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Celsion Corporation Announces Positive DSMB Review of Phase 1b OVATION Study in Ovarian Cancer
Study to Complete Final Patient Cohort as Planned
LAWRENCEVILLE, N.J., Dec. 01, 2016 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN) today announced that the independent Data Safety Monitoring Board (DSMB) has completed its safety review of data from the first four patient cohorts in the ongoing Phase 1b OVATION Study. Based on the DSMB's recommendation, the study will continue as planned and the Company will proceed with completing dosing in the fourth and final patient cohort, which is currently enrolling patients. The OVATION Study is a dose-escalating clinical trial combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.
"We are very encouraged by the data reported to date. In the first three cohorts, we saw remarkable and consistent responses across a number of clinically meaningful measures, underscoring the potential promise of our immunotherapy approach in this difficult-to-treat patient population," said Michael H. Tardugno, Celsion's chairman, CEO and president. "The OVATION Study continues to progress on schedule and we look forward to reporting additional clinical findings from the fourth patient cohort, as well as translational data, later this month. Furthermore, we expect to report final data from this study in the first quarter of 2017."
"Our OVATION Study is achieving its objective of demonstrating that GEN-1 can be safely administered directly into the peritoneum and is well tolerated by patients when combined with standard neoadjuvant chemotherapy," said Nicholas Borys, M.D., senior vice president and chief medical officer of Celsion. "As we have previously reported, all nine patients in the first three cohorts experienced a clinically meaningful response, ranging from stable disease to one pathologically confirmed complete response. Two-thirds of patients treated in the trial experienced at objective tumor response. We also observed three cases of no visible residual disease at time of surgery (R0 resection). In addition, we saw sustained decreases of 90% or greater of the prospective indicator of the presence of ovarian cancer cells, CA-125 protein, in all patients, as well as highly impressive pathologically responses, which is associated with prolonged survival. We hope to build on these impressive results with our translational data, which will provide further insights on the impact of localized IL-12 production with GEN-1."
The OVATION Study is designed to enroll three to six patients per dose cohort at escalating doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first three cohorts each enrolled three patients. Enrollment in the fourth and final cohort is underway, and Celsion expects to report full data from the OVATION Study by the first quarter of 2017.
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Source: press release, 12/01/16. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=1001705

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Celsion Corporation Announces Positive DSMB Review of Phase 1b OVATION Study in Ovarian Cancer
Study to Continue to Fourth and Final Patient Cohort
LAWRENCEVILLE, N.J., Sept. 15, 2016 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN) today announced that the independent Data Safety Monitoring Board (DSMB) has completed its safety review of data from the first three patient cohorts in the ongoing Phase Ib OVATION Study. Based on the DSMB's recommendation, the study will continue as planned and the Company will proceed with dosing in its fourth and final patient cohort at an escalated dose. The OVATION Study is a dose-escalating clinical trial combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.
"The DSMB's recommendation and the lack of any dose limiting toxicities in the trial to date underscore the improved tolerability of GEN-1 over recombinant IL-12 protein-based therapies," said Nicholas Borys, M.D., senior vice president and chief medical officer of Celsion. "The favorable safety profile we have seen thus far is consistent with the translational data that we reported earlier this year, which show that GEN-1 produces a sustained, localized secretion of IL-12 protein and avoids the high levels of systemic exposure which have limited the development of recombinant IL-12 therapies in the past."
"We could not be more excited to progress with the OVATION Study and look forward to reporting clinical findings from the third patient cohort, as well as translational data from the first two cohorts, early in the fourth quarter. Furthermore, we expect to report final data from this highly promising study in the first quarter of 2017," said Michael H. Tardugno, Celsion's chairman, CEO and president. "We have been encouraged, as have been our Investigators, by the findings to-date in this difficult-to-treat patient population. As we have previously reported, all six patients in the first two cohorts experienced a clinically meaningful response, ranging from stable disease to one pathologically confirmed complete response. In addition, we saw sustained decreases of 90% or greater of the prospective indicator of the presence of ovarian cancer cells, CA-125 protein, in all patients, as well as highly impressive pathologically responses, which is associated with prolonged survival."
The OVATION Study is designed to enroll three to six patients per dose cohort at escalating doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first three cohorts each enrolled three patients. Enrollment in the fourth and final cohort is underway, and Celsion expects to report full data from the OVATION Study by the first quarter of 2017. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin® and Doxil®.
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Source: press release, 9/15/16.

