Clinical trial NCT05116774
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: BCX9930 factor D inhibitor proximal complement inhibitor oral therapy paroxysmal nocturnal hemoglobinuria inadequate response to C5 inhibitor C5 inhibitor eculizumab ravulizumab
Sponsor: BioCryst Pharmaceuticals
Start date: 2021-12-06; Completion date: 2023-09-14
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to determine the efficacy and safety of BCX9930 monotherapy for the treatment of PNH compared to continued C5 inhibitor therapy in adult PNH participants with residual anemia despite treatment with a C5 inhibitor.

Detailed description:
This was a randomized, active comparator-controlled, open-label, parallel-group, 2-part study. Parts 1 and 2 were conducted in the same participants.

Part 1 of the study was designed to evaluate the efficacy, safety, and tolerability of oral BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in participants with PNH with inadequate response to their current C5 inhibitor therapy. Participants were randomized to either discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor therapy for the 24-week randomized treatment period. The primary efficacy and safety analyses were based on Part 1.

Part 2 of the study was designed to evaluate the long-term safety, tolerability, and effectiveness of BCX9930 monotherapy when administered through Week 52. All participants in Part 2 received BCX9930. Participants who were randomized to BCX9930 monotherapy in Part 1 continued to receive BCX9930 in Part 2. Participants who were randomized to C5 inhibitor therapy in Part 1 discontinued that therapy at the Week 24 visit and received BCX9930 in Part 2.

Arms: arm 1: Participants were randomized to receive BCX9930 during Part 1 and continued to receive the same during Part 2. Per protocol amendment, participants who previously received 500 mg twice daily (BID) and remained on study treatment were dose adjusted to 400 mg BID. For all newly enrolled participants, at the initiation of BCX9930 dosing, participants were administered a dose of 200 mg BID for the first 14 days of treatment before increasing to 400 mg BID. The maximum treatment duration on BCX9930 in Part 1 was 24 weeks. The overall maximum treatment duration on BCX9930 was 377 days. arm 2: Participants randomized to this group continued the existing C5-INH therapy during Part 1. After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants entered Part 2 where they switched to open-label BCX9930 monotherapy prior to Week 24, if earlier. The maximum treatment duration on C5-INH in Part 1 was 24 weeks. The maximum treatment duration on BCX9930 was 197 days.
Interventions: intervention 1: Eculizumab intervention 2: Ravulizumab intervention 3: BCX9930
Intervention descriptions: intervention 1: Administered by intravenous infusion per current dose regimen intervention 2: Administered by intravenous infusion per current dose regimen intervention 3: Administered orally twice daily

Protocol documents:
Prot_000.pdf: 
 
 
 
BIOCRYST 
PHARMACEUTICALS, INC. 
BCX9930 
PROTOCOL No. BCX9930-202 
IND No. 142,217 
EudraCT No. 2020-004438-39 
 
A Randomized, Open-Label, Multicenter, Parallel-Group 
Study to Evaluate the Efficacy, Safety, and Tolerability of 
Oral BCX9930 Monotherapy for the Treatment of 
Paroxysmal Nocturnal Hemoglobinuria in Subjects with 
Inadequate Response to C5 Inhibitor Therapy 
 
 
Version 4.0: 01 August 2022 
 
 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Boulevard, Suite 200 
Durham, North Carolina 27703, USA 
Phone: +1 919-859-1302 
Fax: +1 919-851-1416 
 
CONFIDENTIAL 
The information in this document contains proprietary and confidential information belonging to 
BioCryst Pharmaceuticals, Inc. As a result, no part of this document should be copied, referred 
to, released, published or otherwise disclosed in any manner or media without prior written 
approval from BioCryst Pharmaceuticals, Inc. 




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INVESTIGATOR AGREEMENT 
 
Protocol No. BCX9930-202 
A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate 
the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the 
Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects with 
Inadequate Response to C5 Inhibitor Therapy 
Version 4.0: 01 August 2022 
 
I have received and read the Investigator’s Brochure (IB) for BCX9930. 
I have carefully read this protocol and agree that it contains all of the necessary information 
required to conduct this study. I agree to conduct this study as described and according to the 
Declaration of Helsinki, International Council for Harmonisation guidelines for Good Clinical 
Practice, and all locally applicable regulations. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol. 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
Signature of Investigator 
 
 
 
 
Date 


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STUDY INFORMATION  
Protocol No.: 
BCX9930-202 
Study Title: 
A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate 
the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for 
the Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects with 
Inadequate Response to C5 Inhibitor Therapy 
IND No.: 
142,217 
EudraCT No.: 
2020-004438-39 
Investigational Product: 
BCX9930 
Indication Studied: 
Paroxysmal nocturnal hemoglobinuria (PNH) 
Sponsor: 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Boulevard 
Nottingham Hall, Suite 200 
Durham, North Carolina 27703, USA 
Sponsor Medical 
Monitor: 
 
 
Office: 
 
Mobile: 
 
Email: 
 
(Note: See Section 12.4.1 for contact information for SAE reporting.) 
Sponsor Clinical Study 
Manager: 
 
 
Office: 
 
Mobile: 
 
Email: 
 
Lead or Coordinating 
Investigator: 
 
 
 
Compliance Statement: 
This study will be conducted in accordance with the ethical principles that 
have their origin in the Declaration of Helsinki and clinical research 
guidelines established by the Code of Federal Regulations (Title 21, CFR 
Parts 50, 56, and 312), International Council for Harmonisation Guidelines, 
and all locally applicable regulations. Essential study documents are 
currently archived in accordance with applicable regulations. 
Final Protocol Date: 
Version 4.0: 01 August 2022 (Amendment 3) 
Previous Version(s): 
Version 3.0: 29 June 2022 (Amendment 2) 
Version 2.0: 27 May 2021 (Amendment 1) 
Version 1.0: 18 March 2021 (Original) 
 


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2. 
SYNOPSIS 
Name of Sponsor/Company: 
BioCryst Pharmaceuticals, Inc. 
Name of Investigational Product: 
BCX9930 
Name of Active Ingredient: 
 
Title of Study: 
A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and 
Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal 
Hemoglobinuria in Subjects with Inadequate Response to C5 Inhibitor Therapy 
BioCryst Protocol No.: BCX9930-202 
Study Centers: 
This study will be conducted at study centers in multiple countries/regions 
Lead or Coordinating Investigator: 
 
 
Phase of development: 2 
Objectives: 
Part 1 Primary Objective: 
• 
To determine the efficacy of oral BCX9930 monotherapy administered for 24 weeks, 
compared to continued complement component 5 (C5) inhibitor therapy, in subjects with 
paroxysmal nocturnal hemoglobinuria (PNH) with an inadequate response to C5 inhibitor 
therapy 
Part 1 Secondary Objectives: 
• 
To evaluate the safety and tolerability of BCX9930 monotherapy administered for 24 weeks, 
as compared to continued C5 inhibitor therapy, in subjects with PNH 
• 
To characterize the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor 
therapy, using clinical and laboratory measurements, including complement and thrombosis 
biomarkers, PNH clone size, and C3-opsonization of red blood cells (RBCs) in subjects with 
PNH 
• 
To evaluate the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor 
therapy, on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale 
and other patient-reported outcomes (PROs) in subjects with PNH 
• 
To characterize BCX9930 plasma concentrations and pharmacokinetic (PK) parameters in 
subjects with PNH 


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In Part 1 of this study, unless indicated otherwise, endpoints will be assessed at or to Week 24. 
Part 1 Primary Endpoint: 
• 
Change from baseline (CFB) in hemoglobin (Hb) [mean of values at Weeks 12, 16, 20, 
and 24] 
Part 1 Key Secondary Endpoints: 
1. Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 
2. Number of units of packed red blood cells (pRBCs) transfused [from Week 4 to Week 24] 
3. CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
Part 1 Other Secondary Endpoints: 
• 
Percent CFB in lactate dehydrogenase (LDH) [mean of values at Weeks 12, 16, 20, and 24] 
• 
Percent reduction in the rate of pRBC units transfused [from Week 4 to Week 24 vs. 
prestudy transfusion rate] 
• 
Proportion of subjects with Hb ≥ 12 g/dL [at Week 24] 
• 
Proportion of subjects with Hb stabilization, defined as avoidance of a > 2 g/dL decrease in 
the absence of transfusion [from Week 4 to Week 24] 
• 
CFB in C3-opsonized RBCs [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in total PNH RBC clone size [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in ratio of total PNH RBC clone size to PNH white blood cell (WBC) clone size 
(ie, ratio of percent PNH RBCs / percent PNH WBCs) [mean of values at Weeks 12, 16, 20, 
and 24] 
• 
CFB in absolute reticulocyte count (ARC) [mean of values at Weeks 12, 16, 20, and 24] 
• 
Proportion of subjects with ARC in the normal range [at Week 24] 
• 
CFB in haptoglobin [mean of values at Weeks 12, 16, 20, and 24] 
• 
Proportion of subjects with haptoglobin ≥ lower limit of normal reference range (LLN) [at 
Week 24] 
• 
CFB in total bilirubin [mean of values at Weeks 12, 16, 20, and 24] 
Part 1 Exploratory Endpoints: 
• 
 
• 
 
Part 1 Other Health-related Quality of Life (HRQoL) Endpoints: 
• 
Proportion of subjects achieving a within-subject meaningful change for the FACIT-Fatigue 
scale [at Week 24] 
• 
CFB in Quality of Life Questionnaire for patients with Aplastic Anemia/Paroxysmal 
Nocturnal Hemoglobinuria (QLQ-AA/PNH) Physical Functioning and other domain scores 
[at Week 24] 
• 
Proportion of subjects with improvement on individual PNH symptom items (ie, frequency, 
severity, and/or interference) from baseline as assessed using the modified Patient-Reported 
Outcome Questionnaire for Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria 
(PRO-AA/PNH) [at Week 24] 
• 
CFB in individual PNH symptom items on the modified PRO-AA/PNH [at Week 24] 


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• 
CFB in EuroQoL 5-dimension, 5-level (EQ-5D-5L) utility and visual analog scale (VAS) 
scores [at Week 24] 
• 
Treatment Satisfaction Questionnaire for Medication (TSQM) scale score [at Week 24] 
• 
Patient global impression of change in fatigue, impact of fatigue, and physical functioning as 
assessed using the Patient Global Impression of Change (PGIC)-Fatigue, PGIC-Impact of 
Fatigue, and PGIC-Physical Functioning scores, respectively [at Week 24] 
• 
CFB in patient global impression of severity of fatigue, impact of fatigue, and physical 
functioning as assessed using the Patient Global Impression of Severity (PGIS)-Fatigue, 
PGIS-Impact of Fatigue, and PGIS-Physical Functioning scores, respectively [at Week 24] 
Part 1 Safety Endpoints: 
• 
Number and proportion of subjects with a treatment-emergent adverse event (TEAE) 
• 
Number and proportion of subjects who discontinue treatment due to a TEAE 
• 
Number and proportion of subjects who experience a treatment-emergent serious adverse 
event (TESAE) 
• 
Number and proportion of subjects who experience a Grade 3 or Grade 4 TEAE assessed 
using the Common Terminology Criteria for Adverse Event (CTCAE) grading scales 
• 
Number and proportion of subjects who experience a treatment-emergent CTCAE Grade 3 
or Grade 4 laboratory abnormality 
Part 2 Primary Objective: 
• 
To evaluate the long-term safety and tolerability of oral BCX9930 monotherapy 
administered over a 28- to 52-week treatment period in subjects with PNH with an 
inadequate response to C5 inhibitor therapy 
Part 2 Secondary Objectives: 
• 
To assess the effectiveness of BCX9930 monotherapy in the treatment of PNH over a 28- to 
52-week treatment period 
• 
To characterize the effects of BCX9930 monotherapy using clinical and laboratory 
measurements, including complement and thrombosis biomarkers, PNH clone size, and 
C3-opsonization of RBCs, in subjects with PNH over a 28- to 52-week treatment period 
• 
To evaluate the effects of BCX9930 monotherapy on FACIT-Fatigue scale and other PROs 
in subjects with PNH over a 28- to 52-week treatment period 
• 
To characterize BCX9930 plasma concentrations and PK parameters over time in subjects 
with PNH 
In Part 2, unless indicated otherwise, endpoints will be assessed at or to Week 52. For subjects who 
are switched from C5 inhibitor therapy to BCX9930 monotherapy at the end of Part 1, Part 2 
endpoints will be assessed against Week 24 (ie, Week 52 vs. Week 24). 
Part 2 Primary Endpoints: 
• 
Number and proportion of subjects with a TEAE 
• 
Number and proportion of subjects who discontinue due to a TEAE 
• 
Number and proportion of subjects who experience a TESAE 
• 
Number and proportion of subjects who experience a CTCAE Grade 3 or Grade 4 TEAE 


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• 
Number and proportion of subjects who experience a treatment-emergent CTCAE Grade 3 
or Grade 4 laboratory abnormality 
Part 2 Secondary Endpoints: 
• 
CFB in Hb [mean of values from Weeks 28 to 52 for subjects randomized to BCX9930 in 
Part 1 and from Weeks 36 to 52 for subjects randomized to continue C5 inhibitor] 
• 
Proportion of subjects with Hb ≥ 12 g/dL [at Week 52] 
• 
Proportion of subjects with Hb stabilization (avoidance of a > 2 g/dL decrease in the absence 
of transfusion) [from Weeks 24 to 52 for subjects randomized to BCX9930 in Part 1 and 
from Weeks 28 to 52 for subjects randomized to continue C5 inhibitor] 
• 
Proportion of subjects who are transfusion-free [from Weeks 24 to 52 for subjects 
randomized to BCX9930 in Part 1 and from Weeks 28 to 52 for subjects randomized to 
continue C5 inhibitor] 
• 
Number of units of pRBCs transfused [from Weeks 24 to 52 for subjects randomized to 
BCX9930 in Part 1 and from Weeks 28 to 52 for subjects randomized to continue 
C5 inhibitor] 
• 
Percent reduction in the rate of pRBC units transfused [from Weeks 24 to 52 for subjects 
randomized to BCX9930 in Part 1 and from Weeks 28 to 52 for subjects randomized to 
continue C5 inhibitor vs. prestudy transfusion rate] 
• 
Percent CFB in LDH [mean of values from Weeks 28 to 52 for subjects randomized to 
BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to continue 
C5 inhibitor] 
• 
CFB in ARC [mean of values from Weeks 28 to 52 for subjects randomized to BCX9930 in 
Part 1 and from Weeks 36 to 52 for subjects randomized to continue C5 inhibitor] 
• 
Proportion of subjects with ARC in the normal range [at Week 52] 
• 
CFB in haptoglobin [mean of values from Weeks 28 to 52 for subjects randomized to 
BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to continue C5 
inhibitor] 
• 
Proportion of subjects with haptoglobin ≥ LLN [at Week 52] 
• 
CFB in C3-opsonized RBCs [mean of values from Weeks 28 to 52 for subjects randomized 
to BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to continue 
C5 inhibitor] 
• 
CFB in total PNH RBC clone size [mean of values from Weeks 28 to 52 for subjects 
randomized to BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to 
continue C5 inhibitor] 
• 
CFB in ratio of total PNH RBC clone size to PNH WBC clone size [mean of values from 
Weeks 28 to 52 for subjects randomized to BCX9930 in Part 1 and from Weeks 36 to 52 for 
subjects randomized to continue C5 inhibitor] 
Part 2 Exploratory Endpoints: 
• 
 
 


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• 
 
 
 
Part 2 Health-related Quality of Life Endpoints: 
• 
Durability of FACIT-Fatigue scale, QLQ-AA/PNH domain, modified PRO-AA/PNH, 
EQ-5D-5L utility and VAS, and TSQM scale scores 
• 
Proportion of subjects achieving a within-subject meaningful change for FACIT-Fatigue 
scale 
• 
Proportion of subjects with improvement in individual PNH symptom items on the modified 
PRO-AA/PNH as compared to baseline 
• 
Patient global impression of change in fatigue, impact of fatigue, and physical functioning as 
assessed using the PGIC-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning 
scores, respectively 
• 
CFB in patient global impression of severity of fatigue, impact of fatigue, and physical 
functioning as assessed using the PGIS-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical 
Functioning scores, respectively 
PK and Pharmacodynamic (PD) Endpoints – Parts 1 and 2: 
• 
PK data will be used to estimate PK parameters using appropriate PK analyses based on the 
sampling collection approaches 
• 
PD data will be used to estimate PD parameters as well as in combination with PK data to 
perform PK/PD analyses 
• 
CFB in PD and complement biomarker measurements, including constitutive complement 
levels and ex vivo stimulation assays 
PK and PD data may be analyzed in combination with data from other clinical studies as appropriate. 
Study Design: 
This is a randomized, active-controlled, open-label, multicenter, parallel-group, 2-part study. Parts 1 
and 2 will be conducted in the same subjects. Part 1 of the study is designed to evaluate the efficacy, 
safety, and tolerability of treatment with oral BCX9930 monotherapy for 24 weeks versus continuing 
C5 inhibitor therapy in subjects with PNH with inadequate response to their current C5 inhibitor 
therapy. Subjects will be randomized to either discontinue C5 inhibitor therapy and start BCX9930 
monotherapy or to continue C5 inhibitor therapy for the 24-week randomized treatment period. The 
primary efficacy and safety analyses will be based on Part 1. Part 2 of the study is designed to 
evaluate the long-term safety, tolerability, and effectiveness of BCX9930 monotherapy when 
administered through Week 52. All subjects in Part 2 will receive BCX9930. Subjects who are 
randomized to BCX9930 monotherapy in Part 1 will continue to receive BCX9930 in Part 2. Subjects 
who are randomized to C5 inhibitor therapy in Part 1 will discontinue that therapy and start BCX9930 
in Part 2. 
Methodology: 
Part 1: Eligible subjects will be randomized in a 2:1 ratio to either discontinue C5 inhibitor therapy 
and start BCX9930 monotherapy , or to continue C5 inhibitor therapy at the same dose and regimen 
as previously administered for 24 weeks. Randomization will be stratified based on C5 inhibitor 
(ravulizumab vs. eculizumab) and whether a pRBC transfusion was received within the 6 months 


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prior to baseline (yes vs. no). All subjects will be required to return to the clinic at Weeks 1, 2, and 4, 
and every 4 weeks thereafter through Week 24. Subjects randomized to BCX9930 will be required to 
complete additional safety assessments at Weeks 3, 5, 6, 7, and 10. 
Part 2: Subjects randomized to continue C5 inhibitor therapy during Part 1 will discontinue that 
therapy and be switched to BCX9930 monotherapy for Part 2. These subjects will be required to 
return to the clinic at Weeks 25, 26, 28, 32, and 36, and then every 4 weeks thereafter through 
Week 52. Additional safety assessments will be performed at Weeks 27, 29, 30, 31, and 34. Subjects 
randomized to BCX9930 monotherapy in Part 1 will continue with the every 4 weeks visit schedule 
through Week 52. 
After completion of Part 2, all subjects continuing to derive clinical benefit will be allowed to 
continue treatment with BCX9930 through enrollment in a separate long-term extension study, or via 
another access mechanism, where available. Subjects who do not continue BCX9930 therapy after 
Week 52, or who are prematurely discontinued from BCX9930 treatment prior to Week 52, will be 
monitored for potential hemolysis and may be required to return to the clinic for an additional visit(s) 
to assess for acute symptomatic hemolysis, if and when symptoms occur. Subsequently, they will 
return to the clinic approximately 3 weeks after the date of last dose of BCX9930 for end of study 
assessments. 
An independent BCX9930 program-wide data monitoring committee (DMC) will provide oversight 
of the ongoing exposure of subjects to BCX9930. 
Number of Subjects (Planned): 
Approximately 81 subjects with PNH and an inadequate response to C5 inhibitor therapy (ie, 
approximately 54 subjects in the BCX9930 200/400 mg BID arm and approximately 27 subjects in 
the control arm) will be enrolled. 
Diagnosis and Main Criteria for Inclusion: 
Subjects must meet all of the following inclusion criteria, as applicable, to be eligible for participation 
in this study: 
1. Male or female, aged ≥ 18 years old. 
2. Body weight ≥ 40 kg. 
3. Documented diagnosis of PNH confirmed by flow cytometry with a PNH granulocyte or 
monocyte clone size of ≥ 10% during screening. 
4. Treated with a stable regimen of eculizumab for ≥ 3 months prior to the screening visit or 
ravulizumab for ≥ 6 months prior to the screening visit. 
5. Recorded the following results during screening: 
a. Hb of ≤ 105 g/L (≤ 10.5 g/dL). 
b. ARC of ≥ 100 × 109 cells/L (≥ 100,000 cells/µL; ≥ 100 G/L). 
c. Absolute neutrophil count of ≥ 0.75 × 109 cells/L (≥ 750 cells/µL; ≥ 0.75 × G/L). 
d. Platelet count of ≥ 30 × 109/L (≥ 30,000/µL; ≥ 30 G/L). 
e. Adequate iron reserve based on ferritin ≥ LLN or total iron binding capacity ≤ upper limit 
of the normal reference range (ULN). 


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f. Estimated glomerular filtration rate of ≥ 60 mL/min/1.73 m2 using the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation (Levey and Stevens 2010) and no 
evidence of clinically relevant abnormal renal function unrelated to underlying PNH 
disease. 
6. Contraception requirements: 
Female participants must meet at least one of the following requirements: 
a. Be a woman of nonchildbearing potential. 
b. Be a woman of childbearing potential who agrees to use a highly effective contraceptive 
method throughout the study and for a duration of 30 days after the last dose of study drug. 
c. Alternatively, true abstinence is acceptable for women of childbearing potential when it is 
in line with the subject’s preferred and usual lifestyle. 
Male participants must meet at least one of the following requirements: 
a. Males with a female partner of childbearing potential must use condoms throughout the 
study and for a duration of 90 days after the last dose of study drug unless their partner is 
using a highly effective contraceptive method independent of the study. 
b. Alternatively, true abstinence is acceptable when it is in line with the subject’s preferred 
and usual lifestyle. 
Additional details are provided in Section 11.2.1. 
7. Documentation of current vaccinations against Neisseria meningitidis types A, C, W, and Y, 
and Streptococcus pneumoniae, or willingness to start vaccination series at least 14 days prior 
to Day 1. 
(Note: Vaccination for N. meningitidis type B and for Haemophilus influenzae type B [Hib] is 
strongly encouraged where authorized and available.) 
8. In the opinion of the investigator, the subject is expected to adequately comply with all 
required study procedures and restrictions for the study, including compliance with the twice 
daily (BID) dosing schedule for BCX9930. 
9. Willing and able to provide written informed consent. 
Subjects must not meet any of the following exclusion criteria to be eligible for participation in the 
study: 
1. Known history of or existing diagnosis of hereditary complement deficiency. 
2. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for 
transplantation during the study. 
3. Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current 
and uncontrolled clinically significant cardiovascular or cerebrovascular condition, including 
unstable angina, severe congestive heart failure, unexplained syncope, arrhythmia, and critical 
aortic stenosis. 
4. History of malignancy within 5 years prior to the screening visit, with exception of adequately 
treated non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ of 


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the cervix, or other curatively treated solid tumor deemed by the investigator and medical 
monitor to be at low risk for recurrence. 
5. Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to 
screening. 
(Note: Suspected or confirmed coronavirus disease [COVID-19]; persistent or recurrent 
positive test(s) for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] nucleic 
acids or antigens; and worsening of dyspnea not due to PNH, vasculitic rash, and persistent 
fever or other symptoms consistent with multisystem inflammatory syndrome in adults 
[MIS-A] are exclusionary.) 
6. Current participation in any other investigational drug study or participation in an 
investigational drug study within 30 days prior to the screening visit, or 5.5 half-lives of the 
investigational drug, whichever is longer. 
7. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit. 
8. Initiation of treatment with an erythropoiesis-stimulating agent (eg, erythropoietin), a 
thrombopoietin receptor agonist (eg, eltrombopag), or danazol within 28 days prior to the 
screening visit. 
(Note: Treatment with these medications initiated > 28 days prior to the screening visit is not 
exclusionary, if the dose is stable and there is a reasonable expectation that treatment will be 
continued.) 
9. Receiving iron supplementation with an unstable dose in the 28 days prior to the screening 
visit. 
10. Clinically significant abnormal electrocardiogram (ECG) at the screening visit. 
(Note: This includes, but is not limited to, a QT interval corrected using Fridericia’s method 
[QTcF] of > 450 msec in males or > 470 msec in females, or ventricular and/or atrial premature 
contractions that are more frequent than occasional, and/or as couplets or higher in grouping.) 
11. Subjects with any of the following results at the screening visit: 
a. Alanine aminotransferase (ALT; also serum glutamic-pyruvic transaminase [SGPT]) 
> 3 × ULN. 
b. Aspartate aminotransferase (AST; also serum glutamic-oxaloacetic transaminase [SGOT]) 
> 3 × ULN. 
(Note: Subjects may be enrolled with AST > 3 × ULN if explained by hemolysis.) 
c. Total serum bilirubin > 2 × ULN. 
(Note: Subjects may be enrolled with total serum bilirubin > 2 × ULN if explained by 
hemolysis or Gilbert’s syndrome. In the case of hemolysis, total serum bilirubin must be 
< 5 × ULN and in the case of Gilbert’s syndrome, total serum bilirubin must be 
< 11 × ULN.) 
12. Current use of a prohibited concomitant medication within 7 days prior to Day 1 as detailed in 
Section 9.8.1. 
13. Positive serology for human immunodeficiency virus, or active infection with hepatitis B virus 
or hepatitis C virus, unless receiving antiviral therapy and viral load is undetectable. 


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14. Positive drugs of abuse screen, unless by prescription. 
15. Pregnant, planning to become pregnant, or breastfeeding. 
16. Known hypersensitivity to BCX9930 or any of its formulation excipients. 
17. History of severe hypersensitivity to any medicinal product, which was associated with 
swelling, severe rash requiring treatment/hospitalization, or anaphylaxis. 
18. Any other clinically significant medical or psychiatric condition that, in the opinion of the 
investigator or sponsor, would interfere with the subject’s ability to participate in the study or 
increase the risk of participation for that subject. 
Investigational Product, Dosage, and Mode of Administration: 
Subjects who previously received 500 mg BID and remain on study treatment will be dose adjusted to 
400 mg BID. For all newly enrolled subjects, at the initiation of BCX9930 dosing, subjects will be 
administered a dose of 200 mg BID for the first 14 days of treatment before increasing to 400 mg 
BID. The appropriate quantity of BCX9930 tablets will be taken orally twice a day, approximately 
12 hours apart, without regard to food. Adequate hydration should be maintained to prevent the 
formation of highly concentrated urine. 
Duration of Treatment: 
In Part 1, either continued C5 inhibitor therapy or BCX9930 monotherapy for 24 weeks. In Part 2, all 
subjects will receive BCX9930 monotherapy for 28 weeks. 
Reference Therapy, Dosage and Mode of Administration: 
Eculizumab or ravulizumab administered by intravenous infusion will be maintained at the same dose 
and posology received at screening. 
Criteria for Evaluation: 
Safety: TEAEs, laboratory analyses (clinical chemistry, hematology, coagulation, urinalysis 
including microscopy), vital signs, 12-lead ECGs, and physical examination findings. 
Clinical and Laboratory Measurements of PNH: Hb, number of pRBC transfusions and number of 
pRBC units administered, LDH, ARC, haptoglobin, bilirubin; assessment of PNH-associated clinical 
symptoms (eg, fatigue, dyspnea, chest pain/discomfort, dysphagia, abdominal pain, headache, erectile 
dysfunction, hemoglobinuria, and jaundice); acute symptomatic hemolysis; major adverse vascular 
events (MAVEs), including thrombotic events. 
PROs: FACIT-Fatigue scale, QLQ-AA/PNH, modified PRO-AA/PNH, EQ-5D-5L, TSQM, and 
PGIC/PGIS items for fatigue, impact of fatigue, and physical functioning. 
PK: Plasma BCX9930 concentrations (via sparse sampling in all subjects and serial sampling for 0 to 
6 hours post-first dose and at steady state in an optional PK/PD substudy) and PK parameter 
estimation. Urine for parent BCX9930/metabolite concentration. PK samples will not be collected 
from subjects randomized to continue C5 inhibitor therapy in Part 1. 
PD: Blood samples for analysis of ex vivo AP Wieslab; alternative pathway (AP)-activated 
complement biomarkers Factor Bb, C3a, and C5a; and constitutive Factor D (as the pharmacologic 
target), Factor Bb, and sC5b-9. PNH clone size (total PNH RBC, PNH WBC, and the ratio of total 
PNH RBC to PNH WBC) will be assessed, along with C3 deposition (ie, C3 RBC opsonization). 
Acute symptomatic hemolysis will be evaluated, where possible, with analysis of ex vivo 




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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
INVESTIGATOR AGREEMENT...................................................................................................3 
STUDY INFORMATION ...............................................................................................................4 
2. 
SYNOPSIS ...................................................................................................................5 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............15 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................23 
5. 
INTRODUCTION ......................................................................................................28 
5.1. 
Background .................................................................................................................28 
5.1.1. 
The Complement System ............................................................................................28 
5.1.2. 
The Role of Factor D ..................................................................................................29 
5.1.3. 
Paroxysmal Nocturnal Hemoglobinuria .....................................................................29 
5.1.3.1. 
Currently Licensed Treatments for PNH ....................................................................30 
5.1.3.2. 
Unmet Medical Need ..................................................................................................31 
5.2. 
BCX9930 ....................................................................................................................33 
5.2.1. 
Nonclinical Findings for BCX9930 ............................................................................33 
5.2.2. 
Clinical Findings for BCX9930 ..................................................................................34 
5.2.2.1. 
Study BCX9930-101 ..................................................................................................34 
5.2.2.2. 
Study BCX9930-201 ..................................................................................................36 
5.2.2.3. 
Study BCX9930-102 ..................................................................................................36 
5.2.2.4. 
Other Clinical Studies .................................................................................................36 
5.3. 
Rationale for Study .....................................................................................................37 
5.3.1. 
Rationale for Study Design .........................................................................................37 
5.3.2. 
Rationale for Study Population ...................................................................................37 
5.3.3. 
Rationale for Comparator ...........................................................................................38 
5.3.4. 
Rationale for Study Endpoints ....................................................................................38 
5.3.5. 
Rationale for Dose Selection ......................................................................................40 
5.3.5.1. 
Summary of Hematologic Response at 400 and 500 mg BID – Studies 101 
and 201 ........................................................................................................................40 
5.3.5.2. 
Summary of PPK and PK/PD Modeling ....................................................................41 


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5.3.5.3. 
Clinical Safety and Tolerability ..................................................................................43 
5.4. 
Benefit-Risk Assessment ............................................................................................43 
5.4.1. 
Potential Risks of Bacterial Infections .......................................................................44 
5.4.2. 
Potential Risks of SARS-CoV-2 Infection and Vaccination While Receiving 
BCX9930 Therapy ......................................................................................................44 
5.4.3. 
Potential Risks for Hemolysis After Discontinuation or Interruption of Study 
Treatment ....................................................................................................................45 
5.4.4. 
Potential Risks of Adverse Events with BCX9930 ....................................................45 
5.4.4.1. 
Potential Risks for Headache ......................................................................................45 
5.4.4.2. 
Potential Risks for Dermatologic Reactions ...............................................................45 
5.4.4.3. 
Potential Risks for Renal or Hepatic Effects ..............................................................45 
5.4.5. 
Overall Benefit-Risk Analysis ....................................................................................46 
6. 
STUDY OBJECTIVES ..............................................................................................47 
6.1. 
Objectives ...................................................................................................................47 
6.1.1. 
Part 1 Primary Objective ............................................................................................47 
6.1.2. 
Part 1 Secondary Objectives .......................................................................................47 
6.1.3. 
Part 2 Primary Objective ............................................................................................47 
6.1.4. 
Part 2 Secondary Objectives .......................................................................................47 
6.2. 
Endpoints ....................................................................................................................48 
6.2.1. 
Part 1 Primary Endpoint .............................................................................................48 
6.2.2. 
Part 1 Key Secondary Endpoints ................................................................................48 
6.2.3. 
Part 1 Other Secondary Endpoints ..............................................................................48 
6.2.4. 
Part 1 Exploratory Endpoints ......................................................................................49 
6.2.5. 
Part 1 Other Health-related Quality of Life Endpoints ...............................................49 
6.2.6. 
Part 1 Safety Endpoints ..............................................................................................49 
6.2.7. 
Part 2 Primary Endpoints ............................................................................................50 
6.2.8. 
Part 2 Secondary Endpoints ........................................................................................50 
6.2.9. 
Part 2 Exploratory Endpoints ......................................................................................51 
6.2.10. 
Part 2 Health-related Quality of Life Endpoints .........................................................51 
6.2.11. 
Pharmacokinetic and Pharmacodynamic Endpoints – Parts 1 and 2 ..........................52 
7. 
INVESTIGATIONAL PLAN .....................................................................................52 
7.1. 
Overall Study Design ..................................................................................................52 
7.2. 
Number of Subjects ....................................................................................................55 


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7.3. 
Treatment Assignment ................................................................................................55 
7.4. 
Individual and Study Termination Criteria .................................................................55 
7.4.1. 
Subject Withdrawal from Study Treatment ................................................................55 
7.4.2. 
Criteria for Study Termination ...................................................................................56 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................57 
8.1. 
Subject Inclusion Criteria ...........................................................................................57 
8.2. 
Subject Exclusion Criteria ..........................................................................................58 
8.3. 
Subject Withdrawal ....................................................................................................59 
8.4. 
End of Study Definition ..............................................................................................60 
8.5. 
BCX9930 Access at Study Completion ......................................................................60 
9. 
TREATMENT OF SUBJECTS ..................................................................................61 
9.1. 
Description of Study Drug and Study Drug Product ..................................................61 
9.1.1. 
BCX9930 ....................................................................................................................61 
9.1.2. 
Eculizumab or Ravulizumab .......................................................................................61 
9.2. 
Description of Study Drug Packaging, Labelling, and Storage ..................................61 
9.2.1. 
BCX9930 ....................................................................................................................61 
9.2.2. 
Eculizumab .................................................................................................................62 
9.2.3. 
Ravulizumab ...............................................................................................................62 
9.3. 
Randomization and Blinding of Study Treatment ......................................................62 
9.3.1. 
Blinding ......................................................................................................................62 
9.3.2. 
Randomization ............................................................................................................62 
9.4. 
Study Drug Administration.........................................................................................63 
9.4.1. 
BCX9930 ....................................................................................................................63 
9.4.2. 
Continued C5 Inhibitor Therapy .................................................................................63 
9.4.3. 
Treatment Interruption or Dose Reduction .................................................................64 
9.4.4. 
Dose Tapering .............................................................................................................64 
9.5. 
Treatment Compliance ................................................................................................64 
9.6. 
Missed Doses and Special Considerations for Dosing ...............................................65 
9.6.1. 
Missed Doses ..............................................................................................................65 
9.6.2. 
Special Considerations for Dosing, Including Inability to Take Medication 
Orally ..........................................................................................................................66 
9.7. 
Study Drug Accountability .........................................................................................66 
9.7.1. 
C5 Inhibitors ...............................................................................................................66 


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9.8. 
Prior and Concomitant Medications ...........................................................................66 
9.8.1. 
Prohibited and Restricted Medications .......................................................................67 
9.8.1.1. 
Prohibited and Restricted Medications for Subjects Receiving BCX9930 ................67 
9.8.1.2. 
Prohibited and Restricted Medications for Subjects Randomized to Continue 
C5 Inhibitor Therapy in Part 1 ....................................................................................68 
9.9. 
Vaccination Requirements, Vaccinations During Study, and Prophylactic 
Antibiotic Coverage ....................................................................................................69 
10. 
STUDY CONDUCT ...................................................................................................70 
10.1. 
Overview .....................................................................................................................70 
10.2. 
Schedule of Assessments ............................................................................................71 
10.3. 
Study Visits .................................................................................................................80 
10.3.1. 
Screening ....................................................................................................................80 
10.3.2. 
Rescreening/Retesting ................................................................................................81 
10.3.3. 
Baseline Visit (Day 1) ................................................................................................81 
10.3.4. 
On-study Visits for Part 1: Weeks 1, 2, 4, 8, 12, 16, 20, and 24 ................................83 
10.3.5. 
On-study Visits for Part 2: Weeks 25, 26, 28, 32, 36, 40, 44, 48, and 52 ..................85 
10.3.6. 
Additional Assessments for Renal and Hepatic Safety Monitoring ...........................86 
10.3.7. 
Unscheduled Visits (Including for Assessment of Acute Symptomatic 
Hemolysis) ..................................................................................................................87 
10.3.8. 
End-of-Study Visit/Early Termination Visit ..............................................................88 
11. 
STUDY ASSESSMENTS ..........................................................................................89 
11.1. 
Chronology of Assessments .......................................................................................89 
11.2. 
Demographic Information, Medical and Medication History ....................................89 
11.2.1. 
Contraception Requirements ......................................................................................89 
11.3. 
Immunity Assessment .................................................................................................91 
11.4. 
Efficacy/Effectiveness Assessments ...........................................................................91 
11.4.1. 
Clinical and Laboratory Measurements of PNH ........................................................91 
11.4.2. 
Blood Transfusions .....................................................................................................91 
11.4.3. 
Clinical Measurements of Iron, Folate, and Vitamin B12 ...........................................92 
11.4.4. 
Patient-reported Outcomes .........................................................................................92 
11.4.4.1. 
FACIT-Fatigue Scale ..................................................................................................92 
11.4.4.2. 
QLQ-AA/PNH ............................................................................................................93 
11.4.4.3. 
Modified PRO-AA/PNH ............................................................................................93 


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11.4.4.4. 
TSQM .........................................................................................................................94 
11.4.4.5. 
EQ-5D-5L ...................................................................................................................94 
11.4.4.6. 
PGIS-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical Functioning .................94 
11.4.4.7. 
PGIC-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning ................94 
11.5. 
Pharmacokinetic and Pharmacodynamic Assessments ..............................................95 
11.5.1. 
Blood Sampling for Pharmacokinetic Analysis ..........................................................95 
11.5.1.1. 
Optional Pharmacokinetic/Pharmacodynamic Substudy ............................................96 
11.5.2. 
Urine Collection for Measurement of Parent-Metabolite Concentration ...................97 
11.5.3. 
Blood Sampling for Analysis of Pharmacodynamic and Complement 
Biomarkers ..................................................................................................................97 
11.6. 
Optional Pharmacodynamic Analyses ......................................................................101 
11.7. 
Safety Assessments ...................................................................................................101 
11.7.1. 
Vital Signs ................................................................................................................101 
11.7.2. 
Body Weight, Height, and Body Mass Index ...........................................................101 
11.7.3. 
Physical Examination ...............................................................................................101 
11.7.4. 
Electrocardiogram .....................................................................................................101 
11.7.5. 
Clinical Chemistry, Hematology, Urinalysis, and Other Laboratory 
Assessments ..............................................................................................................102 
11.7.5.1. 
Urine Collections for Urinalysis, Microscopy, and Biomarker Testing ...................104 
11.7.6. 
Menopause and Pregnancy Testing ..........................................................................105 
12. 
ADVERSE EVENTS................................................................................................105 
12.1. 
Definition of Adverse Events ...................................................................................105 
12.1.1. 
Adverse Event ...........................................................................................................105 
12.1.2. 
Serious Adverse Event ..............................................................................................107 
12.1.3. 
Events of Special Monitoring ...................................................................................107 
12.2. 
Definition of Severity ...............................................................................................108 
12.3. 
Relationship to Study Drug ......................................................................................108 
12.4. 
Method, Frequency, and Time Period for Detecting Adverse Events and 
Reporting Serious Adverse Events ...........................................................................109 
12.4.1. 
Serious Adverse Events and Suspected Unexpected Serious Adverse 
Reactions ...................................................................................................................110 
12.4.2. 
Pregnancy .................................................................................................................111 
12.5. 
Adverse Event Management .....................................................................................111 


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12.5.1. 
Potential Drug-induced Liver Injury: Monitoring, Evaluation, and 
Discontinuation Criteria ............................................................................................111 
12.5.2. 
Renal Events .............................................................................................................112 
12.5.2.1. 
Monitoring, Evaluation, and Subject Discontinuation Criteria ................................112 
12.5.2.2. 
Study Stopping Rule .................................................................................................113 
12.5.3. 
Risk of Hemolysis After Missed Doses, Treatment Interruption, or 
Permanent Discontinuation .......................................................................................113 
12.5.3.1. 
BCX9930 ..................................................................................................................113 
12.5.3.2. 
C5 Inhibitor Therapy ................................................................................................114 
12.5.4. 
Acute Symptomatic Hemolysis ................................................................................114 
12.6. 
Overdose ...................................................................................................................115 
12.7. 
Data Monitoring Committees ...................................................................................115 
13. 
STATISTICS ............................................................................................................116 
13.1. 
Hypotheses ................................................................................................................116 
13.1.1. 
Controlling for Multiplicity ......................................................................................117 
13.2. 
Sample Size Considerations .....................................................................................117 
13.3. 
Sample Size Re-estimation .......................................................................................117 
13.4. 
Stratification .............................................................................................................117 
13.5. 
Statistical Methods ....................................................................................................118 
13.5.1. 
Analysis Populations ................................................................................................118 
13.5.1.1. 
Screen Failures ..........................................................................................................118 
13.5.1.2. 
Intent-to-Treat Population ........................................................................................118 
13.5.1.3. 
Safety Population ......................................................................................................118 
13.5.1.4. 
Per Protocol Population ............................................................................................118 
13.5.1.5. 
Completers Population ..............................................................................................118 
13.5.1.6. 
Pharmacokinetic Population .....................................................................................118 
13.5.1.7. 
Pharmacodynamic Population ..................................................................................119 
13.5.2. 
General Considerations for Data Analysis ...............................................................119 
13.5.3. 
Subject Demographic and Disposition Data .............................................................119 
13.5.4. 
Analysis of Efficacy Variables .................................................................................119 
13.5.4.1. 
Primary Efficacy Analysis ........................................................................................119 
13.5.4.2. 
Analyses of Key Secondary, Other Secondary, and Exploratory Efficacy 
Endpoints ..................................................................................................................120 


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13.5.5. 
Analysis of Safety Variables ....................................................................................124 
13.5.6. 
Acute Symptomatic Hemolysis ................................................................................125 
13.5.7. 
Breakthrough Hemolysis ..........................................................................................126 
13.5.8. 
Major Adverse Vascular Events ...............................................................................126 
13.5.9. 
Pharmacokinetic Analyses ........................................................................................126 
13.5.10. 
Pharmacodynamic and Biomarker Analyses ............................................................126 
14. 
STUDY ADMINISTRATION .................................................................................127 
14.1. 
Study Monitoring ......................................................................................................127 
14.2. 
Audits and Inspections ..............................................................................................128 
14.3. 
Ethics Committee ......................................................................................................128 
14.4. 
Serious Breaches of GCP ..........................................................................................128 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................128 
16. 
ETHICS ....................................................................................................................129 
16.1. 
Ethics Review ...........................................................................................................129 
16.2. 
Ethical Conduct of the Study ....................................................................................129 
16.3. 
Written Informed Consent ........................................................................................129 
17. 
DATA HANDLING AND RECORDKEEPING .....................................................130 
17.1. 
Inspection of Records ...............................................................................................130 
17.2. 
Retention of Records ................................................................................................130 
17.3. 
Confidentiality of Information and Data ..................................................................130 
18. 
PUBLICATION POLICY ........................................................................................131 
19. 
LIST OF REFERENCES ..........................................................................................132 
 


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LIST OF TABLES 
Table 1: 
List of Abbreviations and Specialist Terms ................................................................23 
Table 2: 
Anemia, Need for Transfusions, and PNH Symptoms Persist in Many 
Patients Despite C5 Inhibitor Treatment ....................................................................32 
Table 3: 
Study 101 Part 3/Study 201: Key Efficacy Parameters at Last Visit for 
400 and 500 mg BID ...................................................................................................41 
Table 4: 
Study BCX9930-202: Part 1 Schedule of Study Assessments/Procedures 
(Screening to Week 24) ..............................................................................................72 
Table 5: 
Study BCX9930-202: Part 2 Schedule of Study Assessments/Procedures 
(Weeks 25 to 52) .........................................................................................................76 
Table 6: 
Summary of Pharmacokinetic and Pharmacodynamic Blood Sampling ..................100 
Table 7: 
Clinical Laboratory Evaluations ...............................................................................103 
 
