VolitionRx Limited (VNRX) Earnings Call Transcript & Summary

[Audio Gap] from Edison Group. Today I'm joined by the Volition team to update -- to provide the update on rapid sepsis screening. This follows on the heels of the last update in early cancer detection and the company's recent Capital Markets Day. The Volition team has prepared a video presentation that we'll share shortly, and it'll be followed up by Q&A, hosted with Dr. Andrew Retter. He is leading U.K.-based hematologist and medical consultant volition and Louise Batchelor, Group Chief Marketing and Communications Officer. If you have any questions during the presentation, please feel free to submit them through the Q&A tab at the bottom of your Zoom panel. We'll try our best to answer all of them. Let's get started.

Thank you, Soo, and good morning, everyone. Thanks for joining our webinar. So I will start with a short intro about Volition and then hand it over to Andy and add a few more words about our commercial strategy at the end. So first, Volition. Our mission is to save lives and improve outcomes for millions of people and animals worldwide. We are a diagnostic company focused on epigenetic marks. We have different type of application on the human as well as on the animal side, screening, monitoring -- disease monitoring, and you'll see that in our presentation and the clinical use case that Andy will outline. We started our commercial journey and our monetization of our IP. We believe our addressable market is very sizable. We started with vet and we are entering now into the human space. We have 2 key areas where we will be focusing in the short-term. Vets, so we have our cancer products, now we are working towards scaling this product, and then NETosis. And on the human side, obviously, we have the NETosis product line that we're going to discuss. We also have something that is a little more on the early side, but I think it's important to mention it quickly. It's our licensing opportunity on the oncology around the CTCF-ChIP technology. So, now I'll pass on to Dr. Andy Retter for his presentation, and I'll come back quickly at the end.

