On June 3, 2024 STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, reported 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) (Free ASCO Whitepaper) Annual Meeting, held in Chicago, US (Press release, STORM Therapeutics, JUN 3, 2024, View Source [SID1234644048]).
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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 (Free ASCO Whitepaper) 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 (Free ASCO Whitepaper) 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 (Free ASCO Whitepaper) 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.