An Open-Label, Safety, Tolerability, and Proof-of-Concept Study of Oral BCX9930 Therapy in Subjects With Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, or Primary Membranous Nephropathy
Phase: PHASE2
Conditions: Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, Membranous Nephropathy
Sponsor: BioCryst Pharmaceuticals

BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
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BIOCRYST 
PHARMACEUTICALS, INC. 
BCX9930 
PROTOCOL BCX9930‑211 
EudraCT NUMBER: 2020-005855-19 
An Open-Label, Safety, Tolerability, and Proof-of-Concept 
Study of Oral BCX9930 Therapy in Subjects with 
Complement 3 Glomerulopathy, Immunoglobulin A 
Nephropathy, or Primary Membranous Nephropathy 
 
Version 4.0: 04 August 2022 
BioCryst Pharmaceuticals, Inc. 
4505 Emperor Blvd., Suite 200 
Durham, NC 27703 
Phone: (919) 859-1302 
Fax: (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’S AGREEMENT 
 
Protocol No. BCX9930-211 
An Open-Label, Safety, Tolerability, and Proof-of-Concept Study of Oral 
BCX9930 Therapy in Subjects with Complement 3 Glomerulopathy, 
Immunoglobulin A Nephropathy, or Primary Membranous Nephropathy 
Version 4.0: 04 August 2022 
 
I have received and read the Investigator’s Brochure 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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2. 
SYNOPSIS 
Name of Sponsor/Company: BioCryst Pharmaceuticals, Inc. 
Name of Investigational Product: BCX9930 
Name of Active Ingredient: 
  
Protocol Number: BCX9930-211 
Title of Study: An Open-Label, Safety, Tolerability, and Proof-of-Concept Study of Oral BCX9930 
Therapy in Subjects with Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, or 
Primary Membranous Nephropathy 
Study Center(s): This study is planned to be conducted at study centers in countries in Europe, North 
America, Asia Pacific and other regions. 
Lead or Coordinating Investigator:  
 
Central Pathologist: 
 
Phase of Development: 2 
The objectives and endpoints in this proof-of-concept (POC) study of orally administered BCX9930 
are applicable to the 3 parallel treatment cohorts of subjects with complement 3 glomerulopathy 
(C3G), immunoglobulin A nephropathy (IgAN), or primary membranous nephropathy (PMN). 
Primary Objectives: 
• 
To evaluate the therapeutic potential of BCX9930 as assessed by proteinuria  
Secondary Objectives: 
• 
To evaluate the safety and tolerability of BCX9930 
• 
To evaluate the therapeutic potential of BCX9930 as assessed by other measures of 
clinical benefit  
• 
To evaluate effects on kidney biopsy morphologic findings (C3G cohort only)  
Exploratory Objectives:  
•
 
 
 
 
 
 
 

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state  
Primary Endpoint: 
• 
Change in 24-hour urinary protein excretion normalized to urine creatinine as measured 
by percentage change in urine protein-to-creatinine ratio (uPCR) from baseline  
Secondary Endpoints: 
• 
Number and proportion of subjects with a uPCR response defined as: 
− 
Partial remission, ≥ 50% reduction from baseline 
− 
Complete remission, ≤ 500 mg/g 
− 
Normalization, ≤ 200 mg/g 
• 
Change from baseline in 24-hour urinary protein excretion as measured by percentage 
change in urinary protein from baseline  
• 
Change from baseline in estimated glomerular filtration rate (eGFR)  
• 
Change from baseline in serum albumin  
• 
Number and proportion of subjects with the following parameters: 
− 
Protein ≥ 3.5 g in a 24-hour urine collection 
− 
Serum albumin ≤ 2.5 g/dL 
• 
Number and proportion of subjects with a morphologic response in each of the following 
categories (C3G cohort only at Week 24): 
− 
Decreased endocapillary hypercellularity, mesangial hypercellularity, active crescents 
(if present), glomerular leukocyte infiltration, fibrinoid necrosis, 
membranoproliferative glomerulonephritis pattern 
− 
Decreased acute tubular injury, interstitial inflammation, interstitial edema 
− 
Reduction in C3 glomerular staining 
− 
Reduction in the extent of deposits, clearing of deposits, or no additional active 
deposits as assessed by electron microscopy (EM) 
− 
No progression of chronic changes (ie, global, segmental glomerulosclerosis, tubular 
atrophy/interstitial fibrosis, arteriosclerosis) 
• 
Number and proportion of subjects with a treatment-emergent adverse event(s)(TEAE) 

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• 
Number and proportion of subjects who discontinue 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 4 TEAE based on 
Common Terminology Criteria for Adverse Events (CTCAE) 
• 
Number and proportion of subjects who experience a CTCAE treatment-emergent 
Grade 3 or 4 laboratory abnormality 
Exploratory Endpoints:  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Design:  
This is a Phase 2, open-label, multicenter, POC study to evaluate the safety, tolerability, and 
therapeutic potential of BCX9930, an oral Factor D inhibitor, administered for up to 52 weeks in adult 
(≥ 18 years old) subjects with C3G, IgAN, or PMN. After up to a 56-day screening qualification 
period, approximately 14 eligible subjects will be enrolled into each of three parallel study treatment 
cohorts and will receive BCX9930 200 mg twice daily (BID) for the first 14 days and 400 mg BID on 
Day 15 and for the remainder of the treatment period, up to a total duration of 52 weeks. Each cohort 
may be analyzed separately. 
Methodology:  
During the study, recruitment into each of the cohorts will be managed independently with a total of 
approximately 42 subjects enrolled into the study. For the C3G cohort only, up to 7 subjects with at 
least 6 months of treatment with a stable dosing regimen of mycophenolate mofetil/mycophenolate 
sodium prior to the Day 1 Visit will be allowed to enroll in the study.  
The independent BCX9930 DMC will regularly review cumulative safety data from this study, as 
well as accumulating, long-term safety data across all BCX9930 studies in all indications.  
After providing appropriate written informed consent to participate in the study and confirming that 
all other study eligibility criteria have been met during screening, subjects will undergo a 
percutaneous needle biopsy of the kidney per local practice and guidelines. Renal biopsy images and 
details from the local pathology report will be reviewed by the central pathologist for confirmation of 
a protocol-defined diagnosis of C3G, IgAN, or PMN. The screening biopsy procedure may be waived 
with approval of the central pathologist and agreement with the medical monitor for any subject who 
has undergone a renal biopsy procedure as follows: within 3 months prior to screening for the C3G 
cohort, or within 6 months prior to screening for the IgAN cohort and PMN cohorts, provided that 
required materials are adequate for pathology evaluation per protocol procedures.  
After the Day 1 Visit, subjects will return to the clinic at Weeks 1, 2, and 4, and then every 4 weeks 
thereafter through Week 24. Additional safety assessments will be performed at Weeks 3, 5, 6, 7, and 
10, either at the investigative site, or at a local laboratory more convenient for the subject or via a 
home health service. At the Week 24 Visit, the clinical benefit of BCX9930 treatment will be 
assessed by the investigator. Subjects who are assessed with deriving clinical benefit at the Week 24 
Visit will continue study treatment and visits up to Week 52.  
An on-treatment, percutaneous needle biopsy of the kidney will be performed at the following visit 
after completion of all other assessments, or during the time specified below by treatment cohort: 
• 
Week 24 or within 7 days after the visit for subjects with C3G 
• 
Week 36 or within 7 days after the visit for subjects with IgAN (optional) 
• 
Week 48 to within 3 days after the Week 52 Visit for subjects with PMN (optional) 
Images of LMs, IFs or IHCs, EMs, and details from the local pathology reports from the on-treatment 
biopsies will be reviewed by the central pathologist. Protocol-specified, on-treatment biopsies will not 
be required for subjects who are discontinued from BCX9930 treatment. 
Subjects who complete BCX9930 dosing through Week 52 or who discontinue BCX9930 dosing 
prior to Week 52 will return to the clinic approximately 4 weeks (28 ± 3 days) after the date of their 
last dose of BCX9930 for the Safety Follow-up (FU) Visit prior to study completion or 
discontinuation.  

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An optional serial PK/PD substudy will include subjects who provide consent from each of the 3 
cohorts to evaluate the PK and PD of BCX9930 at the Day 1 Visit and/or at a subsequent visit prior to 
the Week 24 Visit. Serial sampling of urine and blood will be performed over a period of 6 hours. 
Subjects who do not participate in the Baseline (Day 1) PK/PD sample collection are eligible to 
participate at a subsequent clinic visit prior to the Week 24 Visit.  
All subjects will have a single blood sample drawn for PK analysis at each clinic visit. For subjects 
participating in the serial PK/PD substudy, a single blood sample will be drawn for PK analysis at 
visits where serial blood samples are not collected through 6 hours post dose.  
All subjects who sign a separate informed consent, will participate in exploratory pharmacogenomics 
testing at a single visit from Day 1 up to the Week 24 Visit (including the Safety FU Visit, if 
applicable). 
Number of Subjects (Planned):  
This study will enroll approximately 14 adult subjects in each of the 3 cohorts: C3G, IgAN and PMN 
for a total enrollment of approximately 42 subjects.  
Inclusion Criteria: 
Subjects must meet all of the following inclusion criteria (where applicable) prior to first dose of 
BCX9930 on Day 1 or specified time below: 
1. Willing and able to provide written informed consent. 
2. Male or non-pregnant, non-lactating female subjects ≥ 18 years of age. 
3. Body weight ≥ 40 kg. 
4. Primary diagnosis of C3G, IgAN, or PMN with evidence of disease activity, as confirmed by 
central pathology review of digital images and pathology reports of renal biopsy samples 
obtained during screening (or within 3 months prior to screening for subjects with C3G,and 
within 6 months prior to screening for subjects with IgAN and PMN with approval of the 
central pathologist and agreement with the medical monitor). 
• 
All: ≤ 50% global glomerulosclerosis 
• 
All: ≤ 50% tubulointerstitial fibrosis 
5. For subjects with C3G only, documentation of duration of illness of at least 90 days by either 
a prior biopsy collected ≥ 90 days prior to screening confirming a diagnosis of C3G OR a 
clinical diagnosis of C3G with at least one documented proteinuria assessment ≥ 90 days 
prior to initial screening visit. 
6. For subjects with C3G only, proteinuria defined as ≥ 1 g of urinary protein per 24 hours at 
screening that has not shown a ≥ 25% decrease from the most recent documented proteinuria 
assessment, which was collected ≥ 30 days prior to and ≤ 180 days of initial screening visit. 
7. For subjects with IgAN only, proteinuria defined as 1 g to ≤ 4 g of urinary protein per 
24 hours at screening that has not shown a ≥ 25% decrease from the most recent documented 
proteinuria assessment, which was collected ≥ 30 days prior to and ≤ 180 days of initial 
screening visit. 
8. For subjects with PMN only, an anti-phospholipase A2 receptor antibody (aPLA2Rab) 
immunoglobulin G (IgG) titer of ≥ 150 U/mL and 3.5 g to ≤11 g of urinary protein per 

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24 hours at screening that has not shown a ≥ 25% decrease from the most recent documented 
proteinuria assessment, which was collected ≥ 30 days prior to and ≤ 180 days of initial 
screening visit. 
9. An eGFR ≥ 50 mL/min/1.73 m2 (or ≥ 30 mL/min/1.73 m2 after DMC recommendation) 
calculated using the serum creatinine-based Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) formula. 
10. Resting supine vital signs within the following ranges: 
• 
Systolic blood pressure, 80 to 150 mm Hg, inclusive 
• 
Diastolic blood pressure ≤ 90 mm Hg  
11. Treatment with a stable, maximum recommended or maximum tolerated dose of an 
angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at 
least 60 days prior to the Day 1 Visit and in the opinion of the investigator the expectation of 
continuing the same dose and regimen for such treatment during the study. 
12. Contraception requirements: 
Female subjects must meet at least one of the following requirements: 
a. Be a woman of nonchildbearing potential, defined as postmenopausal (without menses 
for ≥ 12 months [without an alternative medical cause] with a follicle-stimulating 
hormone [FSH] > 40 mIU/mL, or who have had a hysterectomy, bilateral salpingectomy, 
or bilateral oophorectomy). 
b. 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. 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) 
c. 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. 
Male subjects must meet at least one the following requirements: 
d. Subjects with female partners of childbearing potential (defined as without menses 
≤ 12 months, or a non-menopausal female who has not had a hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy) must agree to utilize a contraceptive method 

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throughout the study and for at least 90 days after the last dose of study drug. The 
following methods during the study are acceptable: 
− 
surgical sterilization (ie, vasectomy that has been medically assessed to be successful, 
or bilateral tubal occlusion of a female partner) 
− 
partner’s use of an IUD or IUS 
− 
partner’s use of combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 
− 
partner’s use of progestogen-only hormonal contraception associated with inhibition 
of ovulation (oral, injectable, implantable) 
− 
use of a condom 
13. 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 Hemophilus influenzae [Hib] is strongly 
encouraged, where authorized and available.) 
14. In the opinion of the investigator, the subject is likely to comply adequately with all required 
study procedures and restrictions for the study, including compliance with the BID dosing 
schedule for BCX9930. 
Exclusion Criteria:  
Subjects must meet none of the following exclusion criteria (where applicable) prior to first dose of 
BCX9930 on Day 1 or specified time below: 
1. Known congenital deficiency of C1s, C1r, C1q, C2, C4. Known variants in complement 
Factor H, complement Factor I, C3, and complement Factor B or genomic rearrangements in 
the complement Factor-H-related proteins are not exclusionary. 
2. Receiving hemodialysis or peritoneal dialysis or anticipated to receive dialysis during the 
duration of this study. 
3. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for 
transplantation during the study. 
4. History of transfusion with blood or blood products, or plasmapheresis or plasma exchange, 
within 30 days prior to screening. 
5. 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. 
6. History of malignancy within 5 years prior to the screening visit, with the 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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7. Any clinical or pathological evidence of monoclonal gammopathy of unclear or renal 
significance, lupus or other systemic autoimmune disease, or other conditions 
(eg, infection-associated disease or associated with another systemic disease, 
anti-phospholipid antibody syndrome with significant clinical disease, immune complex 
glomerulonephritis, immunoglobulin A [IgA] vasculitis with nephritis [Henoch-Schönlein 
purpura] or morphologic features of secondary membranous nephropathy). Presence of C3 or 
C5 nephritic factors (eg, autoantibodies directed at C3 or C5 convertase), in the absence of 
known infection or other systemic disease, are not exclusionary for this study. 
8. Treatment with azathioprine, canakinumab, cyclophosphamide, cyclosporine, eculizumab, 
everolimus, hydroxychloroquine, infliximab, sirolimus, ravulizumab, systemic corticosteroids 
(including budesonide), tacrolimus, or any other systemic immunosuppressive or 
immunomodulatory therapies (eg, complement inhibitors) within 90 days OR mycophenolate 
mofetil/mycophenolate sodium treatment within 60 days OR anti-CD20 antibody therapies 
(eg, rituximab) within 180 days prior to the screening visit. 
a. For subjects with C3G only, ongoing treatment with a stable dosing regimen of 
mycophenolate mofetil/mycophenolate sodium for at least 6 months prior to Day 1 Visit 
is allowed.  
9. Treatment with renin inhibitors (eg, aliskiren) or sodium-glucose-cotransporter 2 (SGLT2) 
inhibitors within 60 days prior to Day 1. 
10. 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. 
11. Any of the following laboratory values at the screening visit: hemoglobin < 8.5 g/dL; total 
white blood cell (WBC) < 2.5 × 109/L; absolute neutrophil count (ANC) < 1.0 × 109/L; 
platelet count < 90 × 109/L; alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), alkaline phosphatase (ALP), or total bilirubin > 1.5 × upper limit of normal (ULN); 
serum albumin < 1.5 g/dL; or international normalized ratio (INR) > 1.4. 
a. Subjects with Grade 1 elevated bilirubin due to Gilbert’s syndrome are allowed to enroll. 
To document that a subject has Gilbert’s syndrome, a diagnosis from the medical record 
must be provided, or the investigator may make a presumptive diagnosis of Gilbert’s 
syndrome in subjects with unconjugated hyperbilirubinemia on repeated testing (at least 
2 samples separated in time) who have ALT, AST, and ALP ≤ 1.5 × ULN, and a normal 
complete blood count. 
12. Any laboratory parameter at screening that, in the judgment of the investigator, is clinically 
significant and would represent a safety concern.  
13. Clinically significant abnormal electrocardiogram (ECG) prior to dosing at the Day 1 Visit. 
14. Current use of a prohibited concomitant medication within 7 days prior to Day 1.  
15. Active serious bacterial, viral, or fungal infection or any other serious infection, including 
suspected or confirmed severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] 
infection, within 14 days of screening. Dyspnea, vasculitic rash, and persistent fever or other 
symptoms consistent with multisystem inflammatory syndrome [MIS] are exclusionary in the 
setting of recent SARS-CoV-2 infection. 

