On June 28, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported recent advancements in electroporation (gene electro-transfer) for immunotherapy in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Engineering and Physical Sciences in Oncology in Boston (Press release, OncoSec Medical, JUN 28, 2016, View Source [SID:1234513598])1. New data related to OncoSec’s Tissue-based Real-time Adaptive Controlled Electroporation (TRACE) technology and helical integrated applicator (Helix) showed that these technologies have the potential to reduce procedural frequency as well as enhance usability by physicians. Together, these novel technologies may improve a patient’s experience to gene electro-transfer and improve therapeutic outcomes, which will help broaden the adoption of gene-electro transfer technologies in immunotherapy.

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The TRACE and Helix technologies are central to OncoSec’s next-generation device development and represent a significant advancement in electroporation technology. Existing electroporation systems apply fixed pulses, independent of tissue conditions, that are typically optimized by heuristics. The new TRACE technology brings together OncoSec’s research and engineering efforts to adapt the pulses to tissue conditions in real time and detect when optimal conditions have been achieved to complete electroporation treatment. The new Helix applicator integrates engineering advancements to function synergistically with the TRACE technology. The TRACE and Helix technologies have the potential to improve delivery of new therapeutic agents and access a variety of new tumor types and locations.

"The new TRACE and Helix technologies are a testament to the expertise of OncoSec’s engineering and research teams," said Punit Dhillon, President and CEO. "Electroporation is a powerful gene delivery tool, and we believe that these novel technologies are a breakthrough in the field of electroporation therapy. As we look beyond the proof-of-concept stage for our intratumoral immunotherapy programs, these advancements are a major step forward in being able to consistently deliver more advanced therapeutic agents with the potential to target multiple facets of tumor immune subversion."

TRACE Technology
The poster presentation entitled "Feedback Optimized Gene Electro-Transfer for Immunotherapy" highlights the efficacy of modulating pulse durations in real-time for the intratumoral delivery of plasmid DNA in mouse tumor models. OncoSec’s generator incorporating TRACE technology was used to perform electroporation with electrochemical impedance spectroscopy feedback operating in a closed-loop configuration to optimize each pulse duration in real-time.

Preclinical studies demonstrated electroporation integrating TRACE technology is capable of achieving maximum expression of reporter genes with minimal energy delivered. Based on these findings, it is hypothesized that this technology will minimize collateral cell death and reduce treatment variability observed in patients. These findings represent a significant advancement in gene electro-transfer, because retaining the viability of transfected cells is critical for treatment success.

Helix Technology
The poster presentation entitled "A Novel Applicator for Endoscopic Gene Electro-Transfer" discusses the role of DNA dispersion during intratumoral gene delivery and its impact on gene electro-transfer efficiency. OncoSec researchers developed a single-helical injection needle that anchors the target tissue and delivers plasmid DNA. This achieves delivery of the plasmid to an area three times larger than that of a standard injection needle. Helix combines the helical needle with electroporation electrodes on a single applicator, which may enhance gene delivery by increasing surface area for tissue-DNA-electroporation interaction.

The Helix technology showed enhanced efficacy of IL-12 plasmid electroporation in an aggressive B16.F10 mouse melanoma model, significantly reducing tumor growth rate and increasing survival after a single treatment. The anchoring associated with the helical needle and the close proximity of the electrodes ensures co-localization of the electric field with the injected plasmid DNA as well as repeatable treatment of malleable tumors. In addition, the compact design of the electrodes and helical needle could make the applicator compatible with standard medical devices, including trocars, endoscopes, and other catheter based devices, thus enabling the application of intratumoral gene immunotherapy to a broad range of deep tissue cancers.

The poster presentations are available in the Publications section of OncoSec’s website.

On June 28, 2016 FUJIFILM Corporation (President: Kenji Sukeno) reported the progress in a Phase I clinical trial of radioimmunotherapeutic anti-cancer agent FF-21101 in the United States in patients with advanced solid cancers (Press release, Fujifilm, JUN 28, 2016, View Source [SID:1234513609]). In imaging, tumor uptake of antibody FF-21101 was demonstrated in administered patients. Taking these results, it is expected to treat diseases with emission from the radiolabeled antibody. Fujifilm will proceed with the clinical trial and evaluate FF-21101 as an anti-cancer agent.

