Undisclosed YTHDC1 inhibitor / Transition Bio - LARVOL DELTA

Discovery of first-in-class YTHDC1 small molecule inhibitors for the treatment of MYC-driven cancers (AACR 2026) - "Moreover, YTHDC1 inhibition shows pronounced synergy with standard of care agents such as venetoclax in AML. Collectively, these findings establish YTHDC1 as a tractable therapeutic target for MYC-driven malignancies."

Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • YTHDC1

Condensate dynamics drive adaptive METTL3 inhibitor resistance (AACR 2026) - "Therapeutically, co-targeting with a newly developed YTHDC1 inhibitor or the clinically approved BCL-2 inhibitor venetoclax synergistically enhances METTL3i efficacy in vitro and in vivo in clinically relevant models including AML patient-derived xenografts.Together, these findings uncover adaptive reorganization of the m6A machinery across hematologic and solid cancers. The YTHDC1 pathway and its condensate state act as predictive biomarkers and enhancers of therapeutic efficacy in METTL3-targeted cancers. Combinatorial targeting of METTL3 and YTHDC1/BCL-2 as a strategy to overcome therapeutic resistance."

IO biomarker • Hematological Malignancies • Oncology • Solid Tumor • METTL3 • MYC • YTHDC1

Selective Inhibition of the m6a RNA Reader, YTHDC1, As a Novel Therapeutic Strategy for MYC-Driven Acute Myeloid Leukemia (ASH 2024) - "Gene expression profiling of MOLM13 tumors also demonstrate inhibition of MYC target gene sets among the most significant changes upon dosing with YTHDC1 inhibitor. Overall, our data suggests that pharmacological inhibition of YTHDC1 condensates utilizing our optimized small molecule inhibitors presents a viable strategy for treatment of MYC-driven AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • MYC • YTHDC1

YTHDC1 inhibition as a therapeutic strategy with potent preclinical activity alone and in combination with BCL-2 inhibitors (AACR-NCI-EORTC 2025) - "Among agents tested, strong synergy was observed with the clinically approved BCL2 antagonist, Venetoclax, across a panel of AML cell lines. Synergistic combinatorial activity was also observed in vivo, producing tumor regressions with the combination of sub-efficacious doses of each agent. Together, our data provide a rationale for the clinical development of YTHDC1 inhibition both as a single agent and in combination with standard-of-care treatments, including BCL2 inhibitors."

Combination therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD34 • MCL1 • MYC • YTHDC1

Discovery of potent, selective, and orally bioavailable small molecule inhibitors of YTHDC1 for the treatment of MYC-driven cancers (AACR 2025) - "Here, we describe the identification of YTHDC1 inhibitors optimized utilizing structure-based drug design (SBDD)...Further, we demonstrate a dose-dependent PK/PD/efficacy relationship, suggesting on-target YTHDC1 activity through suppression of the MYC pathway. Thus, our data demonstrate that targeting YTHDC1 condensates represents a novel approach to the treatment of MYC-driven tumors."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD34 • MYC • MYCL • MYCN • YTHDC1