Circle Pharma Unveils First Preclinical Data from Cyclin D1 Program at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

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SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Oct 23, 2025--

Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, today presented preclinical data related to the company’s cyclin D1 development program at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. The data highlight the therapeutic potential of Circle Pharma’s first-in-class oral macrocyclic inhibitors to preserve retinoblastoma protein (Rb) tumor-suppressor activity by selectively blocking its interaction with cyclin D1, a key driver of cell cycle progression and proliferation in multiple hematological and solid tumor cancer types.

“Cyclin D1 has long been recognized as a key driver in many cancers, but it has remained an elusive direct therapeutic target,” said Marie Evangelista, Ph.D., senior vice president and head of cancer biology at Circle Pharma. “Using our MXMO™ platform, we have engineered orally bioavailable, cell-permeable macrocycles that selectively inhibit cyclin D1-Rb binding while sparing related isoforms such as cyclin D3—an approach aimed at reducing hematologic toxicities commonly observed with dual CDK4/6 inhibitors. These data mark a significant step forward in developing novel, macrocycle-based therapies for patients with cyclin D1-driven cancers.”

“We are excited by the strong selectivity and anti-tumor activity we’re seeing across multiple cyclin D1-driven cancer models including mantle cell lymphoma and ER-positive breast cancer,” said David J. Earp, J.D., Ph.D., president and chief executive officer of Circle Pharma. “Our approach has the potential to open a new class of therapeutics for patients, including for use in combination with other therapies, and we are on track to declare a development candidate for our cyclin D1 program by end of 2025.”

Presentation Highlights:

In cyclin D1-dependent preclinical tumor models, Circle’s oral macrocyclic cyclin D1 RxL inhibitors:

• Potently and selectively disrupt the cyclin D1–Rb interaction with >2,000-fold selectivity over cyclin D3–Rb binding, leading to phospho-Rb suppression and G1 cell cycle arrest in cyclin D1-dependant tumor cells.
• Demonstrate robust anti-tumor activity in mantle cell lymphoma (MCL) and ER-positive breast cancer models, including enhanced efficacy in combination with CDK4-selective, CDK4/6-dual, and endocrine therapies.
• Show a substantially improved in-vitro hematopoietic safety profile compared to dual CDK4/6 inhibition.

The poster presentation will be made available on the Circle Pharma website at https://circlepharma.com/publications.

About Circle Pharma’s Oral Cyclin D1 RxL Inhibitor Program

Cyclin D1 is a regulatory protein that plays a crucial role in cell cycle progression and is overexpressed in many solid tumors and hematologic malignancies. In these cancers, the cyclin D1/CDK4 complex drives cell proliferation by binding to the tumor suppressor retinoblastoma protein (Rb) and promoting its phosphorylation and inactivation. Using its MXMO™ platform, Circle Pharma has developed oral macrocyclic inhibitors that potently and selectively disrupt the cyclin D1-Rb interaction, demonstrating robust anti-tumor activity in cyclin D1-driven cancers.

About Circle Pharma

Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. 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, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.

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SOURCE: Circle Pharma, Inc.

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PUB: 10/23/2025 12:30 PM/DISC: 10/23/2025 12:30 PM

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