Eisai Presents Latest Non-Clinical Data on Its First Antibody-Drug Conjugate MORAb-202 at 8th Annual World ADC
2017年9月22日 - 10:56AM
JCN Newswire (英)
Eisai Co., Ltd. announced today that the latest non-clinical
data on MORAb-202, Eisai's first antibody-drug conjugate (ADC)
developed by its research subsidiary Morphotek, Inc., was presented
at the 8th Annual World ADC.(1-2)
MORAb-202 is a new ADC which combines farletuzumab, an
investigational anti-folate receptor alpha (FRA) antibody, with a
payload* of Eisai's in-house developed anticancer agent eribulin
(generic name: eribulin mesylate, product name: Halaven).
The presentation at the 8th Annual World ADC covered the results of
non-clinical studies investigating MORAb-202. MORAb-202
demonstrated high selectivity for FRA-positive cancer cells, which
are expressed in approximately 60% of triple-negative breast cancer
patients, as well as strong antitumor activity. Furthermore, there
was a confirmed bystander effect**, with MORAb-202 also exhibiting
antitumor activity on the FRA-negative cancer cells surrounding the
FRA-positive cancer cells. MORAb-202 showed high selectivity for
FRA-positive cancer cells and a long half-life in the blood
(111-178 hours), and in mouse models inoculated with cancer, a
60-day tumor regression effect was observed based a single dose
using only a fifth of eribulin's clinical dosage.
After MORAb-202 enters the target cancer cells, the linker is
enzymatically cleaved, separating eribulin, the payload, from the
antibody. The released eribulin then displays its original high
antitumor effects. Additionally, ADCs have been known to have high
aggregation levels due to the influence of hydrophobic payloads,
but since MORAb-202 employs the water-soluble eribulin as a
payload, aggregation is under 1%. Due to this characteristic of
reaching the cancer cells without aggregating in the blood,
MORAb-202 suggests a high safety profile. With its base of Eisai's
in-house developed eribulin, MORAb-202 demonstrates new generation
ADC characteristics, namely, internalization into target cancer
cells, an antitumor effect followed by a bystander effect after its
releasing its drug payload, and aggregation inhibition. Eisai plans
to move MORAb-202 into the clinical stage during the latter half of
FY 2017.
Eisai positions oncology as a key therapeutic area, and is aiming
to discover revolutionary new medicines with the potential to cure
cancer. The company will continue to create innovation in the
development of new drugs based on cutting-edge cancer research, as
it seeks to contribute further to addressing the diverse needs of,
and increasing the benefits provided to, patients with cancer,
their families, and healthcare providers.
* Payload: An anticancer agent connected to an antibody via a
linker in an ADC.
** Bystander effect: When the anticancer agent and antibody parts
of an ADC are separated inside a targeted antigen-positive cancer
cell, the released anticancer agent also affects neighboring
antigen-negative cancer cells and the component cells of the cancer
microenvironment.
About Morphotek, Inc. and MORAb-202
Morphotek, Inc., a subsidiary of Eisai Inc.in the United States, is
a biopharmaceutical company specializing in the development of
protein and antibody products through the use of a novel and
proprietary gene evolution technology. Morphotek, Inc. developed
MORAb-202, which combines anticancer agent farletuzumab, an IgG1
monoclonal antibody that binds to the folate receptor alpha, and
Eisai's in-house developed anticancer agent eribulin using an
enzyme cleavable linker. After entering the target cancer cells,
the linker is enzymatically cleaved, separating eribulin from the
antibody, which is thought to create a therapeutic effect on the
cancer cells and surrounding cancer microenvironment. Morphotek,
Inc. is currently preparing MORAb-202 for Phase I clinical trials.