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16. Positive serology for human immunodeficiency virus (HIV), or active infection with 
hepatitis B virus (HBV) or hepatitis C virus (HCV). 
17. Positive test for drugs of abuse during screening, unless by prescription. 
18. Pregnant, planning to become pregnant, or breastfeeding. 
19. Known or suspected hypersensitivity to BCX9930 or any of its formulation excipients. 
20. History of severe hypersensitivity to any medicinal product, which was associated with 
swelling, severe rash requiring treatment/hospitalization, or anaphylaxis. 
21. Any clinically significant medical or psychiatric condition, including known or suspected 
substance abuse (including alcohol) 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, subjects will initially receive BCX9930 200 mg BID for 
the first 14 days of treatment before increasing the dose to 400 mg BID on Day 15 for the remainder 
of the treatment period. 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:  
Subjects will receive open-label BCX9930 for up to 52 weeks. 
Reference Therapy, Dosage and Mode of Administration:  
N/A 
Criteria for Evaluation: 
Safety: Safety will be evaluated by TEAEs, laboratory analyses (clinical chemistry, hematology, 
coagulation, urinalysis including microscopy), vital signs, ECGs, and physical examination findings. 
In addition, potential drug-induced liver injury, potential drug-induced kidney injury, and SARS-
CoV-2 infection (asymptomatic and symptomatic) events, including non-serious events, may have 
enhanced data collection.  
Clinical Laboratory and Anatomical Pathology Evaluations of C3G, IgAN, or PMN: Proteinuria 
as assessed by intended 24-hour urine collection for total daily proteinuria, albuminuria, uPCR, and 
urine-albumin-to-creatinine ratio (uACR); other kidney biomarkers may be assessed. uPCR, uACR, 
and other kidney biomarkers may also be assessed by the single void urine collection; serum albumin, 
serum creatinine, and other analytes for eGFR; percutaneous needle biopsies of the kidney with 
images of LMs, IFs or IHCs, EMs, and details from the local pathology reports from 
Screening/Baseline and on-treatment biopsies (optional for subjects with IgAN or PMN) reviewed by 
the central pathologist to confirm eligibility and to evaluate and describe changes from the baseline 
pre-treatment digital images. For the PMN cohort only,
 will be measured at 
Screening, Baseline, and every 4 weeks until Week 52.  
Patient-Reported Outcomes: 
 
Clinical Laboratory 
 

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 circulating in plasma. The capacity of the complement system will be 
assessed by measuring these analytes and by using ex vivo stimulation assays, such as the AP 
Wieslab, which activates the alternative pathway (AP) in blood samples using a specific stimulus. 
Additional exploratory assays may be evaluated. Samples collected may be run in more than one 
assay to elucidate the PD effects of BCX9930. 
Single void urine samples will be analyzed for levels of 
 
 
Single void urine samples will also be analyzed for select chemokines and cytokines (eg, 
 
normalized to urinary creatinine. Additional exploratory
 
 
Pharmacokinetics:  
Plasma: A single venous blood sample for measurement of plasma BCX9930 concentrations will be 
collected at each study visit from all subjects receiving BCX9930 (sparse sampling to support 
population PK and PD modeling). In addition, at selected 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 PK parameters of BCX9930 in these patient populations.  
The extent of plasma protein binding may be assessed for selected timepoints. 
Urine: Subjects participating in the PK/PD substudy will have single void urine samples collected to 
evaluate renal excretion of BCX9930 and potentially metabolites, if warranted.  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
Statistical Methods:  
This is a Phase 2, open-label, POC study to estimate the safety, tolerability, and therapeutic potential 
of BCX9930 administration in subjects with C3G, IgAN, or PMN. As such, no formal power or 
sample size calculations were performed to determine each cohort size. 
 

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Outcome Analyses:  
For continuous efficacy variables, descriptive summaries (for the recorded value, change from 
baseline, and percentage change from baseline) will be presented by study visit and treatment cohort. 
Point estimates and confidence intervals will be presented for change from baseline and percentage 
change from baseline by post-baseline study visit and treatment cohort.  
For binary efficacy endpoints, summaries will be presented as counts and frequencies by 
post-baseline study visit and treatment cohort. Confidence intervals will be provided using the 
Clopper-Pearson Exact method by post-baseline study visit and treatment cohort.  
Categorical efficacy data will also be summarized by study visit and treatment cohort.  
The following safety outcomes will be summarized in tables and/or figures: TEAEs, clinical 
laboratory values, morphological response, vital signs, and ECGs. Summaries will be presented by 
treatment cohort and, where appropriate, by visit or pooled across the three treatment cohorts. 
In addition, PK, 
; and QoL measurements.  
Interim analyses may be conducted for each study cohort based on ongoing review of individual 
subject safety and preliminary efficacy data. 
Safety Analyses: 
Safety endpoints that will be summarized, at a minimum, will include the proportion of subjects 
1) with TEAEs; 2) who discontinue BCX9930 due to TEAEs; 3) with TESAEs; 4) with Grade 3 or 
4 TEAEs; and 5) with treatment-emergent Grade 3 or 4 laboratory abnormalities. 
Pharmacokinetic Analyses (PK/PD Substudy): 
Plasma concentrations of BCX9930 and PK parameters will be summarized by dose regimen and 
study visit. The plasma concentration data for BCX9930 (collected via serial sampling) will be 
analyzed using non-compartmental techniques to obtain estimates of standard non-compartmental PK 
parameters. 
Pharmacodynamic Analyses: 
Descriptive statistics, including change from baseline, will be provided by study visit and dose 
regimen. Point estimates and 95% confidence intervals will be presented for change from baseline 
and percent change from baseline by parameter, post-baseline study visit and treatment cohort.  
The plans for analysis of other biomarkers may be modified based upon emerging data. 
Sample Size Justification:  
The proposed sample size of up to approximately 14 subjects per cohort should provide an estimate of 
uPCR reduction up to 52 weeks to assess the therapeutic potential for BCX9930 in these renal 
indications and inform sample sizes for future studies of BCX9930. 
 

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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’S AGREEMENT ...............................................................................................3 
2. 
SYNOPSIS ...................................................................................................................4 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............15 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................23 
5. 
INTRODUCTION ......................................................................................................27 
5.1. 
Background .................................................................................................................27 
5.1.1. 
The Complement System ............................................................................................27 
5.1.2. 
Factor D in the Complement System ..........................................................................28 
5.2. 
Indications ...................................................................................................................28 
5.2.1. 
Complement 3 Glomerulopathy .................................................................................28 
5.2.2. 
Immunoglobulin A Nephropathy ................................................................................29 
5.2.3. 
Primary Membranous Nephropathy ...........................................................................30 
5.3. 
BCX9930 ....................................................................................................................30 
5.3.1. 
Nonclinical Findings for BCX9930 ............................................................................31 
5.3.2. 
Clinical Findings for BCX9930 ..................................................................................32 
5.4. 
Rationale for Study .....................................................................................................33 
5.4.1. 
Rationale for Study Design and Study Population .....................................................33 
5.4.2. 
Dose Rationale ............................................................................................................34 
5.4.2.1. 
Summary of Hematologic Response in Subjects with PNH with BCX9930 at 
400 and 500 mg BID – Studies 101 and 201 ..............................................................34 
5.4.2.2. 
Summary of PPK and PK/PD Modeling ....................................................................35 
5.5. 
Benefit-Risk Analysis .................................................................................................37 
5.5.1. 
Potential Risks of Bacterial Infections .......................................................................38 
5.5.2. 
Potential Risk of SARS-CoV-2 Infection and Vaccination ........................................38 
5.5.3. 
Potential Risks of Adverse Events with BCX9930 ....................................................39 
5.5.3.1. 
Potential Risks for Headache ......................................................................................39 
5.5.3.2. 
Potential Risks for Drug Rash ....................................................................................39 
5.5.3.3. 
Potential Risks for Hepatic Effects .............................................................................39 

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5.5.3.4. 
Potential Risks for Renal Effects ................................................................................39 
5.5.4. 
Risks of Potential Adverse Events with Trial-Mandated Procedures .........................40 
5.5.5. 
Overall Benefit-Risk Analysis ....................................................................................40 
6. 
STUDY OBJECTIVES AND PURPOSE ..................................................................40 
6.1. 
Objectives ...................................................................................................................40 
6.1.1. 
Primary Objective .......................................................................................................40 
6.1.2. 
Secondary Objectives .................................................................................................41 
6.1.3. 
Exploratory Objectives ...............................................................................................41 
6.1.4. 
..41 
6.2. 
Endpoints ....................................................................................................................41 
6.2.1. 
Primary Endpoints ......................................................................................................41 
6.2.2. 
Secondary Endpoints ..................................................................................................42 
6.2.3. 
Exploratory Endpoints ................................................................................................43 
6.2.4. 
43 
7. 
INVESTIGATIONAL PLAN .....................................................................................43 
7.1. 
Overall Study Design ..................................................................................................43 
7.2. 
Number of Subjects ....................................................................................................45 
7.3. 
Treatment Assignment ................................................................................................45 
7.4. 
Individual and Study Termination Criteria .................................................................45 
7.4.1. 
Study Drug Treatment Discontinuation Criteria .........................................................45 
7.4.2. 
Subject Withdrawal Criteria .......................................................................................46 
7.4.3. 
Criteria for Study Termination ...................................................................................47 
7.4.4. 
End of Study Definition ..............................................................................................47 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................47 
8.1. 
Subject Inclusion Criteria ...........................................................................................47 
8.2. 
Subject Exclusion Criteria ..........................................................................................50 
9. 
TREATMENT OF SUBJECTS ..................................................................................52 
9.1. 
Prior/Concomitant Medications ..................................................................................52 
9.2. 
Prohibited and Restricted Medications .......................................................................52 
9.3. 
Treatment Compliance ................................................................................................54 
9.3.1. 
Missed Doses: .............................................................................................................54 
9.4. 
Randomization and Blinding ......................................................................................55 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................55 

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10.1. 
BCX9930 ....................................................................................................................55 
10.2. 
Description of Study Drug Packaging, Labelling, and Storage ..................................55 
10.3. 
Administration ............................................................................................................55 
10.3.1. 
Treatment Interruption or Dose Reduction .................................................................56 
10.3.2. 
Dose Tapering .............................................................................................................56 
10.4. 
Study Drug Accountability .........................................................................................56 
11. 
STUDY CONDUCT ...................................................................................................57 
11.1. 
Overview .....................................................................................................................57 
11.2. 
Schedule of Assessments ............................................................................................58 
11.3. 
Study Visits .................................................................................................................67 
11.3.1. 
Screening ....................................................................................................................67 
11.3.2. 
Rescreening/Retesting ................................................................................................68 
11.3.3. 
Baseline Visit (Day 1) ................................................................................................68 
11.3.4. 
On-study Visits (Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 
52) ...............................................................................................................................69 
11.3.5. 
Additional Assessments for Renal and Hepatic Safety Monitoring ...........................71 
11.3.6. 
Safety follow-up Visit .................................................................................................72 
12. 
STUDY ASSESSMENTS ..........................................................................................72 
12.1. 
Chronology of Assessments .......................................................................................72 
12.2. 
Demographic/Medical History ...................................................................................73 
12.2.1. 
Vaccination Requirements ..........................................................................................73 
12.3. 
Immunity Assessment .................................................................................................74 
12.4. 
Efficacy/Effectiveness Assessments ...........................................................................74 
12.4.1. 
Intended 24-hour Urine Collection .............................................................................74 
12.4.2. 
Percutaneous Needle Biopsy of the Kidney ...............................................................74 
12.4.2.1. 
Central Pathologist ......................................................................................................75 
12.4.3. 
76 
12.5. 
Patient-reported Outcomes .........................................................................................76 
12.5.1. 
.77 
12.5.2. 
.77 
12.5.3. 
.77 
12.5.4. 
Optional Entry and Exit Phone Interviews .................................................................77 

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12.6. 
Blood Pharmacokinetic and Pharmacodynamic Assessments at Scheduled 
Visits ...........................................................................................................................77 
12.7. 
Urine Collection for Measurement of BCX9930 and Metabolite 
Concentrations ............................................................................................................78 
12.8. 
Urine Pharmacodynamic and Biomarker Assessments ..............................................79 
12.8.1. 
Urine Biomarkers of Kidney Injury ............................................................................79 
12.9. 
Pharmacokinetic and Pharmacodynamic Substudy ....................................................79 
12.9.1. 
Plasma Pharmacokinetic and Pharmacodynamic Assessments in Substudy ..............79 
12.9.2. 
Urine Assessment of BCX9930 and Metabolite Concentrations in PK/PD 
Substudy .....................................................................................................................80 
12.9.3. 
Urine Pharmacodynamic Assessments in PK/PD Substudy .......................................80 
12.10. 
Optional Pharmacodynamic and/or Pharmacogenomic Analyses ..............................81 
12.11. 
Safety Assessments .....................................................................................................81 
12.11.1. 
Vital Signs ..................................................................................................................81 
12.11.2. 
Weight, Height, and Body Mass Index .......................................................................81 
12.11.3. 
Physical Examination .................................................................................................82 
12.11.4. 
Electrocardiogram .......................................................................................................82 
12.11.5. 
Clinical Chemistry, Hematology, Urinalysis, and Other Laboratory 
Assessments ................................................................................................................82 
12.11.5.1. Urine Collections for Urinalysis, Microscopy, and Biomarker Testing .....................84 
12.11.5.2. Calculations for estimating Glomerular Filtration Rate .............................................84 
12.11.6. 
Menopause and Pregnancy Testing ............................................................................85 
13. 
ADVERSE EVENTS..................................................................................................85 
13.1. 
Definitions ..................................................................................................................85 
13.1.1. 
Adverse Event .............................................................................................................85 
13.1.2. 
Adverse Reaction ........................................................................................................86 
13.1.3. 
Serious Adverse Event ................................................................................................87 
13.1.4. 
Events of Special Monitoring .....................................................................................87 
13.2. 
Definition of Severity .................................................................................................88 
13.3. 
Relationship to Study Drug ........................................................................................88 
13.4. 
Method, Frequency, and Time Period for Detecting Adverse Events and 
Reporting Serious Adverse Events .............................................................................89 
13.4.1. 
Serious Adverse Events and Suspected Unexpected Serious Adverse 
Reactions .....................................................................................................................90 

