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

Phase 2 development program for coronary microvascular dysfunction

  • Interventional, open label, exploratory trial
  • Men and women over 18 years of age with coronary microvascular dysfunction
Primary Endpoint
  • Adverse events (including SAEs); laboratory investigations; physical exams; MACE
Efficacy Endpoints
  • Change from baseline to 6 months in: coronary flow reserve; endothelial-dependent microvascular function; peripheral arterial tonometry measurements; time to angina; total exercise time; time to ST depression; activity recorded by Fitbit during one-week period
  • Change from baseline to 3 and 6 months in: angina frequency; nitroglycerin use; health-related quality of life
Study Size
  • 20 patients (U.S. centers - Cedars Sinai, Los Angeles & Mayo Clinic, Rochester)
  • CLBS16 (G-CSF mobilized peripheral blood derived autologous CD34+ cells)
Mode of Administration
  • Single intracoronary infusion
  • Positive complete results presented at SCAI Scientific Sessions (May 2020)
  • Study funded to completion in current budget projections (including NIH grant R44HL135889)


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.; 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.