IMB-101

For the Treatment of
Cardiovascular Diseases

IMB-101 is currently in Phase 2 clinical development for multiple cardiovascular diseases, common as well as rare.

IMB-101 is designed to enhance cellular energy metabolism by increasing the amount of energy produced per molecule of oxygen consumed.

IMB-101 Mechanism of Action

The heart is a voracious consumer of energy, more than any other organ. Like every other cell and organ in the body, the heart’s energy currency is adenosine triphosphate, or ATP. The heart runs through approximately six kilograms of ATP every day, which is 20 to 30 times its own weight. The heart must generate all of the ATP it needs in real time.

Under normal circumstances, both glucose (sugars) and free fatty acids (fats) are fuels for metabolism in the heart. In heart disease, oxygen levels available to cells may be lower than usual, and as a result the heart may rely to a greater extent on fatty acids to make energy. However, ATP generation is less efficient because 10% to 15% more oxygen is required to generate the same amount of ATP from fatty acids as compared to glucose.

IMB-101 Mechanism of Action

IMB-101 is a novel, investigational cardiac mitotrope in development for the treatment of cardiovascular disease. As a partial fatty acid oxidation (pFOX) inhibitor, IMB-101 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.

IMB-101 Development Status

IMB-101 for the Treatment of Refractory Angina

IMB-101 is currently being investigated in three Phase 2 proof-of-concept clinical trials in patients with hypertrophic cardiomyopathy, stable angina, and type 2 diabetes at risk for diabetic cardiomyopathy. In Phase 1 clinical trials, IMB-101 was shown to be safe and well tolerated.

IMB-101 IMPROVE-DiCE Phase 2a Study: Cardiac Energetics in Patients with Type 2 Diabetes

IMPROVE-DiCE is an open-label pharmacodynamic study that will assess the activity of IMB-101 on cardiac energetic reserve at rest and during stress, and to assess the safety and tolerability of IMB-101 in patients with Type 2 diabetes. The primary outcome will measure the change in cardiac PCr/ATP ratio at rest and with dobutamine stress (i.e., dobutamine stress-induced drop in PCr/ATP ratio from its resting value at the same time point) measured by 31P-MRS over an eight-week period, while also examining the safety and tolerability of IMB-101.

Please refer to www.clinicaltrials.gov for additional clinical trial information.

IMB-101 IMPROVE-Ischemia Phase 2 Study: Obstructive Coronary Artery Disease

IMPROVE-Ischemia is a randomized, double-blind, placebo-controlled, exploratory study that will examine the safety and tolerability of IMB-101 in patients with obstructive 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 IMB1018972 over an 8-week period. The measure of incidence and severity of treatment emergent Adverse Events (AEs), as well as well as incidence of treatment emergent Severe Adverse Events (SAEs) will also be examined.

Please refer to www.clinicaltrials.gov for additional clinical trial information.

IMB-101 IMPROVE-HCM Phase 2 Study: Non-obstructive Hypertrophic Cardiomyopathy

IMPROVE-HCM is a randomized, double-blind, placebo-controlled study that will assess the safety, tolerability, and efficacy of IMB-101 in patients with non-obstructive hypertrophic cardiomyopathy (HCM). This study will measure the change from baseline of peak oxygen consumption (VO2) and oxygen uptake efficiency slope (OUES), measured by standardized cardiopulmonary exercise testing (CPET) in 60 non-obstructive HCM patients treated with 200 mg BID of IMB-1018972 over a 12-week period. Incidence and severity of treatment emergent Adverse Events (AEs), as well as incidence of treatment emergent Severe Adverse Events (SAEs) will also be examined.

Please refer to www.clinicaltrials.gov for additional clinical trial information.