clinical-stage biotechnology company focused on developing ... · looking information contained...

Clinical-stage Biotechnology Company Focused on Developing Innovative Therapies for Inflammatory Heart Disease

TSX: CRDL | OTCQX: CRTPF

October 2020

TSX: CRDL OTCQX: CRTPF 2

In this presentation, all amounts are in Canadian dollars, unless otherwise indicated. Any graphs, tables or other information in this presentation demonstrating the historical performance of Cardiol or any

other entity contained in this presentation are intended only to illustrate past performance of such entities and are not necessarily indicative of future performance of Cardiol or such entities.

FORWARD-LOOKING INFORMATIONThis presentation contains forward-looking information, within the meaning of applicable securities laws in Canada, that relate to Cardiol’s current expectations and views of future events (“forward-looking information” or “forward-looking statements”). In some cases, these forward-looking statements can be identified by words or phrases such as “market opportunity”, ‘revenue opportunity” “may”,

“might”, “will”, “expect”, “anticipate”, “estimate”, “intend”, “plan”, “indicate”, “seek”, “believe”, “predict”, or “likely”, or the negative of these terms, or other similar expressions intended to identify forward-looking information. Statements containing forward-looking information are not historical facts. Cardiol has based these forward-looking statements on its current expectations and projections about future events and financial trends that it believes might affect its financial condition, results of operations, business strategy, and financial needs. These forward-looking statements include, among other

things, statements relating to: Cardiol’s business strategy; Cardiol’s plans and objectives; the ability for Cardiol’s oral and subcutaneous formulation to deliver cannabinoids and other anti-inflammatory drugs to inflamed tissue in the heart; the plan to commercialize Cortalex; the market opportunity for cannabidiol; the expected medical benefits, viability, safety, efficacy, and dosing of cannabidiol; Cardiol’s

expectation of the revenue opportunity from the sale of our products; Cardiol’s 12 month milestones; enrolment for a Phase II/III COVID 19 clinical trial; Cardiol’s plans for a Phase II international trial of CardiolRx™ in acute myocarditis; its proposed IND application for a Phase II trial planned Q1 2021; the improvement of outcomes from COVID-19. Forward-looking information contained herein reflects the current expectations or beliefs of Cardiol based on information currently available to it and is subject to a variety of known and unknown risks and uncertainties and other factors that could cause the actual

events or results to differ materially from any future results, performance or achievements expressed or implied by the forward-looking information. These risks and uncertainties and other factors include the risks and uncertainties referred to in the Company’s Annual Information Form dated March 30, 2020, including the risks and uncertainties associated with product commercialization, regulatory

approvals and clinical studies, and uncertainties in predicting treatment outcomes. These risks, uncertainties and other factors should be considered carefully, and investors should not place undue reliance on the forward-looking information. Any forward-looking information speaks only as of the date on which it is made and, except as may be required by applicable securities laws, Cardiol disclaims any intent or obligation to update or revise such forward-looking information, whether as a result of new information, future events or results or otherwise. Although Cardiol believes that the expectations reflected in

the forward-looking information are reasonable, they do involve certain assumptions, risks, and uncertainties and are not (and should not be considered to be) guarantees of future performance. It is important that each person reviewing this presentation understands the significant risks attendant to the operations of Cardiol.

Disclaimer

20201027


Strong scientific rational for developing cannabidiolas an anti-inflammatory agent

Lead clinical programs targeting large opportunities in inflammatory heart disease

Commercial cannabidiol product addressing significantunmet medical markets

Strong leadership with extensive industry experience and expertise in commercializing proprietary drugs

Cardiol Therapeutics Today

Proprietary cannabidiol oral formulation enteringPhase II/III development- strong innovative pipeline


Evidence Supporting Cannabidiol Use for Inflammatory Heart Disease

• Attenuates cardiac dysfunction and reduces inflammation in a model of diabetic cardiomyopathy

• Significantly decreases cardiac fibrosis (scarring of the heart muscle) in a non-ischemic model of heart failure

• Reduces cardiac inflammatory cytokine levels in a model of experimental autoimmune myocarditis (inflammatory heart failure)

