Circle Pharma Begins Phase 1 Trial of CID-078 for Advanced Solid Tumors

Circle Pharma, Inc., a clinical-stage biopharmaceutical company in South San Francisco, is pioneering the development of macrocycle therapies. On October 15, 2024, the company announced that the first patient cohort has been dosed in the Phase 1 trial of CID-078. CID-078 is an innovative oral cyclin A/B RxL inhibitor designed to treat advanced solid tumors, including those with elevated E2F transcription factor activity, such as small cell lung cancer, triple-negative breast cancer, and ER+ HER-2- breast cancer following CDK 4/6-inhibitor treatments.

David J. Earp, JD, Ph.D., the CEO of Circle Pharma, expressed excitement over the rapid progression of CID-078 into human trials following a swift 30-day regulatory review clearance. This milestone allows the company to gather important clinical proof-of-concept data, which will be crucial in assessing CID-078’s potential impact in areas of high unmet medical need. Additionally, the trial aims to validate Circle Pharma’s proprietary MXMO™ macrocycle platform, designed to target difficult-to-drug proteins in cancer and other serious diseases.

CID-078 operates by selectively inhibiting crucial protein interactions involving cyclins A and B, which are important in cancer cell proliferation and survival. The underlying research is based on the work of Nobel Laureate William G. Kaelin Jr., MD, who serves as Circle Pharma’s Scientific Advisory Board Chair. Dr. Kaelin's research demonstrated that disrupting cyclins A and B can induce synthetic lethality in cancer cells with dysregulated cell cycles and elevated E2F activity.

Dr. Geoffrey Shapiro, MD, Ph.D., senior vice president of Development Therapeutics at Dana-Farber Cancer Institute and a professor at Harvard University, highlighted the significance of this advancement. He noted that previously, there has been no selective therapeutic agent to exploit the disruption of E2F-driven cancer cells’ ability to regulate the cell cycle, which is essential for inducing apoptosis. Dr. Shapiro expressed great enthusiasm for the clinical advancement of Circle Pharma’s cyclin A/B RxL inhibitor.

The initial patient cohort for the trial is enrolled at The START Center for Cancer Research in Grand Rapids, Michigan. Other active clinical sites include The START Center in West Valley City, Utah, and NEXT Oncology in San Antonio, Texas, with additional sites expected to open soon.

This Phase 1 clinical trial (NCT06577987) is an open-label, multi-center study designed to escalate and expand doses. The trial aims to enroll up to 100 patients and will evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of CID-078 in solid tumors. Preliminary safety and anti-tumor data from the trial are anticipated to be available in 2025.

CID-078 is an investigational orally bioavailable macrocycle that inhibits both cyclin A and B RxL, selectively targeting tumor cells with oncogenic alterations leading to cell cycle dysregulation. In both biochemical and cellular studies, Circle Pharma’s cyclin A/B RxL inhibitors have shown potent and selective disruption of the protein interactions between cyclins A and B and their key substrates and modulators, such as E2F and Myt1. Preclinical studies have indicated that these inhibitors can cause significant tumor regressions in various xenograft models, paving the way for the current Phase 1 clinical study.

Circle Pharma is based in South San Francisco and is at the forefront of developing cell-permeable macrocycles that can be delivered orally. Their MXMO™ platform integrates structure-based drug design and advanced synthetic chemistry to create innovative therapies targeting challenging proteins. Circle Pharma's primary focus is on cyclins, which are crucial regulators of cell cycle progression and key drivers in numerous cancers.