Mr. David Elsley reports

CARDIOL THERAPEUTICS TO ADVANCE CARDIOLRX INTO A LATE-STAGE TRIAL IN PATIENTS WITH RECURRENT PERICARDITIS

Cardiol Therapeutics Inc. plans to expand the Maveric clinical development program and advance CardiolRx into a late-stage clinical trial (Maveric-2) to evaluate the impact of CardiolRx in recurrent pericarditis patients following cessation of interleukin-1 (IL-1) blocker therapy. Maveric-2 is expected to be initiated during Q4 at major pericardial disease centres in the United States and Europe and to report results ahead of the company's planned pivotal phase III study in recurrent pericarditis.

"Maveric-2 provides an exciting opportunity to expand the market potential for CardiolRx through the execution of a cost-effective study and potentially provides a path for an accelerated regulatory approval timeline," said David Elsley, president and chief executive officer of Cardiol Therapeutics. "This important new study, designed in collaboration with an international panel of advisers comprised of experts in pericarditis, will also augment data from our planned phase III Maveric-3 trial by exploring the potential for our lead oral drug candidate to assist the growing number of recurrent pericarditis patients who seek alternative options to chronic use of immunosuppressant biologics."

Maveric-2 is a randomized, double-blind, placebo-controlled phase II/III trial in approximately 110 patients. Patients with stable disease who are receiving IL-1 blocker treatment will be randomly assigned to receive either CardiolRx or placebo following cessation of the IL-1 blocker. The primary clinical objective of the trial will be to assess the impact of CardiolRx versus placebo on freedom from a new episode of recurrent pericarditis. Other clinical end points of interest include time to a new episode of pericarditis recurrence and change in patient-reported pericarditis chest pain score and the inflammatory marker C-reactive protein (CRP).

IL-1 is a key pro-inflammatory cytokine in the pathophysiology of recurrent pericarditis. It is generated downstream following activation of the NLRP3 inflammasome and amplifies the autoinflammatory response characteristic of the disease. IL-1 blockers (rilonacept or anakinra) target and negate the activity of IL-1, but, given their expense and immunosuppressant risks, they are generally prescribed as a third-line intervention in difficult-to-treat patients. There is a growing body of evidence indicating pericarditis recurrence rates are as high as 75 per cent and onset is rapid following cessation of IL-1 blocker therapy. Currently, many patients who discontinue IL-1 blocker therapy and subsequently suffer a recurrence require rescue treatment with further administration of these biologics, potentially leading to IL-1 blocker dependence.

"CardiolRx has been shown experimentally to inhibit assembly and activation of the NLRP3 inflammasome and the subsequent generation of IL-1 and, following oral administration, has led to marked reductions in pericarditis pain in patients suffering from chronic pericardial disease," said Dr. Andrew Hamer, Cardiol Therapeutics' chief medical officer and head of research and development. "In addition to potentially offering a more accessible and non-immunosuppressive therapy to thousands of patients who are non-responsive or intolerant to current therapies, CardiolRx may also have therapeutic potential to prevent recurrences following discontinuation of IL-1 blockers, which would address an unmet need in a growing subset of patients dependent on long-term IL-1 blocker therapy."

The company previously announced positive top-line data from Maveric-Pilot investigating CardiolRx for recurrent pericarditis, which showed a substantial reduction in the primary efficacy end point of patient-reported pericarditis pain at the end of the eight-week treatment period (TP) as well as normalization of inflammation -- as measured by CRP -- in 80 per cent of the patients with elevated CRP at baseline. Eighty-nine per cent of patients (24 out of 27) progressed from the TP into the now completed extension period (EP) of the study, defined as the additional 18-week period where background therapy was weaned and patients were followed on monotherapy of CardiolRx. Full clinical data will be reported in an oral presentation on Nov. 18, 2024, at the American Heart Association Scientific Sessions 2024 and will include freedom from pericarditis recurrence during the 18-week EP, 26-week pericarditis pain score and inflammatory marker levels, and safety and tolerability outcomes. The totality of the Maveric-Pilot data will support and further inform the company's plans related to a second late-stage study called Maveric-3, a phase III pivotal trial designed to assess CardiolRx for the treatment of the broader population of pericarditis patients to prevent recurrence.

Pericarditis

Pericarditis refers to inflammation of the pericardium (the membrane or sac that surrounds the heart), frequently resulting from a viral infection. Following that initial episode, patients may have multiple recurrences, and the primary goal of treatment is recurrence prevention. 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 (U.S. Food and Drug Administration) therapy for recurrent pericarditis, launched in 2021, is costly and is primarily used as a third-line intervention. On an annual basis, the number of patients in the United States having experienced at least one recurrence is estimated at 38,000. Approximately 60 per cent of patients with multiple recurrences (greater than one) still suffer for longer than two years and one-third are still impacted at five years. 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.

About Cardiol Therapeutics Inc.

Cardiol Therapeutics 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 disease. The company's lead small-molecule drug candidate, CardiolRx (cannabidiol) oral solution, is pharmaceutically manufactured and in clinical development for use in the treatment of heart disease. It is recognized that cannabidiol inhibits activation of the inflammasome pathway, an intracellular process known to play an important role in the development and progression of inflammation and fibrosis associated with myocarditis, pericarditis and heart failure.

Cardiol has received investigational new drug application authorization from the U.S. FDA to conduct clinical studies to evaluate the efficacy and safety of CardiolRx in two diseases affecting the heart: recurrent pericarditis and acute myocarditis. The Maveric program in recurrent pericarditis, an inflammatory disease 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, comprises the phase II Maveric-Pilot study (NCT05494788), the phase II/III Maveric-2 trial, and the planned phase III Maveric-3 trial. The Archer trial (NCT05180240) is a phase II study 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. The U.S. FDA has granted orphan drug designation to CardiolRx for the treatment of pericarditis, which includes recurrent pericarditis.

Cardiol is also developing CRD-38, a novel subcutaneously administered drug formulation 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.

We seek Safe Harbor.