AMXT 1501 / Aminex Therap - LARVOL DELTA

Sequential multi-agent therapy eradicates tumours in preclinical models of Diffuse Midline Glioma (EANO 2026) - "Inspired by the curative "Total Therapy" approach in ALL, we hypothesised that a sequentially administered multi-agent regimen could achieve meaningful benefit in DMG by targeting key vulnerabilities: epigenetic/chromatin (CBL0137-Panobinostat, CP), polyamine metabolism (DFMO-AMXT1501, DA), and the NFκB pathway (ACT001). This rationally designed sequential multi-agent "Total Therapy" approach achieves profound tumour regression and long-term survival in aggressive DMG preclinical models. The strategy warrants further optimisation and clinical translation, offering new hope for children with this devastating disease."

Preclinical • Acute Lymphocytic Leukemia • Brain Cancer • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Enhancing anti-tumor immunity by targeting polyamines in the head and neck tumor microenvironment (AHNS 2026) - "Human CD8+ T cells were isolated from healthy human donor peripheral blood mononuclear cells (PBMCs), activated, and exposed to TIF-equivalent (TIF-Eq) polyamines with or without a polyamine transporter inhibitor (AMXT 1501) to test the effect on cytokine responses... TIF polyamine levels were up to 500 times higher than that found in healthy human donor plasma (Figure). Median (interquartile ranges) for plasma vs TIF polyamines were as follows: ornithine 177 μM (101 μM, 349 μM) and 43 μM; putrescine 10-5 μM (10-5 μM, 1.13 uM) and 33 μM (15 μM, 79 μM); spermidine 5 μM (1 μM, 7 μM) and 36 μM (12 μM, 121 μM); spermine 0.8 μM (0.7 μM, 1.4 μM) and 30 μM (11 μM, 155 μM). CD8+ T cells rapidly acquire exogenous polyamines over the first 24 hours of activation, catabolize the excess, and excrete acetylated polyamines."

Biomarker • Tumor microenvironment • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • HLA-A

Dual polyamine pathway blockade synergises with irinotecan to eradicate MYC-driven medulloblastoma (ISPNO 2026) - "DFMO+AMXT-1501 is currently being evaluated in an ongoing Phase 1B/2A clinical trial in paediatric solid and CNS tumours. The potent synergy with irinotecan - already used in relapsed disease - warrants further clinical testing."

Brain Cancer • CNS Tumor • Medulloblastoma • Solid Tumor • ANXA5 • MYC

Clinical trial in progress: BCC020 a dose escalation study using difluoromethylornithine (DFMO) and AMXT-1501 followed by a randomized controlled trial of DFMO with or without AMXT-1501 for neuroblastoma, CNS tumors, and sarcomas (AACR 2026) - P1/2 | "Enrollment will occur at up to 50 Beat Childhood Cancer (BCC) Research Consortium hospitals. The study is currently open to enrollment at 3 centers, with additional centers pursuing activation."

Clinical • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Embryonal Tumor • Ewing Sarcoma • Glioma • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • LIN28B • MYCN • SLC3A2

Aminex Therapeutics Receives Second FDA Orphan Drug Designation for AMXT 1501 for Malignant Glioma Including DIPG - a Highly Aggressive Childhood Brain Cancer (PRNewswire) - "The Beat Childhood Cancer Research Consortium at Penn State College of Medicine, in partnership with Aminex, is actively enrolling patients in a national Phase 1/2 clinical trial of AMXT 1501 plus DFMO in pediatric patients with DIPG, neuroblastoma, sarcomas and other high-risk childhood cancers. The trial is planned to open at 50 clinics nationwide and enroll patients."

Orphan drug • Trial status • Diffuse Intrinsic Pontine Glioma • Glioma

Aminex Therapeutics…announced the initiation of a Phase 1b/2 clinical trial of AMXT 1501 in combination with difluoromethylornithine (DFMO) in patients with breast cancer or metastatic melanoma (PRNewswire) - "The multicenter, open-label trial (NCT07287917) will evaluate the safety, tolerability and preliminary efficacy of oral AMXT 1501 in combination with oral DFMO together with standard of care in metastatic melanoma or in pre- and post-menopausal women with ER+ HER2- breast cancer who have progressed after prior therapies. The study will include safety and dose expansion cohorts."

Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Melanoma

Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=92 | Recruiting | Sponsor: Aminex Therapeutics, Inc.

New P1/2 trial • Breast Cancer • Genetic Disorders • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

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 • 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