Circle Pharma Achieves Major Milestone with the Selection of a Clinical Development Candidate Directly Inhibiting Cyclins A and B

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  • CID-078 is a first-in-class oral macrocycle that drives synthetic lethality in a wide range of cancers
  • Circle expects to initiate clinical studies in 2024

SAN FRANCISCO, Calif., July 19, 2023— Circle Pharma, a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles, announced today the selection of CID-078 for its first clinical development program. CID-078 is the first-and-only-in-class dual inhibitor of Cyclins A and B, which play essential roles in regulating cell cycle progression. Inhibiting Cyclins A and B selectively induces synthetic lethality in certain cancers exhibiting cell cycle dysregulation while sparing healthy cells.

Circle Pharma recently presented pre-clinical data for its dual Cyclin A/B inhibitors at this year’s American Association for Cancer Research (AACR) Annual Meeting. The data demonstrated activity across a wide range of human tumor cell lines including tumor regression in xenograft models of small cell lung carcinoma (SCLC) and ovarian cancer. SCLC has a five-year survival rate of 3.5%, and its treatment has seen minimal progress in the last 30 years. Ovarian cancer patients commonly face poor outcomes and resistance to the current standard of care. In advance of human clinical trials for CID-078, further preclinical studies using patient-derived models (PDX) are underway in breast cancer (including triple negative breast cancer), non-small cell lung cancer, gastric cancer, pancreatic cancer, and other tumor types.

“The selection of CID-078 represents a major milestone for our team; we are excited to advance this molecule into clinical development and to realize its potential to bring new hope for the many cancer patients who currently have woefully inadequate treatment options,” said David Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma. “This achievement is also a reflection of the capabilities of our macrocycle discovery platform as the cyclins have until now been considered undruggable.”

CID-078 is an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types. In biochemical and cellular studies, CID-078 has been shown to potently and selectively disrupt the protein-protein interaction between Cyclins A and B and their key substrates, including E2F (a substrate of Cyclin A) and Myt1 (a substrate of Cyclin B). Preclinical studies have demonstrated the ability of CID-078 to cause pronounced tumor regression in multiple xenograft models. Circle Pharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for CID-078 and initiate clinical development in 2024.

Macrocycles are a class of molecules that have properties outside of the conventional “rule of five” for oral small molecule drugs. They have the potential to address important therapeutic targets, such as protein-protein interactions, that are refractory to other drug classes, but their larger size and chemical complexity present additional challenges to drug developers. Circle Pharma’s proprietary technology platform, MXMO™, introduces a highly differentiated ability to develop precision macrocycle therapeutics that are passively cell-permeable and orally bioavailable. Circle Pharma’s macrocycles also have desirable pharmacokinetics, are exquisitely selective, and can be directed to both intra- and extra-cellular therapeutic targets.

South San Francisco-based Circle Pharma is advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle Pharma’s MXMO™ platform combines structure-based rational drug design and advanced synthetic chemistry to develop first-in-class macrocycle therapeutics for challenging targets to address unmet clinical needs. Circle Pharma is focusing its development efforts on cyclins, which are master regulators of the machinery that controls progression of cells through the cell cycle and are key drivers in many cancers.
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Circle Pharma Media Contact:
Roslyn Patterson

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