N4 Pharma PLC Interim Results (6738M)

TIDMN4P

RNS Number : 6738M

N4 Pharma PLC

18 September 2019

N4 Pharma Plc

("N4 Pharma" or the "Company")

Interim Results

N4 Pharma Plc (AIM: N4P), the specialist pharmaceutical company developing Nuvec(R), a novel delivery system for vaccines and cancer treatments, announces its unaudited interim results for the six months ended 30 June 2019.

Key events:

   --      Placing of 10,500,000 ordinary shares to raise approximately GBP1.0m net of expenses

-- Commissioned repeat of its successful in vivo study using Ovalbumin ("OVA) pDNA at University of Queensland ("UQ") to try and identify causes of inconsistent results seen working with University of Adelaide and other CROs

   --      Commenced search for other asset opportunities to add to the Company portfolio 
   --      Appointment of Dr John Chiplin as non-executive Chairman 
   --      Appointment of Dr Chris Britten as non-executive Director 
   --      Cash balance at period end of approximately GBP1.2 million

Post period end:

-- Received successful results for UQ OVA pDNA study, confirming the ability of Nuvec(R) to increase antibody responses using multiple injections at certain doses

-- Commenced work to improve dispersity of Nuvec(R) formulations loaded with pDNA and initiate further in vivo work to test improved formulation

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

"In this period, we have confirmed that Nuvec(R) works for both DNA and mRNA delivery, having produced an antibody response for both. We have also made progress in understanding how Nuvec(R) behaves once loaded with DNA and mRNA. We have put in place a clear plan to investigate how we can improve the dispersion of Nuvec(R) once loaded with DNA. We will then test this improvement in both in vitro and in vivo studies and conduct an oncology efficacy model.

The development and improvement of our Nuvec(R) particle once loaded with DNA and mRNA is an essential step on its path towards use in clinical trials and usual for the evolution of any delivery system. Nuvec(R) still shows great potential as a delivery system for nucleic acids and we remain excited and confident about its future."

Enquiries:

 
 N4 Pharma Plc              Via Scott PR 
  Nigel Theobald, CEO 
 
 Allenby Capital Limited    Tel: +44 (0)203 328 5656 
  James Reeve/Asha Chotai 
 
 Scott PR                   Tel: +44 (0)1477 539 539 
  Georgia Smith

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(R).

N4 Pharma's business model is to partner with companies developing novel antigens for vaccines and cancer treatments to use Nuvec(R) 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 up front payments, milestone payments and ultimately royalty payments once products reach the market.

Chairman's Statement

Half year results

During the six months to 30 June 2019, the Company raised an additional GBP1.0m net of expenses through the issue of 10,500,000 new ordinary shares.

The operating loss for the period was GBP550,573 (2018: GBP553,379).

Cash balance at 30 June 2019 was GBP1,167,547 (30 June 2018: GBP1,586,474).

Board changes

During the period, the Company appointed John Chiplin as non-executive Chairman and Chris Britten as a non-executive Director. Paul Titley stood down as a director and employee of the Company. David Templeton became an executive director, taking responsibility for the technical aspects of Nuvec(R) development. These changes bring considerable experience and expertise to the Board in order to take the Company forward.

Nuvec(R) development work

The first part of 2019 has seen the Company make considerable progress in enhancing the understanding and performance of the Nuvec(R) system through a series of its own studies and research collaborations. Following this work, and together with previous studies, the Company has established that:

-- a range of DNA and mRNA antigens can be loaded onto the Nuvec(R) particles and successfully transfect cells in vitro;

-- Nuvec(R) mechanism of action to transfect cells is via endocytosis into the cell and release of payload into the cytoplasm;

-- Nuvec(R) has a good safety profile, degrades naturally in the body and, since it is not lipid in composition, is devoid of potential lipid induced liver damage;

-- importantly, Nuvec(R) works for pDNA and mRNA having shown in vivo antibody response for both;

   --      Nuvec(R) currently delivers a good antibody response from 2-3 injections; and

-- evidence from in vitro studies suggests that Nuvec(R), when prepared for in vivo dosing, does not produce a monodisperse suspension after the addition of DNA, which the Directors believe is the most likely cause of the inconsistent results observed across certain studies.

The data generated so far is encouraging and shows that, with proposed enhancements, Nuvec(R) has the potential to be an effective delivery system for nucleic acids.

Repeat University of Queensland Study

The recent repeat of the University of Queensland (UQ) study using OVA pDNA was performed because work with other CROs and collaborators, undertaken subsequently to the initial UQ studies, showed inconsistent results. The repeat study with UQ added an additional arm to investigate the response with one injection as well as three injections, and at different dose levels. The repeat study confirmed a good response using Nuvec(R) at higher doses using three injections but no response with just one injection. The original UQ study had not tested the response using just one injection.

