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The second part of the symposium started with the talk of Dr. Oliver Rausch from Storm Therapeutics. Their research focuses on the discovery and development of small molecules modulating RNA epigenetics.[5,6] The company is particularly interested in the inhibition of m6A methyltransferase METTL3 which is a novel target for acute myeloid leukemia (AML), using ligand activity mapping and SAMalogue library. After the development of a first potent and selective small molecule compound for METTL3, the screening was later extended to different chemical series. Initially, Dr. Rausch used different panels of cell lines from which the most sensitive ones were those of pancreatic, ovarian, lung and hematologic origins. Later, in vivo testing was performed which demonstrated efficacy in AML models as well as inhibition of lung cancer xenograft growth. Mass spectrometry was used to confirm the engagement of METTL3 in cell lines and in vivo and multiple pharmacodynamic biomarkers were used to demonstrate METTL3 inhibition in these models. With this strong preclinical data in hand, STC-15 has been selected for first stage clinical trials as the first-in-class drug candidate targeting METTL3.

DMCCB Basel Symposium on 'Targeting RNA by Small Molecules' Online, 4th February, 2021