February 2014
N4 Pharma was established
June 2014
Exclusive rights signed for Nuvec® for DNA and mRNA delivery
Following review of possible applications for UQ technology, N4 Pharma signs exclusive rights for the development of a delivery system for use in nucleic acid vaccine and therapeutics using UQ’s patent-pending technology.
January 2016
Exclusive rights signed for Nuvec® for DNA and mRNA delivery
Following review of possible applications for UQ technology, N4 Pharma signs exclusive rights for the development of a delivery system for use in DNA and mRNA vaccine and therapeutics using UQ’s patent-pending technology.
November 2016
Completed first set of in vitro experiments
Work with University of Queensland established optimum size and shape of Nuvec® particle as 180nm and using Polyethylenemine (PEI) to allow binding and release of pDNA for successful transfection.
June 2017
Established no toxicological effects from single high dose administration
A study to assess the systemic tolerability of the Nuvec® silica nanoparticles when administered as a high single dose via subcutaneous injection to rats found that Nuvec® did not cause any toxicological effects considered likely to be of long-term concern.
November 2017
Pre-clinical in vivo study identified localised protein expression
N4 Pharma conducts a study to determine the in vivo capacity for the company's silica nanoparticles to deliver DNA to generate local expression of a protein. It found that a single injection of the SiNPs is effective in delivering DNA to generate localised protein expression at the site of the injection and draining lymph nodes and release cytokines into the systemic circulation.
January 2018
Cellular mode of action confirmed
N4 Pharma completes studies for both pDNA and mRNA showing intracellular mode of action to release nucleic acid for protein expression.
November 2018
Cellular mode of action confirmed
Further analysis of the earlier pDNA OVA findings demonstrates that the immune response observed after 3 injections was sufficient to have produced strong levels of antibodies specific for OVA.
May 2019
Review of collaborative research projects identifies particle agglomeration
A review of collaborative research projects highlighted inconsistencies for in-vivo studies compared to in-vivo tests, most likely caused by particle agglomeration once partners compound had been loaded onto Nuvec®. N4 decides to bring development in house and repeat earlier successful antibody work to identify impact of agglomeration.
August 2019
Received repeat results for UQ OVA pDNA study
Successful repeat of the pDNA OVA study shows Nuvec® is capable of an immune response but that agglomerated particles causes variability in results.
September 2019
Commenced in house programme of CMC and pre-clinical studies
A series of studies were commissioned to investigate causes of agglomeration and impact on In vivo study results once agglomeration was removed and a monodisperse formulation was injected..
April 2020
New patent filed by N4 for use of Nuvec® to improve performance of viral vectors
Nuvec® loaded with lentivirus viral vectors can achieve the same high levels of transduction but with significantly less lentivirus added. This could lead to reduced cost og goods of lentivirus products and a potential reduction in toxicity as less virus is used
May 2020
N4 announces a program of proof of concept work using a covid-19 plasmid DNA
N4 announced it would investigate the ability to load and transfect a covid-19 plasmid alongside the in house work it was conducting with Nanomerics on monodisperse formulations.
November 2020
Successful monodisperse formulations established which improves formulation stability
The in house work shows that monodisperse formulations of Nuvec® loaded with plasmid DNA can be dried, stored and reconstituted without any drop off in performance. The new dried monodisperse formulations would be tested compared to original fresh formulations which continued to show inconsistent in vivo results.
May 2021
Signing of first Material Transfer agreement and own lab resource
Data from Nuvec® proof of concept studies show enough evidence to sign two MTAs with companies developing their own DNA and mRNA products. N4 also announces it has taken lab space at the Medicines Discovery Catapult to allow it to support MTA work and further investigate optimisation of Nuvec® once loaded with DNA and mRNA to avoid agglomeration.
August 2021
Pilot on intravenous injection and oral study grant
Having demonstrated Nuvec® can be formulated into a monodisperse solution investigation starts on using it as an intravenous injection for tumour reduction using a TNF-alpha plasmid DNA.
A 3 year research grant established with the Australian Research Council to investigate oral delivery of formulations loaded onto Nuvec®
September 2021
N4 announces positive in-vitro results using Nuvec® loaded with Covid-19 plasmid
N4 announced it successfully demonstrated in-vitro a good dose response to produce SARS-COV-2 spike protein production. Further establishing that Nuvec® is always capable of delivering its payload successfully into the cell.
December 2021
Strategic review of in house development work to focus on oncology and gene therapy
Despite positive in vivo results for the covid-19 plasmid in-vivo testing did not show the same results. Initial work on using Nuvec® as an i.v injection for cancer was successful showing good tumour regression for two different doses. N4 therefore decided to switch its internal resource to investigate i.v. treatments and continue vaccine development work with MTA partners as vaccine work clearly showed each project requires a strong degree of product optimisation to produce an appropriate vaccine response
January 2022
Patent grants in key territories
The patent licensed from UQ now granted in USA and China along with Europe and Japan strengthening the Company’s IP portfolio.
June 2022
First siRNA work and early oral success
Loading of siRNA onto Nuvec® shown to produce much greater consistency than DNA and mRNA as it is a much smaller compound. First studies showed that Nuvec® loaded with a single siRNA was able to successfully produce the required gene silencing. Work at UQ shows that if Nuvec® is coated with a ph controlled polymer it can be successfully delivered into the upper intestine to produce a localised transfection.
October 2022
Double siRNA success
N4 demonstrates Nuvec® can be loaded with multiple siRNA with each individual siRNA able to silence its target gene in the same cell. N4 announces its own research program to show how loading two different siRNA, one to suppress tumour growth (EGFR) and one to promote cell death (BCL-2) in a lung cancer model as proof of concept for its potential as an siRNA delivery system.