CLBS16

Product Candidate for Coronary Microvascular Dysfunction (CMD)

CLBS16 is being studied in a 20-patient proof-of-concept ESCaPE-CMD Phase 2 study at two centers in the United States. The trial is financially supported by a grant awarded from the National Heart, Lung and Blood Institute of the National Institutes of Health. The first patient was enrolled in April 2018 and results are expected by the end of 2019.

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

Design
  • 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
Treatment
  • CLBS14 (G-CSF mobilized peripheral blood derived autologous CD34+ cells
Mode of Administration
  • Cell infusion into a coronary artery
Timing
  • Fully-enrolled; Top-line data expected late 2019

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.