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13.4.2. 
Pregnancy ...................................................................................................................91 
13.5. 
Adverse Event Management .......................................................................................91 
13.5.1. 
Potential Drug-induced Liver Injury: Monitoring, Evaluation, and 
Discontinuation Criteria ..............................................................................................91 
13.5.2. 
Renal Events: Monitoring, Evaluation, and Discontinuation Criteria ........................92 
13.5.3. 
SARS-CoV-2 and COVID-19 ....................................................................................93 
13.6. 
Overdose .....................................................................................................................93 
13.7. 
Data Monitoring Committees .....................................................................................93 
14. 
STATISTICS ..............................................................................................................94 
14.1. 
Hypotheses ..................................................................................................................94 
14.2. 
Sample Size Considerations .......................................................................................94 
14.3. 
Stratification ...............................................................................................................94 
14.4. 
Statistical Methods ......................................................................................................94 
14.4.1. 
Analysis Populations ..................................................................................................95 
14.4.1.1. 
Full Analysis Set Population ......................................................................................95 
14.4.1.2. 
Pharmacokinetic Population .......................................................................................95 
14.4.1.3. 
Pharmacokinetic Substudy Population .......................................................................95 
14.4.1.4. 
Pharmacodynamic Population ....................................................................................95 
14.4.2. 
General Considerations for Data Analysis .................................................................95 
14.4.3. 
Subject Demographic and Disposition Data ...............................................................95 
14.4.4. 
Analysis of Efficacy Variables ...................................................................................96 
14.4.5. 
Analysis of Safety Variables ......................................................................................96 
14.4.6. 
Patient-reported Outcomes .........................................................................................97 
14.4.7. 
Pharmacokinetic Analyses ..........................................................................................97 
14.4.8. 
Pharmacodynamic and Biomarker Analyses ..............................................................97 
15. 
STUDY ADMINISTRATION ...................................................................................98 
15.1. 
Study Monitoring ........................................................................................................98 
15.2. 
Audits and Inspections ................................................................................................99 
15.3. 
Ethics Committee ........................................................................................................99 
15.4. 
Serious Breaches of GCP ............................................................................................99 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................99 
17. 
ETHICS ......................................................................................................................99 
17.1. 
Ethics Review .............................................................................................................99 

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17.2. 
Ethical Conduct of the Study ....................................................................................100 
17.3. 
Written Informed Consent ........................................................................................100 
18. 
DATA HANDLING AND RECORDKEEPING .....................................................101 
18.1. 
Inspection of Records ...............................................................................................101 
18.2. 
Retention of Records ................................................................................................101 
18.3. 
Confidentiality of Information and Data ..................................................................101 
19. 
PUBLICATION POLICY ........................................................................................102 
20. 
LIST OF REFERENCES ..........................................................................................103 
APPENDIX 1. STUDY INFORMATION ..................................................................................106 

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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................23 
Table 2: 
Study 101 Part 3/Study 201: Key Efficacy Parameters at Last Visit for 
400 and 500 mg BID ...................................................................................................35 
Table 3: 
Schedule of Assessments (Screening - Week 24) .......................................................59 
Table 4: Schedule of Assessments (Week 28-Week 52) ...............................................................63 
Table 5: 
Timing of Blood Sample and Urine Collection for PK/PD Substudy at 
Baseline (Day 1 Visit) and a Visit prior to Week 24 ..................................................66 
Table 6: 
Clinical Laboratory Evaluations .................................................................................83 
 

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LIST OF FIGURES 
Figure 1: 
Complement Pathways ...............................................................................................27 
Figure 2: 
Comparison of PK/PD Model-Estimated IC Values (95% CI) for 
AP Wieslab, LDH, and C3 Opsonization in Subjects with PNH with Median 
(10th to 90th percentile) PPK Model-Estimated Ctau at 200, 400, and 500 mg 
BID .............................................................................................................................37 
Figure 3: 
Study Schema .............................................................................................................45 
 
  

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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: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ACEi 
Angiotensin-converting enzyme inhibitor 
ACIP 
Advisory Committee on Immunization Practices 
ADL 
activities of daily living 
AE 
adverse event 
aHUS 
atypical hemolytic uremic syndrome 
AKI 
acute kidney injury 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AP 
alternative pathway 
 
 
ARB 
angiotensin receptor blocker 
AST 
aspartate transferase 
BID 
twice daily 
BMI 
body mass index 
BQL 
below quantification level 
C3 
complement 3 
C3bBb 
C3 convertase of the AP 
C3G 
complement 3 glomerulopathy 
CDC 
Centers for Disease Control and Prevention 
CI 
confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CP 
classical pathway 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DDD 
dense deposit disease 
DDI 
drug-drug interaction 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 

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Abbreviation or Specialist Term 
Explanation 
eCRF 
electronic case report form 
EFD 
embryo-fetal development 
eGFR 
estimated glomerular filtration rate 
EM 
electron microscopy or “electron micrograph” images 
EOSM 
event of special monitoring 
ESRD 
end-stage renal disease 
 
 
FDA 
Food and Drug Administration 
FU 
Follow-up 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
Hb 
hemoglobin 
HBV 
hepatitis B virus 
hCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
Hib 
Haemophilus influenzae Type B 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
IC50 
50% of maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IF 
immunofluorescence  
Ig 
immunoglobulin 
IgA 
immunoglobulin A 
IgG 
immunoglobulin G 
IgAN 
immunoglobulin A nephropathy 
IHC 
immunohistochemistry  
IMP 
investigation medicinal product or study drug 
INR 
international normalized ratio 

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Abbreviation or Specialist Term 
Explanation 
IRB 
institutional review board 
IRT 
Interactive Response Technology 
IST 
immunosuppressive therapy 
ITT 
intent-to-treat 
IUD 
intrauterine device 
IUS 
intrauterine system 
KDIGO 
Kidney Disease Improving Global Outcomes 
 
 
LC-MS/MS 
liquid chromatography- tandem mass spectrometry assay 
LDH 
lactate dehydrogenase 
LP 
lectin pathway 
MAC 
membrane attack complex 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
NSAID 
non-steroidal anti-inflammatory drug 
NRMWG 
Nephrology Risk Mitigation Working Group 
PD 
pharmacodynamic(s) 
PG 
pharmacogenomic(s) 
 
 
 
 
PK 
pharmacokinetic(s) 
PMN 
primary membranous nephropathy 
PNH 
paroxysmal nocturnal hemoglobinuria 
POC 
proof-of-concept 
PPK 
population pharmacokinetic 
PRO 
patient-reported outcome 
QoL 
quality of life 
QTcF 
QT interval corrected using Fridericia’s method 
RBC 
red blood cell 
REB 
research ethics board 
RNA 
ribonucleic acid 
SAE 
serious adverse event 

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Abbreviation or Specialist Term 
Explanation 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
sC5b-9 
soluble C5b-9 
sCr  
serum creatinine 
SGLT2 
sodium-glucose-cotransporter 2 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
uACR 
urine albumin-to-creatinine ratio 
 
 
uPCR 
urine protein-to-creatinine ratio 
ULN 
upper limit of normal 
US 
United States 
VZV 
varicella-zoster virus 
WBC 
white blood cell 
WSI 
whole slide image 

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5. 
INTRODUCTION 
5.1. 
Background 
5.1.1. 
The Complement System 
Complement activation is an innate defense mechanism that, when uncontrolled, leads to 
inflammation and local tissue damage. The complement system consists of 3 linked pathways: 
the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP). Dysregulation of 
AP activity by germ line or somatic genetic mutations of complement regulatory proteins or 
enzymes, neutralizing antibodies to complement regulatory proteins, or stabilizing antibodies to 
complement enzyme complexes predisposes individuals to diverse disorders, including 
paroxysmal nocturnal hemoglobinuria (PNH), age-related macular degeneration, atypical 
hemolytic uremic syndrome (aHUS), and complement 3 glomerulopathy (C3G) (Holers 2008, 
Brodsky 2014, Zipfel, Skerka et al. 2015, Ricklin, Reis et al. 2016). 
Figure 1: 
Complement Pathways 
 
Abbreviations: AP= alternative pathway; CP= classical pathway; FB = protease Factor B; FD = Factor D; 
LP = lectin pathway; MAC = membrane attack complex; MASP = MBL-associated serine proteases; 
MBL = mannose-binding lectin; P = properdin. 
Source: Adapted from (Thurman and Holers 2006). 
The complement system is constitutively activated at low levels; the AP is continuously 
activated via “tick over,” which is a slow spontaneous hydrolysis of an internal thioester within 
complement component 3 (C3), a key component of the complement cascade, thereby generating 
C3(H2O) at low concentrations. C3(H2O) pairs with Factor B and is then cleaved by serine 
protease Factor D to form C3(H2O)Bb (tick over C3 convertase) that eventually forms low levels 
of C3b via the AP.  
The complement system can be activated by each of the 3 complement pathways (ie, the CP, the 
LP, or the AP) and subsequently amplified by the AP amplification loop. Initial activation of the 
complement system by any of the 3 pathways results in the production of C3b fragments, which 

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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 deposits, 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 complement component 5 (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. 
Factor D in the Complement System 
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 30 kD N-terminal Ba fragment 
and retention of the 60 kD C-terminal Bb fragment that is required for the 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, 
Narayana 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. 
5.2. 
Indications 
5.2.1. 
Complement 3 Glomerulopathy 
Complement 3 glomerulopathy (C3G) is a group of rare kidney diseases in which dysregulation 
of the complement system results in prominent C3 fragment deposition within the glomerulus 
(Caravaca-Fontán, Lucientes et al. 2020). C3G is an extremely rare disorder with an estimated 
incidence between 0.2 to 3 cases per 1 million people in the United States (US) and Europe 
(Smith, Appel et al. 2019). 

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The resultant glomerular damage commonly leads to end-stage renal disease (ESRD) and often 
recurs after renal transplantation (Barbour, Ruseva et al. 2016). C3G is commonly categorized 
into 2 subsets: 1) dense deposit disease (DDD), which is diagnosed based on linear, 
hyperosmiophilic electron-dense deposits occupying the middle layer of the glomerular basement 
membrane; and 2) C3 glomerulonephritis, which refers to those cases of C3G in which dense 
deposits do not have the characteristics indicative of DDD. Abnormal glomerular accumulation 
of C3 fragments occurs due to uncontrolled C3b production via the AP of complement 
(Pickering, D'Agati et al. 2013). In some patients with C3G, acquired or genetic defects in AP 
regulation can be demonstrated. In others, autoantibodies to complement proteins and complexes 
that stabilize C3 convertase lead to C3 consumption and deposition of C3 fragments. Current 
standard of care includes supportive care including blood pressure control, inhibition of the 
renin-angiotensin system to minimize proteinuria, and the use of corticosteroids plus 
mycophenolate mofetil. In a recently published retrospective, multicenter, observational cohort 
study of 97 patients with C3G, mycophenolate mofetil/mycophenolate sodium in combination 
with corticosteroids was reported to have higher rate of remission (79%) as compared with 
patients treated with other immunosuppressives (24%) (Caravaca-Fontán, Díaz-Encarnación et 
al. 2020). Investigational therapy with the C5 inhibitor, eculizumab, has produced mixed results 
(Bomback, Smith et al. 2012). 
5.2.2. 
Immunoglobulin A Nephropathy 
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease 
worldwide, with an estimated incidence of 2.5 cases per 100,000 individuals per year among 
adults (McGrogan, Franssen et al. 2011), with geographic, racial, and ethnic variations in 
prevalence (Barratt and Feehally 2005, Rodrigues, Haas et al. 2017). The prevalence of IgAN 
may be higher in individuals of Pacific Asian and southern European descent versus those of 
North American and northern European descent (Barratt and Feehally 2005, Nair and Walker 
2006). A diagnosis of IgAN is associated with a reduction in life expectancy by 6 to 10 years 
(Nair and Walker 2006, Jarrick, Lundberg et al. 2019), and approximately 30% of adult patients 
with IgAN will develop ESRD (Gutierrez, Carvaca-Fontan et al. 2020). IgAN is an autoimmune 
disease, caused by abnormal synthesis of IgA1 that is galactose-deficient (Gd-IgA1); Gd-IgA1 
and anti-Gd-IgA1 immunoglobulin G (IgG) autoantibodies deposit in the kidney, along with IgG 
and C3, resulting in mesangial cell proliferation and glomerular inflammation with consequent 
kidney damage. Although the pathogenesis of kidney injury in IgAN is incompletely understood, 
associations between IgAN and glomerular and blood markers of complement activation have 
been established. In addition, C3 is found in glomerular deposits in 80% to 90% of patients with 
IgAN, implicating involvement of the AP. Currently, there are no complement directed therapies 
available for the treatment of IgAN. The standard of care for reducing proteinuria is the blockade 
of the renin-angiotensin-aldosterone system and to control blood pressure. On 17 December 
2021, TARPEYO™ (budesonide) was approved by the Food and Drug Administration (FDA) 
under accelerated approval based on a reduction in proteinuria in adults with primary IgAN at 
risk for rapid disease progression, generally a urine protein-to-creatinine ratio (uPCR) ≥ 1.5 g/g. 
It has not been established whether this corticosteroid slows kidney function decline and 
continued approval may be contingent upon verification and description of clinical benefit in a 
confirmatory clinical trial. 

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5.4. 
Rationale for Study 
5.4.1. 
Rationale for Study Design and Study Population 
BCX9930 is a small-molecule inhibitor of human Factor D that is being developed as a chronic, 
oral treatment for PNH and other diseases associated with the dysregulation of the AP. As 
overactivity of the AP and/or AP amplification loop is the common pathogenesis underlying 
C3G, IgAN, PMN, and PNH, inhibiting Factor D with BCX9930 provides a unified 
pharmacological approach for the treatment of these complement-mediated disorders. In 
addition, ex vivo complement activation assays using samples from healthy subjects dosed orally 
with BCX9930 in Study BCX9930-101 show that BCX9930 can also reduce activity of the LP 
and CP via inhibition of the C3 amplification loop, which is driven by Factor D. Thus, treatment 
with BCX9930 has the potential to address the unmet medical needs of patients with C3G, IgAN, 
and PMN, in addition to other diseases associated with the dysregulation of complement, 
including PNH.   
BCX9930-211 (Study 211) is an open-label, multicenter, exploratory, proof-of-concept (POC) 
study to evaluate the safety, tolerability, and preliminary efficacy of treatment with an oral 
Factor D inhibitor, BCX9930, administered for up to 52 weeks in adult (≥ 18 years old) subjects 
with C3G, IgAN, or PMN. This study will enroll approximately 14 subjects into each of the 3 
parallel study treatment cohorts of C3G, IgAN, and PMN to evaluate BCX9930 activity, 
preliminary clinical outcomes, and safety in all 3 renal diseases to inform future development of 
BCX9930. Subjects will be qualified for inclusion on the basis of pathologic confirmation of 
specific diagnosis, active disease, and complement deposition in recent biopsy samples. As the 
diseases under study are rare and necessitate the enrollment of subjects across multiple sites and 
countries, a central laboratory and a central pathologist will be used to standardize laboratory and 
pathology data for consistent evaluation of eligibility, safety, and efficacy across study sites.   
Due to the limited sample sizes across 3 rare renal diseases, an open-label design is being used to 
increase the number of subjects who receive BCX9930 in each cohort to measure changes from 
baseline to inform designs of future studies. As there are limited treatment options available to 
patients with C3G, IgAN, or PMN, subjects who are assessed by investigators as deriving 
clinical benefit at Week 24 will be allowed to continue in the study through up to 52 weeks. The 
up to 52-week study duration will allow the capture of longer-term safety and clinical outcome 
data to inform future, pivotal study designs across all 3 diseases including the assessment of 
primary efficacy measures after 24 weeks of BCX9930 treatment for IgAN and PMN. For the 
C3G treatment cohort, a duration of at least 24 weeks is anticipated to provide adequate time to 
measure changes from baseline in clinically relevant laboratory parameters (eg, proteinuria), and 
in morphological findings in kidney biopsies such as C3 deposits and cellular infiltration and 
other markers of inflammation.  
Factor D, the target of BCX9930, is cleared renally, and the concentration of Factor D in blood 
increases with declining renal function due to decreased clearance, most notably below a 
creatinine clearance of ≤ 30 mL/min/1.73 m2. Factor D blood concentration levels were reported 
to be > 20-fold that of normal in patients with ESRD who are receiving hemodialysis (Volanakis, 
Barnum et al. 1985, Pascual, Steiger et al. 1988). To limit the variation of Factor D blood 
concentrations in this study, only subjects with an estimated glomerular filtration rate (eGFR) of 
≥ 30 mL/min/1.73 m2 will be included. This eGFR cutoff is further supported by Factor D 

