Novel inhaled delivery of anti-IL-13 mAb (Fab fragment): preclinical efficacy in allergic asthma

Background: IL-13 is a key cytokine in the pathogenesis of allergic asthma. Efficacy with systemically administered anti-IL-13 mAb therapies is mixed; inhaled mAbs may provide targeted treatment for patients. Aim: To investigate the efficacy of CDP7766, an inhaled anti-IL-13 mAb Fab fragment, in a cynomolgus macaque model of allergic asthma. Methods: Nebulised CDP7766 (0.1–60 mg/day) or vehicle was delivered via inhalation (days -2, -1, 1, 2 and 3) to cynomolgus macaques naturally sensitised to Ascaris suum . Concentrations of bronchoalveolar lavage (BAL) allergen-induced cytokines and chemokines were determined on days 1 and 2 using electrochemiluminescence immunoassay. CDP7766 was nebulised using a vibrating-membrane nebuliser based on eFlow ® technology. The aerosol was analysed for particle size profile, biophysical and functional properties of CDP7766. Results: Inhaled CDP7766 was well tolerated (no adverse effects related to local irritation) and significantly inhibited BAL allergen-induced cytokine and chemokine upregulation (60 mg vs vehicle: eotaxin-3 p ® nebuliser generated a respirable aerosol of CDP7766 with no evidence of degradation, loss of potency, aggregation or formation of particulates. Conclusions: Inhaled CDP7766 inhibited allergen-induced lung and airway responses in cynomolgus macaques. This is the first report of an inhaled anti-IL-13 mAb in a non-human primate model and demonstrates the therapeutic potential of this mAb in allergic asthma. Funding: UCB Pharma.