Cytokine Networks Awarded Four Small Business Innovation Grants.

SEATTLE--(BUSINESS WIRE)--July 22, 1998--Cytokine Networks, Inc. (CNI) today announced it has been awarded four Small Business Innovation Research Grants (SBIR) from the National Institutes of Health. The grants are all related to new approaches to cancer therapy and two of the programs involve the company's lead small molecule drug, CNI-1493.

One grant is focused on studying the mechanisms underlying the potent effects of CNI-1493 in blocking toxicities involving interleukin-2 (IL-2) treatment. In preclinical studies by Dr. Margaret Kemeny, M.D. at North Shore University Hospital in Manhasset, New York, and recently published in part in The Proceedings of the National Academy of Sciences (April 1998), CNI-1493 administered at low and infrequent dosing allowed for greater than 50-fold the lethal dose of IL-2 to be administered without inhibiting the anti-tumor activity of IL-2. CNI has recently commenced a multi-center Phase I human clinical study of CNI-1493 as an inhibitor of the toxic side effects of IL-2 therapy in patients with melanoma and renal cell carcinoma. In the past, extreme toxicity has severely limited use of IL-2 as an anti-cancer therapy despite its demonstrated anti-tumor activity.

CNI-1493 has also been shown in preliminary preclinical work by Dr. James W. Mier, M.D. of Beth Israel Hospital, Harvard Medical School to block the toxicities of interleukin 12 (IL-12) an additional cytokine that is being tested in clinical trials. A second SBIR recently awarded will support study on the mechanisms underlying the protection of CNI-1493 against IL-12 toxicities. "IL- 12 is currently in Phase II clinical trials and although its anti-tumor activity is promising, it may be even more limited clinically than IL-2 because of the systemic toxicities," said Dr. Glenn Rice, Ph.D., Vice President of Research for Cytokine Networks, Inc. "We hope that CNI- 1493 will help us understand and separate the systemic toxicities vs. anti-tumor mechanisms of IL-12, and provide an adjunctive therapeutic for ongoing IL-12 clinical trials, and potentially other cytokines useful in cancer therapy."

A third SBIR will examine the potential for a newly discovered antigen-presenting cell, termed a fibrocyte, to be utilized as a cancer vaccine therapy. In preclinical studies led by Dr. Richard Bucala at the Picower Institute in Manhasset New York and also published in The Proceedings of the National Academy of Sciences (June 1997), fibrocytes have been shown to be as potent as dendritic cells in generating immune responses to native T-cells, the standard for designation of "professional antigen presenting cell". "However, there are significant advantages of fibrocytes over dendritic cells," said Dr. Rice. "They are easy to isolate using proprietary methods, they do not require a cocktail of expensive cytokines and growth factors, and they are highly transfectable with foreign genes for gene therapy purposes." CNI has initiated Phase I testing of fibrocytes for cancer therapy at the University of Michigan under the direction of Drs. James Mul , Ph.D. and Bruce Redman, D.O.

A fourth SBIR grant will examine and extend the activity of a newly synthesized class of small molecule inhibitors that antagonize polyamine activity. Dr. Kevin Tracey, M.D. and colleagues, also at the Picower Institute, have recently shown that polyamines, which are secreted to high levels in a variety of human tumors, potently inhibit intratumoral macrophage activation and production and activity of TNF. Polyamines can be considered endogenous immunomodulators capable of stemming local immune responses. Restoring TNF activity via blocking the activity of secreted polyamines with this new class of small molecule drugs results in enhanced anti-tumor activities in preclinical animal models. These results suggest that this new class of drugs may act by revealing tumor cells to host immune system and may benefit cancer patents to stimulate immune responses.

Cytokine Networks, Inc. is a privately held biopharmaceutical company focused on the development of pharmaceuticals for the treatment of infectious diseases, inflammatory diseases and cancer. CNI was formed in 1993 to develop, for clinical use, a range of breakthrough medical discoveries and important developmental drug candidates for a number of significant human diseases, which were discovered at The Picower Institute for Medical Research, an independent, not-for-profit based in Manhasset, New York.

Cytokine Networks, Inc. is headquartered at 101 Elliott Avenue West, Seattle, WA 98119.

   CONTACT:  George J. Todaro, MD
              Chief Executive Officer
              Cytokine Networks, Inc.
              206-285-3400
                    or
              Fredric J. Spar
              Kekst and Company
              212-521-4800