ANTIVIRAL:
CLOUDBREAK® AVCs

Cidara is developing a new generation of immunotherapeutic antivirals from its Cloudbreak platform that couple potent antivirals to a human antibody fragment. These long-acting, antiviral conjugates (AVCs) directly inhibit viral proliferation while simultaneously engaging the immune system to maximize viral clearance.

Overview

Influenza

HIV, RSV, Coronavirus
And Other Viruses

Influenza (“the flu”) is a contagious viral infection that can cause mild to severe illness, sometimes resulting in death. While today’s flu vaccines are credited with significant public health benefits and offer our current best defense, only 49% of Americans get an annual flu vaccine1, and a majority of those people do not respond. As a result, most Americans are still at risk of getting the flu yearly. In fact, during the 2018-19 flu season, a staggering 71% did not respond to vaccination and 34,200 people died of flu-related illness in the US alone. The estimated average annual total economic burden of influenza to the healthcare system and society is more than $11.2 billion. For more information about influenza, visit the CDC website.

1 Calculated as a weighted average using census data as of July 2019 and flu vaccination coverage data from the US Centers for Disease Control

In the last five years, flu vaccines have only been effective in about 20-50% of people.

ANTIVIRAL CONJUGATES (AVCs) FOR INFLUENZA PREVENTION: CD377

Currently, the only preventative measure against influenza is the seasonal flu vaccine. While it is critical to global health, the vaccine has significant limitations including:

The vaccine must be redesigned every year based on a prediction for the next season’s dominant circulating strains

The vaccine is significantly less effective in immune-compromised individuals and the elderly

Protection doesn’t begin until 14 days after vaccination

Cidara is developing its lead flu candidate, CD377, to achieve universal prevention of seasonal and pandemic influenza with a single dose. As an antiviral conjugate (AVC), CD377 is not a vaccine or a monoclonal antibody. Its targeting domains are small molecule antivirals that bind to a highly conserved target on the influenza cell surface, which is essential for viral proliferation and enables universal influenza coverage. CD377 has the potential to offer significant advantages over the current flu vaccine:

• True universal protection, against all influenza strains and for all people, including those with a compromised immune system

• Near-immediate protective effects

Cidara is currently conducting IND-enabling studies for CD377 for influenza prevention in order to begin Phase 1 clinical trials. Preclinical studies with CD377 demonstrate:

Universal coverage against influenza

A single subcutaneous dose of CD377 is highly potent against strains of influenza responsible for pandemics in a lethal influenza mouse model.

REFERENCE: Efficacy of CD377, a Novel Antiviral Fc-Conjugate, Against Seasonal Influenza in Lethal Mouse Models [ECCMID 2020 Abstract 5793]

Long-term, single dose protection

A single dose of CD377 demonstrated potential for long-term protection in mice subjected to pandemic strains of influenza.

REFERENCE: Preclinical Efficacy, Pharmacokinetics, and Safety of CD377, a Novel Antiviral Fc-Conjugate Against Influenza [ECCMID 2020 Abstract 5126]

Efficacy with multiple routes of administration

Single 0.1 mg/kg intravenous (IV), intramuscular (IM) and subcutaneous (SC) doses of CD377 afford equivalent protection in mice dosed 2 hours post infection.

ANTIVIRAL CONJUGATES (AVCs) FOR INFLUENZA TREATMENT: CD377

There are currently four drugs recommended by the CDC for treating influenza. All have one or more of the following limitations:

Short half-life and limited efficacy window

Susceptibility to resistance

Multi-dose regimens

Limited routes of administration

Cidara’s lead AVC candidate for flu treatment, CD377, is designed to disrupt the current standard of care. CD377’s targeting domains are small molecule antivirals that bind to a highly conserved target on the cell surface of all influenza viral strains which is essential for viral proliferation. With this mechanism, CD377 has the potential for universal coverage of influenza A and B, as well as all major clinically characterized drug-resistant strains.

Cidara is currently conducting studies in support of an investigational new drug application for CD377. Preclinical treatment studies with CD377 demonstrate:

Lower resistance

CD377 demonstrated a lower resistance potential compared to approved influenza treatments, baloxavir and oseltamivir, against a pandemic strain of influenza.

REFERENCE: CD377, a Novel Antiviral Fc-Conjugate, Demonstrates a Lower Resistance Potential than Baloxavir and Oseltamivir against Pandemic Influenza A/H1N1 [ECCMID 2020 Abstract 5707]

Serial Passage (MOI 0.01)

Improved efficacy window

CD377 extends the treatment window, demonstrating improved efficacy with a single dose three days post-infection compared to multiple doses of oseltamivir starting at three days post-infection in a lethal influenza mouse model.

Rapid onset of efficacy

A single dose of CD377 is immediately elevated in both plasma and epithelial lining fluid (ELF) of the respiratory tract in mice.