Circle Pharma, a startup working on macrocycles for the “undruggable,” is seeking about $117 million for a Series D.
The company recently closed the first part of the round, reeling in about $54 million from a dozen investors, according to an SEC filing on Wednesday. The Bay Area biotech last disclosed a $66 million Series C in June 2021. Investors included The Column Group, Nextech Invest, Pandect Bioventures and Eli Lilly. Its website also lists Pfizer as an investor.
The preclinical biotech is developing cyclin A/B, D and E inhibitors for various solid tumors. Earlier this week, Circle said it requested its first clinical trial clearance in the US, aiming to test its experimental oral medicine CID-078 in various tumor types. It gathered preclinical data in small cell lung, triple-negative breast, ER-low breast and HR-positive breast cancers.
Leading the biotech is CEO David Earp. Its chair is John Josey, who steered Peloton Therapeutics for about six years until Merck acquired it in 2019. Nobel laureate William Kaelin chairs Circle’s scientific advisory board.
Macrocycles promise the best of both worlds. Small molecule drugs can struggle with certain targets, such as the protein-protein interactions behind a wide range of diseases, including cancer. Antibodies, which boast that specificity, can’t be given as a pill.
Macrocycles, however, can potentially bind very specific targets and they can be delivered in pill form.
Aside from macrocycle drugs discovered in nature, drug developers haven’t paid much interest to macrocycles because they couldn’t readily pass through membranes — a key quality for making drugs into pills.
But improvements to the scientists’ toolkit have made it feasible to design these peptides with specific qualities, igniting new interest in the field.
Circle Pharma said that it screens vast libraries to identify potential compounds and then uses artificial intelligence to help it design potentially better versions of those compounds. Another part of Circle’s pitch is unnatural amino acids — chemical building blocks that aren’t part of the ones our bodies typically use to make proteins.
Other companies that are developing macrocycle drugs include Vilya, a “Lord of the Rings”-inspired biotech from the lab of protein design pioneer David Baker and ARCH Ventures. Orbis Medicines launched in February with a €26 million seed round from Forbion and Novo Holdings. The same month, Insamo unveiled with a $12 million seed round backed by the VC arm of Merck, a key pharma in the space.