Potential Use of Enzo’s Drug Candidate SK1-I

For the Prevention and/or Treatment of Cytokine Release Syndrome and Respiratory Failure in COVID-19 Patients
 

Enzo has been developing a patented small molecule sphingosine kinase 1 inhibitor, called SK1-I, as a therapeutic for cancer and autoimmune disorders. The compound has previously demonstrated potent immune modulating activity on human immune cells in vitro and in whole-animal models. SK1-I has recently shown strong activity in a mouse model of lupus, including the ability to decrease levels of the inflammatory cytokines IL-6, TNF-alpha, and both Interferon-alpha and -beta. (See Mohammed et al., Regulatory role of SphK1 in TLR7/9-dependent type I interferon response and autoimmunity, FASEB J. 2020 Mar; 34(3): 4329-4347.) Further, in unpublished work performed by Enzo, SK1-I was able to suppress Influenza antigen-mediated release of Interferon-gamma by human peripheral blood mononuclear cells (PBMCs) obtained from an Influenza-vaccinated donor. Significantly, elevated levels of IL-6 have been shown to be predictive of respiratory failure in COVID-19 patients (see Herold et al., Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients, medRxiv 2020.04.01.20047381; doi: https://doi.org/10.1101/2020.04.01.20047381 ) and it is reported that cytokine release syndrome or “cytokine storm” is associated with poor prognosis and mortality. Preclinical animal toxicology work with SK1-I suggests that the compound could be safely dosed in humans at levels that correlate with those found to reduce inflammatory cytokines in animal models. Accordingly, Enzo believes that SK1-I may have potential for preventing and/or treating cytokine release syndrome and respiratory failure in COVID-19 patients. The Company is reaching out to the Food and Drug Administration for guidance on the further development of SK1-I for COVID-19.