Together with other data, this work also showed that once the Nuvec(R) particles were loaded with OVA pDNA, the formulation was not ideally dispersed. This lack of dispersion is not an issue for in vitro work but is also a key likely explanation as to the inconsistency seen when using Nuvec(R) in vivo and may also contribute to previous study inconsistencies using just one injection.

Going forward

The work the Company has undertaken itself and with collaborators shows that the focus now needs to be on improving the formulations of Nuvec(R) once loaded with DNA and RNA to ensure delivery of maximum antibody generation in vivo. This is standard work in the evolution of any delivery system. The focus of this work is not to alter the basic silica nanoparticle, but rather to look at the processes of how to load a linker to the silica particle to enable DNA or RNA to be loaded to the particle and also how the DNA or RNA is then loaded onto the Nuvec(R) particle. The objective of the work is to improve these processes so that a more monodisperse formulation of DNA loaded Nuvec(R) is achieved and any agglomeration is minimized.

It is anticipated that a more monodisperse formulation would likely lead to improved transfection efficiency in vivo, greater consistency of results and may also increase the response from a single injection.

To that end, the Company has put the following top-level plan in place. The work is divided into two distinct phases, each of which has certain stages upon which the Company will provide updates as they progress.

The first is to generate Nuvec(R) with better potential for dispersion in aqueous suspensions, improve dispersion techniques, and optimise the addition of DNA. In doing so the Company will seek to address the issues it perceives may have been causing inconsistencies to date. The work to be done will involve four, sequential, stages:

1. Nuvec(R) manufacturing process alterations (i.e. addition of PEI onto silica nanoparticles which allows for subsequent loading of DNA/mRNA)

   2.   Nuvec(R) dispersion testing 
   3.   Improved Nuvec(R) DNA loading process

4. Analyse the effect of the Nuvec(R) concentration, the DNA:Nuvec(R) ratio and solution composition on DNA: Nuvec(R) agglomeration

These four stages of the first phase of work are expected to take approximately six months and conclude by early Q2 2020.

Following a successful conclusion of phase one, phase two will be to focus on in vitro testing of the improved product, followed by in vivo testing seeking an improved transfection and immune response, before finally conducting an in vivo cancer model study. Subject to the phase one timetable being achieved, it is expected that these three stages of phase two would conclude before the end of 2020.

These two phases will be key milestones to achieve in order for the Company to start working with partners in any clinical programs and embark on licencing discussions.

In parallel to the work outlined above, the Company continues to see progress on its licensed patent application from UQ. The UQ patent application is now going through dialogue with the European and US patent examiners and has entered Australia, China, India and Japan national phases where examiner response is awaited. Should the grant be received in 2020, it would dovetail well with the conclusion of the ongoing work on Nuvec(R) and further support any discussions with potential partners.

The Company is still awaiting feedback from the European Nanomedicine Characterisation Laboratory ("EUNCL") characterisation program for Nuvec(R), initially estimated for the end of this quarter. The characterisation program aims to provide state-of-the-art pre-clinical characterisation of innovative nanomaterials such as Nuvec(R) in order to accelerate their development towards regulatory approval by the European Medicines Agency ("EMA") and the national agencies. Whilst these results will further enhance our data package and increase our understanding of the variables which may affect Nuvec(R) it is not expected that they would impact on the work plan identified to address the findings of other studies to date. A further update will be provided once these results have been received.

Outlook

Fundamentally, our strategy remains the same and therefore the prospects and value potential for Nuvec(R) remain as previously stated. To date, we have focused on generating our own in vitro and in vivo data using Nuvec(R) and undertaking research collaborations with third parties to gather extra information. The ultimate aim of doing this work is to get to a point where we could begin widescale commercial collaboration and licensing in 2020. The recent learnings and subsequent proposed plan still keep us on track to start these discussions, albeit towards the end of 2020. In terms of typical pharmaceutical development time lines, this is a relatively minor delay.

The use of DNA and RNA as vaccines and treatments, especially in oncology, is increasingly of interest clinically and, consequently, the market potential is substantial. A consistent theme in all discussions about the potential for DNA and RNA antigens to become products is the need for a safe and effective delivery system and it is the Boards opinion that Nuvec(R) could have a significant role in that market.

The Board remains very optimistic about the future of the Company and its prospects. We are aware that the change in timelines can be viewed as disappointing, but it is vital to remember that we are a Lifescience Company and as such need to take the appropriate time and degree of accuracy to ensure that we will be able to commercialise Nuvec(R). Regular updates will be provided on the progress of the workplan.

The Board also recognises the need to investigate other assets and opportunities that the Company can add to its portfolio and continue to seek such opportunities.

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.

By order of the Board

John Chiplin

Chairman

N4 Pharma Plc

Glossary of technical terms

Monodisperse: containing particles of uniform size

Agglomeration: particles clumping together