N4 Pharma “path to the commercialisation of Nuvec® is clearer now than perhaps at any time previously”

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 2021.

Highlights:

·      Following extensive in vivo work and the commencement of Material Transfer Agreements (“MTAs”) in 2021 N4 Pharma has a clear focus in 2022 as to where best to deploy resources in the short term

·      Positive findings from the evaluation studies looking at the potential of Nuvec® as a nano-carrier of a DNA plasmid expressing TNFalpha

·      Commenced work with Medicines Discovery Catapult to extend the observations to allow it to identify suitable loads to add to Nuvec® to take to clinic

·      In the process of identifying alternatives to TNF as immunomodulators or gene therapy which may use Nuvec® as a delivery system

·      Commenced working with MTA partners assessing how Nuvec® may enhance their proprietary technologies

·      Granting of (or notice of intention to grant) patents now in Europe, Australia, Japan, China and in January of this year the critical market of the US

·      Operating loss for the period was £1,843,290 (2020: £1,564,421)

·      Cash balance at period end of approximately £1.8m

Nigel Theobald, Chief Executive Officer of N4 Pharma, commented: “Following our most extensive in vivo work to date and having worked with MTA partners in 2021 we have a clear focus in 2022 as to where best to deploy our R&D resources in the short term. As a result of the positive findings from the evaluation studies looking at the potential of Nuvec® as a nano-carrier of a DNA plasmid expressing TNFalpha, which demonstrated a significant inhibition of tumour growth derived from a human cell line, the Company has commenced work with Medicines Discovery Catapult to extend the observations to allow us to identify suitable loads to add to Nuvec® to take to clinic. 

‘We felt from the outset it could be a pivotal year for the Company and believe it has proved to be so. On the back of increased data and results we are now in a position to narrow our R&D focus onto the hugely exciting oncology and gene therapy market. In parallel, we will continue to seek further MTA partners to work with us and assess how Nuvec® may enhance their proprietary technologies. Whilst we are not there yet and it will be results driven, our path to the commercialisation of Nuvec® is clearer now than perhaps at any time previously.”

Key Operational Events and Opportunities

Following the optimisation of Nuvec® with the improved manufacture and dispersion of the particle in 2020, 2021 focussed on in vivo studies with Nuvec® for both vaccines and in oncology as well as the pursuit of MTAs with partners to begin exploring potential collaborations.

In Vivo study results

The optimised Nuvec® in vivo studies in mice were 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 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 involved the Coronavirus plasmid and another generic plasmid. In vitro performance with the optimised Nuvec® loaded with a new SARS-COV-2 plasmid demonstrated an improved response in terms of transfection and SARS-COV-2 spike protein secretion in HEK 293 cells. In addition this combination also showed a dose-related SARS-COV-2 spike protein production.

Whilst the in vitro results were very positive using the SARS-COV-2 plasmid the results from the mouse in vivo immunogenicity studies carried out by Evotec did not show any meaningful immunological response. In addition, the initial mRNA OVA in vivo immunogenicity study showed sub optimal responses. These results again highlighted that a number of variables such as dose, route of administration, timing of injection and formulation could require extensive optimisation for each plasmid loaded onto Nuvec®. With the Company now getting traction with MTAs (as detailed further below) the strategic decision was taken to concentrate ongoing vaccine work on specific products linked to proprietary DNA or mRNA sequences under MTA.

Aside from the in vivo work, The Medicines Catapult has recently assessed, in vitro, Nuvec® loaded with DNA that had been stored at room temperature for six months. Cell transfections was successful demonstrating the stability of the Nuvec® loaded with DNA and the potential storage advantages of Nuvec®. Thus, it has been shown that both mRNA and DNA loaded on Nuvec® are conferred a high level of stability which may be an important feature in the MTA related studies.

Oncology programme

In December, the Company announced it had successfully completed an in vivo confirmatory oncology study which reinforced the results from a pilot study earlier in the year. The initial pilot study was designed to test the ability to use a monodispersed Nuvec® formulation in an intra venous (“i.v”) route of administration using a DNA plasmid (pDNA) encoding TNF alpha to assess the tolerance of different doses and to look at tumour regression.

The confirmatory study incorporated the following control and test groups: TNF alpha pDNA alone, unloaded Nuvec®, Nuvec® loaded with 50ug of the TNF alpha pDNA and Nuvec® loaded with 20ug of TNF alpha pDNA. The study was conducted in untreated tumour-bearing mouse models with dosing for each cohort completed intravenously.

The results showed a clear inhibition of tumour progression for the groups where Nuvec® was loaded with TNF alpha pDNA when compared to the other three groups. In addition, the use of Nuvec® was shown to improve animal survival rates in the life of the study.

