Safety and Effectiveness of Endoscopic Intestinal Re-Cellularization Therapy in Individuals With Type II Diabetes

Inclusion Criteria:

• 22- 70 years of age, inclusive.

• T2D diagnosis for at least 6 months.

• HbA1C of 7.5-10.5%, inclusive, determined by the central laboratory.

• BMI 27-40 kg/m2, inclusive.

• On 2-4 non-insulin glucose lowering mediations or on monotherapy with either GLP-1or GLP-1/GIP medications, with no changes in medication or dosing for at least 12weeks prior to the baseline visit.

• Individualized metabolic surgery (IMS) score ≤ 95.

• Weight stability (≤5% weight change) for at least 12 weeks prior to the screeningvisit.

• Agree not to donate blood during participation in the study.

• Able to comply with study requirements and understand and sign the Informed ConsentForm.

• Women of childbearing potential must be not pregnant and using an acceptable methodof contraception throughout the study.

• Willing and able to comply with study visits and study tasks as required perprotocol.

Exclusion Criteria:

• Diagnosed with type 1 diabetes.

• History of diabetic ketoacidosis or hyperosmolar nonketotic coma.

• Fasting serum C-peptide <1 ng/mL (333pmol/l).

• Current use of insulin, or previous use of any types of insulin for >1 month at anytime (except for treatment of gestational diabetes) in last 2 years.

• Hypoglycemic unawareness.

• History of ≥1 severe hypoglycemia episode in past 6 months

• Discontinuation of a GLP-1RA or a GLP-1/GIP dual-agonist within 6 months of thescreening visit following at least one month of treatment.

• Known autoimmune disease, including but not limited to, celiac disease, orpre-existing symptoms of systemic lupus erythematosus, scleroderma or otherautoimmune connective tissue disorder, or as evidenced by a positive anti-glutamicacid decarboxylase (GAD) test.

• Previous GI surgery that has changed GI anatomy or could limit treatment of theduodenum, such as Billroth 2, Roux-en-Y gastric bypass, gastric band or othersimilar procedures or conditions.

• Known history of a structural or functional disorder of the upper GI tract that mayimpede passage of the device through the upper GI tract or increase risk of tissuedamage during an endoscopic procedure, including eosinophilic esophagitis,stricture/stenosis, varices, diverticula, or other disorder of the esophagus,stomach and duodenum.

• History of gastroparesis.

• Acute gastrointestinal illness in the last 7 days.

• Known history of irritable bowel syndrome, radiation enteritis or other inflammatorybowel disease, such as Crohn's disease and Celiac disease.

• History of chronic or acute pancreatitis.

• Active hepatitis or active liver disease, or alanine aminotransferase (ALT) level >3.0 times the upper limit of normal (ULN) for the reference range, as determined bythe central laboratory at screening visit. Patients with NAFLD are eligible if theirALT level is ≤3.0 times the ULN.

• Current use of vitamin K antagonists, such as warfarin, or current use ofdirect-action oral anticoagulants (DOCAs) that cannot be safely discontinuedperiprocedurally.

• Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot bediscontinued for 7 days before the procedure.

• Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) from treatmentthrough 4 weeks following the procedure. Alternative use of acetaminophen and lowdose aspirin is allowed.

• Use of systemic glucocorticoids (excluding topical or ophthalmic application orinhaled forms) for more than 10 consecutive days within 12 weeks prior to thescreening visit.

• Use of medications known to affect GI motility (e.g. metoclopramide/ Reglan)

• Current use of weight loss medications such as Saxenda [liraglutide ], Xenical® [orlistat], Acutrim® [phenylpropanolamine], Sanorex® [mazindol], Adipex® [phentermine], BELVIQ® [lorcaserin], Qsymia® [phentermine/topiramate combination],Contrave® [naltrexone/bupropion], or other weight loss medications includingover-the-counter [OTC] medications [for example, Allī®]) or have discontinued weightloss medications within 6 months.

• Participation in any structured weight loss program or endoscopic weight lossintervention within 6 months of the screen visit.

• Persistent anemia, defined as hemoglobin <10 g/dL.

• Known history of hemoglobinopathy, hemolytic anemia or sickle cell anemia, or anyother traits of hemoglobin abnormalities known to interfere with the measurement ofHbA1c.

• History of blood donation or transfusion within 3 months prior to the ScreeningVisit.

• Unstable or paroxysmal cardiac arrhythmia.

• Any of the following cardiovascular conditions within 6-months prior to screeningvisit: acute myocardial infarction, cerebrovascular accident (stroke),hospitalization due to congestive heart failure.

• History of valvular heart disease or chronic heart failure (NYHA III or IV).

• Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 calculated by CKD-EPICreatinine Equation as determined by the central laboratory.

• Known immunocompromised status, including but not limited to individuals who haveundergone organ transplantation, chemotherapy, or radiotherapy within the past 12months, who have clinically significant leukopenia, who are positive for the humanimmunodeficiency virus (HIV) or whose immune status makes the participant a poorcandidate for clinical trial participation in the opinion of the investigator.

• History of secondary hypothyroidism or inadequately controlled primaryhypothyroidism (TSH value outside the normal range at screening).

• Presence of any implanted electronic devices that cannot be turned off during theprocedure

• Presence of duodenal or biliary stents.

• Not a candidate for upper GI endoscopy or general anesthesia.

• Active illicit substance abuse or alcoholism (>2 drinks/day regularly).

• Active malignancy within the last 5 years (excluding non-melanoma skin cancers).

• Women who are breastfeeding.

• Participating in another ongoing clinical trial of an investigational drug ordevice.

• Binge eating disorder, or any other mental or physical condition which, in theopinion of the study investigator, makes the participant a poor candidate forclinical trial participation.

• Critically ill or has a life expectancy <5 years.

• Are investigator site personnel directly affiliated with this study and/or theirimmediate family member. Immediate family is defined as a spouse, parent, child, orsibling, whether biological or legally adopted.