Evaluate the Efficacy and Safety of FB825 in Adult With Allergic Asthma

Inclusion Criteria:

1. Male or females 18-75 years old.

2. Subjects diagnosed with moderate-to-severe allergic asthma [Global Initiative forAsthma [GINA]; GINA, 2021) at least 12 months prior to Visit 1.

3. Documented reversibility from historical data within 3 years of Visit 1 of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcgalbuterol/salbutamol (or other standard office practice) OR documented airwayhyperresponsiveness (methacholine PC20 < 8 mg/mL [or PC20 < 16 mg/mL on ICS]) within 3 years of Visit 1. If documented reversibility data is not available, thebronchodilator test should be finished before randomization.

4. Subjects must have a pre-bronchodilator FEV1 value of ≥ 40% and ≤ 80% predictedwithin 2 months from randomization .

5. Subjects must have received a physician-prescribed asthma regimen with medium- orhigh-dose ICS plus LABA for at least 3 month prior to Visit 1 and the dose of ICSmust be stable for at least 30 days prior to Visit 1 and throughout the screeningperiod.

6. High-dose ICS is defined as total daily dose of >500 mcg fluticasone propionateor equivalent

7. Medium-dose ICS is defined as a total daily dose of 250 to 500 mcg fluticasonepropionate or equivalent.

8. Equivalence ICS doses will be based upon the GINA guidelines (GINA, 2019),shown in Appendix 12.1

9. According to the medical history, subject have no more than a maximum of 2000mcg/day equipotent ICS daily dosage of fluticasone propionate or equivalent in 3 months before entry of study.

10. Prior to screening, subjects must be on a stable dose of any of the following dosesand formulations of ICS/LABA combination therapy for at least 1 month:

11. Fluticasone/salmeterol combination therapy

• Advair® Diskus - dry powder inhaler (DPI): 250/50 μg BID or 500/50 μg BID,or
• Advair® HFA - metered dose inhaler (MDI): 230/42 μg BID or 460/42 μg BID,or

2. Budesonide/formoterol combination therapy (Symbicort® -160/9 μg BID or 320/9 μgBID), or

3. Mometasone/formoterol combination therapy (Dulera® -200/10 μg BID or 400/10 μgBID).

4. Subjects must have a documented history of protocol-defined severe asthmaexacerbation at least 1 or more times within the 12 months.

5. A total serum IgE ≥ 360 IU/mL.

6. Subjects must have at least one positive in skin prick test or at least oneenvironmental allergen-specific IgE greater than normal range.

7. Uncontrolled asthma demonstrated both during the screening period and at the time ofrandomization defined as ACQ-5 (5-item Asthma Control Questionnaire) ≥ 1.5

8. If recently treated for respiratory tract infection, the treatment must have beencompleted at least 4 weeks prior to screening. Subjects who have an upperrespiratory tract infection during screening are allowed to be rescreened 4 weeksafter resolution.

9. Female subjects of childbearing potential must use at least two forms of birthcontrol. One must be barrier protection (i.e., condom or female condom) and theother is one of acceptable method of birth control (ie, diaphragm, intrauterinedevice, hormonal contraceptives, or abstinence) throughout the study. Subjects whoare surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateraloophorectomy), or postmenopausal (defined as amenorrhea for 12 consecutive monthsand documented serum follicle stimulating hormone level >40 mU/mL) will beconsidered as no childbearing potential. All female subjects of child-bearingpotential must have a negative serum pregnancy test at screening. Note: The subject must use the methods of contraception mentioned above during studyperiod and at least 120 days after the last dosing of FB825.

10. The subject has a body weight ≥ 40 kg at screening.

11. The subject has a normal, as determined by the investigator, 12-leadelectrocardiogram (ECG).

12. The subject is able to provide written informed consent.

13. The subject agrees to comply with all protocol requirements.

Exclusion Criteria:

1. Asthma exacerbation or any other reason requiring systemic steroids in the 30 daysprior to randomization. Subjects are allowed to be rescreened 30 days aftercompletion of treatment.

2. >20% relative change in FEV1 between screening and randomization.

3. Female subjects who are pregnant or lactating.

4. A positive human immunodeficiency virus (HIV) test (e.g., HIV Ag/Ab combo test) atscreening or subject taking antiretroviral medications, as determined by medicalhistory.

5. Patients with positive HBeAg or HCV RNA results should be excluded as they areindications of active Hepatitis B virus and Hepatitis C virus replication.

