TIDMN4P
RNS Number : 0367S
N4 Pharma PLC
06 July 2020
6 July 2020
N4 Pharma plc
("N4 Pharma" or the "Company")
Work Programme and Strategic 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 update on its optimisation
programme, proof of concept work on Covid-19 and a new initiative
to explore Nuvec(R)'s potential as an oral delivery system.
Optimisation Programme
Work has continued on the Company's optimisation programme
during the Covid-19 pandemic and resulting lock down. That said,
contrary to initial expectations, progress has been slower than
originally hoped as the rota system employed by the main
laboratories contracted for this work has seen the optimisation of
the DNA loading take longer than expected and this work remains
ongoing. However, these delays have been supplemented by the proof
of concept work utilising Nuvec(R) being undertaken by Evotec
International Gmbh ("Evotec") as detailed below.
In respect of the Company's collaboration work with Nanomerics
at UCL School of Pharmacy, N4 Pharma is pleased to announce that
with effect from 13 July 2020, Nanomerics will be able to undertake
a gradual return to the laboratories to continue its work under the
research collaboration agreement announced on 11 February 2020.
Prior to suspension of activities due to the lockdown, Nanomerics
had demonstrated that polyethylenimine ("PEI") loaded Nuvec(R)
could be dispersed and resuspended in an aqueous solution ready for
the loading of DNA. Assessment of the DNA loading characteristics
will be the starting point when work resumes.
Covid-19 Studies
With respect to studies involving Covid-19, Evotec remains on
track with the in vitro testing of Nuvec(R) loaded with the
Covid-19 plasmid and, in conjunction with the Company, continues to
look at ways in which it can accelerate the commencement of Stage 3
of the Covid-19 work (as set out in the Company's announcement on
16 April 2020) and perform the in vivo protein expression testing
in parallel with the in vitro studies. Assays to detect the spike
protein antigen arising from the plasmid transfection and the
antibodies produced in vivo have been established by Evotec.
Strategic Update - Potential Oral Applications
The more work undertaken and data that has been collected on
Nuvec(R), the more the Directors have gained an understanding of
the potential applications for Nuvec(R) which could give it a
competitive advantage over existing delivery systems that are
currently in use. To date, the majority of work to explore
Nuvec(R)'s potential has been centred on administering it by
injection, in keeping with the vast majority of vaccines (both
existing and in development) which use a parenteral administration
of a dosage through injection; be it intravenous, subcutaneous or
intramuscular. However, recent research on Nuvec(R) indicates that
its unique spiky structure could give it a significant competitive
advantage as a potential delivery system for use in oral
vaccines.
Oral vaccine delivery offers a number of potentially significant
advantages over other routes of administration, such as:
-- oral vaccines are cheaper to administer, since they can be
delivered outside of a formal clinical setting without the need for
trained personnel;
-- the elimination of needles from the vaccination process can
minimize patient and caregiver trauma;
-- it negates concerns regarding the reuse and disposal of
needles, which has been shown to be responsible for a number of
vaccination-related infections;
-- oral vaccines may also be cheaper to produce, due to less
stringent regulatory requirements for preparations that are
administered orally compared with parenterally e.g. the reduced
need for sterile manufacture; and
-- as an enteric capsule lyophilised final product, storage
conditions are less onerous than injectable products.
Notwithstanding all these potential commercial benefits, taken
together, these advantages could make an oral vaccine particularly
valuable to less developed countries where vaccinations can be
particularly important in the protection of life of the most
vulnerable.
Despite these potential advantages, there are a number of issues
that need to be addressed to establish an orally delivered vaccine,
and existing delivery systems used in the parenteral space are not
well placed for this. In each case the data the Company has
accumulated suggests that Nuvec(R) could be a viable solution to
address these issues.
1. For effective oral immunisation, vaccine antigens (protein or
DNA/RNA) must be protected from the acidic environment of the
stomach and also protected from the proteolytic milieu of both the
stomach and intestine. Lipid nanoparticles ("LNP") are not suited
to lyophilisation but rather must be retained as a liquid or
semi-solid formulation.
