This is a multi-center, randomized, double blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of CM326 in patients with chronic rhinosinusitis with nasal polyps.

The study consists of 3 periods, a Screening Period, a Treatment Period and a Safety Follow-up Period.

Subjects who meet eligibility criteria will be randomized to receive either CM326 or placebo subcutaneously.

Inclusion Criteria:

• Subjects who are capable of understanding the nature of the study and voluntarily signing the ICF.
• Male or female subjects, aged between 18 and 70 years old (inclusive), with a body mass index (BMI) ≥ 19 kg/m2.
• Diagnosed with Chronic Rhinosinusitis With Nasal Polyps.
• The total NPS score should be at least 3 points, with at least 1 point in each side of the nasal cavity.
• Prior treatment with systemic corticosteroids (SCS) within two years before screening, and/or contraindicate to or intolerance to systemic corticosteroids, and/or with prior surgery to nasal polyps 6 months before the screening.
• Ongoing symptoms for at least 4 weeks before screening：1) Nasal congestion/obstruction; 2) Other symptom, e.g., loss of smell or rhinorrhea.

Exclusion Criteria:

• Allergic or intolerant to mometasone furoate spray or CM326/placebo.
• Have used of systemic immunosuppressants for inflammatory or autoimmune diseases within 8 weeks or 5 half-lives prior to randomization.
• Have initiated leukotriene receptor antagonist therapy within 4 weeks prior to randomization.
• have received allergen-specific immunotherapy that initiated within 3 months prior to randomization or planned to be initiated during the study period.
• Have undergone nasal surgery (including nasal polypectomy) within 6 months prior to screening.
• Have received medium- and short-acting systemic corticosteroids (including oral, intravenous, intramuscular corticosteroids), nasal dripping corticosteroids, traditional Chinese medicine (including systemic and local herbal products preparations) for chronic rhinosinusitis (CRS) within 4 weeks prior to screening, or long-acting systemic corticosteroids.
• With concomitant asthma (including suspected diagnosis of asthma) will be excluded if they meet the following conditions: predicted FEV1 of≤ 60%, or acute exacerbation of asthma within 3 months prior to screening requiring SCS or hospitalization (> 24 hours), or using inhaled corticosteroids (ICS) of > 1000 μg fluticasone propionate or others at equivalent doses
• With antrochoanal polyps.
• With severe deviation of the nasal septum occludes at least one nostril.
• With persistent rhinitis medicamentosas.
• With allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, cystic fibrosis.
• With acute sinusitis, nasal infection, or upper respiratory tract infection at screening.
• Have symptoms or whose CT scan suggests allergic fungal sinusitis.
• With malignant or benign neoplasm of nasal cavities.
• With other uncontrolled serious diseases or recurrent chronic diseases.
• Have severe hepatic and renal impairment.
• Have received live attenuated vaccines within 12 weeks prior to randomization, or during the planned study; or have received inactivated vaccines (e.g., novel coronavirus vaccines) within 30 days prior to randomization.
• With known or suspected immunosuppression, including, but not limited to, the history of invasive opportunistic infections.
• Subjects who are pregnant or planning to become pregnant, or breastfeeding during the study.
• With a history of large alcohol consumption or a history of drug abuse within 3 months prior to screening.
• With other medical or non-medical conditions that are not suitable for participation in the study in the opinion of the investigator.