6. Active lung diseases (e.g., bronchitis, chronic obstructive pulmonary disease) otherthan allergic asthma.

7. Use of any experimental drug within 30 days or 5 half-lives, whichever is longer,prior to or during the screening period.

8. Current or history of treatment with a monoclonal antibody, for example, interleukin (IL)-4, IL-5, IL-13 or IL-15 antibody treatment within 6 months prior to thescreening.

9. Current or history of treatment with anti-IgE antibody treatment within 6 months or 5 half-lives, whichever is longer.

10. The subject has a history of alcohol or drug abuse that would impair or risk thepatients' full participation in the study, in the opinion of the investigator.

11. The subject has any condition that, in the opinion of the investigator, wouldcompromise the study or the well-being of the subject or prevent the subject frommeeting or performing study requirements.

12. The subject has indication of severe liver disease, defined by serum levels ofeither alanine aminotransferase (ALT), aspartate transaminase (AST) above 3x upperlimits of normal (ULN) or elevated total bilirubin >2x ULN as determined atscreening.

13. The subject has severe kidney disease, defined as estimated glomerular filtrationrate (GFR)<30ml/min/1.73m2 or creatinine > 3x ULN.

14. The subject has known or suspected history of immunosuppression or immunodeficiency.

15. Known history of active tuberculosis (TB) or evidence of tuberculosis infection asdefined by a positive purified protein derivative (PPD) skin test and/orinterferon-gamma release assay. The interferon-gamma release assay should berepeated in case of an indeterminate result.

16. The subject has history of malignancy within 5 years before the screening period.Patients with non-invasive carcinoma in-situ of the cervix, basal cell carcinoma orsquamous cell carcinoma of the skin may be eligible if they have undergone curativeresection at least 12 months prior to screening.

17. Current smoker with > 10 packs year prior to screening. A smoker is defined as asubject who has taken inhaled nicotine containing products (e.g. cigarette, cigar,pipe), including e-cigarettes prior to screening.

18. High risk of parasite infection

• Risk factors for parasitic disease (living in an endemic area, travel within thelast 6 months to regions where geohelminthic infections are endemic, and/or chronicimmunosuppression). AND

• Evidence of parasitic colonization or infection on stool evaluation for ova andparasites. Note: stool ova and parasite evaluation will only be conducted in patients with riskfactors and an eosinophil count more than twice the upper limit of normal.

19. The subject has received live vaccine within 12 weeks prior to dosing or plannedlive attenuated vaccinations during the study.

20. The subject has a history of any clinically relevant arrhythmias as determined bythe investigator.

21. The subject has a history of respiratory failure or near fatal asthma events whichresulted in intensive care unit admission or intubation within five years before thescreening period.

22. History of anaphylaxis to any biologic therapy.

23. The subject has major surgery, for example organ replacement, joint replacement,full hysterectomy, heart surgeries, within 8 weeks before the screening. The subjectwho has major surgery prior to 8 weeks of screening should have fully recovered fromany surgical procedures.

24. The subject has comorbid disease that might interfere with the evaluation of IMP (investigational medicinal product) or conduct of study procedures (eg,bronchodilator test).

25. The subject requiring non-selective beta-adrenergic receptor blockers for any reasonand initiation or dose change of a selective beta-1 adrenergic receptor blockerwithin 3 months prior to Visit 1.

26. The subject who received bronchial thermoplasty within 3 years of Visit 1 ORpatients who plan to begin therapy during the Screening Period or the RandomizedTreatment Period.

27. The subject with active autoimmune disease (excluding atopic dermatitis) or patientsusing immunosuppressive therapy for autoimmune disease (excluding atopic dermatitis) (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis,systemic lupus erythematosus, multiple sclerosis, etc.) or patients with high titerautoantibodies at screening who are suspected of having high risk for developingautoimmune disease at the discretion of the Investigator or the Sponsor.

28. Use of Traditional Chinese Medications in the treatment of asthma within 3 monthsprior to screening. (To be listed in Prohibited Medications)

29. Aggravating factors that are inadequately controlled e.g., medication uncontrolledgastroesophageal reflux disease.

30. The subject has adrenal insufficiency (ACTH-resistant) by rapid ACTH stimulationtest due to known history of adrenal insufficiency or being suspected of adrenalinsufficiency or long-term use of systemic corticosteroids (annual average more than 6 months in the past two years).

Adrenal insufficiency: after 30 minutes of ACTH injection, the cortisol level ≦20 mg/ml in rapid ACTH stimulation test.