LIST OF FIGURES 
Figure 1: 
The Complement Pathways ........................................................................................28 
Figure 2: 
Comparison of PK/PD Model-Estimated IC Values (95% CI) for 
AP Wieslab, LDH, and C3 Opsonization with Median (10th to 90th 
percentile) PPK Model-Estimated Ctau at 200, 400, and 500 mg BID ........................42 
Figure 3: 
BCX9930-202 Study Schema (Parts 1 and 2) ............................................................54 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
List of Abbreviations and Specialist Terms 
Abbreviation or 
Specialist Term 
Explanation 
AA 
aplastic anemia 
ACIP 
Advisory Committee on Immunization Practices 
ADL 
Activities of Daily Living 
AE 
adverse event 
aHUS 
atypical hemolytic uremic syndrome 
AKI 
acute kidney injury 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase (also SGPT) 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance 
AP 
alternative complement pathway 
ARC 
absolute reticulocyte count 
AST 
aspartate transferase (also SGOT) 
BCRP 
breast cancer resistance protein 
BID 
twice daily 
BMF 
bone marrow failure 
BMI 
body mass index 
BQL 
below the quantification level 
BTH 
breakthrough hemolysis 
C3 
complement component 3 
C3b 
end product of the alternative complement pathway 
C3bB 
Factor B in complex with C3b 
C3G 
complement 3 glomerulopathy 
C4 
complement component 4 
C5 
complement component 5 
CAC 
complement-activating condition 
CDF 
cumulative density function 
CFB 
change from baseline 


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Abbreviation or 
Specialist Term 
Explanation 
CI 
confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration equation 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
coronavirus disease 2019 
CP 
classical complement pathway 
CSR 
clinical study report 
Ctau 
trough concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
EOSM 
events of special monitoring 
EQ-5D-5L 
EuroQoL 5-dimension, 5-level questionnaire 
E-R 
exposure-response 
ET 
early termination 
EU 
European Union 
EVH 
extravascular hemolysis 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FDA 
US Food and Drug Administration 
FIH 
first in human 
 
 
FSH 
follicle-stimulating hormone 
FXa 
activated Factor X 
FXIIa 
activated Factor XII 
GCP 
Good Clinical Practice 
Hb 
Hemoglobin 
HBV 
hepatitis B virus 


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Abbreviation or 
Specialist Term 
Explanation 
HCV 
hepatitis C virus 
Hib 
Haemophilus influenzae type B 
HIPAA 
US Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
IB 
Investigator’s Brochure 
IC50 
50% of maximal inhibitory concentration 
IC90 
90% of maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
ITT 
intent-to-treat 
IV 
Intravenous 
IVH 
intravascular hemolysis 
IWRS 
interactive web-based response system 
J2R 
Jump-to-Reference 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal (reference range) 
LP 
lectin complement pathway 
MAC 
membrane attack complex 
MAD 
multiple ascending dose 
MAVE 
major adverse vascular event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model repeated measures 
N, n 
number of subjects or events (uppercase is total population; lowercase is 
subgroup population) 
NCI 
US National Cancer Institute 
NRMWG 
Nephrology Risk Mitigation Working Group 
NSAID 
non-steroidal anti-inflammatory drug 
PD 
pharmacodynamic(s) 
PDF 
probability density function 


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Abbreviation or 
Specialist Term 
Explanation 
P-gp 
P-glycoprotein 
PGIC 
Patient Global Impression of Change 
PGIS 
Patient Global Impression of Severity 
PK 
pharmacokinetic(s) 
PK/PD 
pharmacokinetic/pharmacodynamic 
PNH 
paroxysmal nocturnal hemoglobinuria 
PP 
per-protocol 
PPK 
population pharmacokinetic(s) 
pRBC 
packed red blood cell 
PRO-AA/PNH 
Patient-Reported Outcome Questionnaire for Aplastic Anemia/Paroxysmal 
Nocturnal Hemoglobinuria 
Q12h 
every 12 hours 
Q24h 
every 24 hours 
QLQ-AA/PNH 
Quality of Life Questionnaire for patients with Aplastic Anemia and Paroxysmal 
Nocturnal Hemoglobinuria 
QoL 
quality-of-life 
QTcF 
QT interval corrected using Fridericia’s method 
RBC 
red blood cell 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
sC5b-9 
soluble C5b-9 
sCr 
serum creatinine 
SGOT 
serum glutamic-oxaloacetic transaminase (also AST) 
SGPT 
serum glutamic-pyruvic transaminase (also ALT) 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
half-life 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TSQM 
Treatment Satisfaction Questionnaire for Medication 


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Abbreviation or 
Specialist Term 
Explanation 
uACR 
urine albumin to creatinine ratio 
ULN 
upper limit of normal (reference range) 
uNGAL 
urine neutrophil gelatinase-associated lipocalin 
US 
United States 
VAS 
visual analog scale 
VZV 
varicella-zoster virus 
WBC 
white blood cell 
WHO 
World Health Organization 




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The complement system is activated to high levels by the 3 complement pathways (ie, the CP, 
the LP, or the AP) and amplified by the AP amplification loop. Activation of the complement 
system by any of the 3 pathways results in production of C3b fragments, which can covalently 
attach to available surfaces (ie, opsonization) (Holers 2008, Brodsky 2014, Zipfel, Skerka, et al. 
2015, Ricklin, Reis, et al. 2016). Deposited C3b fragments trigger a positive feedback loop, 
called the AP amplification loop, by pairing with Factor B to form C3bB, which then is cleaved 
by Factor D to generate a second form of AP C3 convertase, C3bBb. Membrane-bound C3bBb 
then cleaves additional C3 to generate further C3b fragments, which bind additional Factor B 
molecules to repeat and amplify the cycle. Ultimately, activation of the AP amplification loop, 
whether initially by the AP, LP, or CP, leads to opsonization with C3b, release of the 
anaphylatoxins C3a and C5a, and assembly of the terminal membrane attack complex (MAC, 
also known as C5b-9) on the target surface, resulting in cell lysis (Ricklin, Reis, et al. 2016). 
Several studies have shown that the AP amplification loop may account for up to 80% of the C5a 
and MAC generated via CP or LP activation, substantially more than previously appreciated 
(Thurman and Holers 2006, Ekdahl, Mohlin, et al. 2019). 
In summary, regardless of whether complement is initially activated via the AP, CP, or LP, 
activation of the AP amplification loop results in opsonization of cell surfaces by C3b, formation 
of the C5 convertase C3bBb(3b)n, cleavage of C5, release of the anaphylatoxins C3a and C5a, 
and assembly of the terminal MAC on the target surface resulting in cell lysis (Ricklin, Reis, et 
al. 2016). 
5.1.2. 
The Role of Factor D 
Factor D is the rate-limiting enzyme of the AP (Volanakis and Narayana 1996) and the AP 
amplification loop and is made constitutively by adipocytes (White, Damm, et al. 1992). The 
only natural substrate for Factor D is complement Factor B bound to C3b (Volanakis and 
Narayana 1996). Factor D cleaves Factor B only after the latter is bound to C3b or C3(H2O) at 
the bond between Factor B amino acid residues 259 and 260, releasing the 30kD N-terminal Ba 
fragment and retention of the 60kD C-terminal Bb fragment that is required for production of the 
C3 convertases of the AP [ie, C3bBb and C3(H2O)Bb] (Torreira, Tortajada, et al. 2009). In 
addition, Factor D is essential for the AP amplification loop following generation of C3b by the 
AP, LP, or CP (Lesavre and Muller-Eberhard 1978, Volanakis and Narayana 1996, Xu, Ma, et al. 
2001). Based on in vitro studies using human serum, this AP amplification loop appears to 
account for up to 80% of the C5a and MAC generated from initial activation of complement by 
the CP or LP, or other proteolytic enzymes (eg, renin) in the plasma or other body fluids 
(Thurman and Holers 2006, Ekdahl, Mohlin, et al. 2019) (BioCryst internal data on file). As 
such, Factor D plays a central role in the activation and amplification of the AP, as well as in the 
amplification of the LP and the CP. 
5.1.3. 
Paroxysmal Nocturnal Hemoglobinuria 
PNH is an acquired, rare, serious, and potentially life-threatening disorder characterized by 
destruction of red blood cells (RBCs) resulting from uncontrolled activity of complement. PNH 
is caused by a somatic mutation in the phosphatidylinositol glycan anchor biosynthesis class A 
(PIG-A) gene in hematopoietic stem cells that leads to a deficiency of the membrane-displayed 
complement regulatory proteins CD55 and CD59 that normally protect RBCs from effective 
opsonization and lysis by the complement system. These deficiencies result in unrestrained 


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complement activity that attacks RBCs leading to episodes of intravascular hemolysis (IVH), 
extravascular hemolysis (EVH), chronic hemolytic anemia, bone marrow failure (BMF), and 
thrombosis (Parker 2009, Pu and Brodsky 2011, Parker 2012), and EVH in patients treated with 
C5 inhibitors (Risitano, Notaro, et al. 2009, Hill, Rother, et al. 2010). PNH affects men and 
women equally and is more common in people of Asian than Caucasian ethnicity (Hill, DeZern, 
et al. 2017, Jalbert, Chaudhari, et al. 2019). The onset of PNH can occur at any age. The median 
(interquartile range) age of patients with PNH at diagnosis reported in a large series was 44 years 
(30 to 60 years) (Curran, Kernan, et al. 2012, Ge, Shi, et al. 2015, Mercuri, Farruggia, et al. 
2017, Narita, Muramatsu, et al. 2017, Cannizzo, Raia, et al. 2019, Griesser, Myskiw, et al. 2020). 
IVH in PNH is associated with gastrointestinal, cardiovascular, pulmonary, neurological, and 
urogenital symptoms, as well as clotting disorders (Rother, Bell, et al. 2005, Savage and Brodsky 
2007). A classic symptom experienced by patients with PNH is discoloration of the urine due to 
hemoglobinuria following hemolysis. Patients report attacks of abdominal pain, difficulty 
swallowing, and pain during swallowing, as well as erectile dysfunction in men (Borowitz, 
Craig, et al. 2010, Rachidi, Musallam, et al. 2010). Other common symptoms related to anemia 
of patients with PNH are those such as debilitating fatigue, shortness of breath, and palpitations 
(Parker, Omine, et al. 2005). 
Patients with PNH also have an increased risk for splanchnic, portal, and hepatic vein 
thrombosis, the latter leading to Budd-Chiari syndrome (Graham, Rosse, et al. 1996, Hauser, 
Brichta, et al. 2003, Yin, Liu, et al. 2009, Jain 2010, Torres, De Vroey, et al. 2010). 
Other nonhematological clinical findings include acute or chronic renal failure (Sechi, 
Marigliano, et al. 1988, Jackson, Noble, et al. 1992, Chow, Lai, et al. 2001, Nair, Khaira, et al. 
2008, Guasch 2010, Hillmen, Elebute, et al. 2010) and pulmonary hypertension (Heller, 
Grinberg, et al. 1992). 
PNH is associated with significant morbidity and mortality (Harris, Koscick, et al. 1999, Rachidi, 
Musallam, et al. 2010). Median survival in the era prior to use of C5 inhibitors was reported in 
one study as 10 years (Hillmen, Lewis, et al. 1995); a retrospective analysis found that 
approximately 20% of patients with only supportive care died within 6 years of diagnosis 
(Loschi, Porcher, et al. 2016). Thrombosis was the leading cause of death in PNH patients, 
accounting for up to 67% of deaths (Loschi, Porcher, et al. 2016). While thrombosis is relatively 
rare as a presenting symptom, it has historically occurred in up to 40% of patients during the 
course of disease (Pu and Brodsky 2011); a history of major adverse vascular events (MAVEs), 
including thromboembolism, was reported in 19% of patients with PNH in a large series 
(Schrezenmeier, Roth, et al. 2020). Visceral thrombosis, cerebrovascular events, and pulmonary 
embolism predict a poor outcome (Ziakas, Poulou, et al. 2008). 
5.1.3.1. 
Currently Licensed Treatments for PNH 
There are currently three therapeutic agents approved for the treatment of PNH in various parts 
of the world: eculizumab, ravulizumab, and pegcetacoplan. 
Eculizumab (approved in the United States [US] and European Union [EU] in 2007 and in Japan 
in 2010) and ravulizumab (approved in the US in 2018 and in the EU and Japan in 2019) were 
the only therapeutic agents approved for the treatment of PNH. Both eculizumab and 
ravulizumab are monoclonal antibodies directed against C5 and each is administered by 


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intravenous (IV) infusion. After loading doses have been administered, eculizumab is 
label-indicated for administration once every 14 days and ravulizumab once every 8 weeks 
(Alexion Pharmaceuticals Soliris PI 2020, Alexion Pharmaceuticals Ultomiris PI 2020). 
On 14 May 2021, the US Food and Drug Administration (FDA) granted approval for 
pegcetacoplan for the treatment of PNH. In December 2021, the European Commission granted 
approval for pegcetacoplan for the treatment of adult patients with PNH who are anemic after 
treatment with a C5 inhibitor for at least 3 months. Pegcetacoplan, which is administered by 
subcutaneous administration twice a week, is a synthetic cyclic peptide conjugated to a 
polyethylene glycol polymer that binds specifically to C3 and C3b (Apellis Pharmaceutical 
Empaveli PI 2021). 
5.1.3.2. 
Unmet Medical Need 
Although survival has improved with the introduction of C5 inhibitors, significant unmet need 
remains (Marti-Carvajal, Anand, et al. 2014, Risitano, Marotta, et al. 2019). 
C5 Inhibitors Do Not Control Extravascular Hemolysis 
Blockade of the terminal complement pathway by eculizumab (Rother, Rollins, et al. 2007) 
reduces IVH, decreasing the levels of plasma lactate dehydrogenase (LDH), a sensitive 
biomarker for IVH. Eculizumab binds C5, blocks its cleavage to C5a and C5b, and thus protects 
PNH RBCs from MAC formation and lysis. However, due to the absence of CD55, the PNH 
RBCs in patients with PNH receiving eculizumab treatment continue to be opsonized by C3b and 
thus are susceptible to EVH (Risitano, Notaro, et al. 2009). With control of IVH, the PNH RBC 
Type III clone size increases, and patients administered eculizumab demonstrate selective, 
uncontrolled opsonization of PNH Type III RBCs, leading to EVH (Risitano, Notaro, et al. 2009, 
Hill, DeZern, et al. 2017). Chronic EVH can result in a continued need for RBC transfusions 
(Hillmen, Young, et al. 2006, DeZern, Dorr, et al. 2013). Ravulizumab has the same mechanism 
of action as eculizumab and patients receiving ravulizumab are similarly susceptible to EVH 
(Kulasekararaj, Hill, et al. 2019, Lee, Sicre de Fontbrune, et al. 2019). 
Continuing Hemolysis, Anemia, Need for Transfusions, and PNH Symptoms 
The hematological benefits for patients receiving C5 inhibitor treatment for PNH are 
heterogeneous. Complete normalization of hemoglobin (Hb) is seen in no more than one-third of 
patients, while the remaining patients continue to experience some degree of anemia, in some 
cases requiring regular RBC transfusions (Table 2) (Lee, Sicre de Fontbrune, et al. 2019). 
Different factors contribute to residual anemia during eculizumab treatment, including 
underlying bone marrow dysfunction, C3-mediated EVH, and inadequate plasma levels of 
eculizumab with standard dose schedules in many patients associated with residual intravascular 
hemolysis (Risitano, Marotta, et al. 2019, Wijnsma, Ter Heine, et al. 2019). Clinicians have been 
dosing eculizumab at levels higher than recommended by the drug label in an attempt to address 
this last issue with limited success (McKinley, Richards, et al. 2017, Cheng, Sarda, et al. 2020). 


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Table 2: 
Anemia, Need for Transfusions, and PNH Symptoms Persist in Many 
Patients Despite C5 Inhibitor Treatment  
C5 Inhibitor 
RBC 
Transfusions 
Hb not 
Stabilized 
Fatigue 
Hemoglobinuria 
Dyspnea 
Ravulizumab 
26% 
32% 
29% 
10% 
14% 
Eculizumab 
33% 
35% 
30% 
9% 
14% 
Abbreviations: C5 = complement component 5; Hb = hemoglobin; PNH = paroxysmal nocturnal hemoglobinuria; 
RBC = red blood cell. 
Source: (Lee, Sicre de Fontbrune, et al. 2019) 
Breakthrough Hemolysis 
The reappearance of IVH symptoms during C5 inhibitor treatment for PNH is described as 
breakthrough hemolysis (BTH), which results in anemia and fatigue, dyspnea, and abdominal 
pain (Brodsky, Peffault de Latour, et al. 2021). Two types of BTH are recognized (Risitano, 
Marotta, et al. 2019). The first describes the regular reappearance of IVH symptoms towards the 
end of the dosing interval in about 10% to 15% of patients treated with eculizumab (Marti-
Carvajal, Anand, et al. 2014, Risitano, Marotta, et al. 2019). This is associated with low trough 
concentrations of the drug and is referred to as “pharmacokinetic (PK) breakthrough”. In 
response, it has become commonplace to either increase the label-recommended maintenance 
dose of eculizumab to 1200 mg or 1500 mg, or to shorten the label-recommended dosing interval 
of eculizumab to 10 to 12 days (Marti-Carvajal, Anand, et al. 2014, Risitano, Marotta, et al. 
2019, Bektas, Copley-Merriman, et al. 2020, Cheng, Sarda, et al. 2020). The second type of 
breakthrough hemolysis is less predictable and occurs in response to complement-activating 
conditions (CACs), including bacterial and viral infections, surgery, and other trauma. This has 
been referred to as “pharmacodynamic (PD) breakthrough”, since it occurs independently of 
C5 inhibitor concentrations, and is limited by resolution of the triggering event and does not 
usually require changes in the C5 inhibitor dose regimen. 
Genetic Resistance 
A small proportion of patients (up to 3.5% of patients, (Nishimura, Yamamoto, et al. 2014) have 
a disease with C5 polymorphisms that are resistant to eculizumab inhibition. The efficacy of a 
Factor D inhibitor would not be impacted by these polymorphisms in C5. 
Burden of Therapy with Intravenous Treatments for PNH 
The IV route of administration of current treatments and the frequency of infusions negatively 
impacts patients’ quality of life (QoL) (Fattizzo and Kulasekararaj 2020). A recent publication 
showed that a treatment with less frequent IV infusions (ravulizumab) is preferred over a 
treatment that has a treatment schedule with more frequent IV infusions (eculizumab) (Peipert 
and Hays 2019), inferring that patients’ preference leans towards the least amount of infusions 
possible, preferably none at all if they have a choice. 
The challenges linked to current treatments in turn result in a significant burden on patient QoL 
(Acaster, Dickerhoof, et al. 2015), with persistent anemia leading to fatigue and subsequently 
impacting daily activities (Brodsky, Peffault de Latour, et al. 2021). Inadequate control of IVH 
and the appearance of EVH may require a continued need for RBC transfusions. In clinical 


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studies, 4.0% and 10.7% of patients with PNH treated with ravulizumab and eculizumab, 
respectively, experienced BTH (Lee, Sicre de Fontbrune, et al. 2019). 
Based on the above considerations, there exists a significant unmet need for an efficacious and 
safe alternative therapeutic option that addresses the shortcomings of the available therapies, 
including dependence on lifelong IV infusion, ongoing EVH, and for those that do not respond 
adequately to available therapies, persistent anemia, PNH symptoms, and transfusion 
dependence. 
5.2. 
BCX9930 
BioCryst Pharmaceuticals, Inc. (“BioCryst”) is developing BCX9930, a potent and selective, 
orally bioavailable, small-molecule inhibitor of complement Factor D. 
 
 
 
 
 
 
 
indicating that BCX9930 has the potential to inhibit both IVH and EVH. 
Targeting Factor D with a pharmacologic inhibitor is expected to block the formation of MAC 
and also inhibit the formation of C3 fragments, opsonization and, therefore, prevent both IVH 
and EVH in patients with PNH. 
Inhibiting Factor D with BCX9930 as a treatment strategy for PNH has at least 2 potential 
clinical advantages over C5 inhibitors: 1) C3b opsonization is blocked by Factor D inhibition, 
whereas it is not blocked by C5 inhibitors, with the result that opsonized PNH RBCs undergo 
EVH despite C5 inhibitor therapy; and 2) small-molecule therapeutics inhibiting Factor D could 
be administered orally, abrogating the need for lifelong IV infusions of C5 inhibitors. 
Therefore, targeting Factor D is a promising therapeutic strategy to inhibit AP activation for the 
treatment of AP-mediated diseases such as PNH. 
 
 
 
 
5.2.1. 
Nonclinical Findings for BCX9930 
The results of nonclinical pharmacology, PK, and toxicology studies of BCX9930 are described 
briefly below; additional details can be found in the Investigator’s Brochure (IB). 
 
 
 


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In rats and dogs, BCX9930 is rapidly absorbed. Increases in exposure of BCX9930 were 
approximately proportional to increases in dose in both species. 
 
 
 
 
 
 
The data from safety pharmacology studies indicate that BCX9930 has a low potential to affect 
the respiratory, cardiovascular, and central nervous systems. 
 
 BCX9930 has a low risk to prolong the QT 
interval. 
 
 
 
 
 
The weight of evidence suggests BCX9930 has a low risk for genotoxicity. BCX9930 is not 
fetotoxic and is not teratogenic in pregnant rats and rabbits. There is a low concern for 
phototoxicity. 
5.2.2. 
Clinical Findings for BCX9930 
5.2.2.1. 
Study BCX9930-101 
The multipart first-in-human (FIH) study (BCX9930-101; Study 101) of single ascending dose 
(SAD) and multiple ascending dose (MAD) oral treatment with BCX9930 in 152 healthy 
subjects (Parts 1 and 2) and ascending doses in 16 PNH subjects (Part 3) commenced in 2019 
and has fully enrolled. 
Safety and tolerability were evaluated through assessments of treatment-emergent adverse events 
(TEAEs), laboratory analyses (clinical chemistry, hematology, and urinalysis), vital signs, 
electrocardiograms (ECGs; 12-lead and telemetry), and physical examinations. 
5.2.2.1.1. Healthy Subjects (Study 101, Parts 1 and 2) 
Part 1 of Study 101, a SAD study in 56 healthy subjects, has completed enrollment. No clinically 
significant dose-related trends in laboratory values, vital signs, or ECGs were noted in subjects 
receiving single doses ranging from 10 to 2000 mg. The most frequently reported TEAE 
assessed as possibly related to study drug was headache. 
Part 2 of Study 101, a MAD study in 96 healthy subjects, has completed enrollment. No 
clinically significant dose-related trends in laboratory values, vital signs, or ECGs were noted in 
any cohort. BCX9930 was safe and generally well tolerated following multiple doses of 
BCX9930 50 to 500 mg administered every 12 hours (Q12h) and 1000 to 2000 mg every 


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24 hours (Q24h). The most frequently reported TEAE assessed as possibly related to study drug 
was rash that was self-limiting and not associated with mucosal involvement. No clinically 
significant dose-related trends in adverse events (AEs), laboratory values, vital signs, or ECGs 
were noted. 
In healthy subjects, BCX9930 exposure was linear and dose-proportional, with no evidence of 
dose- or time-dependent PK. Food effect (of a high-fat meal) on exposure was modest with an 
approximate 30% increase in exposure. Steady state was reached within 48 hours after repeat 
dosing, with modest accumulation (approximately 1.5-fold for Q12h regimens). The effective 
half-life (t1/2) was approximately 6 to 8 hours. 
BCX9930 showed rapid and dose-related suppression of the AP. After multiple doses of 
BCX9930 at dose levels ≥ 100 mg Q12h and ≥ 1000 mg Q24h, AP Wieslab activity was 
inhibited by > 95%. 
5.2.2.1.2. Subjects with PNH (Study 101, Part 3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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5.2.2.2. 
Study BCX9930-201 
 
 
 
 
 
5.2.2.3. 
Study BCX9930-102 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2.2.4. 
Other Clinical Studies 
Four additional Phase 1 clinical studies in adult subjects have been initiated. Enrollment has 
completed for an absorption, distribution, metabolism, and excretion (ADME) study 
(Study BCX9930-103), a renal impairment study (Study BCX9930-104), an ethnobridging study 
to evaluate the safety, PK, and PD of SAD and MAD of BCX9930 in healthy subjects of 
Japanese origin (Study BCX9930-105), and a relative bioavailability study of BCX9930 tablet 


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and capsule formulations in healthy subjects (Study BCX9930-106). Results from these studies 
are described in the current version of the IB. 
5.3. 
Rationale for Study 
The current study, BCX9930-202 (Study 202) will evaluate the efficacy, safety, and tolerability 
of BCX9930 monotherapy versus continued C5 inhibitor therapy in subjects with PNH with 
inadequate response to C5 inhibitor therapy. 
5.3.1. 
Rationale for Study Design 
Study 202 is divided into two parts, conducted on the same population of subjects. Part 1 will 
include BCX9930 monotherapy administered for 24 weeks in comparison to continued 
complement C5 inhibitor therapy. Data collected through Week 24 will constitute the primary 
efficacy data set for the study. Subjects randomized to continue C5 inhibitor therapy in Part 1 
will discontinue that therapy in Part 2 and switch to BCX9930 monotherapy, so that all subjects 
will receive BCX9930 in Part 2. The second part of the study will evaluate the long-term safety 
and effectiveness of BCX9930 monotherapy.  
Evidence from other studies of complement inhibitors in PNH supports the conclusion that 
24 weeks of dosing is an ample duration to demonstrate the efficacy of BCX9930 versus 
continued C5 inhibitor therapy. The 24-week duration of the randomized treatment phase of 
Study 202 is consistent with the 26-week duration of the pivotal studies for eculizumab and 
ravulizumab (Hillmen, Young, et al. 2006, Kulasekararaj, Hill, et al. 2019, Lee, Sicre de 
Fontbrune, et al. 2019). A 24-week duration rather than 26 weeks was chosen for practical 
reasons because of the every 8-week dose schedule of ravulizumab and the convenience of a 
monthly (4-week) visit schedule for participants. The 28-week duration of Part 2, with subjects 
dosed through Week 52, will allow for evaluation of the long-term safety, tolerability, and 
effectiveness of BCX9930 monotherapy as a potential treatment for PNH. 
5.3.2. 
Rationale for Study Population 
The current study is designed to evaluate the superiority of a BCX9930 monotherapy compared 
to continued C5 inhibitor therapy in subjects with an inadequate response to C5 inhibitors. For 
the purposes of this study, determination of an “inadequate response” will be based on residual 
anemia, defined as a Hb value of ≤ 10.5 g/dL at screening. Prospective subjects must have been 
treated with a stable regimen of eculizumab for at least 3 months or a stable regimen of 
ravulizumab for 6 months prior to the screening visit to allow adequate time to assess their 
response to that therapy. In addition to residual anemia, prospective subjects must show evidence 
of reticulocytosis (absolute reticulocyte count [ARC] of ≥ 100,000 cells/µL) as further evidence 
of ongoing hemolysis and an ability to mount a hematopoietic response to treatment with 
BCX9930. To exclude patients with evidence of significant underlying aplastic anemia (AA) or 
BMF, who are unlikely to benefit from treatment with a complement inhibitor, and to minimize 
the risk of infection to participants, subjects will additionally need to meet minimum thresholds 
at screening for platelet count (≥ 30,000 µL) and absolute neutrophil counts (≥ 750 cells/µL). 
LDH was not included in the definition of an inadequate responder because blockade of the 
terminal complement pathway by the C5 inhibitor is expected to have abrogated IVH and 
decreased LDH in this population. 


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This population of patients currently has no approved treatment alternatives other than 
continuing C5 inhibitor therapy and, therefore, is a population of unmet medical need. In clinical 
practice, these patients would not be characterized as non-responders and would remain on 
C5 inhibitor therapy. As such, it is considered clinically and ethically acceptable to continue 
C5 inhibitor therapy in this population of patients, as these inadequate responders derive some 
benefit from the C5 inhibitor therapy in controlling IVH, but continue to have an unmet need 
regarding control of EVH. Inhibition of Factor D by BCX9930 should control both IVH and 
EVH, and should result in a superior treatment effect, compared to C5 inhibitor therapy. 
5.3.3. 
Rationale for Comparator 
This is an active-controlled study. Eculizumab and ravulizumab represent the current standard of 
care for the treatment of PNH in jurisdictions where these drugs have received regulatory 
approval and are commercially available. To encompass as broad a patient population as 
possible, prospective subjects with an inadequate response to either eculizumab or ravulizumab 
may be enrolled in this study. The dose of C5 inhibitor must have been stable for a minimum of 
3 months prior to the screening visit for eculizumab and 6 months prior to the screening visit for 
ravulizumab to ensure that adequate time has been allowed to assess the subject’s response to 
C5 inhibitor therapy. Enrollment will not be limited only to inadequate responders who are being 
treated with the label-indicated regimen of eculizumab. Instead, patients with an inadequate 
response to eculizumab therapy despite dose or dose interval adjustment (Brodsky 2021), 
representing a subgroup with clear unmet medical need, will be allowed to enroll in the current 
study. However, they must still meet the 3-month requirements for dose stability. In addition, the 
same dose regimen of eculizumab or ravulizumab that the study subject was receiving at 
screening will be maintained during Part 1 of the study. 
5.3.4. 
Rationale for Study Endpoints 
Patients with an inadequate response to C5 inhibitors present with fatigue from low Hb levels 
and may be transfusion-dependent, but due to control of IVH by the C5 inhibitor, may have 
normal or only modestly elevated LDH and aspartate aminotransferase (AST, also serum 
glutamic-oxaloacetic transaminase [SGOT]) concentrations (Risitano 2016). Therefore, the 
primary endpoint selected for this study is the change from baseline (CFB) in Hb, which is a 
direct measure of the correction of anemia and an objective biomarker that has generally been 
accepted as a surrogate for clinical benefit in this patient population, as reflected in its use as an 
endpoint in randomized controlled trials (Hillmen, Szer, et al. 2021) and in the draft 
hematological response categorization criteria proposed by the Severe Aplastic Anaemia 
Working Party of the European Bone Marrow Transplantation group (Risitano, Marotta, et al. 
2019). 
Key secondary endpoints have been selected to characterize the clinical benefit of treatment with 
BCX9930. In particular, secondary endpoints include the proportion of subjects who are 
transfusion-free over the 24-week treatment period and reductions in transfusions as reflected in 
the number of units of packed RBC units (pRBCs) transfused, and improvement in subject 
health-related quality of life (HRQoL) as reported using the established Functional Assessment 
of Chronic Illness Therapy (FACIT)-Fatigue scale. Although RBC transfusion criteria vary, 
reductions in RBC transfusion burden, as reflected in the proportion of subjects who remain 
transfusion-free and the number of units of RBCs transfused, is an important benefit of treatment 


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of PNH. Fatigue is a key symptom of PNH which is frequently, sometimes constantly, 
experienced by patients and significantly impacts their HRQoL (Escalante, Chisolm, et al. 2019). 
The FACIT-Fatigue scale has been used in prior PNH clinical studies to assess self-reported 
fatigue and its impact upon daily activities and function, including pivotal clinical trials that 
supported the approvals of eculizumab and ravulizumab (Hillmen, Young, et al. 2006, Weitz, 
Meyers, et al. 2013, Kulasekararaj, Hill, et al. 2019, Lee, Sicre de Fontbrune, et al. 2019). 
Additional secondary endpoints will characterize the effects of BCX9930 on EVH by measuring 
the CFB in C3-opsonized RBCs, the CFB in the total PNH RBC clone size, and the change in the 
ratio of total PNH RBCs to PNH white blood cells (WBCs) (ie, percent PNH RBCs/percent PNH 
WBCs) after 24 weeks. Preventing complement-mediated destruction of PNH RBC cells will 
increase the size of the total PNH RBC clone, but not impact the PNH WBC clone size, as 
WBCs are not materially affected by complement, so the total PNH RBC clone size should 
increase to approximate the PNH WBC clone size, as the theoretical maximum. 
Disease-specific instruments to measure HRQoL in patients with PNH are currently lacking and, 
as is often the case with ultra-rare diseases, evaluation of HRQoL is either incomplete or 
assessed using measures designed for other conditions. As a result, symptoms and impacts not 
relevant to patients with PNH are often measured and, most importantly, those that are of 
primary importance to patients are often not captured. The effect of BCX9930 monotherapy on 
HRQoL will be evaluated using a PNH-specific instrument, the Quality of Life Questionnaire for 
patients with Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria (QLQ-AA/PNH). This 
instrument is currently being used in the International PNH Registry (Groth, Singer, et al. 2017, 
Niedeggen, Singer, et al. 2019). In addition, improvement on individual PNH symptom items 
(ie, frequency, severity, and/or interference) will be captured using a modified form of the 
PNH-specific symptom measure, the Patient-Reported Outcome Questionnaire for Aplastic 
Anemia and Paroxysmal Nocturnal Hemoglobinuria (PRO-AA/PNH) (Weisshaar, Ewald, et al. 
2020). These disease-specific measures will be supplemented by established patient-reported 
outcome (PRO) measures, including the EuroQoL 5-dimension, 5-level (EQ-5D-5L) 
questionnaire and the Treatment Satisfaction Questionnaire for Medication (TSQM). 
Because of the potential adverse effects of coronavirus disease (COVID-19) and other 
unpredictable CACs on otherwise well-controlled IVH and EVH, the primary and relevant 
secondary endpoints will be assessed as the average of values obtained at visits from Weeks 12 
through 24. Preliminary data from PNH patients treated with BCX9930 in Study 101 
(Section 5.2.2), supported by data reported for other proximal complement inhibitors, including 
the C3 inhibitor, pegcetacoplan, and orally administered inhibitors of Factor B, iptacopan 
(LNP 023) and Factor D, danicopan (ACH-0144471), suggests that treatment through 12 weeks 
is sufficient to show maximal or close to maximal responses in Hb, C3 opsonization of RBCs, 
PNH clone size, and the FACIT-Fatigue scale (Kulasekararaj, Hill, et al. 2019, Wong, Ignatova, 
et al. 2020, Risitano, Roth, et al. 2021). In addition, transfusion avoidance and related endpoints 
will be assessed over an effective treatment period from Week 4 through Week 24 to account for 
the initial 2-week BCX9930 200 mg BID dose titration and turnover of PNH RBCs (Ninomiya, 
Sato, et al. 2008, Risitano, Notaro, et al. 2009). 


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5.3.5. 
Rationale for Dose Selection 
The dose regimen selected for this study is 400 mg BID, modified from 500 mg BID in previous 
versions of this protocol based on efficacy and safety observations. The following observations 
support this dosing regimen: 
• 
 
 
 
 
 
 
 
 
 
 
5.3.5.1. 
Summary of Hematologic Response at 400 and 500 mg BID – Studies 101 
and 201 
Available clinical efficacy data support the potential for lowering the target dose of BCX9930 
from 500 to 400 mg BID in the ongoing clinical studies. As dosing of BCX9930 was titrated in 
the initial cohort of subjects with PNH enrolled in Study 101 Part 3, that study and the long-term 
extension study (Study 201) provide a comparison of efficacy during at least 6 weeks of initial 
treatment with 400 mg BID and with ongoing treatment at 500 mg BID (Table 3). Nine subjects 
in Studies 101/201 had at least 6 weeks of dosing at 400 mg BID prior to escalating to 500 mg 
BID; 7 of these subjects were naïve to C5 inhibitors and provide a meaningful comparative 
dataset. Mean Hb, CFB in Hb, PNH Type II+III RBC clone size, its CFB, and the CFB in the 
ratio of RBC clone size to WBC clone size were very similar at both dose levels. No subjects 
required red blood cell transfusions during treatment at either dose level. 
 
 


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5.3.5.2. 
Summary of PPK and PK/PD Modeling 
The primary efficacy consideration for the dose selection in this study was the development of 
PPK and PK/PD models using data from Studies 101 and 201. 
PD endpoints in these models included AP Wieslab in healthy and PNH subjects, LDH in 
subjects with PNH naïve to C5 inhibitors, and C3 opsonization in PNH subjects with inadequate 
response to ongoing C5 inhibitor therapy. AP Wieslab was used as a real-time marker of overall 
complement activation. LDH was used as a marker of IVH (terminal complement inhibition) and 
C3 opsonization was used as a marker of the potential for EVH (proximal complement 
inhibition) in PNH subjects. Target occupancy of Factor D is not expected to be affected by a 
terminal complement inhibitor, allowing for models of IVH and EVH to be extrapolated to all 
subjects with PNH regardless of C5 inhibitor status. 
 
 
 
 
 
 
Separate PK/PD models were constructed for AP Wieslab, LDH, and C3 opsonization of RBCs. 
Overall, the models performed well and were able to describe trends in the observed data. 


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The LDH model in C5 inhibitor-naïve PNH subjects was characterized by indirect inhibition, 
 
 
 
 
 
 
  
 
 
 
 
 
Outcomes of PK/PD modeling are summarized in Figure 2 (comparison of predicted inhibitory 
concentrations with PPK-predicted Ctau). 
Figure 2: 
Comparison of PK/PD Model-Estimated IC Values (95% CI) for 
AP Wieslab, LDH, and C3 Opsonization with Median (10th to 90th percentile) 
PPK Model-Estimated Ctau at 200, 400, and 500 mg BID 




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Potential risks associated with complement inhibitors for the treatment of PNH, as well as 
potential risks associated with BCX9930 based on nonclinical and clinical data to date are 
described in the IB for BCX9930 and summarized below. 
5.4.1. 
Potential Risks of Bacterial Infections 
The most significant risk associated with complement inhibitor therapies is the risk of 
life-threatening or fatal meningococcal infections (Figueroa and Densen 1991, Hillmen, Young, 
et al. 2006). This risk is well-known and included as a warning in the relevant labels for both 
Soliris (eculizumab) and Ultomiris (ravulizumab) (Alexion Pharmaceuticals Soliris PI 2020, 
Alexion Pharmaceuticals Ultomiris PI 2020). 
As BCX9930 blocks the AP of complement, subjects may have increased susceptibility to 
bacterial infections, especially infections with encapsulated organisms, such as Neisseria 
meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, but also with 
unencapsulated strains of N. meningitidis and other bacteria such as N. gonorrhoeae (Ram, 
Lewis, et al. 2010). Study subjects receiving BCX9930 will be monitored closely for signs and 
symptoms of infection; infection risk will be mitigated by requiring subjects to have up-to-date 
vaccinations against appropriate bacterial strains. If required on an individual basis, prophylactic 
antibiotic administration will be allowed. 
5.4.2. 
Potential Risks of SARS-CoV-2 Infection and Vaccination While Receiving 
BCX9930 Therapy 
Complement inhibitors do not inhibit cellular or humoral immunity. Therefore, BCX9930 is not 
expected to increase the risk of contracting COVID-19 following infection with the severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) or to increase the risk of severe illness with 
COVID-19. 
All study activity will be conducted in accordance with relevant local, regional, and national 
guidance around COVID-19. In order to minimize the risk of COVID-19 transmission, additional 
procedures or assessments (which may include but are not limited to symptom assessment, 
temperature, viral ribonucleic acid [RNA] testing, and antibody testing) may be implemented at 
the discretion of the investigator and sponsor medical monitor beyond those required for this 
protocol. 
Vaccination against SARS-CoV-2, the causal agent for COVID-19 infection, is allowed, if 
authorized and available in country or area, and based on investigator’s judgment. 
The sponsor’s current risk assessment, relative to COVID-19 vaccination in clinical trials with 
BCX9930, is that authorized or available COVID-19 vaccinations are unlikely to have any 
potential interaction or added safety risk, if given in combination with BCX9930. Also, 
currently, there is no theoretical concern or data to suggest that complement inhibition with 
ongoing BCX9930 treatment would impact the potential efficacy of vaccinations against 
SARS-CoV-2. While there is a known or expected higher risk of some bacterial infections in 
patients treated with complement inhibition and in patients with certain hereditary complement 
deficiencies, there is no clear known increased or compounded risk with vaccinations in the 
setting of complement inhibition; however, there have been reports of hemolysis in patients with 
PNH after SARS-CoV-2 vaccination (Gerber, Yuan, et al. 2021). 


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5.4.3. 
Potential Risks for Hemolysis After Discontinuation or Interruption of Study 
Treatment 
Similar to available complement inhibitors used to treat PNH, discontinuation of BCX9930 may 
result in increased risk of hemolysis of PNH RBCs (Alexion Pharmaceuticals Soliris PI 2020, 
Alexion Pharmaceuticals Ultomiris PI 2020). Accordingly, subjects who discontinue or interrupt 
study treatment, whether BCX9930 or C5 inhibitor, may be at increased risk of hemolysis. 
Subjects should be instructed to immediately contact the investigative site if they miss any 
BCX9930 (or C5 inhibitor) doses and experience new or worsening symptoms of hemolysis. In 
addition, subjects who discontinue permanently BCX9930 (or C5 inhibitor therapy) will be 
monitored for potential hemolysis. Assessments to detect hemolysis should be performed as 
described in Section 12.5.3.1 and Section 10.3.6. 
5.4.4. 
Potential Risks of Adverse Events with BCX9930 
5.4.4.1. 
Potential Risks for Headache 
In Phase 3 studies of adult patients with PNH who received eculizumab or ravulizumab, 
headache was one of the most frequently reported adverse drug reactions 
(Alexion Pharmaceuticals Soliris PI 2020, Alexion Pharmaceuticals Ultomiris PI 2020). 
Headaches that were considered related to ravulizumab and eculizumab commonly occurred 
early after the initiation of treatment. These headaches may be associated with a transient surge 
in plasma nitric oxide levels induced by the cessation of the depletion of nitric oxide by free 
hemoglobin (Hillmen, Young, et al. 2006, Brodsky 2008, Hillmen, Muus, et al. 2013, Roth, 
Rottinghaus, et al. 2018). In Study 101, early-onset headache was the most common TEAE in 
subjects with PNH treated with BCX9930, likely consistent with restoration of nitric oxide 
homeostasis due to improved control of hemolysis with BCX9930. 
5.4.4.2. 
Potential Risks for Dermatologic Reactions 
A benign maculopapular rash with consistent onset and clinical course has been observed with 
multiple-day dosing of BCX9930 in both healthy subjects and subjects with PNH. Clinical 
experience to date indicates that this rash resolves with no intervention while continuing dosing 
of BCX9930. Although there is no evidence for any systemic hypersensitivity, more severe 
reactions may be possible, and any subject with a rash believed to be related to BCX9930 should 
be evaluated, as deemed medically appropriate. Currently, the risk of discontinuing BCX9930 in 
PNH patients is greater than the potential risk of continuing with treatment; all PNH subjects 
with rash have recovered while continuing dosing and in the same timeframe as healthy subjects 
who stopped dosing of BCX9930. 
5.4.4.3. 
Potential Risks for Renal or Hepatic Effects 
Toxicities identified in nonclinical studies and detailed in the IB for BCX9930 are monitorable 
with standard blood and urine clinical chemistry tests. 
Renal Effects 
 
 
 


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Monitoring of renal function will be undertaken in the study using standard measures (eg, sCr, 
estimated glomerular filtration rate [eGFR], and urinalysis including microscopy and biomarker 
analysis). Further information can be found in Section 11.7.5. Based on the timing of the 
early-onset sCr increases, the frequency of laboratory assessments is increased to monitor for any 
changes in renal function. Any renal events occurring on study should be evaluated as detailed in 
Section 12.5.2. 
Hepatic Effects 
Serum chemistries, including liver transaminases, bilirubin, and alkaline phosphatase (ALP), will 
be followed closely in this study to monitor for any hepatocellular and biliary system changes. 
Hepatic synthetic function will be monitored by prothrombin time, international normalized ratio 
(INR), albumin, and total protein levels in blood. The additional laboratory measurements 
conducted through the first 12 weeks of BCX9930 treatment include monitoring for hepatic 
toxicities. 
5.4.5. 
Overall Benefit-Risk Analysis 
Treatment-emergent increases in 
 
 Based on the sponsor’s preliminary investigations, reducing 
the BCX9930 dose to 400 mg BID and introducing a step-up regimen (ie, starting dosing at 
200 mg BID for 2 weeks before escalating to 400 mg BID) is anticipated to mitigate the risk of 
 while maintaining the potential for demonstrating clinical benefit in the PNH patient 
population. 
BCX9930 is expected to provide greater efficacy than the currently available C5 inhibitors by 
not only preventing IVH, but also by preventing C3-mediated EVH, thereby reducing symptom 
burden, reducing hemolysis, including EVH and BTH, improving patient function, changing the 
administration route from IV to oral, and improving HRQoL. Study subject selection criteria, 
dose selection, and study monitoring assessments have been included to optimize benefit and to 
minimize the risk of toxicities to study participants. Regular monitoring of safety parameters, 
including AEs, clinical laboratory abnormalities, vital signs measurements, ECGs, and physical 
examination findings, will ensure that the benefit-risk profile supports continued dosing. In 
addition, an independent, program-wide data monitoring committee (DMC) will provide 
oversight of the ongoing exposure of subjects to BCX9930 in this and other clinical studies. The 
overall benefit-risk balance is, therefore, considered to be acceptable. 


