REG - N4 Pharma PLC - N4 101 In Vitro Results

N4 PharmaAnnouncement

12/12/2024 07:00

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RNS Number : 7672P  N4 Pharma PLC  12 December 2024

12 December 2024

N4 Pharma plc

("N4 Pharma" or the "Company")

 

N4 101 in vitro Results

Latest data demonstrate key benefits of the Nuvec® delivery platform

 

N4 Pharma Plc (AIM: N4P), the UK biotech developing Nuvec® its proprietary
gene delivery system to enable advanced therapies for cancer and other
diseases, is pleased to provide a progress update on the in vitro pre-clinical
development of its lead Nuvec® proof-of-concept programme, N4 101, an oral
anti-inflammatory product for the treatment of Inflammatory Bowel Disease
(IBD).

 

The size of the global RNA therapeutics market was $13.7 billion in 2023 and
is expected to reach $18.0 billion by 2028¹.  Challenges associated with the
manufacturing and delivery of RNA therapeutics are known to impact this market
growth - challenges which N4 Pharma is addressing with its Nuvec® technology,
aiming to become an industry leading delivery platform used by multiple
pharmaceutical partners.

 

N4 Pharma's oral IBD product, N4 101, is designed to showcase the key benefits
of the Nuvec® delivery technology where other approaches struggle: i) it can
straightforwardly load multiple RNA therapeutics onto the same particle, ii)
it protects the payload from enzyme degradation to allow oral delivery to the
gut and iii) it can be functionalised to target specific cells.

 

The Company has completed a series of in vitro experiments (see Methodology
below for details) which clearly demonstrate these competitive advantages.

 

Key Highlights:

 

·    The efficiency of delivery and efficacy of an siRNA and an mRNA
therapeutic used to treat IBD are demonstrably enhanced when delivered by
targeted Nuvec® particles compared with untargeted delivery;

·    A Nuvec® formulation dual loaded with both therapeutics at the same
time shows equivalent efficacy to the separate treatments;

·    A patent has been filed reflecting the clear advantages of Nuvec®
for targeting and dual loading; and,

·    The Company is awaiting ethics committee approval to build on these
excellent in vitro data and begin an in vivo study in an appropriate animal
model early in 2025 at the University of Queensland.

 

 

 

 

Find more information and an additional video by Nigel Theobald, CEO and
submit any questions via the N4 Pharma investor hub:
https://investors.n4pharma.com/link/4PK87y
(https://investors.n4pharma.com/link/4PK87y) .

 

¹Marketsandmarkets: RNA Therapeutics Market size and share sep 2024

 

 

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

 

"RNA therapeutics are set to impact the treatment of a wide range of diseases
and the ability to deliver multiple therapies in a targeted fashion is going
to be central to the success of these new treatments.

 

"The data we have generated using our IBD proof-of-concept programme, N4 101,
clearly demonstrates the dual loading capability of Nuvec® and the ability to
target Nuvec® to specific cells, both of which are difficult to achieve in a
controlled way with other delivery approaches such as lipid nanoparticles.

 

"Targeting two RNA therapies simultaneously means they act on different
pathways in the same cell and the data we have released today show that a dual
loaded Nuvec® treatment results in a decrease in pro-inflammatory TNF-alpha
together with an increase in anti-inflammatory IL-10 in this in vitro
cell-based assay.

 

"These data represent further excellent validation of our Nuvec® platform and
for the potential of N4 101 to make a difference in the future to patients
with IBD.

 

"We will continue to strengthen our pre-clinical data and work towards
first-in-human clinical data for Nuvec® with the aim of securing multiple
commercial partnerships for the platform."

 

Methodology

 

The objective of RNA therapeutics is to deliver RNA into specific cells to
stimulate a reduction or an increase in the production of certain proteins
depending on the disease that is being treated.

 

In the recent In vitro experiments, mouse macrophage cells were used to
establish the ability of Nuvec® delivered RNA to:

1.    to reduce the production of TNF-alpha which is a chemical produced by
the immune systems that causes inflammation, and

2.    to increase the expression of IL-10 which is a molecule that has an
anti-inflammatory role.

 

In the treatment of an inflammatory condition such as IBD a reduction in
TNF-alpha production and an increase in IL-10 is desirable.

