Inclusion Criteria:
* Male or female adults age 18 and older at Visit 1
* Have a previous history of dry eye disease, clinician diagnosed or self-reported, for at least 3 months
* Total SPEED score ≥ 6 on SPEED questionnaire at Visit 1 Screening \& Baseline
Exclusion Criteria:
* History of ocular surgery (excluding LASIK or PRK) in the past 3 months
* History of LASIK or PRK in the past 12 months
* Initiation, discontinuation or change in dose of a systemic medication known to cause ocular drying (e.g., antihistamines or tricyclic antidepressants) less than 14 days prior to Visit 1 or a change in dosage is anticipated during the study.
o Note: occasional short-term use of medications such as systemic antihistamines will be permitted provided that use was not within 24 hours of Visit 1 or anticipated use within 24 hours of any study visit.
* Active ocular infection or inflammation unrelated to dry eye disease (e.g., uveitis, blepharitis requiring antibiotics).
* Use of Restasis, Xiidra, Miebo, or any other topical anti-inflammatory medications within 30 days of Visit 1 and for the duration of the study.
* Use of varenicline nasal spray within 30 days of Visit 1 and for the duration of the study.
* Eyelid hygiene (such as "lid scrubs") is allowed but should be continued without change to current regiment at Visit 1 Baseline for the duration of the study.
* Use of other DED medications within 30 days of Visit 1 Baseline Use of artificial tears is allowed but must be preservative free and the dosing should not change from current regiment at Visit 1 Baseline.
* Use of amniotic membranes or serum tears within 90 days of Visit 1 Baseline
* Use of lid heating therapy (i.e., LipiFlow, iLUX, TearCare) within 90 days of Visit 1 Baseline and for the duration of the study.
* Punctal or intracanalicular plug inserted in either eyelid within 90 days prior to Visit 1 Baseline or anticipated plug insertion or occlusion at any time during the study.
* Current evidence of other significant ophthalmic disease requiring topical medication (e.g., glaucoma, ocular hypertension) or other disease the investigator believes may interfere with study findings or interpretation.
* Use of any topical ocular glaucoma medication within 30 days prior to the Screening visit or anticipated use during the study.
* Use of systemic medications that affect tear production (e.g., isotretinoin, antihistamines) unless on stable doses for \> 30 days.
* Severe ocular surface disease or damage (e.g., corneal ulcers, neurotrophic keratopathy).
* Have had a corneal transplant in either or both eyes.
* Use of contact lenses in either eye within 7 days prior to the Baseline visit or planned use during the study and unwilling to discontinue use during the duration of the study.
* Known allergy or hypersensitivity to acoltremon or formulation ingredients.
* Current pregnancy or breastfeeding
* Women of childbearing potential who are not using an acceptable means of contraception. Acceptable means of contraception include hormonal contraceptives (i.e. oral, implantable, injectable, or transdermal contraceptives, with a barrier such as a diaphragm or a condom) or intrauterine devices. For non-sexually active females, abstinence may be regarded as an adequate method of birth control.