These excellent findings show that injection of a TNF alpha plasmid loaded onto Nuvec® into tumour bearing mice successfully leads to the transfection and release of TNF alpha which results in the suppression of tumour growth and increased survival rates.

The results from the successful oncology study open up the field of gene therapy and in vivo protein production as a key opportunity for Nuvec®. This will become an important area of focus moving forward as discussed further in Future Prospects below. This advancement is the result of the ongoing optimisation work to produce a consistently monodispersed product, presenting potentially huge market opportunities for Nuvec®.

MTAs

During 2020 the Company entered into three MTAs covering vaccine delivery and gene therapy. The MTAs are subject to strict confidentiality which means the Company is limited in any meaningful information it can divulge. Since the year end, work on one of these MTAs has recently ceased as the partner has decided to stop investigating alternative delivery systems to the one it is already using in respect of the delivery of its proprietary Covid pDNA plasmid. In addition, the Company has been informed by the Gene Therapy MTA partner that, following the departure of the individuals engaged on working on the MTA, they do not intend to undertake any further work under the MTA. Work on the third MTA continues.

The MTAs have shown us that the level of engagement is entirely dependent on the personnel and resource deployed by partners which, sometimes in very large organisations, can vary greatly and sees the Company at the mercy of the partner as to timings and advancement of such studies. However, the pursuit of MTAs remains a key strategy as a means to see how Nuvec® may work with proprietary technologies.

As soon as the Company is in a position to publicly disclose material progression or otherwise in respect of MTAs it will do so. In the meantime, it will only announce further MTAs when able to without restrictions of confidentiality or in respect of a defined commercial agreement.

Intellectual Property

2021 was a very productive year in the advancement of the protection of our intellectual property. The University of Queensland (“UQ”) has seen the granting of (or notice of intention to grant) patents now in Europe, Australia, Japan, China and in January of this year the critical market of the US. N4 Pharma has the exclusive worldwide rights to Nuvec® for therapeutic uses in humans and animals.

Future Prospects

Following our most extensive in vivo work to date and the commencement of MTAs in 2021 we have a clear focus in 2022 as to where best to deploy our resources in the short term. As a result of the very positive findings from the evaluation studies looking at the potential of Nuvec® as a nano-carrier of a DNA plasmid expressing TNFalpha, which demonstrated a significant inhibition of tumour growth derived from a human cell line, the Company has commenced work with Medicines Discovery Catapult to extend the observations to allow us to identify suitable loads to add to Nuvec® to take to clinic. 

To date, the Company has established that Nuvec® can deliver an appropriate biological load and this new study will help determine the mechanism of action that produced the tumour suppression. Amongst other things, it will seek to identify whether the Nuvec® loaded with TNF alpha was directly taken up by the tumour cells to produce the active TNF within the tumour or whether other organs such as the liver took up the Nuvec® and produced the TNF and released it systemically to suppress the tumour. If it can be demonstrated that Nuvec® can selectively deliver the plasmid to the tumour this may indicate the potential use of Nuvec® to deliver to tumours with a reduced systemic effect and inform the scope of any clinical studies or collaboration discussions. In addition, studies will use labelled Nuvec® particles to allow the organ and tissue distribution of Nuvec® to be followed. 

The Company is also in the process of identifying alternatives to TNF as immunomodulators or gene therapy which may use Nuvec® as a delivery system. The selection process is expected to conclude shortly and the Company intends to conduct a study programme similar to the work being undertaken using TNF.

The oncology, gene therapy and protein replacement markets are huge and we believe will provide us with the quickest route for Nuvec® to move into clinical trials with a product and far quicker than with vaccines. That said, the potential for Nuvec’s® use in the delivery of vaccines remains but we feel any advance in this area will be best done via MTAs. In addition, through our grant with UQ, we continue our longer term proof of concept work in respect of oral applications for Nuvec®.

2021 has been a mixed year for the Company. We felt from the outset it could be a pivotal year for the Company and believe it has proved to be so. On the back of increased data and results we are now in a position to narrow our focus onto the hugely exciting oncology and gene therapy market. In parallel, we are working with a number of MTA partners assessing how Nuvec® may enhance their proprietary technologies. Whilst we are not there yet and it will be results driven, our path to the commercialisation of Nuvec® is clearer now than perhaps at any time previously.

The opportunity for Nuvec® as a delivery system for immune-oncology is substantial. Market Watch 2022* highlights that the global Immuno-oncology therapy market size is expected to grow from $US 1.23 billion in 2020 to $US 1.65 billion by 2027; an expected CAGR of 4.5% during 2022-2027.

Immuno-oncology Therapy Market 2022 Research Report Analysis by Competition, Countries Data, Sales, Revenue, Industry Size, Share and Forecasted 2027

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

John Chiplin

Chairman N4 Pharma

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