Okay, welcome everyone to our next session here on the first day of Oppenheimer's 35th Annual Life Sciences Healthcare Conference. Leland Gershell, I'm one of the biotech analysts here at Oppenheimer, and I'm really pleased to have with us as our next presenting company, Cardiol Therapeutics. Cardiol is developing novel therapies for cardiac disease, taking an innovative approach we'll hear more about from the company's President and CEO, David Elsley, who I'll turn the podium over to in a moment. Please ask any questions you'd like through the Zoom or through the web, and I'll do my best to ask those on your behalf toward the end. With that, I'll hand it over to David.
Thank you, Leland, and good afternoon, folks. It's a great pleasure to present an overview on our work, the important work we're doing in heart disease, what the Cardiol team is doing in heart disease, where we're looking to develop innovative therapies to address chronic inflammation, which underlies the development and progression of a number of important heart diseases that can be life-threatening and very debilitating. I think our mission statement really exemplifies the work we're doing, where our mission is to introduce innovative therapies that not only modify disease progression, but importantly, they alleviate symptoms and restore quality of life for patients living with inflammatory heart conditions. We're currently executing a strategy which is aimed at advancing what we believe will be transformational medicines that target inflammation and heart disease.
Importantly, we have now entered a late-stage clinical development Phase 3 program, which we believe has the potential to be a pivotal Phase 3 registrational trial in support of a new drug application into an important area of cardiac medicine, where this trial is designed to definitively demonstrate the impact of our lead drug candidate on recurrent pericarditis. Importantly, entry into this program was based on very compelling results that were presented during an oral presentation at the American Heart Association, where administration of our lead drug, CardiolRx, was shown to result in marked rapid and sustained reductions in the key feature that is disabling in patients with the disease, which is pericarditis pain or chest pain. Importantly, CardiolRx was also shown to decrease frequency of disease recurrence, as well as normalize levels of a key inflammatory marker, systemic inflammatory blood marker called C-reactive protein.
We are pursuing and targeting a well-characterized mode of action. Our products are targeting a mechanism of action that is essentially targeting inflammasome activation, which then leads to the consequential production of pro-inflammatory mediators, which are central to the development and progression of a whole range of cardiac diseases. We're looking to downregulate this disease-causing mechanism in a disease-modifying way, but not an immunosuppressing way. I think that's a key therapeutic advantage our oral therapeutic approach has. From a market opportunity point of view, the initial market is very significant for our product, with the IL-1 blocker therapies, which are immunosuppressant, now generating about $500 million revenue, annual revenue run rate, with Wall Street forecasts expecting that therapeutic intervention to grow to $1 billion in revenue.
I think that underscores the size and scope of the initial market opportunity for our product, and understanding that that is just the U.S. market. We see our product being deployed internationally beyond the U.S. market, and we also have other indications in development of great importance. Importantly, we have been awarded the FDA Orphan Designation for our lead program, which encompasses the entire pericarditis landscape in the United States, which is a patient population of about 160,000 patients, of which recurrent pericarditis is approximately a 38,000 patient population subgroup. We had initially anticipated being awarded a designation for the recurrent pericarditis, but we're very pleased to find that we were awarded the broader designation. In terms of near-term catalysts for the organization, we have a number and very exciting leading into 2025, where we plan to imminently enroll our first patient in the international Phase 3 Maverick program.
We look forward to reporting top-line data from our global Archer program, which is addressable to myocarditis or acute myocarditis. We also look forward to advancing our subQ asset, which is our next-generation technology in heart failure. We are fortunate to be working with many of the preeminent thought-leading centers in the world today. Our programs are in collaboration with many renowned cardiovascular centers from around the world, which include the Cleveland Clinic, the Mayo Clinic, Mass General, and international centers with representation from Canada, Germany, France, Israel, and Latin America. These organizations, these vast preeminent cardiovascular research centers provide access to really industry-leading expertise with respect to drug development in the cardiac setting, particular to cardioinflammation and fibrosis, cardiovascular disease, and clinical trial design and execution. In terms of our pipeline, it now comprises our lead drug, which is now in two phase late-stage programs.
