ARTEMISIA: A JAK1 inhibitor mechanistic study to advance molecular understanding and precision medicine in respiratory diseases

Patients with uncontrolled asthma, particularly those with non-type 2 (T2) phenotypes, have a great unmet need for new treatments and for a deeper molecular understanding to enable precision medicine. AZD4604 is a potent and selective inhibitor of Janus kinase 1 (JAK1), with potential to treat airway pathology beyond T2 inflammation, that is being evaluated for clinical efficacy in uncontrolled moderate-to-severe asthma patients in the Ph2a AJAX study (<ext-link>NCT06020014</ext-link>). ARTEMISIA, a parallel, multi-omics mechanistic study with AZD4604 was designed to understand the effect on T2 and non-T2 inflammatory mechanisms in the lungs and identify associated peripheral biomarkers. This double-blind, placebo-controlled study will enrol 48 moderate-to-severe asthma patients undergoing bronchoscopy prior to first dose and after 4 weeks of treatment. The primary endpoint will evaluate the effect of AZD4604 on the expression of established JAK1-related bronchial epithelial gene signatures. 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.