The purpose of this study is to learn about the safety and effects of 2 study medicines (PF-07275315 and PF-07264660) for the treatment of atopic dermatitis (AD). AD is a long- lasting itchy red rash, caused by a skin reaction.

This study is seeking participants who:

• are 18 years of age or more.
• Were confirmed to have AD at least 6 months ago.
• Are not having an effective treatment result from medicines that are applied on skin for AD.
• Are considered by their doctors to have moderate to severe AD.

In Stage 1 of the study, participants will receive either PF-07275315 or PF-07264660 or placebo. Stage 1 is complete. In Stage 2 of the study participants will receive either PF-07275315 or placebo. In Stage 3 of the study participants who have received anti-inflammatory proteins, will receive either PF-07275315 or placebo. In Stage 4 of the study participants will receive either PF-07264660 or placebo. A placebo does not have any medicine in it but looks just like the medicines being studied.

PF-07275315 or PF-07264660 or placebo will be given as multiple shots in the clinic over the course of each Stage.

The experiences of people receiving PF-07275315 or PF-07264660 will be compared to people who do not. This will help determine if PF-07275315 and PF-07264660 are safe and effective.

Participants in Stages 1, 2 and 4 will be involved in this study for up to 40 weeks (10 months). Participants in Stage 3 will be involved in this study for up to 52 weeks (13 months).

Inclusion Criteria:

Must meet the following AD criteria:

1. Participants aged 18 years or older

2. Clinical diagnosis of chronic atopic dermatitis:

   1. for at least 6 months prior to Day 1 with diagnosis confirmed by photograph;
   2. Either an inadequate response to treatment with standard of care treatments (excluding systemic immunosuppressant treatments) for at least 4 consecutive weeks within 6 to 12 months of the first dose of the study intervention; OR documented reason why topical treatments are considered medically inappropriate;
   3. Moderate to severe AD defined as having an affected BSA ≥10%, vIGA ≥3, and EASI ≥16 at both the screening and baseline visits).
   4. Bio-experienced cohort-partial or non-responder to anti-inflammatory proteins (also known as biologics), intolerance or AEs to anti-inflammatory proteins or loss of access to anti-inflammatory proteins with ≥12 weeks of treatment within 5 years.

   Other Inclusion Criteria:

3. BMI of 17.5 to 40 kg/m2; and a total body weight >45 kg (100 lbs).

4. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

- Medical Conditions:

1. Significant allergic or autoimmune diseases, other than AD and well controlled mild to moderate including but not limited to: SLE or other complement disorders; Type 1 diabetes; IBD; Multiple Sclerosis.

2. History of significant allergic reactions, including anaphylaxis and reactions to protein therapeutics, including hypersensitivity to PF-07275315 or PF-07264660 or to the excipients of the formulated drug products. Participants with significant reactions to single, identified, avoidable allergens (eg, peanut allergy) may be eligible if avoidance of these allergens during the study is feasible.

3. Any of the following acute or chronic infections or infection history:

   1. Active infection (including helminth or parasitic) requiring treatment within 2 weeks prior to screening;
   2. Infection requiring hospitalization or systemic (parenteral) antimicrobial therapy within 60 days prior to Day 1;
   3. Active chronic or acute skin infection requiring treatment with systemic [(not IV)] antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections (requiring no more than topical anti-infective treatments) within 1 week prior to Day 1.
   4. Any infection judged to be an opportunistic infection or clinically significant by the investigator, within 6 months prior to Day 1;

4. History of or current evidence of inflammatory skin conditions (eg, psoriasis, seborrheic dermatitis, lupus) at the time of Day 1 that could interfere with evaluation of AD or response to treatment.

5. 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.

   - Prior/Concomitant Therapy:

6. Current use of any prohibited concomitant medication(s).

7. Phototherapy narrowband UVB (NB UVB) or broadband phototherapy or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to Day 1.

   - Prior/Concurrent Clinical Study Experience:

8. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).

9. HIV infection, or infection with hepatitis B or hepatitis C viruses according to protocol-specific testing algorithm.

10. Evidence of active or latent TB, or inadequately treated infection with Mycobacterium TB. A participant who is currently being treated for active or latent TB infection must be excluded from 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.