Expected to be first RNA epigenetic drug programme globally to enter the clinic in 2022

STORM Therapeutics, the biotechnology company focused on the discovery of small molecule therapies modulating RNA epigenetics, today announces that it has published a scientific paper in the internationally recognised scientific journal Nature.

The paper entitled ‘Small molecule inhibition of METTL3 as a strategy against myeloid leukaemia’ reveals findings that further establish and validate STORM’s ground-breaking work on targeting RNA modifying enzymes for the development of new anti-cancer therapeutics and describes recent progress made with the METTL3 inhibitor programme. 

STORM has identified novel, potent and selective first-in-class inhibitors of METTL3 that are orally bioavailable and show pronounced anti-tumour efficacy in physiologically relevant, proof of concept animal models of Acute Myeloid Leukaemia (AML), as well as solid tumours. The paper demonstrates that METTL3 small molecule inhibition is effective as a new therapeutic strategy against AML, prolonging survival in a variety of AML models, by specifically targeting key stem cell subpopulations of AML. Additionally, it confirms anti-tumour activity against different AML driver mutations demonstrating that targeting METTL3 is not limited by specific mutations (in contrast to other approaches such as FLT3 or IDH inhibition) and so may have a broad range of patients who might respond to this therapy.

Professor Tony Kouzarides, Founder of STORM Therapeutics and Director of the Milner Therapeutics Institute, University of Cambridge, said: “At STORM we are proud to be leading the field in development of drugs targeting RNA epigenetics and are making rapid progress. This paper has provided comprehensive proof of concept that targeting RNA modifying enzymes represents a promising new avenue for anti-cancer therapy and confirms the findings in our 2017 Nature paper made using genetic approaches.”

In October 2020, STORM announced that STC-15, its first-in-class drug candidate targeting METTL3, had been selected for development towards first in human clinical studies in 2022. STC-15 is an orally bioavailable, small molecule METTL3 inhibitor targeting an entirely new mechanism of action (modulation of RNA epigenetics) to treat AML and other solid and haematological cancers. This publication utilises STM2457, an earlier compound than STC-15.

Keith Blundy, CEO of STORM Therapeutics, said:

“I am delighted to see the publication of our ground-breaking research on STM2457 in a world leading journal. We are excited to be leading the field having selected STC-15, STORM’s first-in-class clinical candidate targeting METTL3 for development towards first in human clinical studies in 2022, addressing AML patients refractory to chemotherapy treatment with limited other options in addition to exploring combinations with standard of care.”

STORM’s work was carried out in collaboration with the University of Cambridge (Gurdon and Milner Institutes) and Wellcome Sanger Institute, and was supported by grants from Cancer Research UK.