The purpose of the study is to learn how the study medicine called PF-07868489 is tolerated and acts in healthy adult people and people with pulmonary arterial hypertension (PAH).

Part A:

An investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose study to assess the safety, tolerability, and pharmacokinetics (PK) of PF-07868489 in healthy adult participants.

Part B:

A 24-week, randomized, double blind, placebo-controlled study to assess the safety, tolerability, PK, and pharmacodynamics (PD) of PF-07868489 in adult participants with PAH.

Key Inclusion Criteria Part A:

• overtly healthy
• Body mass index (BMI) of 16 to 32 kg/m2; and a total body weight >50 kg.

Key Exclusion Criteria Part A:

• clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, infections or allergic disease.
• smoking more than 10 cigarettes (or equivalent) per day or smoking history ≥10 pack-years.

Key Inclusion Criteria Part B:

• diagnosis of pulmonary arterial hypertension (PAH)
• stable dose of standard of care PAH vasodilators
• BMI 16 to 40 kg/m2; and a total body weight >45 kg.
• 6MWD ≥ 150 and ≤ 450.
• Pre-randomization RHC documenting a minimum of PVR ≥ 400 dyn ∙sec/cm5.

Key Exclusion Criteria Part B:

• Any medical or psychiatric condition or laboratory abnormality.
• Stopped receiving pulmonary hypertension chronic general supportive therapy 90 days prior to Day 1.
• Pulmonary capillary wedge pressure > 15 mmHg on right heart catheterization (RHC) conducted during Screening.
• History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.
• Major surgery within 8 weeks prior to randomization.
• Participants who smoke more than 10 cigarettes (or equivalent) per day or has a smoking history ≥10 pack-years.

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.

Part A is an investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose.

Part B is a 24-week, randomized, double blind, placebo-controlled study.