EG-011 / E2DG, Oncology Institute of Southern Switzerland - LARVOL DELTA

A first-in-class Wiskott-Aldrich syndrome protein activator with anti-tumor activity in hematologic cancers. (PubMed, Haematologica) - "Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form...Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization."

Journal • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Primary Immunodeficiency

The first-in-class WASP activator EG-011 is active in lymphoma and multiple myeloma cell lines resistant to FDA approved compounds (AACR-NCI-EORTC 2022) - "The anti-tumor activity of EG-011 was maintained in the resistant cell line derived from the MZL VL51 with secondary resistance to ibrutinib (IC50: 500 nM in both parental and resistant), while it was higher in the MZL model with resistance to PI3Kdelta inhibitor derived from VL51 (IC50: 100 nM). The copanlisib-resistant MZL VL51 (IC50: 2 μM) and Karpas1718 idelalisib-resistant (5 nM) showed a slightly decreased sensitivity to EG-011 (Karpas1718 parental, IC50: 1 nM)...A 4-fold increase in sensitivity was observed in both RPMI-8266 bortezomib resistant and in RPMI-8266 carfilzomib resistant cells compared to parental (IC50: 2.5 vs 10 μM for both models). Conclusions. These data indicate that the first-in-class WASP activator EG-011 was active also after acquisition of resistance to different FDA approved agents such as PI3K, BTK and proteasome inhibitors in MZL and MM models."

FDA event • Preclinical • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Oncology