– Cohort 1 Exceeds Predetermined
Non-Progression Threshold in the Ongoing Phase 1b Study –
– ME-344 in Combination with Bevacizumab was
Generally Well-tolerated with no Evidence of Overlapping Toxicity
–
– MEI to Continue Advancing ME-344 via
Development of a New Formulation with the Potential to Increase
Biological Activity, Patient Convenience and Commercial Opportunity
–
MEI Pharma, Inc. (Nasdaq: MEIP), a clinical-stage pharmaceutical
company evaluating novel drug candidates to address known
resistance mechanisms to standard-of-care cancer therapies, today
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 today 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.
"The data reported today, including progression-free survival,
overall survival, and safety results of the combination, represent
an important development supporting the potential of ME-344 in
combination with Avastin to induce synthetic lethality in tumors
using a completely novel therapeutic strategy,” said Richard
Ghalie, chief medical officer of MEI Pharma. “The development of a
new formulation with enhanced biologic activity is aimed at further
improving patient outcomes and treatment convenience in a
well-tolerated manner.”
“At MEI we are committed to our mission of developing novel drug
candidates to address known resistance mechanisms to
standard-of-care cancer therapies, and ME-344 holds significant
potential as a novel therapeutic strategy to advance this mission,”
said David Urso, president and chief executive officer of MEI
Pharma. “We believe that the best approach to optimize the
potential of ME-344 for patients, prioritize resource utilization,
and build value for shareholders, is to continue advancing the
program via development of a new formulation of ME-344. In the
short term, this plan will reduce expenditures on the ME-344
program and ultimately, if successful, create an improved
formulation for continued clinical development.”
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.
About ME-344
ME-344, an investigational drug candidate, is a novel inhibitor
of mitochondrial oxidative phosphorylation (OXPHOS), a fundamental
metabolic pathway involved in the production of adenosine
triphosphate (ATP) in the mitochondria. ATP provides energy to
drive many metabolic cell processes, including division,
proliferation, and growth. By disrupting the production of ATP,
ME-344 has been shown to induce cancer cell death in nonclinical
models and was associated with antitumor activity in clinical
studies.
The two main sources of ATP production in cells are OXPHOS and
glycolysis; the latter is highly active in most tumors.
Anti-angiogenics, like the vascular endothelial growth factor
(“VEGF”) inhibitor bevacizumab (Avastin®), have the potential to
normalize vasculature and decrease reliance on glycolysis. The
resulting reduction in glycolysis may trigger an increased
dependence on mitochondrial ATP production for energy to support
continued tumor proliferation. In such cases of tumor plasticity,
the combination of ME-344 and bevacizumab may induce metabolic
synthetic lethality, providing a novel therapeutic strategy.
Specifically, leveraging the ability of antiangiogenics like
bevacizumab to reduce glycolysis and force tumor cells to switch to
mitochondrial respiration via OXPHOS, which is inhibited by ME-344,
may reduce access to ATP needed for cell division and growth in
tumors.
This approach was first clinically evaluated in a multicenter,
investigator-initiated, randomized, open-label, window of
opportunity clinical study, evaluating ME-344 (3 doses) plus
bevacizumab (1 dose) in 42 women with early HER2-negative breast
cancer. Study results demonstrated significant biological antitumor
activity as measured by a reduction in the proliferative biomarker
Ki-67 compared to placebo. The combination appeared to be generally
well tolerated. The data from this study were consistent with
preclinical data suggesting that combining ME-344 can augment
anti-angiogenic therapy and provided support for continued
evaluation of the combination of ME-344 with bevacizumab and other
VEGF inhibitors. An earlier Phase 1 clinical study evaluating
ME-344 as a single-agent in patients with refractory solid tumors
also demonstrated anti-tumor activity, further supporting the
potential of inhibition of OXHPOS by ME-344 as a promising
therapeutic modality.
About MEI Pharma
MEI Pharma, Inc. (Nasdaq: MEIP) is a clinical-stage
pharmaceutical company committed to developing novel and
differentiated cancer therapies. We build our pipeline by acquiring
promising cancer agents and creating value in programs through
development, strategic partnerships, out-licensing and
commercialization, as appropriate. Our approach to oncology drug
development is to evaluate our drug candidates in combinations with
standard-of-care therapies to overcome known resistance mechanisms
and address clear medical needs to provide improved patient
benefit. The drug candidate pipeline includes voruciclib, an oral
cyclin-dependent kinase 9 ("CDK9") inhibitor, and ME-344, a novel
small molecule inhibitor of mitochondrial oxidative phosphorylation
(OXPHOS). For more information, please visit www.meipharma.com.
Follow us on X (formerly Twitter) @MEI_Pharma and on LinkedIn.
Forward-Looking Statements
Certain information contained in this press release that are not
historical in nature are “forward-looking statements” within the
meaning of the “safe harbor” provisions of the Private Securities
Litigation Reform Act of 1995 including, without limitation,
statements regarding: the potential, safety, efficacy, and
regulatory and clinical progress of our product candidates,
including the anticipated timing for initiation of clinical trials
and release of clinical trial data and our expectations surrounding
potential regulatory submissions, approvals and timing thereof, our
business strategy and plans; the sufficiency of our cash, cash
equivalents and short-term investments to fund our operations; and
our ability to fund future capital returns. You should be aware
that our actual results could differ materially from those
contained in the forward-looking statements, which are based on
management’s current expectations and are subject to a number of
risks and uncertainties, including, but not limited to our failure
to successfully commercialize our product candidates; the
availability or appropriateness of utilizing the FDA’s accelerated
approval pathway for our product candidates; final data from our
pre-clinical studies and completed clinical trials may differ
materially from reported interim data from ongoing studies and
trials; costs and delays in the development and/or FDA approval, or
the failure to obtain such approval, of our product candidates;
uncertainties or differences in interpretation in clinical trial
results; uncertainty regarding the impact of rising inflation and
the increase in interest rates as a result; potential economic
downturn; geopolitical conflicts; activist investors; our inability
to maintain or enter into, and the risks resulting from, our
dependence upon collaboration or contractual arrangements necessary
for the development, manufacture, commercialization, marketing,
sales and distribution of any products; competitive factors; our
inability to protect our patents or proprietary rights and obtain
necessary rights to third party patents and intellectual property
to operate our business; our inability to operate our business
without infringing the patents and proprietary rights of others;
general economic conditions; the failure of any products to gain
market acceptance; our inability to obtain any additional required
financing; technological changes; government regulation; changes in
industry practice; and one-time events. We do not intend to update
any of these factors or to publicly announce the results of any
revisions to these forward-looking statements. Under U.S. law, a
new drug cannot be marketed until it has been investigated in
clinical studies and approved by the FDA as being safe and
effective for the intended use.
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version on businesswire.com: https://www.businesswire.com/news/home/20240411126658/en/
David A. Walsey MEI Pharma Tel: 858-369-7104
investor@meipharma.com
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