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.

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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.

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."

On November 19, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that the dose escalation part of the ongoing Phase 1 trial of FPA144 has been completed and that dose expansion has begun at a selected dose in new cohorts of gastric cancer patients whose tumors overexpress FGFR2b (Press release, Five Prime Therapeutics, NOV 19, 2015, View Source [SID:1234508293]). FPA144 is an isoform-selective antibody in development as a targeted therapy for tumors that over-express FGFR2b, and has been engineered for enhanced ADCC, increasing direct tumor cell killing by recruiting natural killer (NK) cells. FGFR2 gene amplification is found in a number of tumors, including approximately 5% of gastric cancers, and is associated with poor prognosis.

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Part 1 of the Phase 1 study evaluated the safety and pharmacokinetics (PK) of escalating doses of FPA144 in 27 patients with solid tumors, including unselected gastric cancer patients. Data from Part 1 will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) 2016 Gastrointestinal Cancers Symposium in San Francisco. The poster entitled, "FPA144-001: A first in human study of FPA 144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody in patients with advanced solid tumors," is scheduled during the session entitled, "Cancers of the Esophagus and Stomach," on Thursday, January 21, 2016 from 12:30-2:00 and 5:30-7:00 Pacific Time. Abstracts are expected to be posted on the meeting website on Tuesday, January 19, 2016.

Enrollment has begun in Part 2 of the trial, evaluating the efficacy of biweekly infusions of FPA144 in approximately 70 metastatic gastric cancer patients, with the aim of exploring the correlation between efficacy and FGFR2b overexpression. Tumor testing for FGFR2b overexpression is being conducted centrally, using a proprietary immunohistochemistry assay. Tumors are also being assessed for FGFR2 gene amplification by FISH analysis. Trial endpoints include safety, pharmacokinetics, response rate and duration of response.

"We are really pleased with the progress we are making in this study and to now be moving into our target population of gastric cancer patients," said Julie Hambleton, M.D., Executive Vice President and Chief Medical Officer of Five Prime. "This is an orphan indication in the U.S. and given the unmet need in this disease and the potential for patients to benefit greatly from new treatment options, we aspire to develop the program expeditiously. In the Phase 1 study, we are already enrolling at global sites, including in Asia where gastric cancer is most prevalent. We are also running preclinical studies to evaluate therapeutic combinations with FPA144 for future testing in gastric cancer patients and to identify other indications that may be suitable for FPA144 therapy."

About FPA144

FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Additionally, FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), increasing direct tumor cell killing by recruiting natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

On November 18, 2015 Cancer Research Technology (CRT) is pleased to reported that a major drug discovery feasibility study with Merck Serono, the biopharmaceutical business of Merck, focused on the role of the Hippo pathway in cancer (Press release, Cancer Research Technology, NOV 18, 2015, View Source [SID1234523508]).

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Under normal circumstances the Hippo pathway regulates cell size, controlling the growth of tissues during development and regeneration. Deregulation of the Hippo pathway has been implicated in inducing tumours in a broad range of cancers, making it a potentially attractive target for cancer therapy.

Scientists from CRT Discovery Laboratories (CRT-DL) will work together with Merck Serono scientists to validate the target, using CRT-DL’s expertise in building cell screening assays.

The establishment of this relationship exemplifies CRT-DL’s drug discovery model of bringing together complementary skills from academia and industry to build on novel insights within an exciting area of biology, which we hope will lead to new therapies for cancer patients.

On November 18, 2015 Pfizer Inc. reported that PROFILE 1029, a Phase 3 study of anaplastic lymphoma kinase (ALK) inhibitor XALKORI (crizotinib), met its primary objective of significantly prolonging progression-free survival (PFS) in previously untreated East Asian patients with ALK-positive advanced non-small cell lung cancer (NSCLC) when compared to a standard chemotherapy doublet (Press release, Pfizer, NOV 18, 2015, View Source [SID:1234508282]). In this study, XALKORI was used as the first systemic therapy for patients with advanced ALK-positive NSCLC, and patients could have received therapy and/or surgery for early stage disease before they were diagnosed with metastatic disease.

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The adverse events observed with XALKORI in the study were generally consistent with findings from previous trials. No unexpected adverse events were observed. Efficacy and safety data from PROFILE 1029 will be submitted for presentation at a future medical meeting.

PROFILE 1029 is the second positive Phase 3 study for XALKORI in the first-line setting and the third positive Phase 3 study for XALKORI in ALK-positive NSCLC. The PROFILE 1014 and PROFILE 1007 trials demonstrated that XALKORI was superior to chemotherapy in the first-line and the second-line settings, respectively.

