AMXT 1501 / Aminex Therap - LARVOL DELTA

Fusion-specific regulation of polyamine synthesis sensitizes to BCL-XL inhibition in TCF3::PBX1+ B-ALL (ASH 2025) - "In vivo combination of DFMO + polyamine-transport inhibitor AMXT-1501 and BCL-XL PROTAC DT2216 in TCF3::PBX1+ PDX models demonstrated promising antileukemic efficacy seen byreduced leukemic burden in spleen and bone marrow at the end of treatment.Collectively, our findings identify the fusion TF TCF3::PBX1 as a previously unrecognized positive regulatorof polyamine synthesis, acting via ODC1 upregulation, positioning ODC1 as a promising target in thissubtype. We further demonstrated that targeting polyamine synthesis induces transcriptional changes inessential B-cell developmental and metabolic programs, uncovering opportunities to target syntheticlethal principles through BCL-XL. The recent approval of DFMO for neuroblastoma maintenance therapyhighlights its translational potential not only in TCF3::PBX1+ B-ALL but warrants exploration of thisrational combination in other MYC-driven and/or polyamine-addicted B-ALL, especially in therelapsed/refractory context."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Neuroblastoma • Pediatrics • Solid Tumor • Targeted Protein Degradation • BCL2L1 • MYC • ODC1 • PBX1 • TCF3

Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas (clinicaltrials.gov) - P1/2 | N=289 | Recruiting | Sponsor: Milton S. Hershey Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Embryonal Tumor • Ewing Sarcoma • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Sarcoma • Solid Tumor

Polyamine pathway blockade sensitises MYC-driven medulloblastoma to chemotherapy (EANO 2025) - "Inhibition of polyamine synthesis with DFMO, a clinically safe ODC1 inhibitor, showed limited efficacy alone; however, compensatory activation of polyamine transport led us to combine it with a transport inhibitor (AMXT 1501). Targeting the polyamine pathway represents a promising, clinically translatable strategy across aggressive paediatric brain tumours. Synergy with irinotecan—a chemotherapeutic already used in relapsed medulloblastoma—underscores the translational relevance of this approach, which is currently being evaluated in an ongoing Phase 1B/2A clinical trial in children with solid tumours, including CNS malignancies."

Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Medulloblastoma • Neuroblastoma • Oncology • Solid Tumor • ANXA5 • MYC

Aminex Therapeutics, Inc. is currently preparing to initiate clinical trials to further evaluate the safety and efficacy of AMXT 1501 in combination with DFMO in metastatic melanoma and in breast cancer. (PRNewswire)

New trial • Breast Cancer • Melanoma

Aminex Therapeutics Announces FDA Orphan Drug Designation Granted to AMXT 1501 in Combination with DFMO for the Treatment of Neuroblastoma (PRNewswire) - "The Beat Childhood Cancer Research Consortium at Penn State College of Medicine is currently initiating a Phase 1/2 clinical trial in pediatric patients who will be administered AMXT 1501 in combination with DFMO entitled 'A Dose Escalation Study Using Eflornithine (DFMO) and AMXT 1501 Followed by a Randomized Controlled Trial of DFMO with or without AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas'"

Orphan drug • Trial status • Neuroblastoma

Phase I dose-escalation trial of AMXT 1501 dicaprate plus difluoromethylornithine: a dual-agent approach targeting immunosuppressive polyamine metabolism. (PubMed, ESMO Open) - P1 | "Overall, AMXT 1501 in combination with DFMO was safe and tolerated with evidence of preliminary clinical activity. The RP2D was determined to be AMXT 1501 600 mg twice daily plus DFMO 500 mg."

Journal • P1 data • Oncology • Solid Tumor

Polyamine depletion limits progression of acute leukaemia. (PubMed, Int J Cancer) - "Responsiveness to DFMO was linked to decreased levels of its molecular target, the rate-limiting polyamine biosynthesis enzyme ODC1, and of the polyamine transporters ATP13A2 and ATP13A3. Increased expression of c-MYC was associated with enhanced sensitivity to the combination of DFMO and AMXT 1501, suggesting this oncoprotein as a potential predictive marker of response to the drug combination. In conclusion, targeting polyamine biosynthesis and polyamine uptake limits disease progression in models of acute leukaemia, supporting further preclinical and clinical investigation into this approach for acute leukaemia."

Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • KMT2A • MYC

The polyamine transporter ATP13A3 mediates difluoromethylornithine-induced polyamine uptake in neuroblastoma. (PubMed, Mol Oncol) - "This finding resulted in the clinical development of polyamine transport inhibitors, including AMXT 1501, which is presently under clinical investigation in combination with DFMO...An association between high ATP13A3 expression and poor survival in neuroblastoma further supports a role of this transporter in neuroblastoma progression. Thus, this study identified ATP13A3 as a critical regulator of basal and DFMO-induced polyamine uptake and a novel therapeutic target for neuroblastoma."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

Difluoromethylornithine (DFMO) and AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas (clinicaltrials.gov) - P1/2 | N=253 | Not yet recruiting | Sponsor: Milton S. Hershey Medical Center | Initiation date: Feb 2025 ➔ Oct 2025

Trial initiation date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ewing Sarcoma • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Sarcoma • Solid Tumor

Oral AMXT 1501 Dicaprate in Combination With IV DFMO (clinicaltrials.gov) - P1/2 | N=15 | Terminated | Sponsor: Aminex Therapeutics, Inc. | N=56 ➔ 15 | Active, not recruiting ➔ Terminated; Required re-formulation of DFMO from IV to capsule to maintain safety

Enrollment change • Trial termination • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colon Cancer • Colorectal Cancer • Diffuse Midline Glioma • Endocrine Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Malignant Glioma • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Phase I dose-escalation trial of AMXT 1501 dicaprate plus difluoromethylornithine: a dual agent approach targeting immunosuppressive polyamine metabolism (SITC 2024) - "An informed consent document approved by each study center's IRB was signed by the patient or their legally authorized representative and the authorized person obtaining the informed consent before the patient was entered in the study. Institutional Review Boards (IRBs) included The University of Texas MD, Anderson Cancer Center, Institutional Review Board (approval number 2018-0524_MOD004) for MD Anderson; Salus IRB Ethical Review Board (approval number NXSAT18.18) for Texas Oncology, San Antonio Medical Center; Integ Review Ethical Review Board (approval number NXSAT18.18) for Texas Oncology, Austin Midtown, and WCG IRB (approval number 20182572) for Virginia Cancer Specialists."

P1 data • Oncology • Solid Tumor

Difluoromethylornithine (DFMO) and AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas (clinicaltrials.gov) - P1/2 | N=253 | Not yet recruiting | Sponsor: Milton S. Hershey Medical Center | Trial completion date: Jul 2034 ➔ Dec 2034 | Initiation date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Jul 2032 ➔ Dec 2032

Trial completion date • Trial initiation date • Trial primary completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ewing Sarcoma • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Sarcoma • Solid Tumor

Oral AMXT 1501 Dicaprate in Combination with IV DFMO (clinicaltrials.gov) - P1/2 | N=56 | Active, not recruiting | Sponsor: Aminex Therapeutics, Inc. | Suspended ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colon Cancer • Colorectal Cancer • Diffuse Midline Glioma • Endocrine Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Oral AMXT 1501 Dicaprate in Combination With IV DFMO (clinicaltrials.gov) - P1/2 | N=56 | Suspended | Sponsor: Aminex Therapeutics, Inc. | Recruiting ➔ Suspended