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Figure 2: 
Comparison of PK/PD Model-Estimated IC Values (95% CI) for 
AP Wieslab, LDH, and C3 Opsonization in Subjects with PNH with Median 
(10th to 90th percentile) PPK Model-Estimated Ctau at 200, 400, and 500 mg 
BID 
Abbreviations: AP = alternative pathway; BID = twice daily; CI = confidence interval; IC = inhibitory 
concentration; LDH = lactate dehydrogenase PK/PD = pharmacokinetic/pharmacodynamic; PPK = population 
pharmacokinetic(s). 
Notes: Each simulation assumes perfect adherence and optimal spacing of BID doses (ie, every 12 hours). 
5.5. 
Benefit-Risk Analysis  
Subjects may derive a benefit in improving surrogate clinical markers of disease progression 
(eg, reducing proteinuria) and controlling the symptoms of their disease with BCX9930. Study 
subject selection criteria, dose selection, assessment of clinical benefit at Week 24, and study 
monitoring assessments have been designed to maximize the potential benefit-risk ratio of 
BCX9930 in subjects with C3G, IgAN, and PMN.  
Regular monitoring of safety parameters, including AEs, laboratory assessments, vital signs, 
ECGs, and physical examination findings, will be mandated to ensure that the benefit-risk profile 
supports continued dosing.  
The DMC will regularly review the cumulative safety data from this study, as well as the 
accumulating, long-term safety data across all BCX9930 studies in all indications per 
Section 13.7. 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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It is anticipated that BCX9930 will continue to be made available in each country until such time 
as BCX9930 either receives commercial approval or until BioCryst discontinues development of 
the product, whichever comes first. 
Potential risks associated with complement inhibitors for the treatment of C3G, IgAN, and PMN 
as well as potential risks associated with BCX9930 based on nonclinical and clinical data to date 
are described in the IB for BCX9930 and are summarized below. 
5.5.1. 
Potential Risks of Bacterial Infections  
The most significant risk associated with complement inhibitor therapies, including the approved 
therapies eculizumab or ravulizumab, 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 relevant labels for both Soliris® (eculizumab) and Ultomiris® 
(ravulizumab) (Alexion Pharmaceuticals 2020, Alexion Pharmaceuticals 2021). 
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 Neisseria meningitidis and other bacteria such as Neisseria 
gonorrhoeae (Ram, Lewis et al. 2010). Study subjects receiving BCX9930 will be monitored 
closely for signs and symptoms of infection, and 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. 
5.5.2. 
Potential Risk of SARS-CoV-2 Infection and Vaccination  
Complement inhibitors do not inhibit cellular or humoral immunity. Therefore, BCX9930 is not 
expected to increase the risk of contracting coronavirus disease (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 ongoing investigational 
product BCX9930. While there is a known or expected higher risk of certain bacterial infections 
in patients treated with complement inhibition (including with BCX9930 treatment), or in 
patients with certain hereditary complement deficiencies, there is no clear known increased or 
compounded risk with vaccinations (such as currently authorized COVID-19 vaccinations) in the 
setting of complement inhibition. Also, currently there is no theoretical concern or data to 

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6.2.2. 
Secondary Endpoints 
The secondary endpoints of this study are: 
• Number and proportion of subjects with a uPCR response defined as: 
− Partial remission, ≥ 50% reduction from baseline 
− Complete remission, ≤ 500 mg/g 
− Normalization, ≤ 200 mg/g 
• Change from baseline in 24-hour urinary protein excretion as measured by percentage 
change in urinary protein from baseline  
• Change from baseline in eGFR 
• Change from baseline in serum albumin  
• Number and proportion of subjects with the following parameters: 
− Protein ≥ 3.5 g in a 24-hour urine collection 
− Serum albumin ≤ 2.5 g/dL 
• Number and proportion of subjects with a morphologic response in each of the 
following categories (C3G cohort only at Week 24): 
− Decreased endocapillary hypercellularity, mesangial hypercellularity, active 
crescents (if present), glomerular leukocyte infiltration, fibrinoid necrosis, 
membranoproliferative glomerulonephritis pattern 
− Decreased acute tubular injury, interstitial inflammation, interstitial edema 
− Reduction in C3 glomerular staining 
− Reduction in the extent of deposits, clearing of deposits, or no additional active 
deposits as assessed by electron microscopy (EM) 
− No progression of chronic changes (ie, global, segmental glomerulosclerosis, 
tubular atrophy/interstitial fibrosis, arteriosclerosis) 
• 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 treatment-emergent serious 
adverse event (TESAE) 
• Number and proportion of subjects who experience a Grade 3 or 4 TEAE based on 
Common Terminology Criteria for Adverse Events (CTCAE) 
• Number and proportion of subjects who experience a CTCAE treatment-emergent 
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qualification period, approximately 14 eligible subjects will be enrolled into each of 3 parallel 
study treatment cohorts and will receive BCX9930 200 mg BID for the first 14 days and will 
increase to BCX9930 400 mg BID on Day 15 for the remainder of the treatment period.  
During the study, recruitment into each of the cohorts will be managed independently with a total 
of approximately 42 subjects enrolled into the study. For the C3G cohort only, up to 7 subjects 
with at least 6 months of treatment with a stable dosing regimen of mycophenolate mofetil or 
mycophenolate sodium prior to the Day 1 Visit will be allowed to enroll in the study per 
Section 8.2. Sites will be notified when enrollment is complete for subjects with C3G receiving 
mycophenolate mofetil/mycophenolate sodium.  
After providing written informed consent to participate in the study and confirming that all other 
study eligibility criteria have been met during screening, subjects will undergo a percutaneous 
needle biopsy of the kidney per local practice and guidelines. Renal biopsy images and details 
from the local pathology report will be reviewed by the central pathologist for confirmation of a 
protocol-defined diagnosis of C3G, IgAN, or PMN. The screening biopsy procedure may be 
waived with approval of the central pathologist and agreement with the medical monitor for any 
subject who has undergone a renal biopsy procedure as follows: within 3 months prior to 
screening for the C3G cohort, within 6 months prior to screening for the IgAN or PMN cohorts, 
provided that required materials are adequate for pathology evaluation per protocol procedures.  
After the Day 1 Visit, subjects will be required to return to the clinic at Weeks 1, 2, and 4, and 
then every 4 weeks thereafter through Week 24. Additional safety assessments will be performed 
at Weeks 3, 5, 6, 7, and 10, either at the investigative site, or at a local laboratory more 
convenient for the subject or via a home health service (where permitted and available). At the 
Week 24 Visit, the clinical benefit of BCX9930 treatment will be assessed by the investigator. 
Subjects who are assessed as deriving clinical benefit will continue treatment up to Week 52. 
described in Table 2 and Table 3. 
An on-treatment, percutaneous needle biopsy of the kidney will be performed at the following 
visit after completion of all other assessments, or during the time specified below by treatment 
cohort: 
• Week 24 or within 7 days after the visit for subjects with C3G 
• Week 36 or within 7 days after the visit for subjects with IgAN (optional) 
• Week 48 to within 3 days after the Week 52 Visit for subjects with PMN (optional)  
The on-treatment biopsy is optional for subjects with IgAN or PMN. For subjects with PMN, if 
the biopsy is scheduled after the Week 52 Visit, then dosing with BCX9930 will continue until 
the day of the biopsy procedure. WSIs of LMs, digital IFs or IHCs, digital EMs, and details from 
the local pathology reports from the on-treatment biopsies will be reviewed by the central 
pathologist. Protocol-specified, on-treatment biopsies will not be required for subjects who are 
discontinued from BCX9930 treatment.  
Subjects who complete BCX9930 dosing through Week 52 and who are discontinued from 
BCX9930 dosing prior to Week 52 will return to the clinic approximately 4 weeks (28 ± 3 days) 
after the date of their last dose of BCX9930 for the Safety Follow-up (FU) Visit prior to study 
completion/discontinuation.  

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A study schema is shown in Figure 3. 
An optional serial PK/PD substudy will include subjects who provide consent from each of the 
3 cohorts to evaluate the PK and PD of BCX9930 at the Day 1 Visit and/or at a subsequent visit 
prior to the Week 24 Visit. Serial sampling of urine and blood will be performed over a period of 
6 hours. Subjects who do not participate in the Baseline (Day 1) PK/PD sample collection are 
eligible to participate at a subsequent clinic visit prior to the Week 24 Visit.  
All subjects will have a single blood sample drawn for PK analysis at each clinic visit (“sparse 
sampling” to support PPK and PK/PD modeling). For subjects participating in the serial PK/PD 
substudy, a single blood sample will be drawn for PK and PD analysis at visits where serial 
blood samples are not collected through 6 hours post dose.  
All subjects who sign a separate informed consent (optional) will participate in exploratory 
pharmacogenomics testing at a single visit from Day 1 up to the Week 24 Visit (including the 
safety FU Visit, if applicable). 
Figure 3: 
Study Schema 
 
7.2. 
Number of Subjects 
This study will enroll approximately 14 adult subjects in each of the C3G, IgAN and PMN 
cohorts for a total enrollment of approximately 42 subjects.  
7.3. 
Treatment Assignment 
All eligible subjects will receive BCX9930 200 mg BID for the first 14 days and will increase to 
BCX9930 400 mg BID on Day 15 for the remainder of the treatment period; doses should be 
taken approximately 12 hours apart. The first dose of BCX9930 will be administered at the Day 
1 Visit after completion of all baseline procedures and under supervision of clinic staff.  
7.4. 
Individual and Study Termination Criteria 
7.4.1. 
Study Drug Treatment Discontinuation Criteria 
A subject will be permanently withdrawn from BCX9930 for any of the following reasons: 
• Pregnancy in a female subject. 

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• 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. 
• Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) > 3 × ULN combined with either laboratory abnormalities indicative of 
significant hepatic toxicity (ie, meeting Hy’s law, total bilirubin > 2 × ULN OR with 
an INR > 1.5) or with symptomatology of acute hepatitis (ie, severe fatigue, nausea, 
vomiting, right upper quadrant pain and tenderness, fever, rash, and/or eosinophilia 
[> 5%]) and assessed by the investigator as probably, or definitely related to 
BCX9930 treatment. 
• Treatment-emergent increase in sCr ≥ 3 × ULN (confirmed by repeat testing) without 
any other potential cause of renal dysfunction  
• In the investigator’s opinion it is in the best interest of the subject to discontinue from 
further dosing. 
• Invasive meningococcal infection or any serious invasive bacterial infection that 
occurs after BCX9930 is initiated. 
• Subject request to discontinue for any reason. 
• 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 are 
discontinued from BCX9930 dosing prior to Week 52 will return to the clinical site 
approximately 4 weeks (28 ± 3 days) after the date of their last dose for a safety FU Visit prior to 
discontinuation from the study. 
7.4.2. 
Subject Withdrawal Criteria 
Participation in the study is strictly voluntary. Subjects have the right to withdraw from study 
drug or from the study at any time and for any reason. A subject’s participation may be 
terminated for any of the reasons delineated 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 

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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 7.4.1 and Section 13.4. Vigorous attempts will be made for 
follow-up of all subjects who miss a study visit. 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. 
Once subjects have withdrawn from the study, the sponsor will no longer provide treatment 
through the study. 
7.4.3. 
Criteria for Study Termination 
The following study stopping criteria will be used to stop the study (permanent termination or 
suspension of enrollment/treatment) or the participation of a particular investigational site: 
• Emergence of unacceptable risk, toxicity, or negative change in the benefit-risk 
assessment 
• In the event that 3 subjects are determined by the NRMWG to have confirmed 
elevations of sCr ≥ 3 × ULN considered related to BCX9930  
• Request of the relevant competent authority or ethics committee 
• 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 to exercise this right only 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. 
7.4.4. 
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. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following inclusion criteria (where applicable) prior to first dose of 
BCX9930 on Day 1 or specified time below: 
1. Willing and able to provide written informed consent (or, for subjects who have not 
reached the age of maturity, willing and able to provide written assent with written 
informed consent additionally provided by the subject’s parent[s] or legal guardian). 
2. Male or non-pregnant, non-lactating female subjects ≥ 18 years of age. 
3. Body weight ≥ 40 kg. 

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4. Primary diagnosis of C3G, IgAN, or PMN with evidence of disease activity, as confirmed 
by central pathology review of digital images and pathology reports of renal biopsy 
samples obtained during screening as described in Section 12.4.2.1 (or within 3 months 
prior to screening for subjects with C3G and 6 months prior to screening for subjects with 
IgAN and PMN with approval of the central pathologist and agreement with the medical 
monitor). 
• All: ≤ 50% global glomerulosclerosis 
• All: ≤ 50% tubulointerstitial fibrosis 
5. For subjects with C3G only, documentation of duration of illness of at least 90 days by 
either a prior biopsy collected ≥ 90 days prior to screening confirming a diagnosis of 
C3G OR a clinical diagnosis of C3G with at least one documented proteinuria assessment 
≥ 90 days prior to initial screening visit. 
6. For subjects with C3G only, proteinuria defined as ≥ 1 g of urinary protein per 24 hours 
at screening that has not shown a ≥ 25% decrease from the most recent documented 
proteinuria assessment, which was collected at least 30 days prior to and within 180 days 
of initial screening visit.  
7. For subjects with IgAN only, proteinuria defined as 1 g to ≤ 4 g of urinary protein per 24 
hours at screening that has not shown a ≥ 25% decrease from the most recent documented 
proteinuria assessment, which was collected at least 30 days prior to and within 180 days 
of initial screening visit. 
8. For subjects with PMN only, an 
 
 of ≥ 150 U/mL and 3.5 g to ≤ 11 g of urinary protein per 24 hours at screening 
that has not shown a ≥ 25% decrease from the most recent documented proteinuria 
assessment, which was collected ≥ 30 days prior to and ≤ 180 days of initial screening 
visit. 
9. An eGFR ≥ 50 mL/min/1.73 m2 (or ≥ 30 mL/min/1.73 m2 after DMC recommendation) 
calculated using the serum creatinine-based Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) formula. 
10. Resting supine vital signs within the following ranges: 
• Systolic blood pressure, 80 to 150 mm Hg, inclusive 
• Diastolic blood pressure ≤ 90 mm Hg  
11. Treatment with a stable, maximum recommended or maximum tolerated dose of an 
angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) 
for at least 60 days prior to the Day 1 Visit and in the opinion of the investigator the 
expectation of continuing the same dose and regimen for such treatment during the study. 
12. Contraception requirements: 
Female subjects must meet at least one of the following requirements: 
a. Be a woman of nonchildbearing potential, defined as postmenopausal (without 
menses for ≥ 12 months [without an alternative medical cause] with a follicle-

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stimulating hormone [FSH] > 40 mIU/mL, or who have had a hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy). 
b. 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. 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) 
c. 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. 
Male subjects must meet at least one the following requirements: 
d. Subjects with female partners of childbearing potential (defined as without menses 
≤ 12 months, or a non-menopausal female who has not had a hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy) must agree to utilize a contraceptive 
method throughout the study and for at least 90 days after the last dose of study drug. 
The following methods during the study are acceptable: 
− surgical sterilization (ie, vasectomy that has been medically assessed to be 
successful, or bilateral tubal occlusion of a female partner) 
− partner’s use of an IUD or IUS 
− partner’s use of combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation (oral, intravaginal, 
transdermal) 
− partner’s use of progestogen only hormonal contraception associated with 
inhibition of ovulation (oral, injectable, implantable)  
− use of a condom 
13. Documentation of current vaccinations against N. meningitidis Types A, C, W, and Y, 
and S. pneumoniae vaccine, or must be vaccinated or willingness to start vaccination 
series for any of the missing protocol required vaccines at least 14 days prior to Day 1 per 
Section 12.2.1. 

