Cardiol Therapeutics (TSX:CRDL, NASDAQ:CRDL) is a clinical-stage life sciences company focused on the research and clinical development of anti-inflammatory and anti-fibrotic therapies for the treatment of heart diseases. The company’s lead product candidate, CardiolRx™ (cannabidiol), is a pharmaceutically manufactured oral solution formulation that is being clinically developed for use in heart diseases. It is recognized that cannabidiol inhibits activation of the inflammasome pathway, an intracellular process known to play an important role in the inflammation and fibrosis associated with myocarditis, pericarditis, and heart failure.
Cardiol has received Investigational New Drug Application (IND) authorization from the United States Food and Drug Administration (FDA) to conduct clinical studies to evaluate the efficacy and safety of CardiolRx™ in two diseases affecting the heart: (1) a Phase II multi-national, randomized, double-blind, placebo-controlled trial (the ARCHER trial) in acute myocarditis, an important cause of acute and fulminant heart failure in young adults and a leading cause of sudden cardiac death in people less than 35 years of age; and (2) a Phase II multi-center open-label pilot study in recurrent pericarditis (inflammation of the pericardium), which is associated with symptoms including debilitating chest pain, shortness of breath, and fatigue, and results in physical limitations, reduced quality of life, emergency department visits, and hospitalizations.
Cardiol is also developing a novel subcutaneously administered drug formulation of cannabidiol intended for use in heart failure – a leading cause of death and hospitalization in the developed world, with associated healthcare costs in the United States exceeding $30 billion annually.
Cardiol enrolled its first patient in ARCHER in August 2022 after it received regulatory clearance in multiple jurisdictions, including IND authorization from the FDA, and is expected to enroll 100 patients at major cardiac centers in North America, Europe, Latin America and Israel.
Cardiol also recently announced the first patient has been enrolled in the company-sponsored Phase II open-label pilot study investigating the tolerance, safety, and efficacy of CardiolRx™ in patients with recurrent pericarditis. In addition to standard safety assessments, the study is designed to evaluate improvement in objective measures of disease, and during an extension period, assess the feasibility of weaning concomitant background therapy including corticosteroids, while taking CardiolRx™.
In collaboration with researchers and opinion leaders at international centers of excellence, including the Houston Methodist DeBakey Heart & Vascular Center and the TecSalud del Tecnológico de Monterrey, Mexico, Cardiol is leveraging multidisciplinary expertise in drug delivery, drug formulation, cardiac physiology, and heart failure.
Cardiol’s management team has extensive experience in the research and commercial development of novel therapeutics. Additionally, insiders and employees are invested in the company, holding approximately 10 percent of the outstanding shares.
- Experienced leadership with extensive expertise in developing therapeutics for inflammatory heart diseases
- Compelling evidence demonstrating the anti-inflammatory and anti-fibrotic properties of CardiolRx™ – the company’s oral cannabidiol formulation in clinical development for underserved heart diseases
- Phase II clinical programs initiated in acute myocarditis and recurrent pericarditis
- Research focused on developing a novel subcutaneously administered drug for heart failure
- Comprehensive intellectual property portfolio
- Strong financial position to support research and clinical development programs into 2026, with zero debt and cash equivalents of C$65.5 million as of September 30, 2022.
Orphan Drug Program for Recurrent Pericarditis
In January 2023, Cardiol announced that the first patient has been enrolled in the company-sponsored Phase II open-label pilot study investigating the tolerance, safety, and efficacy of CardiolRx™ in patients with recurrent pericarditis. The study will also assess the improvement in objective measures of disease, and during an extension period, assess the feasibility of weaning concomitant background therapy including corticosteroids, while taking CardiolRx™.
Recurrent pericarditis refers to inflammation of the pericardium (the membrane or sac that surrounds the heart) that follows an initial episode (frequently resulting from a viral infection). These recurrences appear in 15 percent to 30 percent of acute cases and usually within 18 months. Further, up to 50 percent of patients with a recurrent episode of pericarditis experience more recurrences. Symptoms include debilitating chest pain, shortness of breath, and fatigue, resulting in physical limitations, reduced quality of life, emergency department visits, and hospitalizations. Significant accumulation of pericardial fluid and scarring can progress to life-threatening constriction of the heart. The only FDA-approved therapy for recurrent pericarditis, launched in 2021, is costly and is primarily used as a third-line intervention. The number of patients seeking and receiving treatment for recurrent pericarditis annually in the US is estimated at 38,000. Hospitalization due to recurrent pericarditis is often associated with a six- to eight-day length of stay, and cost per stay is estimated to range between $20,000 and $30,000 in the United States.
