Tacere Therapeutics this week announced that it has licensed its preclinical hepatitis C therapy TT-033 to Pfizer in a deal that marks the first time a big pharma has signed on to commercialize an expressed RNAi drug.
According to Tacere CEO Sara Hall, the arrangement, which gives the drug giant worldwide rights to TT-033 except in Asia, is a major de-risking milestone for the expressed RNAi field and helps validate her company’s decision against pursuing small-molecule drugs — something Tacere had expected to do when it was founded in late 2006 (see RNAi News, 10/12/2006).
“The dogma around the more gene therapy-type approach [to RNAi] for people who have not been in the gene therapy field is that pharma would not be interested, and we’d never be able to partner a drug,” she told RNAi News this week. “Obviously, this [deal] proved that resoundingly wrong.”
Under the terms of the transaction, the companies will assemble a joint steering committee to oversee the preclinical research and development of TT-033, all of which will be funded by Pfizer. Hall noted that while Tacere anticipates doing a portion of the investigational new drug application-enabling preclinical work that remains, “larger [toxicology] and bio-distribution studies will be outsourced.”
Hall said that the firms plan to file an IND with US regulators in about 15 months, after which TT-033’s development will be handed off to Pfizer. She added that Tacere, however, is likely to play a role in the drug’s clinical development.
“Nothing has been set in stone as far as what each company will do specifically” following the IND filing, Hall said. “But the general tone from all the discussions so far is that we are the RNAi people … so we’ll continue to be pretty heavily involved” until later-stage clinical trials, which “Pfizer is much more capable of handling.”
She added that Pfizer will pay for any clinical work on TT-033 Tacere might conduct. Tacere will also be paid an undisclosed upfront fee and stands to received development and commercialization milestones, which, in addition to the preclinical funding, could total more than $145 million.
Hall said that Tacere is also eligible for high single-digit to mid-double-digit royalties on net sales of TT-033.
Additional terms of the partnership were not disclosed.
Hall noted that the Pfizer arrangement does not change a deal Tacere struck with Oncolys BioPharma in June for the Asian rights to TT-033 (see RNAi News, 6/21/2007).
“Oncolys still retains the option for the Asian rights [to TT-033] … up through mid-phase I [development of the drug],” she said, adding that Oncolys’ CEO sits on Tacere’s board and has been “very much involved in all of the discussions” with Pfizer.
“Pfizer would really like to strike a collaborative tone [with Oncolys] as we move forward,” Hall said. “So there have been some pretty open discussions about what role the various companies would play [in TT-033’s development] and the potential for [a collaboration] between Oncolys and Pfizer.”
Officials from Pfizer were not available for comment by press time.
‘Seal of Approval’
When Tacere was founded, Hall had told RNAi News that while the company’s initial focus was on TT-033, which had been licensed from Australia’s Benitec in the summer of 2006 after that company ran into dire straits (see RNAi News, 6/29/2006), it would also explore developing small-molecule therapeutics.
“By the time we really got operations up and running, we decided against it,” she said this week. “We very quickly realized [that expressed RNAi] is what we know.”
Further cementing the decision to stick with expressed RNAi was the Pfizer deal, which Hall characterized as “a kind of Good Housekeeping seal of approval.
“So we’ll continue down [the expressed RNAi] road; that’s where our expertise lies,” she said. “The space is too crowded on the siRNA side, and … this is the world we’re most comfortable in.”
“The dogma around the more gene therapy-type approach [to RNAi] for people who have not been in the gene therapy field is that pharma would not be interested, and we’d never be able to partner a drug. Obviously, this [deal] proved that resoundingly wrong.”
But having essentially handed off its sole drug candidate to Pfizer, Tacere is now left with decisions on what to pursue next.
“We had a board meeting [this week] where we spent quite a bit of time … [discussing] where we want to go from here,” Hall said. “With TT-033 now basically funded, and an upfront on top of that, we’re significantly cash flow positive. We’re going to spend probably the next six months … looking at pipeline development — and that [involves examining both] product opportunities and intellectual property.”
In terms of product opportunities, Hall said that Tacere would be evaluating indications for which there is an unmet need and matching them to the appropriate delivery vector.
“We have a few thoughts [about possible indications to pursue next] but it’s really going to come down to the availability of programs,” she said. “From a druggable target standpoint, RNAi can go after anything with a genetic basis, but to get it into the cells [is a challenge]. So delivery … is the main issue.”
As far as IP goes, matters become a little murky. The IP covering TT-033 that was licensed from Benitec includes composition-of-matter patent applications, as well as a US patent — No. 6,573,099 — that broadly claims the knocking down of gene expression in plants and animals using DNA that transcribes double-stranded RNA.
Under previous management, Benitec launched a series of lawsuits claiming infringement of the ‘099 patent, including one against rival expressed RNAi firm Nucleonics. When Nucleonics refused to license the patent, the companies embarked on a long road of patent re-examination requests and litigation that has resulted in the US Patent and Trademark Office preliminarily rejecting all claims in the patent.
At the same time, Nucleonics has been pushing to reinstate Benitec’s original lawsuit, which was dismissed by a Federal Court at Benitec’s request, in order to obtain a court ruling on the validity of the patent (see RNAi News, 10/11/2007). This week, Benitec announced that Nucleonics has asked the US Supreme Court hear the case.
According to Hall, the USPTO is expected to render a final decision on the ‘099 patent some time this year, perhaps as early as the next few months. Should the patent office uphold the patent, she said that Tacere would likely discuss licensing Benitec’s IP for other drug programs.
If the patent does not survive, “then the larger [IP] umbrella over expressed RNAi becomes public domain,” she said. “So then it really comes down to composition-of-matter patent applications like what we have for TT-033.
“What we’ll be looking at then is very program-specific IP,” she added.