Next-Generation Bispecific Nanobody Targeting FGF2 and VEGF for Innovative Lung Cancer Therapy
VHH-P494 is an advanced bispecific biologic composed of two humanized nanobodies that specifically target fibroblast growth factor 2 (FGF2) and vascular endothelial growth factors (VEGF). This novel molecule is currently in the Biological Testing stage, with promising potential for the treatment of lung cancer. Engineered to leverage the powerful anti-angiogenic effects of FGF2 and VEGF inhibition, VHH-P494 harnesses state-of-the-art antibody design for effective disruption of tumor vascularization. By combining dual specificity for these key growth factors, VHH-P494 aims to address major therapeutic challenges faced in lung cancer management.
| Candidate | VHH-P494 |
| Target | fibroblast growth factor 2 (FGF2) Vascular endothelial growth factors (VEGF) |
| Modality | humanized bispecific VHH |
| Indication | Lung Cancer |
Licensing Opportunity
VHH-P494 is available for out-licensing and strategic partnerships. We welcome collaboration opportunities with industry leaders and academic partners interested in advancing this promising program toward clinical and commercial success.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P494 |
Modality
VHH-P494 is a bispecific nanobody-based therapeutic, consisting of two humanized single-domain antibodies fused to an Fc fragment of human IgG1. Each nanobody is engineered to recognize and bind independently to VEGF and bFGF, resulting in targeted and simultaneous inhibition of both signaling pathways. The single-domain structure enables a significantly smaller molecular size compared to conventional antibodies, which leads to improved tissue penetration, especially in solid tumors such as lung cancer. Nanobodies are known for exceptional stability and solubility, and their fusion with an Fc domain offers prolonged half-life and effector function. Expression in CHO cells ensures scale-up feasibility and regulatory compatibility.
Target
FGF2 and VEGF are key molecular targets intimately involved in tumor angiogenesis and progression. FGF2 is a member of the growth factor family, signaling primarily through fibroblast receptors and promoting proliferation, migration, and survival of endothelial and tumor cells. VEGF is a principal driver of angiogenesis via activation of VEGF receptors predominantly expressed on vascular endothelial cells. In lung cancer, upregulation of FGF2 and VEGF is frequently observed, contributing to enhanced neovascularization, tumor growth, and metastatic potential. Simultaneously targeting FGF2 and VEGF with VHH-P494 offers a powerful anti-angiogenic strategy by suppressing two convergent signaling axes. The dual inhibition increases the promise of overcoming resistance mechanisms and positions VHH-P494 as a highly attractive asset in lung cancer research and therapy.
Mechanism of Action
VHH-P494 exerts its anti-cancer effects by competitively binding to FGF2 and VEGF, thereby blocking their interactions with respective cellular receptors. This dual inhibitory action disrupts downstream angiogenic and proliferative signaling pathways that are critical for tumor vascularization and growth. By impairing the cross-talk between cancerous and stromal cells via FGF2 and VEGF, VHH-P494 effectively acts as an angiogenesis inhibitor and signal transduction modulator. The nanobody format further enables modular engineering for the development of advanced therapeutics such as bispecifics and antibody-drug conjugates. This platform technology offers versatility for future innovations in oncology, expanding the application of nanobodies beyond single-target blockade.
Lung Cancer
Lung cancer remains one of the most prevalent and lethal malignancies globally, with significant morbidity and mortality. It encompasses various histologic subtypes, most commonly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Standard treatments include surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapies. Despite advancements in therapeutic modalities, lung cancer diagnosis often occurs at an advanced stage, resulting in poor prognoses and limited long-term survival. Current pharmacological interventions are constrained by drug resistance, adverse effects, and a lack of durable efficacy in unselected patient populations. There remains a high unmet medical need for new agents that can more effectively target tumor biology and microenvironment. Dual inhibition of angiogenic pathways by VHH-P494 represents an innovative approach with the potential to overcome resistance to existing therapies, enhance tumor control, and deliver broader patient benefit.