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6. 
STUDY OBJECTIVES 
6.1. 
Objectives 
6.1.1. 
Part 1 Primary Objective 
The primary objective of Part 1 of this study is: 
• To determine the efficacy of oral BCX9930 monotherapy administered for 24 weeks, 
compared to continued C5 inhibitor therapy, in subjects with PNH with an inadequate 
response to C5 inhibitor therapy 
6.1.2. 
Part 1 Secondary Objectives 
The secondary objectives of Part 1 of this study are: 
• To evaluate the safety and tolerability of BCX9930 monotherapy administered for 
24 weeks, as compared to continued C5 inhibitor therapy, in subjects with PNH 
• To characterize the effects of BCX9930 monotherapy, as compared to continued 
C5 inhibitor therapy, using clinical and laboratory measurements, including 
complement and thrombosis biomarkers, PNH clone size, and C3-opsonization of 
RBCs, in subjects with PNH 
• To evaluate the effects of BCX9930 monotherapy, as compared to continued 
C5 inhibitor therapy, on the FACIT-Fatigue scale and other PROs in subjects with 
PNH 
• To characterize BCX9930 plasma concentrations and PK parameters in subjects with 
PNH 
6.1.3. 
Part 2 Primary Objective 
The primary objective of Part 2 of this study is: 
• To evaluate the long-term safety and tolerability of oral BCX9930 monotherapy 
administered over a 28- to 52-week treatment period in subjects with PNH with 
inadequate response to C5 inhibitor therapy 
6.1.4. 
Part 2 Secondary Objectives 
The secondary objectives of Part 2 of this study are: 
• To assess the effectiveness of BCX9930 monotherapy in the treatment of PNH over a 
28- to 52-week treatment period 
• To characterize the effects of BCX9930 monotherapy using clinical and laboratory 
measurements, including complement and thrombosis biomarkers, PNH clone size, 
and C3-opsonization of RBCs, in subjects with PNH over a 28- to 52-week treatment 
period 
• To evaluate the effects of BCX9930 monotherapy on FACIT-Fatigue scale and other 
PROs in subjects with PNH over a 28- to 52-week treatment period 


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• To characterize BCX9930 plasma concentrations and PK parameters over time in 
subjects with PNH 
6.2. 
Endpoints 
In Part 1 of this study, unless indicated otherwise, endpoints will be assessed at or to Week 24. In 
Part 2, unless indicated otherwise, endpoints will be assessed at or to Week 52. For subjects who 
are switched from C5 inhibitor therapy to BCX9930 monotherapy at the end of Part 1, Part 2 
endpoints will be assessed against Week 24 (ie, Week 52 vs. Week 24). 
6.2.1. 
Part 1 Primary Endpoint 
The primary endpoint of Part 1 of this study is: 
• CFB in Hb [mean of values at Weeks 12, 16, 20, and 24] 
6.2.2. 
Part 1 Key Secondary Endpoints 
The key secondary endpoints of Part 1 of this study are: 
1. Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 
2. Number of units of pRBCs transfused [from Week 4 to Week 24] 
3. CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
6.2.3. 
Part 1 Other Secondary Endpoints 
Other secondary endpoints of Part 1 of this study are: 
• Percent CFB in LDH [mean of values at Weeks 12, 16, 20, and 24] 
• Percent reduction in the rate of pRBC units transfused [from Week 4 to Week 24 vs. 
prestudy transfusion rate] 
• Proportion of subjects with Hb ≥ 12 g/dL [at Week 24] 
• Proportion of subjects with Hb stabilization, defined as avoidance of a > 2 g/dL 
decrease in the absence of transfusion [from Week 4 to Week 24] 
• CFB in C3-opsonized RBCs [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in total PNH RBC clone size [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in ratio of total PNH RBC clone size to PNH WBC clone size (ie, ratio of 
percent PNH RBCs / percent PNH WBCs) [mean of values at Weeks 12, 16, 20, and 
24] 
• CFB in absolute reticulocyte count (ARC) [mean of values at Weeks 12, 16, 20, and 
24] 
• Proportion of subjects with ARC in the normal range [at Week 24] 
• CFB in haptoglobin [mean of values at Weeks 12, 16, 20, and 24] 


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• Proportion of subjects with haptoglobin ≥ lower limit of normal reference range 
(LLN) [at Week 24] 
• CFB in total bilirubin [mean of values at Weeks 12, 16, 20, and 24] 
6.2.4. 
Part 1 Exploratory Endpoints 
The exploratory endpoints of Part 1 of this study are: 
• 
 
 
 
6.2.5. 
Part 1 Other Health-related Quality of Life Endpoints 
Other HRQoL endpoints of Part 1 of this study are: 
• Proportion of subjects achieving a within-subject meaningful change for the 
FACIT-Fatigue scale [at Week 24] 
• CFB in QLQ-AA/PNH Physical Functioning and other domain scores [at Week 24] 
• Proportion of subjects with improvement on individual PNH symptom items 
(ie, frequency, severity, and/or interference) from baseline as assessed using the 
modified PRO-AA/PNH [at Week 24] 
• CFB in individual PNH symptom items on the modified PRO-AA/PNH [at Week 24] 
• CFB in EQ-5D-5L utility and visual analog scale (VAS) scores [at Week 24] 
• TSQM scale score [at Week 24] 
• Patient global impression of change in fatigue, impact of fatigue, and physical 
functioning as assessed using the Patient Global Impression of Change 
(PGIC)-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning scores, 
respectively [at Week 24] 
• CFB in patient global impression of severity of fatigue, impact of fatigue, and 
physical functioning as assessed using the Patient Global Impression of Severity 
(PGIS)-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical Functioning scores, 
respectively [at Week 24] 
6.2.6. 
Part 1 Safety Endpoints 
The safety endpoints of Part 1 of this study are: 
• Number and proportion of subjects with a TEAE 
• Number and proportion of subjects who discontinue treatment due to a TEAE 
• Number and proportion of subjects who experience a treatment-emergent serious 
adverse event (TESAE) 


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• Number and proportion of subjects who experience a Grade 3 or Grade 4 TEAE 
assessed using the US National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Event (CTCAE) grading scales 
• Number and proportion of subjects who experience a treatment-emergent CTCAE 
Grade 3 or Grade 4 laboratory abnormality 
6.2.7. 
Part 2 Primary Endpoints 
The primary endpoints of Part 2 of this study are: 
• Number and proportion of subjects with a TEAE 
• Number and proportion of subjects who discontinue due to a TEAE 
• Number and proportion of subjects who experience a TESAE 
• Number and proportion of subjects who experience a CTCAE Grade 3 or Grade 4 
TEAE 
• Number and proportion of subjects who experience a treatment-emergent CTCAE 
Grade 3 or Grade 4 laboratory abnormality 
6.2.8. 
Part 2 Secondary Endpoints 
The secondary endpoints in Part 2 of this study are: 
• CFB in Hb [mean of values from Weeks 28 to 52 for subjects randomized to 
BCX9930 in Part 1 and mean of values from Weeks 36 to 52 for subjects randomized 
to continue C5 inhibitor] 
• Proportion of subjects with Hb ≥ 12 g/dL [at Week 52] 
• Proportion of subjects with Hb stabilization (avoidance of a > 2 g/dL decrease in the 
absence of transfusion) [from Weeks 24 to 52 for subjects randomized to BCX9930 
in Part 1 and from Weeks 28 to 52 for subjects randomized to continue C5 inhibitor] 
• Proportion of subjects who are transfusion-free [from Weeks 24 to 52 for subjects 
randomized to BCX9930 in Part 1 and from Weeks 28 to 52 for subjects randomized 
to continue C5 inhibitor] 
• Number of units of pRBCs transfused [from Weeks 24 to 52 for subjects randomized 
to BCX9930 in Part 1 and from Weeks 28 to 52 for subjects randomized to continue 
C5 inhibitor] 
• Percent reduction in the rate of pRBC units transfused [from Weeks 24 to 52 for 
subjects randomized to BCX9930 in Part 1 and from Weeks 28 to 52 for subjects 
randomized to continue C5 inhibitor vs. prestudy transfusion rate] 
• Percent CFB in LDH [mean of values from Weeks 28 to 52 for subjects randomized 
to BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to continue 
C5 inhibitor] 


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• CFB in ARC [mean of values from Weeks 28 to 52 for subjects randomized to 
BCX9930 in Part 1 and mean of values from Weeks 36 to 52 for subjects randomized 
to continue C5 inhibitor] 
• Proportion of subjects with ARC in the normal range [at Week 52] 
• CFB in haptoglobin [mean of values from Weeks 28 to 52 for subjects randomized to 
BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to continue 
C5 inhibitor] 
• Proportion of subjects with haptoglobin ≥ LLN [at Week 52] 
• CFB in C3-opsonized RBCs [mean of values from Weeks 28 to 52 for subjects 
randomized to BCX9930 in Part 1 and mean of values from Weeks 36 to 52 for 
subjects randomized to continue C5 inhibitor] 
• CFB in total PNH RBC clone size [mean of values from Weeks 28 to 52 for subjects 
randomized to BCX9930 in Part 1 and mean of values from Weeks 36 to 52 for 
subjects randomized to continue C5 inhibitor] 
• CFB in ratio of total PNH RBC clone size to PNH WBC clone size [mean of values 
from Weeks 28 to 52 for subjects randomized to BCX9930 in Part 1 and mean of 
values from Weeks 36 to 52 for subjects randomized to continue C5 inhibitor] 
6.2.9. 
Part 2 Exploratory Endpoints 
• 
 
 
 
 
 
 
6.2.10. 
Part 2 Health-related Quality of Life Endpoints 
• Durability of FACIT-Fatigue scale, QLQ-AA/PNH domain, modified PRO-AA/PNH, 
EQ-5D-5L utility and VAS, and TSQM scale scores 
• Proportion of subjects achieving a within-subject meaningful change for 
FACIT-Fatigue scale 
• Proportion of subjects with improvement in individual PNH symptom items 
(ie, frequency, severity, and/or interference) on the modified PRO-AA/PNH as 
compared to baseline 
• Patient global impression of change in fatigue, impact of fatigue, and physical 
functioning as assessed using the PGIC-Fatigue, PGIC-Impact of Fatigue, and 
PGIC-Physical Functioning scores, respectively 
• CFB in patient global impression of severity of fatigue, impact of fatigue, and 
physical functioning as assessed using the PGIS-Fatigue, PGIS-Impact of Fatigue, 
and PGIS-Physical Functioning scores, respectively 


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6.2.11. 
Pharmacokinetic and Pharmacodynamic Endpoints – Parts 1 and 2 
The PK and PD endpoints of Parts 1 and 2 of this study are: 
• PK data will be used to estimate PK parameters using appropriate PK analyses based 
on the sampling collection approaches 
• PD data will be used to estimate PD parameters as well as in combination with PK 
data to perform PK/PD analyses 
• CFB in PD and complement biomarker measurements, including constitutive 
complement levels and ex vivo stimulation assays 
PK and PD data may be analyzed in combination with data from other clinical studies as 
appropriate. 
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is a randomized, active-controlled, open-label, multicenter, parallel-group, 2-part study. 
Part 1 of the study is designed to evaluate the efficacy, safety, and tolerability of treatment with 
oral BCX9930 monotherapy for 24 weeks versus continued C5 inhibitor therapy in subjects with 
PNH with an inadequate response to the C5 inhibitor. Subjects will be randomized to either 
discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor 
therapy for the 24-week randomized treatment period. Part 2 of the study is designed to evaluate 
the long-term safety and tolerability and effectiveness of BCX9930 monotherapy when 
administered through Week 52. Subjects who are randomized to BCX9930 monotherapy in 
Part 1 will continue to receive BCX9930 in Part 2. Subjects who are randomized to C5 inhibitor 
therapy in Part 1 will discontinue that therapy at the Week 24 visit and start BCX9930 in Part 2. 
Data collected through Week 24 will constitute the primary data set for the study; hence, the 
primary database will be locked and analyzed following capture of available data for all subjects 
through Week 24. 
Part 1: 24-week, randomized, open-label evaluation of efficacy, safety, and tolerability of 
BCX9930 monotherapy versus continued C5 inhibitor therapy 
Patients with PNH who have been treated with a stable regimen of eculizumab for ≥ 3 months or 
ravulizumab for ≥ 6 months and who have had an inadequate response to that therapy may be 
screened for this study. Following confirmation of study eligibility, Day 1 will be scheduled such 
that it occurs on or within 2 weeks prior to the date that the subject is scheduled to receive the 
next dose of eculizumab, or within 2 weeks prior to the date on which the subject is scheduled to 
receive the next dose of ravulizumab, as applicable (see the study schema shown in Figure 3). On 
that day, after completion of all baseline procedures, subjects randomized to BCX9930 
monotherapy will receive the first dose of BCX9930 administered under the supervision of clinic 
staff, with the second dose administered later that day. Subsequent doses of BCX9930 are taken 
BID, approximately 12 hours apart, through Week 24. For subjects randomized to continue 
C5 inhibitor therapy, Day 1 may be scheduled at any time within the 2 weeks prior to the next 
dose of the C5 inhibitor. All subjects will be required to return to the clinic at Weeks 1, 2, and 4, 


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and every 4 weeks thereafter through Week 24. Subjects randomized to BCX9930 will be 
required to complete additional safety assessments at Weeks 3, 5, 6, 7, and 10. 
Part 2: 28-week open-label evaluation of the long-term safety, tolerability, and effectiveness 
of BCX9930 monotherapy 
Subjects randomized to continue C5 inhibitor therapy during Part 1 will be switched to 
BCX9930 monotherapy in Part 2. The timing of the final dose of the C5 inhibitor on or prior to 
Week 24 will be determined by the dose schedule for each individual subject. These subjects will 
be required to return to the clinic at Weeks 25, 26, 28, 32, and 36, and every 4 weeks thereafter 
through Week 52. Additional safety assessments will be performed at Weeks 27, 29, 30, 31, and 
34. Subjects randomized to BCX9930 monotherapy in Part 1 will continue with the every 
4 weeks visit schedule, ie, omitting the visits at Weeks 25 and 26, returning to the clinic at 
Week 28 and every 4 weeks thereafter through Week 52. 
After completion of Part 2, all subjects continuing to derive clinical benefit will be allowed to 
continue treatment with BCX9930 through enrollment in a separate long-term extension study, 
or via another access mechanism, where available (see Section 8.5). Subjects who do not 
continue BCX9930 therapy after Week 52, or who are prematurely discontinued from BCX9930 
treatment prior to Week 52, will be monitored for potential hemolysis, and may be required to 
return to the clinic for an additional visit(s) to assess for acute symptomatic hemolysis, if and 
when symptoms occur. Subsequently, they will return to the clinic approximately 3 weeks after 
the date of last dose of BCX9930 for end of study assessments. 
 


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Figure 3: 
BCX9930-202 Study Schema (Parts 1 and 2) 
 
Abbreviations: BID = twice daily; D1 = Day 1; q8wk = every 8 weeks; q14d = every 14 days. 
Note: First dose of BCX9930 administered (1) within 2 weeks prior to the next scheduled dose of ravulizumab, or (2) on or within 2 weeks prior to the next 
scheduled dose of eculizumab. Subjects will not receive their next scheduled dose of C5 inhibitor (exception: subjects receiving eculizumab may receive their 
final dose on the day they initiate BCX9930 if scheduled for that day (blue triangle). Assessments occurring below the x-axis require a visit to the 
investigational site; assessments shown above the x-axis may be completed at the investigational site, at a laboratory local to the subject, or via a home health 
service (where permitted and available) for as long as enhanced safety monitoring procedures are required. 


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7.2. 
Number of Subjects 
This study will enroll approximately 81 subjects with PNH and an inadequate response to 
C5 inhibitor therapy. In Part 1 of this study, approximately 54 subjects will be randomized to 
discontinue C5 inhibitor therapy and start BCX9930 200/400 mg monotherapy and 
approximately 27 subjects will be randomized to continue C5 inhibitor therapy. 
7.3. 
Treatment Assignment 
In Part 1, eligible subjects will be randomized in a 2:1 ratio through an interactive web-based 
response system (IWRS) to either discontinue C5 inhibitor therapy and start BCX9930 
monotherapy or to continue C5 inhibitor therapy through Week 24: 
• BCX9930 to be administered orally BID (experimental arm) 
OR 
• Continuation of current C5 inhibitor therapy (control arm) 
Randomization will be stratified based on each subject’s current C5 inhibitor (ravulizumab vs. 
eculizumab) and receipt of a pRBC transfusion within the 6 months prior to baseline (yes vs. no). 
In Part 2, all subjects will receive BCX9930 monotherapy: 
• BCX9930 to be administered orally BID (experimental arm) 
7.4. 
Individual and Study Termination Criteria 
7.4.1. 
Subject Withdrawal from Study Treatment 
Subjects randomized to continue C5 inhibitor therapy will be managed according to local or 
institutional practice guidelines, and which the investigator prescribes as being in the best 
interests of the subject.  
A subject will be permanently discontinued from BCX9930 in either study part for any of the 
following reasons: 
• Subject request to discontinue for any reason. 
• Pregnancy in a female subject. 
• Emergence of an AE, including a laboratory abnormality, or other unacceptable 
toxicity that, in the judgment of the investigator, compromises the ability of the 
subject to continue study-specific procedures or it is considered not to be in the 
subject’s best interest to continue due to an altered benefit-risk profile. 
• Intercurrent illness or the emergence of a new medical condition that would, in the 
judgment of the investigator, affect assessments of clinical status to a significant 
degree. 


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• Treatment-emergent ALT (serum glutamic-pyruvic transaminase [SGPT]) > 3 × ULN 
(confirmed by repeat testing) combined with either: 
− laboratory abnormalities indicative of significant hepatic toxicity (ie, meeting 
Hy’s law, total bilirubin > 2 × ULN or with a new increase in INR > 1.5 in the 
absence of warfarin therapy) 
OR 
− symptomatology of acute hepatitis (ie, severe fatigue, nausea, vomiting, right 
upper quadrant pain and tenderness, fever, rash, and/or eosinophilia [> 5%] that 
has not been part of the subject’s history of PNH symptomatology) 
AND 
− assessed as probably or definitely related to BCX9930 
AND 
− without clinical and/or laboratory evidence of hemolysis or any other potential 
alternative etiology. 
• Treatment-emergent increase in sCr ≥ 3 × ULN (confirmed by repeat testing) without 
clinical and/or laboratory evidence of hemolysis or any other potential cause of renal 
dysfunction. 
• Invasive meningococcal infection or invasive encapsulated bacterial infection. 
Discontinuation of BCX9930 (or C5 inhibitor) may occur after subject stabilization to 
prevent uncontrolled hemolysis. 
• In the investigator’s opinion it is in the best interest of the subject to discontinue from 
further dosing. 
• Subject noncompliance (eg, protocol deviation), as assessed by the sponsor or 
investigator, to be detrimental to study or subject benefit-risk profile. 
• Discontinuation at the request of the sponsor, relevant competent authority, or the 
governing institutional review board (IRB), research ethics board (REB), or 
independent ethics committee (IEC), collectively referred to as “ethics committee”. 
Whenever possible, the investigator will consult with the sponsor medical monitor (or designee) 
before discontinuing study treatment. The reason for discontinuation of study treatment will be 
recorded in the source documents and electronic case report form (eCRF). 
Subjects who discontinue complement inhibition (ie, BCX9930 or C5 inhibitor) for any reason 
(other than protocol-mandated cessation of C5 inhibitor on Day 1 or Week 24, as applicable) will 
be monitored for hemolysis as described in Section 12.5.3 and Section 10.3.6. 
7.4.2. 
Criteria for Study Termination 
The following study stopping criteria will be used to terminate either the study or the 
participation of a particular investigational site: 
• Request of the relevant competent authority or ethics committee 


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• Emergence of unacceptable risk, toxicity, or negative change in the benefit-risk 
assessment 
• Non-compliance with the study protocol, including inaccurate or incomplete 
recordkeeping, that jeopardizes the scientific integrity of the study or subject safety 
BioCryst reserves the right to discontinue the study prior to inclusion of the planned number of 
subjects but intends only to exercise this right for valid scientific or administrative reasons. If 
BioCryst does discontinue the study, the investigator must contact all participating subjects 
immediately after notification of study termination. 
If the study is halted due to safety concerns, re-start of the study will occur only following the 
appropriate authorization via a substantial amendment. 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following criteria, as applicable, to be eligible for participation in 
this study: 
1. Male or female, aged ≥ 18 years old. 
2. Body weight ≥ 40 kg. 
3. Documented diagnosis of PNH confirmed by flow cytometry with a PNH granulocyte or 
monocyte clone size of ≥ 10% during screening. 
4. Treated with a stable regimen of eculizumab for ≥ 3 months prior to the screening visit or 
ravulizumab for ≥ 6 months prior to the screening visit. 
5. Recorded the following results during screening: 
a. Hb of ≤ 105 g/L (≤ 10.5 g/dL). 
b. ARC of ≥ 100 × 109 cells/L (≥ 100,000 cells/µL; ≥ 100 G/L). 
c. Absolute neutrophil count of ≥ 0.75 × 109 cells/L (≥ 750 cells/µL; ≥ 0.75 G/L). 
d. Platelet count of ≥ 30 × 109/L (≥ 30,000/µL; ≥ 30 G/L). 
e. Adequate iron reserve based on ferritin ≥ LLN or total iron binding capacity ≤ ULN. 
f. eGFR of ≥ 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) equation (Levey and Stevens 2010) and no evidence of 
clinically relevant abnormal renal function unrelated to underlying PNH disease. 
6. Contraception requirements: 
Female participants must meet at least one of the following requirements: 
a. Be a woman of nonchildbearing potential. 
b. Be a woman of childbearing potential who agrees to use a highly effective 
contraceptive method throughout the study and for a duration of 30 days after the last 
dose of study drug. 
c. Alternatively, true abstinence is acceptable for women of childbearing potential when 
it is in line with the subject’s preferred and usual lifestyle. 


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Male participants must meet at least one of the following requirements: 
a. Males with a female partner of childbearing potential must use condoms throughout 
the study and for a duration of 90 days after the last dose of study drug unless their 
partner is using a highly effective contraceptive method independent of the study. 
b. Alternatively, true abstinence is acceptable when it is in line with the subject’s 
preferred and usual lifestyle. 
Additional details are provided in Section 11.2.1. 
7. Documentation of current vaccinations against N. meningitidis types A, C, W, and Y, and 
S. pneumoniae or willingness to start vaccination series at least 14 days prior to Day 1. 
(Note: Vaccination for N. meningitidis type B and for H. influenzae type B (Hib) is 
strongly encouraged where authorized and available.) 
8. In the opinion of the investigator, the subject is expected to adequately comply with all 
required study procedures and restrictions for the study, including compliance with the 
BID dosing schedule for BCX9930. 
9. Willing and able to provide written informed consent. 
8.2. 
Subject Exclusion Criteria 
Subjects must not meet any of the following exclusion criteria to be eligible for participation in 
the study: 
1. Known history of or existing diagnosis of hereditary complement deficiency. 
2. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate 
for transplantation during the study. 
3. Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or 
current and uncontrolled clinically significant cardiovascular or cerebrovascular 
condition, including unstable angina, severe congestive heart failure, unexplained 
syncope, arrhythmia, and critical aortic stenosis. 
4. History of malignancy within 5 years prior to the screening visit, with exception of 
adequately treated non-melanoma skin or superficial bladder cancer, curatively treated 
carcinoma in situ of the cervix, or other curatively treated solid tumor deemed by the 
investigator and medical monitor to be at low risk for recurrence. 
5. Active bacterial, viral, or fungal infection or any other serious infection within 14 days 
prior to screening. 
(Note: Suspected or confirmed COVID-19; persistent or recurrent positive test(s) for 
SARS-CoV-2 nucleic acids or antigens; and worsening dyspnea not due to PNH, 
vasculitic rash, and persistent fever or other symptoms consistent with multisystem 
inflammatory syndrome in adults [MIS-A] are exclusionary.) 
6. Current participation in any other investigational drug study or participation in an 
investigational drug study within 30 days prior to the screening visit, or 5.5 half-lives of 
the investigational drug, whichever is longer. 
7. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit. 


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8. Initiation of treatment with an erythropoiesis-stimulating agent (eg, erythropoietin), a 
thrombopoietin receptor agonist (eg, eltrombopag), or danazol within 28 days prior to the 
screening visit. 
(Note: Treatment with these medications initiated > 28 days prior to the screening visit is 
not exclusionary, if the dose is stable and there is a reasonable expectation that treatment 
will be continued.) 
9. Receiving iron supplementation with an unstable dose in the 28 days prior to the 
screening visit. 
10. Clinically significant abnormal ECG at the screening visit. 
(Note: This includes, but is not limited to, a QT interval corrected using Fridericia’s 
method of QTcF > 450 msec in males or > 470 msec in females, or ventricular and/or 
atrial premature contractions that are more frequent than occasional, and/or as couplets or 
higher in grouping.) 
11. Subjects with any of the following results at the screening visit: 
a. ALT (SGPT) > 3 × ULN. 
b. AST (SGOT) > 3 × ULN. 
(Note: Subjects may be enrolled with AST > 3 × ULN if explained by hemolysis.) 
c. Total serum bilirubin > 2 × ULN. 
(Note: Subjects may be enrolled with total serum bilirubin > 2 × ULN if explained by 
hemolysis or Gilbert’s syndrome. In the case of hemolysis, total serum bilirubin must 
be < 5 × ULN and in the case of Gilbert’s syndrome, total serum bilirubin must be 
< 11 × ULN.) 
12. Current use of a prohibited concomitant medication within 7 days prior to Day 1 as 
detailed in Section 9.8.1. 
13. Positive serology for human immunodeficiency virus (HIV), or active infection with 
hepatitis B virus (HBV) or hepatitis C virus (HCV), unless receiving antiviral therapy and 
viral load is undetectable. 
14. Positive drugs of abuse screen, unless by prescription. 
15. Pregnant, planning to become pregnant, or breastfeeding. 
16. Known hypersensitivity to BCX9930 or any of its formulation excipients. 
17. History of severe hypersensitivity to any medicinal product, which was associated with 
swelling, severe rash requiring treatment/hospitalization, or anaphylaxis. 
18. Any other clinically significant medical or psychiatric condition that, in the opinion of the 
investigator or sponsor, would interfere with the subject’s ability to participate in the 
study or increase the risk of participation for that subject. 
8.3. 
Subject Withdrawal 
Participation in the study is strictly voluntary; a subject may withdraw consent to contribute 
additional study information at any point. Subjects have the right to withdraw from the study at 
any time and for any reason. In addition, a subject’s participation may be terminated for any of 


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the reasons described in Section 7.4.1. Whenever possible, the investigator will consult with the 
sponsor medical monitor before halting a subject’s participation in the study. 
Although a subject may withdraw from the study at any time without specifying a reason for 
withdrawal, the reason for withdrawal, if provided by the subject, will be recorded in the 
subject’s medical records (source documents) and also in the eCRF. If the reason for subject 
withdrawal is not known, attempts to contact the subject must be documented to establish 
whether the reason was due to an AE, and if so, this must be reported in accordance with the 
procedures outlined in Section 12.4.1. Vigorous attempts will be made for follow-up of all 
subjects who miss a study visit, given the potential for acute symptomatic hemolysis if BCX9930 
(or C5 inhibitor) dosing is interrupted. If at any point in the study the clinic is unable to contact 
the subject after appropriate attempts have been made, the subject will be considered lost to 
follow-up. If a subject’s participation in this study is terminated, the responsible 
investigator/clinical staff member will document termination in the source documents.  
Unless consent is withdrawn, subjects who discontinue study treatment in Parts 1 or 2 will be 
monitored for potential hemolysis, and may be required to return to the clinic for an additional 
visit(s) to assess for acute symptomatic hemolysis, if and when symptoms occur. An early 
termination (ET) visit will be completed approximately 3 weeks after the date of last dose of 
BCX9930. See Section 10.3.6 and Section 10.3.8, respectively. 
Once subjects have withdrawn from the study, the sponsor will no longer provide treatment 
through the study. 
Subjects are not eligible for treatment with BCX9930 in Part 2 if they discontinue study 
treatment in Part 1. 
8.4. 
End of Study Definition 
The end of the study will be defined as the date when the last subject completes the last 
protocol-scheduled visit. 
8.5. 
BCX9930 Access at Study Completion 
Subjects who are assessed as deriving clinical benefit from BCX9930 will be offered continued 
access to BCX9930 through participation in a separate long-term extension study, or via another 
treatment access mechanism, where available and approved by the relevant competent authority. 
Assuming continued approval of the competent authority, it is anticipated that BCX9930 will 
continue to be made available in each country until such time as BCX9930 is available through 
other means (eg, commercial approval) or until BioCryst discontinues development of the 
product for this indication. 


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9. 
TREATMENT OF SUBJECTS 
9.1. 
Description of Study Drug and Study Drug Product 
9.1.1. 
BCX9930 
BCX9930 is a small-molecule inhibitor of Factor D and will be supplied by BioCryst as tablets 
for oral administration. The active ingredient is BCX9930 drug substance. 
BCX9930 tablets contain the active ingredient blended with the 
 
 
 
 
Dosage forms include BCX9930 tablets of 100-, 200-, and 250-mg strength, which are all from a 
dose-proportional blend compressed into tablets of the desired weight. 
Additional details of the chemical and physical characteristics of BCX9930 may be found in the 
IB for BCX9930 and the investigational medicinal product (IMP) manual for the study. 
9.1.2. 
Eculizumab or Ravulizumab 
Eculizumab and ravulizumab are humanized, anti-C5 monoclonal antibodies. 
Eculizumab is an IgG2/4 kappa immunoglobulin consisting of human constant regions, and 
murine complementarity-determining regions grafted onto human framework light- and 
heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and 
two 214 amino acid light chains. 
Ravulizumab was designed through minimal targeted engineering of eculizumab by introducing 
4 unique amino acid substitutions to its heavy chain to extend antibody half-life. 
See the relevant prescribing information, product monograph, or summary of product 
characteristics for a more detailed description of Soliris (eculizumab) or Ultomiris (ravulizumab) 
(Alexion Pharmaceuticals Soliris PI 2020, Alexion Pharmaceuticals Ultomiris PI 2020). 
Where required by local regulation, provision of C5 inhibitor therapies will be coordinated by 
the sponsor in accordance with local practice. 
9.2. 
Description of Study Drug Packaging, Labelling, and Storage 
9.2.1. 
BCX9930 
BCX9930 tablets will be packaged in an appropriate size bottle. Each bottle will be labeled with 
the information required per local law, which may include sponsor name, study protocol number, 
description of the contents, a statement regarding the investigational (clinical study) use of the 
study drug and expiry date. 
The bottles of BCX9930 tablets should be stored at 15°C to 25°C (59ºF to 77ºF). 
Additional details on the packaging, labeling, shipment, storage, and dispensing of BCX9930 
tablets will be provided in the IMP manual for the study. 


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9.2.2. 
Eculizumab 
Soliris (eculizumab) drug product is supplied as 300 mg single-use vials containing 30 mL of 
10 mg/mL solution per vial. 
Soliris vials must be stored in the original carton until time of use under refrigerated conditions 
at 2°C to 8°C (36°F to 46°F). 
See the relevant prescribing information, product monograph, or summary of product 
characteristics for any updates. 
9.2.3. 
Ravulizumab 
Ultomiris (ravulizumab-cwvz) drug product is supplied as single-use vials containing 
300 mg/30 mL (10 mg/mL), 300 mg/3 mL (100 mg/mL), or 1,100 mg/11 mL (100 mg/mL) 
solution per vial. 
Ultomiris vials should be refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to 
protect from light. Do not freeze. Do not shake. 
See the relevant prescribing information, product monograph, or summary of product 
characteristics for any updates. 
9.3. 
Randomization and Blinding of Study Treatment 
9.3.1. 
Blinding 
This is an open-label study; no study treatments (ie, BCX9930 or C5 inhibitor in Part 1 and 
BCX9930 in Part 2) will be blinded or masked. 
9.3.2. 
Randomization 
In Part 1 of the study, approximately 81 subjects will be randomized in a 2:1 ratio to either 
discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor 
therapy through Week 24. Randomization for individual subjects will occur prior to Day 1 after 
completion of all screening procedures and confirmation of study eligibility. 
 
Randomization will be stratified based on C5 inhibitor (ravulizumab vs. eculizumab) and 
whether a pRBC transfusion was received within the 6 months prior to baseline (yes vs. no). 
Thus, there will be 4 strata as shown below. 


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Stratum No. 
Stratum Description 
1 
Treated with eculizumab, received pRBC transfusion within previous 6 months 
2 
Treated with eculizumab, did not receive pRBC transfusion within previous 
6 months 
3 
Treated with ravulizumab, received pRBC transfusion within previous 6 months 
4 
Treated with ravulizumab, did not receive pRBC transfusion within previous 
6 months 
Details on the processes to be followed for randomization will be provided in a separate manual. 
9.4. 
Study Drug Administration 
9.4.1. 
BCX9930 
Subjects who previously received 500 mg BID and remain on study treatment will be dose 
adjusted to 400 mg BID. 
For newly enrolled subjects randomized to BCX9930 in Part 1, and subjects who are switched to 
BCX9930 for Part 2, BCX9930 will be taken at a dose of 200 mg BID for the first 14 days of 
treatment before increasing to 400 mg BID. The appropriate quantity of BCX9930 tablets will be 
taken orally, twice a day, at approximately the same times (ie, at intervals of approximately 
12 hours) without regard to food. Adequate hydration should be maintained to prevent the 
formation of highly concentrated urine. 
No additional study drug preparation is required. BCX9930 tablets will be taken from the 
provided bottles. 
Subjects will be dispensed a sufficient number of bottles and BCX9930 tablets to cover the 
dosing period until the next study visit. 
Drug dispensation will occur in-clinic but may be delivered to subjects by other means 
(eg, traceable courier) if warranted due to extenuating circumstances (eg, COVID-19 
restrictions) which will be determined individually for each site and/or subject taking into 
account applicable local law or regulation. 
Subjects will be instructed to bring all bottles of study drug (both unused and used bottles) with 
them for each study visit (including any unscheduled visits, when possible). Accountability and 
adherence will be reviewed at these visits. 
9.4.2. 
Continued C5 Inhibitor Therapy 
Soliris (eculizumab) for injection and Ultomiris (ravulizumab) for injection are each 
administered via continuous IV infusion after dilution to a final admixture concentration in an 
appropriate diluent; see the relevant prescribing information, product monograph, or summary of 
product characteristics for additional details. 
For subjects randomized to continue C5 inhibitor therapy, the same prescribed dose regimen of 
eculizumab or ravulizumab that the subject was receiving at screening will be maintained during 
Part 1 of the study.  


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Administration of the C5 inhibitor infusions may be scheduled to occur during study visits if 
consistent with the subject’s regular infusion schedule. However, subjects who receive their 
infusions outside of the clinic, eg, at an infusion center or at home, may continue to do so. 
Additional clinic visits needed to accommodate an individual’s C5 inhibitor infusion schedule 
that fall outside of the time window for a scheduled study visit will not be considered a study 
visit. In this case, subjects will need to return to the clinic to complete the study visit within the 
indicated time window. 
While continuing therapy with eculizumab or ravulizumab in Part 1, subjects should be managed 
according to local or institutional practice guidelines, and which are in the best interests of the 
subject. 
9.4.3. 
Treatment Interruption or Dose Reduction 
Treatment interruption or dose reduction as a result of investigator management of AEs 
potentially related to study drug is permissible with appropriate monitoring for potential 
hemolysis as described in Section 12.5.3.1. Any treatment interruption or dose reduction will be 
recorded in the eCRF and source documents, including the reason for the interruption or 
reduction. Resumption of study drug administration is also permissible upon resolution of the 
event, as assessed by the investigator, with a plan for monitoring of the subject for recurrence of 
the AE, as appropriate. See Section 9.4.4 for potential dose reduction options. 
9.4.4. 
Dose Tapering 
In the event of permanent discontinuation of BCX9930, 
 
 
 
 
 
 
The decision to taper the dose and duration of any taper should be based on the investigator’s 
medical judgement, taking into account the reason for discontinuation of the drug, the severity of 
any reported signs or symptoms, and/or any reported worsening of signs or symptoms. The 
tapering schedule should be discussed with the sponsor medical monitor (or designee), ideally 
prior to implementation, and adjusted, as appropriate, for the individual subject. 
9.5. 
Treatment Compliance 
For subjects randomized to discontinue C5 inhibitor therapy and initiate treatment with 
BCX9930, the first dose of BCX9930 will be administered in the clinic on Day 1 under 
supervision. All subsequent doses can be taken at home; subjects do not need to withhold any 
doses on clinic days or take a dose at the clinic, unless the clinic visit falls during the subject’s 
normal time of dosing, or the subject is participating in the optional PK/PD substudy on a given 
visit. Subjects will be provided instructions for taking the twice-daily doses of BCX9930 at 
home, including frequency and time of administration. Where possible, the BCX9930 doses 


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should be taken at the same times each day as close as possible to 12 hours apart (eg, 8:00 AM 
and 8:00 PM). 
It is anticipated that subject compliance with the BID dosing schedule for BCX9930 is critical to 
the overall success of this study. Missing more than 2 consecutive doses of BCX9930 increases 
the risk of subjects experiencing a hemolytic episode. Therefore, participants must be educated 
about and understand the importance of compliance with the dosing schedule, be reminded about 
the risks associated with breakthrough hemolysis, and the need to promptly report new or 
worsening signs and symptoms of potential hemolysis to staff, especially when associated with 
missed doses. Participants are expected to have become accustomed to life receiving IV 
infusions administered by others at approximately 2- or 8-week intervals. Once enrolled in this 
study and randomized to BCX9930 in Part 1, or after transitioning to BCX9930 therapy in Part 2, 
each participant will need to be responsible for taking BCX9930 twice a day, at approximately 
the same times and as close as possible to 12 hours apart. Investigators are requested to meet 
with each participant and discuss with them the importance of treatment compliance prior to 
qualifying the participant for the study. Consideration should be given to strategies that will help 
reinforce these behaviors, such as asking subjects to voluntarily set up reminder alarms on their 
mobile phones or at their homes to remind them to take their doses, at least until they become 
adjusted to their new treatment regimen. BioCryst will provide materials that can be used to 
communicate the importance of compliance. Subjects will be asked to report new or worsening 
signs or symptoms of hemolysis to staff. Subjects will be required to bring the bottles of 
BCX9930 to clinic visits, including any unscheduled visit to assess for potential hemolysis, when 
possible. Investigators should remind participants who regularly miss doses of BCX9930 about 
the importance of treatment compliance. 
9.6. 
Missed Doses and Special Considerations for Dosing 
If BCX9930 needs to be withheld (eg, to assess a potentially drug-related TEAE), consideration 
for potential hemolysis as described in Section 12.5.3.1 should be given. 
9.6.1. 
Missed Doses 
Ideally, BCX9930 doses should be taken 12 hours apart at the same times each day without 
missing doses. If a subject does not take a BCX9930 dose at the scheduled time, the missed dose 
can be taken up to 6 hours after the scheduled dose time. If more than 6 hours has passed, the 
missed dose should not be taken. Regardless of whether the missed dose was made up, dosing 
should resume with the next dose taken at the scheduled time. For example, a subject who 
normally takes the BCX9930 doses at 8:00 AM/PM each day can take a missed morning dose as 
late as 2:00 PM with the evening dose administered on schedule at 8:00 PM. A missed evening 
dose can be taken as late as 2:00 AM the next day, with the next dose taken on schedule at 
8:00 AM. 
Subjects should be instructed to immediately contact the investigator if they miss any BCX9930 
doses and have new or worsening signs or symptoms consistent with acute symptomatic 
hemolysis (see Section 12.5.3.1). 


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9.6.2. 
Special Considerations for Dosing, Including Inability to Take Medication 
Orally 
It is imperative that study subjects take study drug as scheduled without missing doses. Under 
certain circumstances, when a subject cannot take or absorb BCX9930 (including acute illness 
with vomiting, dysphagia due to symptomatic hemolysis, and unplanned circumstances requiring 
hospitalization), there are provisions that can be taken. 
For acute vomiting, treatment of nausea and/or vomiting with an oral, orally dissolving, or rectal 
suppository anti-emetic 30 minutes to an hour (as a suggestion) before attempting to swallow the 
BCX9930 tablets could be attempted. If a subject vomits after receiving a dose of BCX9930, the 
subject may be redosed (ie, take two new tablets) if the intact tablets or pieces of the tablets are 
seen in the vomitus (vomit contents). 
Please refer also to the IMP manual for specific instructions. 
9.7. 
Study Drug Accountability 
Accountability of BCX9930 dispensed and returned (as applicable) will be performed at Day 1 
and at each subsequent study visit (including at unscheduled visits, when possible). Returned 
study drug bottles must be retained and reviewed during monitoring visits by the study monitor. 
The investigator or designee (eg, pharmacist) must maintain accurate records of the disposition 
of all study drugs received from the sponsor, directly administered to the subject (including date 
and time) or dispensed to the subject. At the end of the study, information describing study drug 
accountability must be maintained at the site. 
All study drug not administered and any returned study drug (including empty bottles) will be 
returned to the sponsor or destroyed on site as instructed by the sponsor following IMP 
accountability by the study monitor, abiding by appropriate standard operating procedure(s) at 
the participating institution. 
9.7.1. 
C5 Inhibitors 
In jurisdictions in which the sponsor is required to supply or reimburse for the C5 inhibitor, 
appropriate drug accountability requirements will be performed. 
9.8. 
Prior and Concomitant Medications 
Details of all prior treatments for PNH (ie, C5 and other complement inhibitors) will be recorded 
in the source documentation and eCRF, where known; all other medications will be documented 
beginning 30 days prior to the screening visit. All concomitant medication use, beginning with 
the screening visit, will be recorded in the source documentation and eCRF. 
Prior to enrollment, the investigator should review the subject’s medication list for potentially 
nephrotoxic medications and consider, when medically feasible, whether these medications may 
be stopped or substituted with non- or less nephrotoxic medications. Caution should be exercised 
with the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) while taking BCX9930. 
With the exception of any changes to nephrotoxic medications and prohibited and restricted 
medications detailed below (Section 9.8.1), subjects should continue their normal medications. 
Medications that increase infection risk (including oral corticosteroids and other 


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immunosuppressants) and erythropoietin (and analogs) should remain stable until at least the 
Week 24 visit, and then tapered as per the investigator’s judgement, unless taper or 
discontinuation during Part 1 needs to be done for safety reasons (eg, hemosiderosis). 
Prophylactic use of antibacterial and antiviral medications, other than those expressly prohibited 
on the prohibited medication list, may be considered if clinically indicated (eg, acyclovir for 
varicella-zoster virus [VZV]) and after discussion with the sponsor medical monitor (or 
designee), with consideration of the list of prohibited and restricted medications separate from 
this protocol (see Section 9.8.1). 
Please refer to inclusion criterion 7 and Section 9.9 for vaccination requirements. 
9.8.1. 
Prohibited and Restricted Medications 
Drug interactions with concomitant medications (including supplements) may affect plasma 
concentrations of that medication or of BCX9930. Adjustments in the dosing regimen of 
concomitant medications and/or increased safety monitoring may be necessary based on the 
potential for interaction. Additional detail regarding potential for interaction with specific 
medications may be found in the prohibited and restricted medications list. 
9.8.1.1. 
Prohibited and Restricted Medications for Subjects Receiving BCX9930 
All subjects should observe the prohibitions and restrictions on concomitant use described in 
Section 8.2 and in the following text for the appropriate window prior to screening or Day 1 in 
anticipation of potential randomization to the BCX9930 treatment arm. In addition, all subjects 
must have discontinued all prohibited medications for a minimum of 7 days prior to Day 1 and 
have an agreed plan in place for monitoring any restricted medications that will be continued. 
Similarly, dose adjustments to restricted medications that are necessary for enrollment should be 
completed at least 7 days prior to Day 1. Subjects randomized to continue C5 therapy may restart 
any prohibited medications after randomization. The same process will need to be repeated for 
subjects randomized to continue C5 therapy prior to the transition to treatment with BCX9930 at 
the Week 24 visit. 
Use of the following medications is currently excluded while subjects are receiving treatment 
with BCX9930, beginning 7 days prior to Day 1 (or the Week 24 visit for subjects randomized to 
continue C5 inhibitor therapy), as is the planned initiation of treatment with such medications 
during the study: 
• 
 
 
• 
 
  
 
 
 
 
 
 


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• 
 
• 
 
 
 
 
 
 
 
 
 
 
The sponsor will provide a list separate from the protocol of prohibited and restricted 
medications for which there may be a drug interaction with BCX9930 based upon regulatory 
labeling for individual medications, regulatory guidance, peer-reviewed literature, and regularly 
updated drug interaction reference databases (eg, University of Washington School of Pharmacy 
Drug Interaction Database, Pharmapendium). The sponsor may modify this list of prohibited 
medications based upon available PK and safety data on concomitant medications, ongoing 
clinical findings, and continued review of labeling, regulatory guidance, literature, and reference 
databases. A memorandum of any such changes to this list will be provided to all clinical sites. 
Phase 1 DDI studies may be conducted and resulted during the conduct of this study. Should the 
guidance for individual medications change, the use of currently prohibited medications may be 
subsequently allowed based upon the quantitative data generated in the DDI study. A summary 
and justification of the updated allowance/guidance will be provided to all clinical sites along 
with a revised list of prohibited medications. 
 