The Phase II pilot study is expected to enroll 25 patients at clinical centers in the United States that specialize in pericarditis care. The protocol has been designed in collaboration with thought leaders in pericardial disease. The study chairman is Dr. Allan L. Klein, director of the Center of Pericardial Diseases and professor of medicine, Heart and Vascular Institute at the Cleveland Clinic. The primary efficacy endpoint is the change, from baseline to eight weeks, in patient-reported pericarditis pain using an 11-point numeric rating scale (NRS). The NRS is a validated clinical tool employed across multiple conditions with acute and chronic pain, including previous studies of recurrent pericarditis. Secondary endpoints include the pain score after 26 weeks of treatment, and changes in circulating levels of C-reactive protein (CRP), a commonly used clinical marker of inflammation.
“We are excited to be the first clinical center to administer this investigational drug in a patient with recurrent pericarditis, a debilitating inflammatory heart disease associated with symptoms that adversely affect quality of life and physical activity,” commented Dr. Paul C. Cremer, cardiologist, Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, and study site principal investigator. “Along with other collaborating research centers throughout the U.S., we look forward to full enrollment of participants into this pilot study and to determining the potential of this therapy to treat pericarditis and to reduce the risk of its recurrence.”
In the US, an orphan drug designation is granted for pharmaceuticals being developed to treat medical conditions affecting fewer than 200,000 people. These conditions are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy in many countries and has yielded medical breakthroughs that might not otherwise have been achieved. In the US and the European Union, orphan drugs are eligible for accelerated marketing approvals and companies developing orphan drugs typically receive other incentives, including a prolonged period of market exclusivity that can extend over seven years, during which the drug developer has sole rights to market the drug.
Recurrent pericarditis is an orphan disease in the United States, thereby making CardiolRx™ eligible for orphan drug status under the FDA’s Orphan Drug Designation program.
Independent advisors and key investigators comprising six highly distinguished thought leaders in cardiology from the Cleveland Clinic, the Mayo Clinic, the Monash Victoria Heart Institute, the University of Virginia, and Virginia Commonwealth University, have been established to design, oversee, and guide Cardiol’s Phase II multi-center open-label pilot study in patients with recurrent pericarditis.
Orphan Drug Program for Acute Myocarditis
In August 2022, Cardiol enrolled its first patient in ARCHER, the company’s multi-center, international, double-blind, randomized, placebo-controlled trial designed to study the safety and tolerability of CardiolRx™, as well as its impact on myocardial recovery, in patients presenting with acute myocarditis.
Myocarditis is an acute inflammatory condition of the heart muscle (myocardium) characterized by chest pain, impaired cardiac function, atrial and ventricular arrhythmias, and conduction disturbances. Although the symptoms are often mild, myocarditis remains an important cause of acute and fulminant heart failure and is a leading cause of sudden cardiac death in people under 35 years of age. In addition, some patients proceed to develop chronic dilated cardiomyopathy which continues to be the leading indication for cardiac transplantation. Although viral infection is the most common cause of myocarditis, the condition can also result from administration of therapies used to treat several common cancers, including chemo-therapeutic agents and immune checkpoint inhibitors. Acute myocarditis should be managed with guideline directed therapies for heart failure, arrhythmia and conduction disturbances; however, there is no uniformly accepted treatment for the underlying inflammatory processes associated with this condition.
The most recent data from the ‘Highlights in General Cardiovascular Medicine: 2021’ suggests that the prevalence of myocarditis is approximately 16.2 per 100,000 population. Cardiol believes there is a significant opportunity to develop an important new therapy for acute myocarditis that would also be eligible for designation as an orphan drug in the United States.
“The US orphan drug program was successfully utilized to accelerate the first FDA approval of CBD for the treatment of rare forms of pediatric epilepsy, and significant shareholder value was created in the process,” stated Cardiol president and CEO David Elsley. “Given the mortality and significant morbidity risk associated with acute myocarditis, we believe there is a similar opportunity in pursuing an expedited development program of our CardiolRx™ pharmaceutical CBD formulation for this serious orphan disease which has no accepted standard of care.”
The primary endpoints of the ARCHER trial, which will be evaluated after 12 weeks of double-blind therapy, consist of the following cardiac magnetic resonance imaging measures: left ventricular function (ejection fraction and longitudinal strain) and myocardial edema/fibrosis (extracellular volume), each of which has been shown to predict long-term prognosis of patients with acute myocarditis.
