CLXR-001 is based on a specific immunomodulatory progenitor or iMP cell that is designed to survive and persist in the cardiac environment following administration during coronary artery bypass graft (CABG) surgery. The therapeutic effect is mediated through a combination of immune modulation, vascular repair, and extracellular matrix remodelling. CLXR-001 expresses a distinctive set of receptors and secretory molecules, including CD304, EGFR, CD363, and IL-8R, which contribute to its regenerative capabilities. They promote cardiomyocyte proliferation, reduce apoptosis, and modulate the activity of matrix metalloproteinases (MMPs) by increasing the expression of tissue inhibitors, such as TIMP1 and TIMP2. This leads to a reduction in scar tissue and remodelling of the extracellular matrix, which is critical for restoring heart function.

Cardiogeni’s Phase IIa clinical trial (ID: NCT01753440), conducted at AHEPA University Hospital in Thessaloniki, Greece, was designed to assess the safety and efficacy of the company’s lead candidate, CLXR-001, in patients with heart failure undergoing coronary artery bypass grafting (CABG). Initiated in November 2012 and completed in December 2014, the study enrolled eleven patients diagnosed with ischemic cardiomyopathy (LVEF < 40%), a serious condition characterised by weakened cardiac muscle resulting from inadequate blood supply due to coronary artery disease or prior myocardial infarction. Participants were monitored for up to five years, with primary endpoints including assessments of cardiac function, scar volume reduction, and quality of life. Safety was also a key focus. The trial reported no mortality and no major adverse cardiac events (MACE) at 30 months. There were some transient post-operative complications, such as atrial fibrillation and gastrointestinal bleeding, but none were considered treatment-related or clinically significant in the long term.

The technology has shown significant clinical promise. Left Ventricular Ejection Fraction (LVEF) is a key measure of how well your heart is functioning, specifically, how effectively the left ventricle pumps blood out to the rest of the body. It is a key measure of heart function.

• LVEF 55-70%: Normal heart function

• LVEF 41-54%: Mildly reduced heart function

• LVEF 30-40%: Moderately reduced heart function

• Below 30%: Severely reduced heart function

In the Phase IIa trials, patients treated with CLXR-001 during CABG demonstrated a 30.8% improvement in LVEF, a key measure of heart function, at six months post-surgery. This is in comparison to a 13.9% improvement with CABG alone. The long-term benefits are also notable, with LVEF improvement reaching 33.8% at 12 months post-surgery for those treated with CLXR-001.

The Phase IIa trial also provided a crucial feature of CLXR-001 in improving the proportion of healthy cardiac tissue volume vs. scar tissue volume. The heart is a muscular pump made of specialised cells called cardiomyocytes. When these cells are damaged, typically due to a heart attack or side effect in cardiac surgery, they die and are replaced by scar tissue, which is made of collagen and fibroblasts. Unlike cardiomyocytes, scar tissue is non-contractile and stiff, meaning it doesn’t contribute to pumping and can actually impair it.

With CLXR-001, scar volume was reduced by 33.5% at four months post-surgery and continued to improve at 37.8% at 12 months post-surgery, far exceeding the 1.1% reduction seen with surgery alone at six months.

Following heart surgery, the Minnesota Living with Heart Failure (MLHF) Questionnaire is a widely used, validated tool designed to measure how heart failure affects a patient’s quality of life. It’s a patient-reported outcome measure that captures the physical, emotional, and social limitations caused by heart failure.

Following administration of CLXR-001, quality of life improvements was also substantial, with a 69.8% increase in MLHF scores at 24 months post-treatment, compared with 39% without Cardiogeni’s treatment. Measures also show that improvement is still remaining five years post-surgery. These outcomes suggest that Cardiogeni’s approach not only alleviates symptoms but actively regenerates heart tissue, offering a potential paradigm shift in the treatment of heart failure.

Below is a case study of a 54-year-old patient with a history of heart attacks and a 40% reduction in Left Ventricular Ejection Fraction. The patient’s heart has a 50% scarring of the left ventricle before treatment (black area on the left picture). Heart scarring is the key pathology associated with mortality or morbidity in heart failure, and CABG surgery and other current medical treatments do not reduce heart scarring. Four months after treatment with CLXR-001, the heart scarring is reduced by ca.50% for this patient.

In this instance, the patient experienced a dramatic reduction in scar tissue, which is particularly noteworthy given that conventional therapies, such as CABG surgery, typically do not address or reverse cardiac scarring. This level of improvement not only highlights the effectiveness of CLXR-001 but also demonstrates its potential to change the prognosis for individuals with significant myocardial damage. The reduction in scarring is directly linked to better cardiac function and a lower risk of adverse outcomes, reinforcing the value of regenerative therapies in heart failure management.