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CytRx Identifies RNAi Drug Candidate for Animal Testing, CEO Downplays Significance of Suits


CytRx announced last week that it will advance an siRNA into animal studies as a treatment for type II diabetes and obesity, marking the first time the company has decided to pursue in vivo testing of an RNAi drug candidate.

Separately this week, CytRx President and CEO Steven Kriegsman downplayed the significance of two lawsuits filed against him recently in relation to his one-time directorship of software firm AuthentiDate, stating that the suits have no impact on CytRx.

CytRx was an early mover in the RNAi drugs space, acquiring from the University of Massachusetts in 2003 the rights to intellectual property related to the use of siRNAs 21 to 23 long as human therapeutics for indications including obesity, type II diabetes, and amyotrophic lateral sclerosis.

Despite heavily promoting itself as a top RNAi therapeutics player, CytRx has recently shifted the majority of its focus away from its preclinical RNAi programs to its small molecule and DNA vaccine efforts, which are in clinical trials. As a result, the company's RNAi work has seemingly taken a back seat to other research and development activities.

But now CytRx has said it plans to move forward on an siRNA targeting RIP140, a ligand-dependent transcriptional repressor that has been shown to play a role in fat burning in animals and fat cells. The company licensed intellectual property related to RIP140 from Imperial College London in May 2004.

n June 2004, an Imperial College London researcher published a paper in the Proceedings of the National Academy of Sciences demonstrating that mice "devoid of the co-repressor protein RIP140 are lean, show resistance to high-fat diet-induced obesity and hepatic steatosis, and have increased oxygen consumption.

"Although the process of adipogenesis is unaffected by RIP140 deficiency], expression of certain lipogenic enzymes is reduced," Parker and his colleagues wrote in PNAS. "In contrast, genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1, are markedly increased. Therefore, the maintenance of energy homeostasis requires the action of a transcriptional repressor in white adipose tissue, and ligand-dependent recruitment of RIP140 to nuclear receptors may provide a therapeutic target in the treatment of obesity and related disorders."

According to Kriegsman, animal studies on a RIP140-targeting siRNA are slated to begin "immediately," and the drug's development will be handled by CytRx Laboratories, a subsidiary of CytRx focused on obesity and type II diabetes.

Kriegsman added that CytRx has established a timeline for when it expects to move the RIP140 program into the clinic, but declined to specify it since it hasn't been publicly disclosed.

Kriegsman told RNAi News that the RIP140 program has become one of the company's lead RNAi drug candidates, and that CytRx is in negotiations with potential big pharma/big biotech partners for the program. He declined to comment on how advanced the talks are, stating that he wasn't prepared to provide a timeframe for when a deal might be struck. However, he characterized the discussions as "active."

The Lawsuits

As reported by RNAi News last month, Kriegsman was recently named in two lawsuits against the directors of AuthentiDate, a security software company (see RNAi News, 8/19/2005). Kriegsman served as a director of the company between 1997 and 2004.

The suits allege that the defendants "caused or allowed AuthentiDate to issue materially false or misleading statements regarding the company's business and prospects," and caused the company's stock to trade at "artificially inflated levels." The company's stock fell 84 percent after a deal with the US Postal Service was not finalized.

According to Kriegsman, the lawsuits are irrelevant to CytRx and its research and development activities.

"I've lost touch with [AuthentiDate]. I haven't been involved with the company for almost two years," Kriegsman told RNAi News. "Most of the [issues in the lawsuits] relate to stuff that happened after I left the board when the stock dropped. Today, in this [regulatory] environment, they sue everybody."

Kriegsman stressed that the lawsuits "have nothing to do with RNAi [and] have nothing to do with CytRx."

"The whole board [of AuthentiDate] was sued, and I've never been served," he added. "I found out about [the suits] when I read RNAi News."

— Doug Macron ([email protected])

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