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Having said that, My view is that they are a nanocap company, with limited no of staff and I expect that the number of commercial collaborators they are speaking to is Small. Having said that if my presumption that the collaborator they refer to is Medimmune, the research arm of a 70 billion pound company I would be more than pleased

Hopefully the current and upcoming results will allow them to play bigger venues than Mello derby. A japan tour would be good- the rns feedback following the last trip was that it provided useful introductions which would be progressed and they provided them with a 3 month supply of nuvec. News of upcoming presentations/ trips seem to boost the share price more than the actual positive results themselves. I expect a drip of conference dates to be announced now with associated videos of NT

Mazik- you are correct to say that my perspective is too narrow
The last nuvec results were presented in this poster:

https://www.n4pharma.com/sites/default/files/documents/vaccine-conference-poster.pdf

Some nice pictures to illustrate the results They brought this to Amsterdam and japan I presume
They have removed it from the n4p website in readiness for the next lot of results

The next bit is NT promoting the results to potential suitors

An important aspect of today is that the commercial collaborations being progressed are most likely with Medimmune. A deal at this point would be too early. Nuvec needs more development to be a trial ready product. It is in both parties interest that further studies will take until first half of 2019. What do others think?

It’s a single pony with multiple tricks ie a platform FWIW I think it will now prove positive in all the small animal research ie phase 1 UoA should pass ok. The immune response should be ok in mice. A challenge will be the large animals and what conditions it is used for. A key result is income. This does need a finished product but a collaboration to produce a trial ready product with CTA authorisation to enter human trials They now will have a collaboration with Medimmune for up to 18 months and Eu ncl characterisation with access to people who understand what the regulatory body ie EMEA need for nanoparticles in which the rules are still being written This is all in my opinion/my prediction Interesting times

It’s good that the ‘commercial collaborations that they continue to progress’were mentioned. Who are these with I wonder. It’s also good that nuvec performed satisfactorily vs other commercially available delivery platforms eg lipid nanoparticles- they are positioning them against these We seem to be 1/2 to 2/3 through the project. Need to optimise the dna loading- still refining it using EM/ nanotypography. We still await immune response data. Safety is a big plus

"Our next research study will focus on demonstrating the ability of Nuvec® to deliver an effective level of immunity using OVA, results of which will be available in first half of 2019'.

Its good that the medi collaboration will ongoing into first half 2019. They have 3 months until the end of the project to express an interest in licensing the data. This puts the UoA and EU NCL work, which started in Sept/Oct into a better perspective.

One problem is that the results can be good but it depends on what you plan with them. Eric Gowan’s put his patent up against electroporation and develops it for hep c and hiv on which there have already been lots of failures

You are right to say that nuvec will live or die on its results, and how these are marketed to potential collaborators. The last results formed the basis of the poster/ PowerPoint presentations which have led to the japan trip, innovate uk funded medi collaboration and Eu ncl programme entry. The results suggested the product is safe in mice and protected dna well from nucleses versus its main rival lipofectin in vitro and it transfected well vs other quoted snps or similar with different nanotypography. The next lots of results will hopefully provide it with a niche to exploit. Previously NT seemed keen to emphasise the positives vs liposomes. The last rns put an emphasis on taking existing vaccines and enhancing them - which is slightly different. I presuming it will not be a total failure as per sildenafil. This one seems more hopeful, and the hype less delusional

Here is an article from 2014 on eric gowans and the work on their cytolytic dna vaccine.
https://www.abc.net.au/news/2014-03-25/adelaide-researchers-develop-dna-vaccine-to-tackle-hiv-and-hep-c/5345068

Clearly they expected it to enter clinical trials in patients with chronic hepatitis C but they failed to find subsequent funding. They had tested it in small and large animals and it is intra-dermal administrated. There was hope the cytolytic element may mimic electroporation to some degree with inflammation/cell lysis/death
They have enhanced it further since (see nature scientific reports feb 2018) with a cocktail of HCV plasmids

They have also developed a virus like particle (VLP) vaccine against hep c, and they have vaccines against HIV and Zika (see 2016-18 project grant 300k A$). In the near term DNA vaccines are more likely to have success with cancer or zika (rather than Hepc or HIV)

N4P plan to use Nuvec to enhance the cytolytic vaccines with plans to use this data to attract other collaborators- we will have results of phase one in the coming 1-2 weeks

What do people make of the Gowan’s laboratory?

One question is why did they commission research from UoA when they are on the cusp of getting results on Medimmune N4p were keen to tweet that there was no risk to AZ investment in uk with brexit last week Was this game playing?

