Nyrada Inc. (NYR) Earnings Call Transcript

Good morning or good afternoon from wherever you come, and welcome to the Nyrada Investor Briefing. My name is Dimitri Burshtein, and I am Nyrada's Director of Corporate Development and Investor Relations. Thank you for joining us again today, wherever in the world you may be. Before we begin the official proceedings, I'd like to cover a few housekeeping matters, please. Firstly, as you may have heard, this webinar is being recorded and will be made available on our website later today. Secondly, the presentation slides that we're using today were released to the ASX last Monday on June 16. We'll be using those very slides during this webinar, although not necessarily in the exact same order they were released. The content remains otherwise unchanged. If I could please draw your attention to Slide 2. And team, can you confirm that Slide 2 is visible, the disclaimer slide?

It is.

Yes. If I could please draw your attention to Slide 2, the compulsory disclaimer slide and encourage you to review it at your convenience. Today's briefing features one representative from the Nyrada Board, our imminent Chair, John Moore; and 3 members of the management team. The format for today is that John will set the scene and do a bit of an intro. He'll hand over to James Bonnar, our CEO; and Jasneet Parmar, our Director of Preclinical Development. I'll be your moderator for the session and may contribute with the odd comment throughout. After the presentation, we'll move into a Q&A session. I'll start by putting forward some of the common questions we received from investors. Following that, we'll open the floor to your questions. If you have a question during the session, please type it into the chat field and I'll ask it on your behalf. And when doing so, could you please indicate whether you're comfortable with me mentioning your name when reading the question out loud. And finally, a small note and a brief apology. Just for your information, James is a little bit under the weather with a cold, so you may notice him pause occasionally to cough. We'll cover that otherwise. With that, let us please start. And so I'll hand over to John Moore, our Chair, to officially open. Thanks, John.

Great. Thank you so much for joining us today. I'm particularly excited about Nyrada because we are living in a new age of metabolic pathway discovery and understanding, things like cell and gene therapy, GLP-1 for weight loss, PD-1 inhibitors for oncology. And we believe that Nyrada has discovered the TRPC channel, which also is going to have a similar position in blockbuster drug development, and we have a very proprietary position in this. And we combine that with a very capital-efficient structure similar to that which James participated in at Neuren. So we have 6.5 employees. We have an outstanding Board that I'll talk about later that has a lot of experience in developing some of these and creating shareholder value through exploiting some of these new metabolic pathways and creating huge amounts of shareholder value. So with that, I'll hand the call over to James Bonnar, our CEO.

Thank you, John. And I'd like to extend a personal welcome to our shareholders and for anyone who's new to the story, I hope you'll get a lot out of today's session. I should start by announcing that Xolatryp is the name we've given to the molecule that was previously referred to as NYR-BI03. The BI in the previous name refers to brain injury and recent efficacy data we've got with the drug has broadened out the application beyond brain injury, stroke and traumatic brain injury to cardiovascular disease, in particular, myocardial infarction and reperfusion injury. All 3 areas are exciting. They represent unmet clinical need. And we really think that this drug has the potential to provide a paradigm shift in the way that these leading killers are treated in the acute setting. So we'll talk a little bit about that today, and we'll give a status update on where the program is at. And I'd like to also, again, for new shareholders and those interested in the company provide some background as to why we believe that this approach we're taking has a very good chance of translating into the clinic and delivering an approvable drug. So often with drug development, we sort of are seen as blind watchmakers, and we're often working on programs where the target is often unknown, let alone the mechanism of action. And that's certainly not the case with Xolatryp. This is a drug that was developed with one specific job in mind, and that is to block TRPC channels. And Jasneet Parmar, who is the Director of R&D at the company, who did her PhD around TRPC channels and their role in stroke is going to talk a little bit more about that. But the -- I guess the key point here is that we're taking very much a rifle approach rather than a shotgun approach to treating these indications. The drug was designed specifically using rational drug design to inhibit these TRPC ion channels. And I guess that's one part to it. The second part to it is the confidence we have in the target, the TRPC channels and the role that they play in these different diseases. And I guess what gives me a lot of confidence is the work that was done in a knockout mouse model where these channels were genetically knocked out. Jasneet will be talking a little bit more about that. And that work started really in the 2010s, and it culminated with a complete TRPC knockout mouse that was bred about 12 years ago almost to the day. And in fact, there's an interesting story behind the development of the TRPC knockout mouse. And if you're interested, you can go and take a look. I think Dimitri has posted that or uploaded that to our website. So that really set the scene for a lot of foundation work that was done in the intervening years, including some pioneering work that was done at UNSW here in Sydney that Jasneet participated in along with Professor Gary Housley. Gary is the Director of the Translational Neuroscience Facility at UNSW and is the Chair of our Scientific Advisory Board. So Jasneet was one of my first hires and has a very specific knowledge and expertise in this area. So what we're dealing with Xolatryp is we're dealing with a novel, very targeted mechanism of action. As I mentioned, the drug was developed initially as a drug to treat brain injury. So it ticks all the boxes in terms of passing the blood-brain barrier, which is a big hurdle for a lot of neurological drugs. The novelty of the drug has been confirmed. We have it covered by a provisional patent at this stage. It's what's referred to as a composition of matter patent, which means that the molecule Xolatryp and anything that looks like it is protected. So a composition of matter patent provides the highest level of protection. So with that, I'll hand over to Jasneet, who'll background the target, and then we'll talk a little bit more about the efficacy data that we've collected to this point, where we are with our clinical program and what the future holds for Xolatryp in the near term. So with that, I'll hand over to you, Jasneet.

