Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3)

Inclusion Criteria:

• Male or female, 30 years of age or older at the Screening visit

• Signs of DED at the Screening and Baseline visits assessed by corneal staining andSchirmer test

• Symptoms of DED at both Screening and Baseline visits assessed by SANDEquestionnaire and ODS-VAS

• Corrected visual acuity (+0.70 LogMAR) or better in both eyes at both the Screeningand Baseline visits

Exclusion Criteria:

• History or presence of any ocular disorder or condition (other than DED) in eithereye that would, in the opinion of the investigator, likely interfere with theinterpretation of the study results or subject safety

• Regular use of lid hygiene within 14 days prior to the Screening visit or anyplanned use during the study

• Use of artificial tears within 2 hours prior to the Screening visit or anticipateduse during the study

• Use of any topical ocular anti-inflammatory medication within 30 days prior to theScreening visit or anticipated use during the study (e.g., ocular cyclosporine [Restasis®, Cequa™], lifitegrast [Xiidra®], or any other prescription ophthalmicproduct for DED, topical ocular corticosteroid- or non-steroidal-anti-inflammatoryagents

• Use of Tyrvaya™ (varenicline solution, nasal spray 0.03mg) within 30 days prior tothe Screening visit or anticipated use during the study

• Use of medications for the treatment of severe DED and/or Meibomian gland diseasesuch as oral pilocarpine, oral cevimeline, oral macrolides, oral tetracyclines, oraltetracycline derivatives, and oral retinoids within 30 days prior to the Screeningvisit or anticipated use during the study.

• Initiation, discontinuation, or change in dose of a systemic medication known tocause ocular drying (e.g., antihistamines or tricyclic antidepressants) less than 14days prior to the Screening visit or a change in dosage is anticipated during thestudy.

• Initiation, discontinuation, or change in dose of a systemic corticosteroid lessthan 60 days prior to the Screening visit or a change in dosage is anticipatedduring the study.

• Initiation, discontinuation, or change in dose of a systemic immunomodulator (e.g.,hydroxychloroquine, methotrexate, cyclosporine) less than 60 days prior to theScreening visit or a change in dosage is anticipated during the study

• History or presence of significant systemic disease (i.e.: cardiovascular,pulmonary, hepatic, renal, hematologic, immunologic)