Celsion Announces FDA Clearance of the OPTIMA Study - A Pivotal Phase III Trial of ThermoDox in Primary Liver Cancer

PRESS RELEASE

Feb. 24, 2014, 8:00 a.m. EST

--Study Developed in Consultation with Clinical Advisors, Statistical Experts and FDA --Compelling Survival Data Supports Development --Trial Advances Global Regulatory Strategy in Key Markets

LAWRENCEVILLE, N.J., Feb. 24, 2014 /PRNewswire/ -- Celsion Corporation CLSN -0.27% announced today that the U.S. Food and Drug Administration (FDA) has reviewed and provided clearance for the Company's planned pivotal, double-blind, placebo-controlled Phase III trial of ThermoDox®, its proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radio frequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC). The trial design is based on a comprehensive analysis of data from the Company's Phase III HEAT Study, which demonstrated that treatment with ThermoDox resulted in a 55% improvement in overall survival in a substantial number of HCC patients that received an optimized RFA treatment.  Celsion expects to launch the study in the first half of 2014.

The Phase III trial, known as the OPTIMA Study, was designed with extensive input from globally recognized HCC researchers and clinicians, and after formal consultation with FDA. The OPTIMA Study is expected to enroll 550 patients globally, with up to 100 sites in the United States, Europe, China and Asia Pacific and will evaluate ThermoDox in combination with RFA, which will be standardized to a minimum of 45 minutes across all investigators and sites for treating lesions 3 to 7 centimeters, versus standardized RFA alone. The primary endpoint for the trial is overall survival (OS).  The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).

"ThermoDox appears to hold great promise as a first-line treatment when used in combination with  optimized RFA, for primary liver cancer, one of the most deadly and prevalent forms of cancer worldwide," stated Nicholas Borys, MD, Celsion's Chief Medical Officer. "Consistency of the retrospective data emerging from the HEAT Study over the past year has been remarkable, and underscores the potential of ThermoDox to extend survival in primary liver cancer patients. Now informed by critical insights from our HEAT Study, I am confident that the OPTIMA Study is robust, well-designed and well-supported by HCC researchers worldwide.  We look forward to initiation and timely completion of this important study."

As reported in January 2014, post-hoc data from the Company's  HEAT Study demonstrate that the patient subgroup in the ThermoDox arm whose RFA procedure lasted longer than 45 minutes (285 patients or 63% of single lesion patients), experienced a 55% improvement in overall survival, with a Hazard Ratio of 0.64 (95% CI 0.41 - 1.00) and a P-value = 0.0495. Median overall survival for this subgroup has not yet been reached. Celsion will continue to follow patients in the HEAT Study on a quarterly basis.

"FDA allowance of the Phase III OPTIMA Study represents a significant step forward in our global development strategy for ThermoDox and establishes a clear regulatory pathway that advances our goal of delivering a new treatment option to patients with this devastating and underserved disease," stated Michael H. Tardugno, Celsion's President and CEO. "In parallel with our efforts in the United States, we continue to advance discussions with regulators in other important global markets, including a recent positive meeting with China FDA (CFDA) and near-term plans to meet with European regulatory authorities."

In support of the Company's global regulatory efforts, Celsion recently met with CFDA to discuss the Phase III trial, including minimum patient enrollment requirements supporting ThermoDox's registration in China. Based on those discussions, Celsion is submitting an application for accelerated approval of the study in China. Celsion will expand its clinical site footprint in Europe and plans to meet with the European Medicines Agency (EMA) in the first half of 2014.

The HEAT Study and prior post-hoc analyses were presented at three medical conferences in 2013, including the World Conference on Interventional Oncology in May; the European Conference on Interventional Oncology in June and the International Liver Cancer Association Annual Conference in September.  Presentations were made by some of the most highly recognized liver cancer researchers and key HEAT Study investigators.  Quarterly overall survival data analyses have been conducted with the full support of these researchers and clinical investigators.

About Celsion Corporation

Celsion is dedicated to the development and commercialization of innovative cancer drugs, including tumor-targeting treatments using focused heat energy in combination with heat-activated liposomal drug technology.  Celsion has research, license or commercialization agreements with leading institutions, including the National Institutes of Health, Duke University Medical Center, University of Hong Kong, the University of Pisa, the UCLA Department of Medicine, the Kyungpook National University Hospital, the Beijing Cancer Hospital and the University of Oxford.  For more information on Celsion, visit our website: http://www.celsion.com .