May 24, 2016
Celsion Announces Presentation of OVATION Study Clinical Trial Design at Upcoming ASCO 2016 Meeting
Company Expects to Report Data from Second Cohort of the OVATION Study by Mid-Year, Followed by Translational Data for the First Two Cohorts in the Third Quarter
LAWRENCEVILLE, N.J., May 24, 2016 /PRNewswire/ -- Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today provided an update on its ongoing OVATION study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. GEN-1 is an IL-12 DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the Interleukin-12 (IL-12) protein loco-regionally to the tumor site.

The Company announced that an abstract detailing the trial design of the OVATION Study has been accepted for presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, which will take place from June 3-7 in Chicago. The abstract, entitled "Phase 1 study of the safety and biological activity of intraperitoneal IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer administered in combination with standard neoadjuvant chemotherapy (NAC) in patients with newly diagnosed ovarian cancer," will be presented in a poster session on Monday, June 6th from 1:00 PM to 4:00 PM.

The Company also announced today that it has completed enrollment of the second cohort of the OVATION Study and expects to report clinical data from that cohort mid-year. Celsion has previously reported highly encouraging data from the first cohort of the OVATION Study. In the first three patients dosed, GEN-1 plus standard chemotherapy produced excellent results, with no dose limiting toxicities and highly promising efficacy signals leading to successful surgical outcomes as summarized below:

Of the three patients treated in the first cohort, two patients demonstrated stable disease (SD) and one patient demonstrated a complete response (CR), as measured by RECIST criteria.
All patients had successful resections of their tumors, with two patients having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and one patient with Stage IV ovarian cancer having an optimal R1 resection.
One patient demonstrated a pathological complete response (pCR). pCRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection, and have been associated with a median overall survival (OS) of 72 months, which is more than three years longer than those who do not experience a pCR.
All patients experienced a dramatic > 96% drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful. All patients' CA-125 levels were below the standard cutoff level of 35 U/mL.
Celsion also expects to report translational data from the first two cohorts of the OVATION Study early in the third quarter of 2016. The translational data will provide further insight into GEN-1's mechanism of action through the evaluation of dose-related changes in the tumor and peritoneal immune cell population, as well as through the peritoneal cytokine levels. Moreover, immune cell density, a common indicator of survival in ovarian cancer patients, will be explored to further demonstrate the therapy's efficacy in these patients.

"We continue to successfully execute our OVATION Study in newly diagnosed ovarian cancer patients, and are pleased to report that our second cohort is now fully enrolled," said Michael H. Tardugno, Celsion's chairman, president and CEO. "The translational and clinical data seen to date underscore the potential efficacy and safety profile of GEN-1, and we look forward to learning more about the utility of our gene-based immunotherapy approach as our data set matures."
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Source: press release, 5/24/16.

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Celsion Corporation Announces Positive Data from the First Cohort of Patients in the OVATION Study

GEN-1 Immunotherapy Together with Standard Chemotherapy in First Line Ovarian Cancer Patients Demonstrates Impressive Outcomes

One Patient of the First Three with Advanced Ovarian Cancer Had a Complete Pathological Response

LAWRENCEVILLE, N.J., May 2, 2016 /PRNewswire/ -- Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today announced data from the first cohort of patients in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. In the first three patients dosed, GEN-1 plus standard chemotherapy produced excellent results, with no dose limiting toxicities and highly promising efficacy signals leading to successful surgical outcomes. The three patients were treated at the University of Alabama at Birmingham.

