Research reveals significant role of Axl receptor in progression, therapeutic resistance of AML

BerGenBio AS ("BerGenBio" or the "Company"), an oncology biopharmaceutical company, announces that a paper entitled "Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine cross-talk of leukemia cells with bone marrow stroma" by Ben-Batalla et al., has been published in Blood, the most cited peer-reviewed research journal in the field of hematology.

The paper reports research directed by Dr. Sonja Loges from the Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology and from the Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, that identifies a significant role for the Axl receptor in the progression and therapeutic resistance of AML. The Hamburg team's results reveal a novel Axl-dependent mechanism where AML cells evade treatment by establishing a protective niche in the bone marrow. Growth Arrest-specific protein 6 (Gas6) is released by bone marrow cells and facilitates AML cell proliferation, survival and resistance by activating the Axl receptor. Blocking Axl activity by the selective inhibitor BGB324 is shown to reduce AML proliferation and induce apoptosis (programmed cell death), leading to enhanced survival in preclinical models. These studies, in part sponsored by BerGenBio, support the development of BGB324 as a novel treatment of Axl-expressing AML.  

In June 2013, BerGenBio announced that BGB324 had begun a Phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug.

Sonja Loges, MD PhD, Group Leader, Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology & Institute of Tumor Biology, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf commented: "Our findings detailed in this paper provide evidence for a specific role of the Gas6-Axl axis in the progression of AML. Additionally, we have shown that the selective Axl inhibitor BGB324 reduces proliferation and induces apoptosis of patient AML cells."  

Richard Godfrey, CEO of BerGenBio commented: "The results of this research support our view that selective Axl-targeting agents hold significant promise in aggressive cancers where this receptor is expressed on tumor cells. As far as we are aware, our novel lead drug, BGB324, is the first Axl-selective inhibitor to enter the clinic and we look forward to future studies exploring the clinical opportunity for BGB324."