Gosselies, Belgium December 8
– A proprietary, highly potent and optimised oral inhibitor of RNA methyltransferase 3 (METTL3) shows low nanomolar IC50 in proliferation assays with several tumor cell lines.
Combination studies with M3i and venetoclax (VENCLEXTA ®, AbbVie Inc. and Genentech Inc.) showed clear synergistic effects to inhibit proliferation of AML cells consistent with the depletion of BCL-2 and MCL1, known targets for venetoclax activity and resistance mechanisms. Single agent dose dependent in vivo efficacy was shown in several animal models using human AML tumor cells.
METTL3, the primary RNA methyltransferase accountable for introducing N-6-methyladenosine (m6A), the most prevalent mRNA modification, plays a crucial role in various cancers. The prevalence of m6A, coupled with the activity and expression of METTL3, has been associated with the onset and advancement of acute myeloid leukemia (AML) and several other tumor types, including non-small cell lung cancer, head and neck squamous cell carcinoma, and more. Epics has developed a collection of highly potent and selective small molecule inhibitors, successfully demonstrating their efficacy across diverse tumor entities.
Graeme Fraser CSO of EPICS Therapeutics said:” Our research team has successfully optimized and presented a METTL3 inhibitor featuring a drug profile that justifies its progression toward clinical development. The strong in vivo effectiveness of our primary candidate offers a distinctive avenue for validating METTL3’s potential as a target, particularly in addressing various types of cancers that lack sufficient treatment options.
Franz Obermayr CEO of EPICS Therapeutics said: “I’m thrilled to announce that we will be showcasing in vivo proof-of-concept data for our optimized developmental candidate at the esteemed American Society of Hematology (ASH) conference. I am confident that in the near future, we will be able to offer a ground-breaking therapeutic option for numerous underserved cancer patients.”
Poster presented: # 2263
Time: 5:30pm to 7:30pm Saturday, December 9th.
https://ash.confex.com/ash/2023/webprogram/Paper189993.html
https://www.sciencedirect.com/science/article/pii/S0006497123088651