Hello, everybody, and thank you to Gael for that introduction. My name is Dr. Andrew Retter. I'm an intensive care consultant and specialist in [ neck and bone ] thrombosis. And I'm here today to take us through sepsis and how it relates to our products and H3.1 going forward. I am going to cover some of the stuff I've talked about previously, but we do have new information to share with you today. Just want to highlight my potential conflicts of interest. I'm really passionate about sepsis. It's my clinical focus, my research focus and most importantly, I'm desperate to try and improve, along with Volition, we share a passion for trying to improve outcomes of patients with sepsis. The views expressed here today are my views, and they do not represent the NHS Foundation Trust I work for in any way. Sepsis derives from the Greek word Sepo literally meaning I rot. If you go back in history, we can see that the Egyptians recognized patients with sepsis as well as the ancient Greeks. Roman literature comments on it as well. But it wasn't really until just before the First World War that traditional definitions were starting to be described and then more recently work in the 1980s, 1990s, early '90s right up until 2016, work has continued to refine the definition of sepsis. The 2016 definition of sepsis is a real step change. It talks about a dysregulated host immune response for the first time. And really, this is where we're targeting the H3.1 test to try and identify those patients who are sickest and are most likely to deteriorate. Sepsis is a life-threatening condition, which arises when the body's response to an infection injures its own tissues and organs. Our immune system is evolved to localize and try and wall off infections, and so the immune response is incredibly, precisely controlled. It's exquisitely localized to the site of infection and to the time of infection as well. So the changes that happen are just really spatially controlled. What we're starting to think now is that sepsis, at least in part, relates to this loss of localized control, and the excessive immune response that's generated ultimately damages other tissues and organs. Sepsis is indiscriminate of age, ethnicity and socioeconomic status. It can be triggered in otherwise healthy people, but people with weakened immune systems are particularly at risk. And given the increasing number of chemotherapy agents and novel cancer drugs, the number of patients vulnerable to sepsis is ever increasing. Sepsis can be thought of a disease of the very sick, but 80% of patients develop their infection outside of hospital and present to the emergency department or emergency room as the first step on their journey into hospital. Sepsis is a spectrum which evolves over time. Sometimes the deterioration is rapid and sometimes the deterioration is slow. And this is, again, where we think H3.1 will be very helpful in identifying the trajectory patients are following. Sepsis is one of the most preventable causes of death worldwide. There are almost 50 million cases a year, resulting in around about 11 million deaths. It's responsible for just over 40% of the deaths in children under the age of 5. In the U.K. alone, 5 people every hour die of sepsis. That's more deaths a year than bowel cancer, breast cancer and prostate cancer combined. What's even worse is that 40% of the survivors have long-term consequences. The most obvious changes are people can lose digits, fingers and toes, but many describe cognitive impairment with impaired memory and concentration, decreased function, decreased exercise tolerance, inability to return to work. And sepsis is a huge cause of lost work hours in the workplace. Despite this overwhelming burden of disease, sepsis receives relatively limited funding compared to other comparative conditions. We would argue there's a great unmet population health requirement. You can see from this slide provided by Professor Djillali Annane that the incidence of sepsis per 100,000 of the population is 377. Again, that's more than heart attacks, strokes and cancer. But you can see the funding, cancer attracts by far the most funding, and yet this disease, which is preventable with the correct treatment on identification in the majority of cases, receives by far and away the smallest amount of funding at approximately $91 million a year. Sepsis is the great mimic. It's extremely hard to diagnose. And indeed, the 2016 definition of sepsis that I mentioned a little while ago, talks about the concept of occult sepsis or hidden sepsis. People can be fine until very late. People don't always have to present with a high temperature. Indeed a low temperature is probably suggestive of more severe disease. Sometimes people just present confused. Sometimes people have a cough and a raging fever. Sometimes patients just have difficulty passing urine. Sometimes people fall over. Given the diversity of symptoms, their vague nature and the inconsistent way they can progress, our hope and the design behind our studies is to try and produce data, which will enable clinicians to identify which patients are more likely to deteriorate and those who are more severely ill. We hope that this will enable us to start treatment in a more timely fashion, which will lead to improved outcomes. The risk of death from sepsis, or from bacterial sepsis increases by 7.6% for every hour in which appropriate antibiotic therapy is delayed. That's an amazing figure. What we should also explore is there are viral and fungal causes of sepsis too. And so there's a huge amount of work to do to try and improve outcomes. Our current diagnostic strategies are empirical and often involve choosing best guess antibiotics. Research tools have been developed to help us identify and track the care and outcomes of patients with sepsis. These are classically the SOFA score, the SAPS II score and APACHE scoring systems. However, I'm really passionate about sepsis. I see a huge number of patients with sepsis. We don't really use them in our day-to-day practice. They're slow. There can be errors in analyzing them up, and they're a bit cumbersome to use. They are very useful for research studies in identifying the sickest patients and making sure that we've recruited the right people, but they are not really used at the bedside. In medicine, as in life in general, we're often trying to oversimplify things. And rather than sepsis presenting as one point in time, it's a spectrum that evolves over time. I've stolen this graph and I've modified the subsequent slides from Professor Hotchkiss' paper, which was published in Nature Review Disease Primers in 2016 and basically is trying to show the evolution of the immune response over time. The prevailing thinking is that when we have an infection and our cells are damaged, a huge number of proteins leak into the blood, which can stimulate an immune response, and ultimately, lead to the body attacking itself. And therefore, at this point, the immune system is down regulated. And so what you can see is we oscillate between a hyperinflammatory phase and an immunosuppressive phase. That's why in this graph, there is a middle line where patient's inflammatory response waxes and wanes over time. Our early data suggests that H3.1 may be able to help us identify this waxing and waning nature. Going forward, we hope that H3.1 will enable us to determine therapeutic strategies to try and interdict as patients become hyperinflammatory to try and understand those who are sicker, and hopefully develop new strategies to improve patient outcome. Pulling these last few slides together, we believe that sepsis represents a huge unmet medical need across the whole population demographic. And there's a desperate need to develop new diagnostic tests and new therapeutic strategies. Diagnostically, we can differentiate 2 groups of tests: those that help us identify the presence of bugs, microbes, bacteria, fungi, viruses; and those that help us identify the host immune response and study the host immune response and potentially lead to modification of the host immune response. If we pause for a second and look at COVID, many of the strategies in COVID manipulated the host immune response. Steroids from the REMAP-CAP study, tocilizumab also from REMAP-CAP, Baricitinib, all attenuated the immune response. And if we can identify strategies to provide a more targeted and precision approach to the management of sepsis, we really hope that we'll be able to improve outcomes. At present, the test takes 45 minutes. We're well on the way with the work to take this down to 20 minutes, and therefore, we potentially have a test which can be run repeatedly to follow patients' trajectories and aid in their diagnosis. We believe this will be a game changer to help clinicians on the bedside monitor the progress of sepsis patients. I'd like to try and bring sepsis to life by walking you through a recent clinical case. This case involves a 34-year old gentleman who actually caught flu from his daughter. He was otherwise fit and well, healthy, walked miles a day as a postman, smoked 5 to 10 cigarettes a day. He felt unwell. Felt unwell with a high temperature, flu like for 2 or 3 days, and then presented to his GP, had a very high temperature and was sent to the emergency room. He rapidly deteriorated. By the time of his arrival in the emergency room, he was blue. Proper name for that is cyanotic. So oxygen saturation in his blood were very low. His chest X-ray showed infiltration in both lung fields, and he was extremely unwell. Shortly there afterwards, he was intubated, let's say breathing tube was placed in his windpipe in the emergency department, and he had lots of lines put in to give him medication to support his blood pressure, to help his heart, to help his kidneys, and obviously, to give him antibiotics too. You can see here on the X-ray, the shadowing in both lung fields, just consistent with the infection and with fluid associated with that. And this is flu, and this is classic flu presentation in a young patient. He also had a secondary infection with something called Group A streptococcus and was very, very unwell and profoundly shocked. He was admitted to intensive care. He continued to deteriorate, and we were no longer able to safely ventilate him. That means that the level of oxygen we were using and the pressures we were using to get oxygen into his blood was so high that they were actually damaging his lungs. And so, we placed him on ECMO, extracorporeal membrane oxygenation. It's essentially a mini lung bypass machine. He spends about 10 days on ECMO and a total of 14 to 15 days in the intensive care unit. We were able to take the breathing tube out successfully and he was stepped down to the ward. We spent another 3 weeks of rehabilitating, getting stronger prior to getting home. He's still not back to work. This is a young, fit, healthy man previously showing the effect that sepsis and infection can inflict on people. He actually lost a few toes. You can imagine a postman losing his toes and having difficulty in pain walking has profound life changing consequences for him and his family. If we can help identify these patients sooner, hopefully we can