On February 22, 2024 STORM Therapeutics Ltd. (STORM), the clinical stage biotechnology company discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, reported that Alexandra Sapetschnig, Group Leader at STORM, will present results and conclusions on its METTL1 tRNA methyltransferase program at the ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies Congress 2024 in Paris, France on 26 February (Press release, STORM Therapeutics, FEB 22, 2024, View Source [SID1234640403]).

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The presentation entitled "Targeting the tRNA methyltransferase METTL1 with small molecule inhibitors in cancer" illustrates STORM’s new data showing that pharmacological inhibition of a tRNA methyltransferase affects tumour growth in animal models.

Data demonstrated that:

Two distinct chemical series exhibit METTL1 inhibition in vitro at low nanomolar concentrations while displaying high selectivity over other RNA and protein methyltransferases.
Mechanistically, METTL1 inhibition leads to reduced tRNA methylation and stability of a subgroup of tRNAs.
In several cancer cell lines, METTL1 inhibition impairs cell proliferation and cell cycle progression accompanied by reduced expression of cell cycle regulators.
In vivo, METTL1 inhibitors induce tumour growth inhibition in both immune-deficient and immune-competent mouse strains.
Oliver Rausch, Chief Scientific Officer at STORM Therapeutics, said: "We are delighted to present this exciting new work which demonstrates that targeting specific tRNA pathways via inhibition of the novel RNA methyltransferase METTL1 results in cancer cell reprogramming and profound cancer growth inhibition in vivo. This follows hot on the heels of our groundbreaking work on METTL3 leading to the discovery of STC-15, currently in clinical testing for advanced malignancies, and highlights the immense potential of targeting RNA modifications for the development of new cancer treatments. As we continue to advance and develop our novel proprietary drug discovery pipeline, these new findings illustrate the advancements that STORM are making to transform the treatment landscape for cancer.

All accepted abstracts will be published online only in the ESMO (Free ESMO Whitepaper) TAT 2024 Abstract Book, a supplement to the ESMO (Free ESMO Whitepaper) journal, ESMO (Free ESMO Whitepaper) open.

Details of the conference and poster presentation are as follow:
Poster Title: Targeting the tRNA methyltransferase METTL1 with small molecule inhibitors in cancer
Presenter: Alexandra Sapetschnig1, Beth Thomas1, Eliza Yankova2, Harry Fischl1, Aleksandra Azevedo1, Sarah Bucknell1, Richard Fosbeary1, Sapphire Sawyer1, Sian Evans2, Carmen Livi1, Byron Andrews1, Jack Rogan1, Natalie Webster1, Matthew Fyfe1, Konstantinos Tzelepis2, Oliver Rausch1
Date and Time: 26 February 2024 at 17:15 – 18:15 CET
Session: Cocktail and Poster Display Session
Location: Hall Bordeaux
Presentation Number: 105P