On November 11, 2024 STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, reported that it presented promising data from its Phase 1 clinical study evaluating its METTL3 RNA methyltransferase inhibitor, STC-15, at the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, held in Houston, US, from 6-10 November 2024 (Press release, STORM Therapeutics, NOV 11, 2024, View Source [SID1234648089]).
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The Phase 1 clinical study enrolled 42 patients across five dose escalation cohorts ranging from 60mg to 200mg and explored daily and thrice weekly oral dosing regimens. Data presented at SITC (Free SITC Whitepaper) follows the Company’s presentation at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October 2024.
The presentation at SITC (Free SITC Whitepaper) titled, ‘Phase 1 dose escalation and cohort expansion study evaluating safety, PK, PD and clinical activity of STC-15, a METTL3 inhibitor, in patients with advanced malignancies’, showed:
Gene expression pathways related to Interferon (IFN) signalling, response to virus and dsRNA binding were enriched in patients with longer duration of STC-15 treatment
Tumor regressions were achieved at all dose levels, 60 mg – 200 mg three times a week (TIW), with three sustained Partial Responses (PRs) at 60 mg, 100 mg, and 200 mg TIW in multiple tumor types
Treatment emergent adverse events, including target-related AE’s (e.g. platelet reductions, rash, pruritis) were mainly mild, transient and well managed with supportive care and were not treatment limiting
No maximum tolerated dose established up to 200 mg TIW
Evidence of M1 macrophages in the TME, consistent with preclinical data
Robust METTL3 target engagement indicated by rapid and long-lasting m6A inhibition
Kyriakos P. Papadopoulos, Co-Director of Clinical Research at START San Antonio, principal investigator for the STC-15 Phase 1 study and lead author of the SITC (Free SITC Whitepaper) presentation, said: "The ability to activate the innate immune system while maintaining tolerability and efficacy is what is truly unique about STC-15. STC-15 targets METTL3, initiating a novel immunologic mechanism that demonstrates remarkable safety for an immuno-oncology drug. The early efficacy and safety data in the advanced cancer setting supports further clinical development in Phase 2, in multiple tumor types."
Jerry McMahon, Chief Executive Officer at STORM Therapeutics, said: "STC-15 is first in its class – first to target METTL3, and first to target a RNA methyltransferase. We are pleased to report encouraging signs of clinical activity and corresponding upregulation of the gene pathways associated with the METTL3 mechanism of action. We look forward to developing and progressing our product into a Phase 2 study following these positive results."