Ariad Receives Fundamental Patent for Pharmaceutical Regulation of Cell Activity.

CAMBRIDGE, Mass.--(BW HealthWire)--Nov. 3, 1998--

Broad Applications in Gene Therapy and Genomics

ARIAD Pharmaceuticals, Inc. (Nasdaq: "ARIA") today announced the issuance of the first in a series of patents (U.S. Patent No. 5,830,462) covering pharmaceutical regulation of fundamental cellular processes through protein dimerization. Dimerization, or the act of bringing molecules together within the cell, is the key initiating step in many cellular processes, including gene activation, protein secretion, cell growth and cell death. The claims in the ARIAD patent cover methods for controlling such cellular events using small-molecule pharmaceuticals that dimerize intracellular proteins. The patent establishes a proprietary base for the commercial development of ARGENT(TM), ARIAD Regulated Gene Expression Technology.

The lead ARGENT product under development at ARIAD is orally active protein therapy. Conventional protein therapeutics require administration of the protein to the patient by frequent injections. This can be inconvenient and uncomfortable to the patient and can result in circulating protein levels that fluctuate well above and below the optimal dose, thereby limiting both the safety and efficacy of such therapies. ARGENT products are generating great interest in the biomedical research community, because they have the potential to produce precisely controlled levels of a specific therapeutic protein in response to a small-molecule dimerizer drug delivered as a pill. This approach could provide physicians with the ability to deliver therapeutic proteins in a manner consistent with conventional pharmaceutical dosing.

ARIAD, in collaboration with its partner Genovo, Inc. (Sharon Hills, PA), is currently testing ARGENT orally active protein therapy in animal models. Studies have been completed successfully using both human growth hormone (hGH) and erythropoietin (EPO). In these studies, mice and nonhuman primates received a single administration of a conventional gene therapy vector. The vector delivered the genes necessary to produce ARGENT regulatory components and the therapeutic gene for either hGH or EPO. The animals then received doses of a dimerizer drug. This drug activated expression of the therapeutic gene causing regulated, steady-state and dose-dependent production of the therapeutic protein. Further preclinical studies in nonhuman primates and manufacturing scale-up efforts are under way.

ARIAD and its collaborators are employing ARGENT in multiple additional areas of drug discovery. For example, by dimerizing the Fas "cell death" receptor, specific cell populations can be eliminated in vivo upon administration of a dimerizer drug. ARIAD is developing this type of ARGENT product to treat graft-versus-host disease in allogeneic bone marrow transplant patients by eliminating transplanted T cells that are attacking normal tissue. In other studies, researchers are using ARGENT products to grow rare and valuable cells, such as certain bone marrow cells, which are otherwise very difficult to obtain in large quantities. Genomics researchers are using ARGENT in animal and cellular studies to selectively activate or deactivate genes of interest. The ability to precisely regulate the expression of a gene can yield important information about its function in a given disease. ARIAD has provided ARGENT materials to over 150 laboratories around the world for use in a variety of additional research programs.

"The issuance of this fundamental patent on the use of ARGENT products is an important step in ARIAD's commercialization of this versatile and powerful technology," said Harvey J. Berger, M.D., ARIAD's chairman and chief executive officer. "Our development plans include clinical evaluation of ARGENT in the treatment of bone marrow transplant patients who have developed graft-versus-host disease and in the delivery of therapeutic proteins, such as EPO, in response to one of ARIAD's orally active dimerizer drugs."

"Currently, a strong need exists for a regulated gene expression technology suitable for human therapeutic use," said Michael Gilman, Ph.D., ARIAD's chief scientific officer. "This patent, combined with ARIAD's recent research and preclinical development progress, supports our belief that ARGENT products can become the leading choice for regulation of in vivo protein therapy, cell therapy and functional genomics research. In fact, ARGENT products could be the key to the successful clinical application of gene therapy generally."

ARGENT was conceived by Stuart Schreiber, Ph.D. of Harvard University and Gerald Crabtree, M.D. of Stanford University, both of the Howard Hughes Medical Institute, and their colleagues, who first published their findings in the November 1993 issue of Science. ARIAD Gene Therapeutics, Inc., a subsidiary of ARIAD, obtained an exclusive worldwide license to the technology in December 1993.

A copy of the ARIAD Patent (U.S. Patent No. 5,830,462) will be posted on the World Wide Web at www.patents.ibm.com.

ARIAD Pharmaceuticals 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 and functional genomics.

Some of the matters discussed in this news release are forward-looking statements that involve risks and uncertainties. For example, there can be no assurance that if a patent is issued, any such patent would be enforceable or provide meaningful protection. Other risks and uncertainties include, but are not limited to, risks and uncertainties regarding the success of the company's preclinical studies, the ability of the company to commence clinical trials and the success of such clinical trials, as well as economic, competitive, governmental and technological factors affecting ARIAD's operations, markets, products, services and prices, 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, 1997 filed with the Securities and Exchange Commission.