Arcturus Therapeutics

Technologies

We believe our two proprietary technology platforms solve major hurdles in nucleic acid medicine development such as
delivery challenges, limited potency, and narrow therapeutic index.

LUNAR

Our first platform is a novel lipid-mediated delivery system called Lipid-enabled and Unlocked
Nucleomonomer Agent modified RNA (LUNAR®). LUNAR is a multi-component drug delivery system that is versatile and
with our library of over 150 proprietary lipids, diverse. Our preclinical studies have shown that formulations can
be customized for the indication and target cell type of interest. We have also demonstrated that our formulation
process is scalable and reproducible.

 

LUNAR-mediated delivery of RNA into cells

LUNAR particles associate with the cell membrane of a target cell of interest and quickly enter the cell via endocytosis.

Upon entering the cytosol, the LUNAR formulations then become trapped in the endosomes.

With increased acidity as the endosome ages, a pH-mediated disruption enables release of the nucleic acid payload following rapid biodegradation of the LUNAR components.

Once release of the RNA into the cytosol occurs, the translational machinery can interact with the nucleic acid and processing and/or trafficking can then take place to make functional protein.

Benefits of LUNAR

  • LUNAR delivery technology is not limited to a specific nucleic acid modality. Preclinical studies have
    demonstrated compatibility with different types of nucleic acids, from short double-stranded siRNAs, to long
    single-stranded mRNAs, to double-stranded DNA molecules. This means that we are not restricted in the types of
    nucleic acid medicines that we can develop.
  • LUNAR delivery technology is compatible with multiple routes of administration and can be targeted to diverse
    tissues and cell types. Preclinical studies in both rodents and non-human primates have shown that LUNAR can
    deliver nucleic acid compounds specifically to hepatocytes, to liver stellate cells via intravenous injection,
    muscle cells via intramuscular injection, and lung cells via nebulization.
  • LUNAR can deliver mixtures of different nucleic acids as one drug product. LUNAR can potentially deliver
    mixtures containing multiple nucleic acids to target cells in vivo, as we previously demonstrated for a
    combination of three HBV-targeting siRNAs which was efficacious in multiple mouse models of HBV infection.
  • Ability to repeat dose. Multiple preclinical studies in rodents and non-human primates have shown no reduction
    in efficacy upon repeat dosing of LUNAR formulated siRNA or mRNA. We believe this indicates that LUNAR-delivered
    nucleic acids do not elicit antibody or cell-mediated immunity that can reduce potency upon repeat dosing.

 

UNA

Our second platform is a novel oligonucleotide chemistry technology called Unlocked Nucleomonomer Agent (UNA). UNA can
be used to reduce off-target effects and increase duration of action in siRNA medicines.

UNA

 

  • Arcturus’ UNA oligomer chemistry can improve the in vivo efficiency of small interfering RNA (siRNA)-mediated
    gene silencing and potentially improve the efficiency of messenger RNA (mRNA)-mediated protein replacement.
  • One or more UNAs can be positioned strategically along a nucleic acid strand to manipulate the chemical
    properties of the molecule. Addition of a single UNA in siRNA therapeutics can enable more efficient suppression
    of target protein production and reduce off-targets effects.

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