By Doug Macron
RXi Pharmaceuticals this week announced that it has exercised an option to acquire technology related to self-delivering RNAi molecules from Advirna, a Boulder, Colo.-based biotech firm co-founded by RXi's chief scientific officer.
Separately this week, the company disclosed that it has terminated six of its licensing agreements with the University of Massachusetts Medical School, as well as an invention-disclosure agreement, while amending its license to an oral RNAi drug-delivery technology.
Advirna "is a small firm that was involved in consulting and IP generation in the field of RNAi," RXi President and CEO Tod Woolf told RNAi News.
While RXi had been developing RNAi drugs that don't require a delivery vehicle on its own, an effort led by CSO Anastasia Khvorova, certain aspects of that work "overlapped" with technology being developed at Advirna, he noted. As such, RXi acquired an option to exclusively license the worldwide rights to Advirna's self-delivery technology.
RXi has since made significant strides with the self-delivery approach, which involves four different chemistries that facilitate the delivery of the company's so-called rxRNA molecules into the cytoplasm of a cell, and therefore decided to exercise its option.
Last month, Woolf told RNAi News that although the company's orally deliverable RNAi molecules, dubbed glucan-encapsulated siRNA particles or GERPs, continue to be the most advanced in its pipeline, a self-delivered drug could potentially be the firm's first drug to enter clinical testing (see RNAi News, 6/25/2009).
Still, it isn't entirely clear how the self-delivery technology works, and at the time Woolf said that RXi continues to explore different combinations of the chemistries as it "figur[es] out the optimal formulation."
He added this week that RXi is also looking at combining the self-delivering molecules with, paradoxically, a delivery vehicle.
"A lot of delivery technologies don't necessarily deliver the oligonucleotide into the interior of the cell," Woolf said. And if they do, oftentimes the payload "might just stay in the endosome, get exocytosed, or go the lyososome and be destroyed."
In theory, a delivery vehicle could carry an RNAi agent to the target cell or tissue, where the self-delivering technology would ensure it enters the cytoplasm, he noted.
RXi's growing focus on both self-delivering RNAi and GERPs reflects an ongoing refinement of RXi's focus, which previously included a number of pipeline changeups (see RNAi News, 3/26/2009) that has also led to its termination of several licenses with long-time partner UMMS.
According to UMMS and RXi, they have mutually agreed to "restructure the portfolio of technology licenses" between them. As part of this move, six existing licensing deals have been ended.
Woolf said that the licenses related to research that "hasn't much to do with what we're doing anymore," and he noted that some of them date to before RXi was spun out of one-time RNAi player CytRx in 2007 (see RNAi News, 1/11/2007).
For RXi, the intellectual property covered by the licenses was not relevant and "the biggest issue was that we were paying for the prosecution of patents that we had no particular commercial interest in," Woolf said. He noted that none of the ended agreements involved licenses to fundamental RNAi intellectual property, such as the Tuschl-I patent family.
As for the company's three-year invention-disclosure agreement with UMMS, which was signed in 2007 and provided RXi with the option to license all unrestricted therapeutic RNAi technology developed at the school (see RNAi News, 1/18/2007), Woolf pointed out that it was just months away from expiring.
In addition, since RXi has the right of first refusal on inventions arising from sponsored research at UMMS, the company didn't need "a broader agreement," he said.
With the invention-disclosure agreement, "we'd pay just to have the agreement in place," he added. But terminating the arrangement "frees up [a small amount of] money for actual licenses."
Woolf declined to provide specific details about the amended agreement for the GERP technology, which it licensed from UMMS in late 2008 (see RNAi News, 10/16/2008), but said that the changes relate to "subtleties of the license, the scope of what we were doing, the scope of claims we thought would issue, and such."
Officials from UMMS weren't available for comment. But in a statement, James McNamara, executive director of UMMS' office of technology management, said that the school "fully expect[s] to identify suitable licensees for the technology RXi has returned to us."