Recombinant Human Antithrombin Demonstrates Therapeutic Potential in Endotoxemia Model of Sepsis.

FRAMINGHAM, Mass. and SYDNEY, Australia -- Today, at the 20th Congress of the International Society of Thrombosis and Haemostasis in Sydney, Australia, Dr. Judith Leitner, working with Dr. Bernd Jilma's team at the Medical University of Vienna, presented the results of a study that described the therapeutic potential of recombinant human antithrombin, supplied by GTC Biotherapeutics, Inc. ("GTC", Nasdaq: GTCB), in a human model of sepsis. This physician-sponsored trial showed that supra-physiological levels of antithrombin without concomitant heparin have potent dose-dependent anticoagulant effects and anti-inflammatory properties in human experimental endotoxemia.

Severe sepsis still carries a high mortality rate despite advances in intensive care medicine and antimicrobial therapy. Every year, more than 750,000 people in the United States develop severe sepsis, a syndrome characterized by an overwhelming systemic response to infection, which can lead to organ dysfunction and ultimately death. Approximately 215,000 people in the US die from severe sepsis every year. The death rate can be as high as 60% for people with underlying medical problems.

Three natural anticoagulants have been tested in large phase III trials in sepsis: recombinant human activated Protein C, tissue factor pathway inhibitor and antithrombin. In all three trials, concomitant administration of heparin could have compromised clinical efficacy of the drugs under investigation. This study team hypothesized that antithrombin infused without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin induced cytokine production.

Results in Coagulation and Inflammation

Coagulation: In vivo thrombin formation decreased in a dose dependent fashion as measured by prothrombin fragment, thrombin antithrombin complexes (TAT) and D-dimer.

Inflammation: Infusion of recombinant human antithrombin rapidly decreased neutrophil and monocyte counts before endotoxin challenge, demonstrating a direct interaction with these leukocyte subsets. Antithrombin treatment significantly decreased peak interleukin-6 (IL-6) release by 40%.

Study Design

The study was a randomized, double-blind and placebo-controlled trial, consisting of three parallel groups totaling 30 healthy male subjects. Volunteers were randomly assigned to receive either a bolus primed continuous infusion of recombinant human antithrombin at 500% or 200% of normal antithrombin level or an equal volume of placebo (0.9% NaCl) over 4 hours. Immediately after the recombinant human antithrombin bolus infusion, an intravenous bolus of 2 ng/kg National Reference Endotoxin (LPS, Escherichia coli; USP, Rockville, MD) was given to all subjects.

About GTC Biotherapeutics

GTC Biotherapeutics is a leader in the development, production, and commercialization of therapeutic proteins through transgenic animal technology. GTC currently has five products in its internal pipeline and a portfolio of external program production opportunities. GTC's lead program is ATryn(R), its recombinant form of human antithrombin. A Market Authorization Application is under review by the European Medicines Agency for the use of ATryn(R) in patients with a hereditary antithrombin deficiency. In addition to the ATryn(R) program, GTC is developing a recombinant human alpha-1 antitrypsin, a recombinant human albumin, a malaria vaccine, and a CD137 antibody to stimulate the immune system as a potential treatment for solid tumors. In its external programs, GTC's technology is used to develop transgenic production of its partners' proprietary products, including both large-volume protein therapeutics as well as products that are difficult to produce in significant quantities from conventional recombinant production systems. One of the external programs is in clinical trials with a transgenically produced product. Additional information is available on the GTC web site, http://www.gtc-bio.com.

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including the potential for further study and eventual use of recombinant human antithrombin in the treatment of sepsis or endotoxemia. Such forward-looking statements are subject to a number of risks, uncertainties and other factors that could cause actual results to differ materially from future results expressed or implied by such statements. Factors that may cause such differences include, but are not limited to, the risks and uncertainties discussed in GTC's most recent Annual Report on Form 10-K and its other periodic reports as filed with the Securities and Exchange Commission, including the risks and uncertainties inherent in the performance of demonstration studies and the clinical development of therapeutics. GTC cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this document, and GTC undertakes no obligation to update or revise the statements, except as may be required by law.