ME-344 / Lite Strategy, Ligand - LARVOL DELTA

Identification of NDUFV2, NDUFS7, OPA1, and NDUFA1 as biomarkers for Alzheimer's disease: Insights from oxidative stress and mitochondrial dysfunction in the hippocampus. (PubMed, J Alzheimers Dis) - "These genes showed good diagnostic performance. Potential drugs, like ME-344 and metformin hydrochloride, may be useful in AD treatment.ConclusionsNDUFV2, NDUFS7, OPA1, and NDUFA1 can serve as biomarkers for AD diagnosis."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders

Comprehensive analysis the role of cuproptosis related genes in abdominal aortic aneurysm. (PubMed, Ann Med Surg (Lond)) - "Eight NDUF subunits, including NDUFA1, NDUFA4, and NDUFB1, may also play an important role in this process. In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis."

Journal • Cardiovascular • CD4 • CDKN2A • FDX1 • LIPT1 • NDUFB1

A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer. (PubMed, Invest New Drugs) - P1 | "(Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022)."

Journal • P1 data • Colorectal Cancer • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Oncology • Pain • Solid Tumor

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=23 | Terminated | Sponsor: MEI Pharma, Inc. | N=40 ➔ 23 | Active, not recruiting ➔ Terminated; Company decision to wind down operations, close all clinical programs and evaluate strategic options

Enrollment change • Metastases • Trial termination • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Correlation of disulfidptosis and periodontitis: New insights and clinical significance. (PubMed, Arch Oral Biol) - "SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis."

Journal • Dental Disorders • Periodontitis • LRPPRC • NDUFS1 • SLC3A2 • SLC7A11

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: MEI Pharma, Inc. | Trial primary completion date: Apr 2024 ➔ Jul 2024

Metastases • Trial primary completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MEI Pharma Reports Third Quarter Fiscal Year 2024 Results and Operational Highlights (Businesswire) - "Recent Highlights...While the threshold was met to proceed to Cohort 2, following a strategic review the Company decided to continue to advance ME-344 via its ongoing development of a new formulation rather than through the addition of a new cohort of patients. The Company has already initiated research and development activity of the new formulation...The Company expects to provide an update on our formulation efforts in the first half of calendar 2025...Research and development expenses decreased by $9.9 million to $5.2 million for the quarter...The decrease was primarily related to a reduction in zandelisib program costs, as well as reduced personnel and related costs from our reductions in headcount. These decreases were partially offset by increases related to clinical trials, reformulation and manufacturing costs associated with ME-344 and increased clinical costs for the ongoing clinical study with voruciclib."

Commercial • Pipeline update • Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: MEI Pharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MEI Pharma Reports Initial Data from Clinical Study Evaluating ME-344 in Combination with Bevacizumab (Avastin) in Relapsed Metastatic Colorectal Cancer Patients (Businesswire) - P1b | N=40 | NCT05824559 | Sponsor: MEI Pharma, Inc. | "MEI Pharma...eported that 25% of evaluable patients with relapsed metastatic colorectal cancer ('mCRC') in Cohort 1 of the ongoing Phase 1b study evaluating ME-344...in combination with bevacizumab (Avastin) had no disease progression at Week 16....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."

P1 data • Colorectal Cancer

MEI Pharma Reports Second Quarter Fiscal Year 2024 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib - Oral CDK9 inhibitor in Phase 1 Study: We expect to report clinical data from the dose escalation portion of the ongoing Phase 1 clinical trial evaluating voruciclib plus venetoclax in patients with R/R AML in the first calendar quarter of 2024; (ii) ME-344 – Mitochondrial inhibitor in Phase 1b Study: We have completed enrollment in Cohort 1 of the Phase 1b clinical study evaluating ME-344 plus bevacizumab in patients with relapsed colorectal cancer. We expect to report data from Cohort 1 in the first half of calendar-year 2024."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer

A phase 1b study of the OxPhos inhibitor ME-344 in combination with bevacizumab in refractory metastatic colorectal cancer. (ASCO-GI 2024) - P1/2 | "In a CT26 colon carcinoma syngeneic murine model, ME-344 in combination with regorafenib showed significantly reduced tumor growth compared to regorafenib alone (Navarro et al... This is an open-label phase 1b study in patients ≥18 years old with metastatic colorectal cancer after failure of standard therapies, including fluoropyrimidine-, irinotecan-, and oxaliplatin-based regimens, anti-EGFR if RAS wild-type, PD/L-1-blocking antibody if MSI-H/dMMR, and BRAF-targeted therapy if BRAF V600E mutated...The study is actively enrolling, funded by MEI Pharma, and registered under NCT02100007. Clinical trial information: NCT02100007."

Combination therapy • Metastases • P1 data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • MSI

MEI Pharma to Present Design of Ongoing Clinical Study Evaluating ME-344 at ASCO GI Cancers Symposium 2024 (Businesswire) - "MEI Pharma...announced the design of the ongoing Phase 1b study of the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor ME-344 in combination with bevacizumab (Avastin) in refractory metastatic colorectal cancer patients will be presented during a poster session at the 2024 ASCO Gastrointestinal Cancers Symposium to be held January 18 – 20, 2024."

Clinical protocol • Colorectal Cancer

Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro. (PubMed, Biochem Pharmacol) - "Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy...Further, lometrexol, a purine biosynthesis inhibitor, synergistically enhanced VEN-induced apoptosis in AML cell lines...In vivo studies revealed significantly prolonged survival upon combination therapy of ME-344 and VEN in NSGS mice bearing parental or AraC-resistant MV4-11 leukemia compared to the vehicle control. This study demonstrates that ME-344 enhances VEN antileukemic activity against preclinical models of AML by suppressing OXPHOS and/or purine biosynthesis."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: MEI Pharma, Inc. | Phase classification: P1b ➔ P1

Metastases • Phase classification • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MEI Pharma Reports Fiscal Year 2023 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib - Oral CDK9 inhibitor in Phase 1 Study: Report clinical data from the ongoing Phase 1 clinical trial evaluating voruciclib plus Venclexta® (venetoclax) in patients with AML early in calendar 2024; (ii) ME-344 - Mitochondrial inhibitor in Phase 1b Study: Report clinical data from the Phase 1b clinical trial evaluating ME-344 plus Avastin® (bevacizumab) in patients with relapsed colorectal cancer in the first half of calendar-year 2024."

P1 data • Acute Myelogenous Leukemia • Colorectal Cancer

MEI Pharma Announces First Patient Dosed in Clinical Study Evaluating ME-344 Plus Bevacizumab (AVASTIN) in Patients with Previously Treated Metastatic Colorectal Cancer (MEI Pharma) - P1b | N=82 | "'As one of the most commonly diagnosed cancers, and a leading cause of cancer-related deaths in both men and women in the United States, there is a high medical need for new therapies to treat colorectal cancer, particularly for patients who have failed standard therapy and have metastatic disease,' stated Dr Howard Hochster...'This clinical study presents an important opportunity to evaluate a novel approach to treatment with the potential to bring improved benefit to patients. This target is quite unlike other treatments for colorectal cancer, and will be studied by investigators at the Rutgers Cancer Institute Metabolomics Center of Excellence in conjunction with the trial. We are excited to join with our colleagues nationally in the Academic GI Cancer Consortium (AGICC) to investigate this promising agent.'"

