Conditions: Complement 3 Glomerulopathy Immunoglobulin A Nephropathy Membranous Nephropathy
Keywords: BCX9930 factor D inhibitor oral therapy Complement 3 Glomerulopathy Immunoglobulin A Nephropathy Primary Membranous Nephropathy
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 2
Healthy volunteers: no

Brief summary:
The objective of this study was to determine the safety and therapeutic potential of BCX9930 in participants with C3G, IgAN, or PMN.

Detailed description:

Arms:
arm 1: Approximately 14 eligible participants with C3G will be enrolled. arm 2: Approximately 14 eligible participants with IgAN will be enrolled. arm 3: Approximately 14 eligible participants with PMN will be enrolled.

Interventions: intervention 1: BCX9930
Intervention descriptions: intervention 1: Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily

Protocol document:
Prot_000.pdf: 
BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
1 
 
 
CONFIDENTIAL 
 
 
 
 
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. 
 
 




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
3 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
4 
 
 
CONFIDENTIAL 
 
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:  
•
 
 
 
 
 
 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
5 
 
 
CONFIDENTIAL 
 
 
  
 
 
 
 
 
 
 
 
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) 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
6 
 
 
CONFIDENTIAL 
 
• 
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:  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
7 
 
 
CONFIDENTIAL 
 
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.  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
8 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
9 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
10 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
11 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
12 
 
 
CONFIDENTIAL 
 
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 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
13 
 
 
CONFIDENTIAL 
 
 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. 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
14 
 
 
CONFIDENTIAL 
 
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. 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
15 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
16 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
17 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
18 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
19 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
20 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
21 
 
 
CONFIDENTIAL 
 
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 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
22 
 
 
CONFIDENTIAL 
 
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 
 
  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
23 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
24 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
25 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
26 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
27 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
28 
 
 
CONFIDENTIAL 
 
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). 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
29 
 
 
CONFIDENTIAL 
 
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. 








BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
33 
 
 
CONFIDENTIAL 
 
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 








BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
37 
 
 
CONFIDENTIAL 
 
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.  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
38 
 
 
CONFIDENTIAL 
 
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 








BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
42 
 
 
CONFIDENTIAL 
 
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 
Grade 3 or 4 laboratory abnormality 




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
44 
 
 
CONFIDENTIAL 
 
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.  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
45 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
46 
 
 
CONFIDENTIAL 
 
• 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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
47 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
48 
 
 
CONFIDENTIAL 
 
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-


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
49 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
50 
 
 
CONFIDENTIAL 
 
(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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
51 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
52 
 
 
CONFIDENTIAL 
 
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, 




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
54 
 
 
CONFIDENTIAL 
 
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 




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
56 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
57 
 
 
CONFIDENTIAL 
 
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.  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
58 
 
 
CONFIDENTIAL 
 
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. 
   


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
59 
 
 
CONFIDENTIAL 
 
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








BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
63 
 
 
CONFIDENTIAL 
 
 
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






BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
66 
 
 
CONFIDENTIAL 
 
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. 
 
 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
67 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
68 
 
 
CONFIDENTIAL 
 
• 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  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
69 
 
 
CONFIDENTIAL 
 
• 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: 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
70 
 
 
CONFIDENTIAL 
 
− 
 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). 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
71 
 
 
CONFIDENTIAL 
 
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. 




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
73 
 
 
CONFIDENTIAL 
 
• 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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
74 
 
 
CONFIDENTIAL 
 
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  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
75 
 
 
CONFIDENTIAL 
 
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 
images. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
76 
 
 
CONFIDENTIAL 
 
• 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 












BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
82 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
83 
 
 
CONFIDENTIAL 
 
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) 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
84 
 
 
CONFIDENTIAL 
 
• 
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: 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
85 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
86 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
87 
 
 
CONFIDENTIAL 
 
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  




BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
89 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
90 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
91 
 
 
CONFIDENTIAL 
 
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 






BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
94 
 
 
CONFIDENTIAL 
 
≥ 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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
95 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
96 
 
 
CONFIDENTIAL 
 
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.  


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
97 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
98 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
99 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
100 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
101 
 
 
CONFIDENTIAL 
 
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 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
102 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
103 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
104 
 
 
CONFIDENTIAL 
 
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. 


BioCryst Pharmaceuticals, Inc. 
Protocol BCX9930-211 
 
Version 4.0: 04 August 2022 
 
105 
 
 
CONFIDENTIAL 
 
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. 



SAP_001.pdf: 
BioCryst Pharmaceuticals, Inc. 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
14 February 2023 
1
 
 
STATISTICAL ANALYSIS PLAN 
PHASE 2 
VERSION: 1.0 
DATE OF PLAN: 14 February 2023 
BASED ON: 
Protocol Version 4.0: 04 August 2022 
STUDY TITLE: 
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 DRUG: 
BCX9930 
PROTOCOL NUMBER: 
BCX9930- 211 
SPONSOR: 
BioCryst Pharmaceuticals Inc. 
4505 Emperor Boulevard Suite 200 
Durham, North Carolina 27703 USA 
1-(919) 859-1302 
This study is being conducted in compliance with good clinical practice, including the archiving 
of essential documents. 
The information in this document contains proprietary and confidential information belonging to 
BioCryst Pharmaceuticals, Inc. As a result, no part of this document should be copied, referred 
to, released, published, or otherwise disclosed in any manner or media without prior written 
approval from BioCryst Pharmaceuticals, Inc. 
CONFIDENTIAL






BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
4 
 
 
  
 
TECHNICAL SUMMARY REPORT (TSR) 
Name of Sponsor/Company 
BioCryst Pharmaceuticals, 
Inc. 
Individual Study Table 
Referring to Part of the 
Dossier: 
Volume: 
(For National Authority Use 
Only): 
Name of Finished Product: 
BCX9930 
Page: 
 
Name of Active Ingredient: 
 
 
 
 
Title Of Study: 
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 
Lead or Coordinating Investigator: 
 
 
Studied period : 
52 weeks 
Phase of development: 2 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
5 
 
 
  
 
Objectives: 
Primary: 
x To evaluate the therapeutic potential of BCX9930 as assessed by proteinuria  
Secondary: 
x To evaluate the safety and tolerability of BCX9930 
x To evaluate the therapeutic potential of BCX9930 as assessed by other measures of clinical 
benefit 
x To evaluate effects on kidney biopsy morphologic findings (C3G cohort only)  
Exploratory: 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
Methodology: 
This was 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 were to be enrolled into each of three parallel study 
treatment cohorts. Under protocol versions prior to Protocol Version 4.0, subjects were to receive 
BCX9930 500 mg twice daily (BID). Each cohort was to be analyzed separately. Under Protocol 
Version 4.0, subjects were to 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. 
Note: BioCryst stopped development of BCX9930 in December of 2022 based on changes in the 
competitive environment. Therefore, this study was discontinued. 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
6 
 
 
  
 
Number of Subjects (planned and analyzed): 
This study planned to enroll approximately 14 adult subjects in each of the 3 cohorts: C3G, IgAN and 
PMN for a total enrollment of approximately 42 subjects.  
Note: At the time the study was discontinued there were three screened subjects with a C3G history, 
and among them, two with confirmed C3G diagnosis who received study drug. All subjects were 
recruited prior to implementation of Protocol version 4.0. No subjects were enrolled under the other 
two cohorts.  
 
