First Clinical Evidence of Vascular Remodelling Effects of Halaven® (eribulin) in Advanced Breast Cancer Published in the British Journal of Cancer[1]

Hatfield, England (ots/PRNewswire) -

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S.
JOURNALISTS

- Optical imaging confirms differences in oxygen saturation levels
between breast tumour tissue treated by eribulin and bevacizumab[2]
- Biomarker analyses show suppression of cancer cell driver
transforming growth factor beta 1 (TGF-1) by eribulin could have
favourable anti-angiogenic effect[2]

New data[2] published today in the British Journal of Cancer
validate the distinct vascular remodelling activity of Halaven®
(eribulin) compared to bevacizumab in breast tumour tissue. Optical
imaging techniques for haemodynamic analysis and blood tests for
biomarker analysis show that eribulin increases the oxygen saturation
of breast tumour tissue and suppresses TGF-1, a driver of cancer
progression associated with poor outcomes for women with advanced
breast cancer.

"This research sheds light on the biology of vascular remodelling
and oxygenation response to eribulin. Contrary to normal cells,
cancer cells thrive in a deoxygenated environment. These data show
that eribulin is able to increase the density of tiny blood vessels
and supply of oxygenated blood to breast cancer tissue. This has the
potential to reduce the risk of cancer spreading as the cancer cells
can no longer thrive in this environment," comments Shigeto Ueda,
Department of Breast Oncology, International Medical Center, Saitama
Medical University, Saitama, Japan.

Haemodynamic analysis shows that oxygen saturation levels increase
on day seven after treatment with eribulin (p=0.04) while
deoxy-haemoglobin concentrations decrease (p=0.01).[2] This trend was
not observed for bevacizumab. There was no change in oxygen
saturation at day seven (p=0.02), but instead a significant decrease
in the concentration of oxy-haemoglobin (p=0.0003) for
bevacizumab.[2]

Results of the biomarker analyses show that both eribulin and
bevacizumab decrease blood concentrations of VEGF and bFGF.[2] A
significant decrease in blood TGF-?1 concentrations is seen in
patients treated with eribulin but not bevacizumab (p=0.002).[2]
These findings clearly indicate that the mechanism of action of these
two agents differs.[2]

In the study, women with Stage 3/4 breast cancer were assigned
either eribulin (n=14) or single-agent bevacizumab (N=15). To
determine the change in the oxygenated breast tumour tissue,
concentrations of oxy-haemoglobin, deoxy-haemoglobin and oxygen
saturation were measured using Diffuse optical spectroscopic imaging
(DOSI), prior to and seven days after the first infusion. Blood
samples were collected for biomarker studies (VEGF, bFGF, and
TGF-?1).

"Scientific research and innovation is very important to Eisai. It
affords a greater understanding of our treatments and allows us to
better serve people living with cancer. These results are of
particular importance to us as they help us better understand how
eribulin works and the benefit it may offer to women with advanced
breast cancer," commented Gary Hendler, Chief Commercial Officer
Oncology Business Group, Chairman and CEO EMEA.

Eribulin is currently indicated for the treatment of adult
patients with locally advanced or metastatic breast cancer who have
progressed after at least one chemotherapeutic regimen for advanced
disease.[3] Prior therapy should have included an anthracycline and a
taxane unless patients were not suitable for these treatments.[3]

Eribulin is the first in the halichondrin class of microtubule
dynamics inhibitors with a novel mechanism of action. Structurally
eribulin is a simplified and synthetically produced version of
halichondrin B, a natural product isolated from the marine sponge
Halichondria okadai. Eribulin has antimitotic effects and promotes
vascular remodeling. It effectively inhibits microtubule growth and
prevents normal mitotic spindle formation in cells[4] that results in
cell death by apoptosis.[3],[5] It also increases microvessel density
in the tumour, which increases oxygen flow to deoxygenated (hypoxic)
regions.[6]

Eisai is dedicated to discovering, developing, and producing
innovative oncology therapies that can make a difference and impact
the lives of patients and their families. This passion for people is
part of Eisai's human health care (hhc) mission, which strives for
better understanding of the needs of patients and their families to
increase the benefits health care provides.

