Study of Safety and of the Mechanism of BLZ945 in ALS Patients

Inclusion Criteria:

- Able to communicate well with the investigator, to understand and comply with the
study visits and procedures of the study

- Written informed consent must be obtained before any assessment is performed.

- Male and female participants who are 18 years old or older at screening, and who are
diagnosed with familial or sporadic ALS according to the World Federation of
Neurology Revised El Escorial criteria of either bulbar or limb onset.

- Disease duration from symptoms onset no longer than 48 months at the screening
visit.

- Females of childbearing potential must have a negative pregnancy test at screening
and/or baseline.

- Treatment with approved ALS therapies is allowed, but participants need to be on a
stable dose and regimen for at least 30 days prior to baseline.

- Having completed the Core Treatment Period to be able to continue in the Extended
Treatment Period.

Exclusion Criteria:

- A history of clinically significant ECG abnormalities

- Active medical or neurologic diseases other than ALS, that in the opinion of the
investigator would limit their participation in the current study.

- Use of other investigational drugs within 5 half-lives of screening, or until the
expected PD effect has returned to baseline, whichever is longer; or longer if
required by local regulations.

- History of hypersensitivity to any of the study treatments or excipients or to drugs
of similar chemical classes.

- Presence of human immunodeficiency virus (HIV) infection based on screening lab
results.

- Evidence of active or latent tuberculosis as assessed by Quantiferon testing at the
screening visit.

- Positive serology for hepatitis B surface antigen, or hepatitis C antibodies
confirmed by an appropriate licensed test at screening.

- Signs or symptoms, in the judgement of the investigator, of a clinically significant
systemic viral, bacterial or fungal infection within 30 days prior to the screening
visit.

- Cardiac disorders, such as recent cardiac history (within 6 months of screening) of
acute coronary syndrome, acute heart failure, or significant ventricular arrhythmia
at the screening visit or participants with a history of severe pulmonary
hypertension. Participants with cardiac failure class 3 or 4 of the NYHA
classification, or history of reduced LVEF or individuals with implanted cardiac
pacemaker, or defibrillator.

- Significant hematological laboratory abnormalities.

- Clinical evidence of liver disease or liver injury or any of the following hepatic
conditions at the screening visit:

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 14 days after last dose of BLZ945.

- Pregnant or nursing female participants

- Sexually active males unless they use a condom during intercourse while taking the
drug during treatment, for 14 days after stopping BLZ945 and should not father a
child in this period.

- History or presence of impaired renal function at the screening visit.

- Active suicidal ideation.

- History of drug abuse or harmful alcohol use within the 12 months prior to dosing
within the judgement of the investigator, or evidence of such abuse as indicated by
the laboratory assays conducted during screening.

- Active GI conditions such as Barrett's esophagus, achalasia, esophageal varices and
active or history of esophageal cancer, pre-existing pancreatic disease at screening
visit.

- History of active vasculitis or history of autoimmune disease autoimmune disease
associated with vasculitis (eg., RA, SLE, Sjögrens disease, scleroderma).

- History or active cardiac valve disorder, congenital valve disease, or other
clinical condition that might affect cardiac valve function

- Use of systemic anticoagulation that cannot be temporarily paused before study
procedures

- Abnormal values on CT scan or echocardiography, signs of vasculitis, or evidence of
a significant medical condition meeting treatment discontinuation criteria will be
exclusionary for continuation in the extended treatment period.

- Participants who are planning to initiate treatment with an additional approved ALS
therapy in the next 24 weeks are not allowed to continue in the extended treatment
period.