Sirnaomics could begin phase I testing of its siRNA-based wound-healing drug candidate STP-705 as soon as next year and expects to run the trial in China, a company official told Gene Silencing News this week.
At the same time, the company is dipping its toes into the microRNA drugs waters, and recently published a paper with colleagues from the University of Tennessee examining the role of microRNA-132 in ocular angiogenesis.
ATP-705 has long been a key part of Sirnaomics' pipeline, and the company had at one time been expecting the drug to move into human testing in 2009 (GSN 7/31/2008). The company did not meet that goal, and later pegged the start of a phase I trial in 2010, guidance which it also missed (GSN 2/5/2009).
After establishing a Chinese subsidiary and finding a partner for STP-705 in that region with an undisclosed Chinese pharmaceutical firm, however (GSN 12/2/2010), Sirnaomics' wound-healing program has been on the fast track and is now finally nearing the clinic, President and CEO Patrick Lu said this week.
The drug comprises siRNAs against two targets, TGF-beta 1 and Cox-2, delivered topically with a next-generation version of Sirnaomics' proprietary histidine lysine polymer nanoparticles.
The company recently received a one-year, $221,350 grant from the National Institutes of Health to test the polymer technology in combination with the cationic polysaccharide chitosan and targeting peptides to deliver siRNAs for wound-healing applications, but Lu said that this work doesn't specifically apply to STP-705.
“This grant is helpful for [advancing] the delivery technology” in general, and will provide data useful for other pipeline programs, he noted. But Sirnaomics has already optimized the delivery vehicle for STP-705 and successfully completed early-stage toxicology work.
As such, the company expects to file an investigational new drug application on the compound around the end of the year.
Lu said that Sirnaomics could submit the application to US regulators, but plans to first file in China pursuant to its agreement with the Chinese pharmaceutical firm, which is providing a large portion of the funding needed to develop STP-705. He noted that the regulatory process in China is much different than in the US, and that it typically takes longer to receive clearance for an IND.
“Usually it takes six to eight months, [although] we hope it can be faster for us,” he said. “But even [if this is the case], it's going to be five to six months” before the Chinese IND would likely be approved. A phase I trial could begin shortly thereafter.
Once clinical testing is underway in China, Sirnaomics is free to pursue clinical studies in the US, where it retains the rights to STP-705, Lu noted. Importantly, a portion of the data from the Chinese IND is expected to be suitable for inclusion in an IND submitted to the US Food and Drug Administration.
Lu said that Sirnaomics has already gotten positive feedback from FDA officials on the matter, adding that the contract research and manufacturing firms handling much of the preclinical work with STP-705 are also based in the US, “so the documentation should be, partially at least, applicable to a US [IND] application.”
Before beginning any human trials with STP-705 in the US, however, Sirnaomics hopes to find a partner that can provide the support and financing needed to conduct clinical work — a milestone that may be reached in the near term as the company has already entered into a pilot agreement with an unnamed international big pharmaceutical player to evaluate the drug. Details about the arrangement remain undisclosed.
Although RNAi remains Sirnaomics' therapeutic focus, the company is also weighing the value of its technology for the miRNA space, and recently published the results of a collaboration with the lab of Barry Rouse, a researcher at the University of Tennessee and a Sirnaomics scientific co-founder.
Last month, Rouse and Sirnaomics reported in The American Journal of Pathology on the potential use of miRNA antagonism to treat the ocular lesions associated with herpes simplex virus infection.
“Herpes simplex virus causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis,” according to the paper.
Noting that miR-132 is induced in endothelial cells in response to growth factors, the team found that the miRNA is significantly up-regulated following HSV infection, and that blocking vascular endothelial growth factor-A significantly lowered its expression.
“Silencing of miR-132 by the provision of anti-miR-132 nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished [stromal keratitis] lesions,” they wrote. “To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease.
“Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness,” they added in the paper.
Lu said that the results from the study “look fantastic,” and that Sirnaomics has filed relevant patent applications. He stressed, however, that the study was only a “testing ground” for potential future work with the small, non-coding RNAs.