Cloudbreak Overview
Our proprietary Cloudbreak immunotherapy discovery platform has the potential to do for infectious disease what immunotherapy has done for cancer. Cloudbreak is a fundamentally new approach for the treatment of infectious disease which redirects the immune system to destroy fungal, bacterial and viral pathogens.
The design of the Cloudbreak immunotherapy platform recognizes that most infectious disease is due to a temporary deficiency in the function of the immune system. Our Cloudbreak candidates are designed to address this deficiency by recruiting components of the patient’s immune system to the site of infection. Cloudbreak supports the engineering of bi-specific agents that target the pathogen and prime the immune system to generate a more effective anti-infective response.
We are developing initial Cloudbreak candidates for the treatment of serious gram-negative bacterial infections. Learn more about CD201 >>
The modular composition of Cloudbreak compounds allows for rapid exploration of combinations of targeting moiety (TM), effector moiety (EM), and linker domains, potentially enabling efficient discovery of anti-infective components with the desired potency, specificity and physical properties.
Potential Platform Advantages
The Cloudbreak immunotherapy discovery platform is similar to certain cancer immunotherapies in that it uses components with two binding sites, one that binds to a cell surface target and a second that binds to specific receptors on immune cells.
Our Cloudbreak candidates have the potential to feature the following attributes:
- Small or large molecule components with well-defined targets and efficient testing
- Selective binding to pathogens to amplify their immunogenicity (recognition by the immune system) and thereby efficiently recruit the innate or adaptive immune system to assist in the rapid eradication of the pathogen
- Use as adjunctive therapy along with standard of care regimens
- Broad applicability in the treatment of infectious diseases
Ex vivo proof of concept
We have developed an assay to measure mobilization of neutrophils directly to the pathogen in the presence and absence of our initial Cloudbreak compounds. Aspergillus spores, or conidia, were placed in experimental chambers of approximately the same size as human alveoli into which human primary neutrophils were allowed to migrate.
In the absence of a Cloudbreak compound (left), very few neutrophils were attracted to the fungus and the conidia matured into growing hyphae, the invasive form of Aspergillus. When a Cloudbreak compound is added at a concentration approximately one thousand-fold below the MIC of the TM, the conidia and hyphae were rapidly killed by neutrophils and subsequent hyphal growth was arrested (right).
No Drug
Cloudbreak Small Molecule Compound
ICAAC/ICC | San Diego, CA | September 2015
Publications
- A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis Open Forum Infect Dis | February 2016
- Human Neutrophils Are Primed by Chemoattractant Gradients for Blocking the Growth of Aspergillus fumigatus J Infect Dis | February 2016
Opportunity
We are developing initial Cloudbreak candidates for the treatment of serious gram-negative bacterial infections.