STORM Therapeutics Presents STC-15 Preclinical Data Supporting Treatment of Patients with AML at the AACR Acute Myeloid Leukemia and Myelodysplastic Syndrome Conference
pharmafile | January 25, 2023 | News story | Business Services |
25 January 2023, Cambridge, UK: STORM Therapeutics Ltd. (STORM), the clinical stage biotechnology company discovering and developing novel small molecule therapies targeting RNA modifying enzymes (RMEs) for oncology and other diseases, presented new data on its lead candidate, the METTL3 inhibitor STC-15. The new data in AML preclinical models was presented at the American Association for Cancer Research (AACR) Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome, hosted in Austin, Texas on the 23-25 January.
The presentation entitled “STC-15, a novel METTL3 inhibitor, and its combination with venetoclax confer anti-tumour activity in AML models” detailed the study of the pharmacological inhibition of METTL3 as monotherapy or in combination with venetoclax (FDA approved for AML treatment) in models of acute myeloid leukemia (AML) in vitro and in vivo.
Preclinical data demonstrated that:
- STC-15 inhibited proliferation in some AML cell lines with sub- micromolar IC50 values
- STC-15 inhibited the growth of 12 patient-derived AML samples in vitro with IC50 values reflecting a mean of approximately 1 micromolar
- STC-15 reduced BCL2 protein levels in a dose-dependent manner in the majority of AML cell lines tested
- STC-15 showed synergistic inhibition of tumor cell growth in vitro when combined with venetoclax
- In an AML patient-derived in vivo model, STC-15 extended survival when compared to a vehicle-treated control group and a venatoclax-treated group of animals
- In addition, STC-15 showed a decrease in circulating human CD45+ cells and decreased spleen weight when compared to vehicle treated animals
STORMS lead candidate STC-15 is advancing its ongoing Phase 1 study. The details of the study can be found on clinicaltrials.gov under the identifier NCT05584111.
Oliver Rausch, Chief Scientific Officer of STORM Therapeutics, said: “These studies provide evidence for the utility of METTL3 inhibitors as a new therapeutic approach to treat AML. We are delighted with the outcome of the data which further validates our previous publication that treatment with METTL3 inhibitors led to the downregulation of BCL2 protein levels in several AML cell lines and in vivo models and provides the rationale for conducting a clinical trial in AML with STC-15.”
Jerry McMahon, Chief Executive Officer & President of STORM Therapeutics, said: “We are excited to present this new data with patient-derived tumor samples supporting the future clinical development of STC-15 in AML. Our ongoing Phase 1 multiple-ascending dose study in solid tumors is focused on establishing a potential dose and regimen of STC-15 to conduct future clinical studies in AML and solid tumors.”
Details of the conference and presented poster are as follow:
Poster Presented Title: STC-15, a novel METTL3 inhibitor, and its combination with venetoclax confer anti-tumour activity in AML models
Presenting Authors: Lina Vasiliauskaitė1, Yaara Ofir-Rosenfeld1, Mark Albertella1, Coralie Hoareau-Aveilla2, Jerry McMahon1, Oliver Rausch1
Date and Time: Tuesday, 24 January, 07.15 – 21.30 ET
1Storm Therapeutics Ltd., Cambridge, UK
2Evotec SAS, Toulouse, FR
The Poster and Abstract are available on the STORM Therapeutics website: Publications.
STORM has developed potent and selective METTL3 inhibitors which include the first-in-class clinical candidate STC-15, an orally bioavailable, highly selective METTL3 inhibitor which commenced a clinical trial in cancer patients with solid tumors in November 2022.
