Introduction

The IMUNON team is pioneering technologies that provide the foundation for a range of therapeutics for common, difficult-to-treat forms of cancer as well as technologies for the development of DNA vaccines against infectious diseases and cancers. We are committed to developing innovative treatments that harness the body’s natural mechanisms to generate safe, effective, and durable responses across a broad array of human diseases.

TheraPlas™ is a novel, nonviral delivery system for the development of immunotherapies and other anti-cancer nucleic acid-based therapies.

PLACCINE is a novel platform for the development of nucleic acid vaccines for infectious diseases and cancer that leverages a multivalent approach to generate a robust humoral immune response as well as a robust and durable T-cell response.

TheraPlas™

TheraPlas™ is a technology platform that can deliver nucleic acid-based therapeutics via novel synthetic delivery systems that are independent of viral vectors or devices. Capable of providing cell transfection with double-stranded DNA plasmids as well as large therapeutic RNA segments, it represents a novel approach to improving the safety and efficacy of gene-based therapies.

A distinct, viable alternative to current gene delivery approaches

There are 2 components of the TheraPlas system: a plasmid DNA (pDNA) or an mRNA payload encoding a therapeutic protein or peptide, and a delivery system. Based on a chemically modified low-molecular-weight polymer, the delivery system is designed to protect the DNA/RNA from degradation and promote trafficking into cells and through intracellular compartments. Biocompatibility of the polymers reduces the risk of adverse immune reactions, allowing for repeat administration. Compared to naked DNA or cationic lipids, TheraPlas is generally safer, more efficient, and more cost effective.

The design of the TheraPlas delivery system is based on molecular functionalization of polyethyleneimine (PEI), a cationic delivery polymer with a distinct ability to escape from the endosomes, due to heavy protonation at acidic pH. The transfection activity and toxicity of PEI is tightly coupled to its molecular weight, heretofore limiting its clinical application. We have used molecular functionalization strategies to improve the activity of low-molecular-weight PEIs without augmenting their cytotoxicity

Another approach to improve PEI activity involves crosslinking low-molecular-weight PEIs through degradable linkages, to create larger and degradable structures. Two cross-linked polymers have been synthesized with this approach and optimized for transfection activity. Both cross-linked polymers expressed several-fold higher transfection activity than their respective monomers and lower cytotoxicity than a commercially available 25kDa polymer.

Products utilizing TheraPlas: GEN-1

GEN-1 is the first product designed using the TheraPlas platform technology. GEN-1 works by instructing the body to produce safe and durable levels of powerful cancer fighting molecules, such as interleukin-12 (IL-12) and interferon gamma (IFN-γ), at the tumor site. It is a gene therapy that combines TheraPlas with a plasmid DNA encoding IL-12. Its nanoparticle profile enables cell transfection followed by persistent, local secretion of the IL-12 protein at therapeutic levels while avoiding the toxicities associated with recombinant IL-12.

GEN-1 is currently being evaluated in clinical programs as a treatment for patients with advanced ovarian cancer

PLACCINE

IMUNON are conducting pre-clinical proof-of-concept studies to validate our PLACCINE nucleic acid vaccine platform and its application to the development of vaccines against infectious diseases using a plasmid DNA vaccine construct targeting SARS-CoV-2 virus.

We are pursuing a multivalent approach to vaccines in an effort to generate robust immune responses that not only result in a strong neutralizing antibody response, but also a more robust and durable T-cell response. The PLACCINE platform is designed for multiple antigens or variants and in some instances, in conjunction with a potent immune modifier(s) to improve the quality of humoral and/or cellular responses.

 

IMUNON’s approach for proof-of-concept of the PLACCINE platform utilizes a vaccine design comprising a single plasmid DNA molecule containing the sequence encoding more than one of the SARS-CoV-2 spike antigen variants. Delivery is currently being evaluated intramuscularly (IM) with a non-viral synthetic DNA delivery carrier that facilitates pDNA delivery into the cells of the injected tissue and has potential immune adjuvant properties. Future iterations may include immune system modifiers, such as cytokines or chemokines, to further enhance durable immunogenicity. Unique designs and formulations of IMUNON’s vaccine candidates offer several key advantages as outlined below.

  • Durability of protection: Durable antigen expression induces robust immunological response
  • Breadth of protection: Multicistronic vectors increase the breadth of immune response and allows for combination vaccines
  • Transmission advantage: Option for co-expression of potent immune modifiers increases the immune response and lowers the risk of viral shedding
  • Safe and convenient: Synthetic delivery systems present no risk of genotoxicity or cytotoxicity. No need for a device. Convenient handling for pandemic control.
  • Flexible Manufacturing: Truly versatile platform enables rapid response to changing pathogens. Stability at normal refrigerator temperatures simplifies handling and distribution.