Since people with acute myocarditis have impaired heart function, current treatment is based on standard-of-care recommendations for heart failure. This includes diuretics, ACE inhibitors, angiotensin receptors blockers, beta blockers, and aldosterone inhibitors. For those with a severe and sudden onset presentation, intensive care is often required, with the use of inotropic medications (to increase the force of the heart muscle contraction) and occasionally, heart-lung bypass or ventricular assist devices. There is otherwise no specific treatment for acute myocarditis although some patients have responded to immuno-suppressive therapy (azathioprine) in combination with steroids, but the data are not conclusive enough for this to be the recommended therapy.
An independent clinical steering committee, comprising nine highly distinguished thought leaders in cardiology from the Cleveland Clinic, the Mayo Clinic, the Houston Methodist DeBakey Heart and Vascular Center, the University of Ottawa Heart Institute, McGill University Health Centre, the University of Pittsburgh Medical Center, Tel Aviv Medical Center, and São Paulo University Medical School, has been established to design, oversee, and guide Cardiol’s Phase II multi-national ARCHER trial in acute myocarditis.
Cardiol Therapeutics’ Heart Failure Program
People with heart failure suffer from a variety of ailments, including shortness of breath, rapid heart rate, edemas, reduced exercise capacity. This can often result in a struggle with simple daily activities, causing frequent hospitalization. Many of these symptoms can significantly reduce the quality of life for an individual.
There are two types of heart failure: systolic and diastolic. Systolic heart failure, or heart failure with reduced ejection fraction (HFrEF), occurs when the left ventricle cannot adequately pump blood from the heart and into circulation. Diastolic heart failure, or heart failure with preserved ejection fraction (HFpEF), occurs when the left ventricle becomes stiff and does not relax as it should; and, as a result, cannot fill properly, causing pressure to build in the left side of the heart and in the lungs. This results in a patient feeling shortness of breath and is associated with health concerns such as obesity, hypertension, and diabetes.
Another complication that can be experienced by those suffering from HFpEF is chronic inflammation, which can lead to a decrease in blood vessel function, impairment of heart muscle function, and fibrosis, which results in stiffness in the heart and a reduction in pumping efficiently. Over the past 20 years, there have been little to no significant treatments developed for HFpEF, as therapies have primarily remained focused on diuretics.
Cardiol is developing a novel subcutaneously administered drug formulation of cannabidiol intended for use in heart failure – a leading cause of death and hospitalization in the developed world, with associated health-care costs in the United States exceeding $30 billion annually. In addition, Cardiol has an active discovery program focused on developing additional novel therapeutic approaches to address inflammation and fibrosis associated with the development and progression of heart diseases.
Published third-party research has shown that cannabidiol reduces inflammatory activation of the endothelial lining of blood vessels and aids endothelial vasorelaxation, resulting in improved blood flow. Cannabidiol has also been shown to attenuate a number of measures of inflammation in models of diabetes, a common comorbidity in heart failure patients, and to reduce myocardial fibrosis in a model of inflammatory heart disease.
Cannabidiol is lipid soluble, virtually insoluble in water, highly sensitive to deactivation in the liver via first-pass metabolism when taken orally and is rapidly cleared from the body. This results in a low overall bioavailability when taken orally. Cardiol’s subcutaneously administered drug formulation is designed to minimize first-pass metabolism, optimize and maintain blood levels of the drug, and target inflammation and increased fibrosis in the heart. Cardiol believes that overcoming the low bioavailability issues associated with cannabidiol will significantly broaden the therapeutic potential of this molecule.
Cardiol Therapeutics’ Strategic Partnership
Dalton Pharma Services
Cardiol has established an exclusive manufacturing arrangement with Dalton Pharma for the supply of pharmaceutical cannabidiol for Cardiol’s research programs using CardiolRx™.
Located in Toronto, Dalton is a Health Canada-approved, FDA registered, cGMP manufacturer of over 200 active pharmaceutical ingredients (APIs), including pharmaceutical cannabinoids, with manufacturing capability scalable to support all stages of the regulatory process (Phase I, II, III, and commercial).
