Prisys Biotech’s Cynomolgus Monkey Psoriasis Model: Advancing Preclinical Pharmacodynamics Evaluation

Introduction: The Need for Psoriasis NHP Models

Psoriasis is a chronic inflammatory skin disease whose complex pathogenesis and clinical heterogeneity present significant challenges for drug development. Preclinical pharmacodynamics studies are a crucial part of new drug development, and selecting an appropriate animal model is essential. The commonly used imiquimod (IMQ)-induced rodent psoriasis model has played a role in early-stage drug development. However, the physiological and immunological differences between rodents and humans limit the translational value of findings from these models. Non-human primates (NHPs), due to their evolutionary, physiological, and immunological similarities to humans, offer more clinically relevant models for psoriasis research.

Immune Mechanisms in Psoriasis

The pathogenesis of psoriasis is a complex process of immune network dysregulation, involving the interaction of innate and adaptive immunity. Various cytokines, particularly IL-17, TNF-α, and IL-23, play key roles in initiating skin inflammation and hyperproliferation. Biologic agents targeting these key cytokines and pathways (such as anti-TNF-α, anti-IL-17, and anti-IL-23 antibodies) have become essential in the treatment of psoriasis.

Non-human primates, such as cynomolgus monkeys, have a skin anatomy, keratinocyte differentiation process, immune cell composition, and function that are highly homologous to humans. This close physiological similarity makes the NHP psoriasis model particularly advantageous for simulating human psoriasis pathogenesis, evaluating drug efficacy, and predicting clinical translational potential.

Compared to rodent models, the NHP psoriasis model more accurately:

• Simulates Disease Pathophysiology: NHP skin barrier function and immune response pathways are closer to humans, allowing for a more authentic simulation of the complex immune-inflammatory cascade seen in psoriasis.
• Evaluates Drug Targeting and Efficacy: The drug metabolism enzyme systems of NHPs are more similar to humans, making their pharmacokinetic profiles and target effects more clinically predictive.
• Conducts Long-Term Pharmacodynamics and Safety Evaluations: The physiological parameters of NHPs are more aligned with humans, making them more suitable for long-term drug administration and chronic disease model studies.

Prisys Biotech has developed an IMQ-induced psoriasis model using cynomolgus monkeys to support preclinical pharmacodynamics studies for psoriasis-related therapeutic agents.

Model Development Strategy: This model uses the topical application of imiquimod (IMQ) to induce skin inflammation in cynomolgus monkeys. IMQ, a TLR7/8 agonist, activates innate immune cells and induces Th17 and Th1-mediated immune responses, simulating key immune pathophysiological mechanisms of psoriasis.

Experimental Design Overview:

• Animals: Adult female cynomolgus macaques (Cynomolgus Macaque).
• Induction: Topical application of IMQ cream for transdermal absorption.
• Application Site: Specific area on the back (standardized area).

Groups:

• Vehicle Group: IMQ stimulation + vehicle control (petroleum jelly).
• Treatment Group: IMQ stimulation + therapeutic drug (Daivobet).

Evaluation Metrics:

• Skin Lesion Scoring: Quantitative severity scoring system based on erythema, exudation, desquamation, etc.
• Skin Histopathology: HE staining of tissue sections to assess epidermal hyperplasia, inflammatory cell infiltration, and other pathological features.
• Inflammatory Cytokine Analysis: Expression levels of key cytokines in skin homogenates or serum (e.g., IL-17, IL-23, IL-22, and TNF-α).
• Gene Analysis: RT-qPCR to assess the expression of psoriasis-related genes, including inflammatory cytokines (IL-17, IL-23, IL-22, TNF-α) and psoriasis-related keratin markers such as keratin 17.
• Other Metrics: Skin weight, lesion area, epidermal thickness, etc. (optional).

Sample Experimental Data:

• Lesion Score Trend: After IMQ stimulation, the lesion scores in both the Vehicle and Treatment groups significantly increased, confirming successful model induction. After Daivobet treatment, lesion scores decreased significantly (p<0.05), indicating therapeutic efficacy. The Vehicle group showed consistently higher lesion scores.

• Histological Results: Histopathological analysis revealed thickening of the epidermal spinous layer, hyperkeratosis, and dermal inflammatory cell infiltration in the model group, similar to human psoriasis pathology. The Daivobet treatment group showed significant relief from these pathological changes.

• Cytokine Expression: qPCR results showed significantly elevated levels of IL-17A, IL-23, IL-22, and other key cytokines in the model group, consistent with psoriasis pathogenesis. In the Treatment group, these cytokine levels were significantly reduced after drug intervention.
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• High Disease Mimicry: The NHP model closely replicates the pathophysiological and immunological features of human psoriasis, providing a more reliable foundation for clinical translational research.
• Comprehensive Evaluation System: A multidimensional evaluation system allows in-depth assessment of drug efficacy in terms of pathology, immunology, and clinical relevance.
• Mature Technical Platform: Standardized model development and evaluation processes ensure the reliability and reproducibility of experimental data.
• Accelerating Drug Development: Provides high-quality preclinical data for new psoriasis drug development, facilitating faster clinical trial progression.

Conclusion: Prisys Biotech's cynomolgus monkey IMQ-induced psoriasis model offers a more clinically relevant animal model for preclinical pharmacodynamics research. This model enables more effective evaluation of new drug efficacy, supports clinical translational research, and accelerates innovation in psoriasis treatment.

Contact Us: For more information on Prisys Biotech's IMQ-induced psoriasis model, please visit our website at www.prisysbiotech.com, or contact our business team at bd@prisysbiotech.com / +86-21-50435616.

About Prisys Biotech: Prisys Biotech, located in Shanghai, is a high-tech enterprise specializing in preclinical and translational assessments of new drugs and technology development. The company is AAALAC fully certified and provides a variety of animal models for disease research, pharmacology studies, safety evaluations, biomarker research, and mechanism validation. Prisys Biotech collaborates with top pharmaceutical companies, biotechnology firms, and academic institutions to support drug discovery and development.