Genta Inc. is looking to expand its DNA- and RNA-based drug programs through two separate transactions - an acquisition for which it could pay up to $30 million, and a nonexclusive license to a broad siRNA patent.

The Berkeley Heights, N.J.-based company entered an agreement to acquire privately held Salus Therapeutics Inc., which specializes in antisense and small interfering RNA (siRNA) drugs, as well as delivery systems for such DNA- and RNA-based drugs. Upon closing, Genta will issue about $13 million worth of stock to Salus shareholders as an up-front payment. Following certain preclinical and clinical milestones, an additional $17 million could be paid in stock or cash at Genta's option.

In a separate but related transaction, Genta acquired a nonexclusive license to a broad patent covering siRNA from the Carnegie Institution of Washington. The potential of RNA interference fits with Genta's oligonucleotide-based programs.

"This is simply a direction of our resources to areas that we know very well, signifying our confidence in the platform of DNA- and RNA-based medicines as the breakthrough medicines of the future," Genta CEO Raymond Warrell Jr. told BioWorld Today. "RNAi is simply another oligo-based approach toward knocking down gene targets that are of interest, and for us, as they apply to cancer patients. Those technologies would include antisense, our historic strength. A second platform relates to decoys that are DNA medicines that directly go after protein transcription factors. The third would be aptamers and now the fourth area is RNA interference using small interfering or micro-RNAs."

He called the patent license fundamental to Genta's RNAi work going forward. The patents derive from work first reported by Andrew Fire, Craig Mello and colleagues at the Carnegie Institution and The University of Massachusetts in Amherst. Genta was drawn to the patents given their fundamental importance in broadly covering processes for introducing RNA into cells to control gene expression.

"It's one of the early, seminal patents, and anyone in this space must have a license," said Warrell, who declined to specify terms of Genta's license. Other companies also have acquired nonexclusive licenses to the patent, but Warrell distinguished Genta's work from most others. "Very few companies that have this license are working on RNAi for therapeutics. Most of them are using it for expression profiling and that kind of work - very early target validation - as opposed to the development of these agents as direct human therapeutics."

The Salus acquisition provides Genta added tools and personnel through its discovery platforms for antisense and siRNA drugs. Founded in 1999 with seed funding from Utah Ventures and vSpring Capital, the Salt Lake City-based company has developed a trio of programs that attracted Genta. Salus has a screening system to identify target areas in messenger RNA that can be attacked using both antisense and RNAi, methods of using single-stranded siRNA and micro-RNA molecules to knock down gene expression in target cells, and a delivery platform to improve the pharmaceutical properties of oligonucleotides.

"We believe that we can dramatically accelerate our drug discovery efforts," Warrell said. "The systems that will be applied will be primarily directed toward the scanning of new oncologically important target genes, and identifying regions of interest in those genes. We'll then very rapidly generate lead drug candidates based on either antisense or RNAi."

Salus' OptiSense oligonucleotide target identification technology is a cell-based discovery process to identify drug candidates for any gene of interest. From that, its RNAi therapeutics use a siRNA approach to knock down mRNA of targeted genes. Salus' PolyBus drug delivery technology uses biocompatible and nontoxic polymers that allow direct complexing of drug and carrier to maximize intracellular delivery.

Both boards approved the purchase, as have a majority of Salus' stockholders. Genta said it expects the acquisition to close this quarter.

Warrell said Genta would continue to operate and expand the 11,000-square-foot lab facility managed by Salus, whose 12 employees are being brought on board at Genta. He added that Genta would recruit further personnel for the scientific operations in Utah, and direct currently outsourced programs related to oligonucleotide drug discovery and development into the Salus facility.

Genta's lead drug, the anticancer product Genasense (oblimersen sodium), remains in four Phase III trials. The drug brought the company a $480 million deal with Strasbourg, France-based Aventis SA last year. (See BioWorld Today, April 30, 2002.)

Out of its small-molecule program, Genta's lead drug is Ganite (gallium nitrate injection), which it expects to launch in the second half of this year for cancer-related hypercalcemia resistant to hydration.

Genta's shares (NASDAQ:GNTA) lost 8 cents Friday to close at $12.49.