On December 17, 2025 Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, reported 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.
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Cyclin D1 is a regulatory protein that plays a crucial role in cell cycle progression and is overexpressed or translocated in malignancies, including ER-positive breast cancer and lymphomas. In these cancers, cyclin D1 drives cell proliferation by binding to the tumor suppressor retinoblastoma protein (Rb) leading to uncontrolled cell division. In preclinical studies, CID-165 has been shown to potently and selectively disrupt the cyclin D1-Rb interaction allowing Rb to remain active and suppress cancer cell proliferation. CID-165 demonstrates robust anti-tumor activity in cyclin D1-driven preclinical cancer models including in combination with other therapies such as 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, a central driver of tumor proliferation, while avoiding adverse events associated with broader CDK4/6 blockade. We look forward to advancing CID-165 toward IND submission in late 2026 and potentially translating the compelling preclinical activity into benefit for patients."
(Press release, Circle Pharma, DEC 17, 2025, View Source [SID1234661500])