A Study to Evaluate Mesenchymal Stem Cell Product StromaForte's Effect on Cardiovascular Events

Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels including, among other coronary heart, cerebrovascular, and peripheral arterial diseases that are difficult to reverse once clinically verified. According to the WHO, CVDs are the leading cause of death globally, taking an estimated 17.9 million lives each year. More than four out of five CVD deaths are due to heart attacks and strokes, and one third of these deaths occur prematurely in people under 70 years of age (1). The onset of CVD may seem binary for the individual patient, one day one is healthy and the next one has suffered an event such as a myocardial infarction or a stroke. Thereby a vast majority of the treatments are interventions when a cardiovascular event happens, and consequently preventative efforts are mostly secondary prevention oriented, and therapies are often reduced to a monitoring of symptoms.

However, while some people are genetically predisposed to develop CVDs, everyone is at risk. CVDs is a group of aging- related chronic diseases, similarly to diabetes and arthritis, with an earlier onset than an eventual cardiovascular event. The vascular pathophysiology leading up to the first CVD event has often been gradually developing asymptomatically over years, driven by among other things tissue inflammation, endothelial dysfunction, and increased blood pressure, before the individual becomes aware of it. It is widely shown that ageing related diseases, like CVDs, are a huge challenge for societies around the globe, and that these groups consume up to 70-80 % of healthcare resources. Thus, healthy longevity is not only of interest for the individual but to society as well. If we are to reach the UN Sustainable Development Goal (SGD) #3 - Good Health and Wellbeing, prevention of diseases at an earlier stage is thought to play a key role.

The concept of preventive medicine is in its prime but there is a need for more research and scientific evidence around how to foster healthy longevity by retarding or preventing, among other things, the chronic inflammation that often drives the development of ageing related diseases. Acknowledging the gradual development of CVD, not only secondary prevention but also primary preventative treatment is an interesting strategy to examine further. Stem cells hold promise for mitigating the risk factors and reducing the incidence of these major health conditions. Due to their anti-inflammatory, regenerative, and immunomodulatory effects MSCs are an especially interesting candidate of preventive treatments, i.e., even for individuals without clinical symptoms, since ageing related diseases and vascular degeneration are partly driven by inflammation accelerated or slowed down by individual lifestyle, comorbidities, inherited genetics, age, and many other factors.

The Mesoblast DREAM-HF study published in 2023, indicated that there may be a potential secondary preventative effect of MSC on CVD. Mesenchymal Precursor Cell (MPC) therapy with local injection in the heart muscle did not meet its primary and secondary endpoints but resulted in significant reduced risk for time-to-first Major Adverse Cardiac Event (MACE) defined as cardiovascular death, Myocardial Infarction (MI) or stroke over a mean follow-up of 30 months with the most benefit seen in patients with evidence of systemic inflammation. The study also demonstrated a strengthened heart function, which was measured by the left ventricular ejection fraction (LVEF) for patients receiving the treatment compared to the control group.

To investigate the preventive, mitigating, and/or retarding effects of MSCs for the gradual disease development and/or degeneration across multiple cohorts of different risks this study is designed to follow a large and diverse study participant population over a long period of time (five years). All enrolled study participants will be risk stratified and categorized into different cohorts based on the well-established cardiovascular risk assessment tool Atherosclerotic Cardiovascular Disease (ASCVD) Risk calculator developed by American College of Cardiology and complementary questionnaires. All enrolled study participants will receive an initial dose of 100 x 106 MSCs that can be repeated at a minimum interval of 3 months. The endpoints collected from enrolled study participants will be compared to baseline as well as with the expected rates/outcomes from risk matched cohorts/patients in relevant open label registries (Real World Data - RWD) across the globe.

The study will assess changes in study participants' risk and life/lifestyle (based on the gold standards) from baseline throughout the study to account for external factors that might impact the disease's development. The study will also identify subgroups of study participants based on the number of doses received and the treatment frequency to assess the potential cumulative effects of the MSCs to provide new insights around host and dose response. To have a rich dataset and a more accurate comparison to cohorts in other registries, the ambition is to include data from follow-up visits and, by written consent from the study participants, study participants own general medical records, health scans and additional blood works. Ultimately, this study seeks to investigate the safety and efficacy of MSC therapy for preventing cardiovascular diseases by comparing individuals of the same risk-level that have received a MSC treatment against matched controls from RWD