CLI x-ray image of two feet

Critical Limb Ischemia (CLI) - CLBS12 (HONEDRA in Japan)

What is Critical Limb Ischemia (CLI) and Buerger’s Disease?

Also known as Chronic Limb-Threatening Ischemia (CLTI)

Critical limb ischemia (CLI) is an advanced form of peripheral arterial disease (PAD) caused by a severe blockage in the arteries of the lower extremities. PAD is caused by atherosclerosis, the hardening and narrowing of the arteries over time due to the buildup of fatty deposits called plaque. 

CLI is a chronic condition that results in severe pain in the feet or toes, even while resting. Complications can include sores and wounds on the legs and feet that won’t heal due to the lack of circulating blood (carrying oxygen) essential to our body’s healing process. Left untreated, the complications of CLI can result in amputation of the affected limb. 

Buerger’s disease is a rare disease of the arteries and veins in the arms and legs. In Buerger’s disease – also called thromboangiitis obliterans – your blood vessels become inflamed, swell and can become blocked with blood clots. This eventually damages or destroys skin tissues and may lead to infection and gangrene (the death or decay of body tissues).(1). In some cases, amputation may be required. (2).

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CLI represents a large unmet medical need

In Japan, there are approximately 300,000 patients with CLI, of whom approximately 51,000 are not candidates for revascularization, making them the addressable population for CLBS12. The addressable population is approximately 560,000 patients in the EU and 300,000 in the U.S.

Buerger’s disease is extremely rare in the U.S. and Europe, but more common in Asia and the Middle East. The incidence in the U.S. has been estimated to 12.6-20 per 100,000 people in the general population. Buerger’s disease occurs with greater frequency in countries that have heavy tobacco use. (3)

Our Approach: CLBS12 (HONEDRA in Japan)

The goal of treatment with HONEDRA®, an experimental regenerative medicine, is to prevent the serious adverse consequences of CLI and Buerger’s disease by improving blood flow in the affected limb.

Mechanism of Action in Critical Limb Ischemia

MOA CLI

CLBS 12 (HONEDRA in Japan):

A registration-eligible study in Japan for Critical Limb Ischemia and Buerger’s Disease

The Company’s randomized and open-label, registration-eligible study of HONEDRA® in Japan for the treatment of CLI and Bueger’s disease, diseases with limited therapeutic options, has shown promising results to date. The initial clinical responses are consistent with a positive therapeutic effect and safety profile and are consistent with previously published clinical trials of CD34+ cell therapy in Japan and elsewhere.

Study Design


Primary Endpoint:

Continuous CLI-free (CLI-free for 2 consecutive monthly visits, adjudicated independently)


Study size:

30 subjects with no-option CLI + 7 Buerger’s Disease pts.; all Rutherford category 4 or 5; recruited across 12 centers in Japan


Dose:

Up to 106 cells/kg of HONEDRA® to the most seriously affected limb (target limb)


Control/Comparator

Standard of Care: wound care plus drugs approved in Japan

  • Including antimicrobials, antiplatelets, anticoagulants and vasodilators

Mode of administration:

Intramuscular, 20 injections in the target limb in a single treatment


Timing:

  • Enrollment completion/results target:  2Q2021/2Q2022, respectively
  • Early approval target: 1H2023
  • Timing subject to COVID-19 pandemic influence


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