One of the problems with cancer drugs is their broad effect: Besides killing cancer cells, they also harm healthy tissue. Bicycle Therapeutics is developing a new class of drugs that it says can offer a more targeted approach, and it has raised $52 million to support plans to bring its lead drug into clinical trials.
New investor Vertex Ventures led the Series B round of investment in Bicycle, which is headquartered in Cambridge, U.K., and has U.S. operations in Cambridge, MA. Also joining the financing were new investors Cambridge Innovation Capital and Longwood Fund. Earlier investors in Bicycle—Novartis Venture Fund, SROne, SVLS, and Atlas Venture—also participated in the round. Bicycle says it will use the proceeds to continue work on multiple drug candidates, including its lead drug, which the company hopes to develop into a treatment for cancers.
Bicycle’s drugs are formed from peptides, chains of amino acids. The company draws its name from these compounds, which it calls “bicyclic peptides.” Peptide drugs offer the ability to tweak how a drug is distributed, absorbed, and ultimately, eliminated from the body. Bicycle says it can adjust these properties to reduce the toxic effects of a drug to the kidneys and the gut.
But Bicycle goes further, claiming that its drugs combine the advantages of other types of drugs. Large molecule drugs, made from proteins, offer the ability to bind to specific sites on a cell’s surface. But their large size keeps them from penetrating the cell itself. Meanwhile, the size of small molecule drugs allows them to reach almost anywhere in the body, and including the inside of cells. Bicycle says its bicycle drug conjugate (BDC) technology can produce compounds that have the targeting specificity of large molecule drugs along with the ability to distribute throughout the body and penetrate cells the way that small molecule drugs do.
Bicycle’s lead drug, BT1718, was developed to deliver a toxic chemical payload directly to tumors. The drug targets an enzyme on tumor cells called Membrane Type 1 Matrix Metalloproteinase (MT1-MTP). That enzyme is expressed in many solid tumors, including those of triple negative breast cancer and non-small cell lung cancer. Bicycle says that it plans to bring its cancer drug into clinical trials later this year in partnership with Cancer Research UK.
A handful of other companies, including two from Cambridge, MA, are also trying to develop drugs that offer properties of both small and large molecule drugs. Ensemble Therapeutics is developing “mid-sized” drugs that could potentially treat cancer and other conditions. Aileron Therapeutics has technology that it describes as a “stapled peptide” drug that has the ability to get into the nucleus of cells. Aileron is testing cancer drug candidates in several early and mid-stage clinical trials.
Meanwhile, Bicycle’s own progress has enabled the company to collaborate with larger pharmaceutical companies. Last year, Bicycle began a partnership with AstraZeneca (NYSE: AZN) to discover and develop drugs for respiratory, cardiovascular, and metabolic conditions. The agreement calls for Bicycle to identify the bicyclic peptides for undisclosed targets specified by AstraZeneca. AstraZeneca will be responsible for further developing those compounds, and if they succeed in clinical trials, commercialize them. If the partnership is successful, Bicycle stands to gain up to $1 billion in milestone payments, plus royalties from drug sales.
Bicycle also has an eye drug partnership with Belgium-based ThromboGenics. In April, Bicycle reported that it reached a preclinical milestone in a program developing a potential treatment for diabetic macular edema.
Bicycle’s technology is based on research from the MRC Laboratory of Molecular Biology, a Cambridge, UK-based research institute. The company raised $32 million in a 2014 Series A round of investment. Last year, Bicycle opened a U.S. office in Cambridge’s Kendall Square, hiring GlaxoSmithKline executive Rosamund Deegan as its president and chief business officer.