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Celsion Corporation Enrolls First Patient in the OVATION Study

On September 30, 2015 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, reported 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 (Press release, Celsion, SEP 30, 2015, View Source [SID:1234507612]).

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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."

About GEN-1 Immunotherapy

GEN-1, designed using the TheraPlas platform technology, 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. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer and in combination with PEGylated doxorubicin in patients with platinum resistant ovarian cancer. GEN-1 has also demonstrated preclinical activity in glioblastoma multiforme (brain cancer) and the Company plans to initiate a Phase I study in this indication.

Nine FierceBiotech’s 2015 Fierce 15 Awards to Oncology Companies

On September 30, 2015 Fierce Biotech disclosed the 15 selected companies for the Fierce 15 Award. No less than nine of these have solid ties to drug development in oncology (Press release, Fierce Biotech, SEP 30, 2015, View Source [SID:1234507611]). In fact Fierce Biotech has by this choice of companies highlighted the importance of gene editing and cellular therapy in the field of immunotherapy for developing future cures in cancer.

List of Oncology Associated Companies Among this Year Recipients of the Fierce 15 Award:
Arvinas (USA)
Cell Medica (UK)
CRISPR Therapeutics (Switzerland)
Intellia Therapeutics (USA)
NGM Biopharmaceuticals (USA)
SQZ Biotech (USA)
Surface Oncology (USA)
Syros Pharmaceuticals (USA)
Unum Therapeutics (USA)

CARsgen Enters into Partnership Agreement with Shanghai Cancer Institute and to Develop Novel CAR-T Technology

On September 29, 2015 CARsgen Therapeutics, a private and venture backed company focused on the development of CAR-T-based autologous immunotherapy to treat solid tumors, reported a business and clinical update on its immunotherapy programs (Press release, Carsgen Therapeutics, SEP 29, 2015, View Source [SID:1234514784]).

New Partnership Agreements
In September 2015, CARsgen and Shanghai Cancer Institute entered into a five year research and development agreement for the advancement of CARsgen’s CAR-T cancer immunotherapeutics. The partners will work together to identify and develop novel CAR-T candidates as well as next-generation CAR-T technologies. Under terms of the agreement, CARsgen will own commercial rights of any intellectual assets generated from the collaboration. Financial terms of the agreement were not disclosed.

In May 2015, CARsgen entered an agreement with Shanghai Jiaotong University (affiliated with Renji Hospital) to conduct development of CARsgen’s glypican-3 (GPC3) CAR-T therapeutic designed to treat relapsed or refractory hepatocellular carcinoma, or advanced liver cancer, in addition to other CARsgen immunotherapeutics.

Progress in Immunotherapy Program for Advanced Liver Cancer
In March 2015, CARsgen and Renji Hospital initiated a Phase 1 clinical study to evaluate the safety and early-stage efficacy of CARsgen’s GPC3 chimeric antigen receptor T-cell (CAR-T) therapy. To date, six patients with relapsed and/or refractory hepatocellular carcinoma (HCC) have been enrolled and treated with escalating doses of GPC3-CAR-T infusions (up to ~1.1×109 cells). Two of the six patients (33%) demonstrated more than a 90 percent decline in levels of alpha-fetoprotein (AFP), a liver biomarker indicating the activity of liver cancer. Glypican 3 (GPC3) is expressed in a variety of tumors, with a high frequency in HCC. In in vivo and in vitro preclinical studies, GPC3-CAR-T effectively killed GPC3 positive HCC cells.

GPC3-CAR-T was safe and well tolerated in all six patients treated to date, with no serious adverse events observed. The most frequent treatment-related adverse events were moderate temperature elevations, which CARsgen believes resulted from the expected cytokine storm. GPC3-CAR-T cells persisted in the peripheral blood circulation throughout the treatment period. Αlpha-fetoprotein (AFP), a surrogate HCC biomarker for liver, was found having 90% decline in two patients. In one of these patients, just two months following treatment, AFP levels were determined to be in the normal range.

