The purpose of this study is to evaluate the efficacy and safety of verekitug (UPB-101) in participants with severe asthma. The study will evaluate the incidence of asthma exacerbations, other pharmacodynamic (PD) parameters such as lung function and asthma control, and the safety and tolerability of verekitug (UPB-101) compared to placebo.

This is a multicenter, randomized, placebo-controlled, parallel group study to assess the efficacy and safety of verekitug (UPB-101) administered subcutaneously (SC). A total of approximately 436 adult participants with severe asthma are planned for enrolment and will be randomized in a 1:1:1:1 ratio to receive verekitug (UPB-101) at doses of 100 mg every 12 weeks (Q12W), 400 mg every 24 weeks (Q24W), and 100 mg every 24 weeks (Q24W), or placebo administered SC. In order to maintain the blinding of different doses, all participants will receive 2 SC injections at each dosing visit. This study consists of a Screening/Run-In Period (approximately 4 weeks), Treatment Period (up to 60 weeks with a minimum of 24 weeks) and Follow-up Period (ending approximately 16 weeks after the last administration of study intervention).

Inclusion Criteria:

• Signed, dated, and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF).
• Age 18 to 80 years of age (inclusive) at the time of consent.
• Physician-diagnosed asthma for at least 12 months prior to Visit 1.
• Participant has evidence of bronchodilator (BD) reversibility as documented by either historical reversibility (within 12 months prior to study entry) or reversibility during screening.
• Documented treatment with a total daily dose of either medium or high dose inhaled corticosteroids (ICS) for at least 3 months. Participants on medium dose ICS must also have been taking at least one additional maintenance asthma controller medication for at least 3 months.
• Documented history of asthma exacerbation(s) within 12 months of Visit 1.
• Asthma Control Questionnaire-6 (ACQ-6) score greater than or equal to (>=) 1.5 at screening and randomization.
• Participant must have a pre-BD FEV1 value of >=30 percent (%) and <=80% predicted at Screening.
• Minimum compliance with daily diary and background asthma medication(s) as captured in the daily diary during the Run-in Period.
• Agrees to follow the required contraceptive techniques/methods.
• Female or male participant agrees not to donate eggs or sperm, respectively, for a period of 120 days after the last dose of the study drug intervention or at the Final Visit, whichever occurs last.

Exclusion Criteria:

• Inpatient hospitalization due to asthma at any time within 4 weeks prior to Visit 1 or during the Screening/Run-in Period.
• Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients.
• Previous biologics, including those for asthma treatment, for which the appropriate washout period is not fulfilled prior to Visit 1. If the half-life is not known, a 24-week washout period prior to Visit 1 should be applied.
• Allergen immunotherapy (unless maintenance dose) within 12 weeks prior to Visit 1 or plans to begin therapy or change dosing during the study.
• For participants taking oral corticosteroids (OCS), the dose has not been stable for at least 2 weeks prior to Visit 1 and/or is >10 milligram (mg) daily, or >20 mg every other day.
• Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 1.
• History compatible with or diagnosis of a parasitic infection and has not been treated or has not responded to standard of care therapy.
• Current tobacco smokers, nicotine vapers (including electronic cigarettes), snuff users or participants with a smoking history >=10 pack years. (Former nicotine smokers with a smoking history of <10 pack years, former nicotine vapers and former snuff users must have stopped for at least 6 months prior to Visit 1 to be eligible).
• Positive coronavirus disease 2019 (COVID-19) test with lower respiratory tract symptoms within 28 days before Visit 1.
• Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study or unwilling to use adequate birth control, if of reproductive potential and sexually active.