162 - CD377, a Novel Antiviral Fc-conjugate, Demonstrates Potent Viral Burden Reduction Against Influenza a (H1N1) in Mouse and Ferret Models

Background: AVCs (antiviral Fc-conjugates) are novel, long-acting immunotherapeutic conjugates of potent antivirals conjugated to the Fc domain of human IgG1. CD377, an AVC development candidate for the prevention and treatment of influenza A and B, comprises multiple copies of a novel neuraminidase inhibitor conjugated to IgG1 Fc. CD377 demonstrated potent, broad-spectrum activity in vitro and in lethal mouse models. Herein, we characterize the activity of CD377 on viral lung burden in lethal mouse models and in a ferret model of influenza A (H1N1) infection.

Methods: BALB/c mice were challenged intranasally with 3 x 10² PFU of influenza A/PR/8/1934 (H1N1) or with 3 x 10⁴ PFU A/CA/07/2009 (H1N1)pdm. Ferrets were challenged sub-lethally at 1 x 10⁶ PFU with influenza A/CA/07/2009 (H1N1)pdm. A single dose of CD377 was given 2 h post-challenge in the mouse (subcutaneous dose ranging from 0.1 – 3 mg/kg) or 24 h prior to challenge in the ferret (intravenous dose ranging from 0.3 – 30 mg/kg). In mice, oral oseltamivir was given at  5 mg/kg (human equivalent dose, HED) or at 50 mg/kg BID x 4 days starting at 2 h post-challenge and in ferrets at 20 mg/kg (4x HED) BID x 4 days starting at 4 h prior to infection. Viral burden was determined on day 4 (mouse) or days 2 and 4 (ferret) post-challenge by plaque assay.

Results: In mice, CD377 demonstrated dose-dependent reduction in viral lung burden (1.1 logs at 0.1 mg/kg, 2.1 logs at 0.3 mg/kg, 3.1 logs at 1 mg/kg and 3.6 logs at 3 mg/kg) compared to PBS against influenza A/PR/8/1934 (H1N1) (Fig. 1A). In the same study, oseltamivir reduced viral lung burden only by 0.8 logs at both 5 mg/kg (HED) and 50 mg/kg. No significant reduction in lung burden was observed between negative controls, PBS and hIgG1 Fc. Similarly, CD377 demonstrated a dose-dependent, multi-log reduction in viral lung burden against influenza A/CA/07/2009 (H1N1)pdm (Fig. 1B). In ferrets, CD377 reduced viral load with dose dependency at days 2 (Fig. 1C) and 4 post-infection (Fig. 1D). CD377 at 3 mg/kg or higher dose was superior compared to oseltamivir at 4x HED on days 2 and 4 post-challenge.Figure 1. CD377 demonstrates dose-dependent reduction in viral burden in mice (A, B) and ferrets (C, D)


Conclusion: CD377 demonstrated superior viral load reduction compared to oseltamivir in lethal influenza A (H1N1) mouse and ferret models. These data support further development of CD377 for prevention and treatment of influenza infection.

Presenting Author(s)

• 

  Simon Döhrmann, PhD

  Senior Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)

  Slides Slides and Audio

Co-Author(s)

• AA

  Amanda Almaguer, Bachelors

  Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)
• ND

  Nicholas Dedeic, n/a

  Research associate
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Employee)
• KA

  Karin Amundson, BSc

  Senior Research Associate
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics: Shareholder
• KS

  Kim Shathia, B.S.

  Contract Researcher
  Cidara Therapeutics
  San Diego, California

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TB

  Thomas P. Brady, PhD Chemistry

  Principal Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Employee)
• AN

  Alain Noncovich, Ph.D.

  Senior Scientist II
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)
• QZ

  Qiping Zhao, BS

  Scientist
  Cidara
  San Diego, California

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• GH

  Grayson Hough, MS - Chemistry

  Senior Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Employee)
• AB

  Allen Borchardt, PhD

  Director
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Employee)
• JL

  Jeffrey B. Locke, PhD

  Director, Microbiology
  Cidara Therapeutics, Inc.
  San Diego, California

  Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)
• JC

  Jason Cole, PhD

  Senior Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)
• 

  James Levin, PhD

  Senior Director
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)