N4 Pharma Plc (LON:N4P), the specialist pharmaceutical company developing Nuvec®, a novel delivery system for cancer treatments and vaccines, has announced its audited results for the year ended 31 December 2020.
Nigel Theobald, Chief Executive Officer of N4 Pharma Plc, commented:
“The last 12 months have seen us make considerable progress in the dispersion and formulation work for Nuvec® which will put us in a stronger position for our collaboration discussions as we continue to present our data to potential licensing partners. The next few months will generate further important in vivo antibody response data using a SARS COV-2 plasmid both with our original and optimised Nuvec® formulations.
We have also recently announced that the European Patent Office has notified The University of Queensland of the intention to grant the patent that we have licensed the exclusive rights to. This has been followed more recently by the Australian patent office confirming its intention to grant a patent and we expect other key territories to follow suit in 2021. This again strengthens our commercial discussions.
This is a pivotal time for the Company, we are now finalising the data we feel will give third parties the confidence to explore testing of Nuvec® with their own constructs and we continue to expand that dataset all the time.
We are continuing work on other applications for Nuvec® both for cancer treatment and also to explore the potential for oral delivery of vaccines. This work on oral delivery will continue in the background as there is much that needs doing to establish the potential for Nuvec® in this area as no one experiment will provide a definitive conclusion either way on this potential.”
In the comparative year results N4 Biotech also forms part of the Group. N4 Biotech was dissolved on 14 January 2020.
N4 UK is a specialist pharmaceutical company engaged in the development of mesoparticulate silica delivery systems to improve the cellular delivery and potency of vaccines.
The Board has not presented a Strategic Report for the year. All relevant information on the strategy and performance of the Group is included in the Chairman’s report below and the Directors’ Report on page 9 of the annual report.
Review of operations for the financial year ended 31 December 2020
During the year to 31 December 2020, as anticipated, no revenue was generated by the Group (31 December 2019: £nil).
The operating loss for the year was £1,564,421 (31 December 2019: £947,340 loss). Expenditure was broadly in line with budget and increased in line with study results determining the next expenditure requirements to progress work streams.
During the course of the year the Company raised in excess of £4.15m, through a placing of 50,731,250 new ordinary shares in May and a further 25,000,000 shares in December with the remainder being through the exercise of warrants and options. In total the Company issued 79,617,812 new ordinary shares of 0.4p in 2020.
Cash at the year-end stood at £3,555,579 (31 December 2019: £965,752). Our cash position is the strongest it has ever been and leaves us well positioned to complete our current work streams, plan for follow on work and fund our costs in any initial collaboration work.
Key Operational Events and Opportunities
The first part of 2020 saw the Group focus on the optimisation of Nuvec® starting with the improved manufacture and dispersion of the particle. In parallel, we entered into a research collaboration agreement with Nanomerics Limited (“Nanomerics”) to focus on the stability of a number of different formulations of Nuvec® using both a well characterised plasmid DNA and a novel small interfering RNA (siRNA). Whilst these work streams remained ongoing, the advent of the Covid-19 pandemic presented significant local and global challenges but also created an opportunity as to how Nuvec® may be applied as a potential delivery technology to any of the multiple Covid-19 vaccines recently approved and in development across the world.
Whilst we did not initially envisage a material disruption to our studies, the scale of lockdown created minor but inevitable delays to our optimisation work. As working practices have evolved against the backdrop of the pandemic, these work streams are now very much on track and continue to expand our data set for Nuvec®. With such attention on Covid-19 and potential vaccines, we took the decision to undertake a proof of concept study prior to a full in vivo study to assess the efficacy of Nuvec® loaded with the Coronavirus plasmid DNA. This work was undertaken by an experienced contract research organisation, Evotec, and concluded having demonstrated the successful in vitro transfection of HEK cells resulting in the decision to move to a full in vivo study as set out further below.
As announced previously our current strategy has been divided across three work streams:
1. Completion of the optimisation work including the establishment of optimal dispersion, loading ratios and the tech transfer for consistent manufacture of naked nanosilica particles;
2. The scoping and implementation of our most comprehensive in vivo study to date; and
3. Feasibility studies on other applications for Nuvec® such as for oral vaccines and in oncology.
Updates on each stream are as follows:
Optimisation and tech transfer
Over the last 12 months, our program of optimisation work has been undertaken to further characterise Nuvec® nanoparticulate silica with the objective of developing a colloidally stable monodisperse formulation suitable for scaled manufacture. This work has been successful, and a process has been developed which results in a monodisperse nanoparticulate formulation which can be freeze dried and reconstituted without loss of colloidal stability. Importantly this formulation also retains in vitro transfection activity when stored dry for up to 14 days at 0-4C and room temperature, before reconstitution. Longer term stability assessment will be conducted in due course.
Other studies have also been conducted to optimise the PEI content, determine need for phosphonation and to assess the optimal pH and buffer capacity of the medium in which Nuvec® is dissolved.