Test product, dose and mode of administration: 
Under protocol versions prior to Protocol Version 4.0, subjects were to receive BCX9930 500 mg 
twice daily (BID). Under Protocol Version 4.0, subjects were to 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. The appropriate quantity of BCX9930 tablets were to be taken 
orally, twice a day, approximately 12 hours apart, without regard to food. Subjects were advised that 
adequate hydration should be maintained to prevent the formation of highly concentrated urine. 
 
 
 
 
Duration of treatment: 
Subjects were to receive open-label BCX9930 for up to 52 weeks. 
Reference therapy, dose and mode of administration: 
Not applicable. 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
7 
 
 
  
 
Statistical methods: 
This was 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. 
Outcome Analyses to be Conducted:  
The analyses will be conducted for the following:  
x 
Disposition by C3G cohort and all screened subjects, 
x 
Demographics and baseline characteristics by C3G cohort, 
x 
Concomitant medications by dosing group, 
x 
Exposure by dosing group, 
x 
Key efficacy endpoints: 24-hour uPCR, 24-hour urine protein excretion and eGFR 
(Descriptive statistics on observed value, change from baseline, percent change from 
baseline, and ratio to baseline by scheduled visit and dosing group), 
x 
TEAEs by dosing group (Overall summary of TEAEs, and TEAEs by SOC and PT), 
x 
Laboratory tests by dosing group (Maximum elevation in post-baseline liver function tests 
and serum creatinine) 
For continuous variables, descriptive summaries will be presented. For categorical variables, 
summaries will be presented as counts and frequencies.  
Baseline characteristics and all safety data collected in the study will be listed. 
Due to the study discontinuation at a total of 2 treated subjects, efficacy analyses will be limited to 
descriptive statistics for the key efficacy endpoints noted above. Source data collected for all efficacy 
endpoints (primary, secondary, and exploratory endpoints) will be listed.  
PK concentration, PK parameters, PD/ biomarkers, and healthcare outcomes will be listed. 
Sample Size Justification:  
The proposed sample size of up to approximately 14 subjects per cohort was chosen to provide an 
estimate of 24-hour urine protein-to-creatinine ratio (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.  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
8 
 
 
  
 
Table of Contents 
ITLE PAGE .....................................................................................................................................1 
TECHNICAL SUMMARY REPORT (TSR) ..................................................................................4 
LIST OF TABLES .........................................................................................................................12 
1. 
LIST OF ABBREVIATIONS.....................................................................................13 
2. 
INTRODUCTION ......................................................................................................16 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................18 
3.1. 
Study Objectives .........................................................................................................18 
3.1.1. 
Primary Objective .......................................................................................................18 
3.1.2. 
Secondary Objectives .................................................................................................18 
3.1.3. 
Exploratory Objectives ...............................................................................................18 
3.1.4. 
18 
3.2. 
Study Endpoints ..........................................................................................................18 
3.2.1. 
Primary Endpoint ........................................................................................................18 
3.2.2. 
Secondary Endpoints ..................................................................................................19 
3.2.3. 
Exploratory Endpoints ................................................................................................20 
3.2.4. 
.20 
3.3. 
Statistical Hypotheses .................................................................................................20 
4. 
STUDY DESIGN .......................................................................................................21 
4.1. 
Summary of Study Design ..........................................................................................21 
4.2. 
Definition of Study Drugs ..........................................................................................22 
4.3. 
Sample Size Considerations .......................................................................................23 
4.3.1. 
Sample Size Justifications ..........................................................................................23 
4.3.2. 
Sample Size Re-Estimation ........................................................................................23 
4.4. 
Randomization ............................................................................................................23 
4.5. 
Clinical Assessments ..................................................................................................23 
5. 
PLANNED ANALYSES ............................................................................................32 
5.1. 
Interim Analyses .........................................................................................................32 
5.2. 
Final Analyses ............................................................................................................32 
6. 
GENERAL CONSIDERATIONS FOR DATA HANDLING AND 
ANALYSIS POPULATIONS ....................................................................................33 
6.1. 
General Summary Table and Individual Subject Data Listing Considerations ..........33 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
9 
 
 
  
 
6.2. 
General Post Text Summary Table and Individual Subject Data Listing 
Format Considerations ................................................................................................33 
6.3. 
Data Management .......................................................................................................33 
6.4. 
Data Presentation Conventions ...................................................................................34 
6.5. 
Analysis Populations ..................................................................................................34 
6.5.1. 
Screened Subjects .......................................................................................................34 
6.5.2. 
Screen Failures ............................................................................................................34 
6.5.3. 
Safety Population ........................................................................................................34 
6.6. 
Baseline Definition .....................................................................................................34 
6.7. 
Derived and Transformed Data ..................................................................................34 
6.7.1. 
Baseline Age ...............................................................................................................34 
6.7.2. 
Study Day ...................................................................................................................34 
6.7.3. 
Change from Baseline, Percent Change from Baseline and Ratio to Baseline ..........35 
6.7.4. 
Fold Change ................................................................................................................35 
6.7.5. 
Questionnaire Assessments ........................................................................................35 
6.7.6. 
Visit Windows ............................................................................................................35 
6.7.7. 
Multiple Assessments in a Visit Window ...................................................................35 
6.8. 
Handling of Missing Data ...........................................................................................35 
6.8.1. 
Missing Efficacy Endpoints ........................................................................................35 
6.8.2. 
Missing Start and Stop Dates for Prior and Concomitant Medication .......................35 
6.8.3. 
Missing Start and Stop Dates for Adverse Events ......................................................36 
7. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ...................................37 
7.1. 
Treatment group Descriptors ......................................................................................37 
8. 
DATA DISPLAYS RELATED TO THE STUDY POPULATION ..........................38 
8.1. 
Subjects Disposition ...................................................................................................38 
8.2. 
Screen Failures ............................................................................................................38 
8.3. 
Protocol Deviations ....................................................................................................38 
8.4. 
Demographic and Baseline Characteristics ................................................................38 
8.5. 
Listing of Subject Inclusion and Exclusion Criteria ...................................................38 
8.6. 
Medical History and Medical Conditions Present at Entry ........................................38 
8.7. 
Prior Medication History and Medications Present at Entry ......................................38 
8.8. 
Baseline Physical Examination ...................................................................................38 
8.9. 
Baseline Vital Signs ....................................................................................................39 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
10 
 
 
  