In 2016 and 2017, Dalton Pharma received the Leadership Award for Contract Manufacturing Organizations (CMO) in the following categories: quality, capabilities, expertise, compatibility and development. Dalton is also the manufacturer of Nabilone, the largest prescription pharmaceutical cannabinoid in the world, with annual sales of C$100 million. As part of the partnership, Dalton is also a significant shareholder in Cardiol. Dalton’s founder, owner and CEO, Peter Pekos, is on Cardiol’s board.
Cardiol Therapeutics’ Research Collaborations
DeBakey Heart and Vascular Center
Cardiol is conducting experimental research at the Houston Methodist DeBakey Heart & Vascular Center, designed to investigate the activity of the company’s proprietary subcutaneous cannabidiol formulation in a model of heart failure.
The Houston Methodist DeBakey Heart & Vascular Center is recognized internationally as a center of excellence for the treatment of heart failure. The center was the birthplace of cardiovascular bypass surgery in 1964 and is currently ranked the 15th best hospital for care in cardiology and heart surgery out of 592 hospitals in the United States.
TecSalud del Tecnológico de Monterrey
Cardiol is collaborating with DeBakey Heart & Vascular Center and TecSalud del Tecnológico de Monterrey (TecSalud) on developing a novel subcutaneously administered drug for the treatment of heart failure. The primary objective of this collaboration is to develop the experimental evidence necessary to support advancing breakthrough treatments for heart failure into clinical development
David Elsley – President, Chief Executive Officer, and Director
David Elsley is the founder and CEO of Vasogen Inc. and has an MBA degree. Elsley has over 25 years of experience developing, financing, and managing all aspects of corporate development in biotechnology and high-growth organizations. Elsley founded Vasogen Inc., a biotechnology company focused on the research and commercial development of novel therapeutics for the treatment of heart failure and other inflammatory conditions. Elsley assembled a team of management, directors and scientific advisors comprising industry professionals and thought leaders from North America and Europe.
Dr. Andrew Hamer - Chief Medical Officer and Head of Research and Development
Dr. Andrew Hamer has an MBChB degree. He is the former executive director at Amgen, responsible for leading global development of Repatha®. Hamer is the former chief cardiologist at Nelson Hospital, New Zealand. He has over 19 years of experience practicing cardiology and internal medicine.
Chris Waddick - Chief Financial Officer and Director
Chris Waddick has an MBA degree, is a chartered professional accountant, and is a certified management accountant. He has over 30 years of experience in financial and executive roles in the biotechnology and energy industries. Waddick is the former chief financial officer and chief operating officer of Vasogen Inc.
Bernard Lim - Chief Operating Officer
Bernard Lim has over 30 years of experience in the life sciences industry, spanning biotechnology, diagnostics, medical devices, and high-technology companies. He is the founder and CEO of a highly successful drug delivery company that he led from research and development through to commercialization, and facilitated its eventual acquisition by Eli Lily. Lim is a chartered engineer per UK standards and is a member of the institution of engineering and technology.
Andrea B. Parker – Senior Director of Clinical Operations
Dr. Andrea Parker is the former chief scientific officer at Peter Munk Cardiac Center, University Health Network. Parker is a clinical epidemiologist with more than 30 years’ experience in clinical trials design, management, and execution in industry and academic settings.
John A. Geddes – Vice-president, Business Development
John Geddes has over 25 years of experience in the healthcare industry, comprising roles within pharmaceutical, biotechnology, clinical diagnostics, and life science research technology companies. Geddes has an MBA degree and is the former corporate senior director, business development at Luminex Corporation, a DiaSorin Company.
Blagoja Ristevski – Director of Chemical Engineering and Manufacturing
Blagoja Ristevski is a chemical engineer with over 25 years of experience in the biopharmaceutical industry, performing in senior executive roles in eight Canadian pharmaceutical companies. He contributed to the research and discovery of drug products. Ristevski served as vice president of product development at the AMRIC Institute in Ontario.
Anne Tomalin - Director of Regulatory and Quality
Anne Tomalin is the founder of CanReg and TPIreg, regulatory firms previously sold to Optum Insight and Innomar Strategies, respectively. Tomalin is an expert in regulatory affairs in Canada, the United States, and Europe.
Board of Directors
Guillermo Torre-Amione - Chairman
Guillermo Torre is the president of TecSalud academic medical center and school of the Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM), Mexico. He is the former director of Cardiac Transplantation at the Houston Methodist DeBakey Heart & Vascular Center.
