STORM Therapeutics Unveils New Clinical Data on METTL3 Inhibitor STC-15 at SITC 2024

STORM Therapeutics Ltd. (STORM) recently unveiled promising findings from its Phase 1 clinical study of STC-15, a METTL3 RNA methyltransferase inhibitor. This announcement was made at the Society of Immunotherapy for Cancer (SITC) 39th Annual Meeting in Houston, US, held from November 6-10, 2024.

The Phase 1 clinical trial included 42 patients, divided into five dose groups ranging from 60 mg to 200 mg. The study examined both daily and three-times-weekly oral dosing schedules. The key data presented at SITC builds upon earlier findings shared at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in October 2024.

The SITC presentation, 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,' highlighted several significant outcomes. Gene expression pathways associated with Interferon (IFN) signaling, response to viruses, and dsRNA binding were notably enriched in patients receiving extended STC-15 treatment. Tumor regressions were observed across all dose levels, with three sustained Partial Responses (PRs) documented at 60 mg, 100 mg, and 200 mg dosages taken three times weekly, in various tumor types.

Adverse events related to the treatment, such as reductions in platelets, skin rash, and itching, were generally mild, temporary, and manageable with supportive care. Importantly, these adverse events did not limit the treatment. No maximum tolerated dose was identified up to 200 mg taken three times a week. The presence of M1 macrophages in the tumor microenvironment was consistent with preclinical data, and robust METTL3 target engagement was indicated by rapid and sustained m6A inhibition.

Kyriakos P. Papadopoulos, Co-Director of Clinical Research at START San Antonio and principal investigator for the STC-15 Phase 1 study, emphasized the unique ability of STC-15 to activate the innate immune system while maintaining a high level of tolerability and efficacy. He noted that STC-15 targets METTL3, initiating a novel immunologic mechanism with impressive safety for an immuno-oncology drug. The early efficacy and safety data support the further clinical development of STC-15 in Phase 2 trials across multiple tumor types.

Jerry McMahon, Chief Executive Officer at STORM Therapeutics, expressed satisfaction with the encouraging signs of clinical activity and the corresponding upregulation of gene pathways associated with the METTL3 mechanism of action. He looks forward to advancing STC-15 into Phase 2 studies based on these positive results.

STORM Therapeutics is a clinical-stage biotechnology company dedicated to the development of small molecule drugs targeting RNA modifying enzymes (RME) to treat cancer and other diseases. The company's lead product, STC-15, is the first RNA modifying enzyme inhibitor to enter human clinical development. Preclinical data suggest that METTL3 inhibition stimulates immune cells and activates interferon pathways, leading to tumor cell destruction. Additionally, preclinical studies have shown enhanced anti-tumor properties when STC-15 is combined with checkpoint inhibitors.

STORM Therapeutics is leveraging its pioneering position to advance additional RME inhibitor programs into investigational new drug (IND) activities in 2024. The company is also seeking partners to collaborate in accelerating the development of these novel drugs for applications beyond oncology.