Imbria Pharmaceuticals Completes Enrollment in Phase 2 IMPROVE-HCM Trial of Ninerafaxstat in Patients With Non-Obstructive Hypertrophic Cardiomyopathy

Imbria Pharmaceuticals, Inc. recently announced it has completed enrollment in the IMPROVE-HCM Phase 2 placebo controlled clinical trial of ninerafaxstat with 67 patients with non-obstructive hypertrophic cardiomyopathy (nHCM) randomized. Imbria expects to report topline results from this trial in the fourth quarter of 2023.

“Completing enrollment in the Phase 2 IMPROVE-HCM trial is an important step toward our goal of providing a potential new therapy to address the large unmet need for symptomatic and functional improvements in patients with nHCM,” said Anne Prener, MD, PhD, President and Chief Executive Officer of Imbria. “The data from our Phase 2 trial, assessing cardiac energetics and function, patient symptoms, and exercise capacity, will serve as an integral part of our planned regulatory strategy and potentially support a Phase 3 registrational trial. We look forward to reporting topline data from this trial in the fourth quarter of this year.”

Imbria currently has two additional ongoing Phase 2 clinical trials: IMPROVE-ISCHEMIA, a randomized, placebo controlled clinical trial in patients with stable angina with expected topline data in the fourth quarter of 2023 and IMPROVE-DiCE, an open label clinical trial, currently enrolling patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF) and expected interim data in the fourth quarter of 2023.

IMPROVE-HCM is a randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of ninerafaxstat in patients with nHCM. The primary objective of the study is to evaluate the safety and tolerability of ninerafaxstat in patients with symptomatic nHCM and objective evidence of exercise limitation through evaluation of incidence and severity of treatment emergent adverse events. Efficacy evaluations include assessments of myocardial energetics, myocardial diastolic and systolic function, maximal and submaximal exercise responses, and recovery measured by standardized cardiopulmonary exercise testing, arrhythmia burden, symptoms, and patient-reported health status in patients with nHCM treated with 200mg BID of ninerafaxstat over a 12-week period.

Hypertrophic cardiomyopathy is the most common inherited cardiac disease with an estimated prevalence in the general population of 1:200 – 1:500.  It is characterized by the abnormal thickening of the heart muscle, which can lead to various complications. One of the key issues in HCM is a deficiency in cardiac energy, resulting from increased energy demands during contraction, and inefficient energy utilization by the cardiac muscle. This energy deficiency has a significant impact on the functioning of the heart, impairing the relaxation and filling of the heart, and leading to symptoms such as breathlessness and reduced exercise capacity. The mismatch between the supply and demand of cardiac energy, as well as impaired energetics, occurs early in the progression of HCM, even before the development of heart muscle thickening. Within HCM, a third of patients have no left ventricular outflow tract obstruction at rest or after provocation and are referred to as having non-obstructive disease (nHCM). Patients with nHCM experience a high burden of symptoms of heart failure and are at risk for adverse disease complications yet have no proven pharmacotherapies.

Our lead product candidate, ninerafaxstat, is an innovative treatment for cardiac diseases characterized by energy imbalance of the heart. To maintain normal pump function and cell viability, the heart requires a significant amount 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, aims 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.