On November 21, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported the Company’s presentations at the CNS Anticancer Drug Discovery and Development Conference and Society for NeuroOncology Annual meeting, which was held November 16-20, 2016 in Scottsdale, Arizona (Press release, DelMar Pharmaceuticals, NOV 21, 2016, http://ir.delmarpharma.com/news/detail/838/delmar-pharmaceuticals-delivers-an-address-and-presents-an-overview-of-upcoming-gbm-trials-with-val-083-at-the-cns-anticancer-drug-discovery-development-conference-and-society-for-neurooncology-annual-meeting [SID1234516708]).

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During the conference, DelMar’s chairman and CEO, Jeffrey Bacha, delivered an oral address during CNS Anticancer Drug Discovery and Development sessions. Mr. Bacha described DelMar’s research and recent clinical trial results and how these data position VAL-083 as a potential solution for newly diagnosed GBM patients whose cancer exhibits features, such as a high expression of MGMT, implicated in resistance to currently approved chemotherapy.

"It was an honor to be invited to share and discuss our research with leaders in the global neuro-oncology community," stated Mr. Bacha. "Overcoming the unique challenges in treating brain tumors requires cooperation among experts across a range of medical and scientific disciplines. We look forward to continuing to advance VAL-083 as a potential new chemotherapy in collaboration with leading cancer centers and researchers."

DelMar also provided an overview of three upcoming clinical trials with VAL-083 for the treatment of chemo-resistant GBM. A copy of the company’s poster presentation entitled ‘Clinical Trials of VAL-083 in Patients with Chemo-Resistant Glioblastoma’ can be viewed at View Source The planned trials include:

1. A pivotal, randomized multi-center Phase 3 study measuring survival outcomes compared to a "physicians’ choice" control for the treatment of bevacizumab-failed GBM. A summary of the proposed clinical trial design includes:

Approximately 180 patients with histologically confirmed recurrent GBM who have failed both standard chemo-radiation and bevacizumab will be randomized in a 2:1 fashion to receive either VAL-083 or a commonly used salvage chemotherapy;
The proposed study is projected to be enrolled at approximately 25 centers;
The proposed primary endpoint is overall survival (OS);
The proposed statistical design between the two arms of the study is 90% power, and is proposed to include an interim analysis at 50% events for futility with O’Brien-Fleming superiority boundary and non-binding, gamma (-5) futility boundary; and
The estimated length of the proposed study is less than two years from initiation.
The proposed trial design is subject to feedback from the FDA and other regulatory authorities. DelMar plans to submit the protocol to the FDA in coming weeks.

2. An open label, single-arm, biomarker-driven, Phase 2 study of VAL-083 in patients with MGMT-unmethylated, bevacizumab-naïve recurrent GBM (clinicaltrials.gov identifier: NCT02717962)

This single arm, biomarker-driven study will enroll 48 patients to determine if treatment of MGMT-unmethylated recurrent glioblastoma with VAL-083 improves overall survival (OS), compared to historical reference control;
The lomustine arm of the recently published EORTC26101 trial will serve as the reference control; and
The study is initially being enrolled at the University of Texas MD Anderson Cancer Center as a single center trial, but may be expanded to include additional centers.
This trial is being conducted in collaboration with the University of Texas MD Anderson Cancer Center ("MDACC"). The MDACC Institutional Review Board (IRB) has approved the protocol for this Phase II Study, and DelMar has completed a formal site initiation visit. DelMar and MDACC anticipate commencing enrollment and initiating patient treatment in the coming weeks.

3. An open label, single-arm, biomarker-driven, Phase 2 study of VAL-083 and radiation therapy patients in newly diagnosed MGMT-unmethylated GBM

This single-arm trial will enroll up to 30 newly diagnosed (temozolomide-naïve) GBM patients to examine whether VAL-083 is active in patients with newly diagnosed GBM with MGMT-unmethylated compared to historical control;
If successful, data from the trial will serve as a lead-in to a global randomized Phase II/III clinical trial of VAL-083 in newly diagnosed GBM patients with MGMT-unmethylated;
Progression free survival (PFS) will serve as the primary endpoint to assess VAL-083 treatment activity;
The study will also confirm the safety and tolerability of VAL-083 in combination with a standard-of-care radiation regimen; and
The study will initially be enrolled at the Sun-Yat Sen University (Guangzhou, China) as a single center trial, but may be expanded to include additional centers.
This trial is being conducted in collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co. Under the terms of the company’s collaboration agreement Guangxi Wuzhou Pharmaceuticals is providing drug product and funding for the trial. The Sun-Yat Sen University Clinical Review Committee has approved the protocol and DelMar is completing the final remaining regulatory steps required for initiation of the trial and expects to begin enrollment in early 2017.

