MEI Pharma, Inc. reported that 25% of evaluable patients with relapsed metastatic colorectal cancer (mCRC) in Cohort 1 of the ongoing Phase 1b study evaluating ME-344, an investigational inhibitor of mitochondrial oxidative phosphorylation (OXPHOS), in combination with bevacizumab (Avastin®) had no disease progression at Week 16. This landmark analysis exceeded the 20% threshold set in the Clinical Study Protocol to add an additional 20 patients to the study via the initiation of Cohort 2. The combination was also observed to be generally well-tolerated to date. While the threshold was met to proceed to Cohort 2, it was separately reported that following a strategic review, the Company decided to continue to advance ME-344 development via its ongoing development of a new formulation rather than through the addition of a new cohort.

The Company believes this represents the optimal approach to leveraging the potential of the program. The company has already initiated research and development activity of the new formulation with encouraging results, with the goal of increasing biological activity, improving convenience of administration and increasing commercial opportunity. Phase 1 Study Details: The ongoing Phase 1b study is evaluating ME-344 in combination with bevacizumab in patients with relapsed metastatic colorectal cancer (mCRC) after failure of standard therapies.

The combination of ME-344 and bevacizumab is intended to create metabolic synthetic lethality by leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis, forcing tumors to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344. The study was designed to evaluate ME-344 plus bevacizumab in up to two cohorts of approximately 20 patients each. The option to enroll the second cohort was conditioned upon Cohort 1 reaching a predetermined non-progression threshold of at least 20% at four months.

Patients in the study are treated until disease progression or intolerability. The primary endpoint of the study is 16-week progression free survival (?PFS?), and secondary endpoints include overall PFS, duration of response, overall survival and safety. ME-344 is administered at 10 mg/kg once weekly for 3 weeks in combination with bevacizumab every two weeks in 28-day cycles.

Cohort 1 enrolled a total of 23 patients with relapsed mCRC, with a median age 58 years (range 42-83). Patients were generally heavily pretreated; the median number of prior lines of therapy was 4 (range 1-8), 18 (78%) patients had =3 prior lines, and all patients had previously received bevacizumab and standard chemotherapy. In the first cohort, 5 of 20 (25%) evaluable patients completed 16 weeks of therapy without evidence of disease progression, exceeding the 20% predetermined threshold as set forth in the Clinical Study Protocol to proceed to Cohort 2. Although Cohort 1 exceeded the predetermined PFS threshold, the Company decided not to initiate enrollment in a second cohort in favor of continuing to advance ME-344 development via a new formulation.

Two patients are currently enrolled in Cohort 1. The Phase 1b study is being conducted at member centers of the Academic GI Cancer Consortium (AGICC), an oncology consortium dedicated to identifying new drugs to treat gastrointestinal cancers. ME-344 Plus Bevacizumab Combination: Initial Safety and Tolerability Data: ME-344 in combination with bevacizumab at the dose and schedule evaluated was generally well tolerated with no overlapping toxicities observed. Two patients (9%) discontinued therapy due to an adverse event: fatigue considered related to study drugs and sepsis considered unrelated.

The most common (=10% of patients) drug-related adverse events (all grades/grade =3) were fatigue in 8 (35%) /3 (13%) patients and abdominal pain in 3 (13%) /2 (9%) patients. ME-344 Plus Bevacizumab Combination: Initial Efficacy Data: Of the 23 patients enrolled in Cohort 1, three patients were not evaluable for 16-weeks disease progression analysis due to early discontinuation prior to first disease assessment on therapy. Of the 20 patients that were evaluable, 5 (25%) completed at least 16 weeks of therapy without disease progression, exceeding the predetermined threshold of 4 (20%) patients defined by the protocol as the condition to initiate enrollment in a second cohort.

The median PFS was 1.9 months, the 4-month PFS rate was 31.2%, and the median overall survival was 6.7 months with 15 patients censored at the time of analysis. Nine (45%) of the 20 evaluable patients had stable disease.