Signing on to help Novartis identify lead candidates, Cengent Therapeutics Inc. will use its Genes To Leads drug discovery platform to screen for lead compounds against multiple targets.

Cengent entered the contract agreement with the Novartis Institutes for BioMedical Research in Basel, Switzerland, for an undisclosed amount of money that includes up-front and milestone payments.

Genes To Leads is a lead-generation service that selects closely related structural proteins - called anti-targets - for analysis using structure-based and sequence-based methods.

"This is a source of ongoing revenue for us," said Cengent's CEO and president, Ed Maggio. "We've been involved in this business since 1998."

While Maggio declined to give further financial details, he did say the company is looking at financing options.

"We have sufficient cash, certainly for the next year or so, but we're actively looking to stabilize it and bolster our cash situation," he said.

The Genes To Leads service was borne out of Structural Bioinformatics Inc., which acquired GeneFormatics Inc. last year, then changed its name to Cengent. Both companies were based in San Diego. (See BioWorld Today, Jan. 7, 2003.)

Privately held Cengent has worked with a number of companies using Genes To Leads to find drug leads for conditions such as cancer, infection and inflammation. In March, the company entered a similar Genes To Leads drug discovery collaboration with GlaxoSmithKline plc, of London.

Maggio said the whole Genes To Leads process takes about 60 to 120 days.

"One of the attractive aspects of our technology is it works equally as well for protein-protein interactions as it does for enzyme inhibitors," he told BioWorld Today.

The process combines computational prescreening of millions of potential drug-lead structures with the actual laboratory screening of about 200 to 400 compounds. Typical hit rates average about 10 percent over 14 diverse targets.

The compounds may be selected from about 5 million commercially available compounds, millions of compounds in Cengent's virtual CombiLib libraries or from clients' in-house compound collections.

Automated docking methodologies require a high-resolution X-ray structure and only work for enzymes.

"We don't need an X-ray crystallographic structure to get there," Maggio said. "We can work off of certain modeling technologies we've developed in-house."

Cengent used its Genes To Leads process to produce candidates in its lead preclinical program of nanomolar PTP-1B inhibitors. The inhibitors demonstrated prolonged glucose-lowering activity and obesity control in a diabetes animal model.

"We hope to pick the safety assessment candidate sometime within the next three to six months," Maggio said.

Once a six-month safety assessment is completed, the company would file an investigational new drug application to bring the candidate to the clinic, although Cengent does not intend to take the product through the clinic itself.

"We have discussions with a number of pharmaceutical companies to potentially partner this program out," Maggio said. "We hope to put together a collaboration in the next few months." He added that a number of biotech companies also are interested.

In addition to the PTP-1B program, Genes To Leads and a National Institutes of Health grant led the company to anthrax lethal factor inhibitors that prevent macrophage destruction. The small-molecule compounds are inhibitors of the zinc metalloprotease anthrax lethal factor, the most toxic component of the anthrax bacillus. Cengent has pursued another grant from the NIH that would take the program into the clinic.

The company's third preclinical program, at the earliest stage, is its HER-2 breast cancer program involving non-peptide small molecules that need to be optimized.

Aside from its internal programs, Cengent offers several technologies providing access to protein structural information, including X-ray crystallography, high-field NMR, homology modeling and computational methods.

Last year, it formed a deal to provide X-ray crystallography services to AGY Therapeutics Inc., of South San Francisco. (See BioWorld Today, July 1, 2003.)