The first company to get FDA approval for a T cell receptor (TCR) bispecific therapy is showcasing its approach to improving the ease of development of these complex drugs.

Immunocore, which gained approval for Kimmtrak last year, says its method depends on a close relationship between product research and development.

“Having a close interaction between research and development groups tends not to happen in organizations,” notes Shahid Uddin, PhD, senior director of formulation and stability, Immunocore.

Scheduled to speak at the Bioprocessing Summit Europe next week, he says he will showcase how the company links early development, and Chemistry, Manufacturing and Controls (CMC)—something he says is novel within the industry.

“This [topic] is hot and current,” Uddin adds. “Most companies want to bring this into their drug development process, as it mitigates risk early on to save money and resources.”

Hard to stabilize and manufacture

Bispecific T-cell receptors are notoriously hard to stabilize and manufacture because, unlike monoclonals, they don’t exist in nature. They’re also a relatively new class of biological therapy, meaning there’s less information available on how they behave.

For this reason, explains Uddin, assessing their ease of development is important. “We need to really interrogate these molecules to understand their behavior and, as we don’t have as big a dataset [as with monoclonals antibodies], we’re trying to build this.”

Unlike traditional developability approaches, where researchers will identify one or two candidate molecules to screen, Uddin explains, Immunocore does an initial screen on hundreds of molecules. This will involve a simple assessment of yield, solubility, and whether it’s likely to be formulated as a powder or need refrigerating. Any molecules that produce a low yield, which can’t be produced at the right concentration without precipitating out of solution, or which are difficult to store are rejected, Uddin explains.

Once the candidate list has reduced to a handful of proteins, the company will do more detailed—and long-winded—studies, such as assessing the temperature the protein will unfold (i.e., its stability), and how easily it can be produced in small batches.

The initial studies take around a month, with later ones taking eight to 12 weeks—a timescale factored into development.

According to Uddin, Immunocore has been refining their approach for the last couple of years. He tells GEN that as a mature company, they’ve been able to be early adopters of developability, whereas a startup wouldn’t necessarily have the infrastructure or investment in analytics.

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