start treating them sooner. H3.1 may give us a new therapeutic target too to improve outcomes, and so, extremely hopeful for its use and adaptation in the future. In the next few slides, what I'm going to do is explain how H3.1 works, and I'm going to try and tie it together with our immune response and how when that immune response goes a bit awry, you can get organ damage. And I'm going to tie it up with the clinical cases we just mentioned. This slide here shows a healthy Neutrophil in the bloodstream just circulating. Upon exposure to a bug, it becomes activated and it releases these Neutrophil Extracellular Traps behind it. These NETs are decorated with proteins that are toxic to bacteria and viruses and fungi. The proteins -- some of these proteins also signal to other immune cells to say, "Come here and help guys." And then these NETs actually act as sort of a physical scaffold to trap some bacteria. And we know actually that a number of bugs can manipulate NETs as a way of trying to survive a bit longer. If we think about our postman, our postman had a very severe pneumonia, and severe chest infection and activation of immune system. And his immune response was such and his organ failure was such that he actually developed kidney failure and heart failure. And if we think about it for a second, it's a bit odd. Someone has got a low level of oxygen in the blood, but we correct that with medical therapy, with a ventilator and extra oxygen and we're treating the infection. But why do their kidneys fail? Why does their liver fail? Why do their heart fail? Why do they get confused? It's very complicated, that immune response and H3.1 is a small part of that. But if we can identify that and understand that more, that's really useful as a diagnostic and therapeutic area going forward. What happens when NETs become excessively activated is, our endothelium can be damaged and we can get loss of the localization and coordination of the immune response. And that's why you can see organ damage to these tissues below, to your heart, to your lung, to your liver, kidneys, to your bowel, and to your brain, through multiple system problem. Volition's test, the H3.1 assay, is picking up nucleosomes which are a key building block, a part of Neutrophil Extracellular Traps. Nucleosomes are DNA wrapped around histones, and you can see here the antibody test specifically picks up histone H3.1 and then has a second binding motif, which makes it specific for nucleosomes. Our research has shown that this correlates extremely well with Neutrophil Extracellular Traps. So, for the first time, we have a test which can potentially show activation of our innate immune system, which can be scaled rapidly, which is cheap and can be delivered in a meaningful time frame; 45 minutes to run this test, and we hope to get it down to 20 minutes very soon to show clinicians what's happening and give us a window into our immune response. Outside of PhDs and thousands of pounds on complex research tests or thousands of dollars on complex research tests, we've never been able to do this before. And that's why we hope that H3.1 is potentially game changing. Just to preempt some questions. How do we know that Neutrophil Extracellular Traps are essentially sepsis? Well, we've got a large amount of experimental data from animal and now from some human models suggesting that elevated levels of Cell-free DNA and elevated levels of [ mitosis ] are found in patients with sepsis. The highest levels are found in those patients with the most severe sepsis. And there's increasing data to suggest that the high levels are associated with a worse outcome. How can we show that H3.1 is an excellent marker of NETs? That's been a really key research question for Volition. And we have just submitted a paper working on a novel synthetic model of sepsis. Some model of sepsis in a test tube basically, and I'm really excited to say what we've shown in that is that we can use biological triggers to stimulate neutrophils and model sepsis. And we've shown that H3.1 correlates extremely well with neutrophil activation. And so we have now got a clear scientific data showing that H3.1 directly links to neutrophil activation. Do we know that removal of NETs improve outcomes in sepsis? There are 2 potentially extremely exciting areas where it's been shown that removal of H3.1 Nucleosomes potentially leads to improved outcomes. It hasn't been done in humans yet, but there is a pig model of sepsis using a capture, an immunoadsorption column. What does that mean? It's a column of blood outside the body that blood passes through, and it's lined with antibodies to capture and pull out Nucleosomes. And in a pig model of sepsis, that improve the outcome of pigs. Very recently, a paper has been published on a sheep model of sepsis. And in that model, a specific drug was given to bind to and attenuate the effect of circulating nucleosomes. And again, that paper showed improved outcomes for the animals with sepsis. They had -- they required less organ support, and they had less of an inflammatory response. To me, that's really, really exciting because you've got 2 independent methods by which we've lowered H3.1 levels and shown improved outcomes. It's not absolute proof, but it's a really great insight into a new potential therapeutic target, which shows the huge potential benefit of this test in identifying patients, in monitoring patients and actually targeting their care. We have several large scale clinical studies underway, where we're working with a number of key opinion leaders and Centers of Excellence across the field. And we hope to have more concrete data to show at conferences and publish later in 2024. Our aim is to launch a low-cost, rapid, easy-to-use, accessible diagnostic test, which is affordable not just to first world, tertiary referral, high-income, specialist hospitals, but is accessible everywhere. Sepsis is a global disease, 50 plus million people a year, and so our aim has always been in a very broad market, not just teaching hospitals. We hope that H3.1 will enable us to identify and personalize care in sepsis and enable, hopefully and most importantly for patients, swifter diagnosis and a faster recovery. Going forward, I'd like to take you through some of our published data and our future studies, which we're trying to address specific questions. We were incredibly lucky to host a key opinion leader event in Athens in September last year. And as a doctor who's always been interested in sepsis, it was amazing, a little bit intimidating as we had 7 professors of intensive care and sepsis in the room and there was a really good and robust and detailed discussion about ways forward, and everyone could see the potential for the H3.1 assay. And very much those discussions have informed the design of studies going forward. We've got 2 papers published thus far and a lot more in the works. The first paper was the [indiscernible] paper, published in July 2022, and really, that showed that H3.1 correlated with the severity of sepsis. In particular, it correlated very well with the H3.1 levels, correlated well with the SOFA score. If you remember, I mentioned the SOFA score a little while ago as really a research tool for just assessing how sick people are with sepsis. The next paper was published by Professor Gila Monterreys Group at the -- just before the European Society of Intensive Care Medicine meeting in October. And that showed an association between NETs -- between H3.1 levels and mortality in patients with septic shock. Those patients who were sickest, those patients who are more likely to die had the highest nucleosome levels. And actually, we could see a change in trajectory of those patients who were going to survive. For those patients who survived their NET levels, their H3.1 levels fell more rapidly than those patients who had a worse outcome. You heard me mention a few months ago, our novel rapid high-throughput method for NETosis induction. We're really excited by this paper and actually are tremendously proud of our scientific team in California and the work they've done to identify triggers to stimulate Neutrophils -- to stimulate neutrophils in a reliable, reproducible and consistent fashion, and actually to show the release of Neutrophil Extracellular Traps and then show how H3.1 correlates extremely well with the release of these -- with the release of Neutrophil Extracellular Traps. This is actually a key scientific plank for Volition. It underpins the validity of the test and shows that H3.1 does correspond with Neutrophil Extracellular Traps. We've got 2 more papers we hope to publish to reinforce and reiterate the scientific validity and actually the unwinding of DNA in the next 12 months. What are we doing to prove the clinical utility? Well, we have 2 large studies ongoing at the moment. The first is with the Mars study group and the second is with the [ German SEP NEP ] study group in Jena. Together, this will look at the evolution of sepsis in around 2,500 patients. So we're really excited to put H3.1 to this test. Again, we hope to publish this data in the autumn or perhaps early in Q4 for 2024. Finally, we have a study open at Guy's and St Thomas' Hospital dealing with fresh samples. We aim to recruit around 500 patients, 50 patients undergoing cardiac surgery and then 450 patients with sepsis and to compare the two, to see their evolution. Again, the questions we're asking there, how good is H3.1 at discriminating illness? How good is it at identifying severity of sepsis? And how good is it at tracking, following the trajectory or the severity of a patient's illness? We expect to finish that study in Q2 of 2025. So we've got a huge amount of work underway to really reinforce, improve the clinical utility of the test combined with our refinement of the manufacturing process I mentioned earlier. We hope to have much of this data available for a data room at the European Society of Intensive Care Medicine Congress in October 2024. We're going to look at key measures; the disease severity, ICU mortality, ICU length of stay, 28-day mortality, duration, severity and total volume of organ support required and length of stay. As you heard me mention at the beginning of the talk, 80% of patients develop sepsis outside of hospitals. So, our work is looking at patients presenting to the emergency room and to intensive care. It's not quite so focused on geography, because we're taking our care to the patients. We're hoping to show its predictive value, its prognostic value, and potentially its therapeutic value too. These studies are across a variety of clinical settings, across a variety of patients. The aspiration here is to show its depth and breadth of use in clinical scenarios. And hopefully, if we can produce good data, that will speed and enable rapid adoption and roll out to clinicians across the world. Thank you for listening, and I hope I've shared some of my passion for sepsis and trying to improve outcomes for these patients or for our patients. I'd like to hand you back to Gael now to take you through the commercial strategy. I'll be here till the end, and I'd be delighted to answer any questions anyone might have.

