The objective of the Treatment Phase of the study is to evaluate the safety and efficacy of 4 weeks of once daily oral administration of BLI5100 low dose, BLI5100 high dose, or placebo in patients with NERD. The objective of the Extension Phase of the study is to evaluate the safety of extended exposure to once daily oral administration of BLI5100 low dose and BLI5100 high dose in patients with NERD.

Inclusion Criteria:

1. Aged ≥18 years at the time of signing informed consent;
2. Have experienced heartburn (burning sensation, pain at posterior bony thorax) for at least 6 months prior to Screening;
3. Have documented history of symptomatic GERD;
4. Have no mucosal break(s) on the upper GI endoscopy performed during Screening;
5. Have reported heartburn on ≥4 days during any consecutive 7-day period of the Screening Period as recorded in the eDiary;
6. Able to understand and comply with the protocol requirements;
7. Willing and able to provide written informed consent at Screening;
8. 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.
9. 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.
10. 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. Diagnosed with erosive gastroesophageal reflux disease, acute upper GI bleeding, gastric ulcer or duodenal ulcer, or acute gastritis within 2 months prior to the upper GI endoscopy;

4. 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;

5. History or suspicion of functional upper gastrointestinal disorders, such as:

   • Functional heartburn, as described in the Rome IV criteria, or
   • Functional dyspepsia, as described in the Rome IV criteria.

6. History of a connective tissue disorder associated with GI symptoms (eg, scleroderma or systemic lupus erythematous) or inflammatory bowel disease, or documented history of delayed gastric emptying;

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

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

8. 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.

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

10. 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.

11. 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.

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

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

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

15. Requirement of persistent (>3 times per week for >30 days) 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.

16. 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;

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

18. Positive test result for H. pylori at Screening or diagnosis and treatment of H. pylori within 4 to 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.

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

    • Aspartate aminotransferase (AST), alanine aminotransferase (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 \