FF-21101 is an anti-cancer agent consisting of a radioisotope labeled antibody (armed antibody*1), and uses radiation emitted by the radioisotope to directly attack cancer cells. This is why it is expected to have a higher level of efficacy, regardless of the state of patient’s immune system. In addition, its accumulation in cancer tissue can be confirmed by imaging with an administration of antibodies labeled with a radioisotope. To date, tumor uptake of antibody was demonstrated in 3 of 4 patients who have undergone imaging with an administration of radiolabeled FF-21101.
These results were presented on June 27th at the World Innovative Networking in Personalized Cancer Medicine Symposium 2016 (Paris, France) by principal investigator, Vivek Subbiah MD, of The University of Texas MD Anderson Cancer Center*2 (MD Anderson Cancer Center, hereafter), Houston, TX, USA.

Fujifilm has organized the technologies of its Group companies to develop FF-21101. The bio-venture, Perseus Proteomics, has contributed to antibody drug discovery, while the biopharmaceutical contract manufacturer, FUJIFILM Diosynth Biotechnologies, has taken charge of antibody production. The radiopharmaceutical company, FUJIFILM RI Pharma, utilized its technology for developing the diagnostic and therapeutic radiopharmaceuticals.

Fujifilm initiated the Phase I clinical trial of radiolabeled FF-21101 in patients with advanced solid cancers at MD Anderson Cancer Center in the United States, one of the world’s most distinguished facilities for cancer research and treatment, in January 2016. In this trial, FF-21101(111In), antibodies labeled with Indium-111*3, were administered prior to therapy and its biodistribution to normal and cancerous tissues were visualized and quantified by imaging procedures. In addition, for safety estimation in advance, radiation absorbed doses of Yttrium-90*4 in organs were calculated from these data, after which, patients were moved on to the therapeutic dosing of FF-21101(90Y), antibodies labeled with Yttrium-90.

Although the trial is still underway, preliminary observations include:
Imaging revealed tumor uptake in 3 of 4 patients administered FF-21101(111In).
FF-21101 was well tolerated in all patients who went on to receive the therapeutic dose of FF-21101(90Y).

Fujifilm will continue the study to further evaluate tolerability and efficacy in multiple advanced solid tumors at MD Anderson Cancer Center, and will move on to the phase IIa study.

Fujifilm is working on the R&D of innovative pharmaceutical products and creation of their production processes by combining the technologies and know-how accumulated in the photographic film business including analysis technology, nanotechnology, and production technology, with the technological expertise of its core pharmaceutical affiliates such as Toyama Chemical. Defining "oncology", a field with numerous unmet medical needs as its focal area, the company will actively promote R&D to expand business deployment and supply innovative pharmaceutical products so as to contribute to resolving challenges social issues.

*1： Armed antibody: Antibody conjugated with toxin or radioisotope via a chemical linker. It is expected to have a potent anti-tumor effect.
*2：One of the world’s largest cancer centers based in Houston. Texas (USA), specializing in cancer treatment, research, education and prevention. It was established in 1941 with a mission to eliminate cancer. Under the core values of "Caring", "Integrity" and "Discovery", the Center has developed numerous new cancer treatments and is as an international leader in oncology.
*3：A radioisotope which emits gamma rays appropriate for imaging. Its physical half-life is, approximately 67 hours.
*4：A radioisotope which emits beta particle radiation with a range of 5 mm in human body, appropriate for treatment. Its physical half-life is, approximately 64 hours.
　　
About anti-cancer agent FF-21101:
FF-21101 uses antibodies that target P-cadherin*5, which is overexpressed on the surface of solid cancer cells, including lung, pancreatic and colon cancers, and is implicated in tumor growth and cancer metastasis. For the clinical application of FF-21101, tumor uptake will be confirmed in patients administered antibodies radiolabeled with emitter, such as Indium-111 or other radioisotopes. Antibodies labeled with Yttrium-90 namely FF-21101(90Y), will be subsequently administered and directly attacks cancer cells by radiation emitted from the 90Y radioisotope. FF-21101 is expected to be more effective than therapy using the P-cadherin targeted antibody without the 90Y. In animal testing, it has already demonstrated a high efficacy in shrinking human tumors implanted in mice.

