DelMar Pharmaceuticals Presents Additional Clinical Data from Ongoing Brain Cancer Study at ASCO Activity with VAL-083 Observed in Recurrent Malignant Glioma and Progressive Secondary Brain Tumors

Company Plans to Expand Clinical Development of VAL-083

VANCOUVER, British Columbia and MENLO PARK, Calif., June 3, 2013 /PRNewswire/ -- DelMar Pharmaceuticals, Inc. (OTCQB: DMPI) ("DelMar") announced that the company presented a poster entitled "Phase I/II Study of VAL-083 (dianhydrogalactitol) in Patients with Recurrent Malignant Glioma or Progressive Secondary Brain Tumor" at the American Society of Clinical Oncology (ASCO) Annual Meeting, on June 1, 2013 in Chicago.

DelMar presented additional clinical data from the company's ongoing Phase I/II clinical trial with VAL-083.  The trial is a dose-escalation study designed to assess the safety and activity of VAL-083 as a potential treatment for brain cancer patients suffering from glioblastoma or secondary-progressive brain tumor who have failed standard therapies and have no viable treatment options. Three cohorts of patients have been enrolled so far, testing VAL-083 at 1.5mg/m2; 3.0mg/m2 and 5.0mg/m2.  A link to the company's poster can be found at: http://www.delmarpharma.com/DelMarASCO2013-11x17.pdf

Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals, noted, "These new data presented at ASCO continue to demonstrate promise for VAL-083 as a potential treatment for cancer patients suffering from GBM as well as patients who are suffering from other cancers that have spread to the brain. Tumors of the brain are among the most challenging malignancies to treat. Median survival for patients with recurrent disease is approximately 6 months for glioblastoma multiforme.  Central nervous system metastases have evolved as a major contributor to cancer mortality because many new systemic therapies cannot reach tumors spreading to the brain."

Highlights of the DelMar ASCO data presentation include:

  • VAL-083 therapy is well tolerated in glioblastoma multiforme (GBM) and secondary-progressive brain tumor patients with no drug-related serious adverse events at doses studied to date.
  • At doses in cohorts 1-3, 25% (2/8) of GBM patients and 17% (1/6) of secondary-progressive brain cancer patients showed stable disease or tumor regression in response to VAL-083 treatment at the doses tested to date. These patients had failed prior therapy. The doses tested in these cohorts were well below those used in historical clinical studies.
  • Cohort 3 was expanded to gather additional data on central nervous system (CNS) metastatic patients at the 5mg/m2 dose level.
  • Maximum tolerated dose (MTD) has not been reached after completion of cohort three.   Continued dose escalation is planned.
  • Pharmacokinetic analysis shows dose-dependent increase in plasma exposure following doses of VAL-083.

"We are pleased to see continued responses to VAL-083 at these dose levels," added Mr. Bacha. Based on the linearity of the pharmacokinetic data, we anticipate enhanced response rates as we reach higher doses. We elected to expand cohort three to gather additional data on patients with CNS metastases of solid tumors in order to solidify our plans for further development of this important drug candidate."

"The need for new therapies for the treatment of GBM continues to be highlighted by the failure of targeted therapies, including those that have shown good results in other indications, to have an impact on the survival of these patients.  We believe that the unique cytotoxic mechanism of VAL-083 may provide physicians with much needed new therapeutic option for patients suffering from this devastating disease," added Mr. Bacha.

As part of DelMar's ASCO presentation, the Company also announced plans to split the protocol into two separate studies: one focusing solely on refractory glioblastoma and the other focusing on metastatic brain cancers. Due to prior chemotherapy and radiation therapy, patients with secondary brain tumors are likely more prone to myelosuppression and may have a different MTD than patients with GBM.

"VAL-083 demonstrated activity against a range of tumor types in historical clinical studies sponsored by the U.S. National Cancer Institute.  We believe the strategy of splitting the trial into two separate studies will enable us to focus on accelerating the development of VAL-083 as a potential new treatment for glioblastoma while appropriately exploring the potential of the drug to treat patients with solid tumor brain metastases," said Mr. Bacha. 

About VAL-083
VAL-083 represents a 'first-in-class' small-molecule chemotherapeutic. VAL-083 has been assessed in multiple NCI-sponsored clinical studies in various cancers including lung, brain, cervical, ovarian tumors and leukemia.  Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types.  VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer.

Based on published research, the mechanism of action of VAL-083 is understood to be a bi-functional alkylating agent; however, the functional groups associated with alkylating events has been shown to differ from other alkylating agents used in the treatment of GBM.

