Innovative Bispecific Nanobody Targeting LPAM-1 and TNF for Autoimmune Disease Therapy

VHH-P395 is an advanced humanized bispecific nanobody fusion protein designed to target both integrin alpha4beta7 (LPAM-1) receptor and tumor necrosis factor (TNF). Currently in the Biological Testing stage, VHH-P395 leverages the therapeutic potential of simultaneously modulating key inflammatory pathways in autoimmune diseases. By binding to both LPAM-1, a adhesion molecule implicated in immune cell trafficking, and TNF, a central pro-inflammatory cytokine, this molecule holds promise for targeted, dual-mechanism intervention in complex immune-mediated disorders. VHH-P395 is engineered for potent activity and high specificity, aiming to address significant unmet needs in autoimmune disease management.

Licensing Opportunity

VHH-P395 is available for global licensing and co-development partnerships. We invite collaboration from pharmaceutical and biotechnology partners interested in advancing next-generation therapies for autoimmune diseases.

Development Phase

Modality

VHH-P395 is a bispecific fusion protein consisting of two single-domain antibodies: one directed against human integrin alpha4beta7 and the other against TNF-alpha. These are linked via a flexible (G4S)3 peptide linker, and the construct is fused to a human IgG1 Fc domain to enhance stability and effector function. The molecule is expressed in human embryonic kidney 293 cells to enable efficient and scalable production. The nanobody scaffold offers advantages such as small molecular size, increased tissue penetration, high stability, and reduced immunogenicity. These characteristics contribute to improved targeting of inflamed tissues and better therapeutic outcomes for autoimmune diseases by facilitating effective blockade of both LPAM-1 and TNF within affected sites.

Target

LPAM-1 and TNF are critical molecular targets in the pathophysiology of autoimmune disease. LPAM-1 is a cell adhesion molecule highly expressed on the surface of lymphocytes and plays a decisive role in mediating their migration to inflamed tissues. TNF is a key pro-inflammatory cytokine produced by several immune cell types and drives many inflammatory pathways involved in tissue destruction and autoimmunity. LPAM-1 blocking impairs abnormal lymphocyte trafficking, while TNF inhibition reduces tissue inflammation and immune activation. The dual targeting approach of VHH-P395 harnesses the strategic value of addressing both LPAM-1 and TNF to comprehensively modulate immune responses. By neutralizing LPAM-1 and TNF concurrently, VHH-P395 aims to deliver enhanced clinical benefit and address the multifactorial nature of autoimmune disease.

Mechanism of Action

VHH-P395 exerts its mechanism of action through simultaneous engagement of LPAM-1 and TNF. By binding to LPAM-1, the molecule disrupts lymphocyte adhesion and migration to inflamed tissues, thereby reducing immune cell infiltration. Concurrently, the anti-TNF domain of VHH-P395 neutralizes TNF, limiting downstream inflammatory signaling and dampening cytokine cascades central to autoimmune pathology. This dual signal transduction modulation is designed to interrupt both cellular trafficking and inflammatory amplification, potentially offering superior efficacy over monospecific approaches. The modular nanobody platform underlying VHH-P395 also supports future expansion to various multi-specific formats, enabling broader applicability in immune-mediated diseases.

Autoimmune Disease

Autoimmune diseases constitute a group of disorders characterized by inappropriate immune responses targeting self-antigens, leading to chronic tissue inflammation and organ damage. They affect millions globally, manifesting as conditions such as inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. Current major therapeutic approaches include immunosuppressive agents, small molecule inhibitors, and monoclonal antibodies directed against specific cytokines or cell-surface proteins. However, these treatments often exhibit incomplete efficacy, risk of systemic immunosuppression, and potential adverse effects. Significant unmet medical needs remain in achieving sustained disease control, minimizing side effects, and preventing long-term organ damage. VHH-P395, with its bispecific targeting and nanobody-derived benefits, holds potential to redefine therapeutic paradigms for autoimmune diseases—offering targeted and durable immunomodulation with an improved safety and pharmacokinetic profile.