Hi, good morning everyone. Thank you for joining us. My name is Edward Nash, Senior Biotech Analyst here at Canaccord Genuity. I have the pleasure of having with us the management team of Cardiol. It's a name we cover with a buy rating. From the company, we have the President and CEO, David Elsley, and Dr. Andrew Hamer, who is the Chief Medical Officer and the Head of Research and Development for the company. Thank you both for joining us today. Thanks for having us. Pleasure to be here. I wanted to kind of kick off the conversation at a 10,000-foot level, but maybe you can give some background to the audience on Cardiol as a company and the clinical programs you have right now. Happy to. Cardiol Therapeutics is focused on developing anti-inflammatory strategies for key underlying disease-causing mechanisms in heart disease, and these mechanisms span a broad spectrum of heart diseases, including pericarditis, myocarditis, and heart failure. Our lead program is MAVRIC, that is a pivotal Phase III trial now operational in the United States enrolling patients. We look forward to adding prominent centers to that study from Europe, as well as another prominent center from Canada in the very near future. That program is designed to support a new drug application, subject obviously to outcomes in the trial, but we're encouraged by strong data from the Phase II trial that was presented at last year's American Heart Association. We also have a second late-stage program that's recently reported top-line data, which is called ARCHER, in acute myocarditis, a devastating life-threatening condition that takes young lives unnecessarily and for which there is no current standard of care. We couldn't be happier with the data that we've just announced top-line from, where we've shown key impacts on MRI-based measures that are associated with prognosis, diagnosis, and long-term outcomes. We look forward to further exploring those data and presenting them at a scientific congress in the not-too-distant future. Thirdly, we have a very exciting asset that we are developing for one of the, I'd say one of the greatest medical challenges of medicine today, which is heart failure, which is an epidemic of sorts. It continues to rise around the world, one of the leading causes of mortality, morbidity. It's driven by underlying forces such as diabetes, hypertension, and obesity, and all those factors continue to rise, continue to increase this challenge. We're very excited because we've just published data in the Journal of the American College of Cardiology concerning the role of our sub-Q asset that we believe shows great promise to address the most challenging form of heart failure, which is diastolic heart failure or heart failure with preserved ejection fraction. Thank you for that. I guess heart failure also significantly dwarfs the other two significantly by patient numbers. Orders of magnitude difference. The lead programs, which are orphan designation conditions for which we have the FDA orphan designation for the lead program in recurrent pericarditis. In fact, we have the orphan designation for the entire pericarditis landscape of which the recurrent patients is about a 40,000 patient subset. ARCHER is also eligible. Myocarditis is eligible for orphan designation, and we look forward, based on the data from ARCHER, to discussing the prospects of an orphan designation based on the data we've just announced. Heart failure is a condition that at any one time affects 6 million Americans and is probably one of the leading, if not the leading, cause of hospital admission and readmission. I wanted to maybe kind of jump into the recurrent pericarditis program, which is in Phase III development, as you mentioned. Could you help us understand the positioning of CardiolRx™ as it relates to treating recurrent pericarditis? I ask this because you've got that enrolling, but it's specifically in patients who are looking to stop the IL-1 trap drug. I just wanted to kind of understand that design. The goal with CardiolRx™ in recurrent pericarditis is very much to replace corticosteroids within the treatment paradigm. However, the best trial to do for your registration is a trial where you have a very predictable event rate in the placebo arm. That is an enrichment strategy. One of the reasons why people are wanting a drug to replace corticosteroids is because whilst Rilonazepam and other IL-1 inhibitors are very effective at controlling the disease and preventing recurrence while you're on them, they are immunosuppressive. Recurrent pericarditis is a time-limited disease, but it's found that it doesn't matter how long you're on them, when you come off them, you have a 75% recurrence rate within the first three months. That is a very homogeneous population in which to prove benefit of CardiolRx™ in preventing recurrences by taking patients that are trialing off their IL-1 inhibitor and randomizing them to placebo or CardiolRx™, knowing you're going to have an event rate in the placebo arm of 75% in three months. The patients are not on any other therapies for recurrent pericarditis, so it's a very clean population. It has been very clear that that is a trial that's therefore potentially registrational for a much broader population that does cover exactly where we see the market and the opportunity and the need. I want to bring up the design of this trial. I think one of the big important parts of this is lots of biotechs, obviously most biotechs have SAB, but I think you guys really stand out with regards to the significant depth that your SAB has. Maybe you could just speak to that quickly