Nyrada Inc. (NYR.AX) Earnings Call Transcript & Summary

Good morning, and welcome to this webinar from Nyrada. Thank you for joining us. My name is Dimitri Burshtein. I'm Nyrada's Director of Investor Relations and Corporate Development. If I could just introduce the team with us today. To my left is James Bonnar...

Hello.

Our Managing Director and CEO. To James' left is Dr. Alex Suchowerska, our Director of Clinical Development and Regulatory Affairs; and to Alex's left is Dr. Jasneet Parmar, who's our Head of Research and Development. If I could just -- before we get to the body of the webinar, a couple of housekeeping matters. This webinar is being recorded and will be made available on our website someday -- sometime today or tomorrow. You will have also seen a new slide deck that was released this morning to the market and a Phase IIa clinical trial fact sheet. We'll be referring to the slides throughout. If I could draw your attention to Slide 2 of the investor deck, the disclaimer page. So if you could just familiarize yourself with that. This morning's webinar will be not a presentation format. It will be kind of a discussion amongst ourselves, addressing many of the questions that we've received along the way. But there is an opportunity for you to ask your own questions. So if you could please put your question into the chat system, and we will, time permitting, read them out. We have a hard close today at 9:55 Australia Time. But if we don't get to your question, please feel free to e-mail us at [email protected], and we will attempt to address it as quickly as we can. So without further ado, I'll throw the first question to James. James, can you please tell the audience about Nyrada and the problems it's seeking to address?

Sure. So Nyrada is a Sydney-based biotech. We were formed in 2018. We listed on the ASX in early 2020 under the stock ticker, NYR. We are a developer of novel small molecule drugs and our particular interest is in therapeutic areas where there's unmet clinical need. We have a lead candidate called Xolatryp and Xolatryp is a small molecule inhibitor of a new class of -- it's a new class of drugs. It inhibits a family of ion channels called TRPC channels, which we'll talk about today. We started off when we listed with a first-generation molecule. In the interim, we've developed that into a third-generation molecule, which we've tested in preclinical models of ischemic stroke, where we showed efficacy. Also traumatic brain injury, and we did that in collaboration with the U.S. Department of Defense. And again, we showed efficacy in traumatic brain injury. And more recently, following the publication of some interesting research work that was done outside of Nyrada, we've looked closely at myocardial infarction reperfusion injury. So this is the indication that we are going to take forth initially. And we're about to just enter a Phase II study due to begin next month. So we're at an exciting point in the development of the company.

Well, this is an important, good juncture to ask or tell the audience, what is ischemia reperfusion injury?

So ischemia reperfusion injury is -- if you speak to a cardiologist, it's considered the last frontier of emergency cardiac medicine. This is an injury that occurs following a procedure called percutaneous cardiac intervention, or PCI, commonly referred to as an angioplasty. And to sort of understand what Xolatryp might be able to do for these patients, it's worth looking at how they're currently treated. So when someone suffers a coronary heart attack, which is a blockage of the artery, the standard of care treatment, and this is a treatment that's been around since the mid-1970s. It's a life-saving treatment. It involves inserting a balloon into the blocked artery, inflating the balloon to clear the blockage and then placing the stent. And despite this technique being life-saving and being the standard of care for these patients, there is a problem associated with it, and it's an unavoidable problem up to this point. And that is, with the reintroduction of the oxygenated blood to the ischemic tissue, that sets off a cycle of damage that results in cells dying basically. So it results in an infarct forming. What Xolatryp is intended to do, it will be given at the time of the PCI. It will prevent this damage from occurring. And we know that infarct size is correlated with poor outcomes for the patient. So by minimizing infarct size, we can improve outcomes for these patients and reduce the risk of follow-on cardiac events.

Great. Well, you touched on Xolatryp in the Phase II, but can you just describe the Xolatryp's development journey?

