CD388: A universally protective Drug-Fc Conjugate that targets influenza virus neuraminidase

SUMMARY The ability of the influenza virus to elude humoral immunity by rapid antigenic shift presents a sustained and urgent threat to human health. Globally, seasonal influenza causes an estimated 3 - 5 million cases of severe disease and 300,000 - 500,000 deaths annually, with increased potential for mortality during pandemics 1 . The recent outbreaks of avian H5N1 in bird populations, subsequent spread to cattle and appearance in humans, highlight the need for effective broad-spectrum influenza antivirals for treatment, prophylaxis and pandemic preparedness. The narrow, strain-specific immunity induced by current seasonal vaccines and mismatches between vaccine strains and circulating viruses result in limited vaccine effectiveness (VE) rates 2 . Furthermore, VE is even lower in immune-compromised and - senescent populations 3 . Strategies that provide durable, universal influenza protection in healthy and high-risk populations are urgently needed. Here, we describe CD388, a first-in-class antiviral drug-Fc conjugate (DFC) in clinical trials for seasonal influenza prevention ( NCT05285137 and NCT05523089 ). CD388 comprises a multivalent small molecule inhibitor of influenza virus neuraminidase (NA) linked to a C H 1-Fc hybrid domain of human IgG1 engineered for extended half-life. CD388 demonstrated potent, universal activity across influenza A and B viruses, including high pathogenicity and NA resistant strains, a low potential for resistance development, and efficacy in lethal mouse infection models. CD388 is the first therapeutic with the potential for universal prevention of influenza A and B in healthy and high-risk populations.