In September we appointed Ardena as our contract development and manufacturing organisation (‘CDMO’) partner for the technology transfer and upscaling manufacturing of Nuvec®. Work has been on schedule and Ardena is currently working on the process optimisation and scale-up resulting in the manufacture and analysis of a non-GMP 50g batch of Nuvec® prior to moving towards the manufacture, testing and product certification of Nuvec® for GMP status.
In Vivo study plans and implementation
The in vivo study to compare the reactions of the original Nuvec® loaded with the Coronavirus plasmid and another generic plasmid in generating relevant antibodies, has recently commenced at the University of Queensland. The commencement of this work is a little later than originally envisaged, following delays in obtaining the relevant customs clearance to transport the Coronavirus plasmid expressing the spike protein into Australia.
Having optimised Nuvec® as described above, we are now planning the commencement of further in vivo studies to determine whether the improved properties noted in vitro can also be seen in vivo. These studies will be undertaken by Evotec with study initiation expect by early March.
The optimised Nuvec® in vivo studies in mice are planned to assess the following points:
(1) to determine antibody production following dosing with optimised Nuvec®;
(2) To explore dose relationship to determine minimum and maximum plasmid dose required for effect. This information may also provide information on dose-sparing i.e. reduced DNA use; and
(3) to confirm activity is retained after freeze drying and reconstitution at different intervals.
These studies will again involve the Coronavirus plasmid and another generic plasmid. Results from both studies should be known during the first half of 2021.
Oral and oncology applications
In November we announced the launch of our Nuvec® oncology treatment programme with Nanomerics Limited. The programme will explore the role of Nuvec® as a delivery system for DNA and SiRNA in a proof of concept preclinical tumour model. The two-stage programme will focus initially on the formulation of Nuvec® with a therapeutic DNA plasmid, whilst stage two will see the candidate formulation evaluated in vivo in a subcutaneous tumour model to examine tumour regression following multiple local or systemic injections.
Our work to understand the viability of Nuvec® in oral delivery remains ongoing and is currently focussed on extensive in vitro work. In particular we are assessing the ability to transfect epithelial cells in the gut as well as the impact of mucus and other variables. Whilst the commercial potential of successfully demonstrating Nuvec’s® efficacy in oral delivery would be huge we are still at the early stages of establishing whether it is feasible. As this work continues in the background our primary focus remains Nuvec’s® potential use to improve the cellular delivery and potency of vaccines.
The strengthening of our balance sheet through the funds raised in May of this year, means that we are well funded to complete all our currently planned work streams whilst the recent placing in December means we can plan for more supplementary studies whilst being able to budget for the next stage of work following the current in vivo studies and the oral and oncology work.
As announced on 11 February the University of Queensland (“UQ”) has been notified by the European Patent Office (“EPO”) of its intention to grant a European Patent in relation to Nuvec® specifically in respect of its composition, particulate materials and methods for making the particulate materials (the “Patent”). N4 Pharma has the exclusive worldwide rights to Nuvec® for therapeutic uses in humans and animals.
Having received the notification, the next steps prior to formal grant will require UQ to confirm the particulars and translations with the EPO prior to publication of the grant after which the Patent will be validated on a country by country basis throughout Europe as determined by UQ and the Company. This process, resulting in the full grant of the Patent in each chosen territory, should take six to eight months.
The Patent application process for other jurisdictions remains on course and the board is optimistic that now the Patent has successfully been processed by the EPO other jurisdictions should follow suit in due course. In line with this optimism I am delighted to announce that the Australian patent office has also notified UQ of its intention to grant an Australian Patent.
On 15 July 2020 Luke Cairns, previously a Non-Executive Director, became an Executive Director, overseeing the Group’s finance, corporate and investor relations activities allowing Nigel Theobald, Chief Executive Officer, more time to focus on driving the Group’s development programmes and potential commercial collaborations.
What is increasingly clear with the ongoing Coronavirus pandemic is that even with the great success of the recently approved vaccines, as the virus evolves, so will the vaccines and there will be multiple iterations in the years to come. Cost effective storage, transportation and effective delivery are areas where any improvements could have a material impact on the successful role out of vaccines, particularly in emerging markets where wide scale accessibility to vaccines remains challenging. It is our hope that as we look to conclude our most comprehensive Nuvec® studies to date, we will be able to present Nuvec® as a viable delivery solution to vaccine developers.
It is important to stress that we see Nuvec® as a platform delivery technology and whilst it may suit some plasmids better than others it is our intention that it be used across multiple vaccines and not just those addressing Coronavirus. Through our oral studies we are also examining how Nuvec® could simplify the way vaccines are administered. Whilst the majority of our data has been gathered using plasmid DNA we are increasing our work with mRNA. Together with our oncology programme, 2021 could turn out to be a pivotal year for N4 Pharma, as our various applications for Nuvec® advance to the point where we can engage further with potential collaborators and partners. In parallel we are also exploring other assets that could be complimentary to Nuvec®.
On behalf of the Board, I would like to thank all of our shareholders for their continued patient support and look forward to providing further updates on our progress.
By order of the Board