'Cutting Edge’ T-knife Gets €66m Series A Financing
To Fund Biotech’s Next-Generation Mouse-Based T-Cell Therapies
Executive Summary
T-knife, a developer of T-cell receptors intended for T-cell therapy in solid tumor cancers, says the series A gives its development program three years of financial runway.
Two-year-old German biotech T-knife GmbH has closed a €66m series A financing that the next-generation adoptive T-cell specialist will use to advance its proprietary humanized T-cell receptor mouse platform to treat solid tumors, its CEO told Scrip.
The Berlin-based group uses its humanized TCR mice platform to carry human TCRαβ gene loci and recombine a broad repertoire of human TCRs, enabling creation and virtual selection of cell receptors for any human tumor antigen.
T-knife was spun out in late 2018 from the Max-Delbrück-Center (MDC), funded by seed capital of €1.5m ($1.8m). The series A financing, completed on 6 August, was led by Versant Ventures and RA Capital Management. Existing investors Andera Partners and Boehringer Ingelheim Venture Fund also participated.
T-knife’s proprietary humanized T-cell receptor mouse expresses only human TCRs that are restricted to human HLA, the human version of the major MHC gene group.
Mammalian T-cell receptors, which generate immunity by responding to billions of unfamiliar ligands, exist in two main heterodimeric isoforms: αβ TCR and γδ TCR. The αβ TCR is expressed on most peripheral T-cells. Most αβ T-cells recognize peptides presented at the cell surface in major histocompatibility complex (MHC) molecules.
Alex Mayweg of Versant Venture noted that while CAR-T based therapies have demonstrated effectiveness in treating hematological cancers, their attempts to treat solid tumors has so far been less successful. “T-knife has developed an exciting technology as its TCRT cell therapy targets tumor antigens in an MHC-restricted manner, allowing it to be one of the few platforms that is able to target solid tumors,” Mayweg said.
T-knife CEO Elisa Kieback Kieback said proceeds from the series A round would be used to advance at least four programs into the clinic, as well as ramping-up preclinical work for additional selected proprietary pipeline candidates and discovering TCRs against novel targets.
T-knife has so far demonstrated preclinical proof-of-concept with its lead asset, TCRD 1367, which is currently in Phase I clinical development.
T-knife has also validated the platform for over 90 undisclosed cancer targets, with several follow-on drug candidates being already in preclinical development. The biotech expects to bring three additional TCRs into the clinic by 2022.
“This platform is applicable in many therapeutic indications, but the company only wants to focus on solid tumor indications,” explained CEO Kieback, who is also scientific co-founder of T-knife.
“What we bring new to the table is a very new way of how these T cell receptors are designed in mice,” she said.
“Our approach progresses on from the development in transgenic mice of fully human monoclonal antibodies. We are basically the first platform that can also do that for T cell receptors.”
Due to its natural in vivo selection of high affinity TCRs, T-knife says its TCR-T-cell platform has the potential to be a marked improvement over existing TCR technologies in treating solid tumors.
“These humanized T-cell receptors are generated naturally in both people and mice, which gives them unique properties. One is that, due to their natural selection they have a very defined specificity which we believe makes them more specific for their intended target.
“Also, the TCRs have a high affinity, so when you generate the T cell receptor in the mouse, you can basically avoid the tolerance that tumor cells generate in humans, so the idea is to really generate a strong immune response to human/human antigens inside the mice, which are not tolerant to these antigens.”
T-knife has so far demonstrated preclinical proof-of-concept with its lead asset, TCRD 1367, which is currently in Phase I clinical development as a treatment for an as-yet undisclosed solid tumor.
The series A adds to the €1.5m ($1.8m) raised by the biotech initially in December 2018. “This financing will fund us for the next three years,” Kieback said. “By then, we hope to have the Phase I read out from our lead asset and hope also to have moved up to three additional assets into the clinic.”
She said T-knife would eventually be open to partnering both its assets and its platform with third parties.
“It’s a broadly applicable technology that T-knife have, and we’ve already had business development discussions with many with potential partners who want TCRs generated for their targets."
“Also, before the company was spun out in 2018, there was a lot of validation work done and we generated receptors for more than 90 targets, and we are already discussing possibly out-licensing certain TCR assets. So, there is already much interest being shown in what we have – and what we can produce in future,” she concluded.