Efficacy of Inhaled Exosome EXO-CD24 in Severe ARDS

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. ARDS is a major health concern with 3 million new cases annually. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. EXO-CD24 was designed as a targeted therapy for hyperactive immune systems in the context of ARDS induced by COVID-19.

Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS).

Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. The analysis was performed simultaneously using an array-based multiplex ELISA system.

Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital.

Conclusions: EXO-CD24 shows potential as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favourable safety profile without any apparent side effects with promising efficacy. EXO-CD24 has the potential to be a platform for addressing hyper-inflammatory states, which needs further exploration.. However, validation of these preliminary findings requires further research and larger-scale clinical trials.