AZD4604 / AstraZeneca - LARVOL DELTA

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

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) - P2a | N=320 | Not yet recruiting | Sponsor: AstraZeneca

New P2a trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Clinical Trial in Healthy Volunteers and Patients With Mild Asthma to Investigate a New Medicine (AZD4604) for the Treatment of Asthma (clinicaltrials.gov) - P1 | N=110 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | N=169 ➔ 110

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

Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma. (PubMed, Drug Des Devel Ther) - "AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma."

Journal • Asthma • Eosinophilia • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL13 • IL5 • STAT3 • STAT5 • TSLP

"...though a separate $AZD inhaled Jak for asthma, AZD4604, remains in ph1" (@JacobPlieth)

Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

"Other $AZN Q3 pipeline movements: AZD4604 (inhaled Jak1) into ph1; MEDI5395 (GM-CSF-expressing oncolytic virus) discontinued." (@JacobPlieth)

Oncolytic virus • Infectious Disease • CSF2 • JAK1

A Clinical Trial in Healthy Volunteers to Investigate a New Medicine (AZD4604) for the Treatment of Asthma (clinicaltrials.gov) - P1; N=169; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting

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