Evaluation of the Safety and Efficacy of Revita® DMR on Body Weight Maintenance in Subjects with Obesity Who Have Achieved At Least 15% Weight Loss on Tirzepatide

Inclusion Criteria:

1. Participant-provided, written informed consent to participate in the study inaccordance with local regulations

2. Adult participants aged 21-70 years, inclusive

3. Prior to tirzepatide therapy, have a BMI of ≥ 30 kg/m2 (obesity) and ≤ 45 kg/m2.

4. Have achieved at least 15% weight loss on tirzepatide therapy at Visit 7 (Participants in Stage 1, who enter the study on tirzepatide, must have a documentedpre-tirzepatide weight confirming they have lost at least 15% body weight ontirzepatide)

5. Have a history of at least 1 self-reported, unsuccessful, dietary effort to losebody weight

6. All female participants of childbearing potential must have a negative urinepregnancy test at screening and a negative urine pregnancy test at study visit 7prior to study intervention. Postmenopausal females with amenorrhea for at least 2years will be eligible if they are > 50 years of age. Postmenopausal females withamenorrhea for at least 2 years, who are ≤ 50 years, must also have documented serumfollicle stimulating hormone levels > 35 mUI/mL

7. Able to walk at least 400 yards (roughly the distance of a track) and climb a flightof stairs without difficulty due to either musculoskeletal injuries/diseases orcardiopulmonary diseases

8. If sexually active, WOCBP must use one of the following birth control methods duringthe entire course of the study as specified:

• Intrauterine device in place for at least 3 months before the first dose oftirzepatide and throughout the study

• Barrier method (condom, diaphragm) with spermicide for at least 14 days beforethe first dose of tirzepatide and throughout the study

• Surgical sterilization of the male partner(s) (vasectomy for at least 6 monthsbefore first dose of tirzepatide) or

• Hormonal contraceptives with a barrier method for at least 3 months before thefirst dose of tirzepatide and throughout the study

Exclusion Criteria:

1. Medical conditions that contraindicate the use of tirzepatide for weight management,as detailed in the tirzepatide prescribing information

2. BMI ≥ 40 kg/m2 at Visit 7

3. Females who are or intend to be pregnant or breastfeeding during the study

4. Known serious hypersensitivity to tirzepatide or any of the excipients intirzepatide

5. History of infectious liver disease excluding recovered Hepatitis A infection

6. History of pancreatitis within 6 months of screening or any prior history ofrecurrent pancreatitis (i.e., two or more episodes of pancreatitis)

7. Potentially unreliable participants or those judged by the investigator to beunsuitable for the study

8. Unable or unwilling to follow the dietary restrictions specified by the clinicalprotocol

9. Known history of or active binge eating disorder or suspected binge eating disorderbased on binge eating disorder assessment questionnaire

10. Known history of or active substance abuse including alcohol within the past 2 yearsthat, in the opinion of the investigator, may preclude the participant fromfollowing the protocol and completing the study

11. Have history of use of marijuana or tetrahydrocannabinol (THC)-containing productswithin 3 months of screening or unwillingness to abstain from marijuana orTHC-containing products use during the study Diabetes-related conditions:

12. History of type 1 or type 2 diabetes (T2D) or screening values consistent with T2D,or history of any genetic form of diabetes

13. HbA1c > 6.5% or fasting glucose > 125 mg/dL consistent with T2D diagnosis accordingto the American Diabetes Association Standards of Care 2024 (Participants withisolated impaired fasting glucose [100 to 125 mg/dL, inclusive] may enroll in thestudy) Laboratory values or clinical abnormalities:

14. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 at screening, asassessed by serum creatinine using the revised 2021 CKD-EPI equation

15. Serum calcitonin level ≥ 20 ng/L at screening if eGFR ≥ 60 mL/min/1.73m2 or serumcalcitonin level ≥ 35 ng/L if eGFR < 60 mL/min/1.73m2

16. Fasting triglycerides > 500 mg/dL (> 5.6 mmol/L)

17. Abnormal liver function at screening, defined as any of the following: aspartateaminotransferase (AST) > 3X upper limit of the normal reference range (ULN), ALT > 3X ULN, or serum total bilirubin (TB) > 3X ULN

18. Values of systolic blood pressure (SBP) > 180 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg

19. Any ECG or clinical laboratory abnormality which precludes safe involvement in thestudy in the opinion of the investigator Gastrointestinal

