Conversations from ESMO Targeted Anticancer Therapies Congress 2024 

DDW’s Megan Thomas caught up with Oliver Rausch, Chief Scientific Officer at Storm Therapeutics, following the ESMO Targeted Anticancer Therapies Congress 2024, a global meeting focusing on promising new anticancer targets and agents, focusing on those in early phase clinical development. Rausch gave an update on the latest developments from the conference and scientific findings the company presented at the meeting.

MT: What are the key takeaways from this year’s ESMO TAT?
OR: The presentations at ESMO TAT 2024 highlighted our advances in targeted and more personalised anti-tumour therapies. For example, progress made in developing gene mutant-specific inhibitors, antibody-drug conjugates (ADC), or cellular therapies. More importantly, it also highlighted that significant challenges remain in selecting the right therapies for the right patients despite the progress made through genomic testing and implementation of circulating tumour (ct) DNA analyses. Additional approaches, such as profiling of RNA and proteins, and the use of artificial intelligence (AI), could be key to providing a more comprehensive picture of a patient’s tumour and enable the use of optimised treatments.

MT: Why was STORM attending the conference?
STORM has established 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 results and conclusions from our METTL1 tRNA methyltransferase program. We were there to present the latest findings from our research.

MT: What data did you present at the conference?
OR: In a presentation entitled “Targeting the tRNA methyltransferase METTL1 with small molecule inhibitors in cancer”, we unveiled new data showing how the pharmacological inhibition of tRNA methyl transferase affects tumour growth in animal models.

We were excited to unveil data showing that two distinct chemical series exhibit METTL1 inhibition in vitro at low nanomolar concentrations with minimal interference with other RNA and protein methyltransferases.

METTL1 inhibition leads to reduced tRNA methylation and stability of a subgroup of tRNAs and in several cancer cell lines impairs cell proliferation and cell cycle progression, accompanied by reduced expression of cell cycle regulators.

In vivo, METTL1 inhibitors induce tumour growth inhibition in both immune-deficient and immune-competent mouse strains.

MT: What’s next for STORM’s research?
OR: We are going to build on the work that led to the discovery of STC-15, a METTL3 inhibitor, which is in Phase I development in advanced cancer. Results of that Phase I trial are expected to be presented later this year. We hope to advance this program into Phase Ib/II combination studies, leveraging preclinical evidence that METTL3 inhibition enhances the cytotoxicity of various anti-cancer treatments, such as chemotherapy and checkpoint inhibitors.

The variety of our programs showcases the broad applicability and versatility of the STORM platform. In addition to STC-15 and our METTL1, our pipeline contains a number of preclinical programs that are advancing rapidly for the treatment of viruses, neurodegeneration, cancer, and immuno-inflammatory conditions.