IBL-202 / Inflection Biosci - LARVOL DELTA

Combination of the Dual Pan-PI3K/PIM Inhibitor Ibl-202 with the BCL-2 Inhibitor Venetoclax Enhances Apoptotic Priming and Is an Effective Targeted Treatment Approach in Mantle Cell Lymphoma (ASH 2024) - "Moreover, we observed an increased MCL-1 dependence with I+V compared to untreated cells (cytochrome c release 26% vs 9%, p=0.02) and an increased BCL-XL dependence in I + V compared to I or V alone (cytochrome c release : 51% I+C vs 37% V, p=0.03; vs 27% I, p<0.002). Hence, dynamic BH3 profiling reveals that I+V accumulates apoptotic vulnerabilities.To validate the anti-lymphoma activity of the I+V combination in vivo, a CAM assay showed effective, albeit not significant tumor growth inhibition upon treatment with I alone and in combination with V compared to V alone, without any detectable toxicity.Conclusion : We showed for the first time that the novel dual pan-PI3K/PIM inhibitor IBL-202 is an effective and selective targeted treatment approach in MCL in both, in vitro and in vivo settings, and cooperates with venetoclax, presumably by altering the cellular dependencies on anti-apoptotic proteins, suggesting it a valuable candidate for combination therapy with..."

IO biomarker • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA5 • BCL2 • BCL2L1 • CD40LG

Dual Targeting of Pim and PI3 Kinases in Mature T-Cell Lymphoma. (PubMed, Eur J Haematol) - "Strikingly, IBL-202 strongly induced cell-cycle-dependent cell death in cell lines of different mTCL subtypes. Together, our study provides mechanistic evidence supporting a therapeutic strategy of dual Pim- and PI3-kinase inhibition in mature T-cell lymphoma."

Journal • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2L1

IBL-202 is synergistic with venetoclax in CLL under in vitro conditions that mimic the tumor microenvironment. (PubMed, Blood Adv) - "Synergy between IBL-202 and venetoclax against primary CLL cells cultured under conditions that mimic the tumor microenvironment suggests this drug combination may be effective against CLL cells within the lymph nodes and bone marrow. Furthermore, the efficacy of the combination against the TP53-KO OSU-CLL cell line suggests the combination may be a highly effective treatment strategy for high-risk CLL."

IO Biomarker • Journal • Tumor microenvironment • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • CD40LG • CXCL12 • CXCR4 • MCL1

Combination of the dual PIM/PI3-kinase inhibitor IBL-202 and venetoclax is effective in diffuse large B-cell lymphoma. (PubMed, Leuk Lymphoma) - "The results support the efficacy of simultaneously targeting inter-related molecules to overcome apoptotic escape in this biologically heterogeneous disease. As venetoclax, pan-PIM-kinase and pan-PI3-kinase inhibitors have, or are currently being studied in clinical trials, it may be rational to consider these drugs in combination for the treatment of DLBCL."

IO Biomarker • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • MCL1

The dual PI3/PIM-kinase inhibitor, IBL-202, is synergistic with venetoclax against TP53-deficient CLL cells under conditions that mimic the lymph node microenvironment (iwCLL 2019) - No abstract available.

The dual inhibitor of the phosphoinositol-3 and PIM kinases, IBL-202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment. (PubMed, Br J Haematol) - "Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway. The significant effects of IBL-202 on CD49d and CXCR4 expression and migration, cycle and proliferation of CLL cells suggest the drug may also interfere with the migratory and proliferative capacity of the leukaemic cells. Collectively, these data demonstrate that dual inhibition of the PIM and PI3 kinases by IBL-202 may be an effective strategy for targeting CLL cells, particularly within the environmental niches known to confer drug-resistance."

Journal • Tumor microenvironment