Multi-Center Study of Panosyl-Isomaltooligosaccharides Adjunctive to PPI Therapy to Treat GERD

Inclusion Criteria:

• In the opinion of the investigator or sub-investigators, the subject is capable ofunderstanding and complying with protocol requirements, including compliance withcompleting nightly online questionnaires in one of the IRB-approved languages.

• Subject signs and dates an electronic (Screening Phase Part 1) and site-specificwritten informed consent form (ICF) and any required privacy authorization prior tothe initiation of any study procedures.

• Ability, during Remote Screening Phase 2-Week Assessment, to complete all requiredonline nightly RESQ-eD questionnaires, medication questionnaires, 4-item PatientHealth Questionnaire for Depression and Anxiety (PHQ-4) questionnaire andParticipant Global Assessment questionnaire.

• Access to a computer/tablet/phone with internet access and active email account inorder to complete online questionnaires daily throughout study participation.

• Males or females ≥18 and ≤75 years of age, with a BMI ≥ 18 and < 35 kg/m2.

• Female subjects must be postmenopausal or surgically sterile or, if of childbearingpotential, must agree to use a medically acceptable form of contraception from thetime of signing the informed consent form through completion of study. If only thebarrier method is used, a single barrier or better is adequate. Postmenopausal womenmust have had ≥ 12 months of spontaneous amenorrhea. Surgically sterile women aredefined as those who have had a hysterectomy, bilateral ovariectomy, or bilateraltubal ligation. All women of childbearing potential must have a negative pregnancytest result before administration of study drug.

• Must be on stable doses of medications, if any, prescribed for chronic conditionsother than GERD.

• Subject must be taking daily PPI (defined as 5-7 days/week on average) for at leastfour (4) consecutive weeks with self-reported symptom improvement (frequency and/orseverity) prior to the Screening Call selected from the following list ofmedications:

• omeprazole

• esomeprazole

• lansoprazole

• dexlansoprazole

• pantoprazole

• rabeprazole

• Onset of GERD-related heartburn symptoms for a minimum of 3 months prior toScreening Call (i.e., "burning feeling behind the breastbone" and/or "pain behindyour breastbone" and/or "heartburn" per questions 1, 2 or 3 of RESQ-eD).

• Subject has maintained a stable diet and exercise regimen for ≥ 30 days prior to theScreening Call and is willing to maintain that diet and exercise regimen for theduration of the study (i.e., if subject is currently following diets including, butnot limited to, Keto, FODMAP, Vegan, Vegetarian, s/he must be willing to continuethis dietary lifestyle through end-of-study visit).

Exclusion Criteria:

• Current use of any mouthwash (e.g., Listerine, Scope, others) or unwilling todiscontinue use for the duration of the study (requires 3-day washout prior tostarting the Remote Screening Phase 2-Week Assessment)

• Teeth whitening within 7 days of Screening Call or current use of teeth whiteningsubstances (not including teeth whitening toothpaste) or unwilling to discontinueuse for the duration of the study (requires 7-day washout prior to starting theRemote Screening Phase 2-Week Assessment).

• Current use of histamine 2 receptor antagonists (H2RAs) (requires 7-day washoutprior to starting the Remote Screening Phase 2-Week Assessment).

• Surgical procedure requiring general anesthesia within 60 days of the Screening Call

• Colonoscopy, high colonic, colonic cleanse or barium enema in the past 30 days, orscheduled for colonoscopy or barium enema at any time for the duration of the study,and unwilling to postpone until after study completion.

• History of cancer diagnosis and/or treatment (other than basal cell carcinoma of theskin) within the preceding five (5) years.

• Concomitant illness with potential to confound outcome assessments for this study,including, but not limited to:

• History of untreated peptic or gastric ulcer, Zollinger-Ellison syndrome, orHelicobacter pylori (H. pylori) positivity without a history of successfultreatment

• History of ulcerative colitis or Crohn's disease.

• Stomach ulcers, pancreaticobiliary disorder (e.g., gallstones bile duct stones,pancreatic stones, pancreatitis), diverticulitis symptomatic within the past 6months.

• Acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV), or humanimmunodeficiency virus (HIV) infection.

• Significant current morbidity of the heart, kidney, liver or lung.

• History of Long QT Syndrome

• History of Torsades de pointes (TdP)

• Current neurological or psychiatric disorder (e.g., Parkinson's, Huntington'schorea, schizophrenia, seizure, bi-polar disorder, major depressive disorder).

• Known or suspected alcoholism, drug addiction, or significant drug abuse within 1year of the Screening Call based on subject reporting and PI assessment.

• Active history of tobacco or nicotine use (of any type) in the last 6 monthsaveraging more than 1 cigar/cigarette per week. Vaping products and e-cigarettesthat contain nicotine and/or tobacco are not allowed. Chewing tobacco and nicotinegum are prohibited at any level. Nicotine patches are NOT exclusionary.

• Alcohol abuse (for alcohol defined as: > 14 drinks/week or 4 drinks/day for men, 7drinks/week or 3 drinks/day for women).

• Intake of acetylsalicylic acid (i.e., aspirin) at doses > 162 mg/day.

• Non-steroidal anti-inflammatory pain relievers (NSAIDs) such as ibuprofen (Advil®,Motrin® IB, others) >/= 4 days/week on average not to exceed half the recommendedmaximum prescription daily dosing as listed in the Physician's Desk Reference.

