Drug-Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice

  • Nat Microbiol. 2025 Apr;10(4):912-926. doi: 10.1038/s41564-025-01955-3.
Simon Döhrmann  #  1 ,  James Levin  #  1 ,  Jason N Cole  #  1 ,  Allen Borchardt  #  1 ,  Karin Amundson  1 ,  Amanda Almaguer  1 ,  Elizabeth Abelovski  1 ,  Rajvir Grewal  1 ,  Douglas Zuill  1 ,  Nicholas Dedeic  1 ,  Grayson Hough  1 ,  Joanne Fortier  1 ,  Joanna Donatelli  1 ,  Thanh Lam  1 ,  Zhi-Yong Chen  1 ,  Wanlong Jiang  1 ,  Travis Haussener  1 ,  Alain Noncovich  1 ,  James M Balkovec  1 ,  Daniel C Bensen  1 ,  Voon Ong  1 ,  Thomas P Brady  1 ,  Jeffrey B Locke  1 ,  Shawn Flanagan  1 ,  Robert M Hughes  1 ,  Jeffrey L Stein  1 ,  Leslie W Tari  2
Affiliations
  • 1. Cidara Therapeutics, San Diego, CA, USA.
  • 2. Cidara Therapeutics, San Diego, CA, USA. [email protected].
  • # Contributed equally.
PMID: 40097766 DOI: 10.1038/s41564-025-01955-3
Abstract

The ability of Influenza Virus to undergo rapid antigenic shift to elude humoral immunity highlights the need for effective broad-spectrum influenza antivirals for treatment, prophylaxis and pandemic preparedness. Strategies providing durable, universal influenza protection in healthy and high-risk populations are urgently needed. Here we describe the design and preclinical characterization of CD388, a first-in-class Antiviral drug-Fc conjugate (DFC), in mice and cynomolgus macaques. CD388 comprises a multivalent conjugate of the Influenza Virus Neuraminidase inhibitor zanamivir, linked to a CH1-Fc hybrid domain of human IgG1 engineered for extended half-life. CD388 improves the Antiviral activity of zanamivir, demonstrating potent, universal activity across influenza A and B viruses, including high pathogenicity and neuraminidase inhibitor resistant strains, a low potential for resistance development and potent efficacy in lethal mouse Infection models. These results suggest that CD388 has the potential for universal prevention of influenza A and B in healthy and high-risk populations.

Products