An RNA-modifying enzyme inhibitor has shown positive results in treating sarcoma patients during a Phase I trial. 

STC-15, developed by STORM Therapeutics, demonstrated a disease control rate of 54% at 12 weeks and a median progression-free survival of six months. The trial enrolled 42 patients with advanced malignancies across five dose-escalation cohorts. 

The enzyme inhibitor also showed robust target engagement, demonstrated by an average reduction by over 50% in m6A (methylated adenosine) marks on mRNA within 24 hours of dosing across dose cohorts, and evidence of downstream effects on gene transcription. 

STORM says STC-15 is the first RNA-modifying enzyme inhibitor to enter human clinical trials. The candidate specifically inhibits METTL3, an RNA-modifying enzyme that regulates stem cell transformation and differentiation, a critical process in the development of sarcomas and other tumours. 

Results from the subset analysis will be presented by STORM at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place 29 May – 2 June in Chicago, US. 

“These data from the Phase I sarcoma subset provide encouraging early clinical and molecular evidence supporting STC‑15’s differentiation‑focused mechanism of action,” said Jerry McMahon, CEO of STORM Therapeutics. 

“Importantly, we observed a connection between target engagement, downstream transcriptional effects and signals of clinical benefit. For heavily pretreated sarcoma patients with limited treatment options, these results support our ongoing Phase II trial and highlight STC-15’s potential to transcriptionally reprogramme tumour cells.”