STORM Therapeutics Presents STC-15 Preclinical Data Supporting Treatment of Patients with AML at the AACR Acute Myeloid Leukemia and Myelodysplastic Syndrome Conference

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  • Data show that STC-15, an oral METTL3 inhibitor, is effective as monotherapy and in combination with venetoclax using patient-derived tumor models

  • STC-15 Phase 1 trial in solid tumors aims to identify doses and regimen for potential clinical trials in AML and solid tumors

January 25, 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 preclinical AML models was presented at the American Association for Cancer Research (AACR) Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome, held in Austin, Texas on January 23-25.

The presentation entitled “STC-15, a novel METTL3 inhibitor, and its combination with venetoclax confer anti-tumor activity in AML models” describes 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 empathize.

Preclinical data showed that:

  1. STC-15 inhibited proliferation in some AML cell lines with sub-micromolar IC50 values
  2. STC-15 inhibited the growth of 12 patient-derived AML samples in vitro with IC50 values ​​reflecting an average of approximately 1 micromolar
  3. STC-15 reduced BCL2 protein levels in a dose-dependent manner in most AML cell lines tested
  4. STC-15 showed a synergistic inhibition of tumor cell growth in vitro in combination with venetoclax
  5. In an AML patient derived empathize model, STC-15 extended survival compared to a vehicle-treated control group and a venatoclax-treated group of animals
  6. In addition, STC-15 showed a decrease in circulating human CD45+ cells and lower spleen weight compared to vehicle-treated animals

STORMS lead candidate STC-15 is advancing its ongoing Phase 1 trial. 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 pleased with the outcome of the data further validating our previous publication that treatment with METTL3 inhibitors led to the downregulation of BCL2 protein levels in several AML cell lines and empathize 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 pleased to present this new data with patient-derived tumor samples that support the future clinical development of STC-15 in AML. Our ongoing multi-ascending phase 1 trial in solid tumors is aimed at establishing a potential dose and regimen of STC-15 to conduct future clinical trials in AML and solid tumors.”

Details of the conference and the poster presented are as follows:

Poster Presented Title: STC-15, a novel METTL3 inhibitor, and its combination with venetoclax confer antitumor activity in AML models

Presenting authors: Lina Vasiliauskaite1Yaara Ofir-Rosenfeld1Mark Albertella1Coralie Hoareau-Aveilla2Jerry McMahon1Oliver Raush1

Date and time: Tuesday, January 24, 7:15 AM – 9:30 PM 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, including the first-in-class clinical candidate STC-15, an orally bioavailable, highly selective METTL3 inhibitor that entered a clinical trial in November 2022 in cancer patients with solid tumors.

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