Human heart with blood vessels rendering

Coronary Microvascular Dysfunction (CMD) - CLBS16

What is Coronary Microvascular Dysfunction (CMD)?

Also known as coronary microvascular disease, microvascular angina, cardiac syndrome x, ischemic heart disease, non-obstructive coronary artery disease, small vessel disease, small artery disease, and ischemia with no obstructive coronary arteries (INOCA)

Coronary microvascular dysfunction (CMD) is a disease that causes narrowing of the small blood vessels that are responsible for supplying oxygen-rich blood to the heart muscle. This condition decreases the amount of blood flow to the heart, leading to frequent chest pain (angina), affecting approximately 8.3 million people in the U.S. (1),(2); however, many people with CMD don’t even know they have it, as angiography reveals no blockage of the large vessels supplying the heart, such that the angina is often attributed to other causes.

Clogging or narrowing of the arteries that supply blood to your heart can occur not only in your heart’s largest arteries (the coronary arteries), but also in your heart’s smaller blood vessels (the microvasculature). Coronary artery disease (CAD) involves plaque formation that can block blood flow. In CMD, the heart’s small blood vessels do not have plaque, but instead have damage to the inner walls of the blood vessels that can lead to spasms and decreased blood flow to the heart muscle, causing chronic chest pain (angina), shortness of breath, fatigue, heart attack and heart failure.(3)

Women more frequently develop CMD than men, particularly younger women (4),(5). Conditions that increase a person’s risk of having coronary microvascular dysfunction include high blood pressure (hypertension), diabetes, high cholesterol, smoking, autoimmune disease, prior breast cancer treatment, as well as other unknown factors.

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CMD represents a large unmet medical need

  • ~112 million people globally are affected by angina (6)
  • 10% – 30% of patients with angina have no significant large vessel CAD on invasive coronary angiography (7), (8)
  • 50% – 65% of patients with angina without obstructive large vessel CAD are believed to have CMD (9)

Our Approach: CLBS16

Mechanism of Action in Coronary Microvascular Dysfunction

MOA CMD

What is CLBS16 cell therapy?

CLBS16 is an experimental regenerative medicine that was studied in a recently completed positive Phase 2a trial (known as the ESCaPE-CMD trial), which study showed statistically significant improvement in coronary flow reserve (CFR) along with a reduction in angina frequency and severity, and improvements in quality of life (11), (12). CLBS16 is currently being studied in a newly initiated Phase 2b study (known as the FREEDOM trial) taking place in the United States for the treatment of CMD.

CLBS16 cell therapy is made from a patient’s own blood cells (meaning it is autologous), specifically, special blood vessel forming cells called CD34+ cells. CLBS16 is intended for people who experience chronic chest pain (angina) due to impaired blood flow to the heart (despite not having visibly blocked arteries). Previous research revealed that CD34+ cells play an important part in the body’s natural healing process and have the ability to promote the development and formation of new microvasculature, thereby leading to increased flow of oxygen-rich blood to the heart muscle.

FREEDOM Trial:

A placebo-controlled Phase 2b study of CLBS16 in subjects with Coronary Microvascular Dysfunction

This double-blind, randomized, placebo-controlled Phase 2b trial will evaluate the efficacy and safety of delivering autologous CD34+ cells in subjects with CMD and without obstructive CAD. To learn more about this ongoing clinical trial, please visit: clinicaltrials.gov, Identifier: NCT04614467, or the FREEDOM trial website at www.freedom-trial.com.

Study Design


Endpoints:

  • Change from baseline in angina frequency
  • Change from baseline in total exercise time 
  • Change from baseline in health-related quality of life 
  • Change from baseline in peak coronary flow reserve

Study size:

105 subjects (~10 sites in the U.S.)


Dose:

1 x 106 to 300 x 106 CD34+ cells or placebo


Mode of administration:

Single intracoronary infusion


Timing:

  • Study initiated 4Q2020
  • Complete Enrollment: Year-End 2021
  • Top-line Data Target: 3Q2022

References

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