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On June 27, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported the successful completion of enrollment in the first and second dosing cohorts as well as the initiation of enrollment in a third cohort in the Company’s ongoing multi-center Phase 1 study of Ad-RTS-hIL-12 + orally administered veledimex to treat recurrent or progressive glioblastoma (GBM) or grade III malignant glioma (Press release, Ziopharm, JUN 27, 2016, View Source [SID:1234513578]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer immune response.

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The primary objective of the study is to determine the safety and tolerability of a single intratumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the maximum tolerated dose, the immune responses elicited, and assessment of biologic response. The first cohort of seven patients received 20 mg doses of veledimex, the second cohort of six patients received 40 mg doses of veledimex, and the third cohort will receive 30 mg doses of veledimex to refine the effect of activating the immune response within the tumor. The resultant immunologic activity that follows IL-12 expression in the brain suggests that no further dose escalation will be necessary and the optimal dosing may be reached sooner than initially anticipated.

Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM, commented: "With the RheoSwitch (RTS) technology, the only switch currently in the clinic that operates on gene transcription, we have demonstrated the ability for veledimex to cross the human blood brain barrier and activate production of IL-12 in GBM tumors in a dose-dependent manner, giving us the potential to precisely tune the balance between activity and tolerability."

Data from 11 patients with recurrent high-grade gliomas were recently presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. All of these patients failed at least two prior lines of therapy and underwent partial resection leaving residual tumors, in certain cases with significant tumor burden. Ad-RTS-hIL-12 was administered through direct injection into the brain tumor and veledimex was taken orally to activate the production of IL-12 from the tumor site and stimulate an immune response.

As of May 18th, the date of data collection for the ASCO (Free ASCO Whitepaper) presentation, overall median follow up was 6.2 months, with 10 of 11 recipients alive. IL-12 in the bloodstream was measured and was found to be proportional to the amount of veledimex administered, demonstrating that this orally-delivered activator crossed the blood brain barrier to turn on the RheoSwitch technology in a dose-dependent manner.

To date, toxicities in both dose cohorts were consistent with those previously reported, with a higher incidence of grade 3 or greater adverse events in the 40 mg dose group. All related side effects were reversed upon cessation of veledimex. No subsequent deaths have been reported.

The Company expects to present updated results from the study at a scientific meeting later in the year.

"Overall survival remains the gold standard of therapeutic success in glioblastoma, particularly in high-grade, recurrent disease, where survival is too often measured by just a few months," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "We remain encouraged by the outcomes of Ad-RTS-hIL-12 as a single agent tuning the immune system in this GBM study. We believe that these early results also have positive implications for our combination approach utilizing this novel gene therapy with immune check point inhibitors. We look forward to additional follow up as we work to fine-tune dosing levels using the RheoSwitch technology."

Ad-RTS-hIL-12 + veledimex has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with malignant glioma.

About Glioblastoma

Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v

On June 27, 2016 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ("HSR"), with respect to its proposed acquisition of Celator Pharmaceuticals, Inc. ("Celator"; Nasdaq: CPXX) expired effective June 24, 2016, at 11:59 p.m. (Eastern Daylight Time) (Press release, Jazz Pharmaceuticals, JUN 27, 2016, View Source;p=RssLanding&cat=news&id=2180005 [SID:1234513579]).

