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March 15, 2005

Repligen and Bipolar Disorder

Repligen Corporation (NASDAQ: RGEN) today announced that the Company has entered into a development agreement with the Stanley Medical Research Institute under which Repligen will receive funding for a Phase 1 clinical trial to assess the oral bioavailability of Repligen's proprietary formulation of uridine.

This Phase 1 study is expected to enroll patients next quarter and follows Repligen's preliminary findings in animal models and patients that uridine may be useful in treating the depressive symptoms of bipolar disorder. The Stanley Medical Research Institute is the largest nonprofit provider of funding for research on schizophrenia and bipolar disorder in the United States.

"This clinical study will provide us valuable information to help design a Phase 2 study to assess the potential of uridine in bipolar disorder," stated Dr. Michael Knable, Executive Director of The Stanley Medical Research Institute.

In 2004, Repligen completed a 6-week Phase 1 clinical trial of a prodrug of a uridine (RG2133) in patients with bipolar disorder or major depression. The results demonstrated that administration of RG2133 in this patient population appeared to be safe, did not induce mania, a potential side effect of existing therapies, and provided early evidence of a clinical effect of the drug. The trial evaluated 19 patients and was carried out by investigators at McLean Hospital, the largest psychiatric clinical care, teaching and research affiliate of Harvard Medical School.

Uridine is a biological compound essential for the synthesis of DNA and RNA, the basic hereditary material found in all cells, and numerous other factors essential for cell metabolism. Uridine is synthesized by the power plant of the human cell known as the mitochondria. The rationale for uridine therapy in neuropsychiatric disorders is supported by pre-clinical and clinical research. Researchers at McLean Hospital previously demonstrated that uridine is active in a well-validated animal model of depression. Recent reports indicate that certain genes that encode for mitochondrial proteins are significantly down regulated in the brains of bipolar patients. This new insight suggests that the symptoms of bipolar disorder may be linked to dysregulation of energy metabolism of the brain.

For more information:
About Repligen Corporation
Repligen Corporation is a biopharmaceutical company committed to being the leader in the development of novel therapeutics for profound neuropsychiatric disorders and autoimmune disease with particular emphasis on applications for children. Repligen's corporate headquarters are located at 41 Seyon Street, Building #1, Suite 100, Waltham, MA 02453. Additional information may be obtained from www.repligen.com.

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