So thank you very much, Andy, for your presentation. So now a few words about our commercial strategy. As you know, we are focusing on the R&D at core. This is something we're very strong and we're doing it internally as well as with selected partners. And then, when the product is ready, we are working with global players for the distribution side. In certain markets, whether it's fragmented or it makes sense, we might also add some regional companies. So, we partner with those established diagnostic companies to sell, to process or test, and the goal here is really to leverage their network and expertise, and -- as well as the 2 principles that we outline, make sure we're not scaling our OpEx massively. So effectively, the model that we're working with is low CapEx for partners. And I'll mention in the next slide, again why that is the case, and low OpEx for us, because we're relying on the distribution partner for the scaling of our products. And then the second key principle that is very important to us is to be accessible price-wise, but also accessible worldwide. So now, the building blocks of our NETs strategy, if you will, how do we build up the value for commercial partners and for their clinicians? So, first, the platform and the products, we're effectively working on the transfer of our technology to different platforms. So that's linked to what I was mentioning about the low CapEx. Our partners don't have to onboard new machines. We're working with their existing systems, that also help accelerate the scalability of our products. Then we're working on the improvement of our products. As always, we incorporate the feedback of the clinicians, of the partners, and we iterate to bring to the market what we think is the best product. Market access. So this is the continued nurture of KOLs, networks and then the Centers of Excellence that we mentioned. So we held a key event last year. We have another one coming in September 2024. This is really building the connection with the key people in the sepsis world, and it's yielding a lot of benefits to Volition. So, the third building block, if you will, is regulatory. So now we have a clear pathway for the U.S. 510(k). In the EU, we have already an IVDD and we are -- we will look into the timing of applying for IVDR. And then finally, and linked to what Andy was discussing, we're really building the clinical evidence of our products. And this will really translate in adoption by clinician as well as build up the value for the commercial partners that we're discussing with. So, the commercial strategy, based on those building blocks, and as I mentioned earlier, we're really focusing on licensing. That doesn't mean we don't do a couple direct sales with the Centers of Excellence. But really at core, we're focusing on building a strong distribution partnership. You heard about the Heska [ and the ] Mars agreement. It had the component of an upfront of milestone payments. So, when we sign, we receive $10 million upfront with Heska. Again, no Mars. We received recently the $13 million milestone payment, and we have more coming. We also are working on a different structure around royalties as well as the sale of key components. So, you will see in most of the transaction we do, at least 3 of the 4 components that I mentioned; the upfront, the milestone, the royalty, as well as the sale of the key components. But effectively, once we license a product, we are receiving those payments at the beginning and during the regulatory journey, if you will. But we also have ongoing sales, and I think that's really important. We're not giving away the product. We have this style of sales and growing sales. Now, in terms of strategic partnership, we initiated a partnership with IDEXX. So this is a technology partner. Now it's moving into distribution agreement. IDEXX has an installed base worldwide, but here, we're focusing only EU. It's an outreach program, early access.. We can call it a pilot for now. And subject to the feedback and the progress that we're making, we hopefully are going to dial up this activity. So, I can make a little comparison, for those familiar with our vet products, we had this kind of similar initial partnership with Texas A&M. We're applying some of the same principles here. Now, in terms of key milestones that you can expect over the next year. As I mentioned, this early access program with IDEXX. We also have the Centers of Excellence. Some of them are going to convert now into routine. We are going to -- based on the feedback and as well the timing of some negotiation, roll the same program in the U.S., but this time not as a regulated product, but as REO. This might take a little bit of time, so it could be later in the year as well as in Asia. We're working on a new generation to incorporate the feedback that we got from partners of the product. So that's what we call the Gen 2. Lot of incremental improvements that help with the workflow of clinicians. It's not as much the performance, it's really focusing on the workflow and making it easier for clinicians and for commercial partners on board. Then we have the core of the discussion today, the clinical utility, and demonstrate with strong data. So June or mid-year is kind of a turning point for us. We will hopefully have established the cutoff, the value proposition and it will be really the time for us to push this commercial partners. And we are discussing with them already. Some are very interested, but we need additional data to really crystallize the value. And just to clarify, the Gen 2 is what will be used for licensing and the pivotal and regulatory studies for the one we might be conducting. Obviously, for the partners, it will be their version of our products. And then finally, I think in October, you can expect public presentation of this data at the ESICM. Looking forward, very excited to launch our Nu.Q NET product. It's a low cost, rapid, easy to use and accessible test to help save and improve millions of lives worldwide. So with that said, now I'll turn over back to Soo for question and answers. Thank you.

