The primary purpose of this study is to assess the effect of verekitug (UPB-101) on the endoscopically determined size and extend of nasal polyps in participants with chronic rhinosinusitis with nasal polyps (CRSwNP) and to assess 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) in participants with CRSwNP on background therapy with stable dosage of intranasal corticosteroids (INCS). Approximately 70 participants will be randomized. Participants will receive verekitug (UPB-101) or placebo over a 24-week treatment period. In addition, this study consists of a 3 to 5-week Screening Period and a 4-week Follow-up Period.

Inclusion Criteria:

• Participant has signed, dated and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF).

• Participant is aged 18 to 85 years of age (inclusive) at the time of signing the ICF.

• Participant has physician diagnosed CRSwNP for at least 6 months prior to Visit 1 that fulfills all of the following:

  • Severity consistent with need for surgery as defined by an endoscopic bilateral NPS of at least 5 out of 8 and a minimum score of 2 in each nasal cavity at Visit 1 based on central reading, as well as reconfirmed at Visit 2 based on local reading.
  • Average NCS greater than and equal to (>=) 2 over 14 days before Visit 2.
  • Ongoing symptoms of CRSwNP for at least 8 weeks prior to Visit 1 such as rhinorrhea and/or reduction in smell.

• Participant has at least one of the following:

  • In the 24 months prior to Visit 1, had a documented exacerbation of nasal polyposis requiring treatment with systemic corticosteroid.
  • A medical contraindication/intolerance to systemic corticosteroid.
  • Had prior surgery for NP (cannot be within 6 months prior to Visit 1

• Stable standard of care treatment for CRSwNP for at least 30 days prior to Visit 1.

• At Visit 2, at least 21 days of background mometasone furoate nasal spray (MFNS) (or equivalent) background therapy.

• >=70 percent (%) dosing compliance for MFNS (or equivalent) in the 14 days prior to Visit 2.

• 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:

• Has undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to Visit 1.
• Expected need, in the opinion of the Investigator, for NP surgery within 12 weeks of Visit 2.
• Comorbid asthma having forced expiratory volume in 1 second (FEV1) 50% or less of predicted normal at Visit 1.
• Conditions making participants non-evaluable at Visit 1 for the primary endpoint such as sino-nasal or sinus surgery changing the lateral wall structure of the nose, antrochoanal polyps, nasal septal deviation occluding at least one nostril, acute sinusitis, upper respiratory infection, ongoing rhinitis medicamentosa, fungal rhinosinusitis, nasal cavity benign or malignant tumors.
• Concurrent participation in a clinical study or has been treated with an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to Visit 1.
• Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients.
• Biologic therapy or systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 6 months or 5 half-lives before Visit 1, whichever is longer, with the exception of oral c corticosteroids.
• Any vaccination within the Screening Period and treatment with a live (attenuated) vaccine within 12 weeks before Visit 2.
• Abnormal medical history, physical finding or safety finding and any clinical laboratory test result outside of the reference ranges that in the opinion of the Investigator may obscure the study data or interfere with the participant's safety. Participants with any clinically significant cardiac disease and/or ECG abnormality, in the opinion of the Investigator, obtained during the Screening Period should be excluded from the study.
• Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliar syndromes, concomitant cystic fibrosis.
• Participant with comorbid asthma that also has a history or evidence of a clinically significant pulmonary condition (other than asthma).
• History of chronic alcohol or substance use disorder within 12 months prior to Visit 1.