Quark Pharmaceuticals last week announced it has developed proprietary siRNA structures that it claims will enable it to develop drug candidates based entirely on its own intellectual property. The company has, however, disclosed very few details about the molecules.
“We no longer need to rely on other people’s patents as far as the structure of the siRNA,” Quark CEO Danny Zurr told RNAi News this week. Patent applications covering the structures are completely owned by Quark and “we have ascertained through two independent … IP law firms that, indeed, we have the freedom to operate.
“We looked at all the issued patents, and more importantly, all the patent applications that have been published,” he said, adding that Quark’s new siRNAs are “totally outside” of existing IP in the field, including the Tuschl-1, Tuschl-2, Kreutzer-Limmer, and Crooke patents, which are primarily controlled by Alnylam Pharmaceuticals.
Besides professing their IP edge, Zurr said he expects the new structures to enable Quark to forge technology-licensing deals, which could prove to be a sorely needed source of cash in a down market.
Zurr remained tight-lipped on the specific details about the siRNAs, stating that more information will be made available once the relevant patent applications are published. He did note, however, that the various siRNAs that the company develops based on the new technology will each incorporate different structural modifications based on their targets.
“There is no such thing as … a generic structure,” he said. “You have to have a number of different structures tailor-made to the actual [target] sequence. [Ours] is a family of several structures that we can use as a basis to look for the best structure” for a particular sequence.
Importantly, Zurr said, this family of structures does not trigger any immune responses, such as the activation of Toll-like receptors, which has become a key hurdle facing RNAi-based drug makers.
In March, a team of researchers reported in Nature that all siRNAs suppress neovascularization regardless of their sequences or targets due to the activation of TLR3 (see RNAi News, 3/27/2008). Five months later, investigators from Tekmira Pharmaceuticals published data suggesting that many earlier reports of therapeutic effects of siRNAs were actually due to immune responses (see RNAi News, 9/4/2008).
Quark’s new siRNAs, however, are “absolutely free” from either suppression or activation of any TLRs, Zurr said. At the same time, they cause “almost no off-target activity” because of a novel RISC-loading mechanism.
“We no longer need to rely on other people’s patents as far as the structure of the siRNA. We have ascertained through two independent … IP law firms that, indeed, we have the freedom to operate.”
The first of Quark’s drugs to use the novel structures, as reported by RNAi News this summer, will be its preclinical glaucoma therapy, now renamed QPI-1007 (see RNAi News, 7/17/2008).
Although Quark has not disclosed QPI-1007’s target, Zurr said that the drug candidate is designed to prevent the retinal ganglion cell death believed to cause the vision loss characteristic of glaucoma, a process in which the molecule’s target is “the main player.”
Quark said it and academic collaborators evaluated QPI-1007 in two animal models: one of retinal ganglion cell death by optic nerve crush and one of cell death induced by optic nerve axotomy.
In both studies, the drug “displayed neuroprotective activity” towards retinal ganglion cells and “significantly” protected retinal neurons against delayed degeneration, while reducing injury-induced cell death, the company said.
Zurr noted that Quark could file an investigational new drug application for QPI-1007 as early as the second quarter of 2009.
At the same time, Quark is considering incorporating the new siRNA structures into its other preclinical products, including a second-generation wet age-related macular degeneration therapy that would be administered topically via eye drops.
Quark’s most-developed drug is an intravitreally injected therapy for AMD and diabetic macular edema that is in phase II trials. Quark licensed that drug, RTP801i-14, to Pfizer in 2006 (see RNAi News, 9/28/2006). Zurr noted that the new AMD program is not covered by that arrangement.
By developing its own proprietary siRNA structures, Quark has taken a big step forward in leaving behind a licensing arrangement that had become a thorn in its side.
All of Quark’s drugs that are either in the clinic or have been cleared for human testing are covered by structural IP the company licensed either from Alnylam or Silence Therapeutics.
In the past, Quark has taken issue with the extent to which Silence has portrayed its involvement in those drugs. For instance, earlier this year Zurr told RNAi News that Silence had been “trying to create the image that [our pipeline] is their pipeline.” At the time, a Quark spokeswoman told RNAi News that the companies had reached a “compromise” that improved, but did not rectify, the situation.
Meanwhile, having an IP-protected family of novel siRNA structures has moved Quark beyond its role as an RNAi drug developer to what Zurr called a “platform company,” something he said would put it in a position to strike technology-licensing deals to raise the money needed to fund in-house programs in a difficult financial environment.
Quark had at one time actively pursued an initial public offering in the US, but scuttled those plans last summer when it couldn’t generate enough interest in its stock at a price with which it was comfortable (see RNAi News, 8/2/2007).
Although Zurr at the time told RNAi News that the company was considering another IPO bid, the current turmoil in the credit and equities markets will likely quash that hope. As a result, Quark will need to look elsewhere for cash.
Despite closing a $27 million private financing round in April (see RNAi News, 4/10/2008), Quark remains “a small company” with “extensive clinical programs” and requires more cash than it has, Zurr said.
And while “there are always unique situations where you may attempt to go for an IPO,” Zurr said, licensing arrangements will likely be Quark’s principal avenue for raising cash for its in-house programs.
He noted that Quark is currently engaged in talks with a number of undisclosed companies interested in licensing the new technology. In terms of the form a potential deal might take, he said that Quark is being “opportunistic” and considering arrangements on individual targets, indications, or disease areas.