The Maverick program is a phase 3 program that is international, and we believe is positioned to be potentially a registrational trial in support of a new drug application. We also have an international program focused at the Phase 2 level in acute myocarditis, which is now nearing a data readout anticipated in early Q1 or, sorry, early Q2 of this year. We look forward to advancing our subQ formulation of the lead drug agent cannabidiol into clinical development towards year-end. We are targeting a mechanism which is of great interest, certainly in cardiovascular disease and other medical challenges, which is inflammasome activation. Inflammasome activation, which is typically secondary to infection or tissue damage, leads to an outpouring or an increased production of pro-inflammatory mediators such as the interleukins, interleukin 1, interleukin 6, which is implicated. Interleukin 1 is certainly implicated in mild pericarditis.
Interleukin 6 is implicated in heart failure. We are targeting a well-characterized mechanism which underlies the development and progression of a number of important areas of cardiac medicine, including pericarditis, myocarditis, and heart failure. We believe by downregulating the activation of these pathways, our novel drug agent provides an important therapeutic approach in addressing cardiac inflammation. Our most advanced program is Maverick. This is a Phase 3 study with a focus on developing our lead asset in a definitive study for recurrent pericarditis. For those that may not be familiar with this medical challenge, this disease affects people in their prime of life, typically 45, 50 years of age. These folks are generally healthy and often athletic when they come down with this condition, which is thought to be primarily secondary to a viral infection. That is pericarditis, which leads to severe chest pain, shortness of breath, depression.
Recurrent pericarditis is the returning of a recurrent episode or a pericarditis episode four to six weeks after a symptom-free period. This has a marked debilitating effect on people's lives. Basically, it's a miserable condition that destroys quality of life, can lead to hospital admissions and emergency care interventions. First-line therapies include nonsteroidals and the generic colchicine, but the challenge there is a very large segment of the recurrent pericarditis population is nonresponsive and/or intolerant to first-line medication. That really only leaves second-line therapy, which is steroids, which has concomitant toxicity, resistance, and dependency issues. They're used sparingly only in cardiologists' cardiology practice. Patients want to avoid steroids because of their toxicity. The more severe patients can become eligible for a third-line therapy called IL-1 blockers, which are prohibitively expensive. In the US, list price for the IL-1 blocker is approximately $280,000 per patient per year.
They are immunosuppressive biologics that can increase or may increase risk for cardiorespiratory infection. There is now a growing concern about dependency as well. Once patients start on these IL-1 blockades, they have a tremendous difficulty weaning off them without very high disease relapse rate. This leaves the opportunity for a new therapeutic entrant that is oral non-immunosuppressant that can potentially be disease-modifying and manage the symptoms of this disease. This is what we believe we're developing now in collaboration with the key opinion leaders from around the world. We're thrilled to have a steering advisory panel comprising many of the thought leaders in pericarditis disease today, collaborating with Dr. Allan Klein and Alan Lewis, who lead the two largest pericardial disease centers in the world today. Paul Cremer is a globally renowned imaging expert and the architect of our Phase 3 program from Northwestern.
Antonio Abbate is renowned for his work in cardiac inflammation. Massimo Imazio sets really the guidelines for myo and pericardial care for the European Union, and Steve Nicholis is a clinical trial expert from Australia. It is this panel that has collaborated with Cardiol Therapeutics on the overall development of our pericarditis program, which comprised the recently reported Maverick pilot Phase 2 study, which enrolled 27 patients at eight preeminent cardiovascular research centers in the United States. The largest enrolling centers were Cleveland Clinic, Mayo, and Mass General. The primary efficacy endpoint in this study, which is really what is most important to patients, is the change in pericarditis pain as measured by the standardized NRS score at eight weeks.
Key secondary measures in this study included change in C-reactive protein or the ability to normalize that blood marker, NRS pain scale at 26 weeks, as well as freedom from recurrence of the condition. Clinical trial design is a pretty standard design, followed in the pathway of the Phase 2 program that led to the pivotal registration trial that underpinned approval of the IL-1 blockades. In this trial, we enrolled 27 patients. Patients were titrated up to max dose, which is 10 mg per kilo twice daily. Patients were treated on top of standard of care. The key enrollment criteria, essentially adults, they had to have a pain scale. They had to measure four or greater on the 11-point numeric pain scale, where zero is no pain at all and 10 is incapacitating pain. Patients needed a four or greater on the scale to meet the inclusion criteria.
