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Tekmira Presents Results Of Preclinical Studies With Hepatitis B Therapeutic

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Tekmira Pharmaceuticals Corporation (Nasdaq: TKMR) (TSX:TKM), a leading developer of RNA interference (RNAi) therapeutics, announced today the presentation of preclinical results characterizing TKM-HBV, a therapeutic agent targeting human hepatitis B virus (HBV), at the 10th Annual Meeting of the Oligonucleotide Therapeutics Society. Tekmira's Chief Technical Officer, Dr. Ian MacLachlan delivered a podium presentation titled, "Update on the Preclinical Development of an LNP-Based HBV Therapeutic." The conference is taking place in San Diego, California, from October 12 – 15, 2014.

Among the results reported is the potent and rapid reduction in hepatitis B surface antigen (HBsAg) demonstrated by TKM-HBV in several preclinical models including the chronically infected humanized (chimeric) mouse.

"These results reflect the rigorous approach we have taken to the design and characterization of our novel hepatitis B therapeutic," said Dr. Mark J Murray, President and CEO, Tekmira Pharmaceuticals. "TKM-HBV employs a unique combination of three RNAi triggers, in a third generation LNP formulation, which results in broad and effective knockdown of viral mRNAs and viral proteins including hepatitis B surface antigen, our primary therapeutic target. This data supports the utility of TKM-HBV as a new therapeutic option for treating patients with chronic HBV infection. Our plan is to file an IND, or equivalent document, by the end of this year, and initiate clinical trials in early 2015."

Key summary points from the presentation include:

Preclinical studies employed several well validated models including true-infection models that support the full viral replication/re-infection cycle and the production of covalently closed circular DNA (cccDNA).

In these models, TKM-HBV treatment resulted in rapid and potent reductions in both intrahepatic and serum HBsAg, as well as reductions in HBV DNA, cccDNA, HBeAg and HBcAg.

A rapid 1 log reduction in serum HBsAg was achieved with a single 1 mg/kg dose of TKM-HBV in the chronically infected humanized mouse model, which mimics human hepatitis B infection. 1-2 log viral reductions from similar single-dose LNP treatments in two other true-infection animal models have also been demonstrated.

Tekmira's data suggests inclusion of three RNAi triggers results in a more broadly effective knockdown of viral products than a single trigger alone.

By targeting three distinct and highly conserved sites on the HBV genome:

TKM-HBV is designed to achieve "universal" activity in chronic HBV patients infected with genotypes A through H. Studies conducted on infected primary human hepatocytes showed that TKM-HBV had robust and consistent activity against different viral strains representing the major clinical genotypes A, B, C and D.

TKM-HBV is designed to achieve a higher threshold against development of antiviral resistance. Preclinical investigation targeting the closely related woodchuck hepatitis virus suggests that the use of a single stand-alone RNAi trigger can result in viral resistance.

The mode of action of TKM-HBV complements standard of care nucleoside/nucleotide (NUC) therapy, and lack of drug antagonism has been demonstrated with entecavir, lamivudine and tenofovir on infected primary human hepatocytes.

The drug mechanism of action is well-understood and RNAi-mediated site-specific cleavage of viral mRNA by TKM-HBV has been confirmed using RLM-RACE sequence analysis.
A copy of Tekmira's presentation from the 10th Annual Meeting of the Oligonucleotide Therapeutics Society Meeting will be available on the Tekmira website on the "Events" section at:

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