Product Candidate for Coronary Microvascular Dysfunction (CMD)

KPR-003 like cells were studied in a 20-patient proof-of-concept ESCAPE-CMD Phase 2 study at two centers in the United States. Results showed that a single administration of caused a highly significant improvement in coronary flow reserve correlating with symptom relief or patients with coronary microvascular dysfunction (p=0.009). The clinical effect of relieving chest pain lasted past the 6 month follow up assessment. There were no reported adverse events.

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. KPR-003, 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.

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

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-