AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

AMX0035 is a combination therapy designed to reduce neuronal death through blockade of key
cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). This
clinical trial is designed to demonstrate that treatment is safe, tolerable, and able to slow
decline in function as measured by the ALSFRS-R. The trial will also assess the effects of
AMX0035 on muscle strength, vital capacity, and biomarkers of ALS including markers of
neuronal death and neuroinflammation.

Key Inclusion Criteria:

1. Male or female, aged 18-80 years of age

2. Sporadic or familial ALS diagnosed as definite as defined by the World Federation of
Neurology revised El Escorial criteria

3. Less than or equal to 18 months since ALS symptom onset

4. Capable of providing informed consent and following trial procedures

5. Slow Vital Capacity (SVC) >60% of predicted value for gender, height, and age at the
Screening Visit

6. Subjects must either not take riluzole or be on a stable dose of riluzole for at least
30 days prior to the Screening Visit. Riluzole-naïve subjects are permitted in the
study.

7. Women of child bearing potential (e.g. not post-menopausal for at least one year or
surgically sterile) must agree to use adequate birth control for the duration of the
study and 3 months after last dose of study drug. Women must not be planning to become
pregnant for the duration of the study and 3 months after last dose of study drug

8. Men must agree to practice contraception for the duration of the study and 3 months
after last dose of study drug. Men must not plan to father a child or provide for
sperm donation for the duration of the study and 3 months after last dose of study
drug

Key Exclusion Criteria:

1. Presence of tracheostomy

2. Exposure to PB, TUDCA or UDCA within 3 months prior to the Screening Visit or planning
to use these medications during the course of the study

3. History of known allergy to PB or bile salts

4. Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the
normal

5. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of
normal

6. Poorly controlled arterial hypertension (SBP>160mmHg or DBP>100mmHg) at the Screening
Visit

7. Pregnant women or women currently breastfeeding

8. History of cholecystectomy

9. Biliary disease which impedes biliary flow including active cholecystitis, primary
biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gallbladder polyps,
gangrene of the gallbladder, abscess of the gallbladder.

10. History of Class III/IV heart failure (per New York Heart Association - NYHA)

11. Severe pancreatic or intestinal disorders that may alter the enterohepatic circulation
and absorption of TUDCA including biliary infections, pancreatitis and ileal resection

12. The presence of unstable psychiatric disease, cognitive impairment, dementia or
substance abuse that would impair ability of the subject to provide informed consent,
according to Site Investigator judgment

13. Clinically significant unstable medical condition (other than ALS) that would pose a
risk to the subject if they were to participate in the study

14. Active participation in an ALS clinical trial evaluating a small molecule within 30
days of the Screening Visit

15. Exposure at any time to any biologic under investigation for the treatment of subjects
with ALS (off-label use or investigational) including cell therapies, gene therapies,
and monoclonal antibodies.

16. Implantation of Diaphragm Pacing System (DPS)