tives. These results also demonstrate the ability of BioNumerik's Karenitecins to bypass common drug resistance mechanisms (MDR, MRP & LRP) to which many other camptothecins appear to be susceptible. Because its compounds are lipophilic, BioNumerik believes its Karenitecins will have enhanced tissue penetration, drug delivery and bioavailability compared to water soluble camptothecins.

Camptothecins, described as Topoisomerase I inhibitors, represent some of the most active anticancer drugs in existence. Due to formulation problems, however, the great majority of camptothecins in development or on the market have been made water soluble to allow easier drug dissolution and administration. BioNumerik believes that this approach may limit the utility of these drugs and the Company has developed a new generation of proprietary highly lipophilic (fat loving) camptothecins, known as Karentitecins, that have been designed to overcome problems that exist with camptothecin and the current camptothecin derivatives.

Using its mechanism-based approach, BioNumerik used its Cray supercomputers to construct a detailed computational model involving human Topoisomerase I and DNA in order to understand and more precisely target the key interactions between camptothecin-Topo I/DNA. BioNumerik used this information to guide and complement the discovery and optimization of novel compounds for laboratory synthesis and preclinical testing.

In a presentation titled "BNP7787: Administration In Vivo Results in Increased Therapeutic Index and Toxicity Reduction of Platinum Drugs", BioNumerik also presented data on its proprietary agent BNP7787, a novel water soluble disulfide that was engineered to increase the therapeutic index of cisplatin and carboplatin, two widely used anticancer drugs.

Although platinum chemotherapy is widespread, formulations of cisplatin and carboplatin have a major risk of kidney toxicity (cisplatin), nausea and vomiting, bone marrow suppressio
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Contact: Neil Cohen
neil@noonanrusso.com
212-696-4455 x. 205
Noonan/Russo Communications
30-Mar-1998

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