Circle Pharma submits initial IND for novel oral cyclin A/B inhibitor for advanced solid tumors

Circle Pharma, Inc., based in South San Francisco and known for its leadership in macrocycle drug discovery, has announced a pivotal milestone: the submission of its first Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for CID-078. This innovative candidate is a unique cyclin A/B RxL inhibitor, marking a significant step forward in fighting difficult-to-treat cancers and other serious diseases.

CID-078 is an orally available macrocycle that has shown promising preclinical results across various tumor types that exhibit high E2F expression. These include small cell lung cancer, triple-negative breast cancer, ER-low breast cancer, and HR-positive breast cancer post-CDK 4/6 inhibitor treatment. The IND application for CID-078 includes comprehensive preclinical data demonstrating its safety, efficacy, and pharmacokinetic profile, laying the groundwork for proposed phase 1 clinical trials.

The primary function of CID-078 is to selectively inhibit crucial protein interactions involving cyclins A and B. Cyclins are essential proteins that regulate the cell cycle. Early research by Nobel Laureate and Circle Pharma’s Scientific Advisory Board Chair William G. Kaelin Jr., MD, revealed that disrupting cyclin function in certain cancer cells with dysregulated cell cycle control could be synthetic lethal, selectively killing cancer cells while sparing normal cells. This insight underscores CID-078's innovative mechanism of action, which offers a potential new therapeutic pathway for patients with advanced solid tumors who have limited treatment options.

David J. Earp, CEO of Circle Pharma, expressed pride in reaching this critical milestone, noting the team's dedication in advancing CID-078 from discovery to preclinical development. The IND filing is a significant stride in Circle Pharma's mission to leverage macrocycle therapies to develop effective treatments for cancer and other serious illnesses.

Michael Cox, head of Early Development and senior vice president, emphasized the transformative potential of CID-078 based on preclinical data, highlighting the excitement to move this candidate into clinical studies. This step reinforces Circle Pharma’s commitment to pioneering therapeutics that target challenging and previously undruggable proteins.

Pending regulatory approval, Circle Pharma aims to begin a phase 1 clinical trial of CID-078 in patients with advanced solid tumors. The trial will involve dose escalation and dose expansion phases to assess safety, tolerability, pharmacokinetics, and anti-tumor activity, measured by objective response rate and duration of response.

Circle Pharma's Cyclin A/B RxL Inhibitor Program focuses on CID-078, an orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity. This drug selectively targets tumor cells with oncogenic alterations causing cell cycle dysregulation. Biochemical and cellular studies have shown that CID-078 can effectively disrupt key protein interactions between cyclins A and B and their substrates and modulators, such as E2F and Myt1. Preclinical studies have demonstrated the inhibitor’s capability to induce single-agent tumor regression in multiple xenograft models.

South San Francisco-based Circle Pharma is at the forefront of developing intrinsically cell-permeable macrocycles. These can be administered through various routes, including oral administration. The company's proprietary MXMO™ platform merges structure-based rational drug design with advanced synthetic chemistry. This platform is designed to create a new generation of macrocycle therapies for challenging targets, addressing unmet clinical needs. Circle Pharma focuses particularly on cyclins, the master regulators of cell cycle progression, which are crucial in many cancers.