 
 
Throughout the course of the study, investigators should inquire about newly initiated, daily, 
chronic-use medications; the investigator should compare these medications to the prohibited 
medication list. 
Similarly, subjects should be aware that there may be restricted medications in this study and 
should inform all treating physicians of their participation in this study and the possibility of 
potential interactions with BCX9930. 
Please contact the sponsor medical monitor for specific questions regarding prohibited and 
restricted medications if needed. 
9.8.1.2. 
Prohibited and Restricted Medications for Subjects Randomized to Continue 
C5 Inhibitor Therapy in Part 1 
Subjects randomized to continue C5 inhibitor therapy should follow any restrictions or 
prohibitions per the relevant prescribing information for that product. 
For Part 2, the same prohibitions and restrictions on the use of concomitant medications 
described above for subjects randomized to BCX9930 must be followed, with prohibited 


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medications discontinued beginning 7 days prior to planned administration of the first dose of 
BCX9930, and have an agreed plan in place for monitoring and/or dose adjustment of any 
restricted medications that will be continued post Week 24. 
9.9. 
Vaccination Requirements, Vaccinations During Study, and 
Prophylactic Antibiotic Coverage 
BCX9930 blocks the alternative pathway of complement activation; therefore, subjects may have 
increased susceptibility to bacterial infections, especially infections with encapsulated organisms 
such as N. meningitidis, S. pneumoniae, and H. influenzae, but also with unencapsulated strains 
of N. meningitidis and other bacteria such as N. gonorrhoeae (Ram, Lewis, et al. 2010). Effective 
and current vaccination coverage must be documented for N. meningitidis types A, C, W, and Y 
and for S. pneumoniae. Vaccination for N. meningitidis type B and for H. influenzae type B (Hib) 
is strongly encouraged where authorized and available. 
For those who have not received all of the required vaccines (including boosters) or vaccine 
series, administration of any needed vaccines should start no later than 14 days prior to Day 1. 
If the recommended vaccination coverage requires more than a single dose, then the additional 
dose(s) may be administered after Day 1 to complete the recommended vaccination coverage. 
If a vaccine is not available, the sponsor medical monitor (or designee) should be contacted to 
discuss potential options in order to satisfy eligibility requirement prior to completing the Day 1 
visit. 
Antibiotic prophylaxis must be given from Day 1 until a subject is considered fully vaccinated 
(ie 2 weeks after a booster and 2 weeks after the last vaccination in a series) for those who 
receive a N. meningitidis vaccine less than 14 days before the first dose of study drug. Local 
treatment guidelines should be followed for prophylactic antibiotic therapy for patients with 
PNH at the discretion of the investigator for those receiving treatment with complement 
inhibition. The screening window can be extended for required vaccinations as per 
Section 10.3.2. 
Unless local guidelines are more stringent, the US Centers for Disease Control and Prevention 
Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal 
vaccination and ACIP guidance for altered immunocompetence (including complement 
inhibition therapy) should be followed (Mbaeyi 2020, Kroger, Bahta, et al. 2021). For vaccines 
against serogroups A, C, W, and Y, a booster vaccine should be given every 5 years while on 
complement inhibitor therapy; the available vaccines are interchangeable. For vaccines against 
serogroup B, a booster vaccine should be given 1 year after the series completion and every 2 to 
3 years thereafter; the available vaccines are not interchangeable (Mbaeyi 2020). 
S. pneumoniae vaccination is also required; vaccination with both conjugate and polysaccharide 
vaccines is preferred. 
Vaccination or a booster vaccine against Hib is strongly encouraged for all study participants 
where authorized and available. 
Prior to randomization, each study participant’s vaccination record will be reviewed by the 
sponsor medical monitor or designee, and a plan for required vaccinations will be made based on 
ACIP guidelines, any national guidance, local practice, authorized vaccines, and vaccine 
availability. Investigators will also review each subject’s vaccination status at periodic intervals 


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to ensure that any needed booster vaccinations are administered at the optimal timing during the 
study. Please contact the sponsor medical monitor or designee for any questions. 
If a live vaccine needs to be given during the study, please contact the sponsor medical monitor 
or designee. 
10. 
STUDY CONDUCT 
10.1. 
Overview 
Prospective subjects will be qualified for the study during a screening period of up to 28 days 
prior to Day 1 (baseline). Once randomized, subjects will complete 2 consecutive treatment 
periods with a total duration of approximately 52 weeks. In the first, 24-week treatment period, 
subjects will be randomized to either discontinue C5 inhibitor therapy and start BCX9930 
monotherapy or to continue that C5 inhibitor therapy through Week 24. In the second, 28-week 
treatment period, subjects who are randomized to BCX9930 monotherapy in Part 1 will continue 
to receive BCX9930, while those subjects who are randomized to continue C5 inhibitor therapy 
in Part 1 will discontinue that therapy at the end of the first 24 weeks and start BCX9930 
monotherapy through Week 52. At the end of the study, it is anticipated that subjects who have 
completed treatment with BCX9930 and, in the opinion of the investigator, would benefit from 
continued treatment with BCX9930 will be allowed to do so. Subjects who do not qualify for 
continued treatment with BCX9930, or who choose not to continue treatment, will be required to 
complete an end-of-study (EOS) visit approximately 3 weeks after the last dose of BCX9930. 
During the combined 52-week treatment period, all subjects will be required to attend at least 
16 in-clinic study visits: Day 1 (Baseline), Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), 
Week 8 (Day 57), Week 12 (Day 85), Week 16 (Day 113), Week 20 (Day 141), Week 24 
(Day 169), Week 28 (Day 197), Week 32 (Day 225), Week 36 (Day 253), Week 40 (Day 281), 
Week 44 (Day 309), Week 48 (Day 337), and Week 52 (Day 365). Subjects who are randomized 
to continue C5 inhibitor treatment will complete two additional visits at Week 25 (Day 176) and 
Week 26 (Day 183). Additional visits will be required for subjects who experience acute 
symptomatic hemolysis on-study and/or who require additional post-treatment hemolysis 
assessment, or who require unscheduled visits for additional or repeat evaluations. 
Additional safety assessments will be required as part of the renal and hepatic safety monitoring 
program for all subjects when they initiate treatment with BCX9930, ie, Weeks 3, 5, 6, 7, and 10 
for subjects randomized to BCX9930 and Weeks 27, 29, 30, 31, and 34 for subjects randomized 
to continue C5 inhibitor therapy after switching to BCX9930 for Part 2. These additional 
assessments may be performed at the investigational site, at a laboratory local to the subject, or 
via a home health service (where permitted and available) and will be continued until sufficient 
data are available to allow for reduction or elimination of the additional assessments. 
Inclusive of the screening and potential post-treatment follow-up periods, each subject’s 
participation in this study is expected to span up to approximately 59 weeks. 


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10.2. 
Schedule of Assessments 
The schedule of study assessments/procedures for Part 1 of this study is presented in Table 4 and 
for Part 2 in Table 5. 
Assessments in the study are intended to be conducted in clinic; they may be conducted remotely 
under extenuating circumstances (eg, COVID-19 restrictions) which will be determined 
individually for each site and/or subject. 


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Table 4: 
Study BCX9930-202: Part 1 Schedule of Study Assessments/Procedures (Screening to Week 24) 
Assessment/ 
Procedure 
Screening 
(D-28 to D-
1)a 
Baselineb 
D1 
Part 1 Treatment (Study Week/Dayc) 
Unscheduled 
Visit 
(including for 
hemolysis 
assessment)d 
ETe 
Wk1 / D8 
Wk2 / D15 
Wk3 / D22 
Wk4 / D29 
Wk5 / D36 
Wk6 / D43 
Wk7 / D50 
Wk8 / D57 
Wk10 / D71 
Wk12 / D85 
Wk16 / D113 
Wk20 / D141 
Wk24 / D169 
Site visit 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
X 
Site visit or remote assessmentf 
 
 
 
 
X 
 
X 
X 
X 
 
X 
 
 
 
 
X 
 
Written informed consentg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical & medication historyh 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, body weight & BMIi 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
X 
Physical examinationj 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
12-lead ECGk 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
X 
Vital signsl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
Clinical chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis including 
microscopym 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation & haptoglobin 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
Drugs of abuse screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy testn 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
X 
FSHo 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBV, HCV, HIV, VZV 
testingp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Assessment/ 
Procedure 
Screening 
(D-28 to D-
1)a 
Baselineb 
D1 
Part 1 Treatment (Study Week/Dayc) 
Unscheduled 
Visit 
(including for 
hemolysis 
assessment)d 
ETe 
Wk1 / D8 
Wk2 / D15 
Wk3 / D22 
Wk4 / D29 
Wk5 / D36 
Wk6 / D43 
Wk7 / D50 
Wk8 / D57 
Wk10 / D71 
Wk12 / D85 
Wk16 / D113 
Wk20 / D141 
Wk24 / D169 
Urine for urinary biomarkersq 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PRO questionnairesr 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FACIT-Fatigue scale 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
 
QLQ-AA/PNH 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
 
Modified PRO-AA/PNH 
 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
 
TSQM 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
EQ-5D-5L 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
PGIS-Fatigue/Impact of 
Fatigue/ Physical 
Functioning 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
PGIC-Fatigue/Impact of 
Fatigue/ Physical 
Functioning 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Iron assessmentss 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
PK blood sample collectiont 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PD blood sample collectionu 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
Optional PK/PD substudyv 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK urine collectionw 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Randomizationx 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BCX9930 dispensingy 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
 
Drug accountability 
 
 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
Record AEs, concomitant 
medications & transfusionsz 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Abbreviations: AE = adverse event; BID = twice daily; BMI = body mass index; C5 = complement component 5; ECG = electrocardiogram; 
EQ-5D-5L = EuroQoL 5-dimension, 5-level; ET = early termination; 
; FACIT = Functional Assessment of Chronic Illness Therapy; 
FSH = follicle-stimulating hormone; Hb = hemoglobin; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; 
ICF = informed consent form; IWRS = interactive web response system; PD = pharmacodynamic(s); PGIC = Patient Global Impression of Change; 
PGIS = Patient Global Impression of Severity; PK = pharmacokinetic(s); PNH = paroxysmal nocturnal hemoglobinuria; pRBC = packed red blood cells; 
PRO = patient-reported outcome; PRO-AA/PNH = Patient-Reported Outcome Questionnaire for Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria; 
QLQ-AA/PNH = Quality of Life Questionnaire for patients with Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria; TSQM = Treatment Satisfaction 
Questionnaire for Medication; VZV = varicella-zoster virus. 
Note: X = procedure to be performed only at visits to investigational site. 
a All screening procedures do not need to be completed on the same day, but all screening procedures must be completed and the results reviewed and approved 
by the investigator (or designee) prior to randomizing a subject. 
b The baseline visit will be scheduled on or within 2 weeks prior to the date that the subject is scheduled to receive the next dose of eculizumab or within 2 weeks 
prior to the date on which the subject is scheduled to receive the next dose of ravulizumab, as applicable. 
c Visits may be performed within a window of ± 1 day for Week 1 and Week 2, and ± 3 days thereafter. 
d Subjects should be instructed to immediately contact the investigator if they have new or worsening symptoms of hemolysis. Following the permanent 
discontinuation of BCX9930, subjects may be required to complete an additional visit(s) to assess for acute symptomatic hemolysis if and when symptoms 
occur. 
e Subjects who discontinue the study for any reason will be asked to complete an ET visit approximately 3 weeks (± 3 days) after last dose of BCX9930 (or the 
decision to discontinue the study for subjects randomized to continue C5 inhibitor therapy). 
f Subjects randomized to BCX9930 will be required to complete additional assessments for enhanced renal and hepatic safety monitoring purposes. These 
assessments may be performed at the investigational site or remotely using a laboratory more convenient for the subject or via a home health service (where 
permitted and available); results from local laboratory testing must be provided to the investigational site. 
g Signing of the written ICF may occur in advance of the screening visit and must be obtained from the subject as required by national or local law and 
institutional practice, prior to conducting any study-related assessments/procedures. 
h Medical history will include baseline PNH clinical characteristics and disease burden and review of current and prior renal health. Medication history will 
include all medications administered specifically for PNH (including C5 and other complement inhibitors) and within 30 days prior to screening visit for all 
other medications taken. 
i Body weight will be captured at all assessments; height will be measured and BMI calculated at screening only. 
j A full physical examination will be completed at screening; all other physical examinations may be abbreviated (ie, symptom-driven) examinations, targeted to 
new or worsening signs and symptoms. 
k Bedside 12-lead ECGs will be conducted in triplicate pre-dose on Day 1 for all subjects, and at Week 24 for subjects randomized to continue C5 inhibitor 
before the first dose of BCX9930 is administered; all other ECGs may be single assessments. Subjects should rest quietly for 10 minutes in a supine position 
prior to the ECGs being performed. Any blood draws scheduled at the same time should occur after obtaining the ECG. 
l Vital signs (to include blood pressure, pulse rate, and temperature) will be performed at investigational site visits only (ie, excluding remote visits). Prior to 
obtaining blood pressure and pulse rate, subjects should rest quietly for a brief period. 
m Urine microscopy will be performed on urine collected at investigational site visits (and, where possible, at remote visits where the lab has appropriate on-site 
testing capability). Urine microscopy should be performed using the site’s local laboratory (assuming appropriate on-site testing capability exists) in lieu of the 
central laboratory. 


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n A serum pregnancy test will be administered to women of childbearing potential or who are postmenopausal for ≤ 2 years at screening. All other pregnancy 
tests performed during the study may be urine pregnancy tests (for women of childbearing potential only, or as required by normal institutional practice). The 
subject’s continued use of contraception should be reviewed throughout the study. 
o FSH will be measured at screening to confirm postmenopausal state in women who report being postmenopausal for < 2 years. 
p Tests for HIV serology and active HBV and HCV infection – to include hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, HIV 
antibody – and VZV immunoglobulin G titer. 
q Urine will be collected at investigational site visits (ie, excluding remote visits) and aliquots frozen for possible future analysis of urine biomarkers. 
r All PRO instruments except QLQ-AA/PNH will be administered electronically using a tablet or equivalent device; QLQ-AA/PNH will be administered in 
paper form. 
s Iron, ferritin, iron binding capacity, vitamin B12, and folate levels will be measured at screening. At baseline (Day 1), Week 24, and any ET visit performed, 
blood samples will be drawn for assessment of iron, total iron binding capacity, transferrin, ferritin, hepcidin, and erythroferrone at baseline and Week 24; urine 
collected at baseline and Week 24 will be analyzed for hemosiderin. 
t Single venous blood samples for analysis of plasma BCX9930 concentration will be collected from all subjects randomized to BCX9930 at each scheduled 
study visit, beginning Week 1, and at any unscheduled visits to the investigational site to assess for acute symptomatic hemolysis or perform additional safety 
assessments. The blood sample may be drawn without regard to BCX9930 dosing. PK samples will not be collected from subjects randomized to continue 
C5 inhibitor therapy, unless participating in the optional PK/PD substudy. 
u Blood samples for analysis of PD and clinical laboratory biomarkers will be collected at each study visit (including screening and Day 1) from all subjects 
regardless of treatment, including any unscheduled visit to assess for acute symptomatic hemolysis. 
v For subjects randomized to BCX9930 who participate in the optional PK/PD substudy, additional blood samples for analysis of plasma BCX9930 concentration 
will be drawn on Day 1 and at Week 2 or a later visit. For subjects randomized to continue C5 inhibitor therapy, additional blood samples will be collected at 
Week 24 only. In addition, where possible, additional blood samples for analysis of PD and clinical laboratory biomarkers will be drawn at each substudy visit. 
See Section 11.5.1.1 for additional details of the PK/PD substudy.  
w Spot urine samples will be collected for analysis of the concentration of BCX9930 and metabolites at investigational site visits (ie, excluding remote visits). PK 
samples will not be collected from subjects randomized to continue C5 inhibitor therapy. 
x Subjects will be randomized to receive BCX9930 or continue C5 inhibitor therapy using an IWRS prior to the planned baseline (Day 1) visit. 
y For subjects randomized to BCX9930 monotherapy, the first dose of BCX9930 will be administered in the clinic under the supervision of staff after completion 
of all pre-dose procedures. At the initiation of BCX9930 dosing, subjects will be administered a dose of 200 mg BID for the first 14 days of treatment before 
increasing to 400 mg BID. BCX9930 doses will be administered orally, approximately 12 hours apart and at approximately the same times each day, without 
regard to food. Subjects randomized to continue C5 inhibitor therapy will continue on that therapy at the same dosing regimen through the Week 24 visit. At 
the Week 24 visit, subjects will be transitioned to BCX9930 monotherapy. 
z AEs will be assessed and recorded from the time of signing of the ICF through the appropriate follow-up period. At each visit, subjects should be assessed for 
new or worsening signs and symptoms of PNH, including acute symptomatic hemolysis. Starting at randomization, subjects will be assessed for possible pRBC 
transfusion as described in Section 11.4.2. 
 


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Table 5: 
Study BCX9930-202: Part 2 Schedule of Study Assessments/Procedures (Weeks 25 to 52) 
Assessment/Procedure 
Part 2 Treatment (Study Week/Daya) 
Unscheduled 
Visit 
(including for 
hemolysis 
assessment)b 
EOS/ 
ETc 
Wk25 / D176d 
Wk26 / D183d 
Wk27 / D190 
Wk28 / D197 
Wk29 / D204 
Wk30 / D211 
Wk31 / D218 
Wk32 / D225 
Wk34 / D239 
Wk36 / D253 
Wk40 / D281 
Wk44 / D309 
Wk48 / D337 
Wk52 / D365 
Site visit 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Site visit or remote 
assessmente 
 
 
X 
 
X 
X 
X 
 
X 
 
 
 
 
 
X 
 
Body weight 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Physical examinationf 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGg 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Clinical chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis including 
microscopyi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation & haptoglobin 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testj 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Urine for biomarkersk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PRO questionnairesl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FACIT-Fatigue scale 
 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
 
QLQ-AA/PNH 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
 
Modified PRO-AA/PNH 
X 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
X 
 
 
TSQM 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 




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b Subjects should be instructed to immediately contact the investigator if they have new or worsening symptoms of hemolysis. Following the permanent 
discontinuation of BCX9930, subjects may be required to complete an additional visit(s) to assess for acute symptomatic hemolysis if and when symptoms 
occur. 
c Subjects who complete the study through Week 52 and who do not continue into the long-term extension study, and any subject who discontinues the study 
prior to Week 52 (for any reason), will be asked to complete an end-of-study or early termination visit, as applicable, approximately3 weeks (± 3 days) after 
last dose of BCX9930. 
d Subjects switched to BCX9930 for Part 2 will be required to complete additional investigational site visits at Weeks 25 and 26. 
e Subjects switched to BCX9930 for Part 2 will be required to complete additional laboratory assessments for enhanced safety monitoring purposes. These 
assessments may be performed at the investigational site or remotely using a laboratory more convenient for the subject or via a home health service (where 
permitted and available); results from local laboratory testing must be provided to the investigational site. 
f Abbreviated (ie, symptom-driven) physical examinations, targeted to new or worsening signs and symptoms. 
g Subjects should rest quietly for 10 minutes in a supine position prior to the ECGs being performed. Any blood draws scheduled at the same time should occur 
after obtaining the ECG. 
h Vital signs (to include blood pressure, pulse rate, and temperature) will be performed at investigational site visits only (ie, excluding remote visits). Prior to 
obtaining blood pressure and pulse rate, subjects should rest quietly for a brief period. 
i Urine microscopy will be performed on urine collected at investigational site visits (and, where possible, at remote visits where the lab has appropriate on-site 
testing capability). Urine microscopy should be performed using the site’s local laboratory (assuming appropriate on-site testing capability exists) in lieu of the 
central laboratory. 
j Urine pregnancy tests (for women of childbearing potential only, or as required by normal institutional practice). The subject’s continued use of contraception 
should be reviewed throughout the study. 
k Urine will be collected at investigational site visits and aliquots frozen for possible future analysis of urine biomarkers. 
l All PRO instruments except QLQ-AA/PNH will be administered electronically using a tablet or equivalent device; QLQ-AA/PNH will be administered in 
paper form. 
m At Week 52, and at any EOS/ET visit performed, blood samples will be drawn for assessment of iron, total iron binding capacity, transferrin, ferritin, hepcidin, 
and erythroferrone; urine will be analyzed for hemosiderin. 
n Single venous blood samples for analysis of plasma BCX9930 concentration will be collected at each scheduled study visit, and at any unscheduled visits to the 
investigational site to assess for acute symptomatic hemolysis or perform additional safety assessments. 
o Spot urine samples will be collected for analysis of the concentration of BCX9930 and metabolites at investigational site visits only (ie, excluding remote 
visits). 
p Blood samples for analysis of clinical laboratory biomarkers will be collected at each study visit from all subjects, including any visit to assess for acute 
symptomatic hemolysis. 
q For subjects previously randomized to continue C5 inhibitor therapy who participate in the optional PK/PD substudy, additional blood samples for analysis of 
plasma BCX9930 concentration will be drawn during the Week 26 or any later visit. In addition, where possible, time-matched blood samples for analysis of 
PD and clinical laboratory biomarkers will be collected at the same timepoints as the PK samples. See Section 11.5.1.1 for additional details of the PK/PD 
substudy. 
r For subjects randomized to continue C5 inhibitor therapy in Part 1 and newly switched to BCX9930 for Part 2, BCX9930 will be administered a dose of 
200 mg BID for the first 14 days of treatment before increasing to 400 mg BID. Subjects randomized to BCX9930 in Part 1 will continue BCX9930 400 mg 
BID. BCX9930 doses will be administered orally, approximately 12 hours apart and at approximately the same times each day, without regard to food. 


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s At each visit, the investigator (or designee) will assess the subject for new or worsening signs and symptoms of PNH, including acute symptomatic hemolysis. 
The need for pRBC transfusion will be assessed as described in Section 11.4.2. 


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10.3. 
Study Visits 
Unless indicated otherwise, all subjects are expected to complete all scheduled study 
assessments/procedures, regardless of treatment assignment. 
10.3.1. 
Screening 
Subjects with PNH who have been treated with C5 inhibitor therapy and who have had an 
inadequate response to that therapy, based on ongoing residual anemia, may be screened for this 
study. 
Written informed consent must be obtained from each subject before initiation of any screening 
assessments or procedures. Signing of the informed consent form (ICF) may occur prior to the 
first on-study visit, which is defined as the visit where site-conducted procedures are first 
performed. 
A 28-day window is provided to qualify subjects for the study. All screening procedures do not 
need to be completed on the same day, but all screening procedures must be completed and the 
results reviewed and approved by the investigator (or designee) prior to randomizing a subject. 
An important consideration for the timing of the screening visit is the collection of blood for 
hematological testing relative to any pRBC transfusion that may have been administered or is 
planned to be administered. Where possible, the screening visit should be scheduled such that the 
hematology sample is drawn prior to any planned pRBC transfusion, or at least 14 days after the 
subject’s last pRBC transfusion, as applicable. 
For subjects who are being treated with ravulizumab, which requires infusions to be administered 
at approximately 8-week intervals, screening and randomization should be scheduled to allow 
the baseline (Day 1) visit to be performed in the 2 weeks prior to administration of the next 
scheduled ravulizumab dose. For subjects who are being treated with eculizumab, with infusions 
administered at approximately 2-week intervals, screening and randomization should be timed to 
allow the baseline (Day 1) visit to be performed on or within 2 weeks prior to the date that the 
subject is scheduled to receive the next dose of eculizumab. It is acceptable for subjects to 
receive another dose of eculizumab before randomization to avoid limiting the screening window 
to 14 days. 
The following assessments will be performed at the screening visit(s): 
• Obtain written informed consent 
• Obtain demographic information 
• Review of inclusion-exclusion criteria 
• Medical history, including collection of PNH history, current and prior renal health, 
and confirmation of adequate vaccination status and either providing any 
protocol-required vaccinations and/or scheduling with local health care provider to 
have the subject vaccinated, as needed, where vaccination status cannot be confirmed; 
see Section 11.3. 
• Review medication history, including prohibited and restricted medications (see 
Section 9.8.1). All medications administered specifically for PNH (including C5 and 


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other complement inhibitors) and within 30 days prior to screening visit for all other 
medications will be recorded. 
• Record all blood transfusions administered in at least the 12 months prior to the 
screening visit 
• Full physical examination 
• 12-lead ECG 
• Height, weight, and body mass index (BMI) estimation 
• Vital signs (resting blood pressure and pulse rate, and temperature) 
• Blood collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), coagulation 
testing, and iron, ferritin, total iron binding capacity, folate, and vitamin B12 
− Blood for HBV, HCV, HIV, and VZV testing 
− Serum pregnancy test for female subjects of childbearing potential or who are 
postmenopausal for ≤ 2 years at screening 
− Blood collection for follicle-stimulating hormone (FSH) to confirm 
postmenopausal state in women who are postmenopausal for ≤ 2 years at 
screening 
• Blood collection for PD and clinical laboratory biomarkers 
• Blood collection for 
 
• Urine collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Urinalysis including microscopy 
− Urine drug screen 
A screening failure eCRF page will be completed for those subjects who do not proceed with 
study dosing, recording the reason for screening failure. 
10.3.2. 
Rescreening/Retesting 
Rescreening of ineligible subjects, where there is a reasonable expectation that the subject will 
become eligible, is permitted up to 2 times. If a subject is unable to be qualified in the 28-day 
window, eg, due to recent pRBC transfusion or acute illness, the screening window may be 
extended up to 14 additional days. Retesting of specific assessments without entirely rescreening 
a subject may be permitted with the approval of the sponsor medical monitor (or designee). 
10.3.3. 
Baseline Visit (Day 1) 
Subjects should be qualified for the study in time to allow the Day 1 visit to be scheduled no 
earlier than 2 weeks prior to the date on which the subject is due to receive the next scheduled 
dose of his or her current C5 inhibitor treatment. Where possible, the baseline (Day 1) visit 
should be scheduled such that the hematology sample is drawn prior to any planned pRBC 
transfusion, or at least 14 days after the subject’s last pRBC transfusion, as applicable. 


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Before any study drug is administered, the following assessments will be completed: 
• Administer PRO questionnaires; where possible, the questionnaires should be 
completed by the subject prior to other assessments to prevent influencing subject 
perceptions: 
− FACIT-Fatigue scale 
− QLQ-AA/PNH 
− Modified PRO-AA/PNH 
− EQ-5D-5L 
− PGIS-Fatigue, PGIS-Impact of Fatigue, PGIS-Physical Functioning 
• Review and update medical history, including PNH history, as needed 
• Review and update medication history, including prohibited and restricted 
medications. Record all medications administered specifically for PNH (including 
C5 and other complement inhibitors) and all other medications since screening visit. 
• 12-lead ECG (triplicate ECGs) 
• Targeted physical examination 
• Body weight 
• Vital signs (resting blood pressure and pulse rate, and temperature) 
• Blood collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), and 
coagulation testing 
− Blood for iron, total iron binding capacity, transferrin, ferritin, hepcidin, and 
erythroferrone 
• Blood collection for PK for subjects randomized to BCX9930 if participating in the 
optional PK/PD substudy; a total 4 samples will be drawn through 6 hours post-dose 
as described in Section 11.5.1.1. 
• Blood collection for PD and clinical laboratory biomarkers (all subjects). 
Note: if participating in the optional PK/PD substudy, where possible, a total of 
5 samples will be drawn through 6 hours post-dose as described in Section 11.5.1.1. 
• Blood collection for 
 
• Urine collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 
− Urine collection for hemosiderin 


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• Urine pregnancy test for female subjects of childbearing potential (or as required by 
local or institutional practice). A negative pregnancy test result must be recorded in 
order for the subject to receive study drug. 
• Review of inclusion-exclusion criteria (to confirm study eligibility) 
• Randomization (if not done previously) 
• Review/record AEs since screening visit 
• Record any blood transfusions administered since the screening visit 
After completion of all baseline procedures, subjects randomized to BCX9930 monotherapy will 
receive the first dose of BCX9930 administered under the supervision of clinic staff. Subjects 
participating in the optional PK/PD substudy will remain in the clinic for approximately 6 hours 
post-dose to allow for the collection of the additional post-dose PK and PD blood samples as 
described in Section 11.5.1.1. 
10.3.4. 
On-study Visits for Part 1: Weeks 1, 2, 4, 8, 12, 16, 20, and 24 
In Part 1, all subjects will return to the clinic during Week 1 (Day 8 ± 1 day), Week 2 
(Day 15 ± 1 day), Week 4 (Day 29 ± 3 days), Week 8 (Day 57 ± 3 days), Week 12 
(Day 85 ± 3 days), Week 16 (Day 113 ± 3 days), Week 20 (Day 141 ± 3 days), and Week 24 
(Day 169 ± 3 days). 
Subjects randomized to BCX9930 do not need to withhold any doses on clinic days or take a 
dose in the clinic, unless the clinic visit falls during the subject’s normal time of dosing or the 
subject is participating in the optional PK/PD substudy on that day. 
The following assessments will be performed at each visit unless otherwise indicated: 
• Administer PRO questionnaires; where possible, the questionnaires should be 
completed by the subject prior to other assessments to prevent influencing subject 
perceptions: 
− FACIT-Fatigue scale at Weeks 2, 4, 8, 12, 16, 20, and 24 
− QLQ-AA/PNH at Weeks 4, 8, 12, 16, 20, and 24 
− Modified PRO-AA/PNH at Weeks 1, 2, 4, 8, 12, and 24 
− TSQM at Weeks 4, 12, and 24 
− EQ-5D-5L at Week 24 
− PGIS-Fatigue, PGIS-Impact of Fatigue, PGIS-Physical Functioning at Week 24 
− PGIC-Fatigue, PGIC-Impact of Fatigue, PGIC-Physical Functioning at Week 24 
• 12-lead ECG (single ECGs, except at Week 24 for subjects randomized to continue 
C5 inhibitor for Part 1, when triplicate ECGs are required) 
• Targeted physical examination 
• Body weight at Weeks 4, 8, 12, 16, 20, and 24 
• Vital signs (resting blood pressure and pulse rate, and temperature) 


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• Blood collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), and 
coagulation testing 
− Blood for iron, total iron binding capacity, transferrin, ferritin, hepcidin, and 
erythroferrone at Week 24 
• Blood collection for PK. A single sample will be collected on each visit for subjects 
receiving BCX9930 unless the subject is participating in the optional PK/PD 
substudy. If participating in the PK substudy, a total of 4 or 5 samples will be drawn 
over an approximately 6-hour period at the selected substudy visit as described in 
Section 11.5.1.1 (Week 2 or later for subjects randomized to BCX9930 or at Week 24 
for subjects randomized to continue C5 inhibitor). 
• Blood collection for PD and clinical laboratory biomarkers. If participating in the 
optional PK/PD substudy, where possible, a total of 5 samples will be drawn over an 
approximately 6-hour period at the PK/PD substudy visit as described in 
Section 11.5.1.1 (Week 2 or later for subjects randomized to BCX9930 or at Week 24 
for subjects randomized to continue C5 inhibitor). 
• Blood collection for 
 
• Urine collection for clinical laboratory evaluations (see Table 4 and Table 7): 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 
− Urine collection for hemosiderin at Week 24 
• Urine collection for PK for subjects randomized to BCX9930 
• Urine pregnancy test for female subjects of childbearing potential (or as required by 
local or institutional practice) at Weeks 4, 8, 12, 16, 20, and 24. A negative pregnancy 
test result must be recorded in order for the subject to continue receiving BCX9930. 
• Study drug dispensing and drug accountability review (all visits for subjects 
randomized to BCX9930 and at Week 24 only for subjects randomized to continue 
C5 inhibitor therapy) 
• Review/record AEs, concomitant medication use, including prohibited and restricted 
medications, and blood transfusions 
At Week 24, subjects who were randomized to continue C5 therapy will receive the first dose of 
BCX9930 administered under the supervision of clinic staff. The timing of the final dose of the 
C5 inhibitor on or prior to Week 24 will be determined by the dose schedule for each individual 
subject. Subjects participating in the optional PK substudy will remain in the clinic for 
approximately 6 hours post-dose to allow for the collection of the additional post-dose PK blood 
samples as described in Section 11.5.1.1. 


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10.3.5. 
On-study Visits for Part 2: Weeks 25, 26, 28, 32, 36, 40, 44, 48, and 52 
In Part 2, all subjects will return to the clinic during Week 28 (Day 197 ± 3 days), Week 32 
(Day 225 ± 3 days), Week 36 (Day 253 ± 3 days), Week 40 (Day 281 ± 3 days), Week 44 
(Day 309 ± 3 days), Week 48 (Day 337 ± 3 days), and Week 52 (Day 365 ± 3 days). Subjects 
who are randomized to continue C5 inhibitor treatment in Part 1 will complete two additional 
visits at Week 25 (Day 176 ± 1 day) and Week 26 (Day 183 ± 1 day). The Week 25 and 
Week 26 visits do not need to be completed by subjects randomized to BCX9930 monotherapy 
in Part 1. 
Subjects do not need to withhold any BCX9930 doses on clinic days or take a dose in the clinic, 
unless the clinic visit falls during the subject’s normal time of dosing or the subject is 
participating on the optional PK/PD substudy on that day. 
The following assessments will be performed at each visit unless otherwise indicated (* = only 
subjects randomized to C5 inhibitor therapy in Part 1) 
• Administer PRO questionnaires; where possible, the questionnaires should be 
completed by the subject prior to other assessments to prevent influencing subject 
perceptions: 
− FACIT-Fatigue scale at Weeks 26*, 28, 32, 36, 40, 44, 48, and 52 
− QLQ-AA/PNH at Weeks 28, 32, 36, 40, 44, 48, and 52 
− Modified PRO-AA/PNH at Weeks 25*, 26*, 28, 32, 36, 48, and 52 
− TSQM at Weeks 28, 36, and 52 
− EQ-5D-5L at Week 52 
− PGIS-Fatigue, PGIS-Impact of Fatigue, PGIS-Physical Functioning at Week 52 
− PGIC-Fatigue, PGIC-Impact of Fatigue, PGIC-Physical Functioning at Week 52 
• 12-lead ECG 
• Targeted physical examination 
• Body weight at Weeks 28, 32, 36, 40, 44, 48, and 52 
• Vital signs (resting blood pressure and pulse rate, and temperature) 
• Blood collection for clinical laboratory evaluations (see Table 5 and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), and 
coagulation testing 
− Blood for iron, total iron binding capacity, transferrin, ferritin, hepcidin, and 
erythroferrone at Week 52 
• Blood collection for PK. A single sample will be collected on each visit unless the 
subject is participating in the PK/PD substudy. If participating in the optional PK/PD 
substudy, a total of 5 samples will be drawn over an approximately 6-hour period at 
the selected substudy visit as described in Section 11.5.1.1 (Week 26 or later). 


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• Blood collection for PD and clinical laboratory biomarkers. If participating in the 
optional PK/PD substudy, where possible, a total of 5 samples will be drawn over an 
approximately 6-hour period at the selected substudy visit as described in 
Section 11.5.1.1 (Week 26 or later). 
• Blood collection for 
 
• Urine collection for clinical laboratory evaluations (see Table 5 and Table 7): 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 
− Urine collection for hemosiderin at Week 52 
• Urine collection for PK 
• Urine pregnancy test for female subjects of childbearing potential (or as required by 
local or institutional practice) at Weeks 28, 32, 36, 40, 44, 48, and 52. A negative 
pregnancy test result must be recorded in order for the subject to continue receiving 
BCX9930. 
• Study drug dispensing and drug accountability 
• Review/record AEs, concomitant medication use, including prohibited and restricted 
medications, and blood transfusions 
10.3.6. 
Additional Assessments for Renal and Hepatic Safety Monitoring 
Additional assessments to monitor for potential renal toxicity will be performed during the first 
12 weeks of study treatment for subjects randomized to BCX9930 in Part 1 and for subjects 
newly switched to BCX9930 for Part 2 as specified in the schedule of events specified in Table 4 
for Part 1 or Table 5 for Part 2. The assessments may be performed at the investigational site, at 
a remote laboratory more convenient for the subject, or via a home health service (where 
permitted and available) and will be continued until sufficient data are available to allow for 
reduction or elimination of the additional assessments. 
The minimum procedures to be completed at each assessment will depend on whether the subject 
is assessed at the investigational site or remotely. 
For subjects assessed at the investigational site: 
• Review/record AEs, concomitant medication use, and blood transfusions 
• Vital signs (resting blood pressure, pulse rate, and temperature) 
• Blood collection for clinical laboratory evaluations 
− Clinical chemistry 
• Blood collection for PK 
• Urine collection for clinical laboratory evaluations: 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 


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• Urine collection for PK 
These assessments will also be performed for subjects identified with potential renal 
events and required to return to the investigational site on a weekly basis (see 
Section 12.5.2). 
For subjects assessed remotely: 
• Blood collection for clinical laboratory evaluations: 
− Clinical chemistry (to include at a minimum: sCr, eGFR, blood urea nitrogen, 
ALT, AST, ALP, and bilirubin [total and direct]) 
• Urine collection for clinical laboratory evaluations: 
− Urinalysis (to include at a minimum specific gravity, pH, protein, and blood) 
− Urine microscopy (only if the facility is deemed sufficiently qualified to perform 
this analysis) 
− Urine albumin to creatinine ratio (uACR) 
The enhanced safety assessments described in this amendment (ie, the additional assessments to 
be completed during the first 12 weeks of BCX9930 therapy) will be revisited and reviewed with 
the DMC after an additional approximately 15 subjects with PNH have completed through the 
first 8 weeks of monitoring between the current study and Study 203. 
10.3.7. 
Unscheduled Visits (Including for Assessment of Acute Symptomatic Hemolysis) 
At the investigator’s discretion, an unscheduled visit may be completed at any time during the 
study prior to the EOS/ET visit. Depending on the reason for the visit, any of the assessments 
described below may be performed, as appropriate. 
Following the permanent discontinuation of BCX9930 (or C5 inhibitor therapy), subjects may be 
required to complete an additional visit(s) to assess for acute symptomatic hemolysis if and when 
symptoms occur (see Section 12.5.3). 
If subjects attend an unscheduled visit to assess acute symptomatic hemolysis (see 
Section 12.5.3), all of the following assessments should be performed. If applicable, dosing 
compliance should also be reviewed to ensure that the subject is taking the drug correctly. Any 
missed doses should be recorded. 
• Review/record AEs, concomitant medication use, including prohibited and restricted 
medications, and blood transfusions 
• Vital signs (resting blood pressure and pulse rate, and temperature) 
• Targeted physical examination 
• Blood collection for clinical laboratory evaluations (see Table 4 [Part 1] or Table 5 
[Part 2] and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), and 
coagulation testing 
• Blood collection for PK 


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• Blood collection for PD and clinical laboratory biomarkers 
• Urine collection for clinical laboratory evaluations (see Table 4 [Part 1] or Table 5 
[Part 2] and Table 7): 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 
• Urine collection for PK 
• Any additional testing needed to evaluate for etiology of hemolysis (including acute 
symptomatic hemolysis), if applicable. This should include review of recent CACs 
(eg, infection, trauma, or surgery) that could have contributed to the hemolytic event. 
Consider testing for acute SARS-CoV-2 infection (the causative agent of COVID-19) 
in the correct setting. 
10.3.8. 
End-of-Study Visit/Early Termination Visit 
All subjects who complete the Week 52 visit, and either do not qualify for or choose not to 
continue treatment with BCX9930, will be asked to return to the clinic approximately 3 weeks 
(21 ± 3 days) after the date of the last dose of BCX9930 for an EOS visit. In addition, any 
subject who discontinues study treatment prior to Week 52 will be asked to complete the same 
procedures at an ET visit approximately 3 weeks (21 ± 3 days) after the date of the last dose of 
BCX9930 or the decision to withdraw from the study (for C5 inhibitor subjects in Part 1). 
The following assessments will be performed at the EOS/ET visit: 
• 12-lead ECG 
• Targeted physical examination 
• Body weight 
• Vital signs (resting blood pressure and pulse rate, and temperature) 
• Blood collection for clinical laboratory evaluations (see Table 4 [Part 1] or Table 5 
[Part 2] and Table 7): 
− Blood for hematology, clinical chemistry (including haptoglobin), and 
coagulation testing 
− Blood for iron, total iron binding capacity, transferrin, ferritin, hepcidin, and 
erythroferrone 
• Blood collection for PD and clinical laboratory biomarkers 
• Blood collection for 
 
• Urine collection for clinical laboratory evaluations (see Table 4 [Part 1] or Table 5 
[Part 2] and Table 7): 
− Urinalysis including microscopy 
− Urine collection for biomarker testing 


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− Urine collection for hemosiderin 
• Urine pregnancy test for female subjects of childbearing potential (or as required by 
local or institutional practice) 
• Drug accountability (if not completed earlier) 
• Review/record AEs, concomitant medication use, and blood transfusions 
If an AE, including a clinically significant laboratory abnormality, is ongoing at the end of study 
visit, additional clinic visit(s) or telephone contact(s) may be required (see Section 12.4). 
11. 
STUDY ASSESSMENTS 
11.1. 
Chronology of Assessments 
It is preferred that the PRO questionnaires be administered prior to completing other study 
procedures, and clinic procedures, such as ECGs, physical examinations, and vital signs 
measurements, should be completed prior to any blood collection. 
11.2. 
Demographic Information, Medical and Medication History 
Demographic information, and medical and medication history will be captured for each subject 
participating in the study at the screening visit. The medical and medication history review 
should include review of the subject’s current and prior renal health, and potential risk factors, 
including pre-existing chronic kidney disease, renal complications of PNH, inter-current illness, 
including the potential for renal tuberculosis in areas where the disease is endemic, vaccinations, 
and the use of potentially nephrotoxic medications. Medical history, medication review, and 
review of inclusion and exclusion criteria, potentially nephrotoxic medications, and prohibited 
and restricted medications will also be updated and rechecked at baseline (Day 1) as outlined in 
Section 10. 
A PNH history will be taken to document PNH clinical characteristics and disease burden, 
including time since diagnosis and history of MAVEs (including thrombotic events), bone 
marrow failure, pRBC transfusions, and PNH-related symptoms. Medication history will include 
details of all treatments administered specifically for PNH (including C5 and other complement 
inhibitors); all other medications will be documented beginning 30 days prior to screening. 
11.2.1. 
Contraception Requirements 
The following represents the minimum contraception that should be used by study participants 
and their partners. Additional contraceptive requirements (eg, requiring the female partners of 
male subjects to additionally use highly effective contraception) may be required by local site 
practice and/or the governing ethics committee. It is anticipated that that not all contraceptive 
methods may be available in all countries/regions, so the list should be modified accordingly. 
For the purposes of this study, females are considered fertile following menarche and until 
becoming postmenopausal, unless permanently sterile (ie, premenopausal with one of the 
following: documented hysterectomy, documented bilateral salpingectomy, or documented 


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bilateral oophorectomy). Documentation can come from site personnel’s review of the subject’s 
medical records, medical examination, or medical history interview. 
Female participants must meet at least one of the following requirements: 
1. Be a woman of nonchildbearing potential, either postmenopausal (defined as without 
menses for ≥ 12 months without an alternative medical cause with an FSH > 40 mIU/mL) 
or had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. 
2. Be a woman of childbearing potential (defined as a female following menarche and prior 
to becoming post-menopausal who has not had a hysterectomy, bilateral salpingectomy, 
or bilateral oophorectomy) who agrees to use a highly effective contraceptive method 
while enrolled in the study and for a duration of 30 days after last dose of study drug. 
Note: If the minimum period of contraceptive use recommended in the relevant prescribing 
information after the last dose of eculizumab or ravulizumab, as applicable, is longer than 
30 days after the last dose of BCX9930, then the subject should continue to use contraception for 
that longer period. 
The following methods are acceptable: 
− surgical sterilization (ie, bilateral tubal occlusion or vasectomy of the sole male 
partner and the vasectomized partner has received medical assessment of surgical 
success) 
− intrauterine device (IUD) or intrauterine system (IUS) 
− combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, transdermal) 
− progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable) 
Women of childbearing potential who declare themselves sexually abstinent or exclusively 
having female sexual partners do not need to use highly effective contraception. Abstinence in 
this study is defined as true abstinence, when it is in line with the subject’s preferred and usual 
lifestyle. If a subject is usually not sexually active but becomes active, she, with her partner, 
must meet the requirements listed above. 
Female subjects must abstain from egg donation throughout the study and for a duration of 
30 days after last dose of study drug. 
Male participants must meet at least one of the following requirements:  
1. Males with a female partner of childbearing potential (as defined above) must agree to 
use condoms while enrolled in the study and for at least 90 days after the last dose of 
study drug unless their partner is using a highly effective contraceptive method as defined 
above independent of the study. 
2. Males who declare themselves sexually abstinent or having exclusively male partners are 
not required to use contraception. Abstinence in this study is defined as true abstinence, 
when it is in line with the subject’s preferred and usual lifestyle. If a subject is usually not 
sexually active but becomes active, the criteria listed above must be met. 


