Ninerafaxstat: For the Treatment of Life-Altering Cardiometabolic Disorders

Ninerafaxstat is currently in Phase 2 clinical development for multiple cardiometabolic diseases, common as well as rare.

Ninerafaxstat is designed to enhance cellular energy metabolism by increasing the amount of energy produced per molecule of oxygen consumed.

Ninerafaxstat mechanism of action
Ninerafaxstat is a novel, investigational cardiac mitotrope in development for the treatment of cardiovascular disease. As a partial fatty acid oxidation (pFOX) inhibitor, ninerafaxstat is designed to shift myocardial substrate utilization in favor of glucose oxidation to generate more ATP per unit of oxygen consumed thereby increasing myocardial metabolic efficiency.


Ninerafaxstat development status
Ninerafaxstat is currently being investigated in three Phase 2 proof-of-concept clinical trials in patients with non-obstructive hypertrophic cardiomyopathy (nHCM), stable angina, and heart failure with preserved ejection fraction (HFpEF). In Phase 1 clinical trials, ninerafaxstat was shown to be safe and well tolerated.

Non-obstructive hypertrophic cardiomyopathy

IMPROVE-HCM Phase 2 Clinical Trial

IMPROVE-HCM is a randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of ninerafaxstat in patients with nHCM. This trial will measure the change from baseline of peak oxygen consumption and oxygen uptake efficiency slope, measured by standardized cardiopulmonary exercise testing in 60 nHCM patients treated with 200 mg BID of ninerafaxstat over a 12-week period. Incidence and severity of treatment emergent adverse events, as well as incidence of treatment emergent serious adverse events will also be examined.


Heart failure with preserved ejection fraction

IMPROVE-DiCE Phase 2 Clinical Trial: Part 1: Cardiac Energetics in Patients with Type 2 Diabetes and early stage heart failure (pre-HFpEF), Part 2: Cardiac energetics, function and symptoms in patients with Type 2 Diabetes and HFpEF.

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.


Stable angina

IMPROVE-ISCHEMIA Phase 2 Clinical Trial: Obstructive Coronary Artery Disease

IMPROVE-ISCHEMIA is a randomized, double-blind, placebo-controlled, Phase 2 study that will examine the safety and tolerability of ninerafaxstat in patients with obstructive coronary arterial disease (CAD) and inducible ischemia. The study will examine the change in number of ischemic segments during hyperemia (ischemia defined as absolute MBF ≤2.3 ml/kg/min) as measured by adenosine stress 15O-H2O PET in 60 obstructive CAD patients treated with 200 mg BID of ninerafaxstat over an 8-week period. The measure of incidence and severity of treatment emergent Adverse Events will also be examined.



Please refer to for additional clinical trial information.