Lilly helps Circle round up $66M for intractable target R&D

Circle Pharma has raised $66 million to take cyclin-targeted programs toward clinical development. The Eli Lilly-backed series C round sets Circle up to build on its years of research into cell-permeable macrocyclic peptide therapeutics with the potential to hit previously undruggable targets.

South San Francisco-based Circle first made headlines back in 2014 when it emerged equipped with seed funding from Pfizer as well as two collaborations with the Big Pharma company. The work with Pfizer led to the publication of a paper on an orally bioavailable macrocycle modulator of the CXCR7 chemokine receptor, but Circle had a low profile by the standards of Big Pharma-partnered biotechs.

That started to change last year, when Circle raised $45 million to develop inhibitors of Cyclin A and Cyclin E and began to grow its team. Now, with clinical development on the horizon, Circle has added another $66 million to its bank balance in a series C round.

The Column Group and Nextech Invest co-led the round with the support of new investors including Euclidean Capital, Pavillion Capital, Hartford HealthCare Endowment and Lilly. Existing backers such as Pandect Bioventures also participated in the series C.

Circle will use the cash to advance preclinical candidates with applications in Rb-dysregulated cancers and cyclin-E-dependent malignancies. The two opportunities cover indications such as small cell lung cancer and ovarian cancer.

The macrocyclic peptides in development at Circle have the potential to unlock targets that biologics and small molecules are unable to hit. Specifically, Circle sees its drugs as ways to hit targets that lack binding sites for small molecules and are hidden from biologics inside cells. Unlike those modalities, macrocycles may be able to enter cells to inhibit processes such as protein-protein interactions. 

There is a long history of using macrocycle drugs such as the immunosuppressant cyclosporine and the antibiotic erythromycin. However, efforts to systematically develop macrocycles have run into a range of challenges related to pharmacokinetics, cell permeability and oral bioavailability. Circle has worked to overcome those challenges and unlock the potential of the molecules.

The series C funding will move Circle closer to showing whether its efforts have resulted in clinically efficacious therapies while also equipping the biotech to apply its platform to other targets that are thought to be undruggable with small molecules.