Pyxis Oncology, Inc.

Pyxis Oncology is a clinical-stage oncology company focused on developing treatments for solid tumors, specifically head and neck squamous cell carcinoma (HNSCC). The company's main product candidate, micvotabart pelidotin (MICVO, formerly PYX-201), is an investigational antibody-drug conjugate (ADC). MICVO targets extradomain-B of fibronectin (EDB+FN), a specific variant of fibronectin found in the extracellular matrix (ECM) within the tumor microenvironment (TME). EDB+FN is an isoform of fibronectin that is highly expressed in various solid tumors but negligibly expressed in normal adult tissues. This protein contributes to cancer progression by promoting cell proliferation, adhesion, and migration, activating integrin signaling, stimulating angiogenesis and vascular remodeling, driving epithelial-mesenchymal transition (EMT), and establishing pre-metastatic niches. MICVO is composed of a fully human IgG1 monoclonal antibody linked to an optimized auristatin (Aur0101) microtubule inhibitor payload via a cleavable linker. Unlike traditional ADCs that bind to antigens on cancer cell surfaces, MICVO is designed to bind to EDB+FN in the tumor ECM. Extracellular proteases in acidic conditions cleave the linker, releasing the Aur0101 payload. This payload then diffuses into cancer cells, directly killing them. The dying cancer cells release the payload, which then diffuses into nearby cancer cells, killing them through a bystander effect. Additionally, the dying cancer cells release neoantigens, triggering immunogenic cell death (ICD). This three-pronged mechanism of action is believed to offer improved stability and anti-tumor activity compared to conventional ADCs.