On November 20, 2015 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) (Aptose or the Company), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported that the Food and Drug Administration (FDA), following a voluntary suspension of dosing by the Company and discussions with the Company, placed the Phase Ib clinical trial of APTO-253 in patients with hematologic cancers on clinical hold (Press release, Aptose Biosciences, NOV 20, 2015, View Source;p=RssLanding&cat=news&id=2114349 [SID:1234508462]). This hold is intended to ensure patient safety on the trial and to ensure manufacturing and dosing procedures are consistent with the appropriate documented quality standards.

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The voluntary suspension of dosing by the Company was initiated as a result of a planned preliminary review, which was accelerated to evaluate manufacturing processes and procedures upon the report of an operational difficulty with an IV infusion pump at a clinical site. The pump experienced back pressure during IV patient dosing at the point of the filter. Further review discovered preliminary concerns regarding the documentation records of the manufacturing procedures of the drug product associated with APTO-253.

The Company stated that a complete safety review of all patient files had been completed prior to initial discovery of the manufacturing documentation irregularities, and there have been no drug-related serious adverse events (SAEs) reported. The observed pharmacokinetic levels in the patients treated were within the expected range.

"We are disappointed by these events and have engaged an independent third party review. Importantly, this finding does not undermine the positive safety profile that APTO-253 has demonstrated in clinical development, and we remain confident in its potential as a promising therapeutic option for patients with acute myeloid leukemia and other hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and CEO. "While we expect some delay in the clinical trial, we are committed to ensuring that upon re-initiation of clinical dosing the drug product is of the highest standards. We plan to provide updated timeline guidance as soon as practical."

Key Points:

An internal review identified potential documentation irregularities and the Company voluntarily and immediately suspended dosing of patients out of an abundance of caution to ensure safety.

Aptose currently possesses a sufficient supply of API to create fresh batches of drug product for the resumption of clinical dosing upon FDA approval and guidance.

New contract manufacture organizations have been identified to manufacture fresh batches of cGMP clinical supply upon completion of investigation and in coordination with FDA guidance.

Overall effect to the Phase Ib trial timeline is expected to be partially mitigated by initiation of the new trial sites and updated timeline will be reported as soon as determined.

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.