MEI Pharma, an oncology company focussed on the clinical development of novel therapies for cancer, announced that the first patient has been dosed in the cohort-expansion stage of the Company's phase Ib clinical study of investigational drug candidate ME-344 in combination with topotecan in patients with small cell lung or ovarian cancer who failed initial therapy.

The cohort expansion comes after the initial stage of the study confirmed the maximum tolerated dose (MTD) of ME-344 in combination with topotecan is 10mg/kg, the same dose defined for single agent use. Now the study will enroll an additional 40 patients into two cohorts: locally advanced or metastatic small cell lung cancer and ovarian cancer.

"This milestone represents another important step forward for the clinical development of ME-344," said Robert D. Mass, MD, chief medical officer of MEI Pharma. "While we remain focussed on our lead drug candidate Pracinostat, we continue to be very excited by the potential of this novel mitochondrial inhibitor. ME-344 has shown broad and potent anti-tumour activity in pre-clinical studies, followed by promising single-agent activity in the clinic. Now we look forward to assessing its clinical activity in combination with chemotherapy and reporting on its progress in the months ahead."

The phase Ib study is evaluating the combination of intravenous ME-344 and topotecan (trade name Hycamtin), a drug approved by the US Food & Drug Administration for the treatment of small cell lung, ovarian and cervical cancers. Following the initial stage of the study, an independent Safety Committee determined the recommended phase II dose for continued testing of ME-344 to be 10 mg/kg in combination with 4 mg/m2 of topotecan. The combination of ME-344 and topotecan has been generally well tolerated; the most frequent side effects of the combination are fatigue and gastrointestinal disturbances.

In October 2013, results from a phase I clinical study of ME-344 were presented showing preliminary evidence of single-agent activity in patients with refractory solid tumours, including eight of 21 evaluable patients (38 per cent) who achieved stable disease or better. Notably, one patient with small cell lung cancer achieved a confirmed partial response and remained on study for 104 weeks. ME-344 was generally well tolerated in the study at doses equal to or less than 10 mg/kg delivered on a weekly schedule for extended durations. Dose limiting toxicities were observed at both the 15 and 20 mg/kg dose levels, consisting primarily of Grade 3 peripheral neuropathy.

ME-344 is a mitochondrial inhibitor drug candidate derived from MEI Pharma's isoflavone-based technology platform. In preclinical studies, ME-344 has been shown to cause cell death in multiple human tumor cell lines, including ovarian cancer stem cells, by interfering with mitochondrial energy generation. In April 2013, Ayesha Alvero, MD, Yale University School of Medicine, presented data at the American Association for Cancer Research Annual Meeting showing the ability of ME-344 to decrease tumour burden and delay recurrence in a pre-clinical in vivo model of recurrent epithelial ovarian cancer, the most lethal of all gynaecological malignancies.

MEI Pharma owns exclusive worldwide rights to all of its drug candidates, including ME-344.