Protection from the stomach acid and pepsin proteolysis can be
achieved readily by delivering the product in acid resistant
tablets or capsules. This is a well-established principle in
pharmaceutical development and would be readily applicable to
Nuvec(R) which has been shown to be suitable for lyophilisation.
The monodisperse nanoparticulate product would be suitable for
inclusion in an acid resistant capsule.
2. There are multiple types of lipid nanoparticles and some may
be disrupted in the small intestinal fluid exposing the payload to
digestion before it can be presented to the absorptive cells.
Lipases may trigger lipid digestion and disruption of the LNP,
while proteases/nucleases will initiate protein/DNA digestion.
In general, a preformed silica nanoparticle will be more
resistant to the digestive actions of the intestinal milieu.
Previous studies have demonstrated that Nuvec(R) reduced the
digestive effect of nuclease enzymes on DNA/RNA when added to the
incubation medium.
3. The other important feature of the gastrointestinal tract is
the mixing and propulsive movement of contents in an oral-anal
direction. Solid, undissolved matter will traverse the gut and be
expelled without delivering the payload.
Mucoadhesive properties of Nuvec(R), resulting from the
engineered design of long silica spikes coated with a cationic
charge provided by PEI, will encourage binding to the mucosa
cells.
Whilst there will be multiple other challenges to be addressed,
the Directors feel that Nuvec(R)'s properties has the potential to
position it as a superior delivery technology for oral vaccines.
Furthermore, whilst agglomeration has presented itself in certain
parenteral studies with Nuvec(R), and this is being addressed
through the optimisation work, it may be less of a concern in oral
administration. In exploring the potential for Nuvec(R)'s use for
oral delivery, the Company's focus will be on addressing the issues
identified above to increase the viability of oral administration
of vaccines, in order to benefit from the vast commercial prospects
and advantages identified above.
Notwithstanding the indicative evidence that Nuvec(R) could work
orally, there are a number of steps to be taken to progress this
potential. To that end the Company will working with Evotec to
undertake some preliminary in vitro studies to establish first that
Nuvec(R) can be optimised to transfect murine intestinal cells and,
secondly, that it can transfect human gastrointestinal
mucosal/epithelial cells. Without being able to efficiently
transfect gut cells, any oral application would not be possible, so
it is essential to complete these studies prior to progressing any
further with this initiative. The completion of these additional
studies will not be at a significant cost to the Company and will
not detract from the Company's existing workstreams.
Nigel Theobald, Chief Executive Officer of the Company,
commented:
"Our focus remains on the optimisation of the formulation and
the continued generation of data for Nuvec(R)'s use as an
injectable delivery system for vaccines and cancer treatments and
we are pleased with the progress made to date and look forward to
building on this and accelerating the work programme as the lock
down continues to ease.
"Our research has indicated that certain characteristics of
Nuvec(R) could make it particularly well suited as a delivery
system for oral vaccines. The ability to demonstrate potential for
success in this area would give us a very clear and strong
competitive advantage over other delivery systems which are less
suited for oral delivery of vaccines.
"As our work streams become more defined, so do our learnings
from each, including how they can enhance the work moving forward.
As our knowledge grows so does our ability to assess and pursue the
opportunities that give us what we believe to be the greatest
competitive advantage and our quickest route to commercial
success."
Enquiries:
N4 Pharma Plc
Nigel Theobald, CEO Via Scott PR
Allenby Capital Limited Tel: +44(0)20 3328
(Nominated Adviser and Joint Broker) 5656
James Reeve/Asha Chotai
Turner Pope Investments (TPI) Limited Tel: +44(0)20 3657
(Joint Broker) 0050
Andy Thacker
Scott PR Tel: +44(0)1477 539
Georgia Smith 539
About N4 Pharma
N4 Pharma is a specialist pharmaceutical company developing a
novel delivery system for cancer and vaccine 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 cancer and vaccine 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.
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