Versant, RA Capital tee up T-knife to apply TCRs to solid tumors

Berlin-based T-knife is planning a U.S. unit will lead business development activities. (Questex)(Image: Questex)

T-knife has raised €66 million ($78 million) to take four prospects from its TCR-T-cell platform into the clinic. Versant Ventures and RA Capital Management came together to lead the series A round in the belief T-knife can realize the potential of cell therapies in the treatment of solid tumors. 

Thomas Blankenstein, the Max-Delbrück-Center professor who co-founded T-knife, started to create the platform that gave rise to the Berlin-based biotech in the early 2000s and published a paper on the use of transgenic mice to express a diverse range of T-cell receptors (TCR) in 2010. Back then, TCR-T cell therapy was just making its way on to the radars of investors. Today, the approach is seen as one of the best chances of bringing the power of cell therapies to solid tumors. 

Against that backdrop of rising interest, T-knife has tapped an A-list investor syndicate for a big series A round. Versant Ventures and RA Capital Management came across the Atlantic to co-lead the series A. T-knife also benefited from the “significant participation” of its existing investors, Andera Partners and Boehringer Ingelheim Venture Fund.

The investors put up the money on the strength of early evidence that T-knife can develop TCR-T cell therapies that deliver substantial responses, up to and including cures, in solid tumor patients. 

Biotechs such as Adaptimmune and Immatics already have TCR-T cell therapies in the clinic. What may set T-knife apart is the nature of its platform. The transgenic mouse platform carries the entire human TCRαβ gene loci, enabling T-knife to generate TCRs that it claims have particularly high affinity and specificity.  

“They are very naturally selected in an organism. We do not artificially modify them, but you really use this natural selection that T cells undergo in an organism to select really specific receptors,” T-knife CEO Elisa Kieback said.

That selection process explains the specificity. The claimed high affinity stems from the use of mice. By avoiding immune tolerance mechanisms, T-knife thinks it can discover high-affinity TCRs. 

Alex Mayweg of Versant Ventures has bought into the idea, arguing the platform is one of the few that can target solid tumors in a statement to disclose his firm’s participation in the series A. Mayweg zeroed on the ability of TCR-T cell therapies to target tumor antigens in an MHC-restricted manner as a key element of the technology.

If T-knife lives up to the expectations of its early supporters, it will unlock the use of cell therapies against solid tumors. That prospect reflects a belief T-knife’s platform addresses the big problem that has held the field back to date.

“It really comes down to the properties of the receptors, which have not been optimal in the past,” Kieback said.

T-knife plans to complete a phase 1 trial of its lead asset, which is already in the clinic, using the cash and have enough money left over to take three other candidates into humans by 2022. Another slice of the series A funding will support T-knife’s aspirations to expand in the U.S. 

Kieback said Berlin will remain the focus of the technology side of T-knife’s operation, giving it a star role in developing the platform and taking assets through preclinical, but a planned U.S. unit will lead business development activities.