Innovative Bispecific Nanobody Therapeutic Targeting IL1RL2 and IL-23 for Inflammatory Disorders
VHH-P348 is a humanized nanobody therapeutic candidate designed to target two key molecules involved in immune regulation: interleukin 1 receptor like 2 (IL1RL2) and interleukin 23 complex (IL-23). Currently in the Biological Testing phase of development, VHH-P348 harnesses bispecific antibody technology to simultaneously modulate distinct inflammatory pathways. This program holds significant promise for the treatment of diverse inflammatory disorders, leveraging the dual blockade of IL1RL2 and IL-23 to address unmet clinical needs. By focusing on well-characterized molecular targets, VHH-P348 represents a cutting-edge approach to precision immunotherapy.
| Candidate | VHH-P348 |
| Target | interleukin 1 receptor like 2 (IL1RL2) Interleukin 23 complex (IL-23) |
| Modality | humanized bispecific VHH |
| Indication | Inflammatory Disorders |
Licensing Opportunity
VHH-P348 is available for out-licensing and collaborative development opportunities. We welcome discussions with potential partners interested in advancing this innovative bispecific nanobody program for inflammatory disorders.
Contact UsDevelopment Phase
| Program | Research | Preclinical | Phase 1 |
|---|---|---|---|
| VHH-P348 |
Modality
VHH-P348 is a bispecific antibody fusion construct consisting of a humanized monoclonal IgG1 kappa antibody targeting IL-23, with each heavy chain’s N-terminus fused to a humanized single-domain antibody targeting IL1RL2 via a flexible (G4S)2 linker. The incorporation of nanobody elements (single-domain VHH antibodies) confers structural advantages such as small size, increased tissue penetration, and superior stability. These features are particularly beneficial in the context of inflammatory disorders, where deep tissue infiltration and sustained activity are required. Furthermore, Fc region modifications (L234A/L235A mutations) are designed to optimize effector function, enhancing safety and therapeutic precision.
Target
IL1RL2 and IL-23 are pivotal mediators of immune and inflammatory pathways. IL1RL2 is a receptor primarily found on immune effector cells such as dendritic cells, monocytes, and epithelial cells, where it modulates cytokine responses linked to inflammation. IL-23, a heterodimeric cytokine mainly produced by antigen-presenting cells, orchestrates pathogenic responses by activating and maintaining Th17 lymphocytes. The aberrant signaling of IL1RL2 and IL-23 is implicated in a spectrum of inflammatory disorders. Targeting both IL1RL2 and IL-23 allows VHH-P348 to disrupt these pro-inflammatory cascades at multiple levels, providing strategic and potentially synergistic benefits. The dual targeting strategy of VHH-P348 positions it as a compelling asset in the inflammatory disease treatment landscape.
Mechanism of Action
VHH-P348 operates by selectively binding IL1RL2 and IL-23, blocking their respective signaling cascades. This dual antagonism interrupts both the IL-36 and IL-23 mediated pathways implicated in chronic inflammation. Through inhibition of these receptors, VHH-P348 modulates inflammatory cytokine production, dampening pathogenic immune activation while preserving normal host defenses. The bispecific configuration not only enables coordinated suppression of complementary pro-inflammatory signals but also exemplifies the flexibility and platform potential of nanobody-based drug engineering. Such constructs can be further developed into multi-functional therapeutics, including antibody-drug conjugates and other next-generation biologics.
Inflammatory Disorders
Inflammatory disorders encompass a broad range of chronic and acute diseases characterized by immune-mediated tissue damage, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and others. These conditions affect millions globally, resulting in significant morbidity and health care burden. Current therapeutic strategies involve systemic immunosuppression, targeted biologics, and disease-modifying agents, yet challenges such as incomplete response, loss of efficacy, and adverse effects persist. Many patients experience relapsing courses or inadequate disease control. The need for novel targeted therapies remains urgent. By engaging both IL1RL2 and IL-23, VHH-P348 aims to deliver improved clinical outcomes, potentially overcoming resistance mechanisms and providing broader disease coverage compared to single-pathway inhibitors. Its innovative bispecific nanobody format supports deep tissue penetration and a favorable safety profile, offering promising advances for patients with inflammatory disorders.