By Mary Welch

Versicor Inc. signed an up-to-$38 million collaboration agreement with Novartis Pharma AG to discover antibacterials that inhibit deformylase and the Mur pathway.

¿It¿s our first deal, and others will come,¿ said George Horner, CEO of Fremont, Calif.-based Versicor, who called it ¿an integrated collaboration, the way biotech-pharma deals should be ¿ and most often are not.¿

Versicor, a subsidiary of Sepracor Inc., of Marlborough, Mass., and Novartis, of Basel, Switzerland, will combine forces for three years in the deal, which includes an up-front payment as well as equity, research funding, milestone payments and royalties. Versicor has co-promotion rights for the North American hospital sector. Horner declined to provide more details about Novartis¿ financial commitment.

A private company, Versicor uses functional genomics with high-throughput screening and combinatorial chemistry.

In a process essential to bacterial growth, the enzyme deformylase removes the formyl group from methionine, releasing the protein. None of the currently used antibacterials inhibit deformylase, although many work by inhibiting protein synthesis. Biochemical evidence indicates the inhibition of deformylase is responsible for the observed activity against whole cells.

Versicor has developed cell-free and cell-based deformylase assays that have resulted in identification of in vivo inhibitors, active in the low nanomolar range against both Gram-negative and Gram-positive organisms, including methicillin-resistant staphylococci aureus.

The Mur enzymes A through F catalyze the synthesis of a critical bacterial cell-wall precursor, UDP-MurNAc-pentapeptide. Versicor screens all six Mur enzymes simultaneously, thus eliminating the problem of accessing the complex substrates that have been a significant obstacle. Several hits already have been identified, and are undergoing further study.

¿Because we have had in vivo active compounds, we will be moving these compounds quicker into drugs,¿ Horner said. ¿It¿s a unique class and we¿re very advanced in it.¿

Last year, Versicor obtained an exclusive license from Harvard Medical School for the use of GAMBIT, a method for identifying essential genes in bacteria. GAMBIT uses a combination of polymerase chain reaction, transposon mutagenesis and genetic footprinting. Versicor is applying GAMBIT to Haemophilus influenzae and Streptococcus pneumoniae.

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