PIK-001 / University of Toronto - LARVOL DELTA

PIKfyve inhibition in myeloma disrupts autophagy and the lysosome, increasing MHC expression and cholesterol metabolism. (PubMed, Blood) - "PIK001 demonstrated potent anti-MM activity in vitro, as well as synergistic activity with established anti-MM agents (including venetoclax and selinexor), while retaining efficacy in lenalidomide-resistant models. Beyond MM, PIKfyve inhibition also shows selective cytotoxicity in acute myeloid leukemia, melanoma, and renal cancer, highlighting broader therapeutic potential. These findings establish PIKfyve inhibition as a valid target for MM and other hematologic malignancies, provide insights into mechanisms of sensitivity and resistance, and a compelling foundation for further pre-clinical (particularly with respect to the role of cholesterol metabolism and tumor immunity) and clinical development."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Kidney Cancer • Leukemia • Melanoma • Multiple Myeloma • Oncology • Renal Cell Carcinoma • Solid Tumor

A New Pikfyve Inhibitor Shows Subnanomolar Potency in Multiple Myeloma (IMS 2025) - "PIK085 also displayed an improved metabolic stability, with increased plasma concentrations following oral and IV administrations in mice when compared to PIK001 and apilimod.PIKfyve inhibitors displayed synergistic activity with relevant anti-MM therapeutics, including selinexor, venetoclax, and iberdomide. We present PIK085 as a promising preclinical candidate with subnanomolar potency in MM. Validation of PIKfyve inhibition as a single agent and in combination with other disease relevant therapeutics in in vivo models are n ongoing. Collectively, our work encourages further exploration of autophagy disruption in MM via PIKfyve inhibition, highlighting the potential of targeting plasma cell biology when investigating innovative treatment strategies."

Hematological Malignancies • Multiple Myeloma • SQSTM1

PIK-001 a Novel Small Molecule Inhibitor of Pikfyve for Treatment of Multiple Myeloma (MM) (ASH 2021) - "One panel drug APY-0201 and related drugs such as apilimod were initially developed as suppressors of production of interleukin (IL)-12 and IL-23 production and entered clinical trials for inflammatory diseases but subsequently were found to be primary inhibitors of PikFyve. Preliminary murine studies with PIK001 have shown high efficacy in preventing myeloma growth using a transplantable VKappa*myc cell line and daily oral delivery of drug. This pre-clinical data sets the stage for future clinical testing."

Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • Transplantation • IL12A • MYC • SDC1