just so people kind of understand that that was how this trial was informed from the design was by this SAB and who's on it. Chairing committee. Oh yes, we're very pleased to have really the global leaders in pericarditis that are leading our program. We have Program Chairs. Our Program Chair is Dr. Allan Klein from Cleveland Clinic, runs the biggest pericarditis service in the world. Our Co-Chair is Dr. Massimo Imazio, who is really the European expert in pericarditis and has been for 30 years and writes the guidelines, leads the guidelines, and the expert groups over there. We have a Principal Investigator for our Phase III trial is Dr. Paul Cremer. He's a real expert in clinical trials, imaging of the heart, and runs the cardiovascular research services at Northwestern University in Chicago. Dr. Allan Lewis, who ran the pilot trial, is Principal Investigator for that. He runs the second biggest pericarditis service in the world at Mayo Clinic. We have other experts in our group. You've discussed a bit of the attributes of how this trial was designed. As you're talking to KOLs, the key opinion leaders in this area, how do you see them or do they tell you that this is how they would actually incorporate CardiolRx™ into their treatment practice? Or is it more of a broader aspect besides just the coming off of the IL-1? They perceive, as we do, and as I can reassure you, the regulators do as well, that simply what we're doing is a very enriched population for events, and that this is proof of prevention of recurrence of pericarditis to be then used in the broader population. Their goal and their need is to replace corticosteroids in the treatment paradigm with a drug that doesn't have any evidence of immunosuppressive effect. Basically getting earlier in that treatment. Getting early in the treatment paradigm. As David says, we actually have the orphan drug designation for the entire breadth of pericarditis. The future holds a lot of potential. I think one of the key advantages is we're an oral therapy. Theoretically, this is a more accessible therapy. When you look at the biologics and the immune suppressants, they're prohibitively expensive and difficult to access through reimbursement. Reimbursement needs to be reassured annually. You have the steroids, which have toxicity and resistance. When a patient is non-responsive or intolerant to first-line therapy, such as non-steroidals and/or colchicine, they really only have two paths. They go to steroids or they go to immune suppressant injectable biologics, which are very hard to access because of their price. We believe there's a tremendous opportunity to intervene in that intermediate step and help those thousands of patients that are non-responsive to first-line therapy with an oral that is accessible to patients and has really quite an extraordinary safety profile that's been borne out across multiple populations. I think you have something very unique here in the fact that you have an indication where there are no current approved medications or drugs out there for it. You have recurrent pericarditis where there is an approved drug, so you know kind of what the FDA is looking for and what's important in order to get approval. There are shortcomings, obviously, with that drug where you fit in. Would you see that your regulatory path for CardiolRx™ will be very similar as far as the regulatory aspects as the drug gets in front of the FDA? Would you expect that the agency would, it's pretty clear given what the competing drug that's out there has gone through, that the path is very clear and obvious for CardiolRx™? Absolutely. It's very reassuring to have an established regulatory path. Lots of times in development of new medicines, you don't have an established path, so you're in negotiations with regulators as to how should this drug be developed. The interesting aspect of the recurrent pericarditis landscape is we benefit from a drug having gone through Phase II, Phase III. We're mirroring that design, which is published internationally. You can overlay the design of our Phase II program and our Phase III program, and there's complete consistency between those. We know the question the agency wants to answer, and we've designed a trial that has answered that question previously. That's a major de-risking of that trial. We couldn't be more excited about the prospects of MAVRIC and the encouragement of all the clinical sites behind it. Great. Now I wanted to talk now, maybe kind of jumping over to acute myocarditis, you understanding that you're also very limited on what you can say beyond what was in the release, given that you're submitting this for presentation at an upcoming meeting, as you mentioned. Could you maybe just give us some highlights from that Phase II ARCHER trial, the things that really stood out that you think are going to be really important and kind of what's driving, what kind of has triggered you to be excited about moving into a potential pivotal trial? Yeah, sure. I'll sort of summarize our take from the study, and then I'll let Andrew provide some more details on why we're so excited about the observations. First and foremost, it was, as I said in my quote in the press release, an ambitious study. This is a landmark program, one of the largest, if not the largest, undertaken by a corporate sponsor in a disease that is life-threatening, for which there is no standard of care. I think that's the important aspect. It was a very well-designed Phase II trial to answer two important questions: safety, and does it underpin the advancement of the drug's development? I believe if you read