SOUTH SAN FRANCISCO, Calif. — Circle Pharma announced the nomination of CID-165, a first-in-class, orally bioavailable macrocyclic cyclin D1 RxL inhibitor, as the development candidate for its second oncology program.
Cyclin D1 is a regulatory protein that controls cell cycle progression and is overexpressed or translocated in cancers including ER-positive breast cancer and lymphomas. In these malignancies, cyclin D1 binds the tumor suppressor retinoblastoma protein (Rb), driving uncontrolled cell proliferation. In preclinical studies, CID-165 selectively disrupted the cyclin D1–Rb interaction, allowing Rb to remain active and suppress cancer cell growth. The compound demonstrated anti-tumor activity in cyclin D1-driven preclinical models and showed activity in combination with CDK4/6-dual inhibitors, CDK4-selective inhibitors, and endocrine therapies.
“Cyclin D1 has long been recognized as a key oncogenic driver across many solid tumors and hematologic malignancies, yet it has remained an elusive direct therapeutic target,” said Marie Evangelista, Ph.D., senior vice president and head of cancer biology at Circle Pharma. “Our MXMO platform has allowed us to design a novel macrocyclic molecule, CID-165, with the precision and selectivity needed to directly block cyclin D1–Rb signaling while minimizing effects on related cyclins, such as cyclin D3, an approach aimed at reducing side effects commonly observed with dual CDK4/6 inhibitors.”
“Despite the transformative impact of CDK4/6 inhibitors for the treatment of ER-positive breast cancer, many patients eventually experience disease progression or adverse events that impact their quality of life,” said Anne Borgman, M.D., chief medical officer of Circle Pharma. “CID-165 is designed to address these limitations through selective inhibition of cyclin D1 while avoiding adverse events associated with broader CDK4/6 blockade. We plan to advance CID-165 toward IND submission in late 2026.”
Circle Pharma is a clinical-stage biopharmaceutical company developing next-generation targeted therapies for cancer using macrocycles. The company’s MXMO platform is intended to enable intrinsically cell-permeable and orally bioavailable therapies, including for targets considered historically undruggable. The pipeline focuses on cyclins, key regulators of the cell cycle. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, California. More information is available at circlepharma.com.
Media contact: Josie Butler, 1AB, [email protected]
Leave a Reply