1283 - New Generation Antiviral Conjugate (AVC): Stable, Safe, and Single

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Presenting Author(s)

VO

Voon Ong

Executive Director, Preclinical Development
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)

Co-Author(s)

James Levin

Senior Director of Preclinical Development
Cidara Therapeutics
San Diego, CA
Disclosure: Cidara Therapeutics (Shareholder)
AB

Allen Borchardt

Director
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Employee)
TB

Thomas P. Brady

Principal Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Employee)
TL

Thanh Lam

Senior Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
AN

Alain Noncovich

Senior Scientist II
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
JF

Joanne Fortier

Research Associate
Cidara Therapeutics
San Diego, CA
Disclosure: Cidara Therapeutics (Employee, Shareholder)
JL

James Levin

Senior Research Associate
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
JL

Jeffrey B. Locke

Sr. Director Microbiology
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)
AA

Amanda Almaguer

Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)
ND

Nicholas Dedeic

Research associate
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Employee)
GH

Grayson Hough

Senior Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Employee)
JC

Jason Cole

Senior Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
Simon Döhrmann

Senior Scientist
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
RG

Rajvir Grewal

Senior Research Associate
Immunology
San Diego, California
Disclosure: Cidara Therapeutics, Inc. (Employee, Shareholder)
EA

Elizabeth Abelovski

Senior Research Associate
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)
JB

James M. Balkovec

Senior Research Advisor
Cidara Therapeutics, Inc
San Diego, California
Disclosure: Cidara Therapeutics (Consultant, Shareholder)
MS

Mike Schlosser

Consultant
Cidara Therapeutics
San Diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KB

Ken Bartizal

Consultant
Cidara Therapeutics, Inc.
San Diego, California
Disclosure: Cidara Therapeutics, Inc. (Consultant, Shareholder)
JL

James Levin

Senior Vice President
Cidara Therapeutics
San Diego, California
Disclosure: Cidara Therapeutics (Shareholder)

Background: CD377 is a novel antiviral Fc-conjugate (AVC) development candidate for influenza prevention and treatment, comprising multiple copies of a novel potent small-molecule antiviral and the Fc domain of human IgG1. CD377 was designed as a stable, long-acting molecule for treatment and prevention of influenza A and B. Studies were conducted to characterize CD377 stability/pharmacokinetics (PK), single-dose efficacy in influenza models, and safety/toxicology.

Methods: PK in the mouse (1-100 mg/kg), rat (5-50 mg/kg), ferret (3 mg/kg), and monkey (5-20 mg/kg) were studied by sampling plasma over a 1-2 week interval. Plasma levels of intact molecule and total Fc were measured by neuraminidase (NA)-capture and Fc-capture with Fc-detection ELISA, respectively. Two-week safety/toxicology (bodyweight, coagulation, clinical signs, chemistries, hematology, cytokines, urinalsis, histopathology) was evaluated in monkeys (5-20 mg/kg on days 1 and 8). Prophylaxis efficacy was studied in a lethal influenza mouse model using a single dose of CD377 (0.3–3 mg/kg) 28 days prior to intranasal (IN) challenge with 3x the LD₉₅ of A/California/07/2009 (H1N1)pdm, A/Hong Kong/1/68 (H3N2), or B/Malaysia (Victoria lineage). Treatment efficacy was studied in a similar mouse model using a single dose of CD377 (0.3–3 mg/kg) administered 2 hours after IN challenge with A/CA/12/2012 (H1N1)pdm.

Results: Plasma concentrations measured by Fc-capture/Fc-detection and NA-capture/Fc-detection were comparable, indicating that CD377 remained intact in vivo. In species tested, CD377 t_1/2 was 3–10 days. Dose proportional increases in exposure were observed, notably from 1–100 mg/kg in mouse. High bioavailability (77%) was observed after subcutaneous (SC) or intramuscular (IM) administration. A single SC dose of 1 mg/kg administered 28 days prior to infection provided 100% protection against H1N1, B, and H3N2 subtypes in mouse (Fig. 1). Treatment efficacy was observed with a single 0.3 mg/kg IM dose. The 2-week monkey toxicology study showed no adverse effects. Figure 1. Efficacy (Survival and Body Weight) of CD377 in a 28-Day Prevention Model Against Influenza H1N1, H3N2, and B Subtypes in Mouse (IN infection challenge on Day t=0 and CD377 dosed t–28 days).

Conclusion: The stability and safety of CD377, together with its long half-life and efficacy with a single dose, support the potential of CD377 as a long-acting, novel AVC for the prevention and treatment of influenza.