In a separate poster presentation, DelMar provided additional non-clinical data regarding VAL-083’s unique anti-cancer mechanism and potential combination therapies. DelMar’s poster presentation, entitled ‘Molecular Mechanisms of Dianhydrogalactitol (VAL-083) in Overcoming GBM Chemo-resistance’ can be viewed on the company’s website at: View Source

In summary, DelMar’s data indicates that:

The mechanism of action of VAL-083 is distinct from other alkylating agents used in the treatment of CNS tumors;
VAL-083 induces irreparable DNA double strand breaks, irreversible S/G2-phase arrest and activation of the homologous recombination DNA repair pathway;
VAL-083’s cytotoxic activity is MGMT-independent and able to overcome TMZ-resistance in GBM cancer stem cells and non-stem cells in vitro;
VAL-083 potentiates radiation in GBM cancer stem cells in vitro;
VAL-083’s activity appears independent of p53; and
VAL-083 displays synergy with a number of agents used in the treatment of GBM and other CNS tumors, including temozolomide, topoisomerase inhibitors, and platinum-based chemotherapy.
"These data are particularly valuable because they demonstrate the potential to combine VAL-083 with topoisomerase inhibitors, which are regularly used in the treatment of recurrent GBM," added Mr. Bacha. "Topoisomerase inhibitors such as irinotecan and etoposide have a relatively narrow therapeutic window and require cells to be in the ‘S-phase’ of the cell cycle for activity. Because VAL-083 causes cell-cycle arrest in the S-phase these data suggest an opportunity to combine VAL-083 with a lower and better tolerated dose of a topoisomerase inhibitor while maintaining or improving efficacy."

About Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common and most malignant form of brain cancer. Approximately 15,000 people are diagnosed with GBM each year in the U.S., with similar incidence in Europe. Standard of care is surgery, followed by either radiation therapy, or radiation therapy combined with temozolomide. Approximately 60 percent of GBM patients treated with temozolomide experience tumor progression within one year. More than half of glioblastoma patients will fail the currently approved therapies and face a very poor prognosis.

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.

DelMar’s research has demonstrated that VAL-083 is active against GBM cell lines that are resistant to standard-of-care chemotherapy due to features such as high expression of MGMT, in vitro.

DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following Avastin (bevacizumab) failure compared to published literature where survival of approximately two to five months has been reported.

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

DelMar believes that data from its upcoming clinical trials, if successful, will form the basis of a new paradigm in the treatment for all GBM patients who fail, or whose tumors exhibit features that make them unlikely to respond to currently available chemotherapy.

Further details can be found at View Source

On November 21, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold placed on its clinical trials evaluating the LADD (live, attenuated double-deleted) immunotherapy platform, enabling patient enrollment to resume in all Aduro-sponsored clinical studies (Press release, Aduro BioTech, NOV 21, 2016, View Source [SID1234516707]).

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"We are pleased to come to a rapid agreement with the FDA to resume new patient enrollment in our LADD clinical studies," said Stephen T. Isaacs, chairman, president and CEO of Aduro Biotech. "With slight protocol modifications implemented, we remain on track to initiate a Phase 2 clinical study using our LADD-based therapy CRS-207 in combination with an anti-PD-1 compound for patients with mesothelioma in the first half of 2017. Additionally, we continue to make significant progress with our STING Pathway Activator and B-select Antibody programs and with our three diverse immunotherapy platforms, we believe we are uniquely positioned to bring innovative therapies to patients with late-stage cancers."

In agreement with the FDA, Aduro’s LADD-based clinical trial protocols have been modified to include extended patient surveillance, to exclude patients with certain prosthetic devices that are not easily removed, and to add guidance to administer prophylactic antibiotics following LADD-based treatment for patients who may receive immune-suppressive treatments.

On November 18, 2016 Immunovo reported on the successful development of a peptide-based vaccine enabling a successful active anti-tumor immunization therapy targeting the growth hormone Vascular Endothelial Growth Factor (VEGF) (Press release, Immunovo, NOV 18, 2016, View Source [SID1234516684]). An academic research team, in collaboration with Immunovo, has established that treatment with vaccine caused suppression of tumor growth in mice. These encouraging preclinical results were published last week in the leading international journal "Proceedings of the National Academy of Sciences of the USA" (PNAS). An exploratory Phase I/II studie in patients is now well underway at VU Medical Center (Amsterdam, The Netherlands).