"These results, while early, are very impressive and speak to the potential of GEN-1 to improve patient outcomes in ovarian cancer," said Ronald D. Alvarez, M.D., Professor, Division of Gynecologic Oncology at the University of Alabama at Birmingham. "In particular, we see improvements across a number of important and meaningful measures used to assess ovarian cancer, which reinforce our confidence in this IL-12 immunotherapy approach and provide a strong rationale for continued development of GEN-1 for the treatment of ovarian cancer."

OVATION Study - First Cohort Results

Of the three patients treated in the first cohort, two patients demonstrated stable disease (SD) and one patient demonstrated a complete response (CR), as measured by RECIST criteria.
All patients had successful resections of their tumors, with two patients having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and one patient with an optimal R1 resection.
One patient demonstrated a pathological complete response (pCR). pCRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection, and have been associated with a median overall survival (OS) of 72 months, which is more than three years longer than those who do not experience a pCR¹.
All patients experienced a dramatic > 96% drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful. All patients' CA-125 levels were below the standard cutoff level of 35 U/mL.
"These results build on the impressive clinical findings we observed in the GOG Study as well as the translational data from this same study reported earlier this year. As we move closer towards initiating a Phase I/II trial to evaluate the synergistic anti-cancer effects of GEN-1 together with Avastin® and Doxil®, these results also provide strong validation for the potential of GEN-1 in ovarian cancer," said Michael H. Tardugno, Celsion's chairman, president and chief executive officer. "We will continue to evaluate the maturing dataset from the OVATION study, and may evaluate ways to leverage insights from this trial to help accelerate the clinical development of this highly promising therapy and inform the design of future studies."

The OVATION Study will continue into 2016 at higher doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. Celsion has initiated four clinical sites at the University of Alabama at Birmingham; Oklahoma University Medical Center; Washington University in St. Louis and the Medical College of Wisconsin. The trial is designed to enroll three to six patients per dose cohort and will evaluate safety and efficacy and attempt to define an optimal dose. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin® and Doxil®. With the second cohort fully enrolled, Celsion expects to complete the OVATION Study this year.

GOG Study - GEN-1 Data

Celsion also recently announced clinical data from a dose-escalation study evaluating GEN-1 plus Doxil® in platinum resistant ovarian cancer (the GOG Study). In the GOG Study, at the highest dose level, GEN-1 plus Doxil® produced an objective response rate (ORR) of 29%. This compares favorably to the data from the Phase 3 AURELIA trial in platinum-resistant ovarian cancer, which demonstrated that Avastin® plus chemotherapy produced an ORR of 27%. Historical data for trials evaluating Doxil® monotherapy in platinum resistant ovarian cancer suggest an ORR of only 8% to 12%.

Translational data from the GOG Study reported in January 2016 is highlighted below:

Intraperitoneal administration of GEN-1 in platinum-resistant ovarian cancer patients resulted in a significant increase in IL-12 levels in peritoneal fluid samples. IL-12 levels were quantifiable in 91% of evaluable fluid samples collected post GEN-1 treatment. None of the evaluable pre-treatment peritoneal fluid samples had any detectable IL-12 levels.
The IL-12 levels were detectable for at least seven days after GEN-1 treatment.
In comparison to peritoneal fluid, the IL-12 levels in plasma samples (systemic exposure) following GEN-1 treatment were not detectable or were very low in quantity.
Significant increases in levels of IFN-γ, a key downstream mediator of IL-12 action, were observed in peritoneal fluid but not in plasma samples. At least a 5-fold increase above pre-treatment level in IFN- γ was observed in most samples, with the highest increase observed at 120-fold. Similar results were observed with TNF-α levels, with the highest increase observed at 77-fold over pre-treatment control.
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Source: press release, 5/02/16. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=968357

