Imbria Reports Positive Topline Results for Investigational New Drug Ninerafaxstat in Patients with Non-obstructive Hypertrophic Cardiomyopathy

– The IMPROVE-HCM Phase 2 clinical trial met the primary endpoint of safety and tolerability; 12-weeks treatment with ninerafaxstat also demonstrated a statistically significant improvement, compared to placebo, in a robust functional cardiopulmonary exercise test (CPET) measure and improvement in patient-reported symptoms –

– Results support the advancement of ninerafaxstat into Phase 3 clinical development in nHCM, and further supports the development in heart failure with preserved ejection fraction (HFpEF), a disease that shares core pathophysiological and symptomatic features with non-obstructive hypertrophic cardiomyopathy (nHCM) –

BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Imbria Pharmaceuticals, Inc., a clinical stage, cardiometabolic company developing novel therapies designed to improve patient symptoms and function by enhancing cellular energetics, today announced positive topline 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.

Treatment with ninerafaxstat was well tolerated and no safety signals were observed.

At 12-weeks, treatment with ninerafaxstat showed a statistically significant improvement in a robust functional cardiopulmonary exercise test (CPET) measure of established prognostic significance in patients with nHCM and heart failure with preserved ejection fraction (HFpEF). This was associated with a clinically relevant improvement in patient-reported outcomes.

"Ninerafaxstat is the first investigational drug to demonstrate an improvement in a functional measure assessed by cardiopulmonary exercise test in nHCM, which combined with a clinically meaningful improvement in patient symptoms measured by the KCCQ heart failure questionnaire, bodes well for patients suffering from nHCM,” said Martin Maron, M.D., Ph.D., Director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center in Burlington, Massachusetts, and principal investigator of the IMPROVE-HCM trial.

“Based on the topline results from IMPROVE-HCM, we are focused on advancing ninerafaxstat into a Phase 3 clinical trial of patients with nHCM and plan to meet with regulatory agencies within the coming months to confirm trial design. As cardiac energy deficiency is a hallmark feature of a range of cardiac diseases, the results of the IMPROVE-HCM clinical trial support the potential of ninerafaxstat to improve symptoms and function, not only in patients with nHCM, but also in patients with HFpEF,” said Anne Prener, M.D., Ph.D., president and chief executive officer of Imbria Pharmaceuticals.

Imbria anticipates sharing full data from the IMPROVE-HCM Phase 2 clinical trial at an upcoming medical conference.

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.

About non-obstructive hypertrophic cardiomyopathy (nHCM)
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.

About ninerafaxstat
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.

About Imbria
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 additional information, please visit

Komal Joshi
Imbria Pharmaceuticals, Inc.