N4P N4 Pharma Plc

23 April 2024

N4 Pharma plc

("N4 Pharma" or the "Company")

Final Results

N4 Pharma Plc (AIM: N4P), the specialist pharmaceutical company developing Nuvec®, a novel delivery system for cancer treatments and vaccines, is pleased to announce its audited results for the year ended 31 December 2023.

Highlights:

Nigel Theobald, Chief Executive Officer of the Company, commented:

"2023 was a year of good progress for the Company with material advancements in the capabilities of Nuvec® both in its ability to dual load and in its potential for oral delivery. We achieved our objective of expanding our portfolio through our interest in Nanogenics which brings us a clear path for taking a product to market and the potential for orphan drug designation.

"Our IP position has strengthened and we believe we are closer than ever before to agreeing a collaboration which would see Nuvec® being applied to other technologies with a view to co-marketing the resultant technology to big pharma and I look forward to making further announcements on this in the near future.

"We continue to manage our cash position tightly and look forward to the rest of 2024 with great optimism."

Enquiries:

About N4 Pharma

N4 Pharma is a specialist pharmaceutical company developing a novel delivery system for oncology, gene therapy and vaccines using its unique silica nanoparticle delivery system called Nuvec®.

N4 Pharma's business model is to partner with companies developing novel antigens in these fields to use Nuvec® as the delivery vehicle for these antigens. As these products progress through pre‐clinical and clinical programs, N4 Pharma will seek to receive upfront payments, milestone payments and ultimately royalty payments once products reach the market.

For further information on the Company visit www.n4pharma.com or sign up at investors.n4pharma.com.

Chairman's Report

N4 Pharma Plc ("N4 Pharma" or the "Company"), is the Parent Company for N4 Pharma UK Limited ("N4 UK") and Nanogenics Limited ("Nanogenics"), and together form the group (the "Group").

N4 UK is a specialist pharmaceutical company engaged in the development of silica nanoparticle delivery systems to improve the cellular delivery of cancer treatments, gene therapy and vaccines.

Nanogenics is a specialist pharmaceutical company engaged in the development of a Liptide@ platform to deliver a proprietary siRNA sequence to silence a fibrotic gene for the treatment of glaucoma.

Review of operations for the financial year ended 31 December 2023

During the year to 31 December 2023 £1,953 of revenue was generated by the Group (31 December 2022: £nil).

The operating loss for the year increased to £1,276,778 (31 December 2022: £1,029,261 loss). Expenditure was broadly in line with budget and increased compared to prior year as more work was undertaken on in vivo vaccine and oncology studies in 2023.

Cash at the year-end was £1,027,112 (31 December 2022: £1,919,529) having raised £350,000 towards the end of 2023 primarily to fund the investment into Nanogenics. Our cash position remains sufficient to continue our current work streams albeit further funds may be required to expand our activities as set our further in the Directors' Report.

Section 172 Disclosures

In discharging their duties, the Directors of the Group give due regard to their duties to promote the success of the Group under Section 172(1) of the Companies Act 2006.

Given the size and nature of the Group all key decisions in the promotion of the success of the Group are taken at board level with delegation to the Executive Directors for the execution of such decisions.

All actions and decisions taken are in good faith with the long-term success of the Group in mind and in doing so the Directors have considered (amongst other matters):

n the likely consequences of any decision in the long term - all key decisions are taken at board level and are focussed on what is required to achieve commerciality for the Group's core projects, Nuvec® and ECP105, the glaucoma product being developed by Nanogenics;

n the interests of the Group's employees - save for the Directors, the Company has no other employees. The interests of the Directors are very much aligned with the success of the Group and Company;

n the need to foster the Group's business relationships with suppliers, customers and others - the Group is reliant on third party providers such as clinical research organisations ("CROs") to progress the business and maintains good work relationships with all its counterparties;

n the impact of the Group's operations on the community and the environment - all CROs are required to adhere to strict ethical standards particularly in the use of animals in studies;

n the desirability of the Group maintaining a reputation for high standards of business conduct; and

n the need to act fairly between stakeholders of the Group.

Where or to the extent that the purposes of the Group consist of or include purposes other than the benefit of its members, subsection (1) has effect as if the reference to promoting the success of the Group for the benefit of its members were to achieve those purposes.

The duty imposed by this section has effect subject to any enactment or rule of law requiring Directors, in certain circumstances, to consider or act in the interests of creditors of the Group.

Key Operational Events and Opportunities

The Company has continued to add further pre-clinical proof of concept data to the significant data accumulated in the prior periods in respect of the potential for the use of Nuvec®.  For 2023, the Company's focus for Nuvec® was threefold:

·      to expand its knowledge around Nuvec® in oncology and gene therapy using siRNA to silence genes;

·      to continue to investigate the oral delivery of Nuvec® to the intestine; and

·      to further investigate the use of Nuvec® to improve the performance of viral vectors.