the quotes in the press release from some of the foremost experts in the world in myocarditis, including Dr. Dennis McNamara from the University of Pittsburgh, who heads the heart failure program and the transplant program there, and Dr. Leslie Cooper, who's the founder of the American Myocarditis Foundation, there's very strong encouragement. In fact, they use the word strongly support advancing this medicine not only in myocarditis, but also in other inflammatory cardiac indications, including heart failure. This has created the pathway to a much larger opportunity based on the consistency of the improvements in the MRI-based measures during this study, which Andrew is certainly happy to speak to. Please. Yeah, and as you say, we are guided about what we're saying because it's so important that this data is put in front of the cardiology community, that it gets critiqued, but also disseminated so people are aware of it, can think about it, and also know that it's been looked at in a very objective and unbiased way by experts in the area, both that have been involved in the program, but also that haven't been involved in the program. What we can say at this time is that yes, we are very interested in the changes of the left ventricular mass. That is very nice to see and that it translates from data that we have in the JACC article about effects of CRD-38 on the size of myocardial cells. That's exciting for any inflammation condition of the myocardium, myocarditis being the most inflammatory condition of the myocardium, but also heart failure, particularly heart failure with preserved ejection fraction, where left ventricular mass is a very important part of the prediction of bad outcome in those patients. We know now increasingly it's low-grade inflammation and diffuse scarring that are an important part of that, that we know from preclinical data our CRD-38 effects. Seeing that translation from animal data to human data is not only very exciting for the potential for myocarditis, but also for CRD-38 and heart failure with preserved ejection fraction, and also for the MAVRIC program because it's really nice to see that translation to human data at the doses that we're also using in the MAVRIC trial. Yeah, I was going to ask you to kind of beg the question of maybe just the significance of a reduction in left ventricular mass. Why is that so important? Left ventricular mass is a global measure of the thickness of the heart walls. We often talk about thickness of the heart walls, but it's the entire mass, so it's a more sensitive marker. Usually we think about that over years of patients taking things like blood pressure medications. These patients had completely normal blood pressure, didn't change at all on treatment, and in 12 weeks we saw a real change in left ventricular mass. The only way you can, what we're told is the only way you could do that is if you've affected the inflammatory, what's going on inflammatory-wise within that myocardium. 70% of your left ventricular mass is the muscle cells and 30% is the interstitial tissue around the muscle cells. To have affected it that much, you must have affected both of those from a point of swelling as far as we can see and the experts tell us. We don't want to say anything more about the data until it's been peer-reviewed and presented. I think a key feature of this observation, which is important, we're studying an anti-inflammatory, antifibrotic agent in life-threatening cardiac disease here. To the extent that you can observe a reduction in this cellular volume or the swelling in cells, if that is not interrupted, those cells can go, that can lead to fibrosis, which then becomes very challenging or is not reversible. Young, healthy people can develop heart failure, can develop chronic disease at an age that typically, or with a disease that typically does not present until much later in life. These folks are typically 35 years. The leading cause of sudden cardiac death in people under the age of 35 is acute myocarditis. There's never been an effective treatment. There's never been a drug observed to improve it. We have seen the first improvements in this condition. Not only does that inform work in further potential life-threatening forms of myocarditis, as indicated by Dr. Cooper in his quote in the press release, it also creates an accelerated pathway to interest from large pharma in our sub-Q asset for one of the greatest medical challenges in the world and one of the most costly diseases to care for, which is heart failure. Over $40 billion is spent annually in the United States alone on heart failure, and those costs are forecasted by multiple statistical firms to only grow. You've touched on this a bit, but one of the questions that comes into me most frequently from investors was wanting to understand if the ARCHER data would be able to give us a read-through into the recurrent pericarditis MAVRIC trial. I had historically said that it would be very helpful on the safety side, but on efficacy, there are very different endpoints. There are very different cardiac diseases. That seems to have changed a bit with the ARCHER data that we've seen now. Maybe you could talk a little bit about that as a potential read-through. This is a significant read-through to the Phase III program. The underlying theme across pericarditis, myocarditis, and heart failure is inflammation, whether it's acute or chronic. We now have proof of concept or clinical proof of concept in men, in patients that was presented firstly in pericarditis patients or recurrent pericarditis patients at the American Heart. We now have this