Publications
First characterization of tRNA modifications that dysregulate mRNA stability of signaling pathways in cancer
Umlaut.bio is an EMBL spin-off creating cancer and autoimmune therapeutics through small molecule inhibition of tRNA modifications
With its senior executive team and a world-class advisory board, Umlaut.bio has started operations funded by HTGF, LBBW Venture Capital and L-Bank through the InnoGrowth BW program. Additionally, the company is backed by Eli Lilly and Ono Pharmaceutical through the Mission BioCapital Platinum Program and Abbvie through the Golden Ticket initiative
Heidelberg, Germany, May 13, 2025 – Umlaut.bio GmbH (“Umlaut”), a German/Swiss oncology/autoimmunity biotech company, announced the publication of its molecular mode-of-action today. The publication supports its first-in-biology approach to develop small molecules to block pathologically dysregulated tRNA modifications that are associated with aggressive disease progression in cancer. The publication in Cell shows, for the first time, that tRNA modifications act by increasing the stability of protein-coding mRNAs and that this mechanism is upregulated in cancer cells (https://www.cell.com/cell/fulltext/S0092-8674(25)00415-5).
Umlaut, an EMBL spin-off, is pioneering the development of small molecules that inhibit enzymes involved in tRNA modifications, addressing the shortcomings of current cancer and autoimmune treatments with the promise of circumventing treatment resistance as well as a favorable side effect profile. Foundational to its approach is its novel, proprietary platform that enables high-throughput screening and mass spectrometry-based validation of the inhibition of such enzymes.“This publication marks a change in our understanding of how RNA modifications influence posttranscriptional gene regulation” said Bastian Linder, Ph.D., Co-founder, Chief Scientific Officer at Umlaut and first author of the publication.
“Our approach showed that modified nucleotides in mRNA and tRNA can functionally interact in vivo and that this interaction serves to regulate gene expression at the level of mRNA decay”.
In the publication, the scientists demonstrated that the mRNA modification N6-methyladenosine (m6A) leads to a deoptimization of specific codons that ultimately results in the decay of m6A-modified mRNAs. The tRNA modification mcm5s2U counteracts this process by enhancing the decoding of m6A-modified codons and stabilizing m6A-modified mRNAs. The expression of both RNA modification pathways is coordinated, but dysregulated in cancer, where increased mcm5s2U is responsible for the overactivation of multiple oncogenic pathways.
Karsten Fischer, Ph.D., Chief Executive Officer at Umlaut added: “Addressing such a fundamentally novel biological principle is highly promising, potentially allowing a leap forward in treatment of cancer and autoimmune diseases. Combining these findings with our proven technology suite and classical small molecule development expertise is maximizing the chances of success to do so.”
Umlaut has assembled a world-class executive and corporate advisory team with a century of relevant expertise to maximally leverage the value of this novel field of biological regulation. The company is seed funded by the HTGF and LBBW Venture Capital, supported by L-Bank through the InnoGrowth BW programme. In addition, Umlaut.bio benefits from the support of Ono Pharmaceutical and Eli Lilly through the Mission BioCapital Platinum Program and Abbvie through the Golden Ticket.
Umlaut.bio GmbH(D)
(c/o BioLabs Heidelberg)
Nikola-Tesla-Str. 1
D-69124 Heidelberg
Germany
Umlaut.bio GmbH (CH)
Breitenstrasse70C
CH-8832 Wilen bei Wollerau
Switzerland
info@umlaut.bio
www.umlaut.bio
About Umlaut.bio GmbH
Umlaut.bio GmbH is a pioneering biotech company focused on developing first-in-biology therapies targeting cancer and autoimmune diseases. Small molecules will be developed to inhibit key steps in tRNA modification synthesis, thereby preventing overactivation of a multitude of signalling molecules at scale. This is a hallmark of uncontrolled cancer growth as well as autoimmune diseases which can not be addressed with chemotherapy or targeting individual proteins.