 
8.10. 
Baseline Laboratory Data ...........................................................................................39 
8.11. 
Baseline Primary and Secondary Efficacy Evaluations ..............................................39 
9. 
EFFICACY .................................................................................................................40 
9.1. 
General Considerations ...............................................................................................40 
9.2. 
Testing Statistical Assumptions Including Comparability at Baseline .......................40 
9.3. 
Statement of the Null and Alternate Hypotheses ........................................................40 
9.4. 
Subgroup Analyses .....................................................................................................40 
9.5. 
Multiple Comparisons and Multiplicity......................................................................40 
9.6. 
Analysis of the Primary Efficacy Endpoint ................................................................40 
9.6.1. 
Primary Efficacy Analysis ..........................................................................................40 
9.6.2. 
Sensitivity Analyses of the Primary Efficacy Results ................................................40 
9.7. 
Analysis of the Secondary Efficacy Endpoints ..........................................................40 
9.8. 
Summary of Reasons for Exclusion from the Per Protocol Efficacy Analyses ..........40 
10. 
SAFETY AND TOLERABILITY ..............................................................................41 
10.1. 
Adverse Event Preferred Term and Body/Organ System Summary Tables ...............41 
10.1.1. 
Summaries of Adverse Event Incidence Rates for All Subjects.................................41 
10.1.2. 
Missing and Partial AE Onset Dates ..........................................................................41 
10.1.3. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death ..........................................................................42 
10.2. 
Total Duration of Therapy, Average Daily Dose, Maximum Daily Dose, 
Final Daily Dose of Study Medication, and Compliance ...........................................42 
10.3. 
Concomitant and Other Medications ..........................................................................42 
10.4. 
Routine Laboratory Data ............................................................................................42 
10.5. 
Vital Signs ..................................................................................................................43 
10.6. 
Electrocardiograms .....................................................................................................43 
10.7. 
Physical Examination .................................................................................................44 
10.8. 
Pregnancy ...................................................................................................................44 
10.9. 
Study Termination Status ...........................................................................................44 
11. 
HEALTH OUTCOMES .............................................................................................45 
12. 
PHARMACOKINETIC/ PHARMACODYNAMIC ANALYSIS .............................46 
12.1. 
Pharmacokinetics ........................................................................................................46 
12.2. 
Pharmacodynamics and Complement Biomarkers .....................................................46 
13. 
REFERENCES ...........................................................................................................47 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
11 
 
 
  
 
14. 
APPENDIX.................................................................................................................48 
14.1. 
Table of Contents for Data Display Specifications ....................................................48 
14.2. 
Data Display Specifications ........................................................................................50 
14.3. 
 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
12 
 
 
  
 
LIST OF TABLES 
Table 1: 
List of Abbreviations ..................................................................................................13 
Table 2: 
Protocol Revision Chronology: ..................................................................................16 
Table 3: 
Schedule of Assessments (Screening - Week 24) .......................................................24 
Table 4: 
Schedule of Assessments (Week 28-Week 52) ..........................................................28 
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 ..................................................31 
Table 6: 
 
 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
13 
 
 
  
 
1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations 
Abbreviation  
Term 
ADaM 
Analysis data model 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ALP 
Alkaline phosphatase 
AP-activated 
Alternative pathway activated 
 
 
AST 
Aspartate transferase 
ATC 
Anatomical therapeutic class  
BID 
Twice daily 
BMI 
Body mass index 
C3 
Complement 3 
C3G 
Complement 3 glomerulopathy 
CFB 
Change from baseline  
CI 
Confidence interval 
CKD-EPI 
Chronic kidney disease epidemiology collaboration 
CP 
Classical pathway 
CRF 
Case report form 
CRO 
Contract research organization 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DDI 
Drug-drug interaction 
DHHS 
Department of Health and Human Services 
DMC 
Data monitoring committee 
DNA 
Deoxyribonucleic acid  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EM 
Electron microscopy or “electron micrograph” images 
 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
14 
 
 
  
 
Abbreviation  
Term 
F/ET 
Follow-up/End of Treatment 
FSH 
Follicle-stimulating hormone 
GN 
Glomerulonephritis  
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
Hib 
Haemophilus influenzae Type B 
HIV 
Human immunodeficiency virus 
IA 
Interim analysis 
ICH 
International Council for Harmonisation 
IgAN 
Immunoglobulin A nephropathy 
IgG 
Immunoglobulin G 
INR 
International normalized ratio 
 
 
LDH 
Lactate dehydrogenase 
LDL 
Low-density lipoprotein 
LLN 
Lower limit of normal006 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
PD 
Pharmacodynamic(s) 
 
 
 
 
PK 
Pharmacokinetic(s) 
PMN 
Primary membranous nephropathy 
POC 
Proof-of-concept 
PRO 
Patient-reported outcome 
PT 
Preferred term 
QoL 
Quality-of-life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAS 
Statistical analysis system  
sC5b-9 
Soluble c5b-9 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
15 
 
 
  
 
Abbreviation  
Term 
SCr  
Serum creatinine 
SD 
Standard deviation 
SDTM 
Study data tabulation model 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
uACR 
Urine albumin-to-creatinine ratio 
ULN 
Upper limit of normal 
 
 
uPCR 
Urine protein-to-creatinine ratio 
VZV 
Varicella-zoster virus 
WHO 
World health organization  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
16 
 
 
  
 
2. 
INTRODUCTION 
BioCryst stopped development of BCX9930 in December of 2022 based on changes in the 
competitive environment. Therefore, this study was discontinued. 
Due to the BCX9930 program discontinuation, data collected in study BCX9930-211 will be 
reported using an abbreviated Clinical Study Report (CSR). The purpose of this statistical 
analysis plan (SAP) is to describe the planned analyses for the CSR in study BCX9930-211.  
At the time of BCX9930 program discontinuation, there were only three screened subjects with 
one screen failure and two treated subjects in this study. The focus of the CSR will be on 
collected safety data. Summary tables will be presented for key safety variables. As this study 
had only a total of 2 treated subjects, only key efficacy endpoints described in the study protocol 
will be summarized using descriptive statistics. All data collected in this study including safety, 
efficacy and exploratory endpoints will be presented in data listings.  
The SAP is based on:  
x Protocol No. BCX9930-211 Version 4.0, dated 04 August 2022 
x ICH guidelines E4 and E9 (Statistical Principles for Clinical Trials)  
Table 2: 
Protocol Revision Chronology: 
Version 
Date 
Change 
Protocol v1.0 
16 April 2021 
Original 
Protocol v2.0 
23 June 2021 
1. Simplified acute kidney injury and acute kidney 
disorder language  
2. N. Meningitidis Type B and H. influenza 
vaccinations are now strongly encouraged 
Protocol v2.1 
13 August 2021 
1. Preliminary drug-drug interaction (DDI) results 
from BCX9930-102 (Study 102) in healthy subjects 
were provided in "Section 5.3.2-Clinical Findings 
for BCX9930" and corresponding updates were 
made to "Section 9.2.2-Prohibited and Restricted 
Medications". 
2. Change in title to "Vice President, Clinical 
Development Sciences". 
Protocol v3.0 
27 January 2022 
1. Study duration increased from 24 weeks to up to 52 
weeks 
2. On-treatment kidney biopsies were aligned by 
cohort. 
3. Refer to Summary of Changes (Protocol v2.1. to 
v3.0) 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
17 
 
 
  
