The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07275315) for the potential treatment of moderate-to-severe asthma. Asthma is a condition that makes it challenging to breathe, which negatively impacts the quality of life and functioning of people who are affected.

This study is seeking participants who:

• Are 18 to 70 years old
• Have had moderate-to-severe asthma for at least 12 months that is not well controlled
• Have been taking their regular maintenance treatment(s) for asthma over the last 12 months

All participants will receive PF-07275315 or a placebo. A placebo does not have any medicine in it but looks just like the medicine being studied.

PF-07275315 or placebo will be given as multiple shots in the clinic over the course of 12 weeks. We will compare the experiences of people receiving PF-07275315 to those of the people who do not. This will help us determine if PF-07275315 is safe and effective.

Participants will be involved in this study for about 7.5 months. During this time, they will have 9 visits at the study clinic.

Inclusion Criteria:

Must meet the following asthma criteria:

1. History of persistent, moderate-to-severe asthma for at least 12 months prior to screening.

2. Must have experienced at least 1 asthma exacerbation requiring treatment with systemic steroids (oral or parenteral) for 3 days or more within 12 months of the screening visit.

3. At least 2 of the 3 pre-bronchodilator FEV1 values collected in the run-in period and the mean of the of pre-bronchodilator FEV1 values collected in the run-in period are ≥30% to <80% of predicted normal values.

4. Positive bronchodilator responsiveness as evidenced by increase in FEV1 of at least 12% and 200 mL for spirometry conducted during screening period.

5. Maintenance (controller) treatment that minimally includes a medium to high dose ICS - LABA combination consistent with GINA Step 4/5 (either Track 1 or Track 2) for 12 months prior to the screening visit and at a stable dose for at least 3 months prior to the screening visit.

6. ACQ-5 score of ≥1.5 at screening visit and prior to randomization.

   Other Inclusion Criteria:

7. Body mass index between 18 40 kg/m2 at screening.

Exclusion Criteria:

Medical Conditions:

1. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

2. Evidence of lung disease(s) other than asthma, either clinical evidence, spirometry, or imaging (Chest X-ray, CT, MRI) within 12 months of the screening visit, as per local standard of care, including but not limited to: Chronic obstructive pulmonary disease, Other emphysematous lung disease such as alpha-1 antitrypsin disease, Cystic fibrosis, Emphysema, Idiopathic pulmonary fibrosis, Churg-Strauss syndrome, Allergic bronchopulmonary aspergillosis, Sarcoidosis

3. Diagnosed with any of the following acute or chronic infections or infection history:

   • Active helminth or parasitic infection requiring treatment within 2 weeks prior to screening;
   • Infection requiring hospitalization or systemic (parenteral) antimicrobial therapy within 60 days prior to Day 1;
   • Any infection judged to be an opportunistic infection or clinically significant by the investigator, within 6 months prior to Day 1.

   Prior/Concomitant Therapy:

4. Prior or current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s).

5. Prior or concurrent treatment with either approved or experimental biologic treatment (such as inhibitors of IL-4, IL-13, IL-33/ST2, IL-4Rα, TSLP, IL-5, OX40/OX40L or IgE) or targeted synthetic drugs (such as JAK inhibitors) for the treatment of asthma or other type 2 inflammatory diseases, including but not limited to: AD, EoE, CRS.

6. Treatment with any dose level of systemic (oral, injectable, or intraarticular) corticosteroids within 28 days of the screening visit.

7. Prior (within 12 weeks prior to screening) or planned concomitant treatment with immunoglobulin supplementation (eg, IV Ig or SC Ig).

8. History of anaphylaxis to antibody therapeutic or to PF-07275315 or to the excipients of the formulated drug products.

9. Bronchial thermoplasty within the previous 24 months.

   Prior/Concurrent Clinical Study Experience:

10. Administration of an investigational drug product within 30 days or 5 half lives preceding the screening visit (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.