• Protects against cardiac injury in a model of doxorubicin cardiotoxicity

• Reduces inflammation and improves arterial vasorelaxation in a model of diabetes

TSX: CRDL OTCQX: CRTPF

PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3

Indication Formulation

COVID-19 with prior history of Cardiovascular Disease (CVD) Oral Solution

Acute Myocarditis and other inflammatory heart disease Oral Solution

Diastolic Heart Failure Subcutaneous

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Clinical Development Program


CardiolRx™Oral Cannabidiol Formulation

• High concentration cannabidiol formulation for acute inflammatory heart disease

• Manufactured under cGMP to meet the highest standards for product purity, consistency, and stability

• IND approval received from the FDA for a phase II/III clinical program in COVID-19 patients with prior history of CVD to investigate cardioprotective properties of cannabidiol

• Planning international Phase II program in acute myocarditis under direction of distinguished international steering committee

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COVID-19Phase II/III Trial in Patients

with Prior History of, or Risk Factors for, Cardiovascular

Disease


COVID-19 Patients with CV Complications Have Lower Survival Rates

Reference: Shaobo Shi et al., ‘Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China’, JAMA Cardiology, 25 March 2020

• COVID-19 patients with cardiac injury had a higher mortality rate than those without cardiac injury

• Patients with cardiac injury were more likely to require mechanical ventilation

• Complications were more common in patients with cardiac injury

Journal of the American Medical Association


How Cannabidiol Protects the Heart in Models of Cardiovascular Disease

• Reduces inflammation and improves endothelial dysfunction• Reduces cardiac inflammatory cytokine levels in a model

of myocarditis (inflammatory heart failure) • Reduces cardiac injury associated with elevated troponin

T levels• Improves left ventricular dysfunction in the heart – improving

blood flow to vital organs • Significantly decreases cardiac fibrosis (scarring of the heart

muscle)

Evidence Supporting Therapeutic Potential in High-risk COVID-19 Patients

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COVID-19 Clinical Development Program

IND Application Approved by FDA for Phase II/III Trial

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Multi-center, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of

CardiolRxTM in Patients with COVID-19 and cardiovascular disease or risk factors

422 patients randomized

Up to 10 U.S. sites

211 to CardiolRxTM, 211 to placebo

Treatment

Oral Administration: Starting at 5 mg/kg of body weight/day to a maximum of 15 mg/kg/day administered twice daily with food for 28 days

Primary Efficacy Endpoints*:

• All-cause mortality• ICU admission and/or ventilatory support• Cardiovascular (CV) complications:

Heart Failure, Acute Myocardial Infarction (heart attack), Myocarditis, New sustained or symptomatic arrhythmia, and Stroke

Secondary Efficacy Endpoints:

• CV complications at 28 days post randomization• Increase in cardiac injury marker (hs-Troponin)• Change in inflammatory marker (TNF-alpha)

*Experience one of the following events during the first 28 days


Steering Committee for COVID-19 and Acute Myocarditis

Carsten Tschöpe, MDProfessor of Medicine and Cardiology and Vice Director of the Department of Internal Medicine and Cardiology, University Medicine Berlin. For his outstanding research work, Dr. Tschöpe was awarded the prestigious Arthur Weber Prize by the German Cardiac Society –Cardiovascular Research.

Leslie T. Cooper, Jr., MDCo-ChairGeneral cardiologist and the chair of the Mayo Clinic Enterprise Department of Cardiovascular Medicine, as well as chair of the Department of Cardiovascular Medicine at the Mayo Clinic in Florida.

Matthias Friedrich, MDFull Professor with the Departments of Medicine and Diagnostic Radiology at the McGill University in Montreal and Chief, Cardiovascular Imaging at the McGill University Health Centre. Dr. Friedrich founded one of the first large Cardiovascular Magnetic Resonance centres in Germany at the Charité University Hospital in Berlin.

Arvind Bhimaraj, MDSpecialist in Heart Failure and Transplantation Cardiology and is Assistant Professor of Cardiology, Institute for Academic Medicine, at Houston Methodist and at Weill Cornell Medical College, NYC.

