A Safety, Pharmacokinetic, and Pharmacodynamic Study of Once Daily Inhaled AZD8630 in Adults With Asthma

Inclusion Criteria:

1 Participants who have documented physician-diagnosis of asthma for at least 12 months, as evidenced by any of the following:

1. Post-bronchodilator (BD) reversibility of FEV1 ≥ 12% and ≥ 200 milliliters (mL)within 5 years prior to Visit 1, at Visit 1 or

2. Peak expiratory flow (PEF) average daily variability > 10% over a 2-week periodwithin 5 years prior to Visit 1, or

3. Variability of FEV1 > 12% and 200 mL between any 2 clinical visits within 5 yearsprior to Visit 1, or

4. Positive bronchial challenge test within 5 years prior to Visit 1. A positive testis defined as a fall in FEV1 from pre-challenge of ≥ 20% with standard doses ofmethacholine or ≥ 5% with standardised hyperventilation, hypertonic saline, ormannitol challenge, or

5. Positive exercise challenge test within 5 years prior to Visit 1. A positive test isdefined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge, or

6. Significant increase in lung function after 4 weeks of Inhaled Corticosteroids (ICS)anti-inflammatory treatment within 5 years prior to Visit 1, defined as an increasein FEV1 > 12% and 200 mL (or PEF by > 20%).

3 Treated with medium or high dose ICS (as per GINA 2023) in combination withlong-acting beta-agonists (LABA) (GINA step 4 or 5 therapy); the dose of ICS must bestable for at least 30 days prior to Visit 1. The ICS can be contained within anICS-LABA fixed-dose combination product.

• Treatment with additional asthma controller therapies (eg, long-actingmuscarinic-agonists) at a stable dose ≥ 30 days prior to Visit 1 is allowed.

4 Asthma Control Questionnaire-6 (ACQ-6) score in the range 0.75-3 at both screeningand randomisation.

5 Pre-bronchodilator FEV1 ≥ 40%. 6 FeNO ≥ 30 parts per billion (ppb) at bothscreening and randomisation. 7 At least 70% compliance with usual asthma backgroundmedication during the screening period (14 days prior to randomisation) based on thedaily asthma ePROs. At least 70% compliance with electronically recorded participantreported outcomes (ePRO) device completion during the screening period (14 daysprior to randomisation). This is defined as completing the ePRO any 10 mornings and 10 evenings in the last 14 days prior to randomisation.

8 Minimum 70% compliance with PEF measurements during the screening period (14 daysprior to randomisation). This is defined as performing PEF for any 10 mornings andany 10 evenings in the last 14 days prior to randomisation.

9 Body mass index (BMI) within the range 18 to 35 kilograms per meter (kg/m2)inclusive and weight at least 45 kg at the time of signing the informed consent.

Exclusion Criteria:

1. Life-threatening asthma defined as a history of significant asthma episode(s)involving intubation, respiratory arrest, hypoxic seizures, or asthma-relatedsyncopal episode(s).

2. Completed treatment for respiratory infection and/or asthma exacerbation withsystemic corticosteroids and/or antibiotics in the 4 weeks prior to Visit 1 orduring the screening period.

3. Clinically important pulmonary disease other than asthma; including but not limitedto participants with co-existent chronic obstructive pulmonary disease (COPD).

4. 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 theopinion of the investigator and could:

5. Affect the safety of the participant throughout the study.

6. Influence the findings of the study or the interpretation.

7. Impede the participant's ability to complete the entire study.

8. Participants who, in the opinion of the investigator, have evidence of activetuberculosis (TB) or are currently on treatment for active or latent TB.Investigation for active or latent TB with interferon gamma release assay (IGRA)and/or chest X-ray should only be considered if deemed clinically indicated by thePrincipal Investigator.

