Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 2)

Inclusion Criteria: * Age ≥18 * Diagnosed as having CRS * Bilateral ethmoid disease confirmed on CT * Mean 3 cardinal symptom (3CS) score * Undergone at least 2 trials of medical treatments in the past * Has been informed of the nature of the study and provided written informed consent * Agrees to comply with all study requirements * If currently on a waiting list for sinonasal surgery, willing to be removed from the waiting list or have preplanned surgery date cancelled for the duration of the study. \[Note: this does not preclude a participant from receiving or being recommended for sinonasal surgery as rescue treatment during the study\]. Exclusion Criteria: * Inability to tolerate topical anesthesia * Previous nasal surgery * Presence of nasal polyp grade 2 or higher * Seasonal allergic rhinitis * Perennial rhinitis with symptoms that are well controlled by regular use of intranasal corticosteroids * Severe asthma * History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, atrophic rhinitis, or odontogenic sinusitis * Obstruction preventing proper placement and retention of LYR-210 as seen on endoscopy * Anatomic variation that, in the opinion of the investigator, would adversely impact placement of LYR-210 as seen on CT * Known history of hypersensitivity or intolerance to corticosteroids * Known history of hypothalamic pituitary adrenal axial dysfunction * Previous pituitary or adrenal surgery * Dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit. * Past or present acute or chronic intracranial or orbital complications of CRS * History or diagnosis (in either eye) of glaucoma or ocular hypertension * Past or present functional vision in only 1 eye * Past, present, or planned organ transplant or chemotherapy with immunosuppression * Currently positive for COVID-19 or residual sinonasal symptoms from a previous COVID-19 infection * Pregnant or breast feeding. Females of child-bearing potential must test negative for pregnancy at the time of screening * Evidence of disease or condition expected to compromise survival or ability to complete follow-up assessments * Currently participating in an investigational drug or device study * Determined by the investigator as not suitable to be enrolled