Dublin, Ireland, July 30, 2020 – Inflection Biosciences Ltd, a company developing innovative therapeutics for the treatment of cancer, today announced the publication of pre-clinical data showing that the company’s first-in-class PIM/PI3K inhibitor, IBL-202, has promise as a treatment for diffuse large B-cell lymphoma (DLBCL). This research has recently been published in the peer reviewed Journal Leukaemia & Lymphoma. The publication titled ‘Combination of the dual PIM/PI3-kinase inhibitor IBL-202 and venetoclax is effective in diffuse large B-cell lymphoma’ can be accessed here.
The publication is the result of a collaboration with Dr. Giles Best of the Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Australia, and member of the CLL Australian Research Consortium (CLLARC), Sydney, Australia.
Dr. Best, the lead author on the publication, commented: “The combination of IBL-202 and venetoclax was highly synergistic against DLBCL cells, which may permit the utilization of lower drug concentrations and mitigate against adverse effects.”
DLBCL is the most common type of non-Hodgkin lymphoma (NHL) worldwide with a global incidence of over 150,000. It is considered an aggressive lymphoma and 30-40% of patients fail standard chemoimmunotherapy due to underlying biological heterogeneity.
The BCL-2 inhibitor, venetoclax, has proven to be highly effective in the treatment of chronic lymphocytic leukaemia (CLL) but has limited effects in DLBCL. A major determinant of this resistance is up-regulation and co-expression of MCL-1 and compensatory activation of pro-survival signalling via the PI3K-AKT pathway following venetoclax exposure. All four PI3-kinase isoforms are involved in different stages of malignancy, suggesting signalling via alternate isoforms may compensate in cells treated with selective PI3K inhibitors, resulting in drug-resistance. PIM kinase has been shown to be highly expressed in DLBCL, correlating with poor prognosis. PIM kinase is one of the drivers of dysregulated PI3-kinase signalling. Therefore, the combination of venetoclax with inhibition of the PIM and PI3-kinases, may be beneficial in DLBCL.
These published results show that IBL-202 simultaneously suppresses interacting signalling pathways, which down-regulate MCL-1, contributing to the synergy of IBL-202 with the BCL-2 inhibitor and abrogates the proliferation and survival of DLBCL cells. This work builds on previously published data showing that IBL‐202 may be an effective strategy for targeting CLL cells alone and in combination with venetoclax.
About Inflection Biosciences
Inflection Biosciences Ltd is developing small molecule therapeutics for the treatment of cancer. The company's pipeline was licensed from the Spanish National Cancer Research Centre (CNIO). IBL-202 is a first-in-class, dual PIM kinase and PI3K inhibitor in development for B-cell malignancies, AML and multiple myeloma. The IBL-100 series comprises selective pan-PIM kinase inhibitors. The partnered pipeline comprises AUM302, a PIM/PI3K/mTOR inhibitor being developed by AUM Biosciences. For more information please visit www.inflectionbio.com
For Further Information Contact:
Inflection Biosciences Ltd
Darren Cunningham, Chief Executive Officer
E: dcunningham@inflectionbio.com
T: +353 (0)1 4003615
