STORM Therapeutics publishes data in Cancer Discovery showing induction of anti-tumour immunity by METTL3 inhibition

STORM Therapeutics publishes data in Cancer Discovery showing induction of anti-tumour immunity by METTL3 inhibition

Pre-clinical data strongly supports progression of a METTL3 inhibitor in an immuno-oncology setting

STC-15 is the first molecule specifically targeting METTL3 to enter clinical development

8 August 2023, Cambridge, UK: STORM Therapeutics Ltd. (STORM), a clinical stage biotechnology company focused on discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, is pleased to announce that it has published a scientific manuscript in the internationally recognised scientific journal Cancer Discovery.

The paper, entitled ‘Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity’, has been published in collaboration with Professor Mark Dawson’s laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia, and reveals recent findings that demonstrate the therapeutic potential of drugs targeting METTL3 as immuno-oncology agents. Using pre-clinical cancer models, the study shows that pharmacological inhibition of METTL3 induces double-stranded RNA formation and a profound cell-intrinsic interferon response that potentiates T-cell killing of cancer cells. Whilst METTL3 inhibitors are equally efficacious to anti-PD1 therapy in pre-clinical models, the combination of the two agents has far greater activity, leading to tumour regression and durable anti-cancer immunity. A detailed investigation of the mechanism of action of the two treatments revealed that they act orthogonally and provides a strong rationale for their combination.

Oliver Rausch, Chief Scientific Officer of STORM Therapeutics and joint senior author of the study, said, “We are pleased to share this new data with the scientific community. Our study identifies a novel therapeutic mechanism triggered by METTL3 inhibition that opens a significant opportunity for METTL3 inhibitors in immuno-oncology. This work follows on from our previous work published in 2021 in Nature, demonstrating the efficacy of METTL3 inhibition in acute myeloid leukemia models, and illustrates the broad potential of this new class of drugs in oncology.”

Dr. med. Josefin-Beate Holz, Chief Medical Officer of STORM Therapeutics, commented, “This exciting new data strengthens our hypothesis for the clinical development of STC-15 as a novel anticancer therapeutic in monotherapy and in combination with standard of care, including checkpoint inhibitors. We are looking forward to exploring these concepts following the conclusion of the current Phase 1 multiple ascending dose study with STC-15 in patients with relapsed solid tumours.”

Jerry McMahon, Chief Executive Officer and President of STORM Therapeutics, added, “STORM is the first company devoted to pursuing RNA-modifying enzymes as drug targets, and our new study highlights the opportunities for new therapeutics targeting RNA modifications. We are encouraged by the progress of our ongoing Phase 1 trial of STC-15 in solid tumours and look forward to exploring its utility as an immuno-oncology drug in specific tumour types.”

Citation:

Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity. Andrew A Guirguis, Yaara Ofir-Rosenfeld et al, 2023, Cancer Discovery (advanced online publication) https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0007