• Acetaminophen > 2,000 mg/day

• Inhalation or ingestion of products containing delta-9-tetrahydrocannabinol (THC) > 2 days/week on average.

• Any known medical condition, clinical signs and symptoms, vital signs, abnormallaboratory, or other testing that are not well controlled on stable dosing ofmedication for at least 90 days prior to the Screening Call or are consideredclinically significant by the Principal Investigator (PI), that could interfere withthe subject's participation in and completion of the study. Examples of medicalconditions including, but not limited to:

• Uncontrolled hypertension

• Uncontrolled diabetes

• History of adrenal disease, diabetic nephropathy, or gastroparesis

• Uncontrolled hypothyroidism

• Untreated mental disorder

• Paraplegia or Quadriplegia

• Cerebrovascular event (stroke) or myocardial infarction (MI) within the last 6months.

• Structural abnormality of the GI tract, or disease or condition that can affect GImotility (e.g., achalasia, esophageal atresia), or defecation.

• Planned travel outside the US during the study period or routine travel within theUS during the study period that results in >2-hour time zone difference.

• Cyclical work shift (e.g., routinely switching between day shifts and night shifts)

• Any of the following current (within the past 6 months) symptomatic conditions:

• pseudo-obstruction,

• malignant polyps (requiring surgery),

• abdominal adhesions confirmed via laparoscopy,

• intestinal ischemia without colitis,

• laxative or enema abuse.

• History of ischemic colitis in the past 5 years.

• Current COVID19 infection, or a history of a prior COVID19 infection with ongoingsymptoms suggestive of "Long COVID".

• Endoscopic evidence of any of the following:

• Eosinophilic esophagitis, scleroderma, Barrett's esophagus, esophageal cancer,Candida esophagitis confirmed by histopathology.

• LA grade B, C, or D erosive esophagitis, esophageal stricture or scarring.

• History of surgery or endoscopic treatment including fundoplication and/ordilation for esophageal stricture.

• History of fecal impaction that required hospitalization or emergency room treatmentwithin 3 months of the Screening Call.

• History of eating disorder within the last 2 years.

• Symptomatic condition (e.g., polycystic kidney disease, endometriosis, ovariancysts, etc.) during the 12 months prior to the Screening Call that requiredintervention (i.e., clinic or emergency room visit or hospitalization) that may beassociated with chronic abdominal pain or discomfort and might confound theassessments in this study.

• Surgical history that meets any of the following criteria:

• Gastric bypass surgery or invasive procedure for the treatment of obesity or surgeryto remove a segment of the GI tract at any time prior to the Screening Call

• Gastric band present within the past 60 days

• Open surgery of the abdomen, pelvis, or retroperitoneal structures within 6 monthsprior to the Screening Call

• Laparoscopic appendectomy or cholecystectomy or other instrumentation of the bowel < 60 days prior to the Screening Call. NOTE: Endoscopic removal of benign polyps isnot exclusionary.

• Prior use of the study medication MHS-1031 or ISOThrive Prebiotic Nectar.

• Use of fructo-oligosaccharides (FOS) or inulin.

• Symptomatic condition (e.g., angina, rumination, or other conditions involving themouth and/or throat) during the 12 months prior to the Screening Call.

• Use of any of the following medications that have not been stable dosing for atleast 90 days at time of Screening Call:

• Anticholinergics, such as oxybutynin (e.g., Ditropan XL®)

• Theophylline (e.g., Elixophyllin®, Theochron)

• Bisphosphonates taken orally, such as alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel®, Atelvia®)

• Quinidine

• Anticoagulants (e.g., Coumadin, Heparin)

• Iron supplement (other than contained in multi-vitamin)

• Potassium supplements in pill form (Elixirs are NOT exclusionary)

• Asthma medications

• Prescription medication to control Irritable Bowel Syndrome or ChronicIdiopathic Constipation

• Use of Nitrates within the last 12 months.

• Medication for depression, anxiety, or sleep (e.g., benzodiazepines such as diazepam (Valium®) and temazepam (Restoril) with uncontrolled symptoms or medication dosingthat has not been stable for at least 90 days at time of Screening Call.

• Antibiotic use within 60 days of the Screening Call.

• Narcotic (e.g., opiate) or illicit drug (i.e., illegal at both the Federal and Statelevels; e.g. Cocaine, Heroin, Methamphetamine) use within 60 days of the ScreeningCall.

• Use of any investigational product within 90 days prior to the Screening Call.

• Use of GLP-1 agonists (e.g., Dulaglutide (Trulicity), Exenatide, Semaglutide (Ozempic/Wegovy), Liraglutide) or prescription medications used for weight losswithin 6 months of Screening Call.

• Pregnancy, lactation, planned pregnancy or planned ova donation during the studyperiod.

• Participation in another investigation (clinical trial) during the course of thisstudy.

• Any major lifestyle change, such as getting married, change in residence, change injob, or other highly stressful event planned during the study periods.

• Sustained daily use of PPIs without self-report of improvement of heartburnsymptoms.

• Self or relative employed directly or indirectly by the Sponsor or relative oremployee of investigator or investigator's staff.

• Other conditions or situations that, in the Investigator's opinion, may put thesubject at significant risk, may confound the study results, or may interferesignificantly with the subject's participation in the study.