Dr. Zonghai Li, president & CEO of CARsgen, commented, "The preliminary clinical data accumulated from the first six patients is very encouraging. It helps us to identify additional parameters including on-target off-tumor toxicity, effective dose regime, and pre-infusion operations. We plan to continue our clinical test and to enroll up to 20 patients in the ongoing Phase 1 study, in support of our commitment to bring effective treatments to HCC patients through our unique and proprietary immunotherapy."
Future Development Programs

In addition to its GPC3-CAR-T program, CARsgen has a broad range of CAR-T candidates for lung, brain and stomach cancers. CARsgen and RenJi Hospital began enrolling up to 10 patients in a Phase 1 clinical study of an anti-EGFR CAR-T therapy designed to treat glioblastoma multiforme (GBM or brain cancer).

About GPC3-CAR/CSG-GPC3
GPC3-CAR/CSG-GPC3 T cell therapy is the world’s first CAR-T solution indicated for late-stage HCC. CARsgen is enrolling patients in a Phase 1 clinical study in China, with results expected in [Mid-2016]. For more information or to find a study site, please visit www.clinicaltrials.gov, identifier NCT02331693.

Clovis Oncology Announces U.S. and E.U. Regulatory Milestones for Rociletinib in the Treatment of Advanced EGFR-Mutant T790M+ Non-Small Cell Lung Cancer

On September 29, 2015 Clovis Oncology, Inc. (NASDAQ: CLVS) reported two major regulatory milestones for rociletinib, its investigational therapy for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation (Press release, Clovis Oncology, SEP 29, 2015, View Source;p=RssLanding&cat=news&id=2091515 [SID:1234507613]). The U.S. Food and Drug Administration (FDA) has accepted Clovis’s New Drug Application (NDA) for rociletinib and has granted it priority review status with a Prescription Drug User Fee Act (PDUFA) action date of March 30, 2016.

Additionally, the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for rociletinib. Europe’s Committee for Medicinal Products for Human Use (CHMP) granted Clovis an accelerated assessment for the drug, which reduces the time limit for CHMP to reach an opinion from 210 days to 150 days. Accelerated assessment is granted in recognition of the likelihood that a therapeutic will be of major public health interest in the EU, given the importance of therapeutic innovation in a patient population that exhibits a high unmet need.

Rociletinib is the company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. Rociletinib was given Breakthrough Therapy designation by the FDA in May 2014.

Eagle Pharmaceuticals Receives New Patent for Bendamustine Rapid Infusion Product

On September 29, 2015 Eagle Pharmaceuticals, Inc. (NASDAQ:EGRX) ("Eagle") reported that the United States Patent and Trademark Office (USPTO) has granted U.S. Patent No. 9,144,568, which pertains to the use of the bendamustine hydrochloride (HCl) formulation administered in a 50mL bag within ten minutes (the "rapid infusion" product) (Press release, Eagle Pharmaceuticals, SEP 29, 2015, View Source [SID:1234507608]). The patent issued today expires on March 15, 2033. This new patent, along with three previously issued Patents (Nos. 8,609,707, 9,000,021, and 9,034,908), further expands and protects Eagle’s bendamustine HCI intellectual property estate.

"Today’s patent issuance further strengthens our intellectual property for the bendamustine rapid infusion product, for which a New Drug Application (NDA) is currently under review by the U.S. Food and Drug Administration (FDA)," said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals. "We believe that approval of and subsequent launch by Teva of this important product, along with royalty payments earned on sales and the potential for additional milestone payments, will expedite Eagle’s ability to deliver long term, sustainable growth."

The Prescription Drug User Fee Act (PDUFA) goal date for a decision on the NDA by the FDA is December 2015. The NDA requests FDA approval of the rapid infusion bendamustine HCl product for the treatment of patients with chronic lymphocytic leukemia (CLL) and patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. The NDA for Eagle’s rapid infusion bendamustine product is supported by data from a clinical trial completed in November 2014, which demonstrated that the rapid infusion bendamustine HCl product can be administered in ten minutes in a low- volume, 50 mL admixture.

The rapid infusion product candidate has received Orphan Drug Designations for both CLL and indolent B-cell NHL, and therefore may be eligible for seven years of exclusivity upon approval.

In February 2015, Eagle and Teva Pharmaceutical Industries Ltd. entered into an exclusive license agreement for the rapid infusion bendamustine product. Teva will be responsible for all U.S. commercial activities for the product including promotion and distribution. Eagle has responsibility for obtaining all regulatory approvals, conducting post-approval clinical studies, if required, and initially supplying drug product to Teva.