Novel silica delivery system Nuvec (R) enters final pre-clinical development stage

N4 Pharma Plc (AIM: N4P), a specialist pharmaceutical company, has announced results fromthe company’s latest research study into its novel silica nanoparticle for cancer treatments and vaccines, Nuvec®. The work, which repeated and expanded on a previouspDNA OVA study, has demonstrated that Nuvec® is capable of working in vivo when using multiple injections at specific doses.

Together with previously acquired data, these results also confirm that Nuvec®, under the appropriate conditions, can promote transfection using both DNA and RNA. N4 Pharma will now focus its final pre-clinical development programmes on optimising the Nuvec® loading process in order to increase the consistency of the in vivo performance. Once successful, this will allow the company to move from exploratory collaborations to engage in full licensing discussions.

Nuvec® silica nanoparticles have a unique irregular (spiky) surface structure, coupled with polyethyleneimine (PEI), that simply and effectively traps and protects nucleic acid (such as mRNA / pDNA) as it travels to the cells. Once inside the cell, the nucleic acid is released to activate the immune system. Nuvec® is also a natural adjuvant so it attracts large numbers of antigen presenting cells which, in turn, leads to a strong activation of T-cells, increasing the level of immune response against the target cancer cells.

Studies so far have shown that Nuvec® is well tolerated, even at high doses, with no major toxicology findings across rat/mouse in vivo and PBMC/spleen in vitro studies.

Nigel Theobald, CEO of N4 Pharma commented: “The objective of this repeat non-clinical study was to reconfirm that Nuvec® is capable of generating an effective pDNA OVA antibody response and we are pleased to have shown that it is. The work also enabled us to learn a lot abouthow the particle behaves and we have identified that improving dispersion should result in greater in vivo consistency. We will now focus on improving the Nuvec® loading process to increase the consistency of the in vivo results. We will be in a much stronger position to advancelicencing discussions once this work has been successfully concluded.”

Dr Allan Hey, Head of Nuvec® CMC Program Development added: “Analysis of the recent pDNA OVA findings has again demonstrated that, after three injections, Nuvec® produces an immune response capable of delivering a very clear increase in the number of antibodies specific for OVA in the 1:20 and 1:30 doses, where all test cases (6/6) responded. However, there was only a small response at the 1:10 ratio in 50 per cent. (3/6) of the cases tested.Analysis after a single injection at a ratio of 1:30 showed a negligible response where only one case responded (1/6). This is in line with previous studies, where inconsistent results had been observed when the CRO had only used one injection in its study.

These results clearly demonstrate that, under the appropriate conditions and with multiple injections, Nuvec® can promote transfection by plasmid DNA and lead to the production of the relevant circulating antibody.”

A program of CMC and pre-clinical studies has been identified which will culminate in further in vivo testing of the more monodispersedNuvec®formulations with OVA pDNA in antibody and oncology efficacy models. It is anticipated that this program of work will extend over the next 12 months.

In other developments, the company has recently appointed Dr John Chiplin as non-executive Chairman and Dr Chris Britten as non-executive Director. Previous Chairman, David Templeton, has moved into an executive role as Technology Director.These changes bring considerable experience and expertise to the Board as the Company takes Nuvec®forward.