NEW YORK – Sirnaomics this month said it has filed to begin Phase I testing of its siRNA-based treatment for hypertrophic skin scars in China, marking its first major step toward becoming a clinical-stage drug developer since it was founded nearly eight years ago.
The company is also aiming to get the drug, dubbed STP705, into human trials in the US, President and CSO Patrick Lu told GenomeWeb. This, however, will require that Sirnaomics find a source of new funding, either through an investment or industry alliance, he said, noting that the firm has had to cut back work on a number of its less-developed drug candidates amid financial constraints.
When Sirnaomics was first established by Lu — who was also a co-founder of RNAi drug shop Intradigm, which was later acquired by Silence Therapeutics — the company set an ambitious path forward, focusing on RNAi drugs that hit multiple gene targets for a variety of indications including ocular neovascularization, influenza, and cancer.
It also early on set up a subsidiary in China to take advantage of that country's low cost of labor and research materials — a move that led to Sirnaomics inking a partnership for STP705 in China with Guangzhou Xiangxue Pharmaceutical, as well as it securing Chinese government grants for its flu drug, called STP702.
Unable to find partners for its other programs in the US, the company has sharpened its focus on STP705 and STP702 in China, and recently submitted an investigational new drug application with the China Food and Drug Administration to begin Phase I testing of the scar-healing drug. STP705 comprises siRNAs against TGF-beta 1 and Cox-2, which are delivered with Sirnaomics' proprietary histidine lysine polymer nanoparticles. The planned clinical study is being funded by Guangzhou Xiangxue, and will test multiple doses of the drug both in healthy volunteers, who will receive injections of the agent into uncompromised skin, as well as people undergoing scar-revision surgery who will receive treatment topically on their open wounds, according to Lu. He added that Sirnaomics is optimistic about STP705's potential, especially in light of preclinical data showing that it can reduce the size of human hypertrophic scar tissue that had been grafted onto mice. Those data are currently being prepared for publication.
But just when the Phase I study will start remains unclear given the relatively long review time of INDs by Chinese regulators. In China, such regulatory filings typically take between six and 18 months to be approved, compared with 30 days in the US — a situation partially driven by the need for approval by regulators at both the provincial and federal levels, Lu noted.
Further complicating matters is that fact that no oligonucleotide drug, let alone an RNAi one, has been approved in China, he added.
In the meantime, Sirnaomics is looking into getting clearance to test STP705 in the US, and has scheduled a pre-IND meeting with the US Food and Drug Administration for early next month. But even if the company gets the green light from the FDA, it would still need to find the money to run a clinical study in the US.
Sirnaomics CEO Marc Lemaitre, who joined the firm in early 2014, said that he has been holding talks with investment groups and potential pharmaceutical industry collaborators, but has yet to finalize anything. Positive data from the Phase I trial in China, he said, would likely help in such negotiations.
Despite its emphasis on STP705 and financial limitations, Sirnaomics hasn't put all of its other programs on the backburner. Work with STP702, as well as an earlier-stage project centered on fighting human papilloma virus infection, is ongoing, Lu said.
Notably, Sirnaomics is also looking beyond RNAi to microRNAs. In 2012, the company and one of its co-founders, University of Tennessee researcher Barry Rouse, reported on the use of an miRNA inhibitor to treat the ocular lesions associated with herpes simplex virus infection. Specifically, they showed that miR-132 is upregulated following HSV infection, and that blocking the miRNA reduced corneal neovascularization and diminished stromal keratitis lesions.
While these data were encouraging, Lu said this week that the company is now focusing on an miRNA-replacement for colon cancer. Academic collaborators in China, he said, have demonstrated that high levels of miR-150 expression is associated with improved cancer patient response to chemotherapy — findings Sirnaomics has replicated in vivo.
That project, he said, is poised to enter IND-enabling studies shortly.