Hi, thank you for joining us on TD Cowen's 46th Annual Healthcare Conference. I'm Joshua Fleishman, associate on the team of senior analyst Richard Brawl . Today we're joined by Cardiol Therapeutics CEO David Elsley and the CMO. David, please take us away.
Okay. Good morning. It's a pleasure to speak about our important work in heart disease. Cardiol Therapeutics is focused on targeting a key disease-causing mechanism, which is inflammation, in the heart disease landscape. We have important orphan drug indications in advanced stage development, we also have earlier stage developments addressing much larger challenges in heart disease, which is heart failure, which is a growing and very significant impact on human health and medicine for challenges. I think the key features of Cardiol is the late stage program, which is the MAVERIC study, which is targeting inflammation and recurrent pericarditis.
We see a very exciting opportunity in this area of medicine, a potential billion-dollar opportunity for a new drug entrant that offers greater accessibility, an oral therapeutic option for patients, and one with a non-immune suppressing profile. We also have compelling research just recently reported out of our global ARCHER trial in a related condition called myocarditis, which we believe de-risks the lead MAVERIC program because of the association of inflammation in the two indications. We have a number of very significant near term catalysts, which include completion of enrollment in MAVERIC, a top-line readout of that data.
We're exploring new opportunities, as a result of the exciting data recently presented at the European Society meeting with respect to the ARCHER trial, where we believe we've shown the first biological impact on that disease ever by any medicine, and we look forward to accelerating the development of our next generation concept in focused on heart disease. All of these developments are fully funded, and we believe these will underpin the acceleration and ultimate completion of a strategic alliance for the ultimate commercialization of our drug assets. Our lead program, MAVERIC, is now progressing very well in phase III. In fact, enrollment is accelerating in this program. We have preeminent cardiovascular research centers involved throughout the United States. Very large centers have recently joined this program also in Europe, and Canada is also involved.
This program has been awarded the Orphan Drug Designation by the U.S. FDA for the entire pericarditis landscape, of which recurrent pericarditis, our primary area of focus, is approximately a 25% patient subset of that group. ARCHER has just recently reported. Happy to share that data and review that data with you and the key outcomes of that and where we see that taking us in the future into new opportunities. With respect to heart failure, I think that's the key next stage of evolution, which we believe has transformative potential because that offers the possibility of a very efficient treatment schedule for patients in really what is an epidemic. Heart failure is driven by forces such as obesity, diabetes, and hypertension.
There's really no end in sight to the rise of those underlying drivers of the condition, and that's leading to this epidemic, called heart failure, which still has a 50% 5-year mortality rate, which clearly underscores the need for new therapeutic interventions. MAVERIC is the key focus of the organization. MAVERIC is targeting recurrent pericarditis. This is a condition that affects people in their prime of life, causes very severe chest pain, shortness of breath, marked impact on quality of life. Patients can endure this condition sometimes as long as six years. really the only treatment options for the more advanced patients are biologics that have challenges such as immune suppression, and they're very costly. In terms of the really the treatment algorithm for this condition, first-line therapy is nonsteroidals or the generic colchicine.
The challenge here, though, is that thousands of patients each and every year do not respond or are intolerant to these first-line, and then that patient group, numbering, in the thousands of patients really only have two choices, either to go with steroids, which have toxicity and resistance over time, or the hard-hitting immunosuppressant drugs, which can increase risk for infection, are tough to access for patients because of their cost, and require regular injections, which people in their prime of life, 45, 50 years of age, really don't prefer. They would rather have an oral treatment option, from a convenience point of view, most certainly.
From a reimbursement point of view, they'd prefer to have a treatment that is more accessible from a price point. We ran a phase II program that was essentially modeled after the phase II program that led to the rapid approval of the biologics in this indication. 8 leading centers in pericarditis were involved, including Cleveland and Mayo, the two largest pericardial disease centers we believe in the world today. Primary efficacy endpoint in this phase II program was what is in most important to patients, which is pericarditis pain. From a secondary point of view, we looked at primary was at 8 weeks. We also looked at pain at 26 weeks, looked at freedom from recurrence, and then looked at biological markers of inflammation associated with the pain syndrome. This is the study design.
We're an oral medication, which we believe is a key advantage of our therapeutic approach. Patients are titrated up over 10 days on top of background medications. Importantly, these patients were receiving optimal drug therapy for recurrent pericarditis, which included colchicine, non-steroidals, and/or steroids in any combination on stable dose. Notwithstanding that, these patients had a very debilitating level of pain as measured at least a 4 out of 10 on an 11-point Numeric Pain Scale, where 0 is no pain and 10 is incapacitating pain. On top of that background medication, we added CardiolRx and looked at the change in their pain syndrome at eight weeks as well as 26 weeks.