So I mentioned that we have impressive efficacy data in ischemic stroke and traumatic brain injury. More recently, we've focused on this cardiac indication. And in a preclinical model, which we ran at 2 different labs independently, we got a very impressive cardio protection in terms of reducing infarct size. We were also able to show improvements in heart function, and we also saw a reduction in biomarkers -- injury biomarkers. And on top of that, we were able to show a 90% reduction in arrhythmias. And this is important for patients who suffer a heart attack because arrhythmias are the leading cause of sudden cardiac death following a myocardial infarction. So that was the preclinical efficacy studies we ran. More recently, through last year, we ran a Phase I study. And this Phase I study was in healthy human volunteers. And the idea of this study was primarily to show that the drug was safe and well tolerated. And pleasingly, that's what we showed in this study. We dosed 48 healthy volunteers, and this was a placebo-controlled randomized double-blind study and 36 participants received Xolatryp. There were no SAEs or dose-limiting toxicities that we saw in that study. So that sets the platform for moving into Phase II. One other thing I'll say about the Phase I study was that we looked very closely at pharmacokinetics, that's blood levels of the drug, just to see how it performs in the human body. And pleasingly, we were able to show or demonstrate super therapeutic levels, as predicted, for the duration of the infusion, which was a 6-hour infusion in this patient population. And that's the time of dosing we'll be using in the Phase II study.

Great. Thanks, James. Actually, Alex, is a good spot to ask you a question. Tell us about the Phase II trial design as you're the overseer of the trial for Nyrada.

Sure, Dimitri. So PROTECT-MI is a Phase II trial looking to dose patients experiencing their first heart attack with Xolatryp. So someone that's experiencing a heart attack, they'll typically enlist the help of an ambulance. And on the way to hospital, the paramedic will assess the patient and they can do this by an ECG, which measures how their heart is working, and they'll be able to determine that the patient is having a heart attack. So this typically means that, as James described, one of the coronary arteries is blocked. And they will call ahead to the hospital to let them know that they've got a heart attack patient coming in. This means that when they arrive, cardiology is already down in the emergency department, and they can assess the patient and move as quickly as possible. So as James described the PCI procedure, it is a standard of care. It is life-saving, but they do need to obtain consent from the patient. And when the cardiologist is doing this, they will also invite them to join the PROTECT-MI study. They can then start screening procedures and ensure that the patient is eligible for PROTECT-MI and is eligible to receive Xolatryp. And a few of the eligibility criteria we have is that it has to be their first cardiac event. And this is mainly because someone that's previously had a heart attack will have a lot of scar tissue and that makes it difficult to ascertain the actual infarct size, and there's a lot of variability in that. So they -- although they're having a heart attack, they have to be relatively healthy and they have to be stable. So there's a lot going on, and we just need to make sure that all these patients are eligible. So we anticipate that about 300 patients will provide consent, but of these, about 200 will actually be dosed with Xolatryp.

All placebo?

All placebo, correct. So it's a randomized controlled, double-blinded study, as James indicated, which is the gold standard. And, yes, so these patients will then move on to receive a PCI, so the opening of the vessel. And at the same time, they will receive Xolatryp, which will be administered over 6 hours. And these patients will remain in hospital typically about 48 hours up to 5 days, and all of this is dependent on their cardiology team. And they'll be monitored throughout this period, and they will also come in for a follow-up on day 30.

Great. So what are the study endpoints and why were they selected?

Great. So, as I think James and I both alluded to, there's quite a lot of standard of care in these patients. So there's a lot of standard measures which need to be put in place to make sure that everything is properly monitored. One of these is telemetry. So it's standard of care for all of these patients that have a heart attack and have PCI, to have their hearts monitored for 48 hours after the procedure. And during this time, we'll be looking for the incidence of arrhythmias, and we can then compare between the placebo and the Xolatryp patients for the number of arrhythmias and see if there's a reduction or a change. Taking blood biomarkers is also standard of care. And in the protocol, we've regimented how that should be done so that we can accurately compare between the placebo and the control group. We will also be looking at -- so it's also standard of care. There's [ always ] standard of care. So we'll also be looking at echocardiograms since this is an ultrasound of the heart, and this is done a standard of care before they leave hospital. But in the protocol, we've stipulated how this should be done so that again, we can measure everything accurately. And when patients are having the PCI procedure, the cardiologists will go in with a special catheter, a camera, and they will visualize which artery is blocked, how much it's blocked. And this really helps give them information about where the stent needs to be placed and how to reopen the vessel. So there could be one effective vessel or multiple. And this is all done prior to reopening those vessels. So at that point, they will determine what their -- it's called their pre-PCI TIMI flow [ is ]. And that basically is an indicator of if the artery is completely blocked, that indicates TIMI 0, or TIMI 3 is there's no blockage. And the patients that have a TIMI 0 or a TIMI 1 and they have no collateral, so no smaller vessels that are allowing blood flow, these patients will be invited to have a cardiac MRI, and this is the gold standard for measuring infarct size.

