Higher Concentrations of Doxorubicin Accumulation and Distribution within the Bladder Wall Were Achieved with
ThermoDox® Combined with Mild Local Hyperthermia Compared to Free Doxorubicin Alone
The Study Reinforces ThermoDox’s Unique, Proprietary Mechanism of Action
LAWRENCEVILLE, N.J., April 13, 2017 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN) today announced
publication of the article, “Lyso-Thermosensitive Liposomal Doxorubicin for Treatment of Bladder Cancer,” in the
International Journal of Hyperthermia. The article describes the results of porcine in vivo studies to evaluate ThermoDox® in
combination with loco-regional mild hyperthermia for targeted drug delivery to the bladder wall as a potential treatment for
bladder cancer. Swine bladder walls are similar in proportion and composition to human bladders. Doxorubicin
accumulation and distribution within the bladder wall with ThermoDox® plus mild bladder hyperthermia was achieved at concentrations
nearly ten times higher than with free intravenous doxorubicin combined with mild bladder hyperthermia. The study was conducted
under a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health (NIH) to evaluate whether
ThermoDox® combined with mild heating of the bladder can target drug delivery in the bladder.
It is estimated that over 79,000 new cases of urinary bladder cancer will be diagnosed in the United States in
2017 and over 16,800 people will die of the disease during this same period. Approximately 70 percent of new cases of bladder
cancer present with non-muscle invasive disease and are typically treated by a technique called transurethral resection of the
bladder which removes as much of the tumor as possible. However, 40 percent of patients with high risk non-muscle invasive
disease experience a recurrence and another 33 percent experience disease progression. To reduce this high rate of
recurrence, intravesical (in the bladder) therapy is used. Intravenous administration of free doxorubicin is commonly used as
part of an effective standard perioperative chemotherapy regimen for muscle invasive disease; however results with intravesical
doxorubicin have been less effective presumably from inability to deliver doxorubicin across the bladder urothelium (epithelial
surface of the bladder).
The NIH studies were conducted under the direction of Dr. Bradford Wood, MD, Director, NIH Center for
Interventional Oncology and Chief, NIH Clinical Center Interventional Radiology. The results of the studies are summarized
below:
• Range of doxorubicin concentrations from the urothelium to the serosa (outer surface of the bladder):
- 20.32 – 3.52 ug/g for ThermoDox® + hyperthermia (HT)
- 2.34 – 0.61 ug/g for free doxorubicin + hyperthermia
- 2.18 – 0.51 ug/g for ThermoDox® with no hyperthermia
• Average doxorubicin concentrations in the urothelium/lamina:
- 9.7 +/- 0.67 ug/g for ThermoDox® + hyperthermia (HT)
- 1.2 +/- 0.39 ug/g for free doxorubicin + hyperthermia
- 1.15 +/- 0.38 ug/g for ThermoDox® with no hyperthermia
• Average doxorubicin concentrations in the muscularis:
- 4.09 +/- 0.81 ug/g for ThermoDox® + hyperthermia (HT)
- 0.86 +/- 0.24 ug/g for free doxorubicin + hyperthermia
- 0.62 +/- 0.15 ug/g for ThermoDox® with no hyperthermia
Computational model results were similar to the measured doxorubicin levels and suggest that adequate
temperatures were reached within the bladder for drug release from the lyso-thermosensitive liposomal doxorubicin, ThermoDox®.
"The incomplete response of bladder tumors to intravesical drugs, like doxorubicin and mitomycin C, has been
attributed in part to inadequate drug delivery and poor penetration across the urothelium resulting in sub-therapeutic drug
concentrations in the bladder wall,” said Dr. Bradford Wood, MD, Director, NIH Center for Interventional Oncology and Chief, NIH
Clinical Center Interventional Radiology. “To address this limitation, one promising strategy to enhance the permeability of
the bladder wall to improve the efficacy of intravesical chemotherapy is the use of hyperthermia to stimulate the release of
chemotherapeutic agents from thermosensitive nanocarriers for patients who have failed standard first line therapy for bladder
cancer.”
