• Phase 1 healthy volunteer study demonstrates that oral administration of IMB-101 is well tolerated and exhibits predictable pharmacokinetic characteristics
  • Pre-clinical study showed that IMB-101 improves cardiac contractile function and fibrosis post-myocardial infarction, highlighting its therapeutic potential in the context of myocardial ischemia and heart failure

BOSTON, MA, USA I May 17, 2021 I Imbria Pharmaceuticals, a clinical stage biopharmaceutical company developing novel therapies designed to enhance cellular energetics whose impairment is a hallmark of major forms of heart disease and specific inborn errors of metabolism, today announced that IMB-101, a novel partial fatty acid oxidation (pFOX) inhibitor designed to shift myocardial substrate utilization in favor of glucose oxidation to increase the efficiency of mitochondrial energy generation, was well tolerated in a Phase 1 study of healthy volunteers. In a separate preclinical study, IMB-101 improved cardiac remodeling and function in a clinically relevant disease model of heart failure (murine permanent coronary artery ligation). The two studies were featured in presentations at The American College of Cardiology 70th Annual Scientific Session & Expo (ACC.21).

“Our Phase 1 healthy volunteer study data add to the growing evidence that oral administration of IMB-101 is a well-tolerated metabolic agent,” said Anne Prener, M.D., Ph.D., President and CEO of Imbria Pharmaceuticals. “In our preclinical study, we found IMB-101 administered in a murine surgical model of post-myocardial infarction heart failure mice progressively improved left ventricular systolic function while reducing myocardial fibrosis. These findings together support a therapeutic strategy for pFOX inhibition using IMB-101, and we look forward to sharing data from our three ongoing Phase 2, proof-of-concept clinical trials in patients with hypertrophic cardiomyopathy, stable angina and type-2 diabetes at risk for diabetic cardiomyopathy, respectively.”

ACC.21 Session 2251: Phase 1 Safety and Tolerability Study of IMB-1018972, a Novel Oral Modulator of Myocardial Substrate Utilization Designed to Improve Cardiac Metabolic Efficiency and Bioenergetics

This Phase 1 multi-part study was conducted to assess the safety, tolerability, and pharmacokinetics of oral IMB-1018972 (IMB-101). A total of 88 healthy adult volunteers (HV) participated in the study and received either IMB-101 (66 HV) or placebo (14 HV) in single ascending dose (SAD) and multiple ascending dose (MAD) settings; and a further 8 HV receiving trimetazidine as a single dose. The SAD part had five dosing cohorts (n=8 each) with: 50, 150, or 400 mg of immediate-release (IR) IMB-101 or placebo; one with trimetazidine 35 mg MR; and one cohort receiving single doses in the fed and fasted state with 150 mg IMB-101 or placebo to study the effect of food. The MAD part (n=12/cohort) used 50 and 150 mg IMB-101 or placebo twice per day for 14 days. The modified-release (MR) part used single doses of 50 or 200 mg in the fed and fasted states, and a final cohort (n=12) with multiple dosing used 200 mg IMB-101 twice per day for five days.

Key highlights from the Phase 1 study:

  • Orally administered IMB-101 was well tolerated at all doses and formulations evaluated and exhibited predictable pharmacokinetic characteristics.
  • Oral administration of IMB-101 had no impact on hemodynamics or ECG indices and resulted in no adverse trends in clinical laboratory measures in the study population of healthy adult subjects.
  • No treatment-related, serious adverse events (SAEs) were reported.
  • A recommended phase 2 dose and formulation was selected for further study.

ACC.21 Session 1034: IMB-1018972, a novel first-in-class partial fatty acid oxidation (pFOX) inhibitor improves cardiac remodeling and function post-myocardial infarction

Myocardial fatty acid (FA) and glucose metabolism are tightly regulated in health to meet the heart’s high energy demands. This relationship is perturbed in acute ischemia (reliance on anaerobic glycolysis to generate ATP) and on reperfusion there is a marked increase in mitochondrial FA oxidation, further repressing glucose oxidation. In heart failure (HF), glycolysis is also partially uncoupled from glucose oxidation due to reduced pyruvate dehydrogenase (PDH) activity, thereby reducing the efficiency of energy generation. Importantly, FA metabolism yields less ATP than glucose for the same oxygen consumption. Partial inhibition of FA oxidation shifts metabolism toward glucose, increasing PDH activity and the efficiency of energy production. This pre-clinical study examined the ability of IMB-101 to mitigate left ventricular (LV) dysfunction and remodelling in a murine model of post-myocardial infraction (MI) heart failure.

Key highlights from the pre-clinical study:

  • IMB-101 administered to mice post-coronary artery ligation resulted in progressive improvement in LV systolic function when compared to vehicle-treated control mice undergoing the same surgery.
  • Mice treated with IMB-101 exhibited reduced myocardial fibrosis post-MI.
  • IMB-101 administration tended to reduce elevated LV end-diastolic pressure post-MI, a surrogate measure of LV preload and diastolic operating compliance.

About IMB-101

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 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, respectively.

About Imbria Pharmaceuticals

Imbria Pharmaceuticals uses a deep understanding of energy metabolism to develop novel therapies designed to substantially improve the lives of patients with life-altering diseases. Our clinical stage pipeline is focused on restoring or improving the cell’s ability to produce energy in disorders where energetic impairment is a fundamental contributor, including cardiovascular disease and specific inborn errors of metabolism. The lead program, IMB-101, is currently in Phase 2 clinical development in three indications, hypertrophic cardiomyopathy, stable angina and type-2 diabetes at risk for diabetic cardiomyopathy.

Our pipeline also includes IMB-203, which is designed to address the energy deficiency in patients with rare inborn errors of mitochondrial metabolism. For additional information, please visit www.imbria.com.

SOURCE: Imbria Pharmaceuticals