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Male subjects must abstain from sperm donation throughout the study and for a duration of 
90 days after last dose of study drug. 
Methods of contraception, as applicable, for both male and female participants should be 
documented in the source documentation. 
11.3. 
Immunity Assessment 
In Study 101, a subject with PNH and multiple risk factors including occupation, concomitant 
corticosteroids, and additional immunosuppression developed disseminated varicella infection as 
an unrelated SAE. Antibodies to VZV will be tested in all subjects at screening. If an exposure to 
VZV occurs during the study, this will help the investigator assess the risk for developing 
primary varicella for non-immune subjects. Any subject who has an exposure to someone with 
primary varicella (chickenpox) or herpes-zoster (shingles), or who has recently received a live 
varicella vaccine should contact the investigator and administration of varicella zoster immune 
globulin or other medications should be considered, where available. 
11.4. 
Efficacy/Effectiveness Assessments 
11.4.1. 
Clinical and Laboratory Measurements of PNH 
Clinical measurements of PNH include clinical laboratory testing for Hb, LDH, ARC, 
haptoglobin, and bilirubin; number of pRBC transfusions and number of pRBC units 
administered; assessment of PNH-associated clinical symptoms (eg, fatigue, dyspnea, chest 
pain/discomfort, dysphagia, abdominal pain, headache, erectile dysfunction, hemoglobinuria, and 
jaundice); and the incidence of acute symptomatic hemolysis and MAVEs, including thrombotic 
events. 
At each visit, the investigator (or designee) will assess the subject for new or worsening signs 
and symptoms of PNH, including acute symptomatic hemolysis. Starting at randomization, 
subjects will be assessed for possible pRBC transfusion as described in Section 11.4.2. 
11.4.2. 
Blood Transfusions 
At screening, the number of and type of blood transfusions administered within at least the prior 
12 months will be recorded. During the study, all blood transfusions will be documented, 
including the number of units and the type of blood product administered. 
In order to standardize the approach to transfusions on-study, beginning at randomization 
through completion of the Week 52 visit, it is recommended that pRBC transfusion be 
administered to subjects who meet either of the following criteria: 
• Hb value of ≤ 9 g/dL and, in the opinion of the investigator, with symptoms 
warranting transfusion, or 
• Hb value of ≤ 7 g/dL regardless of symptoms 
Transfusions will be administered based on the results of local laboratory Hb values (or central 
laboratory values if local laboratory values are not available) and, where applicable, the 
investigator’s assessment of the subject’s PNH symptoms. The investigator (or designee) will 
determine the appropriate number of units of pRBCs to be transfused. Administration of each 


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pRBC transfusion, including the date of transfusion, the Hb result and source (ie, local or central 
laboratory, as applicable) and associated symptoms warranting transfusion (if applicable) that 
triggered the transfusion, and the number of units transfused, will be documented in the eCRF. 
11.4.3. 
Clinical Measurements of Iron, Folate, and Vitamin B12 
Most patients with PNH who are not receiving C5 inhibitor therapy are iron‐depleted due to IVH 
and loss through the kidneys. When treated with eculizumab, C5 blockade results in increased 
C3 levels upstream in the complement cascade. The resulting increase in EVH, in combination 
with chronic blood transfusion, is reported to contribute to iron load in some patients over time 
(Risitano, Notaro, et al. 2012, Roth, Rottinghaus, et al. 2018). 
To investigate the iron status in the study participants, all subjects will have blood samples 
drawn for assessment of iron, total iron binding capacity, transferrin, ferritin, hepcidin, and 
erythroferrone at baseline, Week 24, Week 52, and the EOS/ET visit; urine collected at these 
visits will be analyzed for hemosiderin. Iron, ferritin, total iron binding capacity, vitamin B12, 
and folate levels will also be measured at screening to assess the status of these analytes. 
11.4.4. 
Patient-reported Outcomes 
The following PRO instruments will be used during this study, where translations into the local 
language are available: 
• FACIT-Fatigue scale 
• QLQ-AA/PNH 
• Modified PRO-AA/PNH 
• TSQM 
• EQ-5D-5L 
• PGIS-Fatigue, PGIS-Impact of Fatigue, PGIS-Physical Functioning 
• PGIC-Fatigue, PGIC-Impact of Fatigue, PGIC-Physical Functioning 
With the exception of the QLQ-AA/PNH, the available PRO instruments will be administered 
electronically using a tablet or equivalent device; the QLQ-AA/PNH will be administered in 
paper form. For all subject-completed forms, clinic staff should ensure the subject reads the 
instructions and completes the questionnaire in full. The investigator and clinic staff are not 
permitted to provide any assistance, interpretation, or clarification of information or questions 
contained in the questionnaires. Where possible, the questionnaires should be completed by the 
subject prior to other assessments for that visit to prevent assessments from influencing subject 
perceptions (Section 11.1). 
11.4.4.1. FACIT-Fatigue Scale 
The FACIT-Fatigue scale was derived from instrument development work conducted in 1994 
and 1995 to evaluate fatigue associated with anemia in cancer patients (Yellen, Cella, et al. 
1997). It contains 13 items which assess self-reported tiredness, weakness, and difficulty 
conducting usual activities due to fatigue. Items are measured on a 5-point Likert-type scale of 
0 to 4 from “Not at all” to “Very much”, respectively. The FACIT-Fatigue total score is derived 


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by summing all items and ranges from 0 to 52; items are reverse scored, when appropriate, to 
provide a scale in which a higher score indicates better functioning or less fatigue (Cella, Lai, et 
al. 2002). Experience and Impact scores may also be obtained by aggregating the 5 Experience 
items and the 8 Impact items separately (Cella, Lai, et al. 2011). The recall period for each 
question is the past 7 days. Content validation of the FACIT-Fatigue scale was examined in a 
cross-sectional validation study involving cognitive debrief interviews with patients with PNH 
(Weitz, Meyers, et al. 2013). The FACIT-Fatigue scale total score has been shown to be 
responsive to change in both clinical and observational studies. Using both anchor- and 
distribution-based methods, the minimal important difference (MID) for the FACIT-Fatigue 
scale total score is 3 points. Currently, there are no published interpretation thresholds for the 
FACIT-Fatigue Experience and Impact scores (Cella, Lai, et al. 2002). 
The FACIT-Fatigue scale will be administered at baseline (Day 1) and at Weeks 2, 4, 8, 12, 16, 
20, 24, 28, 32, 36, 40, 44, 48, and 52 for all subjects, and at Week 26 for subjects randomized to 
continue C5 inhibitor therapy. 
11.4.4.2. QLQ-AA/PNH 
The QLQ-AA/PNH is a 54-item patient-reported instrument developed to assess symptom 
burden and HRQoL in patients with AA and/or PNH (Groth, Singer, et al. 2017, Niedeggen, 
Singer, et al. 2019). It consists of 10 preliminary hypothesized domains including: 1) Social 
Support, 2) Fear of Progression and Illness Intrusiveness, 3) Fatigue, 4) Other Symptoms, 
5) Infections, 6) Physical Functioning, 7) Role Functioning, 8) Emotional Functioning, 
9) Stigmatization, and 10) Body Image. The recall period varies by items with a recall of 7 days 
for items 1 to 52, and a recall period of 6 months for items 53 and 54. Response options for all 
items are “Not at all”, “A little”, “Moderately”, and “Very” or “A lot”. 
The QLQ-AA/PNH will be administered at baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 
28, 32, 36, 40, 44, 48, and 52 for all subjects. 
11.4.4.3. Modified PRO-AA/PNH 
The PRO-AA/PNH is modified from the patient-centered version of the PRO-AA/PNH 
questionnaire developed by Weisshaar and colleagues (Weisshaar, Ewald, et al. 2020). As 
modified, the questionnaire includes the 11 PNH symptom questions from the original 
PRO-AA/PNH patient-centered questionnaire (ie, excluding the 3 AA-specific questions): 
1) Fatigue, 2) Bleeding, 3) Shortness of Breath, 4) Mood, 5) Memory and Concentration, 
6) Heart Palpitations, 7) Gastrointestinal Problems, 8) Pain, 9) Dark Urine [Hemoglobinuria], 
10) Difficulty Swallowing [Dysphagia], and 11) Itching, plus the Erectile Dysfunction question 
from the physician-centered version of the PRO-AA/PNH questionnaire. For symptoms other 
than Bleeding and Dark Urine, additional questions assess the frequency, severity and/or impact 
of the symptoms on the subject’s usual or daily activities. The bleeding-related questions follow 
the modified World Health Organization (WHO) bleeding scale for locations and severity 
grading. The recall period is the last 7 days. 
The modified PRO-AA/PNH will be administered at baseline (Day 1) and at Weeks 1, 2, 4, 8, 
12, 24, 28, 32, 36, 48, and 52 for all subjects and at Weeks 25 and 26 for subjects randomized to 
continue C5 inhibitor therapy. 


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11.4.4.4. TSQM 
The TSQM (Version 1.4) consists of 14 items of which 13 items are made up of 3 specific scales 
(effectiveness, side effects, and convenience) and a global satisfaction scale (global satisfaction). 
In addition, 1 item (Item 4) questions whether the subject experienced any side effects at all as a 
result of taking this medication, which can be answered by yes or no. Scale scores are calculated 
for each scale and are transformed into scores ranging from 0 to 100, with higher scores 
indicating higher satisfaction. The recall period is the last 2 to 3 weeks, or since the medication 
was last used. 
The TSQM will be administered at Weeks 4, 12, 24, 28, 36, and 52. 
11.4.4.5. EQ-5D-5L 
The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale 
(EQ VAS). The descriptive system (EQ-5D-5L) comprises 5 dimensions: mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no 
problems, slight problems, moderate problems, severe problems, and extreme problems. The 
patient is asked to indicate his/her health state by ticking the box next to the most appropriate 
statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses 
the level selected for that dimension. The digits for the 5 dimensions can be combined into a 
5-digit number that describes the patient’s health state. There is no recall period; the health status 
captured by EQ-5D-5L reflects the respondent’s status at the time of completion. 
The EQ VAS records the respondent’s self-rated health on a 20-cm vertical VAS. The VAS is 
numbered from 0 to 100 with 0 meaning “the worst health you can imagine” and 100 meaning 
“the best health you can imagine”. This information can be used as a quantitative measure of 
health as judged by the individual respondents. The EQ VAS asks respondents to simply “mark 
an X on the scale to indicate how your health is TODAY” and then to “write the number you 
marked on the scale in the box below”. 
The EQ-5D-5L will be administered at baseline (Day 1) and at Weeks 24 and 52. 
11.4.4.6. PGIS-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical Functioning 
Subjects will be asked to rate the severity of their fatigue, the impact of their fatigue on their 
usual activities, and how much their PNH symptoms interfere with physical functioning using 
the PGIS-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical Functioning, respectively. The 
recall period is the past 7 days. The severity and impact of fatigue will both be assessed on a 
4-point scale with responses ranging from 1 = “None” to 4 = “Severe”. Interference will be 
assessed using a 5-point scale with responses ranging from 1 = “Not at all” to 5 = “Very much”. 
The PGIS-Fatigue, PGIS-Impact of Fatigue, and PGIS-Physical Functioning will be administered 
at baseline (Day 1) and at Weeks 24 and 52. 
11.4.4.7. PGIC-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning 
Subjects will be asked to rate changes in the severity of their fatigue, the impact of their fatigue 
on their usual activities, and how much their PNH symptoms interfere with physical functioning 
using the PGIC-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning, respectively. 
At Week 24, all subjects will be asked how the severity and impact of their fatigue, and 


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interference of their PNH symptoms with physical functioning have changed since the start of 
the study. At Week 52, subjects who switched from the C5 inhibitor to BCX9930 will be asked 
to rate the change since stopping their C5 inhibitor and starting BCX9930. All other subjects will 
be asked how their fatigue, the impact of their fatigue, and interference of their PNH symptoms 
with physical functioning have changed, thinking back over the past 6 months. All changes will 
be assessed on a 7-point Likert scale ranging from 1 = “Very much improved” to 7 = “Very 
much worse”. 
The PGIC-Fatigue, PGIC-Impact of Fatigue, and PGIC-Physical Functioning will be 
administered at Weeks 24 and 52. 
11.5. 
Pharmacokinetic and Pharmacodynamic Assessments 
Detailed instructions for collection, processing, storage, and shipment of PK and PD samples 
will be provided in a separate laboratory manual. 
11.5.1. 
Blood Sampling for Pharmacokinetic Analysis 
For subjects randomized to BCX9930, single venous blood samples for measurement of plasma 
BCX9930 concentrations (“sparse sampling” to support PPK and PK/PD modeling) will be 
collected at each scheduled study visit to the investigational site, beginning at Week 1, and at any 
visits to the investigational site to assess for acute symptomatic hemolysis or perform additional 
safety assessments. PK samples will not be collected at the baseline (Day 1) visit unless subjects 
participate in the optional PK/PD substudy. For subjects randomized to continue C5 inhibitor 
therapy, PK samples will not be collected until after they have been switched to BCX9930 in 
Part 2 (ie, beginning at the Week 25 visit for subjects not participating in the PK/PD substudy). 
Sparse PK blood samples may be drawn at any time without regard to BCX9930 dosing. 
However, where feasible, investigators are requested to vary the timing of non-PK/PD substudy 
visits to facilitate PK sampling at different times relative to the previous dose. It is preferred that 
the cumulative sparse PK data for each subject will contain samples drawn within each of the 
following intervals (all relative to the previous dose for BID dosing): 0.5 to 2 hours, 2 to 5 hours, 
and 10 to 12 hours post-dose. 
Subjects do not need to withhold any BCX9930 doses during these visits or take a dose in the 
clinic, unless the visit falls during the subject’s normal dose time or the subject is participating in 
the PK/PD substudy on that day (see Section 11.5.1.1). 
For each sample collected, the actual date and time of sample collection, the actual date and time 
of the last two BCX9930 doses taken prior to the blood draw (where applicable), and whether 
those doses were taken with or without food will be recorded in the eCRF. 
Plasma samples for determination of BCX9930 will be analyzed using validated liquid 
chromatography-mass spectrometry assays. The plasma concentration of BCX9930 metabolites 
may also be analyzed using these samples. 
Any unused portion of the plasma samples collected for PK purposes will be retained for 
possible repeat or future PK analysis of BCX9930 and/or identified metabolites. Subjects can 
request for these samples to be destroyed at the end of the study, but any data previously 
collected will be retained. 


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11.5.1.1. Optional Pharmacokinetic/Pharmacodynamic Substudy 
At study centers with appropriate facilities for the collection and processing of serial plasma 
samples, an optional PK/PD substudy will be performed to characterize the single-dose and 
steady-state PK parameters of BCX9930 in this patient population and contribute to PPK and 
PK/PD models. 
At these centers, subjects consenting to participate in the optional PK/PD substudy will be asked 
to complete up to two serial PK sample collections. The first sample collection will assess the 
single-dose PK of BCX9930, with samples collected on Day 1 for subjects randomized to 
BCX9930 or during the Week 24 visit for subjects randomized to continue C5 inhibitor therapy 
in Part 1 of the study. The second sample collection will assess the PK of BCX9930 at steady 
state, with samples collected during the Week 2 or any later visit for subjects randomized to 
BCX9930 or during the Week 26 or any later visit for subjects randomized to continue 
C5 inhibitor therapy in Part 1 of the study. 
For subjects randomized to BCX9930: 
• On Day 1, 4 PK blood samples will be collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours after administration of the first dose of BCX9930. 
• At the Week 2 or later visit, 5 PK blood samples will be collected; the first sample 
will be collected prior to BCX9930 dosing (≤ 15 minutes), with subsequent samples 
collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. 
For subjects randomized to continue C5 inhibitor therapy: 
• At the Week 24 visit, 4 PK blood samples will be collected at 0.5 (± 0.25), 
1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours after administration of the first dose of 
BCX9930. 
• At the Week 26 or later visit, 5 PK blood samples will be collected; the first sample 
will be collected prior to BCX9930 dosing (≤ 15 minutes), with subsequent samples 
collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. 
For the second sample collections (ie, on or after Week 2/Week 26 or later visit), the subject’s 
scheduled dose of BCX9930 should not be taken at home but administered in the clinic after 
collection of the pre-dose sample, as close as possible to the subject’s regularly scheduled dose 
time (and as close as possible to 12 hours after the previous dose), with the remaining samples 
collected after dosing in the clinic. The pre-dose blood sample should be collected immediately 
(≤ 15 minutes) prior to dosing.  
On both occasions, the actual date and time of each blood sample collection and the actual date 
and time of observed BCX9930 dose will be recorded in the eCRF. In addition, for the 
steady-state collection at the Week 2/Week 26 or later visit, the actual date and time of the last 
two BCX9930 doses taken prior to the pre-dose blood collection (assumed to be the two doses 
taken the previous day), and whether those doses were taken with or without food will also be 
recorded in the eCRF. 
In addition, where possible, taking into account blood volume requirements, subjects will have 
5 PD samples collected at each substudy visit. 


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For subjects randomized to BCX9930: 
• On Day 1, the first sample will be collected prior to BCX9930 dosing (≤ 2 hours), 
with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 
6 (± 1) hours post-dose.  
• At the Week 2 or later visit, the first sample will be collected prior to BCX9930 
dosing (≤ 15 minutes), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours post-dose. 
For subjects randomized to continue C5 inhibitor therapy: 
• At the Week 24 visit, the first sample will be collected prior to BCX9930 dosing 
(≤ 2 hours), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), 
and 6 (± 1) hours post-dose.  
• At the Week 26 or later visit, the first sample will be collected prior to BCX9930 
dosing (≤ 15 minutes), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours post-dose. 
As applicable, PD blood samples will be collected at the same time as the corresponding PK 
blood sample (ie, excluding the pre-dose sample on Day 1 or Week 24). Additional guidance on 
prioritizing sample collections where there are blood volume concerns will be provided in the 
separate laboratory manual. 
Ideally, subjects will participate in both serial PK/PD sample collections. However, subjects who 
do not participate at the Day 1/Week 24 serial PK/PD sample collection can still participate in 
the later steady-state PK/PD collection. 
Plasma PK parameters of BCX9930 metabolites may also be assessed using these samples. 
A tabular summary of the PK and PD sampling is provided in Table 6. 
11.5.2. 
Urine Collection for Measurement of Parent-Metabolite Concentration 
Spot urine samples will be collected for analysis of the concentration of BCX9930 and 
metabolites during Part 1 for subjects randomized to BCX9930 and from all subjects in Part 2. 
Urine samples for determination of BCX9930 will be analyzed using validated liquid 
chromatography-mass spectrometry assays. The concentration of BCX9930 metabolites may also 
be analyzed using these samples. 
For each sample collected, the actual date and time of sample collection, the actual date and time 
of the last two BCX9930 doses taken prior to the urine collection (where applicable), and 
whether those doses were taken with or without food will be recorded in the eCRF. 
11.5.3. 
Blood Sampling for Analysis of Pharmacodynamic and Complement 
Biomarkers 
Blood samples will be analyzed for concentrations of complement cleavage products 
(eg, Factor Bb and sC5b-9). The capacity of the complement system will be assessed by 
measuring these analytes or the activity of the AP using ex vivo stimulation assays, such as 
AP Wieslab, that activate the AP in blood samples using a specific stimulus. Deposition of 


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complement byproducts onto cell membranes (such as C3-opsonized RBCs) will be measured 
using flow cytometry to assess potential drug-induced changes in opsonization of PNH RBCs. 
Additional exploratory assays (eg, for chemokines or cytokines) may be evaluated. Samples 
collected may be run in more than one assay to elucidate the PD effects of BCX9930. The 
analyses variously need serum, plasma, and whole blood, so more than one collection tube type 
will be needed. 
Blood samples for analysis of PD and complement biomarkers will be collected at each study 
visit (including screening and baseline [prior to dosing on Day 1]) from all subjects regardless of 
treatment, including any visit to assess for acute symptomatic hemolysis or hemolysis 
monitoring following discontinuation of therapy. Where feasible, and as applicable, blood 
samples for PD analyses should be collected at the same time as sparse PK samples. Subjects 
randomized to continue C5 inhibitor therapy in Part 1 should have their Week 24 PD sample 
collected prior to administration of the first dose of BCX9930. 
The PD and complement biomarkers for assessment may include, but are not limited to: 
• Ex vivo AP activity (as assessed by AP Wieslab assay) 
• Ex vivo AP-activated complement biomarkers: Factor Bb, C3a, and C5a 
• Constitutive complement biomarkers: Factor D (as the pharmacologic target), 
Factor Bb, and sC5b-9 
Acute symptomatic hemolysis will be evaluated, where possible. The PD and complement 
biomarkers for assessment of acute symptomatic hemolysis may include, but are not limited to: 
• Ex vivo AP activity (as assessed by AP Wieslab) 
• Ex vivo AP-activated complement biomarkers: Factor Bb, C3a, and C5a 
• Constitutive complement biomarkers: Factor D (as the pharmacologic target), 
Factor Bb, total C3*, C3a, total C4*, C4a*, and sC5b-9 
* In subjects experiencing acute symptomatic hemolysis, as applicable, these additional analytes 
will also be evaluated in previously collected samples to provide internal reference values for the 
acute symptomatic hemolysis values. 
The following are considered key clinical laboratory blood biomarkers of AP activity: 
AP Wieslab and constitutive levels of Factor Bb and sC5b-9. Not all PD and complement 
biomarkers will be assessed at all timepoints. The plans for analysis of other biomarkers may be 
modified based on emerging data, eg, if data show that a particular biomarker is redundant or the 
assay is of poor quality. 
PNH clone size (total PNH RBC [ie, Type II plus Type III], PNH WBC, and the ratio of total 
PNH RBC to PNH WBC) will be assessed at each visit, along with C3 deposition (ie, C3 RBC 
opsonization) as a marker of the potential for EVH. 
 
 
Any unused portion of the whole blood, plasma, or serum collected for PD purposes will be 
retained for possible repeat or future analysis of biomarkers related to PNH and other 
complement-mediated disease. Subject can request for these samples to be destroyed at the end 
of the study, but any data previously collected will be retained. 


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A tabular summary of the PD sampling is provided in Table 6. 
(Note: Some PD and complement biomarkers may not be analyzed, depending on the availability 
of validated assays at the designated regional bioanalytical laboratory.) 


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Table 6: 
Summary of Pharmacokinetic and Pharmacodynamic Blood Sampling 
PK or PD 
Sampling 
Screening 
Day 1 
Study Week 
Hemolysis 
Assessment/ 
Monitoring 
Wk1 
Wk2 
Wk4 
Wk8 
Wk12 
Wk16 
Wk20 
Wk24 
Wk25 
Wk26 
Wk28 
Wk32 
Wk36 
Wk40 
Wk44 
Wk48 
Wk52 
Randomized to BCX9930 
PKa 
- 
- 
X 
X 
X 
X 
X 
X 
X 
X 
NA 
NA 
X 
X 
X 
X 
X 
X 
X 
X 
PDb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
NA 
NA 
X 
X 
X 
X 
X 
X 
X 
X 
Optional PK/PD Substudyc 
PK 
- 
4d 
- 
< ------------------------------------------------------------------ 5e ------------------------------------------------------------------- > 
- 
PD 
- 
5f 
- 
< ------------------------------------------------------------------ 5e ------------------------------------------------------------------- > 
- 
Randomized to Continue C5 inhibitor 
PKg 
 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PDb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Optional PK/PD Substudyh 
PK 
- 
- 
- 
- 
- 
- 
- 
- 
- 
4d 
- 
< ------------------------------ 5e ----------------------------- > 
- 
PD 
- 
- 
- 
- 
- 
- 
- 
- 
- 
5f 
- 
< ------------------------------ 5e ----------------------------- > 
- 
Abbreviations: C5 = complement component 5; PD = pharmacodynamic; PK = pharmacokinetic 
a Single venous blood samples for measurement of plasma BCX9930 concentrations will be collected at each scheduled study visit, beginning at Week 1, and at any visit to the 
investigational site to assess for acute symptomatic hemolysis (if and when symptoms occur) or to perform additional safety assessments (not shown). 
b Blood samples for analysis of PD and complement biomarkers will be collected at each study visit (including screening and Day 1) from all subjects regardless of treatment, 
including at any visit to assess for acute symptomatic hemolysis if and when symptoms occur. 
c The first sample collection will be performed on Day 1 and the second sample collection during the Week 2 or any later visit. 
d Four blood samples will be collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours after administration of the first dose of BCX9930. 
e Five blood samples will be collected, where possible; the first sample will be collected prior to BCX9930 dosing (≤ 15 minutes), with subsequent samples collected at 
0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. As applicable, PD blood samples will be collected at the same time as the corresponding PK blood samples. 
f Five blood samples will be collected, where possible; the first sample will be collected prior to BCX9930 dosing (≤ 2 hours), with subsequent samples collected at 0.5 (± 0.25), 
1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. As applicable, PD blood samples will be collected at the same time as the corresponding PK blood samples. 
g Single venous blood samples for measurement of plasma BCX9930 concentrations will be collected at each scheduled study visit, beginning at the Week 25 visit, and at any visit 
to the investigational site to assess for acute symptomatic hemolysis (if and when symptoms occur) or to perform additional safety assessments (not shown). 
h The first sample collection will be performed during the Week 24 visit and the second sample collection during the Week 26 or any later visit. 


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11.6. 
Optional Pharmacodynamic Analyses 
All study participants will be asked to consent to the storage of unused and/or residual PD 
samples collected in the study for possible additional research. The stored PD samples may be 
used for exploratory PD assays to evaluate the PD or PK of BCX9930. If a participant does not 
agree to have his or her PD samples stored, he or she can still participate in this study; all PD 
samples collected during the study will be destroyed upon completion of the study and all 
protocol-mandated analyses. All PD samples for which consent has been obtained will be stored 
for up to 10 years after completion of the study (or according to local regulations) for possible 
additional research. Stored samples will be coded throughout the sample storage and analysis 
process and will not be linked to any personal identifiers. Analysis of these samples is not 
intended for diagnostic or prognostic purposes and results will not be communicated back to the 
investigator or subjects. The research may begin at any time during the study or following 
completion of the study during the post-study storage period. 
11.7. 
Safety Assessments 
11.7.1. 
Vital Signs 
Vital signs comprising blood pressure, pulse rate, and temperature will be obtained per the 
schedule of assessments specified in Table 4 for Part 1 and Table 5 for Part 2. 
Measurements of vital signs should be obtained after the subject has rested for at least 5 minutes 
in a quiet room at a comfortable temperature, with the subject’s arm unconstrained by clothing or 
other material. Blood pressure measurements will be obtained with the appropriate cuff size, 
with the subject’s arm supported at the level of the heart, while the subject is resting in a 
semi-supine position. It is acceptable to obtain a pulse rate from the blood pressure or ECG 
machine. 
11.7.2. 
Body Weight, Height, and Body Mass Index 
Body weight will be recorded per the schedule of assessments presented in Table 4 for Part 1 and 
Table 5 for Part 2; height and BMI will be recorded at screening only. For determination of 
height and body weight, subjects should be clothed with shoes removed. 
11.7.3. 
Physical Examination 
Subjects will undergo a physical examination per the schedule of assessments specified in 
Table 4 for Part 1 and Table 5 for Part 2. 
A full physical examination should be performed per normal site practice as part of the screening 
evaluation (eg, genitourinary and breast examinations may be omitted when not required by 
normal site practice). A targeted (ie, symptom driven) physical examination will be performed at 
subsequent study visits to assess for any changes from the previous examination, including, at a 
minimum, evaluation of new or worsening signs or symptoms. 
11.7.4. 
Electrocardiogram 
A 12-lead ECG will be obtained per the schedule of assessments specified in Table 4 for Part 1 
and Table 5 for Part 2. 


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A standard bedside 12-lead ECG machine system that calculates heart rate and measures the PR, 
QRS, QT, RR, and corrected QT (QTc) intervals will be utilized. Twelve-lead ECGs will be 
measured after the subject has rested quietly in the supine position for a minimum of 10 minutes. 
All ECGs will be single assessments, with the exception of the baseline (Day 1) ECG, which will 
be recorded in triplicate. Triplicate ECGs will also be collected at the Week 24 visit for subjects 
randomized to C5 inhibitor before they are switched to BCX9930 in Part 2. 
Qualified site personnel should review the ECGs and automated findings in real time for gross 
abnormalities and interval measurements of concern (absolute readings and change from 
baseline). An ECG should be repeated after at least an additional 10-minute rest in a supine 
position in the event of a CFB (mean of pre-dose triplicate values on Day 1, or where applicable, 
Week 24 for subjects randomized to C5 inhibitor therapy) in QTcF (QT / ³√RR) of > 60 msec or 
an absolute QTcF interval of > 500 msec. 
For all ECGs, the clinical interpretation of the ECG should be recorded (including 
re-adjudication of any automatic findings) directly on a hard copy of the ECGs. Copies of the 
subject identifier-redacted ECGs may be requested by the sponsor. 
11.7.5. 
Clinical Chemistry, Hematology, Urinalysis, and Other Laboratory Assessments 
Blood and urine samples will be obtained per the schedule of assessments specified in Table 4 
for Part 1 and Table 5 for Part 2. Individual laboratory tests are specified in Table 7.  
In general, laboratory samples collected at visits to the investigational site should be collected 
using kits provided by the designated central laboratory. However, at the investigator’s 
discretion, local laboratories may be used in place of the central laboratory (eg, for logistical 
reasons such as delays in transport due to COVID-19) or for analysis of samples collected for 
assessment of possible AEs (eg, when emergent safety concerns require expedited turnaround 
times for safety laboratory assessments). Urine microscopy for samples collected at the 
investigational site will be performed at the site’s local laboratory, where appropriate on-site 
testing capability exists (see Section 11.7.5.1). The additional renal and hepatic safety 
assessments may be performed at the investigational site or remotely at a location more 
convenient for the subject or via a home health service. If the use of a home health service is 
permitted, testing may be performed at the central laboratory or at a remote laboratory. The 
results from laboratory testing performed at a local or remote must be provided to the 
investigational site. The use of a local or remote laboratory in this manner, and any differences in 
analyte panels with the central laboratory, based on the availability of testing at the local or 
remote laboratory, will not be considered protocol deviations for the purposes of this protocol. 
Reference ranges for each local or remote laboratory used will be provided to the sponsor and 
included in data listings. 
Results from laboratories should be reviewed as received by the investigator. Evidence of this 
review should be provided in the source records and may include printing of the laboratory 
reports with a signature attesting to a review. For out-of-range laboratory findings, the 
interpretation of clinically significant or not clinically significant should be denoted in the source 
records. Clinically significant laboratory findings, as assessed by the investigator, should be 
recorded as AEs as described in the protocol (Section 12.1). 


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Table 7: 
Clinical Laboratory Evaluations 
Serum Chemistry 
Urinalysisa 
Albumin 
Alanine aminotransferase (ALT) (SGPT) 
Alkaline phosphatase (ALP) 
Amylaseb 
Aspartate aminotransferase (AST) (SGOT) 
Bicarbonate or carbon dioxidec 
Bilirubin (total and direct) 
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Cholesterol (total, high- and low-density 
lipoprotein) 
Creatine (phospho)kinase (C[P]K) 
Creatinine (sCr) 
Glucose 
Haptoglobin 
Lactate dehydrogenase (LDH) 
Magnesium 
Potassium 
Sodium 
Protein (total) 
Triglycerides 
Uric acid 
Albumin 
Bilirubin 
Blood 
Creatinine 
Glucose 
Ketones 
Leukocytes 
Nitrites 
pH 
Protein 
Specific gravity  
Urobilinogen 
Urine Drug Screen 
Amphetamines 
Barbiturates 
Benzodiazepines 
Ecstasy 
Methamphetamine 
Opiates 
Pregnancy/Menopause 
Follicle-stimulating hormone (FSH) 
β-human chorionic gonadotropin (hCG)d 
Urine pregnancy teste 
Hematology 
Hemoglobin (Hb) 
Hematocrit (Hct) 
Mean corpuscular hemoglobin (MCH) 
Mean corpuscular hemoglobin concentration 
(MCHC) 
Mean corpuscular volume (MCV) 
Platelet count (PLT) 
Red blood cell (erythrocyte) count (RBC) 
Reticulocyte count 
White blood cell count (WBC) with differential 
Iron, Folate, and Vitamin B12 
Erythroferrone 
Ferritin 
Folate 
Hepcidin 
Hemosiderin (urine) 
Iron 
Total iron binding capacity 
Transferrin 
Vitamin B12 
Other Testing 
C3 opsonized RBCs 


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Coagulation/Fibrinolysis 
C-reactive protein 
Cystatin C (in blood) 
Estimated glomerular filtration rate(eGFR)f 
HBV surface antigen (HBsAg) 
HBV core antibody (HBcAb)g,h 
HCV antibody (HCVAb)i,h 
HIV antibodyj,h 
PNH RBC clone size (total) 
PNH WBC clone size 
VZV immunoglobulin G (IgG) titer 
Activated partial thromboplastin time (aPTT) 
 
Prothrombin time (PT) 
International normalized ratio (INR) 
 
Thrombin time 
Urine Biomarkersk 
β-2-microglobulin 
Cystatin C (in urine) 
Kidney injury molecule 1 (KIM-1) 
Liver-type fatty acid-binding protein (L-FABP) 
Urine albumin to creatinine ratio (uACR) 
Urine neutrophil gelatinase-associated lipocalin 
(uNGAL) 
Urine aliquots for storagel 
Abbreviations: DNA = deoxyribonucleic acid; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; PNH = paroxysmal nocturnal hemoglobinuria; RNA = ribonucleic acid; SGOT = serum 
glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase; VZV = varicella-zoster virus. 
Note: Some analytes may not be analyzed, depending on the availability of validated assays at the designated 
regional central laboratory. 
a For local laboratory testing, urinalysis analytes may be different. 
b If amylase is elevated, reflex to lipase. 
c In those regions where bicarbonate or carbon dioxide is analyzed and reported. 
d Serum (screening) or urine (all other scheduled visits) for women of childbearing potential or post-menopausal for 
≤ 2 years (or as required by institutional practice). 
e For women of childbearing potential (or as required by local or institutional practice). 
f To be calculated by the designated central reference laboratory using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) equation using the serum creatinine method (Levey and Stevens 2010). 
g Subjects with a positive HBV core antibody (HBcAb) test at screening will be reflexed to confirmatory HBV DNA 
viral load. 
h Confirmatory sample for serology may be collected at screening visit in some regions but analysis will be 
performed only if serology result is positive. Otherwise, confirmatory sample will be discarded. 
i Subjects with a positive HCV antibody test at screening will be reflexed to confirmatory HCV RNA viral load. 
j Subjects with a positive HIV antibody test will be reflexed to confirmatory HIV RNA viral load. 
k KIM-1 and L-FABP will not be tested at screening. Additional biomarkers may be recommended by the 
Nephrology Risk Mitigation Working Group. 
l Urine will be aliquoted, frozen, and sent to the central laboratory for possible future analysis of urine biomarkers. 
11.7.5.1. Urine Collections for Urinalysis, Microscopy, and Biomarker Testing 
Investigators should emphasize to staff and the subjects the importance of collecting fresh, 
high-quality urine specimens (clean-catch, mid-void, etc.) and ensuring appropriate handling and 
prompt analysis of the samples for urinalysis. Urine microscopy will be performed on all urine 
samples collected for urinalysis at investigational site visits. Because of the potential for 
extended transit times to the central laboratory, where possible, the urine microscopy should be 
performed using the site’s local laboratory (where appropriate on-site testing capability exists) in 


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lieu of the designated central laboratory. Urine microscopy should also be performed at any 
remote laboratory where appropriate on-site testing capability exists. If the local or remote 
laboratory does not have on-site testing capability, the sample may be sent to the designated 
central laboratory. 
Urine will be collected at all investigational site visits for analysis of uACR, β-2-microglobulin, 
cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule 1 
(KIM-1), and liver-type fatty acid-binding protein (L-FABP). In addition, aliquots of urine will 
be frozen and shipped to the central laboratory for storage for possible future analysis of urine 
biomarkers. 
11.7.6. 
Menopause and Pregnancy Testing 
FSH will be measured at screening in women declaring themselves postmenopausal ≤ 2 years to 
confirm non-childbearing status if above the reference range. At screening, a serum pregnancy 
test should also be drawn in the event that a female subject who is postmenopausal ≤ 2 years is 
found to be of childbearing potential. 
For all women of childbearing potential, a serum β-human chorionic gonadotropin (β-hCG) test 
will be performed at screening. Urine pregnancy tests will be assessed at baseline (Day 1) and 
every 4 weeks thereafter as specified in the schedule of events presented in Table 4 for Part 1 and 
Table 5 for Part 2, or as required per normal site practice. Urine pregnancy tests will be provided 
by the central laboratory, but will be administered and read at the clinical site. A serum 
pregnancy test should immediately be drawn and sent for analysis for any positive urine 
pregnancy test. Where required, pregnancy testing may be performed using the local laboratory, 
and using serum testing in lieu of the supplied urine pregnancy tests. 
For female participants who meet the criteria for postmenopausal status, an FSH can be 
measured during the study; pregnancy testing will continue until postmenopausal status by the 
above definition is met. 
12. 
ADVERSE EVENTS 
In this section, “study drug/IMP” is intended to refer to BCX9930 and/or C5 inhibitor therapy, 
unless otherwise noted. 
12.1. 
Definition of Adverse Events 
12.1.1. 
Adverse Event 
An AE is any untoward medical occurrence in a clinical study subject. No causal relationship 
with the study drug/IMP or with the clinical study itself is implied. An AE may be an 
unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during 
the clinical study. Clinically relevant abnormal results of diagnostic procedures including 
abnormal laboratory findings (eg, requiring unscheduled diagnostic procedures or treatment 
measures, or resulting in withdrawal from the study) are considered to be AEs. Abnormal results 
of diagnostic procedures that are incidental or not clinically relevant are not reportable as AEs. If 
the diagnostic procedure prompts no additional treatment, visits, or monitoring, it will not meet 
the definition of an AE. 


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This includes the following: 
• AEs not previously observed in the subject that emerge during the protocol-specified 
AE reporting period (see Section 12.4.1). 
• Findings from protocol-mandated interventions. This can include laboratory 
assessments performed in the course of the clinical study. AEs should be reported 
only if the abnormalities are changes from baseline and are clinically significant as 
described above. 
• Pre-existing medical conditions (other than the condition being studied) judged by the 
investigator to have worsened in severity or frequency or changed in character during 
the protocol-specified AE reporting period. When recording such events on an 
AE/SAE eCRF page, it is important to convey the concept that the pre-existing 
condition has changed by including applicable descriptors (eg, “more frequent 
headaches”). 
• In addition, for this study, the disease-related events of acute symptomatic hemolysis 
and MAVEs (including thromboembolic events) will be reported as AEs, even if 
deemed related to the disease under investigation. 
An adverse reaction is defined in International Council for Harmonisation (ICH) E6 guideline as 
follows: all untoward and unintended responses to a study drug/IMP related to any dose 
administered. The definition covers also medication errors and uses outside what is foreseen in 
the protocol, including misuse and abuse of the product. The definition implies a reasonable 
possibility of a causal relationship between the event and the study drug/IMP. This means that 
there are facts (evidence) or arguments to suggest a causal relationship. 
Hospitalization scenarios do not require reporting as an SAE where there is no occurrence of an 
AE. These scenarios include a planned hospitalization or prolonged hospitalization to: 
• Perform a routine control screening for a pre-existing illness or to diagnose a 
suspected illness. In the case of the latter, the symptomatology should be reported as 
an AE and amended if a diagnosis is confirmed. 
• Undergo a diagnostic or elective surgical procedure for a pre-existing medical 
condition that has not changed (eg, a joint replacement for which the subject was on a 
waiting list). 
• Undergo medical observation without the occurrence of an AE due to standard of care 
in the region or hospital. 
Surgical procedures should not be reported as AEs. The condition for which the surgery is 
required should be reported as the AE if it occurs or is detected during the study period. Planned 
surgical measures permitted by the clinical study protocol and the conditions(s) leading to these 
measures are not AEs if the condition(s) was (were) known before the start of study treatment. In 
the latter case, the condition should be reported as medical history. 
AEs are designated as “nonserious” or “serious”. 