 
Version 
Date 
Change 
Protocol v4.0 
04 August 2022 
1. Dose and dosing regimen 
x 
Recommended dose of BCX9930 reduced from 
500 mg BID to 400 mg BID for all subjects. 
x 
For newly randomized subjects, treatment with 
BCX9930 will begin at 200 mg BID for the first 
14 days before escalation to 400 mg BID. 
2. Refer to Summary of Changes (Protocol v3.0. to 
v4.0) 




BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
19 
 
 
  
 
x Change in 24-hour urinary protein excretion normalized to urine creatinine as 
measured by percentage change in uPCR from baseline 
3.2.2. 
Secondary Endpoints 
The secondary endpoints of this study per protocol were: 
x 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 
x Change from baseline in 24-hour urinary protein excretion as measured by percentage 
change in urinary protein from baseline  
x Change from baseline in eGFR 
x Change from baseline in serum albumin  
x 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 
x 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) 
x Number and proportion of subjects with a TEAE 
x Number and proportion of subjects who discontinue due to a TEAE 
x Number and proportion of subjects who experience a treatment-emergent serious 
adverse event (TESAE) 
x Number and proportion of subjects who experience a Grade 3 or 4 TEAE based on 
Common Terminology Criteria for Adverse Events (CTCAE) 
x Number and proportion of subjects who experience a CTCAE treatment-emergent 
Grade 3 or 4 laboratory abnormality 




BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
21 
 
 
  
 
4. 
STUDY DESIGN 
4.1. 
Summary of Study Design 
This was 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 either C3G, IgAN, or PMN. Under protocol versions prior to 
Protocol Version 4.0, after up to a 56-day screening qualification period, approximately 14 
eligible subjects were to be enrolled into each of 3 parallel study treatment cohorts and receive 
BCX9930 500 mg twice daily (BID). With protocol Version 4.0, subjects were to 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. The appropriate quantity of 
BCX9930 tablets was to be taken orally, twice a day, approximately 12 hours apart, without 
regard to food. Subjects were advised that adequate hydration should be maintained to prevent 
the formation of highly concentrated urine. 
The BCX9930 program was discontinued (see Section 2 for details) prior to any subject enrolling 
under Protocol Version 4.0. 
The overall study design is described in section 7.1 in each protocol version. 
Study schemas of Protocol Version 3.0 and Version 4.0 are shown in Figure 1. Note: No subjects 
were enrolled under protocol Version 4.0. 
After the Day 1 Visit, subjects were required to return to the clinic at Weeks 1, 2, and 4, and then 
every 4 weeks thereafter through Week 24. Additional safety assessments were to 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 would be assessed by the investigator. 
Subjects who were assessed as deriving clinical benefit would continue treatment up to Week 52. 
described in Table 3 and Table 4. 
Subjects who completed BCX9930 dosing through Week 52 or subjects who were discontinued 
from BCX9930 dosing prior to Week 52 were to 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.  
An optional serial PK/PD substudy was to include subjects who provided consent 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 was to be performed over a period of 6 hours. Subjects 
who did not participate in the Baseline (Day 1) PK/PD sample collection were eligible to 
participate at a subsequent clinic visit prior to the Week 24 Visit.  
All subjects were to 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 was to be drawn for PK and PD analysis at visits where 
serial blood samples were not collected through 
 post dose.  
All subjects who signed a separate informed consent (optional) were to 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). 


BioCryst Pharmaceuticals, Inc.
BCX9930-211
Statistical Analysis Plan Version 1.0
14 February 2023
22
Figure 1:
Study Schema by Protocol Version
Protocol Version 3.0
Protocol Version 4.0
4.2.
Definition of Study Drugs
BCX9930 is a small-molecule inhibitor of Factor D and was provided as tablets for oral 
administration. The active ingredient is BCX9930 drug substance.
BCX9930 tablets contain the active ingredient blended with the excipients microcrystalline 
cellulose, mannitol, crospovidone, colloidal silicon dioxide, and magnesium stearate, and are 
film-coated with Opadry white, which is a hydroxypropyl methylcellulose based non-functional 
coating.
Dosage forms include BCX9930 tablets of 100-, 200-, and 250-mg strength, which are all from a 
dose proportional blend compressed into tablets of the desired weight.
Additional details of the chemical and physical characteristics of BCX9930 may be found in the 
Investigator’s Brochure for BCX9930 and investigational medication product manual. Please 
note both IMP and study drug refer to BCX9930 in this protocol.


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
23 
 
 
  
 
4.3. 
Sample Size Considerations 
4.3.1. 
Sample Size Justifications 
No formal power or sample size calculations were planned to determine the sample size for each 
cohort. The proposed sample size of approximately 14 subjects per cohort was expected to 
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).  
4.3.2. 
Sample Size Re-Estimation 
No sample size re-estimations were planned. 
4.4. 
Randomization 
This is an open-label, non-randomized study. No study treatments were blinded or masked. 
4.5. 
Clinical Assessments 
The planned schedule of assessments for this study is presented in Table 3 (Screening through 
Week 24) and Table 4 (Week 28 through Week 52). The planned schedule of assessments for the 
PK/PD substudy is presented in Table 5. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
24 
 
 
  
 
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








BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
28 
 
 
  
 
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
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






BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
31 
 
 
  
 
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.  
 b 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. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
32 
 
 
  
 
5. 
PLANNED ANALYSES 
5.1. 
Interim Analyses 
The protocol states that interim analyses may be conducted for each study cohort based on 
ongoing review of individual subject safety and preliminary efficacy data. 
At the time of study discontinuation, an interim analysis plan and shells were under 
development. No formal interim analyses were conducted prior to the study discontinuation. 
5.2. 
Final Analyses 
The final analyses will be conducted to support the CSR. The final analyses will be conducted 
after the clinical database has been cleaned, quality checked, and locked. 
At the time of BCX9930 program discontinuation, there were only three screened subjects with 
one screen failure and two treated subjects in this study. The focus of the CSR will be on 
collected safety data. Summary tables will be presented for key safety variables. As this study 
had only a total of 2 treated subjects, only key efficacy endpoints described in the study protocol 
will be summarized using descriptive statistics. All data collected in this study including safety, 
efficacy and exploratory endpoints will be presented in data listings.  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
33 
 
 
  
 
6. 
GENERAL CONSIDERATIONS FOR DATA HANDLING AND 
ANALYSIS POPULATIONS  
Derived datasets are created using SAS® software. Data analyses and summary tables are 
generated using SAS version 9.4 or higher. 
6.1. 
General Summary Table and Individual Subject Data Listing 
Considerations 
Summary tables and listings will include “footers” providing: 
1. Date of data extraction. 
2. Date of output generation. 
3. SAS program name, including the path that generates the output. 
4. Any other output specific details that require further elaboration. 
Medications will be coded using the World Health Organization (WHO) drug dictionary version 
B3 March 2021. AEs will be mapped to MedDRA version 24 preferred term (PT) and system 
organ class (SOC). AEs will be graded according to the CTCAE scales (Version 5.0, 
27 November 2017). 
6.2. 
General Post Text Summary Table and Individual Subject Data 
Listing Format Considerations 
Tables, listings, and figures will be numbered using a decimal system to indicate the main levels 
of unique displays and sub-levels of replicate displays. The first level represents the appendix 
within which the tables, figures, and listings will appear. This will be 14 for tables and figures and 
16.2.x for listings.  
Listings will include all the key variables collected on the corresponding CRF page(s) and will 
present the data as it appears in the database. For example, the start date and time and end date 
and time of an AE will be displayed as reported on the eCRF (ie, any imputed values will not be 
listed). 
All tables and listings must have explanatory notes that give the definition of all derived 
variables and decodes for coded data. 
6.3. 
Data Management 
The standard operating procedures (SOPs) of Rho, the selected data management and statistical 
and programming vendor for this study, are used. A data management plan has been developed 
and approved prior to commencement of data entry. Data were captured using the Medidata 
electronic data capture system. Electronic validation steps (edit checks) were used, and data 
cleaning occurred in conjunction with each site. Prior to transfer of data provided by vendors (eg, 
laboratory data), a data transfer agreement including specifications for the type of file, 
definitions of variables, and contact information for the sending and receiving parties was 
developed and finalized. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
34 
 
