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.

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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.

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]).

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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.

On September 29, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has received additional approval for the vascular embolization device DC Bead (specially controlled medical device, "DC Bead") to be used for the treatment of hypervascular tumors and arteriovenous malformations (AVM) in Japan (Press release, Eisai, SEP 29, 2015, View Source [SID:1234507598]). The product will be able to be reimbursed for this newly approved purpose once procedures are completed for insurance reimbursement listing as a specially controlled medical device (the original purpose for treatment of hepatocellular carcinoma is already eligible for reimbursement).

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DC Bead contains hydrophilic microspheres made from cross-linked polyvinyl alcohol polymer. Developed by Biocompatibles UK Limited (Biocompatibles), a BTG International group company, as an intravascular embolization device, it is injected via catheter into targeted blood vessels to achieve selective embolization. Eisai acquired the exclusive rights to develop and market DC Bead in Japan from Biocompatibles in July 2009 and received manufacturing and marketing approval for the device from Japan’s Ministry of Health, Labour and Welfare (MHLW) in April 2013 for use in transcatheter arterial embolization in hepatocellular carcinomas. Eisai subsequently launched DC Bead in Japan in February 2014.

A hypervascular tumor most commonly refers to hepatocellular carcinoma, certain metastatic liver cancers, renal cell carcinoma, soft tissue sarcoma, uterine fibroids and other tumors that are nourished via a sophisticated vascular network developed in tumor tissue. An AVM is a congenital vascular malformation that leads to various functional, organic and developmental disorders that are caused by an abnormal connection between the arteries and veins disrupting the normal circulation of blood. By selectively embolizing the sections of blood vessels that are supplying nutrients to tumor tissue and malformations, it is possible to necrose or reduce tumors, and improve associated symptoms.

It was recommended at the MHLW’s Study Council for the Early Introduction of Highly Needed Medical Devices that DC Bead be made available as soon as possible as a device indicated for the treatment of hypervascular tumors as well as AVM. Upon receiving this recommendation, Eisai conducted clinical studies aiming to confirm safety and efficacy of using DC Bead as an embolization material on hypervascular tumors and AVM (excluding central nervous system, heart and lung AVM) in Japan in order to secure an indication expansion. Results of these studies suggested safety and efficacy for DC Bead as replenishment material to promote embolization within the arteries of the central circulatory system, which led Eisai to submit an application for an additional purpose in September 2014.

Through the approval of this indication expansion for DC Bead, Eisai seeks to further contribute to addressing the diverse needs of, and increasing the benefits provided to, patients and their families as well as healthcare providers.

On September 29, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, http://www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or the "Company"), reported that the Journal of Clinical and Cellular Immunology has published a paper titled, "The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses (Filing, 8-K, Provectus Pharmaceuticals, SEP 29, 2015, View Source [SID:1234507601])." The paper can be found online at View Source

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Authors Ajay V Maker, Bellur Prabhakar, and Krunal Pardiwala state that their "article serves to evaluate the potential of intralesional rose bengal [RB] to stimulate T-cell mediated anti-tumor responses in in-vitro, pre-clinical, and clinical studies." The review covers findings in both animal models and human clinical trials covering the use of intralesional RB in the treatment of: melanoma, breast cancer, ovarian cancer, gastric cancer and sarcoma.

They conclude, "Our current research is establishing the role of RB in generating anti-tumor immune responses in gastrointestinal cancer and liver metastases. Decrease in tumor burden and stimulation of an immune response with PV-10 has been demonstrated in animal models of metastasis, and correlations of these responses in clinical studies is consistent with such results. That PV-10 treatment can potentially increase circulating cytotoxic T-cells, even in patients who were previously treated with immune-activating checkpoint blockade, supports the possibility that RB induced cytotoxicity may activate T-cells that are responsible for the bystander effect on untreated lesions. As such, intralesional therapy with RB may be a promising new mode of therapy to stimulate T-cell mediated anti-tumor immune responses."

On September 29, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it will present an abstract entitled, "Dianhydrogalactitol (VAL-083) Offers Potential Therapeutic Alternatives in the Treatment of Pediatric Brain Tumors," at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Advances in Pediatric Research: From Mechanisms and Models to Treatment and Survivorship conference being held November 9–12, 2015 in Fort Lauderdale, FL (Press release, DelMar Pharmaceuticals, SEP 29, 2015, View Source [SID:1234507607]).

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The Company will present on Tuesday, November 10th during Poster Session A scheduled to begin at 4:30 p.m. The poster presentation will summarize the potential of VAL-083 as a new treatment for malignant pediatric brain tumors in the context of historical clinical trials sponsored by the U.S. National Cancer Institute and DelMar’s recent research.

The Company recently presented an update from its ongoing multicenter Phase I/II clinical study for the treatment of adult refractory glioblastoma multiforme (GBM) at the GBM2015 Conference. VAL-083 demonstrated a favorable safety-profile and doses up to 40mg/m2 were well tolerated by patients receiving three daily doses in a 21 day cycle. A sub-group analysis of patients receiving up to 5 mg/m2 daily x 3 every 21 days (low dose) versus those patients receiving 30mg/m2 or 40mg/m2 (high dose) of VAL-083 demonstrated a dose-related survival benefit in adult GBM patients failing standard front-line therapy and bevacizumab.

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory GBM in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA) at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes following front-line treatment with Temodar (temozolomide).