SIM0718 Treatment of Asthma Clinical Study

Inclusion Criteria:

• Age 12 to 75 years, weight ≥ 40 kg, diagnosed with asthma for at least 12 months；

• Currently receiving medium- to high-dose inhaled corticosteroids (ICS) incombination with 1 or 2 control medications and have been on a stable dose for atleast 28 days prior to randomization；

• Pre-bronchodilator (trough) FEV1 ≤ 80% of predicted normal for adults and ≤90% ofpredicted normal for adolescents ；

• Positive bronchodilator response within 12 months prior to randomization or duringthe screening period;

• Asthma Control Questionnaire (ACQ-5) score ≥ 1.5;

• At least one severe asthma exacerbation within 12 months prior to the screeningvisit and no occurrence within 28 days prior to randomization;

• Based on the investigator judgment, the subject demonstrates acceptable inhaler,peak flow meter, and spirometry techniques;

• Compliance with usual asthma controller use ≥ 80% based on the patient diary in 7days prior to dosing;

• Voluntarily participate in this clinical study and sign the informed consent formand be able to comply with the clinical visit schedule and study-related procedures;

• Female subjects of childbearing potential who are sexually active withnon-sterilized male partners, male subjects, and their female partners ofchildbearing potential agree to use adequate and effective contraception throughoutthe study;

Exclusion Criteria:

• Current respiratory disease that may impair lung function as judged by theinvestigator;

• Diagnosis of helminth parasitic infection within 24 weeks prior to randomization andwho have not received or have not responded to standard therapy;

• Within 28 days prior to randomization, with acute or chronic infection; or have asevere viral infection;

• Has a known or suspected history of immunosuppression or frequent, recurrent, orlong-term infection;

• History of active tuberculosis; or untreated latent tuberculosis or tuberculosis notreceiving standard treatment, unless the investigator judges that the patient hasbeen adequately treated;

• People with hepatitis B, hepatitis C, or HIV infection;

• History of malignancy;

• Major surgery within 8 weeks prior to signing the informed;

• Bronchial thermoplasty within 12 months prior to randomization;

• Treatment of systemic glucocorticoid during 4 weeks prior to signing informed torandomization;

• Previous use or ongoing use of systemic immunosuppressants or biologics for thetreatment of autoimmune or inflammatory diseases in 8 weeks or 5 half-lives prior torandomization;

• Within 16 weeks or 5 half-lives prior to randomization, received a biologic agentwith the same therapeutic purpose;

• Participated in an interventional clinical trial of any drug or medical devicewithin 3 months or 5 half-lives prior to randomization;

• Poor response to or intolerance to prior anti-IL-4Rα antibody therapy;

• Within 3 months prior to randomization, received specific immunotherapy；

• Receipt of intravenous human immunoglobulin (IVIG) or blood products within 30 daysprior to randomization;

• Vaccination with live(attenuated) vaccine within 30 days prior to randomization orplan to receive live (attenuated) vaccine during the study;

• Are using concomitant medications or treatments that are prohibited in the protocol;

• The following laboratory abnormalities occurred during the screening period:eosinophils≥1500 cells/mm3 or 1.5×109/L; Platelets≤80,000 cells/mm3 or 80×109/L;phosphocreatine kinase (CPK) ≥5 times the upper limit of normal (ULN); alanineaminotransferase (ALT) ≥3-fold ULN; aspartate aminotransferase (AST)≥ 3-fold ULN;Bilirubin ≥ 2x ULN;

• History of alcohol abuse or drug abuse within 12 months prior to randomization;

• Current smokers, or those who have been smoking in recent 6 months, or formersmokers who have not been smoking for 6 months with a smoking history of ≥10 packyears;

• Allergy to L-histidine, trehalose, or Tween 80, or history of systemichypersensitivity to any biologic products;

• Females of childbearing potential have a positive pregnancy test result during thescreening period; Females planning to become pregnant or breastfeeding;

• Any clinically significant examination abnormality or serious and/or uncontrolleddisease that, in the opinion of the investigator, may affect the subject safety, oraffect the evaluation of efficacy, or preclude the subject completion of the entirestudy.