A Dose Finding Study With an Anti-TSLP Antibody (GSK5784283) in Adults Aged 18 to 75 Years of Age With Uncontrolled Asthma

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Informed Consent: Capable of giving signed informed consent which includescompliance with the requirements and restrictions listed in the informed consentform (ICF) and this protocol. The participant must be willing and able to complywith trial and follow-up procedures.

• Age: Participants must be 18 to 75 years of age inclusive, at the time of signingthe informed consent.

• Documented physician-diagnosed asthma for >= 2 years that meets the National Heart,Lung, and Blood Institute guidelines

• Evidence of variable airflow obstruction consistent with asthma.

• Documented history of asthma exacerbation within 12 months prior to Visit 1.

• An asthma exacerbation defined as a worsening of asthma symptoms.

• A well- documented requirement for regular treatment with medium or high-dose ICSfor at least 6 months prior to screening.

• At least one additional maintenance asthma controller medication is requiredaccording to standard practice of care (e.g., long-acting beta 2 agonist (LABA),leukotriene receptors antagonists (LTRA), theophylline, long-acting muscarinicantagonist (LAMA), chromones, etc.). Use of additional asthma controller medicationsmust be documented for at least 3 months prior to Visit 1.

• Weight >=40 kg.

• Male or eligible Female.

• Female participants: A female participant is eligible to participate if she is notpregnant, not breastfeeding, and at least one of the following conditions applies:

• Not a woman of childbearing potential (WONCBP) OR

• Is a WOCBP and using a contraceptive method that is highly effective, with afailure rate of <1%, 28 days prior to the 1st dose of the study drug and duringthe study intervention period and follow-up period. The investigator shouldevaluate potential for contraceptive method failure (e.g. non-compliance,recently initiated) in relationship to the first dose of study intervention.

• A WOCBP must have a negative serum pregnancy test at screening and a highlysensitive pregnancy test ([urine or serum] as required by local regulations)within 24 hours before each dose of study intervention.

• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), aserum pregnancy test is required. In such cases, the participant must beexcluded from participation if the serum pregnancy result is positive.

• The investigator is responsible for review of medical history, menstrualhistory, and recent sexual activity to decrease the risk for inclusion of awoman with an early undetected pregnancy.

• Contraceptive use by women should be consistent with location regulationsregarding the methods of highly effective contraception for those participatingin clinical trials.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (e.g., current upper or lower respiratory tract infection, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, primary ciliary dyskinesia).

Helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.

• Active or latent tuberculosis:

• Participants with a diagnosis or evidence of active or latent tuberculosis areexcluded from the study.

• Diagnosis of vocal cord dysfunction, dysfunctional breathing, or pseudo steroidresistant asthma.

• Malignancy: A current malignancy or previous history of cancer in remission for lessthan 5 years prior to screening (Participants that had localized carcinoma of theskin which was resected for cure will not be excluded).

• History of an unresolved clinically significant infection within 30 days prior toVisit 1.

• A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than thatexplained by the use of corticosteroids taken as therapy for asthma.

• Participants who have known, pre-existing, clinically significant cardiac,endocrine, autoimmune, rheumatologic, metabolic, neurological, renal,gastrointestinal, hepatic, hematological or any other system abnormalities that areuncontrolled with standard treatment including eosinophilic conditions such ashyper-eosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA).

• Any clinically relevant abnormal findings in physical examination, hematology,clinical chemistry, urinalysis, vital signs at Visit 2 which in the opinion of theinvestigator, may put the subject at risk because of his/her participation in thestudy, or may influence the results of the study, or the subject's ability toparticipate in the study.

• Receipt of any marketed or investigational biologic agent within 4 months or 5half-lives prior to Visit 1, whichever is longer and up until the end of study.

• Receipt of any investigational non-biologic agent within 30 days or 5 half-livesprior to screening, whichever is longer and up until the end of study.

• Experimental vaccines are not permitted within 30 days prior to randomization and upuntil the end of the study.

• Use of immunosuppressive medication (e.g., methotrexate, troleandomycin, oral gold,cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, systemic (oral) corticosteroids) within 3 months prior to Visit 1 and up until the end ofstudy.

• Systemic corticosteroid burst including taper within 15 days prior to Visit 1 orduring the screening/run-in period.

• Subjects who have not responded to Tezepelumab treatment.

• Receipt of live or live attenuated vaccine(s) within 30 days prior to randomizationor plans to receive such vaccines up until the end of study.

• A positive human immunodeficiency virus (HIV) test at screening or subject takingantiretroviral medications, as determined by medical history and/or subject's verbalreport.

• Positive test for hepatitis B virus (HBV) defined as either:

1. positive for hepatitis B surface antigen (HBsAg) OR

2. positive for HBV DNA

• Positive Hepatitis C antibody test result.

• Positive Hepatitis C RNA test result at screening or within 3 months prior to firstdose of study intervention.

• Current smokers (tobacco and marijuana) or former smokers with a smoking history >=10 pack years and subjects using vaping products, including electronic cigarettes.

• History of chronic alcohol or drug abuse within 2 years.

• History of severe allergic reaction, anaphylaxis or documented immune complexdisease (Type III hypersensitivity reactions) to any biologic therapy.

• History of sensitivity to any component of the investigational product formulationor a history of drug or other allergy that, in the opinion of the investigator ormedical monitor contraindicates their participation.

• Participants who have known evidence of lack of adherence to controller medicationsand/or ability to follow physician's recommendations.

• Participants who meet the following based on results from sample taken at Visit 2:

1. Alanine aminotransferase (ALT) >2x upper limit of normal (ULN)

2. Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable ifbilirubin is fractionated and direct bilirubin <35%)

3. Current or chronic history of liver disease or known hepatic or biliaryabnormalities (with the exception of Gilbert's syndrome or asymptomaticgallstones).

• QTcF >= 450 msec or QTcF >= 480 msec for patients with bundle branch block or anabnormal ECG finding that is considered to be clinically significant and wouldimpact the participant's participation during the study, based on the evaluation ofthe investigator in the 12-Lead ECG central over-read from screening Visit 2.