STM9005 / STORM Therap - LARVOL DELTA

First-in-class inhibitors of the tRNA methyltransferase METTL1 for the treatment of cancer (AACR 2024) - "Studies on cell-line derived xenograft or syngeneic in vivo mouse models were conducted to assess tumor growth inhibition after oral or intraperitoneal administration of the potent METTL1 small molecule inhibitor STM9005...Here, we describe the discovery of first-in-class inhibitors of METTL1 tRNA methyltransferase. To our knowledge, our data provide the first evidence that pharmacological inhibition of a tRNA methyltransferase reduces tumor growth in vivo."

Late-breaking abstract • Brain Cancer • CNS Tumor • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Glioblastoma • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • ATF4 • METTL1

Pharmacological inhibition of METTL1 as a novel therapeutic strategy against aggressive malignancies (AACR 2025) - "The impact of STM9005 was measured by cellular mechanistic assays and modification-induced misincorporation tRNA sequencing, revealing decreased m7G methylation and lower levels of target tRNAs. The efficacy of STM9005 was determined in a panel of cancer models, including AML, melanoma, and PDAC. METTL1 inhibition impaired cell proliferation and viability in multiple cancer models, with no effects in non-cancerous cells, suggesting a cancer-specific mechanism of action."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • METTL1

PHARMACOLOGICAL INHIBITION OF METTL1 AS A NOVEL THERAPEUTIC STRATEGY AGAINST AML (EHA 2024) - "Collectively, we describe the discovery and characterization of first-in-class inhibitors of METTL1 tRNAmethyltransferase. We show that pharmacological inhibition of METTL1 in vivo leads to strong anti-tumoreffects in physiologically and clinically relevant models of AML. To our knowledge, our data provide the firstevidence that pharmacological inhibition of a tRNA methyltransferase reduces AML growth in vivo."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • METTL1

STORM Therapeutics to Present Data on its First-in-Class METTL1 tRNA Methyltransferase Inhibitors at AACR Annual Meeting 2024 (PRNewswire) - "STORM Therapeutics...today announced that Alexandra Sapetschnig, Group Leader at STORM, will present late breaking data on STORM's METTL1 inhibitors at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, California, held 5-10 April 2024. The presentation entitled 'First-in-class inhibitors of the tRNA methyltransferase METTL1 for the treatment of cancer' details the discovery of STORM's first-in-class inhibitors of METTL1 tRNA methyltransferase and supporting evidence of its potential as a novel target for anti-cancer drugs."

Clinical data • Late-breaking abstract • Oncology