Imbria Presents Positive Clinical Data from Phase 2 IMPROVE-DiCE Trial of Ninerafaxstat in Patients with Cardiometabolic HFpEF at ACC.25

– Ninerafaxstat improves cardiac energetics, cardiac reserve capacity, 6-minute walk distance and heart
failure-related health status (KCCQ) in cardiometabolic HFpEF –

– Findings support further development of ninerafaxstat in HFpEF and adjacent CV indications
such as non-obstructive hypertrophic cardiomyopathy (nHCM) –

/EIN News/ -- BOSTON, March 29, 2025 (GLOBE NEWSWIRE) -- Imbria Pharmaceuticals, Inc., a clinical stage, cardiometabolic company developing novel therapies designed to enhance cellular energetics, today announced positive clinical results from Part 2 of the IMPROVE-DiCE Phase 2 trial demonstrating that ninerafaxstat improved cardiac energetics, left ventricular reserve capacity, exercise capacity and patient-reported heart failure symptoms and physical limitations in patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF). The results were presented at the American College of Cardiology’s Annual Scientific Session & Expo (ACC.25) in Chicago, IL during the moderated poster session titled “Innovations and Insights in Heart Failure With Preserved Ejection Fraction: Emerging Therapies, Biomarkers and Mechanistic Studies.”

“These findings validate the mechanistic rationale for targeting impaired myocardial energetics in HFpEF and demonstrate ninerafaxstat’s potential to restore resting cardiac energetics and enhance functional cardiac reserve,” said Oliver Rider, MRCP(UK), DPhil (Oxon), Professor of Cardiovascular Medicine, University of Oxford. “Importantly, these results suggest ninerafaxstat could improve daily symptoms and physical capacity for people living with HFpEF, a condition with few effective treatments available today.”

Key findings from the trial include:

• Treatment of patients with cardiometabolic HFpEF with ninerafaxstat for 12 weeks resulted in a statistically significant (P=0.02) increase from baseline in cardiac phosphocreatine to adenosine triphosphate (PCr/ATP) ratio, consistent with an improvement in cardiac energy reserves and meeting the trial’s primary objective. Of note, the largest energetic responses to ninerafaxstat were observed in those with the most severe energy deficit at baseline.
• Significant improvement in left ventricular (LV) systolic reserve capacity with exercise, reflecting an increase in the heart’s ability to augment its stroke volume during exercise (P=0.03), a key abnormality in patients with HFpEF.
• Consistent with enhanced LV reserve capacity, an increase in 6-minute walk distance of ~14 m (P=0.02) was observed.
• Statistically significant and clinically meaningful improvements in heart failure-related health status, measured by the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), were observed in patients most symptomatically limited at baseline, pre-specified as those with KCCQ-CSS ≤80 (~8 points; P=0.04).

“Approximately 50% of heart failure cases are related to HFpEF. In the U.S. alone, the prevalence is expected to rise to 8.5 million by 2030. Within the HFpEF population, at least 80% are living with type 2 diabetes mellitus (T2DM) and obesity. There are no current treatments aimed at targeting mitochondrial energy generation to improve patient symptoms, quality of life, and functional capacity. We believe these validating results pave the way to support further investigation of ninerafaxstat in cardiometabolic HFpEF,” said Jai Patel, MRCP(UK), Chief Medical Officer at Imbria. “Ninerafaxstat’s unique therapeutic profile has the potential to make a meaningful impact in cardiometabolic HFpEF and pathophysiologically adjacent disease states such as nHCM.”

A copy of the poster will be available in the “Media Center” section of the Imbria website at www.imbria.com.

About ninerafaxstat
Ninerafaxstat is an innovative treatment for cardiac disorders 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 adenosine triphosphate (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 with no dose titration or monitoring required, no clinically significant drug-drug interactions and can be used on top of standard of care cardiovascular treatments.

About IMPROVE-DiCE
IMPROVE-DiCE is the first clinical trial utilizing multi-nuclear spectroscopy, including state-of-the-art hyperpolarized MR spectroscopy, and MRI to quantify the cardiac energetic, metabolic and functional responses to an investigational metabolic modulator in cardiovascular disease. It is a two-part, Phase 2 clinical trial evaluating the safety, tolerability and pharmacodynamic effects of ninerafaxstat. Part 1 enrolled pre-HFpEF patients with type 2 diabetes and obesity and demonstrated normalization of cardiac energetics, significant reduction in cardiac steatosis and improvements in left ventricular diastolic filling rate, an important component of heart failure. The results of Part 1 were presented at the European Society of Cardiology Congress in August 2022. Part 2 of IMPROVE-DiCE enrolled symptomatic patients with cardiometabolic HFpEF and assessed the impact of ninerafaxstat on cardiac energetics, cardiac reserve function, exercise capacity and heart failure symptoms. The trial was conducted at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Radcliffe Department of Medicine at the University of Oxford, UK and was led by Professor Oliver Rider. For more information, please visit www.clinicaltrials.gov (Identifier: NCT04826159).

About heart failure with preserved ejection fraction (HFpEF)
Over half of all patients with heart failure have preserved ejection fraction, a clinical syndrome characterized by an inability of the heart to pump blood adequately to the body without pathological increases in filling pressures at rest or during exertion. As with other forms of heart failure, HFpEF is associated with cardiac energy deficiency resulting from impaired mitochondrial energy generation. This leads to impaired cardiac functional reserve on exertion and is associated with exercise-induced pulmonary congestion, resulting in hallmark heart failure symptoms of exertional breathlessness, fatigue, and markedly reduced exercise capacity leading to severe impairment in quality of life. Despite being associated with severe morbidity and mortality, HFpEF has few evidence-based therapies. Within the clinical syndrome of HFpEF, the cardiometabolic HFpEF phenotype, in which chronic cardiometabolic stress resulting from type 2 diabetes and obesity are key drivers of heart failure pathophysiology, is rapidly emerging as the most prevalent form.

About Imbria
Imbria is a privately held, clinical stage company developing novel therapies for patients with life-altering cardiometabolic disorders. Our clinical pipeline is focused on restoring or improving the cell’s ability to produce energy in cardiometabolic disorders where energetic impairment is a fundamental contributor to disease pathogenesis, symptoms and functional deficits. The lead product candidate, ninerafaxstat, has completed multiple Phase 2 clinical trials in three indications: nHCM, stable angina, and HFpEF. In Phase 1 and 2 clinical trials, ninerafaxstat was shown to be well tolerated. For additional information, please visit www.imbria.com.

Contact
Komal Joshi
Imbria Pharmaceuticals, Inc.
kjoshi@imbria.com