Product Candidate for Critical Limb Ischemia (CLI)

Kuiper plans to develop its product candidate, KPR-001, in China, EU countries and South Africa under relevant regenerative medicine law. These laws enables an expedited path to conditional approval for regenerative medicine products which shows sufficient safety evidence and signals of efficacy in a phase 2 study. The Clinical Trial Notification by CLBS of their equivalent of the Kuiper-001 product for a pivotal phase 2 trial investigation was submitted to the Japanese Pharmaceutical and Medical Device Agency (PMDA) and was cleared to proceed. The protocol design was agreed with PMDA and if successful, could provide the basis for conditional approval under Japan’s favorable regenerative medicine law and be used to support Kuiper filings in China, the EU and South Africa.. We are seeking to collaborate with development and/or manufacturing partners.

No-Option Critical Limb Ischemia

The goal of CKRP-001 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 our product would have potential a variety of other ischemia induced tissue injury diseases.

KPR-001 LIKE THERAPY IS SUPPORTED BY A PROFOUND BODY OF CLINICAL EVIDENCE

KPR-001 CELLS HAVE BEEN INVESTIGATED IN CLINICAL STUDIES ENCOMPASSING >700 PATIENTS

  • Pre-clinical studies document improved microcirculation
  • Phase 2 clinical studies consistently show benefits in safety and function
  • Reduced amputation in critical limb ischemia
  • Improved function in claudication
  • Reduced angina and improved ETT in refractory angina
  • Improved mortality and LVEF in dilated cardiomyopathy

Opportunities exist across multiple underserved cardiovascular indications

  • 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.

Received SAKIGAKE designation for expedited review. Phase 2 study is completed awaiting results.

Design

  • Prospective, open label, controlled, randomized trial
  • Patients with no-option CLI

Advantageous Primary Endpoint

  • Time to continuous CLI-free status (defined as 2 consecutive monthly visits)

Study Size

  • 35 patients enrolled across multiple centers in Japan

Treatment

  • Up to 106autologousG-CSF-mobilized peripheral blood-derived CD34+ cells/kg per affected limb

Control/comparator

  • SOC pharmacotherapy with drugs approved in Japan (e.g. antiplatelets, anticoagulants and vasodilators)
  • The choice of pharmacotherapy will be made by the investigators

Mode of Administration

  • Intramuscular, 20 injections in affected lower limb in single administration

Timing

  • First patient-in targeted for 4Q17/1Q18 with preliminary data expected within 6 months of initiation

References1. 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 published4. 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. 9:1576-1585.5. 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.