Milnacipran Effective Analgesic in an Animal Model to Assess Analgesic Efficacy in Persistent Pain, According to Cypress Bioscience CSO.

Business Editors and Health/Medical Writers

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SAN DIEGO--(BUSINESS WIRE)--Oct. 28, 2002

Cypress Bioscience Inc. (NASDAQ:CYPB) announced today its chief scientific officer, Srinivas Rao, M.D., Ph.D., made a presentation entitled "Analgesic Efficacy of Repeated Milnacipran in Persistent Pain" at the American College of Rheumatology Annual Scientific Meeting in New Orleans, Louisiana on Saturday Oct. 26, 2002.

The studies described were conducted in collaboration with Dr. Frank Porreca, Department of Pharmacology, University of Arizona Health Science Center.

Antidepressants of all types represent a common form of therapy for a variety of chronic pain conditions, and studies have demonstrated that the analgesic effects of these drugs are independent of their influence on mood. Agents that interfere with the reuptake of norepinephrine, particularly tricyclic antidepressants (TCAs), have demonstrated superior analgesic efficacy compared to agents that selectively block the reuptake of serotonin. Unfortunately, many patients are unable to tolerate the side effects associated with TCAs. Thus, there has been an effort to find agents that have similar effects on norepinephrine reuptake, while improving upon the side effect profile of TCAs.

Milnacipran is a norepinephrine serotonin reuptake inhibitor (NSRI) being developed for the treatment of fibromyalgia syndrome and other chronic pain disorders. Pharmacologically, this agent is differentiated from serotonin norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Eli Lilly), by its preferential blockage of norepinephrine reuptake over serotonin.

The experiments presented at the American College of Rheumatology meeting assessed the effects of milnacipran on weight bearing, mechanical hypersensitivity (increased sensitivity to touch) and on thermal hyperalgesia (increased sensitivity to heat) in an experimental nerve injury model known as spinal nerve ligation (SNL). SNL induces behavioral signs in rats that are similar to human states of neuropathic pain, including increased sensitivity to light touch (mechanical hypersensitivity) and thermal hypersensitivity.

The results of these studies indicated that chronic administration of milnacipran caused a reduction in SNL induced pain in rats, as indicated by improved weight bearing in the injured paw. In addition, milnacipran showed a positive analgesic effect on thermal hypersensitivity, in both SNL and normal rats. The profile exhibited by milnacipran is consistent with that demonstrated in previous experiments by the same laboratory with amitryptyline (a TCA which blocks the reuptake of norepinephrine and serotonin).

Milnacipran is currently being evaluated as a potential treatment for fibromyalgia syndrome. In September 2002 the company completed enrollment in its Phase II clinical trial that was initiated in the first quarter of this year to evaluate milnacipran as a treatment for fibromyalgia syndrome (FMS). The company expects to announce the results of the trial in early 2003.

About Cypress Bioscience Inc.

Cypress is committed to be the innovator and commercial leader in providing products for the diagnosis and treatment of patients with Functional Somatic Syndromes, such as Fibromyalgia Syndrome, or FMS, and other related chronic pain and central nervous system disorders. In January 2001, the company began a strategic initiative focusing on FMS. In August 2001, Cypress licensed its first product for clinical development, Milnacipran. Milnacipran, the first of a new class of agents known as NSRI's, or Norepinephrine Serotonin Reuptake Inhibitors, shares a pharmacological profile with the tricyclic antidepressants (TCAs), considered the most effective drugs for treatment of FMS, while appearing to lack the side effects associated with the latter. Milnacipran is currently being evaluated as a potential treatment for FMS in a Phase II clinical trial. For more information about Cypress, visit the company's Web site at www.cypressbio.com. For more information about FMS, visit www.FMSresource.com.

This press release, as well as Cypress' SEC filings and web site at http://www.cypressbio.com, contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results could vary materially from those described as a result of a number of factors, including those set forth in Cypress Annual Report on Form 10-K and any subsequent SEC filings. In addition, there is the risk that we may not be able to successfully develop or market any products for the treatment of FMS under the Pierre Fabre agreement or at all; that our clinical development plan or timeline for milnacipran may be delayed, including our Phase II clinical trial; that the capital that we raised will not allow us to execute our business plans into 2003; that we may encounter regulatory or other difficulties in the development of milnacipran for FMS; and that milnacipran may not significantly improve the treatment of FMS. Cypress undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this press release, except as required by law.