159 - efficacy of CD377, a Novel Antiviral Fc-conjugate, Against Seasonal Influenza in Lethal Mouse Infection Models

Background: Cidara’s AVCs (antiviral Fc-conjugates) are novel conjugates of potent, antiviral agents with the Fc domain of human IgG1. CD377 is an AVC development candidate for prevention and treatment of influenza that has broad anti-neuraminidase activity in both enzymatic and cell-based assays and the potential to engage the immune system, as well as a long half-life.

Methods: Efficacy studies were conducted in BALB/c mice lethally challenged intranasally at 3x the LD₉₅ with influenza A (H1N1, H3N2) and influenza B (both lineages).  CD377 was administered as a single dose subcutaneously (SC) 2 hours after viral challenge.  Body weights (BW) and health scores were monitored daily, with 20% BW loss recorded as a mortality.

Results: In mice challenged with a lethal dose of an H1N1 strain (A/California/12/2012), a single 0.3 mg/kg dose of CD377 administered 2 hours post-challenge was fully protective (P=0.0015 relative to vehicle) (Fig 1A).  In a similar study against a mouse-adapted H3N2 subtype (A/Hong Kong/1/1968), a single dose of CD377 at 0.1 mg/kg was fully protective (P=0.0025) (Fig 1B).  In both studies, only a transient loss of BW was observed before mice began recovering weight.
The activity of CD377 was also evaluated against both lineages of influenza B (Fig 1C, 1D).  Against influenza B/Colorado/06/2017 (Victoria), a single CD377 dose of 0.3 mg/kg was fully protective (P=0.0035) while the Fc-only control dosed at 1 mg/kg was not, as expected.  Against the Yamagata lineage (B/Florida/4/2006), CD377 demonstrated full protection at a dose of only 0.03 mg/kg (P=0.0023).

Conclusion: A single dose of CD377 (0.3 mg/kg or less) was protective against lethal challenge with several seasonal influenza A/B subtypes.  The exceptional PK profile of CD377 combined with potent broad-spectrum activity highlight its potential for use as a long-term preventative against seasonal influenza.Seasonal influenza efficacy

Presenting Author(s)

• 

  James Levin, PhD

  Senior Director
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)

  Slides Slides and Audio

Co-Author(s)

• 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.
• AB

  Allen Borchardt, PhD

  Director
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Employee)
• TL

  Thanh Lam, PhD

  Senior Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)
• TB

  Tom Brady, Ph.D.

  Senior Principle Scientist
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)
• AN

  Alain Noncovich, Ph.D.

  Senior Scientist II
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics (Shareholder)
• 

  James Levin, PhD

  Senior Director
  Cidara Therapeutics
  San Diego, California

  Disclosure: Cidara Therapeutics: Shareholder

  Slides Slides and Audio