AZD4604 / AstraZeneca - LARVOL DELTA

AJAX: Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA (clinicaltrials.gov) - P2 | N=339 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

ARTEMISIA: Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Late Breaking Abstract - Distinct effects of londamocitinib, AZD6793 and dexamethasone on gene expression in sputum macrophages from asthma and COPD (ERS 2025) - "Janus kinase 1 inhibitor, londamocitinib, and Interleukin-1 receptor-associated kinase 4 inhibitor, AZD6793, are in clinical development for respiratory diseases, offering potentially broader anti-inflammatory effects than single- cytokine biologics. Importantly, the GESs from the selective inhibitors were not meaningfully altered by Dex in either asthma or COPD (Figure). This study shows that AZD4604 and AZD6793 can target broad respiratory pathology, including non-type 2 and steroid-resistant inflammation, with the potential to address unmet needs in the management of patients with asthma and COPD."

Late-breaking abstract • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases • IL13 • IL4 • IL6 • IRAK4

Absorption, distribution, metabolism, and elimination (ADME) study strengthens clinical pharmacology package of londamocitinib (ERS 2025) - P1, P2 | "Londamocitinib (AZD4604) is an orally inhaled selective Janus kinase 1 inhibitor, currently being assessed in patients with asthma in the AJAX Phase 2a study (NCT06020014)...This study characterised the PK and mass balance of londamocitinib in healthy male and non-pregnant, non- lactating female participants. These results strengthen the clinical pharmacology package to support the future clinical development of londamocitinib."

Clinical • Asthma • Immunology • Respiratory Diseases

ARTEMISIA: Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Oct 2025 | Trial primary completion date: Apr 2026 ➔ Oct 2025

Biomarker • Enrollment closed • Trial completion date • Trial primary completion date • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

AJAX: Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA (clinicaltrials.gov) - P2 | N=327 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma. (PubMed, Respir Res) - P2 | "ARTEMISIA commenced recruitment in 2024 and is poised to deliver a deep understanding of the mechanism of action of londamocitinib and its potential to impact on a population of asthmatics with high unmet need. The multiomic analysis of paired central and peripheral samples may reveal novel insights into the connection and translation between these compartments, deepen understanding of airways disease, and identify novel candidate biomarkers for asthma and JAK activity. In addition to sampling the airway directly, with parallel nasal and peripheral bio-sampling mirrored by the Phase 2a AJAX study (NCT06020014), the ARTEMISIA study may provide a unique link between bronchial assessed mechanisms of action and clinical outcomes."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Study to Evaluate the Pharmacokinetics and Pharmacodynamics of AZD4604 Given Via the Turbuhaler® Device in Adults With Mild Asthma. (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ May 2025 | Trial primary completion date: Sep 2025 ➔ May 2025

Trial completion • Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Evaluate the Pharmacokinetics and Pharmacodynamics of AZD4604 Given Via the Turbuhaler® Device in Adults With Mild Asthma. (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled AZD4604 in Healthy Japanese and Chinese Participants. (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

Study to Evaluate the Pharmacokinetics and Pharmacodynamics of AZD4604 Given Via the Turbuhaler® Device in Adults With Mild Asthma. (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled AZD4604 in Healthy Japanese and Chinese Participants. (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

AZD4604 PK assessment using finger-prick microsampling (ERS 2024) - "This data suggests that FPB sampling may be adequate to evaluate the PK of an inhaled drug. FPB sampling warrants further rigorous evaluation as an option to enable simplified and innovative clinical trial design, reducing burden on both sites and participants."

Asthma • Immunology • Respiratory Diseases • JAK1

ARTEMISIA: A JAK1 inhibitor mechanistic study to advance molecular understanding and precision medicine in respiratory diseases (ERS 2024) - P2 | "Molecular biomarkers in more easily accessible matrices, such as nasal lining fluid and nasal cells, blood, and urine will be correlated to phenotype-specific gene signatures amenable to AZD4604 modulation, as derived from bronchoscopy, in order to identify tractable diagnostic signals. Complementary minimally invasive precision sampling in AJAX and ARTEMISIA will enable the exploration of a link between lung mechanisms and clinical efficacy to identify biomarkers predictive of a response to AZD4604 and inform patient subgroups across respiratory diseases."

Asthma • Immunology • Inflammation • Respiratory Diseases • JAK1

ARTEMISIA: A Randomised, Double-blind, Parallel Group, Placebo Controlled, 4-Week, Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • JAK1

A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled AZD4604 in Healthy Japanese and Chinese Participants. (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: AstraZeneca

New P1 trial

Inhaled AZD4604: Local Janus Kinase 1 Inhibition Without Systemic Activity (ATS 2024) - "We determined the half-maximal inhibitory concentrations (IC50s) of AZD4604, abrocitinib, upadacitinib (JAK1 selective inhibitors) and deucravacitinib (a TYK2 inhibitor) in vitro in three JAK-dependent pathways (IFN-α, GM-CSF, IL-12) in whole blood. Currently marketed oral JAKis showed broad systemic activity on JAK pathways at therapeutic dose. In contrast, at anticipated therapeutic exposure, inhaled AZD4604 would lead to minimal systemic target engagement on any of the investigated JAK signaling pathways, reducing the risk of potential systemic side effects experienced with oral JAKis. The efficacy and risks of this approach will be further evaluated in clinical trials."

Asthma • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • IFNA1 • IL12A • JAK1 • JAK3 • TYK2

ARTEMISIA: A Randomised, Double-blind, Parallel Group, Placebo Controlled, 4-Week, Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: AstraZeneca

Biomarker • New P2 trial • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • JAK1

An ADME Study of [14C]AZD4604 and the Absolute Bioavailability of AZD4604 (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

An ADME Study of [14C]AZD4604 and the Absolute Bioavailability of AZD4604 (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

An ADME Study of [14C]AZD4604 and the Absolute Bioavailability of AZD4604 (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

AZD4604, An Inhaled, Selective JAK1 Inhibitor Reduces Fractional Exhaled Nitric Oxide in Patients with Mild Asthma; A Randomized, Single-Blind Phase 1 Study (AAAAI 2024) - P1 | "AZD4604 caused rapid FeNO reduction in patients with mild asthma, at dose levels that were well tolerated and with minimal systemic TE. Further research is required to determine the clinical benefit and safety in more severe asthma populations receiving current standard of care."

Clinical • P1 data • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL4 • STAT6

AJAX: Phase 2a Study to Assess the Efficacy and Safety of AZD4604 in Adult Patients With Moderate-to-Severe Asthma Uncontrolled on Medium-High Dose ICS-LABA (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

An ADME Study of [14C]AZD4604 and the Absolute Bioavailability of AZD4604 (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Discovery of the Potent and Selective Inhaled Janus Kinase 1 Inhibitor AZD4604 and Its Preclinical Characterization. (PubMed, J Med Chem) - "Compound 16 has progressed into clinical trials. Using 16, we found JAK1 inhibition to be more efficacious than JAK3 inhibition in IL-4-driven Th2 asthma."

Journal • Preclinical • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL4 • JAK1 • JAK3