Canadian firm hopes to file for IND approval to start clinical trials with TKM-Ebola in 2011.

Vancouver-based Tekmira Pharmaceuticals has negotiated a new license to Alnylam Pharmaceuticals’ InterfeRx™ technology for the development and commercialization of an RNAi therapeutic against Ebola virus infection. Tekmira says it now has broad access to Alnylam’s IP for the development of eight RNAi therapeutics. Financial aspects of the latest agreement include the payment of royalties to Alnylam on future sales of the marketed Ebola virus product.

Tekmira’s development of the currently preclinical-stage TKM-Ebola candidate is being funded through to commercialization by a $140 million U.S. government contract, signed earlier in 2010. Tekmira hopes to file an IND application with FDA during the second half of 2011, to enable the start of clinical trials.

TKM-Ebola exploits Tekmira’s LNP (lipid nanoparticle) siRNA encapsulation and delivery platform, which the firm is harnessing for the systemic delivery of variety of nucleic acid molecules such as siRNA. In July the firm was awarded up to a $140 million from the U.S. government’s Transformational Medical Technologies (TMT) program to advance TKM-Ebola. The initial phase of the contract provides for up to $34.7 million over the next three years for development of TKM-Ebola through preclinical development, and IND filing to the completion of a Phase I safety trial.

Tekmira’s early clinical lead candidate, TKM-ApoB, is being developed for the treatment of hypercholesterolemia. The product comprises an ApoB-silencing siRNA delivered using Tekmira’s LNP technology. Having completed an initial Phase I trial at the start of 2010, Tekmira is now continuing development of the ApoB candidate by selecting a new siRNA payload and evaluating new LNP formulations for TKM-ApoB.

A second candidate, TKM-PLK1, is being developed for the treatment of cancer. Tekmira says it has selected gene targets for its oncology applications that will act in synergy with conventional drugs.  TKM-PLK1 targets the PLK1 (polo-like kinase 1) protein, which is involved in tumor cell proliferation. The firm suggests TKM-PLK1 has the potential to result in both direct tumor cell killing and sensitization of tumor cells to the effects of chemotherapy drugs. Phase I trials are expected to start by the end of 2010.

LNPs are particularly well suited for the delivery of siRNA to treat cancer because the lipid nanoparticles preferentially accumulate within tissues and organs having leaky blood vessels, such as tumors, Tekmira claims. Once at the target site, LNPs are taken up by tumor cells, and the siRNA payload is delivered inside the cell where it reduces expression of the target protein.

Tekmira and Alnylam have a somewhat reciprocal licensing agreement. Alnylam has access to Tekmira’s LNP technology for the delivery of RNAi therapeutics, and Tekmira has rights to develop a number of RNAi therapeutics based on access to Alnylam’s intellectual property.

In April, 2009, Alnylam initiated a Phase I clinical trial with ALN-VSP, an LNP delivery-based product for the treatment of advanced liver cancers. In July 2010 the firm started a separate Phase I clinical trial for another LNP-formulated product, ALN-TTR, for the treatment of transthyretin (TTR) amyloidosis.

The latest license agreement with Tekmira comes just 24 hours after Alnylam and Medtronic announced a collaboration with the nonprofit Huntingdon disease organization, CHDI Foundation, to advance ALN-HTT, a drug-device combination for the treatment of Huntington’s disease. ALN-HTT comprises an RNAi therapeutic targeting the huntingtin gene, using an implantable infusion system developed by Medtronic. Under this new collaboration CHDI has agreed to initially fund up to 50% of the IND application-enabling activities.

The agreement between Alnylam and Medtronic will remain as a 50-50 partnership in the U.S., with Medtronic commercializing the product. Alnylam does retain the opportunity to invest in clinical development of the product through to product launch in the U.S., in return for a proportional share of the profits. In Europe, Medtronic is solely responsible for development and commercialization, and Alnylam is eligible to receive milestones and royalties.

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