Great. Thanks, James, and welcome all. So in this slide, I'd like to take you through the normal function of the TRPC ion channels and how dysregulation of the activity of these channels can contribute to worsening of the outcome following both brain and heart injury. So the TRPC channels are activated downstream of a major class of proteins in the body. These are called G proteins and activation of the G proteins leads to production of a molecule known as DAG. And DAG binds to and activates the TRPC 3, 6 and 7 ion channels. Now these 3 particular TRPC subtypes are expressed dominantly throughout the brain and the heart in different cells in these systems. And the functional channel is a tetramer, meaning that is formed by 4 subunits. Now these 4 subunits can either be the same TRPC type or a combination of different TRPC types. Now TRPC channels are nonselective cation channels. And what I mean by that is they allow positively charged ions to enter into the cell. And the most particular and notable ion of them all is calcium. And that is because calcium levels in the cells are very tightly regulated because calcium can act as a second messenger and is involved in vital functions within the cells. So in the context of brain injury and heart injury, neurotransmitters are released in excessive quantities, and this can trigger the activation of the G protein, which is slow and sustained. And the sustained activation of the G protein can cause the activation of the TRPC channels. Again, this activation is sustained, meaning that large amounts of calcium is now flowing through these channels into the cell. And this causes a calcium buildup in the cell, and that can trigger cell death and thus cause tissue damage. So the table in the slide below highlights how different cells that express these TRPC channels in an activated stage, how they can lead to neuronal death increase in inflammation in the brain. And in the heart, they can lead to calcium overload and the death of cardiomyocytes, which are the functional cells of the heart. And also it can impair blood flow and further scarring of the heart tissue. So studies that were done in knockout animals where multiple TRPC subtypes, including TRPC 3, 6 and 7 have been deleted in these animals. It really confirmed that not only the cells in these animals have significantly less calcium accumulation, but they're also significantly protected from brain injury as well as heart injury. And this really formed the basis of our approach, which is by blocking these channels with our small molecule Xolatryp, we can achieve this neuroprotection and cardio protection. Next slide, please, Dimitri. Thank you. So this slide demonstrates the efficacy of Xolatryp in a well-established preclinical model of ischemic stroke, known as the photothrombotic model, which mimics permanent clot formation. So in this model, the injury was delivered to one side of the animal's brain, so the other side could be used for direct comparison. And 30 minutes following the injury, the animals were given either Xolatryp or they were given just [ Weko ] for 3 days as a continuous intravenous infusion. Now once the drug treatment concluded at the end of the third day, the brains from these animals were imaged using a very specialized MRI technique known as fractional anisotropy or FA. Now the FA technique is used to determine the integrity of the tissue. So imagine this, there's millions of axons running throughout the brain and water molecules tend to move towards the direction of these axons. Now in contrast, where the brain is damaged and the axons are damaged, the water molecules move more randomly or are disorganized and the FA technique picks up on that. The FA values were then compared between the injured and the uninjured side, and that gave us a delta FA value, which is what is plotted on the Y-axis in this graph here. What we noticed is the animals who received Xolatryp had 42% less damage compared to the animals that were treated with [ Weko ] only. And that is because the larger the delta FA value, the larger the damage is in the brain. And this really demonstrated the significant neuroprotective effect of Xolatryp. So this neuroprotection was then further demonstrated in a model of traumatic brain injury, which is a model specifically developed by our collaborators at the brain trauma neuroprotection branch at Walter Reed to emulate gunshot and trap wounds to the brain. This model is really classified as a model of TBI. And similar to the stroke study, the drug treatment was initiated 30 minutes following the injury. But in this model, it was only delivered for 2 days as a continuous intravenous infusion. We used the exact same FA technique to look at the integrity of the tissue in the injured and the uninjured sides and then compare it between the treated and the untreated animals. So what is presented in the graph here are the delta FA values across multiple consecutive slices in the brain. So if you look at slice 14, the delta FA value is the largest, and that is because the slices from the middle of the injury where the injury is the greatest. And then we move back through from slice 14 to slice 9 to the back of the brain as the injury is resolving. And what we found again was that animals that were treated with Xolatryp had a significantly smaller delta FA value throughout the brain regions compared to the animals that were only treated with vehicle. And this further validated our approach in that targeting the TRPC 3, 6, 7 ion channels with our small molecule conferred neuroprotection following brain injury. So with that, I'll pass on to James to discuss the efficacy of Xolatryp in the acute myocardial ischemia models. Thank you.

