Just six months after its establishment, startup Sirnaomics is already setting its sights on launching a phase I clinical trial of an siRNA-based ocular disease therapy early next year — an ambitious timeline the company expects it can meet by running the study in China, where regulatory hurdles are fewer compared with the US, Sirnaomics President, CEO, and founder Patrick Lu told RNAi News last week.
Sirnaomics’ drug candidate is a cocktail of multiple siRNAs targeting three genes associated with neovascularization: vascular endothelial growth factor, or VEGF; and MMP-9 and MMP-2, two genes in the matrix metalloproteinase pathway.
It is being developed as a locally administered drug capable of treating diabetic retinopathy, herpetic stromal keratitis, and wet age-related macular degeneration.
The company chose ocular diseases for its first pipeline program because “RNAi therapeutics were first tested in this area,” Lu said, noting that there are three clinical trials of siRNA drugs for ocular diseases ongoing.
These include Opko Health’s bevasiranib, which is in phase III testing for AMD (see RNAi News, 6/28/2007); Allergan’s Sirna-027, an AMD drug developed by Sirna Therapeutics (see RNAi News, 10/7/2005); and Pfizer’s RTP-801i, which was licensed from Quark Pharmaceuticals (see RNAi News, 9/28/2006).
“The safety profiles from these studies are very good, [and] we believe with our drug that we can immensely improve the efficacy [of such treatments while keeping] the safety profile pretty much … the same,” Lu said.
To test this hypothesis, Sirnaomics is planning to begin a phase I study of its ocular disease drug in China sometime in early 2008 — much sooner than would be possible in the US, Lu said.
Because the Chinese pharmaceutical field is not as developed as that in the US, Chinese regulators are “more willing” to approve human trials of new drug candidates than the US Food and Drug Administration, he explained. “That clearly gives us more room to see if this new candidate really works.”
Lu declined to comment on the possible design of the trial, but said that it is expected to lay the groundwork for follow-on clinical testing in the US.
“We want to use our data [from the Chinese study] to support our filing for a US-based phase I” trial and eventually an investigational new drug application filing with the FDA, he said.
Further, the Chinese study will help showcase Sirnaomics’ multi-targeted RNAi technology as the firm looks to raise capital and forge industry partnerships, Lu noted.
“The [company’s] key technology … is the design of multi-targeted siRNA therapeutics,” which is what “we believe the future success of siRNA therapeutics will largely rely on.”
Sirnaomics isn’t alone in that thought. As early as 2003, Benitec had been discussing the notion of targeting multiple genes with its expressed RNAi technology in order to address drug-resistance issues (see RNAi News, 10/24/2003).
In late 2005, an official from Sirna Therapeutics (now a part of Merck) disclosed to RNAi News that his company was experimenting with modifying siRNAs so that both the sense and antisense strands could be used to silence distinct genes (see RNAi News, 11/11/2005).
But should it meet its phase I timeline, Sirnaomics would likely be the first to actually test a multi-targeted RNAi therapy in humans, a move that Lu said would “open the door for many other similar approaches for other diseases.
“Not only will we be providing the community with a new drug candidate, but we’ll also provide a [new] platform: multi-targeted [RNAi] drugs,” he said.
Lu conceded that the targeting of multiple genes with an RNAi drug has the potential to increase the number of possible off-target effects, and said that this “is a question we want to address” in the late-stage preclinical and phase I studies.
Fundraising on the Front Burner
Before the phase I testing of its RNAi drug can begin, Sirnaomics has to contend with one of the more mundane aspects of business development: fundraising.
Currently, the company occupies a 3,500-square-foot facility in Gaithersburg, Md., and has five full-time employees, including Lu, two senior managers responsible for corporate development and R&D management, and two lab technicians. Lu had previously founded another RNAi drug company, Intradigm, but left in January when that company assembled a new management team and moved to California (see RNAi News, 11/22/2006).
“We are going to have more [employees], of course, and are currently trying to generate more funding to support our activities,” Lu said. “The direction, the technology, the business model [of Sirnaomics are], in my mind, very clear. We just need the resources to push the company ahead.”
“If you have an siRNA cocktail, the particular design of that cocktail — with particular sequences as composition of matter, a particular delivery system as method of use, and a particular therapeutics application showing utility — is going to be stand-alone IP.”
Specifically, Lu is in the process of finalizing a Series A financing round he hopes will bring in between $10 million and $15 million to build on undisclosed seed financing that has already been secured.
“Very likely, we can secure that in six months because we have some early responses [from potential investors] that are very positive,” he said. Those interested investors are not just venture capitalists but include possible drug-development partners.
Sirnaomics is pursuing “big pharma collaborations in the US [and] all around the world,” Lu said.
”We have potential partnerships in the US, in Europe, in Japan, and in China. Hopefully we get several major deals nailed and the valuation of the company will be dramatically improved.”
As its most advanced drug-development effort, Sirnaomics’ ocular disease program is perhaps the most likely candidate for an industry tie-up. However, the company is also pursuing a variety of other indications amenable to locally delivered RNAi drugs including wound healing and respiratory diseases such as influenza.
One thing Sirnaomics isn’t worrying about, at least in the near term, is intellectual property.
Though the company expects to license the fundamental Fire-Mello patent, which is widely available from the Carnegie Institute, it does not see the value in rushing to license IP held by RNAi drugs leader Alnylam Pharmaceuticals.
Though Alnylam has touted licenses to its IP estate as a necessity for any firm looking to play in the RNAi therapeutics space, Lu isn’t so sure this is the case for his company.
“If you have an siRNA cocktail, the particular design of that cocktail — with particular sequences as composition of matter, a particular delivery system as method of use, and a particular therapeutics application showing utility — is going to be stand-alone IP,” he said.
And even if Sirnaomics eventually decides that it does need access to IP held by another company, he said that he feels the company would be in a better position to negotiate for a license once it has established its own patent portfolio.
Once Sirnaomics has begun building up its own IP estate, “then we’ll find out which IP we need to license,” Lu said. Additionally, at that point Sirnaomics will hopefully have its own key IP that it will be able to use as leverage when it negotiates for “high-level IP” like that held by Alnylam or Merck.