PRESS RELEASES

McLean Hospital and Repligen Announce Results of Brain Imaging Study of Secretin

FOR IMMEDIATE RELEASE:
November 01, 2002

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Belmont, MA and Waltham, MA - Researchers from the Brain Imaging Center at McLean Hospital and Repligen Corporation (Nasdaq: RGEN) reported today the results of a clinical trial designed to assess the neurological activity of secretin by functional magnetic resonance imaging (fMRI).

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The results demonstrate for the first time in humans, that secretin is active in the central nervous system and that it potentiates activity in the amygdala, a region of the brain involved in social integration and implicated in autism. The findings were presented today by Deborah Yurgelun-Todd, Ph.D., of McLean Hospital, the study's Principal Investigator, at the International Meeting for Autism Research, a satellite meeting of the Society for Neuroscience.

"Our results demonstrate for the first time that secretin is a neuroactive peptide in humans and that it acts on a brain region known to be important for social interaction," stated Yurgelun-Todd, Director of Cognitive Neuroimaging at the Brain Imaging Center at McLean Hospital. "These findings suggest that secretin may have a role in modulating certain social behavior in humans."

The study was a double-blind, placebo-controlled clinical trial in 12 healthy men. Each subject was presented with a series of pictures of faces with either a neutral, happy or fearful facial expression to establish a baseline response. Following an injection of either secretin or a placebo, the subjects were again presented with the series of facial expressions. Throughout the experiment, the activation of the amygdala was recorded with MRI. There was a significant activation (p=0.001) of the right amygdala by secretin when the subjects viewed pictures of a fearful face compared to both the placebo group and the baseline response to the pictures in the secretin group. By contrast, there was no difference in amygdala activation when subjects viewed pictures of neutral or happy faces. Failure to activate the amygdala when viewing fearful faces is a characteristic of people with autism and patients with amygdala damage. The current study was initiated as part of ongoing research efforts to understand secretin as a neurologically active peptide. Repligen previously reported a finding that treatment of rats with secretin specifically activates the neurons in the amygdala. Repligen is currently developing secretin for autism in a Phase 3 clinical trial program.

"These studies show that secretin is active in a part of the human brain involved in social interaction and potentiates its activity during a social task known to be difficult for people with autism," stated Walter C. Herlihy, Ph.D., President and Chief Executive Officer of Repligen Corporation. "These data provides a plausible biological mechanism for the improvements in social interaction we observed in our Phase 2 clinical trial."

The Amygdala and the Social Deficits of Autism

The amygdala is part of a complex neural system that is critical for ascribing emotional value to stimuli and influencing affective responsiveness and emotional learning. One of the core deficits of autism is impaired reciprocal social interaction, including eye contact, joint attention and an inability to deduce the mental states of others from facial expressions. Reduced activation of the amygdala in patients with autism has been documented using fMRI with specific impairment noted in their ability to respond to facial expressions of fear. Other studies indicate that patients with either surgical or congenital amygdala damage show similar face recognition defects. Lack of activation of the amygdala is recognized as an important correlate of the social deficits of autism.

Repligen's President and CEO Walter C. Herlihy, Ph.D. also presented data from its Phase 2 clinical trial. The Phase 2 study evaluated three administrations of secretin or a placebo in 126 patients aged 3 years to 6 years 11 months with moderate to severe symptoms of autism and gastrointestinal disorders. The primary finding of the Phase 2 clinical trial was that younger children, 3 and 4 year olds, showed improvements in reciprocal social interaction as judged by a standardized clinical instrument for the assessment of autistic symptoms. Repligen is currently conducting a Phase 3 clinical trial of secretin for the improvement of reciprocal social interaction in young children with autism.

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. Repligen has a specialty pharmaceuticals business comprised of rProtein A™ and SecreFlo™, the profits from which will be used to support the development of our proprietary products. rProtein A™ is a consumable reagent used by the pharmaceutical industry to produce a class of drugs called monoclonal antibodies and SecreFlo™, secretin for injection, is marketed to gastroenterologists for pancreatic assessment. Repligen's corporate headquarters are located at 41 Seyon Street, Building #1, Suite 100, Waltham, MA 02453. Additional information may be requested from www.repligen.com.

This release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934. The forward-looking statements in this release do not constitute guarantees of future performance. Investors are cautioned that statements in this press release which are not strictly historical statements, including, without limitation, statements regarding current or future financial performance, management's strategy, plans and objectives for future operations, clinical trials and results and product plans and performance such as the anticipated growth in the monoclonal antibody market and projected growth in product sales, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including, without limitation, risks associated with: the success of current and future collaborative relationships, the market acceptance of our products, our ability to compete with larger, better financed pharmaceutical and biotechnology companies, new approaches to the treatment of our targeted diseases, our expectation of incurring continued losses, our uncertainty of product revenues and profits, our ability to generate future revenues, our ability to raise additional capital to continue our drug development programs, the success of our clinical trials, our ability to develop and commercialize products, our ability to obtain required regulatory approvals, our compliance with all Food and Drug Administration regulations, our ability to obtain, maintain and protect intellectual property rights for our products, the risk of litigation regarding our intellectual property rights, our limited sales and manufacturing capabilities, our dependence on third-party manufacturers, our ability to hire and retain skilled personnel, our volatile stock price, and other risks detailed in Repligen's filings with the Securities and Exchange Commission. Repligen assumes no obligation to update any forward-looking information contained in this press release or with respect to the announcements described herein.

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