Thanks, Jasneet. So back in October last year, we announced the results of a study looking at Xolatryp in a model of myocardial infarction. And here, you can think of myocardial infarction as coronary heart attack. This work was followed on from some literature that was published looking at cardioprotection conferred by knocking out TRPC 6. And there was also some further research looking at knocking out TRPC 3 as well, which confirmed the potential for cardioprotection. And in this first study, we looked at infarct size in the heart. This is a rat model. And in this study, rats were dosed with Xolatryp for 24 hours. And the results are shown here, and they're fairly profound. What you can see in that top panel, these are the hearts of the rats following injury and a period of ischemia followed by reperfusion. And the tissue is stained using a special dye. It's called TTC staining. And what this does is it stains healthy tissue red and dead tissue doesn't stain, so it shows up as gray. And you can see from this slide here, if you look at the sham and the third image along, you can see that treatment with Xolatryp or as it was called then NYR-BI03 offers significant protection of the tissue against cell death. We also ran in the study a positive control. This is an FDA-approved drug called Captopril, which is an ACE inhibitor. And it works pretty well in protecting the cardiac tissue, but not as well as Xolatryp. In the graph below, Dimitri, if you click back to the main graph. You can see that this is quantified, and it shows that with the treatment of NYR-BI03 for 24 hours, we get an 86% cardioprotection with a strong statistical p-value. So we were very excited by this result. In addition, as part of the study, we also looked at what we call functional outcome measures. We looked at how the heart was performing in these animals that were treated and untreated. And we pleasingly found that we got a significant improvement, a 43% increase in left ventricular ejection fraction. And that's a measure of how much blood the heart pumps with each beat. We also got a significant 50% increase in fractional shortening, and that is a measure of the strength of each contraction, each heartbeat. So this confirmed that not only are we preserving tissue in these animals, but we're also able to improve cardiac function. In addition to the functional outcome measures, we also looked at a panel of blood biomarkers. And these are proteins that are given off in the blood following tissue damage. And one that you may be familiar with is Troponin I. It's very specific to cardiomyocytes or the contractile tissue that makes up the heart muscle. And we got a significant decrease in troponin I. So we're very pleased with that. That was also confirmed by 2 other injury biomarkers as well, LDH and AST, where we got significant reductions. So we were very pleased with the study, and it opened up a new indication for Xolatryp. Next slide, Dimitri. So following on from that, we ran a second study. And again, this was based on some literature that was published in the knockout mouse where knocking out TRPC 6 and TRPC 3 were shown to be antiarrhythmogenic, so basically prevent arrhythmias from occurring following myocardial infarction. So we effectively ran the same study again. But this time, we were specifically looking for the incidence of arrhythmias. And we did that with continuous echocardiogram. And we got a significant result in knocking down arrhythmias by 90%. But one other thing that we found in the study, which was really interesting was that with a short dosing period, these animals were only dosed for 3 hours as opposed to 24 hours in the first study. We also again got significant cardioprotection in terms of reducing infarct size. Now we didn't quite get the 86%, but we got a 42% reduction, which, again, is a pretty profound result. So we learned from the study 2 things that the drug is effective in preventing arrhythmias and also that we can get prevention of growth in the infarct size with a much shorter duration infusion. We also were able to confirm in the study, again, that we got a reduction in the injury blood biomarkers. Again, we got the same decrease in troponin, which is the cardiomyocyte or heart tissue injury biomarker. We also got another reduction in a biomarker, which is specific really to the liver, and that's ALT. And when you think about it, that kind of makes sense because when the heart stops beating, that stops the blood flow to other organs or where there's a blockage in the heart artery, that stops blood flow to other organs as well. So we showed that there is protection from other organs as well, which is interesting. The images along the bottom there confirm what we found in the first study as well. This is again TTC staining, which show that the heart tissue is much healthier in the animals that received Xolatryp. So we're very encouraged by these results. And -- another point to make is that this study was done at a different laboratory to the first study, further validating the results and the findings. There is one other graph, Dimitri, if you've got it there, that plots out the arrhythmias.

Yes, yes, yes. This -- what we're using here is not a special slide deck. These were our announcements. So this is the May 8, 2025 announcement where we disclosed the results of this study. So it should be here. This is the one you're looking for.

So what this graph shows is the reduction in ventricular premature beats. And this is a form of arrhythmia that develops into life-threatening ventricular fibrillation and ventricular tachycardia. And they're the leading cause of sudden cardiac death. And so preventing arrhythmias is critical to this indication. And what we showed here was that after 1 hour and after 3 hours, this is continuous monitoring, we were able to significantly reduce the number of these ventricular premature beats. And this is something that we didn't really expect to find at the outset, but it's another example of the ongoing research into this family of ion channels and their role in cardioprotection. So with that, Dimitri, I'll talk now about the current status of the program. So we're at a very exciting stage of development. We've taken Xolatryp into a Phase I clinical trial. This is a trial in healthy volunteers, where we are giving them an infusion of up to 6 hours. Now initially, the study was designed as around a 3-hour infusion. But following the results that I was just talking about, we asked the ethics committee if we would be able to extend that out to 6 hours. And given the pleasing safety profile of the drug in the first 4 cohorts that we've dosed or 3 cohorts at that point, they agreed to that. They also were okay with us skipping a dose, again, because the safety profile was often very clean. So that Phase I trial is going very well. It's a double-blind placebo-controlled randomized study. So there is a placebo arm in this. We're dosing 48 participants in 6 cohorts. And of the 8 participants per cohort, 6 are on Xolatryp and 2 are receiving placebo. So we're just about to commence Cohort 5. We anticipate reporting on that study in the September quarter. And so far, so good. It's all looking very, very positive. And was that Dimitri? Yes. So just talk a little bit about the potential market for a drug like Xolatryp. It's always good to look at the markets and see what the potential market size is. I think with a drug like Xolatryp, given that it's first-in-class in pretty much all these indications, it's very hard to put a dollar figure on it. But as you can see here, the markets are very large. I would perhaps look at this in terms of the number of patients that suffer from these conditions where Xolatryp may assist. And it's probably between 2 million and 4 million per indication. So you can see that the potential market size is significant, very large. So with that, I'll hand back to you, Dimitri.

Thanks, James. And just in conclusion, just a few -- just to wrap up, Nyrada is pioneering a technology that's relatively new, inhibiting TRPC ion channels. Xolatryp is currently in Phase I. It's 2/3 through. Cohort 5 is shortly to commence and we'll report soon and following that, obviously, Cohort 6, but the reporting of the Phase I will be before the end of the September quarter. We have demonstrated preclinical efficacy in 3 indications, stroke, TBI and myocardial infarction. We could -- there is lots of literature emerging all the time indicating other areas, but we are a fairly lean organization, and we have to allocate our capital to where the best returns are. And our focus at the moment is the Phase I, at which point the company will need to make an assessment about where to from here. We are currently investigating our options for a Phase II. We have 3 indications that we can pursue into a Phase II. Each one has different risks, rewards and opportunities, and we have to trade those off and make a recommendation to the Board to pursue -- to decide which way to pursue. At the end of our last quarter in March, we had $4.76 million of cash in the bank. Obviously, we'll be reporting on our cash position for this current quarter, but that will be next month. By way of news flows and catalysts, we'll obviously have our cash flow update in a week -- in a couple of weeks. Our audited accounts are scheduled for August 2025. We'll have a Cohort 5 update again early sometime next month. And we're expecting the final Phase I clinical trial results in September. As indicated, the company is investigating pathways for Phase II. And in due course, we will disclose to the market what our intentions are in that direction. So that's the formal part of the presentation. I will now open it up to question and answer. Again, we -- I'll put to some of the more common questions we've received, but then I'll ask some of the questions that have been asked.