 
  
 
Data are mapped to Study Data Tabulation Model (SDTM)-compliant datasets prior to creation 
of Analysis Data Model (ADaM)-compliant derived datasets for use in the creation of summary 
tables. 
6.4. 
Data Presentation Conventions 
A table of contents, at the end of this SAP, provides the expected titles and numbers of the 
tables, listings, and figures of the final report. Changes to titles or numbering in the final report 
will not necessitate a revision to the SAP, nor will it be considered a deviation from planned 
analyses. Additional data listings supporting the tables will not be considered a deviation from 
the planned analyses. 
6.5. 
Analysis Populations 
The populations used for data analysis of this study are defined below. 
6.5.1. 
Screened Subjects 
Screened subjects are those subjects who are screened for this study and are either screen failures 
or treated. 
6.5.2. 
Screen Failures 
Subjects who provide informed written consent but do not receive study treatment are considered 
screen failures.  
6.5.3. 
Safety Population 
The Safety population is defined as all subjects who receive at least one dose of study 
medication. This population will be used in the assessment and reporting of safety data. In 
addition, efficacy summaries will be based on this population. 
6.6. 
Baseline Definition 
For a given subject and assessment, baseline will generally be defined as the latest non missing 
result prior to administration of the first dose of study drug. If a subject is enrolled, but fails to 
receive study drug, baseline will be the last non-missing result. 
The baseline ECG values will be the average of the triplicate ECG readings obtained on Day 1 
(or screening if the Day 1 average is missing). 
6.7. 
Derived and Transformed Data 
6.7.1. 
Baseline Age  
The subject’s baseline age in years will be the age provided in the eCRF as collected at the time 
of informed consent. 
6.7.2. 
Study Day 
If the date of interest occurs on or after the date of the first dose, then study day will be 
calculated as (date of interest – date of first dose) + 1. If the date of interest occurs prior to the 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
35 
 
 
  
 
first dose date, then study day will be calculated as (date of interest – date of first dose). There is 
no study day 0. 
6.7.3. 
Change from Baseline, Percent Change from Baseline and Ratio to Baseline 
The following changes from baseline will be derived:  
x Change from baseline will be calculated as (post-baseline result – baseline result)  
x Percent change from baseline will be calculated as (change from baseline/baseline 
result * 100)  
x Ratio to baseline will be calculated as post-baseline result divided by baseline result 
If either the baseline or the post-baseline result is missing, then the changes from baseline 
described above will be missing. If the baseline value is 0, the percent change from baseline or 
ratio to baseline will be missing. 
Note: The CKD-EPI formula will use the serum creatinine in the computation of eGFR included 
in the efficacy summary table. 
6.7.4. 
Fold Change 
Fold change from the ULN will be calculated as (result/ULN), and fold change from the LLN 
will be defined similarly as (result/LLN). 
6.7.5. 
Questionnaire Assessments 
Scale scores and total scores resulting from questionnaire assessments will be calculated per the 
official assessment guidelines. Details are provided in Section 14.3. 
6.7.6. 
Visit Windows 
Visit windows will not be applied.  
6.7.7. 
Multiple Assessments in a Visit Window 
Visit windows will not be applied. 
For lab parameters where a central lab and local lab were collected at the same scheduled visit, 
the central lab value will be used. Local lab will be used if central lab data are not available. 
6.8. 
Handling of Missing Data 
6.8.1. 
Missing Efficacy Endpoints 
Not applicable. 
6.8.2. 
Missing Start and Stop Dates for Prior and Concomitant Medication 
An incomplete time has either the hours or minutes missing, but not both; or a time may have 
hours and minutes but be recorded on a 12-hour clock and AM/PM cannot be determined from 
other information. For calculation purposes, incomplete times will be treated as completely 
missing. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
36 
 
 
  
 
If the medication start date is completely missing and the medication stop date is after the start 
date of the first dose of study drug (or the medication is ongoing) then the medication will be 
considered concomitant. If both dates being compared are present and either or both times are 
missing, then dates alone will be compared. 
An incomplete date has at least one of the day, month, or year unknown, but at least one is 
present. For analysis of medications, a complete date should be established to identify 
medication as occurring during treatment or not. For the purposes of handling partially reported 
start and stop dates for medication, the following algorithm will be applied: 
x Missing start day, but month and year present: 
If study medication had been taken in the same month and year as the occurrence of 
the medication, then the start day of the medication will be assigned to the day of first 
dose of study medication. 
Otherwise, the start day will be set to the first day of the month. 
x Missing start day and month, but year present: 
If study medication had been taken in the same year as the occurrence of the 
medication, then the start date of the medication will be assigned to the date of first 
application of study medication. 
Otherwise, the start day and month will be set to 01 January. 
x Missing end day, but month and year present: 
The day will be set to the last day of the month. 
x Missing end day and month, but year present: 
The end day and month will be set to the date of trial termination for the subject. 
If after following the steps above, an imputed start date comes after an end date (either actual or 
imputed), the start date will be imputed to be equal to the end date. 
In subject data listings, start and stop date of medication will be displayed as reported on the 
eCRF. 
6.8.3. 
Missing Start and Stop Dates for Adverse Events 
The same conventions to address incomplete dates for prior and concomitant medications (see 
Section 6.8.2 above) will also be used for AEs.  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
37 
 
 
  
