CRUK, Biotecnol team up for T-cell engager trial

Biotecnol is going after a target previously pursued by Pfizer.

Biotecnol has teamed up with Cancer Research UK (CRUK) to take its T-cell engager into the clinic. The agreement sees CRUK take a stake in the Anglo-Portuguese biotech in return for help testing a 5T4-CD3 bispecific antibody in patients with lung cancer and other solid tumors.

CRUK’s drug development center will support a Biotecnol-sponsored phase 1 trial of the antibody, Tb535H. That study will start the process of assessing the effect of the candidate on patients with mesothelioma, small and non-small cell lung cancer (SCLC/NSCLC) and renal cell carcinoma (RCC).

The collaborators pulled together the list of target indications by looking for cancers with high unmet needs that express 5T4, an oncofetal tumor antigen also known as WAIF1. Studies suggest 5T4 is found in most cases of mesothelioma, NSCLC and RCC.

Two of the arms of Tb535H bind to 5T4 on the surface of tumor cells. The third links to CD3 on the surface of T cells. This mechanism is designed to bring T cells into contact with tumor cells to start an immune response against the cancer. Others, notably Amgen and the BiTE platform that gave rise to Blincyto, are using molecules with different structures to achieve similar ends. 

Teaming with CRUK positions Biotecnol to join the clutch of companies with T-cell engagers in the clinic sooner than would otherwise have been possible. 

“Without this collaboration it might have been years before this treatment reached patients so we‘re pleased to work with Biotecnol to elevate their novel drug development platform,” Nigel Blackburn, Ph.D., director of drug development at CRUK, said in a statement.

The advance of Tb535H into human testing has already taken longer than anticipated. Two years ago Biotecnol said it expected to start a phase 1/2 trial in 2016. That study would have started with a dose-escalation phase in solid tumors expressing 5T4 before expanding into a small test of the clinical benefits of Tb535H in patients with malignant mesothelioma. But having come through in vitro and in vivo testing, the progress of Tb535H stalled.

CRUK has now come on board to get the program moving forward again.

The nonprofit’s decision to collaborate with Biotecnol reconnects it to science it originated. CRUK scientists published research in 2003 linking 5T4 to the spread of cancer. That triggered research into immunotherapies against the target. 

Pfizer moved a 5T4-targeted antibody-drug conjugate into the clinic in 2013, only for the program to fall victim to a shift in priorities at the Big Pharma. And Oxford Biomedica, which provided Pfizer with its 5T4 tumor antigen, got cancer vaccine TroVax as far as phase 3 before weak efficacy data set it back.    

Biotecnol is now on the path to finding out whether its approach to tackling the target can fare better.