DelMar Pharmaceuticals Presents Updated Clinical Data On Phase I/II Study Of VAL-083 In Refractory Glioblastoma Multiforme (GBM)

VANCOUVER, British Columbia and MENLO PARK, Calif., April 20, 2015 /PRNewswire/ -- DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) (DelMar and the Company), a biopharmaceutical company focused on developing and commercializing proven cancer therapies in new orphan drug indications, today announced updated clinical data on the identification of maximum tolerated dose (MTD) from its Phase I/II study of its lead product candidate VAL-083 (dianhydrogalactitol) in patients with refractory glioblastoma multiforme (GBM), the most common and deadly form of human brain cancer.

Results from DelMar's clinical study titled, "Phase I/II study of dianhydrogalactitol in patients with recurrent malignant glioma," were presented during a poster session featuring clinical trials in progress at the 106th Annual Meeting of the American Association for Cancer Research (AACR), being held April 18-22, 2015, in Philadelphia, Pennsylvania.

VAL-083 is a 'first-in-class' small molecule chemotherapeutic, which DelMar is developing as a potential new therapy for the treatment of GBM.  VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

The Company is conducting a multicenter Phase I/II clinical study with VAL-083 to determine the MTD using an optimized dosing scheme. Once MTD is determined, enrollment will be expanded by up to an additional 14 patients in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA) in preparation for advancing VAL-083 into Phase II/III registration directed trials. Based on historical and recent data, in the Phase I/II dose-escalation study there was an observation of Grade 3 and Grade 4 thrombocytopenia (low platelet counts) at the current (50mg/m²).

"While we have only observed one patient with Grade 4 thrombocytopenia, which is defined as dose-limiting toxicity (DLT), in the cohort to date, the strong trend suggested by multiple observations of Grade 3 thrombocytopenia confirm that we have reached the end of the dose-escalation phase of our clinical trial," stated Jeffrey Bacha, DelMar's president and CEO. "Through our optimized dosing regimen, we have successfully achieved our goal of delivering higher doses of VAL-083 than prior promising NCI-sponsored clinical trials with VAL-083 in GBM.  We are pleased to achieve this milestone with VAL-083 as a potential new therapy for GBM patients who fail, or are unlikely to respond to, current standard of care."

"The goal of our current Phase I/II clinical trial is to establish a modernized dosing regimen for advancement into registration directed trials in the United States as a potential new therapy for the treatment of refractory GBM."

"The final decision on the dose chosen for the expansion phase of our Phase I/II trial and advancement into to Phase II/III registration directed studies will be determined by analysis of the totality of the data from the dose-escalation portion of the trial and discussion with our scientific and clinical advisors," added Mr. Bacha.

DelMar's trial is an open-label, single arm, safety and tolerability dose-escalation study utilizing a standard dose escalation design, until the maximum tolerated dose (MTD) or the maximum specified dose has been reached. Eligible GBM inclusion criteria requires previous treatment with surgery and/or radiation, if appropriate. Subjects must have failed both bevacizumab (Avastin^®) and temozolomide (Temodar^®), unless either of these therapies was contraindicated. The study utilizes a 3+3 dose-escalation design (ClinicalTrials.gov Identifier NCT01478178).

The study was designed for patients to receive VAL-083 on days 1, 2, and 3 of a 21-day cycle. Tumor response is assessed according to RANO criteria prior to every other 21-day treatment cycle, and patients exhibiting stable disease or tumor regression remained on VAL-083. Determination of MTD is based on 3+3 design. Currently, 37 patients have been enrolled across 8 dose cohorts ranging from 1.5 to 50mg/m²/d.

In accordance with the protocol, six patients have been enrolled at dose level 8 (50mg/m²/d).  In this cohort, one DLT consisting of Grade 4 thrombocytopenia has been observed at dose level 8  to date and three additional patients in the cohort experienced Grade 3 thrombocytopenia. The DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment. Prior to this cohort, other treatment related toxicities have been mild to moderate. Pharmacokinetic analyses show dose-dependent linear systemic exposure with a short plasma 1-2h terminal half-life; Cmax ranged from 7391130 ng/mL (5.17.7µM) at 40mg/m²/d.

Compared to historical trials, the present regimen delivers substantively more drug as measured by single dose and overall exposure. A dose intensity of 25 mg/m²/wk in combination with radiation was previously shown superior to radiation alone against GBM; a higher dose and dose intensity is achieved by DelMar's dosing regimen in the current trial.

In the dose-escalation portion of the DelMar trial, three GBM patients were observed to have a response (stable disease or partial response) reporting improved clinical signs (maximum response of 84 weeks). In addition, VAL-083 has been assessed in multiple historical NCI-sponsored clinical studies as chemotherapy in the treatment of newly diagnosed and recurrent brain tumors and other cancers. In general, tumor regression in brain cancer was achieved following therapy in greater than 40% of patients treated and stabilization was achieved in an additional 20% to 30%. In published clinical studies VAL-083 has previously been shown to have a statistically significant impact on median survival in high grade glioma brain tumors when combined with radiation versus radiation alone with results similar or superior to other chemotherapies approved for use in GBM.

A Summary of Published Data adapted from Separate Sources Comparing the Efficacy of VAL-083 and Other Therapies in the Treatment of GBM:

In addition to promising historical data, DelMar's research demonstrates that VAL-083's cytotoxic anti-cancer mechanism is different than other chemotherapies approved for the treatment of GBM.   The Company has presented research results at peer-reviewed scientific meetings demonstrating that VAL-083 is active in patient-derived tumor cell lines and cancer stem cells that are resistant to other chemotherapies. Of particular importance is resistance to Temodar due to activity of the repair enzyme known as MGMT, which results in chemoresistance in many GBM patients. At AACR in 2012, DelMar presented data demonstrating that VAL-083 is active independent of MGMT resistance in laboratory studies. VAL-083 has more potent activity against brain tumor cells in comparison to TMZ and overcome resistance associated with MGMT suggesting the potential to surpass the current standard-of-care in the treatment of GBM. 

The VAL-083 Phase 1/2 clinical study poster presented at AACR may be found on the DelMar Pharmaceutical website under http://www.delmarpharma.com/products/publications/.

About VAL-083
VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase 1 and 2 clinical studies sponsored by the National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. As a potential treatment for glioblastoma, VAL-083's mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to front-line treatment with Temodar^® (temozolomide). DelMar is currently studying VAL-083 in a Phase I/II clinical trial for patients with refractory glioblastoma multiforme.

About DelMar Pharmaceuticals, Inc.
DelMar Pharmaceuticals, Inc. was founded to develop and commercialize proven cancer therapies in new orphan drug indications where patients are failing or have become intolerable to modern targeted or biologic treatments. The Company's lead drug in development, VAL-083, is currently undergoing clinical trials in the U.S. as a potential treatment for refractory glioblastoma multiforme. VAL-083 has been extensively studied by 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 that could provide improved treatment options for patients.

For further information, please visit http://delmarpharma.com/; or contact DelMar Pharmaceuticals Investor Relations:  ir@delmarpharma.com / (604) 629-5989 follow us on Twitter @DelMarPharma or Facebook.com/delmarpharma.

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.

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SOURCE DelMar Pharmaceuticals, Inc.