Jennifer M. Chao - Director
Jennifer M. Chao has over 25 years of experience in the biotech and life sciences industries, focused primarily on finance and corporate strategy. Chao is the managing partner of CoreStrategies Management, a company she founded in 2008 to provide transformational corporate and financial strategies to biotech and life science companies with a view to maximizing core valuation. She currently serves on the board of directors of Endo Pharmaceuticals and is a member of the audit committee and compliance committee. Prior to joining Endo, Chao served as chairman of the board of BioSpecifics Technologies from October 2019, until its acquisition by Endo for approximately US$660 million in December 2020. She also served as chair of BioSpecifics' compensation committee and as a member of the audit committee, strategy committee, intellectual property committee, and nominating and corporate governance committee from 2015 to 2020.
Peter Pekos - Director
President and CEO at Dalton Pharma, Peter Pekos has broad experience in research, development, and commercialization of pharmaceuticals, products, and services.
Colin Stott - Director
Colin Stott has over 30 years of experience in pre-clinical and clinical development, with specific expertise in the development of cannabinoid-based medicines. Stott is the chief operating officer of Alterola Biotech Inc. and the former scientific affairs director, international, and research and development operations director for GW Pharmaceuticals, a world leader in the development of cannabinoid therapeutics.
Teri Loxam - Director
Teri Loxam has over 25 years of experience in biotech, life sciences and entertainment industries with diverse roles spanning strategy, investor relations, finance and communications. Loxam is the chief operating officer and chief financial officer of Kira Pharmaceuticals. In this role, she oversees finance, operations and strategic functions for the company. Prior to joining Kira, Loxam served as SQZ Biotech’s chief financial officer where she led the company’s financial operations, investor relations and communications/public relations functions. While at SQZ, she was instrumental in helping the company raise over $200M in private and public funding, including taking the company public through an IPO on the NYSE in October 2020.
Michael Willner - Director
Michael Willner has practiced as both an attorney and a certified public accountant. He graduated from Emory University Law School as a member of the Emory Law Review. Subsequently, he practiced real estate and corporate law with New York City-based Milbank, Tweed, Hadley & McCloy, one of the nation’s most prominent international law firms. Prior to his legal career, Willner was employed by the former Arthur Andersen & Company, a national accounting firm, where he practiced in the tax department.
Scientific Advisory Board
Dr. Paul Ridker
Dr. Paul Ridker is director of the Center for Cardiovascular Disease Prevention, a translational research unit at Brigham and Women’s Hospital in Boston (BWH). A cardiovascular medicine specialist, he is also the Eugene Braunwald Professor of Medicine at Harvard School of Medicine (HSM). Ridker received his medical degree from HSM, and then completed an internal medicine residency and a cardiology fellowship at BWH. He is board certified in internal medicine. Ridker’s clinical interests include coronary artery disease and the underlying causes and prevention of atherosclerotic disease. He is the author of over 900 peer-reviewed publications and reviews, 64 book chapters, and six textbooks related to cardiovascular medicine.
Dr. Bruce McManus
Dr. Bruce McManus is professor emeritus of the Department of Pathology and Laboratory Medicine at the University of British Columbia. He has served as CEO of the Center of Excellence for Prevention of Organ Failure (PROOF Center), director of the UBC Center for Heart and Lung Innovation, and scientific director, Institute of Circulatory and Respiratory Health, CIHR. McManus received BA and MD degrees from the University of Saskatchewan, an MSc from Pennsylvania State University, and a PhD from the University of Toledo. McManus pursued post-doctoral fellowships at the University of California, Santa Barbara in environmental physiology and at the National Heart, Lung, and Blood Institute in Bethesda. McManus served as MD in cardiovascular and pulmonary pathology, and completed residency training at the Peter Bent Brigham Hospital, Harvard University, in Internal Medicine and Pathology.
Dr. Joseph Hill
Dr. Joseph Hill is a professor of internal medicine and molecular biology, chief of cardiology at UT Southwestern Medical Center, in Dallas, and is the director of the Harry S. Moss Heart Center. Hill holds both the James T. Willerson, MD, distinguished chair in cardiovascular diseases, and the Frank M. Ryburn Jr. Chair in Heart Research. He graduated from Duke University with an MD and a PhD in 1987. Hill’s PhD dissertation research was in the field of cardiac ion channel biophysics. He then worked for five years as a postdoctoral fellow at the Institut Pasteur in Paris, studying central and peripheral nicotinic receptors. He next completed an internal medicine internship and residency, as well as a clinical cardiology fellowship, at the Brigham and Women’s Hospital, Harvard Medical School.