 
7. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Continuous variables (eg, age) are summarized using descriptive statistics (the number of 
subjects with available data, the mean, standard deviation (SD), median and minimum and 
maximum). Categorical variables (eg, race) are summarized using counts and percentages.  
The following conventions are applied to all data presentations and summaries. 
x For continuous variables, all mean and median values are formatted to one more 
decimal place than the measured value. Standard deviation values are formatted to 
two more decimal places than the measured value. Minimum and maximum values 
are presented with the same number of decimal places as the measured value. 
x For categorical variables, the number and percentage of responses are presented in the 
form XX (XX.X%) where the percentage is in the parentheses. 
x Date variables are formatted as DDMMMYYYY for presentation. Time is formatted 
to 24-hour format as HH:MM for presentation, if applicable. 
x Wherever possible, data will be decimal aligned. 
x Any row with all zeros will not appear except with reasons for not completing the 
study. Summary tables will clearly indicate the number of subjects to which the data 
apply. If a table, listing, or figure has no available data, then the body should read ‘No 
data to report.’ 
7.1. 
Treatment group Descriptors 
There were only 3 screened subjects who had historical C3G in this study. Two of them had 
confirmed C3G per central pathologist and started BCX9930 under 500 mg BID. The 
unconfirmed C3G subject was a screen failure. No subjects were enrolled under the other two 
cohorts (IgAN and PMN).  
Disposition summaries will be presented by the ‘C3G’ cohort and all screened subjects.  
Demographics and baseline characteristics summaries will be presented by the ‘C3G’ cohort. All 
other summaries will be presented by the following dosing groups: 
x C3G 500 mg BID 
x C3G 500 mg Total Daily Dose 
x Total All Doses (Efficacy summaries will not have this column). 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
38 
 
 
  
 
8. 
DATA DISPLAYS RELATED TO THE STUDY POPULATION 
8.1. 
Subjects Disposition 
Subject disposition will be summarized by C3G cohort and all screened subjects. The number of 
subjects who screened, had historical C3G, had confirmed C3G and among them, the number 
and percentage who were screening failures (along with the reasons) will be summarized. The 
number of subjects in safety population (treated), and among them, the number and percentage of 
subjects who discontinued from the study (along with the reasons) and those who completed the 
study will be presented. These data will also be listed.  
A consort diagram will also be provided to display a graphical view of the study status. 
8.2. 
Screen Failures 
Screening failure information will be summarized in the subject disposition table (see Section 8.1 
above) and listed. 
8.3. 
Protocol Deviations 
Protocol deviations will be identified by major or minor status, category, and importance per the 
protocol deviations plan. Protocol deviations will be listed.  
8.4. 
Demographic and Baseline Characteristics 
Demographic data and baseline characteristics including age at time of consent, age category at 
time of consent (< 18, 18 – 64, ≥ 65 with subcategories 65 – 74 and ≥ 75), sex at birth, 
childbearing potential (females only), ethnicity, race, height, weight, and BMI will be 
summarized by the C3G cohort.  
Demographic data and baseline characteristics data will be listed. 
8.5. 
Listing of Subject Inclusion and Exclusion Criteria 
Inclusion/exclusion criterion not met will be listed. 
8.6. 
Medical History and Medical Conditions Present at Entry 
Medical history, including disease specific medical history, will be coded using the Medical 
Dictionary for Regulatory Affairs (MedDRA) version 24 and listed.  
8.7. 
Prior Medication History and Medications Present at Entry 
Any medication that was received and stopped prior to the date of first dose will be considered 
prior medications. Prior medications will be listed.  
8.8. 
Baseline Physical Examination 
Baseline physical examination data will be listed. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
39 
 
 
  
 
8.9. 
Baseline Vital Signs 
Baseline vital sign data will be listed. 
8.10. 
Baseline Laboratory Data 
Baseline laboratory data will be listed. 
8.11. 
Baseline Primary and Secondary Efficacy Evaluations 
See Section 9. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
40 
 
 
  
 
9. 
EFFICACY  
Due to the study discontinuation at a total of 2 treated subjects, efficacy analysis will be limited 
to descriptive statistics for the following key efficacy endpoints: 24-hour uPCR, 24-hour urine 
protein excretion and eGFR.  
Descriptive statistics will be presented on observed values, change from baseline, percent change 
form baseline and ratio to baseline by scheduled visit using nominal visits. Source data of these 
key efficacy endpoints will be listed.  
Source data collected for all other efficacy endpoints will be listed.  
9.1. 
General Considerations 
Not applicable. 
9.2. 
Testing Statistical Assumptions Including Comparability at Baseline 
Not applicable. 
9.3. 
Statement of the Null and Alternate Hypotheses 
Not applicable. 
9.4. 
Subgroup Analyses 
Not applicable. 
9.5. 
Multiple Comparisons and Multiplicity 
Not applicable. 
9.6. 
Analysis of the Primary Efficacy Endpoint 
See introduction to Section 9 above. 
9.6.1. 
Primary Efficacy Analysis 
See introduction to Section 9 above. 
9.6.2. 
Sensitivity Analyses of the Primary Efficacy Results 
Not applicable. 
9.7. 
Analysis of the Secondary Efficacy Endpoints 
See introduction to Section 9 above. 
9.8. 
Summary of Reasons for Exclusion from the Per Protocol Efficacy 
Analyses 
Not applicable. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
41 
 
 
  
 
10. 
SAFETY AND TOLERABILITY 
All AEs and SAEs, regardless of investigator attribution, will 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]). TEAEs are defined, within a dosing group, as AEs that started on or after the 
first dose of study treatment through 30 days after the last dose of study drug.  
An overall summary of TEAEs will be presented by dosing group for the followings: 
x Number and proportion of subjects with a treatment-emergent adverse event (TEAE) 
x Number and proportion of subjects with an investigator rated TEAE of mild, 
moderate, or severe. 
x Number and proportion of subjects with a TEAE related to study drug 
x Number and proportion of subjects with a TEAE leading to treatment interruption 
x Number and proportion of subjects with a TEAE leading to treatment discontinuation 
x Number and proportion of subjects with a TEAE leading to study discontinuation 
x Number and proportion of subjects who experience a Common Terminology Criteria 
for Adverse Events (CTCAE) Grade 3 or 4 TEAE 
x Number and proportion of subjects who experience a treatment-emergent serious 
adverse event (TESAE) 
x Number and proportion of subjects with a TEAE leading to death 
With respect to severity, if a subject has the same event more than once, the event with the 
highest severity will be counted. Likewise, if a subject has the same event more than once, the 
event with the highest relationship to investigational product will be counted. If the relationship 
between the AE or SAE and the study drug is determined to be possibly, probably, or definitely 
related, the event will be considered related to the study drug. If an adverse event has a missing 
severity or relationship, it will be classified as having the highest severity and/or strongest 
relationship to study treatment. 
All AEs will be listed. 
10.1. 
Adverse Event Preferred Term and Body/Organ System Summary 
Tables 
TEAEs will be summarized by SOC and PT by dosing group. For a given event, a subject will be 
counted once for the subject count, if the subject reported one or more of the same events. Each 
event will be counted separately for the number of events.  
10.1.1. 
Summaries of Adverse Event Incidence Rates for All Subjects 
Not applicable. 
10.1.2. 
Missing and Partial AE Onset Dates 
See Section 6.8.3  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
42 
 
 
  
