24 September 2024

N4 Pharma Plc

("N4 Pharma" or the "Company")

Interim Results

N4 Pharma Plc (AIM: N4P), the specialist pharmaceutical company developing Nuvec®, a novel delivery system for vaccines and cancer treatments, announces its unaudited interim results for the six months ended 30 June 2024.

Highlights:

·      Two exciting therapeutic areas identified for the development of products utilising Nuvec® and Liptide®.

·      Positive results from collaboration with SRI International ("SRI") demonstrating the ability for Nuvec® to target cells and maintain efficacy in the target gene cell.

·      Further positive in vivo results from ongoing oral studies at the University of Queensland to show the successful delivery of a Nuvec® capsule into the intestine where it released its plasmid DNA payload to produce localised protein expression.

·      Application made to FDA for orphan drug designation in respect of ECP105, for the prevention of scarring following glaucoma surgery.

·      Reduced operating loss for the period £491,705 (30 June 2023: £646,150) and R&D and general expenditure in line with budget.

·      Cash position remains strong which at 30 June 2024 was £1,204,946 (31 June 2023: £1,289,769), following a successful placing in June to raise gross proceeds of £630,000.

·      Post period end strengthening of the board with the appointment of Mike Palfreyman as an independent Non-Executive Director.

Nigel Theobald, Chief Executive Officer of N4 Pharma Plc, commented:

"We have made excellent progress in the period and have continued to focus our efforts to deliver the best opportunities to progress Nuvec® into the clinic with a shift in emphasis towards product development with our first two potential products now identified. In parallel our collaboration with SRI continues to generate positive results and improves our data set to bring us closer to commercial collaborations across multiple applications dependent on any partner's needs.

"Cash expenditure continues to be tightly controlled to allow us to maximise outcomes whilst preserving our cash resource as far as possible. I look forward with optimism to the continuing the work and crystalising the pathway towards commercially viable and clinically relevant products whilst presenting our data alongside SRI to potential collaborators."

The information contained within this announcement is deemed by the Company to constitute inside information as stipulated under the Market Abuse Regulations (EU) No. 596/2014 which has been incorporated into UK law by the European Union (Withdrawal) Act 2018.  Upon the publication of this announcement via Regulatory Information Service, this inside information is now considered to be in the public domain. 

Enquiries:

About N4 Pharma

N4 Pharma is a specialist pharmaceutical company developing a novel delivery system for vaccines and cancer treatments using its unique silica nanoparticle delivery system called Nuvec®.

N4 Pharma's business model is to partner with companies developing novel antigens for vaccines and cancer treatments to use Nuvec® as the delivery vehicle to get their antigen into cells to express the protein needed for the required immunity. 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.

Chairman's Statement

Half year results

I am pleased to report that in the six months ended 30 June 2024, £3,906 of revenue was generated by the Group (30 June 2023: £nil).

The loss for the period was £491,705 (30 June 2023: £646,150) and in line with planned expenditure.

Our cash balance at 30 June 2024 was £1,204,946 (30 June 2023: £1,289,769), following a placing to raise gross proceeds of £630,000.

Operational update

After spending a significant amount of time investigating Nuvec® and understanding its potential, we are pleased to report meaningful progress in the development of Nuvec® as a delivery system for therapeutics.  We have previously reported on the development of a monodisperse formulation, crucial for intravenous delivery, and the ability to load multiple siRNA molecules onto the same Nuvec® particle.  We are pleased to report that Nuvec® delivery can be targeted to individual tissue types and that there is the potential to use Nuvec® as an oral drug delivery approach for the treatment of gastrointestinal ("GI") disorders.  These new data have led to the prospect of delivering two exciting lead products designed to address unmet clinical needs.

The first, using Nuvec® has the potential to delivery an oral inflammation inhibitor for the treatment of GI disorders including Inflammatory Bowel Disease ("IBD") and Ulcerative Colitis ("UC"). The second product opportunity, via our investment in Nanogenics Ltd, is exploring the use of Liptide® to deliver a product for the prevention of scarring following surgery to treat glaucoma.  In parallel to shifting our focus towards product development, we continue to explore other applications, particularly through our work with SRI which, in turn, and through our marketing agreement with SRI, could lead to further collaborations.

