STORM Therapeutics publishes data in Cancer Discovery showing induction of anti-tumour immunity by METTL3 inhibition

Pre-clinical data strongly supports progression of a METTL3 inhibitor in an immuno-oncology setting

STC-15 is the first molecule specifically targeting METTL3 to enter clinical development

CAMBRIDGE, England, Aug. 8, 2023 /PRNewswire/ -- STORM Therapeutics Ltd. (STORM), a clinical stage biotechnology company focused on discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, is pleased to announce that it has published a scientific manuscript in the internationally recognised scientific journal Cancer Discovery.

The paper, entitled 'Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity', has been published in collaboration with Professor Mark Dawson's laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia, and reveals recent findings that demonstrate the therapeutic potential of drugs targeting METTL3 as immuno-oncology agents. Using pre-clinical cancer models, the study shows that pharmacological inhibition of METTL3 induces double-stranded RNA formation and a profound cell-intrinsic interferon response that potentiates T-cell killing of cancer cells. Whilst METTL3 inhibitors are equally efficacious to anti-PD1 therapy in pre-clinical models, the combination of the two agents has far greater activity, leading to tumour regression and durable anti-cancer immunity. A detailed investigation of the mechanism of action of the two treatments revealed that they act orthogonally and provides a strong rationale for their combination.

Oliver Rausch, Chief Scientific Officer of STORM Therapeutics and joint senior author of the study, said, "We are pleased to share this new data with the scientific community. Our study identifies a novel therapeutic mechanism triggered by METTL3 inhibition that opens a significant opportunity for METTL3 inhibitors in immuno-oncology. This work follows on from our previous work published in 2021 in Nature, demonstrating the efficacy of METTL3 inhibition in acute myeloid leukemia models, and illustrates the broad potential of this new class of drugs in oncology."

Dr. med. Josefin-Beate Holz, Chief Medical Officer of STORM Therapeutics, commented, "This exciting new data strengthens our hypothesis for the clinical development of STC-15 as a novel anticancer therapeutic in monotherapy and in combination with standard of care, including checkpoint inhibitors. We are looking forward to exploring these concepts following the conclusion of the current Phase 1 multiple ascending dose study with STC-15 in patients with relapsed solid tumours." 

Jerry McMahon, Chief Executive Officer and President of STORM Therapeutics, added, "STORM is the first company devoted to pursuing RNA-modifying enzymes as drug targets, and our new study highlights the opportunities for new therapeutics targeting RNA modifications. We are encouraged by the progress of our ongoing Phase 1 trial of STC-15 in solid tumours and look forward to exploring its utility as an immuno-oncology drug in specific tumour types."

Citation:
Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances anti-tumour immunity. Andrew A Guirguis, Yaara Ofir-Rosenfeld et al, 2023, Cancer Discovery (advanced online publication) https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0007

NOTES TO EDITORS

About STORM Therapeutics
STORM Therapeutics (STORM) is a clinical stage biotechnology company creating novel therapies that inhibit RNA modifying enzymes (RME) for use in oncology and other diseases. There are more than 150 RNA modifications reported and approximately 300 RNA modifying enzymes which represent novel therapeutic targets.

STORM has leveraged its first-mover advantage to establish a novel drug discovery and RNA analytics platform leading to the identification of novel targets and a proprietary pipeline of first-in-class small-molecule drug candidates for potential use in oncology, inflammation, viral infection and CNS diseases.

The pipeline is exemplified by STORM's METTL3 inhibitor, STC-15, which has received IND approval and commenced its Phase 1 clinical study in cancer patients in November 2022. STC-15 represents the first ever RNA modifying enzyme inhibitor to enter clinical evaluation in humans. Additional programs are planned for advancement into IND-track activities.

Fierce Biotech named STORM as one of its 2022 "Fierce 15", designating it as one of the most innovative, exciting biotechnology companies in the industry, pioneering novel drug targets.

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

For more information, please visit www.stormtherapeutics.com

About STC-15
STORM's lead clinical program STC-15 is a first-in-class inhibitor of RNA modification and is the first ever RNA methyltransferase inhibitor to enter clinical development. STC-15 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 represent novel immune-regulatory targets.

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

STORM commenced the dosing of the first patient in a Phase 1 clinical study of STC-15 in patients living with solid tumours in November 2022 and anticipates presenting first results from its study in 2024. Details of the study can be found on clinicaltrials.gov under the identifier NCT05584111.

About Peter Mac
Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia's only public health service solely dedicated to caring for people affected by cancer. 

About Cancer Discovery
Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials. As the premier cancer information resource, the Journal also presents Review Articles, Perspectives and Commentaries, News stories, and Research Watch summaries of important journal articles to its readers to keep them informed about the latest findings in the field. Topics span the spectrum of cancer research and medicine from the laboratory to the clinic and epidemiologic studies.