ANCHOR

This study will evaluate the efficacy and safety of depemokimab (GSK3511294) in participants with CRSwNP.

Inclusion criteria:

• Participants with 18 years of age and older inclusive, at the time of signing the informed consent.

• Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator.

• Participants who have had at least one of the following at Visit 1: Previous nasal surgery for the removal of NP; have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP; medically unsuitable or intolerant to systemic corticosteroid.

• Participants (except for those in Japan) must be on daily treatment with intranasal corticosteroids (INCS) (including intranasal liquid steroid wash/douching) for at least the 8 weeks immediately prior to screening.

• Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhea (runny nose) based on clinical assessment by the investigator.

• Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), plus facial pain/pressure and/or reduction or loss of smell.

• Male or eligible female participants.

Exclusion criteria:

• As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study.

• Cystic fibrosis.

• Antrochoanal polyps.

• Nasal cavity tumor (malignant or benign).

• Fungal rhinosinusitis.

• Severe nasal septal deviation occluding one nostril preventing full assessment of nasal polyps in both nostrils

• Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of nasal polyp score.

• Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 weeks prior to screening.

• Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis).

• Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of screening.

• Participants who have undergone any intranasal and/or sinus surgery (for example [e.g.], polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted.

• Participants where NP surgery is contraindicated in the opinion of the Investigator.

• Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.

• Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.

• A known immunodeficiency (e.g. human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma.

• A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.

• Liver Disease: Alanine aminotransferase (ALT) >2 times Upper limit of normal (ULN); Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than [