ADT-030 / ADT Pharma - LARVOL DELTA

Targeting phosphodiesterase 10 unleashes antitumor immunity by inhibiting the RAS-MAPK signaling in cancer cells and myeloid-derived suppressor cells (IMMUNOLOGY 2025) - "Moreover, ADT030-induced immunogenic cell death in cancer cells promoted dendritic cell antigen uptake and maturation. Altogether, our study provides insight into the mechanism of action of ADT-030 and underscores the potential of ADT-030 as a monotherapy or in combination with immunotherapies for treating cancers with mutant or activated RAS.Keywords: Animals Rodent; Cells Dendritic Cells Neutrophils T Cells; Molecules Protein Kinases/Phosphatases"

IO biomarker • Myeloid-derived suppressor cells • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8

A novel dual inhibitor of RAS and β-catenin signaling with advantages over mutant-specific KRAS inhibitors to escape resistance has robust antitumor efficacy and activates antitumor immunity (AACR 2025) - "Finally, deep immunophenotyping studies revealed a significant impact of ADT-030 treatment on the tumor immune microenvironment characterized by selective induction of apoptosis in myeloid-derived suppressor cells (MDSC) while increasing tumor infiltration of CD8+ T cells and natural killer cells. Together, these results support IND-enabling studies of ADT-030 as a monotherapy or in combination with immunotherapy for a broad range of KRAS-driven/dependent cancers."

Clinical • IO biomarker • Breast Cancer • Colon Cancer • Colorectal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BIRC5 • CD8 • KRAS

A novel 1st-in-class RAS/β-catenin inhibitor concurrently targets cancer cells and MDSC to reverse the immunosuppressive tumor microenvironment: antitumor activity in mouse models of breast and other cancers (SABCS 2024) - "Furthermore, ADT-030 treatment of cancer cells led to immunogenic cell death and enhanced dendritic cell activation. These results support further development of ADT-030, a novel PDE10 inhibitor capable of suppressing oncogenic RAS and β-catenin signaling, as a monotherapy or combined with immunotherapy or standard-of-care drugs for treating breast or other cancers with activated RAS and β-catenin signaling."

IO biomarker • Myeloid-derived suppressor cells • Preclinical • Tumor microenvironment • Breast Cancer • Oncology • CD8 • CTNNB1

A novel PDE10 inhibitor targets cancer cells and MDSC to reverse the immunosuppressive tumor microenvironment: antitumor activity in multiple tumor types (EORTC-NCI-AACR 2024) - "Furthermore, ADT-030 treatment of cancer cells led to immunogenic cell death and enhanced dendritic cell activation. These results support further development of ADT-030, a novel PDE10 inhibitor capable of suppressing oncogenic RAS and β-catenin signaling, as a monotherapy or combined with immunotherapy for RAS and β-catenin driven cancers."

Biomarker • IO biomarker • Late-breaking abstract • Myeloid-derived suppressor cells • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8

Survival benefit and tumor regression with a dual RAS/β-catenin inhibitor, ADT-030, in murine models of pancreatic and lung cancer (EORTC-NCI-AACR 2024) - "These results show robust and durable antitumor activity of ADT-030, a novel pan-RAS/β-catenin inhibitor, in highly aggressive and clinically relevant models of RAS-driven cancers. Thus, ADT-030 represents a development candidate for combating the challenges posed by complex mutations in PDAC, NSCLC, and other RAS-driven cancers and support its clinical evaluation as a valuable therapeutic alternative to mutant-specific KRAS or other pan-RAS inhibitors in development."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CTNNB1 • KRAS

A novel pan-RAS/β-catenin inhibitor, ADT-030, produces tumor regression in PDX models of pancreatic cancer (AACRPanCa 2024) - "ADT-030, novel dual pan-RAS/β-catenin inhibitor, showed strong and durable antitumor activity in clinically relevant and aggressive murine models of PDAC and lung cancer. ADT-030 is a promising development candidate for treatment of PDAC and other RAS-driven cancers, particularly given the complex KRAS mutation landscape of many cancers."

Gastrointestinal Cancer • Hepatology • Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ANXA5 • CTNNB1 • KRAS

A Novel RAS/β-Catenin Inhibitor, ADT-030, Induces Tumor Regression and Inhibits Metastasis with "Cures" in Multiple Mouse Cancer Models (DOT 2024) - No abstract available

Preclinical • Oncology • CTNNB1

Evaluation of a novel Pan-RAS/β-Catenin inhibitor, ADT-030, for treatment of pancreatic cancer. (ASCO 2024) - "These compelling results position ADT-030 as a novel dual pan-RAS/β-catenin inhibitor for combating the challenges posed by complex mutations in PDAC and other RAS driven cancers and support its clinical evaluation as a valuable therapeutic alternative to mutant-specific KRAS inhibitors."

Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ANXA5 • CTNNB1 • KRAS

ADT-030 is a novel dual-acting RAS/β-catenin inhibitor that potentiates antitumor immunity (AACR 2024) - "Furthermore, the ability of ADT-030 to augment the antitumor activity of immune checkpoint blockade therapy underlines its potential as a desirable immune-potentiating agent to improve the outcome of cancer immunotherapy. ADT-030 represents a development candidate ready for IND-enabling safety assessment."

IO biomarker • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CTNNB1 • KRAS

ADT-030, a novel dual-acting RAS and β-catenin inhibitor with robust antitumor activity (AACR 2023) - "These results support further development of ADT-030, a novel inhibitor of RAS and β-catenin signaling for the treatment of lung cancer and other RAS driven cancers, including those with co-occurring mutations in the Wnt/β-catenin pathway."

Lung Cancer • Oncology • Solid Tumor • CTNNB1 • EGF • LINC00473

A novel dual-acting RAS/β-catenin inhibitor activates antitumor immunity to potentiate cancer immunotherapy (AACR 2023) - "Bulk and single-cell RNAseq is being conducted to determine the impact of ADT-030 on the cell compositions and transcriptomic changes in the TME. Altogether, our study provides insight into the mechanism of action of ADT-030 and underscores the potential of ADT-030 as a monotherapy or in combination with immunotherapies for RAS and Wnt/β-catenin driven cancers."

Breast Cancer • Oncology • Solid Tumor • CD8