Thank you, Andrew and Gael. And also thank you to the whole team for your efforts in early sepsis detection. Just as a reminder, if you have any questions, please feel free to submit your on the toolbar at the bottom with Q&A, the Q&A tab. Let's get started. We have -- I actually have a few questions. Maybe I'll ask those first, and then we'll kind of go through the whole audience. We have quite a few out there right now. Overall, there's a little bit of a mismatch, I think, with the prevalence of sepsis versus the extent of the investment. Why is that? Especially if you kind of look at cancer and cardiovascular disease, it just doesn't seem like it makes any sense.

Soo, I kind of think about this as the sort of boiling frog metaphor that I think everyone's is familiar with. Everyone knows it's there. We've seen it's been there for a long time. There hasn't been anything new or sexy in sepsis, that's really been a game changer for a long time. There's been lots of work done on processes with the surviving sepsis campaign and lots of other national institutions there. But there's been nothing really new for a long time. I think that has inhibited investment. There's huge interest in improving sepsis outcomes now. Again, so much morbidity and mortality associated with that. And actually, we've now got better papers. The Rudd paper is one that was published in The Lancet about 2 years ago now, and that was funded by the Bill & Melinda Gates Foundation, really starting to put numbers on the volume of the huge burden of disease. That's where this 48 million patients affected a year figure comes from. And I think that's really helped to crystallize this as a problem, and refocus people's minds. There's a huge passion to revisit and improve outcomes in this area.

