Celsion Corporation (NASDAQ: CLSN), an oncology drug development
company, today announced that results from an independent study of
a lyso-thermosensitive liposomal doxorubicin (LTLD) was published
in the peer-reviewed publication, International Journal of
Hyperthermia showing that real-time fluorescence imaging can
visualize uptake of LTLD during delivery, and can predict tumor
drug uptake in response to heat. ThermoDox® is Celsion’s
heat-activated liposomal formulation of doxorubicin currently in
Phase III development for the treatment of primary liver cancer,
also known as hepatocellular carcinoma (HCC). These data clearly
show that high concentrations of tumor fighting doxorubicin can be
delivered at unprecedented levels to tumors using ThermoDox® and
targeted heat. This helps explain why the Phase III HEAT Study
subgroup data is so impressive.
The study, titled, “Real-time fluorescence
imaging for visualization and drug uptake prediction during drug
delivery by thermosensitive liposomes,” may be found here.
Authors were:
- Anjan Motamarry, Department of Drug Discovery & Biomedical
Sciences, and Department of Pediatrics, Medical University of South
Carolina
- Ayele H. Negussie, Center for Interventional Oncology,
Radiology and Imaging Sciences, Clinical Center, National
Institutes of Health
- Christian Rossmann, Department of Pediatrics, Medical
University of South Carolina
- James Small, Department of Public Health Sciences, Medical
University of South Carolina
- Marissa Wolfe, Department of Comparative Medicine, Medical
University of South Carolina
- Bradford J. Wood, Center for Interventional Oncology, Radiology
and Imaging Sciences, Clinical Center, National Institutes of
Health
- Dieter Haemmerich, Department of Pediatrics, Medical University
of South Carolina and Department of Bioengineering, Clemson
University
Both Dr. Wood and Dr. Haemmerich have worked
extensively with Celsion on ThermoDox. Dr. Wood was the lead
investigator on the NIH team that evaluated the Company’s HEAT
Study data and published an article in Journal of Vascular and
Interventional Radiology in August 2019 on an analysis of results
from 437 patients, which found a correlation between baseline tumor
volume and radiofrequency ablation (RFA) heating time. Dr.
Haemmerich performed important computational modeling experiments
that showed higher drug concentrations with increased heating time
at 15, 30, 45 and 60 minutes.
This group used a LTSL-Dox to perform their
experiments and confirmed several characteristics of the compound
and its delivery mechanism that support the use of ThermoDox plus
radiofrequency ablation in the treatment of HCC, as visualized by
fluorescent imaging. Researchers used a custom designed
hyperthermal (HT) probe to heat the tumors in nude mice carrying
Lewis lung carcinoma. Key findings were as follows:
- Fluorescence Intensity Tumor Region of Interest (ROI) of heated
tumors was enhanced:
- 4.6-fold (at 15 mins)
- 9.3-fold (at 30 mins)
- 13.2-fold (at 60 mins)
- Tumor doxorubicin concentration of heated tumors was enhanced:
- 1.9-fold (at 15 mins)
- 2.9-fold (at 30 mins)
- 5.2-fold (at 60 mins)
- Fluorescence intensity of LTSL-Dox increased by:
- 6% when heated to 40°C
- 11% when heated to 43°C
- There was a good correlation between fluorescence of tumor and
tumor drug uptake
- Heat duration predicted tumor drug uptake (drug concentration)
(p=0.02)
Commenting on the study, Dr. Haemmerich said,
“This study provides visual proof of the power of heating LTSL-Dox
and its ability to target tumors with increased concentration of
doxorubicin delivered by a thermally sensitive liposomal
formulation. Following infusion of LTSL-Dox, we found that the
duration of hyperthermia dictated the tumor drug uptake, with each
additional minute of hyperthermia enhancing drug uptake by 0.31
ug/g. We also demonstrated that fluorescence intensity was
predictive of tumor drug concentrations, which may enable methods
for real-time monitoring of drug uptake in patients in the
future.”
“This study appears to support previously
announced findings published by researchers at the NIH based on
ThermoDox® and the HEAT study. There, in a prospective subgroup of
285 patients where RFA was applied for more than 45 minutes, a
clinical benefit greater than two years was found for patients
treated with ThermoDox® plus RFA, compared to RFA alone. These
analyses in combination with our published study summarized above
lend support to the hypothesis underpinning the OPTIMA Study,
Celsion’s Phase III study in newly diagnosed HCC patients,” Dr.
Haemmerich concluded.
Celsion also noted that this study confirms two
previously completed studies as summarized below:
- An independent computational model developed by Dr.
Haemmerich’s group at the Medical University of South Carolina. The
results unequivocally indicate that longer RFA heating times
correlate with significant increases in doxorubicin concentration
around the RFA treated tissue.
- A prospective preclinical study in 22 pigs conducted at
Colorado State University Animal Cancer Center using two different
manufacturers of RFA and human equivalent doses of ThermoDox® that
clearly support the relationship between increased heating duration
and doxorubicin concentrations.
Common Stock Purchase Agreement
Separately, Celsion is commenting on its Common
Stock Purchase Agreement with Aspire Capital Fund, LLC. On October
28, 2019 Celsion entered into a new Common Stock Purchase Agreement
with Aspire Capital Fund, LLC. whereby Aspire is committed to
purchase an aggregate of $10 million of shares of the Company’s
common stock over a two-year period. Celsion filed a Form S-1 to
register up to 4.5 million shares under this facility, which
replaces an earlier agreement. The sale of these securities is at
the discretion of Celsion alone. Given market conditions, the
Company has little or no intention of using this facility at this
time. Celsion reiterates its past comments regarding its strong
balance sheet, and notes that based on its previously disclosed
cash position at June 30, 2019, it believes that it has a cash
runway well into 2021.
About ThermoDox®
Celsion’s most advanced program is a
heat-mediated drug delivery technology that employs a novel
heat-sensitive liposome engineered to address a 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® is positioned
for use with multiple heating technologies and has the potential to
treat of a broad range of cancers including metastatic liver,
recurrent chest wall (RCW) breast cancer and non-muscle invading
bladder 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 the OPTIMA Study
The Phase III OPTIMA Study has enrolled 556
patients in over 60 clinical sites in the United States, Europe,
China and Asia Pacific, and will evaluate ThermoDox® in combination
with optimized RFA, which was standardized to a minimum of 45
minutes across all investigators and clinical sites for treating
lesions three to seven centimeters, versus optimized RFA alone. The
primary endpoint for the trial is overall survival. The OPTIMA
Study is a follow-on study supplemented by post-hoc analyses of
data from the Company's 701-patient HEAT Study in which optimized
RFA demonstrated the potential to significantly improve survival
when combined with ThermoDox®. The OPTIMA Study’s statistical plan
calls for two interim efficacy analyses by an independent Data
Monitoring Committee.
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 development for other cancer indications. The
Company’s product pipeline also includes GEN-1, a DNA-based
immunotherapy for the localized treatment of ovarian cancer.
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 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.
ThermoDox® is a registered trademark of Celsion
Corporation.
Celsion Investor Contact
Jeffrey W. Church Executive Vice President and CFO 609-482-2455
jchurch@celsion.com
Or
LHA Investor RelationsKim
Sutton Golodetz212-838-3777kgolodetz@lhai.com
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