Innovative Biparatopic Nanobody Targeting ALB and LRP5 for Novel Cancer Therapy
VHH-P717 is a humanized nanobody therapeutic currently in the Biological Testing stage, designed to treat cancer by targeting two key molecules: albumin (ALB) and low-density lipoprotein receptor-like protein 5 (LRP5). This advanced construct combines the unique properties of nanobodies with dual specificity for ALB and LRP5, enhancing both stability and targeting precision. The program leverages the growing scientific understanding of ALB and LRP5 involvement in cancer progression and therapeutic resistance. With its favorable developability profile and modular architecture, VHH-P717 holds significant promise as a next-generation anticancer therapy.
| Candidate | VHH-P717 |
| Target | albumin (ALB) LDL receptor related protein 5 (LRP5) |
| Modality | humanized bispecific VHH |
| Indication | Cancer |
Licensing Opportunity
VHH-P717 is available for out-licensing to partners seeking innovative biologics for oncology. We welcome strategic collaborations for further development, clinical validation, and commercialization.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P717 |
Modality
VHH-P717 is a half-life extended, biparatopic nanobody construct comprised of two single-domain antibodies directed against LRP5, further fused with an anti-ALB VHH antibody for enhanced pharmacokinetic properties. Produced via Pichia pastoris expression, the molecule benefits from the inherent stability, low immunogenicity, and small molecular size of nanobodies. These features collectively facilitate superior tissue penetration and tumor access, which are highly advantageous for cancer therapy. The modular and compact structure supports bioengineering flexibility and manufacturability, positioning VHH-P717 as a robust candidate for a diverse range of oncology applications.
Target
ALB and LRP5 are distinct molecular targets with complementary roles in cancer biology. ALB is a major plasma protein involved in molecular transport and homeostasis, ubiquitously present across tissues and serving as a carrier for various drugs, thus facilitating half-life extension in biotherapeutics. LRP5 is a transmembrane receptor predominantly expressed in several tissues and plays a critical role in Wnt/β-catenin signaling, cell proliferation, and differentiation. Dysregulation of LRP5 has been associated with tumorigenesis and metastatic behavior in cancers. Targeting ALB provides pharmacological benefits, while engaging LRP5 offers direct anti-tumor action. Strategic dual targeting in VHH-P717 not only enhances drug delivery but also disrupts tumor-promoting pathways, underscoring its high-value positioning for cancer therapy development.
Mechanism of Action
VHH-P717 functions through a dual-action mechanism: it specifically binds ALB to achieve prolonged systemic circulation, while simultaneously targeting LRP5 to interfere with oncogenic signaling pathways. The anti-ALB component increases serum half-life by leveraging the natural abundance and long persistence of ALB in circulation. The anti-LRP5 domains enable direct engagement and modulation of LRP5-mediated signaling, potentially impacting cancer cell proliferation, migration, and survival. The nanobody platform underlying VHH-P717 allows for further adaptation into advanced therapeutic modalities such as antibody-drug conjugates or bispecific formats, providing a foundation for future multi-functional anticancer agents.
Cancer
Cancer remains one of the leading causes of mortality worldwide, with millions of new diagnoses annually and a significant burden across all populations. Standard therapies include surgery, radiation, chemotherapy, immunotherapy, and targeted small molecules; however, many cancers continue to exhibit resistance, relapse, or unacceptable side-effect profiles. The biological heterogeneity and adaptability of cancer cells present ongoing challenges, resulting in an unmet clinical need for agents with improved selectivity, reduced toxicity, and innovative mechanisms of action. VHH-P717, with its dual targeting of ALB and LRP5, is strategically positioned to address these gaps. By combining extended systemic exposure with the ability to disrupt oncogenic signaling, it offers a differentiated approach with the potential to enhance efficacy and overcome resistance pathways common in existing treatments. This supports its promise as a next-generation candidate in the oncology therapeutic landscape.