A32-37 A Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of AZD8630, Administered Once Daily via Inhalation, for 2 Weeks, in Adults With Asthma on Medium-to-high Dose Inhaled Corticosteroids and Long-acting Beta-agonists

Abstract Rationale AZD8630/AMG 104 is a first-in-class inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen binding (Fab) in development for the treatment of moderate-to-severe asthma, which previously demonstrated linear PK and a 23% reduction in FeNO in adult participants with asthma over 4 weeks’ treatment1. We present the results of a Phase 1 study conducted to assess safety, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD8630/AMG 104 in a population of adult asthmatics following a device and formulation change. Methods In this double-blind, placebo-controlled, multicentre study, 24 asthmatic participants on stable medium-to-high dose ICS/LABA with elevated fractional exhaled nitric oxide (FeNO) ≥ 30 parts per billion (ppb) at baseline were randomised to receive once-daily inhaled AZD8630/AMG 104 (8 mg QD) or placebo via capsule-based dry powder inhaler (DPI) for 14 days in addition to their standard-of-care therapy. Co-primary objectives included evaluation of safety, tolerability and PK; change from baseline in FeNO was the PD secondary endpoint. Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) was evaluated as part of an exploratory analysis. Results Once-daily AZD8630/AMG 104 was well tolerated, with no new safety findings or serious adverse events during the 14-day treatment period. PK parameters were consistent with previously reported data, supporting once-daily dosing in the new device and revised formulation. At day 14, a greater reduction from baseline in FeNO was observed in AZD8630/AMG 104 group (median reduction -12.5 ppb) than in placebo (median reduction -4.8 ppb). In the mixed model for repeated measures analysis, the difference between groups was statistically significant and clinically meaningful (29% reduction versus placebo, one-sided p-value 0.019) (Figure 1a). In patients treated with AZD8630/AMG 104, there was a statistically significant increase in pre-BD FEV1 compared to placebo at Day 14 (mean difference 253mls, one-sided p value 0.027) (Figure 1b). Conclusions Following a device and formulation change, AZD8630/AMG 104 was safe and well tolerated, with linear PK, consistent with previous presented data1 and demonstrated a significant reduction in FeNO, reflecting effective suppression of T2 inflammation in adults with asthma. The clinical impact of this is further supported by the improvements demonstrated in pre-BD FEV₁. Collectively, these results support the further development of AZD8630/AMG 104. 1 Doffman et al. Phase 1 Safety and Efficacy of AZD8630/AMG 104 Inhaled Anti-TSLP in Healthy Volunteers and Patients with Asthma on Medium-High Dose ICS and LABA With Elevated Baseline FeNO [abstract]. AJRCCM 2024;209:A1386. This abstract is funded by: AstraZeneca