Rationale for Study, Population, and Design • The rationale for the study, population, and design was updated to reflect that: Collection of long-term safety and effectiveness data in a controlled study was considered critical, as PNH is a condition requiring lifelong therapy. The study population was chosen to allow for the evaluation of the benefit-risk profile of long-term treatment with BCX9930 in participants who had already taken BCX9930 for up to 52 weeks. The study features (eg, endpoints, withdrawal criteria, assessments, etc.) aligned closely with previous PNH studies of BCX9930 to allow for the continued assessment of risks and benefits in participants previously exposed to BCX9930. Study Duration and Visit Frequency • The study duration was changed from a maximum of 5 years to 48 weeks.The visit schedule was changed from every 12 weeks to every 8 weeks. Dose and Dosing Regimen • The dose of BCX9930 was changed from 500 mg BID to 400 mg BID for all participants. Dosage forms of BCX9930 were added to the protocol. Data Collection and Analysis • The pharmacodynamic (PD) and complement biomarker secondary endpoint was changed to a PD endpoint.The timing of pharmacokinetic (PK) and PD blood sample collection (sparse sampling) was clarified to be at baseline and at every study visit to the investigative site thereafter, including unscheduled visits where feasible. For sparse PK sample collection, investigators were requested to vary the time of collection between visits when possible. The collection of an optional blood sample to be stored for potential pharmacogenomic (PG) analysis was added. •Changes included other non-substantial updates.

• Study Design The original study design had provided treatment with BCX9930 for up to 48 weeks, or until the drug became available by another mechanism (eg., expanded or market access), or until the sponsor discontinued development of the product for PNH, whichever occurred first. As amended, treatment under the protocol was to be provided for up to 96 weeks, as long as the investigator believed it was in the participant's best interest to continue treatment, or until the participant gained access to other effective treatment options for PNH, whichever occurred first. Treatment was discontinued for participants who were deriving no meaningful clinical benefit, who experienced an unacceptable drug-related adverse event, or who were otherwise intolerant of the study intervention. The last on-treatment visit completed for the prior study still served as the baseline visit for BCX9930-205 (Study 205); however, participants were no longer required to complete treatment in their prior study before enrolling in Study 205. For participants who had completed at least 24 weeks of treatment with BCX9930 in their prior study, visits occurred every 8 weeks through Week 48. After Week 48, visits were scheduled every 12 weeks until Week 96. Participants who had not completed 24 weeks of treatment prior to enrolling in Study 205 returned to the clinic every 4 weeks until they had completed 24 weeks of cumulative treatment with BCX9930. • Study Objectives and Endpoints The objectives and endpoints of the study were simplified to focus on providing continued access to BCX9930 and monitoring safety in participants who continued treatment with the drug. • Number of Participants The number of potential participants was changed from approximately 200 to up to 30 participants.

• Inclusion Criteria As amended, to be eligible for the study, participants needed to have completed at least 12 weeks of treatment with BCX9930 in a prior study for PNH (i.e., Study BCX9930-201, BCX9930-202, or BCX9930-203) and, in the opinion of the investigator, had benefited from that treatment, were expected to continue benefiting from treatment, wished to continue treatment, and had no other effective treatment options available. • Study interventional Product and Study intervention Administration The text describing the study intervention product was revised to refer only to the 100 mg tablets. References to the 200 mg and 250 mg tablets were deleted. • Study Procedures/Assessments The protocol was revised to reflect a shift away from prescribed measures of effectiveness, allowing investigators discretion to manage individual participant PNH disease based on their medical judgment and institutional standards of care. • Sections describing effectiveness assessments—including PK, PD, PG, iron testing, and patient reported outcome (PRO) measurements—were deleted. Additionally, 12-lead electrocardiograms (ECGs) were no longer performed as part of the prescribed safety assessments, and body weight was no longer measured at each study visit. • Adverse Events and Toxicity Management The definition of an adverse event (AE) was revised to remove explicit references to reporting events of alcoholic steatohepatitis (ASH) and major adverse vascular events (MAVEs) as AEs. Events of ASH or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (symptomatic or asymptomatic) were no longer reported as End of Study Measures (EOSMs). • Study Populations and Statistical Analyses The text describing planned study populations and statistical analyses was revised. • Changes included other non-substantial updates.

•Clinical trial identification codes (EudraCT, European Union Clinical Trials [EU CT], and Universal Trial Number [UTN] numbers) were added to the synopsis. •The background information from the previous version (version 3.0) of the protocol was rewritten to streamline content. •The text was focused to update on a brief discussion of the complement system, PNH, and the therapeutic rationale for BCX9930. •Changes included other non-substantial updates.