A Randomized, Double-Blind, Placebo Controlled Trial of Aldafermin (NGM282) for Treatment of Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)

• Aged 18 to 75 years, inclusive at Visit 1 Screen.

• Clinical diagnosis of functional diarrhea or IBS with diarrhea according to Rome III or IV criteria at Visit 1 Screen.

• Clinical laboratory evidence of BAM (20-22), with at least one of the following results recorded in their past medical history:

‣ Serum C4 ≥ 52 ng/mL

⁃ Fecal BA \> 2337 µmoles / 48 hours

⁃ Total fecal BA \> 1000 µmoles / 48 hours + 4 % primary BA

⁃ Fecal primary BA \> 10% / 48 hours

• Body mass index (BMI) 18.0 to 45.0 kg/m2, inclusive at Visit 1 Screen

• Understands the study procedures, is willing and able to comply with the study procedures, and is able to give informed consent

• If treated with any of the following medications, dosing must be stable for 30 days prior to Visit 1 Screen. Patient must agree to maintain the same dose of medication throughout the study:

‣ Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs).

⁃ Bile acid sequestrants such as colestipol, cholestyramine and colesevelam.

• Participants must use one highly effective method of contraception for 30 days before the study through 90 days after study completion for males and through 30 days after study completion for females. Highly effective methods of contraception include: Oral, implantable, transdermal or injectable hormonal contraceptives; standard intrauterine device or vaginal ring; Male or female condoms and diaphragms used with spermicide; abstinence from heterosexual intercourse; female partners exclusively sexually active with a surgically sterilized male partner. Females who are surgically sterile having experienced a prior hysterectomy, bilateral salpingectomy, or bilateral oophorectomy or postmenopausal (defined as12 consecutive months with no menses) are not considered to be of childbearing potential.