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ZIOPHARM Announces Data Highlighting Ad-RTS-hIL-12 Activity in Glioma at SNO

On November 19, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported that the Company is presenting initial results from an ongoing Phase 1 dose-escalation study of Ad-RTS-hIL-12 + orally administered veledimex in recurrent or progressive glioblastoma or grade III malignant glioma (Press release, Ziopharm, NOV 19, 2015, View Source [SID:1234508288]). The presentation, titled "Intratumoral Regulated Expression of IL-12 as a Gene Therapy Approach to Treatment of Glioma," will be delivered at 5:15 pm CT, Saturday, November 21, 2015 at the 20th Annual Society for Neuro-Oncology (SNO) Annual Scientific Meeting in San Antonio, Texas. Ad-RTS-hIL-12 + the oral activator veledimex is a novel viral gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T-cell immune response.

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"Immunotherapy is an attractive approach for the treatment of glioma, an aggressive cancer with few treatment options," said Nino Chiocca, MD, PhD, Harvey W. Cushing Professor of Neurosurgery, Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute, Chairman, Neurosurgery, Brigham And Women’s Hospital and Co-Director, Institute for the Neurosciences, Brigham And Women’s Hospital. "IL-12 is among the most potent anti-cancer immune cytokines, yet carries equally significant potential for immune-mediated toxicities. The ability to turn IL-12 expression on and off using an orally activated gene switch, particularly in the brain’s immune privileged environment, is a tremendous advancement in the potential of this therapeutic approach. We look forward to enrolling additional patients and follow up from this study to evaluate Ad-RTS-IL-12’s potential in this challenging, rapidly advancing and lethal disease."

The ongoing multi-center Phase 1 trial of Ad-RTS-hIL-12 + veledimex examines a gene therapy strategy for recurrent high grade gliomas, with the goal of generating a localized anti-tumor immune response. The primary objective of the study is to determine the safety and tolerability of a single intra-tumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 + veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response. The study is expected to enroll up to 72 subjects.

Preclinically, the effects of Ad-RTS-mIL-12 + veledimex were studied in orthotopic glioma animal models, demonstrating veledimex crossed the blood-brain-barrier. In a standard orthotopic glioma mouse model that evaluated dexamethasone, bevacizumab, temozolamide and a PD-1 inhibitor, Ad-RTS-mIL-12 + veledimex demonstrated a dramatic dose-related increase in survival, without significant adverse events, that was superior to all other treatments.

In the current, on-going Phase 1 study, five patients are available for initial assessment, two with recurrent grade III malignant glioma and three with grade IV. Results show IL-12 was detectable in peripheral blood along with downstream IFNg, indicating that veledimex crossed the blood brain barrier activating IL-12 expression from intra-tumorally administered Ad-RTS-hIL-12. Ad-RTS-hIL-12 + veledimex was well tolerated with minimal neurologic toxicity. The most common adverse events were headache, fever, hyponatremia and nausea/vomiting. Related serious adverse events were aseptic meningitis, neutropenia, thrombocytopenia, leukopenia, with all toxicity to date consistent with the "on-target" effects of immunotherapy.

"Observing that veledimex can cross the blood brain barrier and that IL-12 expression can be regulated in the brain, demonstrates a clear translation of results from the laboratory to the clinic," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "We look forward to follow-up of the current recipients and to further enrollment in this multi-center gene therapy study."

DelMar Pharmaceuticals to Present at the 8th Annual LD Micro Main Event on December 2, 2015

On November 19, 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 at the 8th Annual LD Micro Main Event on Wednesday, December 2, 2015, at 3:30 p.m. Pacific Time at the Luxe Sunset Hotel in Los Angeles, California (Press release, DelMar Pharmaceuticals, NOV 19, 2015, View Source [SID:1234508286])O.

Jeffrey Bacha, DelMar’s president and CEO, will provide an update on the Company’s ongoing clinical trial of VAL-083 (dianhydrogalactitol) in patients with recurrent glioblastoma multiforme (GBM) and DelMar management will be available to meet with investors during the conference.

DelMar will be presenting updated safety and efficacy data from the Phase II study in GBM at the Society for Neuro-Oncology Annual Meeting being held November 19-22, 2015. Mr. Bacha will include a review of this new data in his presentation.

The Company recently completed enrollment in the Phase II expansion cohort of the study and confirmed 40mg/m2 as the maximum tolerated dose (MTD) for advancement into its planned registration-directed Phase II/III clinical trials in refractory GBM.