In parallel to this ongoing work, we continued to explore potential collaborations to find appropriate partners with whom to develop Nuvec® in a way that could lead to it being marketed to pharma companies with commercialisation in mind. As stated previously, the Company has always been open to adding further, complimentary assets and this was achieved through investment resulting in a controlling stake in Nanogenics.

siRNA

The Company is focusing its research on the ability of Nuvec® nanoparticles to be loaded with, and deliver at the same time, two different siRNA known to inhibit relevant oncology targets.  This is cutting edge research in the use of nanoparticles as delivery systems in oncology and consequently the Company is proceeding carefully to ensure that it gains the maximum understanding of the cellular processes involved.

Through the use of multiple different siRNA constructs, the Company has demonstrated that two separate siRNA molecules can be loaded onto Nuvec® without changing the size or charge of Nuvec®, both parameters being essential for successful cellular uptake.

The initial work on cell growth involved investigating the combination of inhibition of EGFR (epidermal growth factor receptor) and BCL-2: (B-cell lymphoma 2) using PC-9 cancer cells. Each siRNA when separately loaded onto Nuvec® achieved cell inhibition.  The work identified that the expression level of BCL-2 in PC9 cells was low even though cellular inhibition was observed. The Company then began investigating alternative cellular pathways that may be inhibited using siRNA loaded alongside EGFR.  The first was BRD4 (Bromodomain-containing-protein 4) a target for which inhibitors are currently being evaluated in clinical trials for the treatment of uveal melanoma, leukemia and carcinoma.  The second target was PLK1 (Polo Like Kinase 1), inhibitors of which are in early clinical development for lymphoma and pancreatic cancer.

As with the other siRNAs explored to date, Nuvec® can be loaded with the individual siRNA, as above, and cause knockdown of the respective targets and reduce cell viability in a dose-related manner.

Having confirmed dual loading of Nuvec®, the Company subsequently tested the effect of both BRD4 combined with EGFR and PLK1 combined with EGFR on knockdown and cell viability.  Although individually both siRNA had demonstrated the expected results of a dose-dependent inhibition of cell growth and target knockdown, critically when loaded together there was a synergistic effect  which resulted in a reduction in knockdown of EGFR receptor but importantly the reduction on cell viability was retained. These findings give Nuvec® a unique position in using siRNA to treat oncology and other diseases as multiple siRNA molecules can be loaded onto Nuvec® and different cellular pathways inhibited at the same time, a hugely useful tool for combination therapy treatments.

Oncology Strategy

It is likely that the precise combinations of siRNA, both in terms of target and concentration of siRNA, will vary depending on which cell type they are tested in.  Both these elements will be determined by the clinical outcome desired.

Chemotherapy treatments for cancers are broad stroked and have very high toxicity which has led to the emergence of alternative immuno-oncology treatments.  These have had remarkable success for some cancers but have proved ineffective in curbing the progression of numerous cancers.

Single pathway treatments can have an initial effect but many see the post treatment emergence of cancer cells that have developed "immune escape" pathways leaving retreatment as futile.

Novel approaches to the treatment of cancer that do not rely on the immune response, nor incur the general toxicity induced by chemotherapy or radiotherapy, but rather rely on targeting the well-known growth factor pathways spurring tumour growth are key to addressing the shortfalls of immunotherapeutic and chemotherapeutic approaches.  Although some monoclonal antibody treatments (mAbs) do target tumour growth dependent pathways, they have highly significant off-target effects, must be dosed repeatedly, can be immunogenic, and target only one pathway at a time, allowing for emergence of tumour populations that proliferate by other growth pathways.  None have been curative.

The work the Company is doing shows that Nuvec® can bind not only single, but multiple siRNAs aimed at simultaneously targeting identified pathways responsible for cancer progression after initial treatments.  Knocking down both (or more) pathways will give a greater chance that tumours will not develop resistance, escape and again proliferate by the emergence of a significant alternative growth pathway, which is common in treatments blocking just one growth factor pathway.

Oral Studies at the University of Queensland ("UQ")

During the period UQ has, utilising the grant funding obtained by N4 Pharma and the Australian Research Council, made considerable progress in the longer-term study on oral applications for Nuvec®. We have demonstrated via in vivo pre-clinical studies that an enterically-coated capsule containing Nuvec® loaded with DNA encoding ovalbumin is able to pass through the lining of the stomach to successfully transfect the upper intestine. Using a single dose, ovalbumin expression was observed after 3 days. In a second study a second capsule was administered on day 3 and a much higher sustained level of expression was observed on days 4-7.

This work clearly shows that Nuvec® can be successfully used as an oral delivery system with many potential applications such as a vaccine, a product for gastrointestinal disorders (e.g. Inflammatory Bowel Disease, Ulcerative Colitis etc) or to treat colon cancer among many possible examples.

