STORM Therapeutics’ First-in-Class tRNA methyltransferase inhibitor of METTL1 to be Presented at the 65th Annual ASH Conference

STORM Therapeutics’ First-in-Class tRNA methyltransferase inhibitor of METTL1 to be Presented at the 65^th Annual ASH Conference

• Data demonstrates METTL1 inhibition in vitro at low nanomolar concentrations while displaying high selectivity over other RNA and protein methyltransferases
• Data provides the first proof-of-concept that pharmacological inhibition of a tRNA methyltransferase affects tumour growth in vitro and in animal models

8 December 2023, Cambridge, UK: 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, is pleased to announce that data on its METTL1 tRNA methyltransferase inhibitor will be presented by collaborator Dr Konstantinos Tzelepis at the 65^th Annual ASH Meeting in San Diego, USA on Friday 8 December, 2023.

The presentation entitled “Overcoming Therapy Resistance in AML Using Novel Epitranscriptomic Modalities” details results showing that pharmacological inhibition of a tRNA methyltransferase affects tumour cell growth in in vitro and in vivo models.

Preclinical data demonstrated that:

1. STORM METTL1 inhibitors 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 reduced stability of a subgroup of tRNAs.
3. In several cancer models, METTL1 inhibition impairs cell proliferation and cell cycle progression accompanied by elevation of differentiation markers.
4. In vivo, METTL1i treatment induced strong tumour growth inhibition in cell-line derived xenografts and syngeneic in vivo cancer models (haematological and solid malignancies).

Jerry McMahon, Chief Executive Officer & President of STORM Therapeutics, said: “It is very exciting to be able share for the first time that inhibition of the tRNA methyltransferase METTL1 with a small molecule shows anti-cancer properties. We continue to expand our pipeline of novel and proprietary chemistries to modulate enzymes which modify RNA. We look forward to advancing our first-in-class METTL1 program towards the clinic.”

Dr Konstantinos Tzelepis, Principal Investigator at University of Cambridge and Cambridge Stem Cell Institute, commented: “We are very excited to present novel data on the development and characterisation of the first-in-class bioavailable tRNA methyltransferase inhibitor against METTL1. This is a fantastic collaborative effort which expands significantly the therapeutic landscape of the epitranscriptomics field and capitalises on our previous published work which shown that METTL1 is a key player in oncogenesis.”

Details of the conference and presentation are as follow:

Presented Talk Title: Overcoming Therapy Resistance in AML Using Novel Epitranscriptomic Modalities

Presenter: Dr Konstantinos Tzelepis, Principal Investigator, University of Cambridge and Wellcome-MRC Cambridge Stem Cell Institute

Date and Time: 8 December, 2023 at 2:45pm PST