This is a first time in Asia (FTIA) study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and immunogenicity of efimosfermin alfa to healthy participants of Chinese, Japanese, and White/European ancestry.

Inclusion Criteria:

Participants who are generally healthy as determined by medical evaluation

• Body weight at least 50.0 Kilogram (kg) for male participants or at least 45.0 kg for female participants
• Body mass index (BMI) within the range of 18.0 to 28.0 kilograms per square meter (kg/m^2) (inclusive)
• Male and female participants
• Participants of Chinese ancestry are eligible if born in mainland China, Hong Kong, or Taiwan, and have lived outside China, Hong Kong, or Taiwan for less than 10 years at the time of screening.
• Participants of Japanese ancestry are eligible if born in Japan and Descendant of 2 ethnic Japanese parents and 4 ethnic Japanese grandparents; and. have lived outside Japan for less than 10 years at the time of screening.
• Participants of White/European ancestry are eligible if self-identified as being of White/European ancestry, (i.e., from the original peoples of Europe) irrespective of current place of residence; and.
• Descendant of 2 parents and 4 grandparents of White/European ancestry (that is [i.e.], from the original peoples of Europe) irrespective of place of birth or current place of residence.

Exclusion Criteria:

• History or presence of disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
• Current or chronic history of liver or biliary disease with the exception of Gilbert's syndrome or asymptomatic gallstones.
• History of pancreatic injury, pancreatitis or other pancreatic disease; history of Type one Diabetes Mellitus (T1DM) or positive glutamic acid decarboxylase auto-antibodies, or major Type two Diabetes Mellitus (T2DM) complications including severe gastroparesis and autonomic neuropathy.
• Abnormal blood pressure (defined as systolic Blood Pressure (BP) more than equal (>=)140 millimeters of mercury (mmHg) or diastolic BP >=90 mmHg) measured based on the average of triplicate BP readings).
• History of metabolic bone disorders including osteoporosis, osteopenia, or osteomalacia.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Alanine transaminase (ALT) more than (>)1.5 * upper limit of normal (ULN).
• Total bilirubin >1.5 * ULN
• Known bleeding disorder.
• History of immunodeficiency diseases, including a positive test result for human immunodeficiency virus (HIV).
• Corrected QT Interval using Fridericia's Formula. (QTcF) >=450 millisecond (msec)(male) or >=470 msec (female) at Screening Visit based on the average of triplicate ECGs.
• Use of statins, other lipid lowering medications or hypertension medications unless on a stable dose for at least 3 months.
• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever was longer; or longer if required by local regulations.
• Participants who have received native FGF21 or a FGF21 analog at any time in the past.
• Intended use of over the counter (OTC) or prescription medication (including herbal medications) within 7 days prior to dosing and for the duration of study participation.
• Live vaccine within 14 days prior to dosing and non-live vaccines for 7 days prior study dosing.
• Current enrolment or participation in another clinical trial within the last 30 days before signing consent of current study.
• Presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody at screening or within 3 months prior to the first dose of study intervention
• A positive pre-study drug/alcohol screen

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

This is a double blinded study.