Peter Liu, MDChief Scientific Officer and Vice President, Research, of the University of Ottawa Heart Institute, and Professor of Medicine and Physiology at the University of Toronto and University of Ottawa.

Barry Trachtenberg, MDCardiologist specializing in heart failure and cardiac transplantation. He is also the director of the Michael DeBakey Cardiology Associates Cardio-Oncology program, an evolving field devoted to prevention and management of cardiovascular complications of cancer therapies such as chemotherapy and radiation.

Wai Hong Wilson Tang, MDAdvanced Heart Failure and Transplant Cardiology specialist at the Cleveland Clinic in Cleveland, Ohio. Dr. Tang is also the Director of the Cleveland Clinic’s Center for Clinical Genomics; Research Director, and staff cardiologist in the Section of Heart Failure and Cardiac Transplantation Medicine in the Sydell and Arnold Miller Family Heart & Vascular Institute at the Cleveland Clinic.

Dennis M. McNamara, MDChairProfessor of Medicine at the University of Pittsburgh. He is also the Director of the Heart Failure/Transplantation Program at the University of Pittsburgh Medical Center.

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Acute MyocarditisOrphan Drug Program


Acute Myocarditis

• Inflammatory condition of the heart most often resulting from viral infection

• A major cause of sudden death in children and young adults

• Can progress to dilated cardiomyopathy and heart failure

• Severe cases lead to extensive ICU hospital costs

Acute Myocarditis is eligible for U.S. and European Orphan Drug status

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Myocarditis

Inflammation of Heart Muscle


Acute Myocarditis – Orphan Drug Opportunity

Orphan Drug and Fast Track Eligibility – Market Exclusivity and Expedited Review

• Potential for Fast Track regulatory development and approval • United States: fewer than 200,000 cases required to qualify as Orphan Drug• Orphan drugs typically obtain high reimbursement levels

14(1) Lennox-Gastaut Syndrome(2) Dravet Syndrome

High Prevalence vs. Previously Approved FDA Orphan Drug Cannabidiol Product

Paediatric Epilepsy (1)(2) Acute Myocarditis

U.S. Patient

Estimate (Prevalence)37,250 73,000


Cannabidiol Downregulates Key Markers of InflammationEffect of Cannabidiol on Heart Inflammation and Fibrosis

Sections of Heart Tissue - Fibrosis

HEALTHY TISSUE MYOCARDITIS MYOCARDITIS + CBD

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Experimental Model of Autoimmune Myocarditis (EAM)

Ref: Adapted from Lee W-S et al. (2016). Mol. Med. 22, 136-146


Acute Myocarditis Clinical Development Program IND Filing for Phase II Trial Planned Q1 2021*

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Three co-primary endpoints: • Left ventricular ejection fraction • Extracellular volume• Global longitudinal strain

Secondary endpoints:

• Safety• Improvement in cardiac function• Improvement in quality of life

Multi-center, double-blind, randomized, placebo-controlled, parallel group design: Designed to study impact of CardiolRx™ on Myocardial Recovery

100 patients

15-20 sites

50 to CardiolRxTM, 50 to placebo

Canada, U.S., and Europe

Treatment Period Starting at 5 mg/kg of body weight/day to a maximum of 20 mg/kg/day administered twice daily with food

*Pending completion of ongoing Phase I pharmacokinetic clinical study in Q4

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Heart FailureMass Market Potential


Heart Failure – a Leading Cause of Death and Disability

• Over 6 million adults in Canada and the U.S. suffer from heart failure(1)

• About half of all heart failure patients suffer from Diastolic Heart Failure

• 30% of patients with heart failure die within 1 year; 50%within 5 years(2)

• Leading cause of hospitalization with healthcare costs exceeding $30 billion annually in the U.S.(3)

No significant treatment advances in Diastolic Heart Failure in over 20 years

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(1) Blair et al. Current Cardiology Reviews 9, 128–146 (2013)(2) Taylor et al. European Journal of Heart Failure 14, 176–184 (2012)(3) Cook et al. International Journal of Cardiology 171, 368–376 (2014)