Yeah. That's good to hear. My second one is the VolitionRx assay identifies the H3.1 nucleosome. Can you help me understand why this is a dependable proxy and the applications of measuring NETs?

So, that's a really, really, really key question. And that's actually one of the key questions that I asked when I came to work for Volition. How do we know this test comes from neutrophils? And really, that was one of the key drivers behind [indiscernible] paper that you've heard us mention in the webinar. And when you look into that and look at the figures that we produced in that, we deliberately triggered neutrophil activation in a number of ways. And then we did a number of tests to show that we activated neutrophils and we were able to consistently show that H3.1 was an excellent marker of neutrophil activation. So we're really, really reassured by that. I don't want to get too technical, but H3.1 is classically associated with cells that are more actively dividing in a [indiscernible] cell cycle. And so that particularly pivots them towards being better at picking up neutrophils as well. So we're really confident in the science there. And we absolutely know that these are the building block, which comes from those tails that you see in the diagram being ejected from the neutrophil. So, yes, we're doing more work on this, and I think I mentioned in the webinar that we hope to have 2 more papers in the year to really emphasize and reinforce that benefit.

Yes. And I would just add as well Soo that, that paper has recently been accepted for publication now. So, whilst it's currently is on bio-archives, it will actually be published in the near future. So, certainly a lot of good scientific basis now.

Yes. And that kind of gets to the next question, right? I mean, we're really excited about the potential NETs and Nu.Q to NETs test and monitor patients for sepsis severity and the tracking of progression. It seems like you have a lot of studies going and you're building a lot of the clinical data. Are you also working on developing the next-generation version of the test? And does that -- is there something you need to do before you file?

As I said, going back to the presentation, we're desperate to bring something to market, which is scalable, reproducible, can be run in a rapid time frame to deliver to clinicians and so, we've learned a huge amount from the first version of the assay. And now that's enabling us to make decisions about how we design the next version to enable us to bring the turnaround time down faster and to actually have a slightly better range on the result that we produce. And we're doing that because we want to help practicing nurses and doctors at the bedside to get them a result quickly and get it in a more relevant time frame. So all the work we've done on the first version is helping the development design that we have to put into the second version. And we're well on the way to bring that into laboratories.

Yes. So, you have the details on the 2 trial designs and that's going to be reported before the year-end, all right.

Yes.

Okay. So we're going to take some questions from the queue here. As you achieve more success in sepsis, in the sepsis product development, how will you narrow down the licensing partners and the commercial partnerships? Could there be an update on licensing deals by the end of the calendar year?

