AT-0174 / Antido Therap - LARVOL DELTA

CD73 MODULATES IMMUNE ESCAPE VIA TRYPTOPHAN METABOLIC REPROGRAMMING IN DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - "The therapeutic effect of an IDO1/TDO2 inhibitor was assessed in an A20 mouse model, where both the AT-0174-treated vector and CD73 OE groups showed decreased tumor growth and increased CD8+ T cell and effector CD8+ T cell infiltration compared to the untreated group... Our study uncovers a novel mechanism by which CD73 regulates immune escape in DLBCL through an adenosine-independent pathway. CD73 overexpression upregulates IDO1 and TDO2 levels by inhibiting ERK/c-Jun dephosphorylation via reduced binding to INPPL1. These findings offer new insights for combination therapies targeting CD73 in DLBCL patients with high CD73 expression."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD73 • CD8 • IDO1 • NT5E • TDO2

CD73 MODULATES IMMUNE ESCAPE VIA TRYPTOPHAN METABOLIC REPROGRAMMING IN DIFFUSE LARGE B-CELL LYMPHOMA (EHA 2025) - "The therapeutic effect of an IDO1/TDO2 inhibitor was assessed in an A20 mouse model, where both the AT-0174-treated vector and CD73 OE groups showed decreased tumor growth and increased CD8+ T cell and effector CD8+ T cell infiltration compared to the untreated group... Our study uncovers a novel mechanism by which CD73 regulates immune escape in DLBCL through an adenosine-independent pathway. CD73 overexpression upregulates IDO1 and TDO2 levels by inhibiting ERK/c-Jun dephosphorylation via reduced binding to INPPL1. These findings offer new insights for combination therapies targeting CD73 in DLBCL patients with high CD73 expression."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD73 • CD8 • IDO1 • NT5E • TDO2

Effect of CD73 on immune escape via tryptophan metabolic reprogramming in diffuse large B-cell lymphoma. (ASCO 2025) - "The therapeutic effect of an IDO1/TDO2 inhibitor was assessed in an A20 mouse model, where both the AT-0174-treated vector and CD73 OE groups showed decreased tumor growth and increased CD8+ T cell and effector CD8+ T cell infiltration compared to the untreated group... Our study uncovers a novel mechanism by which CD73 regulates immune escape in DLBCL through an adenosine-independent pathway. CD73 overexpression upregulates IDO1 and TDO2 levels by inhibiting ERK/c-Jun dephosphorylation via reduced binding to INPPL1. These findings offer new insights for combination therapies targeting CD73 in DLBCL patients with high CD73 expression."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD73 • CD8 • IDO1 • NT5E • TDO2

Blocking tryptophan catabolism reduces triple-negative breast cancer invasive capacity (Cancer Res Commun) - "...We tested a newly developed TDO2/IDO1 dual inhibitor, AT-0174, and found that it effectively inhibits TNBC TRP catabolism. Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and protein, while exogenous KYN increased invasion through AhR-mediated ZEB1 expression."

Preclinical • Triple Negative Breast Cancer

Blocking tryptophan catabolism reduces triple-negative breast cancer invasive capacity. (PubMed, Cancer Res Commun) - "Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and protein, while exogenous KYN increased invasion through AhR-mediated ZEB1 expression. Thus, dual inhibition of TDO2/IDO1 may prove efficacious against TNBC progression."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IDO1 • TDO2 • ZEB1

AT-0174, a novel dual IDO1/TDO2 enzyme inhibitor, synergises with temozolomide to improve survival in an orthotopic mouse model of glioblastoma. (PubMed, BMC Cancer) - "AT-0174 exhibited an ideal profile for adjunct treatment of glioblastomas with the first-line chemotherapeutic drug temozolomide to prevent development of CD4+ Treg-mediated chemoresistance."

IO biomarker • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Immune Modulation • Immunology • Oncology • Solid Tumor • CD4 • CD8 • IDO1 • TDO2

AT-0174, a novel dual IDO1/TDO2 enzyme inhibitor, synergises with temozolomide to improve survival in an orthotopic mouse model of glioblastoma (BMC Cancer) - "Temozolomide decreased tumour growth and improved median survival but increased the infiltration of CD4+ Tregs. AT-0174 had no significant effect on tumour growth or survival when given alone, but provided clear synergy in combination with temozolomide, further decreasing tumour growth and significantly improving survival, as well as elevating CD8+ T cell expression and decreasing CD4+ Treg infiltration....AT-0174 exhibited an ideal profile for adjunct treatment of glioblastomas with the first-line chemotherapeutic drug temozolomide to prevent development of CD4+ Treg-mediated chemoresistance."

Preclinical • Glioblastoma

Targeting tryptophan catabolism in ovarian cancer to attenuate macrophage infiltration and PD-L1 expression. (PubMed, Cancer Res Commun) - "The orally available dual IDO1/TDO2 inhibitor, AT-0174, significantly inhibited tumor progression, reduced tumor-associated macrophages, and reduced expression of immune-suppressive proteins on immune and tumor cells. These studies demonstrate the importance of TDO2 and the therapeutic potential of AT-0174 to overcome an immune-suppressed TME."

IO biomarker • Journal • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor • IL6 • PD-L1 • TDO2

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacology, and Preliminary Efficacy of AT-0174 in Subjects with Advanced Solid Malignancies (ANZCTR) - P1 | N=33 | Recruiting | Sponsor: Antido Therapeutics (Australia) Pty Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2023

Enrollment open • Trial initiation date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacology, and Preliminary Efficacy of AT-0174 in Subjects with Advanced Solid Malignancies (ANZCTR) - P1 | N=33 | Not yet recruiting | Sponsor: Antido Therapeutics (Australia) Pty Ltd

Metastases • New P1 trial • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer