Undisclosed JAK2V617F mutant selective inhibitor / Cellarity - LARVOL DELTA

Identification of small molecules that selectively target JAK2V617F driven cytokine-independent megakaryopoiesis by leveraging single cell RNA sequencing maps of myelofibrosis patients samples and a deep learning framework (ASH 2025) - "Biochemical binding assays and single cell transcriptomicsdemonstrated that our lead molecules did not bind JAK2 protein and had different transcriptionalsignatures in JAK2V617F mutant cells compared to the JAK2 inhibitor ruxolitinib. Finally, we demonstrated dose-dependent inhibition of TPO-independentmegakaryopoieis in primary MF CD34+ samples with our lead compound.We have leveraged single cell transcriptomics, ML and iPSC models to identify small molecules that canselectively target aberrant JAK2 mutant HSPCs by using transcriptomics to target distinct pathwaysdownstream of hyperactive JAK2 signaling. Moreover, our strategy decouples mutant JAK2 signalingsparing normal hematopoiesis and reducing the anemia risk seen with current clinical approaches."

Clinical • Anemia • Aplastic Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • CD34