Protocol Version 2: - Exclusion criteria were revised to remove the use of pre-operative anti-fibrinolytics and to expressly state allowance for use of anti-fibrinolytics in the Permitted Therapy section. This was based on exploratory data analysis of surgical procedures in HAVEN 1 and an interim analysis of HAVEN 2, which showed minimal risk in allowing pre-operative use of anti-fibrinolytics, as well as the potential to help with intra- and post-operative bleeding and avoid the use of bypassing agents for bleeding. -Throughout the protocol, references to “days” was revised to “Study Days.” - Objectives and Endpoints language was revised to indicate that applicable endpoints would be determined at the time of patient discharge, rather than a specific number of days after surgery. - Language describing thrombotic microangiopathy (TMA) and thromboembolic events (TE) was revised to reflect number of patients as opposed to number of cases/events. - Protocol references to a bleed/medication questionnaire were replaced with the Bleeds and Medications Diary, to match the Case Report Form. - Language was added regarding the total number of patients in Study BH29884 who received emicizumab prior to the clinical cutoff for the primary analysis. - Language was added to clarify that all bleeds would be recorded in the Bleeds and Medications Diary. - Text was revised to clarify that after surgery, serious adverse events (SAEs) and adverse events of special interest (AESIs) would be reported until 28 days after surgery, not 28 days after the last dose of study drug. - Protocol references to “binary outcome” were revised to “binary efficacy endpoint.”

Protocol Version 3: -The protocol was amended primarily to clarify and differentiate between primary efficacy and safety analysis reporting. -Efficacy and safety endpoints were modified for clarity and consistency. -The background on emicizumab was updated to reflect approval by the United States Food and Drug Administration and to align with the US Package Insert (USPI). -The term “study treatment” was clarified to indicate that the Sponsor is not providing the study drug; rather, treatment with emicizumab is required for all patients during the study. -The Internal Monitoring Committee is no longer a part of the study and its description was removed from the protocol. -The maximum number of patients per procedure category was increased from 7 to 9 patients. -Inclusion criteria were clarified to indicate that patients must plan to receive at least 4 loading doses of emicizumab and have been adherent to emicizumab prophylaxis by the time of the surgery. -Language was updated to indicate that the study treatment regimen may include other approved maintenance regimens, if and when available. -Prohibited therapy was modified to clarify that use of FVIII or BPA to treat a breakthrough bleed within 24 hours prior to surgery is prohibited. -It was clarified that if the screening period extends beyond 60 days, a patient must be re-consented prior to expiration of the original 60-day screening window. Only one extension of a patient’s screening period will be allowed. -Risks associated with emicizumab were updated to align with the USPI. -Language was updated to indicate that all AEs should be reported beginning from the time a patient provides informed consent until the end of the study. -Instructions regarding the reporting of overdoses, medication errors, drug abuse, or drug misuse were added. -A footnote was added to the Schedule of Activities to clarify that a patient’s PK sample must be obtained at the study site 24 hours prior to surgery.

Protocol Version 4: The primary reason for this amendment was to add an additional cohort of study patients: PwHA without inhibitors. -Emicizumab was approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric PwHA (congenital factor VIII deficiency) with or without factor VIII inhibitors. Because of this label change, the following updates were made: -An additional cohort of PwHA without inhibitors was added to provide prospectively collected data surrounding minor surgical procedures in this population. The Phase III trials were not designed to determine surgical outcomes from procedures that may have occurred. The study design, including the total length of the study, was updated to reflect the addition of PwHA without inhibitors. -Inclusion and exclusion criteria were updated to reflect the additional cohort and label change. -Background and other general language was updated to reflect the label change. -The length of study was corrected to begin at the time the first patient was enrolled. -Contraception requirements were updated to align with the Phase III HAVEN studies. -The timing for HIV testing was updated to within 24 weeks of enrollment. -The time window for concomitant therapy was updated to 28 days before enrollment until Study Day 28. -Height was removed as a necessary assessment. -It was clarified that biological samples will be destroyed no later than 5 years after final study results have been reported. -The Background and Safety sections of the protocol were updated with recent clinical data to align with the USPI. -A section on immunogenicity was added to align with the USPI. -The date of patient consent was clarified as the date of study enrollment. Timing for standard-of-care tests or examinations performed prior to obtaining informed consent was clarified. -The list of minor surgical procedures acceptable for entry into the study was updated to include lysis of penile adhesions.