MDX-124 / Medannex - LARVOL DELTA

MDX-124, a first-in-class annexin-A1 targeting antibody, in patients with locally advanced or metastatic solid malignancies: Preliminary safety and activity from a first-in-human phase I trial (ESMO 2025) - "Conclusions Preliminary data indicate promising safety, tolerability and anti-tumour activity of MDX-124, at doses up to and including 30 mg/kg Q2W. Module 2, exploring activity as monotherapy and in combination with standard of care therapy in distinct tumour types, will begin enrolling in 2025."

Clinical • First-in-human • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • ANXA1

MDX-124, a novel anti-ANXA1 antibody, has significant anti-cancer activity in preclinical models of osteosarcoma (Sarcoma-RC 2025) - "OS cell viability following incubation with MDX-124 alone or in combination with standard of care therapies (methotrexate, doxorubicin, cisplatin, ifosamide or etoposide) was assessed via MTT assay. Medannex plans to initiate a phase Ib study of MDX-124 in paediatric OS in late 2025. Legal entity responsible for the study Medannex Limited."

Preclinical • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • ANXA1

Identification of a multi-disease neutrophil extracellular trap (NET) gene signature and anti-NETosis therapeutic targets (SITC 2024) - "Finally, various anti-NET therapeutic targets were identified using the target genes from the disease-specific NET gene signatures, including MDX-124 (ANXA1 inhibitor), Batimastat (MMP1 inhibitor) and Plerixafor (CXCR4 antagonist). The ROC curve shows an AUC of >0.99 and the PRC curve shows an AUC of >0.99View this table:View inline View popup Download powerpoint Abstract 889 Table 1 Across all disease signatures, a combination of sum of median expression values (Sum column) and the number of diseases the gene was identified in the respective NET signature ('D' value) was used to calculate the relevance score. Top 10 scores shown"

Gene Signature • Bladder Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA1 • MMP1

Medannex awarded ‘Transforming Cancer Therapeutics’ grant to accelerate new treatment for bone cancer in children (Medannex Press Release) - "Medannex today announced an Innovate UK grant to fund a £313,000 project developing a new treatment for paediatric osteosarcoma...The ‘Transforming Cancer Therapeutics’ award will allow the Scottish biopharmaceutical company to prepare its first-in-class therapy (MDX-124) for a clinical study in this rare childhood cancer. Medannex will work in close collaboration with senior scientists at ARU (Cambridge) and world-leading paediatric oncologists to deliver this important project....Innovate UK will fund £231,000 of the project costs, with the remainder financed by Medannex."

Financing • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

ATTAINMENT: A phase Ib trial of MDX-124, a first-in-class annexin-A1 targeting antibody, alone and in combination with anti-cancer treatments, in patients with advanced solid tumors. (ASCO 2024) - "The study began enrolling patients at sites in the UK in August 2023. Cohorts at 1, 2.5 and 5 mg/kg have been completed without DLT and enrollment to cohort 4 (10 mg/kg) began in January 2024."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • ANXA1

Medannex unveils First-in-Human study of novel cancer therapy at ASCO 2024 (Medannex Press Release) - P1 | N=73 | ISRCTN78740398 (ATTAINMENT) | Sponsor: Medannex Limited | "Medannex today revealed details of the ATTAINMENT study at the American Society of Clinical Oncology (ASCO) Annual Meeting...The first patient in the ATTAINMENT study was treated with MDX-124 in August 2023. Cohorts at 1, 2.5, 5 and 10 mg/kg have now been completed, with no dose limiting toxicities observed....Once the optimum dose has been established, MDX-124 will be evaluated in newly-diagnosed cancer patients, in combination with standard-of-care chemotherapies. The study’s innovative modular design allows the efficacy of MDX-124 to be evaluated in different tumour types in an efficient manner, as clinical data emerges."

P1 data • Trial status • Oncology • Solid Tumor

A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo. (PubMed, Oncogene) - "Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1."

Journal • Preclinical • Breast Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • ANXA1

Orphan Designation: Treatment of pancreatic cancer (FDA) - Date Designated: 09/15/2023

Orphan drug • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

MDX-124, a novel annexin-A1 antibody, induces significant anti-cancer activity in multiple preclinical models (AACR 2022) - "MDX-124 therefore provides an innovative approach to cancer therapy. Medannex initiated a First-In-Human study in Q4 2021 to evaluate MDX-124 in solid malignancies known to overexpress ANXA1."

Preclinical • Colorectal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ANXA1

Efficacy of MDX-124, a novel anti-annexin-A1 antibody, in preclinical models of pancreatic cancer. (ASCO-GI 2022) - "MDX-124 demonstrated significant anti-tumor efficacy in several preclinical models of pancreatic cancer as a single agent, with increased potency observed when used in combination with 5FU. Medannex will initiate a First-In-Human study in Q4 2021 to evaluate MDX-124 in solid malignancies, including pancreatic cancer."

IO biomarker • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ANXA1

MDX-124, a novel annexin-A1 antibody, shows anti-tumor efficacy in several preclinical models of triple-negative breast cancer (SABCS 2021) - "MDX-124 binds to secreted and extracellular ANXA1 disrupting interactions with FPR1/2. This results in altered expression levels of several key cancer-related proteins preventing the activation of oncogenic signaling pathways that promote cancer progression. MDX-124 has demonstrated anti-cancer activity in several TNBC cell line and mouse models, as both a single agent and in combination with other drugs, including anti-PD-1 immunotherapy."

IO biomarker • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA1

[VIRTUAL] MDX-124, a novel annexin-A1 antibody, induces an anti-tumor immune response and wide-ranging anti-cancer activity in multiple preclinical models (AACR 2021) - "Incubation of a panel of cell lines representing several histological cancer subtypes with MDX-124 for 72h resulted in a statistically significant dose-dependent reduction in cell viability compared to control. ANXA1 expression in the subcellular compartments (nucleus, cytoplasm and membrane) was quantified in a panel of cancer cell lines via imaging flow cytometry and the anti-proliferative effect of MDX-124 was shown to correlate with membrane ANXA1 expression. Using a transwell assay, TNBC and acute myeloid leukemia cell lines exposed to MDX-124 exhibited a statistically significant reduction in migration compared to untreated controls."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Triple Negative Breast Cancer • ANXA1