Developing a Proprietary Subcutaneous Cannabidiol Formulation to TargetInflammation in the Heart


The Issue: Overview of Diastolic Heart Failure

Healthy Heart Diastolic Heart Failure

Occurs when the heart fails to relax normally and fill with blood which is required to oxygenate tissues of the body

Left atrium

Left ventricleRight

ventricle

Rightatrium

Thickenedventricular muscle

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International Research Collaborations

• TecSalud del Tecnológico de Monterrey and DeBakey Heart & Vascular Center

• Research producing scientific and pre-clinical data to support clinical development

• Cardioprotection demonstrated in a non-ischemic model of heart failure

• Findings accepted for Presentation at the American College of Cardiology’s 69th Annual Scientific Session

Developing Subcutaneous Cannabidiol Formulation for Heart Failure

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CardiolRx™Subcutaneous Cannabidiol Formulation

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• Subcutaneous formulation to achieve higher bioavailability than an oral formulation

• Anti-inflammatory activity of cannabidiol to treat inflamed heart tissue

• Anti-fibrotic activity of cannabidiol to prevent progressive fibrosis (scarring) in heart muscle

• New approach to the treatment of chronic heart failure


Groups treated with cannabidiol at 1 or 10 mg/kg show reduced BNP in animals with Angiotensin II-induced Heart Failure.

Reference: Omar Lozano et al., ‘CARDIOPROTECTIVE EFFECT OF CANNABIDIOL IN A NON ISCHEMIC MODEL OF HEART FAILURE’, Journal of the American College of Cardiology 75, no. 11 (March 2020): 705.

Measurements of BNP mRNA expression in heart tissueBNP is a stress marker released as pressure in the heart increases and the muscle is stretched.Raised BNP levels reflect cardiac stretch indicative of heart failure.

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Cardioprotective Properties of Subcutaneous Cannabidiol FormulationDemonstrated in a Non-ischemic Model of Heart Failure


Cardioprotective Properties of Subcutaneous Cannabidiol FormulationDemonstrated in a Non-ischemic Model of Heart Failure

Cardiol’s research shows cannabidiol reduces angiotensin-induced fibrosis: histopathologic analysis of heart tissue, representative slides

Heart sections stained with Masson’s Trichrome, showing the effect on fibrosis of Cannabidiol (CBD) at 1 or 10 mg/kg.Fibrotic tissue stains blue, demonstrating CBD reducing fibrosis in this model of non-ischemic cardiomyopathy.

Reference: Omar Lozano et al., ‘CARDIOPROTECTIVE EFFECT OF CANNABIDIOL IN A NON ISCHEMIC MODEL OF HEART FAILURE’, Journal of the American College of Cardiology 75, no. 11 (March 2020): 705.

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Unique CommercialOpportunity


*<10 ppm

Pharmaceutical Cannabidiol Setting a Higher Product Standard for Patients and Doctors

• Pharmaceutically produced to ensure purity and consistency• Manufactured under cGMP• High concentration 100mg/ml• THC free*


The Market Opportunity in Canada Medical Cannabidiol For Patients Who Should Not Be Exposed to THC

• Total medical cannabinoid market exceeds $600 million annually in Canada(1)

• Growing demand from paediatricians and family physicians for a CBD formulation that does not contain THC (for patients <25 and >65)

• Medical cannabis without THC is recommended for patients <25 years old(2)

• People >65 are Canada’s fastest growing group of cannabis users(3)

Current approved therapies of limited efficacy – need for adjunct therapy

(1) https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=3610012401(2) https://www.cps.ca/en/documents/position/cannabis-children-and-youth(3) https://www150.statcan.gc.ca/n1/daily-quotidien/191030/dq191030a-eng.htm

https://mjbizdaily.com/access-barriers-stall-canadian-medical-cannabis-market/

https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=3610012401


National Supply Agreement with Shoppers Drug MartProviding Access Across Canada for Medical Patients

