This amendment included the following changes to the clinical study protocol version 1.0, dated 02 August 2021. • Addition of patient stopping criteria. • Addition of study stopping criteria. • Change of stratification definition regarding prior transfusions. • Removal of the requirement to have a prior rituximab-based therapy. • Change of inclusion criterion regarding liver dysfunction. • Addition of a subgroup analysis on rituximab-experienced/naïve patients for primary and key secondary endpoints. • Change of the instructions for documentation of temperature control of the study drug at the patient’s residence.

This protocol amendment serves to remove the exploratory measurements of activity/movement by the use of Actigraphy at Baseline, Week 24 and Week 48. In addition, C3 deposition on red blood cells (RBCs) by flow cytometry, which was already included in the study protocol as an assessment, was also described among exploratory endpoints.

This amendment to the protocol adds the following inclusion and exclusion criteria: Added inclusion criterion • An absolute neutrophil count ≥1500 cells/mm3 at Screening. Added exclusion criteria • Protected adults (guardianship, trusteeship) who are unable to express their consent and persons under court protection. • Hypersensitivity to pegcetacoplan or to any of the excipients or placebo compounds. • Unresolved infection caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. • Known or suspected hereditary fructose intolerance. The study endpoints were modified as follows: • The key secondary endpoints were displayed in a different order. • For Hb, LDH, indirect bilirubin, ARC and haptoglobin levels, only time to first normalization from Baseline to Week 24 will be measured, and time from Baseline to Weeks, 48 and 96 was removed. • Addition of separate analysis of the subset of questions in the FACIT-Fatigue scale. In addition, the exploratory objective to evaluate change in patient activity level and energy expenditure has been removed.

Inclusion criteria was adjusted to clarify: o It was noted that the diagnosis of primary cold agglutinin disease (CAD) should be on the basis of the presence of all the criteria at Screening. o The restriction that patients who were not previously vaccinated should not receive multiple vaccines on the same day was removed and replaced with a reminder that vaccinations should be administered following the Advisory Committee on Immunization Practices (ACIP) recommendations for adults or children with complement deficiencies and/or immunocompromising conditions, as was already noted elsewhere in the protocol. • Exclusion criteria was adjusted to clarify: o The exclusion period for sutimlimab was changed from within 4 weeks prior to randomization to within 15 weeks prior to randomization. Patients previously treated with >1 dose of sutimlimab but who have not had experienced a documented increase in hemoglobin (Hb) ≥ 1.0 g/dL during sutimlimab treatment was added as exclusionary. o Belimumab and anti-CD20 antibody other than rituximab were added as exclusionary treatments, and the exclusionary period from other treatments, as monotherapy or in combination, had been set to 16 weeks prior to randomization. o For diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies, it was noted that antinuclear antibodies of long-standing duration without associated clinical symptoms will be adjudicated on a case-by-case basis. o For cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection, it was added that patients with long history of CAD, positive IgM titer and IgG titer without associated clinical symptoms will be adjudicated on a case-by-case basis.