Inclusion Criteria:

• Participant must be 40 to 80 years of age, inclusive, at the time of signing the informed consent.

• History of physician-diagnosed COPD for at least 1 year prior to screening, that is considered moderate-to-very severe, with a post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator FEV1 ≥20% and ≤70% of predicted normal value at Screening (Visit 1)

• Current or former smokers with a smoking history of ≥10 pack-years.

• Chronic Airways Assessment Test (CAAT) score ≥10 at Screening (Visit 1).

• Documented history of high exacerbation risk, with either ≥2 moderate* exacerbations or ≥1 severe** exacerbation within the year prior to Screening (Visit 1). Moderate exacerbations are recorded by the Investigator and defined as AECOPD that requires either systemic corticosteroids for at least 3 days (or 1 injection of depot formulation) and/or antibiotics (see Section 10.11.1). *Severe exacerbations are recorded by the Investigator and defined as AECOPD requiring hospitalization or emergency room (or urgent care facility) visit lasting >24 hours.

For both moderate and severe AECOPD events to be counted as separate events, they must be separated by at least 14 days between any course of systemic steroids/antibiotics or 14 days between discharge and new admission in case of hospitalization (severe AECOPD events only).

• Participant must be on triple controller therapy (LABA+LAMA+ICS) for at least 12 weeks prior to randomization, with a stable dose of medication for ≥ 4 weeks prior to Screening (Visit 1). Additionally, there must have been at least 1 exacerbation while on the current regimen (dual controller therapy with LABA+LAMA is allowed in case of ICS contraindication).

• Evidence of T2 inflammation: Participants with blood eosinophil counts ≥150 cells/μL at Screening (Visit 1).

• Body mass index (BMI) between 18.0 and 40.0 kg/m2, inclusive, at Screening (Visit 1) with a minimum body weight of 40.0 kg.

• All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 2 months after the last administration of study intervention: • Refrain from donating or cryopreserving sperm PLUS, either: - OR - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent Must agree to use contraception/barrier as detailed below - A male condom and an additional highly effective contraceptive method as described in Appendix 4 (Section 10.4: Contraceptive and barrier guidance) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.

Female participants:

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: - Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 4 (Section 10.4: Contraception and barrier guidance). OR - Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, as described in Appendix 4 (Section 10.4: Contraception and barrier guidance) during the study intervention period (to be effective before starting the intervention) and for at least 2 months after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.

• A WOCBP must have a negative highly sensitive pregnancy test. Serum pregnancy test will be performed at Screening (Visit 1) and urine pregnancy test will be performed before first administration of study intervention (Visit 2), at the early discontinuation visit, and at the EOS (Visit 16) (see Section 8.4.5). - A urine pregnancy test will be performed prior to each IMP administration and until the EOS visit.

• Capable of giving signed informed consent as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative (LAR).

Exclusion Criteria:

• A current diagnosis of asthma or documented history of asthma, including pediatric asthma and documented asthma-COPD overlap syndrome (ACOS), according to the 2024 Global Initiative for Asthma (GINA) guidelines (25) or other accepted guidelines.

• Significant pulmonary disease other than COPD (eg, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis) or another diagnosed pulmonary or systemic disease associated with elevated peripheral blood eosinophil counts.

• Long-term treatment with oxygen at a flow rate >4.0 L/min, or if a participant requires >2.0 L/min in order to maintain oxygen saturation >88%.

• Hypercapnia requiring bi-level positive airway pressure (BiPAP). Continuous Positive Airway Pressure (CPAP) for Obstructive Sleep Apnea Syndrome (OSAS) without hypercapnia is allowed.

• Participants who are <80% compliant with controller therapy (ie, LABA+LAMA+ICS, see details in Section 6.9.2.1) during screening.

• AECOPD within 4 weeks prior to or during the screening period. If a participant experiences an AECOPD during the screening period, the screening period can be extended by up to 12 additional weeks, ensuring that Randomization (Visit 2) occurs no sooner than 4 weeks after the completion of treatment (systemic corticosteroids or antibiotics) for the AECOPD.

• Clinically symptomatic respiratory tract infection within 4 weeks prior to screening, or during the screening period. If a participant experiences a respiratory tract infection during the screening period, the screening period can be extended by up to 12 additional weeks, ensuring that Randomization (Visit 2) occurs no sooner than 4 weeks after the completion of treatment or stabilization of symptoms, whichever occurs later.

• Confirmed, COVID-19 infection at Screening (Visit 1), during the screening period, or at Randomization (Visit 2); these participants may be rescreened 4 weeks after the resolution of symptoms or, if asymptomatic at time of testing and thereafter, 4 weeks after a positive test.

• History of, or planned pneumonectomy or lung volume reduction surgery. Participants who are participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation <4 weeks prior to screening (Note: Participants in the maintenance phase of a rehabilitation program can be included).

• Diagnosis of alpha-1 antitrypsin deficiency.

• A participant with a history of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular conditions, substance and/or alcohol abuse, or a prior history of malignancy or active malignancy, including lymphoproliferative diseases (except successfully-treated carcinoma in-situ of the cervix, non-metastatic squamous cell, or basal cell carcinoma of the skin) within 5 years prior to Screening (Visit 1), or other significant medical illness or disorder which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study. Specific examples include, but are not limited to, poorly controlled insulin-dependent diabetes and uncontrolled hypertension.

• Major surgery within 8 weeks before Screening (Visit 1).

