VAL-083 drug compound shows promise against non-small cell lung cancer

DelMar Pharmaceuticals, Inc., (OTCQB: DMPI), a clinical-stage oncology company, today announced the presentation of promising new data supporting the activity of its lead drug compound, VAL-083, in the treatment of non-small cell lung cancer (NSCLC) at the AACR's New Horizons in Cancer Research: Harnessing Breakthroughs – Targeting Cures. The conference takes place October 9th to 12th in Pudong, Shanghai.

"The data presented today showed that VAL-083 is superior to cisplatin in both tumor models that are sensitive and resistant to tyrosine kinase inhibitors and has synergistic effect in combination with cisplatin," said Jeffrey Bacha, president and CEO of DelMar Pharmaceuticals. "This data suggests important clinical and market potential of VAL-083 in non-small cell lung cancer."

DelMar's lead clinical compound, VAL-083 (dianhydrogalactitol) is a first-in-class alkylating agent with a novel cytotoxic mechanism distinct from other alkylating agents used in the treatment of cancer.

In historical studies sponsored by the National Cancer Institute in the United States, VAL-083 exhibited clinical activity against a range of tumor types including CNS tumors, solid tumors and hematologic malignancies. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer (Approval No. Guoyao Zhunzi H45021133; manufactured by Guangxi Wuzhou Pharmaceutical (Group) Co. Ltd.)

NSCLC is usually treated with either tyrosine kinase inhibitors (TKIs) (e.g. gefitinib) or platinum-based regimens (e.g. cisplatin). TKIs have resulted in vastly improved outcomes for patients with EGFR mutations; however, TKI resistance has emerged as a significant unmet medical need, and long-term prognosis with platinum-based therapies is poor. Compared to other countries, Asian patients with NSCLC have a higher incidence of EGFR mutations (up to 60 percent; compared to 10-20 percent in Western populations) and are more susceptible to TKI resistance.

Additionally, NSCLC patients have a high incidence of brain metastases, which is associated with a poor prognosis. The median overall survival time for patients with stage IV NSCLC is four months, while one-year and five-year survival is less than 16 percent and 2 percent, respectively. VAL-083 can cross the blood-brain barrier and is currently being evaluated in the United States in a Phase 1/2 clinical trial to treat the most common form of brain cancer, glioblastoma multiforme (GBM).

"Rates of lung cancer have been rising steeply over the past decade and are a significant public health problem in China," explained Mr. Bacha. "China has one-third of the global deaths from lung cancer, and non-small cell lung cancer accounts for more than 85 percent of all lung cancer cases, of which almost half are diagnosed at an advanced stage of the disease. Because VAL-083 is already approved in China for the treatment of non-small cell lung cancer and has known activity in treating brain cancer, we have the potential to have a near-term option for doctors and millions of Chinese patients who today have not known this treatment was available."

DelMar's data presented at the AACR New Horizons in Cancer Research meeting seeks to answer three simple, fundamental questions:

• How does the activity of VAL-083 compare to standard platinum therapy?
• Can VAL-083 be combined with platinum based therapy?
• Can VAL-083 treat NSCLC that is resistant to platinum-based chemotherapy or TKIs?

In in vivo models of lung cancer, significant survival benefit was observed with VAL-083 in comparison to platinum-base chemotherapy in both TKI-susceptible (A549) and TKI-resistant (H1975) models of NSCLC. These observations suggest that VAL-083 maintains activity where cisplatin fails to gain a statistically significant benefit.

In a separate, standard model of anti-cancer activity, VAL-083 was superior to cisplatin in tumor growth delay. Interestingly, VAL-083 in combination with cisplatin produced a more than additive effect by delaying growth in vivo. These observations are supported by separate in vivo studies which reveal the potential for synergistic benefit for a combination of VAL-083 and platinum-based therapies against both TKI-susceptible (A549) and TKI-resistant (H1975) NSCLC tumor cell lines.

Taken together, the results suggest that VAL-083 is superior to cisplatin in both TKI-sensitive and resistant tumor models, has synergistic effect in combination with cisplatin, and suggest clinical potential in TKI-resistant NSCLC. This data provides direction to clinical research aimed at influencing practice patterns under VAL-083's current approval in China and support expanded global development.

"We believe these observations have important immediate implications in the treatment of NSCLC in China, where VAL-083 is approved for as chemotherapy for the treatment of lung cancer, and for future clinical development in the rest of the world," added Mr. Bacha. "Next steps include clinical validation of these promising results in a clinical study. Such work could be initiated in China in a post-approval setting."