Nuvec®

We are now clear on a number of benefits of Nuvec® including the following:

·      Its unique spikey surface structure allowing the binding of DNA/RNA;

·      It is relatively straightforward to manufacture and scale up;

·      In contrast to Lipid Nanoparticles which are known to evoke an immune response, the inert nature of nanosilica particles makes this an unlikely (subject to confirmation) feature of Nuvec®;

·      The addition of specific peptides and other ligands enables cellular targeting;

·      Any payload is protected from enzymatic digestion and pH exposure;

·      It is a simple process to load multiple siRNAs onto the same nanoparticle for combination therapies;

·      There is quick and efficient cellular uptake and endosomal release enabling delivery of large numbers of siRNA copies into each cell; and

·      It is capable of oral delivery or oligonucleotides including siRNA and DNA.

Liptide®

Liptide's® benefits include:

·      The encapsulation of the payload by the lipid element to protect it;

·      The peptide element allows efficient take up by the target cell;

·      Higher delivery rates and specificity than traditional liposomal vectors;

·      High tolerability making it suitable for regular, repeat dosing;

·      Improved safety profile compared to viral vectors; and

·      Like a virus, Liptide® can bind to specific cell surface.

Oral Delivery

In April 2024, we announced that the Company had, through its research program with the University of Queensland ("UQ"), undertaken further testing, in vivo, to show the successful delivery of a Nuvec® capsule into the intestine where it released its plasmid DNA payload to produce localised protein expression. This work has reinforced the potential of Nuvec® as an oral delivery system for multiple nucleotide payloads. 

In this experiment, an enterically-coated capsule containing PEGylated Nuvec® loaded with plasmid DNA expressing ovalbumin was administered on day 0 and subsequent capsules on day 3, day 6, day 9 with a booster capsule at day 21.  Protein expression was measured to be significantly higher in the upper gastrointestinal tract of the subject than controls (DNA alone and non-PEGylated DNA loaded Nuvec®) up until day 25. In addition, a significantly higher ovalbumin antibody response was measured at day 36 in the PEGylated Nuvec® sample compared to control.

The work at UQ will now focus on combining the oral delivery work we have done with our ability to multiple load Nuvec® with more than one RNA. The aim for this is to show how an oral product can both reduce the unwanted inflammation in the gut associated with IBD whilst simultaneously helping the body's anti-inflammatory response fight back. In vitro testing of this has begun and we hope to have in vivo testing underway before the end of the year.

We believe the market for such an oral product to treat GI inflammation to be significant. Current therapies for immune-medicated inflammatory diseases, such as IBD, are sub-optimal requiring regular, painful, injections which can result in reduced patient compliance.   Injectable products to treat these disorders represented 78% of a market worth $20.4bn in 2023 and is expected to grow by a CAGR of 3.9% to over $27.6nn by 2030¹.   The ability to deliver an oral medication targeting the same mechanism as the antibody-based therapeutics would represent a preferable form of treatment. With 5 million sufferers of the two main types of IBD (Crohn's disease and ulcerative colitis) there is huge potential for a product to address this market and it is estimated that the oral segment of this market could be worth $7bn by 2030. There is a huge market opportunity for such a product, mainly as an oral substitute for the largest sector already of TNF inhibitors and to compete with the inhibitor drugs being developed. If such a product could take 50% share of the existing TNF inhibitor market and 25% of the oral market, it would potentially be worth $12bn.  Even achieving just 10% of this at $1.2bn would give the product significant potential.

(¹ 2023 Grand View Research, Inc. Inflammatory Bowel Disease Treatment. MARKET ANALYSIS, 2018-2030).

Liptide® Glaucoma product - ECP105

ECP105 represents a simple and effective anti-fibrotic therapeutic approach which maximises and increases surgical success in the treatment of Glaucoma by reducing post-surgical scarring whilst avoiding exposing patients to the risk of cytotoxic medication. Using Liptide® as a delivery system, ECP105 contains a siRNA sequence to silence the fibrotic gene MRTF-B without cytotoxic side effects.

