Circle’s next cycle

Armed with $90m raised in a series D round a year ago, and enrolling patients into its first clinical trial, the macrocycle specialist Circle Pharma is slowly expanding its reach. The company’s focus is turning to cyclin D1-driven cancer, where it has just nominated CID-165 as its next pipeline project. This molecule is a cyclin D1 RxL inhibitor, which at the recent Triple (EORTC-NCI-AACR) symposium featured in a poster describing its potential especially in ER-positive breast cancers. Here CDK4/6 inhibitors like Ibrance and Verzenio have transformed treatment, but their therapeutic index is constrained by neutropenia resulting from inhibition of the cyclin D3-CDK6 complex, Circle argues. CID-165 is said to target cyclin D1 specifically while avoiding cyclin D3-related toxicity, and might in future be combined with CDK4/6 or CDK4-selective inhibitors. Meanwhile, CID-078, which started phase 1 last year, remains Circle’s lead; this molecule inhibits RxL-mediated binding of substrates to cyclins A and B, and has potential in retinoblastoma-dysregulated cancers. The company, which has raised $208m from venture capitalists, is also working on a molecule that inhibits cyclin E/CDK2. However, an IND submission for CID-165 isn’t planned until late next year.

Projects with activity at cyclin D1

Source: OncologyPipeline.