Curacyte announces successful completion of Phase II study for PHP in distributive shock

Study results corroborate pharmacodynamic activity and tolerability of PHP and provide favorable trends in the future primary endpoints

Munich, January 21^st 2004 ….. Curacyte AG, a Munich-based drug development company, has announced the successful completion and data analysis of a Phase IIc study of its lead product, PHP (Pyridoxalated Hemoglobin Polyoxyethylene), in patients suffering from shock associated with Systemic Inflammatory Response Syndrome, also referred to as distributive shock. These latest Phase II study results corroborate the pharmacodynamic activity and tolerability of PHP from earlier Phase II trials and provide favorable trends in the future primary endpoints. The Phase IIc study provides comprehensive information on PHP’s activity and safety in the targeted patient population receiving the envisioned therapeutic dose rate and paves the way for a pivotal Phase III study.

Distributive shock represents a critical health condition requiring patients to be admitted to Intensive Care Units (ICUs). This type of shock is characterized by peripheral vasodilation, hypotension and resultant tissue ischemia mediated by an over production of nitric oxide (NO). Prolonged shock states lead to multiple organ failure and, frequently, to death. Distributive shock affects approx. 1.2 million patients annually and is associated with significant mortality, morbidity and cost.

Dr Helmut Giersiefen, co-founder and Chief Executive Officer of Curacyte, stated: “The results from the Phase IIc study have definitively exceeded our expectations. The data are convincing and suggest that PHP will be successful in a large Phase III trial. The consistency and quality of the data is rarely seen in the clinical development of new drugs and establishes an encouraging basis for Curacyte to partner the product with a suitable pharmaceutical company to conduct a pivotal trial and to seek marketing approval.”

The new clinical data come from a randomized, placebo-controlled, multi-center trial that involved 15 centers in the United States . This Phase II trial was conducted following the protocol for PHP’s future pivotal Phase III study that has already been accepted by the FDA. A total of 62 patients were randomized to receive either standard treatment of conventional catecholamine plus placebo or PHP plus catecholamine. Distributive shock is managed by administration of large doses of pressor agents including catecholamines, hormonal neurotransmitters that increase the volume of work placed on the already stressed heart of shock patients and neglect the cause of the vasodilation. Since PHP addresses the root cause of vasodilation and not the symptom hypotension, it is expected that PHP will provide favorable outcomes compared to therapy with catecholamines.

A dual primary endpoint will be applied in the future pivotal study of PHP. This endpoint was accepted by the FDA to determine the efficacy of PHP and is composed of 28-day mortality and morbidity, defined as days alive and free of cardiovascular dysfunction and days alive and free of ventilation.

In the Phase II study, PHP was administered by continuous infusion at the envisioned therapeutic dose rate of 20 mg/kg/day up to maximum dose of 200g or until patients resolved shock. Patients on the PHP-treatment group were allowed to discontinue catecholamines depending on improvements of their blood pressure and resolution of shock.

The data from this new Phase IIc study will be presented by Dr Gary Kinasewitz, University of Oklahoma, a principal investigator in the Phase II study, at the 24^th International Symposium on Intensive Care and Emergency Medicine (ISICEM) on March 30 – April 2, 2004 in Brussels ( Belgium ).

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Notes to Editors

1.         Background to PHP

Distributive shock is caused by an overproduction of nitric oxide (NO) through an inducible nitric oxide synthase (iNOS). NO is a physiological regulator of blood pressure. However, when produced in toxic levels, NO causes excessive vasodilation resulting in shock. PHP is a chemically modified hemoglobin derived from human blood that can deliver a physiological function of hemoglobin in a therapeutic way. The pharmacological activity of PHP is based on the ability of the hemoglobin molecule to bind NO and to metabolize it to non-toxic nitrate. Unlike erythrocyte-bound hemoglobin, PHP can extravasate into the interstitial space, scavenge and metabolize toxic levels of NO. This mode of action leaves the system with sufficient levels of NO that are necessary to maintain other essential physiological functions.

PHP, a potent scavenger of NO, is a chemically modified hemoglobin derived and synthesized from human red blood cell. Until now the safety and effectiveness of PHP has been studied in four clinical trials, one Phase I study and three Phase II studies. The recent Phase IIc study substantiates the existing clinical data base. A total of 120 individuals have now been studied in the four trials. Because this new study was conducted based on the FDA-accepted pivotal trial protocol, the data not only corroborates the findings from previous studies, but more importantly, it delivers important information regarding the likelihood of success of PHP in its future large pivotal trial, particularly in terms of providing trends in the primary clinical endpoints.

2.         Background on Curacyte www.curacyte.com

Curacyte was founded in 1999 as a research-based biopharmaceutical company dedicated to the discovery and development of innovative and clinically meaningful new medicines. In 2002 the Company announced its merger with VitaResc Biotech AG, a development-stage company focused on novel treatments of inflammatory diseases, thrombotic disorders and cancer.

The Company’s lead product, Pyridoxalated Hemoglobin Polyoxyethylene (PHP), has reached Phase III clinical development as a treatment for patients suffering from distributive shock and there are several other programs in pre-clinical development. In July 2003 Curacyte received clearance from the FDA for initiating clinical trials of PHP as an adjunct to IL-2 cancer therapy.

Curacyte also focuses on inhibition of therapeutically relevant proteases. Several development projects are derived from Curacyte’s proprietary protease technology, including small molecule inhibitors of Factor Xa, plasma kallikrein and urokinase. Inhibitors of Factor Xa are currently in the lead optimization stage as oral anticoagulants. In October 2003 Curacyte announced that it had been awarded a €1.2M grant for its Factor Xa program. Plasma kallikrein inhibitors are being evaluated for preventing activation of the blood clotting cascade on surfaces of hemodialysis membranes. CJ-463 represents the first highly specific inhibitor of urokinase and has been in formal preclinical development since Q3 2002. Curacyte anticipates initiating first clinical studies with this anti-metastatic agent in 2004. Curacyte intends to apply its technology to other pathomechanisms that involve serine proteases and received a grant (€ 0.5 M) in December 2003 to pursue serine protease targets in cancer research.

Eileen Paul, Account Manager, Northbank Communications

Phone: +44 (0)1260 296 500, Mobile: +44 (0)7793 630 240