Imbria Pharmaceuticals Completes Enrollment in the Phase 2 Clinical Trial of Ninerafaxstat in Patients With Stable Angina

Imbria Pharmaceuticals, Inc. recently announced it has completed enrollment in the IMPROVE-ISCHEMIA Phase 2 placebo-controlled clinical trial of the investigational therapy, ninerafaxstat, in patients with stable angina. Imbria expects to report topline results from this trial in the fourth quarter of 2023.

“The randomized, placebo-controlled IMPROVE-ISCHEMIA trial will provide detailed insights into the anti-ischemic effects of ninerafaxstat in symptomatic patients with chronic coronary syndromes, including the burden of angina,” said Juhani Knuuti, MD, PhD, Professor and Director of Turku PET Centre in Turku, Finland and chief investigator of the IMPROVE-ISCHEMIA trial. “Given the large projected future increases in the prevalence of ischemic heart disease and the limited level of therapeutic innovation, there is a pressing need to address the high symptomatic burden of angina with novel effective oral therapies.”

“Ninerafaxstat has a unique mode of action that is complementary to the current standard of care, such as beta blockers and calcium channel blockers. This could give physicians and patients an additional option to control angina symptoms without adversely impacting hemodynamics,” added Jai Patel, MRCP (UK), Chief Medical Officer of Imbria. “We look forward to sharing topline data from the trial in the fourth quarter of this year.”

Imbria currently has two additional ongoing Phase 2 clinical trials with ninerafaxstat: IMPROVE-HCM, a randomized, placebo-controlled clinical trial in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) with topline data expected in the fourth quarter of 2023, and IMPROVE-DiCE, an open label clinical trial, which is currently enrolling patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF) with interim data also expected in the fourth quarter of 2023.

IMPROVE-ISCHEMIA is a randomized, double-blinded, placebo-controlled, Phase 2 trial evaluating the safety, anti-ischemic and anti-anginal effects of ninerafaxstat administered for 8 weeks in patients with stable angina.

Stable angina is characterized by recurrent episodes of reversible cardiac oxygen demand/supply mismatch typically resulting in pain or heaviness in the anterior chest, epigastrium, neck, lower jaw, shoulder and/or either arm. In some patients, breathlessness may be the only symptom of angina, or it may be accompanied by fatigue, faintness, nausea, and restlessness resulting in poor quality of life. Stable angina is usually precipitated by physical exertion, and may be triggered by cold weather, emotional stress or after a heavy meal.

In the US alone, the overall prevalence of stable angina is estimated at approximately 4% of all adults (> 10 million, Tsao et al., Circulation 2023) with 500,000 new cases of angina occurring annually.

Angina may, in a minority of patients, be due to obstructive epicardial coronary artery disease. In such cases, invasive revascularization procedures, such as percutaneous coronary intervention or coronary artery bypass surgery, may improve symptoms; however, within 5 years, over half of patients develop recurrent angina or anginal equivalent symptoms (Stone et al., J Am Coll Cardiol 2023). In contrast, most patients with stable angina have ischemia due to non-obstructive causes, such as coronary microcirculatory dysfunction, which are not amenable to coronary revascularization, with multiple mechanisms co-existing in some patients.

Traditionally, pharmacological treatment of angina has focused on manipulating hemodynamics to reduce cardiac oxygen demand by lowering blood pressure, cardiac contractility, and/or heart rate using beta blockers, calcium channel antagonists, and nitrates frequently in combination. However, when titrated to effect, these agents often reach a plateau of hemodynamic suppression, where adding further dose increments or agents with a similar hemodynamic mechanism of action confers little additive symptomatic benefit, while adverse effects increase, which may limit tolerability and prevent adequate symptom relief.

Although cardiac ischemia is a metabolic disorder disrupting cellular energetics, there are currently no approved pharmacological therapies in the US that directly address this by targeting the cardiomyocyte. Such an approach may have the potential for synergy with existing hemodynamic approaches across a breadth of ischemic mechanisms to achieve optimal relief of angina, maximize patient function and improve quality of life.

Our lead product candidate, ninerafaxstat, is an innovative treatment for cardiac diseases characterized by an imbalance of energy supply and demand in the heart. To maintain normal pump function and cell viability, the heart requires substantial amounts of energy, which is produced in the form of ATP. The heart normally uses two primary fuels for energy generation: fatty acids and glucose. Ninerafaxstat, a partial fatty acid oxidation (pFOX) inhibitor, acts to shift the heart’s preference from fatty acids towards glucose. This shift in metabolism leads to more efficient energy generation with the potential for improved cardiac function both at rest and during exercise. Currently, ninerafaxstat is in Phase 2 clinical development for three indications: nHCM, stable angina, and HFpEF.

Imbria is a privately held, clinical-stage company developing novel therapies for patients with life-altering cardiometabolic disorders. Our clinical-stage pipeline is focused on restoring or improving the cell’s ability to produce energy in cardiovascular disorders where energetic impairment is a fundamental contributor to symptoms and functional deficits. The lead product candidate, ninerafaxstat, is currently in Phase 2 clinical development in three indications: nHCM, stable angina, and HFpEF. For more information, visit www.imbria.com.