VAL-083 has previously demonstrated activity in cyclophosphamide, BCNU and phenylanine mustard resistant cell lines and no evidence of cross-resistance has been encountered in published clinical studies.  Based on the presumed alkylating functionality of VAL-083, published literature suggests that DNA repair mechanisms associated with Temodar® and nitrosourea resistance, such as 06-methylguanine methyltransferase (MGMT), may not confer resistance to VAL-083. 

VAL-083 readily crosses the blood brain barrier where it maintains a long half-life in comparison to the plasma.  Published preclinical and clinical research demonstrates that VAL-083 is selective for brain tumor tissue.

VAL-083 has been assessed in multiple studies as chemotherapy in the treatment of newly diagnosed and recurrent brain tumors.  In general, tumor regression was achieved following therapy in greater than 40 percent of patients treated and stabilization was achieved in an additional 20 to 30 percent.  In published clinical studies, VAL-083 has previously been shown to have a statistically significant impact on median survival in high-grade gliomas when combined with radiation versus radiation alone. 

The main dose-limiting toxicity related to the administration of VAL-083 in previous clinical studies was myelosuppression.  No significant hepatic, renal or pulmonary toxicity has been reported in the literature or overseas commercial experience. 

About Glioblastoma Multiforme (GBM)
GBM is the most common and most malignant form of brain cancer. Of the estimated 17,000 primary brain tumors diagnosed in the U.S. each year, approximately 60 percent are gliomas. Attention was drawn to this form of brain cancer when Senator Ted Kennedy was diagnosed with glioblastoma in 2008 and ultimately died from the disease fifteen months later.

Newly diagnosed patients suffering from GBM are initially treated through invasive brain surgery, although disease progression following surgical resection is nearly 100 percent. Temodar in combination with radiation is the front-line therapy for GBM following surgery. Temodar currently generates more than US$950 million annually in global revenues primarily from the treatment of brain cancer.

Approximately 60 percent of GBM patients treated with Temodar® experience tumor progression within one year. Avastin® has been approved for the treatment of GBM in patients failing Temodar®. According to the Avastin® label, approximately 20 percent of patients failing Temodar® respond to Avastin® therapy.   Analysts anticipate annual Avastin® revenues for the treatment of brain cancer may reach US$650 million by 2016.

Approximately 48 percent of patients who are diagnosed with GBM will fail both front-line Temodar® therapy and Avastin®. DelMar estimates that the market for treating GBM patients the post-Avastin failure exceeds US$200 million annually in North America.

About the VAL-083 Clinical Study
The Phase I/II study is an open-label, single arm dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of VAL-083 in patients with histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (GBM), now recurrent.  Patients with prior low-grade glioma or anaplastic glioma are eligible, if histologic assessment demonstrates transformation to GBM.  Patients with secondary brain tumors due to CNS metastases are also eligible for the study.

GBM patients must have been previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both Avastin and Temodar, unless either or both are contra-indicated. 

Response to therapy and disease progression will be evaluated by MRI prior to each treatment cycle.  An initial phase of the study will involve dose escalation cohorts until a maximum tolerated dose (MTD) is established in the context of modern care.  Once the modernized dosing regimen has been established, additional patients will be enrolled at the MTD (or other selected optimum dosing regimen).

DelMar is conducting the study under the direction of Dr. Howard Burris at the Sarah Cannon Research Institute in Nashville, Tennessee with a second center in Sarasota, Florida. 

Please refer to clinicaltrials.gov identifier NCT01478178 for further details on this clinical trial or visit: http://www.clinicaltrials.gov/ct2/show/NCT01478178?term=VAL--083&rank=1

About DelMar Pharmaceuticals
DelMar Pharmaceuticals was founded in 2010 to develop and commercialize proven cancer therapies in new orphan drug indications where patients are failing modern targeted or biologic treatments. The Company's lead asset, VAL-083, is currently undergoing clinical trials in the United States as a potential treatment for refractory glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. VAL-083 benefits from extensive clinical research sponsored by the U.S. National Cancer Institute, and is currently approved for the treatment of chronic myelogenous leukemia (CML) and lung cancer in China. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types via a novel mechanism of action.

Safe Harbor Statement
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations, but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in our filings with the SEC, including, our current reports on Form 8-K. We do not undertake to update these forward-looking statements made by us.

For further information, please visit www.delmarpharma.com; or contact Jeffrey A. Bacha, President & CEO  (604) 629-5989 or Booke & Company Investor Relations, admin@bookeandco.com

SOURCE DelMar Pharmaceuticals, Inc.



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