Human heart with blood vessels rendering

Coronary Microvascular Dysfunction (CMD) - XOWNA®

What is Coronary Microvascular Dysfunction (CMD)?

Also known as coronary microvascular disease, microvascular angina, cardiac syndrome X, non-obstructive coronary 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 (microvasculature) 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) Many people with CMD are unaware of their condition, as during evaluation for chest pain, angiography reveals no blockage of the large vessels supplying the heart. Often, their angina is attributed to other causes.

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.

Our Approach: XOWNA® (LSTA16) for the treatment of coronary microvascular dysfunction

What is XOWNA®?

XOWNA® is an experimental regenerative therapy for the treatment of CMD. It is made from a patient’s own blood cells (meaning it is autologous), specifically, special blood vessel forming cells called CD34+ cells. XOWNA® 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.

XOWNA®  was previously studied in a positive Phase 2a clinical trial (known as the “ESCaPE-CMD trial”), which 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). XOWNA® was also evaluated in a U.S. Phase 2b study (known as the “FREEDOM Trial”) for the treatment of CMD.

about cell therapies

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)

In the United States, there is an addressable population of approximately 400,000 to 1,600,000 patients with CMD, while the addressable population is roughly 1,200,000 to 4,800,000 in the EU and between 43,000 and 166,000 in Japan (10).

Patient Testimonial

Investigational Clinical Trial of XOWNA®

As previously disclosed, in December 2020, the Company commenced enrollment in its Phase 2b FREEDOM Trial of XOWNA®, a double-blind, randomized, placebo-controlled clinical trial designed to further evaluate the efficacy and safety of intracoronary artery delivery of autologous CD34+ cells in subjects with Coronary Microvascular Dysfunction (CMD) and without obstructive coronary artery disease and was expected to complete enrollment in approximately 12 months. While early enrollment proceeded to plan with the first patient treated in January 2021, the COVID-19 pandemic resulted in insurmountable enrollment rate challenges and population heterogenicity. As a result, in May 2022, the Company announced that enrollment in the FREEDOM Trial had been suspended and that it intended to conduct an interim analysis of the data from not less than the first 20 patients enrolled using the 6-month follow-up data to evaluate the efficacy and safety of XOWNA® in subjects with CMD. Following the analysis of results of the FREEDOM Trial subjects completing 6-month follow-up along with Key Opinion Leaders’ input, the Company’s board of directors determined that execution of a redesigned FREEDOM-like trial would be the appropriate next step, but the cost of such a trial would be prohibitively expensive to undergo alone without a strategic partner. Accordingly, the Company’s board of directors concluded that XOWNA® development will only be continued if a strategic partner that can contribute the necessary capital for a redesigned trial is identified and secured. There can be no assurance that we will be able to identify such a partner and enter into an agreement with such partner on acceptable terms or at all.

XOWNA® (LSTA16) (U.S.)
Pre ClinicalPhase 1Phase 2Phase 3
Phase 2b (FREEDOM)
Phase 2
Indication: Coronary Microvascular Dysfunction
Partner/Sponsor: Lisata | Location: United States
Next Development Milestone: Partner sought to advance development
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References

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