Good morning and welcome once again to TD Cowen's 45th Annual Healthcare Conference. I'm Phil Nadeau, a biotech analyst here at Cowen. It's my pleasure to introduce the next presenting company, Cardiol Therapeutics. We have with us today David Elsley, the President and CEO, and I believe also, Andrew Hamer, the CMO and Head of Research and Development, is around as well. David. Thanks, Phil, and good morning, everyone. It's a great pleasure to provide an overview on Cardiol Therapeutics and our work in heart disease and provide an update on our progress. Essentially, the major objective or goal of this organization is to develop therapies that can improve quality of life for people living with the challenges of heart disease. Underlying this mission is a focus on advancing therapies that target a key underlying pathological process in heart disease, which is inflammation, which is a key culprit in the development and progression of a number of life-threatening and debilitating cardiac conditions. We're fortunate to now be in the late stage of development. We've recently announced the phase III MAVERIC P rogram, which is now being operationalized in the United States. This trial is designed to essentially definitively demonstrate the impact of our lead asset, CardiolRx, in a very debilitating condition called recurrent pericarditis. Recurrent pericarditis is the initial market opportunity, and I think the opportunity there is, the unmet need in patients with recurrent pericarditis, I think, is exemplified by the fact that immune suppressants are currently generating $500 million in this market, with many Wall Street analysts forecasting their revenues will grow to $1 billion. We're not just targeting the underlying aspect of recurrent pericarditis. We have a validated target, which is inflammasome activation, which is an underlying mechanism driving a number of important areas of cardiac medicine. We're fortunate to have world-class collaborations with thought leaders and preeminent cardiovascular research centers from around the world. We're fortunate to be working with the renowned Mayo and Cleveland Clinics, supporting our research in cardiac disease, and we have international centers of excellence throughout the world. We have a number of near-term drivers. We look forward to enrolling the first patient in our pivotal phase III registration trial. We look forward to progressing and reporting on the ARCHER program in myocarditis, which is due to readout in the second quarter. We look forward to accelerating and speaking more about the development of CRD-38, which is a novel sub-Q asset, which we're developing for heart failure. In terms of the pipeline, the lead asset is a fully synthetic cannabidiol formulation that is manufactured for scale, purity, and industry-leading stability. This molecule, this small molecule agent, has very important cardioprotective properties that are now being borne out across all of our research. CardiolRx is the subject of two advanced stage programs in recurrent pericarditis and myocarditis. We also have CRD-38, which is now progressing. The data from many years of fundamental research has just been published in the tier one high impact journal, Journal of the American College of Cardiology, and we're very excited about that. It's garnering a lot of attention in cardiovascular medicine. With respect to the mechanism, essentially we're looking at modulating inflammasome activation pathways. We're working upstream of interleukin blockers, for example, and modulating essentially the inappropriate levels of production of cytokines, initially like the interleukins that are implicated, like interleukin alpha, beta, in pericarditis and interleukin -6 in the heart failure setting. The most advanced program is the MAVERIC study. This is a late-stage clinical program now in phase III, and it is designed to explore and definitively demonstrate the impact of our lead agent on recurrent pericarditis, which is a very debilitating, it's a miserable condition that strikes people in their prime of life, in their forties and fifties, causes shortness of breath, severe chest pain, depression, and a marked reduction in functionality and people's quality of life. This condition can destroy quality of life for several years. It leads to frequent hospital admissions, and it affects thousands of patients. Really the only FDA-approved drug for this condition, which is typically reserved as patients for multiple recurrences or as a third-line therapy, is an immunosuppressant, which is prohibitively expensive at a list price of $280,000 per patient per year. In terms of the treatment challenges, really the treatment pathway for patients is first-line therapy, which are nonsteroidals and colchicine, but a high percentage of patients are either intolerant or nonresponsive. The only therapeutic options available today are either steroids, where you have toxicity and resistance issues, or the hard-hitting, costly immunosuppressants, which have been associated with increased risk in cardiorespiratory infection rates. We believe there's a unique opportunity for a non-immunosuppressive oral therapeutic option, that can be potentially disease-modifying. The data that was presented late last year from our phase II program, which was also called MAVERIC, from eight preeminent centers in the United States, we believe shows great hope. This data exceeded our every expectation in terms of its impact on the key features of this condition, which is pericarditis pain, which was measured at eight weeks and at 26 weeks on the standardized NRS scale, which is a zero to 10 pain scale. This trial enrolled 27 patients at major centers in the United States. The key enrolling centers were Cleveland Clinic, Mayo Clinic, which are the largest pericardial disease units perhaps in the world. Mass General here in Boston was also a key contributor. Importantly, all centers enrolled patients. This is the study design. Patients, to meet