The objective of the Healing Phase of the study is to evaluate the safety and efficacy of up to 8 weeks of once daily oral administration of BLI5100 versus a PPI control in healing EE. The objective of the Maintenance Phase of the study is to evaluate the safety and efficacy of 24 weeks of once daily oral administration of BLI5100 (low or high dose) versus a PPI control in the maintenance of healed EE.

Inclusion Criteria:

1. Aged ≥18 years at the time of signing informed consent;
2. Have experienced both heartburn and regurgitation within 7 days prior to the Screening Visit;
3. Current evidence of EE of LA grades A to D based on an upper GI endoscopy;
4. Able to understand and comply with the protocol requirements;
5. Willing and able to provide written informed consent at Screening;
6. A female of reproductive potential defined as a non-post-menopausal female who has not had a bilateral oophorectomy or medically documented ovarian failure; or If a female of childbearing potential, agrees to use an acceptable form of birth control and avoid egg donation from the Screening Visit until 6 months after the last dose of study drug.
7. If a male, agrees to use an acceptable form of birth control from the Screening Visit until 3 months after the last dose of study drug.
8. If a male, agrees to abstain from sperm donation through 3 months after administration of the last dose of study drug.

Exclusion Criteria:

1. Unable to undergo an upper GI endoscopy;

2. Presence of esophageal stricture, gastroesophageal varix (including post sclerotherapy or ligation), untreated Barrett's esophagus, gastric bleeding, infection, tumor, or gastric or duodenal ulcer on the upper GI endoscopy;

   o Note: Patients with diagnosis of Schatzki's ring (mucosal tissue ring around lower esophageal sphincter) are eligible to participate.

3. Alarm symptoms such as odynophagia, severe dysphagia, upper GI bleeding, weight loss, anemia, or hematochezia within 4 weeks prior to Screening, unless the presumed malignancy is ruled out;

4. History of eosinophilic esophagitis, achalasia, or other primary esophageal motility disorder; functional heartburn; physiochemical trauma (including radiation, mucosal resection, or cryotherapy); or documented history of delayed gastric emptying;

5. History of a connective tissue disorder associated with GI symptoms (eg, scleroderma or systemic lupus erythematous) or inflammatory bowel disease;

6. History of acid-suppressive, esophageal, or gastric surgery;

   o Note: This is not applicable to appendectomy, cholecystectomy, or endoscopic excision of benign tumor.

7. History of malignancy within the past 5 years (with the exception of resected basal cell or squamous cell carcinoma of the skin);

   o Note: This is not applicable to patients who had complete response or pathological complete response and whose tumor had not recurred for at least 5 years from the date of last treatment, or patients whose tumor had been removed by endoscopic resection without any findings indicating recurrence of the tumor within 3 years.

8. History of an allergic disease, or hypersensitivity or intolerance to the active ingredient or excipients of the study drug;

9. History of alcoholism, chronic opiate use, or substance addiction in the 12 months before Screening or a positive urine drug screen for opiates or substances of abuse;

   • Note: Patients on prescribed opioids are eligible to participate if they have been on a stable dose for >3 months prior to Screening.
   • Note: Retesting of a positive urine drug screen requires Medical Monitor approval. Positive urine drug screen for all drugs will require verification of prescription for the positive tested substance.

10. Presence of manic-depression, anxiety disorder, panic disorder, somatoform disorder, personality disorder, or other psychological disorder;

    o Note: A diagnosis of manic-depression, anxiety disorder, panic disorder, somatoform disorder, personality disorder, or other psychological disorder is not exclusionary, as long as the patient is asymptomatic and well-controlled on stable treatment (ie, stable dose for >6 months prior to Screening), including non-medical therapy.

11. Current use of antipsychotics, antidepressants, anxiolytics, or prescription sleeping medications, with the exception of a stable dose for >6 months prior to Screening;

12. Use of any gastric acid-suppressive agents, including PPIs, within 2 weeks prior to the upper GI endoscopy at Screening;

13. Use of 2 or more commercial doses of ref lux esophagitis-related medications (including H2 blockers, prostaglandins, mucosal protective agents, and prokinetics) within 1 week prior to the upper GI endoscopy at Screening;

14. Requirement of persistent use of non-steroidal anti-inflammatory drugs (NSAIDs) during the course of the study;

    o Note: Low-dose (≤100 mg/day) aspirin is allowed provided that it has been used for prophylaxis prior to study participation.

15. If a female, is pregnant, breastfeeding, or planning to become pregnant during the study or within 6 months after the last dose of study drug;

16. Positive test result for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at Screening;

17. Positive test result for H pylori at Screening or diagnosis and treatment of H pylori within 6 weeks prior to randomization;

    o Note: Patients who test positive for H pylori at Screening will be offered treatment according to local standard of care and may be re-screened for eligibility following completion of treatment.

18. Abnormal laboratory results with clinical relevance at Screening as follows:

    • Aspartate aminotransferase (AST), ALT, or alkaline phosphatase level of ≥2 × upper limit of normal (ULN);
    • Total bilirubin level of ≥2 × ULN, unless Gilbert's syndrome is confirmed when direct bilirubin is ≤0.3 mg/dL;
    • Estimated glomerular filtration rate <30 mL/min; or
    • Serum magnesium < lower limit of normal.

19. Abnormal ECG of clinical significance (eg, major arrhythmia, multifocal premature ventricular contractions, or 2° atrioventricular block anomaly);

20. Presence of any gastric acid hypersecretory conditions, such as Zollinger-Ellison syndrome;

21. Involvement in another clinical study within 4 weeks of initiation of study drug;

22. Any other clinically relevant condition that would confound study endpoints or adversely affect patient compliance with the study procedures in the medical judgment of the Investigator or Medical Monitor based on previous medical history or findings on Screening assessments.