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Michael H. Tardugno, President and CEO, commented on upcoming milestones, including the OVATION, Euro-DIGNITY and OPTIMA studies. He stated, "With regards to milestones, upcoming milestones over the next six to twelve months, there is a lot going on. We expect to be able to on a cohort, as I mentioned earlier on a cohort by cohort basis provide results from the dose escalation neoadjuvant study in OVATION. we will be presenting data from the first two cohorts, the translational data from the tissue analysis from the patients enrolled in the first two cohorts. We expect to provide final data from this neoadjuvant study by the end of the year. We expect to submit and initiate the Avastin combination study in quarter four, 2016 and initiate the Euro-DIGNITY study, again with data is an open label study being presented throughout the year and completion of that study in 2017 and of course if things continue to be on track by the end of 2017 announce the completion of enrollment in the OPTIMA study."
Source: Q4 2015 earnings conference call, 3/30/16.

Michael H. Tardugno, President and CEO, commented on the ongoing phase-I dose finding study for Gen-1 in ovarian cancer, the OVATION study. He stated, "We are now conducting a phase-I dose escalation study in newly diagnosed ovarian cancer patients in the neoadjuvant setting known as the OVATION Study. This trial is designed to enroll 3 to 6 patients per dose cohort and will evaluate safety and efficacy. It will define an optimal dose for follow-on phase-I/II Study combining GEN-1 with Avastin and Doxil the standard of care for platinum-resistant recurrent patients. In February we reported that the first two patients in the OVATION Study who completed treatment have shown promising results. Both patients demonstrated improvement with a dramatic drop in the CA-125 protein levels of 89% and 98% respectively. For context we would note that a 50% reduction in CA-125 levels is considered meaningful. Now for those of you who are asking the question CA-125 is a protein, it is a prognostic indicator of tumor cell burden for lower levels are better. Last week our DMC met and gave the okay to enroll the second cohort at 30% increase in dose with the first cohort now completed I am pleased to report that the first three patients in this novel proof second cohort have been identified. Assuming no DLTs we can expect the third and perhaps final cohort to enroll beginning in the third quarter."
Source: Q4 2015 earnings conference call, 3/30/16.

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Celsion Reports Translational Research Data from its Phase 1b Study of GEN-1 Immunotherapy in Recurrent Ovarian Cancer
Treatment with GEN-1 Results in Sustained, Targeted Production of Immunologically Active IL-12
Cytokine Activation to GEN-1 Immunotherapy is Limited to Targeted Area in the Peritoneum of Patients
Exciting Development Shows Potential for Significant Advantages over Recombinant IL-12 Dosage Options

LAWRENCEVILLE, N.J., Jan. 7, 2016 /PRNewswire/ -- Celsion Corporation (NASDAQ: CLSN), today announced new translational data from its Phase 1b study of GEN-1 in patients with platinum-resistant ovarian cancer. GEN-1 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. The new data demonstrate that intraperitoneally-administered GEN-1 produces an immunologically distinct IL-12 protein that is localized at the tumor site and lasts for up to one week after a single treatment. Furthermore, concomitant increases in IFN-γ and TNF- α indicate that the IL-12 produced following treatment with GEN-1 treatment is immunologically active. Celsion Corporation is a fully integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases.

"We now have clear clinical evidence that treatment of platinum-resistant ovarian cancer with GEN-1 produces a sustained, localized immune response, which then translates to the compelling activity and tolerability profile we have seen in early clinical studies," said Khursheed Anwer, Ph.D., executive vice president and chief scientific officer of Celsion. "These data also provide additional evidence of GEN-1's ability to overcome the limitations associated with recombinant IL-12, which has a very short half-life and results in high systemic levels of IL-12, leading to potentially severe toxicities. We plan to build on these data and advance our understanding of GEN-1's mechanism of action further with additional translational research as part of our ongoing OVATION Study."

The Phase 1B dose escalating study enrolled 16 patients with platinum-resistant ovarian cancer and evaluated the safety, tolerability and efficacy of GEN-1 in combination with pegylated doxorubicin as well as the effect of intraperitoneal injection of GEN-1 on IL-12 and tumor cytokine levels. Patients received pegylated liposomal doxorubicin on day 1 and GEN-1 on days 1, 8, 15 and 22. This treatment regimen was repeated every 28 days in the absence of disease progression or toxicity.