During the period and year to date, the work at Nanogenics has progressed positively despite being a little slower than we would have liked. The in vitro proof of concept work carried out at the University of Strathclyde demonstrated siRNA inhibition of proteins related to fibrosis in ophthalmic indications. Delays in providing the formulation of the product to Kings College London has resulted in an initial pilot in vivo study. The results of the pilot have shown that the new formulation made using microfluidics is stable and is not toxic when administered in vivo.

One of the strategic decisions taken during the period was to apply for orphan drug designation in respect of ECP105 for which we submitted an application to the U.S. Food and Drug Administration ("FDA") in early July, for the prevention of scarring following glaucoma surgery. Obtaining orphan drug status in the USA is expected to bring substantial cost and time savings on the development work and once approved, seven years of exclusivity.  The result of the orphan drug application is expected in the next six to eight weeks.

Nanogenics has also filed a patent application in the UK for novel siRNA sequences that can be used as part of the ECP105 development work.

Glaucoma currently affects 80 million people worldwide and the incidence of the disease is estimated to grow to nearly 112 million by 2040. Trabeculectomy is the current principal approach to glaucoma filtration surgery with an estimated 300,000 surgeries a year worldwide.  Fibrosis following surgery can result in significant failure rates as high as 50% after five years. Current treatment for this involves using Mitomycin C off label to prevent surgery failure but this is a highly toxic solution and one which ideally should be avoided. With ECP105 designed to get approval for this approach but without all the associated side effects, we believe it could represent a significant market opportunity and one that we are in the process of seeking to define though consultation with market practitioners.

SRI International

As announced in August 2024, SRI has successfully completed its chemistry work to show that a Fox Three Molecular Guidance System ("MGS") can be linked to Nuvec® without altering its loading capacity.  siRNA molecules can then be attached to the combined Nuvec®/Fox Three MGS and SRI has demonstrated that this molecular complex is internalised only by the targeted cell type.  Further testing of the targeted modified Nuvec® has shown efficacy can be maintained in the target cell.  These two sets of data indicate that Nuvec® can be modified to target individual tissue types with no loss of function with respect to delivery of its payload.  This ability to target different tissue types, using a modified Nuvec®, represents a key differentiator to competing nucleic acid delivery approaches  

On the back of this data we have begun work on a combined marketing pitch deck allowing SRI and N4 Pharma to present this data and its implications to major pharma and biotech companies who may be seeking a targeting delivery system for their nucleic acid programs.

Going Forward

As outlined above, whilst we continue to seek partners to work with based on the data accumulated to date and with the work undertaken with SRI, our focus is very much on gearing our studies towards two initial products utilising N4's Nuvec® and Nanogenics' proprietary LipTide® technologies. 

The addition of Mike Palfreyman to our board is, we consider, a real coup for a company of our size and a fantastic endorsement of our assets. His experience is second to none in our space and we believe he will prove invaluable in assisting us in the advancement and commercialisation of Nuvec® and LipTide® both in Europe and the US.

Outlook and strategy

Whilst our core strategy remains unchanged - to generate sufficient proof-of-concept data to attract larger pharmaceutical and biotechnology partners to enter into collaborations with us to explore using Nuvec® as their chosen delivery system for therapeutic agents - it has evolved. The collaboration with SRI has served to enhance this data pool for our core strategy with the significant ability of Nuvec® now being able to target cells. Through our investment in Nanogenics and the successful oral work we are now in a position to focus some of our resources on the development of products with clearly addressable and potentially material markets, these initially being IBD and Glaucoma.

We believe that this is the right strategy for the Company given where we sit today and increasingly are able to attract the right partners and personnel to help us achieve our goals.

On behalf of the Board, I would like to thank all of our shareholders for their continued support and look forward to providing further updates on our progress.

Chris Britten

Chairman

24 September 2024

All activities derive from continuing operations.

The notes below form an integral part of these financial statements.