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; FDA and regulatory uncertainties and risks; the significant expense, time, and risk of failure of conducting clinical trials; HEAT Study data is subject to further verification and review by the HEAT Study Data Management Committee; the need for Celsion to evaluate its future development plans; possible acquisitions or licenses of other technologies, assets or businesses or the possible failure to make such acquisitions or licenses; 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. ChurchSr. Vice President and CFO609-482-2455jchurch@celsion.com

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Celsion Corporation's ThermoDox® HEAT Study Findings Reviewed at the International Liver Cancer Association (ILCA) 2013 Annual Conference in Washington, D.C. on September 14, 2013

Updated Overall Survival in Large Subgroup Continues to Show Positive Clinical Benefit

Company Sponsors Symposium on Directions in Early-Intermediate HCC

LAWRENCEVILLE, N.J., Sept. 16, 2013 /PRNewswire/ -- Celsion Corporation (NASDAQ: CLSN) announced today that Ronnie T.P. Poon, MD, MS, PhD, FRCS (Edin), FACS, Professor of Surgery at the University of Hong Kong and Lead Asia Pacific Principal Investigator for Celsion's Phase III HEAT Study of ThermoDox® in hepatocellular carcinoma (HCC) reviewed the official clinical trial results from the HEAT Study including findings from the HEAT Study post-hoc analysis at the International Liver Cancer Association 7^th Annual Conference held on September 13-15, 2013 in Washington D.C.  Following Professor Poon's presentation on September 14, 2013, the Company sponsored a symposium of leading liver cancer experts to discuss new directions in the treatment of early-intermediate HCC.

Professor Poon's oral presentation, titled "Phase 3 Randomized, Double-Blind, Dummy Controlled Trial of Radiofrequency Ablation (RFA) + Lyso-Thermosensitive Liposomal Doxorubicin for Hepatocellular Carcinoma (HCC) Lesions 3-7 cm," was held on September 14, 2013 at 12:00 p.m. (local time) during the Plenary Session.  Professor Poon's presentation also included the most recent Overall Survival data from the HEAT Study post-hoc analysis which continues to suggest positive progression-free survival (PFS) and Overall Survival (OS) in ThermoDox® treated patients when heating cycles from the radiofrequency ablation (RFA) procedure were optimized.

The data from the HEAT Study post-hoc analysis presented by Professor Poon demonstrate that ThermoDox® markedly improves Overall Survival, when compared to the control group, in patients if their lesions undergo RFA for 45 minutes or more.  These findings apply to single HCC lesions (63% of the HEAT Study population) from both size cohorts of the HEAT Study (3-5 cm and 5-7 cm) and represent a subgroup of approximately 300 patients (42% of the patients in the HEAT Study).

• In the patient subgroup treated in the ThermoDox® arm whose RFA procedure lasted longer than 45 minutes and was completed within 90 minutes (40% of single lesion patients) Overall Survival improved by 71% (Hazard Ratio of 0.585) when compared to the control arm of RFA treatment only.
• In the patient subgroup treated in the ThermoDox® arm whose RFA procedure lasted longer than 90 minutes (23% of single lesion patients), Overall Survival improved by similar 71% (Hazard Ratio of 0.584) when compared to the control arm of RFA treatment only.
• When combined, these two subgroups show clinical results that indicate a 61% improvement in Overall Survival, a Hazard Ratio of 0.623 and a P-value = 0.058.
• In contrast, the patient subgroup treated with ThermoDox® whose RFA procedure lasted less than 45 minutes in duration (37% of single lesion patients) indicated that the control arm had a slightly improved Overall Survival benefit when compared to the ThermoDox® arm.
• The Hazard Ratio reported above should be viewed with caution since they are not statistically significant and the HEAT Study has not reached its median point for Overall Survival analysis.  Celsion continues to follow all patients in the HEAT Study to the secondary endpoint, Overall Survival, and will update the subgroup analysis based on RFA heating duration.

Celsion also sponsored a symposium in conjunction with the ILCA conference moderated by Professor Riccardo Lencioni, MD, FSIR, EBIR, the Director of the Division of Diagnostic Imaging and Intervention at Pisa University School of Medicine in Italy.   Participants included Professor Josep Llovet, MD, PhD, Professor of Medicine and Director, Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine; Ghassan K. Abou-Alfa MD, PhD, Associate Attending Memorial Sloan-Kettering Cancer Center, New York, NY, Associate Professor, Weill Medical College at Cornell University, New York, NY, and Associate Professor, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; and Professor Ronnie T.P. Poon, MD, PhD.  The discussion focused on new developments in the treatment of early-intermediate HCC including the updated data from the Company's HEAT Study post-hoc analysis as well as computer modeling with supplementary preclinical animal studies supporting the relationship between heating duration and clinical outcomes.