Celsion reported clinical findings from the Phase 1b study at the 2015 American Society of Clinical Oncology (ASCO) Meeting in June 2015 demonstrating an overall clinical benefit of 57% for all treatment arms. The overall clinical benefit observed at the highest dose cohort in this difficult-to-treat patient population was 100% (PR=33% and SD=67%) in all six evaluable patients. A maximum tolerated dose was not reached and studies evaluating higher doses of GEN-1 are currently underway.

The new translational data reported today is highlighted below:

Intraperitoneal administration of GEN-1 in platinum-resistant ovarian cancer patients resulted in a significant increase in IL-12 levels in peritoneal fluid samples. IL-12 levels were quantifiable in 91% of evaluable fluid samples collected post GEN-1 treatment. None of the evaluable pre-treatment peritoneal fluid samples had any detectable IL-12 levels.
The IL-12 levels were detectable for at least seven days after GEN-1 treatment.
In comparison to peritoneal fluid, the IL-12 levels in plasma samples (systemic exposure) following GEN-1 treatment were not detectable or were very low in quantity.
Significant increases in levels of IFN-γ, a key downstream mediator of IL-12 action, were observed in peritoneal fluid but not in plasma samples. At least a 5-fold increase above pre-treatment level in IFN- γ was observed in most samples, with the highest increase observed at 120-fold. Similar results were observed with TNF-α levels, with the highest increase observed at 77-fold over pre-treatment control.
A publication of this data is being prepared for submission for major scientific review which will detail all cytokine levels observed in this study.
Celsion intends to collect additional translational data, including cellular responses in primary tumor tissue and peritoneal ascites, in its ongoing OVATION Study, a Phase I dose escalation study in newly diagnosed ovarian cancer patients in the neoadjuvant setting.

"With these remarkable findings we feel confident that the data we expect to collect from the OVATION Study will provide further evidence that GEN-1, our gene-mediated immunotherapy, has significant potential in oncology generally and in ovarian cancer specifically," noted Michael H. Tardugno, Celsion's chairman, CEO and president. "Our clinical development program for ovarian cancer is now well positioned with compelling clinical and biological data, fully supporting our thesis for combining GEN-1 with Doxil® and Avastin® to treat platinum-resistant ovarian cancer patients in a study we expect to launch later this year."
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Source: press release, 1/07/16. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=949315

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Celsion Corporation Enrolls First Patient in the OVATION Study

First Line, Phase 1b Trial to Assess Immunotherapy Combining GEN-1 with Neo-Adjuvant Therapies in Newly Diagnosed Ovarian Cancer Patients

LAWRENCEVILLE, N.J., Sept. 30, 2015 /PRNewswire/ -- Celsion Corporation (Celsion) (NASDAQ:CLSN), a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases, today announced the enrollment of the first patient in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed ovarian cancer patients who will undergo neoadjuvant chemotherapy. The first patient in the OVATION Study was enrolled at the University of Alabama at Birmingham (UAB). In addition to UAB, Oklahoma University Medical Center is now also recruiting patients in the OVATION Study. Celsion plans to initiate two additional sites in the coming months. Interim findings from this open label study are expected in the fourth quarter of 2015. The study will continue into the first half of next year at higher doses of GEN-1.