 
10.1.3. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death 
SAEs will be listed. 
10.2. 
Total Duration of Therapy, Average Daily Dose, Maximum Daily 
Dose, Final Daily Dose of Study Medication, and Compliance 
The duration of exposure (Days), within a dosing group, is calculated as follows: 
x Duration of Exposure (Days) = the later of (the last date returned or final treatment 
end date) minus the treatment start date+1. 
The Total duration of exposure (Days) is computed as the sum of the individual study drug 
durations across dosing groups.  
Descriptive statistics will be presented for the duration of exposure (in days) by dosing group. 
The following duration of exposure categories will also be summarized by dosing group: at least 
1 day, at least 7 days, at least 14 days, at least 28 days, at least 56 days, at least 84 days, at least 
112 days, and at least 140 days. 
Drug compliance for each study visit is captured in eCRF.  
Study treatment exposure and drug compliance data will be listed. 
10.3. 
Concomitant and Other Medications 
Any medication that was ongoing, started, or ended on or after the initiation of study drug will be 
considered concomitant. Concomitant medications will be summarized by dosing groups. 
For the subject who received study drug under two different dosing groups, medications taken on 
or after the initiation of study drug in the first dosing group through one day before the start of 
the second dosing group will be considered concomitant medications for the first dosing group. 
Medications taken on or after the start of the second dosing group will be considered 
concomitant medications for the second dosing group.  
Concomitant medications will be listed. 
10.4. 
Routine Laboratory Data 
An assessment of drug induced liver injury (DILI) for elevations in liver function tests will be 
performed. For ALT, AST, total bilirubin and international normalized ratio (INR) within a 
dosing group, the maximum post-baseline value across a subject’s visits (scheduled and 
unscheduled, out to 30 days post dose) will be determined for each test. The maximum value for 
each parameter will then be summarized per the categories given below: 
 
 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
43 
 
 
  
 
 
ALT/ AST/ ALT and AST/ 
ALT or AST  
Total Bilirubin  
INR 
ALT or AST and Total Bilirubin 
> 1.5X ULN 
> 3X ULN 
> 5X ULN 
> 10X ULN 
> 20X ULN 
> ULN 
> 1.5X ULN 
> 2X ULN 
> 1.5 
 
ALT > 3X ULN and Total Bilirubin 
> 1.5X ULN 
ALT > 3X ULN and Total Bilirubin 
> 2X ULN 
AST > 3X ULN and Total Bilirubin 
> 1.5X ULN 
AST > 3X ULN and Total Bilirubin 
> 2X ULN 
(ALT > 3X ULN or AST > 3X ULN) 
and Total Bilirubin > 1.5X ULN 
(ALT > 3X ULN or AST > 3X ULN) 
and Total Bilirubin > 2X ULN 
Within a specific outcome (eg, ALT, AST, etc.), the categories are descending cumulative and 
not mutually exclusive. 
In addition, for serum creatinine, within a dosing group, the maximum post-baseline value across 
a subject’s visits (scheduled and unscheduled, out to 30 days post dose) will be determined. The 
maximum value will then be summarized by dosing group for the categories given below: 
x > ULN but ≤ 1.5 × ULN 
x > 1.5 × ULN but < 3 × ULN  
x ≥ 3 × ULN 
x ≥ 0.3 mg/dL increase from baseline. 
Laboratory abnormalities will be graded according to CTCAE (Version 5.0, 27 November 2017). 
Any graded abnormality that occurs following the initiation of study drug (within 30 days post 
last dose) and represents at least 1-grade increase from the baseline assessment is defined as 
treatment emergent. A listing of all liver function test results for subjects experiencing a 
treatment-emergent Grade 3 or 4 liver function test will be provided. 
All laboratory data will be listed. 
10.5. 
Vital Signs 
Vital sign data will be listed. 
10.6. 
Electrocardiograms 
ECG values and findings will be listed. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
44 
 
 
  
 
10.7. 
Physical Examination 
Physical examination data will be listed. 
10.8. 
Pregnancy 
Pregnancy test results will be listed. 
10.9. 
Study Termination Status 
Study termination status will be summarized on the subject disposition table. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
45 
 
 
  
 
11. 
HEALTH OUTCOMES 
  


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
46 
 
 
  
 
12. 
PHARMACOKINETIC/ PHARMACODYNAMIC ANALYSIS 
12.1. 
Pharmacokinetics  
PK concentration and PK parameters will be listed. 
12.2. 
Pharmacodynamics and 
 
PD and 
 will be listed. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
47 
 
 
  
 
13. 
REFERENCES 
ICH E3 (1996). "Structure and Content of Clinical Study Reports." 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
48 
 
 
  
 
14. 
APPENDIX 
14.1. 
Table of Contents for Data Display Specifications 
Title 
Population 
 
Tables 
14.1.1.1 
Subject Disposition  
All Subjects 
14.1.2 
Demographics and Baseline Characteristics 
Safety 
14.1.3 
Concomitant Medications 
Safety 
14.1.4.1 
Exposure to Study Medication 
Safety 
14.2.1 
Summary of Key Efficacy Endpoints 
Safety 
14.3.1.1 
Overall Summary of Treatment-emergent Adverse 
Events 
Safety 
14.3.1.2 
Treatment-emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
14.3.2.1 
Maximum Elevations in Post-baseline Liver 
Function Tests 
Safety 
14.3.2.2 
Maximum Elevations in Post-baseline Serum 
Creatinine 
Safety 
Figures 
 
14.1.1.2 
Consort Diagram 
All Subjects 
Listings 
Listing 
Number 
Title 
Population 
16.2.1.1 
Informed Consent and Screen Failures 
All Subjects 
16.2.1.2 
Subject Disposition 
All Subjects 
16.2.2.1 
Inclusion/Exclusion Criteria Not Met 
All Subjects 
16.2.2.2 
Protocol Deviations 
All Subjects 
16.2.3 
Analysis Populations 
All Subjects 
16.2.4.1 
Demographic and Baseline Characteristics 
All Subjects 
16.2.4.2 
Medical History 
All Subjects 
16.2.4.3 
Disease Specific Medical History 
All Subjects 
16.2.4.4 
Prior and Concomitant Medications 
All Subjects 
16.2.4.5 
C3G/IgAN/PMN (Medication) History 
All Subjects 
16.2.5.1 
Treatment Administration 
All Subjects 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
49 
 
 
  
 
16.2.5.2 
Treatment Compliance 
All Subjects 
16.2.6.1 
24-Hour Urine   
All Subjects 
16.2.6.2 
Pathology Scoring 
All Subjects 
16.2.6.3 
Constitutive Blood Levels of Complement Biomarkers 
All Subjects 
16.2.6.4 
Single Void Urine Levels of Complement Biomarkers 
All Subjects 
16.2.6.5 
Complement Biomarker Measurements of Ex Vivo Stimulation 
Assays 
All Subjects 
16.2.6.6.1 
 
