Delivering loaded liposomes

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VANCOUVER—April 17, 2007—At the annual meeting of the American Association for Cancer Research in Los Angeles, Alnylam Pharmaceuticals announced it will advance a systemically delivered RNAi therapeutic, ALN-VSP01, for treatment of liver cancer and potentially other solid tumors. The product was developed as part of a collaboration between Alnylam and Inex Pharmaceuticals, which is now eligible for milestone payments as the therapeutic moves through development.
VANCOUVER—Drug-delivery company Inex Pharmaceuticals and RNAi specialist Alnylam announced recently the signing of an exclusive research collaboration to combine the two technologies into better therapeutics. The liposomal work will be performed by Inex spin-off Tekmira Pharmaceuticals, which will leverage its Targeted Immunotherapy platform involving delivery of oligonucleotides encapsulated within liposomes.
"We have been working with many companies and actively investigating a variety of delivery strategies for systemic delivery of RNAi therapeutics," explains Barry Greene, Alnylam COO. "Liposomes have an established history as a delivery technology and are actually used in more than 12 FDA-approved products. We chose to work with Inex because they have long been a pioneer in the development of liposomal delivery systems for drugs in various classes."
The collaboration will evaluate the application of RNAi delivery to multiple therapeutic targets, including a protein involved in cholesterol metabolism. The present agreement builds off of research performed by Alnylam and another collaborator, Burnaby, British Columbia-based Protiva Biotherapeutics, which showed that systemic RNAi delivery could significantly reduce blood cholesterol levels. This work was recently published in Nature.
"Liposomes can provide a number of advantages for the systemic delivery of nucleic acids, including RNAi therapeutics," says Ian Mortimer, Inex's vice president of finance and CFO. "Inex's liposome technology protects against nuclease digestion and targets the appropriate cells or organs for the delivery of the payload to carry out its therapeutic function."
Frost & Sullivan analyst Giridhar Rao touched on this point in a December-2004 report on advances in RNAi technology. "Determining the most effective snippet of RNA for each gene of interest usually requires testing more than three to four different RNAi sequences," Rao says. "To test and compare any given RNAi sequence, researchers need to monitor and optimize RNAi purity, integrity, uptake and cell viability. The key is to attain optimal stability."
According to Greene, Inex will provide Alnylam with access to key technology and capabilities that further reinforce its leadership position in delivering RNAi therapeutics systemically and enhances Alnylam's product platform for RNAi therapeutics. Under the terms of the agreement, Alnylam has the option to take worldwide exclusive licenses to use Inex's liposomal technology for RNAi therapeutics directed to specific gene targets.
As such, the deal is just part of a larger effort by Alnylam to explore the liposomal delivery market and fits closely with its recent announcement of another research agreement with Massachusetts Institute of Technology professor Dr. Robert Langer (see E050618). Alnylam expects to advance a systemic program into the clinic within the next 18 to 24 months, Greene says, but the company is also actively investigating a variety of delivery strategies—both chemical modifications and a variety of formulations.
For Inex spin-off Tekmira Pharmaceuticals, however, this agreement may be even bigger as it potentially adds to the market clout of the nascent company.
"This collaboration with Alnylam builds on the technology that Tekmira will be developing and gives Tekmira participation with Alnylam in the very promising field of RNAi therapeutics," Mortimer says. "Tekmira will focus its efforts on developing its own products, such as INX-0167, and will complement these efforts with collaborations and partnerships where Tekmira can provide significant experience and technology to its partner." 

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