the inclusion criteria, they had to have an NRS scale. They had to be on the NRS scale at four or greater. NRS zero is no pain, 10 is incapacitating pain. These patients needed to be four or greater. They also had to have either an elevated CRP or abnormalities on cardiac MRI or both. They also had to be on optimal treatment or standard of care medications, which included colchicine, nonsteroidals, and/or steroids on stable dose going into the study. They could not be on immunosuppressants. These are the data that was presented at the American Heart Association. Interestingly, we enrolled 27 patients in this trial. All patients at the eight-week primary endpoint were asked if they wanted to volunteer to enter a four-month extension. Remarkably, 24 of 27 or 90% of the patients agreed to go into the four-month extension. We think this speaks to drug tolerance and the impact of the drug. Typically, patients don't take a drug for an intractable condition that causes chest pain for eight weeks and then agree to go on taking it for another four months if they're not deriving some impact. I think this is borne out in the data. These patients had a very debilitating level of pain at baseline. They were essentially six out of 10 on the NRS. Within five days, the median time to resolution, or near or within five days, we had resolution in the median group of these patients, which we think is quite striking given that patients don't get to max dose of our oral therapy until 10 days in. During the extension period, patients who were on nonsteroidals and steroids were weaned off those background medications down to monotherapy. At the primary endpoint, we had a clinically significant or clinically relevant impact on the NRS with a 3.7 reduction, which is remarkably comparable to the most potent medications or immunosuppressants deployed in this condition. When we weaned them off background medications, this impact on pain was sustained. We also had a clinically meaningful impact on C-reactive protein. Normal is 0.5. These patients as a group were at two going into the trial. They approached the normal range at eight weeks and intriguingly reached the normal range or entered the normal range while we were weaning them off background medications. Again, we're seeing a sustained impact on a key marker of systemic inflammation. Perhaps the most striking finding was the impact on pericarditis events per year. These patients were very unwell going into this trial. They were essentially having six events, which can go on for days or weeks leading into the trial. That was reduced to 0.9 during the study, and 71% of patients remained recurrence-free during the extension period. These data have now supported going into what we believe will be a pivotal phase III registration trial, which is well-powered to show the impact of our drug. This study is designed to enroll 110 patients across 20 major cardiac centers in the United States, and we also anticipate centers being involved from Europe. The primary efficacy endpoint in this trial is freedom from recurrence at 24 weeks. Secondary endpoints include median time to new recurrence, and exploratory endpoints will be change in NRS and CRP. We anticipate enrolling the first patient in this important study in the first quarter, and our objectives are to complete the enrollment over the next 12 months following the initiation of all clinical trial centers, which are being operationalized currently. We're very pleased to have, really the many of the preeminent KOLs from around the world, who have collaborated with the company in the design of this trial. Paul Kantor from Northwestern was the architect of this study. He's renowned for his work in cardiac imaging and recurrent pericarditis care. Allan Klein and Allen Luis lead the two perhaps largest pericardial disease units, in the world today. Massimo Imazio sets the guidelines for pericarditis care and myocarditis care for many of the major regions, country members, states of the European Union. Stephen Nicholls is a clinical trialist, and Antonio Brucato is a specialist in inflammatory disease. They designed this study to be enriched essentially for high relapse rates because we're enrolling a patient population at the highest risk for recurrence, which are patients being weaned off interleukin-1 blockers. Patients will go prior to the enrollment in this trial, they will have been on 12 months of IL-1 blocker. We know from real-world evidence and now a number of publications that inside of 12 weeks, these patients, 75% will relapse, and that grows to about 80% or higher at six months. We essentially know the relapse or the recurrence rate in the placebo group. This study is designed to enroll patients essentially who are stable, who are planning or wishing to withdraw from IL-1 blocker therapy after being on it for at least 12 months. They will then be randomized one-to-one to either CardiolRx or placebo, and then the treatment period will go 24 weeks, and then endpoints will be assessed. We believe this study is designed to provide entrant into a very significant market opportunity, which is essentially the 38,000 patients who suffer from recurrent pericarditis each and every year in the United States. A very significant percentage of these patients fail first line and then really only have steroids or other immune suppressants to choose from. We believe CardiolRx offers an interesting therapeutic option because it's oral, because it's potentially disease-modifying, and it's non-immunosuppressant. We also have an interesting and equally important program that is now reaching conclusion in acute myocarditis. This is a global program, designed to explore the impact of our drug on acute myocarditis, which remains the leading cause of sudden cardiac death in young people, people under the age of 35, for which there is no standard of care. This is typically caused by a viral infection. It leads to immune activation against heart cells, which can