Combination therapy • Trial suspension • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colon Cancer • Colorectal Cancer • Diffuse Midline Glioma • Endocrine Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Oral AMXT 1501 Dicaprate in Combination With IV DFMO (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Aminex Therapeutics, Inc. | Phase classification: P1b/2a ➔ P1/2 | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Combination therapy • Phase classification • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colon Cancer • Colorectal Cancer • Diffuse Midline Glioma • Endocrine Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth. (PubMed, Cell Death Differ) - "In contrast, a combination lorlatinib/AMXT-1501 treatment resulted in synergistic inhibition of cell growth in ALK-driven NB cell lines. Taken together, our results identify a novel role for the ALK receptor tyrosine kinase (RTK), working in concert with the MARCH11 E3 ligase, in regulating SLC3A2 protein stability and function in NB cells. The synergistic effect of combined ALK and polyamine transport inhibition shows that ALK/MARCH11/SLC3A2 regulation of amino acid transport is important for oncogenic growth and survival in NB cells."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • ALK • ALKAL2 • SLC3A2

Difluoromethylornithine (DFMO) and AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas (clinicaltrials.gov) - P1/2 | N=253 | Not yet recruiting | Sponsor: Milton S. Hershey Medical Center

New P1/2 trial • Brain Cancer • CNS Tumor • Embryonal Tumor • Ewing Sarcoma • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Sarcoma • Solid Tumor

AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria. (PubMed, Emerg Microbes Infect) - "AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens."

Gram positive • Journal • Infectious Disease • Pneumonia

Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation in Streptococcus pneumoniae. (PubMed, Biomolecules) - "This study highlights the complexity of polyamine-mediated regulation in S. pneumoniae, particularly capsule biosynthesis. Our findings offer valuable insights into potential therapeutic targets for modulating capsules in a polyamine-dependent manner, a promising avenue for intervention against S. pneumoniae infections."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Oral AMXT 1501 Dicaprate in Combination With IV DFMO (clinicaltrials.gov) - P1b/2a | N=56 | Recruiting | Sponsor: Aminex Therapeutics, Inc. | Trial completion date: Mar 2024 ➔ Sep 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colon Cancer • Colorectal Cancer • Diffuse Midline Glioma • Endocrine Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Addition of AMXT1501 (polyamine uptake inhibitor) plus DFMO (polyamine synthesis inhibitor) to standard-of-care chemotherapy/anti-GD2 antibody in the TH-MYCN mouse neuroblastoma model, enhances efficacy compared to addition of DFMO alone. (AACR-NCI-EORTC 2023) - No abstract available

Preclinical • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • MYCN

Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jan 2026 ➔ Sep 2027 | Initiation date: Mar 2023 ➔ Aug 2023 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial initiation date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

A first-in-human pharmacodynamic evaluation of dual polyamine depletion for patients with high-grade gliomas. (ASCO 2023) - P1 | "Background: No drug has improved survival for patients with high-grade gliomas (HGGs) since temozolomide in 2005...As such, in a Phase 0 trial, we will evaluate in situ glioma responses to polyamine depletion via ODC inhibition (Difluoromethylornithine, DFMO), with or without blockade of polyamine uptake (AMXT 1501), to identify candidate extracellular biomarkers of target engagement and cytotoxicity...The secondary outcomes of this study are to (1) determine the impact of polyamine depletion on polyamine abundance and the global extracellular metabolome within live human gliomas, in situ, and (2) assess the feasibility of longitudinal microdialysis for pharmacodynamic analysis within live human gliomas in situ in the post-operative setting. Clinical trial information: NCT05717153."

Clinical • P1 data • PK/PD data • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Glioma Metabolic Feedback In Situ: A First-In-Human Pharmacodynamic Trial of Difluoromethylornithine + AMXT-1501 Through High-Molecular Weight Microdialysis. (PubMed, Neurosurgery) - "Limited mechanistic feedback from individual patients' gliomas hampers clinical translation of novel therapies. This pilot Phase 0 study will provide in situ feedback during DFMO + AMXT-1501 treatment to determine how high-grade gliomas respond to polyamine depletion."

Journal • P1 data • PK/PD data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Oral AMXT 1501 Dicaprate in Combination With DFMO (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Aminex Therapeutics, Inc. | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Glioblastoma • Lung Cancer • Oncology • Solid Tumor • ALK