New Generation of Long-Acting Immunotherapeutic Antivirals Aim to Prevent COVID-19/Flu ‘Twindemics’

A new generation of long-acting therapeutics designed for patients facing serious viral infections is aiming to prevent “twindemic” double threats of influenza and COVID-19.

Cidara Therapeutics, Inc. (San Diego, CA, USA), a biotechnology company, 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.


Cidara’s Cloudbreak antiviral platform is a fundamentally new approach to treating and preventing viral infections. By applying the principles of immuno-oncology to infectious disease, Cidara is creating a new generation of antivirals that stably couple a potent antiviral targeting domain, a small molecule or a peptide, to an effector domain, a proprietary variant of a human antibody fragment (Fc). These long-acting, bispecific AVCs are designed to directly inhibit viral proliferation while simultaneously directing immune-mediated clearance of the virus. The two distinct and complementary mechanisms are designed to maximize antiviral activity of AVCs.

Cidara is developing its lead flu candidate, CD377, to achieve universal prevention of seasonal and pandemic influenza with a single dose. As an 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. 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. CD377 has the potential to offer significant advantages over the current flu vaccine such as true universal protection, against all influenza strains and for all people, including those with a compromised immune system; and near-immediate protective effects

In preclinical studies, CD377 demonstrated that a single subcutaneous dose was highly potent against strains of influenza responsible for pandemics in a lethal influenza mouse model. A single dose of CD377 demonstrated potential for long-term protection in mice subjected to pandemic strains of influenza. Single 0.1 mg/kg intravenous (IV), intramuscular (IM) and subcutaneous (SC) doses of CD377 afforded equivalent protection in mice dosed two hours post infection. CD377 also demonstrated a lower resistance potential compared to approved influenza treatments, baloxavir and oseltamivir, against a pandemic strain of influenza. CD377 extended 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. Additionally, a single dose of CD377 was immediately elevated in both plasma and epithelial lining fluid (ELF) of the respiratory tract in mice. Cidara is currently conducting studies in support of an investigational new drug application for CD377 for influenza prevention in order to begin Phase 1 clinical trials.

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Cidara Therapeutics, Inc.