Great. Thanks, Alex. What would a successful trial look like?

So, in the Phase I, success was safety in the healthy volunteers. In a Phase IIa, success is safety in the patient population. But naturally, we wouldn't be going into this study if we didn't think it would bring benefit to these patients. So success in the first instance is safety, but success is also bringing benefit to these patients. And that's why we have all of these secondary and exploratory endpoints to actually determine which one of these is the one that brings the most benefit to these patients. We have our hypothesis, but we do need to see what happens in humans.

Great. Bear with me for a second while I shuffle some papers around. How long will the trial run? How long do you expect it to run?

Yes. So as James indicated, we're looking to start enrollment end of next month, and we're expecting it to run over 12 -- sorry, 9 to 18 months. So initially, we're looking at about 6 sites, and it's been really pleasing to go out to these sites and talk to these cardiologists. They're the real experts and they're so -- obviously, we're really keen, but so are they. As James said, it's the last frontier and everyone wants to find a treatment for reperfusion injury. So we're looking at dosing about 200 patients over that 9 to 18-month period. And, yes.

We'll be pausing -- I mean, we'll be providing the market regular updates on recruitment and safety. But what are the strategies the company is employing just in case recruitment is going a bit slower than expected?

Yes. So, we have our 6 initial sites which we're talking to. There are more sites across Australia that have indicated interest, and we are working with these sites to try and see how that all fits in. We've also had the option of opening up sites in New Zealand or also potentially the U.S.

Well, the U.S. will be subject to an IND. So perhaps you can just briefly tell the audience what is an IND and when Nyrada intends to submit it?

Sure. So an IND is an Investigational New Drug application, and it's submitted to the FDA in the U.S. prior to investigating an investigational drug such as Xolatryp in humans. So this -- Nyrada can submit the application at any time, and we're currently working on the application and getting everything aligned to submit that application.

Great. Now it's probably a good time to switch over to our R&D program. I'll hand -- I'll ask a couple of questions of our R&D Director, Jasneet. What are the origins of TRPC inhibition technology? And how does TRPC inhibition work?

Right, Dimitri. So the scientific foundation of TRPC inhibition comes from decades of academic research, whereby the role of these channels was established in the context of cellular stress. A major contribution to this field comes from the work of Professor Lutz Birnbaumer. His team used genetically modified, genetically engineered animals, whereby these animals were designed to lack these TRPC channels to understand how they regulate calcium in the body, particularly in the context of disease and injury. And a striking finding from these studies was in that when you took these channels away from these animals where these channels weren't present in these animals and these cells, the cell's ability to cope with either injury or distress or calcium overload was much better. And so that really formed the key foundation for -- or the key evidence really that TRPC channels are involved in pathophysiological calcium dysregulation. In fact, during my PhD, I used these genetically modified models to understand and to show that TRPC ion channels were a major contributor to expansion of secondary brain injury following stroke as well as calcium dysregulation in the neurons following stroke. These findings were published in 2023 in Stroke Translational Research journal. So we can think of TRPC channels as gateways that allow calcium in, and calcium is very important for normal signaling in the cell. However, in the context of injury, such as ischemic reperfusion injury in the heart, these channels become overactivated, and they allow a lot of calcium to come in. And that triggers signaling pathways within the cell that either mark them for damage or for death. So Xolatryp blocks 3 of these 6 subtypes of TRPC channels that are found in the human body. This is TRPC3, TRPC6 and TRPC7. These channels are often present in similar cell types. They are activated by a common mechanism, and they often come together to form a functional channel. These 3 subtypes are widely present in the heart and in the brain. And the whole idea is that by blocking these channels with Xolatryp, we are enabling the cell to better cope with the stress that comes after this ischemic reperfusion injury and stop those pathways that are linked to calcium overload and cause damage and death in the cell.