The OVATION Study will seek to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The trial is designed to enroll three to six patients per dose level and will evaluate safety and efficacy and attempt to define an optimal dose for a follow-on Phase I/II study combining GEN-1 with Avastin® and Doxil®. In addition, the OVATION Study establishes a unique opportunity to assess how cytokine-based compounds such as GEN-1, directly affects ovarian cancer cells and the tumor microenvironment in newly diagnosed patients. The study is designed to characterize the nature of the immune response triggered by GEN-1 at various levels of the patients' immune system, including:

infiltration of cancer fighting T-cell lymphocytes into primary tumor and tumor microenvironment including peritoneal cavity, which is the primary site of metastasis of ovarian cancer;
changes in local and systemic levels of immuno-stimulatory and immunosuppressive cytokines associated with tumor suppression and growth, respectively; and
expression profile of a comprehensive panel of immune related genes in pre-treatment and GEN-1-treated tumor tissue.
These extensive mechanistic studies will assist in the design of novel combination approaches with immunotherapies and other anti-cancer agents driven by potential synergistic action mechanisms, and define an enhanced patient population based on molecular characteristics inherent to tumor tissue or the immune system.

GEN-1 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. GEN-1 has demonstrated encouraging safety and efficacy data in a Phase Ib trial in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer. The findings from this trial demonstrated an overall clinical benefit of 57% for all treatment arms, with a partial response (PR) rate of 21% and a stable disease (SD) rate of 36%. The overall clinical benefit observed at the highest dose cohort in this difficult-to-treat patient population was 100% (PR=33% and SD=67%) in all six evaluable patients. GEN-1 was well tolerated, with no dose limiting toxicities and no overlapping toxicities between GEN-1 and pegylated doxorubicin.

"Developing more effective immunotherapy approaches for ovarian cancer is a high priority for those of us who care for the thousands of patients affected by advanced ovarian cancer. GEN-1 is a novel IL-12 expressing lipopolymer that has demonstrated promising activity in preclinical and early phase clinical trials in ovarian cancer," stated Premal H. Thaker, M.D., associate professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine. "In preclinical and clinical studies performed to date, GEN-1 has demonstrated good safety and impressive immune system stimulation and activity, and this trial will evaluate its value as an adjuvant to chemotherapy in patients with a relatively healthy immune system."

"GEN-1 is designed to locally activate IL-12 production, which can stimulate the patient's immune system to attack and destroy cancer," stated Dr. Nicolas Borys, Celsion's senior vice president and chief medical officer. "Increases in IL-12 concentrations at the tumor site could create a potent immune environment against tumor activity resulting in a more robust and durable antitumor response compared to chemotherapy alone. We are conducting this trial in newly diagnosed patients with good immune systems in order to maximize the success of GEN-1's novel mechanism."

"GEN-1 holds tremendous promise as a potential treatment in the rapidly emerging area of immuno-oncology. Unlike the toxicities, poor tolerability, and poor pharmacokinetics of systemically administered recombinant IL-12, the beauty of GEN-1 is that it inspires secretion of highly-tolerable endogenous IL-12," said Michael H. Tardugno, Celsion's chairman, president and chief executive officer. "Designed in consultation with clinicians, this Phase I trial is expected to define an optimal dose and potentially an enhanced population. It will also provide insights on powering for a registration program as the candidate progresses through development."
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Source: press release, 9/30/15. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=934423

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A Phase I Study of the Safety and Biological Activity of Intraperitoneal GEN-1 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered In Combination With Standard Neoadjuvant Chemotherapy in Patients Newly Diagnosed With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Estimated Enrollment: 15
Study Start Date: September 2015
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
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Source: clinical trials.gov. https://clinicaltrials.gov/ct2/show/NCT02480374?term=GEN-1&rank=1

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Gen-1 (EGEN-001)OncologyOvarian CancerGene therapeuticTumor cells

Mechanism of action: Gen-1 (EGEN-001) is a novel non-viral vector consisting of a plasmid DNA encoding the human gene for interleukin 12 (IL-12) and a biocompatible, biodegradable delivery polymer with potential antineoplastic activity. EGEN-001 is designed to increase the local concentration of IL-12 in the tumor microenvironment. IL-12 stimulates T-cell-independent production of IFN-gamma by peripheral blood mononuclear cells (PBMCs); enhances natural killer (NK) cell lytic activity; acts as a growth factor for T- and NK-cells; and is important for T-cell differentiation. IL-12 may potentiate antitumoral functions of the host immune system, resulting in immune-mediated tumor regression.

