While oligonucleotide-based drugs have demonstrated significant promise, the ability to unlock the ultimate potential of this therapeutic approach has been limited by key delivery challenges.
Limitations of Conventional Delivery Technology
Oligonucleotides are associated, with high instability, low bioavailability, and poor cellular uptake, making their delivery to targeted cells/tissues in the body a significant challenge.
NapaJen’s Targeted Delivery Solution
To address these challenges and harness the full promise of this drug class, NapaJen has developed a novel immune cell-targeted oligonucleotide delivery technology.
Embracing Innovative Science to Unlock a Potential of Oligonucleotide
NapaJen’s drug delivery system (DDS) technology is the world’s first platform capable of selectively and efficiently delivering nucleic acids to target immune cells, unlocking the potential of oligonucleotide drugs for a range of immune-related therapeutic areas including immune disease, cancer, transplantation, and infectious disease
Technology Platform Overview
Oligonucleotide drug development has generated great excitement as a therapeutic modality that uses nucleic acids such as RNA to impact disease causing processes within the body. However, the development of oligonucleotide drugs has been significantly limited by the challenge of safely and efficiently delivering nucleic acids to target organs and cells.
The NapaJen Solution
To address this challenge, NapaJen is developing proprietary oligonucleotide drugs by leveraging its unique DDS technology that is able to deliver nucleic acid-based drugs to target immune cells for the first time. NapaJen’s DDS technology is built upon schizophyllan (SPG), a beta-glucan that specifically binds to Dectin-1, a cell surface receptor expressed on antigen presenting immune cells, such as dendritic cells and macrophages. By complexing oligonucleotides with SPG, NapaJen’s delivery platform enables the efficient and selective delivery of oligonucleotides to cells playing key roles in regulating immune responses.
To date, the company’s DDS technology has demonstrated:
- Efficient delivery of oligonucleotide drugs to target cells
- Advantageous safety profile highlighted by demonstrated lack of toxicity at the highest dose evaluated in non-human primate studies, as well as ongoing first-in-human clinical trial
First Approach for the Prevention of Acute Immune Diseases
NJA-730, NapaJen’s lead program, is designed for the prevention of acute immune diseases associated with bone marrow transplants, such as acute graft-versus-host disease (GvHD). The novel oligonucleotide drug candidate targets CD40, a protein that is found on antigen-presenting immune cells and triggers their activation. By selectively and efficiently silencing the activity of CD40, NJA-730 is expected to prevent the body’s immune response to organ transplantation.
NJA-730 Development Program:
NapaJen has completed dosing of all subjects in its Phase 1 study in Australia, with no reporting of dose-limiting toxicities or other noteworthy findings at any evaluated doses. The company intends to initiate a proof-of-concept Phase 2 clinical trial of NJA-730 in acute GvHD in 2021 in both United States and Australia.
Results from a preclinical study in an animal model of hematopoietic stem cell transplantation demonstrated statistically significant improvements in mouse survival rate up to 45 days following administration of a single injection of NJA-312, a murine orthologue of NJA-730 as compared to the vehicle control, suggesting the treatment’s potentially preventative nature in GvHD.
While NJA-730 is initially being developed as a prophylaxis for acute GvHD, evaluation of the compound has the potential to be expanded to several other inflammatory immunoreactive conditions.
GvHD is an immune reaction by which donor lymphocytes originating from organ transplantation attack patients as heterogenous, potentially resulting in a range of damaging health impacts. It can take the form or acute GvHD which occurs in the weeks immediately following transplantation, or chronic GvHD, which occurs several months post-transplantation and is typically less serious than acute GvHD.
Current preventative therapies for acute GvHD sometimes induce relapse of malignancies or infections in patients. As such, there is a critical unmet need for novel GvHD therapeutics capable of safely preventing the disease.
Creating the Future of TLR9 Agonists, Today
NapaJen is developing Napa9-SPG, a potent toll-like receptor 9 (TLR9) agonist, as a novel immuno-oncology drug, as well as a new potent vaccine adjuvant with potential applications against SARS-CoV-2, the novel coronavirus. The compound is currently in preclinical development.
TLR9 agonists have been shown to activate immune cells and combat the protective immunosuppressive microenvironment that many cancers create around tumors. These mechanisms are complementary to many cancer therapies, supporting the belief that Napa9-SPG may result in synergistic anti-tumor effects when used in combination with checkpoint inhibitors and/or cancer immunotherapies such as cancer vaccines.
In both in vivo and in vitro preclinical studies, Napa9-SPG has demonstrated greater IFN-α induction potency when compared to multiple competing other TLR9 agonists. Additional preclinical findings highlight the ability of Napa9-SPG to potently activate cytotoxic lymphocytes to kill antigen-specific cells.
Vaccine Adjuvant Application:
TLR9 agonists have generated significant excitement as potential vaccine adjuvants based on their proven ability to stimulate humoral and cell-mediated immunity. Preclinical research has demonstrated that Napa9-SPG possesses more potent immunostimulatory activity than other TLR9 agonists, potentially positioning the compound as a best-in-class TLR9 agonist vaccine adjuvant. The company is continuing its preclinical development of Napa9-SPG as a potential vaccine adjuvant and expects to conduct early-stage clinical trials in combination with various vaccine candidates, including those for SARS-CoV-2.