April 08, 2024

Positive Results for Patients with Non-obstructive Hypertrophic Cardiomyopathy Treated with Ninerafaxstat in the Phase 2 IMPROVE-HCM Trial Presented During a Late-Breaking Clinical Trial Session at ACC.24

Positive Results for Patients with Non-obstructive Hypertrophic Cardiomyopathy Treated with Ninerafaxstat in the Phase 2 IMPROVE-HCM Trial Presented During a Late-Breaking Clinical Trial Session at ACC.24

– Improvements in both patient-reported symptoms of heart failure and ventilatory efficiency during exercise testing were demonstrated –

– Results support initiation of the Phase 3 FORTITUDE-HCM clinical trial of ninerafaxstat in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM) and its continued development in heart failure with preserved ejection fraction (HFpEF) –

– Results published in the Journal of the American College of Cardiology (JACC) –

BOSTON, Mass., April 8, 2024 – Imbria Pharmaceuticals, Inc., a clinical stage, cardiometabolic company developing novel therapies designed to improve patient symptoms and functional capacity by enhancing cellular energetics, today announced that results from the Phase 2 IMPROVE-HCM clinical trial, evaluating ninerafaxstat in patients with symptomatic nHCM, were presented in a late-breaking clinical trial session at the American College of Cardiology’s Annual Scientific Session & Expo (ACC.24) and published in the Journal of the American College of Cardiology (JACC).

“There is significant unmet need among patients impacted by nHCM for novel treatment options that improve symptoms and functional capacity; issues that severely affect their quality of life and ability to perform daily activities,” said Martin S. Maron, M.D., Director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center in Burlington, Massachusetts, and principal investigator of the IMPROVE-HCM trial. “The improvements observed with ninerafaxstat in both symptoms and function in these patients who have no approved treatment options, clearly support further clinical evaluation.”

“Ninerafaxstat was safe and well tolerated in this trial with no significant change in left ventricular ejection fraction, blood pressure or heart rate at week 12 and demonstrated strong improvements in key efficacy endpoints associated with exercise performance and health status, including statistically significant improvements in ventilatory efficiency during exercise and favorable changes in KCCQ-CSS,” said Jai Patel, MRCP (U.K.), chief medical officer of Imbria Pharmaceuticals.

“We are pleased with the IMPROVE-HCM clinical trial results presented today at ACC and simultaneously published in JACC, confirming the importance of these results for patients living with nHCM,” said Anne Prener, M.D., Ph.D., president and chief executive officer of Imbria Pharmaceuticals. “Based on these positive results, we plan to initiate the Phase 3 FORTITUDE-HCM clinical trial in patients with symptomatic nHCM later this year. Ninerafaxstat is also currently being investigated in a Phase 2 clinical trial in patients with cardiometabolic HFpEF and we look forward to sharing results in early 2025.”

Summary of Key Results from IMPROVE-HCM

Safety and Tolerability (Primary Endpoint)

Twelve-week treatment with ninerafaxstat was well tolerated and no safety signals were observed, including no fall in left ventricular ejection fraction. Most treatment emergent adverse events (AEs) were self-limiting and mild to moderate in severity occurring in 24 ninerafaxstat treated patients (70.6%) vs. 20 patients on placebo (60.6%).

Efficacy Findings

Twelve-week treatment with ninerafaxstat demonstrated statistically significant improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) in the subgroup of patients limited by heart failure symptoms as defined by a baseline score of ≤80 points, representing the target patient population for the Phase 3 FORTITUDE-HCM clinical trial. In this post-hoc analysis, patients on ninerafaxstat experienced a mean change from baseline to week 12 in KCCQ-CSS from 52 points to 64 compared to 59 points to 61 for placebo, with LS mean difference in change between the groups of 9.3 points (p=0.04).

Statistically significant improvements were also observed in ventilatory efficiency during exercise (VE/VCO2 slope) a robust CPET measure of prognostic significance in both HCM and HFpEF. From baseline to week 12, VE/VCO2 slope decreased (i.e. improved) from 31.2 to 30.9 in the ninerafaxstat treated group and worsened from 32.7 to 34.3 in the placebo group. The LS mean difference between the groups was -2.1 (p=0.005). Ninerafaxstat also significantly reduced left atrial size, a marker of diastolic dysfunction and disease severity.

Please refer to the publication titled “Safety and Efficacy of Metabolic Modulation with Ninerafaxstat in Nonobstructive Hypertrophic Cardiomyopathy: Phase 2 Study” in JACC for further details of the findings of the IMPROVE-HCM trial. Link: https://www.jacc.org/doi/10.1016/j.jacc.2024.03.387

About ninerafaxstat
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. Ninerafaxstat is a simple orally administered compound without dose titration or monitoring required, no clinically significant drug-drug interactions and can be used on top of cardiovascular standard of care treatments.

About the Phase 2 IMPROVE-HCM Clinical Trial
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 non-obstructive hypertrophic cardiomyopathy (nHCM). The primary objective of the trial 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
Hypertrophic cardiomyopathy (HCM) 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 its relaxation and filling, 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 Imbria
Imbria Pharmaceuticals is a privately held, clinical stage company developing novel therapies for patients with life-altering cardiometabolic disorders. Our clinical programs are 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, has 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 early 2025. For additional information, please visit www.imbria.com.

Komal Joshi
Imbria Pharmaceuticals, Inc.