First patient dosed with novel RNA modifying enzyme inhibitor

STC-15, a first-in-class ribonucleic acid (RNA) modifying enzyme inhibitor, has been dosed in the first patient in a clinical trial, making it the first molecule targeting an RNA methyltransferase to enter clinical development.

Storm Therapeutics oral METTL3 inhibitor is being assessed in the Phase I study (NCT05584111) to examine the drug’s effect on solid tumours.

First-in-human clinical trial for first RNA modifying enzyme inhibitor

The trial is a multiple ascending dose escalation trial anticipated to enrol 40-60 patients to measure the safety, pharmacokinetics, target engagement, biomarkers related to mechanism and anti-tumour efficacy of STC-15.

Pre-clinical studies of STC-15

Certain RNA methyltransferases regulate RNA sensing and innate immune activation and represent novel immune-regulatory targets. Preclinical data indicated enhanced interferon signalling and synergy with T cell checkpoint blockade as an important mechanism of action of STC-15, resulting in tumour regression and anti-cancer immunity in rodent models. In addition, STC-15 has shown efficacy in leukaemia models via mechanisms including inhibition of leukaemia stem cell function.

Dr Jerry McMahon, CEO of Storm Therapeutics asserted: “We intend to exhibit preclinical data related to STC-15 at future medical conferences this year as we execute our Phase I study in patients with solid tumours. We anticipate presenting results from our Phase I study in 2023.”

Dr Josefin-Beate Holz, CMO of Storm Therapeutics added: “Clinical development allows us to establish meaningful clinical benefit with RNA modifying enzyme inhibitors in cancer patients. This first trial is a ground-breaking milestone for the drug class.”

Professor Tony Kouzarides, founder of Storm Therapeutics and Director of the Milner Therapeutics Institute, University of Cambridge stated: “… targeting RNA modifying enzymes represent a promising new avenue for anti-cancer therapy…” The comment was based on data published in Nature in 2021, demonstrating Storm’s first-in-class METTL3 inhibitor was effective as a new therapeutic strategy against acute myeloid leukaemia (AML).