This study is a multi-center, randomized, double-blind, placebo-controlled Phase II clinical study to evaluate the efficacy, safety, PK characteristics, PD effects and immunogenicity of CM326 in subjects with moderate to Severe Chronic Obstructive Pulmonary Disease.

The study consists of a screening period of up to 4 weeks, a randomized treatment period of 24 to 52 weeks, and a 12-week safety follow-up period.

Inclusion Criteria:

1. Understand the study and voluntarily sign the informed consent form.
2. Age ≥40 and ≤85 years old, male or female, at the time of signing the informed consent.
3. weight ≥40 kg.
4. Diagnosed with COPD for at least 12 months.
5. Post-bronchodilator FEV1/FVC ratio <0.70 and post-bronchodilator FEV1 % predicted ≥20% and <80%.
6. Background therapy for 3 months prior to screening with a stable dose of medication for ≥1 month prior to screening.
7. Exacerbation history of ≥2 moderate or ≥1 severe AECOPD within the year prior to screening.
8. COPD assessment test (CAT) Total Score ≥10.
9. Blood eosinophils ≥0.15×10^9 /L at screening.
10. Current smoking or a history of smoking ≥ 10 pack-years, or exposure to biomass smoke (including but not limited to biomass fuel, secondhand smoke, and the like) for ≥ 10 years.
11. Voluntarily use highly effective contraception from the time of signing the informed consent form until 3 months after the last dose.

Exclusion Criteria:

1. A current diagnosis of asthma or history of asthma according to the Global Initiative for Asthma (GINA) guidelines（asthma alone or asthma as the primary diagnosis, including but not limited to asthma with COPD）
2. Subjects with significant pulmonary disease other than COPD (e.g., sarcoidosis, interstitial lung disease, primary pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome, active tuberculosis or non-tuberculous mycobacterial infection, etc.), in the opinion of the investigator. Or other conditions that could lead to elevated eosinophils.
3. The presence of any severe and/or uncontrolled medical condition that in the judgment of the investigator would affect the evaluation of the drug, including but not limited to: severe neurological disease (eg, epilepsy, dementia, etc), history of severe mental disorder, major cardiovascular disease, diabetes mellitus poorly controlled by intensive treatment, QTcF interval prolongation（male >450 msec, female >470 msec）, or persistent arrhythmia.
4. History of malignancy.
5. Previous history of known or suspected immunosuppression; Or the presence of unusual frequent, recurrent, or prolonged infections, per investigator's judgment.
6. Prior autoimmune disease or inflammatory treatment with biologic agents/systemic immunosuppressive agents within 8 weeks or 5 half-lives (whichever is longer) prior to informed consent.
7. Heart failure NYHA Class IV, uncontrolled Cor pulmonale as judged by the investigator or with evidence of right cardiac failure.
8. Myocardial infarction, unstable angina, or stroke occurring within 6 months prior to signing the informed consent form (ICF).
9. Parasitic infection diagnosed within 24 weeks prior to signing the informed consent form (ICF), which has not received standard treatment or is refractory to standard treatment.
10. Acute moderate or severe exacerbation of COPD from 4 weeks before signing consent to the time of randomization.
11. Acute infection requiring systemic anti-infective therapy from 4 weeks before signing consent to the time of randomization.
12. Major surgery within 8 weeks prior to consent or planned surgery requiring general anesthesia or hospitalization for > 1 day during the study period.
13. History of or planned pneumonectomy or lung volume reduction surgery for COPD 12 months prior to screening.
14. As judged by the investigator, long-term daily oxygen therapy for more than 15 hours per day due to medical necessity, or concurrent hypercapnia requiring the use of bilevel positive airway pressure (BiPAP) non-invasive ventilation.
15. Patients who are participating in the acute phase of a pulmonary rehabilitation program, ie, who start rehabilitation <4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program could be included).
16. Patients who are treated with systemic corticosteroids (topical, ophthalmic, or intranasal corticosteroids are excluded) from 4 weeks before signing the informed consent to the date of randomization. Except for short-term (≤7 days) use of systemic glucocorticoids to prevent or treat non-autoimmune allergic diseases.
17. Use of macrolide antibiotics (eg, azithromycin) unless stable >3 months prior to screening visit and maintain the treatment during the planned study period.
18. Treatment with a PDE-4 inhibitor (roflumilast) (unless on stable treatment for ≥ 3 months with a plan to maintain stable treatment throughout the study period).。
19. Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days before consent or any other biologic therapy (including other anti-IL4R mAb, anti-IL5 mAb, anti-IL5R mAb, anti TSLP mAb, anti-IL33 mAb, anti-ST2 mAb) within 3 months or 5 half-lives before signing consent, whichever is longer.
20. Have been enrolled in a clinical trial of any drug or medical device within 3 months before signing informed consent, or are within the follow-up period of a clinical study or the five half-lives of the trial drug (whichever is longer) before signing informed consent.
21. Received immune globulin or blood products within 30 days before informed consent.
22. Receipt of traditional Chinese medicines (TCMs), ethnic medicines, or natural medicines approved by the National Medical Products Administration (NMPA) for the indication of COPD treatment within 4 weeks prior to randomization.
23. Receipt of live or attenuated vaccine within 3 months before consent signing or during the planned study period.
24. Non-negative HIV serological test result at screening, or Treponema pallidum infection requiring treatment.
25. Subjects infected with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) must meet the following laboratory criteria during the screening period: a. HBsAg positive b. HBsAg negative , HBcAb positive, HBV DNA exceed the lower limit of quantitation (LLOQ) or 1000 copies/mL c. HCV antibody positive, HCV RNA exceed the LLOQ.
26. At screening, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN), or serum creatinine (Cr) > 1.5 × ULN or serum creatinine > 1.5 × ULN.
27. Females with a positive pregnancy test, pregnant females, or lactating females.
28. Allergy or intolerance to components of CM326 injection or placebo or history of severe drug allergy or anaphylactic shock.
29. History of drug abuse within 5 years before signing informed consent.
30. <70% compliance with usual COPD controller therapy in subjects during the screening phase.
31. The investigator considers that there are any conditions that may prevent the subject from completing the study .