STORM Therapeutics Presents New Clinical Data on its First-in-Class METTL3 Inhibitor STC-15 at SITC 2024

STC-15 is well tolerated and demonstrates promising signs of clinical activity observed in multiple tumor types
Gene expression data shows upregulation of innate immunity pathways 
Tumor regressions observed at all dose levels, 60-200 mg TIW

CAMBRIDGE, England, Nov. 11, 2024 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, today announces 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) 39^th Annual Meeting, held in Houston, US, from 6-10 November 2024.

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 follows the Company's presentation at the 36^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in October 2024. 

The presentation at SITC 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 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."

NOTES TO EDITORS

About STORM Therapeutics
STORM Therapeutics is a clinical-stage biotechnology company pioneering cellular reprogramming through RNA modifications to treat disease. Its world leading understanding of RNA modifying enzymes (RME) has led to the discovery of breakthrough small molecule drugs that precisely reprogram cells through RNA biology for the treatment of cancer, inflammation, viruses and CNS diseases.

STORM's lead product, STC-15, is the first RNA modifying enzyme inhibitor to enter human clinical development. STC-15 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors, establishing a data set allowing development in future clinical studies. Preclinical data have revealed that METTL3 inhibition stimulates immune cells and activates interferon pathways, leading to the destruction of tumor cells. Additional preclinical studies have demonstrated enhanced anti-tumor properties in combination with checkpoint inhibitors, supporting clinical development in tumor types where an augmented immune response may result in anti-cancer activity. STORM is building on its first-mover advantage by positioning additional RME inhibitor programs to advance into IND-track activities in 2024. STORM is seeking partners to collaborate and accelerate development of these novel drugs for disease applications outside of oncology.

STORM's specialist healthcare investors include M Ventures, Pfizer Ventures, Taiho Ventures LLC, Seroba Life Sciences, Cambridge Innovation Capital Limited, IP Group plc, UTokyo Innovation Platform Co., Ltd. and the Fast Track Initiative (FTI).

For more information, please visit www.stormtherapeutics.com

About STC-15
STORM's lead product, STC-15, is the first RME inhibitor to enter human clinical evaluation. This agent is an oral small molecule that inhibits METTL3, an RNA methyltransferase implicated in oncology and other diseases. Certain RNA methyltransferases are important regulators of RNA sensing and innate immune activation and, as such, represent novel immune-regulatory targets.

STC-15 has also been shown preclinically to inhibit tumor growth through mechanisms involving anti-cancer immune responses, such as changes in interferon signaling and constructive interaction with T cell checkpoint blockade.

STORM is studying the safety and pharmacology of STC-15 in a Phase 1 clinical study in patients with solid tumors. Details of the study can be found on clinicaltrials.gov under the identifier NCT05584111.

About SITC Annual Meeting
The Society for Immunotherapy of Cancer Annual Meeting is the largest cancer immunotherapy conference, hosted by the leading member-driven organization focused on cancer immunotherapy, SITC. The Annual Meeting brings together international leaders from academia, regulatory and government agencies, as well as industry representatives for unmatched education, scientific exchange and networking with the scientists driving the field.