Asthma Research: Why Non-Human Primate Models Are Pivotal For Novel Drug Development

Asthma, a globally prevalent chronic respiratory disease, presents significant unmet medical needs due to its complexity, including the lack of curative treatments and suboptimal efficacy in some patient populations. Traditional preclinical models often fall short in accurately predicting clinical efficacy, highlighting an urgent need for superior models that better recapitulate human disease to propel novel asthma drug development. This article elucidates the core value of Non-Human Primate (NHP) models, particularly cynomolgus monkeys, in accelerating this critical R&D process.

Asthma is characterized by core pathophysiological features including chronic airway inflammation, airway hyperresponsiveness (AHR), and reversible airflow limitation. The disease exhibits significant heterogeneity, with various phenotypes such as allergic and non-allergic asthma driven by distinct underlying mechanisms. Current asthma therapies, like inhaled corticosteroids (ICS) and β2-agonists, primarily manage symptoms but often lack disease-modifying effects, and a subset of severe asthma patients remains treatment-resistant. This heterogeneity necessitates preclinical models capable of reflecting diverse disease subtypes.

Non-Human Primate (NHP) models are considered an ideal translational bridge between preclinical research and clinical trials due to their high biological similarity to humans. In asthma and other immune-inflammatory diseases, NHPs offer distinct advantages:

• Highly Similar Immune System: NHP immune response mechanisms, particularly T-cell responses, cytokine profiles, and IgE-mediated allergic reactions, are highly conserved with humans. This is crucial for evaluating innovative immunomodulatory therapies like biologics.
• Similar Respiratory Anatomy and Physiology: NHP airway anatomy, branching patterns, lung parenchyma, and responses to bronchoconstrictors closely resemble those of humans. This similarity enhances the clinical relevance of studies on airway remodeling, inflammation, and hyperresponsiveness.
• Capacity for Chronic Disease Modeling: NHPs can develop chronic asthma phenotypes through long-term allergen exposure, effectively mimicking the longitudinal nature and recurrent exacerbations of human asthma.

Cynomolgus monkeys, a commonly used NHP species, offer specific advantages in asthma research:

• Susceptibility and Phenotype Induction: Cynomolgus monkeys are susceptible to common allergens (e.g., ovalbumin - OVA) and can be sensitized and challenged to induce typical allergic asthma phenotypes, including AHR, airway inflammation, and mucus hypersecretion.
• Translational PK/PD Studies: Their closer genetic and physiological resemblance to humans facilitates the translation of pharmacokinetic (PK) and pharmacodynamic (PD) data.
• Superior Recapitulation: Compared to rodent models, which have significant differences in immune pathways, lung architecture, and limited ability to fully mimic chronic airway remodeling, cynomolgus monkey models more accurately simulate the complex pathophysiology of human asthma.

Prisys Biotech is dedicated to providing high-quality NHP models and preclinical research services for various therapeutic areas, including respiratory diseases. Our 4,000 m² state-of-the-art facility in Shanghai houses a significant NHP capacity and is equipped with clinical-grade instrumentation, including CT, MRI, Doppler ultrasound, endoscopy, laminar flow surgical suites, and an ICU, all designed to enhance the translational value of research data.

Prisys Biotech has established comprehensive NHP models for allergic diseases, including an asthma model in cynomolgus monkeys induced by sensitization and challenge with ovalbumin (OVA) plus adjuvant. This model is designed to concurrently simulate features of atopic dermatitis (AD), allergic rhinitis (AR), and asthma with high success rates and reproducibility.

Our model offers comprehensive evaluation endpoints for robust efficacy assessment:

• Lung Function Assessment: Including evaluation of airway hyperresponsiveness (AHR), e.g., using acetylcholine (ACh) challenge for PC50 determination, reflecting airway sensitivity.
• Bronchoalveolar Lavage Fluid (BALF) Analysis: Cytology to assess inflammatory cell infiltration (e.g., eosinophils, lymphocytes, neutrophils) and quantification of key inflammatory cytokines (e.g., IL-4, IL-5, IL-13, IFN-γ).
• Serological Testing: Assessment of total and OVA-specific IgE levels, reflecting the intensity of the allergic immune response and sensitization success.
• Lung Histopathology: Evaluation of key pathological features such as inflammatory cell infiltration, mucus hypersecretion (goblet cell hyperplasia), and airway wall thickening, indicative of airway remodeling.

Prisys Biotech's cynomolgus asthma model can be utilized to evaluate various novel asthma therapies, including but not limited to:

• Biologics targeting specific cytokines (e.g., anti-IL-5, anti-IL-4Rα, anti-IgE).
• Novel inhaled formulations or small molecule drugs.
• Immunomodulators, gene therapies, and mRNA-based therapeutics.

Prisys Biotech emphasizes standardized protocols to ensure data reliability and reproducibility. By integrating advanced imaging (e.g., CT for lung assessment) and specialized drug delivery techniques (e.g., nebulization, bronchoscopic instillation), our cynomolgus asthma model provides high-quality, translationally relevant data, effectively accelerating the preclinical development of innovative asthma therapies.

Conclusion

As our understanding of asthma's complexity deepens, the demand for preclinical models with higher translational validity grows. NHP models, particularly cynomolgus monkeys, are increasingly pivotal in asthma drug discovery. Prisys Biotech, with its expert NHP model platforms, advanced facilities, and comprehensive assessment capabilities, is committed to providing efficient and precise preclinical research services to advance global respiratory drug development.