PRESS RELEASES

Repligen Announces Initiation of Clinical Trial of Uridine

McLean Hospital study will assess changes in brain chemistry in bipolar and major depression

FOR IMMEDIATE RELEASE:
January 23, 2003

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617/855-2110

Belmont, MA - Repligen Corporation (Nasdaq: RGEN) has announced the initiation of a Phase 1/2 trial of RG2133, a prodrug of uridine, in patients with either bipolar disorder or major depression. In addition, to standard clinical evaluations of safety and efficacy, the trial will evaluate potential changes in brain chemistry by magnetic resonance spectroscopy (MRS). The trial is being carried out by investigators at McLean Hospital, a teaching affiliate of Harvard Medical School, and McLean's Brain Imaging Center. The open-label trial will evaluate oral administration of RG2133 in 20 patients.

"Uridine therapy is a novel approach to the treatment of bipolar disorder and major depression," said Andrew Stoll, MD, director of the Psychopharmacology Research Laboratory at McLean Hospital. "We need new approaches for these patients whose disabling and life-threatening symptoms are not adequately treated with existing therapies."

The Phase 1/2 trial is based on pre-clinical animal studies conducted by researchers at McLean demonstrating that uridine is active in a well-validated animal model of depression. The clinical trial will assess the impact of RG2133 on the depressive symptoms associated with bipolar disorder and with unipolar major depression, neither of which is adequately treated with existing drugs including SSRIs such as Prozac® or Zoloft®. In both diseases, evidence from MRS suggests that there are imbalances in the levels of chemical compounds involved in normal brain metabolism. In this trial each patient will be assessed by MRS before and after a six-week treatment to determine if RG2133 can correct these chemical imbalances.

"We are pleased to announce the initiation of our first clinical trial for RG2133," stated Walter C. Herlihy, president and CEO of Repligen. "The use of brain imaging techniques has the potential to provide a quantitative assessment of the impact of uridine so that we can better understand its effect in these patients before designing and initiating larger scale clinical studies."

About Bipolar Disorder and Unipolar Major Depression

Bipolar disorder, also known as manic depression is an illness marked by extreme changes in mood, thought, energy and behavior in which a person's mood can alternate between the "poles" of mania (highs) and depression (lows). Bipolar disorder affects more than two million adults in the United States and is usually diagnosed in late adolescence or early adulthood. When symptoms of mania are left untreated, they can lead to dangerous or even life-threatening situations because mania often involves impaired judgment and reckless behavior. According to the American Academy of Child and Adolescent Psychiatry, up to one-third of the 3.4 million children and adolescents with depression in the United States may actually be experiencing the early onset of bipolar disorder. Unipolar major depression is an extremely common condition characterized by a sustained low mood or loss of interest in one's usual activities, combined with low energy, poor concentration, changes in appetite and sleep, and often, suicidal urges. There are approximately 20 million adults in the United States that experience major depression and the World Health Organization considers major depression the second leading cause of disability on earth.

Current drug therapy for bipolar disorder includes the use of lithium or valproic acid, however side effects are frequent and troublesome, and patients don't respond fully, leading to frequent recurrences of mania and depression. While there are a number of drugs available to treat major depression, current therapy is limited by side effects including weight gain, anxiety and sexual dysfunction. In addition, as in bipolar disorder, many patients with major depression remain recalcitrant to therapy.

About McLean Hospital

McLean Hospital maintains the largest research program of any private, U.S. psychiatric hospital. It is the largest psychiatric teaching facility of Harvard Medical School, an affiliate of Massachusetts General Hospital and a member of Partners HealthCare. The Brain Imaging Center at McLean is one of the largest imaging centers in the world, actively engaged in clinical research studies of brain function. Researchers at McLean were part of the team that first identified regional abnormalities in brain activation in patients with schizophrenia and in normal aging, as well as regional changes in blood flow and metabolism in patients with Alzheimer's disease.

About Repligen Corporation

Repligen Corporation is a biopharmaceutical company committed to being the leader in the development of new drugs for pediatric developmental disorders including autism, immune and metabolic disorders. Additional information may be requested from www.repligen.com.

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