Warren Pharmaceuticals publishes results of preclinical evaluation

07/07/04

Successful separation of beneficial from undesireable activities achieved in new compounds

OSSINING, N.Y., July 9, 2004--Warren Pharmaceuticals, Inc. (Warren), a company engaged in developing novel treatments for devastating injuries and diseases, today announced the publication of a study showing the effectiveness of its compounds in a variety of neurologic injury and disease models. Working in collaboration with its partner, the Danish pharmaceutical company H. Lundbeck A/S, and collaborators at the Mario Negri Pharmacological Institute (Milan, Italy), University of Messina (Messina, Italy) and Dokuz Eylul University (Izmir, Turkey), Warren has shown for the first time that separation of two distinct biological activities of erythropoietin (EPO) can be achieved by a variety of modifications to the molecule. The article, entitled "Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic" was published in today's issue of the journal Science.

EPO is a naturally-occurring protein that increases red blood cell production, and recombinant human EPO is marketed for the treatment of anemia. Millions of cancer patients and those in kidney failure have received EPO for treatment of low blood count, generating over $9 billion in annual worldwide sales. This compound has attracted special interest recently because of its newly discovered role in protecting tissues from diverse injuries. The surprising discovery several years ago by Warren scientists that EPO crosses the blood brain barrier opened the way for development of protective compounds that can safely be administered by injection. Despite a positive early clinical trial in human stroke, long-term use of EPO will be limited because of increased red cell and platelet counts above normal and the potential for blood clots or hypertension.

Warren and its collaborators have synthesized molecules exhibiting only the tissue-protective effects of EPO, with no effect on the classical EPO receptor. This permits the administration of and sustained use in non-anemic patients without the appearance of classical EPO side effects. This new work demonstrates that these molecules provide neuroprotection against stroke, spinal cord compression, diabetic neuropathy and are effective in a rodent model of multiple sclerosis, while showing no erythropoietic (red blood cell producing) activity nor interfering with the body's natural ability to produce red blood cells. The current and ongoing work shows that these compounds are also candidates for treatment of chronic diseases such as congestive heart failure, diabetic retinal disease, and kidney failure, among many other maladies.

"Use of these compounds has the potential to fundamentally alter current modes of therapy in a number of important diseases. The remarkable efficacy of these compounds in a wide variety of animal models of disease and injury arises because EPO is an endogenous mediator of tissue protection. By separating the bone marrow activating function of EPO from its tissue-protective function, we have been able to target only tissue injury." said Anthony Cerami, Ph.D., CEO of Warren Pharmaceuticals.

"Our collaboration with Warren Pharmaceuticals has generated important advances in the potential treatment of neurological conditions that no current therapies adequately address," said Peter Hongaard Andersen, Vice President of Research at Lundbeck. "Warren's tissue-protective cytokines represent an important part of our research focus in neurological disorders." Lundbeck is a publicly traded Danish pharmaceutical company that focuses entirely on discovering new and effective therapies for the treatment of central nervous system disorders. Lundbeck has partnered with Warren and has been granted global and exclusive rights to the therapeutic areas of the central and peripheral nervous systems. Warren has retained all rights for indications outside of Lundbeck's field, including the eye, cardiovasculature and diabetic complications.

Accompanying the Science article is a commentary written by Hannelore Ehrenreich, a neuroscientist at the Max Planck Institute for Experimental Medicine in Goettingen, Germany. Dr. Ehrenreich emphasizes the clinical need for non-erythropoietic tissue protective compounds, especially for chronic treatment of neurological and psychiatric conditions. She writes: "Any step forward in treatments for stroke, acute brain or spinal cord injury, or for chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or diabetic neuropathy, would be a major contribution to medicine."

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