9. Medical history of or treatment for hepatitis B or hepatitis C, except for curedhepatitis C, as defined by:

10. Positive test for hepatitis B surface antigen (HBsAg).

11. Positive test for anti- hepatitis B core antibody (HBc Ab): Participants whotest positive for anti-HBc Ab but negative for HBsAg may be enrolled if theirhepatitis B virus (HBV) DNA test result is negative.

12. Positive test for anti-hepatitis C antibody: Participants who test positive foranti-hepatitis C antibody may be enrolled if their hepatitis C viralribonucleic acid (RNA) test result is negative in the absence of cirrhosis.

13. Participants with known human immunodeficiency virus (HIV) or with a positive HIVtest at screening.

14. Any other clinically relevant abnormal findings in laboratory testing includinghaematology and clinical chemistry, on vital signs, electrocardiogram (ECG), orphysical examination between consent and randomisation, that in the opinion of theinvestigator or medical monitor, might compromise the safety of the participant inthe study or interfere with evaluation of the study intervention. Abnormal findingsinclude, but are not limited to:

15. Alanine aminotransferase/transaminase (ALT) or aspartateaminotransferase/transaminase AST > 2 × upper limit of normal (ULN).

16. Total bilirubin (TBL) > 1.5 × ULN (unless due to Gilbert's disease).

17. Evidence of chronic liver disease.

18. Congenital long QT syndrome or prolonged QT corrected for heart rate by Fridericia (QTcF) > 470 ms or history of QT prolongation associated with other medications thatrequired discontinuation of that medication.

19. Current untreated or uncontrolled arrhythmia (eg, multifocal premature ventricularcontractions, bigeminy, trigeminy, ventricular tachycardia). Note: Participants withclinically significant sinus nodal disease/bradycardia or Type 2 second- orthird-degree atrioventricular (AV) block can be included if treated with pacemaker.

20. Participants with recent (within 3 months of Visit 1) myocardial infarction,unstable angina pectoris, stroke, percutaneous coronary intervention and coronaryartery bypass grafting (within 6 months of Visit 1).

21. Current smokers, former smokers with > 10 pack-years history, or former smokers whostopped smoking < 6 months before Visit 1 (including all forms of tobacco,e-cigarettes (vaping), and other recreational drugs including marijuana).

22. History of current or previous alcohol or drug misuse in the 12 months prior toscreening. The use of oral cannabis is permitted.

23. Current diagnosis of cancer or unresectable cancer that has not been in completeremission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cellcarcinomas of the skin and cervical carcinoma-in-situ that have been treated andconsidered cured at the time of enrolment are not exclusionary.

24. History of documented immune complex disease (Type III hypersensitivity reactions)to monoclonal antibody (mAb) administration.

25. History of hypersensitivity or anaphylaxis to any components of AZD8630 formulation.

26. History of anaphylaxis or ongoing clinically important serious allergy, as judged bythe investigator, or history of anaphylaxis that required the use ofepinephrine/adrenaline or hospitalisation.

27. A helminth parasitic infection diagnosed within 24 weeks of screening that has notbeen treated or has not responded to standard of care therapy.

28. Use of the following medicines within the specified time before screening:

29. Treatment with marketed or investigational biologics for asthma orimmunological disease within 4 months or a minimum of 5 half-lives, whicheveris longer, prior to the screening visit.

30. Systemic steroids within 4 weeks prior to the screening visit. Note: Intranasalsteroid use is permitted, provided that there has been a stable treatmentregimen for 4 weeks.

31. Live, attenuated, or mRNA vaccine in the 4 weeks prior to screening visit.

32. Any systemic immunosuppressive therapy within 3 months of screening visit untilthe end of the follow-up period.

33. Use of allergen immunotherapy within 3 months of screening visit, except forstable maintenance dose allergen-specific immunotherapy started 4 weeks priorto screening visit.

34. Bronchial thermoplasty in the last 12 months prior to screening visit.

35. Receipt of immunoglobulin or blood products within 4 weeks prior to screeningvisit.

36. Participation in another clinical study with a study intervention administeredwithin 5 half-lives or in accordance with local regulations (whichever is longer)prior to screening.