Phase of Development: Ib

Event Type: Data: Phase Ib trial results

Dates: 2017-01-01 - 2017-03-31

Results:

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Celsion Announces Continuing Positive Data from the OVATION Study - An Immunotherapy Study of Newly Diagnosed Stage III and IV Ovarian Cancer Patients
Third Cohort of Patients Continues to Show Clinically Meaningful Responses in the Evaluation of GEN-1, A Novel IL-12 DNA-based Immunotherapy, in Combination with the Standard of Care
Top Line Translational Data from First Two Cohorts Demonstrates Potential Immune Activation
LAWRENCEVILLE, N.J., Nov. 10, 2016 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN) today announced data from the third cohort of patients in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. In the first nine patients dosed, GEN-1 plus standard chemotherapy produced impressive results, with no dose limiting toxicities and highly promising efficacy signals in this difficult to treat cancer.
"While the patient number in this trial may be small, the consistency and robust nature of the data across all three cohorts and the encouraging clinical responses underscore the potential of GEN-1 to serve as an effective, safe IL-12 immunotherapy in ovarian cancer," said Nicholas Borys, M.D., Celsion's chief medical officer. "I am particularly impressed with the pathological response data, which is known to be associated with prolonged survival in this patient population. The data generated support continued evaluation of GEN-1 in ovarian cancer, and we look forward to seeing how GEN-1 performs in the fourth and final study cohort."
The OVATION Study is designed to enroll three to six patients per dose cohort with the goal of identifying a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first three cohorts each enrolled three patients. Enrollment in the fourth cohort is ongoing, and Celsion expects to complete the OVATION Study this year and report data in early 2017. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin® and Doxil®.
OVATION Study - Totality of Results in the First Three Cohorts
Of the first nine patients dosed, one patient demonstrated a complete response (CR), five patients demonstrated partial response (PR) and three patients demonstrated stable disease (SD), as measured by RECIST criteria. This translates to a 100% disease control rate (DCR), and 66% objective response rate (ORR).
Eight patients had successful resections of their tumors, with four patients having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and three patients with a R1 resection, indicating microscopic residual tumor. One patient had an R2, indicating macroscopic residual tumor. One patient in the second cohort was ineligible for debulking surgery due to a medical complication unrelated to the study or the study drug.
Of the eight surgically treated and evaluable patients, one patient demonstrated a complete pathological response (cPR), three patients demonstrated a micro pathological response (microPR), and four patients demonstrated a macroPR. These data compare favorably to historical data, which indicate that cPRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection. cPRs have been associated with a median overall survival of 72 months, which is more than three years longer than those who do not experience a cPR. In addition, microPRs are seen in approximately 30% of patients, and are associated with a median overall survival of 38 months¹.
Seven patients who completed treatment follow-up experienced a dramatic (greater than 90%) drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful. Six patients maintained CA-125 levels below the standard cutoff level of 35 U/mL.
OVATION Study - Top Line Translational Data from First Two Cohorts
Celsion also reported initial translational data from the first two cohorts of the OVATION study. Tumor and blood samples collected before the start of the neoadjuvant chemotherapy (NACT) and after the completion of GEN-1 treatment at debulking surgery are being analyzed for immune cell populations. Top line data demonstrates intriguing immunological changes in the tumor that are consistent with the activation of the immune system. Specifically,
In tumor tissue, there was an increase in cytotoxic CD8+ T-cell density in three out of four evaluable patients at debulking surgery. There was a decrease in immunosuppressive FoxP3+ T-cells in two out of those 4 patients. The ratio of CD8+/FoxP3+ cells was increased in all four evaluable patients. High tumor infiltrating CD8+ T-cell density, low FoxP3+ T-cell density or high CD8+/FoxP3+ ratio demonstrate a potential shift in tumor environment to favoring immune stimulation following NACT + GEN-1 therapy. For the remaining two patients the post-treatment tumor tissue was not available. In one of those two patients there was complete pathological response hence no tumor tissue was present to provide a post-treatment comparison. In the other patient the debulking surgery was not performed due to disease related complications.
In plasma samples, there appeared to be no significant change in T-cell density following the treatment. The density of myeloid derived suppressor cells that are associated with immunosuppression in ovarian cancer were either decreased or did not increase in post-treatment samples.
Additional immune analysis of biological tissue including cytokine ELISA from the first two patient cohorts and a complete analysis of the two higher dose cohorts is in progress.
"The clinical and translational data generated to date are meaningful and reinforce our confidence in the potential of GEN-1 to address advanced Stage III and IV ovarian cancer, a population clearly in need of effective therapies," said Dr. Khursheed Anwer, Ph.D., MBA, Celsion's chief scientific officer. "We anticipate completion of enrollment in the fourth patient cohort in the coming weeks, and will continue to assess a potential accelerated clinical development path for GEN-1. In parallel, we are currently evaluating translational data from the study, which we expect to report before the end of the fourth quarter."
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Source: press release, 11/10/16. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=998784

