Critical Therapeutics Announces Issuance of U.S. Patent for Novel Anti-Inflammatory Technology.

Business Editors/Health/Medical Writers

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sept. 2, 2003

Company to Develop Therapies Centering on the Nervous System's Role in Controlling Systemic Inflammatory Responses

Critical Therapeutics, Inc. (CTI) today announced the issuance of a U.S. patent covering therapies designed to control destructive inflammatory processes by regulating a key reflex pathway between the central nervous system and the major organs.

U.S. Patent No. 6,610,713, entitled "Inhibition of Inflammatory Cytokine Production by Cholinergic Agonists and Vagus Nerve Stimulation," covers methods of treating a broad range of serious inflammatory diseases. The invention described in the patent embodies novel approaches to inhibit the cellular release of pro-inflammatory cytokines through administration of cholinergic receptor agonists or direct stimulation, including electrical stimulation of the vagus nerve. The vagus nerve is a major signaling pathway for the anti-inflammatory signal between the brain and major organs such as the heart, stomach, liver and small intestine.

For decades, researchers thought the vagus nerve was involved chiefly in the process of regulating the function of internal organs. In recent years, however, scientists have discovered that the vagus nerve plays a vital role in regulating the immune system. Specifically, vagus nerve stimulation has been shown to release a substance known as acetylcholine, which in turn inhibits the production by macrophages of pro-inflammatory, potentially lethal proteins called cytokines. It is the immune system's overproduction of these cytokines, including tumor necrosis factor (TNF), that can contribute to illnesses such as rheumatoid arthritis, Crohn's disease, ulcerative colitis and sepsis.

Patent No. 6,610,713 stems from research conducted by the inventor - CTI co-founder Kevin J. Tracey, M.D. - and his colleagues at North Shore-Long Island Jewish Research Institute's Laboratory of Biomedical Research. CTI in-licensed exclusive rights to the patent from the Institute. In an article published in the December 22, 2002 online edition of Nature, Dr. Tracey and his team identified the essential chemical receptor that dispatches a signal that inhibits the production of TNF. That receptor, which contains the nicotinic a-7 cholinergic receptor subunit, is necessary to inhibit the release of TNF and other pro-inflammatory cytokines.

"Dr. Tracey's research underscores the potential of pharmacological and electrical stimulation therapies that target a -7 subunits on peripheral immune cells," said Walter Newman, Ph.D., CTI's Chief Scientific Officer. "The issuance of this patent enables us to leverage our worldwide exclusive license to develop treatment methods based one or more approaches."

About Critical Therapeutics

Critical Therapeutics, Inc. is a privately held biopharmaceutical company focused on critical care medicine. CTI's mission is the discovery, development and commercialization of novel therapies for the treatment of acute trauma, cardiopulmonary disease and infectious and inflammatory illness. The Company's current research and development portfolio includes the following therapeutic targets: HMGB-1, a pro-inflammatory substance identified as a mediator of TNF-associated tissue damage; development of small molecule and vagal nerve stimulation approaches to treat inflammation; and CTI-01, a proprietary anti-inflammatory drug candidate currently in Phase I clinical trials. The Company is headquartered in Cambridge, Massachusetts. More information about CTI is available at www.criticaltherapeutics.com