STORM Therapeutics to Present Findings on its First-in-Class METTL1 tRNA Methyltransferase Inhibitors at ESMO Targeted Anticancer Therapies Congress

  • Data demonstrates pharmacological inhibition of METTL1 inhibits tumour growth and reduces tRNA methylation and stability of tRNAs

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, today announced that Alexandra Sapetschnig, Group Leader at STORM, will present results and conclusions on its METTL1 tRNA methyltransferase program at the ESMO Targeted Anticancer Therapies Congress 2024 in Paris, France on 26 February.

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 tumor growth in animal models.

Data demonstrated that:

  1. Two distinct chemical series exhibit METTL1 inhibition in vitro at low nanomolar concentrations while displaying high selectivity over other RNA and protein methyltransferases.
  2. Mechanistically, METTL1 inhibition leads to reduced tRNA methylation and stability of a subgroup of tRNAs.
  3. In several cancer cell lines, METTL1 inhibition impairs cell proliferation and cell cycle progression accompanied by reduced expression of cell cycle regulators.
  4. 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 TAT 2024 Abstract Book, a supplement to the ESMO journal, ESMO open.