ARIAD Demonstrates Long-Term Production and Precise Control of Human Growth Hormone With ARGENT Gene Therapy.

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Aug. 3, 1999--

New Publication in the Proceedings of the National Academy of

Sciences U.S.A.

ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) today announced new findings on sustained delivery of therapeutic proteins with its proprietary, regulated gene therapy technology.

In a paper published in the latest issue of the Proceedings of the National Academy of Sciences U.S.A. (96:8657-62, 1999), ARIAD scientists, working with collaborators from the Institute for Human Gene Therapy at the University of Pennsylvania, demonstrated precise control of the level and duration of production of human growth hormone (hGH) in experimental animals for approximately one year.

ARIAD is developing ARGENT(TM) as a broad delivery platform for secreted therapeutic proteins. Using ARGENT gene therapy, frequent injections of recombinant proteins can be replaced with one-time or infrequent administrations of a viral vector containing a regulated gene for the therapeutic protein. Production of protein is activated by oral administration of one of ARIAD's small-molecule drugs, known as Dimerizer Drugs(TM). Rapamycin and specially designed rapamycin analogs are used as Dimerizer Drugs in ARGENT gene therapy. As well as decreasing patient discomfort and non-compliance, ARGENT gene therapy is designed to allow the levels of secreted therapeutic proteins to be maintained consistently within an optimal therapeutic range. The University of Pennsylvania has licensed its technology relating to these advances to Genovo, a company founded by James M. Wilson, M.D., Ph.D., Director of the Institute for Human Gene Therapy at UPenn. 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.

In the latest work by Rivera, et al, mice were injected intramuscularly with adeno-associated viral (AAV) vectors containing a regulated hGH gene. No hGH was produced until the Dimerizer Drug (rapamycin) was administered, which induced secretion of hGH into the blood at therapeutic levels. The amount of hGH produced could be controlled within the target therapeutic range by varying the rapamycin dose, and multiple doses could be used to maintain constant levels of hGH. When rapamycin treatment was stopped, levels of hGH dropped to undetectable levels. Regulation was sustained for approximately one year, illustrating the long-term stability of the system. Overall, the study suggests that the rapamycin-based ARGENT system, delivered intramuscularly by AAV, should permit safe and effective delivery of therapeutic proteins by gene therapy.

This work builds on ongoing studies by ARIAD, Genovo and University of Pennsylvania investigators reported earlier this year in Science, in which regulated production of erythropoietin (EPO) was described. The present studies extend this work by demonstrating that ARGENT gene therapy can be used to deliver a second clinically important protein and that the system is stable for prolonged periods in vivo. Delivery of hGH is, in many respects, more challenging than EPO, since hGH has a very short serum half-life (a few minutes) and far higher levels are needed to achieve therapeutic benefit.

Commenting on the latest results, Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD said, "This study highlights the pace of progress in development of regulated gene therapy as a delivery platform for secreted therapeutic proteins." Dr. Berger added, "The recent recommendation of a U.S. Food and Drug Administration Advisory Panel in favor of the approval of rapamycin as a transplant drug should facilitate our development program for rapamycin-based ARGENT gene therapy."

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.

ARIAD Pharmaceuticals (www.ariad.com) is a leader in the discovery and development of orally administered therapeutics based on signal transduction technology. ARIAD is developing diverse products in multiple businesses, including signal transduction inhibitors, gene and cell therapy (based on ARGENT(TM)) and functional genomics. ARIAD recently announced the successful completion of a Phase 1 human clinical trial on its small-molecule drug (AP1903) to treat graft-versus-host-disease (GvHD) using ARGENT(TM) in patients undergoing allogeneic bone marrow transplants.

Some of the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, including, but not limited to, risks and uncertainties regarding the success of the Company's operations, as well as risks and uncertainties relating to economic conditions, markets, products, competition, intellectual property, services and prices, key employees, future capital needs, dependence on our collaborators and other factors discussed under the heading "Cautionary Statement Regarding Forward-Looking Statements" in ARIAD's Annual Report on Form 10-K for the fiscal year ended December 31, 1998 filed with the Securities Exchange Commission.