Great. Thanks, Jas. Nyrada has indicated in its last quarterly update that it has commenced some preclinical studies looking at the potential for Xolatryp in oncology, just moving away from stroke, TIMI and cardiac. Why oncology? And what is the status of that?

Right. So within oncology, there are 2 very distinct opportunities that we want to explore. While our initial focus is myocardial ischemic reperfusion injury and the Phase II, we see cardio protection as a much broader opportunity. So it has shown that chemotherapy agents lead to cardiac damage. In fact, some of the most broadly and widely used chemotherapy drugs, they are limited in their use in the clinic because they cause progressive damage to the heart muscle. They lead to oxidative stress and they lead to mitochondrial dysfunction. And the underlying cause that we're trying to address here is calcium overload via the TRPC channels and using Xolatryp to mitigate that. So we want to explore whether in this context where we get chemotherapy-induced cardiotoxicity, we can show cardio protection with Xolatryp's use. Now the second and a very distinct opportunity. So this is moving away from this acute care setting, is that in the cancer environment and the tumor cell environment, excessive calcium entry by these TRPC ion channels has been shown to be involved in cell growth, cell migration and cell survival, and this really promotes tumor growth. And in this context, we want to see whether silencing some of these pathways by blocking calcium entry through the TRPC channels using Xolatryp, we're actually able to influence some of this tumor growth and progression that we're seeing. The studies that explore Xolatryp's potential in oncology, they are currently ongoing.

Great. I mean you've suggested multiple studies, but these studies aren't necessarily off the shelf. There's a lot of work that goes in designing this. And a lot of the work we're doing is based off actual research based on using these mice as well.

Yes. So these are not off the shelf experiments, and they are quite complex. There's a range of oncology models. There's a range of cardiotoxicity models that need to be explored. And so we need to ensure that the study that we are designing actually answers the question that we want to ask in this context. So the animal studies have started this quarter to explore Xolatryp's effect in oncology or its -- evaluate its potential in oncology. And they're at a point where these studies normally are in the initial stages, which is acclimatization of the animals as well as tumor implantation in these animals. The tumor that needs to grow in these animals to a particular size and only then we can treat these animals with our drug. And so that time line can vary quite a lot.

So clearly, these studies do take time. So is there a feel for how long it will take particularly?

Not at this stage, but I think when there's anything material that we can say, we will definitely [indiscernible].

We're not thinking -- it would be fair to say it will be a matter of weeks and months rather than years to get some sort of. . .?

Yes. So like I said, the tumor growth within the animals can take somewhere between 6 to 8 weeks and only then can we start the treatment and then there's a particular time that we want to treat these animals for. So we're looking at least that time frame.

Great. Thanks, Jas. Back to you, James. This is an investor briefing. So the most common question you and I get from investors is how much capital does the company have and how much will the Phase II cost?

So the Phase II study, we estimate will cost around $10 million to complete. We have a fairly sound financial status. We have $7.2 million in capital. That was at the end of the December quarter. On top of that, we are expecting to receive about $2.15 million from an R&D rebate. So we're fully funded for the study. We also have had some options exercised recently. I think that brought in around $450,000, $460,000?

That's just for this quarter.

Just for this quarter. And there are other options that we anticipate will be exercised in the coming year. So we're in a good, sound financial position.

It'd be fair to say that it would be reasonable to expect that this Phase II study will also be eligible for the R&D tax rebate?

Absolutely. So we're running the study primarily in Australia. So we will be eligible for the full R&D rebate for anything we spend on the Phase II study.

But from a capital perspective, I mean, the company is only funded for what it said it's going to do. If anything new emerges, we don't have excessive resources to do that?

That's right. So we'll see what the data readouts look like. And if a second Phase II study is justified, we'll look at how we fund that. But there are different options for that. One thing I'll mention is that with traumatic brain injury, for example, we've had this long-standing collaboration with the U.S. Department of Defense. That's a program, for example, that may be eligible for nondilutive funding. So we're always looking at opportunities for bringing in additional funds to fund these programs.

And it's fair to say that just yesterday, the Commonwealth government through the MRFF announced a $5 million grant for acute TBI treatment.

Well, yes, we'll take a look at that for sure.

Great. What is the strategy for growing the company and commercializing Xolatryp?

