This study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of GSK4527363 in healthy participants (Part A), participants with active SLE (Part B), healthy participants of Chinese and Japanese descent (Part C), and participants with interstitial lung disease associated with connective tissue disease (Part D)

Inclusion criteria:

For Part A and Part C (Healthy Participants):

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (vital signs and 12-lead ECG)
• Part C only: Be of Japanese (Cohort C1) or Chinese (Cohort C2) ancestry i. Born in Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2); and ii. Descendent of 2 ethnic Japanese (Cohort C1) or Chinese (Cohort C2) parents and 4 ethnic grandparents; and iii. Have lived outside Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2) for less than 10 years at the time of screening
• Body weight greater than or equals to (>=) 45 kilograms (kg)
• Body mass index (BMI) within the range 18-32 kilograms per square meter (kg/m^2) (inclusive)
• Male or female of non-childbearing potential

For Part B (SLE participants):

• 18 to 65 years of age inclusive, at the time of signing the informed consent form
• Documented clinical diagnosis of SLE according to the (European alliance of associations of rheumatology [EULAR]/ American College of Rheumatology [ACR] SLE classification criteria)
• Body weight >= 45 kg
• BMI within the range 18-32 kg/m^2 (inclusive)
• Male or female
• Capable of giving signed informed consent For Part D (CTD-ILD Participants)
• Participants must be 18 to 65 years of age, at the time of signing the informed consent form
• Documented clinical diagnosis of specific Connective Tissue Diseases in accordance with internationally recognised classification criteria
• Documented clinical diagnosis of interstitial lung disease (ILD) as determined by historical High-resolution computed tomography (HRCT)
• Participants must be on a stable dose of therapy to manage ILD and/or underlying connective tissue disease (CTD)
• Body weight >= 45 kg
• BMI within the range 18-32 kg/m^2 (inclusive)
• Male or female
• Capable of giving signed informed consent

Exclusion criteria:

For Part A and Part C (Healthy Participants):

• History or presence or cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders
• A history of recurrent infections, or treatment of a chronic infection within 3 months prior to the first dose of study drug
• Any acute infection (including upper respiratory tract infections and urinary tract infections) which has not fully resolved within four weeks before dosing
• Symptomatic herpes zoster within 3 months prior to screening
• Have a history of malignancy, or a strong family history of malignancies related to immunosuppression
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions
• Abnormal blood pressure
• Evidence of active or latent Tuberculosis (TB)
• Alanine transaminase (ALT) >=1.1* Upper limit of normal (ULN)
• Total bilirubin >1.0*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >=1.5*ULN as long as direct bilirubin is less than or equal to (<=)1.5*ULN
• Presence of Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
• Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
• Positive Human immunodeficiency virus (HIV) antibody test at screening
• Prior medical history of anaphylaxis
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec)
• Live vaccine(s) within 30 days before the dosing day or plans to receive such vaccines during the study

For Part B (SLE participants):

• Any acute, severe lupus related flare during the Screening Period that needs immediate treatment

• Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the principal investigator (PI), could confound the results of the clinical study or put the participant at undue risk

• Have an acute or chronic infection requiring management as follows:

  i. Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria ii. A serious infection requiring treatment with antibiotics and/or hospitalization if the last dose of antibiotics or the hospital discharge date was within 60 days of the first day of dosing (Day 1). Prophylactic anti-infective treatment is allowed

• Evidence of active or latent TB

• Confirmed Progressive Multifocal Leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms

• ALT >2*ULN

• Total bilirubin >1.5*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN

• Presence of HBsAg and/or HBcAb at screening or within 3 months prior to first dose of study intervention

• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention

• Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention

• History or positive test at Screening for HIV

• QTcF >450 msec

• Solid or hematological malignancy or a history of malignancy (in the past 5 years) of except for basal cell or squamous cell in situ skin carcinomas, Cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix that have been resected with no evidence of metastatic disease for 3 years

• Live or live-attenuated vaccine(s) within 30 days prior to Screening

For Part D Participants:

• A diagnosis of: ILD other than CTD-ILD and/or SLE
• FVC <= 45% predicted at Screening Pulmonary arterial hypertension, as determined by the Investigator, prior to Day 1
• Major surgery (including joint surgery) within 3 months prior to Screening or planned during the duration of the study
• Previous or planned major organ transplant (e.g. heart, lung, kidney, liver) or bone marrow transplant (e.g. autologous stem cell transplant)
• Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to CTD-ILD (i.e., cardiovascular, metabolic, hematologic, GI, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the PI, could confound the results of the clinical study or put the participant at undue risk
• Have an acute or chronic infection including requiring management
• Evidence of active or latent TB
• Confirmed PML or unexplained new-onset or deteriorating neurologic signs and symptoms
• ALT >2*ULN
• Total bilirubin >1.5*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN
• Presence of HBsAg and/or HBcAb at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention
• History or positive test at Screening for HIV
• Solid or hematological malignancy or a history of malignancy (in the past 5 years) of except for basal cell or squamous cell in situ skin carcinomas, CIN or carcinoma in situ of the cervix that have been resected with no evidence of metastatic disease for 3 years
• Live or live-attenuated vaccine(s) within 30 days prior to Screening or plans to receive such vaccines during the Screening period or during the clinical study

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.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 terminated asset(s) 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 will be a double-blind study.