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As previously announced on May 31, 2016, Jazz Pharmaceuticals and Celator entered into a definitive merger agreement under which Jazz Pharmaceuticals has commenced a tender offer for all of the outstanding shares of Celator at $30.25 per share in cash, representing total consideration of approximately $1.5 billion. The expiration of the HSR waiting period satisfies one of the conditions required to consummate the tender offer. The closing of the tender offer remains subject to other customary conditions, including the tender of a majority of the outstanding shares of Celator common stock.

The tender offer and withdrawal rights will expire at one minute following 11:59 p.m., New York City Time, on July 11, 2016, unless the tender offer is extended or terminated earlier in accordance with the terms of the definitive merger agreement. The Offer to Purchase dated June 10, 2016, relating to the tender offer has been filed with the United States Securities and Exchange Commission ("SEC") and can be viewed online, along with any amendments thereto, at www.sec.gov.

On June 27, 2016 Advanced Accelerator Applications S.A. (NASDAQ:AAAP) ("AAA" or "the Company"), an international specialist in Molecular Nuclear Medicine (MNM), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) and granted Priority Review for Lutathera, a Lu-177-labeled somatostatin analogue peptide currently under development for the treatment of gastro entero pancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults (Press release, Advanced Accelerator Applications, JUN 27, 2016, View Source [SID:1234513596]). The Prescription Drug User Fee Act (PDUFA) target action date is December 28, 2016.

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Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions.

The Lutathera NDA is based on the results of a randomized pivotal Phase 3 study, NETTER-1 that compared treatment using Lutathera with a double dose of Octreotide LAR in patients with inoperable midgut NETs progressive under Octreotide LAR treatment and overexpressing somatostatin receptors. The NETTER-1 study met its primary endpoint by demonstrating that treatment with Lutathera was associated with a statistically significant and clinically meaningful risk reduction of 79% in disease progression or death versus a treatment with a double dose of Octreotide LAR. Efficacy and safety data from a large Phase I-II trial conducted in more than 1,200 patients in NET indications is also part of the NDA.

"We are encouraged that the FDA has granted Priority Review for Lutathera as a potential treatment for GEP-NETs," said Stefano Buono, Chief Executive Officer of AAA. "We believe this action emphasizes the need to improve the lives of these patients."

About Neuro Endocrine Tumors (NETs)

Neuro Endocrine Tumors, also known as NETs, are a group of tumors originating in the neuroendocrine cells of many different organs. NETs can remain clinically silent for years delaying the diagnosis in a large number of patients. These cancers are rare but they are the second most common type of gastrointestinal malignancy and their incidence is increasing. The estimated incidence of NETs for the combined populations of the United States and the European Union is approximately 47,300.

NETs are classified as orphan diseases by U.S. and European regulatory authorities, meaning that they affect a relatively small population of individuals in the relevant jurisdiction. In the United States, orphan drugs are defined as drugs that treat diseases or conditions that affect 200,000 or fewer individuals in the country. In the European Union, orphan drugs are defined as drugs that treat diseases or conditions that affect fewer than five out of 10,000 individuals in the European Union.

About Lutathera

Lutathera (or lutetium Lu 177 dotatate) is a Lu-177-labeled somatostatin analogue peptide currently in development for the treatment of gastro entero pancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Lutathera belongs to an emerging form of treatments called Peptide Receptor Radionuclide Therapy ("PRRT"), which involves targeting carcinoid tumors with radiolabeled somatostatin analogue peptides. This novel compound has received orphan drug designation from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Lutathera was also granted fast-track designation by the FDA in April 2015 for the treatment of inoperable progressive midgut NETs. Lutathera is also currently administered on a compassionate use and named patient basis for the treatment of NETs and other tumors over-expressing somatostatin receptors in ten European countries and in the US under an Expanded Access Program (EAP) for midgut NETs. In an analysis of the Phase 3 trial’s primary endpoint of PFS assessment, completed by the Company in September 2015, the Lutathera arm of the trial demonstrated a significant improvement in PFS compared to the PFS for Octreotide LAR 60 mg arm, suggesting a significant therapeutic effect for patients with midgut NETs. NDA and MAA submissions to the FDA and EMA are currently under review.