A Phase 2b Clinical Trial to Study the Efficacy of Longeveron Mesenchymal Stem Cells (LMSCs) to Treat Aging Frailty

Aging Frailty is a biologically driven geriatric syndrome of multisystem physiological decline that is distinct from normal aging and disproportionately increases vulnerability to adverse clinical outcomes. Frailty has an overall prevalence of 10% of those 65 years and older, and there is growing awareness in the geriatric community to diagnose and treat this condition, as it is not an inevitable consequence of aging. The American Geriatrics Society has published a “Geriatrics Evaluation andamp; Management Tools—Frailty” to aid practicing physicians in the diagnosis of Aging Frailty, and frailty-dedicated societies and journals now exist due to the urgent need to develop effective intervention. There are no FDA-approved therapies for treating Aging Frailty, but a biologically driven cell-based therapy could have a major beneficial impact.The pathophysiology of Aging Frailty includes an accentuated pro-inflammatory state that can promote systemic tissue damage, including muscle atrophy. Mesenchymal stem cells (MSCs) have potent anti- inflammatory and pro-regenerative properties, making them an ideal therapeutic candidate for Aging Frailty. Longeveron is a manufacturer of a proprietary formulation of allogeneic MSCs, called LMSCs, which are being evaluated for therapeutic efficacy to treat Aging Frailty in this Phase 2b trial.We recently completed a Phase 1/2 clinical trial to demonstrate the safety and tolerability of this approach for treating Aging Frailty. That trial not only demonstrated the high safety profile of this therapeutic approach, it provided provisional data showing efficacy. The Phase 2b trial of this proposal represents the next step in clinical development of LMSCs as a therapeutic candidate for Aging Frailty. This trial has been designed with guidance from FDA and international leaders in geriatrics, which was used to define enrollment criteria and endpoints. FDA guidance for this clinical program is that a registrational endpoint would need to be a composite of surrogates for long-term clinical outcomes (e.g., falls, fractures, hospitalizations, institutionalization, and death). Specifically, this composite would entail endpoints in 3 domains relevant to Aging Frailty: a metric of functional capacity; a patient-reported outcome (PRO); and a biomarker. This Phase 2b trial is designed to examine endpoints in these 3 domains in order to develop a composite endpoint to ultimately test prospectively in a Phase 3 study for registrational purposes.This proposal addresses a truly novel application of cell-based therapy that could become the first FDA- approved treatment for Aging Frailty. We believe that Aging Frailty is an outstanding candidate indication for LMSC therapy, supported by mechanism of action, preclinical data, and Longeveron’s Phase 1/2 clinical data, and has gained the support and endorsement of key opinion leaders in the field. Accordingly, this study is highly timely, and has a high probability of making an extraordinary impact on a major unmet need, as well as on regenerative medicine.Aging Frailty is a large and growing unmet medical need that affects about 10% of those age 65 years and older. It is a biologically driven geriatric syndrome that is distinct from normal aging, and disproportionately increases vulnerability to adverse clinical outcomes. There are no FDA-approved therapies for treating Aging Frailty. The pathophysiology of Aging Frailty includes an accentuated pro-inflammatory state that can promote systemic tissue damage, including muscle atrophy. Mesenchymal stem cells (MSCs) have potent anti-inflammatory and pro-regenerative properties, making them an ideal therapeutic candidate for Aging Frailty. In this clinical study, Longeveron will test a proprietary formulation of allogeneic MSCs, called LMSCs, for therapeutic efficacy to treat Aging Frailty. This study is highly timely, and has a high probability of making an extraordinary impact on a major unmet need, as well as on regenerative medicine.