Avexitide for Treatment of Post-Bariatric Hypoglycemia

Inclusion Criteria:

• Able to provide written informed consent and understand the purpose and risks of thestudy

• Willing and able to adhere to study requirements, including the use of thestudy-provided CGM device, SMBG device, and eDiary device as well as the other studyevaluations and procedures.

• Is male or female, at least 18 years of age (inclusive) at the time of consent.

• Body mass index (BMI) of up to 40 kg/m2 and has stable body weight-i.e., not varyingby >5% for at least 2 months prior to Screening

• Has undergone documented RYGB performed ≥12 months prior to Screening.

• Has clinical diagnosis of PBH-defined as history of recurrent hypoglycemia withonset after surgery and having ruled out other causes of hypoglycemia as perInvestigator judgment.

• Has recurrent hypoglycemia, as demonstrated by experiencing at least 3 discretehypoglycemic episodes during the 3-week study Run-in period.

• Must agree to consistently follow the dietary management guidance and to maintainconsistent exercise and/or physical activity level throughout the Screening period (including the Run-in period), the Double-Blind study treatment period, and Part Aof the OLE period.

• If female, must meet all of the following:

• Is not breastfeeding or lactating;

• If of childbearing potential, has negative serum pregnancy test result atScreening and on Day 1 ahead of dosing

• If of childbearing potential, must also agree to use a highly effective methodof birth control-and agree not to participate in egg (ova) donation or storage,throughout the duration of study participation and for at least 1 month afterthe last dose of study drug.

• If male and engaging in heterosexual intercourse with a female partner ofchildbearing potential, must utilize a highly effective method of contraception, andagree not to donate sperm, from the time of providing written informed consent untilat least 3 months after the last dose of study drug.

Exclusion Criteria:

• Has received avexitide (exendin 9-39) at any time prior to Screening Visit 1.

• Has received another investigational drug, for any indication, within 5 half-livesof that drug prior to Screening Visit 1.

• Has participated in another interventional clinical study within 30 days prior toScreening Visit 1.

• Presence of gastrostomy tube (G-tube).

• Any known or suspected allergy to one of the investigational medicinal products (avexitide or placebo) or any related product (e.g., exenatide).

• History or presence of insulinoma or other cause of endogenous hyperinsulinism otherthan PBH.

• Active psychiatric disease or active eating disorder (e.g., uncontrolled majordepressive disorder, schizophrenia, bipolar disorder, or other severe mood, anxiety,or eating disorder). Note: prospective participants with stable conditions, perInvestigator judgement, may be considered, provided they are not on an excludedmedication.

• History of major surgery within 6 months prior to Screening.

• History of upper GI surgery, other than RYGB. Note that history of vertical sleevegastrectomy (VSG) with subsequent RYGB conversion may be considered on acase-by-case basis upon discussion with the Medical Monitor.

• Current or prior use of agent(s) that may alter glucose metabolism, or promoteweight loss, within 5 medication half-lives of Screening Visit 1. Such agentsinclude, but are not limited to, the following: acarbose; calcium channel blockers;diazoxide; dipeptidyl-peptidase-4 (DPP-4) inhibitors; GLP-1 agonists;glucocorticoids; glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dualagonists; insulin; lithium; meglitinides; metformin; pentamide;sodium-glucose-linked transporter (SGLT)-1 inhibitors; SGLT-2 inhibitors;somatostatin analogs; sulfonylureas; and thiazolidinediones (TZDs).

• Use of drugs that interfere with the Dexcom G7 sensor within 5 half-lives ofScreening Visit 1. Such drugs include acetaminophen administered at a dosage greaterthan 1000 mg every 6 hours, and hydroxyurea.

• Investigator-assessed evidence of alcohol or drug abuse within 12 months prior toScreening. Unwillingness to restrict alcohol use to no more than 1 drink per day isalso exclusionary.