Imbria Enrolls First Patient in the Phase 2 IMPROVE-DiCE Clinical Trial Evaluating Ninerafaxstat in Patients With Heart Failure With Preserved Ejection Fraction

Imbria Pharmaceuticals, Inc. recently announced the enrollment of the first patient in Part 2 of the IMPROVE-DiCE Phase 2 clinical trial of ninerafaxstat in patients with heart failure with preserved ejection fraction (HFpEF). Ninerafaxstat is currently in Phase 2 clinical development in three indications: non-obstructive hypertrophic cardiomyopathy (nHCM), stable angina, and HFpEF.

“HFpEF is now the most common form of heart failure, affecting over 3 million adults in the US, reflecting the aging of the general population and the global epidemic of type 2 diabetes and obesity,” said Jai Patel, MRCP (UK), Chief Medical Officer at Imbria. “Ninerafaxstat is designed to reduce the over reliance on fatty acids as a fuel choice in the heart that underlies impaired energy generation in HFpEF and leads to debilitating symptoms such as breathlessness, fatigue, and reduced exercise capacity for which there are currently limited treatment options.”

“Part 2 of the IMPROVE-DiCE trial will assess the effects of ninerafaxstat on cardiac energetics, heart failure symptom burden and functional capacity in patients with HFpEF. We look forward to sharing initial results from this trial in 2023 as well as report on the results of our two other Phase 2 trials in nHCM and stable angina,” Dr. Patel concluded.

Anne Prener, MD, PhD, President and Chief Executive Officer of Imbria, said “Initiation of patient enrollment in this Phase 2 clinical trial, assessing the safety and efficacy of ninerafaxstat, in the underserved patient population of HFpEF is yet another important step in the development of ninerafaxstat, as we continue to evaluate its potential to make a meaningful impact on major unmet needs in HFpEF, stable angina, and nHCM.”

Our lead product candidate, ninerafaxstat, is a novel, investigational cardiac mitotrope in development for a range of cardiac diseases characterized by a fundamental imbalance between energy consumption and energy supply in the heart resulting in cardiac energy deficiency. As a partial fatty acid oxidation (pFOX) inhibitor, ninerafaxstat is designed to shift cardiac substrate selection towards glucose oxidation which generates more energy in the form of ATP per unit of oxygen consumed than any other carbon substrate, thus increasing cardiac metabolic efficiency and support better cardiac mechanical efficiency and function. Ninerafaxstat is currently in Phase 2 clinical development in three indications: nHCM, stable angina, and HFpEF.

Over half of all patients with heart failure have preserved ejection fraction (HFpEF), 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 very 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.

IMPROVE-DiCE is the first clinical trial utilizing multi-nuclear and state-of-the-art hyperpolarized MR spectroscopy to quantify the metabolic and energetic 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 to the rate of diastolic filling, 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 enrolls symptomatic patients with cardiometabolic HFpEF and will assess the impact of ninerafaxstat on cardiac energetics, diastolic function, functional capacity and heart failure symptoms. The trial is being conducted at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Radcliffe Department of Medicine at the University of Oxford, UK and is being led by Professor Oliver Rider. For more information, please visit www.clinicaltrials.gov (Identifier: NCT04826159).

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, visit www.imbria.com.