In May 2010, a series of studies demonstrating the ability of an RNAi therapeutic utilizing Tekmira’s LNP technology to protect non-human primates from the Ebola virus were published in The Lancet. Tekmira conducted the studies in collaboration with infectious disease researchers from Boston University and the United States Army Medical Research Institute for Infectious Diseases (USAMRIID). These studies were funded in part by the U.S. Department of Defense’s (DoD) Joint Project Manager Transformational Medical Technologies (JPM-TMT) Office. The results of these preclinical studies demonstrated that when siRNA – delivered by Tekmira's LNP technology – targeted the Ebola virus to treat previously infected non-human primates, the result was 100 percent protection from an otherwise lethal dose of Zaire Ebola virus (Geisbert et al., The Lancet, Vol 375, May 29, 2010).
In 2010, Tekmira signed a $140-million contract with the DoD to advance an RNAi therapeutic, which utilized our LNP technology, to treat Ebola virus infection. In 2013, the collaboration was expanded to include significant advances in LNP formulation technology, including a new LNP formulation that was more potent, the ability to be able to lyophilize (freeze-dry) LNP formulations and an LNP formulation that can be administered intravenously.
In March 2014, we were granted a Fast Track designation from the U.S. Food and Drug Administration (FDA) for the development of TKM-Ebola, our anti-Ebola viral RNAi therapeutic. The FDA's Fast Track is a process designed to facilitate the development and expedite the review of drugs in order to get important new therapies to the patient earlier.
TKM-Ebola is being developed under specific FDA regulatory guidelines called the “Animal Rule.” The Animal Rule provides that under certain circumstances, where it is unethical or not feasible to conduct human efficacy studies, the FDA may grant marketing approval based on adequate and well-controlled animal studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans. Demonstration of the product’s safety in humans is still required.
In January 2014, Tekmira commenced a Phase I clinical trial evaluating TKM-Ebola in healthy volunteers. The TKM-Ebola Phase I clinical trial is a randomized, single-blind, placebo-controlled study involving single ascending doses and multiple ascending doses of TKM-Ebola. The study will assess the safety, tolerability and pharmacokinetics of administering TKM-Ebola to healthy adult subjects.
In May 2014, Tekmira successfully completed the single ascending dose portion of the TKM-Ebola Phase I Clinical Trial in healthy human volunteers.
This study is now subject to a partial clinical hold. The partial hold requires Tekmira to provide additional data related to the mechanism of cytokine release and a potential protocol modification prior to initiating the multiple dose portion of the phase I study. The partial hold enables the use of TKM-Ebola in individuals with a suspected or confirmed Ebola virus infection.
The FDA granted expanded access use of TKM-Ebola under Tekmira’s Investigational New Drug application (IND) and Health Canada established a similar framework. Using emergency protocols, TKM-Ebola has been administered to a small number of patients.
The genomic sequence of Ebola-Guinea, the virus responsible for the outbreak in West Africa, was determined from several viral isolates and published in the New England Journal of Medicine. Tekmira developed a modified RNAi therapeutic to specifically target Ebola-Guinea. The new product, TKM-Ebola-Guinea, is designed to match the genomic sequence exactly, with two RNAi triggers. Results of preclinical studies with TKM-Ebola-Guinea demonstrated efficacy results comparable to those obtained with TKM-Ebola, which has demonstrated up to 100% protection from an otherwise lethal dose of the virus.
Tekmira has entered into a Manufacturing and Clinical Trial Agreement with the University of Oxford to provide the new TKM-Ebola-Guinea therapeutic product for clinical studies in West Africa. The studies are expected to commence in early 2015, subject to finalization of a suitable clinical protocol. The University of Oxford is the representative of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). ISARIC will conduct clinical studies of TKM-Ebola-Guinea in Ebola virus infected patients, with funding provided by the Wellcome Trust.
This work is being conducted under contract with the US Department of Defense's (DoD) BioDefense Therapeutics (BDTX), a Joint Product Manager within the Medical Countermeasure Systems (JPM-MCS) Joint Project Management Office. A component of the Joint Program Executive Office for Chemical and Biological Defense, JPM-MCS aims to provide U.S. military forces and the nation with safe, effective and innovative medical solutions to counter chemical, biological, radiological and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance our nation's biodefense response capability. For more information, visit www.jpeocbd.osd.mil.