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The vascular endothelial growth factor (VEGF) is a pivotal growth factor for angiogenesis (blood vessel formation) in tumor tissue. Therefore, it has been frequently investigated as a target in anticancer therapy. Its inhibition by the monoclonal anti-VEGF antibody bevacizumab (Avastin) has already demonstrated improved survival in patients with several types of cancer.

There are, however, limitations to the effectiveness of this passive immunotherapy strategy since it does not stimulate a patient’s immune system to actively respond to a disease in the way a vaccine does. The starting point of the research now reported in PNAS is that a VEGF vaccination has the potential to outperform the current clinical anti-VEGF treatment strategies.

Vaccination will not only provide durable VEGF suppression, it is also expected that the induced antibodies will have superior VEGF-neutralizing ability in comparison to bevacizumab. Furthermore, vaccination requires only a few intramuscular injections and reduces the number of hospital visits in comparison to treatment with bevacizumab.

However, vaccination with intact VEGF has major drawbacks such as unwanted biological activity and weak immunogenicity. The strategy pursued in the current research therefore is to use a VEGF mimicking peptide as a vaccine. The major challenge here was to identify the minimal peptide able to generate antisera with potent VEGF-neutralizing capacity and tumor-reducing capabilities.

A total of 33 peptide mimics of VEGF with varying levels of structural complexity (linear, conformational, and discontinuous) were designed, synthesized, and tested for the ability to generate potent antisera. It was established that induction of neutralizing antibodies with tumor-growth-inhibiting power was only successful for a 3D-structured 79-mer peptide with a fully intact cysteine-knot fold (covering the complete discontinuous binding site of bevacizumab).

Eradication of tumor growth using this peptide was demonstrated in two different tumor models (mice). It thus became clear that enforcing a native-like, secondary structure in the peptide is the key to success for inducing neutralizing anti-VEGF antibodies with tumor-inhibiting power.

Joost van Bree, CEO of Immunovo explains: "At Immunovo, we think that clinical benefit could be enhanced by inducing a humoral immune response against VEGF through active immunization with VEGF-based peptides. In this study we demonstrated the successful development of a unique synthetic vaccine with potent in vitro and in vivo VEGF-neutralizing activities, as shown in passive and active immunization tumor models. We strongly believe that this strategy has the exciting potential to outperform the current clinical anti-VEGF treatment strategies"

The research team included Professor Peter Timmerman of Pepscan Systems BV and the University of Amsterdam’s Van’t Hoff Institute for Molecular Sciences (HIMS) and Madelon Wentink and Professor Arjan Griffioen, both of VU Medical Center Amsterdam.

On November 18, 2016 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the first data from the dose expansion cohorts of the Phase 1 study evaluating single agent AG-120 in isocitrate dehydrogenase-1 (IDH1) mutant positive glioma and chondrosarcoma (Press release, Agios Pharmaceuticals, NOV 18, 2016, View Source [SID1234516677]). The glioma data were presented today at the Society for Neuro-Oncology (SNO) Annual Meeting in Scottsdale, AZ and the chondrosarcoma data were presented last week at the annual meeting of the Connective Tissue Oncology Society (CTOS) in Lisbon, Portugal.

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"Glioma and chondrosarcomas are extremely difficult-to-treat diseases where patients are in need of new therapies," said Chris Bowden, M.D., chief medical officer at Agios. "These Phase 1 dose expansion data are encouraging, as they continue to demonstrate a well-tolerated safety profile for AG-120 at a fixed daily dose of 500 mg. The prolonged stable disease in both patient populations is encouraging in light of AG-120’s unique differentiation mechanism of action. In addition, our initial experience utilizing centralized volumetric assessments in patients with glioma has been informative, and along with our ongoing AG-881 Phase 1 trial, will help determine the next steps in clinical development."

"In glioma, AG-120 has the potential to help a large number of patients with IDH1 mutations," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "The SNO presentation is the first look at data for AG-120 in a defined cohort of glioma patients where we evaluated the potential for volumetric analyses to improve our understanding of the response patterns beyond the conventional bi-dimensional methods. This methodology could be instrumental in developing more effective, targeted therapies for patients with this disease."

