This is a multi-center, randomized, double blind, placebo-controlled Phase III study to evaluate the efficacy and safety of CM326, and to observe the Pharmacokinetics, Pharmacodynamics and I immumogenicity[c2.1] of CM326 in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).The study consists of four periods, including an up to 4-week screening/run-in period, a 24-week double-blind randomized treatment period, a 28-week open-label treatment period, and an 8-week safety follow-up period.

Inclusion Criteria:

1. Understand the study and voluntarily sign the informed consent form.
2. Age between 18 and 75 years (inclusive) at the time of informed consent signing, regardless of gender.
3. Diagnosis of bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) meeting the diagnostic criteria of the "Chinese Guidelines for the Diagnosis and Treatment of Chronic Rhinosinusitis (2024)".
4. Meet at least 1 of the following 4 items: a. Received SCS treatment for at least 3 consecutive days within 2 years prior to screening; b. Received at least one long-acting SCS (such as triamcinolone acetonide injection) within 2 years prior to screening; c. Had [c8.1]contraindications to SCS treatment or intolerance to SCS treatment; d. Received nasal polyp surgery more than 6 months prior to screening.
5. Concurrent presence of the following symptoms for ≥[c9.1]8 weeks prior to the screening/run-in period: a. nasal congestion; b. Any[c10.1] other symptom such as hyposmia/loss of smell or rhinorrhea
6. Stable dose of intranasal corticosteroids (INCS) for >4 weeks prior to screening (participants using non-mometasone furoate nasal spray [MFNS] products must agree to switch to Mometasone Furoate Nasal Spray (MFNS) during the study). The evaluation during the lead-in period showed that the medication adherence to intranasal mometasone furoate nasal spray (MFNS) was greater than 70%.
7. Bilateral Nasal Polyp Score (NPS) ≥5 (maximum score 8) with ≥2 points per nostril, as assessed by nasal endoscopy during screening and before randomization.
8. Nasal Congestion Score (NCS) ≥2 at the screening visit and before randomization(weekly average score).[c11.1][11.2]
9. 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥30 at screening and before randomization.
10. Eligible participants of childbearing potential (males and females) must agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence, etc.) with their partners during the trial and for 3 months after the last dose; Females of childbearing potential must be non-lactating, have a negative blood pregnancy test at screening, and have a negative blood or urine pregnancy test before randomization.

Exclusion Criteria:

