Cambridge, U.K.-based Crescendo is built on a transgenic mouse platform that generates heavy-chain antibody variable domains. Crescendo uses these domains to create multifunctional drugs designed to effectively engage targets and be free of the stability issues that traditionally held bispecifics back. Working with more than $30 million in seed and series A money, Crescendo has used the platform to create a set of preclinical prospects aimed at targets including PD-1, LAG-3 and PSMA.
Now, with a clutch of candidates progressing through preclinical testing, Crescendo has picked out the drug it wants to move forward internally and pulled in $70 million to bankroll its advance.
Andera Partners, which recently spun out of Edmond de Rothschild, led the round using cash from its €345 million BioDiscovery fund. China’s Quan Capital also participated in the round, as did Sofinnova Partners, Takeda Ventures and backers that participated in Crescendo’s earlier financing.
The money will support further development of the drug Crescendo has chosen as its lead in-house asset, CD137-PSMA bispecific CB307. Crescendo designed the drug to stimulate T-cell activity in the tumor microenvironment by having it target a transmembrane protein expressed by prostate cancer cells and some other types of solid tumors, PSMA, and a costimulatory receptor found on activated T cells, CD137.
The core concept of engaging T cells in this manner was pioneered by Micromet and taken up by Amgen following its $1.2 billion acquisition of the biotech and the drug that became Blincyto.
By targeting both PSMA and CD137, Crescendo thinks it can constrain T-cell responses to the tumor microenvironment, potentially making it safer and more effective than monovalent attempts to drug CD137.
Bristol-Myers Squibb moved an anti-CD137 antibody into human testing more than a decade ago but the hepatotoxicity-related deaths of two patients stopped its progress for several years. Human testing of urelumab resumed at a lower dose in 2012. The link between urelumab, CD137 and hepatotoxicity is unclear and made muddier by the experience of Pfizer, which has performed early-phase trials of an antibody aimed at a different epitope of the same protein without incident.
Crescendo and its backers are betting that engaging two targets will deliver better results than going after just CD137. That thinking underpins other assets Crescendo is advancing internally and trying to offload to buyers. The pipeline of assets available for partnering or licensing includes a PD-1-PD-1 biparatopic drug and a PD-1-LAG-3 candidate.