First-in-Woman Safety, Tolerability, and Pharmacokinetics of Orally Administered #GS441524: A Broad-Spectrum Antiviral Treatment for #COVID19. A 1/7 https://osf.io/am5s8/ 

Part 1 of the study: 750 mg GS-441524 was orally administered as a solution QD for 7 days. D1-5 were performed in the fasted state. D6-7 in the fed state. There was a slight food effect that seemed to hamper drug absorption. Cmax ~2.4-3 uM. AUC ~26-33 uM. 2/7

No AEs or lab abnormalities were observed in Part 1 of the study. Blood chemistry was normal. 3/7

Part 2 of the study: 750 mg GS-441524 was orally administered as a solution TID, every 3 h, for 3 days. PK for D1 shown below. Cmax ~12 uM achieved 3 hours after the third dose, which surpasses that which is necessary to eradicate SARS-CoV-2 in vitro. AUC = 166 uM. 4/7

No AEs or lab abnormalities observed in Part 2 of the study. Blood chemistry was normal. 5/7

How does PO GS-441524 compare to IV RDV? Very favorably. TID dosing easily and surpasses the 10 uM necessary to eradicate SARS-CoV-2 in vitro (Cmax ~12 uM). In contrast, the Cmax of the highest dose of RDV is unable to achieve the 20 uM necessary to eradicate SARS-2 in vitro 6/7

Likewise, GS-441524 demonstrates better human exposure than both #molnupiravir and #AT527, which are currently being investigated in ph2/3 for COVID-19. All this to say: GS-441524 needs be translated to the clinic ASAP. 7/7