This is the key takeaway from this trial, which was presented at the 2024 American Heart Association meeting and has led us into the MAVERIC pivotal Phase III trial now. You can see that at baseline on the Y-axis, these patients were quite impaired with pain, essentially a 6 out of 10, which would be a debilitating level of pain on really any form of physical activity. A constant pain that would significantly impair quality of life. We basically modified that pain to either a manageable level or an undetectable level within two weeks. That was sustained at eight weeks.
Importantly, during the extension phase of this trial, where 24 or 90% of the patients enrolled agreed to go into this extension phase voluntarily, which told us early on the patients are both responding to our drug but also tolerating it very well. Notwithstanding that, the withdrawal of their background medication during the extension phase down to monotherapy with just CardiolRx, its impact on this key feature of the disease, which is pericarditis pain, was sustained. We also observed an interesting observation with respect to CRP. These patients are known to have high C-reactive protein, which is a broad measure of inflammation. They were 4x normal at baseline. Typically, normal CRP levels is 0.5. This patient population as a group in the study was 2. It approached normal at 8 weeks.
Interestingly and encouragingly, even whilst we were withdrawing their background medications down to just monotherapy with our drug, this patient pool entered the normal range, and that was sustained out to 26 weeks. The most striking finding from this trial was the impact on pericarditis events per year. This is really what patients are concerned with. They essentially want to be pain-free. They want to be recurrence-free. Coming into the trial, this patient pool was 5.8 events per year during the study. That was reduced to 0.9. Seventy-one percent of patients in the study remained recurrence-free, or they didn't experience the condition again during the trial. The key takeaways from this study is we've observed a marked rapid and durable reduction in pain. That's what patients want.
We're doing that with a very convenient twice-daily oral therapy that we believe will be far more accessible from a cost perspective and with a vastly superior safety profile. We've also shown a clinically meaningful impact on C-reactive protein. We're not just observing an impact on pain. We're observing one of the potential underlying drivers of the pain. Most importantly, we had a substantial reduction in pericarditis events per year. This is what's really fed into the now pivotal phase III trial, which is now operationalized at the numerous preeminent pericardial disease centers throughout the United States, Canada, and prominent centers in Europe.
We had a very successful end-of-phase II meeting in February of last year with the FDA, and they have alignment on this trial to the extent that we reach our objective of significantly reducing recurrence in this study that this would underpin a New Drug Application. This is the study design. Essentially, we're following what is utilized to study many cardiac indications. We're following a strategy to enrich essentially event rate or, in this case, recurrence rate or relapse rate, because we're enrolling patients that are at a very high level of risk for recurrence. Essentially, we're modeling again, we modeled the phase II program after the program that led to the rapid development of rilonacept or the immune suppressant in recurrent pericarditis today, which is marketed under the name ARCALYST. We're doing the same in our phase III program.
RHAPSODY, which was the phase III trial for rilonacept, they stabilize patients on IL-1 blockade. They randomize them either to continue on IL-1 or go to sham. Here we're bringing patients in on stable IL-1 block, and we're starting them either on CardiolRx or placebo and then withdrawing IL-1. We know based on real-world evidence and various studies that these patients have an extraordinarily high recurrence rate within three months, as high as 75%. That is what we're anticipating to observe in the placebo group during the 24-week treatment period. Based on our phase II program, to the extent that we can replicate the observations of phase II, we would expect to have a highly significant impact on reducing that key endpoint in this condition.
We're fortunate to have many of the thought leaders as collaborators and leadership with respect to this trial. They collaborated with the Cardiol team with respect to the design and filing and ultimately clearance of this by regulators around the world. Allan Klein leads one of the largest, if not the largest, pericardial disease center in the world, the Cleveland Clinic. Massimo Imazio sets the guidelines for pericarditis and myocarditis care throughout major countries in Europe. They're collaborating with international thought leaders that have been involved in really the development of all breakthrough medications across the pericarditis landscape. We're certainly involved in the development of the immune suppressants, which today are the only drug approved for this condition.
In terms of the market opportunity, we certainly see a growing, important market opportunity here, which I think is exemplified by the fact that immunosuppressants, notwithstanding their challenges, in terms of their product profile, be it injectable, being an immunosuppressant, being associated with increased risk of infection, being challenged by injection site reactions and convenience issues and cost. Notwithstanding all of those challenges, there's been a significant uptake, and those drugs are generating approaching $700 million in an annual run rate, with many forecasting they'll reach $1 billion by 2028. Potentially, I believe the company itself is forecasting upwards of $900 million over the next 12 months. That still leaves thousands of patients, we believe well over 10,000 patients, without good treatment options.