Yes. So, I'll take that one on Gael's behalf. So, we are already in discussions with a number of companies, but really to progress those discussions further, we're wanting this data room that Andrew has just been talking about in terms of the very many studies that are ongoing currently. So, we see and June, as Gael said, is a real inflection point for us to pull that data together to progress those discussions further. We have got a list of criteria that we're assessing, partners against in terms of market penetration, and their existing portfolio, their geographic niche, et cetera. So a lot of background work has been done. We do know from our experience with Nu.Q Vet that these licensing deals can take time. But what I would say in answer to the question is, we are hopeful to get some deals done this year, and we'll certainly be keeping people updated as we go through the calendar year and the Qs et cetera.

Are there accepted therapeutic options for those at risk for sepsis and are the costs effective and with good outcomes?

I actually think that's quite a tricky question to answer, and please bear with me. So I think we're all familiar with the concept that time is tissue, and there's sort of -- in cardiovascular, there's a door-to-needle time to get clot-busting drugs to opening arteries if someone's having a heart attack. And there's very much a door-to-antibiotic time that healthcare institutions have to assess the quality or the speed for which they deliver liver care. So the earlier you spot someone with sepsis, the earlier they start antibiotics, the earlier they start fluids, and the earlier they start being treated, the better their outcomes. I talked about it in the presentation, the trouble with sepsis is it's the great mimic. It can be very, very, very hard to diagnose, and people change and their condition changes over time, and therefore, it can be easy -- indeed, it's very easy to miss the diagnosis. And so that's where we really hope and where -- look H3.1 will enable us to make a diagnosis and not miss a diagnosis. It's another string to our bow, so to speak, to try and help diagnose patients early.

Okay. We have another question here. They'd like a little bit more details on the 2 trials to be reported before the year-end.

So, in very broad brush strokes, the 2 trials that we're working with are [indiscernible] in centers with a huge degree of expertise in sepsis and research in sepsis. And we're using H3.1 and they're established by [ banks already ] to compare it to very well-characterized, very high resolution clinical data, and that's extremely exciting for us. So, that work is actively ongoing at the moment, with us processing samples that we hope to be able to analyze the data in -- to be actually analyzing the data by the end of Q1 and have it hopefully finished by Q2 or early Q3. That's really what we're working for, to work towards really enhancing the clinical utility data and bringing that later in the year.

Yes. And what I'd just add on to that is, so that data, we're hoping to publish at the ESICM Congress in October. But we will have it in our hands much earlier than that. So, we'll be able to kind of use that in some of our confidential discussions, which will help progress, hopefully those partnership deals that we mentioned. But also, there is a good summary of the ongoing studies because we've got studies beyond those two projects in the thematic report that was recently published by Edison. So I would also take a look at that table there to give a more complete view of the number of different studies, both retrospective analysis of prospectively collected samples and then also on a large scale prospective study in conjunction with Guy's and St Thomas'.

Thanks for the [ plug there ]. So, we have another one. It was mentioned earlier that Volition is considering looking for new sources of funding in the U.S. for the NETs program. What stage is Volition at in the fundraising process and how much funding is needed to get through the 510(k) pathway front?

So, I'll take this one. I'd rather Cameron was here. But we are actually looking at a range of different funding options, not only in the U.S. but also in Europe as well. You'll be well aware if you've been following Volition for some time that we have managed to generate a great deal of non-diluted funding, especially from Belgian agencies and Belgium government agencies. So we're certainly looking at that. We're also looking really to some of these licensing opportunities that might then come with milestone payments, et cetera, or potential upfronts. And we look to just update people through the quarterly calls as we go through the year.

And I add to that too. So, to bring a successful biomarkers market, we've got to prove the science, which we're really working on and have got publications going forward, and we're confident with got to prove the clinical utility data. Every area we've tested it in so far has worked, and we really got lots of studies ongoing to try and reinforce that prospect as well. And you've got to get the manufacturing sorted and we've learned a lot and we're really, really excited. It works well already, but we've got -- we've learned from what's worked well and improving that for the second version. But then once those are sorted, you do your regulatory study. And so we're really, we're encouraged with our progress in all of those building blocks. So hopefully, that will really help us go towards the regulatory pathway and make it a success. We'll have a lot of clinical utility data before we get there too, which will absolutely drive adoption amongst clinicians.

So I think there is a trajectory -- I think you mentioned earlier that waxes and wanes, right, for sepsis. Does that imply that nucleosome levels are -- also oscillate during the progression of the disease? And if so, how does that affect the interpretation of the data points in clinical studies?

So, we're looking at the assay in 2 particular ways. There's the presentation, when a patient presents what's their level and how does that help you make her diagnosis. So it's ability to predict your risk of sepsis or developing sepsis. And then your question specifically relates to using it as a monitoring test and to see how it changes over time. I can't say too much at the moment, but we do have data coming specifically addressing that question now of, how it evolves.

