A full manuscript detailing this work is now available on medRxiv and this blog serves as a brief introduction to that research. These data were first presented at IDWeek 2024.
GB-0669, an AI-engineered neutralizing monoclonal antibody targeting SARS-CoV‑2, was built for durability against viral evolution. It binds a conserved epitope in the S2 stem helix of the spike protein and incorporates Fc engineering to extend half-life, enabling longer dosing intervals and potentially single-dose administration in treatment settings. Generative, ML-guided optimization was used to improve potency and developability while preserving epitope breadth.
The first-in-human study was a randomized, placebo-controlled, single-ascending-dose (100‑2400 mg) trial in healthy adults. Safety and pharmacokinetics were the primary endpoints; pharmacodynamics included ex vivo serum live virus neutralization against circulating variants (e.g., BA.5.5, XBB.1.5) and a neutralizing-index model relating observed serum concentrations to a therapeutic threshold.
GB-0669 was well tolerated with no dose-limiting toxicities or serious adverse events; most adverse events were Grade 1–2, and a single Grade 2 infusion-related reaction resolved with treatment. Exposure was dose-proportional through 2400 mg with a typical half-life of ~54 days and an apparent volume of distribution of ~6 L. Anti-drug antibodies were infrequent with no observed impact on pharmacokinetics.
In ex vivo viral neutralization assays, patient serum showed clear, dose-dependent increases, separating from placebo at mid-to-high doses and remaining elevated over the two-week sampling window. By the neutralizing-index framework, modeled activity stayed well above the therapeutic index after a single 1200 mg infusion. At 1200 mg, the neutralizing index was 15, well above the therapeutic threshold for efficacy (neutralizing index of 1) throughout the two-week window.
In vitro, GB-0669 combined with remdesivir, nirmatrelvir, or molnupiravir improved neutralization against JN.1 compared with either agent alone. These are laboratory findings, not clinical outcomes, but they support a multi-modality approach using GB-0669 in combination with antivirals for treatment of chronic infection or prevention of infection in high-risk populations.
Given the current commercial landscape, we have deprioritized internal development of GB-0669. The work delivered promising results and produced strong data and learnings. The ability of GB-0669 to target current and future variants makes it a valuable candidate for addressing future viral threats.
Further Reading & Resources
For deeper context and background materials, see the resources below:
- GB-0669, PRO-37587
- GB-0669