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Executive Summary

CIBA-GEIGY INVESTING $30 MIL. IN ISIS FOR JOINT RESEARCH EFFORT with the molecular biology start-up. Research will focus on the development of antisense oligonucleotides, or compounds that inhibit the production of certain proteins associated with disease by blocking the activities of messenger RNA. Announcing the agreement with Carlsbad, Calif.-based ISIS Pharmaceuticals on Oct. 30, Ciba-Geigy said it will "commit more than $30 mil." to the project over the next five years. Ciba-Geigy also will make an undisclosed equity investment in the privately held start-up to become a "significant minority shareholder." Under terms of the agreement, Ciba-Geigy retains an option to license products resulting from the R&D program on a worldwide basis, while ISIS has the opportunity to co-develop and co-market pharmaceutical products in the U.S. ISIS would receive royalties on product sales outside the U.S. The collaboration with Ciba-Geigy will consist of four research projects, three of which will focus on molecular targets thought to be involved in the inflammation process associated with diseases such as rheumatoid arthritis, while the fourth will focus on an undisclosed virus. The projects also may have applications in treating cancer, ISIS said. The more than $30 mil. in funding will be used to support a research program at ISIS involving approximately 20 researchers. At the same time, Ciba-Geigy will staff a laboratory at its central research facility in Basle, Switzerland with 20 researchers to study oligonucleotide chemistry. ISIS announced an agreement with Rhone-Poulenc S.A. on Oct. 31 for collaborative research on a single oncogene protein molecular target. The research collaboration, a three-year agreement similar in structure to the Ciba-Geigy deal, is for an undisclosed amount of funding, but no equity stake. ISIS said it will receive research funding, milestone payments, U.S. co-development rights and product sale royalties. In addition, a visiting Rhone-Poulenc scientist will join the ISIS research staff. The agreement provides ISIS with an opportunity to work with Claude Helene, director of the Laboratoire de Biophysique at the Musee National d'Histoire Naturelle and a leading researcher in antisense technology, the company pointed out. Helene will serve as chairman of the ISIS-Rhone Poulenc Joint Research Management Committee. ISIS was founded in March 1989 by company Chairman Stanley Crooke, MD/PhD, who was formerly president of R&D at SmithKline Beckman and an executive in Bristol-Myers' oncology business. Backed by four initial venture capital investors, ISIS raised$5.2 mil. in its seed round of financing. The company currently has 60-plus employees and expects to have over 100 by the first quarter of 1991. The firm's proprietary research programs focus on four initial targets: herpes, human papilloma, leukotrienes and HIV. ISIS hopes to file for Treatment INDs in 1991 for products for herpes viruses and the human papilloma virus. In animal models, the company's lead compound, ISIS-1082, has shown inhibition of the herpes virus and activity against resistant herpes strains along with a therapeutic index over 2,000. The company is also researching 5-hypoxygenase, an enzyme that produces the disease mediators leukotrienes. The firm's HIV program is focusing on the virus's RNA structure with the aim of developing an HIV therapeutic.

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