As recently announced further studies at UQ show that administering capsules on subsequent days can maintain the protein expression for even longer and produce antibodies. The Company is in active discussions with UQ as to the appropriate next steps and likely costings to maximise this opportunity.

Viral vectors

Viral vectors remain the go to delivery vehicle for use in gene therapy but they remain fraught with problems, most notably they are expensive to make and cause side effects due to their inflammatory nature. 

The Company has taken a novel approach to how Nuvec® might initially be used in this area. The Company has shown that Nuvec® can be combined with the viral vector to significantly improve its efficiency. This could mean products formulated with viral vectors could achieve their same efficacy but from a reduced amount thereby significantly reducing the cost of manufacture and potentially reducing the unwanted side effects from the viral vector.

Post the year end, The Company announced that it had also shown through its research programme with the University of Brunel, that Nuvec® can deliver increased transduction efficacy, when complexed with Adeno-Associated virus 8 ("AAV8"). AAV8 was chosen for investigation as this virus is currently being used for products already in clinical development.

The number of approvals of new gene therapies and the need for appropriate delivery systems have reached unprecedented highs and demand is growing exponentially. For in vivo gene therapy, the Adenovirus (AV) and Adeno-Associated virus (AAV) are acknowledged as the most used delivery vehicles. However relatively high amounts of AV and AAV are needed to be clinically efficient and this appears directly correlated with adverse events in patients such as unwanted immunogenicity and potential safety implications.  The incorporation of Nuvec® into the treatment protocol has the potential to both increase efficacy and reduce side effects.

These three work streams are the focus of the Company in demonstrating both the viability and the flexibility of Nuvec® as a unique delivery system in this space. It remains a key priority for the Company to present this data to third parties developing novel products in this space with a view to licensing Nuvec® to use as part of their developments.

Collaborations

The Company is at advanced stages of finalising a collaboration with an independent global leader in R&D based in the US which, on the back of successful initial studies utilising our combined technologies, would lead to a co-marketing agreement to allow both parties to promote the resultant combined technology. We anticipate being able to make a further announcement on this in the coming weeks.

Additional Assets

We have been investigating potential assets to add to the Company for some time and after seeing a number of opportunities, we were delighted to take a controlling stake in Nanogenics in September 2023. The RNA sector is an exciting one with a lot of investor and commercial interest. The addition of the Liptide® delivery system and siRNA sequence adds significant potential value to our business. As well as glaucoma, the MRTF-B gene is also responsible for fibrosis of the liver and lung, two large areas into which Nanogenics could develop its portfolio.

Non-viral, non-lipid delivery systems are high in demand in the gene therapy space and we now have two such delivery systems and expect considerable technical synergies in developing programmes using both Nuvec® and Liptide®.

Since the investment Nanogenics has been working with the University of Strathclyde on the formulation to take into in vivo studies with Kings College London. These studies are expected to commence in May 2024. In parallel we have been looking into the preparatory work required to undertake safety and toxicology testing and move into clinical trials, achieving pre-IND approval from the FDA and what is required to obtain orphan designation for the product which, if achieved, would potentially give 7 years exclusivity to market our product upon FDA approval which, in itself, would be hugely value enhancing.

Intellectual Property

The Company has the exclusive worldwide rights for therapeutic uses in humans and animals for technology developed by The University of Queensland ("UQ"). 2023 now sees this technology having patents granted in Europe, Australia, Japan, China and the US and post year end the patent was also granted in India.

The Company has also filed its own patent on using Nuvec® to enhance the performance of viral vectors which is now entering the national phases of patent execution.

Future Prospects

As the Company looks forward, we are consolidating our efforts on Nuvec® and actively seeking commercial solutions for the product.  Future development of the product as a drug delivery vehicle requires significant capital so we are seeking a suitable partner to work with us to deliver Nuvec@'s potential.  Through the investment in Nanogenics, the Company has an additional exciting development candidate and we will be looking to progress this opportunity towards clinical trials as quickly as possible.

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

Chris Britten

Chairman

22  April 2024

N4 Pharma Plc

Consolidated Statement of Comprehensive Income for the year ended 31 December 2023

All results were derived from continuing operations.

The notes are an integral part of the Consolidated Financial Statements

N4 Pharma Plc

Consolidated Statement of Financial Position as at 31 December 2023

The Consolidated Financial Statements were approved by the Board of Directors on ________ 2024 and signed on its behalf:

Nigel Theobald

N4 Pharma Plc

Company Statement of Financial Position as at 31 December 2023

The Company recorded a loss of £8,636,650 for the year (31 December 2022: £7,226 loss) primarily attributable to impairment of the intra company loan and investment as set out in the Company Statement of Cash Flows for the year ended 31 December 2023. The policy on impairment is dealt with in 1.14 of the Accounting Policies.

The Company Financial Statements were approved by the Board of Directors on 7 March 2024 and signed on its behalf:

Nigel Theobald