STORM Therapeutics Presented Interim Phase 1 Clinical Data on its METTL3 RNA Methyltransferase Inhibitor STC-15 at ASCO 2024

STC-15 was well tolerated and clinical activity was observed across the pharmacologically active dose range in advanced cancer patients

Primary objectives were achieved to progress STC-15 into combination with checkpoint inhibitor combination studies

CAMBRIDGE, England, June 3, 2024 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, today announces that interim Phase 1 clinical data from its first-in-class lead product, STC-15, was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, US.

The presented poster, entitled, '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 recent findings on STORM's lead product, STC-15, a potent and selective METTL3 inhibitor and the first molecule specifically targeting an RNA methyltransferase enzyme to enter clinical development.

The study was conducted to evaluate the safety, pharmacokinetics, target modulation and clinical activity of STC-15 in patients with advanced malignancies, with the aim of establishing a recommended Phase 2 dose escalation to support future clinical development. The study enrolled 33 patients across five dose escalation cohorts ranging from 60mg to 200mg and explored daily and thrice weekly oral dosing regimens. Data presented at ASCO from 33 patients is outlined below:

• STC-15 is well tolerated across the pharmacologically active dose range
• Treatment emergent adverse events (TEAEs) were manageable: common related adverse events were thrombocytopenia, rash, and pruritus
• As of April 15, 2024, 27 patients were evaluable for response assessment with at least 1 on-treatment scan. Clinical activity was observed, comprising of;
  - 11% Overall Response Rate (3 partial responses)
  - 63% Disease Control Rate (14 stable disease, 3 partial responses)
• PK simulations and safety data support oral administration of STC-15 three times a week (TIW)
• Significant reductions in methylated polyA-RNA in blood samples from all cohorts demonstrated METTL3 target engagement and rapid PD effect
• Additional PD biomarker analysis indicated activation of interferon signaling and innate immune responses, as measured by RNA transcript analysis in blood cells from treated patients
• Recommended Phase 2 doses were identified as between 60mg and 200mg TIW
• Advancement of STC-15 into combination studies with checkpoint inhibitors is expected to commence in 2024

Jerry McMahon, Chief Executive Officer of Storm Therapeutics, said: "This Phase 1 data, to date, demonstrates the encouraging potential of STC-15 and its ability to impact a wide range of cancers. STC-15 is showing excellent safety and pharmacologic properties as it advances further into clinical development. As part of STORM's evolving strategy, we are expanding our studies and structuring clinical trial designs to include patients with cancers such as lung, melanoma, head and neck, and endometrial cancer in the future, and we look forward to providing further updates in due course."

Josi Holz, Chief Medical Officer of STORM Therapeutics, commented: "These data signify great progress for STORM as we continue to develop our pipeline of RNA modifying enzyme inhibitors. We are pleased to be presenting data that demonstrates the potential of STC-15 and its promising signs of tolerability and clinical activity. We look forward to completing the current Phase 1 study and including the addition of checkpoint inhibitors."

Justin Moser, Principal Investigator at HonorHealth Research Institute and First Author, remarked: "These new data presented at ASCO on STC-15 are promising and support future clinical studies with this novel agent and new mechanism. METTL3 inhibition has demonstrated early clinical activity and represents a new way to activate the innate immune system with the potential to treat cancer in patients across a range of tumor types."

Abstracts are available on the ASCO program guide here, and on the STORM website here.

STC-15 is currently under evaluation for the treatment of patients with advanced solid tumors in a first-in-human, Phase 1 clinical study with ongoing with cohorts being expanded to further evaluate safety, food effect, PK/PD, clinical activity, with the goal of determining optimized active doses. Details of the study can be found on clinicaltrials.gov under the identifier NCT05584111.

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 signalling and synergy 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 ASCO

Founded in 1964, the American Society of Clinical Oncology is the world's leading professional organization for physicians and oncology professionals caring for people with cancer.