Notes to Editors

Metastatic Breast Cancer

Over 300,000 women are diagnosed with breast cancer in Europe
every year, of whom about one third subsequently develop metastatic
disease.[7] Metastatic disease is an advanced stage of the disease
that occurs when cancer spreads beyond the breast to other parts of
the body.

TGF-1 is a cytokine (small protein) that performs many cellular
functions, including activation of stromal cells (connective tissue
cells) in the tumour microenvironment, including endothelial cells,
fibroblasts, and immune cells necessary for cancer progression and
metastasis.[8],[9] In early stages of breast cancer this cytokine has
tumour suppressive effects but in advanced cancer it is linked with
increased tumour progression.[8]

Eisai in Oncology

Our commitment to meaningful progress in oncology research, built
on scientific expertise, is supported by a global capability to
conduct discovery and preclinical research, and develop small
molecules, therapeutic vaccines, and biologic and supportive care
agents for cancer across multiple indications.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based
pharmaceutical company headquartered in Japan. We define our
corporate mission as "giving first thought to patients and their
families and to increasing the benefits health care provides," which
we call our human health care (hhc) philosophy. With over 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realise
our hhc philosophy by delivering innovative products in multiple
therapeutic areas with high unmet medical needs, including Oncology
and Neurology.

As a global pharmaceutical company, our mission extends to
patients around the world through our investment and participation in
partnership-based initiatives to improve access to medicines in
developing and emerging countries.

For more information about Eisai Co., Ltd., please visit
http://www.eisai.com.

References

1. Cortes J, et al. Eribulin monotherapy versus treatment of
physician's choice in patients with metastatic breast cancer
(EMBRACE): a phase 3 open-label randomised study. The Lancet.
2011;377:914-23

2. Ueda S, et al. In vivo imaging of eribulin-induced
reoxygenation in advanced breast cancer patients: a comparison to
bevacizumab. Brit J Cancer 2016 Available at:
http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2016122a.pdf
Accessed May 2016

3. SPC Halaven (updated March 2016). Available at:
http://www.medicines.org.uk/emc/medicine/24382/SPC/Halaven

4. Yoshida T, et al. Eribulin mesilate suppresses experimental
metastasis of breast cancer cells by reversing phenotype from
epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial
transition (MET) states. Br J Cancer. 2014;110:1497-1505

5. Kuznetsov G, et al. Induction of morphological and biochemical
apoptosis following prolonged mitotic blockage by halichondrin B
macrocyclic ketone analog E7389. Cancer Res 2004;64:5760-66

6. Funahashi Y, et al. Eribulin mesylate triggers vasculature
remodeling to reduce the abnormality of tumor microenvironment of
human breast cancer models. Submitted. 2014.

7. World Health Organisation. Atlas of Health in Europe. 2003.
World Health Organization, Regional Office of Europe, Copenhagen,
Denmark.

8. Wendt MK, Tian M, Schiemann WP. Deconstructing the mechanisms
and consequences of TGF-beta-induced EMT during cancer progression.
Cell and Tissue Res 2012;347:85-101

9. Principe D, et al. TGF-beta: duality of function between tumor
prevention and carcinogenesis. Journal of the National Cancer
Institute 2014:106:djt369.

ots Originaltext: Eisai
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Eisai
Cressida Robson / Ben Speller
+44(0) 7908 314 155 / +44(0) 7908 409416
Cressida_Robson@eisai.net
Ben_Speller@eisai.net / Tonic Life Communications
Alex Davies / Callum Haire
+44 (0) 7716 324722 / +44 (0) 7867 429637
Alex.Davies@toniclc.com
Callum.Haire@toniclc.com