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Sirnaomics Aims to Move Wound-Healing Drug into Phase I Next Year

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By Doug Macron

Having put on the backburner its one-time lead drug-development program in ocular neovascularization disorders, Sirnaomics is now focusing on an siRNA-based treatment for scarless wound healing and anticipates moving the drug into phase I testing as soon as early next year, according to a company official.

Doing so, however, will require the company to secure additional funding, and it is currently evaluating its options, Sirnaomics President and CEO Patrick Lu told Gene Silencing News this week.

Since it was founded in early 2007, Sirnaomics had been directing most of its efforts toward an siRNA-based anti-angiogenic cocktail called STP-601 for ocular conditions including diabetic retinopathy, herpetic stromal keratitis, and wet age-related macular degeneration.

At one point, the RNAi shop had been predicting it could move the compound into human testing in 2008 (GSN 9/202007). That timeline was later pushed out to 2009.

After failing to meet those goals, Sirnaomics began reevaluating its pipeline and, in light of poor clinical results from other siRNA-based ocular disease drugs, ultimately shelved the program, Lu said.

Specifically, the failure of Opko Health's wet AMD drug bevarianib in a phase III trial (GSN 3/12/2009) and Allergan's decision to drop its own treatment for the eye disease on poor phase II data (GSN 5/28/2009) shook Sirnaomics investors' confidence in STP-601, he explained.

Looking for other "low-hanging fruit," Sirnaomics then began to ramp up a program in wound healing, which Lu noted presents relatively low delivery hurdles since administering siRNAs into compromised skin is not as challenging as, for instance, delivering RNAi molecules systemically.

The wound-healing drug candidate, dubbed STP-705, contains siRNAs targeting two genes identified as having a role in the development of scars following wound repair: transforming growth factor beta-1 and COX2.

"The wound-healing process changes from rapid scarless repair in fetal wounds to a slower repair with scar formation" as humans mature into adulthood, according to Sirnaomics.

Previous studies have identified TGF beta-1 and COX2 as key players in the healing of adult tissue but not in early gestation tissues. As such, the company hypothesized that a cocktail of siRNAs "would be able to knock down these factors simultaneously, providing a prominent switch to improve skin wound healing with reduced scar formation," it said.

According to data presented earlier this year, Sirnaomics formulated siRNAs against TGF beta-1, COX2, and Hoxb13 using a histidine-lysine polymer-based nanoparticle technology it has exclusively licensed from the University of Maryland Medical School (GSN 1/14/2010).

The data showed that nanoparticles delivered topically onto skin wound sites in a mouse model triggered significant improvement in skin excision wound closure. Further experimentation revealed the combination of siRNAs against TGF beta-1 and COX2 to be the most effective.

This cocktail was further tested in a pig skin excision wound model over a 15-day period, and resulted in "remarkable improvement in the rate of wound closure with re-appearance of normal skin structure," Sirnaomics said.

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With these data in hand, Sirnaomics is now conducting the studies necessary to file an investigational new drug application for STP-705, with the goal of doing so before the end of this year.

Having established a Chinese subsidiary in 2008 (GSN 7/31/2008), Sirnaomics is weighing the possibility of conducting the first phase I study of the drug in China, but no final decision has been made, Lu noted.

Either way, Sirnaomics will need to secure additional funding before it can start human testing of STP-705.

Lu said that the company is in discussions with potential industry partners, both in the US and China, that could provide funding for the trial. But it is also talking to venture capital firms that would like to see Sirnaomics take the drug into phase I on its own, and may provide the money for it to do so.

"We are currently very much focused on financing," he said.

Meanwhile, Sirnaomics is also advancing an siRNA-based pandemic influenza treatment, which Lu described as six to nine months behind STP-705.

This agent, called STP-702, is designed to inhibit conserved genomic regions in both the H1N1 and H5N1 strains of the flu virus.

"We think that if we have multiple [siRNAs] against those conserved regions, we may be able to develop an siRNA cocktail therapy against almost all strains [of flu] we are facing," Lu said.

Data Sirnaomics presented earlier this year showed that siRNAs formulated with pegylated polyethylenimine and administered intranasally and intrachacheally into mice challenged with lethal doses of the H5N1 virus had "potent" antiviral activity and protected the mice.

Aiming to develop a "resistance-proof" flu drug, the company said it further determined the antiviral activity of siRNAs targeting multiple influenza A strains including H1N1, H5N1, H3N2, H7N2, and H9N2 in cell culture.

"We are confident that an effective siRNA therapeutic with multi-targeted design and efficient delivery will be developed as STP-702," the company said.

Lu said Sirnaomics is currently finalizing the formulation of this drug.