Last updated on April 18, 2014 at 5:30 EDT

Study Published in Blood Highlights Axl Inhibition as a Novel Therapeutic Approach for Acute Myeloid Leukemia

October 1, 2013

BERGEN, Norway, October 1, 2013 /PRNewswire/ –

Key Points

        - Presence of Axl receptor is an independent prognostic marker in patients
          with Acute Myeloid Leukemia (AML)
        - The Axl receptor is a novel therapeutic target in AML, an aggressive cancer
          that is poorly served by currently available treatments
        - BGB324, a first-in-class, highly selective Axl inhibitor, is currently in
          Phase 1 clinical testing

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”[1] 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

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.”

About the Axl kinase receptor

Axl is a member of the Tyro3, Axl, Mer receptor (TAMR) tyrosine kinase family and is a
fundamental receptor to cancer biology. It plays a crucial role in the
epithelial-mesenchymal transition (EMT) which is a key driver of metastasis (cancer
spread) and a mechanism of drug-resistance. The Axl receptor is regarded as one of the
most promising new therapeutic targets for cancer drug development.

About BGB324

BGB324 is a novel, oral, highly selective small molecule inhibitor of Axl Kinase.
Preclinical in vivo studies have shown that BGB324 has both single agent activity in
hematological and some solid tumors and is very effective in preventing and reversing
acquired resistance to standard of care cytotoxics and targeted therapies. BGB324 is
currently in Phase 1 clinical trial to evaluate its safety, tolerability, pharmacokinetics
and pharmacodynamics.

About Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is an aggressive cancer of the blood and bone marrow. It
is characterized by the rapid growth of abnormal white blood cells that accumulate in the
bone marrow and prevent the production of other normal blood cells. It is estimated that 1
in 243 people will be diagnosed with AML during their lifetime. In the United States, the
five-year overall survival is 24%.[2] It is estimated that 40-45% of patients younger than
65 years can be cured with current therapies, however only 10% of older patients achieve
long-term survival.[3]


        1) Isabel Ben-Batalla, Alexander Schultze, Mark Wroblewski, Robert Erdmann,
          Michael Heuser, Jonas S. Waizenegger, Kristoffer Riecken, Mascha Binder, Denis Schewe,
          Stefanie Sawall, Victoria Witzke, Miguel Cubas-Cordova, Melanie Janning, Jasmin
          Wellbrock, Boris Fehse, Christian Hagel, Juergen Krauter, Arnold Ganser, James B.
          Lorens, Walter Fiedler, Peter Carmeliet, Klaus Pantel, Carsten Bokemeyer and Sonja
          Loges (27 August 2013). Blood; doi:10.1182/blood-2013-03-491431
        2) SEER Stat Fact Sheets: Acute Myeloid Leukemia


        3) Burnett A, Wetzler M, Lowenberg B (2011). Therapeutic advances in acute
          myeloid leukemia. Journal of clinical oncology: official journal of the American
          Society of Clinical Oncology; 29(5):487-494.

About BerGenBio AS

BerGenBio AS is a biopharmaceutical company located in Bergen, Norway. The company is
committed to developing first in class therapeutics that inhibit EMT, preventing the
formation of cancer stem cells and disrupting the important mechanisms of acquired cancer
drug resistance. The company is founded on proprietary platform technology called
CellSelect(TM), which uses information from RNAi screening studies to identify and
validate novel drug targets and biomarkers. BGB324 is the first compound in BerGenBio’s
pipeline to enter clinical trials, with additional compounds and drug targets at different
stages of preclinical development.

About the Department of Hematology, Oncology and Bone Marrow Transplantation with
Section Pneumology, University Comprehensive Cancer Center Hamburg, University Medical
Center Hamburg-Eppendorf

The Department of Hematology, Oncology and Bone Marrow Transplantation with section
Pneumology is part of the Oncologic Center of the Medical University Hospital Hamburg, of
the Hubertus Wald Tumorzentrum and of the University Comprehensive Cancer Center Hamburg
(UCCH). It has been recognized as a Center of Excellence in Oncology (Onkologisches
Spitzenzentrum) by the German Cancer Aid (Deutsche Krebshilfe) since 2007. In the UCCH
more than 7000 inpatients and more than 10000 outpatients are treated per year. The
Department of Hematology and Oncology administers chemotherapy to more than 2500 patients
and treats about 1200 patients in 134 clinical trials per year. Patients with hematologic
malignancies constitute about 23% of patients treated in the department. In addition the
Department hosts extensive programs for basic and translational cancer research.

About the Institute of Tumor Biology, University Comprehensive Cancer Center Hamburg,
University Medical Center Hamburg-Eppendorf

The Department of Tumor Biology is part of the Center of Experimental Medicine and
Member of the University Cancer Center Hamburg. Its research is dedicated to the
identification and characterization of tumor cells that have disseminated from the primary
tumor and may give rise to overt metastases in cancer patients. The early detection of
“dormant” tumor cells is important to estimate the prognosis of patients with breast
cancer and other carcinomas. It may improve the individual management of targeted therapy
options, and in the long term has the potential to contribute to the development of new
innovative cancer therapy approaches. To perform excellent translational research, the
Institute of Tumor Biology collaborates with other institutes within the UKE, as well as
other national and international organizations (Europe, Japan, USA). The Institute also
leads extensive joint research projects and organizes international congresses about
dormancy and dissemination of tumor cells.


Source: PR Newswire