ARIAD Pharmaceuticals, Genovo, and the University of Pennsylvania Announce Publication of Paper in Science On Regulated Gene Therapy System.

CAMBRIDGE, Mass./SHARON HILL, Pa.--(BUSINESS WIRE)--Jan. 5, 1999--ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) and Genovo, Inc. reported, with their colleagues from the Institute for Human Gene Therapy (IHGT) at the University of Pennsylvania, the publication of a paper in the January 1st issue of Science entitled "Regulated Delivery of Therapeutic Proteins After In Vivo Somatic Cell Gene Transfer". In the study discussed in the publication, scientists demonstrated the ability to introduce therapeutic genes into the body and then, further, to precisely control the activity of those genes with a drug that could be given as a simple pill. The novel gene therapy system, developed by researchers at the University of Pennsylvania and at ARIAD, represents a new form of drug delivery, one that may open the door to many therapies not previously possible.

The new system couples advances at the University of Pennsylvania led by James M. Wilson, M.D., Ph.D., director of the IHGT, allowing the long-term introduction of genes into the body with a patented technology from ARIAD (known as ARGENT(TM)) to regulate gene activity. The University of Pennsylvania has licensed its technology relating to these advances to Genovo, a company founded by Dr. Wilson. In 1997, Genovo and ARIAD entered into a joint venture agreement to develop products based on regulated, muscle-directed gene therapy as a means of delivering secreted therapeutic proteins.

The culmination of several years of concerted effort has resulted in researchers from the University of Pennsylvania succeeding in optimizing a gene therapy viral vector to achieve long-term protein production in vivo without generating an immune system reaction. The vector is an engineered version of a virus known as adeno-associated virus, or AAV, which is a very small innocuous virus. For this project, the collaborating scientists stripped two AAVs of their viral genes and reloaded them respectively with a gene for erythropoietin, or EPO, and the genes for a transcription factor complex able to regulate EPO. EPO is a recombinant protein that stimulates red blood cell production and is used to treat anemias.

ARIAD investigators had previously shown that this particular transcription factor could be switched on by a small-molecule drug called rapamycin, which can be taken orally. The amount of rapamycin administered controlled the level of EPO produced by cells exposed to the AAV vectors. The reported results demonstrated that rapamycin given to both mice and rhesus monkeys stimulated a proportionate rise in production of EPO, resulting in higher numbers of red blood cells in the bloodstream. Discontinuing administration of rapamycin shut down production of EPO. The effects of the treatment were tracked for six months in mice and three months in monkeys.

"These results demonstrate the potential of Genovo's gene delivery technology in conjunction with ARIAD's gene regulation system to expand the application of gene therapy products," stated Dr. Eric Aguiar, chief executive officer of Genovo, Inc. "Further development of these technologies may lead to more cost-effective treatments and an expanded utility of certain therapeutic proteins."

"The ability to achieve dosage control of a drug in the context of gene therapy is going to be critical to making a number of new treatments possible," says Dr. Michael Gilman, chief scientific officer at ARIAD and a co-author of the Science study. "Many of the proteins we would like to produce in the body using gene therapy are quite potent and can have side effects, so being able to carefully adjust their levels within a therapeutic window is going to be key."

Genovo, Inc. focuses on the design, manufacture and early stage clinical development of gene-based therapeutic products for the treatment of human disease. Genovo's technology includes intellectual property covering gene therapy vectors, manufacturing and applications. Genovo has a partnership with Biogen, Inc.

ARIAD Pharmaceuticals (www.ariad.com) is engaged in the discovery and development of orally administered therapeutics based on signal transduction technology. ARIAD is developing small-molecule drugs that block intracellular signaling pathways that play a critical role in major diseases, including osteoporosis and immune-related disorders. ARIAD is also developing ARGENT(TM), a proprietary regulated gene expression technology for gene and cell therapy.

Some of the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, which include, but are not limited to, risks and uncertainties regarding ARIAD's and Genovo's preclinical studies, the ability of ARIAD, Genovo, and its potential corporate partners, if any, to conduct clinical trials of the ARGENT(TM) system and the success of such trials, as well as risks and uncertainties relating to economic conditions, markets, products, services, and prices, and other factors under the heading "Cautionary Statement Regarding Forward-Looking Statements" in ARIAD's Annual Report on Form 10K for fiscal year ended December 31, 1997, filed with the Securities and Exchange Commission.