Now Available• Online platform for the sale of medicinal

cannabinoids

• HelloMD telemedicine program available to patients

• Largest national pharmacy chain in Canada - >1,300

stores

• National supplier of specialty drug distribution and

comprehensive patient support services

• Trusted brand with physicians and patients


12-month Milestones

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Initiate and complete enrollment of 422 patients in International Phase II/III COVID-19 trial examining the cardioprotective properties of CardiolRxTM

Submit IND application to the FDA and commence an international Phase II acute myocarditis trial led by highly distinguished Steering Committee

Launch and market CortalexTM, the Company’s commercial cannabidiol product, in the >$600 million Canadian cannabinoid medical market

Complete development of a subcutaneous formulation of CardiolRxTM for treatment of chronic heart failure, a leading cause of death and hospitalization in North America

Up list to NASDAQ with the goal of significantly increasing U.S. investor awareness


Capital Structure


Common Shares Outstanding 32.8 M

Fully Diluted Common Shares (1), (2), (3), (4) 44.8 M

Insider and Employee Ownership 20%

Pharmaceutical Partners & Research Collaborators 8%

Cash and Cash Equivalents as at June 30, 2020 $19.4 M

Working Capital as at June 30, 2020 (5) $25.2 M

Current Debt $0.0 M

(1) Includes 2,652,800 options outstanding with an average exercise price of $3.88, of which 1,738,814 are exercisable.

(3) Includes 824,000 warrants outstanding with an exercise price of $4.00, payment of which is settled through a USD$3.0 M research contract.

(4) Includes 1,420,000 common shares potentially issuable in relation to clinical trial related milestones for future research services to be delivered.

(5) Includes $6.0 M of inventory and prepaid inventory.

(2) Includes 6,796,944 warrants outstanding with an average exercise price of $4.86 and 294,000 warrants outstanding with an exercise price of $2.50, exercisable into units.

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David Elsley, MBAPresident and CEOFounder and former President and CEO of Vasogen Inc. More than 25 years’ experience developing, financing, and managing corporate development of biotechnology and high-growth organizations.

Anthony E. Bolton, PhD, DSc Director of ResearchImmunologist with 20+ years of experience in biotech. Former Chief Scientific Officer of Vasogen Inc. Former Professor and Department Head of Biomedical Sciences (Sheffield, UK).

Eldon R. Smith, OC, LLD (Hon), MD, FCAHS, FCCS, FRCPCChairman and Chief Medical OfficerCardiologist. Former Head of Cardiology, former Chairman ofMedicine, former Dean of Medicine, University of Calgary. ChairSteering Committee, Canadian Heart Health Strategy. Recipient of Order of Canada.

Anne Tomalin, BA, BSc, RACDirector of Regulatory AffairsFounder of CanReg Inc. and TPIreg, regulatory firms previously sold to Optum Insight and Innomar Strategies,respectively. An expert in regulatory affairs in Canada, the United States, and Europe.

Chris Waddick, CPA, CMA, MBA Chief Financial OfficerThirty years of experience in financial and executive roles in thebiotechnology and energy industries, former Chief Financial Officer and Chief Operating Officer of Vasogen Inc.

Thomas Moffatt, BBAChief Commercial Officer Senior operations and retailing executive with an extensive background in the pharmaceutical environment. More than 20 years’ tenure at Shoppers Drug Mart.

Dolly Kao, BSc, JD Intellectual Property CounselCo-Founder of PCK LLP.Highly-experienced IP lawyer with a practice focusedprimarily on patent and trademark matters (procurement, oppositions, and opinions) for clients in the chemical, pharmaceutical, and biotechnologyindustries.

Andrea B. Parker, MSc, PhDDirector of Clinical AffairsClinical Epidemiologist with more than 30 years’ experience in clinical trials design, management, and execution in industry and academic settings. Former Chief Scientific Officer at Peter Munk Cardiac Centre, University Health Network.

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Experienced Executive Team


Strong Board of Directors

Guillermo Torre-Amione, MD, PhD

President of TecSalud Academic Medical CenterPresident of TecSalud academic medical center and school of the

Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM),

Mexico. Formerdirector of Cardiac Transplantation at the Houston

Methodist DeBakey Heart & Vascular Center.