• Results from a finite element method model that simulates temperature, perfusion contours with RFA treatments and allow prediction of drug deposition contour maps with the combined use of RFA and ThermoDox®, show a direct correlation with heating time and amount of drug deposited to the tumor margin, where both adequate heat and tissue perfusion exist.
• Results from recently completed large animal studies (21 subject porcine study) demonstrate that longer RFA heating (dwell) time results in higher local tissue concentrations of ThermoDox® in the surrounding ablation zone.  

Professor Riccardo A. Lencioni commented, "After reviewing the complete and subgroup analysis of the Phase III HEAT Study as well as the recently completed porcine study, I am convinced ThermoDox® demonstrates clinical activity in a highly responsive population of single lesion patients.  The duration of heat from the RFA procedure is an important factor in a successful clinical outcome when combined with ThermoDox® as demonstrated by the growing body of clinical and non-clinical data generated by the Company.  These findings build a solid scientific foundation of understanding that increased perfusion and longer heating duration are key factors for ensuring that the heat-sensitive liposomes are activated to deposit high concentrations of doxorubicin in the tumor and the surrounding liver tissue."

ILCA has selected the HEAT Study presentation to be webcast as part of an online educational program of the ILCA 2013 Annual Conference.  Professor Poon's presentation will also be available on Celsion's website at http://investor.celsion.com/events.cfm.

The International Liver Cancer Association is the only international organization devoted exclusively to liver cancer research for experts from all related disciplines – medical, interventional and surgical oncology as well as hepatology.  ILCA's Executive Committee consists of Dr. Josep M. Llovet (President); Professor Riccardo Lencioni and Dr. Morris Sherman.  Celsion notes that Professors Lencioni and Poon and Dr. Sherman are principal investigators on the HEAT Study.

About Celsion Corporation

Celsion is dedicated to the development and commercialization of innovative cancer drugs, including tumor-targeting treatments using focused heat energy in combination with heat-activated liposomal drug technology.  Celsion has research, license or commercialization agreements with leading institutions, including the National Institutes of Health, Duke University Medical Center, University of Hong Kong, the University of Pisa, the UCLA Department of Medicine, the Kyungpook National University Hospital, the Beijing Cancer Hospital and the University of Oxford.  For more information on Celsion, visit our website: http://www.celsion.com.

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 significant expense, time, and risk of failure of conducting clinical trials; HEAT Study data is subject to further verification and review by the HEAT Study Data Management Committee; the need for Celsion to evaluate its future development plans; termination of the Technology Development Contract or collaboration between Celsion and HISUN at any time; possible acquisitions or licenses of other technologies, assets or businesses or the possible failure to make such acquisitions or licenses; 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.

Investor Contact
Jeffrey W. Church
Senior Vice President and
Chief Financial Officer
609-482-2455
jchurch@celsion.com

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Celsion Receives Positive FDA Guidance for its New Drug Application for ThermoDox to Treat Primary Liver Cancer

From the PharmaLive.com News Archive - Oct. 04, 2010

FDA confirms Celsion's preclinical studies are sufficient to support NDA submission

COLUMBIA, Md., Oct. 4 /PRNewswire/ -- Celsion Corporation (Nasdaq: CLSN), a leading oncology drug development company, announced that the Company has reached agreement with the U.S. Food and Drug Administration (FDA) that the requirements for non-clinical studies have been met for the New Drug Application (NDA) of ThermoDox.

The FDA has provided written guidance that the Company is not required to conduct any additional non-clinical pharmacology, safety pharmacology and general toxicology studies assuming the results of current studies are adequate. The results of these current studies will be reviewed at the time of NDA submission. This agreement takes advantage of an NDA application known as a 505(b)2 which allows a company to reference existing data regarding doxorubicin and other liposomal drugs currently approved by the FDA.

As previously announced, the FDA has granted Fast Track Development for the Company's 600 patient pivotal Phase III clinical trial (the HEAT study) of its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA), The Fast Track Development Program provides for expedited regulatory review including frequent interactions between the FDA. Celsion is eligible to submit its NDA on a rolling basis and review sections of the NDA with the FDA in advance of submitting the complete submission. The HEAT study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA.

"We are very pleased with the FDA's continued willingness to work closely with the Company to identify the most expeditious regulatory pathway forward for ThermoDox® in HCC, a life threatening disorder," stated Mr. Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Our past consultation with the FDA regarding Chemistry Manufacturing and Controls (CMC) has permitted Celsion to implement and validate process improvements to its manufacturing methods used to produce ThermoDox at commercial scale."

