Protocol Version 2.0: • Removed the subject assessment of attack trigger. • Added subject assessment of attack severity. • Clarified that the investigator (or qualified designee) would rate the severity of each attack rather than site staff and removed definitions for the severity ratings. • Provided contact information for Pharmacovigilance for SAE reporting and added that pregnancies would be reported using the pregnancy reporting form using this contact information.

Protocol Version 3.0: • Clarified that subjects were allowed to receive the COVID-19 vaccination before, during, or after participation in the trial. • Extended number of days permitted between completing the run-in period and the randomization visit from 7 days to 10 days and allowed randomization to occur prior to the randomization visit if the site was dispensing the IMP during the in-clinic randomization visit. • Clarified in exclusion criterion 11 that ongoing participation in an investigational COVID-19 vaccine trial was not allowed within 4 weeks of screening. • Allowed for IMP to be dispensed at the trial site instead of direct shipment to subjects required by local regulations or per the site’s local practice. • Provided fax numbers for reporting SAEs. • Removed requirement that subjects had to make reasonable efforts to store IMP at a specific temperature range as IMP was to be stored at room temperature and storage requirements were provided on the label per local regulations. • Clarified that investigators should make every effort possible to follow-up and document the course and outcome of all infants up to 1 year of age born to exposed mothers or born to partners of male subjects. • Clarified when subjects were to begin entering HAE attacks in the eDiary. • Clarified that an investigator must withdraw a subject from the trial if she had a positive pregnancy test during the trial. • Added volume of blood that was to be taken for clinical safety laboratory assessments. • Added clinical safety laboratory hematology tests to match the central laboratory standard panel.

Protocol Version 4.0: • Incorporated the following additional safety criteria: - Subjects with inadequate organ function were excluded from participation in the trial. - Individual and trial stopping criteria were added. • Excluded use of strong CYP3A4 inhibitors and inducers in the absence of a formal drug-drug interaction trial for KVD824. • Clarified the difference between subject’s withdrawal of consent versus subject discontinuation from the trial for other reasons (eg, safety or investigator’s discretion). • Clarified that any relevant diseases occurring between the screening visit and the first dose of IMP were to be captured as medical history. • Clarified that clinically significant laboratory abnormalities, as determined by the treating investigator, were to be recorded as AEs after the start of KVD824 dosing.

Protocol Version 5.0: • Added the trial name of KOMPLETE. • Added laboratory assessments at Week 4 to assess liver enzymes in conjunction with the update to the trial stopping criteria in Section 14 of the trial protocol. • Updated the name of the Pharmacovigilance vendor and fax numbers for SAE reporting. • Clarified the following inclusion criteria: - Clarified that C1-INH retesting could occur any time prior to randomization. - Clarified that historical C1-INH functional diagnostic test results for a subject could be used to confirm diagnosis of HAE type I or II in lieu of central or local lab testing. • Clarified that IMP was to be stored at room temperature as labeled. • Added procedural details of RTSM unblinding for investigators if unblinding a subject was needed. • Clarified on the timing of androgen washout period. • Incorporated the following trial stopping criteria: - The occurrence in any subject of a life-threatening SAE not related to HAE. - Liver-related AE that met Hy’s Law in more than 1 subject: 1. ALT or AST elevation of >3 × ULN 2. TBL elevation of >2 × ULN 3. Absence of initial findings of cholestasis (ie, absence of elevation of ALP to >2 × ULN) 4. No other reason could be found to explain the combination of increased ALT and TBL, such as viral hepatitis A through E; other preexisting or acute liver disease; or another drug capable of causing the observed injury. - Similar grade 3 or higher AE, excluding liver-related AE, in more than 1 subject. • Removed the sentence of “repeat laboratory assessments may be performed” in Section 15.3.4 of the trial protocol. • Clarified timing for the collection of SAE to start at the time of informed consent and to align with other country requirements. • Removed the sentence of “without baseline attack rate as fixed covariate” in Section 18.7 of the trial protocol to correct typographical error. • Added 2 new references.