Okay. And the one thing I would say as well, sorry, just to add on to that is, I think what's interesting to me about some of the ongoing studies now that we have in play is that it's actually looking at patients throughout the hospital. So some are in the emergency room or the emergency department or A&E depending on where in the world you are. Some are in intensive care settings. So we're actually starting to broaden out the potential use cases and the number of longitudinal points So, the 2 studies that Andy mentioned already in terms of the Mars study and the [ Yenna study ], they are both studies of longitudinal samples, so that we can see these multiple time points for the same patient. Then the prospective study at Guy's and St Thomas' is also a longitudinal study with multiple time points. You'll also see the [ RHU ] RECORDS study that's ongoing over in France with Professor Djillali Annane is longitudinal in nature. So again, we'll see that journey. So I think it's a really good question, Soo, that in that you do need to be able to see not just a moment in time, but be able to track that patient over time. I think that's a really good question.

So, we already have data from Catherine Reyes publication in COVID showing that the patients who survived their H3.1 level fell. Those who died their H3.1 level remained higher. So we've got some published data on the trajectory already. And just as Louise says, in all of those studies, describing the kinetics and the evolution of the kinetics of H3.1 over time is a key part of all those studies.

So it's exciting the prospect of developing this technology into personalized treatment with Nu.Q Capture technology. Could you provide some additional clarity on how it's to be used in a practical perspective?

So what I hope is that it's sensitive and specific, and it's essentially more or less used for every patient presenting to a hospital if there's a question of sepsis, to help guide their treatments for people who are sick and admit them to hospital and escalate their therapy and spot people who aren't sick and reassure people and reassure teams to send them home. And no one test will ever be used in complete isolation, but if we can help enrich the diagnostic or a suite of diagnostics that clinicians have, that really should improve and help there. So we're really aiming for a very widespread adoption in a very large number of patients.

Yes. And I think what's exciting for me is that obviously, from a Volition perspective, we're wanting the product to be used widely, as Andy just said. But I think it's opening up those potentials for future therapeutics or future ways of managing the disease or treating the disease, such as nuclear capture, which I think was in your question here. But the thing from a nuclear capture point of view, just to be clear is, that's not a Volition technology. That is technology that [ SYnAbs AG ] has developed, but they're using the Nu.Q NETs as a biomarker within their clinical studies. So they've done some animal work that we've already discussed. They've got some human studies ongoing. But that project itself is outside of Volition. It's just that they're using our test. So I think the beauty of having something that can monitor and measure the outcomes is helping potential new therapeutics here.

Did I hear it correctly that the sheep trial, an antibody or small molecule drug, was used to inert the NETs implying a potential human therapy away from Extracorporeal NETs filtering? Could that be under development?

Yes. So, it a sheep trial, and they used a molecule which found circulating -- free circulating NETs and lowered their pores and they showed improved outcomes. To me, that's really, really encouraging because the second study it was mentioned was the extracorporeal column study outside the body where they were absorbed onto the column. And so we've shown in 2 distinct ways that by reducing the level, reducing the excessive level of NETs, you improve outcome. We improve the amount of organ support that these animals received. Their lactate was lower and they required less support for their blood pressure, their heart, et cetera, et cetera. And that's extremely exciting. Extremely exciting.

Yes. So, how about if sepsis is the great mimic and you mentioned that in your presentation, could H3.1 also be a mimic? And is it extremely specific for sepsis and not other inflammatory diseases?

So H3.1 levels do go up in some lower inflammatory conditions, but they seem to go up to a much, much lower level than they've seen in sepsis and certainly in severe sepsis and septic shock. And so we -- it's one of the key questions for the ongoing studies, we -- to try and identify a cut off or a particular area under the curve or on our identify specific thresholds. So we're trying very much to specifically answer that question from the data we have from Gila Monterreys' paper, you can see that the H3.1 level is just much, much, much higher. It's log times higher in -- and I think in the scales. And so we think that's what enables it to be specific. But it's very, very sensitive for detecting activation of [indiscernible].

So we understand that the majority of research has done so far is focused on septic shock, right? And should we expect similar research to be conducted on patients with less severe forms of this condition? And is that something you're planning to look on?

Yes. So we will do it -- already doing that. We already have data on. I can't share it, but we already have data on healthy populations, patients with benign diseases and patients with less severe stages of sepsis and infection.

Yes. I mean, certainly, I would say that now the breadth of studies that we've got ongoing are already in [ the kind of big way ] will certainly help answer a lot of those questions.

We have a lot of questions, but we're kind of out of time here. So if you have any other questions, please feel free to e-mail the Volition team. The contact information can be found on the press release. And then we also want to kind of recap that we had a thematic out there, and that kind of goes more depth into all the clinical trials that we're looking at here. And, really, thank you for joining us here today. Thank you for all your hard work.

Thank you very much for joining us.