By Mary Welch

For the second time, Cubist Pharmaceuticals Inc. and Merck & Co. have expanded their collaboration for anti-infectives begun in 1996.

Under the new terms, Whitehouse Station, N.J.-based Merck may license compounds and data from Cubist, of Cambridge, Mass., for inclusion in the two companies' research program.

"The original agreement was co-exclusive," said Susan Whoriskey, director of scientific licensing for Cubist. "Cubist was able to conduct research on our own targets to identify new compounds and, as we've done that, we found some interesting things. Merck is now accessing them and wants to tap into these Cubist discoveries."

She said the new terms are "wrapped around the original agreement with some enhancements." She declined to be more specific, but said Merck would fund research and development and make milestone payments in return for access to Cubist's discoveries and compounds, and as certain points are reached.

The original deal, inked in June 1996, called for Merck to pay up to $20.5 million to Cubist, as well as royalties. Cubist was using three targets against Merck's compound library. By October 1997, Cubist had received $3 million from Merck in license fees and research support. That's when the two first expanded their pact. (See BioWorld Today, June 27, 1996, p. 1, and Oct. 10, 1997, p. 2.)

Cubist identifies novel chemical compounds that inhibit intracellular targets needed for cell function in bacteria and fungi. The company uses rational, target-based discovery methods and has more than 135,000 small molecules to screen against each of its proprietary targets.

The expanded agreement with Merck pertains to the discovery and development of novel antibacterial drugs from leads obtained by screening six of Cubist's aminoacyl-tRNA synthetase targets against Merck's compound library. Aminoacyl-tRNA synthetases are a family of 20 enzymes essential to the process of protein translation required by all organisms for survival.

To date, the Merck collaboration has focused on the discovery of novel anti-infectives that inhibit the function of essential bacterial proteins.

Selected Cubist enzyme targets have been screened against Merck's collection of synthetic, small molecule compounds and its collection of natural product extracts.

Research Targets Drug-Resistant Bugs

"We're not tweaking existing compounds," Whoriskey said. "We're looking for compounds that the pathogens have not been exposed to." In particular, Cubist is working on antimicrobial drugs targeting emerging strains of drug-resistant bacteria and fungi. Among the-drug resistant microorganisms are Staphylococcus aureus, Streptococcus pneumoniae, Candida albicans and Mycobacterium tuberculosis.

Since the 1970's, no new antibiotics that inhibit a novel microbial target have been introduced. Many of the anti-infectives on the market are second- or third-generation drugs that are chemical modifications of related compounds.

The deal with Merck is not Cubist's only collaboration. In June 1996, Cubist and Bristol-Myers Squibb Co., of New York, signed an exclusive $56.5 million research and development agreement to discover novel agents to treat bacterial and fungal infections by screening six of Cubist's aminoacyl-tRNA synthetase targets against Bristol-Myers' compound library. Among the diseases this collaboration is targets is tuberculosis. (See BioWorld Today, June 27, 1997, p. 1.)

Cubist expects to begin Phase III clinical studies by the end of this year or early next for daptomycin, a novel anti-infective with potent activity against all Gram-positive bacteria. Given intravenously, daptomycin demonstrated in Phase II trials that it was safe and effective in the treatment of skin and soft tissue infections caused by Gram-positive bacteria such as Staphyloccoccus aureus and Streptococcus progenies.

The company's stock (NASDAQ:CBST) closed Thursday at $5.687, up $1.125. *