New Breast Cancer Research Highlights BGB324 In Overcoming Immunotherapy Resistance

Presentation at San Antonio Breast Cancer Symposium 2016

BERGEN, Norway–(BUSINESS WIRE)–Leading oncology biopharmaceutical company BerGenBio AS, today released
important new preclinical study data on its
first-in-class AXL inhibitor, BGB324
in another major disease
indication. The study in breast cancer showed that AXL, a key factor in
tumor resistance to the emerging class of new immune checkpoint
inhibitors is effectively targeted through combination therapy with
BGB324. The study data was presented in a poster today at the San
Antonio Breast Cancer Symposium 2016.

BGB324 is a highly selective small molecule inhibitor of the AXL
receptor tyrosine kinase
that is associated with poor overall
survival in breast cancer. The new study “BGB324, a selective small
molecule inhibitor of AXL tyrosine kinase, enhances immune checkpoint
inhibitor efficacy in mammary adenocarcinoma”
presented today in the
Immunology and Preclinical Immunotherapy poster session, described a
unique role for AXL in suppressing the anti-tumor immune response in
breast cancer. AXL-targeting with BGB324 enhanced the effect of immune
checkpoint blockade in aggressive mammary adenocarcinomas that display
limited immunogenicity. The results showed that AXL-associated EMT and
expression of immune suppressive cytokines increased in 4T1 tumors in
response to immune therapy and correlated with a lack of response. The
combination of BGB324 + anti-CTLA-4/anti-PD-1 resulted in durable
primary tumor clearance and sustained tumor immunity in animals that
rejected 4T1 tumor cell re-challenge. Importantly, the extensive
metastasis to the lung, liver and spleen characteristic of this breast
cancer model were concomitantly abrogated in the animals responding to
the combination treatment. BGB324 enhanced tumor infiltration of
effector cytotoxic T lymphocytes and NK cells while decreasing immune
suppressive cell types. Notably, BGB324 showed direct effects on human
M2 macrophages, reducing secretion of immune suppressive cytokines.
Hence, selective inhibition of AXL signaling with BGB324 uniquely
targets both tumor intrinsic and microenvironmental immune suppression
mechanisms and increases checkpoint inhibitor efficacy.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented:

“We believe this strong new preclinical data again clearly demonstrates
the rationale for combining BGB324 with immune checkpoint inhibitors to
treat a wide range of aggressive cancers. AXL expression is increased in
tumors in response to checkpoint inhibitor treatment and is an important
resistance mechanism. Treatment with BGB2324 counters this and promotes
the anti-tumor immune response. This supports our intention to combine
the clinical-stage selective Axl inhibitor BGB324 with immune checkpoint
inhibitors to improve treatment of human breast cancer.”


BerGenBio AS
Richard Godfrey, +47 917 86 304