CAD204520 / Cado Biotech - LARVOL DELTA

DRUG RESPONSE PROFILING AS A BRIDGE TO ALLOGENEIC STEM CELL TRANSPLANTATION IN A RELAPSED IMMATURE T-ALL WITH CONCOMITANT AML CLONE (EBMT 2025) - P=N/A | "Exceptional activity also depicted for: fludarabine, mitoxantrone, actinomycin D, CAD204520 (Notch inhibitor). Following our previous experience and supported by early evidence of BCL-2 inhibitors activity in ETP ALL we treated our patient with venetoclax plus bortezomib -VEBO- (PMID: 32923866) as a chemotherapy free regimen to bridge to HSCT...The patient underwent haploidentical HSCT in December 2022, after a fludarabine-based conditioning regimen.As GvHD prophylaxis, post-transplant cyclophosphamide was administered, followed by mycophenolate and sirolimus... HCST remains a potential curative treatment for aggressive leukemia, particularly in R/R cases. We highlight the feasibility of a DRP-guided approach to achieve disease control. Given the lack of chemotherapy prior to HSCT, the procedure proceeded without complications, suggesting that identifying druggable dependencies via DRP may improve the outcome."

IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immunology • Kidney Cancer • Lymphoma • Pediatrics • Solid Tumor • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • BRAF • MECOM • MLLT10 • NOTCH1 • PTPN11 • RUNX1 • SUZ12 • WT1

CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders. (PubMed, Int J Mol Sci) - "Additionally, we tested the potential of CAD204520 in combination with the current first-line treatment of CLL, venetoclax, and ibrutinib. CAD204520 enhanced the synergistic effect of this treatment regimen only in samples harboring the NOTCH1 PEST domain mutations, thus supporting a role for Notch inhibition in these tumors. In summary, our work provides strong support for the development of CAD204520 as a novel therapeutic approach also in chronic lymphoproliferative disorders carrying NOTCH1 PEST domain mutations, emerging as a promising molecule for combination treatment in this aggressive subset of patients."

Journal • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • NOTCH1

Uncovering NOTCH1 as a Promising Target in the Treatment of MLL-Rearranged Leukemia. (PubMed, Int J Mol Sci) - "We also demonstrated that CAD204520 treatment of MLLr cells significantly reduces NOTCH1 and its target genes as well as NOTCH1 receptor expression. This was not observed with a comparable cytarabine treatment, indicating the specificity of the small molecule...In conclusion, our findings uncover the oncogenic relevance of the NOTCH1 pathway in MLLr leukemia. Its inhibition leads to specific anti-leukemic effects and paves the way for further evaluation in clinical settings."

Journal • Hematological Malignancies • Leukemia • Oncology • KMT2A • NOTCH1

Uncovering NOTCH1 as promising target in the treatment of MLL rearranged leukemia (DGHO 2023) - "In contrast to the treatment with cytarabine, commonly used as chemotherapy for AML, CAD204520 significant decreased the NOTCH1 receptor expression, indicating the specificity of the small molecule to target the NOTCH1 pathway. In conclusion, our findings uncover the relevance of the NOTCH1 pathway in MLLr leukemia. Treatment with the less toxic NOTCH1 inhibitor CAD204520 leads to specific anti-leukemic effects and paves the way to be evaluated as a potential new treatment strategy to improve the poor outcome of MLL rearranged leukemia."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • HES1 • HOXA9 • KMT2A • NOTCH1