REG - N4 Pharma PLC - Nuvec® R&D and Strategy Update

N4 PharmaAnnouncement

07/12/2023 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20231207:nRSG9316Va&default-theme=true

RNS Number : 9316V  N4 Pharma PLC  07 December 2023

7 December 2023

N4 Pharma plc

 ("N4 Pharma" or the "Company")

 

Nuvec® R&D and Strategy Update

 

N4 Pharma Plc (AIM: N4P), the specialist pharmaceutical company developing
Nuvec®, a novel delivery system for cancer treatments and vaccines, is
pleased to provide an encouraging update on its ongoing in vitro siRNA
research work.

 

The Company's double loaded siRNA work is ongoing and the Board wishes to
provide an update on the progress achieved so far, as we reach the end of
2023.  The work to date is very encouraging and is demonstrating that Nuvec®
has considerable potential to be able to knockdown two independent pathways
leading to more effective cancer treatments by reducing the ability for tumour
escape.

 

Nuvec® R&D

 

For the past few months, the Company has been investigating 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.

 

Using multiple different siRNA constructs has demonstrated that two separate
siRNA 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.  As previously announced, each siRNA
when separately loaded onto Nuvec® achieved cell inhibition and an assay to
measure BCL-2 had been established. Subsequent work has confirmed that the
expression level of BCL-2 in PC9 cells was at the limits of detection, and
consequently unlike with EGFR, a knockdown response curve could not be
measured.

 

In view of the low BCL-2 expression, the Company has been 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 in uveal
melanoma, leukemia and carcinoma. The second target was PLK1 (Polo Like Kinase
1), inhibitors of which are in early clinical trials for lymphoma and
pancreatic cancer. Additional targets may also be explored as the Company's
work progresses.

 

As with the other siRNAs explored to date, Nuvec® can be loaded with the
individual SiRNA and effect 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 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,
when loaded together there was an interaction which resulted in a reduction in
knockdown of EGFR receptor but importantly the reduction on cell viability was
retained.

 

The mechanism responsible for the interaction between two separate siRNA on
target knockdown, when loaded on Nuvec® is under investigation. One
explanation is that there is not a correlation between the degree of knockdown
and the functional effect on cell death. In particular, the Company is
exploring varying the amount of each siRNA loaded on Nuvec® to see how these
change the degree of interaction whilst also maintaining cellular inhibition.
Investigations will also be undertaken to see how low the dose can be reduced
to still achieve a functional cell inhibition endpoint as dose sparing could
be another useful advantage when using Nuvec®.

 

Oncology Strategy

 

It is likely that the precise combinations of siRNA, both in terms of target
and concentration of siRNA, will vary depending in 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 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 given repetitively, 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.

 

The in vitro findings are highlighting the complex nature of multiple pathway
targeting and the Company we will look at further in vivo studies and their
scope as this work concludes whilst, in parallel, supplying potential
collaborators with in vitro data as it is gathered.

 

The Company's oral and AAV viral vector work is also ongoing and further
updates will be provided in due course, along with news regarding the recent
acquisition of a controlling interest in Nanogenics Limited.

 

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

 

"There has been a lot of work undertaken in what is a highly complex
scientific area and we have repeatedly shown that Nuvec® is successful in
always loading and delivering dual siRNA, however the interactions between the
siRNA vary depending on which two are chosen and which cells they are tested
in so we continue to test these interactions.

 

"The work we have done so far is extremely encouraging and is demonstrating
that Nuvec® has considerable potential to be able to knockdown two
independent pathways leading to more effective cancer treatments by reducing
the ability for tumour escape. This is a highly desirous and innovate approach
in developing novel cancer treatments."

 

For more information please contact:

 

 N4 Pharma plc

 Nigel Theobald, CEO                                          Via IFC Advisory

 Luke Cairns, Executive Director

 Engage with us directly at N4 Pharma Investor Hub            Sign up at www.n4pharma.com (http://www.n4pharma.com)
 SP Angel Corporate Finance LLP                               Tel: +44(0)20 3470 0470

 Nominated Adviser and Joint Broker

 Matthew Johnson/Kasia Brzozowska (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
 IFC Advisory Ltd                                             Tel: +44(0)20 3934 6630

 Financial PR

 Graham Herring

 Zach Cohen

 

 

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
(http://www.n4pharma.com) or sign up at www.investors.n4pharma.com
(http://www.investors.n4pharma.com) .

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  UPDFSWFMMEDSEIE