They also had to have either elevated C-reactive protein and/or cardiac abnormalities on MRI. They also could be receiving stable doses of NSAIDs, colchicine, and/or steroids, but not be on IL-1 blocker immunosuppressants. Importantly, in this study, at baseline, over 80% were on nonsteroidals and colchicine, and they were in a high percentage of patients, almost 50% were on corticosteroids. This was a very well-treated population, notwithstanding that they were still suffering debilitating pain at four or greater. We then applied our drug on top of background medication and measured change in the NRS scale at eight weeks. We then asked all patients if they wished to volunteer to enter into an extension phase. Remarkably, and very encouragingly, 24 of 27 agreed to go into the extension phase of this study, where we weaned off background medications down to monotherapy and looked at the impact.
This is the primary efficacy endpoint data that was presented in an oral presentation in the American Heart Association, as well as the data from our extension phase. You can see that at baseline, patients had a very disabling level of pain on the NRS scale, almost 6 out of 10. Interestingly, we observed a very rapid reduction in this pain. At the eight-week primary endpoint, we showed a clinically relevant impact from essentially 5.8 down 3.7 was the reduction. Anything more than 2 is considered clinically meaningful and relevant and impacting on patients' quality of life. The meantime to resolution or near resolution of pain of just five days was quite remarkable, given that our drug does not meet max dose until 10 days of titration. Interestingly, once the 24 of 27 entered the withdrawal or entered the weaning period, we are all withdrawal of medication.
It's quite striking that this resolution in NRS pain was maintained out six months. Anything under two is considered very manageable pain or perhaps no pain at all. We also observed a very striking impact on C-reactive protein. At baseline, patients were four times normal at 2.5 being normal. By eight-week primary endpoint, they were approaching the normal range. Importantly, during the weaning phase, when background medications were withdrawn just down to monotherapy with Cardiol Therapeutics, this patient population reached the normal level and maintained that. Perhaps one of the most striking findings was the impact on events per year of pericarditis. In the year prior to this trial, patients were experiencing 5.8 episodes. Understand these episodes can go on for several weeks of debilitating chest pain. During the study, these events were reduced to 0.9.
During the extension phase, 71% of patients remained free of recurrent pericarditis. The key features and outcome of this trial that were presented during an oral presentation in the American Heart Association was we demonstrated a marked, sustained, and rapid impact on pericarditis pain. Mean time to resolution was very impressive at just five days. 80% of patients with elevated C-reactive protein by eight weeks were normalized. 71% remained pain-free. We had a very striking impact on pericarditis episodes per year. Importantly, our drug was shown to be extremely well tolerated with 95% drug compliance. This has now supported entry into the Maverick Phase 3 program, which we believe will potentially be a pivotal registration trial in support of a new drug application.
This trial is designed to, it's a very efficient trial because it's very well powered because we have enriched the study for event rates or relapse rates of disease. We plan to enroll 110 patients across 20 preeminent cardiac care centers in the United States, as well as preeminent centers in Europe. The primary efficacy endpoint in this trial is number of patients free from a recurrent pericarditis episode at 24 weeks. Secondary measures including new episode freedom from meantime to new episode of pericarditis, as well as change in NRS and C-reactive protein. Importantly, this trial has been demonstrated to demonstrate the impact of our drug in a patient population at very high risk of recurrence.
We've essentially enriched the population for high recurrence rates by enrolling a patient population who have been on at least 12 months of IL-1 blocker therapy because we know based on the published literature and real-world evidence that these patients, when they wean off IL-1 blocker, wean off immunosuppressants, they have an extraordinarily high level of relapse rate or disease recurrence, which reaches 75% inside of 12 weeks. This trial design, we will enroll adults on stable dose IL-1 blockade who have been receiving IL-1 blockade for up to 12 months or longer and are planning to wean off it. They will be screened and randomized one-to-one to either Cardiol Therapeutics or placebo, and then they'll be followed out 24 weeks. This is a very well-powered trial, and we fully anticipate this will be supportive of registrational application.