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(Note: Vaccination for N. meningitidis Type B and for H. influenzae Type B (Hib) is strongly 
encouraged where authorized and available.) 
14. In the opinion of the investigator, the subject is likely to comply adequately with all 
required study procedures and restrictions for the study, including compliance with the 
BID dosing schedule for BCX9930. 
8.2. 
Subject Exclusion Criteria 
Subjects must meet none of the following exclusion criteria (where applicable) prior to first dose 
of BCX9930 on Day 1 or specified time below: 
1. Known congenital deficiency of C1s, C1r, C1q, C2, C4. Known variants in complement 
Factor H, complement Factor I, C3, and complement Factor B or genomic 
rearrangements in the complement Factor-H-related proteins are not exclusionary  
2. Receiving hemodialysis or peritoneal dialysis or anticipated to receive dialysis during the 
duration of this study. 
3. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate 
for transplantation during the study. 
4. History of transfusion with blood or blood products, or plasmapheresis or plasma 
exchange, within 30 days prior to screening. 
5. 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. 
6. History of malignancy within 5 years prior to the screening visit, with the 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. 
7. Any clinical or pathological evidence of monoclonal gammopathy of unclear or renal 
significance, lupus or other systemic autoimmune disease, or other conditions 
(eg, infection-associated disease or associated with another systemic disease, 
anti-phospholipid antibody syndrome with significant clinical disease, immune 
complex glomerulonephritis, immunoglobulin A [IgA] vasculitis with nephritis 
[Henoch-Schönlein purpura] or morphologic features of secondary membranous 
nephropathy). Presence of C3 or C5 nephritic factors (eg, autoantibodies directed at C3 or 
C5 convertase), in the absence of known infection or other systemic disease, are not 
exclusionary for this study. 
8. Treatment with azathioprine, canakinumab, cyclophosphamide, cyclosporine, 
eculizumab, everolimus, hydroxychloroquine, infliximab, sirolimus, ravulizumab, 
systemic corticosteroids (including budesonide), tacrolimus, or any other systemic 
immunosuppressive or immunomodulatory therapies (eg, complement inhibitors) within 
90 days OR mycophenolate mofetil/mycophenolate sodium treatment within 60 days OR 
anti-CD20 antibody therapies (eg, rituximab) within 180 days prior to the screening visit. 

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a. For subjects with C3G only, ongoing treatment with a stable dose of mycophenolate 
mofetil/mycophenolate sodium for at least 6 months prior to the Day 1 Visit is 
allowed 
9. Treatment with renin inhibitors (eg, aliskiren) or sodium-glucose-cotransporter 2 
(SGLT2) inhibitors within 60 days prior to Day 1. 
10. 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. 
11. Any of the following laboratory values at the screening visit: hemoglobin < 8.5 g/dL; 
total white blood cell (WBC) < 2.5 × 109/L; absolute neutrophil count (ANC) 
< 1.0 × 109/L; platelet count < 90 × 109/L; ALT, AST, alkaline phosphatase (ALP), or 
total bilirubin > 1.5 × ULN; serum albumin < 1.5 g/dL; or INR > 1.4. 
a. Subjects with Grade 1 elevated bilirubin due to Gilbert’s syndrome are allowed to 
enroll. To document that a subject has Gilbert’s syndrome, a diagnosis from the 
medical record must be provided, or the investigator may make a presumptive 
diagnosis of Gilbert’s syndrome in subjects with unconjugated hyperbilirubinemia on 
repeated testing (at least 2 samples separated in time) who have ALT, AST, and ALP 
≤ 1.5 × ULN, and a normal complete blood count. 
12. Any laboratory parameter at screening that, in the judgment of the investigator, is 
clinically significant and would represent a safety concern.  
Note: Enrollment of a subject with laboratory value(s) outside of the reference range may 
be permissible if the abnormality is documented by the investigator to not be of clinical 
significance, or is disease related, and does not pose a safety concern. 
13. Clinically significant abnormal ECG prior to dosing at the Day 1 Visit. 
14. Current use of a prohibited concomitant medication within 7 days prior to Day 1 as 
detailed in Section 9.2.  
15. Active serious bacterial, viral, or fungal infection or any other serious infection, including 
suspected or confirmed severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] 
infection, within 14 days of screening. Dyspnea, vasculitic rash, and persistent fever or 
other symptoms consistent with multisystem inflammatory syndrome [MIS] are 
exclusionary in the setting of recent SARS-CoV-2 infection. 
16. Positive serology for human immunodeficiency virus (HIV), or active infection with 
hepatitis B virus (HBV) or hepatitis C virus (HCV). 
17. Positive test for drugs of abuse during screening, unless by prescription where legal. 
18. Pregnant, planning to become pregnant, or breastfeeding. 
19. Known or suspected hypersensitivity to BCX9930 or any of its formulation excipients as 
detailed in Section 10.1. 
20. History of severe hypersensitivity to any medicinal product, which was associated with 
swelling, severe rash requiring treatment/hospitalization, or anaphylaxis. 

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21. Any clinically significant medical or psychiatric condition, including known or suspected 
substance abuse (including alcohol) 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. 
9. 
TREATMENT OF SUBJECTS 
9.1. 
Prior/Concomitant Medications 
All medications will be documented beginning 30 days prior to the screening visit. All 
concomitant medication use, beginning with the screening visit and including all medications 
administered for the treatment of AEs, will be recorded. 
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 in Section 9.2, subjects should continue their normal medications. Dosing 
of medications that increase infection risk (eg, mycophenolate mofetil/mycophenolate sodium) 
should remain stable until at least the Week 52 visit unless taper or discontinuation needs to be 
done for safety reasons. 
If any dose adjustments to the protocol-required stable, maximum tolerated dose of either an 
ACEi or ARB are needed for the treatment of a subject during the study or if it is discovered that 
the subject’s ACEi or ARB dose has been changed, then the investigator (or qualified designee) 
should notify the medical monitor.  
Prophylactic use of antibacterial and antiviral medications may be considered if clinically 
indicated 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 9.2).  
Please refer to inclusion criterion 13 and Section 12.2.1 for vaccination requirements and 
recommendations. 
9.2. 
Prohibited and Restricted Medications 
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 
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 should be completed at 
least 7 days prior to Day 1.  
All subjects in the study should refrain from taking the following prohibited medications from 
the screening visit through the safety FU visit: 
• Any systemic immunosuppressive or immunomodulatory medications (eg, 
azathioprine, canakinumab, cyclophosphamide, cyclosporine, eculizumab, 

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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.  
During the study, the CYP enzymes and drug transporters of clinical concern may be modified 
based on drug interaction studies. Medications that potentially affect the metabolic pathways or 
transport of BCX9930 may also be added, pending availability of additional data. 
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. 
If any of these prohibited medications are determined to be needed for the treatment of a subject 
during the study or if it is discovered that the subject is already receiving a prohibited medication 
during study participation, then the investigator (or qualified designee) should contact the 
medical monitor. Investigators should contact the sponsor medical monitor for specific questions 
regarding prohibited and restricted medications as needed. 
9.3. 
Treatment Compliance 
The first dose of BCX9930 on Day 1 will occur in the clinic 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. For subjects who are 
participating in the PK/PD substudy and are scheduled to have serial PK/PD collections on a 
clinic day, the morning dose of BCX9930 will need to be withheld until the scheduled visit. 
Subjects will be provided instructions for taking daily doses of study drug, including frequency 
and time of administration. Subjects will be instructed to maintain approximately the same 
approximate 12-hour dosing interval between study drug doses each day (eg, 8:00 AM and 
8:00 PM).  
It is anticipated that subject compliance with the BID dosing schedule for BCX9930 is important 
for the benefit of subjects and for success of this study. Investigators should remind participants 
who regularly miss doses about the importance of treatment compliance. Drug compliance will 
be recorded in the eCRF. 
9.3.1. 
Missed Doses: 
If the subject forgets to take the study drug at the correct time, the dose may be taken as late as 
6 hours after the scheduled dose time. If more than 6 hours has passed, subjects should skip the 
missed dose entirely and take the next dose at the scheduled time. 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 

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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 to all study visits at the investigative site (including any unscheduled visits, when possible). 
Drug accountability and treatment adherence will be reviewed at these visits. 
10.3.1. 
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. 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. Any treatment resumption will be recorded in the eCRF and source 
documents. See Section 10.3.2 for potential dose reduction options. 
10.3.2. 
Dose Tapering 
In the event of permanent discontinuation of BCX9930, the dose of BCX9930 may be tapered 
using the following schedule as a guideline: 
 
 
 
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. 
10.4. 
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) 
or dispensed to the subject. At the end of the study, information describing study drug 
accountability must be maintained at the site. 
At the end of the study, all study drug not administered and any returned study drug (including 
empty bottles) will be returned to the sponsor or destroyed onsite as instructed by the sponsor 

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following IMP accountability by the study monitor, abiding by appropriate standard operating 
procedure(s) at the participating institution. 
11. 
STUDY CONDUCT 
11.1. 
Overview 
A subject’s participation in this study is expected to be up to 64 weeks (including the screening, 
dosing, and follow-up periods) with a minimum of 18 planned in-clinic visits and 5 additional 
safety assessment visits at the investigative site or at a local laboratory more convenient for the 
subject or via a home health service (where permitted and available). 
After confirming that all other study eligibility criteria have been met during a screening period 
of up to 56 days, subjects will undergo a percutaneous needle biopsy of the kidney per local 
practice and guidelines. The screening biopsy will also serve as the baseline, pretreatment biopsy 
for the C3G cohort and for the subjects who choose to have an on-treatment biopsy in the IgAN 
and PMN cohorts. Biopsy eligibility criteria and baseline assessments will be reviewed by the 
central pathologist by review of digital images and details from the local pathology report. In 
addition, unstained EM grids may be shipped from sites to the central pathologist for additional 
baseline EM assessments and reporting. The screening biopsy procedure may be waived after 
review by the medical monitor and central pathologist for any subject who has undergone a renal 
biopsy procedure as follows: within 3 months prior to screening for the C3G cohort, within 6 
months prior to screening for the IgAN or PMN cohorts, provided that required materials are 
adequate for pathology evaluation per protocol procedures.  
Each eligible subject who consents to participate in the study will receive up to 52 weeks of 
BCX9930. All subjects will be required to attend at least 9 in-clinic study visits through 24 
weeks: 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), and Week 24 (Day 169) and 5 
additional safety assessments visits at Weeks 3 (Day 22), Week 5 (Day 36), Week 6 (Day 43), 
Week 7 (Day 50), and Week 10 (day 71), either at the investigative site, at a local laboratory 
more convenient for the subject or via a home health service (where permitted and available). At 
the Week 24 Visit, the clinical benefit of BCX9930 treatment will be assessed by the 
investigator. Subjects who are assessed as deriving clinical benefit will continue treatment up to 
Week 52 and be required to attend at least 7 additional in-clinic visits: 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). All subjects will return to the clinic approximately 4 weeks 
(28 ± 3 days) after the date of their last dose of BCX9930 for the safety FU Visit. 
An on-treatment, percutaneous needle biopsy of the kidney will be performed for subjects with 
C3G at a specified visit after completion of all other assessments, or during the specified times as 
described in Section 12.4.2. The on-treatment biopsy is optional for the IgAN and PMN cohorts. 
All subjects who undergo kidney biopsy should remain on study drug at least until the day of 
biopsy. Digital images and details from the local pathology reports from the on-treatment 
biopsies will be reviewed by the central pathologist to evaluate and describe changes from the 
baseline, pre-treatment digital images.  

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An optional serial PK/PD substudy will include subjects who provide consent from each of the 
3 cohorts to evaluate the PK and PD of BCX9930 at the Day 1 Visit and/or at a subsequent visit 
prior to the Week 24 Visit. Serial sampling of urine and blood will be performed over a period of 
6 hours. Subjects who do not participate in the Baseline (Day 1) PK/PD sample collection are 
eligible to participate at a subsequent clinic visit prior to the Week 24 Visit.  
All subjects who sign a separate informed consent will participate in exploratory 
pharmacogenomics testing at a single visit from Day 1 up to the Week 24 Visit (including the 
safety FU Visit, if applicable). 
11.2. 
Schedule of Assessments 
The schedule of assessments for this study is presented in Table 2 (Screening through Week 24) 
and Table 3 (Week 28 through Week 52). The schedule of assessments for the PK/PD substudy 
is presented in Table 4. 
   

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Table 3: 
Schedule of Assessments (Screening - Week 24) 
 
 
 
 
Screening 
a
Baseline
Safety FU 
Visit d
(Up to 
Day ‑ 56)
1
2
3c
4
5 c
6 c
7 c
8
10 c
12
16
20
24
(± 1 d)
(± 1 d)
(± 1 d)
(± 1 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
Written informed consent e  
X
Review eligibility criteria
X
X
Demographics
X
Medical & medication 
history  
X
Disease Specific Medical 
History Form f
X
Height, body weight, and 
BMI g
X
X
X
X
X
X
X
X
X 
Physical examination h 
X
X
X
X
X
X
X
X
X
X
X 
12-lead ECG i 
X
X
X
X
X
X
X
X
X
X
X 
Vital signs j 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
Hematology and coagulation
X
X
X
X
X
X
X
X
X
X
X 
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
Urinalysis including 
microscopy k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
Intended 24-hour urine 
collection l 
X
X
X
X
X
X
X
X
X
X
X 
eGFR m 
X
X
X
X
X
X
X
X
X
X
X 
Percutaneous renal biopsy n,o 
X
X q
Urine for biomarker testing p 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X 
Drugs of abuse screen
X
Pregnancy test q 
X
X
X
X
X
X
X
X
X
X
X 
FSH r 
X
Dosing Phase (Study Week)
Day 1 b
28 ± 3 days 
after last 
dose
Assessment/Procedure

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Table 4: Schedule of Assessments (Week 28-Week 52) 
 
Safety FU 
Visit a
28
32
36
40
44
48
52
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
(± 3 d)
Height, body weight, and BMI b 
X
X
X
X
X
X
X
X 
Physical examination c
X
X
X
X
X
X
X
X 
12-lead ECG d 
X
X
X
X
X
X
X
X 
Vital signs e
X
X
X
X
X
X
X
X 
Hematology and coagulation
X
X
X
X
X
X
X
X 
Chemistry
X
X
X
X
X
X
X
X 
Urinalysis including microscopy f
X
X
X
X
X
X
X
X 
Intended 24-hour urine collection g 
X
X
X
X
X
X
X
X 
eGFR h
X
X
X
X
X
X
X
X 
Percutaneous renal biopsy  i,j
X 
X
X
Urine for biomarker testing k
X
X
X
X
X
X
X
X 
Pregnancy test l
X
X
X
X
X
X
X
X 
PRO questionnaires m
X
X
X a
X (IgAN 
only)
X (PMN 
only)
X a
PK blood sample collection o 
X
X
X 
X
X
X
X
PD blood sample collection p
X
X
X
X
X
X
X
X
PK urine sample collection q 
X
X
X 
X
X
X
X
Dosing Phase (Study Week)
28 ± 3 days 
after last 
dose
Assessment/Procedure

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Table 5: 
Timing of Blood Sample and Urine Collection for PK/PD Substudy at Baseline (Day 1 Visit) and a Visit prior to 
Week 24 
Collection 
 
Required Post Dose  
Pre-dose 
 
 
 
 
 
 
 
 
PK Blood Sample a 
X b 
X 
X 
X 
X 
PD Blood Sample c 
X 
 
X 
X 
X 
Urine Collection d 
X 
 
 
 
 
Abbreviations: PD = pharmacodynamics; PK = pharmacokinetics 
Note: Subjects who do not participate at the Day 1 serial collection through 6 hours post dose are eligible to participate at another clinic visit prior to the 
Week 24 Visit.  
a The actual date and time of each blood sample collection, the observed BCX9930 dose time, and whether the subject had eaten recently prior to dosing will be 
recorded in the eCRF. For the second (steady-state) PK/PD substudy visit, the date and time of the last 2 doses taken prior to the pre-dose blood collection, and 
whether these were taken with or without food, will also be recorded in the eCRF. 
b A pre-dose PK sample is not required at the Day 1 Visit but is required at the second (steady-state) PK/PD substudy visit. At this visit, the PK sample should be 
collected immediately prior to dosing and as close as possible to 12 hours following the previous dose.  
c PD samples should be taken at the same time as the associated PK samples, where applicable 
d A single void urine sample will be collected pre-dose and up to two single void urine samples can be collected after dosing. If fewer than 2 voids are collected 
during the post-dose period, then subjects will be asked to provide a single void urine sample at the 6-hour post-dose timepoint. 
 
