Repligen Defines Biological Markers for Response to Secretin in Autism
Three Independent Endpoints Show Significant Treatment Effect in Defined Patient Subset

NEEDHAM, MA - June 18, 2001 - Repligen Corporation (Nasdaq: RGEN) announced today that it has found abnormal levels of two gastrointestinal biomarkers in a subset of the patients who participated in its recently completed Phase 2 clinical trial of secretin in autism. Analysis of patients in the trial with normal levels of these two biological markers showed a statistically significant effect of secretin treatment in three endpoints including two assessments carried out by a clinical psychologist and one parental assessment. Secretin-treated patients with normal levels of both biomarkers showed a statistically significant improvement (p=0.016) in social function in evaluations carried out by a trained clinical evaluator utilizing the Autism Diagnostic Observation Schedule ("ADOS"). Additionally, observations of secretin-related improvements by psychologists using the Clinical Global Impression Scale ("CGI") were statistically significant (p=0.02) in patients with normal levels of both biomarkers. A statistically significant improvement (p<0.001) was also found in the CGI assessments by parents of secretin-treated patients compared to those who received a placebo. This represents the first successful use of biological markers to define a set of autistic patients capable of responding to a specific therapy.

"These biological markers have enabled us to document the response to secretin with assessments carried out by both psychologists and parents," stated Walter C. Herlihy, President and CEO of Repligen. "This combination of a global assessment of improvement and a quantitative measurement of social deficits is a potential strategy for assessing secretin in pivotal clinical trials."

The Phase 2 trial evaluated 126 children, 3 to 6 years of age, with moderate to severe symptoms of autism and reported gastrointestinal symptoms. A stool sample was collected from each patient at the beginning of the trial and subsequently analyzed for two proteins: calprotectin, a marker of gastrointestinal inflammation and chymotrypsin, an enzyme released from the pancreas during digestion. For each protein, 25-30% of the patients had an abnormal value prior to treatment with secretin or a placebo. The ability to demonstrate a secretin-related treatment effect was dramatically improved in the 64 patients, or 51% of the total patient population, with normal levels of both proteins. Patients with abnormal levels of one or both of these biomarkers accounted for most of the "placebo responders" in the trial, indicating that they had a high degree of symptom variability over the eight week duration of the trial. These results indicate that it is important to control for gastrointestinal and other non-neurological disease processes in order to reliably measure changes in behavior in young children with autism.

Calprotectin and Chymotrypsin
Calprotectin is a protein with anti-microbial and immunoregulatory properties found in high concentrations in neutrophils, a type of white blood cell. Calprotectin released by neutrophils in the gut is stable and can be detected in stool. Elevated levels of calprotectin in stool have been reported in diseases characterized by intestinal inflammation such as ulcerative colitis and Crohn's disease. It has previously been reported to be elevated in autistic children with gastrointestinal symptoms. Levels of calprotectin did not correlate with severity of gastrointestinal symptoms in these patients.

Chymotrypsin is one of several enzymes released by the pancreas in response to stimulation by secretin and other hormones. Its function is to degrade proteins as part of the digestive process. It is relatively stable in the gut and can be detected in a stool sample. Low levels of chymotrypsin in stool have been used as an indication of pancreatic insufficiency in patients with cystic fibrosis. The reason for low chymotrypsin levels in these patients is currently unknown since other indications of pancreatic insufficiency are absent in this population.

Autism Diagnostic Observation Schedule and Clinical Global Impression
ADOS is a standardized clinical instrument for the diagnosis of autism based on a structured interaction between a psychologist and the child. The interaction consists of a series of tasks designed to assess deficits in communication and social interaction. ADOS is widely accepted as the "gold standard" for the diagnosis of autism in clinical research. The ADOS social domain is a series of activities which enable a clinician to evaluate eye contact, facial expressions, shared enjoyment in interaction, showing of toys or objects, the initiation of joint attention, the response to joint attention and the quality of social overtures. The ADOS produces a score that reflects the number and severity of the social deficits characteristic of autism. All patients were evaluated with ADOS prior to treatment and two weeks after the third administration of secretin or a placebo.

CGI is a standardized assessment of the global change in symptoms in which a patient is rated as "very much improved," "much improved," "minimally improved," etc. It has been used as a primary endpoint in the FDA approval process for many drugs that target behavioral or cognitive symptoms including drugs approved for Alzheimer's disease, depression and schizophrenia. All patients were evaluated with a CGI two weeks after the third administration of secretin or a placebo by a psychologist and independently by their parent.

The clinical trial was carried out at the Southwest Autism Research Center/Phoenix Children's Hospital (Phoenix, AZ), the Rochester Institute for Digestive Diseases and Sciences (Rochester, NY), the University of Maryland Medical Center (Baltimore, MD), the Mayo Clinic (Rochester, MN) and the MIND Institute/University of California, Davis (Sacramento, CA).

Repligen Corporation develops new drugs for debilitating pediatric disorders including autism, cancer, and immune and metabolic disorders. Repligen also manufactures and markets a set of patented products based on Protein A, which are used by the pharmaceutical industry to produce therapeutic antibodies. Its corporate headquarters are located at 117 Fourth Avenue, Needham MA, 02494. Additional information may be requested from www.repligen.com.

This press release contains forward-looking statements based on current management expectations. There are certain key factors which could cause future results to differ materially from those anticipated by management. Such factors include, but are not limited to: uncertainty in the realization of future revenues, the uncertain timelines for clinical activity, required regulatory approvals, results of pending or future clinical trials, the Company's ability to continue to establish collaborative arrangements with third parties; the Company's ability to maintain financial stability; the technical risks associated with development and manufacture of clinical products; the fact that there can be no assurances that patents relating to the Company's potential products will afford adequate protection to the Company, the risks of technological change and competition, and the competitive environment of the biotechnology and pharmaceutical industries. These factors are more fully discussed in the Company's periodic filings with the Securities and Exchange Commission.

CONTACT:                             

Walter C. Herlihy, Ph.D.
President and Chief Executive Officer
(781) 449-9560, ext. 2000

Jennifer Eason (media)
Dan Klores Communication
(212) 981-5251

Isabel Cordova (investors)
The Trout Group
(212) 477-9007, ext. 13

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