Leo James co-founds new UK biotech company with Will McEwan (UK Dementia Research Institute at the University of Cambridge) leveraging the unique properties of TRIM21, discovered at the LMB
TRIMTECH Therapeutics, the latest LMB spinout company, is developing a pipeline of potent, central nervous system penetrant therapeutics to treat severe neurodegenerative and inflammatory disorders, including Alzheimer’s and Huntington’s disease.
Based on over fifteen years of research by Leo James and Will McEwan’s groups, TRIMTECH is utilising the unique properties of the E3 ubiquitin ligase TRIM21, discovered by Leo’s group in the LMB’s PNAC Division, to selectively and potently degrade protein aggregates associated with a range of diseases.
Leo said: “This is a fantastic opportunity to put to work the knowledge we’ve gained through the dedicated research of many scientists in the group over the years and make new types of therapeutic to remove the toxic aggregates that cause neurodegeneration.”
In 2010 the James group, including then postdoc Will McEwan, demonstrated that newly discovered TRIM21 identifies antibody-bound virus particles within the cell and targets them for destruction by the proteosome. Building upon their discovery, in 2017 the team showed that TRIM21 could be re-directed to deplete other molecules by delivering antibodies against the target molecule into the cell. Further research revealed that the ability to degrade difficult substrates is the result of TRIM21s unique clustering-based activation mechanism.
A key feature of many neurodegenerative diseases is the accumulation of abnormally folded proteins in aggregates. Leo and Will’s groups, working across the LMB and the UK Dementia Research Institute (UK DRI) at Cambridge, demonstrated in 2023 that TRIM21 could be re-purposed to destroy tau protein aggregates associated with Alzheimer’s disease. The team went on to develop two new potential therapies – ‘RING-nanobody’ and ‘RING-Bait’ – that selectively remove aggregated tau proteins and improve symptoms of neurodegeneration in mice.
Building further upon this research, TRIMTECH will now harness TRIM21’s unique properties in the form of the Company’s small molecule TRIMTAC and TRIMGLUE degraders that will direct TRIM21 towards disease-causing protein aggregates. These include diseases like Alzheimer’s that have large patient populations with limited treatment options.
Will said: “Fifteen years since our discovery of TRIM21 as the cytosolic antibody receptor, TRIMTECH will take forward our mechanism-based approach for potently and selectively removing assembled protein species. The company has assembled a world-class cluster of scientists and I am incredibly excited to see what the team can deliver.”
Jan Löwe, LMB Director, commented: “The founding of TRIMTECH, for which I wholeheartedly congratulate Leo and Will, is an important and exciting milestone towards using TRIM21 technology as a therapeutic. Applying the technology to neurodegenerative diseases is especially poignant, given how terrifying they are. Founding of the company now, fifteen years after the original discovery, also shows the value and necessity of basic research with a long-term view, as facilitated by the LMB.”
TRIMTECH recently announced the closing of its $31million (£25million) seed funding round, led by Cambridge Innovation Capital (CIC) and SV Health Investors’ Dementia Discovery Fund (DDF). Damian Crowther, joint entrepreneur-in-residence at CIC and DDF, who cofounded TRIMTECH together with academic co-founders Leo and Will, is now Head of Research, and Nicki Thompson joined as CEO in January 2024. Dean Clift and Jonathan Benn, previously postdocs in the respective academic labs, have joined to accelerate translation into the company. TRIMTECH was also one of the winners in the 2025 #21toWatch Cambridge and East of England entrepreneurship awards.
Further references
Leo’s group page
Will McEwan’s group page
TRIMTECH Therapeutics news release
$31m seed round success fires up TRIMTECH Therapeutics’ mission: Cambridge Independent article
Previous Insights on Research
New potential therapy for neurodegeneration removes tau aggregates and improves motor function
Understanding TRIM21 activation allows Trim-Away toolbox expansion
Trim-Away: powerful new tool for studying protein function