 

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11.3. 
Study Visits 
Unless indicated otherwise, all subjects are expected to complete all scheduled study 
assessments/procedures, regardless of treatment assignment. 
11.3.1. 
Screening 
Subjects with C3G, IgAN, or PMN who may require additional treatment to an ACEi or ARB 
may be screened for this study. 
Written consent must be obtained from the subject as required by national or local law and 
institutional practice, prior to conducting any study-related assessments/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 screening procedures are first performed. 
A 56-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 dosing a subject. The 
screening period can be extended up to 28 additional days with approval by the medical monitor 
(or designee) on a case-by-case basis.   
The investigator (or designee) will conduct the following assessments at the screening visit(s), 
including: 
• Signing of the ICF  
• Review of inclusion and exclusion criteria 
• Demographic information 
• Medical and medication history including confirmation of adequate vaccination and 
either providing protocol required vaccinations or scheduling with local health care 
provider to vaccinate prior to Baseline (Day 1); see Section 12.2.1.  
• Disease Specific Medical History Form  
• 12-lead ECG  
• Vital signs (blood pressure, temperature, and pulse rate) 
• Complete physical examination 
• Height/weight/body mass index (BMI) calculation 
• Serum pregnancy test for female subjects of childbearing potential 
• Blood collection for FSH for any woman post-menopausal for ≥ 12 months and 
≤ 2 years (FSH measurement is not needed at screening to confirm postmenopausal 
state in women who report no menses for > 2 years) 
• Blood collection for clinical chemistry, hematology, coagulation, and PD biomarkers 
• Blood collection for HBV, HCV, HIV, and VZV serology 
• Single void collection for urinalysis including microscopy and drugs of abuse screen 

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• Recording of prior medications within 30 days prior to first dose and current 
medications 
• Provide collection containers with instructions for collection and return of an 
intended 24-hour urine sample to the clinic during screening and, if applicable, at the 
Day 1 Visit 
• Register the subject in Interactive Response Technology (IRT) 
• After confirmation that all other study eligibility criteria are met (including intended 
24-hour uPCR criterion), a percutaneous needle biopsy of the kidney per local 
practice and guidelines will be required, unless a kidney biopsy with digital images 
and a pathology report are available within 3 months of the screening visit with C3G 
or 6 months of the screening visit with IgAN or PMN that meets all protocol 
requirements and is confirmed by the medical monitor and central pathologist 
Note: The central pathologist will determine eligibility by confirmation of the 
primary diagnosis of either C3G, IgAN, or PMN and active disease prior to the Day 1 
Visit and first dose of BCX9930 
A screening failure eCRF page will be completed for those subjects who do not proceed with 
study dosing, recording the reason for screening failure. 
11.3.2. 
Rescreening/Retesting 
Rescreening of ineligible subjects, where there is a reasonable expectation that the subject will 
become eligible, is permitted. If a subject is unable to be qualified in the 56-day window, eg, due 
to a dose change of an ACEi/ARB or acute illness or retesting of screening labs or delays related 
to screening biopsy, the screening window may be extended up to 28 additional days with the 
approval of the sponsor medical monitor (or designee). Retesting of specific assessments without 
entirely rescreening a subject may be permitted with the approval of the sponsor medical monitor 
(or designee). 
11.3.3. 
Baseline Visit (Day 1) 
For subjects participating in the PK/PD substudy, please refer to Table 2 and Table 4 for 
procedures and timings.  
Before any study drug is administered, the following assessments will be completed: 
• Administration of questionnaires: 
− 
  
 
 
 
 
• Review of inclusion and exclusion criteria and prohibited medications 
• Review of medical and medication history 
• Review of Disease Specific Medical History Form 
• Weight and BMI  

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• 12-lead ECG (triplicate ECGs) 
• Vital signs (blood pressure, temperature, and pulse rate) 
• Complete physical examination 
• Single void urine collection for urinalysis including microscopy and biomarkers 
• A urine pregnancy test for female subjects of childbearing potential. A negative urine 
pregnancy result must be recorded in order for the subject to receive study drug. 
• Blood collection for clinical chemistry, hematology, coagulation, and PD biomarkers 
• Review concomitant medications and AEs 
• Provide collection container with instructions and return of an intended 24-hour urine 
sample  
• Study drug dispensing (via IRT) 
Where possible, the questionnaires should be completed by the subject prior to other assessments 
to prevent influencing subject perceptions.  
11.3.4. 
On-study Visits (Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) 
Subjects will return to the clinic during Week 1 (Day 8 ± 1 day),Week 2 (Day 15 ± 1 day), 
Week 4 (Day 29 ± 1 day), Week 8 (Day 57 ± 3 days), Week 12 (Day 85 ± 3 days), Week 16 
(Day 113 ± 3 days), Week 20 (Day 141 ± 3 days), Week 24 (Day 169 ± 3 days) 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). 
At the Week 24 Visit, the clinical benefit of BCX9930 treatment will be assessed by the 
investigator. Subjects who are assessed as deriving clinical benefit will continue treatment up to 
Week 52. Subjects who continue BCX9930 treatment will complete study visits and assessments 
through the Week 52 Visit.  
Subjects 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 PK/PD substudy procedures are 
also being conducted. PK/PD substudy visits for participating subjects should be scheduled such 
that the subject’s normal dosing time occurs during the clinical visit, if possible. On these days, 
subjects should be instructed not to take their dose of BCX9930 until they are in clinic and the 
pre-dose PK and PD samples have been collected.  
For subjects participating in the PK/PD substudy, please refer to Table 4 for procedures and 
timings. 
 
The following assessments will be performed: 
• Administration of questionnaires. Where possible, the questionnaire should be 
completed by the subject prior to other assessments: 

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− 
 at Weeks 8, 12, 16, 20, 24, 36, and 52 only (or at the safety FU, if 
applicable) 
− 
 at Weeks 8, 12, 16, 20, 24, 36, and 52 only (or at the safety FU, if 
applicable) 
− 
 at Week 24 Visit for C3G only, Week 36 Visit for IgAN only, and 
Week 52 for PMN only (or at the safety FU, if not previously administered as 
described) 
− 
 at Week 24 Visit for C3G only, Week 36 Visit for IgAN only, and 
Week 52 for PMN only (or at the safety FU, if not previously administered as 
described) 
• 12-lead ECG 
• Vital signs (blood pressure, temperature, and pulse rate) 
• Targeted physical examination (ie, symptom-driven, targeted to new signs and 
symptoms) 
• Weight and BMI (not performed at the Week 1 and Week 2 Visits) 
• Single void urine collection for urinalysis including microscopy, PK and biomarkers 
• A urine pregnancy test for female subjects of childbearing potential 
• Blood collection for clinical chemistry, hematology, coagulation, and PD biomarkers 
• Blood collection for sparse PK plasma sample and documentation of time of sample 
collection, food status and the time of the last two doses of study drug taken 
• Review/capture of concomitant medications and AEs 
• Assessment of the clinical benefit of BCX9930 (at the Week 24 Visit only) 
• Provide collection container with instructions and return of an intended 24-hour urine 
sample  
• Study drug dispensing (via IRT) and accountability, as per Table 2 and Table 3 
A percutaneous needle biopsy of the kidney per local practice and guidelines will be performed 
at Week 24 for subjects with C3G. An optional percutaneous needle biopsy of the kidney can be 
performed at Week 36 for subjects with IgAN or at Week 48-52 for subjects with PMN if a 
subject consents for the optional procedure. The biopsy should be scheduled during the specified 
visit after completion of all other assessments or within the timeframe after the visit as specified 
in Section 12.4.2, but may not be performed prior the specified visit. For subjects with PMN, if 
the biopsy procedure is performed after the Week 52 Visit, the subject will continue dosing until 
the day of the biopsy procedure and study drug return and accountability will occur on the date 
of the biopsy procedure.  
All subjects who sign a separate informed consent will participate in exploratory 
pharmacogenomics testing at a single visit from Day 1 up to the Week 24 Visit (including the 
Safety FU Visit, if applicable). 

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11.3.5. 
Additional Assessments for Renal and Hepatic Safety Monitoring 
Additional assessments to monitor for potential renal and hepatic toxicity will be performed at 
Week 3 (Day 22 ± 1 day), Week 5 (Day 36 ± 3 day), Week 6 (Day 43 ± 3 day), Week 7 (Day 50 
± 3 day), and Week 10 (Day 71 ± 3 day). The assessments may be performed at the investigative 
site, at a local 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 investigative site or assessed at non-investigative site. 
For subjects assessed at the investigative site: 
• Review/record AEs, concomitant medication use 
• Vital signs (blood pressure, temperature, and pulse rate) 
• Blood collection for clinical laboratory evaluations: 
− Clinical chemistry 
• Blood collection for PK 
• Urine collection for clinical laboratory evaluations: 
− Urinalysis including microscopy 
− Urine for biomarker testing 
• Urine collection for PK 
The above assessments will also be performed for subjects identified with potential renal 
or hepatic events who are required to return to the investigative site (Section 13.5). 
For subjects assessed at non-investigative sites: 
• Blood collection for clinical laboratory evaluations: 
− Clinical chemistry (to include at a minimum: sCr, eGFR, blood urea nitrogen 
[BUN], 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 have completed through at least the first 
8 weeks of monitoring across the BCX9930 program. 

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• Blood collection 
It is preferred that the patient-reported outcomes (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.  
12.2. 
Demographic/Medical History 
Demographic information and medical and medication history will be captured for each subject 
participating in the study at the Screening Visit. Medical history, medication review, and review 
of inclusion and exclusion criteria, potentially nephrotoxic medications, and prohibited 
medications will also be updated and rechecked at baseline (Day 1) as outlined in Section 11.3.3. 
A Disease Specific Medical History Form including baseline C3G, IgAN, or PMN clinical 
characteristics and disease burden including prior genetic screening for complement-related 
mutations, nephritic factors, or other disease characteristics, clinical labs (eg, serum creatinine), 
and copies of pathology reports with WSIs (if available) will be captured during screening. 
Medication history will include details of C3G, IgAN, or PMN treatments administered 
(including plasma exchange therapy and other investigational product). 
12.2.1. 
Vaccination Requirements 
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. 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 (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 requirements prior to completing the Day 1 
visit. Appropriate antibiotics for prophylaxis may be given during the study in accordance with 
local standard of care and any relevant vaccination guidance (see Section 9.1). 
Unless local guidelines are more stringent, the Advisory Committee on Immunization Practices 
(ACIP) recommendations for meningococcal vaccination and ACIP guidance for altered 
immunocompetence (including complement inhibition therapy) should be followed (Mbaeyi, 
Pondo et al. 2020). 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, Pondo et al. 2020). 
S. pneumoniae vaccination is also required; vaccination with both conjugate and polysaccharide 
vaccines is preferred. 

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Vaccination or a booster vaccine against Hib is strongly encouraged for all study participants 
where authorized and available. 
Investigators should review each subject’s vaccination status at periodic intervals 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 patient receives a SARS-CoV-2 vaccination, this should be captured as a prior or 
concomitant medication entry. Vaccinations that require more than one inoculation should have a 
separate prior or concomitant medication entry for each injection. 
If patient experiences any AEs related to SARS-CoV-2 vaccination, or any AE in temporal 
relation to the vaccination, these should be entered on the adverse events page. 
If a live vaccine needs to be given during the study, including after screening visit, please contact 
the sponsor medical monitor or designee. 
12.3. 
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 if an exposure occurs. 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. 
12.4. 
Efficacy/Effectiveness Assessments 
12.4.1. 
Intended 24-hour Urine Collection 
An intended 24-hour urine collection will be required prior to each clinic visit except for the 
initial Screening Visit. All subjects will receive a container and patient instructions for the 
collection and return of an intended 24-hour urine sample that will be initiated out of the clinic. 
After completion of the intended 24-hour collection, the sample will be returned to the clinic. A 
phone call to remind subjects to complete the intended 24-hour collection will be conducted 
within a week prior to the scheduled visit. Urine samples are intended to be collected over a 
24-hour period and intended 24-hour samples will be accepted even if there are reports of 
missing a single void collection. 
An aliquot from 24-hour urine collections may be reserved for analysis of the urine concentration 
of BCX9930 and metabolites. 
12.4.2. 
Percutaneous Needle Biopsy of the Kidney 
After confirmation that all other study eligibility criteria are met during screening per local 
practice and guidelines: 
• Subjects will undergo a percutaneous needle biopsy of the kidney during screening  

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Note: The screening biopsy procedure may be waived with approval of the central 
pathologist and agreement with the medical monitor for any subject who has 
undergone a renal biopsy procedure within 3 months prior to initiating screening with 
C3G, and within 6 months prior to initiating screening with IgAN or PMN, provided 
that required materials are adequate for pathology evaluation per protocol procedures 
An on-treatment, percutaneous needle biopsy of the kidney will be performed at the following 
visit after completion of all other assessments, or during the specified times below by treatment 
cohort: 
• 
Week 24 or within 7 days after the visit for subjects with C3G 
• 
Week 36 or within 7 days after the visit for subjects with IgAN (optional) 
• 
Week 48 to within 3 days after the Week 52 Visit for subjects with PMN (optional) 
The on-treatment biopsy is required for subjects with C3G but is optional for subjects with IgAN 
or PMN. For subjects with PMN, if the biopsy is scheduled after the Week 52 Visit, then dosing 
with BCX9930 will continue until the day of the procedure. Protocol-specified, on-treatment 
biopsies will not be required for subjects who are discontinued from BCX9930 treatment.  
12.4.2.1. Central Pathologist 
A pathology manual of procedures will be provided to sites with study-specific methods 
regarding specimen processing, scanning, capture of morphologic/morphometric features, 
computer assessment, and data collection. Each investigator should review the pathology manual 
of procedures with an experienced, on-site renal pathologist. 
Renal biopsy samples will be processed locally according to the pathology manual. Images 
(WSIs of the light microscopy, digital IFs or IHCs, and digital EMs), and details from the local 
pathology report will be reviewed by the central pathologist for confirmation of a protocol 
defined diagnosis of C3G, IgAN, or PMN based on the following inclusion criteria:  
• C3G: a sole or dominant glomerular IF or IHC staining for C3 of at least two orders 
of magnitude greater intensity than for any other immunoreactant (D'Agati and 
Bomback 2012).  
Evidence of disease activity as follows: 
− C3GN with at least 25% of glomeruli with at least segmental mesangial and 
segmental endocapillary hypercellularity. 
−  DDD with at least 2 of the following 3:  
- at least 25% of glomeruli with segmental mesangial hypercellularity 
- at least 25% of glomeruli with segmental endocapillary hypercellularity 
- at least one active crescent 
A minimum of 4 patent glomeruli between the light microscopy and EM thick section 
WSIs is required. At least one patent glomerulus is required for IF or IHC digital 
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• IgAN: IF or IHC staining for IgA and C3, with dominant IgA compared to other 
Igs/immunocomplexes. Disease activity required with M1 and E1 and/or C1, 
including active crescents and/or necrosis as per Oxford IgA scoring (Haas, Verhave 
et al. 2017, Trimarchi, Barratt et al. 2017). A minimum of 8 patent glomeruli between 
the light microscopy and EM thick section WSIs is required. At least one patent 
glomerulus is required for IF or IHC digital images.  
• PMN: IF or IHC capillary wall granular staining for IgG and C3 with at least 50% of 
the deposits being active Ehrenreich and Churg stage I and/or II by EM; stage III 
deposits are allowed (Ehrenreich and Churg 1968). Active crescents ≤ 10% are 
allowed. A minimum of 6 patent glomeruli between the light microscopy and EM 
thick section WSIs is required. At least one patent glomerulus is required for IF or 
IHC digital images.   
• All: Images for LM, IF or IHC, and EM are of sufficient quality to allow for 
interpretation and diagnosis 
• All: ≤ 50% global glomerulosclerosis 
• All: ≤ 50% tubulointerstitial fibrosis 
• C3G and IgAN: ≤ 50% active crescents 
The WSIs of LMs, digital IFs or IHCs, digital EMs, and report findings for study eligibility will 
also serve as the pre-treatment baseline for change from baseline comparisons to the on-
treatment biopsies by the central pathologist. In addition, unstained EM grids will be shipped 
from sites to the central pathologist for additional baseline EM assessments and reporting if a 
biopsy is performed during the screening period. For a biopsy performed prior to the screening, 
unstained EM grids may be shipped to the central pathologist if available. 
If other biopsies not specified per protocol are performed during the study, the available images 
(WSIs of the light microscopy, digital IFs or IHCs, and digital EMs) and details from the local 
pathology report will be reviewed by the central pathologist, if available. 
12.4.3. 
  