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12.1.2. 
Serious Adverse Event  
An SAE is an adverse event/reaction that results in any of the following outcomes: 
• Death 
• Is life-threatening (subject is at immediate risk of death at the time of the event; it 
does not refer to an event that hypothetically might have caused death if it were more 
severe) 
• Requires subject hospitalization (formal admission to a hospital for medical reasons) 
or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (ie, there is a substantial 
disruption of a person's ability to carry out normal life functions) 
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, are not life-threatening, or do not require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, they 
may jeopardize the subject’s health or may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such events may include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, 
or convulsions that do not result in subject hospitalization.  
In addition, the sponsor considers any abortions (elective or spontaneous), fetal demise, and still 
birth to be SAEs for reporting purposes (see Section 14.4). 
Some hospitalization scenarios, as outlined in Section 12.1.1 do not require reporting as SAEs. 
Overdose will be considered an SAE only if any of the seriousness criteria are met. Any clinical 
complication in association with the overdose should be reported as an AE or SAE (as 
applicable) along with the overdose (see Section 12.5.4). Details of signs or symptoms, clinical 
management, and outcome should be reported, if available. Overdose without associated signs or 
symptoms should not be recorded as AEs but should be recorded as protocol deviations. 
12.1.3. 
Events of Special Monitoring 
Events of special monitoring (EOSM) are AEs or safety topics for which special monitoring, 
additional data collection activities, and/or enhanced signal detection activities within BioCryst 
are considered appropriate for this population and study. Identified EOSMs can be of particular 
concern based on findings from the IMP clinical program to date, potential and/or known risks 
generally associated with the underlying disease, or comorbidities and risk factors prevalent in 
the study population. 
EOSM for this study include acute symptomatic hemolysis, SARS-CoV-2 infections 
(asymptomatic and symptomatic), 
 
 
 


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12.2. 
Definition of Severity 
All AEs will be assessed (graded) for severity by the investigator and classified using the US 
NCI CTCAE (Version 5.0, published 27 November 2017). The NCI CTCAE is a descriptive 
terminology that can be used for AE reporting. The CTCAE displays Grades 1 through 5 with 
unique clinical descriptions of severity for each AE based on the following general guideline: 
Mild: 
(Grade 1): Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Moderate: 
(Grade 2): Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADLa. 
Severe: 
(Grade 3): Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADLb. 
Life-threatening: 
(Grade 4): Life-threatening consequences; urgent intervention indicated. 
Death 
(Grade 5): Death related to AEc. 
Abbreviations: ADL = activities of daily living; AE = adverse event. 
a Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
b Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
c Grade 5 (Death) is not appropriate for some AEs and therefore is not an option. 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity, 
as defined above, whereas seriousness is defined by the criteria under Section 12.1.2. An AE of 
severe intensity may or may not be considered serious. 
12.3. 
Relationship to Study Drug 
An investigator who is qualified in medicine must make the determination of relationship to the 
study drug/IMP for each AE (not related, unlikely related, possibly related, probably related, 
definitely related). The investigator should decide whether, in his or her medical judgment, there 
is a reasonable possibility that the event may have been caused by the investigational product. If 
no valid reason exists for suggesting a relationship, then the AE should be classified as “not 
related”. If there is any valid reason, even if undetermined, for suspecting a possible cause-and-
effect relationship between the study drug/IMP and the occurrence of the AE, then the AE should 
be considered “related”. 
Not Related: 
The event can be readily explained by other factors such as the subject’s 
underlying medical condition, concomitant therapy, or accident, and no 
temporal relationship exists between the study drug/IMP and the event. 
Unlikely 
Related: 
The event does not follow a reasonable temporal sequence from drug 
administration and is readily explained by the subject’s clinical state or by 
other modes of therapy administered to the subject. 


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Possibly 
Related: 
There is some temporal relationship between the event and the administration 
of the study drug/IMP and the event is unlikely to be explained by the subject’s 
medical condition, other therapies, or accident. 
Probably 
Related: 
The event follows a reasonable temporal sequence from study drug/IMP 
administration, abates upon discontinuation of the study drug/IMP, and cannot 
be reasonably explained by the known characteristics of the subject’s clinical 
state. 
Definitely 
Related: 
The event follows a reasonable temporal sequence from study drug/IMP 
administration, follows a known or suspected response pattern to the study 
drug/IMP, is confirmed by improvement upon stopping the study drug/IMP 
(dechallenge), and reappears upon repeated exposure (rechallenge, if 
rechallenge is medically appropriate). 
If the relationship between the (S)AE and the investigational product is determined to be 
“possible”, “probable”, or “definite”, the event will be considered to be related to the study 
drug/IMP for the purposes of expedited regulatory reporting (as applicable per country-specific 
regulatory requirements). 
The sponsor may upgrade causality if deemed appropriate. 
12.4. 
Method, Frequency, and Time Period for Detecting Adverse Events 
and Reporting Serious Adverse Events 
Reports of all AEs and SAEs, regardless of investigator attribution, are to be collected from the 
time of signing of the ICF through to the last study visit (ie, through the post-treatment follow-up 
visit). All AEs and SAEs are to be reported on the AE eCRF. 
AEs should be documented on the eCRFs as investigators become aware of them. AEs are to be 
followed until the event resolves. If an event is ongoing at the last follow-up visit, Grade 1 and 
Grade 2 events do not need to be followed if the event is deemed unlikely to be related or not 
related to study drug/IMP (see Section 12.2 for AE grading). For all Grade 3 and Grade 4 events 
or events deemed possibly, probably, or definitely related to use of study drug/IMP, the event 
should be followed until the AE is resolved or the subject is in a clinically stable condition with 
regards to the AE. 
The investigator shall report all SAEs immediately and no later than 24 hours of their knowledge 
of the event to the sponsor by communicating with the medical monitor (phone or email) and by 
entering the event into the AE eCRF and by completion of the SAE eCRF. The SAE eCRF is an 
additional form to the AE eCRF that provides important details on the SAE. The investigator 
should follow all unresolved SAEs observed during the study until they are resolved, or are 
judged medically stable, or are otherwise medically explained. 
The investigator should attempt, if possible, to establish a diagnosis based on the presenting 
signs and symptoms. In such cases, the diagnosis should be documented as the AE and not the 
individual sign/symptom. If a clear diagnosis cannot be established, each sign and symptom must 
be recorded individually. Once a diagnosis is made during evaluation or treatment, the 
investigator will update the AE record with this diagnosis and delete the previously reported 
signs and symptoms. The rapid reporting of SAEs ensures that the sponsor shall have the 


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necessary information to continuously assess the benefit-risk profile of the study drug in clinical 
studies. 
12.4.1. 
Serious Adverse Events and Suspected Unexpected Serious Adverse Reactions 
The investigator must report all SAEs immediately and in no case later than within 24 hours of 
their knowledge of the event. Investigators should adhere to their country or region requirements 
for the reporting timeframe, which may not allow any delay. SAEs should be reported to the 
sponsor medical monitor and via the AE and SAE eCRFs. The SAE eCRF is an additional form 
to the AE eCRF that provides important details on the SAE. All additional follow-up evaluations 
of the SAE must be reported to BioCryst or its designee as soon as they are available by 
amending these eCRFs. The eCRF system automatically sends SAE notifications to the 
following email address: 
 
 
Email: safety@biocryst.com 
In the event the eCRF system is not functioning, the reporting of an SAE must not be delayed. 
Sites will have SAE report forms (electronic Word document) that can be completed and emailed 
to the above recipient. As soon as the eCRF system is functioning, that particular SAE must be 
entered into the AE eCRF. 
Immediate reporting should allow BioCryst to take the appropriate measures to address potential 
new risks in a clinical study. Therefore, the initial report should be submitted by the investigator 
within a very short period of time and under no circumstances should this period exceed 24 hours 
following awareness of the SAE. 
The follow-up report should allow BioCryst to determine whether the SAE requires a 
reassessment of the benefit-risk profile of the study drug/IMP in clinical study, if the relevant 
information was not already available and provided in the initial report. 
Country-specific rules and requirements for safety management will be described in the Safety 
Management Plan prepared for this study.  
Investigators or designees at each site are responsible for retaining copies of all suspected 
unexpected serious adverse reaction (SUSAR) reports (initial and follow-up) and other safety 
information (eg, revised IB) in the investigator site files. 
BioCryst shall ensure that all relevant information about SUSARs that are fatal or 
life-threatening is recorded and reported as soon as possible to all competent authorities, and to 
the applicable ethics committee in any case no later than 7 calendar days after knowledge by 
BioCryst of such a case, and that relevant follow-up information is subsequently communicated 
within an additional 8 days. All other SUSARs shall be reported to the competent authorities 
concerned and to the ethics committees, as applicable, according to local regulations, as soon as 
possible but in no case later than 15 calendar days of first knowledge by BioCryst. BioCryst or 
designee shall also inform the investigator. Although acute kidney injury is considered an 
expected event (see Section 6.11 of the IB), the event will be reported in an expedited manner. 


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12.4.2. 
Pregnancy 
Any female subject who becomes pregnant during the course of the study should have BCX9930 
discontinued immediately and must be followed through the end of the pregnancy. While 
pregnancy is not considered an AE, all cases of fetal drug exposure via the parent as a study 
participant (including partners of study participants) are to be reported immediately to BioCryst 
or its designee. Consent from study partners who become pregnant will be obtained prior to 
reporting any details of the pregnancy. Information related to the pregnancy must be given on a 
“Pregnancy Notification and Outcome” form that will be provided by the sponsor or its designee 
so that the pregnancy may be followed, and an outcome determined. Any AEs or SAEs 
experienced by a pregnant subject are to be reported as directed in Section 12.4.1. Any 
complications reported in a subject’s pregnant partner should be reported on the Pregnancy 
Notification and Outcome form. All pregnancies must be followed to outcome, which occurs 
when an infant is delivered (live or still born), there is fetal demise, or there is an abortion 
(spontaneous or induced). Abortion (spontaneous or induced), fetal demise, and still birth, along 
with congenital abnormalities in the newborn, should be reported as separate SAEs. 
12.5. 
Adverse Event Management 
The investigator (or qualified designee) will grade clinically significant events and laboratory 
abnormalities (if considered AEs) as detailed in Section 12.2. Grade 3 and Grade 4 clinically 
significant laboratory abnormalities should be confirmed by repeat testing and before any 
contemplated study drug/IMP discontinuation, unless such a delay is not consistent with good 
medical practice. 
12.5.1. 
Potential Drug-induced Liver Injury: Monitoring, Evaluation, and 
Discontinuation Criteria 
All treatment-emergent ALT elevations > 3 × ULN should be confirmed, preferably within 
72 hours, with repeat assessment of ALT, AST, total bilirubin, ALP, prothrombin time/INR, and 
complete blood count with differential. These may be repeated at a local laboratory as long as the 
results are reported to the investigator when available and the investigative site contacts the 
subject to ascertain any symptoms. 
Subjects with ALT elevation > 3 × ULN must be assessed to determine whether study drug must 
be withheld or discontinued. In addition, any potentially contributing medications, supplements, 
or over-the-counter medications that are not medically necessary should be discontinued if 
medically feasible. 
Discontinuation of treatment should be considered for any of the following, and should be 
discussed with the sponsor medical monitor prior to BCX9930 discontinuation, considering the 
benefit-risk of discontinuing BCX9930: 
• ALT or AST > 8 × ULN 
• ALT or AST > 5 × ULN for more than 2 weeks 
• ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN [unless there is evidence that 
the increase in bilirubin is due to hemolysis or Gilbert’s syndrome] or 
INR > 1.5 × ULN in the absence of warfarin therapy) 


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• ALT or AST > 3 × ULN with the appearance of fatigue (over baseline fatigue), 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%) 
If subjects are asymptomatic with no other pertinent laboratory abnormality, study drug may be 
continued under close observation. Transaminases, total bilirubin, ALP, and INR should be 
repeated at least twice weekly. Frequency of retesting can decrease to once per week or less if 
abnormalities stabilize or the study drug has been discontinued and the subject is asymptomatic. 
Additionally, several other items should be considered, including obtaining a more detailed 
history of symptoms and prior or concurrent diseases; obtaining a history of concomitant use of 
nonprescriptive medications, herbal and dietary supplements, alcohol intake, recreational drug 
use, or special diets; evaluation for acute viral hepatitis A, B, C, D, and E and potentially other 
serologies; evaluation for others as clinically indicated including alcoholic and autoimmune 
hepatitis, non-alcoholic steatohepatitis (NASH), and biliary tract disease. 
The above criteria will be applied to increases in AST unless there is evidence that the increase is 
due to hemolysis. If both ALT and AST are elevated, subjects will be managed based on their 
ALT level, regardless of whether their AST increase is thought to be due to hemolysis. 
If Hy’s Law criterion is met and is assessed as probably or definitely related per treatment 
discontinuation criterion in Section 7.4.1, then study drug must be discontinued. Prior to 
discontinuation from study drug/BCX9930, the investigator should contact the sponsor medical 
monitor for a discussion regarding the event and assessment. If medically indicated, the 
investigator can discontinue the subject immediately and follow up with the sponsor within 
24 hours. 
12.5.2. 
Renal Events 
12.5.2.1. Monitoring, Evaluation, and Subject Discontinuation Criteria 
There are multiple potential reasons that sCr can increase in those with PNH, including 
hemolysis. For subjects who have a confirmed treatment-emergent increase in sCr, evaluations to 
investigate potential etiology should be chosen considering baseline renal function, history of 
prior renal events including those due to PNH, other comorbidities, concomitant medications, 
and other relevant factors. In addition:  
• For all subjects, ensure adequate hydration, stop or substitute potentially nephrotoxic 
medications, and evaluate for tuberculosis if sterile pyuria is present if potential exposure 
• For treatment-emergent increases in sCr > ULN or ≥ 0.3 mg/dL (≥ 26.5 µmol/L) from 
baseline confirmed by repeat testing, notify sponsor medical monitor 
• A renal ultrasound with doppler should be considered to exclude renal vein thrombosis or 
other incidental causes 
• Subject data may be reviewed by a Nephrology Risk Mitigation Working Group 
(NRMWG) for additional recommendations, including dose reduction, interruption of 
dosing, and permanent discontinuation 


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• If a biopsy is performed, a redacted copy of the biopsy report and available images 
(whole slide images of light microscopy or electron microscopy specimens, 
immunofluorescence, immunohistochemistry, etc.) should be made available 
The following table gives additional actions based on sCr: 
sCr > ULN but ≤ 1.5 × ULN 
• 
Assessment frequency as per the schedule specified in Table 4 
(Part 1) or Table 5 (Part 2) (ie, every 1 to 4 weeks, as applicable) 
until sCr is ≤ ULN 
• 
Consider evaluation by nephrologist 
sCr > 1.5 × ULN but 
< 3 × ULN 
• 
Assessment frequency weekly until sCr is ≤ ULN 
• 
Evaluation by nephrologist 
sCr ≥ 3 × ULN 
• 
BCX9930 should be discontinued, with taper (see Section 9.4.4), 
after confirmation  
• 
If hemolysis or any other potentially reversible cause is 
suspected, contact sponsor medical monitor 
12.5.2.2. Study Stopping Rule 
The NRMWG will be notified promptly of and review any instances of subjects experiencing 
increased sCr ≥ 3 × ULN, and the DMC will be notified of each confirmed case, regardless of 
causality. 
In the event that 3 subjects are determined by the NRMWG to have confirmed elevations of sCr 
≥ 3 × ULN considered related to BCX9930, the study will be stopped. This will apply only to 
newly enrolled subjects treated at a dose of 400 mg BID. 
12.5.3. 
Risk of Hemolysis After Missed Doses, Treatment Interruption, or Permanent 
Discontinuation 
12.5.3.1. BCX9930 
Subjects must be warned of the potential risk of hemolysis following missed doses (particularly 
multiple consecutive missed doses) and treatment interruption, and the definite risk after 
permanent discontinuation of BCX9930. By inhibiting the AP of complement, BCX9930 may 
improve Hb levels and increase circulating RBC clone size by reducing the hemolysis of PNH 
RBCs. Missed doses and treatment interruption of BCX9930 may lead to hemolysis. Subjects are 
at risk of severe hemolysis when BCX9930 is permanently discontinued. Based on available data 
regarding the PK and PD of BCX9930, severe hemolysis, if it occurs, would be expected to 
present within days after discontinuation of therapy. 
Therefore, when subjects permanently discontinue BCX9930 (either at the end of the study for 
those who do not continue treatment or those who permanently discontinue BCX9930 treatment 
prematurely at any time during the study), they must be monitored for hemolysis. When an 
investigator is made aware that a subject has permanently discontinued BCX9930, if the subject 
is asymptomatic, contact with the subject should occur at least daily, for a minimum of 7 days. 
Contact may be conducted by telephone, email, or other means, including in person, if preferred. 
When any sign or symptom of hemolysis occurs, the subject should be promptly evaluated (refer 


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to Section 10.3.6 for a list of minimum laboratory testing). Additional monitoring following the 
first contact after permanent discontinuation should be guided by the medical judgement of the 
investigator. For subjects who are already symptomatic when treatment is discontinued, whether 
the subject should be assessed in person or can be followed with daily contact will be based on 
the investigator’s medical judgement taking into account the severity of the reported signs or 
symptoms and/or any reported worsening of the signs or symptoms. When possible, subjects 
should return to the investigative center; however, when this is not possible, arrangements may 
be made for the subject to be assessed by his or her local hematologist and a local laboratory 
used for clinical laboratory testing. When hemolysis occurs after the permanent discontinuation 
of BCX9930, treatment should be provided according to the judgement of the investigator. 
Treatment with BCX9930 should not be interrupted or withheld unless there is an absolute 
contraindication for continued dosing. Suggestions for anti-emetic therapy for subject with active 
nausea and vomiting when tablet contents are vomited are given in Section 9.6.2. The sponsor 
medical monitor should be contacted for guidance in both cases as soon as possible after the 
investigator is made aware of the event.  
The sponsor medical monitor should be notified in the event of hemolysis symptoms, any 
planned treatment interruption, and permanent discontinuation of BCX9930. Any missed doses, 
treatment interruption, or permanent discontinuation must be recorded in the eCRF and source 
documents, including the reason for the interruption, missed doses, or discontinuation. 
Study assessments for monitoring of potential hemolysis after BCX9930 for missed doses, 
treatment interruption, and permanent discontinuation of BCX9930 for subjects who experience 
signs or symptoms of hemolysis are in Section 10.3.6. 
12.5.3.2. C5 Inhibitor Therapy 
Subjects who permanently discontinue C5 inhibitor therapy, other than to begin treatment with 
BCX9930, should be monitored for hemolysis as described per the relevant prescribing 
information, product monograph, or summary of product characteristics, with standard-of-care 
supportive treatment provided, as needed. 
The sponsor medical monitor should be notified in the event of hemolysis symptoms, treatment 
interruption, and permanent discontinuation of C5 inhibitor therapy. Any missed doses, treatment 
interruption, or permanent discontinuation must be recorded in the eCRF and source documents, 
including the reason for the interruption, missed doses, or discontinuation. 
Study assessments for monitoring of potential hemolysis after C5 inhibitor therapy for missed 
doses, treatment interruption, and permanent discontinuation of C5 inhibitor therapy for subjects 
who experience signs or symptoms of hemolysis are in Section 10.3.6. When possible, subjects 
should return to the investigative center; however, when this is not possible, arrangements may 
be made for the subject to be assessed by his or her local hematologist and a local laboratory 
used for clinical laboratory testing. 
12.5.4. 
Acute Symptomatic Hemolysis 
Subjects should contact the investigator if they experience any new or worsening signs or 
symptoms of hemolysis, including increased fatigue over baseline, abdominal pain, dysphagia, 
shortness of breath, hemoglobinuria, new signs and/or symptoms suggestive of thrombosis, or 


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new or worsening erectile dysfunction, upon first awareness and regardless of treatment 
assignment. Subjects should be evaluated per the investigator’s medical judgement. In-person 
evaluation is preferred, but can include phone or telemedicine contact with documentation, if 
in-person evaluation is not possible. 
For subjects receiving BCX9930, a review of dosing compliance to ensure that the subject is 
taking the drug correctly must be performed, regardless of the method used to evaluate the 
subject (ie, in-person or remote assessment), and any missed doses should be recorded. It should 
also be determined whether the subject has had any recent CACs (eg, infection, trauma, or 
surgery) that may have contributed to the hemolytic event. 
For subjects seen in person for evaluation of possible acute symptomatic hemolysis, the 
assessments outlined in Section 10.3.6 should be performed, as appropriate. 
For this study, “acute symptomatic hemolysis” is defined by the following: 
• ≥ 1 new or worsening acute sign or symptom of IVH (fatigue, hemoglobinuria, 
abdominal pain, dyspnea, MAVE [including thrombosis], dysphagia, erectile 
dysfunction, or acute kidney injury [AKI; defined as an eGFR decrease of ≥ 50% or 
doubling of serum creatinine]) 
AND 
• acute reduction in Hb of > 2 g/dL and a 2-fold increase (ie, doubling) in LDH, as 
compared to the most recent Hb and LDH values while not experiencing symptoms of 
acute symptomatic hemolysis. 
The sponsor medical monitor should be notified when the investigator first becomes aware of a 
potential acute symptomatic hemolysis event. Treatment with BCX9930 for those assigned to 
BCX9930 in Part 1, and all subjects in Part 2, should continue in addition to any other 
treatments. 
12.6. 
Overdose 
To date, there is no experience with overdose of BCX9930. Healthy subjects received BCX9930 
at a dose of 2000 mg administered as single doses and as multiple once-daily doses for 3 days in 
Study 101 with no clinically significant safety concerns. In the event that study personnel 
become aware of an overdose of BCX9930 that is associated with an AE, both the overdose and 
the resultant event should be reported as AEs. Overdose without any symptoms (ie, AEs) does 
not need to be reported as an AE. If overdose occurs with or without associated AEs, subjects 
should undergo clinical and laboratory monitoring, as appropriate, for their clinical condition 
and, if indicated, should receive clinically indicated supportive therapy. See also Section 12.1.2. 
12.7. 
Data Monitoring Committees 
A DMC will be established for interim safety monitoring. The specific responsibilities and 
composition of the DMC are outlined in a separate DMC charter. In addition, the details of 
outputs provided for the meetings will be referenced in this charter. 


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A NRMWG will review and advise on subjects with treatment-emergent increases in sCr and 
other renal events. The specific responsibilities and composition of the NRMWG are outlined in 
a separate charter. 
13. 
STATISTICS 
13.1. 
Hypotheses 
The primary study hypothesis is the differential effect on the CFB in Hb [mean of values at 
Weeks 12, 16, 20, and 24] between BCX9930 and C5 inhibitor therapy. 
The primary null and alternative hypotheses are: 
• Ho: HbB = HbC; BCX9930 does not have a differential effect on the mean of values at 
Weeks 12, 16, 20, and 24 CFB in Hb (g/dL) as compared to C5 inhibitor therapy 
• HA: HbB ≠ HbC; BCX9930 does have a differential effect on the mean of values at 
Weeks 12, 16, 20, and 24 CFB in Hb (g/dL) as compared to C5 inhibitor therapy 
where HbB is the mean of values at Weeks 12, 16, 20, and 24 CFB in Hb for BCX9930 
and HbC is the mean of values at Weeks 12, 16, 20, and 24 CFB for C5 inhibitor therapy. 
Key secondary hypotheses comparing BCX9930 to C5 inhibitor therapy are as follows: 
• Proportion of subjects who are transfusion-free from Week 4 to Week 24 
− Ho: TAB = TAC; BCX9930 does not have a differential effect on the proportion of 
subjects who are transfusion-free from Week 4 to Week 24 
− HA: TAB ≠ TAC; BCX9930 does have a differential effect on the proportion of 
subjects who are transfusion-free from Week 4 to Week 24 
where TAB is the proportion of subjects who are transfusion-free from Week 4 to 
Week 24 for BCX9930 and TAC is the proportion of subjects who are transfusion-free 
from Week 4 to Week 24 for C5 inhibitor therapy. 
• Number of units of pRBCs transfused from Week 4 to Week 24 
− Ho: pRBCB = pRBCC; BCX9930 does not have a differential effect on the number 
of units of pRBCs transfused from Week 4 to Week 24 
− HA: pRBCB ≠ pRBCC; BCX9930 does have a differential effect on the number of 
units of pRBCs transfused from Week 4 to Week 24 
where pRBCB is the number of units of pRBCs transfused from Week 4 to Week 24 
for BCX9930 and pRBCC is the number of units of pRBCs transfused from Week 4 to 
Week 24 for C5 inhibitor therapy. 
• Change from baseline in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 
20, and 24] 
− Ho: FACITB = FACITC; BCX9930 does not have a differential effect on the mean 
of values at Weeks 12, 16, 20, and 24 CFB in FACIT-Fatigue 


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− HA: FACITB ≠ FACITC; BCX9930 does have a differential effect on the mean of 
values at Weeks 12, 16, 20, and 24 CFB in FACIT-Fatigue 
where FACITB is the mean CFB at Week 12, 16, 20, and 24 in FACIT-Fatigue for 
BCX9930 and FACITC is the mean of values at Weeks 12, 16, 20, and 24 CFB for 
C5 inhibitor therapy. 
Inferential testing for the primary endpoint of interest (CFB in Hb) will be conducted at the 
α = 0.05 level of significance. The alpha level for tests of primary and key secondary endpoints 
will be adjusted for multiplicity using hierarchical testing in the order the endpoints are specified 
as described in Section 13.1.1. All hypothesis tests will be 2-sided. 
13.1.1. 
Controlling for Multiplicity 
Four endpoints are being tested: the primary endpoint and 3 secondary endpoints. The Type I 
error rate will be controlled at the study level using a hierarchical testing procedure. 
Statistical testing for the primary hypothesis will be performed using an alpha of 0.05. All 
hypothesis tests will be two-sided. If the null hypothesis associated with the primary endpoint is 
rejected, the key secondary endpoints for Part 1 will be tested in the following order using an 
alpha of 0.05. Testing will stop when an endpoint has an associated p-value ≥ 0.05 or when all 
endpoints have been tested (ie, all p-values are < 0.05). 
1. Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 
2. Number of units of pRBCs transfused [from Week 4 to Week 24] 
3. CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
13.2. 
Sample Size Considerations 
Assuming a Type 1 error rate of 0.05, a common standard deviation for Hb of 2.3 g/dL from Lee 
and colleagues (Lee, Peffault de Latour, et al. 2019) and a randomization ratio of 2:1, a sample 
size of 66 subjects (44 subjects in the BCX9930 200/400 mg BID arm, 22 subjects in the control 
arm) will have 90% power to detect a treatment difference of 2.0 g/dL in Hb from baseline for 
subjects randomized to BCX9930 compared to subjects randomized to continue C5 inhibitor 
therapy, based on a two-sample t-test. To account for potential dropouts, approximately 
81 subjects (ie, approximately 54 subjects in the BCX9930 200/400 mg BID arm and 
approximately 27 subjects in the control arm) will be enrolled. 
13.3. 
Sample Size Re-estimation 
No sample size re-estimation is planned. 
13.4. 
Stratification 
Randomization of subjects will be stratified by C5 inhibitor (ravulizumab vs. eculizumab) and 
whether a pRBC transfusion was received within the 6 months prior to baseline (yes vs. no). 


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13.5. 
Statistical Methods 
A detailed statistical analysis plan (SAP) will be developed to describe the methods of analyses 
and summaries, including all endpoints, time points, populations, missing data, etc. Deviations 
from the analyses outlined in the SAP will be described in the clinical study report (CSR).  
13.5.1. 
Analysis Populations 
The analysis populations for the study are defined below. 
13.5.1.1. Screen Failures 
Subjects who give informed written consent but are not randomized to study treatment and are 
noted as screen failures in the eCRF are considered screen failures. Reasons for screen failure 
will be summarized using this population. 
13.5.1.2. Intent-to-Treat Population 
The intent-to-treat (ITT) population is defined as all randomized subjects, regardless of whether 
study treatment was administered. This population will be the primary population for efficacy 
analyses. Subjects will be analyzed according to the treatment randomized. 
13.5.1.3. Safety Population 
The safety population is defined as all subjects who receive at least 1 dose of study drug, whether 
C5 inhibitor or BCX9930. This population will be used for all analyses of accountability, 
demographics, and safety. Subjects will be analyzed according to the treatment received. 
13.5.1.4. Per Protocol Population 
The per-protocol (PP) population is defined as all subjects who did not violate key protocol 
inclusion or exclusion criteria, received only the study drug to which they were randomized, and 
did not have any protocol deviations or violations that would affect analysis, as determined by 
the sponsor. This population will be used for a sensitivity analysis of the primary efficacy 
analysis. Analyses based on the PP population will be produced for Part 1 only. Subjects will be 
analyzed according to the treatment randomized. 
13.5.1.5. Completers Population 
The subset of subjects in the ITT population who complete Part 1 of the study and 24 weeks of 
study drug will compose the completers population. This population will be used for a sensitivity 
analysis of the primary efficacy analysis for Part 1 only. Subjects will be analyzed according to 
the treatment randomized. 
13.5.1.6. Pharmacokinetic Population 
The PK population will comprise the subset of subjects in the safety population for whom 
BCX9930 concentration data are available. The PK substudy population will include all subjects 
who participate in the optional PK/PD substudy and have one post-dose concentration collected 
during a substudy visit. 


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13.5.1.7. Pharmacodynamic Population 
The PD population will include all safety population subjects for whom at least 1 pre-dose and 
1 post-dose PD or complement biomarker measurement can be obtained. This population will be 
used for all PD and complement biomarker analyses and for correlation with BCX9930 PK 
parameters or BCX9930 concentrations. Subpopulations including subjects for whom at least 
1 pre-dose and 1 post-dose measurement for each PD or complement biomarker may be used for 
analysis. Subjects will be analyzed according to the treatment received. 
13.5.2. 
General Considerations for Data Analysis 
In general, descriptive summaries will include n, mean, standard deviation, median, minimum, 
and maximum for continuous variables and n and percent for categorical variables. Summaries 
will be presented by treatment and study visit. 
All individual subject data will be listed as measured. All statistical summaries and analyses will 
be performed using SAS® software (SAS Institute, Cary, North Carolina, USA). 
13.5.3. 
Subject Demographic and Disposition Data 
Demographic data and baseline characteristics including age, gender, race or ethnicity, height, 
body weight, BMI, and PNH history will be summarized by treatment and overall. 
Baseline measures for Hb and FACIT-Fatigue scale scores will be summarized using descriptive 
statistics. 
Subject disposition will be presented by treatment and overall. The number of subjects who 
completed the study and those that discontinued from the study will be provided. The reasons for 
early discontinuation will be presented. A tabulation of the number of subjects exposed to study 
drug and duration of exposure will also be presented for each treatment and overall. Treatment 
adherence, dose interruptions, and reason for dose interruptions will be provided as summaries or 
listed as appropriate. 
13.5.4. 
Analysis of Efficacy Variables 
The primary efficacy analyses will be based on Part 1 of the study. The efficacy analyses will be 
based on the ITT population. The analyses of the PP population and completers population will 
be used to support the primary efficacy analyses. 
Efficacy data will be summarized by treatment in Part 1. 
13.5.4.1. Primary Efficacy Analysis 
The primary endpoint is the CFB in Hb [mean of values at Weeks 12, 16, 20, and 24]. 
The primary efficacy analysis will be produced using the ITT population. The estimand will be 
based on observed data from subjects who are on study drug. Observed data will be included up 
to the time of discontinuation of study treatment, if applicable. CFB Hb values (in Weeks 12, 16, 
20, and 24) that occur within 14 days after the subject receives a pRBC transfusion (ie, the 
interval between the transfusion day and the current study day is ≤ 13 days) will be replaced with 
an unscheduled CFB Hb value if one is available within the 14-day period prior to the visit and if 
it was not obtained within 14 days after pRBC transfusion or, if an unscheduled value is not 


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available, will be censored unless the CFB Hb is ≤ 0. Central laboratory values will be used. If a 
central laboratory value is missing but a local laboratory is available, the local laboratory value 
will be used in place of the censored laboratory value. Statistical testing will be two-sided. 
CFB in Hb will be summarized by treatment and visit (including mean in Weeks 12, 16, 20, and 
24). 
The difference between treatment groups in CFB Hb [mean of values at Weeks 12, 16, 20, and 
24] will be analyzed using an analysis of covariance (ANCOVA) model. The model will include 
treatment and randomization stratum as categorical covariates and baseline Hb as a continuous 
covariate. 
The primary efficacy analysis will be conducted using Part 1 data and the primary efficacy 
endpoints will be summarized and listed by Part 1 treatment group. 
Plots of mean Hb and mean CFB Hb by visit and treatment will be produced for Part 1, using a 
different color for each treatment. Plots will be updated to include Part 2 data at the final 
analysis. 
Hb and CFB Hb will be listed for each subject and visit.  
The potential impact of missing data on the primary efficacy outcome will be explored. 
Sensitivity analyses will be conducted to support the primary analysis. This will include the 
following analyses: 
1) Analyses based on data from subjects who are in the completers population. 
2) Analyses based on data from subjects who are in the PP population.  
3) An analysis in which missing data are imputed using the method of Jump-to-Reference 
(J2R) (Carpenter, Roger, et al. 2013), an analysis in which data missing not at random are 
imputed to be similar to data observed on the reference treatment (treatment with 
C5 inhibitors) and data missing at random are imputed to be similar to that of the 
randomized treatment group for the subject.  
4) A tipping point analysis will be conducted to further examine the effect of missingness. 
5) A Mixed Models Repeated Measures (MMRM) analysis will be conducted using the 
ITT population and observed data to look at trends over time by treatment. 
Details on sensitivity analyses and missing data imputations will be provided in the SAP. 
Subgroup analyses will be conducted by geographical region and by race. Additional subgroup 
analyses will be described in the SAP. 
13.5.4.2. Analyses of Key Secondary, Other Secondary, and Exploratory Efficacy 
Endpoints 
13.5.4.2.1. Part 1 
Key secondary hypotheses comparing BCX9930 to C5 inhibitor therapy for Part 1 will be 
analyzed as follows: 
1. Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 


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2. Number of units of pRBCs transfused [from Week 4 to Week 24] 
3. CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
The proportion of subjects who are transfusion-free from Week 4 to Week 24 will be 
summarized by treatment. Subjects who either (1) discontinue treatment prior to Week 24, or 
(2) do not receive a transfusion during the Week 4 to Week 24 time period despite recording a 
Hb value ≤ 9 g/dL with symptoms assessed by the investigator as warranting transfusion or a Hb 
value ≤ 7 g/dL regardless of symptoms will not be considered transfusion-free. A 
Cochran-Mantel-Haenszel (CMH) chi-squared analysis will be conducted to test the hypothesis 
of interest and to compute an odds ratio and 95% CI comparing the odds of being transfusion-
free for BCX9930 treatment as opposed to treatment with C5 inhibitor. As a supportive analysis, 
a logistic regression model will be conducted with a fixed effect for treatment and indicator 
variables for the randomization factors. In addition, a sensitivity analysis using CMH will be 
conducted in which subjects who discontinue treatment prior to Week 24 will not be considered 
transfusion-free, but subjects who do not receive a transfusion despite a Hb value ≤ 9g/dL with 
symptoms warranting transfusion or a Hb value ≤ 7g/dL regardless of symptoms will be 
considered as transfusion-free. 
The number of units of pRBCs transfused from Week 4 to Week 24 will be summarized by 
treatment. The van Elteren test will be used to compare the two treatments with respect to the 
number of pRBCs transfused from Week 4 to Week 24. In a supportive analysis, the rate of 
pRBCs units transfused per 28 days will be derived using a negative binomial model. The 
negative binomial model will include the number of units of pRBCs from Week 4 to Week 24 as 
the dependent variable, the treatment and indicator variables for the randomization factors as 
independent variables, and the logarithm of duration on treatment included as an offset variable. 
The model-estimated rate of pRBCs per 28 days from Week 4 to Week 24 will be reported for 
each treatment group. A rate ratio (with 95% CI) comparing BCX9930 to C5 inhibitor treatment 
will be obtained as well as a percent reduction in rate (with 95% CI) for BCX9930 as compared 
to C5 inhibitor treatment. 
The actual and change from baseline in FACIT-Fatigue scale score will be summarized by 
treatment group and visit. The difference between treatment groups in CFB FACIT-Fatigue score 
[mean of values at Weeks 12, 16, 20, and 24] will be analyzed using an ANCOVA model. The 
model will include CFB FACIT-Fatigue score [mean of values at Weeks 12, 16, 20, and 24] as 
the dependent variable with treatment, indicator variables for the randomization factors, and 
baseline FACIT-Fatigue score as independent variables. FACIT-Fatigue values occurring within 
a 14-day window after transfusion (ie, the interval between the transfusion day and the current 
study day is ≤ 13 days) will be censored. An additional supportive analysis of CFB 
FACIT-Fatigue scores will be conducted using a MMRM model with fixed effects for 
randomization stratum, treatment, baseline endpoint, visit, a visit-by-treatment interaction, and a 
random effect for subject. An unstructured covariance structure will be used. The 
Kenward-Roger approximation will be used to estimate denominator degrees of freedom. 
Cumulative density function (CDF) and probability density function (PDF) plots of CFB 
FACIT-Fatigue (mean of Weeks 12, 16, 20, and 24) will be produced. Further sensitivity 
analyses for FACIT-Fatigue scale score to address missing data will be detailed in the SAP 
(eg, J2R and tipping point). 


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Nominal p-values will be provided for the following other secondary and exploratory endpoints: 
• Percent CFB in LDH [mean of values at Weeks 12, 16, 20, and 24] 
• Percent reduction in the rate of pRBC units transfused [from Week 4 to Week 24 vs. 
prestudy transfusion rate] 
• Proportion of subjects with Hb ≥ 12 g/dL [at Week 24] 
• Proportion of subjects with Hb stabilization, defined as avoidance of a > 2 g/dL 
decrease in the absence of transfusion [from Week 4 to Week 24] 
• CFB in C3-opsonized RBCs [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in total PNH RBC clone size [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in ratio of total PNH RBC clone size to PNH WBC clone size (ie, ratio of 
percent PNH RBCs / percent PNH WBCs) [mean of values at Weeks 12, 16, 20, and 
24] 
• CFB in absolute reticulocyte count (ARC) [mean of values at Weeks 12, 16, 20, and 
24] 
• Proportion of subjects with ARC in the normal range [at Week 24] 
• CFB in haptoglobin [mean of values at Weeks 12, 16, 20, and 24] 
• Proportion of subjects with haptoglobin ≥ LLN [at Week 24] 
• CFB in total bilirubin [mean of values at Weeks 12, 16, 20, and 24] 
• 
 
• 
 
Percent CFB in LDH, CFB in C3-opsonized RBCs, CFB in total PNH RBC clone size, CFB in 
ratio of total PNH RBC clone size to PNH WBC clone size, CFB in ARC, CFB in haptoglobin, 
CFB in total bilirubin, 
 will be summarized by 
visit. Analysis of the endpoints represented as the mean of Weeks 12, 16, 20, and 24 will be 
conducted using ANCOVA with effects for treatment, randomization stratum, and baseline 
value. Missing data will not be imputed. For this analysis, CFB total PNH RBC, and CFB ratio 
of total PNH RBC clone size to PNH WBC clone size, CFB in ARC, and CFB in haptoglobin 
values will be censored if the subject had a transfusion within 14 days prior to the visit in which 
the measurement was taken (ie, the interval between the transfusion day and the current study 
day is ≤ 13 days). 
The rate of pRBC units transfused from Week 4 to Week 24 will be calculated and compared to 
the rate of pRBC units transfused prestudy during the 12 months prior to screening. The percent 
reduction in rate of pRBC units transfused is the percent difference in rate relative to the 
retrospective rate, calculated as: (current rate – retrospective rate)/retrospective rate * 100%. 
Summary statistics will be provided for the percent reduction in rate of pRBC units transfused. In 
addition, the proportion of subjects with ≥ 50%/70%/90% reduction in rate will be reported. 
Proportions of subjects with Hb ≥ 12 g/dL [at Week 24], proportion of subjects with Hb 
stabilization [from Week 4 to Week 24], proportion of subjects with ARC in the normal range [at 


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Week 24], and proportion of subjects with haptoglobin ≥ LLN [at Week 24] will be summarized 
and analyzed using the CMH method. For proportion of subjects with Hb ≥ 12 g/dL at Week 24, 
proportion of subjects with ARC in the normal range at Week 24, and proportion of subjects with 
haptoglobin ≥ LLN at Week 24, subjects will be considered as failing to meet these endpoints if 
they had a transfusion within the 14 days prior to Week 24. 
Nominal p-values for other HRQoL endpoints for Part 1 will be provided for: 
• Proportion of subjects achieving a within-subject meaningful change for the 
FACIT-Fatigue scale [at Week 24] 
• CFB in QLQ-AA/PNH Physical Functioning and other domain scores [at Week 24] 
• Proportion of subjects with improvement on individual PNH symptom items 
(ie, frequency, severity, and/or interference) from baseline as assessed using the 
modified PRO-AA/PNH [at Week 24] 
• CFB in individual PNH symptom items on the modified PRO-AA/PNH [at Week 24] 
• CFB in EQ-5D-5L utility and VAS scores [at Week 24] 
• TSQM scale score [at Week 24] 
• Patient global impression of change in fatigue, impact of fatigue, and physical 
functioning as assessed using the PGIC-Fatigue, PGIC-Impact of Fatigue, and 
PGIC-Physical Functioning scores, respectively [at Week 24] 
• CFB in patient global impression of severity of fatigue, impact of fatigue, and 
physical functioning as assessed using the PGIS-Fatigue, PGIS-Impact of Fatigue, 
and PGIS-Physical Functioning scores, respectively [at Week 24] 
The proportion of subjects achieving a within-subject meaningful change for the FACIT-Fatigue 
scale at Week 24 and the proportion of subjects with improvement on individual PNH symptom 
items as assessed using the modified PRO-AA/PNH at Week 24 will be analyzed using the CMH 
method. The level required for meaningful within-person change will be determined for the 
FACIT-Fatigue scale using anchor-based analyses. These analyses will be described in the SAP. 
QLQ-AA/PNH Physical Functioning and other domain scores, the PNH symptom items on the 
modified PRO-AA/PNH, EQ-5D-5L utility and VAS scores, and PGIS for fatigue, impact of 
fatigue, and physical functioning scores will be summarized by visit for both actual and CFB 
values and the Week 24 CFB result will be analyzed using ANCOVA with effects for treatment, 
randomization stratum, and baseline value. Note that for TSQM, a similar analysis will be 
conducted but with the actual Week 24 value rather than CFB Week 24 value as the dependent 
variable. For the QLQ-AA/PNH Physical Functioning domain score, CDF and PDF plots will be 
provided for the CFB score at Week 24. 
PGIC for fatigue, impact of fatigue, and physical functioning scores will be summarized using 
descriptive statistics by treatment group and study visit. For ease of interpretation and 
comparison, the PGIC items will be mapped to the values -3 to 3, from the worst outcome to the 
best outcome, respectively. PGIC items at Week 24 will be summarized by treatment group and 
study visit and analyzed using an ANCOVA model. The model will include effects for treatment, 
randomization stratum, and baseline score. 


