MIT-001 / MitoImmune Therap, LG Chem - LARVOL DELTA

Evaluation of the Safety and Efficacy for Oral Mucositis Prevention of MIT-001 in Auto HSCT (ASH 2023) - "MIT-001 was administered intravenously for 30 minutes once daily before conditioning chemotherapy for four to nine days, depending on the conditioning regimens including high-dose melphalan and BMT (intravenous busulfan, melphalan, thiotepa) for auto-HSCT. The phase IIa part 1 results strongly suggest the therapeutic potential of MIT-001 to prevent severe OM in the patients with lymphoma and MM undergoing melphalan-containing conditioning followed by auto-HSCT."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Mucositis • Multiple Myeloma • Oncology • Stomatitis • Transplantation

Renoprotective Effects of MIT-001 in Ischemia-Reperfusion Injury: Modulation of Ferroptosis, ROS and Fibrotic Markers. (PubMed, J Cell Mol Med) - "In vitro, MIT-001 attenuated ferroptotic cell death and fibrotic responses in HK-2 cells challenged with TGF-β or RSL3. Additionally, MIT-001 inhibited the NF-κB/HMGB1 inflammatory axis and enhanced antioxidant defence via the Nrf2/HO-1 pathway, resulting in decreased immune infiltration and fibrosis. These findings demonstrate that MIT-001 confers renal protection by concurrently targeting oxidative stress, ferroptosis and inflammation, underscoring its promise as a therapeutic strategy to prevent AKI-to-CKD progression."

Biomarker • Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • CDH1 • GPX4 • HMGB1 • TGFB1

Inhibition of SLC25A10 promotes cellular senescence and impedes hepatocellular carcinoma progression. (PubMed, Transl Cancer Res) - "SLC25A10 promotes HCC progression by suppressing cellular senescence. Pharmacological or genetic inhibition of SLC25A10 triggers tumor suppression through HMGB1-mediated SASP signaling, positioning SLC25A10 as a promising therapeutic target for HCC intervention."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CCND1 • CDK4 • CDKN2A • HMGB1 • PCNA

MIT-001 ameliorates ferroptosis-induced mitochondrial dysfunction and enhances embryo quality in preimplantation embryos from aged female mice. (PubMed, Biomed Pharmacother) - "In vitro assays using human granulosa-like KGN cells demonstrated that MIT-001 effectively protected against Ras-selective lethal 3 (RSL3)-induced ferroptosis, restored cell viability, and recovered estradiol synthesis, indicating that steroidogenic function was restored. These findings highlight the role of ferroptosis in deterioration of embryo quality associated with maternal aging and demonstrate that MIT-001 mitigates ferroptosis-induced cellular damage. In conclusion, MIT-001 is a promising candidate for therapeutic intervention to improve clinical reproductive outcomes in aged females by targeting mitochondrial dysfunction and regulated cell death pathways."

Journal • Preclinical • Metabolic Disorders

Suppression of MRPL23 induces cellular senescence in hepatocellular carcinoma by targeting HMGB1. (PubMed, Discov Oncol) - "Finally, we confirmed that MRPL23 regulated cellular senescence by targeting HMGB1 using the inhibitor NecroX-7. These findings laid the foundation for developing potential therapies for HCC by inhibiting MRPL23 or inducing senescence."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • HMGB1 • RPL23

MIT-001 for Prevention of CCRT-Induced OM in HNSCC Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: MitoImmune Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Apr 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

Discovery of New Phenyltetrazolium Derivatives as Ferroptosis Inhibitors for Treating Ischemic Stroke: An Example Development from Free Radical Scavengers. (PubMed, J Med Chem) - "Further screening based on this strategy identified NecroX-7 and Eriodictyol-7-O-glucoside as novel ferroptosis inhibitors with highly polar structural characteristics. This approach bridges the gap between free radical scavengers and ferroptosis inhibitors, providing a foundation for research and insights into novel ferroptosis inhibitor development."