So I think a good strategy for a drug like Xolatryp that we see as like a platform drug, where it's got utility in multiple indications is to lead off with an indication like reperfusion injury and then look to out-license that. That could be by region and then use any upfront payment or licensing fees to fund the other programs.

You -- Before joining Nyrada, you were -- you ran clinical development for Neuren, a company that many investors will be familiar with. So this kind of sounds familiar with that before.

Yes. It's sort of the same playbook that Neuren applied. Yes.

Great. There was a recent study late last year of the only other TRPC drug developer that we're aware of at least, Boehringer Ingelheim, the large German company. They did a study in FSGS. Don't ask me what the acronym stands for, but it's -- it's a chronic kidney disease, but what does that study mean for Nyrada?

So that study was one that we watched with interest because it sort of validates the target. So Boehringer have developed a TRPC6 inhibitor. We know that there are differences in terms of where it binds on the protein to Xolatryp. But what it showed is what we felt anyway from the preclinical work with these genetically modified mice that blocking TRPC channels is a safe thing to do. In the Boehringer study, they dosed patients for 12 weeks, and they -- I think that drug showed a good safety profile. And in fact, they just published that study on what was the...

The Lancet.

On the Lancet just last week. So that was an exciting development for us, I think.

Thanks, James. Now we are trying to answer as many of the questions we expect you guys, the audience to ask. But if you have any questions, please feel free to put it into the chat box, and we'll ask them at the conclusion of our chat. James, what news can the company -- sorry, before we actually get to the news question, what are the company's biggest risks?

So the risk for any drug development program is translation risk. And that is what you see in a mouse, does that translate into a human. We know that the biology is similar in a human to the animal models we looked at, we studied. So we're confident that it will translate, but that is always an area of risk. I guess the operational risk as well is something else to consider. I think we've got an experienced team. I've had 25-plus years in drug development, overseen clinical trials. So I know what the path forward is for Xolatryp. And I spent time working in regulatory affairs as well. And that's another risk, of course, as well as regulatory affairs. And...

So you can just share of INDs...

I have. And it's always a question what do the FDA think about the program. What I think is nice about the indication we're going after initially is that it's a fairly well-trodden path. There have been plenty of cardiac studies done in the past. So we are using outcome measures that are accepted by FDA and so on. So yes, I think the regulatory risk is probably low. But yes, we've got a good team working on this. So I'm confident that the operational risk is low.

And our Board is pretty impressive to help guide and advise on commercialization as well.

Absolutely. Very experienced in commercializing biotech. We -- the bios are on our website, and I invite you to go and have a look at the quality of our Board. But this is a Board that have many years of experience and proven deal-making experience.

Great. The last question for me is, what kind of news, what might the news flow be over the coming weeks and months?

So in addition to all the standard financial updates and corporate updates that we have to lodge, there will be regular updates provided on how the Phase IIa study is progressing. We'll also report on any outcomes from safety review committee meetings, et cetera. As Jasneet mentioned, we've got a lot of work ongoing looking at the drug in other indications. And as data becomes available, we'll be sharing that with investors as well. So there'll be plenty of news flow in the interim while we run the Phase II study.

Great. Well, that's the formal bit of our presentation. So I'm going to just throw to some of the questions that we've received online. And please forgive me, I'm just reading these. I might have to just summarize just in case. I think you can interpret what this says, but it says Nyrada has 3 TRPC inhibitors, and it says Neuren have one. I'm not really -- I think that's probably Boehringer have one. Are any others being developed?

So that's probably a question that's best directed at Jasneet. I think just to sort of start the answer to the question, we have one drug that inhibits 3 subtypes of TRPC channel, whereas Boehringer, their drug is specifically a TRPC6 inhibitor. We think that if you look at how these channels are expressed in the heart and the brain, they're having a 3, 6, 7 inhibitor is advantageous. Jasneet, did you want to add to that?

Yes. So another thing to understand is any injury process, for example, the cardiac reperfusion injury, it's not just one cell type that's involved. It's multiple cell types. And these TRPC channels are present in these multiple cell types. So that can be supporting cells in the heart or in the brain as well as your functional cells, which are cardiomyocytes. So we think that taking that approach by having one inhibitor to block 3 channels is probably going to produce a better net effect than just blocking one channel itself.

