A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation

Key Part A Inclusion Criteria:

• Participants should have a protocol-defined rapidly progressive SOD1 mutation,confirmed by a central reader, or a SOD1 mutation that is approved for inclusion byan external mutation adjudication committee.

• Participants with plasma NfL level less than the protocol-defined threshold.

• Participants who are clinically presymptomatic for ALS (i.e., must not haveclinically manifest ALS).

Key Part A Exclusion Criteria:

• History or positive test result at screening for human immunodeficiency virus (HIV).The requirement for testing at Screening may be omitted if it is not permitted bylocal regulations.

• Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibodyand detectable HCV RNA). Participants with positive HCV antibody and undetectableHCV Ribonucleic Acid (RNA) are eligible to participate in the study (United StatesCenters for Disease Control and Prevention).

• Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity tohepatitis B from previous natural infection (defined as negative HBsAg, positiveanti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligibleto participate in the study.

• History of systemic hypersensitivity reaction to tofersen, the excipients containedin the formulation, and if appropriate, any diagnostic agents to be administeredduring the study.

• History of confounding neuromuscular or neurological disorder that is expected tohave a progressive (i.e., worsening) course during the study, and/or is expected tobe associated with elevations in NF, in the opinion of the Investigator.

• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding thatif not managed optimally could place a participant at an increased risk forintraoperative or postoperative bleeding.

• Significant cognitive impairment, clinical dementia, or unstable psychiatricillness, including psychosis, suicidal ideation, suicide attempt, or untreated majordepression

≤ 90 days of screening, which in the opinion of the Investigator would interferewith the study procedures.

• Treatment with riluzole, edaravone, and/or sodium phenylbutyrate/taurursodiol (alsoknown as ursodoxicoltaurine). If the participant has been on riluzole, edaravone,and/or sodium phenylbutyrate/taurursodiol, the medication(s) must be discontinuedfor at least 5 half-lives prior to Screening.

• Use of off-label treatments for ALS.

• Treatment with another investigational drug (including investigational drugs for ALSthrough compassionate use programs), biological agent, or device within 1 month or 5half-lives of study agent, whichever is longer. Specifically, no prior treatmentwith small interfering RNA, stem cell therapy, or gene therapy is allowed.

• Anticipated need, in the opinion of the Investigator, for administration of anyantiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safelycontinued or held for an LP procedure, if necessary, according to local orinstitutional guidelines and/or Investigator determination.

• Current enrollment or a plan to enroll in any interventional clinical study in whichan investigational treatment, biological agent, device, or approved therapy forinvestigational use. Participation in a noninterventional study focused on ALSnatural history may be allowed at the discretion of the Investigator.

NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.