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CombiMatrix and Benitec Ink Cross-Licensing Deal for RNAi Technologies


Benitec and CombiMatrix announced this week that they have struck a cross-licensing deal that would allow each company to use the technology of the other to pursue the development of RNAi-based therapeutics in their respective areas of interest.

Under the arrangement, Benitec will share with CombiMatrix the exclusive rights to two specific siRNA sequences targeting HIV. The sequences were developed by Spanish non-profit research institute IrsiCaixa under an ongoing collaboration with CombiMatrix (see RNAi News, 3/26/2004). Benitec has also received from CombiMatrix a license to intellectual property related to the use of siRNA cocktails as anti-viral agents.

In exchange, CombiMatrix has received access to certain of Benitec’s IP for use in developing expressed-RNAi treatments for injuries or diseases resulting from exposure to biological, chemical, radioactive, and other weapons.

According to CombiMatrix President and CEO Amit Kumar, each company stands to receive royalties and milestones under the deal. The deal does not include any upfront fees and involves no equity, he added.

Last July, Kumar told RNAi News that CombiMatrix was planning to advance the two IrsiCaixa siRNA sequences into in vivo testing and develop an appropriate delivery method for a related HIV therapeutic (see RNAi News, 7/23/2004).

But the delivery issue appears to have been too great a hurdle for CombiMatrix, which has opted to hand off its HIV IP to Benitec in order to be able to gain access to that company’s expressed-RNAi technology for use in an area where it already has much invested: injuries and diseases associated with unconventional weaponry such as biological agents.

“As we evaluated our program [to develop an HIV drug], we realized that there are a number of things that need to happen including [developing] methods for delivery,” Kumar told RNAi News this week. “CombiMatrix has realized that we can’t do it all ourselves,” he said. “So we’ve decided that we want to establish a number of partnerships and … we felt [Benitec] had a lot more experience” in both HIV and RNAi delivery.

Kumar said that although CombiMatrix’s in-house RNAi drug activities include work in the inflammatory and anti-apoptosis areas, and that its hepatitis C research with IrsiCaixa is continuing, these programs are still in their infancy. As such, the company’s primary focus in terms of RNAi is its effort to develop treatments for conditions resulting from unconventional warfare.

Commenting on the rationale behind this work, Kumar said that while acute exposure to radioactive, biological, or chemical agents often results in death, many people also become sick and die from the secondary effects of such exposure.

“There are a number of physiological mechanisms that get indirectly turned on as a result of acute exposure, and those have to do with various apoptotic mechanisms [and] inflammatory responses,” he explained. “We feel we have an approach to inhibit those secondary responses, thus enabling those individuals — soldiers, most likely — to survive” if immediate exposure does not kill them.

He noted that in addition to RNAi, CombiMatrix is exploring the use of small molecules for this purpose.

CombiMatix already has established a foothold in the unconventional warfare area, having received about $10 million in commitments from the US Department of Defense through 2006 to develop chemical and biological agent detection technology. CombiMatrix has received about $4.5 million of this funding already. The company hopes this work will give it a higher profile when it looks to secure additional government monies to support the development of RNAi compounds that might be of interest to the DoD.

As for Benitec, the deal with CombiMatrix puts another arrow in the company’s quiver of possible RNAi-based HIV treatments.

Currently, the company is working with the City of Hope to develop an HIV/AIDS therapy that involves transducing stem cells — taken from patients with AIDS lymphoma — with vectors containing three components: DNA that encodes for shRNAs targeting the tat-rev exon, a ribozyme that cleaves the mRNA for CCR5, and a nucleolar-localizing TAR decoy (see RNAi News, 9/3/2004). Benitec hopes to begin a phase I trial of this therapy in mid- to late-2005.

Benitec is also working with the City of Hope to develop a T-cell-based immunotherapy for AIDS that could be used on patients for whom highly active anti-retroviral therapy is not an option. This effort involves transducing T-cells with the same vector from the AIDS lymphoma program. Benitec announced this week that this work will be funded through phase I by a portion of a $7.5 million grant awarded to the City of Hope by the National Institutes of Health.

The sequences licensed from CombiMatrix, however, target conserved regions of HIV not addressed by the vector being using in Benitec’s other HIV programs, Benitec CEO Sara Cunningham told RNAi News this week. These sequences would likely be used in conjunction with a non-viral delivery mechanism to target multiple regions of HIV at once, she added.

“This would be a next-generation” HIV treatment, Cunningham noted.

Cunningham and Kumar both stressed that the cross-licensing agreement signed by Benitec and CombiMatrix is expected to be just the first of many deals between the companies — which incidentally share a scientific advisor in Stanford University School of Medicine’s Mark Kay. (Kay and Cunningham co-founded RNAi drugs firm Avocel, which was acquired by Benitec last May [see RNAi News, 5/21/2004].)

“From the outside, it may seem like an odd partnership, but there’s actually a very good synergy between the two companies,” Cunningham said. “We hope this [relationship] will develop to where we can complement one another’s drug-discovery capability with drug-development capability.”

The companies said that they intend on collaborating in the future on using CombiMatrix’s CustomArrays to study the possible off-target effects of RNAi therapeutics. Cunningham also said that the companies may possibly strike an arrangement in the hepatitis C field.

“There are a number of things we have discussed doing together — some very involved, and some without a lot of work together,” Kumar added. “I think we anticipate [that] we will continue to be working and looking at ways of leveraging each others’ strengths. We hope there will be a whole bunch of other things [to announce] that we have discussed already but have not consummated at this point,” he said.

“We’ll see where it all takes us, but this is the beginning of a long and, hopefully, mutually rewarding relationship,” Kumar added.

— DM


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