Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, announced that data demonstrating its ongoing lipid nanoparticle (LNP) technology innovations and manufacturing related advancements were presented at the 15th Annual TIDES Summit: Oligonucleotide and Peptide® Therapeutics from Research through Commercialization taking place in Boston, MA today.
"We are excited about the progress being made by Tekmira scientists, who are leading the continued innovation of LNP delivery to enable the field of RNAi therapeutics. Tekmira's presentation at the TIDES Summit highlights some of the recent innovations we have made surrounding our LNP technology platform, such as industry-leading LNP potency and new lyophilized formulations that maintain the potency of the liquid formulations. In addition, we are presenting data for the first time with formulations administered subcutaneously that further demonstrate our leadership in enabling RNAi therapeutics," said Dr. Mark J. Murray, Tekmira's President and CEO.
TKM-Ebola, an anti-Ebola viral therapeutic, is being developed under a contract with the U.S. Department of Defense's (DoD) Joint Project Manager Transformational Medical Technologies (JPM-TMT) Office, with a total contract value of approximately $140 million. Earlier preclinical studies were published in the medical journal The Lancet and demonstrated that when siRNA targeting the Ebola virus and delivered by Tekmira's LNP technology were used 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).
Tekmira's productive collaboration with the JPM-TMT was recently modified and expanded to include significant advances in LNP formulation technology since the initiation of the program in 2010. Some of the innovations highlighted in Tekmira's session at the TIDES Summit include:
A new formulation, more potent than any LNP currently in clinical trials, is being incorporated into the TKM-Ebola program. This new TKM-Ebola LNP formulation has demonstrated significant increases in potency in non-human primates infected with the Zaire Ebola virus. At 0.5 mg/kg, 100% of the infected animals survived after receiving TKM-Ebola daily for seven days. The previous LNP formulation provided the same level of protection and 100% survival at 2 mg/kg.
Tekmira scientists have developed a lyophilized (freeze-dried) LNP to eliminate cold-chain requirements and facilitate use in tropical climates. Importantly, the lyophilized LNP formulation also provided 100% survival in non-human primates infected with the Zaire Ebola virus with no loss in potency at 0.5 mg/kg dosed daily for seven days. At 0.2 mg/kg, 67% of infected non-human primates survived.
Tekmira has also been working on LNP formulations that can provide significant potency when administered subcutaneously. Tekmira presented data demonstrating that LNP administered subcutaneously in a rodent model can knockdown a liver target by 96% at 1.0 mg/kg with a single administration or 67% knockdown at 0.5 mg/kg after a single administration. Tekmira believes this potent knockdown in the liver after subcutaneous administration compares favorably to other published data using conjugate delivery systems.
Tekmira continues to build upon its leadership position and invest in its RNAi technologies by making advancements in LNP potency, tolerability, biodistribution, targeting, process development, and manufacturing, as well as the evaluation of new RNAi payloads. These LNP innovations will support the advancement of multiple RNAi therapeutics — from both Tekmira and its partners — that address a wide variety of disease indications.