We believe our drug, priced more competitively, with the oral profile and the non-immune suppressant profile, can capture that, ultimately displacing steroids and ultimately becoming the drug that would need to be trialed first before patients would gain access to the immune suppressants, where there's a growing concern with dependency, given that once you start on those drugs, they're very difficult to wean off of or to taper from. That's a concern for both patients as well as payers. In addition to the ARCHER program, we're very excited about the recent data, which we believe is really precedent-setting with respect to the impact on myocarditis. Myocarditis is another inflammatory cardiac indication, very challenging disease, still remains the leading cause of sudden cardiac death in young people. No standard of care can cause frequent hospital admissions that are costly.
Many involve the ICU. High in-hospital mortality rate. It affects a younger demographic. It can cause the development of heart failure in these patients and in severe cases, can necessitate the requirement for heart transplant. Costly condition, no standard of care. It was an ambitious indication to trial, given that no drug has ever shown a biological impact on this. Notwithstanding that, we saw this opportunity to study our drug on a classical inflammatory cardiac condition because it would provide a gateway into the understanding of the impact of our drug on cardiac inflammation, and we believe open doors for many new indications in cardiovascular medicine. This just visually illustrates the early-on data that we observed that encouraged us and excited us to progress with a clinical program in this inflammatory heart disease. On the left, you see normal healthy myocardium.
The center, you see the disorganization of the cardiac infra-- or the cardiac structure. You see the red scarring. In the presence of the induction of disease with concomitant administration of our drug, you can see the majority of the myocardium is preserved and protected. This was very exciting observation several years ago. This interested then Les Cooper, who is the founder of the American Myocarditis Foundation, widely regarded as an international thought leader in this area. Les has agreed to collaborate with thought leaders for major countries around the world, throughout the United States, Canada, major countries of Europe, Latin America. We assembled this international panel to design what we called ARCHER.
ARCHER we believe is one of the most ambitious programs and one of the largest company-sponsored studies in many, many years in this underserved area of medicine. We enrolled 109 patients at five countries at preeminent cardiovascular research centers. The key endpoints we looked at were really markers of inflammation, edema, fibrosis in the heart. We used the gold standard, which is the Lake Louise Criteria, to diagnose these patients definitively using Cardiac MRI. Importantly, over the last decade, MRI has become much more available, so we can now diagnose patients more precisely. We're not left wondering what exactly is causing their shortness of breath or chest pain and impacts on their quality of life. This criteria, the study design here, patients received a baseline CMR. We imaged their hearts at baseline.
We measured that red fiber scarring I showed you on the previous slide or the degree to which that was present at baseline. We randomized the patients one to one to receive placebo or our drug. Patients were treated for 12 weeks twice daily, then we re-imaged the hearts to look at the impact on key features of this condition, which is extracellular volume, which is all the material outside of heart cells so essentially the swelling and edema in the heart. We looked at intracellular volume, which is swelling of heart cells themselves. We looked at left ventricular mass, which is a combination of intracellular and extracellular volume. Interestingly or importantly, increase in LV mass is directly correlated with increased risk for bad outcomes in cardiovascular disease, which include hospitalization and mortality.
These are the impacts of great interest from this study. We had a notable trend to significance with respect to extracellular volume. A very potent impact on reducing the swelling outside of heart cells. We had a directional impact on intracellular volume or the swelling of the cells, the heart cells themselves. The striking observation from this trial and quite unexpected, because the fact that no drug has ever had a biological effect in this indication previously, we had a highly significant 9.2g reduction in LV mass or heart size. That's very important, especially when it's related to the impact on other widely prescribed medications throughout the world today, including the blockbuster GLP-1s, which over 52 weeks have a similar magnitude of reduction, 11g versus CardiolRx at 9.2. We look at SGLT2 inhibitors.
First two here are administered sub-Q, so they're injectable. Third one is oral. You're looking at 26 weeks for a 5g reduction, and then with the widely prescribed Entresto, I believe it's an $8 billion drug from Novartis, that again has a magnitudinally comparable impact to our drug. We achieve this in just 12 weeks. The only way we believe that is possible and the experts in the field is to have had this profound impact on LV mass. The key takeaways from this is we have this observation of a reduction in LV mass, which is directly correlated with increased risk of poor outcomes. We believe this now sets us up for broadening the potential orphan targets in cardiac as well as, and most importantly, accelerating our heart failure asset.