 

Cells were exposed to Nuvec® with and without functionalisation with mannose
that binds to the CD206 mannose receptor, which is expressed on the surface of
macrophages, the cells that are believed to cause the problems associated with
IBD. Functionalisation with mannose has the effect of targeting the Nuvec®
particles to the macrophages.

 

Cells were treated separately in one experiment with Nuvec® loaded with an
siRNA designed to reduce TNF-alpha production and in a separate experiment
with Nuvec® loaded with an mRNA designed to increase IL-10 production. The
mannose receptor-targeted Nuvec® siRNA treatment significantly reduced the
production of TNF-alpha, and showed faster and greater reduction compared to
non-targeted Nuvec®. Targeted particles carrying the mRNA showed a faster and
greater increase in IL-10 expression than non-targeted particles. These data
demonstrate the ability to target active RNA therapeutics to a specific cell
type using Nuvec®.

 

In a separate experiment both the siRNA and mRNA were loaded on the same
mannose-targeting Nuvec® particle in a controlled ratio. A qualitatively
similar reduction in TNF-alpha and increase in IL-10 was observed to the
single loaded versions, showing that Nuvec® can be dual loaded and deliver
active RNA therapies to the same cell simultaneously.

 

 

For more information please contact:

 

 N4 Pharma plc

 Nigel Theobald, CEO                                          Via N4 Pharma Investor Hub

 Luke Cairns, Executive Director

 Engage with us directly at N4 Pharma Investor Hub            Sign up at investors.n4pharma.com (https://investors.n4pharma.com/)

 To hear more, visit
 SP Angel Corporate Finance LLP                               Tel: +44(0)20 3470 0470

 Nominated Adviser and Joint Broker

 Matthew Johnson/Caroline Rowe (Corporate Finance)

 Vadim Alexandre/Abigail Wayne/Rob Rees (Corporate Broking)
 Turner Pope Investments (TPI) Limited                        Tel: +44(0)20 3657 0050

 Joint Broker

 Andy Thacker

 James Pope

Glossary

 

RNA: Ribonucleic acid, present in all living cells

 

mRNA: messenger RNA, whose role is to carry protein information from the DNA
in a cell's nucleus to the cells cytoplasm to produce a particular protein.

 

siRNA: small interfering RNA, a short double-stranded RNA, one of whose
strands can complement and inactivate a sequence mRNA to stop protein
production.

 

IBD: Inflammatory Bowel Disease (Crohns disease & ulcerative colitis)

 

Macrophages: A type of white blood cell that surrounds and kills
microorganisms, removes dead cells, and stimulates the action of other immune
system cells, in IBD the stimulation of inflammation aspect is key.

 

TNF alpha: Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory
cytokine produced by macrophages/monocytes during acute inflammation.

 

Mannose: a sugar important in human metabolism, especially in
the glycosylation of certain proteins.

 

Glycosylation: is the process by which a carbohydrate is covalently attached
to a target macromolecule, typically proteins and lipids but in this case
Nuvec®

 

Ligand: A molecule that binds to another molecule, used especially to refer to
a small molecule that binds specifically to a larger molecule

 

IL10: Interleukin 10, also known as human cytokine synthesis inhibitory
factor (CSIF), is an anti-inflammatory cytokine.

 

Cytokine: A type of protein that is made by certain immune and non-immune
cells and has an effect on the immune system. Some cytokines stimulate the
immune system and others slow it down.

 

 

About N4 Pharma

N4 Pharma is a pre-clinical biotech company developing Nuvec®, its
proprietary gene delivery system, to enable advanced therapies for cancer and
other diseases.

 

RNA therapeutics are set to impact the treatment of a wide range of diseases
and Nuvec® has several key advantages for RNA gene delivery including the
ability to deliver multiple RNA therapies in a single particle, ease of
manufacturing, protection of the RNA payload to allow for oral delivery, no
unwanted immune response and excellent stability and storage.

 

N4 Pharma is building out its preclinical data set, and working towards
first-in-human clinical data, to support significant licensing deals for its
Nuvec® platform with gene therapy partners.

 

N4 Pharma lead programme, N4 101, is an oral anti-inflammatory product for IBD
which serves as a proof-of-concept programme showcasing all the benefits of
the Nuvec® platform.

 

 

For further information on the Company visit www.n4pharma.com
(http://www.n4pharma.com) or sign up at
https://investors.n4pharma.com/auth/signup
(https://investors.n4pharma.com/auth/signup) .

 

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