• History of severe systemic hypersensitivity or anaphylaxis to any biologic therapy, including any excipients.

• Cor pulmonale or evidence of right-sided heart failure.

• Clinically significant abnormal ECG at Randomization (Visit 2) that may affect the conduct of the study in the judgment of the Investigator, including a prolonged QTc interval (>450 msec for males and >470 msec for females, using Fridericia correction).

• Active tuberculosis or non-tuberculous mycobacterial infection, latent untreated tuberculosis, or a history of incompletely treated tuberculosis, unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, as determined by the medical judgment of the Investigator and/or infectious disease specialist.

• Acute myocardial infarction <6 months from Screening (Visit 1).

• Transient ischemic attack (TIA) or stroke <6 months from Screening (Visit 1).

• Hospitalization for any cardiovascular (CV) or cerebrovascular event <6 months from Screening (Visit 1).

• Heart failure New York Heart Association (NYHA) Class III or IV.

• Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation are excluded. Participants with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (ie, selective beta blocker, calcium channel blocker, pacemaker placement, digoxin, or ablation therapy) and stable appropriate level of anticoagulation for at least 6 months may be considered for inclusion.

• Unstable ischemic heart disease or other relevant cardiovascular disorder such as pulmonary embolism, deep vein thrombosis within ≤6 months from enrollment that in the judgment of the Investigator may put the participant at risk or negatively affect the study outcome.

• Females who are lactating, breastfeeding, or pregnant.

• Diagnosed active parasitic infection (helminthes), suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization.

• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, or aspergillosis), despite infection resolution; or unusually frequent, recurrent or prolonged infections, per the judgment of the Investigator.

• Evidence of acute or chronic infection requiring treatment with antibacterials, antivirals, antifungals, antiparasitics, or antiprotozoals within 4 weeks before Screening (Visit 1), significant viral infections within 4 weeks before Screening (Visit 1) regardless of antiviral treatment (eg, influenza receiving only symptomatic treatment).

• Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).

• Live, attenuated vaccinations within 12 weeks prior to Screening (Visit 1) or planned live, attenuated vaccinations during the study, and non-live vaccines (including ribonucleic acid [RNA] vaccines) within 2 weeks prior to Screening (Visit 1) (see Table 6 for the list of allowed, restricted, and prohibited medications, and Section 10.11.4 for the list of prohibited live, attenuated vaccines).

• Participants on long-term macrolide (eg, azithromycin) therapy, unless on stable therapy for >6 months prior to Screening (Visit 1) and have experienced at least 1 exacerbation while on this regimen. Macrolides are allowed to treat COPD exacerbation throughout the trial.

• Participants on phosphodiesterase Type 3 (PDE-3) (eg, ensifentrine) or PDE-4 inhibitors (eg, roflumislast) therapy, unless on stable therapy for >6 months prior to Screening (Visit 1).

• Anti-IgE therapy (eg, omalizumab [Xolair]) within 130 days prior to Screening (Visit 1) or any other biologic therapy (including anti-IL-4/interleukin-4 receptor [IL-4R], IL-5/interleukin-5 receptor [IL-5R]), IL-13, or TSLP) or systemic immunosuppressant (eg, methotrexate) to treat inflammatory or autoimmune diseases (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, or multiple sclerosis) and other diseases, within 8 weeks or 5 half-lives prior to Screening (Visit 1), whichever is longer (see Table 6).

• Participants currently receiving COPD controller therapy that is not locally approved for COPD or receiving medication or therapy that are prohibited as concomitant therapy (see Table 6).

• Current enrollment or past participation in another investigational study in which an investigational intervention (eg, drug, vaccine, or invasive device) was administered within the time frame specified in Table 6.

• History of human immunodeficiency virus (HIV) infection or positive HIV Type 1 (HIV-1)/HIV Type 2 (HIV-2) serology or positive HIV deoxyribonucleic acid (DNA) at Screening (Visit 1).

• Participants with any of the following result at screening: Positive (or indeterminate) Hepatitis B surface antigen (HBsAg), or Positive immunoglobulin M antibody against Hepatitis B core antigen (IgM HBcAb), or Positive total Hepatitis B core antibody (HBcAb) confirmed by positive Hepatitis B virus (HBV) DNA, or Positive Hepatitis C virus (HCV) Ab confirmed by positive HCV RNA.

• Clinically significant laboratory tests at Screening (Visit 1): Alanine transaminase (ALT) or aspartate aminotransferase (AST) >2 times upper limit of normal (ULN) range. Serum total bilirubin >1.5×ULN (participants with Gilbert's syndrome can be included with total bilirubin >1.5×ULN as long as direct bilirubin is <1.5×ULN). Hemoglobin <10 g/100 mL for male and <9 g/100 mL for female. Neutrophils <1500/μL (<1000/μL for those of African descent). Platelets <100 000/μL. Creatinine ≥150 μmol/L.

• Participant who has withdrawn consent before enrollment/Randomization (Visit 2) despite screening of the participant, enrollment/randomization is stopped at the study level.

• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.

• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

• Inability to follow the procedures of the study (eg, due to language problems, psychological disorders) or unable to read, understand and fill out a questionnaire or use an electronic diary (eDiary) without any help.

• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use [ICH]-Good Clinical Practice [GCP] Ordinance E6).

• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

• Any country-related specific regulation that would prevent the participant from entering the study – see Appendix 7 (Section 10.7: Country-specific/region requirements).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/09/2025. Questions regarding updates should be directed to the study team contact.