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Lorus Therapeutics and Ohio State U Partner on Nanoparticle Delivery of siRNA Cancer Rx

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Lorus Therapeutics will collaborate with Ohio State University under a $2 million grant from the National Cancer Institute to explore the use of OSU-developed nanoparticle delivery technology with Lorus' siRNA-based oncology drug candidate, the company said this week.

If the joint research project yields positive data, the collaboration could blossom into a tech-transfer deal between Lorus and OSU under which Lorus would likely seek an exclusive license to use the technology for siRNA drug delivery, a Lorus executive said this week.

In addition, a positive outcome could provide the proof of principle needed to attract additional commercial partners for the OSU technology, which may be useful for targeted delivery of oligonucleotides in several therapeutic indications.

The delivery technology, for which OSU has filed a PCT patent application, was developed primarily in the laboratory of Robert Lee, associate professor of pharmaceutics in the OSU Comprehensive Cancer Center and Nanoscale Science and Engineering Center.

Lee told BTW this week that the lipid-based nanoparticle technology has a novel composition that makes it more effective than previously developed lipid-based nanoparticle delivery systems. In addition, Lee and colleagues have developed a proprietary method for using microfluidics to manufacture the particles.

The collaboration with Toronto-based Lorus will center on its siRNA drug candidate LOR-1284, which targets the R2 component of ribonucleotide reductase.

Under a materials transfer agreement, Lorus has agreed to supply OSU with LOR-1284, as well as other developmental compounds targeting R1 and R2. Although Lorus has published data showing that "naked" LOR-1284 demonstrates anti-tumor activity in vivo, mostly for blood-based cancers such as leukemia and myodysplastic syndrome, combining it with OSU's targeted nanoparticle delivery technology may open new doors for the potential use of the drug.

"This opens up a whole different opportunity for certain indications that we probably would not have gone after," Saeid Babaei, Lorus' vice president of business development, told BTW this week.

Although the company has obtained positive preclinical data for its siRNA-based therapies, "it would be very premature to use naked siRNA to get into the clinic," Babaei added. "We see superb activity and response in liquid cancer … but have difficulties with solid tumors. I think that with a delivery system, this will be more appropriate, and particularly with siRNA, which so far is regarded in the industry as requiring a delivery system for the clinic. We really need this enabling technology if we're going to take this to the [investigational new drug] stage."

Babaei indicated as much in 2007 when he told BTW sister publication RNAi News that in order to progress LOR-1284 to the clinic, Lorus would likely need to secure an R&D partner with an effective siRNA delivery technology (see RNAi News, 3/8/07 – subscription required).

It is unclear whether Lorus explored such partnerships with other companies developing oligonucleotide delivery technology; this week Babaei told BTW that in today's financial environment the expense and unfavorable licensing terms that would likely be involved has precluded Lorus from entering into such a deal.

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"For Lorus to establish any collaboration with a corporate partner would have cost us a lot of money, up-front payments, and a major licensing deal to bring that technology in," Babaei said. "But in this case, without spending any money, we can sort of use non-dilutive funds from the NIH to develop this in collaboration with OSU.

"If we didn't have this opportunity, then we would probably have to … see who else could provide us with delivery technology to take advantage of other tumor types," he added.

Lorus and OSU will investigate the delivery and efficacy of LOR-1284 in proprietary animal models developed in Lee's lab. James Lee, a professor of chemical and biomolecular engineering and director of the NSEC; and Guido Marcucci, professor of medicine and human genetics at the OSU CCC, will also collaborate on the project.

"We basically have these mouse tumor models we established in our labs, and are making these nanoparticles to look at solid tumors in the animals and how the drug affects survival time, especially combined with chemotherapeutic agents," Lee said.

The research will build upon a previous collaboration that Lorus established with James Lee and Marcucci, who have been using a proprietary method for determining the concentration of Lorus' antisense drug LOR-2040 in acute myeloid leukemia cells. That project has progressed to a Phase II clinical study of the LOR-2040 compound for AML, currently being led by Marcucci.

The new collaboration "fits very nicely with all the programs we've already developed" with OSU, Babaei said. "This advanced stage II trial that we're doing is sponsored by Lorus, so this is bringing revenues and funding to their center. Because [Marcucci] understands our drug, his group is very involved with Lorus, and this new opportunity will keep us very much engaged."

Should the new research collaboration produce positive data, Lorus would then likely negotiate with OSU's Technology Licensing & Commercialization office for use of the delivery technology in siRNA-based therapeutics.

Such an agreement could involve co-developed IP or patents filed by OSU alone. Representatives of OSU's TLC office could not be reached for comment, but Lee told BTW that the school in December filed a PCT patent application for the delivery technology.

In fact, discussions between Lorus and OSU have already begun, Babaei said, adding that the company will likely make additional announcements regarding commercialization and tech transfer in the coming months.

"At this stage it is just a research collaboration under an MTA, and the next step will be to have a business arrangement with the university at the tech-transfer level about how we're going to split the pie," Babaei said. "If there is new IP …then we will hopefully have an exclusive license. We definitely will have an exclusive license to our product, but I doubt we'll get an exclusive license to the delivery system, period."

An excusive license to the delivery technology would likely not be appropriate, Babaei said, because it may have far-reaching commercial applications, and OSU would likely want to retain the rights to outlicense it for those purposes.

"This technology has very broad applications for siRNA therapeutics, and also other oligonucleotide therapeutics, and we've been in contact with pharma companies on this," Lee said. "And we're continuing to innovate. Potentially new compositions are coming out."

OSU's collaboration with Lorus could actually prove beneficial to the university in attracting commercial partners for other applications, should the technology help in targeting LOR-1284 to specific solid tumor types.

"They're working exclusively with us on siRNA, but obviously it would be a major … validation of their technology, and we do absolutely encourage them, once we show proof of principle, to talk with other corporate partners and parties for their technology," Babaei said. "We'll have exclusivity for certain things, but this should be good business for them as well."

In fact, OSU has previously collaborated with Genta, another developer of DNA/RNA-based oncology drugs, Lee said. Specifically, OSU and Genta had examined the use of OSU's delivery technology with an oligonucleotide cancer drug called G3139, but that collaboration has fizzled due to the current state of the economy, Lee said.

"We're still interested in that, but that is focusing on a different kind of leukemia," Lee said.

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