Imbria Pharmaceuticals Presents Results From IMPROVE-HCM Trial of Ninerafaxstat 

Imbria Pharmaceuticals, Inc. recently announced the results from the Phase 2 IMPROVE-HCM clinical trial, evaluating ninerafaxstat, a novel cardiac mitotrope and partial fatty acid oxidation (pFOX) inhibitor, in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM), a large orphan disease with no approved therapies, will be presented at the American College of Cardiology’s Annual Scientific Session & Expo (AAC.24), taking place in Atlanta, GA, from April 6-8, 2024.

“We look forward to presenting results of the Phase 2 IMPROVE-HCM clinical trial at ACC.24 next month,” said Anne Prener, MD, PhD, President and Chief Executive Officer of Imbria Pharmaceuticals. “There is tremendous need for new treatment options for patients with nHCM, many of whom are negatively impacted by heart failure symptoms and are at high risk for adverse disease complications.”

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 contractile function, the heart requires substantial amounts of energy, which is produced primarily by the mitochondria in the form of ATP. The heart normally uses two main 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 mitochondrial energy generation with the potential for improved cardiac function both at rest and during exercise.

IMPROVE-HCM (NCT04826185) is a randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of ninerafaxstat 200 mg BID dosed for 12 weeks in 67 patients with nHCM. The primary objective of the study was 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 included exercise responses measured by standardized cardiopulmonary exercise testing and patient-reported symptoms.

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. 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.

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. Our lead investigational product candidate, ninerafaxstat, completed Phase 2 clinical trials in non-obstructive hypertrophic cardiomyopathy (nHCM), stable angina, and in patients at high risk of developing cardiometabolic heart failure with preserved ejection fraction (pre-HFpEF). In Phase 1 and 2 clinical trials, ninerafaxstat was shown to be well tolerated. Part 2 of our Phase 2 trial, IMPROVE-DiCE, in patients with cardiometabolic HFpEF, is ongoing with topline results expected in the fourth quarter of 2024. For more information, visit www.imbria.com.