For the PMN cohort only, 
 will be measured at Screening, Baseline, and 
every 4 weeks until Week 52.   
12.5. 
Patient-reported Outcomes 
The following PRO instruments will be used during this study: 
• 
)  
• 
  
• 
  
• 
 
Each questionnaire will be translated into the local language, as required. For all 
subject-completed forms, clinic staff should ensure the subject reads the instructions and 

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12.11.3. 
Physical Examination 
Subjects will undergo a physical examination according to the schedule of assessments. (Table 2 
and Table 3). 
A full physical examination should be conducted at the Screening Visit and at the Baseline Visit 
(Day 1). All subsequent physical examinations may be targeted (ie, symptom driven) to include, 
at a minimum, evaluation of any new signs or symptoms or infection risk (eg, vaccination 
status). Genitourinary and breast examinations may be omitted when not required by normal site 
practice.  
12.11.4. 
Electrocardiogram 
Electrocardiograms will be obtained per the schedule of assessments as specified in Table 2 and 
Table 3. 
A standard bedside 12-lead ECG machine system that calculates heart rate and measures the PR, 
QRS, QT, RR, and corrected QT (QTcF) intervals will be used. Twelve-lead ECGs will be 
measured after the subject has been in the supine position for a minimum of 5 minutes according 
to Section 11 and the schedule of assessments. All ECGs will be single assessments, with the 
exception of the Day 1 Visit ECG, which will be recorded in triplicate.  
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 change from baseline in QTcF > 60 msec or a QTcF interval 
> 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 
ECGs may be requested by the sponsor. 
12.11.5. 
Clinical Chemistry, Hematology, Urinalysis, and Other Laboratory Assessments 
Blood and urine samples will be obtained per the schedule of assessments as specified in Table 2 
and Table 3. Individual laboratory tests are provided in Table 5.  
In general, laboratory samples collected at visits to the investigative site should be collected 
using kit supplies provided by the 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). The additional renal and hepatic safety assessments may be performed 
at the investigative site or at a local laboratory more convenient for the subject or via a home 
health service. The results from laboratory testing performed at a local laboratory 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. 

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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 findings, the interpretation of 
clinically significant or not clinically significant should be denoted in the source records. 
Clinically significant laboratory findings in the opinion of the investigator should be recorded as 
AEs and handled as described in the protocol (Section 13).  
Table 6: 
Clinical Laboratory Evaluations 
Chemistry 
Coagulation 
• 
Albumin 
• 
Alkaline phosphatase (ALP) 
• 
Alanine aminotransferase (ALT) 
• 
Aspartate aminotransferase (AST) 
• 
Bilirubin (total and direct) 
• 
Blood glucose  
• 
Blood urea nitrogen (BUN) 
• 
Bicarbonate 
• 
Calcium 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Creatine kinase 
• 
Serum creatinine (SCr) and calculated estimated 
glomerular filtration rate (eGFR) 
• 
Serum cystatin C (Scys) 
• 
Lactate dehydrogenase (LDH) 
• 
Total serum protein 
• 
Uric acid 
• 
Amylase 
• 
C-reactive protein 
• 
Lipase (reflex test if amylase elevated) 
• 
Cholesterol, total 
• 
Cholesterol, high-density lipoprotein (HDL) 
• 
Cholesterol, low-density lipoprotein (LDL) 
• 
Triglycerides 
• Prothrombin time (PT) and international 
normalized ratio (INR) 
• Activated partial thromboplastin time (aPTT) 
• Thrombin time 
Pregnancy Test 
• Serum (screening) and urine (other scheduled 
visits) beta human chorionic gonadotropin 
(β-hCG) for women of childbearing potential 
only  
• Follicle-stimulating hormone (FSH) for women 
with no menses for ≥ 12 months and ≤ 2 years 
Hematology 
• Hemoglobin 
• Hematocrit 
• Erythrocyte count 
• Mean corpuscular hemoglobin (MCH) 
• Mean corpuscular hemoglobin concentration 
(MCHC) 
• Mean corpuscular volume (MCV) 
• White blood cell count, with differential 
(lymphocytes, monocytes, neutrophils, 
eosinophils, and basophils) 
• Platelet count 
Urinalysis  
• 
Specific gravity 
• 
Blood 
• 
Bilirubin 
• 
Glucose 
• 
Leukocytes 
• 
Ketones 
• 
Nitrites 
• 
pH  
• 
Protein 
Other 
• 
Hepatitis B virus (HBV) surface 
antigen (HbsAg) 
• 
Hepatitis B Core antibody (positive 
test will reflex to HBV 
deoxyribonucleic acid [DNA] viral 
load assay) 

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• 
Urobilinogen 
• 
Creatinine 
• 
Albumin 
• 
Cystatin C 
• 
 
 
• 
α1-microglobulin 
• 
β2-microglobulin 
• 
 
 
 
• 
 
• 
Protein to creatinine ratio 
• 
Albumin to creatinine ratio 
• 
  
• 
α1-microglobulin to creatinine ratio 
• 
β2-microglobulin to creatinine ratio 
• 
 
 
 
• 
Microscopic evaluation (where capabilities exist) 
• 
 
• 
Hepatitis C virus (HCV) antibody 
(HCVAb) 
o If HCVAb positive, reflex to 
HCV ribonucleic acid (RNA) 
testing 
• 
Human immunodeficiency virus (HIV) 
antibody 
• 
Varicella-zoster immunoglobulin G 
(IgG) titer 
• 
Plasma pharmacokinetics (PK) 
• 
Serum pharmacodynamics (PD) 
• 
Urine PK (PK/PD substudy only) 
• 
Urine PD 
• 
 
 
 
 
 
 
Urine drug screen 
• 
Amphetamines 
• 
Methamphetamine 
• 
Ecstasy 
• 
Barbiturates 
• 
Benzodiazepines 
• 
Opiates 
 
 
12.11.5.1. Urine Collections for Urinalysis, Microscopy, and Biomarker Testing 
Investigators should emphasize to staff and 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 investigative 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 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. 
12.11.5.2. Calculations for estimating Glomerular Filtration Rate 
eGFR will be calculated by the CKD-EPI equation (Levey and Stevens 2010) (SCr method), in 
units of mL/min/1.73 m2, presented below: 

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eGFR (mL/min/1.73 m2) =141 × [min (SCr/κ,1)]α × [max (SCr/κ,1)] -1.209 × (0.993)Age in years 
× (1.018 if female) × (1.159 if African Ethnic Heritage) 
Where: 
• κ = 0.7 for females and 0.9 for males 
• α = −0.329 for females and −0.411 for males 
• min (SCr/κ,1) indicates the minimum of SCr/κ or 1 
• max (SCr/κ,1) indicates the maximum of SCr/κ or 1 
Additional equations and analytes, such as cystatin C, may be used to calculate eGFR for 
purposes of sensitivity analyses. 
12.11.6. 
Menopause and Pregnancy Testing 
Follicle-stimulating hormone (FSH) will be measured at screening in women declaring 
themselves postmenopausal for ≥ 12 months and ≤2 years to confirm nonchildbearing status. 
FSH measurement is not needed at screening to confirm postmenopausal state in women who 
report no menses for > 2 years. 
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 2 and Table 3. 
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. 
13. 
ADVERSE EVENTS 
AEs will be assessed and recorded from the time of signing of the informed consent through the 
appropriate follow-up period.  
13.1. 
Definitions  
13.1.1. 
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 

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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. 
This includes the following: 
• AEs not previously observed in the subject that emerge during the protocol-specified 
AE reporting period (see Section 13.4). 
• 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 preexisting 
condition has changed by including applicable descriptors (eg, “more frequent 
headaches”).  
Symptoms or abnormalities related to the underlying disease (C3G, IgAN, and PMN), such as 
worsening of kidney laboratory parameters, are considered disease progression and are not to be 
recorded as AEs unless the event is an SAE or related to treatment with BCX9930 or related to 
some other cause (eg, concomitant treatment/procedure).  
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.” Serious Adverse Events (SAEs) are described 
in Section 13.1.3. 
Hospitalization scenarios do not require reporting as a 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 preexisting 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 preexisting 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. 
13.1.2. 
Adverse Reaction 
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 

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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.  
13.1.3. 
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 a SAE 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 13.4.2). 
Some hospitalization scenarios, as outlined in Section 13.1.1, 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 13.5.2). 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. 
13.1.4. 
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 are:  
• potential drug-induced liver injury  

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suspecting a possible cause-and-effect relationship between the investigational product 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. 
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 AE/SAE and the investigational product is determined to be 
“possible,” “probable,” or “definite,” the event will be considered to be related to the 
investigational product for the purposes of expedited regulatory reporting (as applicable per 
country-specific regulatory requirements). 
The sponsor may upgrade causality if deemed appropriate. 
13.4. 
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 informed consent through to the last study visit (ie, through the 
post-treatment follow-up visit[s]). All AEs and SAEs are to be reported on the AE eCRF.  
AEs should be entered in 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 
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 13.2 for AE grading). For all Grade 3 and 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 regard 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 onto the AE and SAE eCRFs. The SAE eCRF is an additional form to the AE 

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eCRF that provides important details on the SAE. The investigator should follow all unresolved 
SAEs observed during the study until they are resolved, 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 
necessary information to continuously assess the benefit-risk profile of the study drug in clinical 
studies. 
13.4.1. 
Serious Adverse Events and Suspected Unexpected Serious Adverse Reactions 
All SAEs must be reported immediately and no later than 24 hours of investigator awareness to 
the sponsor medical monitor via the AE and SAE eCRFs. Investigators should adhere to their 
country or region requirements for the reporting timeframe, which may not allow any delay. 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.  
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 below recipients. As soon as the eCRF system is functioning, that particular SAE must be 
entered into the SAE eCRF. All follow-up information on the SAE should be reported via the 
SAE eCRF. The eCRF system automatically sends SAE notifications to the following email 
address: 
Email: safety@biocryst.com 
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. 
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 their 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 IECs/IRBs 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 IECs/IRBs, 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 

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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. 
13.4.2. 
Pregnancy 
Any female subject who becomes pregnant during the course of the study should have study 
drug/IMP 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 13.1.3. 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. 
13.5. 
Adverse Event Management 
The investigator (or qualified designee) will grade clinically significant events and laboratory 
abnormalities (if considered AEs) as detailed in Section 13.2. Grade 3 and 4 clinically significant 
laboratory abnormalities should be confirmed by repeat testing and before any contemplated 
study drug discontinuation, unless such a delay is not consistent with good medical practice. 
13.5.1. 
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 potential drug-induced liver injury (pDILI) meeting this ALT elevation must be 
assessed to determine whether study drug must be withheld or discontinued per Sections 7.4.1. 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, considering the benefit: risk of discontinuing 
BCX9930: 
• ALT or AST > 8 × ULN 
• ALT or AST > 5 × ULN for more than 2 weeks 

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≥ 30 mL/min/1.73 m2 based on an acceptable renal safety profile of BCX9930. Enrollment under 
existing inclusion for subjects with an eGFR ≥ 50 mL/min/1.73 m2 will not be paused during this 
DMC review. 
In the event that a new clinically significant safety signal emerges, a meeting of the DMC may 
be convened by the sponsor to evaluate risk to subjects and recommend appropriate actions. 
Based on the data presented, a decision will be made as to whether to halt the study, to continue 
dosing, or to continue dosing with provisions introduced into the protocol via substantial 
amendment. 
The specific responsibilities and composition of the DMC are outlined in a separate DMC 
charter.  
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. 
14. 
STATISTICS 
14.1. 
Hypotheses 
This is a POC study to estimate the therapeutic potential of BCX9930 administered in subjects 
with C3G, IgAN, or PMN. Post-baseline measurements will be assessed against their applicable 
baseline measurements. 
14.2. 
Sample Size Considerations 
No formal power or sample size calculations are planned to determine the sample size for each 
cohort. The proposed sample size of approximately 14 subjects per cohort should provide an 
estimate of uPCR reduction up to 52 weeks to estimate the safety and therapeutic potential for 
BCX9930 in these renal indications and inform sample sizes for future studies of BCX9930. 
Several recent Phase 2 studies that evaluated investigational products with similar or identical 
mechanisms of action as BCX9930 enrolled 5 to 7 subjects with C3G per study and reported 
reductions in proteinuria after treatment durations ranging from 2 to 48 weeks (unpublished 
data).  
No sample size re-estimations are planned. 
14.3. 
Stratification 
No stratifications are planned. 
14.4. 
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). A 
summary of the methods for interim analyses based on ongoing review of individual subject 

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safety and preliminary efficacy data for each treatment cohort, if conducted, will be provided in 
the SAP. 
14.4.1. 
Analysis Populations 
The analysis populations are defined below.  
14.4.1.1. Full Analysis Set Population 
The Full Analysis Set (FAS) population is defined as all subjects who receive at least one dose of 
study drug. The FAS population will be used as the primary population for demographics, 
baseline characteristics, safety, and efficacy analyses. 
14.4.1.2. Pharmacokinetic Population 
The PK population will include all FAS population subjects for whom PK concentration data are 
available.  
14.4.1.3. Pharmacokinetic Substudy Population 
The PK substudy population will include all FAS population subjects for whom serial PK 
concentration data are available and PK parameters can be estimated. 
14.4.1.4. Pharmacodynamic Population 
The PD population will include all FAS population subjects for whom at least 1 pre-dose and at 
least 1 post-dose PD/biomarker measurement can be obtained. This population will be used for 
all PD/biomarker analyses. 
14.4.2. 
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 percentage for categorical variables. 
Summaries will be presented by treatment cohort and, where appropriate, by visit or pooled 
across the treatment cohorts. 
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). 
14.4.3. 
Subject Demographic and Disposition Data 
Demographic data and baseline characteristics including age, sex, race or ethnicity, height, 
weight, and BMI will be summarized by treatment cohort and overall. 
Subject disposition will be presented by treatment cohort 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 also 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 cohort 
and overall. Treatment adherence, dose interruptions, and reasons for dose interruptions will be 
provided as summaries or listed as appropriate. 

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14.4.4. 
Analysis of Efficacy Variables 
The efficacy analyses will be based on the FAS population. Efficacy data will be summarized by 
treatment cohort and study visit.  
For continuous variables, descriptive summaries (for the recorded value, change from baseline, 
and percentage change from baseline) will be presented by study visit and treatment cohort. For 
specific parameters of interest, point estimates for the changes and percent changes from baseline 
will be summarized along with their 80% CIs, 95% CIs and p-values using the one-sample t-test.  
For binary endpoints (eg, uPCR response), summaries will be presented as counts and 
frequencies by post-baseline visit and treatment cohort. Corresponding confidence intervals 
(80% and 95%) will be provided for specific parameters of interest using the Clopper-Pearson 
Exact method.  
Categorical data will be summarized by study visit and treatment cohort using counts and 
percentages or descriptively (depending on the number of categories and whether the categories 
are nominal or ordered). Details will be provided in the SAP. 
Plots of individual efficacy assessments over time with an overlay of the group mean will be 
provided by treatment cohort. Results will be presented by parameter, with all time points 
reported.  
14.4.5. 
Analysis of Safety Variables 
The safety analyses will be analyzed by treatment cohort and overall. 
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 Grade 3 or 4 AE; and 5) who experience a 
treatment-emergent Grade 3 or 4 laboratory abnormality. In addition, the proportion of subjects 
with a treatment-emergent, treatment-related AE consistent with a drug rash will also be 
summarized. 
Adverse events will be mapped to a Medical Dictionary for Regulatory Activities (MedDRA) 
preferred term and system organ class (SOC). The occurrence of treatment-emergent AEs will be 
summarized using MedDRA preferred terms, SOCs, and severity. Separate summaries of 
TEAEs, TESAEs, 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.  
Descriptive summaries (actual and change from baseline) of vital signs, weight, bedside ECG 
parameters, and clinical laboratory results will be presented. Laboratory and ECG abnormalities 
will be graded according to CTCAE (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 assessment will be 
summarized.  
Clinically significant abnormal morphological ECG findings will be summarized.  

