Cloudbreak®
Cidara is using its proprietary Cloudbreak platform to develop drug-Fc conjugates (DFCs) that couple targeted small molecules and peptides to a human antibody fragment (Fc). These “single molecule cocktails” are designed to inhibit specific disease targets while simultaneously engaging the immune system.
Immuno-oncology therapies have helped to transform the treatment landscape for cancer, driving long term remission in advanced disease. They are increasingly being used to treat earlier stages of disease; however, many patients are still left behind and experience resistance to these therapies. Primary resistance poses an issue, with less than 1 out of 5 patients showing an initial response to immunotherapies. Even among biomarker positive patients, less than half ever show a response. For those patients who do respond, acquired resistance is common, with 85% of people developing resistance within 6 months. In addition, chronic and often debilitating adverse events occur in up to 40% of patients.* These high levels of resistance and toxicity make current immunotherapies unfavorable for many patients.
A major mechanism of resistance starts in the tumor microenvironment (TME). The TME is constantly changing in response to feedback from the tumor itself and the treatments administered. The immunological cells infiltrating the tumor can suppress the immune system, regulate it or modulate it. There is an urgent need for multi-modal therapies that address the TME and these mechanisms of immune evasion without adding toxicity for patients.
DFCs as novel treatments for cancer
Our oncology DFCs act as “single molecule cocktails,” taking a multi-modal approach to targeting immune checkpoint pathways. Our most advanced oncology program targets CD73, an enzyme overexpressed on the surface of tumor cells that suppresses anti-tumor immunity via the adenosine immune checkpoint pathway. Hypoxia, inflammation, tissue repair and oncogenic pathways flood the TME with adenosine, potently inhibiting the host immune response to controlling tumor growth. CD73 is highly expressed on a variety of tumor cells, as well as Treg cells.
Targeting CD73 may help transform the immunosuppressive TME into an environment where immune cells can fight the tumor.
Our DFCs have the potential to augment PD-1/PD-L1 therapies and show great promise as a monotherapy or in combination with standard of care or other A2AR inhibitors.
Preclinical studies in models of colorectal cancer demonstrate CD73 DFCs have robust anti-tumor activity.
Our lead CD73 targeting DFC, CBO241, is in IND-enabling preclinical studies and an IND submission is anticipated in 2024. Additional preclinical studies on CD73/PD-1 dual targeting DFCs are ongoing.
* Patrinely, J. R. Jr et al. Chronic immune-related adverse events following adjuvant anti-PD-1 therapy for high-risk resected melanoma. JAMA Oncol. 7, 744–748 (2021)
