An exosome-based anti-inflammatory drug.
Potential treatment - clinical evidence
EXO-CD24 is an anti-inflammatory formulation combining an immune checkpoint CD24 and an exosomal delivery platform (Shapira et al., 2022). Exosomes are a class of nano-sized cell-derived extracellular vesicles. They carry various types of natural or engineered cellular components or substances (Zhang et al., 2020). CD24 is a membrane-bound protein inhibiting NF-κB signalling pathway. As an immune checkpoint it facilitates discrimination between molecular patterns associated with cellular damage and those derived from pathogens. EXO-CD24 was shown to reduce markers of inflammation in moderate to high severity COVID-19 patients in a phase Ib/IIa clinical trial (Shapira et al., 2022).
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A novel platform for attenuating immune hyperactivity using EXO-CD24 in COVID-19 and beyond
Severe severity Cell-based therapy Cryo-EM Non-randomized non-controlled open trial Novel compound Animal model Phase II clinical trial Phase I clinical trial Moderate severity Mixed substance Extracellular vesicles
|cryo-EM; U937 cells; BALB/c mice; C57bl mice; moderate to severe COVID-19 patients||12.14||
The formulation inhibited PMA-induced secretion of cytokines/chemokines in vitro. A murine version of the formulation did not display organ toxicity in mice, it reduced lung inflammation in a murine ARDS model and increased survival in a sepsis model. In moderate to severe COVID-19 patients, the treatment resulted in lowered respiratory rate, increased blood oxygen saturation, decrease in CRP levels, and generally also subjective improvement in clinical status. The drug had a favourable safety profile. Sample size: 5 (10^8 particles per dose) + 5 (5x10^8 particles per dose) + 19 (10^9 particles per dose) + 5 (10^10 particles per dose). Dosage: From 10^8 up to 10^10 particles inhaled in a dose-escalation scheme. Main outcome: Multiple safety and efficacy endpoints.