BMX-010 / BioMimetix - LARVOL DELTA

Manganese Porphyrin Treatment Improves Redox Status Caused by Acute Compressive Spinal Cord Trauma. (PubMed, Antioxidants (Basel)) - "This study aimed to assess the therapeutic potential of the manganese porphyrins [MnTE-2-PyP]5+ (MnPI) and [MnT(5-Br-3-E-Py)P]5+ (MnPII) in acute compressive spinal cord trauma in rats...Additionally, MnPs improved the expression of IL-6, neurotrophic markers, and apoptotic factors. In conclusion, treatment with MnPs attenuated the oxidative stress and ER stress caused by acute compressive spinal cord trauma and restored spinal expression of neurotrophic mediators."

Journal • Anesthesia • Cardiovascular • CNS Disorders • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Oncology • Psychiatry • GPX1 • HSPA5 • IL6

Redox Regulation of Platelet-Neutrophil Interactions in Acute Lung Injury From Staphylococcus Aureus Pneumonia (ATS 2025) - "We observe the same protective effects in wild-type (WT) mice pre-treated with MnTE-2-PyP SOD mimetic...We show that phosphorylation of CLEC-2 downstream signaling proteins Syk, SHP-2, PLCγ2, and LAT that lead to platelet activation, is subject to redox regulation. Together this work offers an important insight into EC-SOD effects on platelet functionality, and a novel redox-based mechanism of platelet activation in clinically-relevant model of acute lung injury from bacterial pneumonia."

Acute Lung Injury • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • PLCG2 • SYK

Increased Circulating Extracellular Superoxide Dismutase Attenuates Platelet-Neutrophil Interactions. (PubMed, Am J Respir Cell Mol Biol) - "Furthermore, pre-treatment with a MnTE-2-PyP SOD mimetic protects against S. aureus-induced platelet activation, pulmonary neutrophilia, and acute lung injury. Our data highlight the redox regulation of platelet activation as a driver of S. aureus-induced acute lung injury."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Manganese porphyrin-based treatment improves fetal-placental development and protects against oxidative damage and NLRP3 inflammasome activation in a rat maternal hypothyroidism model. (PubMed, Redox Biol) - "This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats...However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface."

Journal • Preclinical • Endocrine Disorders • Gynecology • CASP1 • CAT • GPX1 • HIF1A • HSPA5 • IL10 • IL18 • IL1B • IL6 • NLRP3 • TNFA

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=103 | Terminated | Sponsor: BioMimetix JV, LLC | Trial completion date: Dec 2024 ➔ Apr 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Dec 2023; Funding constraints

Trial completion date • Trial primary completion date • Trial termination • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: BioMimetix JV, LLC | Recruiting ➔ Active, not recruiting | N=224 ➔ 103

Enrollment change • Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=224 | Recruiting | Sponsor: BioMimetix JV, LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=224 | Active, not recruiting | Sponsor: BioMimetix JV, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=224 | Recruiting | Sponsor: BioMimetix JV, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Evaluation of Topical Application of BMX-010 in Subjects With Rosacea (clinicaltrials.gov) - P2 | N=60 | Suspended | Sponsor: BioMimetix JV, LLC | Trial completion date: Nov 2022 ➔ Mar 2025 | Active, not recruiting ➔ Suspended | Trial primary completion date: Sep 2022 ➔ Sep 2024

Trial completion date • Trial primary completion date • Trial suspension • Dermatology • Rosacea

BMX-DERM-02: A Clinical Trial of BMX-010 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - P2 | N=224 | Not yet recruiting | Sponsor: BioMimetix JV, LLC

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure. (PubMed, Redox Biol) - "MnTE-2-PyP reduced myofibroblast differentiation, improved mitochondrial health by releasing the block on the mitochondrial electron transport chain, enhanced ATP production efficiency, and restored mitochondrial dynamics and metabolism in the irradiated-hyperglycemic prostate fibroblasts. Therefore, we are proposing that one of the mechanisms that MnTE-2-PyP protects prostate fibroblasts from irradiation and hyperglycemia-mediated damage is by protecting the mitochondrial health in diabetic prostate cancer patients."

Journal • Diabetes • Fibrosis • Genito-urinary Cancer • Immunology • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor

Thermal Stability Kinetics and Shelf Life Estimation of the Redox-Active Therapeutic and Mimic of Superoxide Dismutase Enzyme, Mn(III) meso-Tetrakis(N-ethylpyridinium-2-yl)porphyrin Chloride (MnTE-2-PyPCl, BMX-010). (PubMed, Oxid Med Cell Longev) - "Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl, BMX-010, and AEOL10113) is among the most studied superoxide dismutase (SOD) mimics and redox-active therapeutics, being currently tested as a drug candidate in a phase II clinical trial on atopic dermatitis and itch. According to the R1 modelling of the isothermal decomposition data, the estimated shelf life value for 10% decomposition (t ) of MnTE-2-PyPCl at 25°C was approximately 17 years, which is consistent with the high solid-state stability of the compound. These results represent the first study on the solid-state decomposition kinetics of Mn(III) 2-N-alkylpyridylporphyrins, contributing to the development of this class of redox-active therapeutics and SOD mimics and providing supporting data to protocols on purification, handling, storage, formulation, expiration date, and general use of these compounds."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Topical Application of BMX-010 in Subjects With Atopic Dermatitis and Plaque Psoriasis (clinicaltrials.gov) - P2; N=139; Completed; Sponsor: BioMimetix JV, LLC; Active, not recruiting ➔ Completed; N=300 ➔ 139; Trial completion date: Dec 2022 ➔ Jul 2021; Trial primary completion date: Dec 2022 ➔ Jul 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Psoriasis

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions. (PubMed, Int J Mol Sci) - "The ortho compounds MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001) and MnTnHex-2-PyP are able to redox cycle with ascorbate whereby producing HO which is subsequently coupled with Cu(I) to produce the OH radical essential for HA degradation. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins."

