TIDMN4P
RNS Number : 9316V
N4 Pharma PLC
07 December 2023
7 December 2023
N4 Pharma plc
("N4 Pharma" or the "Company")
Nuvec (R) R&D and Strategy Update
N4 Pharma Plc (AIM: N4P), the specialist pharmaceutical company
developing Nuvec(R), 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(R) 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) R&D
For the past few months, the Company has been investigating the
ability of Nuvec(R) 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 (R) without changing
the size or charge of Nuvec (R) , 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
(R) 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 (R) 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 (R), 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 (R) 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 (R) 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(R).
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(R) 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 w e have repeatedly shown that Nuvec(R)
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(R) 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 Sign up at www.n4pharma.com
Investor Hub
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(R).
N4 Pharma's business model is to partner with companies
developing novel antigens in these fields to use Nuvec(R) 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 or
sign up at www.investors.n4pharma.com .
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