N4 Pharma plc (LON:N4P) Chief Executive Officer Nigel Theobald caught up with DirectorsTalk for an exclusive interview to discuss their latest operational update, the importance of demonstrating formulation, key milestones for the COVID-19 proof of concept programme, whyan orally administered vaccine has greater challenges than a subcutaneous injection and what news flow investors can expect from the company for the rest of the year.
Q1: Now, an operational update just published in which the optimisation program appears to be progressing quite well. Can you just talk us through the highlights please?
A1: N4 Pharma has been exploring many different aspects of how you can optimise and formulate Nuvec and basically, in this update, we can now confirm that we’ve achieved different ways to make what we called a monodispersed formulation with Nuvec where that will be with no aggregation.
So, that’s good news for us because that really shows the versatility of the Nuvec system but it’s important to point out, the aggregation of monodispersing which means where you’ve got clumps of the material, monodisperse when you’ve got each individual one containing DNA, they both have different roles if you’re developing a vaccine product.
So sometimes aggregation is going to be good because it encourages the material to stay at the site of injection, which would attract T-cells and other times the more monodispersed product is required.
So, showing that we can do both routes just confirms Nuvec’s versatility so it’s fantastic that we’ve managed to get that monodispersed version as well.
Q2: Why is demonstrating formulation stability so important?
A2: Well, any formulated vaccine product, it’s got to be stable over time so showing that Nuvec can be dried, stored, and reconstituted is part of that data that we’re going to need to talk to partners. So, showing this is a really good step forward with this work, but it’s not just about being stable, it’s about how it’s stable.
What’s key for Nuvec is our early data looks like we’ll be able to store it, just at room temperature so storing at room temperature would be fine. That’s a major difference compared to lipid systems, for example, where people are using it for mRNA, that require freezing so the Pfizer product, one of the vaccines for COVID for Pfizer and BioEnTech, that has to be stored at minus 92 degrees. So that’s going to be a major issue when it comes to rolling out that vaccine when it’s proven to be successful.
For us, the next steps will be to demonstrate how long our formulated Nuvec products can be stored in room conditions etc. and then still work.
So, doing that formulation stability work is crucial to helping partnership discussions.
Q3: What are the key milestones for the COVID-19 proof of concept programme and the in vivo study and what the timeframe is on these?
A3: So, the key thing to remember here is that we’re not in the race to develop the first COVID vaccine. We’re using our COVID proof of concept work to show to some extent what we already know that and that’s that Nuvec can deliver antibodies and so, we’ll be showing that Nuvec can deliver COVID antibodies. Showing this is going to be an absolute key milestone for the data pack that we talked about earlier that we’re generating.
It’s also important distinction, I think, to make the difference between what we call vaccine efficacy and vaccine efficiency. So, a vaccine efficacy is ‘does a vaccine work’, and that’s going to be determined by whoever owns the active part of the vaccine, be at Pfizer, Medina. The FDA has already said that they’re going to drop the hurdle rate for vaccine efficacy to just 50% so that means efficiency of the vaccine is going to be vital and what efficiency means is, so you got an effective vaccine, but how many people can the vaccine actually be delivered to and that’s where Nuvec comes in.
So, our key milestones, not only to show that Nuvec works but also to give potential partners both confidence and the belief that Nuvec will be the best delivery system to help them achieve a good vaccine efficiency. So, DNA uses electroporation, an electrical device, mRNA, as I said earlier, uses lipids that need freezing so that’s going to seriously hamper their ability to achieve efficient vaccine coverage so they may well work, but can they be efficiently rolled out?
I think vaccine developers are going to be showing that they have to be reformulating their vaccines in the future to find more efficient delivery systems and that’s how we plan to position Nuvec for that.
So, demonstrating that proof of concept for COVID is also highlighting how Nuvec can be an efficient delivery system for other vaccines as well and not just COVID, they’re going to be key milestones for us.
Q4: Talking about delivery, why does an orally administered vaccine have a significant greater challenges than a subcutaneous injection?
A4: Working with the very hostile environment of the stomach is very difficult so particularly if you look at nucleic acid systems, which is where our focus is, exposure of a nuclear acid like DNA or RNA in the stomach is incredibly difficult to then maintain it. So, the lipid systems that have been used for mRNA just will not work in that environment and electroporation they’re using for DNA is just totally irrelevant.
So, if got a nucleic acid vaccine and you want to look at an oral system then you are going to have to have a different delivery system, that’s going to be essential so that, again, is where Nuvec works.
We’ve already seen with other work, how good Nuvec is at staying in the upper intestine and now we’ve shown that it not only protects DNA from nucleic but also it protects it in the acidic environment., That gives us confidence that we can press on with our investigations for showing how Nuvec can be used as an oral system and I really believe that having an oral delivery for a DNA or RNA vaccine could be a game changer in this this space.
Q5: What other news flow can investors expect from N4 Pharma for the rest of the year?
A5: So, as we said in the RNS, we’re starting our COVID proof of concept in vivo work imminently and that’s for our un-optimised version of the Nuvec system so once we have this data, we shouldn’t take too long, we will then look to do another follow on in vivo study with optimised versions of the product. So, we’re running the optimisation work in parallel to that first study so that we can then pull all the learnings together to come up with a further proof of concept work because the continued updates of the work as we go, enables us to keep reaching out to people to say, this is how Nuvec works.
So, investors can expect a lot more news on both the COVID proof of concept work and the optimisation work and well also be updating progress on the oral programme as soon as we get it, as it goes forward.
Finally, we’ll give an update on other applications, on top of both oral and injectable vaccines, that we see and will be a priority for the development of Nuvec.