"When evaluated specifically in East Asian patients with ALK-positive NSCLC, XALKORI was demonstrated to be superior to chemotherapy in terms of prolonging progression-free survival. This is consistent with the results of previous global randomized clinical trials that included Asian and Western patients, which also demonstrated an improvement in progression-free survival compared to standard-of-care chemotherapy" said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. "These results also underscore the importance of early and routine biomarker testing in patients with advanced NSCLC so that these patients can be identified and treated appropriately."

XALKORI was the first ALK inhibitor approved by regulatory authorities in the United States (U.S.), European Union, China and Japan, and it is now approved in more than 85 countries. XALKORI is widely recognized as a standard of care for patients with ALK-positive advanced NSCLC. To date, more than 20,000 patients have been treated with XALKORI worldwide.1

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is the leading cause of cancer death in both men and women.2 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.3 Approximately 57 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent.4

XALKORI (crizotinib) Indication and Important Safety Information (as per U.S. Prescribing Information)

XALKORI is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of patients treated with XALKORI across clinical trials (n=1669). Transaminase elevations generally occurred within the first 2 months. Monitor with liver function tests including ALT and total bilirubin every 2 weeks during the first 2 months of treatment, then once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Permanently discontinue for ALT/AST elevation >3 times ULN with concurrent total bilirubin elevation >1.5 times ULN (in the absence of cholestasis or hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI as indicated.

Interstitial Lung Disease (Pneumonitis): Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur. Across clinical trials (n=1669), 2.9% of XALKORI-treated patients had any grade ILD, 1.1% had Grade 3/4, and 0.5% had fatal ILD. These cases generally occurred within 3 months after initiation of treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes and permanently discontinue XALKORI in patients with drug-related ILD/pneumonitis.

QT Interval Prolongation: QTc prolongation can occur. Across clinical trials (n=1560), 2.1% of patients had QTcF (corrected QT by the Fridericia method) ≥500 ms and 5.0% had an increase from baseline QTcF ≥60 ms by automated machine-read evaluation of ECG. Avoid use in patients with congenital long QT syndrome. Consider periodic monitoring with ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia. Withhold XALKORI in patients who develop QTc >500 ms on at least 2 separate ECGs until recovery to a QTc ≤480 ms, then resume at a reduced dose.

Bradycardia: Symptomatic bradycardia can occur. Across clinical trials, bradycardia occurred in 12.3% of patients treated with XALKORI (N=1669). Avoid use in combination with other agents known to cause bradycardia. Monitor heart rate and blood pressure regularly. In cases of symptomatic bradycardia that is not life-threatening, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, re-evaluate the use of concomitant medications, and adjust the dose of XALKORI. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring.

Vision Disorders: Most commonly visual impairment, photopsia, blurred vision or vitreous floaters, occurred in 62% of 1669 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had Grade 4 visual impairment. The majority of patients on the XALKORI arms in Studies 1 and 2 (>50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact on daily activities.

Severe Visual Loss: Across clinical trials, the incidence of Grade 4 visual field defect with vision loss was 0.2% (N=1669). Discontinue XALKORI in patients with new onset of severe visual loss (best corrected vision less than 20/200 in one or both eyes). Perform an ophthalmological evaluation. There is insufficient information to characterize the risks of resumption of XALKORI in patients with a severe visual loss; a decision to resume should consider the potential benefits to the patient.

Embryofetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 45 days (females) or 90 days (males) respectively, following the final dose of XALKORI.

Adverse Reactions: Safety was evaluated in a phase 3 study in previously untreated patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169). Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% of patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis. Common adverse reactions (all grades) occurring in ≥25% and more commonly (≥5%) in patients treated with XALKORI vs chemotherapy were vision disorder (71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting (46% vs 36%), constipation (43% vs 30%), upper respiratory infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain (26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher incidence with XALKORI vs chemotherapy were QT prolongation (2% vs 0%), and constipation (2% vs 0%). In patients treated with XALKORI vs chemotherapy, the following occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea (56%) decreased appetite (30%), fatigue (29%), and neuropathy (21%) also occurred in patients taking XALKORI.

Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Avoid concomitant use of CYP3A substrates with narrow therapeutic range in patients taking XALKORI. If concomitant use of CYP3A substrates with narrow therapeutic range is required in patients taking XALKORI, dose reductions of the CYP3A substrates may be required due to adverse reactions.

Lactation: Because of the potential for adverse reactions in breastfed infants, advise females not to breast feed during treatment with XALKORI and for 45 days after the final dose.

Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations. Use caution in patients with hepatic impairment.

Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment.