Pipeline

OMTX705

OMTX705 is a potential first-in-class antibody-drug conjugate (ADC) targeting fibroblast activation protein (FAP) and carrying a novel tubulysin-based payload. It is designed to treat tumors characterized by FAP-expressing cancer-associated fibroblasts (CAFs), which play a key role in tumor microenvironment (TME) remodeling and therapy resistance.

FAP-directed ADCs are engineered to selectively deliver cytotoxic agents to CAFs in the TME. They consist of a monoclonal antibody that specifically binds to FAP—a serine protease highly expressed on CAFs—conjugated to a potent cytotoxic drug. Upon binding to FAP, the ADC is internalized by CAFs, leading to intracellular release of the payload, CAF depletion, and disruption of the TME. This targeted strategy aims to inhibit tumor growth, enhance immune cell infiltration, and improve the efficacy of combination therapies by modulating the tumor-supportive stroma.

In extensive preclinical studies, OMTX705 has demonstrated potent anti-tumor activity across a range of in vitro and in vivo models of digestive tract cancers. These studies support its therapeutic potential in multiple solid tumor types, including pancreatic ductal adenocarcinoma (PDAC), gastric and gastroesophageal junction cancer, head and neck squamous cell carcinoma (HNSCC), esophageal cancer, non-small cell lung cancer (NSCLC), high-grade serous ovarian cancer (HGSOC), breast cancer, colorectal cancer (CRC), and leiomyosarcoma.

Ifebemtinib

The Target: FAP

FAP (fibroblast activation protein) is a type II transmembrane glycoprotein belonging to the prolyl oligopeptidase (POP) family. It is predominantly expressed on cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) across various solid tumors, such as breast, pancreatic, esophageal, and non-small cell lung cancer (NSCLC). In contrast, FAP shows minimal to no expression in most normal adult tissues, underscoring its potential as a selective therapeutic target.
FAP plays a crucial role in tumor progression by remodeling the extracellular matrix (ECM) and facilitating tumor cell invasion and migration. It exhibits both collagenase and gelatinase activities, which contribute to ECM degradation and promote epithelial‑mesenchymal transition (EMT) in tumor cells. Moreover, FAP‑positive CAFs secrete a variety of cytokines and growth factors that further support tumor growth and metastasis. For example, in gastric cancer, FAP expression in CAFs has been linked to enhanced tumor invasion and metastatic potential.

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