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Celsion Announces Positive Data from the OVATION Study - An Immunotherapy Study of Newly Diagnosed Ovarian Cancer Patients
Second Cohort of Stage III and IV Patients Continues to Show Clinically Meaningful Responses in the Evaluation of GEN-1, A Novel IL-12 DNA-based Immunotherapy, in Combination with the Standard of Care
LAWRENCEVILLE, N.J., July 25, 2016 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN) today announced data from the second cohort of patients in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company's DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. In the first six patients dosed, GEN-1 plus standard chemotherapy produced impressive results, with no dose limiting toxicities and highly promising efficacy signals in this difficult to treat cancer.

"The totality of study data available to date suggests that GEN-1 holds great potential to serve as an effective, safe IL-12 immunotherapy in ovarian cancer," said Dr. Premal Thaker, Associate Professor in Gynecologic Oncology, Washington University School of Medicine and OVATION Study Investigator. "Notably, we have seen dramatic decreases of 95% or greater in CA-125 protein levels, which serve as a key indicator of the presence of ovarian cancer cells, as well as impressive pathological response data, which is associated with prolonged survival. We look forward to the completion of this study, and to learning more about how GEN-1 performs in this patient population."

The OVATION Study is designed to enroll three to six patients per dose cohort, and will continue into 2016 at higher doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. The first two cohorts each enrolled three patients. Enrollment in the third cohort is ongoing, and Celsion expects to complete the OVATION Study this year. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin® and Doxil®.

OVATION Study - Results to Date

Of the first six patients dosed, one patient demonstrated a complete response (CR), two patients demonstrated partial response (PR) and three patients demonstrated stable disease (SD), as measured by RECIST criteria.

Five patients had successful resections of their tumors, with two patients having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed and three patients with a R1 resection, indicating microscopic residual tumor. One patient in the second cohort is currently ineligible for debulking surgery due to a medical complication unrelated to the study or the study drug.

Of the five surgically treated and evaluable patients, one patient demonstrated a pathological complete response (pCR), two patients (40%) demonstrated a micro pathological response (microPR), and two patients (40%) demonstrated a macroPR. These data compare favorably to historical data, which indicate that pCRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection. pCRs have been associated with a median overall survival of 72 months, which is more than three years longer than those who do not experience a pCR. In addition, microPRs are seen in approximately 30% of patients, and are associated with a median overall survival of 38 months¹.
"GEN-1 continues to demonstrate impressive activity in patients with advanced Stage III and IV ovarian cancer, a population clearly in need of effective therapies," said Nicholas Borys, M.D., Celsion's chief medical officer. "We anticipate completion of enrollment in the third patient cohort in the coming weeks, and will continue to assess a potential accelerated clinical development path for GEN-1. In parallel, we are currently evaluating translational data from the study, which we expect to report before the end of the third quarter."
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Source: press release, 7/25/16. http://investor.celsion.com/releaseDetail.cfm?ReleaseID=980891

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