“The NIH’s continued research interest in ThermoDox® and its application in the treatment of many difficult to
treat cancers underscores the significance of ThermoDox’s potential and its unique means of locally concentrating doxorubicin in a
highly effective way,” said Michael H. Tardugno, Celsion's chairman, president and chief executive officer. “This study not only
reinforces ThermoDox’s mechanism, it provides further assurance that the conclusions from the NIH’s independent analysis of
ThermoDox® plus radio frequency ablation for the treatment of primary liver cancer are based on a broad set of clinical and
preclinical evidence. The data presented by the NIH at the 2016 RSNA Annual Meeting in November 2016 showed that the longer
the target tissue is heated, the greater is the clinical benefit. Multiple experiments conducted by Celsion suggest that this
is the result of increased doxorubicin tissue concentration, and we believe provides strong validation for our ongoing global Phase
III OPTIMA Study in primary liver cancer. A successful OPTIMA Study will provide the means to expand ThermoDox’s utility for
patients with bladder cancer.”
About ThermoDox®
Celsion's most advanced program is a heat-mediated, tumor-targeting drug delivery technology that employs a
novel heat-sensitive liposome engineered to address a broad range of difficult-to-treat cancers. The first application of this
platform is ThermoDox®, a lyso-thermosensitive liposomal doxorubicin (LTLD), whose novel mechanism of action delivers high
concentrations of doxorubicin to a region targeted with the application of localized heat at 40°C, just above body temperature.
ThermoDox® has the potential to address a broad range of cancers.
Celsion's LTLD technology leverages two mechanisms of tumor biology to deliver higher concentrations of drug
directly to the tumor site. In the first mechanism, rapidly growing tumors have leaky vasculature, which is permeable to liposomes
and enables their accumulation within tumors. Leaky vasculature influences a number of factors within the tumor, including the
access of therapeutic agents to tumor cells. Administered intravenously, ThermoDox® is engineered with a half-life to allow
significant accumulation of liposomes at the tumor site as these liposomes recirculate in the blood stream. In the second
mechanism, when an external heating device heats tumor tissue to a temperature of 40°C or greater, the heat-sensitive liposome
rapidly changes structure and the liposomal membrane selectively dissolves, creating openings that can release a chemotherapeutic
agent directly into the tumor and into the surrounding vasculature. Drug concentration increases as a function of the accumulation
of liposomes at the tumor site, but only where the heat is present. This method damages only the tumor and the area related to
tumor invasion, supporting more precise drug targeting.
About Celsion Corporation
Celsion is a fully-integrated oncology company focused on developing a portfolio of innovative cancer
treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies. The Company's lead program is
ThermoDox®, a proprietary heat-activated liposomal encapsulation of doxorubicin, currently in Phase III development for the
treatment of primary liver cancer and in Phase II development for the treatment of recurrent chest wall breast cancer. The
pipeline also includes GEN-1, a DNA-based immunotherapy for the localized treatment of ovarian and brain cancers. Celsion has
two platform technologies for the development of novel nucleic acid-based immunotherapies and other anti-cancer DNA or RNA
therapies.
The Company has a Cooperative Research and Development Agreement (CRADA) with the NIH. Any reference to
NIH should not be viewed as an endorsement or a recommendation of Celsion, its products or services. For more information on
Celsion, visit our website: http://www.celsion.com. (LTSL/ThermoDox®, HEAT Study/HCC, OPTIMA Study/HCC)
Celsion wishes to inform readers that forward-looking statements in this release are made pursuant to the
"safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that such
forward-looking statements involve risks and uncertainties including, without limitation, unforeseen changes in the course of
research and development activities and in clinical trials; the uncertainties of and difficulties in analyzing interim clinical
data, particularly in small subgroups that are not statistically significant; FDA and regulatory uncertainties and risks; the
significant expense, time, and risk of failure of conducting clinical trials; the need for Celsion to evaluate its future
development plans; possible acquisitions or licenses of other technologies, assets or businesses; possible actions by customers,
suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Celsion's periodic reports and
prospectuses filed with the Securities and Exchange Commission. Celsion assumes no obligation to update or supplement
forward-looking statements that become untrue because of subsequent events, new information or otherwise.
Celsion Investor Contact Jeffrey W. Church Sr. Vice President and CFO 609-482-2455 jchurch@celsion.com