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13.5.4.2.2. Part 2 
The baseline for Part 2 for subjects who switch from C5 inhibitor therapy to BCX9930 at the end 
of Part 1 will be the last value prior to the first dose of BCX9930 in Part 2. The baseline value 
for subjects randomized to BCX9930 treatment will be the same as for Part 1. 
Analysis of Part 2 secondary endpoints will generally be descriptive with summaries of actual 
and CFB values provided by visit for Hb, LDH, ARC, haptoglobin, C3-opsonized RBCs, total 
PNH RBC clone size, ratio of total PNH RBC clone size to PNH WBC clone size, 
 and 
 The mean and standard deviation of CFB values from Weeks 28 to 52 for 
subjects randomized to BCX9930 in Part 1 and from Weeks 36 to 52 for subjects randomized to 
continue C5 inhibitor therapy will be provided.  
The proportion of subjects with Hb ≥ 12 g/dL at Week 52, with Hb stabilization during the 
relevant Part 2 period, with ARC in the normal range at Week 52, with haptoglobin ≥ LLN at 
Week 52, and who are transfusion-free during the relevant Part 2 period will be presented by 
randomized treatment in Part 1.  
The number of units of pRBCs will be summarized using summary statistics. The rate of pRBC 
units transfused during the relevant period in Part 2 will be calculated along with the percent 
reduction in the rate of pRBCs transfused as compared to the prestudy transfusion rate. Summary 
statistics will be provided along with a summary of the number of subjects with a 
≥ 50%/70%/90% reduction in rate of pRBC units transfused. 
Analysis of Part 2 HRQoL endpoints will generally be descriptive with summaries of actual and 
CFB values provided by visit for FACIT-Fatigue scale, QLQ-AA/PNH domain, modified 
PRO-AA/PNH, EQ-5D-5L utility and VAS, and TSQM scale scores.  
Summaries of FACIT-Fatigue scale scores and PNH symptom items by Part 1 treatment group 
and study visit will be provided. The proportion of subjects achieving a within-subject 
meaningful change for FACIT-Fatigue and with improvement in individual PNH symptoms 
items as compared to baseline will be summarized by visit. 
For PGIC and PGIS for fatigue, impact of fatigue, and physical functioning, descriptive 
summaries by treatment group and study visit will show the number and percentage of subjects 
with each choice of response. Descriptive summaries will be provided for PGIC items, PGIS 
items, and CFB PGIS items. For ease of interpretation, PGIC items will be mapped to the values 
-3 to 3, from the worst outcome to the best outcome, respectively. 
13.5.5. 
Analysis of Safety Variables 
Separate safety analyses will be produced for the analysis at the end of Part 1 and again at the 
end of Part 2, based on actual exposure. Subjects enrolled at a starting dose of 500 mg BID will 
be reported separately. 
Safety endpoints that will be summarized include, at a minimum, the number and proportion of 
subjects 1) with a TEAE; 2) who discontinue BCX9930 due to a TEAE; 3) who experience a 
TESAE; 4) who experience a treatment-emergent CTCAE Grade 3 or Grade 4 AE; and 5) who 
experience a treatment-emergent CTCAE Grade 3 or Grade 4 laboratory abnormality. 
AEs will be assessed and recorded from the time of signing of the ICF through the appropriate 
follow-up period. AEs will be mapped to a Medical Dictionary for Regulatory Activities 


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(MedDRA) preferred term and system organ class (SOC). The occurrence of TEAEs will be 
summarized using MedDRA preferred terms, SOCs, and severity. Separate summaries of 
TEAEs, TESAEs and AEs considered to be related to study drug, and AEs leading to study drug 
interruption will be generated. All AEs will be listed for individual subjects showing both 
verbatim and preferred terms. 
Clinical laboratory assessments and corresponding changes from baseline will be summarized 
for each laboratory panel by treatment and study visit. 
Descriptive summaries (actual and CFB) of vital signs, body weight, 12-lead ECG parameters, 
and clinical laboratory results will be presented. Laboratory abnormalities will be graded 
according to the CTCAE scales (Version 5.0, 27 November 2017). 
Any graded abnormality that occurs following the initiation of study drug and represents at least 
a 1-grade increase from the baseline assessment is defined as treatment emergent. The number 
and percentage of subjects experiencing treatment-emergent graded toxicities will be 
summarized. Laboratory toxicity shifts from baseline to worst post-baseline assessments will be 
summarized. 
Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature) and body weight 
and corresponding changes from baseline will be summarized by treatment and study visit using 
descriptive statistics. These data will be listed by subject, treatment, and study visit. 
At each time point ECGs are analyzed, an individual subject’s change from baseline will be 
calculated using the average of the triplicate ECGs performed at baseline (Day 1) and single 
values at each post-dose time point. The number and proportion of subjects with QTcF ≤ 450, 
> 450 to ≤ 480, > 480 to ≤ 500, and > 500 msec; or CFB of ≤ 30, > 30 to ≤ 60, or > 60 msec will 
be summarized. Clinically significant abnormal morphological ECG findings will be 
summarized. 
Physical examination findings will be listed.  
A listing of pregnancy test results will be provided. Other pregnancy data captured in the eCRF 
will also be listed if necessary. 
Concomitant medications will be coded using the WHO drug dictionary and summarized. 
As applicable, safety data will be summarized by treatment and overall. 
No tests of hypothesis are planned for safety data. 
13.5.6. 
Acute Symptomatic Hemolysis 
Acute symptomatic hemolysis is defined as: ≥ 1 new or worsening acute sign or symptom of 
IVH (fatigue, hemoglobinuria, abdominal pain, dyspnea, MAVE [including thrombosis], 
dysphagia, erectile dysfunction, or AKI [defined as an eGFR decrease of ≥ 50% or ≥ doubling of 
serum creatinine]) associated with an acute reduction in Hb of > 2 g/dL and a 2-fold increase 
(ie, doubling) in LDH, as compared to the most recent Hb and LDH values while not 
experiencing symptoms of acute symptomatic hemolysis. The sites will complete the Acute 
Symptomatic Hemolysis eCRF module for each episode of acute symptomatic hemolysis; these 
will be summarized by treatment group. 


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13.5.7. 
Breakthrough Hemolysis 
BTH is defined as: ≥ 1 new or worsening sign or symptom of IVH (fatigue, hemoglobinuria, 
abdominal pain, dyspnea, anemia [Hb < 10 g/dL], MAVE [including thrombosis], dysphagia, or 
erectile dysfunction) in the presence of LDH ≥ 2 × ULN after prior reduction of LDH to 
≤ 1.5 × ULN on treatment. The number of subjects experiencing BTH with and without AKI and 
the number of BTH episodes will be summarized by treatment group. 
13.5.8. 
Major Adverse Vascular Events 
MAVEs are defined as: deep vein thrombosis; pulmonary embolus; myocardial infarction; 
transient ischemic attack; unstable angina; renal vein thrombosis; acute peripheral vascular 
occlusion; mesenteric/visceral vein thrombosis or infarction; mesenteric/visceral arterial 
thrombosis or infarction; hepatic/portal vein thrombosis (Budd-Chiari syndrome); cerebral 
arterial occlusion/cerebrovascular accident; cerebral venous occlusion; renal arterial thrombosis; 
gangrene (nontraumatic; nondiabetic); amputation (nontraumatic; nondiabetic); and dermal 
thrombosis. 
All MAVEs and will be summarized by treatment group; thrombosis events will also be 
summarized separately. 
13.5.9. 
Pharmacokinetic Analyses 
All subjects who are included in the safety population and have available BCX9930 
concentration data will be included in the PK population. 
Plasma and urine samples for analysis of BCX9930 concentration will be collected according to 
the schedules presented in Table 4 to Table 6. Plasma PK sampling will include both sparse (all 
subjects) and serial (subjects participating in the PK/PD substudy only) collection. Urine 
sampling will include spot collections only. 
Sparse plasma and spot urine concentration data will be listed. 
For subjects enrolled in the PK/PD substudy, the plasma concentration data for BCX9930 will be 
summarized by visit (first dose vs. steady state) and nominal timepoint. 
Metabolites of BCX9930 may also be included in PK analyses if deemed appropriate. 
Plasma PK data collected from this study may be pooled with other clinical studies to develop 
population PK models. These analyses will be reported separately from the CSR. 
Further details of the plasma PK analyses for this study will be included in a specific analysis 
plan. 
13.5.10. 
Pharmacodynamic and Biomarker Analyses 
PD assessments include plasma Factor Bb, C3a, and C5a, and serum AP activity (AP Wieslab 
assay), as well as plasma Factor D as the pharmacologic target of BCX9930. Additionally, total 
PNH RBC clone size, PNH WBC clone size, and the ratio of total PNH RBC clone size to PNH 
WBC clone size will be assessed. Biomarkers that would be indicative of disease state, such as 
LDH levels, Hb and RBC counts, ARC, and haptoglobin, will be assessed. Additional PD 
markers may also be analyzed. 


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Descriptive summaries of the above assessments (actual, CFB, and percent CFB) will be 
presented by parameter, time point, treatment, and study part.  
Exposure-response (E-R) analyses of the relationships between BCX9930 plasma concentrations 
and PD endpoints, such as complement biomarkers, may be explored using quantitative, 
model-based techniques. Model-based analyses will possibly incorporate data from other clinical 
studies and will be reported separately from the CSR. 
Further details of the PK/PD and E-R analyses for this study will be included in a specific 
analysis plan. 
14. 
STUDY ADMINISTRATION 
14.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative(s) of BioCryst or 
its designee will assess the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of BioCryst or its designee. This will be 
documented in a Clinical Study Agreement between BioCryst and the investigator. 
During study conduct, BioCryst or its designee will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practice (GCP) are being followed. The monitor(s) will 
review source documents to confirm that the data recorded on eCRFs are accurate. The 
investigator and institution will allow the representative(s) of BioCryst or its designee direct 
access to source documents to perform this verification. 
It is important that the investigator(s) and relevant personnel are available during the monitoring 
visits and that sufficient time is devoted to the process. 
During the study, a representative(s) from BioCryst or its designee will have regular contacts 
with the investigational site personnel for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks 
are being performed 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the subject’s medical records at the hospital or practice, and other records relevant to 
the study. This will require direct access to all original records for each subject (eg, clinic 
charts). 
• Record and report any protocol deviations not previously sent to BioCryst or its designee 


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• Confirm AEs and SAEs have been properly documented on the eCRFs and confirm any 
SAEs have been forwarded to BioCryst or its designee and those SAEs that met criteria 
for reporting have been forwarded to the ethics committee 
The representative(s) of BioCryst or its designee will be available between visits if the 
investigator(s) or other staff needs information or advice. 
14.2. 
Audits and Inspections 
Authorized representatives of BioCryst or its designee, US FDA and other regulatory authorities, 
and/or ethics committee may visit the site to perform audits or inspections, including source data 
verification. The purpose of a BioCryst audit or inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the protocol, 
standard operating procedures, ICH GCP guidelines, and any applicable regulatory requirements. 
The investigator should contact BioCryst immediately if contacted by a regulatory agency about 
an inspection. 
It is important that the investigator and relevant personnel are available during the possible audits 
or inspections and that sufficient time is devoted to the process. 
14.3. 
Ethics Committee 
The investigator must obtain ethics approval for the investigation. Initial ethics approval, and all 
materials approved by the ethics committee, including the ICF and any recruitment materials, 
must be maintained by the investigator and made available for inspection. 
14.4. 
Serious Breaches of GCP 
It is the responsibility of the sponsor to notify the competent authority of any serious breach of 
GCP that is likely to affect, to a significant degree, the safety or mental integrity of the subjects 
of the study or the scientific value of the study. All serious breaches will be notified to the 
relevant competent authority in accordance with locally applicable regulations. The reporting to 
the sponsor will be performed by the party who suspects the serious breach. 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
During study conduct, BioCryst or its designee will conduct periodic monitoring visits to ensure 
that the protocol and GCP are being followed as described in Section 14.1. 
To ensure compliance with GCP and all applicable regulatory requirements, BioCryst or its 
designee may conduct a quality assurance audit. Please see Section 14.2 for more details 
regarding the audit process. The investigator agrees to allow the auditors to inspect the drug 
storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 


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16. 
ETHICS 
16.1. 
Ethics Review 
The final study protocol and the final version of the ICF must be approved or given a favorable 
opinion in writing by an ethics committee, as appropriate. The investigator must submit written 
approval from the ethics committee to BioCryst before he or she can enroll any subject into the 
study. 
The ethics committee will be informed of any amendment to the protocol in accordance with 
local requirements. In addition, the ethics committee must approve any advertising used to 
recruit subjects for the study. The protocol must be re-approved by the ethics committee upon 
receipt of amendments and annually, as local regulations require. 
The ethics committee will be provided with reports of any reportable serious adverse drug 
reactions from any other study conducted with the investigational product, in accordance with 
local regulations. BioCryst will provide this information to the investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the ethics 
committee according to local regulations and guidelines. 
16.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH GCP, applicable regulatory requirements, 
and BioCryst’s policies. 
16.3. 
Written Informed Consent 
In accordance with applicable national or local law, and current institutional practice, written 
informed consent to participate in the study will be obtained from each subject prior to 
conducting any study-related assessments/procedures. 
A signed ICF must be obtained from each subject prior to performing any study-related 
procedures. Each subject should be given both oral and written information describing the 
nature, purpose, and duration of the study. Subjects will be informed that they are free not to 
participate in the study and that they may withdraw consent to participate at any time. They will 
be told that refusal to participate in the study will not prejudice future treatment. They will also 
be told that their records may be examined by competent authorities and authorized persons, but 
that personal information will be treated as strictly confidential and will not be publicly 
available. The informed consent process should take place under conditions where the subject 
has adequate time to consider the risks and benefits associated with participation in the study. 
Subjects must be given the opportunity to ask questions. Subjects will not be screened or treated 
until the subject has signed an approved ICF written in a language in which the subject is fluent.  
The ICF that is used must be approved both by BioCryst and by the governing ethics committee. 
The ICF should be in accordance with the current revision of the Declaration of Helsinki, current 
ICH and GCP guidelines, and BioCryst policies. 
The subject should receive a signed and dated copy of the ICF. The original signed ICF should 
be retained in the study files. 


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The investigator shall maintain a log of all subjects for whom consent was signed and indicate if 
the subject was enrolled into the study or reason for non-enrollment. 
17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
BioCryst or designee will be allowed to conduct site visits to the investigation facilities for the 
purpose of monitoring any aspect of the study. The investigator agrees to allow the monitor to 
inspect the drug storage area, study drug stocks, drug accountability records, subject charts, and 
study source documents, and other records relative to study conduct. 
17.2. 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or BioCryst, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient information 
to link records, eCRFs, and medical/hospital records), all original signed ICFs, all eCRFs, and 
detailed records of study drug accountability and treatment disposition. The records should be 
retained by the investigator according to local regulations or as specified in the Clinical Study 
Agreement, whichever is longer. 
If the investigator relocates, retires, or for any reason withdraws from the study, the study 
records may be transferred to an acceptable designee, such as another investigator, another 
institution, or to BioCryst. The investigator must obtain BioCryst’s written permission before 
disposing of any records and must notify BioCryst before transferring any records to another 
facility. 
All correspondence related to records retention, destruction, or transfer of study documents, 
should be sent directly to BioCryst study personnel, copying the email archives@biocryst.com. 
17.3. 
Confidentiality of Information and Data  
BioCryst affirms the subject’s right to protection against invasion of privacy and secure 
maintenance of the confidential nature of his/her personal data. Only a subject identification 
number and subject identifiers permitted by local regulation will identify subject data retrieved 
by BioCryst. However, in compliance with federal regulations, BioCryst requires the investigator 
to permit BioCryst’s representatives and, when necessary, representatives of the FDA or other 
regulatory authorities to review and/or copy any medical records relevant to the study, 
maintaining pseudo-anonymity. 
All parties will abide by all applicable laws and regulations regarding subject privacy and 
confidentiality, including the Health Insurance Portability and Accountability Act (HIPAA), 
where this rule is applicable, and the requirements of the General Data Protection Regulation 
(GDPR) in the EU, where applicable. A valid authorization and consent must meet the 
specifications of the applicable laws and regulations relating to such personal data and health 
information. It is the responsibility of the investigator and institution to obtain such 
waiver/authorization in writing from the appropriate individual. HIPAA authorizations are 
required for US sites only. 


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18. 
PUBLICATION POLICY 
All data generated from this study are the property of BioCryst and shall be held in strict 
confidence along with all information furnished by BioCryst. Except as provided through written 
agreement between BioCryst, independent analysis and/or publication of these data by the 
investigator or any member of his/her staff is not permitted without prior written consent of 
BioCryst. Such consent will not be withheld unreasonably. BioCryst is in agreement with the 
principle of full disclosure of clinical study results. 


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SAP_001.pdf: 
 
 
STATISTICAL ANALYSIS PLAN 
STUDY BCX9930-202 
 
DATE OF PLAN: 
Final Version 1.0: 22 September 2023 
 
BASED ON: 
Protocol Version (Date): Version 4.0: 01 August 2022 
 
STUDY DRUG: 
BCX9930 
PROTOCOL NUMBER: 
BCX9930-202 
STUDY TITLE: 
A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, 
and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal 
Hemoglobinuria in Subjects with Inadequate Response to C5 Inhibitor Therapy 
SPONSOR: 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Blvd., Suite 200 
Durham, NC 27703 
Phone: (919) 859-1302 
Fax: (919) 851-1416 
This study is being conducted in compliance with Good Clinical Practice, including the archiving 
of essential documents. 
The information in this document contains proprietary and confidential information belonging to 
BioCryst Pharmaceuticals, Inc. As a result, no part of this document should be copied, referred 
to, released, published or otherwise disclosed in any manner or media without prior written 
approval from BioCryst Pharmaceuticals, Inc. 


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TECHNICAL SUMMARY REPORT (TSR) 
Name of Sponsor/Company 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Boulevard 
Nottingham Hall, Suite 200 
Durham, North Carolina 27703, USA 
Individual Study 
Table Referring 
to Part of the 
Dossier: 
Volume: 
(For National Authority Use 
Only): 
Name of Finished Product: 
BCX9930 
Page: 
 
Name of Active Ingredient:  
 
 
 
Title of Study: A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the 
Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal 
Nocturnal Hemoglobinuria in Subjects with Inadequate Response to C5 Inhibitor Therapy (BioCryst 
Protocol BCX9930-202) 
Study Centers/Investigators: 
This study will be conducted at study centers in multiple countries/regions. 
Studied period (years): Approximately 2 
years  
Phase of development: Phase 2 
Introduction 
BioCryst stopped development of BCX9930 in December of 2022 based on changes in the competitive 
environment. This statistical analysis plan contains a detailed description of the statistical methods to 
support the abbreviated clinical study report (aCSR) for this study.  
 
Primary Objective: 
• 
To determine the efficacy of oral BCX9930 monotherapy administered for 24 weeks, 
compared to continued complement component 5 (C5) inhibitor therapy, in subjects with 
paroxysmal nocturnal hemoglobinuria (PNH) with an inadequate response to C5 inhibitor 
therapy 
Secondary Objectives: 
• 
To evaluate the safety and tolerability of BCX9930 monotherapy administered for 24 weeks, 
as compared to continued C5 inhibitor therapy, in subjects with PNH 
• 
To characterize the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor 
therapy, using clinical and laboratory measurements, including complement and thrombosis 


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biomarkers, PNH clone size, and C3-opsonization of red blood cells (RBCs) in subjects with 
PNH 
• 
To evaluate the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor 
therapy, on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and 
other patient-reported outcomes (PROs) in subjects with PNH 
• 
To characterize BCX9930 plasma concentrations and pharmacokinetic (PK) parameters in 
subjects with PNH 
For this study, unless indicated otherwise, endpoints will be assessed at or to Week 24. 
Primary Endpoint: 
• 
Change from baseline (CFB) in hemoglobin (Hb) [mean of values at Weeks 12, 16, 20, 
and 24] 
Key Secondary Endpoints: 
1. Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 
2. Number of units of packed red blood cells (pRBCs) transfused [from Week 4 to Week 24] 
3. CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
Other Secondary Endpoints: 
• 
Percent CFB in lactate dehydrogenase (LDH) [mean of values at Weeks 12, 16, 20, and 24] 
• 
Percent reduction in the rate of pRBC and whole blood units transfused [from Week 4 to 
Week 24 vs. prestudy transfusion rate (12 month prestudy transfusion rate)] 
• 
Proportion of subjects with Hb ≥ 12 g/dL [at Week 24] 
• 
CFB in C3-opsonized RBCs [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in total PNH RBC clone size [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in ratio of total PNH RBC clone size to PNH white blood cell (WBC) clone size (ie, ratio 
of percent PNH RBCs / percent PNH WBCs) [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in absolute reticulocyte count (ARC) [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in haptoglobin [mean of values at Weeks 12, 16, 20, and 24] 
• 
CFB in total bilirubin [mean of values at Weeks 12, 16, 20, and 24] 
Safety Endpoints: 
• 
Number and proportion of subjects with a treatment-emergent adverse event (TEAE) 
• 
Number and proportion of subjects who discontinue treatment due to a TEAE 
• 
Number and proportion of subjects who experience a treatment-emergent serious adverse 
event (TESAE) 
• 
Number and proportion of subjects who experience a Grade 3 or Grade 4 TEAE assessed 
using the Common Terminology Criteria for Adverse Event (CTCAE) grading scales 
• 
Number and proportion of subjects who experience a treatment-emergent CTCAE Grade 3 or 
Grade 4 laboratory abnormality 


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PK and Pharmacodynamic (PD) Endpoints 
• 
PK data will be used to estimate PK parameters using appropriate PK analyses based on the 
sampling collection approaches 
• 
PD data will be used to estimate PD parameters  
 
Study Design: 
This is a randomized, active-controlled, open-label, multicenter, parallel-group, 2-part study. Parts 1 
and 2 will be conducted in the same subjects. Part 1 of the study is designed to evaluate the efficacy, 
safety, and tolerability of treatment with oral BCX9930 monotherapy for 24 weeks versus continuing 
C5 inhibitor therapy in subjects with PNH with inadequate response to their current C5 inhibitor 
therapy. Subjects will be randomized to either discontinue C5 inhibitor therapy and start BCX9930 
monotherapy or to continue C5 inhibitor therapy for the 24-week randomized treatment period. The 
primary efficacy and safety analyses will be based on Part 1. Part 2 of the study is designed to evaluate 
the long-term safety, tolerability, and effectiveness of BCX9930 monotherapy when administered 
through Week 52. All subjects in Part 2 will receive BCX9930. Subjects who are randomized to 
BCX9930 monotherapy in Part 1 will continue to receive BCX9930 in Part 2. Subjects who are 
randomized to C5 inhibitor therapy in Part 1 will discontinue that therapy and start BCX9930 in Part 2. 
Methodology: 
Part 1: Eligible subjects will be randomized in a 2:1 ratio to either discontinue C5 inhibitor therapy 
and start BCX9930 monotherapy , or to continue C5 inhibitor therapy at the same dose and regimen as 
previously administered for 24 weeks. Randomization will be stratified based on C5 inhibitor 
(ravulizumab vs. eculizumab) and whether a pRBC transfusion was received within the 6 months prior 
to baseline (yes vs. no). All subjects will be required to return to the clinic at Weeks 1, 2, and 4, and 
every 4 weeks thereafter through Week 24. Subjects randomized to BCX9930 will be required to 
complete additional safety assessments at Weeks 3, 5, 6, 7, and 10. 
Part 2: Subjects randomized to continue C5 inhibitor therapy during Part 1 will discontinue that 
therapy and be switched to BCX9930 monotherapy for Part 2. These subjects will be required to return 
to the clinic at Weeks 25, 26, 28, 32, and 36, and then every 4 weeks thereafter through Week 52. 
Additional safety assessments will be performed at Weeks 27, 29, 30, 31, and 34. Subjects randomized 
to BCX9930 monotherapy in Part 1 will continue with the every 4 weeks visit schedule through 
Week 52. 
After completion of Part 2, all subjects continuing to derive clinical benefit will be allowed to continue 
treatment with BCX9930 through enrollment in a separate long-term extension study, or via another 
access mechanism, where available. Subjects who do not continue BCX9930 therapy after Week 52, or 
who are prematurely discontinued from BCX9930 treatment prior to Week 52, will be monitored for 
potential hemolysis and may be required to return to the clinic for an additional visit(s) to assess for 


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acute symptomatic hemolysis, if and when symptoms occur. Subsequently, they will return to the clinic 
approximately 3 weeks after the date of last dose of BCX9930 for end of study assessments. 
An independent BCX9930 program-wide data monitoring committee (DMC) will provide 
oversight of the ongoing exposure of subjects to BCX9930. 
Number of Subjects (planned):  
Approximately 81 subjects with PNH and an inadequate response to C5 inhibitor therapy (ie, 
approximately 54 subjects in the BCX9930 200/400 mg BID arm and approximately 27 subjects in the 
control arm) will be enrolled. 
Diagnosis and Main Criteria for Inclusion: 
Subjects must meet all of the following inclusion criteria, as applicable, to be eligible for participation 
in this study: 
1. Male or female, aged ≥ 18 years old. 
2. Body weight ≥ 40 kg. 
3. Documented diagnosis of PNH confirmed by flow cytometry with a PNH granulocyte or 
monocyte clone size of ≥ 10% during screening. 
4. Treated with a stable regimen of eculizumab for ≥ 3 months prior to the screening visit or 
ravulizumab for ≥ 6 months prior to the screening visit. 
5. Recorded the following results during screening: 
a. Hb of ≤ 105 g/L (≤ 10.5 g/dL). 
b. ARC of ≥ 100 × 109 cells/L (≥ 100,000 cells/µL; ≥ 100 G/L). 
c. Absolute neutrophil count of ≥ 0.75 × 109 cells/L (≥ 750 cells/µL; ≥ 0.75 × G/L). 
d. Platelet count of ≥ 30 × 109/L (≥ 30,000/µL; ≥ 30 G/L). 
e. Adequate iron reserve based on ferritin ≥ LLN or total iron binding capacity ≤ upper limit of 
the normal reference range (ULN). 
f. Estimated glomerular filtration rate of ≥ 60 mL/min/1.73 m2 using the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation (Levey and Stevens 2010) and no 
evidence of clinically relevant abnormal renal function unrelated to underlying PNH disease. 
6. Contraception requirements: 
Female participants must meet at least one of the following requirements: 
a. Be a woman of nonchildbearing potential. 


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b. Be a woman of childbearing potential who agrees to use a highly effective contraceptive 
method throughout the study and for a duration of 30 days after the last dose of study drug. 
c. Alternatively, true abstinence is acceptable for women of childbearing potential when it is in 
line with the subject’s preferred and usual lifestyle. 
Male participants must meet at least one of the following requirements: 
a. Males with a female partner of childbearing potential must use condoms throughout the study 
and for a duration of 90 days after the last dose of study drug unless their partner is using a 
highly effective contraceptive method independent of the study. 
b. Alternatively, true abstinence is acceptable when it is in line with the subject’s preferred and 
usual lifestyle. 
Additional details are provided in Protocol Section 11.2.1. 
7. Documentation of current vaccinations against Neisseria meningitidis types A, C, W, and Y, and 
Streptococcus pneumoniae, or willingness to start vaccination series at least 14 days prior to 
Day 1. 
(Note: Vaccination for N. meningitidis type B and for Haemophilus influenzae type B [Hib] is 
strongly encouraged where authorized and available.) 
8. In the opinion of the investigator, the subject is expected to adequately comply with all required 
study procedures and restrictions for the study, including compliance with the twice daily (BID) 
dosing schedule for BCX9930. 
9. Willing and able to provide written informed consent. 
Subjects must not meet any of the following exclusion criteria to be eligible for participation in the 
study: 
10. Known history of or existing diagnosis of hereditary complement deficiency. 
11. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for 
transplantation during the study. 
12. Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current 
and uncontrolled clinically significant cardiovascular or cerebrovascular condition, including 
unstable angina, severe congestive heart failure, unexplained syncope, arrhythmia, and critical 
aortic stenosis. 
13. History of malignancy within 5 years prior to the screening visit, with exception of adequately 
treated non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ of 
the cervix, or other curatively treated solid tumor deemed by the investigator and medical 
monitor to be at low risk for recurrence. 


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14. Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to 
screening. 
(Note: Suspected or confirmed coronavirus disease [COVID-19]; persistent or recurrent positive 
test(s) for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] nucleic acids or 
antigens; and worsening of dyspnea not due to PNH, vasculitic rash, and persistent fever or other 
symptoms consistent with multisystem inflammatory syndrome in adults [MIS-A] are 
exclusionary.) 
15. Current participation in any other investigational drug study or participation in an investigational 
drug study within 30 days prior to the screening visit, or 5.5 half-lives of the investigational 
drug, whichever is longer. 
16. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit. 
17. Initiation of treatment with an erythropoiesis-stimulating agent (eg, erythropoietin), a 
thrombopoietin receptor agonist (eg, eltrombopag), or danazol within 28 days prior to the 
screening visit. 
(Note: Treatment with these medications initiated > 28 days prior to the screening visit is not 
exclusionary, if the dose is stable and there is a reasonable expectation that treatment will be 
continued.) 
18. Receiving iron supplementation with an unstable dose in the 28 days prior to the screening visit. 
19. Clinically significant abnormal electrocardiogram (ECG) at the screening visit. 
(Note: This includes, but is not limited to, a QT interval corrected using Fridericia’s method 
[QTcF] of > 450 msec in males or > 470 msec in females, or ventricular and/or atrial premature 
contractions that are more frequent than occasional, and/or as couplets or higher in grouping.) 
20. Subjects with any of the following results at the screening visit: 
a. Alanine aminotransferase (ALT; also serum glutamic-pyruvic transaminase [SGPT]) 
> 3 × ULN. 
b. Aspartate aminotransferase (AST; also serum glutamic-oxaloacetic transaminase [SGOT]) 
> 3 × ULN. 
(Note: Subjects may be enrolled with AST > 3 × ULN if explained by hemolysis.) 
c. Total serum bilirubin > 2 × ULN. 
(Note: Subjects may be enrolled with total serum bilirubin > 2 × ULN if explained by 
hemolysis or Gilbert’s syndrome. In the case of hemolysis, total serum bilirubin must be 
< 5 × ULN and in the case of Gilbert’s syndrome, total serum bilirubin must be < 11 × ULN.) 
21. Current use of a prohibited concomitant medication within 7 days prior to Day 1 as detailed in 
Protocol Section 9.8.1. 


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22. Positive serology for human immunodeficiency virus, or active infection with hepatitis B virus 
or hepatitis C virus, unless receiving antiviral therapy and viral load is undetectable. 
23. Positive drugs of abuse screen, unless by prescription. 
24. Pregnant, planning to become pregnant, or breastfeeding. 
25. Known hypersensitivity to BCX9930 or any of its formulation excipients. 
26. History of severe hypersensitivity to any medicinal product, which was associated with swelling, 
severe rash requiring treatment/hospitalization, or anaphylaxis. 
Any other clinically significant medical or psychiatric condition that, in the opinion of the investigator or 
sponsor, would interfere with the subject’s ability to participate in the study or increase the risk of participation 
for that subject. 
Investigational Product, Dosage and Mode of Administration: 
Subjects who previously received 500 mg BID and remain on study treatment will be dose adjusted to 
400 mg BID. For all newly enrolled subjects, at the initiation of BCX9930 dosing, subjects will be 
administered a dose of 200 mg BID for the first 14 days of treatment before increasing to 400 mg BID. 
The appropriate quantity of BCX9930 tablets will be taken orally twice a day, approximately 12 hours 
apart, without regard to food. Adequate hydration should be maintained to prevent the formation of 
highly concentrated urine. 
Duration of Treatment:  
In Part 1, either continued C5 inhibitor therapy or BCX9930 monotherapy for 24 weeks. In Part 2, all 
subjects will receive BCX9930 monotherapy for 28 weeks. 
Reference Therapy, Dosage and Mode of Administration:  
Eculizumab or ravulizumab administered by intravenous infusion will be maintained at the same dose 
and posology received at screening. 
Statistical Methods: 
Continuous data will be summarized using the number of subjects with available data, mean, SD, 
median, minimum, and maximum.  Categorical data will be summarized using counts and 
percentages. For specified PK parameters, the geometric n, geometric mean and associated 95% 
confidence interval (CI), and the geometric between-subject coefficient of variation (CV%) will be 
presented in addition to the other descriptive statistics.  There will be no formal hypothesis testing.   
The necessary results for the aCSR will be summarized in tables and figures (see Section 12.1  for the 
list of tables and figures). There will be no formal hypothesis testing.   
All relevant study data for the aCSR will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
1. 
LIST OF ABBREVIATIONS.....................................................................................14 
2. 
INTRODUCTION ......................................................................................................16 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................16 
3.1. 
Objectives ...................................................................................................................16 
3.1.1. 
Part 1  Objective .........................................................................................................16 
3.1.2. 
Part 2 Objective ..........................................................................................................16 
3.2. 
Endpoints ....................................................................................................................17 
3.2.1. 
Primary Endpoint ........................................................ Error! Bookmark not defined. 
3.2.2. 
Key Secondary Endpoints ........................................... Error! Bookmark not defined. 
3.2.3. 
Safety Endpoints ......................................................... Error! Bookmark not defined. 
3.2.4. 
PK and Pharmacodynamic (PD) Endpoints ................ Error! Bookmark not defined. 
4. 
STUDY DESIGN .......................................................................................................17 
4.1. 
Summary of Study Design ..........................................................................................18 
4.1.1. 
Part 1 Study Design ....................................................................................................18 
4.1.2. 
Part 2 Study Design ....................................................................................................19 
4.2. 
Definition of Study Treatments ..................................................................................21 
4.3. 
Sample Size Considerations .......................................................................................21 
4.4. 
Randomization ............................................................................................................22 
4.5. 
Clinical Assessments ..................................................................................................22 
4.6. 
Pharmacokinetic and Pharmacodynamic Blood Sampling .........................................22 
5. 
PLANNED ANALYSES ............................................................................................22 
5.1. 
Interim Analyses .........................................................................................................22 
5.2. 
Final Analyses ............................................................................................................23 
6. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES AND 
HANDLING ...............................................................................................................24 
6.1. 
General Summary Table and Individual Subject Data Listing Considerations ..........24 


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6.2. 
General Post-text Summary Table and Individual Subject Data Listing 
Format Considerations ................................................ Error! Bookmark not defined. 
6.3. 
Data Management .......................................................................................................24 
6.4. 
Data Presentation Conventions ...................................................................................24 
6.5. 
Analysis Populations ..................................................................................................25 
6.5.1. 
Screen Failures ............................................................................................................25 
6.5.2. 
Randomized Population ..............................................................................................25 
6.5.3. 
Safety Population ........................................................................................................25 
6.5.4. 
All Subjects as Treated ...............................................................................................25 
6.5.5. 
PK Substudy Population ............................................. Error! Bookmark not defined. 
6.5.6. 
Pharmacokinetic/Pharmacodynamic Population ........................................................25 
6.6. 
Baseline Definition .....................................................................................................25 
6.6.1. 
Part 1 and Study Baseline ...........................................................................................25 
6.6.2. 
Part 2 Baseline ............................................................ Error! Bookmark not defined. 
6.7. 
Derived and Transformed Data ..................................................................................26 
6.7.1. 
Baseline Age ...............................................................................................................26 
6.7.2. 
Study Day ...................................................................................................................26 
6.7.3. 
Change from Baseline and Percent Change from Baseline ........................................26 
6.7.4. 
Fold Change ................................................................ Error! Bookmark not defined. 
6.7.5. 
Treatment-emergent Adverse Events .........................................................................26 
6.7.6. 
Prior and Concomitant Medications ...........................................................................27 
6.7.7. 
Visit Windows ............................................................................................................27 
6.7.8. 
Multiple Assessments .................................................................................................27 
6.7.9. 
Proportion Endpoints ..................................................................................................28 
6.7.1. 
Number of Units of Packed RBCs Transfused ...........................................................28 
6.8. 
Handling of Missing Data ...........................................................................................28 
6.8.1. 
Missing Efficacy Endpoints ........................................................................................28 
6.8.2. 
Missing Start and Stop Dates for Prior and Concomitant Medication .......................28 


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6.8.3. 
Missing Start Date, Stop Date, Severity, or Relationship for Adverse Events ...........29 
6.8.4. 
Missing Time of First Dose ........................................................................................29 
6.8.5. 
Transfusion-impacted Period ......................................................................................29 
6.8.5.1. 
Transfusion-impacted Period for South Africa........... Error! Bookmark not defined. 
6.8.5.2. 
Transfusion-impacted Period for Other Countries ..... Error! Bookmark not defined. 
7. 
STUDY POPULATION .............................................................................................31 
7.1. 
Subject Disposition .....................................................................................................31 
7.2. 
Analysis Populations ..................................................................................................31 
7.3. 
Demographic and Baseline Characteristics ................................................................31 
7.4. 
PNH History ...............................................................................................................31 
7.5. 
Prior and Concomitant Medications ...........................................................................31 
7.5.1. 
Summary of Concomitant Medications ......................................................................32 
7.5.2. 
Summary of 12-Month Pre-study Transfusion Details ...............................................32 
7.6. 
Exposure to Study Treatment .....................................................................................32 
8. 
EFFICACY .................................................................................................................32 
8.1. 
Primary Efficacy Analysis of Hemoglobin .................................................................33 
8.2. 
Key Secondary Efficacy Endpoints ............................................................................34 
8.2.1. 
Proportion of Subjects Who Are Transfusion-Free from Week 4 to Week 12 ..........34 
8.2.2. 
Number of Packed Red Blood Cells (pRBCs) Transfused from Week 4 to 
Week 12 ......................................................................................................................34 
8.2.3. 
Percent CFB in Lactate Dehydrogenase (LDH) .........................................................34 
8.2.4. 
CFB in FACIT-Fatigue scale ......................................................................................34 
9. 
SAFETY AND TOLERABILITY ..............................................................................34 
9.1. 
Overall Summary of Treatment-emergent Adverse Events ........................................35 
9.2. 
Adverse Event Preferred Term and Body/Organ System Summary Tables ...............35 
9.2.1. 
Treatment-emergent Adverse Events by System Organ Class and Preferred 
Term ............................................................................................................................35 
9.2.2. 
Other Adverse Event Summary Tables ......................................................................36 


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9.2.2.1. 
Treatment-emergent Adverse Events by Preferred Term and Treatment 
Group ..........................................................................................................................36 
9.2.2.2. 
Treatment-emergent Adverse Events by Preferred Term and Dose Group ........ Error! 
Bookmark not defined. 
9.2.2.3. 
Serious Treatment-emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term ...........................................................................................36 
9.2.2.4. 
Renal Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term ............................................................................................................36 
9.2.2.5. 
Hepatic Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term ............................................................................................................36 
9.2.2.6. 
Treatment-emergent Grade 3 and 4 Laboratory Parameters by Visit and 
Overall ........................................................................................................................37 
10. 
PHARMACOKINETICS AND PHARMACODYNAMICS .....................................38 
11. 
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES ....................................42 
12. 
REFERENCES ....................................... ERROR! BOOKMARK NOT DEFINED. 
13. 
APPENDIX............................................. ERROR! BOOKMARK NOT DEFINED. 
13.1. 
Table of Contents for Data Display Specifications ....................................................43 
13.1.1. 
Tables and Figures ......................................................................................................43 
13.1.2. 
Data Listings ...............................................................................................................45 
13.2. 
Data Display Specifications ........................................................................................46 
13.3. 
FACIT-Fatigue Scale ..................................................................................................47 
 
 
 


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LIST OF TABLES 
Table 1: 
List of Abbreviations and Definitions of Terms .........................................................14 
Table 2: 
FACIT-Fatigue Scale ..................................................................................................47 
 
 


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1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Term 
aCSR 
abbreviated clinical study report  
ADaM 
analysis data model 
AE 
adverse event 
AKI 
acute kidney injury 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ARC 
absolute reticulocyte count 
AST 
aspartate aminotransferase 
BID 
twice daily 
BMI 
body mass index 
BQL 
below the quantitation level 
BTH 
breakthrough hemolysis 
CFB 
change from baseline 
COVID-19 
coronavirus disease 2019 
CTCAE 
Common Terminology Criteria for Adverse Event 
eCRF 
electronic case report form 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FDA 
Food and Drug Administration 
ICH 
International Council for Harmonisation 
LLN 
lower limit of normal 
MAVE 
major adverse vascular event 
MedDRA 
Medical Dictionary for Regulatory Activities 
N 
total sample size 
PNH 
paroxysmal nocturnal hemoglobinuria 
pRBC 
packed red blood cells 
PRO 
patient-reported outcome 
PT 
preferred term 


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RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
TDD 
total daily dose 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
WBC 
white blood cell 
WHO 
World Health Organization  


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2. 
INTRODUCTION 
BioCryst stopped development of BCX9930 in December of 2022 based on changes in the 
competitive environment. The purpose of this statistical analysis plan (SAP) is to describe the 
planned analyses and data displays to be included in the abbreviated clinical study report (aCSR) 
for Study BCX9930-202 (Study 202). 
Protocol Revision Chronology: 
Final Protocol Date: 
Version 4.0: 01 August 2022 (Amendment 3) 
Previous Version(s): 
Version 3.0: 29 June 2022 (Amendment 2) 
Version 2.0: 27 May 2021 (Amendment 1) 
Version 1.0: 18 March 2021 (Original) 
This SAP was developed in accordance with the International Council for Harmonisation (ICH) 
E9 guideline. The purpose of this document is to provide details on the statistical methodology 
used to meet the objectives for Study 202. Study population definitions, derivations of variables, 
handling of missing data, and other information necessary for analysis of study data are 
provided. Planned tables, figures, and listings are specified.  
The document may evolve over time, for example, to reflect the requirements of protocol 
amendments or regulatory requests. However, the final SAP must be finalized, approved by the 
sponsor, and placed on file before database is locked. Deviations from the final approved plan 
will be noted in the CSR. 
3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Objectives 
3.1.1. 
Part 1 Objective 
Part 1 of the study will characterize the effects, safety, and tolerability of treatment with oral 
BCX9930 monotherapy for 24 weeks versus continued C5 inhibitor therapy, in subjects with 
PNH with an inadequate response to C5 inhibitor therapy. 
To characterize BCX9930 plasma concentrations and pharmacokinetic (PK) parameters in 
subjects with PNH. 
3.1.2. 
Part 2 Objective 
Part 2 of the study will evaluate the long-term safety and tolerability of oral BCX9930 
monotherapy administered over a 28- to 52-week treatment period in subjects with PNH with 
inadequate response to C5 inhibitor therapy. 


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To characterize BCX9930 plasma concentrations and pharmacokinetic (PK) parameters in 
subjects with PNH. 
 
 
3.2. 
Endpoints 
For this study, unless indicated otherwise, endpoints will be assessed at or to Week 24. 
Primary Endpoint: 
• Change from baseline (CFB) in hemoglobin (Hb) [mean of values at Weeks 12, 16, 20, 
and 24] 
Key Secondary Endpoints: 
• Proportion of subjects who are transfusion-free [from Week 4 to Week 24] 
• Number of units of packed red blood cells (pRBCs) transfused [from Week 4 to 
Week 24] 
• CFB in FACIT-Fatigue scale score [mean of values at Weeks 12, 16, 20, and 24] 
Other Secondary Endpoints: 
• Percent CFB in lactate dehydrogenase (LDH) [mean of values at Weeks 12, 16, 20, and 
24] 
• Percent reduction in the rate of pRBC and whole blood units transfused [from Week 4 to 
Week 24 vs. prestudy transfusion rate (12 month prestudy transfusion rate)] 
• Proportion of subjects with Hb ≥ 12 g/dL [at Week 24] 
• CFB in total PNH RBC clone size [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in ratio of total PNH RBC clone size to PNH white blood cell (WBC) clone size 
(ie, ratio of percent PNH RBCs / percent PNH WBCs) [mean of values at Weeks 12, 16, 
20, and 24] 
• CFB in absolute reticulocyte count (ARC) [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in haptoglobin [mean of values at Weeks 12, 16, 20, and 24] 
• CFB in total bilirubin [mean of values at Weeks 12, 16, 20, and 24] 
Safety Endpoints: 
• Number and proportion of subjects with a treatment-emergent adverse event (TEAE) 
• Number and proportion of subjects who discontinue treatment due to a TEAE 
• Number and proportion of subjects who experience a treatment-emergent serious adverse 
event (TESAE) 


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• Number and proportion of subjects who experience a Grade 3 or Grade 4 TEAE assessed 
using the Common Terminology Criteria for Adverse Event (CTCAE) grading scales 
PK and Pharmacodynamic (PD) Endpoints 
• PK data will be used to estimate PK parameters using appropriate PK analyses based on 
the sampling collection approaches 
• PD data will be used to estimate PD parameters  
 
4. 
STUDY DESIGN 
4.1. 
Summary of Study Design 
This is a randomized, active-controlled, open-label, multicenter, parallel group, 2-part study. Part 
1 of the study is designed to evaluate the efficacy, safety, and tolerability of treatment with oral 
BCX9930 monotherapy for 24 weeks versus continued C5 inhibitor therapy in subjects with 
PNH with an inadequate response to the C5 inhibitor. Subjects will be randomized to either 
discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor 
therapy for the 24-week randomized treatment period. Part 2 of the study is designed to evaluate 
the long-term safety and tolerability and effectiveness of BCX9930 monotherapy when 
administered through Week 52. Subjects who are randomized to BCX9930 monotherapy in Part 
1 will continue to receive BCX9930 in Part 2. Subjects who are randomized to C5 inhibitor 
therapy in Part 1 will discontinue that therapy at the Week 24 visit and start BCX9930 in Part 2. 
Data collected through Week 24 will constitute the primary data set for the study; hence, the 
primary database will be locked and analyzed following capture of available data for all subjects 
through Week 24. 
4.1.1. 
Part 1 Study Design  
Part 1: 24-week, randomized, open-label evaluation of efficacy, safety, and tolerability of 
BCX9930 monotherapy versus continued C5 inhibitor therapy. 
 