If MedImmune announces a deal for an undisclosed amount before end of feb 19 a knowledge of this background helps. Any ongoing connection with MedImmune would be great even if it is for a pittance in return. Nuvec has to show superiority vs competitors ie other silica nanoparticles or liposomes ( these are already in human trials) or others eg polymers such as pei. Nanoparticle delivery seems better than naked plasmids eg liposomes estimated to better x 20. The nuvec patent which relates to the manufacturing process will be important in defining its point of difference. Nuvec also has quite a lot of data now to back it up, with more on the way

Medimmune has been testing its HPV DNA vaccine in combination with nuvec for the past 9 months. The details of this has not been widely publicised by NT or others because of commercial sensitivities. The results due in Q4 will be important in defining the potential of nuvec either way

There are over 1000 DNA vaccines listed in trials but only one product, VGX 3100, is in phase3. The results are due 2020. If nuvec partners with the first product to be licensed in a new market, this will boost milestone payments vs a product in phase 1 trials

Here is a 2minute explanation of VGX3100:
https://www.precisionvaccinations.com/vgx-3100-dna-based-immunotherapy

Here is a longer one:
https://globenewswire.com/news-release/2017/06/08/1010247/0/en/Inovio-Begins-Phase-3-Clinical-Trial-of-VGX-3100-for-the-Treatment-of-HPV-Related-Cervical-Pre-Cancer.html

Medimmune is also trialling MEDI0457-a product which includes VGX3100 for head and neck cancer with some positive recent results
There are more complex articles but here is motley fools simple analysis of inovio
https://www.fool.com/investing/2018/10/02/why-inovio-pharmaceuticals-inc-stock-is-soaring-to.aspx

Medimmune and Inovio seem a very long distance from N4P- but who knows?

Eu ncl ought to provide 3 monthly updates

Alternatively maybe their phase 3 late stage trial is not going as well as they would like. The key aspect to these trials is the immune response and in this case regression of cervical intra epithelial neoplasia ( the primary outcome)Nuvec would be a possible enhancement solution if it worked well. For each of these studies remember that the vaccine is a combined product and results will depend on multiple factors not just one element such as nuvec

BTW electroporation requires an expensive cellectra machine. A vaccine formulated with nuvec would be a much easier solution MedImmune must think?

VGX 3100 dna vaccine. The reveal studies x2. Phase 3 late stage, for cin2/3 pre cervical cancer. Also earlier stage studies for head and neck and other hpv related cancers. It’s likely to be first dna vaccine in humans- there are 3 or 4 in animals VGX 3100 uses plasmid dna in saline administered intramuscularly. Enhanced by electroporation. The latter has been far the best method of enhancement of dna vaccines-for Transfection and immune response to date (landmark study by iNovio/Medimmune in 2015). There are various methods of dna vaccine enhancement though under investigation, two being dna adjuvants eg with cytosolic proteins eg perforin (cf UoA) or use of nanoparticles to deliver the dna Nuvec could enhance delivery of plasmid dna ie why MedImmune are testing it All of this stuff is easy to google.i am sending less links- it was annoying people

MedImmune have up to three months following the end of the project to announce their intentions. The project was expected to last approx 9 months from feb18. The innovate uk grant of approx 60k was paid to manufacture the combined hpv dna/ nuvec vaccine. The N4p rns stated MedImmune would test this on relevant in vitro and in vivo (small animal) models. This would have provided quantitIve data to enter into their models/ simulations from previous extensive vaccine work. They must have a threshold in mind re level of dna loading/ cell Transfection and immune response. Small animals are not good predictors of large animals but bad results ( or not good enough results) preclude further development. It’s taken 9 months and so they must have been thorough. My concern is what the implications of a no deal would be- ie we would need explanations. Would it be a failure specific to MedImmune or generalisable? This if there is no deal of course On a side issue I wonder why MI are testing their vaccine which is currently in ph3 trials and likely to be first approved dna vaccine, with nuvec? Answers on a postcard

To my knowledge N4p owns the data generated by the 9 month project with Medimmune- so not wasted. A deal at present would be important but a suspension for some months is not the end of the world. The focus at present is on ensuring reliable manufacture at industrial scale ie eu-ncl and Allen hey work. It may help for a deal to be negotiated with a collaborator post UoA and eu-ncl results The MedImmune blog last week drew reference to fact that their collaboration with Cornell University on c dots is the first human phase one trial to get the go ahead from the fda on silica nanoparticles It is clearly an area that they want to take a lead in Also bear in mind nuvec is the first silica nanoparticle to be characterised by eu- ncl. There have some first move advantage, although big np developers will not need eu-ncl