Great. Thanks, Jas. Here's another question. What are the -- I mean, I think you may have touched on this already, Jas, but what are the anticipated mechanisms of action in oncology based on the known science?

Right. So as I said, in the tumor environment, high calcium entry in the cells can be very beneficial for these cells because they're continuously dividing, they're migrating, they're invading different types of tissues. And so this entry is -- has been shown in the literature to be mediated by TRPC ion channels in some cancer cell types at least. And so that's really the mechanism. The calcium where in one context of injury is really detrimental to say, brain cells and cardiac cells. In this other context where the cells are rapidly dividing, it's actually really helpful for them.

Great. Thanks, Jas. Another question here. How do you reduce the risks associated with patient variation in the ischemic reperfusion phase trial -- Phase II trial? That's probably best directed to you, Alex.

Yes. So can you repeat the question, just to answer [ the ] question?

How do you reduce the risks associated with patient variation? Okay.

Okay. So the risk with patient variation, specifically, we reduced that through the inclusion and the exclusion criteria in the protocol. So as I mentioned, not every patient will be eligible -- every patient with a heart attack will be eligible to receive Xolatryp. And obviously, that's not the end game. The end game is that we treat everyone that is having a heart attack and is experiencing ischemic reperfusion injury with Xolatryp. But the risk, as this person has pointed out, is that it's the first in patient. And so that's why we have really clear setup markers for who can be eligible and what -- who's ineligible. And these -- we've had great input from cardiac consultants that we have as well as our medical officer. And as James indicated, it's a well-trodden path. There's a clear standard as to what is safe and how that risk should be best mitigated.

Great. I'd just like to draw the audience's attention to the fact sheet we put out this morning. At the back is an appendix with some of the details of the trial, and it has some of the inclusion and exclusion criteria, so you'll see that. But at the bottom of it, you'll see a clinicaltrials.gov, which is the U.S. website -- U.S. government website where most clinical trials registered. You'll find the trial number and its hyperlink. So you can click through and you can see a pretty thorough description of the trial if you want to go down that avenue.

And if I can just add, Dimitri, I think we talk about risk a lot. And one thing that's really stood out is how great these sites are that we are talking to. It's not the first cardiac study that they're running. So that risk, I feel, is being managed. They know -- they have the language to talk to patients that are obviously in a high-stress situation. It's often the first time they've driven in an ambulance. And I feel the trial is safe working with these partners.

And we're being helped along the way with our CRO, Accelagen, who are doing a great job as well.

Correct. So it's also not their first radio. And yes, everyone is working really well together. Everyone's got their jobs. We all work collaboratively, and I think it's a good mix of -- it's a good team.

I should also mention that we're able to secure one of the leading cardiologists in New Zealand -- sorry, in Australia. Professor Will Chan. And he's very enthusiastic about the study. And he sees this indication as being very, very important, very clinically relevant.

Yes.

He's particularly passionate about this...

It's a key interest of his, and he has helped in that -- those inclusion and exclusion criteria that we discussed, to get that right balance between safety and not excluding too many patients.

Here's a question, softball perhaps, James. When are we expecting to receive the R&D rebate? Is there a delay? Why so?

No, I'm not sure there's anything out of the ordinary going on in terms of a delay. You make your submission and you're really at the mercy of [indiscernible] industry and the ATO. So all the paperwork has been submitted. It's under review, and we should receive it in this quarter.

There's nothing to be concerned about?

Absolutely nothing to be concerned about.

I watch a few biotechs myself, and I noticed we're not the only ones who are waiting. So it's not just about us. There's something...

Yes, yes. I think the holiday period has sort of delayed things. But the ball is in the court and the funds will come through when they come through.

Great. Here's another question. I'll throw this out up in the air to see who'll catch it. Calcium inflow into cells occurs through multiple gateways. What makes TRPC signaling particularly unique? And how are we differentiated from other calcium inhibitors that have all failed in reperfusion human trials?

Okay. So I think a lot of research has been done, especially in the context of stroke and calcium cells -- calcium channels, sorry. And those calcium channels are more fast-acting calcium channels. So they're either gated by a voltage or gated by a particular neurochemical. The TRPC ion channels are not directly activated by a particular -- they're not a receptor. So they're not directly activated by a neurochemical. They work downstream of what we call a group of proteins called the G-protein coupled receptors. And so G-protein coupled receptors, when they activate, they sort of downstream signal to these TRPC ion channels and they cause them to activate. An example of that in the heart would be the adrenergic, the angiotensin system. So that activation actually triggers off the activation of the TRPC ion channels. In the brain, an example would be when glutamate is released, it activates the metabotropic glutamate receptor and then by downstream effect activates these TRPC channels. So we're not so much affecting the normal functioning of the cells, which is where these previous trials fail. So when the NMDA receptor was targeted, it's so important in sodium transmission and not just calcium entry that when these patients were given drugs that block the NMDA receptor, they were having all sorts of neurological consequences. But TRPC ion channels are not involved in that sense in the functioning of the body. And so we think that is what makes it distinct. It's also the sustained activation of these channels. So in these injury situations, you get release of chemicals that just stays elevated for a long time. That is activating the G-protein coupled receptor, which in turn is activating these channels in a sustained manner.

Great. Thanks, Jasneet. This is probably best directed to either James or Alex. What is the anticipated success threshold in reduction of reperfusion injury in the coming trial?

Do you want to take that one, Alex? Do you want me to?

I'm not sure what they mean by success threshold.

I think it's talking about the -- the reduction of injury size. And I guess...

Obviously, safety is...

Obviously, safety is the most important thing we're looking at in the study. But there has been a lot of literature published. There was one paper in particular that looked at 10 studies in myocardial infarction reperfusion injury. And it showed that a reduction in infarct size of 5% can lower your risk of a follow-up cardiac event or hospitalization in the following 12 months by 20%. And if your infarct size is in the upper quartile in the top 25%, you have a 7 times higher risk of a cardiac event or hospitalization in that 12 months. So the idea with this drug is -- with Xolatryp is to reduce the risk that these patients who survive a heart attack face. And often, it's the second heart attack which is fatal. And the outcomes following a second heart attack, I think the survival rate is 50% within 5 years. So Xolatryp will reduce that risk and give the patients some peace of mind that they've got a lot of chance of having a follow-up event.

Coincidentally, I think that the study you referred to was referenced in the slide deck [indiscernible] we released this morning. But also from a health system benefit, keeping a patient out of the hospital for a second heart attack, that offers huge benefits to health systems and patients, of course, too.

Yes. And just to put some numbers around it, there are between 15 million and 20 million heart attacks that occur globally each year. And we know that there are about 5 million PCI procedures or angioplasty. So we're talking about a large market, and it is a market that is growing, I think, at about 6%, 7%. So it's an important clinical indication to go after for sure.

And Alex, I mean, in previous company communication, we've mentioned there are around 50,000 PCIs done in Australia. But it doesn't necessarily mean we can tap into that 50,000 because there are some voluntary PCIs that are done, people having second heart attacks. What kind of -- can you just give a bit of color around the kind of numbers? Well, not necessarily numbers, but the -- just prune that back a bit?

So I think the end game is to target all those PCIs. But initially with the Phase II study, it's really about, as I mentioned, the first heart attack. So that was obviously not elective. And we have some parameters around -- they have to be 6 hours from symptom time, 2 hours from the time they arrive the hospital to that balloon time. And typically, most hospitals that we're talking to, they have a door-to-balloon time of less than 1 hour. So we feel these criteria can really be met. And most hospitals are having around 300 STEMI patients a year. Of course, that needs to be broken down into in versus out of hours, the first heart attack versus second heart attack. So that gives a bit of color on numbers.

Great. Any other questions from out there? That's probably all the questions -- well, that's all the questions we have and all the questions provided. So I'll just wait a minute. If there's no more questions, we might wrap it up early, a bit early. Well, it looks like there are no more questions. So again, thank you for your attention. This recording will be on our website today or tomorrow. If you have any questions that pop into your mind afterwards, feel free to drop us an e-mail at [email protected], and we'll get back to you promptly. But thank you for your attention. It's interesting times ahead for the company -- interesting and exciting times ahead for the company. So again, thank you for your time and your attendance.

Thank you.

Thanks, everyone.