Topline safety and pharmacokinetic (PK) data from the Phase I single ascending dose (SAD)/multiple ascending dose (MAD) study of STI-1558 in 58 healthy volunteers in Australia are now available. The SAD portion of the study evaluated doses from 300 mg to 2,000 mg and the MAD portion evaluated 300 mg, 600 mg or 800 mg BID (twice a day daily) for 7.5 days.
Overall, STI-1558 was well-tolerated at these doses with most subjects reporting no adverse events (AEs). There was no dose limiting toxicity during the study. There were no severe or serious AEs, no premature discontinuation of STI-1558 due to an AE, and no deaths. Most AEs were mild and unrelated. The PK profile was dose proportional; the mean AUC (h*µg/mL) in the SAD 300 mg, 600 mg, 1200 mg and 2000 mg cohorts was 14.3, 29.2, 43.8 and 93.3, respectively. In the MAD cohorts (300 mg BID, 600 mg BID and 800 mg BID), no accumulation was seen and trough concentrations (Ctrough) were 225 ng/mL, 475 ng/mL and 506 ng/mL, respectively. Even the lowest dose produced trough levels significantly above the EC90 value for viral inhibition of STI-1558. These data confirm adequate blood levels were achieved without the need for Ritonavir.
A similar Phase I/Ib SAD/MAD study has been fully enrolled in China in both healthy subjects and patients infected with SARS-CoV-2. The PK profile in China was similar to that seen in Australia. Preliminary safety and efficacy data found that the safety profile was comparable between healthy uninfected subjects and infected subjects and that STI-1558 resulted in a dramatic rapid reduction in viral load.
Phase II/III protocols of STI-1558 600 mg BID for 5 days as a standalone treatment of COVID-19 have been submitted to various regulatory agencies including the US FDA, Mexico COFEPRIS and China.
Testing to date has demonstrated that the antiviral activity of STI-1558 on the Mpro protein is not impacted by the spike mutations of emerging variants NMPA.
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