ARIAD Announces Publication of Research Article in Science On Novel Gene Regulation Technology.

Business Editors/Medical &Science Reporters

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 3, 2000

Rapid delivery of insulin with regulated gene therapy achieves

correction of experimental diabetes

ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) today reported, in a research article published in the February 4, 2000 issue of Science, the development of a novel gene regulation technology that allows rapid, pulsatile delivery of therapeutic proteins, such as insulin, using gene therapy regulated by an orally administered drug. This technology is particularly applicable to proteins which need to be delivered in short bursts, such as those used in the management and control of pain, disorders of clotting, neuroendocrine diseases, angiogenesis, and obesity, as well as diabetes. The paper by Rivera et al is entitled &uot;Regulation of Protein Secretion through Controlled Aggregation in the Endoplasmic Reticulum&uot; and is co-authored by collaborators from the Memorial Sloan-Kettering Cancer Center (Professor J. Rothman) and the University of Geneva, Switzerland (Professor L. Orci). In Science's Compass section, there is an accompanying &uot;Perspectives: Drug Delivery&uot; commenting on the research article.

ARIAD's new technology, called &uot;RAPID(TM)&uot; (Regulated Accumulation of Proteins for Immediate Delivery), is based on a proprietary method of storing pre-made therapeutic proteins inside cells as &uot;aggregates&uot; or large clusters. The stored proteins are stable and inactive inside the cell, but they can be released by administering a drug that specifically breaks apart the protein clusters. Because the proteins are pre-made in the cell, they are released almost immediately in fully active form in response to administration of ARIAD's small-molecule drug. The level of protein secretion is directly dependent on the dose of the drug; the larger the dose, the greater the secretion. Without the drug, the protein is secreted at a pre-established basal level, which in some applications is essentially zero.

The Science paper demonstrates the utility of ARIAD's RAPID technology. Human insulin was engineered to accumulate in specific cells in diabetic mice. These mice cannot make their own insulin and consequently have elevated blood sugar levels. Within fifteen minutes of administering ARIAD's drug, insulin appeared in the blood stream and rapidly rose to peak levels within less than two hours, leading to a correction of blood sugar. The level of insulin then subsided over the next two hours and returned towards basal levels.

This experimental study demonstrates that it may be possible to replace repeated daily injections of recombinant insulin with a one-time or infrequent delivery of a vector containing a modified insulin gene, followed by sublingual or oral administration of an ARIAD small-molecule drug at mealtimes and as needed in response to circulating blood sugar levels.

ARIAD's RAPID technology described in Science complements its other proprietary technology for controlling gene expression, ARGENT(TM) (ARIAD Regulated Gene Expression Technology). With ARGENT, circulating levels of protein, such as erythropoietin and human growth hormone, peak after about 24 hours and then are sustained within a therapeutic window for a prolonged period of time. ARIAD scientists have previously demonstrated long-term production of erythropoietin and increased numbers of red blood cells (needed to treat anemia) for over 450 days in rhesus monkeys using ARGENT and adeno-associated viral (AAV) vectors. RAPID products also can be delivered by AAV vectors, which contain no viral genes and are non-pathogenic.

&uot;Along with our ARGENT system for regulation of gene expression, ARIAD's RAPID technology enhances our broad portfolio of innovative technologies for regulated delivery of therapeutic proteins. The new method described in the Science research article further strengthens ARIAD's position as the leader in the development of regulated gene therapies for multiple diseases and provides several new product opportunities for ARIAD,&uot; said Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD.

ARIAD Pharmaceuticals (www.ariad.com) is engaged in the discovery and development of gene-targeted therapeutics based on signal transduction technology. ARIAD is developing gene therapy products, regulated by small-molecule drugs, for protein and cell therapy based on its proprietary gene regulation and gene activation technologies including the ARGENT(TM) and RAPID(TM) systems. The Company also is developing orally administered small-molecule drugs to block intracellular signaling pathways that play a critical role in major diseases, such as osteoporosis and immune-related disorders.

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 the Company's preclinical studies, the ability of the Company to conduct clinical trials of its products and the success of such trials, 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 under the heading &uot;Cautionary Statement Regarding Forward-Looking Statements&uot; in ARIAD's Annual Report on Form 10-K for the fiscal year ended December 31, 1998 filed with the Securities and Exchange Commission.