The Phase 1 trial is assessing the safety and tolerability of AG-120 in advanced solid tumors, including glioma, intrahepatic cholangiocarcinoma (IHCC) and chondrosarcomas that harbor an IDH1 mutation. The dose-escalation phase was followed by four expansion cohorts in the following patient groups.

Low grade glioma with ≥ 6 months prior scans
High grade (metastatic) chondrosarcoma
2nd-line cholangiocarcinoma
Solid tumors not eligible for cohorts 1-3
Enrollment is now complete for the dose escalation and expansion cohorts.

Glioma Expansion Data Presented at SNO Annual Meeting

As of the August 1, 2016 data cut off, 66 patients have been treated with single agent AG-120, and 28 patients (42%) remain on treatment.

Data reported are from 20 patients who received AG-120 administered from 200 mg to 1200 mg total daily doses in the dose-escalation phase.
Forty-six patients who received 500 mg daily doses of AG-120 administered in two expansion cohorts, including 24 patients enrolled in a cohort with non-enhancing glioma and 22 glioma patients with enhancing disease enrolled in a basket cohort.
The median age of these patients is 41 (ranging from 21-71).
The median number of prior therapies was two (ranging from one to six) and included temozolomide (71%). Seventy-four percent of patients received radiotherapy.
A safety analysis conducted for all 66 treated patients as of the data cut-off demonstrated that AG-120 was well-tolerated with a favorable safety profile in glioma patients.

No dose limiting toxicities have been observed.
The majority of adverse events reported by investigators were mild to moderate, with the most common being headache, nausea, diarrhea and vomiting.
There were 11 patients with serious adverse events (SAE) and none of them were drug-related.
Efficacy data from 65 response-evaluable patients as of the data cut-off showed:

Two patients had a minor response according to the Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG).
Forty-one (63%) patients had stable disease, including 27 with non-enhancing disease; the median treatment duration for non-enhancing glioma was 8.1 months (ranging from 1.4 – 17.8 months).
Volumetric analysis conducted centrally demonstrated stabilization or a decrease in tumor growth rate compared to the pretreatment rate in 64% (n=14 of 22) of glioma patients with non-enhancing disease receiving AG-120 and requires further development as a response evaluation tool.
Chondrosarcoma Expansion Data Presented at CTOS Annual Meeting

Agios also analyzed data from 21 chondrosarcoma patients as of September 23, 2016 in the dose escalation (n=12) and expansion cohorts (n=9) and 7 remain on treatment.

Doses received were 100 mg twice daily, and 300, 400, 500, 600, 800, 900 and 1200 mg once a day. Expansion cohort patients received 500 mg once a day. Median treatment duration was 2.6 months (ranging from 0.0–24.4 months).
Prior therapy included surgery (57%), radiotherapy (33%) and chemotherapy (24%). The median number of prior systemic therapies was one (ranging from one to five).
No dose-limiting toxicities were reported; the majority of adverse events reported by investigators were mild to moderate, with the most common being diarrhea, nausea, decreased appetite, QT prolongation and fatigue.
Most SAEs were considered unrelated to treatment with one case of hypophosphatemia (low phosphorous blood level) considered to be possibly related to treatment.
Of 20 response-evaluable patients, 11 (55%) experienced stable disease as their best response; the 3-month progression-free survival rate was 58%.
Baseline plasma levels of the oncometabolite D-2-hydroxyglutarate (2-HG) were elevated above the healthy volunteer range. Treatment with AG-120 resulted in significant reduction of plasma 2-HG compared to baseline. Up to 99.7% tissue 2-HG reduction was documented in paired biopsies obtained from 3 patients treated with AG-120. Together these data indicate the on-target pharmacodynamic effects of AG-120.
About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment neurologic deficits and seizures. The long-term prognosis is poor with a five-year survival rate of 33 percent. Median survival is 12-15 months for glioblastoma and 2-5 years for anaplastic glioma. IDH1 mutations are highly prevalent, accounting for approximately 68-74 percent of low grade glioma and secondary glioblastoma.

About Chondrosarcoma
Chondrosarcoma is a heterogeneous group of cancers that arise from cartilage in the bone and joint. It is the most common type of bone cancer with 700-1,000 people diagnosed per year in the U.S. IDH1/2 mutations occur in approximately 46-63 percent of central chondrosarcomas. The prognosis is based on disease burden – for localized disease, there is curative potential with surgery, but metastatic disease has a low five-year survival rate. Radiation is not effective, and chemotherapy is of limited benefit. Treatment for metastatic disease is mainly palliative.