very important observation from this landmark study in acute myocarditis. That's the connection. We have two proof of concepts in two different conditions using a therapy designed to modulate the inflammasome activation pathway, which leads to, and we believe is disease-modifying to modify the inflammatory state in these patients. Therefore, it can be, it's addressable to conditions as large as heart failure. What are the next steps now that we have the ARCHER data as far as clinical steps? Is this something that you would look to move right into a Phase III or kind of what's the next steps there clinically? We are currently using this time while we prepare for presentation and full presentation of the data and multiple publications of the data to consult with the experts in the field, both in heart failure medicine and myocarditis, and develop the appropriate next steps forward. We're also going to be informing our business development discussion folks. We have an active program where we're in consultation and discussion with a very well-capitalized pharmaceutical industry who has strong interest in these areas because the underlying theme is inflammation. Inflammation in myocarditis can lead to heart failure in a young person. The same phenomena occurs in heart failure in general in people of more advanced age. We have this very thought-provoking connection now to underpin and accelerate our development program, not only of CardiolRx™, but also of what we believe to be a completely undervalued, undiscovered asset within Cardiol 's portfolio, which is CRD-38, which we believe is going to be once weekly or possibly even once monthly treatment for one of the greatest medical challenges in the world, which is chronic heart failure. I assume that the data that you've gleaned from the ARCHER study, specifically on a safety standpoint, that can be used in the filing for a MAVRIC trial as well from a safety database? Absolutely. To have really, you know, as we said, you know, a parent safe and well-tolerated drug is really important when you have actually a much sicker population than you do in pericarditis. Myocarditis patients have a life-threatening condition at the time that you're treating them. You couldn't be happier. It's not like you've gone to normal volunteers and seen safety. You've gone to people that are sicker than what you're going to be planning to get an indication in first, which is the pericarditis population. Got it. With the CRD-38, what are the next steps there of when we could expect to see a Phase I initiate? We are accelerating that program, and that program could not be more important to Cardiol, but the accelerant of that program is our business development discussions. We believe that drug is applicable to heart failure with preserved ejection fraction, which is probably one of the largest medical challenges, perhaps other than perhaps diabetes or maybe Alzheimer's, or maybe just as large. We are going to be partnering this asset with the pharmaceutical industry. There are large dominant players in heart failure medicine. There are drugs that are generating billions of sales in this area, and yet a patient hospitalized with heart failure with preserved ejection fraction still has a 75% mortality rate. Notwithstanding the number of pharmaceutical agents being directed at that condition, that mortality rate and morbidity rate still speaks to a significant area for improvement. Some of these blockbuster, multi-billion dollar drugs being deployed in heart failure do not decrease left ventricular mass. An increase in left ventricular mass is directly associated with increased risk for mortality, morbidity, heart attack, stroke, and heart failure. To be clear, the ability to deliver sub-Q, you already have that work done. Our lead agent, our lead API is a highly lipophilic molecule. We have spent years with our extraordinary organic chemistry development partner, and we have created a solvent system that is proprietary, that is covered by composition of matter protection, that creates a water-like viscosity, which allows a lipophilic or code for fat soluble molecule to be delivered in a water-soluble format. That would allow it to be administered with a pen, for example, auto-administered by patients. We believe that is going to transform the value of Cardiol Therapeutics because if you look at sub-Q administration, you see it across all the autoimmune complexes. You now see it in heart failure complexes. You see it in migraine medicines. There are multiple medications that are sub-Q. Of course, insulin is sub-Q. There is a strong familiarity, and it allows you to deliver a drug more efficiently, bypassing GI, get it directly into the systemic circulation and concentrate, in our case, in cardiac tissue, where it can deliver the most benefit. Fantastic. By having a solvent system that is water viscosity, we can use very straightforward pens to inject. Because it's so lipophilic, it moves into the subcutaneous fat, and that becomes a natural depot from which it is released in a very, over, we're not going to say how long, but we're hoping for weekly or monthly injections. The vast majority of pharmaceuticals dispensed by a pharmacist today are lipophilic. This could be a platform to help improve the efficiency in delivery of other fat-soluble medications. Fantastic. This continues to be what I believe is one of the definitely very undervalued stories in the cardiovascular area. I really appreciate you taking the time to walk us through it and look forward to seeing the full data on the ARCHER trial soon. Thank you. Thank you, Edward. Thank you.