Product Candidates for Coronary Microvascular Dysfunction and Refractory AnginaCLBS14 is a formulation of autologous G-CSF mobilized peripheral blood derived CD34+ cells designed to stimulate the growth of microvasculature in the hearts of patients with myocardial ischemia. Caladrius has two CBLS14 clinical programs targeting similar indications. These CD34+ cell therapies are designed to treat either coronary microvascular dysfunction (CLBS14-CMD) or refractory angina (CLBS14-NORDA) using the patient’s own cells to repair and regenerate the damaged cardiovascular tissue. CLBS14-CMD is being studied in the ongoing ESCaPE-CMD Phase 2 proof-of-concept clinical trial and CLBS14-NORDA (previously CLBS14-RfA) is currently in late-stage development and received RMAT designation from the FDA for treatment of refractory angina.
CLBS14-CMD 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 (CMD), 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. CLBS14-CMD 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.
Nearly 50 percent of patients with coronary artery disease have CMD. Approximately 8.3 million people in the United States1, 6.0 million people in Europe2 and 1.0 million people in Japan3,4 have CMD and could be eligible for CLBS14-CMD. There is currently no available targeted therapy for CMD
CLBS14-NORDA (previously CLBS14-RfA)
CLBS14-NORDA has been studied in Phase 1, Phase 2 and Phase 3 randomized, double-blind placebo-controlled clinical trials.  A recent publication in the European Heart Journal, entitled “Autologous CD34+ cell therapy improves exercise capacity, angina frequency and reduces mortality in no-option refractory angina: a patient-level pooled analysis of randomized double-blinded trials” combines the data from all three studies encompassing over 300 patients and reveals statistically significant improvements in mortality, exercise capacity and chest pain frequency. Under the terms of the RMAT designation, Caladrius is holding discussions with the FDA to determine the most expeditious regulatory pathway to bring this potentially restorative therapy to patients in need.
It is estimated that as many as 1 million people in the United States have chronic symptomatic coronary artery disease (often referred to as refractory angina, or RfA) that is recalcitrant to medical therapy and not amenable to conventional revascularization procedures. Patients have reproducible lifestyle-limiting symptoms such as chest pain and shortness of breath and are easily fatigued. These symptoms are often due to totally occluded coronary arteries or to diffuse coronary atherosclerosis that makes revascularization problematic. As the population ages and the incidence of diabetes mellitus increases, this clinical condition is expected to become more prevalent. Patients with this condition have significant morbidity and experience a lower quality of life.
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 microcirculation9
- Phase 2 clinical studies consistently show benefits in safety and function
- Reduced amputation in critical limb ischemia10
- Improved function in claudication11
- Reduced angina and improved ETT in refractory angina12
- Improved mortality and LVEF in dilated cardiomyopathy13
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
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