Peter Pekos, BSc, MSc

President, CEO, and Founder of Dalton Pharma ServicesBroad experience in the research, development, and

commercialization of pharmaceuticals, products, andservices.

Deborah Brown, BSc, MBA

Partner at Accelera CanadaAdvised pharmaceutical clients on strategy and initiatives, market research,

market access, and regulatory affairs for many years. Former President, EMD

Serono Canada (division of Merck KGaA, Merck Serono).

Colin G. Stott, BSc (Hons)

Chief Operating Officer of Alinova Biosciences LtdThirty years’ experience in pre-clinical and clinical development, with

specific expertise in the development of cannabinoid-based medicines.

Former Scientific Affairs Director, International and R&D Operations Director

for GW Pharmaceuticals plc, a world leader in the development of cannabinoid

therapeutics.

David Elsley, MBA

President and CEOFounder and former President and CEO of Vasogen Inc., with more than

25 years’ experience developing, financing, and managing all aspects of

corporate development of biotechnology and high-growth organizations.

Eldon R. Smith, OC, LLD (Hon), MD, FCAHS, FCCS, FRCPC

Chairman and Chief Medical OfficerCardiologist. Former Head of Cardiology, former Chairman of

Medicine, former Dean of Medicine, University of Calgary. Chair

Steering Committee, Canadian Heart Health Strategy. Recipient of

Order of Canada.

Iain Chalmers, BA, BEd, MBA

Strategic Marketing and InnovationProfessor of Marketing at Centennial College Business School. Former

Vice-President Marketing and Innovation at Diageo, the world’s largest

spirits company. Over 25 years’ experience in consumer products with

Gillette and Procter & Gamble.

31TSX: CRDL OTCQX: CRTPF

Strong Board of Directors

Guillermo Torre-Amione, MD, PhD

President of TecSalud Academic Medical CenterPresident of TecSalud academic medical center and school of the

Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM),

Mexico. Formerdirector of Cardiac Transplantation at the Houston

Methodist DeBakey Heart & Vascular Center.

Peter Pekos, BSc, MSc

President, CEO, and Founder of Dalton Pharma ServicesBroad experience in the research, development, and

commercialization of pharmaceuticals, products, andservices.

Deborah Brown, BSc, MBA

Partner at Accelera CanadaAdvised pharmaceutical clients on strategy and initiatives, market research,

market access, and regulatory affairs for many years. Former President, EMD

Serono Canada (division of Merck KGaA, Merck Serono).

Colin G. Stott, BSc (Hons)

Chief Operating Officer of Alinova Biosciences LtdThirty years’ experience in pre-clinical and clinical development, with

specific expertise in the development of cannabinoid-based medicines.

Former Scientific Affairs Director, International and R&D Operations Director

for GW Pharmaceuticals plc, a world leader in the development of cannabinoid

therapeutics.

David Elsley, MBA

President and CEOFounder and former President and CEO of Vasogen Inc., with more than

25 years’ experience developing, financing, and managing all aspects of

corporate development of biotechnology and high-growth organizations.

Eldon R. Smith, OC, LLD (Hon), MD, FCAHS, FCCS, FRCPC

Chairman and Chief Medical OfficerCardiologist. Former Head of Cardiology, former Chairman of

Medicine, former Dean of Medicine, University of Calgary. Chair

Steering Committee, Canadian Heart Health Strategy. Recipient of

Order of Canada.

Iain Chalmers, BA, BEd, MBA

Strategic Marketing and InnovationProfessor of Marketing at Centennial College Business School. Former

Vice-President Marketing and Innovation at Diageo, the world’s largest

spirits company. Over 25 years’ experience in consumer products with

Gillette and Procter & Gamble.

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Clinical-stage Biotechnology Company Focused on Developing Innovative Therapies for Inflammatory Heart Disease

TSX: CRDL | OTCQX: CRTPF

October 2020

CONTACT INFORMATIONE: [email protected]: +1 (289) 910-0850W: cardiolrx.com

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