As the newest global medical emergency, the COVID-19 (diagnosed SARS-CoV2 infection with lung

involvement) exhibits features that are unlikely ameliorated by antivirals-based approaches

alone. First, although the new coronavirus (SARS-CoV-2) infect lung and intestine, many

patients suddenly take a turn for the worse even when the viral replication appears to be

under control. Second, patients with serious or critical clinical symptoms show remarked T

cell lymphopenia that are more severe and more acute than human immunodeficiency virus (HIV)

infection. Functional exhaustion of T cells is suggested by high expression of T-cell

exhaustion markers, which again appears more acute than in HIV patients. Third, multiple

cytokines are elevated among patients with severe clinical symptoms, which potentially

explains the multiple organ failure associated with COVID-19. For these reasons, treatment of

COVID-19 likely requires a combination of both antivirals and non-antivirals-based

approaches.



CD24Fc is a biological immunomodulator in Phase II/III clinical trial stage. CD24Fc comprises

the nonpolymorphic regions of CD24 attached to the Fc region of human IgG1. We have shown

that CD24 is an innate checkpoint against the inflammatory response to tissue injuries or

danger-associated molecular patterns (DAMPs). Preclinical and clinical studies have

demonstrated that CD24Fc effectively address the major challenges associated with COVID-19.

First, a Phase I clinical trial on healthy volunteers not only demonstrated safety of CD24Fc,

but also demonstrated its biological activity in suppressing expression of multiple

inflammatory cytokines. Second, in Phase II clinical trial in leukemia patients undergoing

hematopoietic stem cell transplantation (HCT), three doses of CD24Fc effectively eliminated

severe (Grade 3-4) acute graft vs host diseases (GVHD), which is caused by over reacting

immune system and transplanted T cells attacking recipient target tissues. Third, in

preclinical models of HIV/SIV infections, we have shown that CD24Fc ameliorated production of

multiple inflammatory cytokines, reversed the loss of T lymphocytes as well as functional T

cell exhaustion and reduced the leukocyte infiltration of multiple organs. It is particularly

noteworthy that CD24Fc reduced the rate of pneumonia in SIV-infected Chinese rhesus monkey

from 83% to 33%. Therefore, CD24Fc maybe a prime candidate for non-antiviral biological

modifier for COVID-19 therapy. The phase III trial will involve 270 patients randomized into

blinded placebo and CD24Fc arms, with time to clinical improvement from critical or severe to

mild symptom as the primary endpoint.