Science & Technology

Success of RNA therapeutics requires optimal delivery to the site of disease

NEED™ Delivery Platform

The NEED™ Delivery Platform — a revolutionary non-LNP formulation system enabling respiratory drug delivery of therapeutics. This cutting-edge platform marks a significant advancement in treating life-threatening respiratory diseases by enabling a precision-targeted oligonucleotide delivery that aligns seamlessly with the body’s own biological pathways, thereby minimizing toxicity risks.

Our technology represents a pivotal engineering breakthrough, providing a robust and effective delivery mechanism crucial for therapeutic success. The NEED™ platform is crafted from components that are not only scientifically verified but also have established applications in human airway treatments. 

A key feature of our platform is its capability to integrate smoothly with an aqueous phase, forming a nano-emulsion that is naturally compatible with respiratory tissues. This unique property not only bolsters the stability of therapeutic agents but also increases the adaptability of the platform. It enables the NEED™ technology to cater to a diverse spectrum of therapeutic requirements, enhancing both the efficiency and effectiveness of treatments. The versatility of the NEED™ technology is demonstrated through its successful application in both topical lung and nasal treatments as well as systemic delivery across various types of nucleic acids. 
NEED™ Delivery Platform
  • High delivery efficiency to nose and lung 
  • Safe and well tolerated in human epithelium
  • Rapid uptake and cellular retention
  • Aerostability demonstrated with conventional nasal sprays and nebulizers 
  • Payloads including RNA, DNA and small molecules
  • Low immunogenicity
  • Phase 1 ready nasal and inhaled formulations

Delivery of RNA Therapeutics

          Critical success requirements for delivery

  • High transfection efficiency (endosomal uptake and escape) 
  • Formulation optimized for lung retention 
  • Formulation can be applied to a diverse and broad range of payloads 
  • Formulation tolerates shear stress post-aerosolization 
  • Good tolerability and safety for acute and chronic applications 

NEED™ proprietary non-LNP nano-emulsion platform overcomes the limitations of LNPs

Lipid Nanoparticle (LNP) Platforms 
RIGImmune Nano-Emulsion 
Ionized LNP cationic lipids interacts with endosomal membranes which destabilizes lipid bilayers resulting in membrane disruption and endosomal escape of the LNP into the cytoplasm
Surfactant based delivery system promoting endosomal escape over a wide range of RNA payloads. Suitable for delivery to other epithelial surfaces including eye and skin. 
Less than 2% of RNA-based LNPs that are taken up by the cell release their cargo into the cytosol.
Safe and well tolerated in human epithelium (non-endolytic nano emulsion) resulting in rapid uptake and cellular retention 
Cholesterol and the PEG-lipid in LNPs contribute to the stability of the drug product while the phospholipid required for fusogenicity
High transfection efficiency (nano-emulsion greater than ~10 fold versus buffer only) 
LNPs are directly toxic to lung epithelium and can induce activation of the immune system resulting in complement activation-related pseudo allergy (CARPA), an acute immunological response
GRAS excipients only with long experience of human safety with respiratory tract delivery 
LNPs are subject to shear stress after aerosol delivery and unable to maintain particle integrity
Maintain particle integrity after nasal spray and aerosol delivery 
Predominantly deliver mRNA cargo to liver and spleen
Phase 1 ready nasal, inhaled and subcutaneous formulations 
 

Broad Therapeutic Applications

The potential of RIGImmune’s NEED™ Delivery Platform extends far beyond respiratory therapies. This versatile platform is poised to transform treatment paradigms across various medical fields where targeted nucleic acid delivery is crucial. Our ongoing research and development initiatives are dedicated to unlocking the full capabilities of the NEED™ platform. The platform is adept at handling a diverse range of payloads including RNA, mRNA, and DNA, demonstrating its capability to cater to a broad spectrum of therapeutic needs.             

RIG-101 & RIG-I Pathway

The lead product development candidate, RIG-101, a RIG-I agonist formulated with the NEED™ technology and delivered by the intranasal (IN) route, is advancing through IND-enabling activities for a clinical program designed for the prevention of asthma exacerbations caused by viral respiratory infections in at-risk patent populations. RIG-101 is specifically designed to prevent infections caused by a broad range of RNA viruses including Human Rhinovirus (HRV), RSV, influenza, and SARS-CoV-2.  IN NEED™ formulation delivers RIG-101 directly to the site of replication in the nasopharynx, thus preventing viral infection and providing a pan-viral profile.

RIG-I activation by RIG-101 triggers and increases the speed of a multi-faceted immune response and preclinical data has shown RIG-101 to be effective in prevention of asthma exacerbations caused by existing and emerging RNA viruses, most notably HRV.