P1 data

MEI Pharma Announces First Patient Dosed in Clinical Study Evaluating ME-344 Plus Bevacizumab (AVASTIN) in Patients with Previously Treated Metastatic Colorectal Cancer (Businesswire) - "MEI Pharma, Inc...announced the dosing of the first patient in a Phase 1b study evaluating ME-344 in combination with bevacizumab (AVASTIN^®) in patients with previously treated metastatic colorectal cancer....The Company anticipates announcing safety and efficacy data from the first cohort of 20 ME-344 patients in the first half of 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b | N=40 | Recruiting | Sponsor: MEI Pharma, Inc. | Initiation date: May 2023 ➔ Aug 2023

Metastases • Trial initiation date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b | N=40 | Recruiting | Sponsor: MEI Pharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MEI Pharma and Infinity Pharmaceuticals Host Video Webcast Providing Overview and Update on Pending Merger to Advance Three Promising Clinical Oncology Candidates (Businesswire) - "MEI Pharma, Inc...and Infinity Pharmaceuticals, Inc...announced today that the companies will host a recorded joint video webcast that will be available at 8:00 am Eastern Time on June 19, 2023. On the webcast Mr. David Urso will provide an update on the pending merger and an overview of the combined company, which joins the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates...the webcast includes commentary and discussion with Dr. Ezra Cohen, a recognized expert in the treatment of squamous cell carcinoma of the head & neck (SCCHN)) and recently the Chief, Division of Hematology-Oncology, and Associate Director of Clinical Science at UC San Diego Moores Cancer Center."

Clinical • M&A • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b | N=40 | Not yet recruiting | Sponsor: MEI Pharma, Inc.

Metastases • New P1 trial • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Infinity Pharmaceuticals Reports Full Year 2022 Financial Results (Businesswire) - "Voruciclib, an oral CDK9 inhibitor, currently being studied in combination with venetoclax (VENCLEXTA®) in patients with hematologic malignancies. MEI has provided guidance that the ongoing Phase 1b trial is expected to report initial results from the combination regimen around the end of 2023. ME-344, a novel tumor selective mitochondrial inhibitor targeting the OXPHOS pathway, to be evaluated in combination with bevacizumab (AVASTIN®) in patients with relapsed colorectal cancer. MEI has provided guidance that data from the Phase 1b trial to support opening enrollment in an expansion cohort are expected to be reported around the end of 2023."

P1 data • Hematological Malignancies • Oncology • Solid Tumor

CNIO-BR-009 trial: Targeting mitochondrial metabolism with ME-344 in breast cancer upon bevacizumab-induced vascular normalization: A phase 0 randomized clinical trial (SABCS 2017) - "Accrual: 13 of 40 planned patients. Contact: acsalgado86@gmail.com"

Clinical • HER2 Breast Cancer

MEI Pharma and Infinity Pharmaceuticals Announce Definitive Merger Agreement to Advance Three Promising Clinical Oncology Candidates (Businesswire) - "MEI Pharma, Inc...and Infinity Pharmaceuticals, Inc...announced today that the companies entered into a definitive merger agreement for an all-stock transaction forming a company combining the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates....'Along with voruciclib and ME 344, this gives us three promising clinical-stage programs that we believe have significant potential to deliver improved therapeutic options for patients'...We prioritized the initiation of a randomized, controlled Phase 2 clinical study combining eganelisib with pembrolizumab in head and neck cancer patients which is intended to demonstrate improved clinical benefit....The merger is expected to close in mid-2023, subject to approvals by MEI Pharma and Infinity shareholders, respectively, and other customary closing conditions."

M&A • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Squamous Cell Carcinoma of Head and Neck

MEI Pharma Reports Second Quarter Fiscal Year 2023 Results and Operational Highlights (Businesswire) - "Expected Drug Candidate Pipeline Developments: (i) Voruciclib:...Report key clinical data from the ongoing Phase 1b trial evaluating voruciclib plus Venclexta® (venetoclax) in patients with acute myeloid leukemia around calendar year-end 2023; (ii) ME-344:...Report key clinical data from the Phase 1b clinical trial evaluating ME-344 plus Avastin in patients with relapsed colorectal cancer around calendar year-end 2023; (iii) Zandelisib:...Provide an update on Kyowa Kirin’s plans for continued zandelisib development in Japan for patients with relapsed or refractory indolent B-cell non-Hodgkin lymphomas."

Commercial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor