Clinical trial NCT03905512
Conditions: Chronic Gout
Sponsor: Selecta Biosciences, Inc.
Start date: 2019-05-07; Completion date: 2020-08-05
Enrollment: 170 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Participants will be randomized 1:1 to receive treatment with SEL-212 or KRYSTEXXA® for 6 months. Efficacy assessments, as measured by serum uric acid (SUA) levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study.

Detailed description:
This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Participants will be randomized 1:1 to receive treatment with SEL-212 \[a combination of pegadricase (SEL-037) and ImmTOR (SEL-110)\] or KRYSTEXXA® for 6 months.

Study participants in the SEL-212 arm will receive study drug every 28 days for a total of up to 6 infusions of SEL-212. Study participants in the KRYSTEXXA® arm will receive study drug according to the manufacturer's prescribing information, i.e., every 14 days for a total of up to 12 infusions of KRYSTEXXA®.

Efficacy assessments, as measured by SUA levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study.

Arms: arm 1: Intravenous (IV) infusion of SEL-212 every 28 days for up to 6 infusions arm 2: IV infusion of KRYSTEXXA® according to the manufacturer's prescribing information every 14 days for up to 12 infusions
Interventions: intervention 1: SEL-212 intervention 2: KRYSTEXXA®
Intervention descriptions: intervention 1: Administered as specified in the treatment arm intervention 2: Administered as specified in the treatment arm

Protocol documents:
Prot_000.pdf: 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
STUDY DRUG: SEL-212 (a combination of SEL-037 and SEL-110.36) 
STUDY NUMBER: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE: 08 Jun 2020 
A STUDY TO COMPARE THE EFFICACY OF SEL-212 TO KRYSTEXXA® IN GOUT 
PATIENTS REFRACTORY TO CONVENTIONAL THERAPY 
Sponsor Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472, USA 
Tel: 
 
Fax: 
 
Approvers: 
 
 
Signature: 
Date: 
 
 
8June2020 
. on behalf of 
 
09June2020 
NCT #: NCT03905512


PROPRIETARY AND CONFIDENTIAL 
PAGE 2 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
SELECTA BIOSCIENCES CLINICAL STUDY PROTOCOL 
 
A STUDY TO COMPARE THE EFFICACY OF SEL-212 TO KRYSTEXXA® IN GOUT 
PATIENTS REFRACTORY TO CONVENTIONAL THERAPY 
STUDY NUMBER: SEL-212/202 
 
 
CONTACT INFORMATION 
 
Sponsor: Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472 
Tel: 
 
Fax: 
 
Email: 
 
Clinical Study Leader: 
 
 
Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472 
Tel: 
 
Fax: 
 
Email: 
 
Medical Contact: 
 
 
Syneos Health 
1030 Sync Street 
Morrisville, North Carolina, USA 27560 
Tel:
 
Email:
 
Pharmacovigilance: Syneos Health and Pharmacovigilance 
Fax Number: 
 
In case of issues with fax, Email: 
 


PROPRIETARY AND CONFIDENTIAL 
PAGE 3 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
 
 
I agree: 
INVESTIGATOR’S AGREEMENT 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
To conduct the study in compliance with applicable regulatory requirements, this protocol, any future 
amendments, and with any other study conduct procedures provided by Selecta Biosciences. (Sponsor). 
• 
Not to implement any changes to the protocol without agreement from the Sponsor and prior review and 
written approval from the Institutional Review Board (IRB) or Independent Ethics Committee (IEC), 
except where necessary to eliminate an immediate hazard to the patients, or for administrative aspects of 
the study (where permitted by all applicable regulatory requirements). 
• 
That I am thoroughly familiar with the appropriate use of the study drug(s), as described in this protocol, 
and any other information provided by the Sponsor including, but not limited to, the following: the current 
Investigator’s Brochure (IB) or equivalent document, any IB supplement as applicable, or any approved 
product label as applicable. 
• 
That I am aware of, and will comply with, “good clinical practices” (GCP) and all applicable regulatory 
requirements. 
• 
That I will provide full and unencumbered access to source documents and medical records needed for the 
Sponsor, representatives of the Sponsor and regulatory authorities to verify source data and related 
documentation with respect to this trial. 
• 
To ensure that all persons assisting me with the study are adequately informed about the Sponsor study 
drug(s) and of their study-related duties and functions as described in the protocol. 
• 
That I have been informed that certain regulatory authorities require the Sponsor to obtain and supply, as 
necessary, details about the Investigator’s ownership interest in the Sponsor or the study drug, and more 
generally about his/her financial ties with the Sponsor. The Sponsor will use and disclose the information 
solely for the purpose of complying with regulatory requirements. 
 
Hence, I: 
• 
Agree to supply Selecta Biosciences with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children); 
• 
Agree to promptly update this information if any relevant changes occur during the course of the study and 
for 1 year following completion of the study; and 
• 
Agree that Selecta Biosciences may disclose any information it has about such ownership interests and 
financial ties to regulatory authorities. 
 
 
 
 
Printed Name of Investigator 
Signature of Investigator 
Date 


PROPRIETARY AND CONFIDENTIAL 
PAGE 4 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
2. 
SYNOPSIS 
 
Name of Sponsor/Company: 
Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472, USA 
Name of Investigational Product: 
SEL-212 (a combination of SEL-037 and SEL-110.36) 
Name of Comparator Product: 
KRYSTEXXA® (pegloticase) 
Name of Active Ingredient in Investigational Product: 
SEL-037 (pegadricase, recombinant pegylated candida urate oxidase) 
SEL-110.36 (a nanoparticle composed of PLA [poly{D,L-lactide}] and PLA-PEG 
[poly{D,L—lactide}-block-poly {ethylene-glycol}] encapsulating rapamycin) 
Title of Study: 
A Study to Compare the Efficacy of SEL-212 to KRYSTEXXA® in Gout Patients Refractory 
to Conventional Therapy 
Study Center(s): approximately 60 study centers in the United States 
Studied Period (years): 
Estimated date first patient enrolled: 28 February 2019 
Estimated date last patient completed: 31 July 2020 
Objectives: 
Primary: 
• To assess the reduction in serum uric acid (SUA) in patients treated with SEL-212 
compared to KRYSTEXXA® 
Secondary: 
Secondary objectives are to assess improvement of the following parameters in patients 
treated with SEL-212 compared to KRYSTEXXA: 
• Gout flares 
• SUA control 
• Joint tenderness and swelling 
• Quality of life (QoL) 
Methodology: 
This study is a randomized, open-label, parallel-arm study to compare the safety and efficacy 
profiles of SEL-212 and KRYSTEXXA. Approximately 150 patients will be randomized 1:1 


PROPRIETARY AND CONFIDENTIAL 
PAGE 5 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
prior to Baseline to receive treatment with SEL-212 or KRYSTEXXA for 6 months. Efficacy 
assessments, as measured by SUA levels, will be conducted at intervals that are appropriate 
to determine treatment effect differences, including at month 3 and month 6. Assessments of 
qualitative endpoints will be conducted on an assessor-blinded basis. Safety will be 
monitored throughout the study. 
Screening Period 
After providing written informed consent, the patient is considered enrolled in the study. 
Patients will be evaluated for inclusion during the Screening Period. For all patients, the 
standard Screening Period will be up to 45 days prior to Baseline. Concurrently with the 
Screening Period, a premedication period with colchicine of at least 7 days prior to Baseline 
for potential gout flare will be required for all subjects, and a washout period of at least 7 
days will be required prior to Baseline for patients on any urate-lowering therapy (ULT). 
Treatment Periods 
The total duration of the treatment will be 6 months. Eligible patients will be randomized 1:1 
prior to Baseline to receive SEL-212 or KRYSTEXXA. 
Study patients in the SEL-212 arm will receive study drug every 28 days coinciding with 
Day 0 of each Treatment Period for a total of up to 6 infusions of SEL-212. 
Study patients in the KRYSTEXXA arm will receive study drug according to the 
manufacturer’s prescribing information, i.e., every 14 days coinciding with Day 0 and Day 14 
of each Treatment Period for a total of up to 12 infusions of KRYSTEXXA. 
Prior to infusion, all patients will receive a standardized regimen of premedication to 
minimize the potential for infusion reactions during study drug administration. After 
completing the study drug infusions, patients will remain at the investigational site for at least 
1 hour for safety assessments. 
With each dose, a blood sample will be drawn for assessment of SUA level immediately prior 
to infusion (ie, Time 0h) with SEL-212 or KRYSTEXXA, and 1 hour after the infusion of the 
second component of SEL-212 or of KRYSTEXXA is completed. SUA levels will be 
assessed through additional post-infusion blood samples at pre-determined time points. Every 
effort will be made to obtain blood samples at the same time of day of each study visit. 
Gout flares will be assessed at every visit. QoL and joint swelling and tenderness will be 
assessed on Day 0 of Treatment Period 1 and 4, and at the end of Treatment Period 6. 
Assessments of qualitative endpoints (health questionnaires and joint assessment) will be 
conducted on an assessor-blinded basis. 
On dosing days, safety laboratory samples will be collected pre-infusion and per Schedule of 
Events in both the SEL-212 arm and the KRYSTEXXA arm. Concomitant medications and 
procedures and adverse events (AEs) will be monitored continuously during the study. 
Follow-Up Period 
Patients will be followed for safety monitoring for 30 (+ 4) days after their final study drug 
infusion and will have an End of Study visit by telephone. Patients who terminate the study 
prematurely will have all Early Termination assessments performed. Patients who terminate 


PROPRIETARY AND CONFIDENTIAL 
PAGE 6 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
the study prematurely who are unable to be on-site for the Early Termination visit will be 
contacted by telephone for safety follow-up. 
Data and Safety Monitoring Committee (DSMC) 
An independent Data and Safety Monitoring Committee (DSMC) will be formed by charter 
to assist in reviewing safety data and may provide recommendations to the Sponsor regarding 
study drug dose adjustment or study termination 
Stopping Rules 
A patient will be withdrawn from study drug for meeting the following stopping rule: 
• In the SEL-212 arm: SUA level > 1.0 mg/dL measured at the Day 21 visit of 
Treatment Period 1 or SUA level > 6.0 mg/dL at the Day 21 visit of Treatment 
Periods 2, 3, 4, or 5 
• In the KRYSTEXXA arm: SUA level > 6.0 mg/dL measured on 2 consecutive 
pre-dose measurements 
If withdrawn from study drug, the patient will continue study visits to the end of Treatment 
Period 6. 
Number of Patients (Planned): 
• Planned Enrollment: Approximately 150 patients randomized (total): 
o SEL-212: approximately 75 patients 
o KRYSTEXXA: approximately 75 patients 
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria: 
A patient must meet all of the following criteria to be eligible for this study: 
1. Has provided written informed consent prior to the conduct of any study specific 
procedures; 
2. Understands and is willing and able to comply with study requirements, including the 
schedule of follow-up visits; 
3. Has a history of symptomatic gout defined as: 
a. ≥ 3 gout flares within 18 months of Screening or 
b. Presence of ≥ 1 tophus or 
c. Current diagnosis of gouty arthritis 
4. At the Screening Visit: male age 21 – 80 years, inclusive, or female of 
non-childbearing potential age 21-80 years, inclusive, where non-childbearing 
potential is defined as: 
a. > 6 weeks after hysterectomy with or without surgical bilateral salpingo- 
oophorectomy or 


PROPRIETARY AND CONFIDENTIAL 
PAGE 7 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
b.  Post-menopausal (> 24 months of natural amenorrhea or in the absence of 
> 24 months of amenorrhea, 1 documented confirmatory FSH measurement) 
5. Has at Screening SUA ≥ 7 mg/dL, with chronic refractory gout defined as having 
failed to normalize SUA and whose signs and symptoms are inadequately controlled 
with xanthine oxidase inhibitors at the medically appropriate dose, or these drugs are 
contraindicated for the subject; 
6. Is negative for anti-PEG antibodies at Screening; 
7. Has not participated in a clinical trial within 30 days of the Screening Visit and agrees 
not to participate in a clinical trial for the duration of the study; 
8. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative 
antibodies to hepatitis C; 
9. Has adequate venous access and able to receive IV therapy; 
10. If applicable, has sufficiently recovered from any prior surgery to allow for successful 
completion of study procedures. 
Exclusion Criteria: 
A patient who meets any of the following criteria will be excluded from this study: 
1. Prior exposure to any experimental or marketed uricase (e.g., pegloticase 
[Krystexxa®], pegadricase [SEL-037], rasburicase [Elitek, Fasturtec]) 
2. History of anaphylaxis or severe allergic reactions to medications; 
3. History of any allergy to pegylated products, including, but not limited to, 
peginterferon alfa-2a (Pegasys®), peginterferon alfa-2b (PegIntron®), pegfilgrastim 
(Neulasta®), pegaptanib (Macugen®), pegaspargase (Oncaspar®), pegademase 
(Adagen®), peg-epoetin beta (Mircera®), pegvisomant (Somavert®) certolizumab 
pegol (Cimzia®), naloxegol (Movantik®), peginesatide (Omontys®), and doxorubicin 
liposome (Doxil®); 
4. Known moderate and severe CYP3A4 inhibitors or inducers must be discontinued 
14 days before dosing and patients must remain off the medication for the duration of 
the study, including natural products such as St. John’s Wort or grapefruit juice. 
5. Drugs known to interact with Rapamune® such as cyclosporine, diltiazem, 
erythromycin, ketoconazole (and other antifungals), nicardipine (and other calcium 
channel blockers), rifampin, verapamil unless they are stopped 2 weeks prior to 
starting the trial and will not be used during the trial. 
6. Initiation or change in dose of hormone-replacement therapy for menopausal women 
less than 1 month prior to the Screening Visit or during the Screening Phase would be 
exclusionary. If after being on a stable dose of hormone-replacement therapy for 
1 month the patient may be considered for the study if she continues to meet all other 
inclusion and exclusion criteria. 
7. A gout flare during Screening that was resolved for less than 1 week prior to first 
treatment with study drug (exclusive of synovitis/arthritis), unless the patient has a 
history of inter-flare intervals < 1 week. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 8 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
8. Uncontrolled diabetes at Screening with HbA1c ≥ 8%; 
9. Fasting Screening glucose > 240 mg/dL 
10. Fasting Screening triglyceride > 300 mg/dL; 
11. Fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; 
12. Glucose-6-phosphate dehydrogenase (G6PD) deficiency; 
13. Uncontrolled hypertension defined as blood pressure >170/100 mmHg at both 
Screening and 1 week prior to dosing 
14. Individual laboratory values which are exclusionary 
o White blood cell count (WBC) < 3.0 x109/L 
o Serum aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) > 3x upper limit of normal (ULN) 
o Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 
o Hemoglobin (Hgb) < 9 g/dL 
o Serum phosphate < 2.0 mg/dL 
15. Patients whose arrhythmia is unstable on current treatment; 
16. History of coronary artery disease, including myocardial infarction or unstable angina, 
within the last 6 months; 
17. Congestive heart failure, New York Heart Association Class III or IV; 
18. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with 
evidence of prior myocardial infarction, clinically significant arrhythmia, or other 
abnormalities that, in the opinion of the investigator, are consistent with significant 
underlying cardiac disease; 
19. History of significant hematological disorders or autoimmune disorders, and/or 
subject is immunosuppressed or immunocompromised; 
20. Subject is currently taking dabigatran (Pradaxa®), rivaroxaban (Xarelto®), 
edoxaban (Savaysa®), warfarin (Coumadin®), or apixaban (Eliquis®); 
21. Subject has received an inactivated vaccine in the previous 3 months with respect to 
the randomization date or has received a live virus vaccine in the previous 6 months 
with respect to the randomization date. Recombinant vaccines are excluded from this 
exclusion criterium. 
22. Subject is planning to receive any live or attenuated virus vaccination during the 
study. 
23. History of malignancy within the last 5 years other than basal skin cancer; 
24. Any condition, that in the opinion of the investigator, would be negatively affected by 
rapamycin. 
25. Subjects with a documented history of moderate or severe alcohol or substance use 
disorder within the 12 months prior to randomization. 
26. Subjects who, in the opinion of the investigator, present with a condition that would 
compromise their safety or that would make study completion unlikely. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 9 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Investigational Product and Comparator Product, Dosage and Mode of Administration: 
INVESTIGATIONAL PRODUCT 
• SEL-212 is comprised of 2 components: SEL-110.36 and SEL-037 
o SEL-110.36: nanoparticle composed of PLA and PLA-PEG encapsulating 
rapamycin for reconstitution with sterile water for injection. 
o SEL-037: pegadricase, a recombinant pegylated candida urate oxidase. 
Dosage of Investigational Drug 
• SEL-110.36: calculation based on patient’s body weight 
o 0.15 mg/kg 
• SEL-037: calculation based on patient’s body weight 
o 0.2 mg/kg 
Mode of Administration (SEL-212) 
• Premedication for SEL-212 (prior to study drug administration) 
o Colchicine 0.6 mg oral (PO) every day starting at least 7 days prior to Day 0 
▪ Patients not already taking colchicine will receive colchicine 1.2 mg as a 
single loading dose followed by the 0.6 mg every day regimen. If the patient 
cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate 
and maintain colchicine at 0.6 mg. 
o Prednisone 40 mg oral (PO) approximately 24 (± 12) hours 
o Fexofenadine 180 mg oral (PO) approximately 12 (± 2) hours 
o Fexofenadine 180 mg oral (PO) approximately 2 (± 1) hours 
o Methylprednisolone 40 mg (or equivalent) IV approximately 1 (± 0.5) hours 
• SEL-110.36 
o IV infusion with a syringe infusion pump at a steady rate of 3.0 mL/hr for the first 
30 minutes, then a rate sufficient to deliver the remaining dose volume over a 
period of 60 minutes concurrently with normal saline 
• SEL-037 
o Administration initiated within 15 minutes after completion of the SEL-110.36 
infusion. 
o Administered via infusion pump over a time period of no less than 120 minutes. If 
an infusion reaction occurs during the administration of SEL-037, the infusion 
may be slowed, or stopped and restarted at a slower rate at the discretion of the 
physician. 
KRYSTEXXA 
• Premedication for KRYSTEXXA (prior to study drug administration) 
o Colchicine 0.6 mg oral (PO) every day starting at least 7 days prior to Day 0 


PROPRIETARY AND CONFIDENTIAL 
PAGE 10 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
▪ Patients not already taking colchicine will receive colchicine 1.2 mg as a 
single loading dose followed by the 0.6 mg every day regimen. If the patient 
cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate 
and maintain colchicine at 0.6 mg. 
o Prednisone 40 mg oral (PO) approximately 24 (± 12) hours 
o Fexofenadine 180 mg oral (PO) approximately 12 (± 2) hours 
o Fexofenadine 180 mg oral (PO) approximately 2 (± 1) hours 
o Methylprednisolone 40 mg (or equivalent) IV approximately 1 (± 0.5) hours 
• KRYSTEXXA (pegloticase injection) will consist of commercially available study 
drug administered at a dosage of 8 mg (uricase protein) given as an IV infusion every 
2 weeks, consistent with the manufacturer’s currently approved labeling 
(KRYSTEXXA Prescribing Information 2018). 
Duration of Treatment: 
All patients are planned to receive study drug during 6 months of treatment. The SEL-212 
treatment arm will receive a total of up to 6 infusions, scheduled every 28 days. The 
KRYSTEXXA treatment arm will receive a total of up to 12 infusions, scheduled every 
14 days, according to the manufacturer’s currently approved label (KRYSTEXXA Prescribing 
Information 2018). 
The total duration of participation in the study will range from approximately 26 to 31 weeks 
(184 to 219 days) for patients randomized to SEL-212 and approximately 28 to 33 weeks 
(198 to 233 days) for patients randomized to KRYSTEXXA as follows: 
• Screening and/or washout and premedication period: up to 45 days (up to 6.5 weeks) 
• Treatment: 168 days (24 weeks) for SEL-212 and KRYSTEXXA 
• Safety Follow-Up: 30 (+ 4) days after the date of last infusion 
o SEL-212: Last scheduled infusion on Study Day 140 
o KRYSTEXXA: Last schedule infusion on Study Day 154 
Criteria for Evaluation: 
Efficacy: 
Primary Endpoint: 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during 
Treatment Period 3 and Treatment Period 6 
Secondary Endpoints: 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during 
Treatment Period 6 


PROPRIETARY AND CONFIDENTIAL 
PAGE 11 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for 100% of the time during Treatment 
Period 6 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during 
Treatment Period 3 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for 100% of the time during Treatment 
Period 3 
• Comparison between patients on SEL-212 vs. KRYSTEXXA in pre-dose SUA values 
> 6 mg/dL during Treatment Periods 2-6. The pre-dose SUA is collected on the 
dosing day prior to the dosing administration or it is collected at the visit where 
dosing would have occurred had the patient not been previously withdrawn from 
study drug. 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change in health 
questionnaires 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare incidence 
per 3-month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare frequency 
per 3-month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from 
Baseline to Treatment Period 6 in number of tender joints 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from 
Baseline to Treatment Period 6 in number of swollen joints 
Safety: 
Safety Endpoints: 
• Safety and tolerability of SEL-212 compared to KRYSTEXXA as assessed by AEs, 
serious AEs (SAEs), deaths, and discontinuations due to AEs 
• Additional safety assessments will include review and evaluation of laboratory testing 
including hematology, coagulation, chemistry, urinalysis; vital signs; 12-lead ECGs; 
and physical examination findings. 
Statistical Methods 
Details of the statistical methods outlined in the protocol for this study, including the 
hierarchical ordering of the secondary endpoints, will be documented in a Statistical Analysis 
Plan (SAP) that will be finalized prior to first patient randomized. The SAP may add 
additional exploratory analyses; modifications to the planned analyses will be identified as 
such in the SAP. 
Analysis Populations 


PROPRIETARY AND CONFIDENTIAL 
PAGE 12 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
• Screened / Randomized Set: The Screened Set will include all patients who signed an 
informed consent. The Randomized Set will include all patients randomized. 
• Safety Set (SS): The Safety Set will include all patients who were administered any 
amount of study medication. Patients will be analyzed according to treatment 
received. The SS will be used for all analyses of safety endpoints and for the 
presentation of patients in all patient listings. 
• Intent-to-Treat (ITT) Set: The Intent-to-Treat (ITT) Set will be used as the primary 
population for the analysis of efficacy. The ITT Set will include all randomized 
patients. Patients will be analyzed according to randomized treatment. 
• Modified ITT (mITT) Set: The modified ITT (mITT) Set will include all randomized 
patients who were administered at least one complete dose of study medication and 
have at least one post-baseline assessment of SUA. Patients will be analyzed 
according to randomized treatment. The mITT will also be used for analyses of 
efficacy endpoints. 
• Per Protocol (PP) Set: The Per Protocol Set (PPS) will include all patients who 1) 
were administered any amount of study medication, and 2) have completed at least 
65% of the study dosing visits with or without receiving study drug (eg at least 4 of 6 
TP Day 0 visits for patients receiving SEL-212 or at least 8 of 12 TP Day 0 or Day14 
visits for patients receiving Krystexxa) unless early termination from the study 
occurred after study drug withdrawal due to meeting stopping rules or due to an 
adverse event, or due to PI discretion (for example where at least one pre-dose SUA 
was >6 mg/dL in the Krystexxa arm and patient was discontinued from study 
treatment), and 3) who have no major Protocol deviations affecting the primary 
efficacy assessments. Patients will be analyzed according to randomized treatment. 
Efficacy Analyses 
Primary Efficacy Analysis 
The primary estimand will take into consideration the treatment policy strategy, ie, Treatment 
Period 6 (and also Treatment Period 3) assessments will be considered for all subjects in ITT 
independently whether the subject has completed the study treatment or has terminated early 
the study treatment. Additionally, the estimand based on the while-on-treatment strategy for 
dealing with study treatment terminators will be defined. For all used estimands of the 
primary efficacy, the estimator for the comparison between the treatment groups is defined as 
the difference in the proportion of responders between subjects receiving SEL-212 versus 
those receiving KRYSTEXXA during Treatment Periods 3 and 6. The statistical testing will 
be performed confirmatory using the Cochran-Mantel-Haenszel (CMH) test – considering the 
randomization stratum of tophus presence (yes/no) – with a one-sided type 1 error rate 
α = 5%. In addition, 90% two-sided confidence intervals for the overall treatment difference 
between SEL-212 and KRYSTEXXA treatment groups without stratification will be 
computed. The analysis of the estimands will be carried out based on the ITT primarily. 
Supportive analyses will be performed on the mITT and the PP. For each defined estimand 
sensitivity analyses will be performed using different imputation approaches for missing 
values. Details of the applied approaches will be presented in the Statistical Analysis Plan. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 13 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
The SUA time curve will be used to estimate the proportion of time that the SUA level is 
below 6 mg/dL. Based on the serum samples collected during Treatment Periods 3 and 6, an 
estimate of the time with SUA < 6 mg/dL can be determined by connecting each two 
neighboring data points with a straight line. If the SUA time curve goes above 6 mg/dL the 
linear interpolation method will be used to estimate the point in time at which the SUA time 
curve intercepts the line between the last SUA value < 6 mg/dL and the first value ≥ 6 mg/dL. 
The proportion of time that the SUA level is < 6 mg/dL will be computed by taking the ratio 
between the time during which the SUA level remains < 6 mg/dL (if necessary, using the 
linear interpolation method) and the entire time interval within Treatment Periods 3 and 6. 
Let T1 be the total time interval in hours for Treatment Period 3 of which W1 hours is the 
time interval during which SUA level is < 6 mg/dL. Similarly, for Treatment Period 6, 
assume T2 is the total time interval in hours of which W2 hours is the time interval during 
which SUA level is < 6 mg/dL. For a subject to be considered a responder, the proportion of 
time that the SUA level is < 6 mg/dL during Treatment Periods 3 and 6 must be at least 80%. 
The proportion of time that the SUA level is < 6 mg/dL, i.e., percentage of non- 
hyperuricemic time, is calculated using the following formula: 
𝑊1 + 𝑊2 
𝑃𝑟𝑜𝑝𝑜𝑟𝑡𝑖𝑜𝑛 = 𝑇1 + 𝑇2 × 100 
A logistic regression model controlling for the distribution of baseline characteristics will be 
performed as supportive analysis. 
Summary tables of the percentage of responder (subjects who achieve and maintain reduction 
of SUA < 6 mg/dL for at least 80% of the time) in each treatment period will be provided by 
treatment group. Additionally, a summary table with the total time a subject has SUA values 
< 6 mg/dL will be provided for each treatment period by treatment group. 
Summary tables of the actual values and change from baseline for SUA results will be 
provided for each scheduled sampling time point by treatment group. Additionally, mean 
SUA level, reduction in mean SUA and percent reduction in mean SUA from baseline during 
Treatment Period 3 or Treatment Period 6 will be presented by treatment group. 
Secondary Efficacy Analyses 
All statistical tests in secondary endpoints for the comparison between SEL-212 and 
KRYSTEXXA will be performed using one-sided tests at a type 1 error rate level of α=5%. 
In addition, 90% confidence intervals for treatment differences between SEL-212 and 
KRYSTEXXA treatment groups will be computed. The efficacy analyses will be carried out 
based on the ITT and PP Sets. mITT analyses will be performed if appropriate. 
For assessment of SUA in the secondary efficacy analyses, summary tables of the number 
and percentage of subjects for each endpoint will be presented by treatment group, and the 
comparison between the treatment groups will be performed similar to the primary efficacy 
endpoint using a CMH-test considering the randomization stratum. 
For the health questionnaires, comparison with regards to change from baseline in health 
questionnaires will be performed using an ANCOVA with the respective change from 
baseline value as dependent variable, treatment group and the randomization stratum as 


PROPRIETARY AND CONFIDENTIAL 
PAGE 14 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
independent fixed factors and the baseline value as independent covariate. For each health 
questionnaire, summary tables of total scores or domain scores and subscale scores will be 
provided for each scheduled assessment time by treatment group. Additionally, summaries of 
the changes from baseline will be provided. 
The number and percentage of subjects reporting gout flares per 3-months period, i.e. 
Treatment Periods 1 to 3 and Treatment Periods 4 to 6, will be summarized by treatment 
group and will be tested using a CMH-test considering the randomization stratum. The 
frequency of gout flares will be summarized per 3-months period, i.e. for Treatment Periods 1 
to 3 and Treatment Periods 4 to 6 for each treatment and will be compared using ANOVA 
considering the randomization stratum and treatment as fixed factors. 
Comparison with regards to change of tender joints and swollen joints from baseline will be 
performed using an ANCOVA with the change from baseline value as dependent variable, 
treatment group and randomization stratum as independent fixed factors and the baseline 
number of tender joints and swollen joints as independent covariates, respectively. In case of 
non-normality, the non-parametric Wilcoxon test will be used for the comparison between the 
treatment groups. Summary tables of the number of tender joints and swollen joints for each 
assessment timepoint and for the change from baseline will be provided by treatment group, 
respectively. 
A subgroup analysis will be conducted for patients who receive “additional gout flare 
treatment” in each arm for these objectives. Details of this subgroup analysis will be provided 
in the SAP. 
Safety Analyses 
All AEs will be coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), 
using the most recent MedDRA Version. All AEs will be summarized by SOC and PT. An 
overall summary will be provided of the number and percentage of patients in each treatment 
group (SEL-212 and KRYSTEXXA) reporting TEAEs, serious TEAEs, treatment-related 
TEAEs, AESIs, TEAEs leading to withdrawal and TEAEs leading to death. The number and 
percentage of patients with TEAEs /serious TEAEs / AESIs / TEAEs leading to withdrawal / 
treatment-related TEAEs will be summarized by SOC and PT for each treatment group 
(SEL-212 and KRYSTEXXA). TEAEs will also be summarized by maximum intensity and 
causality. 
Laboratory data will be summarized by the type of laboratory test and will be presented for 
each scheduled visit stratified by treatment group (SEL-212 and KRYSTEXXA). Normal 
reference ranges and markedly abnormal results will be used in the summary of laboratory 
data. Data will be flagged according to the reference limits (High or Low), if applicable. 
Changes from baseline will be presented for each post-baseline visit. Shift tables of the 
number of patients with low/normal/high values at each scheduled post-baseline visit 
compared to the low/normal/high categorization at baseline will be provided by treatment 
group (SEL-212 and KRYSTEXXA). 
Summary tables of the actual values and changes from baseline will be provided for each 
vital sign parameter at each scheduled visit by treatment group (SEL-212 and 
KRYSTEXXA). 


PROPRIETARY AND CONFIDENTIAL 
PAGE 15 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
For each 12-lead ECG variable the actual value and the change from baseline will be 
summarized for the scheduled visits by treatment group (SEL-212 and KRYSTEXXA). 
Frequency tables of abnormal clinically significant evaluations as well as the number and 
percentage of patients with noteworthy QTcF/QTcB values (> 450, > 480 and > 500 ms) and 
of patients with noteworthy QTcF/QTcB changes from baseline (≥ 30 but <60; ≥ 60 ms) will 
be provided. 
Sample Size Determination 
The primary efficacy criterion in this study is defined as the percentage of subjects who 
achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during 
Treatment Period 3 and Treatment Period 6. The percentage of responders according to the 
above criterion is assumed to be 65% in the SEL-212 arm and 44% in the KRYSTEXXA 
arm. Using the Chi-square test for comparison between the SEL-212 arm and the 
KRYSTEXXA arm, and considering a one-sided α=5% and the statistical power of 80%, 
results in 69 subjects per treatment group. Taking into account that some subjects may be 
excluded from the mITT analyses, 75 subjects per treatment group will be randomized. For 
the sample size estimation, Chi-square test, instead of the Cochran-Mantel-Haenszel test, is 
used although the randomization will be stratified for tophus presence (yes/no) as there is no 
valid assumption of the distribution of this stratification variable within the eligible subject 
population. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 16 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE .......................................................................................................................... 1 
2. 
SYNOPSIS ............................................................................................................................... 4 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ..................... 16 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................... 20 
5. 
INTRODUCTION ................................................................................................................ 23 
5.1 
Gout and Refractory Gout .......................................................................................... 23 
5.2 
Symptoms of Gout ...................................................................................................... 23 
5.3 
Gout and Hyperuricemia: Exacerbation of Existing Comorbidities ........................... 24 
5.4 
Impact on Quality of Life ........................................................................................... 24 
5.5 
Approved  Therapies  for  Chronic  Gout  Refractory  to  Conventional 
Therapy ....................................................................................................................... 25 
5.6 
Unmet Medical Need .................................................................................................. 26 
6. 
STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 28 
6.1 
Study Objectives ......................................................................................................... 28 
6.1.1 
Primary Objective ..................................................................................... 28 
6.1.2 
Secondary Objectives ............................................................................... 28 
6.2 
Study Endpoints .......................................................................................................... 28 
6.2.1 
Primary Endpoint ...................................................................................... 28 
6.2.2 
Secondary Endpoints ................................................................................ 28 
6.2.3 
Safety Endpoints ....................................................................................... 29 
7. 
INVESTIGATIONAL PLAN .............................................................................................. 30 
7.1 
Overall Study Design.................................................................................................. 30 
7.1.1 
Screening Period ....................................................................................... 30 
7.1.2 
Treatment Period ...................................................................................... 30 
7.1.3 
Follow-Up Period ..................................................................................... 31 
7.2 
Number of Patients ..................................................................................................... 31 
7.3 
Treatment Assignment ................................................................................................ 31 
7.4 
Dose Adjustment Criteria ........................................................................................... 32 
7.4.1 
Safety Criteria for Adjustment or Stopping Doses ................................... 32 
7.4.1.1 
SEL-212 ............................................................................. 32 
7.4.1.2 
KRYSTEXXA ................................................................... 32 
7.4.2 
Criteria for Adjustment or Stopping Doses .............................................. 33 
7.5 
Criteria for Study Termination ................................................................................... 33 
7.6 
Study Rationale ........................................................................................................... 33 
7.6.1 
Rationale for the Study Design ................................................................. 33 
7.6.2 
Rationale for the Study Population ........................................................... 34 
7.6.3 
Rationale for the Selected Dose ................................................................ 34 
7.6.3.1 
Phase 1b Study with SEL-212 ........................................... 34 
7.6.3.2 
Phase 2 Study with SEL-212 ............................................. 35 
7.6.4 
Rationale for the Primary Efficacy Endpoint............................................ 35 
7.6.5 
Rationale for Secondary Efficacy Endpoints ............................................ 36 
7.7 
Benefits and Risks ...................................................................................................... 36 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ..................................................... 37 


PROPRIETARY AND CONFIDENTIAL 
PAGE 17 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
8.1 
Patient Inclusion Criteria ............................................................................................ 37 
8.2 
Patient Exclusion Criteria ........................................................................................... 37 
8.2.1 
Patient Completion and Withdrawal Criteria ............................................ 39 
8.2.1.1 
Screen Failures ................................................................... 39 
8.2.1.2 
Patient Completion ............................................................. 39 
8.2.1.3 
Enrolled Patient Withdrawal and 
Discontinuations ................................................................. 39 
9. 
TREATMENT OF PATIENTS ........................................................................................... 41 
9.1 
Description of Study Drug .......................................................................................... 41 
9.2 
Concomitant Medications and Therapies ................................................................... 41 
9.2.1 
Uric Acid Lowering Therapy .................................................................... 41 
9.2.2 
Anticoagulants Use ................................................................................... 42 
9.2.3 
Hormone Replacement Therapy ............................................................... 42 
9.2.4 
CYP3A4 Inducers and Inhibitors .............................................................. 42 
9.2.5 
Other Concomitant Medications ............................................................... 42 
9.3 
Treatment Compliance ................................................................................................ 42 
9.4 
Randomization and Blinding ...................................................................................... 42 
10. STUDY DRUG MATERIALS AND MANAGEMENT .................................................... 43 
10.1 
Study Drug .................................................................................................................. 43 
10.1.1 
SEL-212 .................................................................................................... 43 
10.1.2 
KRYSTEXXA .......................................................................................... 43 
10.2 
Study Drug Packaging and Labeling .......................................................................... 43 
10.3 
Study Drug Storage..................................................................................................... 43 
10.4 
Study Drug Preparation .............................................................................................. 43 
10.4.1 
SEL-037 Preparation................................................................................. 44 
10.4.2 
SEL-110.36 Preparation............................................................................ 44 
10.4.3 
KRYSTEXXA Preparation ....................................................................... 44 
10.5 
Premedication ............................................................................................................. 45 
10.5.1 
Gout Flares (Prevention and Treatment)................................................... 45 
10.5.2 
Premedication with Antihistamines and Steroids ..................................... 45 
10.6 
Administration ............................................................................................................ 46 
10.6.1 
SEL-212 .................................................................................................... 46 
10.6.2 
KRYSTEXXA .......................................................................................... 46 
10.7 
Study Drug Accountability ......................................................................................... 47 
10.8 
Study Drug Handling and Disposal ............................................................................ 47 
11. ASSESSMENT OF EFFICACY .......................................................................................... 48 
11.1 
Activity Assessment ................................................................................................... 48 
11.1.1 
Serum Uric Acid Assessment ................................................................... 48 
11.2 
Gout Assessment......................................................................................................... 48 
11.2.1 
Gout Flare Assessment ............................................................................. 48 
11.2.2 
Joint Assessment ....................................................................................... 48 
11.3 
Health Questionnaires: Patient Reported Outcomes and Quality of Life 
Assessment ................................................................................................................. 48 
11.3.1 
Health Assessment Questionnaire-Disability Index (HAQ-DI)................ 48 
11.3.2 
Provider Global Assessment of Disease Activity ..................................... 48 
11.3.3 
Short Form Health Survey 36 (SF-36)...................................................... 49 


PROPRIETARY AND CONFIDENTIAL 
PAGE 18 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
12. ASSESSMENT OF SAFETY............................................................................................... 50 
12.1 
Safety Parameters ....................................................................................................... 50 
12.1.1 
Demographic/Medical History ................................................................. 50 
12.1.2 
Concomitant Medications and Procedures................................................ 50 
12.1.3 
Vital Signs ................................................................................................ 50 
12.1.4 
Electrocardiogram (ECG) ......................................................................... 50 
12.1.5 
Weight and Height .................................................................................... 50 
12.1.6 
Physical Examination ............................................................................... 50 
12.1.7 
Tophus Assessment................................................................................... 50 
12.1.8 
Laboratory Assessments ........................................................................... 50 
12.1.8.1 
Hematology ........................................................................ 51 
12.1.8.2 
Blood Chemistry ................................................................ 51 
12.1.8.3 
Lipids ................................................................................. 51 
12.1.8.4 
Coagulation ........................................................................ 51 
12.1.8.5 
Urinalysis ........................................................................... 51 
12.1.8.6 
Anti-Drug-Antibodies ........................................................ 51 
12.1.8.7 
Serology ............................................................................. 51 
12.1.8.8 
Pregnancy Screen ............................................................... 51 
12.1.8.9 
Definition of Childbearing Potential and 
Acceptable Contraceptive Methods ................................... 52 
12.1.9 
Premedication Regimen ............................................................................ 53 
12.2 
Adverse and Serious Adverse Events ......................................................................... 53 
12.2.1 
Definition of Adverse Events ................................................................... 53 
12.2.1.1 
Adverse Event (AE) ........................................................... 53 
12.2.1.2 
Serious Adverse Event (SAE) ............................................ 53 
12.2.1.3 
Suspected Adverse Reaction .............................................. 53 
12.2.1.4 
Unexpected Adverse Events and Unexpected 
Suspected Drug Reaction ................................................... 54 
12.2.1.5 
Infusion Reactions / Adverse Events of Special 
Interest................................................................................ 54 
12.2.2 
Recording Adverse Events ....................................................................... 55 
12.2.2.1 
Adverse Event Term/Name/Description ............................ 55 
12.2.2.2 
Relationship to Study Drug ................................................ 55 
12.2.2.3 
Adverse Event Intensity/Severity Grading......................... 56 
12.2.2.4 
Assessment of Outcome ..................................................... 56 
12.2.2.5 
Action Taken with Study Drug .......................................... 57 
12.2.2.6 
Laboratory and Diagnostic Abnormalities as 
Adverse Events .................................................................. 57 
12.2.2.7 
Pregnancy ........................................................................... 57 
12.2.3 
Reporting Adverse Events ........................................................................ 58 
12.2.3.1 
Adverse Event Reporting Period ....................................... 58 
12.2.3.2 
SAE Reporting Procedures ................................................ 58 
12.2.3.3 
Regulatory Reporting Requirements for SAEs .................. 59 
12.2.3.4 
Reporting Safety Information to the IRB/IEC ................... 59 
12.2.4 
Follow-up of Adverse Events ................................................................... 59 
13. STATISTICS ......................................................................................................................... 61 


PROPRIETARY AND CONFIDENTIAL 
PAGE 19 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
13.1 
Sample Size Determination......................................................................................... 61 
13.2 
Analysis Populations ................................................................................................... 61 
13.2.1 
Screened / Randomized Set ...................................................................... 61 
13.2.2 
Safety Set (SS) .......................................................................................... 61 
13.2.3 
Intent-to-Treat (ITT) Set ........................................................................... 61 
13.2.4 
Modified ITT (mITT) Set ......................................................................... 62 
13.2.5 
Per Protocol Set ........................................................................................ 62 
13.3 
Protocol Deviations .................................................................................................... 62 
13.4 
Efficacy Analyses ....................................................................................................... 62 
13.4.1 
Primary Efficacy Endpoint ....................................................................... 62 
13.4.2 
Secondary Efficacy Endpoints and Analyses ........................................... 64 
13.4.3 
Subgroup Analyses ................................................................................... 66 
13.5 
Safety Analyses .......................................................................................................... 66 
13.5.1 
Extent of exposure .................................................................................... 66 
13.5.2 
Adverse Events / Adverse Drug Reactions ............................................... 66 
13.5.3 
Laboratory Assessments ........................................................................... 66 
13.5.4 
Vital Signs ................................................................................................ 67 
13.5.5 
ECG .......................................................................................................... 67 
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS................................................. 68 
15. QUALITY CONTROL AND QUALITY ASSURANCE .................................................. 69 
15.1 
Study Monitoring ........................................................................................................ 69 
15.2 
Audits and Inspections ................................................................................................ 69 
15.3 
Protocol Modifications ............................................................................................... 69 
16. ETHICS AND GOOD CLINICAL PRACTICE COMPLIANCE ................................... 70 
17. DATA HANDLING AND RECORDKEEPING ................................................................ 71 
17.1 
Data Management ....................................................................................................... 71 
17.1.1 
Case Report Forms ................................................................................... 71 
17.1.2 
Retention of Records ................................................................................ 71 
18. REPORTING STUDY RESULTS AND PUBLICATION POLICY ............................... 73 
19. LIST OF REFERENCES ..................................................................................................... 74 
20. APPENDICES ....................................................................................................................... 77 
APPENDIX A 
SCHEDULE OF ASSESSMENTS FOR PATIENTS 
RANDOMIZED TO SEL-212......................................................................... 78 
APPENDIX B 
SCHEDULE OF ASSESSMENTS: SEL-212 DOSING AND 
SUA DURING THE TREATMENT PERIOD ............................................. 80 
APPENDIX C 
SCHEDULE OF ASSESSMENTS FOR PATIENTS 
RANDOMIZED TO KRYSTEXXA .............................................................. 81 
APPENDIX D 
SCHEDULE OF ASSESSMENTS: KRYSTEXXA DOSING 
AND SUA DURING THE TREATMENT PERIOD .................................... 83 
LIST OF IN-TEXT TABLES 
Table 1: 
Investigational Product ................................................................................41 
LIST OF IN-TEXT FIGURES 
Figure 1: 
Study Schematic ..........................................................................................31 


PROPRIETARY AND CONFIDENTIAL 
PAGE 20 OF 84 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
4.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation or Specialist Term 
Definition or Explanation 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
cm 
centimeter 
CR 
Complete Response 
CRF 
case report form 
CRO 
contract research organization 
CT 
computed tomography 
CYP3A4 
Cytochrome P450, family 3, subfamily A 
d 
day 
dL 
deciliter 
DSMC 
Data and Safety Monitoring Committee 
EC 
Ethics Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EEA 
European Economic Area 
EOS 
End-of-Study 
ET 
Early Termination 
FAAN 
Food Allergy & Anaphylaxis Network 
FAS 
Full Analysis Set 
FSH 
Follicle Stimulating Hormone 
G6PD 
glucose-6-phosphate dehydrogenase 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
h 
hour 
HAQ-DI 
Health Assessment Questionnaire-Disability Index 
HbA1c 
hemoglobin A1c 
HBsAg 
hepatitis-B surface antigen 
hCG 
human chorionic gonadotropin 
Hct 
hematocrit 
HCVAb 
hepatitis-C antibody 
HDL 
high density lipoprotein 
Hgb 
hemoglobin 


PROPRIETARY AND CONFIDENTIAL 
PAGE 21 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Abbreviation or Specialist Term 
Definition or Explanation 
HIV 
human immunodeficiency virus 
I 
Improved 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
International Ethics Committee 
IND 
investigational new drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone releasing system 
IV 
intravenous 
kg 
kilogram 
LDL 
low-density lipoprotein 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
mg 
milligram 
mmHg 
millimeters of mercury 
MPV 
mean platelet volume 
MR 
Marked Response 
ms 
millisecond 
mTOR 
mammalian target of rapamycin 
NIAID 
National Institute of Allergy and Infectious Diseases 
NSAID 
non-steroidal anti-inflammatory drug 
PD 
pharmacodynamics 
PD 
Progressive Disease 
PEG 
polyethylene glycol 
PLA 
poly [D,L-lactide] 
Plt 
platelet 
PPS 
Per Protocol Set 
PR 
Partial Response 
PrGA 
Provider Global Assessment of Disease Activity 
PT 
Preferred Term 
PT 
prothrombin time 
QD 
once daily 
RA 
rheumatoid arthritis 
RBC 
red blood cell 
RCTC 
Rheumatology Common Toxicity Criteria 


PROPRIETARY AND CONFIDENTIAL 
PAGE 22 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Abbreviation or Specialist Term 
Definition or Explanation 
RDW 
red cell distribution width 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
Scr 
Screening Period 
SD 
Stable Disease 
SEL-212H 
high dose of SEL-212 
SEL-212L 
low dose of SEL-212 
SF-36 
Short Form Health Survey 
SOC 
System Organ Class 
SS 
Safety Set 
SUA 
serum uric acid 
SVP 
Synthetic Vaccine Particle 
TEAE 
treatment-emergent adverse event 
TID 
three times daily 
UE 
Unable to Evaluate 
ULN 
upper limit of normal 
ULT 
urate lowering therapy 
US 
ultrasound 
US FDA 
United States Food and Drug Administration 
USP 
United States Pharmacopeia 
WBC 
white blood cell 


PROPRIETARY AND CONFIDENTIAL 
PAGE 23 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
5. 
INTRODUCTION 
5.1 
Gout and Refractory Gout 
Gout is an intermittent inflammatory arthritis characterized by elevated uric acid levels and 
caused by the formation of urate crystals in joint fluid leading to intensely painful joint 
inflammation. Chronic hyperuricemia leads to further deposition of uric acid in soft tissues 
resulting in destructive arthritis and formation of tophi and renal calculi (Choi 2005, So 2008, 
Wortmann 2008). Gout is a common disease with increasing incidence, driven mainly by an 
aging population, with some contribution from the increasing prevalence of obesity and the use 
of diuretics (Choi 2006, Luk 2005). 
The incidence of gout increases as circulating uric acid levels increase (Campion 1987) and 
lowering circulating urate levels is a primary means of managing gout. The American College of 
Rheumatology guidelines recommend lowering uric acid level to at least below 6 mg/dL and 
preferably below 5 mg/dL (Khanna 2012a, Khanna 2012b). 
The progression of gout is believed to have 4 pathophysiological stages (Dalbeth 2011): 
1. Hyperuricemia without monosodium urate crystal deposition or gout 
2. Crystal deposition without symptomatic gout 
3. Crystal deposition with acute gout flares 
4. Advanced or severe gout, characterized by tophi, chronic gouty arthritis, and radiographic 
erosions 
 
Refractory gout is a serious condition affecting approximately 50,000 patients in the United 
States and is characterized by uric acid levels that are not adequately controlled by approved 
therapies. 
5.2 
Symptoms of Gout 
Symptoms and their development have a broad spectrum of severity. Most symptoms present as 
intermittent attacks or flares while others present as more severe, chronic disease affecting one or 
more joints with tophi, sometimes referred to as chronic tophaceous gouty arthropathy 
(Khanna 2012a). In chronic gout, tophi commonly develop in the fingers, hands, and feet around 
the olecranon, and under the skin on the ears, but may also develop in other tissues and organs 
such as the kidneys and heart valves (Ryan 2016). Pro-inflammatory cytokines and white cell 
debris are usually present in tophi, which suggest a state of chronic monosodium urate-crystal- 
stimulated inflammation (Dalbeth 2011). These tophi can erupt through the skin, become 
inflamed and painful, and discharge urate crystals and eventually may cause deformities and 
secondary osteoarthritis (Ryan 2016). They can infiltrate into the bone, causing bone erosion and 
joint damage (Dalbeth 2011). Additional complications include obstruction of the joint and 
infection as well as urolithiasis with uric acid stones or calcium oxalate stones (Ryan 2016). The 
presence of tophi is associated with more frequent flares, which may be so painful and 


PROPRIETARY AND CONFIDENTIAL 
PAGE 24 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
debilitating that they lead to joint replacement or surgical excision. Over time, flares become 
polyarticular, additive, and increase in severity (Brook 2010). 
5.3 
Gout and Hyperuricemia: Exacerbation of Existing Comorbidities 
The effect of chronic, severe, refractory gout on quality of life is more pronounced in patients 
with medical comorbidities as these complicate the therapeutic management of their symptoms 
and increase their risk of cardiovascular events and all-cause mortality. It is also well- 
documented that the presence of these comorbidities has a significant impact on patients’ 
physical functioning, healthcare utilization, and quality of life (Khanna 2012a). 
Chronic, uncontrolled gout and hyperuricemia are associated with metabolic disorders, type 2 
diabetes, hypertension, and renal and cardiovascular diseases (Strand 2012; Becker 2009; 
Chandratre 2013). There is strong evidence that shows hyperuricemia contributes to worse 
outcomes under these conditions, and there is increasing mechanistic, epidemiological, and 
clinical data to indicate that elevated serum uric acid (SUA) levels can exacerbate and contribute 
to the progression of comorbidities (Rock 2013; Mallamaci 2015). 
Data from 5707 patients in the National Health and Nutrition Examination Survey (NHANES) 
were obtained from 2007-2008, and prevalence of major gout comorbidities were correlated with 
hyperuricemia levels (Zhu 2012). This analysis revealed the presence of hypertension, chronic 
kidney disease, obesity, diabetes, nephrolithiasis, myocardial infarction, heart failure, and stroke 
was substantially higher in individuals with gout compared to those without gout. Furthermore, 
the prevalence of these comorbidities increased proportionally to the level of hyperuricemia, 
with the incidence of comorbidities being highest among individuals with both gout and 
hyperuricemia. 
5.4 
Impact on Quality of Life 
One longitudinal study in this patient population reports that approximately 70% of patients with 
chronic refractory gout have at least 1 tophus and an average of 7 flares per year. In a separate 
study of chronic refractory gout, patients self-reported more than 60% of these flares as crippling 
(Brook 2010). Symptoms of pain, limited mobility, and disability are debilitating and deeply 
affect physical function and emotional and social functioning, and disease severity correlates 
with a marked compromise in quality of life (Strand 2012, Becker 2009). 
The relationship between self-reported quality of life and disability and disease severity have 
been evaluated in multiple clinical studies. Over 100 subjects with chronic refractory gout 
evaluated using the Medical Outcomes Study Short Form-36 assessment, and results revealed 
that patients with chronic refractory gout have significantly lower subscales analogous to those 
of 75-year old individuals (Becker 2009). Specifically, disease severity, as characterized by 
number of flares in the past year, number of tender or swollen joints, or presence of tophi, 
significantly correlates with worse quality of life scores in all areas, which include bodily pain, 
general health, mental health, physical functioning and vitality. Subjects with comorbidities 


PROPRIETARY AND CONFIDENTIAL 
PAGE 25 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
experienced worse physical functioning. Notably, their scores did not improve over the 52-week 
period despite undergoing maximal medical management (Strand 2012). 
There is also evidence that gout affects workplace productivity, as studies in patients with 
chronic, refractory gout self-report work absences due to flares, losing 25.1 workdays on average 
per year. Another study specifically found employees with gout missed 4.56 more days of work 
per year than those without gout (Edwards 2011). 
Hospitalizations with a principal diagnosis of gout has steadily increased over the past 2 decades 
(Lim 2016). In contrast, hospitalizations due to rheumatoid arthritis (RA) has dramatically 
decreased over this same time period correlating with the development of effective biologic 
drugs to treat RA. In 2005, the number of hospitalizations due to gout exceeded the number of 
hospitalizations due to RA, and this gap has steadily increased. Hospitalization costs for gout and 
RA show a similar trend. Similarly, general population studies have shown a substantial 
reduction in premature death due in RA patients but not in gout patients (Rai 2016). The findings 
likely reflect lack of effective therapies for severe gout. 
Together, these data show that the burden of chronic, severe, refractory gout extends well 
beyond that of physical discomfort, affecting almost every domain of life thus stressing the 
seriousness of the disease and an unmet need for new therapies given its refractory nature. 
Lowering serum urate levels can prevent further deposition of urate crystals, thus leading to a 
reduction in flare incidence and resolution of existing tophi. The American College of 
Rheumatology guidelines recommend a target serum urate of less than 6 mg/dL for patients on 
urate lowering therapy, with a target of less than 5 mg/dL for patients with chronic, severe 
disease, because this level is associated with more rapid resolution of tophi (Dalbeth 2011). 
5.5 
Approved Therapies for Chronic Gout Refractory to Conventional Therapy 
An estimated 160,000 gout patients fail to normalize their levels of SUA, have symptoms that 
are uncontrolled with the currently available treatments aimed at lowering urate levels, or suffer 
from comorbidities that preclude their use of conventional therapies (Richette 2013, Strand 
2012). Lack of treatment options leads to unabated disease progression. 
Currently, conventional therapies for the treatment of gout involve the inhibition of uric acid 
production and the improvement of uric acid renal clearance. The administration of exogenous 
uricase, an enzyme not present in humans that converts uric acid into the water-soluble 
compound, allantoin, is used only in instances of gout that is refractory to first and second lines 
of therapy (Dalbeth 2011). 
There are 2 uricase products currently used to treat hyperuricemia: rasburicase (ELITEK®) and 
pegloticase (Krystexxa®). 


PROPRIETARY AND CONFIDENTIAL 
PAGE 26 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Rasburicase is a recombinant, unpegylated urate-oxidase enzyme produced by genetically 
modified S. cerevisiae. It is indicated for tumor lysis syndrome, and its use in treating gout is off- 
label. Its clinical use in gout is limited because it is highly immunogenic and has a short plasma 
half-life at approximately 18 to 24 hours, making it an unsuitable treatment for chronic refractory 
gout (Terkeltaub 2009). 
Pegloticase is a pegylated recombinant porcine- or baboon-derived uricase. It is currently the 
only FDA-approved product for the treatment of chronic gout refractory to conventional therapy 
(KRYSTEXXA Prescribing Information 2018). While its use is associated with improvements in 
musculoskeletal function, quality of life, and pain, only approximately 42% of patients maintain 
a target serum urate level less than 6 mg/dL after 6 months of the approved dose regimen of 
8 mg once every 2 weeks. The vast majority of patients (92%) develop anti-pegloticase 
antibodies. High titer antibodies appear to adversely affect the pharmacokinetics and 
pharmacodynamics of the enzyme and are associated with a decrease in therapeutic response and 
increased risk of infusion reactions. Approximately 26% of patients taking Krystexxa report 
infusion reactions, 6.5% experience anaphylaxis, and the incidence of infusion reactions 
correlate with high anti-pegloticase antibody titer. These adverse events are typically preceded 
by a loss of urate-lowering effects. 
In addition to infusion reactions and gout flares, the most common adverse reactions with 
Krystexxa are nausea, contusion, nasopharyngitis, constipation, chest pain, anaphylaxis, and 
vomiting. In the 2 pivotal trials, there were 4 reported cases of exacerbations of pre-existing 
congestive heart failure in subjects receiving Krystexxa every 2 weeks. 
The high rate of treatment failure and the potential for anaphylactic reactions have resulted in 
limited use of Krystexxa since its approval. 
5.6 
Unmet Medical Need 
Current, approved uricase products carry substantial safety risks associated with 
immunogenicity, including anaphylaxis, as well as reduced efficacy over time as antibodies 
develop against the exogenous enzyme. 
Selecta Biosciences has developed SEL-212, the first drug product designed to reduce or prevent 
an immunologic response and improve efficacy, safety, and tolerability of a uricase enzyme 
(pegadricase) in patients who require long-term treatment to manage symptoms and progression 
of chronic refractory gout. Selecta uses its proprietary, antigen-specific Synthetic Vaccine 
Particle (SVP) platform to encapsulate the approved immunomodulatory drug, rapamycin, to 
mitigate formation of anti-drug antibodies by inducing antigen-specific regulatory T cells. 
Selecta is leveraging its nanoparticle technology encapsulating rapamycin (SVP-rapamycin) with 
the goal of inducing durable antigen-specific immune tolerance to pegadricase, a pegylated 
uricase. Specifically, SEL-212, in its current formulation, is a combination intravenous drug 
product that consists of a pegylated recombinant uricase (pegadricase; SEL-037) and a 


PROPRIETARY AND CONFIDENTIAL 
PAGE 27 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
biodegradable nanoparticle containing rapamycin (SEL-110.36), a small molecule inhibitor of 
the mammalian target of rapamycin (mTOR) pathway. Pegadricase is derived from Candida 
utilis and metabolizes poorly soluble uric acid to the more soluble metabolite, allantoin. 
Administration of SEL-110.36 just prior to pegadricase is intended to induce immune tolerance 
to prevent the formation of anti-uricase antibodies that may compromise efficacy or safety of 
pegadricase. 
The development of SEL-212 remains focused on mitigating the formation of antidrug antibodies 
with the goal of providing a product with better efficacy and safety profiles in patients than the 
only approved available therapy. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 28 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Study Objectives 
6.1.1 
Primary Objective 
The primary objective of this study is to assess the reduction in SUA in patients treated with 
SEL-212 compared to KRYSTEXXA. 
6.1.2 
Secondary Objectives 
The secondary objectives of this study are to assess improvement of the following parameters in 
patients treated with SEL-212 compared to KRYSTEXXA: 
• Gout flares 
• SUA control 
• Joint tenderness and swelling 
• Quality of Life (QoL) 
6.2 
Study Endpoints 
6.2.1 
Primary Endpoint 
The primary endpoint of this study is the comparison in the percentage of patients on SEL-212 
vs. KRYSTEXXA who achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of 
the time during Treatment Period 3 and Treatment Period 6 
6.2.2 
Secondary Endpoints 
The secondary endpoints of this study are: 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve and 
maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment 
Period 6 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve and 
maintain reduction of SUA < 6 mg/dL for 100% of the time during Treatment Period 6 
• Comparison between patients on SEL-212 vs. KRYSTEXXA in pre-dose SUA values 
> 6 mg/dL during Treatment Periods 2-6 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change in health 
questionnaires 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare incidence per 3- 
month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare frequency per 3- 
month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from Baseline 
to Treatment Period 6 in number of tender joints 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from Baseline 
to Treatment Period 6 in number of swollen joints 


