CLBS14

Phase 2 Product Candidate for Coronary Microvascular Dysfunction

Caladrius is developing a CD34+ cell therapy (CLBS14) for the treatment of coronary microvascular dysfunction using the patient’s own cells to repair and regenerate the damaged cardiovascular tissue in their coronary arteries. CLBS14 has been approved for a Phase 2 exploratory clinical trial in coronary microvascular dysfunction with financial support for the trial coming from a grant awarded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

CLBS14 is Caladrius’ proprietary and patent protected formulation of CD34 cells designed specifically to enhance the potency of the CD34 cells for repair and regeneration of cardiovascular tissue. Its companion product, CLBS12, is specifically formulated for intramuscular administration for the treatment of lower extremity ischemia.

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction, also commonly called cardiac syndrome X or nonobstructive coronary heart disease, is a plaque-less heart disease involving damage to the inner lining of the tiny artery blood vessels in the heart. CLBS14 is designed to reduce the serious adverse consequences caused by the damage to the inner walls of the heart’s blood vessels through CD34 cell’s 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 underserved 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 to be enrolled
Treatment
  • CLBS14 (G-CSF mobilized peripheral blood derived autologous CD34+ cells
Mode of Administration
  • Cell infusion into a coronary artery
Timing
  • First-patient-in targeted for late Q1/early Q2 2018 with preliminary data expected in late 2018

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. ; 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. .

5. Vrtovec, B., et al. (2013). Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circulation Research. 112:165-173.