inhibtors of human complement proteins on the surface of the cells or particles, respectively. In in vitro studies, these producer cells and retroviral particles produced from these cell lines are resistant to human complement and are therefore not eliminated by antibodies and complement.

Thirdly, Alexion's scientists have demonstrated that the firm's proprietary recombinant soluble complement inhibitors enable retroviral producer cells and particles to maintain the ability to transduce target cells in in vitro studies. Each of these three proprietary technologies may enable retroviral gene transfer particles and producer cells to function and resist elimination in vivo in humans and therefore to enable a broad array of in vivo gene therapies.

"Alexion's discoveries related to the molecular mechanisms responsible for the clearance and destruction of retroviral vector particles and producer cells by the immune system represent a potential breakthrough in the long-standing effort to develop a viable, safe in vivo gene transfer technology," said Leonard Bell, M.D., president and chief executive officer of Alexion. "In addition to broad applications in gene delivery, we anticipate the largest early applications of our technology platform to be in the treatment of certain malignances including carcinoma of the lung, liver, colon, and ovary."

Alexion Pharmaceuticals Inc., founded in 1992, is a private, research-based biopharmaceuticals company headquarted 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., 203/776-1790

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NCI Public Relations

Ken Wallace, 609/452-0101