Nuformix plc (LON:NFX) Chief Executive Officer Nick Bridgen caught up with DirectorsTalk to discuss the latest positive NXP002 inhalation study results, the potential therapeutic window, toxicology planning, and ongoing discussions with prospective pharmaceutical partners.
Q1: Nuformix has recently announced positive results from the latest NXP002 preclinical study. Could you start by explaining what this latest study was designed to demonstrate, and what you see as the key from the results?
A1: NXP002 is Nuformix’s lead programme. It’s a treatment we’re looking to develop for a condition called lung fibrosis or idiopathic pulmonary fibrosis. It’s a rare disease, but it’s a very high-mortality condition. If you get diagnosed with this disease, your median survival is about two to four years.
There are therapies for this disease, but they are exclusively oral therapies, which for a lung disease is unusual. These therapies can halt the speed at which sufferers lose lung function. Ultimately, in this condition, you result with lung failure, and that’s what leads to death. These therapies can slow the rate of loss of lung function, but they actually don’t impact mortality, and they have such a poor side-effect profile as oral therapies that patients actually decline their use. Consequently, there’s a huge unmet need for new therapies in this high-mortality condition.
So, we are looking to develop NXP002 as an inhaled treatment for lung fibrosis. The results that we put out recently were really results of preclinical studies looking at inhaled delivery of our drug, NXP002. Then looking to evidence really that our molecule was engaging biology that’s specifically relevant to fibrosis, particularly the lung fibrosis phenotype, and demonstrates really that our drug is able to, post-inhalation and delivery via inhalation, start to be active within the key pathways. We think these are really important in terms of not just beginning to reduce the rate of decline of lung function and stop further progression of fibrosis, which is like a kind of a scar on the lung.
This drug is an approved oral drug. It’s been demonstrated that this drug has the potential not just to halt fibrosis, but also to reverse fibrosis and partially at least restore a function in certain tissues. So, we’re super excited about what this drug can do within this condition.
In the past, we’ve done similar studies where we’ve delivered the drug via inhalation and we’ve seen that we can see the beginnings of a response to inflammation-based challenges. This was a very different kind of study. This was actually looking at whether we could engage the biology of the drug specifically to the sort of fibrosis aspect of the disease, and that’s what we’ve been able to show as a consequence of this study.
Q2: Now, as you say, the study showed that inhaled NXP002 can achieve lung concentrations within the range that you expect to be therapeutically relevant. Alongside evidence of target or pathway engagement, why are these findings important for the development of NXP002?
A2: So, as I mentioned, the existing therapies for this disease are oral, and they come with quite an unpleasant side effect. Oral drugs, as you may well know, they go systemically around your body and as well as having on-target effects associated with therapy, there are lots of off-target effects, and this is common for numerous oral drugs.
So, we’re looking to change that situation by going inhaled. Now, there are two things that you want to know with confidence. Once you’re thinking about those kinds of delivery changes, you want to know that first of all, you can get enough drug into the lung to deliver the biology that you want to be able to leverage. Also, particularly for drugs that have shown that they have issues, potential side effects, our molecule in its oral form at high doses used for long periods does have a side effect associated with its use.
We want to make sure that we have something called a therapeutic window, that we can get enough drug in to deliver the therapeutic benefit that we want to, but also in doing that, make sure that we stay well away from the sorts of drug exposures that are associated with some of the unwanted side effects. So, that’s why we are wanting to do this study in order to have clear evidence that that therapeutic window exists, and that therefore we can sensibly develop NXP002 as an inhaled treatment for IPF.
Now, there’s also a need for us to get into the next stage of development. What some of this data allows us to do is, now that we can understand the exposures that we’re achieving both systemically, but also in the lung, start to design and possibly even execute the next development step as we start to then generate that toxicology data that allows us to then progress into the clinic.
So, for the first time, we’ve got data that now allows us to go off and make those judgement calls in terms of designing that next development step.
