2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03F.03 Orally Bioavailable Cyclin A/B Rxl Macrocycle has Antitumor Effect in SCLC & NSCLC Cell Line Derived (CDX) & Patient Derived Xenograft (PDX) Models

EP.03F.03 Orally Bioavailable Cyclin A/B Rxl Macrocycle has Antitumor Effect in SCLC & NSCLC Cell Line Derived (CDX) & Patient Derived Xenograft (PDX) Models

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The document summarizes research presented by Circle Pharma at the WCLC 2024, detailing their investigational drug CID-078, an orally bioavailable macrocycle targeting cyclins A and B. This compound blocks RxL-dependent interactions, crucial for its antitumor effects on small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) models. CID-078 proves potent against both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC and NSCLC.<br /><br />Key findings include the identification of separase (ESPL1), a mitosis-specific protein inhibited by CID-078, as a biomarker. Data reveal CID-078's efficacy as a single agent in models with high E2F target and G2M checkpoint pathway scores, correlating with elevated tumor biomarkers such as E2F1 and cyclin B1. The compound's mechanism involves inducing DNA damage and G2/M phase arrest, particularly noted in the NCI-H446 SCLC cell line. Additionally, CID-078 treatments are associated with increased levels of p-separase S1126, a phosphoprotein linked with apoptotic cell death, showcasing a strong pharmacodynamic response.<br /><br />Preclinical studies demonstrate CID-078's ability to inhibit tumor growth and cause regression in SCLC and NSCLC models, suggesting potential as a novel therapeutic agent. These promising results will support the subsequent exploration of CID-078's therapeutic potential along with associated biomarkers in the clinical setting during the upcoming first-in-human trial, CID-AB1-24001. The drug's hypothesis posits its usefulness for patients with specific lung cancer types, offering a promising new pathway for treatment.

Asset Subtitle

Michael C. Cox

Meta Tag

Speaker Michael C. Cox

Topic Tumor Biology – Translational Biology

Keywords

Circle Pharma

WCLC 2024

CID-078

macrocycle

cyclins A and B

SCLC

NSCLC

biomarker

E2F target

G2M checkpoint