lead to fibrotic scarring. It affects a significant number of patients each and every year, has high in-hospital mortality, and affects a very young demographic. This is really the data that triggered our initial interest in exploring our lead agent in myocarditis, really a demonstration of the cardioprotective properties. In this model, they induce myocarditis. This leads to fibrotic scarring across the myocardium. Left is healthy heart tissue. Center is induction of disease. In the presence of induction of disease, our lead agent was shown to be profoundly cardioprotective, with the majority of the myocardium being preserved. This interested KOLs from around the world. Dr. Les Cooper and Dennis McNamara, they co-chair this panel. Les Cooper is the founder of the American Myocarditis Foundation, heads a prominent myocarditis unit at the Mayo Clinic in Jacksonville. Dennis McNamara heads a prominent heart transplant unit, understanding that end-stage myocarditis can necessitate the requirement for heart transplant. They are collaborating with thought leaders throughout the United States, Europe, Latin America, and Israel. This panel collaborated with Cardiol Therapeutics on the design of the ARCHER trial. This is one of the largest company-sponsored clinical initiatives in myocarditis in many years. This trial has enrolled over 100 patients. We actually enrolled 109 patients at 34 centers in the United States, Canada, France, Brazil, and Israel. We completed enrollment in Q4 of last year, and we look forward to top-line data from this trial early in Q2. The primary efficacy endpoint here, it's a co-primary endpoint. Patients are baseline using cardiac MRI. We're measuring extracellular volume, which is all of that fibrous scarring material shown on the previous slide. We're also measuring a precision measure of ejection fraction, which is global longitudinal strain, and then EF as a secondary endpoint. Patients are baseline. They have to have an abnormal picture on cardiac MRI. They're then treated for 90 days and then reimaged. Last patient has exited this study just recently, and we fully expect top-line data in early Q2. Beyond the efforts of the oral therapy, we have a very important sub-Q asset that we have innovated. The cannabidiol molecule is a highly lipophilic molecule. We've basically developed a solvent system, which is quite unique, to solubilize this molecule with water-like viscosity to allow it to be administered sub-Q. The potential is to apply this to the mass market of heart failure, which by any measure is a major medical challenge. It's an epidemic of sorts. It's driven by increasing diabetes, hypertension, and obesity around the world. Still has a 53% mortality rate within five years, which I think underscores the need for new therapeutic entrants. Chronic inflammation really hasn't been well addressed by available therapeutic agents. We believe CRD-38 offers the potential to be either a once-weekly or perhaps as efficient as one-monthly therapeutic agent. Based on the data that has recently been published in the Journal of the American College of Cardiology, we're now increasing our focus on the development of this agent to complete the IND enabling work necessary to have it ready for first-in-man or IND enabling or IND filing for phase I. I guess the key feature, the key feature of the data that was published in JACC was a dose-dependent effect on preventing cardiac remodeling and inflammation. This is exemplified by, essentially reducing the myocyte area, fibrotic markers. It was also shown to protect against cardiac dysfunction with impacts on stroke volume, ejection fraction, and cardiac output. The data published in JACC confirmed or was complementary to previous data from a study co-sponsored by the Obesity Research Institute in a classical HFpEF model, which is now fast becoming the gold standard to study new agents in heart failure with preserved ejection fraction. This preclinical system is induced by two challenges. One is obesity, the other is hypertension. You have a metabolic strain combined with a hypertensive strain. This leads to increase in heart weight gain, body weight gain, which was ameliorated by CRD-38. We also saw an intriguing observation where the drug was shown to reduce the distribution of visceral fat in favor of subcutaneous fat. Subcutaneous fat being that dangerous metabolic fat that coats major organ systems in the body, including the heart, that was reduced, which was quite a fascinating observation. Equally importantly was the impact on the key interleukins as well as tumor necrosis factor, which can be elevated in the heart failure state. We showed prevention again of cardiac remodeling with a significant impact on BNP and other remodeling markers. The major milestones we look forward to in the coming 12 to 18 months, this organization is completing the recurrent pericarditis program. We look forward to initiating the first patient enrollment into this important potentially registrational trial in recurrent pericarditis. We look forward to completing our objective is to complete 50% enrollment during second half and then complete enrollment of this trial in first half of 2026. This potentially sets this organization up for a pivotal phase III readout in 2026 that could underpin a new drug application and provide access and entry into a growing $500 million market, which many are forecasting will double over the next two to three years. We also look forward to top-line data readout in acute myocarditis, which we believe will inform not only the heart failure program, but could see this drug agent secondary to a label claim in pericarditis added to guidelines in myocarditis care, because currently there is no standard of care for myocarditis. Cardiologists, myopericardial disease experts commonly use agents that have been trialed in recurrent pericarditis in myocarditis. We look forward to completing the IND enabling work to accelerate the development of our