The data were presented at the Informa Life Science 11th Annual Conference, EuroTIDES, taking place in Barcelona, Spain, as part of a presentation entitled "UsiRNAs and DiLA2-based delivery for RNAi Therapeutics in Oncology," by Michael V. Templin, Ph.D., Senior Vice President of Preclinical Development at Marina Biotech.
"This achievement is a testament to the success of our in-house exploratory efforts as well as experience and knowledge we've gained from our early collaborative efforts," stated J. Michael French, President and CEO of Marina Biotech. "This breakthrough in our delivery capability further strengthens our RNAi drug discovery platform as well as our continuing discussions with potential pharma partners."
Researchers at Marina Biotech identified new DiLA2-based formulations composed of multiple DiLA2 molecules, that when paired with a UsiRNA targeting FVII mRNA in liver (hepatocytes) of mice, provided 50% inhibition (ED50) of FVII protein activity with a single systemically delivered dose of approximately 30 micrograms/kg. In comparison, previous formulations provided ED50's of approximately 300 micrograms/kg. This effective dosing was accompanied by an approximately 30-fold therapeutic window.
"This advancement in siRNA delivery efficiency, and the speed at which we were able to achieve it, validates our research team's approach of integrating chemistry, molecular pharmaceutics, and biology to address the challenges of siRNA delivery, and continues to demonstrate the utility and diversity of our DiLA2 delivery platform," stated Barry Polisky, Ph.D., Chief Scientific Officer of Marina Biotech. "Our team has established a set of assays and a systematic approach to explore the large formulation space provided by the DiLA2 platform. It was through this systematic approach that we were able to quickly achieve 10-fold improvements in delivery efficiency over a three month period. We expect to further enhance the delivery capabilities of the platform, in particular, the identification of formulations for oncology specific indications."
Effective delivery is one of the key challenges for the development of RNAi-based therapeutics, and Marina Biotech is a leader in siRNA delivery with its proprietary DiLA2 delivery platform and extensive research expertise in formulation screening and process development. The versatility of the DiLA2 platform provides for a rapid and scientifically robust process for improving the delivery characteristics of novel formulations to meet the specific requirements of a particular therapeutic application, i.e., administration via systemic or local delivery. In recent months, advanced and improved DiLA2-based delivery formulations have been developed by expanding our delivery capabilities to include both ionizable and amphoteric compositions. The ionizable compositions are based on DiLA2 molecules that demonstrate a pH-dependent phase transition across the physiological pH range to enable effective siRNA delivery inside the cell. Amphoteric compositions rely on the combination of a DiLA2 molecule and another component, to mediate this pH-dependent transition. In addition to research advancements, the development teams at Marina Biotech are focused on the long term commercial requirements for RNAi-based therapeutics such as scale-up, manufacturing and cost-of-goods.