Product Candidate for Critical Limb Ischemia (CLI)
No-Option Critical Limb IschemiaThe goal of CLBS12 is to prevent the serious adverse consequences of no-option CLI (cases where there is no longer the potential for other treatment beyond amputation) by extending the time of continuous CLI free status through improved blood flow in the affected limb. We also believe a CD34 product would have potential in treating chronic heart failure ("CHF"). Published reports have provided evidence that CD34 cells administered into the coronary arteries of patients with CHF can improve survival compared to patients treated with standard medical therapy.
CD34 cell therapy is supported by a profound body of clinical evidence
- 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
- Critical limb ischemia (CLI) in Japan
- Coronary microvascular dysfunction (CMD)
- Refractory angina
Japanese development program for critical limb ischemia
Phase 2 protocol and CMC strategy completed in consultation with Japanese PMDA
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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.