VAL-083 has promising potential to address the modern unmet medical needs in the treatment of a range of cancers, including non-small cell lung cancer (NSCLC), ovarian cancers, malignant pediatric brain tumors, and other solid tumor types, especially where other therapies have failed or are predicted to give sub-optimal outcomes.

A live audio webcast of the presentation will be available by accessing DelMar’s IR Calendar in the Investors section of the Company’s website (www.DelMarPharma.com). The webcast replay will be available approximately two hours after the presentation and will be accessible for one month.

About LD Micro

LD Micro is an investment newsletter firm that focuses on finding undervalued companies in the micro-cap space. Since 2002, the firm has published reports on select companies throughout the year. The annual Main Event micro-cap conference was designed to highlight and showcase the next generation of great companies to private and institutional investors, as well as to analysts, bloggers, and the media. The firm also hosts the LD Micro Invitational. LD Micro is a non-registered investment advisor.

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 clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. 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 malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar recently announced the completion of enrollment in a Phase II clinical trial of VAL-083 in refractory GBM. Patients have been enrolled 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).

In the Phase I dose-escalation portion of the study, VAL-083 was well tolerated at doses up to 40mg/m2 using a regimen of daily x 3 every 21 days. Adverse events were typically mild to moderate; no treatment-related serious adverse events reported at doses up to 40 mg/m2. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed in two of six (33%) of patients at 50 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment, although one patient who presented with hemorrhoids received a platelet transfusion as a precautionary measure.

Sub-group analysis of data from the Phase I dose-escalation portion of the study suggested a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083 in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

Moffitt Cancer Center and Ignyta, Inc. Enter into Cancer Research Collaboration for RXDX-106

On November 19, 2015 Moffitt Cancer Center and Ignyta, Inc. (NASDAQ: RXDX) reported that they have entered into a research collaboration relating to RXDX-106, Ignyta’s small molecule, pseudo-irreversible inhibitor of TYRO3, AXL, Mer (TAM) and cMET that is in late stage preclinical development (Press release, Ignyta, NOV 19, 2015, View Source [SID:1234508295]).\

The collaboration, which will be conducted in the labs of Eric B. Haura, M.D., director of the Lung Cancer Center of Excellence and leader of the Chemical Biology and Molecular Medicine Program at Moffitt, will explore and develop novel protein based diagnostic assays that can assess RXDX-106 signaling activity in relevant solid tumors and associated tumor microenvironments.

"This exciting collaborative partnership with Ignyta will lead to a better understanding of the potential mechanisms of action of RXDX-106 by employing our expertise in cancer proteomic technology," said Haura.

"We continue to work diligently to progress RXDX-106 and the other product candidates we acquired from Teva earlier this year," said Robert Wild, Ph.D., Ignyta’s Chief Scientific Officer and Senior Vice President, Research. "Ignyta’s vision is to be a guiding biotechnology company in precision medicine. We are pleased to be able to collaborate with a world class investigator such as Dr. Haura and his team on the exciting biology relating to RXDX-106."

Genmab Achieves USD 45 Million Milestone in DARZALEX™ (daratumumab) Collaboration with Janssen

On November 19, 2015 Genmab A/S (OMX: GEN) reported it has achieved a USD 45 million milestone in its DARZALEX (daratumumab) collaboration with Janssen Biotech, Inc. (Janssen) (Press release, Genmab, NOV 19, 2015, View Source [SID:1234508294]). The milestone payment was triggered by the first commercial sale of DARZALEX in the United States.

"Today marks a significant moment in the history of Genmab — the day DARZALEX, our second approved antibody therapeutic, is commercially available. We are very pleased to have brought two differentiated antibody products to the market since our inception in 1999," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
This milestone was included in the updated financial guidance for 2015, which was published on November 16, 2015.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,1,2 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,1,2 antibody-dependent cellular phagocytosis3,4 and antibody-dependent cellular cytotoxicity.1,2

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma.

Anti-Cancer Agent “Xeloda®,” Obtained Approval for Additional Indication of “Postoperative Adjuvant Chemotherapy for Gastric Cancer”

On November 20, 2015 Chugai Pharmaceutical Co., Ltd. (Chugai) (TOKYO: 4519) reported that it obtained a supplemental approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) on November 20, 2015, for the anti-cancer agent, capecitabine (brand name: Xeloda Tablets 300) (Xeloda) for the indication of "postoperative adjuvant chemotherapy for gastric cancer" (Press release, Chugai, NOV 19, 2015, View Source [SID:1234508292]).