The key takeaways is we believe this is the first demonstration of structural improvement in myocarditis. CMR improvements align with myocardial recovery. Equally important is this now bridges translationally the observations that we published last year in JACC, the Journal of the American College of Cardiology, concerning the impact of our Sub-Q formulation, which is delivering the same small molecule therapy as the oral, albeit in a more efficient, elegant way for more chronic lifelong conditions. Perhaps, equally important is we see this as a significant de-risking of the pivotal phase III MAVERIC program because this is the second demonstration of proof of concept with respect to our drug, our small molecule impacting a cardiac indication.
That gives us great enthusiasm for our next generation product, which is CRD-38, which we believe holds hope for a very efficient treatment schedule, perhaps as efficient as once monthly. We look forward to addressing this to one of the largest medical challenges facing medicine today, which is heart failure. Our primary area of focus is on an area of heart failure which really hasn't seen major advances with respect to a drug that targets inflammation and fibrosis, which are now recognized to cause the inability of the heart to relax and fill properly. Most importantly, as mentioned earlier, this observation from ARCHER in the human heart in patients has now translated the data that we published last year where we showed an impact on heart size, cardiac cell size, as well as fibrosis.
This was obviously a preclinical experiment, was published in a top-tier journal, but we've now seen that same observation in human hearts. This now sets us up for a very exciting 2026 and 2027. That time horizon importantly is fully funded. We look forward to the continuing momentum in the pivotal phase III program. We look forward to completing enrollment in this study by the end of Q2. That sets us up for a top-line readout potentially in the back half of this year. We're now contemplating new potential orphan drug targets for our lead oral therapy in the area of cardiomyopathies.
From a value proposition point of view, CRD-38, our once-monthly subQ formulation being addressed to the mass market of heart failure, is now garnering ever-increasing attention with strategic partners with dominant positions in the heart failure community, and we look forward to accelerating that program and to securing those strategic alliances over the coming quarters. Just in the interest of time, we have very little left. Very privileged to be working with a veteran team in medicine with three decades experience in their respective areas of expertise. I'm joined today by Dr. Andrew Hamer, our chief medical officer and head of international R&D. Our board is a veteran board, provides amazing stewardship to this organization. I'd encourage everyone to review the biographies on this team at cardiolrx.com.
We also benefit from the stewardship of an amazing scientific advisory panel, comprising Paul Ridker from Harvard, Bruce McManus from UBC, and Joe Hill from UT Southwestern, widely recognized for their work in cardiac inflammation and heart failure. Now I'll turn it to if we have any time for questions.
Sure. Just to start, do we have any questions from the audience? Okay, I will start with my own. It's exciting. You know, in January, you announced 50% enrollment in MAVERIC. As you said, top-line data could be by the end of 2026. Can you go over expectations for what will be included in top-line data, and what would be good data, what would be excellent data?
I'll just speak to the design. I think the trial is very conservatively powered. KOLs in the field or experts in the field have told us that they would be thrilled with a drug that could reduce recurrence rates by 35%-40%. I'll remind you that our phase II program reduced it by 70%. We've powered the study more in line with what the experts are looking at. It's a very conservatively powered trial. The consistency now with the ARCHER data, we have every reason to be optimistic and enthusiastic about the pending outcomes for MAVERICK, importantly for patients in the cardiovascular community.
Mm-hmm. Besides top-line data, you know, you talked about end-of-phase II meeting, are there any other items that could gate CardiolRx's NDA submission to FDA? Like, for example, what is the current state of CMC for the product?
CMC is in very good shape. We partnered many years ago with a GMP manufacturer who's done amazing work for us. They have a large international organic chemistry team, I believe over 120 organic chemists on that team. They've scaled the production and commercialization of drugs around the world, FDA certified. Our CMC is in extraordinarily advanced state, and we can scale to commercial production now.
Excellent. I think we have time for one more question. You mentioned in the presentation that CardiolRx has the potential to be before the interleukin-1 blockers. How do you think physicians will think about placing the product in standard of care treatment?
All our discussions with the physicians has been that they are looking for something that does not have an immunosuppressive effect, does not have difficulties with access through insurance, particularly trying to avoid corticosteroids as because of the long-term side effects and the significant dependency there, and now the dependency issues with the IL-1 blockers. What they wanna know is if we find a medication that patients can come off an IL-1 blocker onto, then they wanna use that before they even consider an IL-1 blocker, and they wanna replace corticosteroids completely with a drug like CardiolRx. Becoming basically second line. You've got non-steroidal anti-inflammatories and colchicine first line, CardiolRx second line, and then IL-1 blockers for those that fail those, the oral, easily accessible, and not immunosuppressive drugs, and that's what we fit into.
Interesting. Well, David, Andrew, thank you both so much for your time.
Thank you.
Great. Thank you.