About ThermoDox® and the Phase III HEAT Study

ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT study, ThermoDox is administered intravenously in combination with RFA. A thermal zone created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially at the targeted tumor.

For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III study at 75 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with RFA when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival (PFS) with a secondary confirmatory endpoint of overall survival. A pre-planned, interim efficacy analysis will be performed by an independent Data Monitoring Committee when enrollment in the trial is complete and 50 percent of the PFS events are realized in the study population. Additional information on the Company's ThermoDox® clinical studies may be found at http://www.clinicaltrials.gov/

About Primary Liver Cancer

Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States and has a worldwide incidence of approximately 650,000 cases, due to the high prevalence of Hepatitis B and C in developing countries. The standard first line treatment for liver cancer is surgical resection of the tumor; however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasingly become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer.

About Celsion

Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the North Shore Long Island Jewish Health System. For more information on Celsion, visit our website: http://www.celsion.com/.


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 by others; possible acquisitions of other technologies, assets or businesses; possible actions by customers, suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission.

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SOURCE Celsion Corporation

CONTACT: Marcy Nanus, The Trout Group, +1-646-378-2927, mnanus@troutgroup.com

Web Site: http://www.celsion.com/

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Celsion Receives Fast Track Designation for ThermoDox® Development Program to Treat Primary Liver Cancer

Celsion Receives Fast Track Designation for ThermoDox® Development Program to Treat Primary Liver Cancer

Supplements Special Protocol Assessment for Global Phase III HEAT Study

COLUMBIA, Md., Aug. 24 /PRNewswire-FirstCall/ -- Celsion Corporation (Nasdaq: CLSN), a leading oncology drug development company, today announced that the U.S. Food and Drug Administration (FDA) has designated the HEAT Study of its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA), as a Fast Track Development Program. ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin, is currently being evaluated under a Special Protocol Assessment (SPA) agreement with the FDA in a 600 patient global Phase III trial in patients with non-resectable hepatocellular carcinoma (HCC), commonly referred to as primary liver cancer. With nearly 70% of patients enrolled in the trial, Celsion is targeting to complete patient enrollment by year end 2010.

"We are very pleased to receive the Agency's Fast Track Designation for ThermoDox," stated Mr. Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Fast Track Designation is an acknowledgement that HCC is a significant unmet medical need representing a life threatening disorder. It also recognizes the challenges facing pharmaceutical companies to develop effective new treatments for this difficult disease. Together with the FDA's SPA agreement, granting accelerated review for the HEAT Study, the Fast Track status provides Celsion with the shortest time to approval. Supported further by the National Cancer Institute's recent designation of the HEAT Study as a Priority Clinical Trial, it is clear that the major U.S. healthcare agencies and the liver cancer medical community recognize the potential of ThermoDox. We look forward to working with the FDA and other regulatory agencies around the world to make ThermoDox available to patients as soon as possible."

The FDA's Fast Track Development Program provides for expedited regulatory review for new drugs that treat serious or life threatening diseases which are not satisfactorily treated by existing therapies, or for drugs that provide a significant advantage over existing therapies for serious diseases. Under the Fast Track Designation, Celsion is now eligible to submit a U.S. New Drug Application (NDA) on a rolling basis. This permits the FDA to review sections of the NDA in advance of receiving the complete submission.

About Primary Liver Cancer

Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States and is rapidly growing worldwide at approximately 1,000,000 cases per year, due to the high prevalence of Hepatitis B and C in developing countries. The standard first line treatment for liver cancer is surgical resection of the tumor; however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasing become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer.

About ThermoDox®

ThermoDox® in combination with hyperthermia has the potential to provide local tumor control and improve quality of life. ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers including breast cancer. Localized mild hyperthermia (40-42 degrees Celsius) releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumor.

For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III study at 75 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with RFA when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival and enrollment is expected to be completed by year end 2010. For recurrent chest wall breast cancer, ThermoDox® is being evaluated in a pivotal Phase I/II open-label, dose-escalating trial that is designed to measure durable local complete response at the tumor site. Celsion expects to enroll approximately 100 patients across the United States and to complete the study by the first half of 2011. Additional information on the Company's ThermoDox® clinical studies may be found at http://www.clinicaltrials.gov/

About Celsion

Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the North Shore Long Island Jewish Health System.

For more information on Celsion, visit our website: http://www.celsion.com/.

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 by others; possible acquisitions of other technologies, assets or businesses; possible actions by customers, suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission.

Investor Contact
Marcy Nanus
The Trout Group
646-378-2927, mnanus@troutgroup.com

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