Journal • Oncology

Ascorbate-dependent and ascorbate-independent Mn porphyrin cytotoxicity: anticancer activity of Mn porphyrin-based SOD mimics through ascorbate-dependent and -independent routes. (PubMed, Redox Rep) - "Six compounds: MnTE-2-PyP with a short ethyl chain on the pyridyl ring; MnTnHexOE-2-PyP and MnTnOct-2-PyP with linear 8-atom alkyl chains, but the former with an oxygen atom within the alkyl chain; MnTE-2-PyPhP and MnTPhE-2-PyP with pyridyl and phenyl substituents, were investigated...Amphiphilic MnPs with suitable structure damage sensitive cellular constituents, leading to the suppression of proliferation and loss of viability. Design of compounds interacting directly with sensitive cellular targets is highly promising in the development of anticancer drugs with high selectivity and specificity."

Journal • Oncology

HO-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways. (PubMed, Oxid Med Cell Longev) - "The lead Mn porphyrins, namely, MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001), and MnTnHex-2-PyP, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP is in Phase II clinical trial on atopic dermatitis and itch."

Journal • Review • Anal Carcinoma • Atopic Dermatitis • Brain Cancer • Dermatitis • Dermatology • Gastrointestinal Cancer • Glioma • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • BCL2

MnTE-2-PyPDisrupts Staphylococcus aureus Biofilms in a Novel Fracture Model. (PubMed, J Orthop Res) - "We postulated that a potent redox-active metalloporphyrin MnTE-2-PyP (chemical name: manganese (II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) that scavenges reactive species and modulates the redox state to a reduced state, would improve the effect of antibiotic treatment for a biofilm-associated infection...In vitrocrystal violet assay of biofilm structure and corresponding NBT assay for reactive oxygen species (ROS) demonstrated that MnTE-2-PyP decreased the biofilm structure,and reduced ROS in a correlated and dose-dependent manner. The biofilm structure is redox-sensitive in S. aureus and an ROS scavenger improved the effectof antibiotic therapy in model of biofilm-associated infections."

Journal • Musculoskeletal Diseases • Orthopedics

Redox-Active Drug, MnTE-2-PyP, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function. (PubMed, Oxid Med Cell Longev) - "Herein, we describe the effects of the redox-active therapeutic Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP), on rat heart as an entry to new strategies to circumvent cardiomyopathies. MnTE-2-PyP prevents and treats cardiac arrhythmias in rats. In contrast to most antiarrhythmic drugs, MnTE-2-PyP preserves cardiac contractile function, arising, thus, as a prospective therapeutic for improvement of cardiac arrhythmia treatment."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular

Evaluation of Topical Application of BMX-010 in Subjects With Acne Vulgaris. (clinicaltrials.gov) - P2; N=2; Terminated; Sponsor: BioMimetix JV, LLC; Suspended ➔ Terminated; Enrollment stopped for chemistry work on investigational product.

Clinical • Trial termination • Acne Vulgaris • Dermatology

Evaluation of Topical Application of BMX-010 in Subjects With Rosacea (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: BioMimetix JV, LLC; Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Rosacea

Evaluation of Topical Application of BMX-010 in Subjects With Acne Vulgaris. (clinicaltrials.gov) - P2; N=2; Suspended; Sponsor: BioMimetix JV, LLC; N=60 ➔ 2; Trial completion date: Nov 2022 ➔ Aug 2020; Recruiting ➔ Suspended

Enrollment change • Trial completion date • Trial suspension • Acne Vulgaris • Dermatology

MnTE-2-PyP Suppresses Prostate Cancer Cell Growth via HO Production. (PubMed, Antioxidants (Basel)) - "However, in LNCaP cells, MnTE-2-PyP caused an increase in low RNA population and sub-G population of cells, which indicates that MnTE-2-PyP treatment may cause cellular quiescence or direct cancer cell death. The protein oxidative modifications and mitotic catastrophes caused by MnTE-2-PyP may be the major contributors to cell growth inhibition in PC3 cells, while in LNCaP cells, tumor cell quiescence or cell death appears to be major factors in MnTE-2-PyP-induced growth inhibition."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNS1

Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo. (PubMed, Blood Adv) - "We show for the first time the therapeutic effectiveness of the redox-active manganese (Mn) porphyrins MnTnBuOE-2-PyP5+ (MnBuOE; BMX-001) and MnTE-2-PyP5+ (MnE; BMX-010, AEOL10113) to treat established vaso-occlusion in a humanized sickle mouse model of an acute vaso-occlusive crisis using intravital microscopy. Our data suggest that Mn porphyrins, likely by repressing NOX-mediated adhesive function of SSRBCs and activated leukocytes, could represent a novel, safe therapeutic intervention to treat or prevent the establishment of acute pain crises. These NOX-targeted antioxidants merit further assessment in SCD clinical trials."

Journal • Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

MnTE-2-PyP, a manganese porphyrin, reduces cytotoxicity caused by irradiation in a diabetic environment through the induction of endogenous antioxidant defenses. (PubMed, Redox Biol) - "MnTE-2-PyP increases NRF2 mediated cytoprotection by increasing NRF2 protein expression and DNA binding. Therefore, we are proposing that, MnTE-2-PyP protects fibroblasts from irradiation and hyperglycemia damage by enhancing the NRF2- mediated pathway in diabetic prostate cancer patients, undergoing radiotherapy."

Journal