Q3: You’ve said that the programme was designed partly to address specific questions raised in discussions with prospective development and licensing partners. What are prospective partners looking for from the programme? Do the latest results assist in addressing those questions?
A3: They’re the first results that we hope to do exactly just as you said. So, we’ve made no secret at the fact that it’s our ambition to now find a future development partner to take this drug forward and those discussions have been going on for some time.
We’ve had interactions with multiple companies that have been through all the data that we’ve generated with a fine-tooth comb and reported back their findings. Essentially, there were three gaps, let’s call them, within the existing package that we had.
One of those, which is particularly helpful for when you’re looking to engage with very large pharma companies from an out-licensing perspective, is to be able to actually very accurately describe exactly what your disease target is whereas NXP002 is a really exciting molecule in terms of its breadth of activity that’s relevant towards fibrosis, we don’t actually have a very specific exact molecular target that this drug actually modulates. There have been a few proposed in the literature and these things, but it would be super helpful if we could actually begin to identify exactly what that target is.
So, we’ve embarked on some work doing exactly just that, and hopefully we’ll be able to report results in the near future on exactly just that work. What this data demonstrates from a surrogate perspective is that we do have engagement of that target because there’s a downstream cascade from modulating that target that tells us that we’re hitting it, and there’s this positive impact then on key disease pathways. So, that’s the first thing.
The second thing, as I was discussing earlier, it was found that the partners that were looking at our data were saying, ‘could we generate data to validate that there was a therapeutic window?’, of course, our instincts were such that, yes, from work that we’ve done already, we were already seeing evidence of the drug exerting its biology. Of course, by giving a lower dose via inhalation to the body, we’d be well south of any exposures that’d be associated with some of the known side effects for this molecule. So, we were able to demonstrate that.
The third gap was, well, how do we know when we’re going into the next development step exactly the kind of exposures and doses that we need to be then into what would be then the beginnings of preclinical toxicology studies. We now have that information as a consequence of this study.
So, the three main questions that various partners came back to us with, we now have answers to two of them, and we have other work ongoing to elucidate that target identity to really help with those discussions with larger pharma companies.
Q4: Looking ahead, what are the next steps for NXP002, including the additional studies and the partner discussions? Can you just remind investors of Nuformix’s current funding position and its ability to deliver the planned programme?
A4: Well, as a consequence of receiving our orphan drug designation approval for the US, we conducted a fundraise there, and we’re currently very well-funded for everything that we need to do. So, we’re not expecting any issues in delivering what we need to deliver with the current funding that we have. We just want to make that absolutely clear.
The next steps for us, as I mentioned, we’ve actually initiated two separate pieces of work on the target identification piece using two different technological approaches. One that’s looking at very specific targets and named molecular targets using a novel technology developed in the UK. The other is looking at some of the broader known pathways in fibrosis that we believe our molecule modulates, which would be very helpful in terms of a broad action in this disease. We’re using a different approach to validate a further pathway activity in addition. So, we’ve got those two pieces of work that are ongoing.
Further development work, we need to start taking this programme forward, and what this data from the recent announcement has allowed us to do is actually to start making progress with that tox work that opens up access to the clinic, which is very important for our partners. Partners are very interested in programmes that are either in clinic or can move very quickly into clinical phases. If we can start generating that data, which we believe we can do very cost-effectively from the data that we have now, that’s also going to be very helpful in moving us forward.
So it’s completing the target discovery work that we’ve initiated, looking to then press ahead and perhaps initiate some of this toxicology work, and then obviously continue those discussions with all of the partners that we’re in discussions with.
There’s a conference coming up in September in Barcelona; it’s the European Respiratory Society Congress. Europe is, as far as the pharmaceutical industry goes, when it comes to respiratory diseases, actually the global centre for that kind of activity. So you have the global who’s who convene in Europe once a year at this Congress and this means that over the series of four or five days, we can go and see every partner that we’ve had discussions with and a handful of other new discussions, which we’re just initiating as well, and just a very efficient use of time.
So, we’ll be going and presenting this new data and progressing those discussions with partners over the coming weeks.