This we believe will provide access to a very important marketplace for Cardiol, where patients who fail first-line therapy really have no other options other than immunosuppressants, which include steroids and IL-1 blockers. We believe we have the potential to offer a disease-modifying non-immunosuppressive approach to the 38,000 patient population who experience recurrent pericarditis and a large percent of whom fail first-line therapy and really have only options of immunosuppression. That is the role we believe we can play in this significant and growing market opportunity. Running in parallel with the Maverick Phase 3 program is an important Phase 2 program that is now on the cusp of completion. This is a trial in an important medical indication called acute myocarditis, which is typically secondary to viral infection. This is a disease that can be quite tragic because it affects a younger demographic still.
This is typically patients under the age of 35, predominantly young healthy men who can develop fulminant heart failure and can progress in severe cases to require cardiac transplantation. Importantly, this condition currently has no recognized standard of care. There is no FDA or EMA-approved drug for the treatment of myocarditis. In-hospital mortality is still quite significant at 4-6%. Our interest in this area followed the observation that our lead API could impact really the key feature of this cardiac indication, where you get an immune insult on the myocardium, which leads to fibrous scarring and an inelasticity in the heart and the ability of the heart to function properly as a pump. That's why the key symptom, not dissimilar to pericarditis, is typically chest pain and shortness of breath in a young, otherwise generally healthy individual.
The observation in this preclinical model was that when the disease was induced in the presence of concomitant administration of our drug agent, the majority of the myocardial tissue was preserved. This led to the interest of a global panel of experts who set the guidelines and are the KOLs in acute myocarditis care. This panel is co-led by Dennis McNamara, who heads a prominent heart transplant unit at the University of Pittsburgh, as well as Les Cooper, who is the founder of the American Myocarditis Foundation and leads a prominent myocarditis unit at the Mayo Clinic in Jacksonville, Florida. This panel is a collaboration of international authorities on myocarditis and heart failure from the U.S., Canada, throughout Europe, Israel, as well as Latin America.
It is this panel in collaboration with the company that designed the Archer program, which is one of the largest company-sponsored clinical programs undertaken on myocarditis in many years. The study has enrolled 100 patients at 34 centers across five countries: U.S., Canada, France, Brazil, and Israel. The primary efficacy endpoints, it's a co-primary endpoint, change in extracellular volume from baseline as well as global longitudinal strain. Patients are baseline with a cardiac MRI. They are then given three months of treatment in a randomized placebo-controlled study. Fifty percent receiving active, 50% receiving sham, and they are reimaged at the 90-day endpoint for change in the co-primary endpoints. This trial completed its enrollment in Q4 of last year, and we now anticipate the last patient will complete the study imminently, and that will set up for a top-line readout of this program in early Q2.
That's where we have the lead programs. That's the lead Cardiol Therapeutics intervention. We've also been very thrilled to have innovated a new formulation of our lead API, which is a sub-Q form that we believe will be able to exploit a depot effect and a more efficient route for a chronic cardiac disease condition, which is heart failure. This is certainly a mass medical challenge. It's arguably one of the largest medical challenges facing the developed world. It is an epidemic of sorts driven by the forces of increasing high blood pressure, obesity, and diabetes throughout the world. Heart failure still has a five-year mortality rate of 53%. Diastolic heart failure, which is about half of heart failure, has an in-hospital mortality rate of approximately 75%.
We studied our sub-Q formulation, which has really now emerged as the gold standard model to explore new medications for diastolic heart failure in a model where the two insults are obesity as well as high blood pressure. This creates a metabolic and a resistance strain on the heart, which leads to an upregulation of a number of inflammatory mediators in the heart, which include the interleukins and tumor necrosis factor, all of which were inhibited in their upregulation with sub-Q administration of our drug, which was also shown to prevent cardiac remodeling as well as to slow body weight gain as well as heart weight gain by altering the distribution in a significant way of visceral fat deposition in favor of subcutaneous fat. Visceral fat is a dangerous metabolic fat.
