Randomized, Double-Blind, Placebo-Controlled First-in-Human Trial of a First-in-Class AI-Designed Monoclonal Antibody (GB-0669) Against the Conserved SARS-CoV-2 Spike S2 Stem Helix
et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiag349, Jul 2026
Phase 1 double-blind, placebo-controlled RCT of 51 healthy volunteers showing that GB-0669 - an AI-designed, half-life-extended monoclonal antibody targeting the conserved SARS-CoV-2 spike S2 stem helix - was well-tolerated, with no dose-limiting toxicities and only grade 1-2 adverse reactions across five ascending single intravenous doses.
Borriello et al., 14 Jul 2026, Double Blind Randomized Controlled Trial, placebo-controlled, peer-reviewed, 19 authors.
GB-0669 is a half-life-extended, AI-designed monoclonal antibody targeting the conserved SARS-CoV-2 spike S2 stem helix, administered as a single intravenous infusion.
DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Antibodies against the SARS-CoV-2 spike receptor-binding domain provided effective COVID-19 treatment until resistant variants emerged. GB-0669 is a half-life-extended monoclonal antibody optimized using artificial intelligence. It targets the conserved spike S2 stem helix, a region subject to limited selective pressure from antibody responses induced by natural infection or vaccination.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>Pre-clinical safety studies were conducted in cynomolgus monkeys. In the first-in-human trial, healthy adults aged 18–55 received single intravenous doses of GB-0669 or placebo in five ascending cohorts (100, 300, 600, 1200, and 2400 mg). Participants were monitored for 43 weeks to evaluate safety, pharmacokinetics (PK), and pharmacodynamics (PD; serum live virus neutralization). In vitro studies assessed neutralization of GB-0669 combined with antiviral drugs (remdesivir, nirmatrelvir, and molnupiravir).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Pre-clinical studies revealed no safety concerns. In the clinical trial (n=51; 36 GB-0669, 15 placebo), GB-0669 was well-tolerated without dose-limiting toxicities; all adverse reactions were mild (Grade 1 or 2). PK showed dose-proportionality up to 2400 mg, with a half-life of 54 days. Dose-dependent increases in serum live virus neutralization occurred at 600 and 1200 mg, with separation from placebo. The estimated neutralizing index that adjusts GB-0669 serum concentrations for its in vitro neutralizing potency supported therapeutic efficacy for two weeks post-administration. Finally, in vitro experiments showed improved neutralization profiles of GB-0669 in combination with antivirals.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>The data support exploring GB-0669 at 1200 mg in a Phase 2 trial for treating COVID-19 in immunocompromised individuals. The combination of GB-0669 with antiviral drugs may offer additional therapeutic benefits.</jats:p>\n </jats:sec>",
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