This article submitted on 3/5/98

NEWTOWN, Pa., March 3 /PRNewswire/ -- Kimeragen, Inc. today announced that researchers at the University of Minnesota (Minneapolis) have utilized the Company's novel patented gene alteration, repair and correction technology, termed chimeraplasty, to introduce a mutation in the Hemophilia B gene in rodents. The results of this study were reported in the March issue of “Nature Medicine.” This study demonstrates for the first time in medical history that alteration of genes within live animals can be efficiently accomplished by intravenous injection of a synthetic drug that targets and changes a pre-selected section of DNA. According to the Minneapolis researchers, the DNA repair technique, chimeraplasty, should be applicable to many other inherited or acquired diseases.

"In this study, we have targeted the Factor IX gene in animals and induced an alteration of that gene in the liver, the site of clotting factor formation, and produced animals with a mutated clotting factor as predicted,"remarked Clifford J. Steer, M.D., Professor of Medicine and Cell Biology at the University of Minnesota Medical Center and lead investigator of the study. "Our research team, through a series of experiments, has demonstrated that this new class of molecules, chimeraplasts, can be designed to target specific sites within genes and efficiently alter an animal's DNA."

"This is the breakthrough in gene therapy that I have been waiting for," commented R. Michael Blaese, M.D., Chief Scientific Officer and President of the Company's Molecular Pharmaceutical Division, and transitioning from Chief, Clinical Gene Therapy Branch, National Human Genome Research Institute at the NIH. "The data being published in Nature Medicine demonstrate that chimeraplasty can modify DNA specifically and give insight to the design of future clinical trials in a large number of diseases. Dr. Steer and colleagues have demonstrated that alteration of the gene, using chimeraplasty, is not only highly specific and efficient but also dose-dependent. These characteristics have been the hallmark of effective drugs for decades and allow for applications tailored to the needs of a wide spectrum of patients. Step-by-step, chimeraplasty has now progressed to the stage where we can produce viable drug products that we anticipate will be effective intravenously in humans."

Hemophilia B, a disease well described in the clinical literature, is marked by low to nearly non-existent levels of the blood protein Factor IX, critical to blood clotting. The disease is most frequently diagnosed when patients present signs such as abnormal bleeding and laboratory findings that demonstrate abnormally slow blood clotting. This disease and its relative Hemophilia A are the classic hemophilias that are characterized by small gene imperfections, called mutations, on the X-chromosome. Males contain a single X-chromosome and therefore, if the gene is defective they inherit hemophilia. Females who have two X-chromosomes, both of which need to be defective to manifest the disease, rarely develop hemophilia. The common treatment for hemophiliacs is the infusion of concentrated clotting factor, administered either prior to surgery or at the time of injury and severe bleeding.

"Chimeraplasty has consistently demonstrated, in multiple laboratories and disease states, that it is a powerful new therapeutic approach," said Gerald L. Messerschmidt, M.D., president and CEO of Kimeragen. "It is our intention to correct Hemophilia A and B in animals and then work with the FDA on human trials beginning as early as 1999. Our highest priority is to demonstrate safety and efficacy in animal models. It is our hope that we are able to provide chimeraplast therapies that correct rather than just treat many diseases based in human genes. The next real hurdle is the application in humans."

Also, in today's Nature Medicine, Dr. Michael Strauss, distinguished molecular geneticist based at the Max Delbruck Center for Molecular Medicine, Berlin, has written an editorial regarding the work of Dr. Steer and colleagues. He comments, "The efficacy of targeted gene mutation achieved in this study is sufficient to correct a large number of genetic diseases -- if it turns out that the technique works reproducibly with a broad spectrum of target genes."

Kimeragen's enabling technology platform, known as chimeraplasty, allows targeted repair or replacement of DNA without the use of viral or other conventional gene delivery vectors. In this site-specific alteration technique, a desirable sequence of DNA is combined with RNA, forming what is known as a chimeraplast. These molecules can be administered intravenously and bind selectively to the portion of the target DNA to be modified. Once bound, the chimeraplast activates a naturally occurring gene-correcting mechanism, which modifies the DNA at the target site precisely. Chimeraplasty is referred to as "precise genetic surgery," because DNA is repaired without affecting non-targeted portions of the gene(s).