Tekmira Expands Biodefense Efforts to Cover Both Ebola and Marburg Virus

Following the successes with its Ebola biodefense program, Tekmira has started to present increasingly promising data for treating a related filovirus, the Marburg virus.  With 100% survival rates in non-human primate models and new RNAi triggers that should cover a broad spectrum of strains and possibly related viruses, the company is well positioned to also take away the Marburg indication from competitor Sarepta which in turn has become preoccupied with its exon-skipping drug candidate for DMD.  

For the Ebola program alone, the $100M market cap company estimates that the successful development of a drug under the so called Animal Rule could result in stockpiling orders from the US government worth about $100M annually.

From guinea pigs...

In a publication last month, Tekmira and their collaborators from the UTMB in Galveston, Texas, reported the successful treatment of guinea pigs infected with a number of different strains of the Marburg virus.  Because the development of treatments for rapidly mutating viruses and viruses with a multitude of divergent strains is hampered by sequence diversity, a broader strain coverage was achieved, like in Tekmira’s Ebola approach or in Arrowhead’s chronic HepB strategy (ARC520), through the concurrent use of two siRNAs in a single formulation.

Given that rodents have limited predictiveness for anti-filoviral efficacy in Man and given that the formulation was apparently a 1^st generation D-LinDMA-based SNALP, I was not all that excited about the publication due to the apparent early stage of development.

...to non-human primates

In a positive surprise therefore, the Chief Scientific Officer of the company, Ian MacLachlan, presented gold standard non-human primate data of SNALP RNAi Therapeutics for Marburg virus at the ongoing OligoDIA regulator-industry conference.  Accordingly, Tekmira’s newer LNP formulations (‘SNALP-G’) were shown to fully protect monkeys from death due to Marburg infection when given at 0.5mg/kg (=the magic safety threshold for SNALP).

As an important comparison, Sarepta last year reported ‘83% to 100%’ protection rates in comparable models when treatment was initiated up to 96 hours after infections with its newer PMOplus morpholino chemistry.   It is therefore of interest to test the impact of further delaying treatment with SNALPs.

As I have been following Tekmira’s biodefense program over the years, one development I noticed, especially in the era of budget cuts, was the apparent push by the Department of Defense for biomergency treatments that can address not just multiple strains of a virus, but multiple viruses all-in-one.  Intriguingly, one of the bullet points in Tekmira’s slide presentation on goals for the Marburg program (slide 36) talks about the ‘Design broad spectrum siRNA to target multiple MARV and Ebola’.  Does this mean that the ultimate prize here are stockpiling contracts for a single drug addressing both Marburg and Ebola?

Having a better ear for and adjusting to the needs of the DoD is also one reason why I believe Tekmira will continue to have the upper hand over competitor Sarepta with its DMD distractions and an investor base that could not care less about the Marburg program.  Although the targets were explicitly not disclosed, I wonder whether there are host factors one could target and which would be beneficial for various viral applications.  This would be an alternative to trying to come up with target sequences that are conserved across the viruses.

Finally, serving as yet another example of illustrating the value of biodefense contracts for platform technology companies, Tekmira disclosed plans that a first clinical trial with a lyophilized SNALP formulation, TKM-EBOLA, is planned for the first quarter of 2014.