Circle Pharma, a pre-clinical stage company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, will present a poster at the American Association for Cancer Research (AACR) Annual Meeting being held April 8-13, in New Orleans, Louisiana.

The Company’s presentation will provide details of its progress towards structure-guided macrocycles that inhibit the protein-protein interaction between the cyclin A:CDK2 complex and key substrates that are phosphorylated by this complex. Inhibition of Cyclin A substrate binding has been postulated to be synthetic lethal in Rb mutated cancers. The data presented include evidence that macrocycle inhibitors of cyclin A induce G₂/M arrest and apoptosis in small cell lung cancer (SCLC) cell lines and have anti-tumor efficacy in SCLC xenograft animal models. Circle plans to advance its cyclin A inhibitor program to the clinic for testing in a range of cancer types, including SCLC where Rb mutations are highly prevalent.

The presentation will be made as part of the Mechanisms of Drug Action / Experimental and Molecular Therapeutics session at the AACR meeting, Abstract No. 5379.

About Circle Pharma, Inc.

Circle is a pre-clinical stage company deploying a platform that 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’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform is applicable across a wide range of serious diseases; the company is initially focusing its development efforts on intracellular protein-protein interactions that are key drivers in cancer. Its lead programs target cyclin proteins, including cyclins A and E, which are part of the regulatory machinery that controls progression of cells through the cell cycle. Inhibition of cyclin A has been reported to be synthetic lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.

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