We've already received a couple, and we'll get to them. Please bear with us. So without further ado, I'll just throw the first question to John Moore, our Chair. If you could please tell the audience about the Board.

Great. Well, thank you, Dimitri. Yes. So I've always believed that a great Board is a tribute to a small company's opportunity and potential market impact. And I've had long-term relationships with 3 of the very important Board members in the company. So Marcus Frampton is the Chief Investment Officer of the Alaska Permanent Fund. Marcus manages $88 billion and is a famous biotech investor. So he and his team created 3 biotech companies from scratch, insisted that they be named after towns in Alaska. And the most notable of those is Juno Therapeutics, which they invested $140 million in at the time. It was a start-up. And that $140 million represented the largest Series A biotech investment at the time. And they sold that company for $9 billion to Celgene. It's now part of Bristol-Myers Squibb. And that was just a remarkable outcome for the citizens of Alaska that benefited from that, but also it was really the first and largest exit of a cell and gene therapy company. So another example of this, find a new metabolic pathway and commercialize it. Second of all, Chris Cox, I met him when I -- back in 2002 when I acquired $148 million of 16 different biotech public and private companies from Elan Pharmaceuticals. And Chris is on the Board of Nyrada, and he's partners with the former CEO of Pfizer and a company called Population Health Partners that focuses on drugs like these cardiovascular drugs that we're developing that target very large segments of the population. And Chris is -- 2 of his most remarkable past successes were the development of and commercialization as of [indiscernible], which was sold for [indiscernible] million and one of the first RNA drugs, siRNA drugs, inclisiran, which was sold for $9.7 billion to Novartis. That was at the time, the largest ever purchase of a single drug. And both of those drugs are cardiovascular drugs. So Chris has incredible business development contacts. He knows the companies that we're going to be going after to license this drug to. So I think it's unusual for a company with AUD 50 million market cap to have this quality of directors. Second of all, Rüdi Weseloh, he is a senior business development person at Merck KGaA, German Merck, and he's done over 100 business development transactions. So we feel like we've really got a world-class team of business development people to advise James. And last but not least, I think I really have to say that this is a bet the Jockey story. James was fundamental to the success of Neuren and it's -- a lot of times when you get a CEO of a biotech company, and I'm involved in a lot, they either come from a medical background or they come from a financial background. And what's really special about James is he comes from a clinical operations background. So a lot of things can go wrong as you develop new drugs. And James has just an outstanding background and a lot of talent and being able to head off those problems and anticipate those problems. So I think that's a huge off-balance sheet asset for the company. So I think that answers your question, Dimitri.

Can I ask you just briefly to mention our 2 local-based directors as well just for the benefit of the audience?

Yes. So Gisela Mautner is a cardiologist doctor, who is also on our Board and Ian Dixon.

One further question, John. What excites you about the prospects of the company?

Well, it just gets back to this idea that, number one, an extremely low cost of operation. Number two, I think Australia is one of the most exciting places to develop new drugs because of the talent, because of the tax credits, because of the terrific retail investor base that likes taking these early-stage risks. And I just -- I think that we're at the right place at the right time. And again, we're in this era of metabolic pathway discovery and understanding that it's a really unique time in history. And I think we all wish we would have been on the ground floor of cell and gene therapy or the [ GPL ] the weight loss drugs that have been developed, the PD-1, you've heard of KEYTRUDA, it's a $22 billion revenue drug. So I honestly believe the TRPC channel with its multifaceted applications, not only as a neuroprotective agent but also as a cardioprotective agent, other areas that we haven't yet discussed that James is investigating, this truly could be a blockbuster drug with multiple market opportunities. So that's -- when you can buy something, the risk-adjusted return of what we're doing is incredibly compelling, and it's the reason that I made a very large investment in our -- when we bought out our Noxopharm's position as well as our other directors.

Thanks, John. Here's a question for James. The company has shown improved efficacy in stroke, TBI and myocardial infarction. Are there any other opportunities for Xolatryp?

There certainly are. There's a lot of literature coming out based on the knockout mouse, which shows that Xolatryp potentially has broader application in protecting the kidney as well. And there are also other indications which are of interest in the neuroprotection side, epilepsy being one of them. And another interesting angle to this as well is that blocking TRPC channels has been shown to have utility in some oncology applications as well in terms of migration of cancer cells, so metastases. So yes, there's a lot of scope with this target. Perhaps Jasneet, you might have a view on that as well.