CLBS16

Product Candidate for Coronary Microvascular Dysfunction (CMD)

CLBS16, the subject of a recently completed positive 20-patient proof-of-concept ESCaPE-CMD Phase 2 study at two centers in the United States. The trial was financially supported by a grant awarded from the National Heart, Lung and Blood Institute of the National Institutes of Health. 

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction, previously known as Syndrome X, is a heart disease in which disease of the microcirculation results in severe myocardial ischemia in the absence of blockages in the large arteries. CLBS16 is designed to reduce the serious adverse consequences caused by the damage to the inner walls of the heart’s blood vessels through CD34+ cells’ innate ability to repair small blood vessels or microcirculation.

CD34+ cell therapy is supported by a profound body of clinical evidence

CD34+ cells have been investigated in clinical studies encompassing >700 patients

  • Pre-clinical studies document improved microcirculation1
  • Phase 2 clinical studies consistently show benefits in safety and function
    • Reduced amputation in critical limb ischemia2
    • Improved function in claudication3
    • Reduced angina and improved ETT in refractory angina4
    • Improved mortality and LVEF in dilated cardiomyopathy5

Opportunities exist across multiple under served cardiovascular indications

  • Critical limb ischemia (CLI) in Japan
  • Coronary microvascular dysfunction (CMD)
  • Refractory angina

FREEDOM trial: Phase 2b double-blind, placebo-controlled

Endpoints

 - Change from baseline in angina frequency [Baseline to 3 and 6 months]

- Change from baseline in total exercise time [Baseline to 6 months]

- Change from baseline in health-related quality of life [Baseline to 3 and 6 months]

- Change from baseline in peak coronary flow reserve [Baseline to 6 months]

Study Size 105 subjects (~10 sites in the USA)
Dose1 x 106 to 300 x 106 CD34+ cells or placebo
Mode of administration Single intracoronary infusion
Timing

 - Study initiated 4Q2020

 - Top-line Data Target: 3Q2022

References:

1. Kalka, C., et al. (2000). Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proceedings of National Academy of Sciences of the United States. 97:3422–3427. http://www.pnas.org/content/97/7/3422.full; Schatteman GC, et al. (2000). Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. The Journal of Clinical Investigation. 106:571–578; Madeddu, P. et al. (2004). Transplantation of low dose CD34+KDR+ cells promotes vascular and muscular regeneration in ischemic limbs. The FASEB Journal. 18:1737-1739.

2. Losordo, DW., et al. (2012). A Randomized, Controlled Pilot Study of Autologous CD34+ Cell Therapy for Critical Limb Ischemia. Circulation: Cardiovascular Interventions. 5: 821–830.

3. From US study (n=17); Not yet published

4. Losordo, DW. et al. (2011). Intramyocardial, Autologous CD34+ Cell Therapy for Refractory Angina. Circulation Research. 109:428-436; Povsic, TJ. et al. (2016).The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34+ Cell Administration in Patients With Refractory Angina. JACC Cardiovascular Interventions. 9:1576-1585.

Recommended Media Related to CMD:

A Typical Heart Documentary
A documentary exploring the deadly disparity between male and female heart disease, via healthcare professionals, researchers, patients, & families.

Underdiagnosed Heart Condition – Coronary Microvascular Dysfunction (CMD)
Dr. Timothy Henry, MD, Lindner Family Distinguished Chair in Clinical Research and Medical Director of The Carl and Edyth Lindner Center for Research at The Christ Hospital discusses coronary microvascular dysfunction (CMD) a type of non-obstructive coronary artery disease that causes decreased blood flow to the heart muscle, affects the smallest arteries, and won’t always show up on a regular exam.

Physician Perspective: Chest Pain Linked to Underdiagnosed Heart Condition Affecting 8.3M Americans
Timothy D. Henry, MD, MSCAI of The Christ Hospital Health Network speaks about his Physician Perspective: Chest Pain Linked to Underdiagnosed Heart Condition Affecting 8.3M Americans.

When Chest Pain Isn't a Heart Attack: A Look at Coronary Microvascular Dysfunction
Cardiologists are learning more about a condition called coronary microvascular dysfunction (coronary MVD). Previously known as cardiac syndrome X, the condition might be the cause of many unexplained cases of chest pain.