Microcide Pharmaceuticals Inc., a California start-upcompany focusing on ways of combating antibioticresistant infections, signed its second major deal Friday inless than a month with Japan-based DaiichiPharmaceutical Co. Ltd., for $10 million.

Jim Rurka, president and CEO of Microcide, in MountainView, Calif., said the collaboration with Daiichi centerson discovering small molecule compounds to preventantibiotic resistance in gram-negative bacteria caused byan efflux pump mechanism, which enablesmicroorganisms to rid themselves of antibiotics. Theefflux pump, Rurka said, is a primary method forpseudomonas to protect itself against drug-inflicteddestruction.

Microcide already has developed several potential smallmolecule compounds to inhibit the mechanism and Rurkaestimated clinical trials are about 18 months away.

The initial research, he said, likely will focus ondeveloping a separate compound that would be takenwith antibiotics such as quinolones, which are anti-infective compounds marketed by Daiichi. Eventually,Rurka added, the efflux pump inhibitor could bechemically linked to the antibacterial agents.

The collaboration with Daiichi gives the Japanesepharmaceutical company worldwide rights to productsdeveloped in the alliance. In addition to $10 million inresearch funding over three years, Microcide will receivemilestone payments and royalties. It also has co-promotion rights for products in North America.

In October 1995, Microcide signed its first corporatepartnership with Johnson & Johnson, of New Brunswick,N.J., for $8 million, including a $5 million equityinvestment. The agreement, which focuses on gram-positive bacteria, involves finding inhibitors to themicrobes' drug resistance and developing improvementsto existing antibiotics. (See BioWorld Today, Oct. 26,1995, p. 2.)

The deals with Daiichi and Johnson & Johnson, Rurkasaid, give Microcide at least two years of cash. Thecompany, whose anticipated burn rate for 1995 is $8million, currently has $10 million.

In another area of research, privately held Microcide,formed in 1992, is conducting antibacterial drugdiscovery using what it calls genetic potentiationtechnology.

The bacterial genetics program is focused onstaphylococcus aureus, which are gram-positivemicroorganisms. The company's initial approach, Rurkasaid, is to discover the estimated 200 genes whose task itis to keep the bacterium alive in vitro. Thestaphylococcus has a total of about 2,000 genes in itsgenome. The 200 targeted by Microcide are called"essential" genes and the company's researchers haveidentified slightly more than 50.

A second stage of the research will isolate a subset of theessential genes activated only to sustain the microbe inhumans.

By identifying the essential genes, Rurka said, Microcidewill be able to pinpoint targets for small moleculecompounds that inhibit the genes' functions and kill thebacterium.

Microcide has not yet entered a collaboration for itsbacterial genetics program. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.