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May 17, 2011

BMS Expands Deal to Evaluate Tekmira’s RNAi Delivery Technology

  • Tekmira Pharmaceuticals expanded its current multiyear collaboration with Bristol-Myers Squibb (BMS) to include evaluation of Tekmira’s newly developed lipid nanoparticle (LNP) formulations designed for delivery to tumors and other tissues outside the liver. In addition, the two companies are expanding ongoing target validation work.

    “We have been successfully collaborating with Bristol-Myers Squibb for several years,” comments Mark J. Murray, Ph.D., Tekmira’s president and CEO. “Last year, we signed a multiyear target validation agreement under which Tekmira provides Bristol-Myers Squibb with LNP formulations designed to validate the function of certain genes.

    “We are now expanding that work to include further evaluation of Tekmira’s proprietary LNP technology to identify formulations capable of targeting tumors and certain tissues outside of the liver. The new work also includes additional cellular targets that were beyond the scope of the original agreement,” Dr. Murray adds. “Bristol-Myers Squibb will continue to share the data from this research with Tekmira.”

    Under the original target validation agreement, BMS paid $3 million to use siRNA molecules formulated by Tekmira in LNPs to silence target genes of interest. BMS is conducting the preclinical work to validate the function of certain genes and is sharing the data with Tekmira. Bristol-Myers Squibb will have a first right to negotiate a licensing agreement on certain RNAi products developed by Tekmira that evolve from gene targets that it validates.

    Tekmira’s LNP technology (formerly referred to as stable nucleic acid-lipid particles, or SNALP) encapsulates siRNAs in uniform lipid nanoparticles that have demonstrated the ability to deliver RNAi therapeutics to disease sites in preclinical models. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.

    The technology relies on the enhanced permeability and retention effect, which occurs because these nucleic acid-containing particles have a long circulation time in the blood. This results in increased accumulation at sites of vascular leaks, such as those found at sites of tumor cell growth, infection, or inflammation. Once at the target site, cells take up the LNP through endocytosis and the nucleic acid payload is delivered inside the cell.

    Besides BMS, Tekmira has partnerships focused on using its LNP delivery technology with Alnylam Pharmaceuticals, Pfizer, Roche, and Takeda Pharmaceuticals. While Pfizer, Roche, and Takeda’s work is at the discovery-to-preclinical stage, Alnylam has two clinical-stage candidates that use Tekmira’s platform.

    ALN-VSP is in Phase I as a treatment for patients with advanced solid tumors with liver involvement including hepatocellular carcinoma. ALN-TTR is also in early-stage clinical trials for TTR amyloidosis. Alnylam also has a third LNP formulation candidate; ALN-PCS is in preclinical development for hypercholesterolemia.

    Tekmira is conducting a Phase I trial with its TKM ApoB (previously ApoB SNALP) in patients with high LDL cholesterol. Also in development by Tekmira is cancer drug TKM PLK1 for cancer and TKM Ebola, both in preclinical studies.


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