In non-clinical studies, MORAb-202 demonstrated high target
selectivity for FRA-positive cancer cells, strong anticancer
activity (50% Inhibitory Concentration (IC50) against FRA-positive
cells IC50 = 0.001-23nM, FRA-negative cells IC50 > 100nM), a
clear bystander effect in the co-culture of positive and negative
FRA-positive cells, long half-life in blood (111-178 hours), and a
long-lasting antitumor effect with only a single dose (In mouse
models inoculated with triple-negative breast cancer cells and
dosed with 5mg/kg, a 60-day tumor regression effect and complete
response in 4 out of 8 mice was observed). Additionally, by
leveraging the combination of eribulin, with its unique mechanism
of action, in-house developed antibodies, and antibody conjugation
technology, Morphotek, Inc. launched a new ADC Services business in
April 2017.
About farletuzumab (development code: MORAb-003)
Farletuzumab is a humanized, IgG1 monoclonal antibody that binds to
the folate receptor alpha (FRA). Farletuzumab is currently
undergoing Phase II clinical trials in Japan, the United States and
Europe, for the treatment of recurrent platinum-sensitive ovarian
cancer with a low CA125 level.
About eribulin (generic name: eribulin mesylate, product name:
Halaven)
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 is believed to work by inhibiting the
growth phase of microtubule dynamics which prevents cell division.
In addition, recent non-clinical studies showed that eribulin is
associated with increased vascular perfusion and permeability in
tumor cores. Eribulin promotes the epithelial state and decreases
the capacity of breast cancer cells to migrate and invade. Eribulin
was first approved in November 2010 in the United States as a
treatment for patients with metastatic breast cancer who have
received at least two chemotherapeutic regimens for the treatment
of metastatic disease. Prior therapy should have included an
anthracycline and a taxane in either the adjuvant or metastatic
setting. Eribulin is currently approved for use in the treatment of
breast cancer in over 60 countries worldwide, including Japan and
countries in Europe, the Americas and Asia. In Japan, eribulin has
been approved to treat inoperable or recurrent breast cancer and
was launched in the country in July 2011. In addition, eribulin has
been approved in countries in Europe and Asia indicated as a
treatment for patients with locally advanced or metastatic breast
cancer who have progressed after at least one chemotherapeutic
regimen for advanced disease. Prior therapy should have included an
anthracycline and a taxane in either the adjuvant or metastatic
setting, unless patients were not suitable for these treatments.
Regarding soft tissue sarcoma, eribulin was approved in the United
States for the treatment of patients with unresectable or
metastatic liposarcoma who have received a prior
anthracycline-containing regimen in January 2016, approved in Japan
for the treatment of soft tissue sarcoma in February 2016, and
approved in Europe for the treatment of adult patients with
unresectable liposarcomas who have received prior anthracycline
containing therapy (unless unsuitable) for advanced or metastatic
disease in May 2016.
(1) Albone E. "MORAb-202 -- A Potent Human Folate Receptor
Alpha-Targeting ADC that Utilizes the Anti-tubulin Agent Eribulin
as Payload" Oral Presentation at the 8th Annual World ADC.
(2) Furuuchi K. et al "MORAb-202, a novel antibody-drug conjugates
(ADC) comprised of farletuzumab conjugated with eribulin, exhibits
long-lasting targeted antitumor activity and payload-mediated
bystander effects on the tumor microenvironment." Scientific Poster
Session at the 8th Annual World ADC.
About Eisai
Eisai Co., Ltd. (TSE:4523; ADR:ESALY) is a research-based human
health care (hhc) company that discovers, develops and markets
products throughout the world. Eisai focuses its efforts in three
therapeutic areas: integrative neuroscience, including neurology
and psychiatric medicines; integrative oncology, which encompasses
oncotherapy and supportive-care treatments; and
vascular/immunological reaction. Through a global network of
research facilities, manufacturing sites and marketing
subsidiaries, Eisai actively participates in all aspects of the
worldwide healthcare system. For more information about Eisai Co.,
Ltd., please visit www.eisai.com.
Source: Eisai
Contact:
Public Relations Department,
Eisai Co., Ltd.
+81-3-3817-5120
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