About EndoTAG®-1: EndoTAG®-1 is a novel composition of the established cytostatic drug
paclitaxel combined with neutral and positive lipids. The positively charged
lipids imply that EndoTAG®-1 interacts with newly developed, negatively charged
endothelial cells, which are primarily required for the growth of tumor blood
vessels. The EndoTAG®-1 paclitaxel component attacks the endothelial cells as
they divide, thus targeting the blood supply to tumors without affecting the
supply to healthy tissue. By doing this, EndoTAG®-1 is expected to prevent the
formation of new tumor blood vessels and to inhibit tumor growth. Medigene has
successfully completed two clinical phase II trials of EndoTAG®-1 in the indications pancreatic cancer and
triple-negative breast cancer (TNBC). EndoTAG®-1 is protected by a number of
patent families. In TNBC, EndoTAG®-1 is protected by granted patents with terms
up to 2029 (USA Europe and other countries, patent
applications in TNBC with a term until 2027 are pending. Additional patent
applications covering the product with terms up to 2031 (USA , Europe, Asia
and other countries) are pending.
About Triple-negative breast cancer (TNBC): Triple-negative breast tumors are malignant
and do not show any HER2 receptors or hormone receptors for estrogen or
progesterone. About 15% of all breast cancer cases rank among this group. There
are very few treatment options available, since conventional anti-hormonal
treatments or treatments targeting HER2 are not appropriate. In case of relapse
following initial surgery, the only remaining treatment option is chemotherapy.
About SynCore Bio: SynCore Biotechnology Co., Ltd, a joint venture between the
publicly listed pharmaceutical company Sinphar Pharmaceutical Co., Ltd and the
National Health Research Institute of Taiwan, is focused on the development of
new drugs. Currently, it is conducting a phase I first-in-man trial on an
anti-cancer new chemical entity. Another anti-cancer NCE project is in the
pre-IND stage. In addition, SynCore Biotechnology Co. also obtained an
exclusive development and commercialization right of an anti-dry AMD new drug,
MC 1101, in Asia at 2011 from a US Biotech company, MacuCLEAR. MC 1101 is
currently undergoing a US FDA phase II/III trial.
About Sinphar Pharmaceutical: Sinphar Pharmaceutical Co, Ltd (Taiwan Stock
Exchange, Symbol: 1734), with subsidiaries in China and Canada, specializes in the sales and
marketing of pharmaceutical products and dietary supplements as well as in
manufacturing for several global pharma companies like Johnson & Johnson,
Takeda, Shionogi and Astellas. Additionally, Sinphar is one of the largest
producers of paclitaxel (Phyxol®) in Asia . It
is also involved in the research and development of botanical new drugs. Two
projects are currently undergoing US FDA phase II trials. Its manufacturing
facilities are approved by the Taiwanese FDA and Japan PMDA according to PIC/s
GMP guidelines. Further information can be obtained at: www.sinphar.com .
ENDOTAG-1®,
A CATIONIC LIPOSOME CONTAINING PACLITAXEL, DEMONSTRATES ANTI-ANGIOGENIC AND ANTI-INFLAMMATORY
ACTIVITY IN RHEUMATOID ARTHRITIS IN VIVO
M.
Schmitt-Sody, P. Metz, O. Gottschalk, B. Schulze, H. Bohnenkamp, U. Michaelis, E.
Guenzi, M. Funk and V. Jansson
Abstract Introduction:
Inflammation and angiogenesis are hallmarks of rheumatoid arthritis (RA) that
contribute largely to the formation of pannus tissue and joint destruction in
patients suffering from RA. We have recently shown that intravenously applied
cationic liposomes target efficiently angiogenic endothelial cells in the
synovial vasculature of rheumatoid joints and therefore may also serve as
potent vehicles for systemic drug delivery and therapy in RA. Therefore the aim
of our study was to quantify the antiangiogenic and antiinflammatory properties
of EndoTAG-1® (paclitaxel formulated in cationic liposomes) in the inflamed
joints of murine models of RA and to compare the therapeutical efficacy of
EndoTAG-1® to Taxol® (paclitaxel in Cremophor EL).
Materials and Methods: Targeting of fluorescently labelled cationic liposomes to the synovial
vasculature in mice with antigen-induced arthritis (AIA) was analysed by
intravital microscopy. Density of functional vessels and adhesion of
fluorescently labelled platelets or leukocytes were determined after treatment
with EndoTAG-1®. Knees were subjected to clinical scoring and histopathological
analysis. Results: EndoTAG-1® treatment of AIA mice with developing or in
established disease showed a strong attenuation of the course of the disease as
well as a potent anti-inflammatory effect. Histological analysis of knee
sections demonstrated a dramatic reduction of the pannus and infiltration of
inflammatory cells. Enrichment of EndoTAG at the synovial vasculature of AIA
mice was observed when compared with healthy mice. Treatment of AIA mice with
EndoTAG-1® concomitant to disease induction showed a complete remission of the
course of the disease as shown by a significant decrease of clinical scores
compared to both control and Taxol® treated groups. A complete inhibition (98%)
of neo-vascularisation was observed in the synovial vasculature of mice with
AIA that were treated with EndoTAG-1® whereas Taxol® alone showed only 50%
inhibitory effect. Rolling and adhesion of platelets were reduced to 53% (paclitaxel
5%) and 98% (paclitaxel 57%), respectively. Discussion: Our in vivo data
clearly demonstrates that anti-angiogenic and anti-inflammatory activity of
Endo-TAG-1® contribute to the therapeutical efficacy of this drug in RA. Notably,
therapeutic efficacy with Endo-TAG-1® was superior to Taxol®. This strongly
suggests that systemic delivery of cationic liposomes is very well suited to
enrich compounds to rheumatoid joints for therapy and could be a promising
treatment option for RA.
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