All Subjects 
16.2.6.7.1 
 
All Subjects 
16.2.6.7.2 
 
All Subjects 
16.2.6.8 
 
All Subjects 
16.2.7.1 
Adverse Events 
All Subjects   
16.2.7.2 
Serious Adverse Events 
All Subjects  
16.2.7.3 
Adverse Events Leading to Study Discontinuation 
All Subjects  
16.2.7.4 
Adverse Events Related to Study Treatment 
All Subjects  
16.2.7.5 
Adverse Events with CTCAE Grade 3 or Grade 4 Severity 
All Subjects  
16.2.7.6 
Rashes 
All Subjects  
16.2.8.1 
Laboratory Results – Clinical Chemistry 
All Subjects  
16.2.8.2 
Laboratory Results – Hematology 
All Subjects  
16.2.8.3 
Laboratory Results – Urinalysis 
All Subjects 
16.2.8.4 
Laboratory Results – Coagulation 
All Subjects 
16.2.8.5 
Single Void Urine Test Results 
All Subjects 
16.2.8.6 
Liver Function Test Results for Subjects Experiencing a 
Treatment-emergent Grade 3 or 4 Liver Function Test 
All Subjects 
16.2.9 
Vital Signs 
All Subjects 
16.2.10 
12-Lead ECG 
All Subjects 
16.2.11 
Physical Examinations 
All Subjects 
16.2.12.1 
Pregnancy Test 
All Women 
16.2.12.2 
 Drug Screen 
All Subjects 
16.2.12.3 
Other Laboratory Results 
All Subjects 
16.2.13.1 
Individual Plasma and Urine BCX9930 Pharmacokinetic 
Concentration-Time Data 
All Subjects 
16.2.13.2 
Individual PK Parameters in plasma and urine 
All Subjects 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
50 
 
 
  
 
14.2. 
Data Display Specifications 
Specifications for data displays will be provided in a separate document. 


BioCryst Pharmaceuticals, Inc. 
 
BCX9930-211 
Statistical Analysis Plan Version 1.0 
 
14 February 2023 
 
51 
 
 
  
 










Electronic Record and Signature Disclosure


ELECTRONIC RECORD AND SIGNATURE DISCLOSURE  
From time to time, BioCryst Pharmaceuticals, Inc. (we, us or Company) may be required by law 
to provide to you certain written notices or disclosures. Described below are the terms and 
conditions for providing to you such notices and disclosures electronically through the DocuSign 
system. Please read the information below carefully and thoroughly, and if you can access this 
information electronically to your satisfaction and agree to this Electronic Record and Signature 
Disclosure (ERSD), please confirm your agreement by selecting the check-box next to ‘I agree to 
use electronic records and signatures’ before clicking ‘CONTINUE’ within the DocuSign 
system. 
 
Getting paper copies  
At any time, you may request from us a paper copy of any record provided or made available 
electronically to you by us. You will have the ability to download and print documents we send 
to you through the DocuSign system during and immediately after the signing session and, if you 
elect to create a DocuSign account, you may access the documents for a limited period of time 
(usually 30 days) after such documents are first sent to you. After such time, if you wish for us to 
send you paper copies of any such documents from our office to you, you will be charged a 
$0.00 per-page fee. You may request delivery of such paper copies from us by following the 
procedure described below. 
 
Withdrawing your consent  
If you decide to receive notices and disclosures from us electronically, you may at any time 
change your mind and tell us that thereafter you want to receive required notices and disclosures 
only in paper format. How you must inform us of your decision to receive future notices and 
disclosure in paper format and withdraw your consent to receive notices and disclosures 
electronically is described below. 
 
Consequences of changing your mind  
If you elect to receive required notices and disclosures only in paper format, it will slow the 
speed at which we can complete certain steps in transactions with you and delivering services to 
you because we will need first to send the required notices or disclosures to you in paper format, 
and then wait until we receive back from you your acknowledgment of your receipt of such 
paper notices or disclosures. Further, you will no longer be able to use the DocuSign system to 
receive required notices and consents electronically from us or to sign electronically documents 
from us. 
 
All notices and disclosures will be sent to you electronically  
 &$#" #$ " "&'$ % #%'$ $& #"
  , 
	
$&% $ &#


Unless you tell us otherwise in accordance with the procedures described herein, we will provide 
electronically to you through the DocuSign system all required notices, disclosures, 
authorizations, acknowledgements, and other documents that are required to be provided or made 
available to you during the course of our relationship with you. To reduce the chance of you 
inadvertently not receiving any notice or disclosure, we prefer to provide all of the required 
notices and disclosures to you by the same method and to the same address that you have given 
us. Thus, you can receive all the disclosures and notices electronically or in paper format through 
the paper mail delivery system. If you do not agree with this process, please let us know as 
described below. Please also see the paragraph immediately above that describes the 
consequences of your electing not to receive delivery of the notices and disclosures 
electronically from us. 
 
How to contact BioCryst Pharmaceuticals, Inc.:  
You may contact us to let us know of your changes as to how we may contact you electronically, 
to request paper copies of certain information from us, and to withdraw your prior consent to 
receive notices and disclosures electronically as follows: 
To contact us by email send messages to: 
 
 
To advise BioCryst Pharmaceuticals, Inc. of your new email address  
To let us know of a change in your email address where we should send notices and disclosures 
electronically to you, you must send an email message to us at 
 and in 
the body of such request you must state: your previous email address, your new email 
address.  We do not require any other information from you to change your email address.  
If you created a DocuSign account, you may update it with your new email address through your 
account preferences.  
 
To request paper copies from BioCryst Pharmaceuticals, Inc.  
To request delivery from us of paper copies of the notices and disclosures previously provided 
by us to you electronically, you must send us an email to
.com and in the 
body of such request you must state your email address, full name, mailing address, and 
telephone number. We will bill you for any fees at that time, if any. 
 
To withdraw your consent with BioCryst Pharmaceuticals, Inc.  
To inform us that you no longer wish to receive future notices and disclosures in electronic 
format you may: 


i. decline to sign a document from within your signing session, and on the subsequent page, 
select the check-box indicating you wish to withdraw your consent, or you may; 
ii. send us an email to 
 and in the body of such request you must state 
your email, full name, mailing address, and telephone number. We do not need any other 
information from you to withdraw consent..  The consequences of your withdrawing consent for 
online documents will be that transactions may take a longer time to process.. 
 
Required hardware and software  
The minimum system requirements for using the DocuSign system may change over time. The 
current system requirements are found here: https://support.docusign.com/guides/signer-guide-
signing-system-requirements.  
 
Acknowledging your access and consent to receive and sign documents electronically  
To confirm to us that you can access this information electronically, which will be similar to 
other electronic notices and disclosures that we will provide to you, please confirm that you have 
read this ERSD, and (i) that you are able to print on paper or electronically save this ERSD for 
your future reference and access; or (ii) that you are able to email this ERSD to an email address 
where you will be able to print on paper or save it for your future reference and access. Further, 
if you consent to receiving notices and disclosures exclusively in electronic format as described 
herein, then select the check-box next to ‘I agree to use electronic records and signatures’ before 
clicking ‘CONTINUE’ within the DocuSign system. 
By selecting the check-box next to ‘I agree to use electronic records and signatures’, you confirm 
that: 
x 
You can access and read this Electronic Record and Signature Disclosure; and 
x 
You can print on paper this Electronic Record and Signature Disclosure, or save or send 
this Electronic Record and Disclosure to a location where you can print it, for future 
reference and access; and 
x 
Until or unless you notify BioCryst Pharmaceuticals, Inc. as described above, you 
consent to receive exclusively through electronic means all notices, disclosures, 
authorizations, acknowledgements, and other documents that are required to be provided 
or made available to you by BioCryst Pharmaceuticals, Inc. during the course of your 
relationship with BioCryst Pharmaceuticals, Inc..