Large levels of it are correlated with increasing cardiovascular mortality and morbidity, whereas subcutaneous fat does not have those metabolic features. This observation was consistent with a previous study conducted at the renowned DeBakey Heart Center, where in a classical HFrEF model of systolic heart failure, our drug agent was shown to normalize or inhibit the upregulation of brain natriuretic peptide, which is an important marker of cardiac stretch elevated in heart failure patients, as well as ameliorate the deposition of fibrosis in the myocardium at two doses, both 10 mg per kilo as well as one-tenth of that dose. This has set this company up for a very exciting 2025 with a number of near-term value drivers. We look forward to the formal initiation of the Phase 3 program in recurrent pericarditis with anticipation of enrolling our first patient in the United States in Q1.
We then look forward to completing 50% of the enrollment this fiscal year and completing enrollment early next year, which would then set up for top-line data in 2026. We also look forward to the top-line data readout from the Archer program in acute myocarditis in early Q2 and presentation of full data set in myocarditis at a scientific meeting in the back half of this year. We also are very pleased to be developing our CRD-38 asset, which has potential to be addressed to one of the largest medical challenges in the world today, which is heart failure. In the interest of time, I'll just refer everyone to the website at cardiolrx.com for the biographies on a distinguished management team that I've had the great pleasure of working with for many years.
They all have over 30 years' experience in the respective areas of expertise developing new important therapeutics for underserved areas of medicine. We also are given, provided wonderful stewardship from the International Board of Experts in various areas of discipline important for the new therapeutic development. We have renowned expertise both in cardiology, pharmacology, pharmaceutical industry, pharmaceutical manufacturing business, and finance. We are very pleased to be guided by a scientific advisory board, which is fully independent of management and the board, led by the renowned Paul Ridker, Head of Cardiology at Harvard, well recognized for his work in cardiac inflammation and dedication. It was Paul's work that led to the discovery of elevated C-reactive protein and its correlation with increased mortality and morbidity risk in the cardiovascular setting. Paul is also senior advisor to many of the big pharmas.
Bruce McManus has dedicated his life's cardiology experience to myocarditis and specialty, and Joe Hill is certainly a thought leader in the area of heart failure medicine with a particular expertise and focus on heart failure with preserved ejection fraction. He's also the editor in chief of the prestigious journal Circulation for the American Heart Association. That is an overview. I'm not sure if we have time for questions, but happy to field any to the extent that we do.
Yeah, no, great, great, David, thank you. We do have a minute or two, so I'll just squeeze in a couple. Just in your lead on pericarditis, obviously a very painful condition, but I just wanted to ask for these patients, if they're inadequately treated, does that go beyond pain or the functional sequelae in the heart that cause further problems in terms of pump function, et cetera?
This condition, if left untreated, certainly can progress and lead to severe complications. In severe cases, it can result in open heart surgery to remove the pericardium. It is a miserable condition, and that is very debilitating. These patients will be bounced around ERs and eventually, hopefully, get to the specialist care centers. The challenge there is if they do not respond to first-line, they only have the immunosuppressant therapeutic options available to them.
Right, right. With the active being CardiolRx, I just wanted to ask in terms of your IP protections as you develop this in the various programs.
Importantly, we have a fully synthetic formulation. We have been working with a phenomenal partner. One of our founding board members, Peter Pekos, is the founder of Dalton Pharma Services , one of the global leaders in organic chemistry.
We innovated a fully synthetic oral formulation as well as a sub-Q formulation. We have patent families with applications to a broad range of cardiac diseases with the myo and pericarditis indications in particular focus of IP claims. Then we have layered on top of that the potential for the orphan drug exclusivities now awarded in the US. We also see it being orphan drug eligible in other regions of the world, including major countries of Europe.
Great. Good. We look forward to upcoming events. It will be moving into your registration program in pericarditis. I think the Phase 2 readout in acute myocarditis is coming not too long from now.
Yes, we look forward to imminently enrolling the first patient in the Phase 3 Maverick program in pericarditis and following that shortly with the top-line data readout from the myocarditis program.
Excellent .
Thanks very much again. Thanks to all of you who tuned in for this session with Cardiol. Have a great rest of the conference.
Thanks, Leland. Thank you.