Meet the team: Leo James, Co-founder and Chief Scientific Adviser, TRIMTECH Therapeutics

Tell us more about your professional and academic career, how that led you to leading a research group at the MRC Laboratory of Molecular Biology, and co-founding TRIMTECH.

After a degree in genetics, I obtained a PhD in structural biology and then undertook a postdoc in protein engineering with Sir Greg Winter. It was working with Greg that inspired me to undertake translational research, which has remained an important goal for me ever since. I established my own lab at the end of the 00s with the aim to determine whether there was a missing component of humoral immunity that allows antibodies to function intracellularly. This led me to discover TRIM21, the mammalian cytosolic antibody receptor. For the last 20 years my lab has defined the molecular mechanism by which TRIM21 works, how it degrades proteins, pathogens and proteopathic agents inside cells, and demonstrated its physiological importance in animal disease models. Once we had amassed sufficient data demonstrating TRIM21’s effectiveness, and obtained small molecules that could be used to recruit it to its targets, I co-founded TRIMTECH together with close collaborator Will McEwan and entrepreneur Damian Crowther.

How are you finding balancing your work with TRIMTECH with your continued academic research?

It takes careful planning to ensure that I can fulfil two roles – in TRIMTECH and in my academic lab – but the synergy between these positions delivers clear benefits to both. I draw on over 20 years of expertise in TRIM21 biology to support the work at TRIMTECH. Conversely, seeing this knowledge being translated into tangible real-world benefit is hugely inspiring for my academic work and helps me consider scientific questions in a new light.

What is it about targeted protein degradation as a therapeutic modality that you find most exciting? How does the approach you developed, and turned into a company with TRIMTECH, stand out compared with others in the field

The term ‘magic bullets’ has often been used when new therapeutic paradigms are developed, and I remember it being applied to therapeutic antibodies – biologics that have undoubtedly transformed medicine. But as powerful as antibodies are, they can only be used to target proteins outside cells. Targeted protein degraders are revolutionary because they are cell-permeable – they can target proteins anywhere in the cell. Moreover, degraders don’t just block disease-causing proteins but remove them entirely. TRIMTECH stands out because we are harnessing a naturally occurring mechanism that has specifically evolved to selectively degrade large assemblies. By replacing the antibodies TRIM21 normally uses with small molecules, we are hugely expanding the range of targets, and thus the diseases it can be effective against.

Soon after TRIMTECH’s launch, you were elected to the Fellowship of the Royal Society. Would you consider 2025 a milestone year in your career so far?

Absolutely! I feel incredibly grateful to have been given the opportunity to translate our fundamental research into something useful and have the work we carried out over many years recognised by our peers in academia. My lab has never worked on fashionable or ‘hot’ areas and this has sometimes made it difficult for us to feel we were making an impact. These events feel like vindication for all the talented people that have worked on TRIM21 in the lab over many years. However, it really is just the beginning, and we also have to deliver real-world results.

Make a bold prediction about the future of targeted protein degradation (TPD) therapies.

The development of small molecule degraders to treat neurodegenerative diseases would be truly transformative. There is a profound unmet medical need in this area, and the availability of small molecules would make treatments accessible to patient numbers on a scale that’s simply not achievable with other therapeutic modalities. Undoubtedly, the combination of this disease area and approach represents one of the biggest challenges imaginable, but I think it can be done. I also think we have only scratched the surface of the kinds of diseases we can treat with TPD and the kinds of mechanisms we can trigger using degradation. In particular, I’d like to see TPD being used to treat infectious diseases such as viral infection – antiviral degraders would be my bold prediction for future medicines.

Could you share any advice for early-career researchers looking into ways to develop and commercialise their ideas?

Build a great team. You need a lot of different types of expertise and experience to take fundamental research to the next level and make a coherent plan for developing it translationally. It also makes the journey so much more fun, and you learn a lot from everyone in the team.