N4 Pharma plc (LON:N4P) Chief Executive Officer Nigel Theobald caught up with DirectorsTalk for an exclusive interview to discuss highlights from their operational update, SiRNA, the strong commercial points of difference for Nuvec and what’s next for the company.
Q1: Nigel, N4 Pharma has just announced an operational update. Can you talk us through the highlights please?
A1: So, over the last few weeks and months, we’ve shown quite a bit of new work with Nuvec. We’ve looked at how we can get it intravenously now into the body and produce a suppression of the tumour, we’ve done two different what we call SiRNA nucleic acids where we’ve put them on and shown that they can knock down the gene that they are targeted for.
So, what we’ve now done is we’ve just done some work where we’ve shown that with other nuclear acids, we can now easily load two or more SiRNA’s onto the same Nuvec, and whilst doing that, maintain a really good dispersion, which means we can use that in our IV work.
We’ve also done that while being very prudent with our cash spend so we’ve been conserving our cash to make sure that we have plenty to do the right work that we want to do.
So, on the back of that, we’ve done a bit of a strategic review and that’s looking at all the work we’ve done in oncology gene therapy, and that’s led us to believe that in this space, we should focus on working with SiRNA and also working on that using the multiple loading approach that Nuvec can give so at least two or more SiRNA’s onto Nuvec at the same time.
Q2: So, why are companies working with SiRNA much more open to using novel delivery systems?
A2: Well, the last three years, has been transformational in the field of vaccine and nucleic acid development with the arrival of COVID. So, what we’ve seen with those companies though, is that they’ve been using really rapid, quick to market strategies and because they were wanting to get to market as quick as possible, they’ve basically all used their existing established delivery systems. With COVID, any issues or side effects that have been seen from those systems have pretty much been glossed over because the importance of getting a vaccine far outweighed any side effect issues in terms of an increased systemic response or something that you might have seen from some of those vaccines.
Now that the COVID vaccine world has moved on again, just as quick as it came, it’s sort of disappeared so companies in this space are no longer developing new novel vaccines, those that are established are bringing new ones to market. These companies are looking at developing new products using SiRNA or other RNA, but in other areas like oncology gene therapy, which is why we’re looking at it, and SiRNA is really up there now at the forefront, along with messenger RNA.
If you look on something like ClinicalTrials.gov, you can see that there’s 106 clinical trials at the moment using SiRNA, and almost all of those are in the early stage of clinical development. When you’re in the early stage of clinical development, and the time you have to get it right, those areas where side effects are far more serious so in cancer and gene therapy, if you have side effects, that’s much bigger problem. So those existing systems that have those side effects issues are far less relevant in that space so that means many, many companies, and they’re 300 of them at the moment in this gene therapy space, are looking at new delivery systems that can deliver their payload into the cell, but not have those associated side effects.
Nuvec, we feel, is right up there as one of those new novel delivery systems that they should be looking at.
Q3: Could you just talk us through the strong commercial points of difference for Nuvec?
A3: So, we’ve already mentioned that Nuvec has got fewer side effects than working with things like viral vectors or lipids, and combination therapy, especially in oncology, is much more important and seems to be the way a lot of companies are going. So, as I say, because we’ve shown that we can get two or more SiRNA onto Nuvec, that means that we can work in that combination therapy space.
It’s quite a simple way of us loading an SiRNA onto Nuvec, it’s straightforward mixing process. Lipids find it probably if not impossible, very, very difficult to do multiple SiRNA’s into one lipid because of the way they’re manufactured, and if they can find a way of doing it, it will turn out to be incredibly expensive and probably difficult to scale up.
So, Nuvec being able to work in this space, we’ve shown how it works with DNA, RNA, and now SiRNA, we’re showing that we’ve got a particularly point of difference relative to double loading combination therapy. It means we have a very strong argument to go and talk to people about using our system and all our other proof of concept relevant areas like we have great cellular uptake. We’ve always shown, you put something on Nuvec, it’ll get into the cell, the associated difficulties in formulation, they’re all relative to the compound that you put on. Nuvec, if you put something on it, it will always get into the cell and we can also freeze dry it and store it for time and then reconstitute it without any problem.
So, all those things together in that double SiRNA or multiple SiRNA space means, I think, we are very uniquely placed to take that product into clinic.
Q4: So, what’s next for N4 Pharma?
A4: We need to get show clinical effect and get into clinic as soon as possible, and that’s something we’ve been trying to do in the past with vaccine collaborators, but for vaccines, that is actually very difficult.
So, we’ve shown in the past antibody production and how you would formulate and achieved that with each different compound is very, very different, but to show an actually immune response in in vivo work in animals, it’s very expensive and takes a very long time. You can show antibody production, but in order to show something that’s effective, to give an animal immunity, you have to spend a long time exposing it to that virus in order to show that it’s immune to it. So, it’s a very expensive and difficult experiment, but with SiRNA, you can do that much, much quicker and, as I say, with our strong commercial point of difference.
So, we plan to use two SiRNA’s loaded onto Nuvec and test that in a clinically relevant and proven lung cancer model so one of those SiRNA’s is designed to stop tumour growth, and the other is designed to kill mutated cancer cells. So, having that combination where you’re stopping the tumour growing and you are killing all those cells that might have escaped elsewhere into the tumour, we’ll do that in a clinically proven model in mice, and that means collaborators will be able to see that Nuvec with that environment actually works and produces an efficacious response. That can be done far quicker and far cheaper than in a vaccine-type model.
As I said before, there are over 300 companies working in these spaces, at our last check, so doing this and focusing on SiRNA will give us a much greater chance of establishing a commercial position in this ever changing world. So, that’s the reason we’re focusing on SiRNA.