METTL3

Ground-breaking discoveries on the characteristics of RNA epigenetics unveiled novel targets to treat diseases CAMBRIDGE, England, June 17, 2024 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, is delighted to announce that its Founder & Director and Professor of Cancer Biology, University of Cambridge, UK, Tony Kouzarides, PhD, FMedSci, FRS, will be honored with a Knighthood for his global impact on disease treatment. Professor Kouzarides, a world leading cancer biologist with a career spanning over 25 years, will be awarded the knighthood at the King's Birthday Honors, 2024, Investiture ceremony. Professor Kouzarides has been dedicated to the conversion of science into patient benefit throughout his career. STORM Therapeutics was spun out from the University of Cambridge in 2015 by Professor Kouzarides and his colleague Professor Eric Miska, following their groundbreaking work in RNA epigenetics. Professor Kouzarides and his research group identified the importance of RNA modifications during the development of cancer, opening the pathway for STORM to develop first-in-class drugs targeting this new mechanism. STORM's platform, eliciting cellular reprogramming through RNA modification, has potential beyond cancer in areas including neurodegenerative diseases, inflammation and infectious diseases. Professor Tony Kouzarides, Founder & Director of STORM Therapeutics, said: "I am honored to receive this award, which reinforces the importance of translating basic research into therapies by engaging academic researchers with healthcare businesses. STORM Therapeutics represents a shining example of this principle." Jerry McMahon, Chief Executive Officer of STORM Therapeutics, commented: "STORM is delighted to see Tony recognized nationally as a pioneer in the field of cellular reprogramming through RNA modification. Receiving this honor from the King is the pinnacle of a tremendous and productive career. Tony's commitment, focus and dedication has been unwavering, and we look forward to continuing to work with him as STORM's programs advance into the clinic as effective treatments for patients." In addition to his role at STORM, Professor Kouzarides is Professor of Cancer Biology at the University of Cambridge and a Senior Group Leader at the university's Gurdon Institute, specializing in developmental biology and cancer biology. He is also the Director and Co-Founder of the Milner Therapeutics Institute at the University of Cambridge, which focuses on building scientific collaborations to transform therapies. Professor Kouzarides also has his own laboratory in Cambridge, The TK LAB and has been studying epigenetic modifications for many years, starting with the identification of the first human enzymes to modify chromatin in 1996. His lab has identified and characterized many chromatin modification pathways and showed their involvement in cancer. The lab is now investigating the functions of mRNA modifications and their connections to cancer. In close collaboration with STORM Therapeutics, The Kouzarides Lab is targeting RNA modification pathways with small molecule inhibitors, to develop drugs against cancer and other diseases. Professor Kouzarides is also the Founder and Director of Cambridge Gravity, an organization for the promotion of science at the University of Cambridge. He is Founder and Patron of the Spanish cancer charity Vencer el Cancer ("Conquer Cancer"). Professor Kouzarides is Co-Founder and ex-Director of antibodies and reagents company Abcam, which was sold to the Danaher Corporation for US$5.7 billion (£4.5bn) in 2023. He was also Co-Founder and ex-Director of Chroma Therapeutics, a drug discovery company based in Oxford. Professor Kouzarides is an elected member of the European Molecular Laboratory Organization (EMBO), fellow of the British Academy of Medical Sciences (FMedSci), fellow of the Royal Society (FRS), fellow of the American Academy of Arts and Sciences (AAAS) and fellow of the Cyprus Academy of Sciences, Letters and Arts. He has also been awarded the Bodossaki Foundation prize in Biology, the Wellcome Trust Award for Research in Biochemistry Related to Medicine, the Tenovus Medal, the Bijvoet Medal, the Biochemical Society Novartis Medal and Prize, the Heinrich Wieland Prize, the Cyprus Excellence in Science Award and the Nemitsas Prize. Find out more about Professor Kouzarides on his Wikipedia page, here. 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 . 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 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. SOURCE STORM Therapeutics

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 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. SOURCE STORM Therapeutics

STC-15 is the first METTL3 inhibitor to enter clinical development Clinical data will include safety, pharmacology, target modulation, and clinical activity CAMBRIDGE, England, May 24, 2024 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, today announces that it will be presenting interim clinical data on its first-in-class lead product, STC-15 at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago, US from May 31 to June 4, 2024. The poster presentation, 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', describes findings from STORM's ongoing dose escalation and expansion Phase 1 clinical study to evaluate STC-15, an oral and highly selective small molecule inhibitor of METTL3, in advanced cancer patients. These interim results will focus on safety, pharmacokinetics, target modulation and tumor assessments to support future clinical studies. STC-15 is the first molecule specifically targeting an RNA methyltransferase enzyme to enter clinical development. Preclinical data has demonstrated that METTL3 inhibition stimulates immune cells and activates interferon pathways, leading to the destruction of tumor cells. The poster presentation will detail the study design, patient demographics, safety data, pharmacokinetics, METTL3 target engagement, mechanistic biomarker data, and assessments of clinical activity. Details of the poster presentation are as follow: Poster Title: 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 Presenter: Justin Moser at HonorHealth Research Institute Authors: Justin Moser[1], Kyriakos Papadopoulos[2], Jordi Rodon Ahnert[3], Yaara Ofir-Rosenfeld[4], Josefin-Beate Holz[4] Organizations: [1]HonorHealth Research Institute, [2]START San Antonio, [3]The University of Texas MD Anderson Cancer Center, [4]Storm Therapeutics Ltd Poster Session: Developmental Therapeutics—Immunotherapy Session Date and Time: Saturday June 1, 2024, 9:00 AM - 12:00 PM CDT Poster Board Number: 65 Abstract Presentation Number: 2586 The Abstract is available on the ASCO online itinerary planner here, and on the STORM website here. 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 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. SOURCE STORM Therapeutics