Circle Pharma, a South San Francisco-based clinical-stage biopharmaceutical company, will present new mechanistic insights into their novel cyclin A/B RxL inhibitors at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago. The late-breaking poster presentation will reveal how these compounds combat cancer through disruption of DNA repair pathways and impact on mitotic progression in E2F-high cancers.
The company's lead compound, CID-078, is an oral macrocycle cyclin A/B RxL inhibitor currently in Phase 1 clinical evaluation (NCT06577987) for patients with advanced solid tumors. This presentation marks a significant advancement in understanding how this novel class of compounds works at the molecular level.
Dual Mechanism of Action Uncovered
The research, conducted in collaboration with the University of Oxford and Dana-Farber Cancer Institute, highlights a previously uncharacterized dual mechanism by which cyclin A/B RxL inhibitors induce tumor regression. According to the abstract, these inhibitors partially exert their anti-cancer effects by disrupting the ATR/Chk1 DNA repair pathway, a critical mechanism that cancer cells rely on for survival.
"This research provides crucial insights into how our cyclin A/B RxL inhibitors work at the molecular level," said a Circle Pharma representative. "Understanding that these compounds disrupt both DNA repair pathways and mitotic progression gives us a clearer picture of their potential in treating E2F-high cancers."
The poster, titled "Anti-cancer effect of Cyclin A/B RxL inhibitors is mediated in part by disruption of the ATR/Chk1 DNA repair pathway," will be presented on April 29, 2025, from 9:00 AM to 12:00 PM CT in Poster Section 52 (Board Number 19, Abstract Number LB296).
Targeting the Undruggable
Circle Pharma specializes in developing cell-permeable macrocycle therapeutics, a class of compounds that can address historically challenging or "undruggable" targets. The company's proprietary MXMO™ platform has enabled the creation of intrinsically cell-permeable and orally bioavailable therapies that can reach previously inaccessible disease targets.
Cyclins, the focus of Circle Pharma's pipeline, are key regulators of the cell cycle that drive many cancers. By specifically targeting the RxL binding site on cyclins A and B, CID-078 represents a novel approach to cancer treatment that differs from traditional cyclin-dependent kinase (CDK) inhibitors.
Collaborative Research Effort
The study brings together expertise from multiple prestigious institutions. Contributing authors include Catherine E. Gleason, Ranya Odeh, Frances Hamkins-Indik, Iolanda Vendrell, Roman Fischer, Benedikt Kessler, Shilpa Singh, Matthew Oser, Marie Evangelista, and Pablo D. Garcia from Circle Pharma, University of Oxford, and Dana-Farber Cancer Institute/Harvard Medical School.
This collaborative approach has allowed for comprehensive characterization of the mechanism of action, combining Circle Pharma's expertise in macrocycle development with Oxford's proteomics capabilities and Dana-Farber's cancer biology insights.
Clinical Implications
The findings presented at AACR 2025 have significant implications for the ongoing Phase 1 clinical trial of CID-078. Understanding the dual mechanism of action may help identify which patients are most likely to respond to treatment and inform combination strategies with other cancer therapies.
E2F-high cancers, which the research specifically addresses, include several aggressive tumor types with poor prognosis and limited treatment options. By targeting cyclins A and B through their RxL binding sites, Circle Pharma's approach represents a potentially important new strategy for addressing these difficult-to-treat malignancies.
About Circle Pharma
Circle Pharma is pioneering the development of macrocycle therapeutics for cancer and other serious illnesses. The company's MXMO™ platform addresses key challenges in macrocycle drug development, enabling the creation of treatments for targets previously considered undruggable.
The company's focus on cyclins as targets reflects their central role in cell cycle regulation and cancer progression. With CID-078 now in clinical development, Circle Pharma is positioned at the forefront of this innovative approach to cancer treatment.
