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Somagenics Holds Back on HCV Clinical Trial Amid Advances by Other Drugmakers

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Despite encouraging preclinical safety and efficacy data for its RNAi-based hepatitis C treatment, Somagenics has decided to step back from its previous plan to push the agent into phase I testing this year as it waits to see how more advanced small-molecule therapies fare in late-stage clinical trials, a company official said this week.

In the interim, however, the company is not standing still. Somagenics CEO Brian Johnston told Gene Silencing News this week that the firm is continuing to refine its HCV treatment to target additional sites on the virus' genome as it explores other therapeutic indications and tests the microRNA diagnostic waters.

About a year ago, Somagenics reported data showing that a cocktail of two of its proprietary short shRNAs, or sshRNAs, which function independently of Dicer, could significantly knock down circulating HCV in mouse models of the disease (GSN 9/29/2011). The effect was long-lasting and there were no treatment-related toxicities observed.

Buoyed by the data, which were generated in collaboration with Roche prior to that company's departure from the RNA drugs field in late 2010, Somagenics was at the time planning to skip a planned non-human primate study of its intravenously delivered HCV therapy and move right into phase I testing in 2012 — assuming it could find a partner to help fund the effort.

However, this week Johnston said that Somagenics has decided to hold off on its preparations for a human trial as a number of non-RNAi HCV drug candidates, many of which are orally delivered, move closer to regulatory approval.

“For us, it's a significant investment to ramp up into the clinic,” he said. And though the animal data on Somagenics' drug “look very good … it would be an injectable, and the market … is moving toward all-oral therapy.”

Among the most promising HCV therapies moving through late-stage human testing is Gilead Sciences' sofosbuvir, a once-daily nucleotide analog polymerase inhibitor. Earlier this month, Gilead announced that the orally delivered drug, given in combination with ribavirin, was able to reduce HCV RNA to undetectable levels in 78 percent of chronically infected patients after 12 weeks of treatment in a phase III study.

Additional phase III studies of sofosbuvir are ongoing, and Gilead has said that it anticipates submitting the drug as part of an all-oral HCV treatment regimen for approval in mid-2013.

As a result of these and other promising data from other companies with HCV agents in advanced human testing, “we're holding back on moving into the clinic” until the final results from these studies are available and it is clear that there is a place in the market for an injectable like Somagenics' drug, Johnston said.

As it waits, Somagenics is continuing to work on its HCV therapy with an eye to increasing the number of viral targets to three or four in order to boost efficacy, he noted. Meantime, the company is considering other liver diseases, although these efforts are still very early stage.

More advanced is Somagenics' effort in wound healing, which is advancing with the support of a one-year, $347,447 grant from the National Institutes of Health. According to that grant's abstract, the company is focused on using its sshRNAs to down-regulate an undisclosed protein that “regulates multiple factors including the synthesis of heat shock proteins, which are known to accelerate wound healing by promoting angiogenesis, vasculogenesis, and macrophage recruitment.

“Intervention with a separate target is expected to enhance keratinocyte growth and motility, two processes critical for wound closure,” it adds.

Notably, the wound-healing program is largely focused on topical delivery, an area in which Somagenics has experience through past collaborations with researchers from TransDerm.

In addition, Somagenics is looking to tweak an miRNA-detection platform, dubbed miR-ID, it had previously developed for diagnostic applications.

According to a paper published in RNA last year, the miR-ID technology involves “circularization of the miRNA by a ligase; reverse transcription of the circularized miRNA, producing tandem repeats of a DNA sequence complementary to the miRNA; and qPCR amplification of segments of this multimeric cDNA using 5'-overlapping primers and a non-specific dye such as SYBR Green.”

“When you put that all together … you end up with a very efficient process that has about six logs of dynamic range, is as sensitive as TaqMan, and has higher selectivity because we're actually using three potentially independent primers,” Johnston said. It is also a cost-effective method since it does not require the use of chemically modified probes, such as those used with TaqMan, or primers.

He said that Somagenics is developing the miR-ID technology for use with formalin-fixed, paraffin-embedded tissue samples, with an initial focus on breast cancer.

“Once we've demonstrated proof of principle of the platform, we intend to use it to validate some existing biomarkers and show we can make a kit that will be superior to the existing breast cancer disease-stratification platforms that are out there,” he said. “Once we have that in place, we expect it will attract diagnostic makers to develop kits for other indications.”

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