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The change from baseline in QTcF will be determined by ECGs. At each time point ECGs are 
analyzed, an individual subject’s change from baseline will be calculated as: 
∆ik= (QTcF for subject at time point k – baseline QTcF) 
Where QTcF measurements will be the average of triplicate ECGs at baseline, and single values 
at each time point.  
For routine ECGs, the number and proportion of subjects with QTcF ≤ 450, > 450 to ≤ 480, 
> 480 to ≤ 500, and > 500 msec; or changes of ≤ 30, > 30 to ≤60, or > 60 msec will be 
summarized.  
Physical examination findings will be listed.  
Concomitant medications will be coded using the World Health Organization drug dictionary 
and summarized.   
As applicable, safety data will be summarized by treatment cohort and overall. 
No formal tests of hypothesis are planned for safety data. 
14.4.6. 
Patient-reported Outcomes 
Patient-reported outcomes (
 will be summarized 
descriptively (actual and change from baseline, as applicable) by study visit and treatment 
cohort. 
14.4.7. 
Pharmacokinetic Analyses 
Sparse plasma and spot urine samples will be collected for analysis of BCX9930 and metabolite 
concentrations as described in Table 2 and Table 3.  
Sparse plasma and urine PK data will be listed. 
Subjects enrolled in the PK/PD substudy will have plasma and urine samples collected as 
described in Table 4. Plasma concentration data will be summarized by visit (first dose vs. steady 
state) and nominal timepoint. Urine concentration data will be summarized by visit and void 
(first or second void within the sample collection period).  
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 PK data analyses for this study will be included in a specific analysis plan. 
14.4.8. 
Pharmacodynamic and Biomarker Analyses 
Descriptive summaries (actual, change from baseline, and percentage change from baseline) will 
be presented by parameter, time point, and treatment cohort (and overall) for each PD parameter. 
Point estimates and 95% CIs will be presented for change from baseline and percentage change 
from baseline by parameter, post-baseline study visit, and treatment cohort. 
Plots of individual and mean PD assessments and biomarkers over time will be provided by 
treatment cohort. 

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PD data may be analyzed in combination with data from other studies as appropriate (which may 
include model-based analyses of population PK and/or PK/PD). These analyses will be reported 
separately from the CSR. 
15. 
STUDY ADMINISTRATION 
15.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of BioCryst 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 representatives. 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 monitors will review 
source documents to confirm that the data recorded on eCRFs are accurate. The investigator and 
institution will allow BioCryst representatives, monitors, or its designees direct access to source 
documents to perform this verification. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and that sufficient time is devoted to the process. 
During the study, a monitor from BioCryst or representative 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. 
• Confirm AEs and SAEs have been properly documented on the eCRFs and confirm any 
SAEs have been forwarded to BioCryst and those SAEs that met criteria for reporting 
have been forwarded to the IEC/IRB. 
The representative(s) of BioCryst or its designee will be available between visits if the 
investigator(s) or other staff needs information or advice. 

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15.2. 
Audits and Inspections 
Authorized representatives of BioCryst, US FDA and other regulatory authorities, and/or ethics 
committees 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 will permit study-related audits mandated by the sponsor, after reasonable notice, 
and inspection by domestic or foreign regulatory authorities. 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. 
15.3. 
Ethics Committee  
Ethics approval for the investigation must be obtained prior to commencing the study. 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. 
15.4. 
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. 
16. 
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 15.1. 
To ensure compliance with GCP and all applicable regulatory requirements, BioCryst or its 
designee may conduct a quality assurance audit. Please see Section 15.2 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. 
17. 
ETHICS 
17.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an ethic committee, as appropriate. For the purposes of this 
protocol, “ethics committee” describes the applicable governing IRB, REB, or IEC. The 

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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 all 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. 
17.2. 
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. 
17.3. 
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, as per local practice. 
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. 

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18. 
DATA HANDLING AND RECORDKEEPING 
18.1. 
Inspection of Records 
BioCryst 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. 
18.2. 
Retention of Records 
The investigator will maintain adequate records for the study, including the identity of all 
participating subjects (sufficient information to link records, eCRFs, and medical/hospital 
records), all original signed ICFs, all original signed assents (if applicable), all eCRFs, drug 
dispensing and disposition records, safety reports, information regarding participants who 
discontinued and other pertinent data.  
All essential documents should be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirement(s) or be an agreement with BioCryst. 
It is the responsibility of BioCryst to inform the investigator/institution as to when these 
documents no longer need to be retained. It is the investigator’s responsibility to notify BioCryst 
if they relocate or retire so that document storage can be addressed. 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. 
18.3. 
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 
(GPDR) in the European Union, 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 

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waiver/authorization in writing from the appropriate individual. HIPAA authorizations are 
required for US sites only. 
19. 
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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20. 
LIST OF REFERENCES  
Alexion Pharmaceuticals, I. (2020). Soliris (eculizumab) injection for intravenous use US 
Prescribing Information, Alexion Pharmaceuticals, Inc. 
Alexion Pharmaceuticals, I. (2021). Ultomiris (ravulizuma-cwvz) injection, for intravenous use 
US prescribing information, Alexion Pharmaceuticals, Inc. 
Barbour, T. D., M. M. Ruseva and M. C. Pickering (2016). "Update on C3 glomerulopathy." 
Nephrol Dial Transplant 31(5): 717-725. 
Barratt, J. and J. Feehally (2005). "IgA nephropathy." J Am Soc Nephrol 16(7): 2088-2097. 
Bomback, A. S., R. J. Smith, G. R. Barile, Y. Zhang, E. C. Heher, L. Herlitz, M. B. Stokes, G. S. 
Markowitz, V. D. D'Agati, P. A. Canetta, J. Radhakrishnan and G. B. Appel (2012). 
"Eculizumab for dense deposit disease and C3 glomerulonephritis." Clin J Am Soc Nephrol 7(5): 
748-756. 
Brodsky, R. A. (2014). "Paroxysmal nocturnal hemoglobinuria." Blood 124(18): 2804-2811. 
Caravaca-Fontán, F., M. M. Díaz-Encarnación, L. Lucientes, T. Cavero, V. Cabello, G. Ariceta, 
L. F. Quintana, H. Marco, X. Barros, N. Ramos, N. Rodríguez-Mendiola, S. Cruz, G. Fernández-
Juárez, A. Rodríguez, A. Pérez de José, C. Rabasco, R. Rodado, L. Fernández, V. Pérez Gómez, 
A. I. Ávila, L. Bravo, J. Lumbreras, N. Allende, M. D. Sanchez de la Nieta, E. Rodríguez, T. 
Olea, M. Melgosa, A. Huerta, R. Miquel, C. Mon, G. Fraga, A. de Lorenzo, J. Draibe, M. Cano-
Megías, F. González, A. Shabaka, M. E. López-Rubio, M. Fenollosa, L. Martín-Penagos, I. Da 
Silva, J. Alonso Titos, S. Rodríguez de Córdoba, E. Goicoechea de Jorge and M. Praga (2020). 
"Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease." Clin J 
Am Soc Nephrol 15(9): 1287-1298. 
Caravaca-Fontán, F., L. Lucientes, T. Cavero and M. Praga (2020). "Update on C3 
Glomerulopathy: A Complement-Mediated Disease." Nephron 144(6): 272-280. 
Couser, W. G. (2017). "Primary Membranous Nephropathy." Clin J Am Soc Nephrol 12(6): 983-
997. 
D'Agati, V. D. and A. S. Bomback (2012). "C3 glomerulopathy: what's in a name?" Kidney Int 
82(4): 379-381. 
Ehrenreich, T. and J. Churg (1968). Pathology of membranous nephropathy. Pathology Annual. 
S. SC. New York, Appleton-Century-Crofts. 3: 145-154. 
Ekdahl, K. N., C. Mohlin, A. Adler, A. Aman, V. A. Manivel, K. Sandholm, M. Huber-Lang, K. 
Fromell and B. Nilsson (2019). "Is generation of C3(H2O) necessary for activation of the 
alternative pathway in real life?" Mol Immunol 114: 353-361. 
Figueroa, J. E. and P. Densen (1991). "Infectious diseases associated with complement 
deficiencies." Clin Microbiol Rev 4(3): 359-395. 
Floege, J., S. J. Barbour, D. C. Cattran, J. J. Hogan, P. H. Nachman, S. C. W. Tang, J. F. M. 
Wetzels, M. Cheung, D. C. Wheeler, W. C. Winkelmayer, B. H. Rovin and P. Conference 
(2019). "Management and treatment of glomerular diseases (part 1): conclusions from a Kidney 
Disease: Improving Global Outcomes (KDIGO) Controversies Conference." Kidney Int 95(2): 
268-280. 

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Gutierrez, E., F. Carvaca-Fontan, L. Luzardo, E. Morales, M. Alonso and M. Praga (2020). "A 
Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges." Nephron 
144(11): 555-571. 
Haas, M., J. C. Verhave, Z. H. Liu, C. E. Alpers, J. Barratt, J. U. Becker, D. Cattran, H. T. Cook, 
R. Coppo, J. Feehally, A. Pani, A. Perkowska-Ptasinska, I. S. Roberts, M. F. Soares, H. 
Trimarchi, S. Wang, Y. Yuzawa, H. Zhang, S. Troyanov and R. Katafuchi (2017). "A 
Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy." J Am Soc Nephrol 
28(2): 691-701. 
Hillmen, P., N. S. Young, J. Schubert, R. A. Brodsky, G. Socie, P. Muus, A. Roth, J. Szer, M. O. 
Elebute, R. Nakamura, P. Browne, A. M. Risitano, A. Hill, H. Schrezenmeier, C. L. Fu, J. 
Maciejewski, S. A. Rollins, C. F. Mojcik, R. P. Rother and L. Luzzatto (2006). "The complement 
inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria." N Engl J Med 355(12): 1233-
1243. 
Holers, V. M. (2008). "The spectrum of complement alternative pathway-mediated diseases." 
Immunol Rev 223: 300-316. 
Jarrick, S., S. Lundberg, A. Welander, J. J. Carrero, J. Hoijer, M. Bottai and J. F. Ludvigsson 
(2019). "Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study." J Am 
Soc Nephrol 30(5): 866-876. 
Koirala, A. and J. A. Jefferson (2020). "How Safe Is a Native Kidney Biopsy?" Clin J Am Soc 
Nephrol 15(11): 1541-1542. 
Lesavre, P. H. and H. J. Muller-Eberhard (1978). "Mechanism of action of factor D of the 
alternative complement pathway." J Exp Med 148(6): 1498-1509. 
Levey, A. S. and L. A. Stevens (2010). "Estimating GFR using the CKD Epidemiology 
Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD 
prevalence estimates, and better risk predictions." Am J Kidney Dis 55(4): 622-627. 
Mbaeyi, S., T. Pondo, A. Blain, D. Yankey, C. Potts, A. Cohn, S. Hariri, N. Shang and J. R. 
MacNeil (2020). "Incidence of Meningococcal Disease Before and After Implementation of 
Quadrivalent Meningococcal Conjugate Vaccine in the United States." JAMA Pediatr 174(9): 
843-851. 
McGrogan, A., C. F. Franssen and C. S. de Vries (2011). "The incidence of primary 
glomerulonephritis worldwide: a systematic review of the literature." Nephrol Dial Transplant 
26(2): 414-430. 
Nair, R. and P. D. Walker (2006). "Is IgA nephropathy the commonest primary glomerulopathy 
among young adults in the USA?" Kidney Int 69(8): 1455-1458. 
Pascual, M., G. Steiger, J. Estreicher, K. Macon, J. E. Volanakis and J. A. Schifferli (1988). 
"Metabolism of complement factor D in renal failure." Kidney Int 34(4): 529-536. 
Pickering, M. C., V. D. D'Agati, C. M. Nester, R. J. Smith, M. Haas, G. B. Appel, C. E. Alpers, 
I. M. Bajema, C. Bedrosian, M. Braun, M. Doyle, F. Fakhouri, F. C. Fervenza, A. B. Fogo, V. 
Fremeaux-Bacchi, D. P. Gale, E. Goicoechea de Jorge, G. Griffin, C. L. Harris, V. M. Holers, S. 
Johnson, P. J. Lavin, N. Medjeral-Thomas, B. Paul Morgan, C. C. Nast, L. H. Noel, D. K. Peters, 
S. Rodriguez de Cordoba, A. Servais, S. Sethi, W. C. Song, P. Tamburini, J. M. Thurman, M. 

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Zavros and H. T. Cook (2013). "C3 glomerulopathy: consensus report." Kidney Int 84(6): 1079-
1089. 
Ram, S., L. A. Lewis and P. A. Rice (2010). "Infections of people with complement deficiencies 
and patients who have undergone splenectomy." Clin Microbiol Rev 23(4): 740-780. 
Ricklin, D., E. S. Reis and J. D. Lambris (2016). "Complement in disease: a defence system 
turning offensive." Nat Rev Nephrol 12(7): 383-401. 
Rodrigues, J. C., M. Haas and H. N. Reich (2017). "IgA Nephropathy." Clin J Am Soc Nephrol 
12(4): 677-686. 
Schrezenmeier, E. V., J. Barasch, K. Budde, T. Westhoff and K. M. Schmidt-Ott (2017). 
"Biomarkers in acute kidney injury - pathophysiological basis and clinical performance." Acta 
Physiol (Oxf) 219(3): 554-572. 
Smith, R. J. H., G. B. Appel, A. M. Blom, H. T. Cook, V. D. D'Agati, F. Fakhouri, V. Fremeaux-
Bacchi, M. Jozsi, D. Kavanagh, J. D. Lambris, M. Noris, M. C. Pickering, G. Remuzzi, S. R. de 
Cordoba, S. Sethi, J. Van der Vlag, P. F. Zipfel and C. M. Nester (2019). "C3 glomerulopathy - 
understanding a rare complement-driven renal disease." Nat Rev Nephrol 15(3): 129-143. 
Thurman, J. M. and V. M. Holers (2006). "The central role of the alternative complement 
pathway in human disease." J Immunol 176(3): 1305-1310. 
Torreira, E., A. Tortajada, T. Montes, S. Rodriguez de Cordoba and O. Llorca (2009). "3D 
structure of the C3bB complex provides insights into the activation and regulation of the 
complement alternative pathway convertase." Proc Natl Acad Sci U S A 106(3): 882-887. 
Trimarchi, H., J. Barratt, D. C. Cattran, H. T. Cook, R. Coppo, M. Haas, Z. H. Liu, I. S. Roberts, 
Y. Yuzawa, H. Zhang, J. Feehally, I. C. W. G. o. t. I. I. N. Network and T. R. P. S. C. 
Participants (2017). "Oxford Classification of IgA nephropathy 2016: an update from the IgA 
Nephropathy Classification Working Group." Kidney Int 91(5): 1014-1021. 
Volanakis, J. E., S. R. Barnum, M. Giddens and J. H. Galla (1985). "Renal filtration and 
catabolism of complement protein D." N Engl J Med 312(7): 395-399. 
Volanakis, J. E. and S. V. Narayana (1996). "Complement factor D, a novel serine protease." 
Protein Sci 5(4): 553-564. 
White, R. T., D. Damm, N. Hancock, B. S. Rosen, B. B. Lowell, P. Usher, J. S. Flier and B. M. 
Spiegelman (1992). "Human adipsin is identical to complement factor D and is expressed at high 
levels in adipose tissue." J Biol Chem 267(13): 9210-9213. 
Xu, Y., S. V. Narayana and J. E. Volanakis (2001). "Structural biology of the alternative 
pathway convertase." Immunol Rev 180: 123-135. 
Zipfel, P. F., C. Skerka, Q. Chen, T. Wiech, T. Goodship, S. Johnson, V. Fremeaux-Bacchi, C. 
Nester, S. R. de Cordoba, M. Noris, M. Pickering and R. Smith (2015). "The role of complement 
in C3 glomerulopathy." Mol Immunol 67(1): 21-30.