ANTIVIRAL:
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.
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
ANTIVIRAL CONJUGATES (AVCs) FOR INFLUENZA PREVENTION: CD377 and CD388
Cidara’s goal is to develop its lead flu AVCs, CD377 and CD388, to achieve universal prevention of seasonal and pandemic influenza with a single dose. Antiviral conjugates are not vaccines or monoclonal antibodies. Their 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. 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.
Flu AVCs have the potential to offer significant advantages over current flu vaccines:
- True universal protection, against all influenza strains and for all people, including those with a compromised immune system
- Near-immediate protective effects
CD388 is a longer acting version of CD377, and differs only in its effector domain, a proprietary variant of a human antibody fragment (Fc). Cidara is conducting IND-enabling studies in order to begin Phase 1 clinical trials in its influenza program.
Preclinical studies 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 and CD388
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 flu AVCs for flu treatment are designed to disrupt the current standard of care. The targeting domains of flu AVCs are potent 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, AVCs have the potential for fast-acting universal coverage of influenza A and B, including all major clinically characterized drug-resistant strains.
Cidara is conducting IND-enabling studies in order to begin Phase 1 clinical trials in its influenza program.
Preclinical studies 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.