1. Presence of nasal conditions affecting NPS evaluation, including but not limited to: a. Antrochoanal polyps; b. Nasal septum perforation or severe nasal septum deviation occluding at least one nostril; c. Nasal surgery that alters the structure of the lateral nasal wall precluding completion of the NPS assessment.
2. Clinically significant comorbidities other than asthma that may affect the efficacy assessment or interfere with the interpretation of the efficacy assessment results, including but not limited to: a. Allergic granulomatosis with polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), allergic bronchopulmonary mycosis, and eosinophilic esophagitis; b. Bronchiectasis, pulmonary fibrosis, cystic fibrosis; c. Primary ciliary dyskinesia, Young's syndrome, Kartagner's syndrome, or other ciliary dyskinesia syndromes; d. Acute sinusitis, nasal infection, or upper respiratory tract infection at the time of the screening visit or within 2 weeks prior to the screening visit; e. Persistent rhinitis medicamentosa; f. Imaging suspected or confirmed fungal sinusitis; g. Malignant or benign tumors of the nasal cavity or paranasal sinuses.
3. Uncontrolled epistaxis within 2 months prior to screening;
4. Concomitant major chronic diseases that are uncontrolled and that, in the opinion of the investigator, may increase the safety risk of the participant's participation in this study;
5. Participants with other concomitant active or clinically significant respiratory diseases that may significantly affect the study, as judged by the investigator;
6. Participants with cardiovascular disease, and whose participation in this trial may affect the safety of the participants or the analysis of the study results at the discretion of the investigator.
7. Active malignancy of any type or history of malignancy;
8. Infection requiring systemic antibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal treatment within 14 days prior to screening; Diagnosed with helminthic parasitic infection within 6 months prior to screening and untreated or refractory to standard therapy;
9. History of active pulmonary tuberculosis within 12 months prior to screening, or old tuberculosis with high risk of recurrence as assessed by the investigator;
10. Known or suspected history of immunosuppression, immune dysfunction or immune dysregulation, including but not limited to invasive opportunistic infections even if the infection has resolved, history of splenectomy, primary immunodeficiency, etc.; or unusually frequent, recurrent, or prolonged infections as judged by the investigator;
11. Participants with comorbid asthma who have any of the following conditions: a. FEV1 ≤ 50% of the predicted normal value during the screening period and before baseline; b. Asthma exacerbation within 90 days prior to screening; c. Participants who are currently using inhaled corticosteroids at a daily dose higher than 1000 μg of fluticasone or equivalent, or who have started inhaled corticosteroids within 4 weeks prior to screening;
12. Nasal surgery within 6 months prior to screening;
13. Received medium- or short-acting SCS (including oral, intravenous, or intramuscular glucocorticoids) or traditional Chinese medicine (including systemic and topical traditional Chinese medicine preparations) for the treatment of chronic sinusitis within 4 weeks prior to screening, or received long-acting SCS (such as triamcinolone acetonide injection) within 6 weeks prior to screening, or plan to receive the above drugs during the study; Use of glucocorticoid-eluting intranasal stents within 6 months prior to screening;
14. Patients who have received treatment with other biological agents other than anti-TSLP monoclonal antibodies, including but not limited to IL-4Rα monoclonal antibodies and anti-IgE monoclonal antibodies, within 8 weeks or 5 half-lives (whichever is longer) prior to screening;
15. Previous treatment with anti-TSLP monoclonal antibody;
16. Received systemic immunosuppressant therapy within 8 weeks or 5 half-lives (whichever is longer) prior to screening;
17. Treatment with leukotriene receptor antagonists within 4 weeks before baseline;
18. Regular use of decongestants (topical or systemic) within 4 weeks prior to screening, except for short-term use for endoscopy;
19. Initiation of allergen-specific immunotherapy (desensitization therapy) within 3 months prior to baseline, or planned initiation of such therapy during the study period;
20. Treatment with immunoglobulin or blood products within 30 days prior to screening;
21. Any of the following infectious disease screening indicators meet the following criteria at screening: a. HBsAg positive or HBcAb positive and HBV-DNA positive; Patients who have received antiviral therapy in the past need to be excluded even if HBV-DNA is negative; b. HCV antibody positive and HCV-RNA positive. Patients who have received previous treatment for hepatitis C should still be excluded even if HCV-RNA is negative; c. Positive Treponema pallidum antibody test (if the Treponema pallidum particle agglutination test is positive, RPR or TRUST for syphilis is required. If the RPR or TRUST test is negative and the investigator judges that the participant has been infected with syphilis in the past but has been cured, he or she is eligible for inclusion); d. Human immunodeficiency virus antibody (Anti-HIV) positive.
22. Clinically[c12.1] significant laboratory abnormalities that, in the opinion of the investigator, pose a risk to or affect the participant's participation in the study; Or meet any of the following criteria: a. Glutamate aminotransferase or aspartate aminotransferase >2.5×ULN; b. Total bilirubin and/or direct bilirubin >2×ULN; c. Absolute neutrophil count <1.5×10^9/L; d. Serum creatinine >1.5×ULN.
23. Clinically significant abnormal findings found during the screening period, including physical examination, vital signs, 12-lead ECG, etc., which in the opinion of the investigator will pose a risk or affect the participant's participation in the study;
24. Hypersensitivity to MFNS or CM326; History of severe systemic allergy to any biologic agent (except local injection site reaction);
25. History of drug abuse, narcotics, and/or excessive alcohol consumption within 6 months prior to screening, as assessed by the investigator;
26. Current smokers or participants with a smoking history of ≥10 pack-years;
27. Vaccination with a live attenuated vaccine within 30 days prior to randomization or planned vaccination with a live attenuated vaccine during the study;
28. Use of any other clinical study drug or medical device within 30 days or 5 half-lives (whichever is longer) prior to screening; Or still participating in or planning to participate in other clinical trials;
29. As assessed by the investigator, the participant's poor compliance with this study (such as a clear history of mental disorder) makes it impossible to complete the study;
30. Other medical or non-medical conditions that, in the opinion of the investigator, make the participant unsuitable for participation in this study.