sub-Q formulation into first-in-man studies as a potential once-weekly or once-monthly new therapeutic option for chronic inflammation and fibrosis in the heart failure state. That is the summary of Cardiol. We look forward to executing on our phase III program in pericarditis. We are targeting a well-characterized mechanism that underlies a number of important cardiac indications. It is the focus of research attention around the world. We are excited and honored to be part of it. We are addressing significant unmet needs, which is really for a disease-modifying non-immunosuppressant option in our lead markets and a more chronic therapeutic intervention for the high mortality rates in heart failure. We continue to collaborate with really the world leaders in cardiac medicine, and we look forward to reporting on a number of important inflection points over the next 6 to 12 months. Thank you. We now would be happy to address any questions folks might have. Yes, Phil. The MAVERIC trial, have you disclosed the powering for the primary endpoint? What number of patients do you assume will be free from new episodes over those 24 weeks? What's the assumption for the comparator on this one? It's powered for, it's got a 90% power, which is ideal for this. We actually have looked at variable outcomes, and we're well powered for all of them, whatever relative risk reduction you may be considering. But, from a clinical point of view, we'd like to see get that 75%-80% down to around 50% would be considered clinically compelling. You mentioned the recent JACC article on your heart failure program. Just wondering if you could provide a little bit more information on that, how it's influencing your development plans going forward. It's really nice to have data peer-reviewed, and from our collaborators, you know, abstracts and presentations at scientific media are all very well. It's really, once it's peer-reviewed in a top-tier journal. Also, what's important about this publication is it really looks right across all the key elements of preclinical work that you need to do. Firstly, you have a, you know, you've got your basic science work looking at receptors. You then have your animal model. Finally, you take specimens from your animal model and show the same receptor effects. That really does put together the story that brings you forward and makes it a much higher chance that you're going to translate that finding in the preclinical models through to a human benefit. Do you discuss the powering for the acute myocarditis trial? The powering for that is very interesting. I mean, it's a bit difficult when you've never shown, no drug has ever shown an effect or benefit in a condition. What's nice about cardiac MRI is it has very minor variability. You can look at some trials. For instance, there was a PIROUETTE trial in heart failure with preserved ejection fraction looking at the same endpoints. They showed a significant effect with what was considered a clinically tiny change in those parameters. It does give you a lot of power when you have something like cardiac MRI, which has such good reproducibility and very low variability. Did that trial translate outcomes? Effects? The problem with PIROUETTE was it was with pirfenidone, about 35% of patients did not tolerate the drug, so it did not go anywhere. Do we get any signal of, as a 12-week study, do we get any signal of events from clinical outc omes in this trial? That is unlikely. We have chosen a population that has a stable situation on a cardiac MRI, and therefore you get a much better outcome as far as your reproducibility and variability. What we can say is that we have shown data showing that the baseline changes in those parameters have been very consistent with what we powered the trial for, which is ideal. No, you'd have to go to a separate, very unwell population to see those clinical outcome changes, which doesn't really suit putting them through cardiac MRIs frequently. Just a follow-on to that question. So, what would be in your mind a proof of concept change in either extracellular volume or GLS in the acute myocarditis trial? Is it really any sense of change is meaningful, or is there a threshold above which it's reasonably likely to predict clinical benefit? I think what we've powered the trial for is a clinically relevant change. What's really important and intriguing is it would be a clinically relevant change in myocarditis. It would be a clinically relevant change in any heart failure patient, in effect, any patient with fibrosis of their heart. We fully anticipate positive outcomes from the myocarditis would garner a lot of attention with respect to CRD-38 because it's really a, a form of heart failure. Would you use this as a principle for, for CRD-38, or is there a chance you'd move into a phase III acute myocarditis? I suspect the pathway would be to pursue the more accelerator program, which is in recurrent pericarditis. Interestingly, the steering committee for the myocarditis program really do write the guidelines for myocarditis care. To the extent that we have a label claim in recurrent pericarditis following MAVERIC, there could be a scenario where we're added to guidelines. We believe the greater prospect for outcomes from myocarditis is to inform and accelerate the program in heart failure. On that note, you mentioned the presentation that, there's been some potential use of RP drugs in acute myocarditis. Has there been any case reports or use of the IL-1 betas used either in the U.S. or off-label in EU myocarditis patients? There was a trial done with the French group with anakinra versus placebo, and they showed no, no benefit with anakinra in that population. Those investigators have joined us. They feel our trial design is much superior and, and very interested in the results of our trial. Comment a bit on the differences between the trials? They didn't do cardiac MRI follow-up. And really, that's where your proof of concept really needs to...