20. Known structural or functional disorder of the esophagus including any swallowingdisorder, esophageal chest pain disorders, drug-refractory esophageal refluxsymptoms, or active and uncontrolled GERD defined as Los Angeles Grade C or Desophagitis

21. Known structural or functional disorder of the stomach including active gastriculcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia ortype II and higher paraoesophageal hernia), cancer, or any other disorder of thestomach

22. Clinically significant gastric-emptying abnormality (i.e., severe gastroparesis orgastric outlet obstruction) including a drug-induced abnormality or an abnormalityexperienced in a person who chronically takes drugs that directly affect GI motilitysuch as metoclopromide or erythromycin

23. Previous GI surgery to treat the duodenum such as participants who have had aBillroth 2, Roux-en-Y gastric bypass, gastric sleeve, or other similar procedures orconditions

24. Known intestinal autoimmune disease including celiac disease, ulcerative colitis,Crohn's disease, lupus erythematosus, scleroderma, or other autoimmune or connectivetissue disorder that affects the small intestine

25. Any history of or current other gastrointestinal condition which would preclude anupper GI endoscopy in the opinion of the investigator Cardiovascular

26. New York Heart Association Class III or IV heart failure within 3 months prior toscreening

27. History of myocardial infarction or stroke within 6 months of screening

28. Unstable symptomatic or life-threatening arrhythmia or heart block. Note:Asymptomatic atrial fibrillation is not considered to be life-threatening, andpatients with asymptomatic atrial fibrillation will be permitted to enter the study Related to other concomitant conditions or medical history:

29. Any concurrent medical condition/disorder or clinically symptomatic cardiovascular,gastrointestinal (including pancreatitis), hematological, pulmonary, psychiatric,acute or chronic infectious disease, active retinal disease or other disorder which,in the investigator's opinion, would interfere with the participant's ability tocomplete the trial, require administration of treatment that could affect theinterpretation of the efficacy or safety variables, or preclude safe involvement inthe study

30. Self-reported weight gain > 5 kg within 3 months prior to screening

31. Family history or personal history of medullary thyroid carcinoma (MTC) or multipleendocrine neoplasia (MEN) syndrome 2

32. History of an active or untreated malignancy or in remission from a clinicallysignificant malignancy within the last 5 years (except for treated basal cell orsquamous small cell carcinoma of the skin with no evidence of recurrence)

33. Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid-stimulating hormone [TSH] value outside the range of 0.4 to 6.0 mIU/L atscreening)

34. Known thyroid cancer

35. Any uncontrolled endocrine condition such as multiple endocrine neoplasia

36. History of hemoglobinopathies (sickle cell anemia, thalassemia major, sideroblasticanemia) or other blood disorder

37. Any uncontrolled psychiatric disorder as assessed by the investigator

38. Any history of known genetic cause of obesity such as Prader-Willi Syndrome

39. History of COVID infection with prolonged symptoms for >4 weeks Related to past or current medication use:

40. Administration of any investigational drug or participation in an interventionalclinical research study within 30 days or 5 half-lives (whichever is longer) ofscreening visit

41. Use of any oral or injectable hypoglycemic agents or any other prescription orover-the-counter diabetes or weight loss medications within 12 months prior toscreening visit, (except in the case of tirzepatide use in the stage 1 training armof the study only)

42. Use of any other medications known to cause weight gain or weight loss in theopinion of the investigator

43. Receiving or have received, within 3 months prior to screening, chronic (>14 days)systemic (excluding inhaled, intraocular, intra-articular or topical) corticosteroidtreatment or likely to require (in the opinion of the investigator) concurrenttreatment with corticosteroids (excluding inhaled, intraocular, intra-articular ortopical) during the course of the study

44. Treatment with antihypertensive or lipid-modifying medications which are not on astable dose for at least 8 weeks prior to screening or anticipated changes or doseadjustments within 30 days following randomization into the study

45. Treatment with thyroid hormones which are not on a stable dose for at least 8 weeksprior to screening

46. Use of anticoagulation therapy (e.g., warfarin, coumadin, or novel oralanticoagulants [NOACs]) or anti-platelet agents (e.g., thienopyridine) which cannotbe discontinued for 5-7 days or 2 drug half-lives before the procedure OtherExclusions

47. Investigator site personnel directly affiliated with this study and/or theirimmediate families. Immediate family is defined as a spouse, parent, child, orsibling, whether biological or legally adopted

48. Fractyl Health employees