With this approval, the indication of Xeloda has been changed into "gastric cancer," covering the current indication of "advanced or recurrent gastric cancer, which is not amenable to curative resection."

"With the approval of the combination therapy of Xeloda and oxaliplatin showing preventive efficacy for postoperative recurrence, we hope the patients will receive the anti-cancer treatment in a positive frame of mind." said Chugai’s Director and Executive Vice President, Dr. Yutaka Tanaka. "We are extremely pleased that Xeloda can contribute to the treatment of patients."

In December 2014, Chugai and Yakult Honsha Co., Ltd. filed an application for approval with the MHLW based on the results of overseas Phase III study (The CLASSIC study) and a Japanese Phase II study.

In The CLASSIC study which was conducted in 1,035 patients with Stage II/III gastric cancer who had received surgical resection, patients were randomized to receive either combination therapy of Xeloda and oxaliplatin (combination group) or surgery alone with follow-up (follow-up group). Disease-free survival (DFS) was evaluated as the primary endpoint. As a result, the three-year DFS rate was 74% in the combination group and 59% in the follow-up group, demonstrating statistically significant prolongation of DFS in the combination group (hazard ratio: 0.56, 95% confidence interval: 0.44 to 0.72, Wald test, p<0.0001). Moreover, for overall survival, a secondary endpoint, five-year survival rate was 78% in the combination group and 69% in the follow-up group, showing significant prolongation in the combination group (hazard ratio: 0.66, 95% confidence interval: 0.51 to 0.85, Wald test, p=0.0015). The safety profile shown in the combination group was comparable to those which have been reported for the two drugs.

The Japanese Phase II study investigated the combination therapy of Xeloda and oxaliplatin, setting Dose Intensity (cumulative dose of each drug actually administered / cumulative planned dose when eight courses of treatment were completed without treatment interruption or dose reduction) as the primary endpoint. The results showed the average of Dose Intensity is 67.2% in the Xeloda and 73.4% in the oxaliplatin respectively, and the tolerability in the Japanese patients was confirmed as both drugs also exceeded threshold which was defined by the study protocol.

Gastric cancer is prevalent in Asian countries including Japan, South Korea and China as well as in South America. In Japan, the number of patients newly diagnosed with gastric cancer continues to rise each year and is estimated to become, on annual average, approximately 142,900 during 2015-2019*.

Chugai strongly believes that Xeloda will make a contribution to patients as a treatment option for "postoperative adjuvant chemotherapy for gastric cancer." Chugai will continue the efforts to contribute to cancer treatment.

* Tomotaka Sobue, et al. "Cancer White Paper 2012 – For data-based cancer control" (Shinoharashinsha Inc.)

About Xeloda
Xeloda was developed by Nippon Roche K.K. (currently Chugai) and approved in 1998 for the first time in the US, Switzerland and Canada, in 2001 in the EU and has been approved in more than 100 countries worldwide. In Japan, Xeloda is marketed by Chugai and it received approval for "inoperable or recurrent breast cancer" in June 2003, "the overseas dosage and administration" and "postoperative adjuvant chemotherapy for colon cancer" in December 2007, "advanced or refractory colorectal cancer, which is not amenable to curative resection" in September 2009 and "advanced or recurrent gastric cancer, which is not amenable to curative resection" in February 2011. It has been authorized for the indication of "gastric cancer" in more than 90 countries.

About oxaliplatin
Oxaliplatin is a platinum complex, anti-cancer agent of which the development and distribution rights in Japan were obtained by Yakult Honsha Co., Ltd. in 1997 from Debiopharm International SA (Switzerland). Oxaliplatin is marketed by Yakult Honsha Co., Ltd. under the brand name of "Elplat I.V. Infusion Solution 50mg" (Elplat). Elplat was approved in March 2005 for an indication of "advanced or recurrent colorectal cancer, which is not amenable to curative resection" and started to be marketed in April 2005. It was approved for additional indications of "postoperative adjuvant chemotherapy for colon cancer" in 2009, "pancreatic cancer, which is not amenable to curative resection" in 2013 and "advanced or recurrent gastric cancer, which is not amenable to curative resection" in 2015.