Journal • Cardiovascular • Ischemic stroke

Capella: Evaluate the Safety and Efficacy for Oral Mucositis Prevention of MIT-001 in Auto HSCT (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: MitoImmune Therapeutics | Recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P2 | Trial completion date: Apr 2024 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Jun 2024

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Lymphoma • Mucositis • Multiple Myeloma • Oncology • Stomatitis • CD34

In vitro broad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses. (PubMed, Virus Res) - "The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • HMOX1 • NQO1

Clinical Trial to Evaluate Pharmacokinetic Characteristics of MIT-001 After SC Administration in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: MitoImmune Therapeutics | Active, not recruiting ➔ Completed

Trial completion

Alleviation of hippocampal necroptosis and neuroinflammation by NecroX-7 treatment after acute seizures. (PubMed, Front Pharmacol) - "Thus, we investigated the therapeutic effects of a novel small molecule, NecroX-7, in TLE using both a low [Mg]-induced epileptiform activity model and a mouse model of pilocarpine-induced status epilepticus (SE)...Finally, western blot analysis demonstrated that NecroX-7 post-treatment after acute seizures could decrease the expression of mixed lineage kinase domain-like pseudokinase (MLKL) and phosphorylated MLKL (p-MLKL), markers for necroptosis. Taken all together, NecroX-7 has potential as a novel medication for TLE with its neuroprotective, anti-inflammatory, and anti-necroptotic effects."

Journal • CNS Disorders • Epilepsy • Inflammation • GFAP

MIT-001 for Prevention of CCRT-Induced OM in HNSCC Patients (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: MitoImmune Therapeutics | Trial completion date: Sep 2023 ➔ Dec 2024 | Trial primary completion date: Sep 2022 ➔ Apr 2024

Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

Clinical Trial to Evaluate Pharmacokinetic Characteristics of MIT-001 After SC Administration in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: MitoImmune Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed

The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice. (PubMed, Pharmaceutics) - "Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • HMGB1 • NF-κβ • TNFA

Capella: Evaluate the Safety and Efficacy for Oral Mucositis Prevention of MIT-001 in Auto HSCT (clinicaltrials.gov) - P2a | N=75 | Recruiting | Sponsor: MitoImmune Therapeutics

New P2a trial • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Lymphoma • Mucositis • Multiple Myeloma • Oncology • Stomatitis • CD34

Clinical Trial to Evaluate Pharmacokinetic Characteristics of MIT-001 After SC and IV Administration in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: MitoImmune Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open

Clinical Trial to Evaluate Pharmacokinetic Characteristics of MIT-001 After SC and IV Administration in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: MitoImmune Therapeutics

New P1 trial

MIT-001 for Prevention of CCRT-Induced OM in HNSCC Patients (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: MitoImmune Therapeutics; Not yet recruiting ➔ Recruiting; Trial completion date: Apr 2023 ➔ Sep 2023; Trial primary completion date: May 2022 ➔ Sep 2022

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

MIT-001 Restores Human Placenta-Derived Mesenchymal Stem Cells by Enhancing Mitochondrial Quiescence and Cytoskeletal Organization. (PubMed, Int J Mol Sci) - "In conclusion, while TNF-α/IFN-γ-exposed MSCs lost homeostasis and mitochondrial quiescence by becoming over-activated in response to inflammatory cytokines, MIT-001 was able to rescue mitochondrial features and cellular phenotypes. Therefore, MIT-001 has therapeutic potential for clinical applications to treat mitochondrion-related inflammatory diseases."

Journal • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • IFNG • TNFA

MitoImmune Received FDA Clearance of IND Application for MIT-001, a Novel Anti-Inflammatory/Anti-Necrotic Therapy for Oral Mucositis in CCRT patients with Head and Neck Cancer (PRNewswire) - "MitoImmune Therapeutics Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for MIT-001...for the treatment of oral mucositis...phase 2 clinical trial for the patients with HNSCC in the United States and Korea...The first HSCT patient administration is planned for the 2nd quarter of this year."

IND • New P2 trial • Head and Neck Cancer • Mucositis • Oncology • Squamous Cell Carcinoma of Head and Neck