Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults With Asthma

Inclusion Criteria: * Documented physician-diagnosed asthma ≥ 12 months prior to screening (Visit 1). * Participants treated with medium-to-high dose ICS in combination with LABA at a stable dose for at least 2 months prior to Visit 1 (the ICS can be contained within an ICS-LABA fixed dose combination product or as separate inhaled products regularly taken together). Treatment with additional asthma controller therapies (eg, long-acting muscarinic antagonist, leukotriene receptor antagonist) at a stable dose ≥ 2 months prior to Visit 1 is allowed. Treatment with maintenance systemic corticosteroids (oral or injectable) is not allowed. * A documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Visit 1 or ACQ-6 ≥ 1.5 at Visit 1. A severe asthma exacerbation is defined as a worsening of asthma that leads to an inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma. * Morning pre-BD FEV1 ≥ 60% predicted at Visit 1. * Able to perform acceptable lung function testing for FEV1 according to American Thoracic Society/ European Respiratory Society (ATS/ERS) 2019 acceptability criteria. * Able and willing to undertake bronchoscopy. There should be no absolute contra-indications to bronchoscopy as outlined in the bronchoscopy manual. * Documented evidence of asthma in the 5 years up to or including Visit 1. * Able and willing to comply with the requirements of the protocol including ability to read, write, be fluent in the translated language of all participant-facing questionnaires used at the study site, and use electronic devices, eg, electronic patient reported outcomes (ePRO) device and spirometer. * Body weight ≥ 40 kg and body mass index \< 35 kg/m2. * All females must have a negative serum pregnancy test result at Visit 1. * Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. * All FOCBP who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control. Highly effective birth control methods include: * Non-hormonalTotal sexual abstinence provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) * A vasectomised partner (with confirmed absence of sperm in semen) * Bilateral tubal occlusion (caveat: failure rate \>1%) * Intrauterine device (copper)Hormonal * Levonorgestrel intrauterine system * Medroxyprogesterone injections * Combined oral or transdermal contraceptives (ethinyl estradiol plus progestin) o Intravaginal device (eg, EE and etonogestrel) The following are not acceptable methods of contraception: * Periodic abstinence (calendar, symptothermal, post-ovulation methods) * Withdrawal (coitus interruptus) * Spermicides only * Lactational amenorrhoea * Female condom and male condom should not be used together Exclusion Criteria: * A severe asthma exacerbation within 8 weeks prior to Visit 1. * History of herpes zoster reactivation (shingles). * Clinically important pulmonary disease other than asthma, eg, active lung infection, chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, and hyper-eosinophilic syndrome. * Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator. * Any clinically significant cardiac or cerebrovascular disease. * History of venous thromboembolism. * Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Positivity for hepatitis B virus (HBV) surface antigen is a reason for exclusion. * Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator. Positive drug screening result that cannot be justified by participant's medical history and its relevant treatment (over-the-counter product or a valid prescription), or history of or current alcohol or drug abuse (including marijuana and marijuana-containing valid prescriptions), as judged by the investigator. * History of malignancy other than superficial basal cell carcinoma. * Treatment with systemic corticosteroid (short-term or maintenance) use within 8 weeks (oral) or 12 weeks (intramuscular) before Visit 1. * Any immunosuppressive therapy (including hydroxychloroquine, methotrexate, cyclosporine, and tacrolimus) within 12 weeks prior to Visit 1. * Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab, and tezepelumab within 6 months or 5 half-lives of Visit 1, whichever is longer. * Inhaled corticosteroid plus fast-acting β2 agonist as a rescue medication (eg, Symbicort, Fostair, or Airsupra Maintenance and Reliever Treatment) is not allowed 30 days prior to Visit 1, during screening, run-in and baseline periods, throughout the treatment period, and preferably until 1 week after the last administration of the IMP. * Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1. * Immunoglobulin therapy or blood products within 4 weeks of Visit 1. * Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the follow-up period. * Anticoagulants (including vitamin K antagonists and Factor Xa inhibitors). Antiplatelet agents are allowable if in the opinion of the investigator they can be safely withheld for 7 days prior to the procedure. * Any history of bronchial thermoplasty * Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product. * Abnormal findings identified on physical examination, ECG, or laboratory testing include, but not limited to: Alanine aminotransferase/transaminase (ALT) or aspartate aminotransferase/transaminase AST ≥ 1.5 × upper limit of normal (ULN), Total bilirubin (TBL) ≥ ULN (unless due to known Gilbert's disease), Evidence of chronic liver disease, International Normalised Ratio (INR) \> 1.5, Platelet count \< 150,000 per microliter, Abnormal vital signs, after 5 minutes of supine or sitting rest (confirmed by 1 controlled measurement), defined as any of the following: Systolic blood pressure (BP) \< 80 mmHg or ≥ 150 mmHg, Diastolic BP \< 50 mmHg or ≥ 95 mmHg, Pulse \< 50 bpm or \> 100 bpm, Signs of pulmonary oedema or volume overload, Any clinically significant rhythm, conduction, or morphology abnormalities in the ECG including but not limited to QT interval corrected using Fridericia's formula (QTcF) \> 450 ms. For female participants only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding. * Current smokers or participants with smoking history ≥ 10 pack-years. * Participants with a known long-term exposure to occupational asbestos, silica, radon, heavy metals, and polycyclic aromatic hydrocarbons. * Positive, first-degree family history of primary lung cancer. * Positive urine cotinine test at Visit 1 and at any timepoint throughout the study. * Major surgery within 8 weeks prior to Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during screening, treatment, or follow-up periods.