Patients with PNH who have been treated with a stable regimen of eculizumab for ≥ 3 months or 
ravulizumab for ≥ 6 months and who have had an inadequate response to that therapy may be 
screened for this study. Following confirmation of study eligibility, Day 1 will be scheduled such 
that it occurs on or within 2 weeks prior to the date that the subject is scheduled to receive the 
next dose of eculizumab, or within 2 weeks prior to the date on which the subject is scheduled to 
receive the next dose of ravulizumab, as applicable (see the study schema shown in Figure 3). On 
that day, after completion of all baseline procedures, subjects randomized to BCX9930 


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monotherapy will receive the first dose of BCX9930 administered under the supervision of clinic 
staff, with the second dose administered later that day. Subsequent doses of BCX9930 are taken 
BID, approximately 12 hours apart, through Week 24. For subjects randomized to continue C5 
inhibitor therapy, Day 1 may be scheduled at any time within the 2 weeks prior to the next dose 
of the C5 inhibitor. All subjects will be required to return to the clinic at Weeks 1, 2, and 4, and 
every 4 weeks thereafter through Week 24. Subjects randomized to BCX9930 will be required to 
complete additional safety assessments at Weeks 3, 5, 6, 7, and 10. 
Data collected through Week 24 will constitute the primary data set for the study; hence, the 
primary database will be locked and analyzed following capture of available data for all subjects 
through Week 24. 
4.1.2. 
Part 2 Study Design 
Part 2: 28-week open-label evaluation of the long-term safety, tolerability, and effectiveness of 
BCX9930 monotherapy. 
Subjects randomized to continue C5 inhibitor therapy during Part 1 will be switched to 
BCX9930 monotherapy in Part 2. The timing of the final dose of the C5 inhibitor on or prior to 
Week 24 will be determined by the dose schedule for each individual subject. These subjects will 
be required to return to the clinic at Weeks 25, 26, 28, 32, and 36, and every 4 weeks thereafter 
through Week 52. Additional safety assessments will be performed at Weeks 27, 29, 30, 31, and 
34. Subjects randomized to BCX9930 monotherapy in Part 1 will continue with the every 4 
weeks visit schedule, ie, omitting the visits at Weeks 25 and 26, returning to the clinic at Week 
28 and every 4 weeks thereafter through Week 52. 
After completion of Part 2, all subjects continuing to derive clinical benefit will be allowed to 
continue treatment with BCX9930 through enrollment in a separate long-term extension study, 
or via another access mechanism, where available (see Protocol Section 8.5). Subjects who do 
not continue BCX9930 therapy after Week 52, or who are prematurely discontinued from 
BCX9930 treatment prior to Week 52, will be monitored for potential hemolysis, and may be 
required to return to the clinic for an additional visit(s) to assess for acute symptomatic 
hemolysis, if and when symptoms occur. Subsequently, they will return to the clinic 
approximately 3 weeks after the date of last dose of BCX9930 for end of study assessments. 
A study schema under Protocol Version 4.0 is shown in Figure 1.   
Figure 1: 
BCX9930-202 Study Schema (Parts 1 and 2) 
 
 


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Abbreviations: BID = twice daily; D1 = Day 1; q8wk = every 8 weeks; q14d = every 14 days. 
Note: First dose of BCX9930 administered (1) within 2 weeks prior to the next scheduled dose of ravulizumab, or (2) on or within 2 weeks prior 
to the next scheduled dose of eculizumab. Subjects will not receive their next scheduled dose of C5 inhibitor (exception: subjects receiving 
eculizumab may receive their final dose on the day they initiate BCX9930 if scheduled for that day (blue triangle). Assessments occurring below 
the x-axis require a visit to the investigational site; assessments shown above the x-axis may be completed at the investigational site, at a 
laboratory local to the subject, or via a home health service (where permitted and available) for as long as enhanced safety monitoring procedures 
are required. 
 
 
 
 


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4.2. 
Definition of Study Treatments 
In Part 1, eligible subjects will be randomized in a 2:1 ratio through an interactive web-based 
response system (IWRS) to either discontinue C5 inhibitor therapy and start BCX9930 
monotherapy or to continue C5 inhibitor therapy through Week 24: 
• BCX9930 to be administered orally BID (experimental arm) 
OR 
• Continuation of current C5 inhibitor therapy (control arm) 
Randomization will be stratified based on each subject’s current C5 inhibitor (ravulizumab vs. 
eculizumab) and receipt of a pRBC transfusion within the 6 months prior to baseline (yes vs. no). 
In Part 2, all subjects will receive BCX9930 monotherapy: 
• BCX9930 to be administered orally BID (experimental arm) 
4.3. 
Sample Size Considerations 
Assuming a Type 1 error rate of 0.05, a common standard deviation for Hb of 2.3 g/dL from Lee 
and colleagues (Lee, Peffault de Latour, et al. 2019) and a randomization ratio of 2:1, a sample 
size of 66 subjects (44 subjects in the BCX9930 200/400 mg BID arm, 22 subjects in the control 
arm) will have 90% power to detect a treatment difference of 2.0 g/dL in Hb from baseline for 
subjects randomized to BCX9930 compared to subjects randomized to continue C5 inhibitor 
therapy, based on a two-sample t-test. To account for potential dropouts, approximately 
81 subjects (ie, approximately 54 subjects in the BCX9930 200/400 mg BID arm and 
approximately 27 subjects in the control arm) will be enrolled. 
 
 
 


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4.4. 
Randomization 
In Part 1 of the study, approximately 81 subjects will be randomized in a 2:1 ratio to either 
discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor 
therapy through Week 24. Randomization for individual subjects will occur prior to Day 1 after 
completion of all screening procedures and confirmation of study eligibility. 
Randomization will be stratified based on C5 inhibitor (ravulizumab vs. eculizumab) and 
whether a pRBC transfusion was received within the 6 months prior to baseline (yes vs. no). 
Thus, there will be 4 strata as shown below. 
 
Stratum No. 
Stratum Description 
1 
Treated with eculizumab, received pRBC transfusion within previous 6 months 
2 
Treated with eculizumab, did not receive pRBC transfusion within previous 6 months 
3 
Treated with ravulizumab, received pRBC transfusion within previous 6 months 
4 
Treated with ravulizumab, did not receive pRBC transfusion within previous 6 months 
The randomization scheme will be generated by an unblinded statistician at PharPoint. 
  
4.5. 
Clinical Assessments 
Table 4 in BCX9930-202 Final Protocol summarizes the Part 1 Schedule of Study 
Assessments/Procedures (Screening to Week 24).  
Table 5 in BCX9930-202 Final Protocol summarizes the Part 2 Schedule of Study 
Assessments/Procedures (Weeks 25 to 52).  
4.6. 
Pharmacokinetic and Pharmacodynamic Blood Sampling 
Table 6 in BCX9930-202 Final Protocol summarizes the Pharmacokinetic and Pharmacodynamic 
Blood Sampling. 
5. 
PLANNED ANALYSES 
5.1. 
Interim Analyses 
No formal interim analyses are planned. DMC analysis will be conducted on an as-needed basis. 


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5.2. 
Final Analyses 
Analysis of the data from Parts 1 and 2 will be conducted after all subjects enrolled complete or 
discontinue the study, the resulting clinical database has been cleaned and quality checked, the 
analysis populations have been finalized, and the final database lock has occurred. 
 
 


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6. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES AND 
HANDLING 
This section addresses the definitions, algorithms, imputations, and conventions that will apply 
to the analysis and handling of the data in general. Rules that are data specific will be addressed 
in the detailed discussions of individual summary tables. 
6.1. 
General Summary Table and Individual Subject Data Listing Considerations 
Version 9.4 or higher of the SAS system will be used to analyze the data and to generate tables, 
figures, and listings. All SAS programs prepared to analyze the data will be properly annotated 
to permit uninvolved outside statistical experts to replicate all the analyses specified in this SAP.  
A table of contents for the tables, figures and listings can be found in Section 12.1.  
6.2. 
Data Management 
The standard operating procedures (SOPs) of PharPoint, the selected data management and 
statistical and programming vendor for this study, will be used. A data management plan will be 
developed and approved prior to commencement of data entry. Data will be captured using the 
Medidata electronic data capture system. Electronic validation steps (edit checks) will be used, 
and data cleaning will occur in conjunction with each site. Prior to transfer of data provided by 
vendors (eg, laboratory data), a data transfer agreement including specifications for the type of 
file, definitions of variables, and contact information for the sending and receiving parties will be 
developed and finalized. 
Data will be mapped to Study Data Tabulation Model (SDTM)-compliant datasets prior to 
creation of Analysis Data Model (ADaM)-compliant derived datasets for use in the creation of 
summary tables. 
6.3. 
Data Presentation Conventions 
 
Summary tables and listings will include “footers” providing:  
1. Date and time of output generation.  
2. SAS® program name that generates the output.  
3. The name(s) and location(s) of any input dataset(s) used in the creation of the output.  
4. Any other output-specific details that require elaboration.  
 
Version 9.4 or higher of the SAS system will be used to analyze the data and to generate tables, 
figures, and listings. All SAS programs prepared to analyze the data will be properly annotated 
to permit uninvolved outside statistical experts to replicate all the analyses specified in this 
statistical analysis plan (SAP).  


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The date of output generation links the output to the locked and archived database to allow 
replication of the results. 
6.4. 
Analysis Populations  
6.4.1. 
Screen Failures 
Subjects who give informed written consent but are not randomized to study treatment and are 
noted as screen failures in the electronic case report form (eCRF) are considered screen failures.  
6.4.2. 
Randomized Population 
The randomized population is defined as all subjects who were randomized regardless of 
whether treatment was taken or not.  
6.4.3. 
Safety Population 
The safety population is defined as all subjects who receive at least 1 dose of study treatment, 
whether C5-INH or BCX9930.  
6.4.4. 
All Subjects as Treated 
The all subjects as treated (ASaT) population is defined as all subjects who received at least 1 
dose of study drug and had a post baseline laboratory assessment.  
6.4.5. 
Pharmacokinetic/Pharmacodynamic Population 
Subjects who have both plasma concentration and PD data for at least one post-dose timepoint 
will be included in the PK/PD population.  
 
6.5. 
Baseline Definition 
6.5.1. 
Study Baseline 
For a given subject and assessment the baseline result generally will be the latest non-missing 
result prior to administration of the first dose of study treatment.  
For determination of Hb, ARC, total PNH RBC clone size, the ratio of total PNH RBC clone size 
to PNH WBC clone size, and haptoglobin, only central lab values that were not impacted by 
transfusions (collected within 14 days after the subject received a pRBC or whole blood 
transfusion) will be used. All Hb values that meet these criteria and were collected at any time 
from the Screening visit up to Day 1 pre-dose will be averaged to determine a baseline value. If 
no central lab values are available but there are local lab values that were not collected within 14 


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days after the subject received a pRBC or whole blood transfusion, local lab values that meet the 
criteria will be used in place of the central lab values.  
Note: For South Africa, the local labs are preferred over the central laboratory values. In 
addition, in the event that other parameters (Hb, ARC, total PNH RBC clone size, the ratio of 
total PNH RBC clone size to PNH WBC clone size, haptoglobin, and FACIT-Fatigue) that are 
impacted by pRBC or whole blood transfusion that were not collected outside the transfusion-
impacted period, the average of pre-transfusion values from the Screening visit up to Day 1 pre-
dose will be used to determine a baseline value, even if these values are themselves impacted by 
transfusion. If pre-transfusion values are not available, any value prior to Day 1 pre-dose will be 
used. 
6.6. 
Derived and Transformed Data 
6.6.1. 
Baseline Age  
The subject’s baseline age in years will be the age provided in the eCRF as collected at the time 
of consent. 
6.6.2. 
Study Day 
If the date of interest occurs on or after the date of first dose of study treatment, then study day 
will be calculated as (date of interest – date of first dose) + 1. If the date of interest occurs prior 
to the date of first dose, then study day will be calculated as (date of interest – date of first dose). 
There is no study day zero. 
6.6.3. 
Change from Baseline and Percent Change from Baseline 
Change from baseline will be calculated as (post-baseline result – baseline result). Percent 
change from baseline will be calculated as (100 × change from baseline/baseline result). If either 
the baseline or the post-baseline result is missing, the change from baseline and percent change 
from baseline will be set to missing as well. If the baseline value is 0, the percent change from 
baseline cannot be calculated under this definition. In these cases, percent change will remain 
missing. 
6.6.4. 
Treatment-emergent Adverse Events 
An AE is considered treatment-emergent if its start date and time is on or after the date and time 
of first dose of study treatment and will be assigned to the relevant treatment depending on when 
the TEAE began. If the AE start date is missing and the AE stop date is after the start date of the 
first dose of study treatment (or the AE is ongoing) then the AE will be considered treatment 
emergent. If either or both times are missing, then dates alone will be compared. See Section 
6.7.3 for incomplete dates or times. 


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AEs occurring 30 days after the last dose for subjects who discontinue study treatment will be 
considered as TEAEs. All AEs that occurred prior to the initiation of study treatment or those 
recorded more than 30 days after the last dose of study treatment will be excluded from the 
tables but will be included in the listings.  
6.6.5. 
Prior and Concomitant Medications 
A medication will be classified as prior if it stopped before the first dose of study treatment; that 
is, its end date and time are on or before the date and time of the first dose of study treatment. 
Otherwise, the medication will be classified as concomitant; that is, its start date and time are on 
or after the date and time of the first dose of study treatment, or its end date and time are after the 
start date and time of the first dose of study treatment, or the medication is flagged as ongoing. If 
either or both times are missing, then dates alone will be compared. See Section 6.7.2 for 
incomplete dates or times. 
6.6.6. 
Visit Windows 
For summary purposes in general, records will be assigned to the scheduled visit collected on the 
eCRF. There will be no time windowing efficacy analyses for this aCSR (i.e., all longitudinal 
efficacy analysis will be based on the values recorded at the scheduled visits). However, 
unscheduled visits values will be used for safety analyses of most severe event.  
All information collected at an unscheduled visit will be identified as such and presented in the 
listings. 
6.6.7. 
Multiple Assessments 
Where multiple planned scheduled measurements are recorded for a given time point, the mean 
of the measurements will be calculated and used in any derivation of summary statistics. All 
available data will be listed. 
For baseline Hb calculation when there are multiple assessments between Screening and Day 1, 
see Section 6.5.1. 
All available data will be listed. The endpoint will be listed and summarized. 
For subjects with multiple lab values on the same day, special rules will be used to choose values 
eligible for display on tables and figures. On days with multiple test results from both central 
labs and local labs, results from the central lab will be used. If central labs are not available, local 
lab test results will be used.  If there are still multiple records on the same date, then the median 
of available records on that date will be used and the median will be graded for toxicity.  
For subjects with multiple lab values during the same nominal visit, special rules will be used to 
choose values eligible for display on tables. For South African sites: on visits with multiple test 
results, results from the local lab will be used. For other sites: on visits with multiple test results, 


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results from the central lab will be used. If there are still multiple records on the same visit, then 
the latest occurring result from the available records on that visit will be used. Results from 
Unscheduled visits are not included. 
6.6.8. 
Proportion Endpoints 
The various endpoints involving proportions are defined below. 
• Proportion of subjects who are transfusion-free from Week 4 to Week 24 is defined 
for each treatment group as the number of subjects who do not receive any 
transfusions (pRBCs or whole blood) during the period of interest from the start to the 
end, inclusive, divided by the total number of subjects in that treatment group at the 
start of the period of interest.  
• Note: Subjects who either (1) discontinue treatment prior to Week 24, or (2) have an 
on-study Hb value ≤ 7 g/dL regardless of symptoms will not be considered 
transfusion-free.  
6.6.9. 
Number of Units of Packed RBCs or Whole Blood Transfused 
The number of units of pRBCs will be the total count per subject of units of pRBCs or whole 
blood that are administered to the subject from Week 4 to Week 24 as recorded in the eCRF. 
Transfusions of 1 unit of whole blood will count as 1 unit of pRBCs. The period of interest is 
Week 4 to Week 24 and includes Week 4 to the time of last dose of BCX9930.  For subjects who 
discontinue treatment, the number of units will be calculated through the date of study treatment 
discontinuation. 
6.7. 
Handling of Missing Data 
Every effort will be made to obtain all data. In cases where this is not possible, various methods 
for handling the missing data will be employed. 
6.7.1. 
Missing Efficacy Endpoints 
For the primary endpoint (change from baseline in hemoglobin at Week 24) as well as key secondary 
endpoints LDH and FACIT-Fatigue Scale, results will be presented for (1) the subjects with a Week 24 
change from baseline and (2) the Week 24 change from baseline using the last observation carried 
forward.  
6.7.2. 
Missing Start and Stop Dates for Prior and Concomitant Medication 
For analysis of medications, a complete date should be established to identify medication as 
occurring during treatment or not. For the purposes of handling partially reported start and stop 
dates for medication, the following algorithm will be applied: 


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• Missing start day, but month and year present: 
If study medication had been taken in the same month and year as the occurrence of 
the medication, then the start day of the medication will be assigned to the day of first 
dose of study medication. 
Otherwise, the start day will be set to the first day of the month. 
• Missing start day and month, but year present: 
If study medication had been taken in the same year as the occurrence of the 
medication, then the start date of the medication will be assigned to the date of first 
application of study medication. 
Otherwise, the start day and month will be set to 01 January. 
• Missing end day, but month and year present: 
The day will be set to the last day of the month. 
• Missing end day and month, but year present: 
The end day and month will be set to the date of trial termination. 
6.7.3. 
Missing Start Date, Stop Date, Severity, or Relationship for Adverse Events 
The same conventions to address incomplete dates for prior and concomitant medications will 
also be used for AEs. Should an event have a missing severity or relationship, it will be classified 
as having the highest severity and/or strongest relationship to study treatment. 
6.7.4. 
Missing Time of First Dose 
In case of missing time for first dose, it will be assumed that baseline measures that were to be 
taken prior to first dose according to the protocol were in fact taken prior to dosing. 
6.7.5. 
Transfusion-impacted Period 
The 14-day period following a transfusion of pRBCs or whole blood is defined as the 
transfusion-impacted period (i.e., the interval between the transfusion day and the current study 
day is ≤ 13 days and includes the day of transfusion). An exception to this rule is that the 
transfusion-impacted period for haptoglobin is the 3-day period following a transfusion (i.e., the 
interval between the transfusion day and the current study day is ≤ 2 days and includes the day of 
transfusion).  
The following parameters are impacted by pRBC or whole blood transfusion: 
• Hemoglobin 


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• Reticulocytes 
• PNH RBC (Type II and III red blood cells) 
• Ratio of PNH RBC to PNH WBC 
• FACIT-Fatigue 
• Haptoglobin (transfusion-impacted period is limited to 3 days instead of 14) 


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7. 
STUDY POPULATION 
All study population data to support the aCSR will be presented in data listings (see 
Section 12.1.2  ‘Data Listings”).  
A CONSORT diagram will be created based on the subject disposition and analysis populations 
summary tables for the study report.  
7.1. 
Subject Disposition 
The subject disposition table for all subjects will summarize the number and percentage of 
subjects that screen failed, were randomized, received at least one dose of study drug, 
discontinued treatment, the reasons for discontinuation, and subjects that completed the study. 
Results will be summarized for the BCX9930 and C5-INH groups and overall.  
The percentages for subjects dosed, discontinued, and completed will be based on the number of 
subjects randomized. Percentages for discontinuation reason will be based on the number of 
subjects that discontinued.  
7.2. 
 Analysis Populations 
The analysis population table for all subjects in the safety population will summarize the number 
and percentage of subjects in the ASaT and PK/PD substudy populations with percentages based 
on the number of subjects in the safety population.  The results will be presented for the 
BCX9930 and C5-INH groups and overall.  
7.3. 
Demographic and Baseline Characteristics 
The subject demographic and baseline characteristics table for the subjects in the safety 
population will descriptively summarize results for age at consent, race, ethnicity, and sex. 
Results will be summarized for the BCX9930 and C5-INH groups and overall.    
7.4. 
PNH History  
The PNH history table for the subjects in the safety population will descriptively summarize 
results for the assessments recorded in the Paroxysmal Nocturnal Hemoglobinuria History CRF 
page. Results will be summarized for the BCX9930 and C5-INH groups and overall. 
7.5. 
Prior and Concomitant Medications 
Medications will be classified as prior or concomitant, coded using the World Health 
Organization (WHO) drug dictionary version B3 March 2021, and summarized by Anatomical 
Therapeutic Class (ATC) 4 term, preferred term (PT), and treatment group. Multiple uses of the 
same medication (by preferred name) will be counted once only per subject per study treatment.  


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7.5.1. 
Summary of Concomitant Medications 
The concomitant medications table for the subjects in the safety population will summarize the 
number and percentage of subjects taking concomitant medication(s) by ATC 4 term and PT. 
Results will be summarized for the BCX9930 and C5-INH groups and overall. 
7.5.2. 
Summary of 12-Month Pre-study Transfusion Details 
The 12-month pre-study transfusion detail history table for the subjects in the safety population 
will descriptively summarize results for the assessments recorded in the Blood Transfusions 
History CRF page. Results will be summarized for the BCX9930 and C5-INH groups and 
overall. 
7.6. 
Exposure and Compliance 
The exposure to study treatment table for the subjects in the safety population will descriptively 
summarize for each treatment group the number and percentage of subjects dosed and 
descriptive statistics (i.e., mean, standard deviation, etc.) for the number of days of exposure.  
The compliance data as reported on the eCRF will be listed. 
8. 
EFFICACY  
All study efficacy data to support the aCSR will be presented in data listings (see Section 12.1.2  
“Data Listings”). 
Summary figures to support efficacy for the aCSR will include: 
• Plot of Hemoglobin, LDH, hemolysis events and transfusion events (see example below) 


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Hypothesis testing will not be conducted due to sponsor discontinuation of the study.  No 
subgroup analyses are planned. 
8.1. 
Primary Efficacy Analysis of Hemoglobin  
Descriptive statistics for the observed values and changes from baseline in hemoglobin in the 
ASaT population will be presented for all scheduled visits during the 24-week treatment period. 
A last observation carried forward to Week 24 summary, based on scheduled visits only, will 
also be provided. Results will be presented for the BCX9930 and C5-INH groups. Values 
recorded within 14 days after the subject received a pRBC or whole blood transfusion will be 
excluded from the summary statistics.  Unscheduled visits will be presented in the data listings 
but not summarized in the table.   
In addition, hemoglobin changes from baseline at the Week 24 scheduled time point will be 
summarized for the following dose groups: BCX9930 200 mg BID, BCX9930 750 mg TDD, 
BCX9930 400 mg BID, BCX9930 500 mg BID, All BCX9930 Subjects, C5-INH as well as the 
total across all groups.    


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8.2. 
Key Secondary Efficacy Endpoints 
8.2.1. 
Proportion of Subjects Who Are Transfusion-Free from Week 4 to Week 24 
The number and percentage of subjects who are transfusion-free in the ASaT population from 
Week 4 to Week 24 will be summarized. Results will be presented for the BCX9930 and C5-
INH groups. Subjects who either (1) discontinue treatment prior to Week 24, or (2) a Hb value 
≤ 7 g/dL regardless of symptoms will not be considered transfusion-free.  
8.2.2. 
Number of Packed Red Blood Cells (pRBCs) and Whole Blood Transfused from 
Week 4 to Week 24 
Descriptive statistics for the number of units of pRBCs and whole blood transfused from Week 4 
to Week 24 in the ASaT population will be summarized. Results will be presented for the 
BCX9930 and C5-INH groups.  
8.2.3. 
Percent CFB in Lactate Dehydrogenase (LDH) 
Descriptive statistics for the observed values, changes from baseline, and percent changes from 
baseline in LDH in the ASaT population will be presented for all scheduled visits during the 24-
week treatment period. A last observation carried forward to Week 24 summary, based on 
scheduled visits only, will also be provided. Results will be presented for the BCX9930 and C5-
INH groups. Unscheduled visits will be presented in the data listings but not summarized in the 
table.   
8.2.4. 
CFB in FACIT-Fatigue scale 
Questions and scoring for the FACIT-Fatigue scale can be found in Section 12.3.  
Descriptive statistics for the observed values and changes from baseline in the FACIT-Fatigue 
scale in the ASaT population will be presented for all scheduled visits during the 24-week 
treatment period. A last observation carried forward to Week 24 summary, based on scheduled 
visits only, will also be provided. Results will be presented for the BCX9930 and C5-INH 
groups. Values recorded within the Transfusion-Impacted period will be excluded from the 
summary statistics.  Unscheduled visits will be presented in the data listings but not summarized 
in the table.   
9. 
SAFETY AND TOLERABILITY 
All study safety data to support the aCSR will be presented in data listings (see Section 12.1.2  
“Data Listings”). 


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Summary figures to support safety for the aCSR will include individual subject profiles of ALT, 
ALP, AST, Hemoglobin, and Total Bilirubin. 
AEs will be assessed and recorded from the time of signing of the informed consent through the 
appropriate follow-up period. AEs will be mapped to MedDRA version 24 preferred term (PT) 
and system organ class (SOC). Relationship to study treatment will be assessed as not related, 
unlikely related, possibly related, probably related, or definitely related. AEs will be graded 
according to the CTCAE scales (Version 5.0, 27 November 2017). AEs not covered by CTCAE 
criteria will be assessed for severity as mild, moderate, severe, or life-threatening, corresponding 
to toxicity Grades 1 through 4. 
9.1. 
Overall Summary of Treatment-emergent Adverse Events 
The overall summary of TEAEs table for all subjects in the safety population will summarize the 
number and percentage of subjects that report at least 1 TEAE, have a treatment-related TEAE, 
have a TEAE leading to treatment withdrawal, have a serious TEAE requiring concomitant 
medication, have a severe (Grade 3) or life-threatening (Grade 4) TEAE, have a serious TEAE, 
have a TEAE leading to study discontinuation, and have a TEAE leading to death. In addition to 
summarizing the number and percentage of subjects that have at least 1 of these events, the table 
will also summarize the total number and percentage for each of these events. Results will be 
summarized for the BCX9930 and C5-INH groups and overall.  The percentages for number of 
subjects will use the safety population sample size as the denominator; the percentages for the 
number of events will use the total number of TEAEs as the denominator. 
In addition, the overall summary of TEAEs results will also be summarized for the following 
dose groups: BCX9930 200 mg BID, BCX9930 750 mg TDD, BCX9930 400 mg BID, 
BCX9930 500 mg BID, All BCX9930 Subjects, C5-INH as well as the total across all groups. 
  
Note: For BCX9930, a subject could appear in more than one dose column. 
9.2. 
Adverse Event Preferred Term and Body/Organ System Summary Tables 
9.2.1. 
Treatment-emergent Adverse Events by System Organ Class and Preferred 
Term  
A summary of the number and percentage of subjects with treatment-emergent adverse events by 
system organ class and preferred term will be presented along with the number of events for all 
subjects in the safety population.  Results will be summarized for the BCX9930 and C5-INH 
groups and overall.  The percentages for number of subjects will use the safety population 
sample size as the denominator. 
In addition, the same summary will be presented by: BCX9930 200 mg BID, BCX9930 750 mg 
TDD, BCX9930 400 mg BID, BCX9930 500 mg BID, All BCX9930 Subjects, C5-INH as well 
as overall. 
   


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Note: For BCX9930, a subject could appear in more than one dose column. 
 
9.2.2. 
Other Adverse Event Summary Tables  
9.2.2.1. 
Treatment-emergent Adverse Events by Preferred Term and Treatment 
Regimen and Dose Group 
A summary of the number and percentage of subjects with treatment-emergent adverse events by 
preferred term will be presented along with the number of events for all subjects in the safety 
population.  Results will be summarized for the BCX9930 and C5-INH groups and overall. The 
percentages for number of subjects will use the safety population sample size as the 
denominator.  In addition, the same summary will be presented by: BCX9930 200 mg BID, 
BCX9930 750 mg TDD, BCX9930 400 mg BID, BCX9930 500 mg BID, All BCX9930 
Subjects, C5-INH as well as overall.    
Note: For BCX9930, a subject could appear in more than one dose column. 
9.2.2.2. 
Serious Treatment-emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
A summary of the number and percentage of subjects with serious treatment-emergent adverse 
events by SOC and PT term will be presented along with the number of events for all subjects in 
the safety population.  Results will be summarized for the BCX9930 and C5-INH groups and 
overall. The percentages for number of subjects will use the safety population sample size as the 
denominator. 
9.2.2.3. 
Renal Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term 
A summary of the number and percentage of subjects with renal treatment-emergent adverse 
events by system organ class and preferred term will be presented along with the number of 
events for all subjects in the safety population.  The table will include events in the Acute Renal 
Failure SMQ, Chronic Kidney Disease SMQ, and Tubulointerstitial Diseases.  The percentages 
for number of subjects will use the safety population sample size as the denominator. 
9.2.2.4. 
Hepatic Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term 
A summary of the number and percentage of subjects with hepatic treatment-emergent adverse 
events by system organ class and preferred term will be presented along with the number of 
events for all subjects in the safety population.  The table will include events in the drug related 


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hepatic disorders (comprehensive search SMQ).  The percentages for number of subjects will use 
the safety population sample size as the denominator. 
9.2.2.5. 
Treatment-emergent Grade 3 and 4 Laboratory Parameters by Visit and Overall 
A summary of treatment-emergent Grade 3 and 4 laboratory parameters will be summarized by 
visit and overall. For each visit the number of subjects meeting the criteria and the total number 
of subjects in the relevant treatment group with observations at the specified visit will be 
presented as well as the resulting percentage.  
 
 
 


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10. 
PHARMACOKINETICS AND PHARMACODYNAMICS 
10.1. 
Pharmacokinetics 
Plasma and urine samples for analysis of BCX9930 concentration will be collected according to 
the schedules presented in Protocol Table 4 to Table 6. Plasma PK sampling will include both 
sparse (all subjects) and serial (subjects participating in the PK/PD substudy only) collection. 
Urine sampling will include spot collections only. 
10.1.1. 
Blood Sample Collection 
At study centers with appropriate facilities for the collection and processing of serial plasma 
samples, an optional PK/PD substudy will be performed to characterize the single-dose and 
steady-state PK parameters of BCX9930 in this patient population. 
At these centers, subjects consenting to participate in the optional PK/PD substudy will be asked 
to complete up to two serial PK sample collections. The first sample collection will assess the 
single-dose PK of BCX9930, with samples collected on Day 1 for subjects randomized to 
BCX9930 or during the Week 24 visit for subjects randomized to continue C5 inhibitor therapy 
in Part 1 of the study. The second sample collection will assess the PK of BCX9930 at steady 
state, with samples collected during the Week 2 or any later visit for subjects randomized to 
BCX9930 or during the Week 26 or any later visit for subjects randomized to continue 
C5 inhibitor therapy in Part 1 of the study. 
Serial PK For subjects randomized to BCX9930: 
• On Day 1, 4 PK blood samples will be collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours after administration of the first dose of BCX9930. 
• At the Week 2 or later visit, 5 PK blood samples will be collected; the first sample 
will be collected prior to BCX9930 dosing (≤ 15 minutes), with subsequent samples 
collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. 
Serial PK For subjects randomized to continue C5 inhibitor therapy: 
• At the Week 24 visit, 4 PK blood samples will be collected at 0.5 (± 0.25), 
1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours after administration of the first dose of 
BCX9930. 
• At the Week 26 or later visit, 5 PK blood samples will be collected; the first sample 
will be collected prior to BCX9930 dosing (≤ 15 minutes), with subsequent samples 
collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 6 (± 1) hours post-dose. 
Sparse PK For All Subjects: 


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• Single venous blood samples for analysis of plasma BCX9930 concentration will be 
collected from all subjects randomized to BCX9930 at each scheduled study visit, 
beginning Week 1, and at any unscheduled visits. 
 
 
 
10.1.2. 
Urine Sample Collection 
Spot urine samples will be collected for analysis of the concentration of BCX9930 and 
metabolites during Part 1 for subjects randomized to BCX9930 and from all subjects in Part 2. 
Urine samples for determination of BCX9930 will be analyzed using validated liquid 
chromatography-mass spectrometry assays. The concentration of BCX9930 metabolites may also 
be analyzed using these samples. 
For each sample collected, the actual date and time of sample collection, the actual date and time 
of the last two BCX9930 doses taken prior to the urine collection (where applicable), and 
whether those doses were taken with or without food will be recorded in the eCRF. 
10.2. 
Pharmacodynamics 
10.2.1. 
Blood Sample Collection 
Subjects will have 5 PD samples collected at each substudy visit. 
For subjects randomized to BCX9930: 
• On Day 1, the first sample will be collected prior to BCX9930 dosing (≤ 2 hours), 
with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), and 
6 (± 1) hours post-dose.  
• At the Week 2 or later visit, the first sample will be collected prior to BCX9930 
dosing (≤ 15 minutes), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours post-dose. 
For subjects randomized to continue C5 inhibitor therapy: 
• At the Week 24 visit, the first sample will be collected prior to BCX9930 dosing 
(≤ 2 hours), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 3.5 (± 0.5), 
and 6 (± 1) hours post-dose.  


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• At the Week 26 or later visit, the first sample will be collected prior to BCX9930 
dosing (≤ 15 minutes), with subsequent samples collected at 0.5 (± 0.25), 1.5 (± 0.5), 
3.5 (± 0.5), and 6 (± 1) hours post-dose. 
As applicable, PD blood samples will be collected at the same time as the corresponding PK 
blood sample (ie, excluding the pre-dose sample on Day 1 or Week 24).  
. 
10.3. 
DATA CONVENTIONS 
10.3.1. 
Handling of Data Below the Limit of Quantification 
10.3.1.1. Pharmacokinetic Data Below the Limit of Quantification 
Concentrations that are BLQ will be presented as “BLQ” in listings. Any table or listing that 
contains concentration data will include the lower limit of quantification (LLOQ) for the 
applicable assay(s) as a footnote. 
For calculation of summary statistics for plasma and urine concentration data, concentrations that 
are below the limit of quantification (BLQ) will be treated as zero. Individual BLQ 
concentrations may alternatively be set to missing if deemed appropriate by the clinical 
pharmacologist (e.g., BLQ result is implausible based on the totality of available data). If any 
values are set to missing for concentration analyses, this will be described in the CSR along with 
the rationale for doing so. These values will be reported as “BLQ” in individual-subject 
summaries (including listings) with a flag to denote the rationale for excluding in calculation of 
summary statistics. 
If ≥ 33% of the available concentration values at a given timepoint (or interval) are BLQ or 
missing, only the number of samples, minimum, and maximum will be included in the summary 
tables. All other descriptive statistics parameters will be reported as “NC” (not calculable). 
For estimation of plasma PK parameters, all BLQ concentrations that occur prior to the first 
quantifiable concentration will be set to 0. All BLQ concentrations that occur after the first 
quantifiable concentration will be treated as missing. Quantifiable concentrations occurring after 
2 consecutive BLQ concentrations and occurring during the terminal elimination phase (as 
assessed by the clinical pharmacologist) will be treated as missing.  
10.3.1.2. Pharmacodynamic Data Below the Limit of Quantification 
For calculation of summary statistics for PD measures, values that are BLQ will be treated as 
zero.  


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For the calculation of change from baseline and percent change from baseline and PD 
parameters, values that are BLQ will be handled the same as for summary statistics (i.e., set to 
zero). 
PD values that are BLQ will be presented as reported by the laboratory (e.g., “<LLOQ”) in the 
listings. Any table or listing that contains PD data should have the LLOQ for the applicable 
assay(s) as a footnote (unless the LLOQ is defined within the body of the listing). 
Alternative approaches to handling BLQ PD data may be considered if scientifically justified, 
and, if used, will be described in the CSR and will also be noted in the statistical outputs, as 
appropriate. 
Note: Some PD assays refer to a “limit of detection” rather than a “limit of quantification”. If 
applicable, BLQ and LLOQ may be updated to BLD (below the limit of detection) and LLOD 
(lower limit of detection), respectively. 
 
10.3.1.3. Rounding 
For reporting, PK and PD data should be rounded to decimal places (DP) or significant figures 
(SF), depending on the variable. SF refers to the number of nonleading zero digits to report, 
always counting from the left. 
Individual-subject plasma and urine concentration data will rounded to 3 significant figures. 
For summary statistics, the following conventions will be applied: 
• Number of subjects/samples (n) will be reported as a whole number. 
• Minimum and maximum values will be reported to the same number of DP or SF as the 
individual-subject data. 
• All other summary statistics will be reported to 3 SF. 
 
10.4. 
Pharmacokinetic Analyses 
Plasma PK parameters for each subject will be estimated over the sampling interval by non-
compartmental analysis (NCA) using Phoenix® WinNonlin® (Certara, New Jersey, USA) 
version 8.3 or higher. 
The following plasma PK parameters will be calculated on days in which serial PK was 
collected, see Section 10.1.1: 
 


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Pharmacokinetic 
Parameter 
Units 
Definition 
Phoenix WinNonlin  
Parameter Output 
N 
N/A 
Number of samples 
N_Samples 
AUC0-last 
ng∙h/mL 
AUC from time zero to the last measurable 
concentration 
AUClast 
Clast 
ng/mL 
Last measurable concentration 
Clast 
Cmax 
ng/mL 
Maximum observed concentration  
Cmax 
Tmax 
h 
Time of Cmax 
Tmax 
Tlast 
h 
Time of Clast 
Tlast 
PK parameters will not be calculated for urine. 
10.5. 
Reporting of Pharmacokinetic Concentration Data and 
Pharmacokinetic Parameters 
Plasma concentrations, urine concentrations, and plasma PK parameters will be listed.  
 
10.6. 
Pharmacodynamic Analyses 
Observed and change from baseline in blood samples for PD and complement biomarkers will be 
listed. 
11. 
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES 
Due to the discontinuation of the BCX9930 drug development by the sponsor, only variables 
relevant to the aCSR will be summarized and listed. Many of the summaries that were planned 
for the full CSR are excluded from the aCSR and this SAP. All hypothesis testing including any 
sensitivity analysis was removed from the SAP. 


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12. 
REFERENCES 
12.1. 
Table of Contents for Data Display Specifications 
This table of contents provides the expected titles and numbers of the tables, listings, and figures 
of the final report. Changes to titles or numbering in the final report, additional data listings 
supporting the tables, or displays being split into multiple smaller displays for clarity will not 
necessitate a revision to the SAP, nor will they be considered a deviation from planned analyses. 
12.1.1. 
Tables and Figures 
Title 
Population 
Study Population Section 
Figures 
14.1.1 
CONSORT Diagram 
All Subjects 
Tables 
14.1.1 
Subject Disposition 
All Subjects 
14.1.2 
Analysis Populations 
Safety 
Population  
14.1.3 
Demographic and Baseline Characteristics 
Safety 
Population 
14.1.4 
PNH History 
Safety 
Population 
14.1.5.1 
Concomitant Medications 
Safety 
Population 
14.1.5.2 
12-Month Pre-study Transfusion Details 
Safety 
Population 
14.1.6.1 
Exposure to Study Treatment by Treatment Group 
Safety 
Population 
14.1.6.2 
Exposure to BCX9930 by Dose 
Safety 
Population 
Efficacy Section 
Figures 


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Title 
Population 
14.2.1 
Subject Profiles of Hemoglobin, LDH, Hemolysis Events and 
Transfusion Events 
ASaT 
14.2.2 
Subject Profiles of Creatinine, Hemoglobin, and LDH  
ASaT 
Tables 
14.2.1.1 
Observed and Change from Baseline Hemoglobin (g/dL) by 
Treatment Group and Visit 
ASaT 
14.2.1.2 
Change from Baseline in Hemoglobin (g/dL) at Week 24 by 
BCX9930 Dose  
ASaT 
Population 
14.2.2.1 
Proportion of Subjects Who Were Transfusion-free from Week 4 
to Week 24 (Subjects Warranting but Not Receiving Transfusion 
Were Not Considered Transfusion-free) 
ASaT 
Population 
14.2.2.2 
Units of pRBCs Transfused from Week 4 to Week 24 
ASaT 
Population 
14.2.2.3 
Observed, Change from Baseline, and Percent Change from 
Baseline LDH by Visit  
ASaT 
Population 
14.2.2.4 
Observed and Change from Baseline FACIT-Fatigue Scale by 
Visit 
ASaT 
Population 
Safety Section 
Figures 
14.3.1 
Subject Profiles of ALT, ALP, AST, Total Bilirubin, and 
Hemoglobin 
Safety 
Population 
Tables 
14.3.1.1 
Overall Summary of Treatment-emergent Adverse Events by 
Treatment Group   
Safety 
Population 
14.3.1.2 
Overall Summary of Treatment-emergent Adverse Events by 
BCX9930 Dose   
Safety 
Population 
14.3.2.1 
Treatment-emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term  
Safety 
Population 
14.3.2.2.1 
Treatment-emergent Adverse Events by Treatment Group and 
Preferred Term 
 
Safety 
Population 


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Title 
Population 
14.3.2.2.2 
Treatment-emergent Adverse Events by Treatment Group and 
Preferred Term and BCX9930 Dose Group 
Safety 
Population 
14.3.2.3 
Serious Treatment-emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term  
Safety 
Population 
14.3.2.4 
Renal Treatment-emergent Adverse Events by System Organ 
Class and Preferred Term: Events in the Acute Renal Failure 
SMQ, Chronic Kidney Disease SMQ, and Tubulointerstitial 
Diseases SMQ  
Safety 
Population  
14.3.2.5 
Hepatic Treatment-emergent Adverse Events by System Organ 
Class and Preferred Term: Events in the Drug related hepatic 
disorders - comprehensive search SMQ  
Safety 
Population 
 
 
 
 
 
12.1.2. 
Data Listings 
Listing 16.2.1 
Listing of Subject Disposition 
All Subjects  
Listing 16.2.2 
Listing of Protocol Deviations 
All Subjects 
Listing 16.2.4.1 
Listing of Demographics and Baseline Characteristics 
Safety Population  
Listing 16.2.4.2 
Listing of PNH History  
Safety Population 
Listing 16.2.4.3 
Listing of Concomitant Medications  
Safety Population 
Listing 16.2.4.4 
Listing of 12-month Pre-study Transfusion Details 
Safety Population 
Listing 16.2.4.5 
Listing of Transfusion Details 
ASaT Population 
Listing 16.2.4.6 
Listing of Medical History 
Safety Population 
Listing 16.2.5.1 
Listing of Exposure to Study Treatment by Treatment 
Group and Dose Level 
Safety Population 
Listing 16.2.5.2 
Listing of Study Drug Compliance 
Safety Population 
Listing 16.2.6.1 
Listing of Hemoglobin and LDH Results, Change from 
Baseline, and Percent Change from Baseline 
ASaT Population 
Listing 16.2.6.2 
Listing of FACIT-Fatigue Total Score Results, Change 
from Baseline, and Percent Change from Baseline 
ASaT Population 


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Listing 16.2.7.1 
Listing of Treatment-emergent Adverse Events by 
Treatment Group 
Safety Population 
Listing 16.2.7.2 
Listing of Serious Adverse Events 
Safety Population 
Listing 16.2.7.3 
Listing of Renal Treatment-emergent Adverse Events 
Safety Population 
Listing 16.2.7.4 
Listing of Hepatic Treatment-emergent Adverse Events 
Safety Population 
Listing 16.2.8 
Listing of Grade 3 or Grade 4 Laboratory Abnormalities 
by CTCAE Scale 
Safety Population 
Listing 16.4.1 
Listing of Serial Plasma BCX9930 Pharmacokinetic 
Concentrations 
Safety Population 
Listing 16.4.2 
Listing of Serial Plasma BCX9930 Pharmacokinetic 
Parameters 
PK/PD Sub-study 
Population 
Listing 16.4.3 
Listing of Observed and Change from Baseline in Blood 
Samples of PD and Complement Biomarkers 
PK/PD Sub-study 
Population 
Listing 16.4.4 
Listing of Sparse Plasma BCX9930 Concentration 
Safety Population 
Listing 16.4.5 
Listing of Spot Urine BCX9930 Concentration 
Safety Population 
 
12.2. 
Data Display Specifications 
Specifications for data displays will be provided in a separate document. 






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