PROPRIETARY AND CONFIDENTIAL 
PAGE 29 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
6.2.3 
Safety Endpoints 
The safety endpoints of this study are: 
• Safety and tolerability of SEL-212 compared to KRYSTEXXA as assessed by AEs, 
serious AEs (SAEs), deaths, and discontinuations due to AEs 
• Additional safety assessments will include review and evaluation of laboratory testing 
including hematology, coagulation, chemistry, urinalysis; vital signs; 12-lead ECGs; and 
physical examination findings. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 30 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
7. 
INVESTIGATIONAL PLAN 
7.1 
Overall Study Design 
This study is a randomized, open-label, parallel-arm study to compare the safety and efficacy 
profiles of SEL-212 and KRYSTEXXA. Approximately 150 patients will be randomized 1:1 
prior to Baseline to receive treatment with SEL-212 or KRYSTEXXA for 6 months. Efficacy 
assessments, as measured by SUA levels, will be conducted at intervals that are appropriate to 
determine treatment effect differences, including at month 3 and month 6. Assessments of 
qualitative endpoints will be conducted on an assessor-blinded basis. Safety will be monitored 
throughout the study. 
The study will be divided into 3 study periods: Screening, Treatment, and Follow-up, described 
below. The study is depicted schematically in Figure 1. 
The total duration of participation in the study will range from approximately 26 to 31 weeks 
(184 to 219 days) for patients randomized to SEL-212 and approximately 28 to 33 weeks (198 to 
233 days) for patients randomized to KRYSTEXXA as follows: 
• Screening and/or washout and premedication period: up to 45 days (up to 6.5 weeks) 
• Treatment: 168 days (24 weeks) for SEL-212 KRYSTEXXA 
• Safety Follow-Up: 30 (+ 4) days after the date of last infusion 
o SEL-212: Last scheduled infusion on Study Day 140 
o KRYSTEXXA: Last schedule infusion on Study Day 154 
7.1.1 
Screening Period 
After providing written informed consent, the patient is considered enrolled in the study. Patients 
will be evaluated for inclusion during the Screening Period. For all patients, the standard 
Screening Period will be up to 45 days prior to Baseline. Concurrently with the Screening 
Period, a premedication period with colchicine of at least 7 days prior to Baseline for potential 
gout flare will be required for all subjects, and a washout period of at least 7 days will be 
required prior to Baseline for patients on any urate-lowering therapy (ULT). 
7.1.2 
Treatment Period 
The total duration of treatment will be 6 months. Eligible patients will be randomized 1:1 prior to 
Baseline to receive SEL-212 or KRYSTEXXA. 
Study patients in the SEL-212 arm will receive study drug every 28 days coinciding with Day 0 
of each Treatment Period for a total of up to 6 infusions of SEL-212. 
Study patients in the KRYSTEXXA arm will receive study drug according to the manufacturer’s 
prescribing information, i.e., every 14 days coinciding with Day 0 and Day 14 of each Treatment 
Period for a total of up to 12 infusions of KRYSTEXXA. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 31 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Prior to infusion, all patients will receive a standardized regimen of premedication to minimize 
the potential for infusion reactions during study drug administration. After completing the study 
drug infusions, patients will remain at the investigational site for at least 1 hour for safety 
assessments. 
Refer to Section 10 for details about study drug administration. 
 
With each dose, a blood sample will be drawn for assessment of SUA level immediately prior to 
infusion (ie, Time 0h) with SEL-212 or KRYSTEXXA, 1 hour after the infusion of the second 
component of SEL-212 or of KRYSTEXXA is completed. SUA levels will be assessed through 
additional post-infusion blood samples at pre-determined time points. Every effort will be made 
to obtain blood samples at the same time of day of each study visit. 
Gout flares will be assessed at every visit. QoL and joint swelling and tenderness will be 
assessed on Day 0 of Treatment Period 1 and 4, and at the end of Treatment Period 6. 
Assessments of qualitative endpoints (health questionnaires and joint assessment) will be 
conducted on an assessor-blinded basis. 
On dosing days, safety laboratory samples will be collected pre-infusion and per Schedule of 
Events in both the SEL-212 arm and the KRYSTEXXA arm. Concomitant medications and 
procedures and adverse events (AEs) will be monitored continuously during the study. 
7.1.3 
Follow-Up Period 
Patients will be followed for safety monitoring for 30 (+ 4) days after their final study drug 
infusion and will have an End of Study visit by telephone. Patients who terminate the study 
prematurely will have all Early Termination assessments performed. Patients who terminate the 
study prematurely who are unable to be on-site for the Early Termination visit will be contacted 
by telephone for safety follow-up. 
Figure 1: 
Study Schematic 
 
 
 
7.2 
Number of Patients 
The study will randomize approximately 150 patients with chronic refractory gout. 
 
7.3 
Treatment Assignment 
Patients will be randomized 1:1 to receive open-label treatment with SEL-212 or KRYSTEXXA. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 32 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
7.4 
Dose Adjustment Criteria 
Unless otherwise specified, study drug will be administered as described in Section 9 and 
Section 10. 
7.4.1 
Safety Criteria for Adjustment or Stopping Doses 
7.4.1.1 
SEL-212 
A patient randomized to treatment with SEL-212 will be withdrawn from study drug for meeting 
the following stopping rule: 
• In the SEL-212 arm: SUA level > 1.0 mg/dL measured at the Day 21 visit of Treatment 
Period 1 or SUA level > 6.0 mg/dL at the Day 21 visit of Treatment Periods 2, 3, 4, or 5 
 
The window for all Day 21 visits is -2/+1 days. 
 
If a Day 21 visit SUA value drawn within the protocol window is not available, but if a SUA 
value drawn at an unscheduled visit after the Day 21 window is available prior to dosing that is 
≤ 1.0 mg/dL during Treatment Period 1 or ≤ 6.0 mg/dL during Treatment Periods 2, 3, 4, or 5, 
the patient will not be required to be withdrawn from study drug and may be eligible to receive 
their subsequent dose. 
If 1) a Day 21 visit SUA value drawn within the protocol window is not available and no 
subsequent SUA results are available or 2) a Day 21 visit SUA value drawn within the protocol 
window is not available and a subsequent SUA drawn at an unscheduled visit after the Day 21 
window is > 1.0 mg/dL during Treatment Period 1 or > 6.0 mg/dL during Treatment Periods 2, 3, 
4, or 5, then the patient will be withdrawn from study drug based on the protocol deviation. 
If withdrawn from study drug, the patient will continue study visits to the end of Treatment 
Period 6. At the discretion of the Investigator, the patient will be permitted to return to urate 
lowering therapy 60 days after the patient’s last study drug treatment. Urate lowering therapy 
shall not be SEL-212 or KRYSTEXXA. 
7.4.1.2 
KRYSTEXXA 
A patient randomized to treatment with KRYSTEXXA and who has started receiving treatment 
with study drug will be withdrawn from study drug for meeting the following stopping rule: 
• In the KRYSTEXXA arm: SUA level > 6.0 mg/dL measured on 2 consecutive pre-dose 
measurements, based on the following assessments: 
o If a pre-dose SUA level is > 6.0 mg/dL, then the Investigator will have the option to 
schedule a second SUA measurement to occur 2 days before the next scheduled 
KRYSTEXXA dosing day. The pre-dose SUA collected on Day 0 of Treatment 
Period 1 shall not be used in determining whether to invoke the stopping rule. 
o If the second measured SUA level is > 6.0 mg/dL, then the Investigator will withdraw 
the patient from study drug per the stopping rule. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 33 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
o If the second measured SUA level is ≤ 6.0 mg/dL, the patient can proceed to dosing 
with KRYSTEXXA. However, SUA will be assessed on the day of dosing, per 
protocol, to be used determining consecutive pre-dose measurements for future 
stopping rules. 
 
If withdrawn from study drug, the patient will continue study visits to the end of Treatment 
Period 6. At the discretion of the Investigator, the patient will be permitted to return to urate 
lowering therapy 60 days after the patient’s last study drug treatment. Urate lowering therapy 
shall not be SEL-212 or KRYSTEXXA. 
7.4.2 
Criteria for Adjustment or Stopping Doses 
An independent Data and Safety Monitoring Committee (DSMC) will be formed by charter to 
assist in reviewing safety data and may provide recommendations to the Sponsor regarding study 
drug dose adjustment or study termination. 
7.5 
Criteria for Study Termination 
The study can be terminated at any time at the Sponsor’s sole discretion. Otherwise, the study 
will be terminated when all patients have completed follow-up assessments (Section 20) or the 
Sponsor or regulatory agency(ies) have determined there is an unacceptable risk to patients or 
additional dosing or procedures are not warranted or necessary. 
The study may be terminated at a particular investigational site under the following conditions: 
• The Investigator fails to enroll patients at an acceptable rate; 
• The Investigator fails to comply with pertinent regulations; 
• There is insufficient adherence (i.e., compliance) to the protocol; 
• Knowingly false information is submitted to the IRB, Sponsor or designee, or regulatory 
authorities. 
7.6 
Study Rationale 
7.6.1 
Rationale for the Study Design 
Study SEL-212/202 is a randomized, open-label, parallel-arm study to compare the safety and 
efficacy profiles of SEL-212 to KRYSTEXXA. 
A randomized, controlled study is the gold-standard for evaluation of efficacy in clinical 
research. Randomized, controlled studies are quantitative, comparative, controlled experiments 
in which treatment effect sizes may be determined with less bias than observational trials. 
Randomization is considered the most powerful experimental design in clinical trials: with other 
variables equal between groups, on average, any differences in outcome can be attributed to the 
intervention. 
The study will be conducted on an open-label treatment basis; therefore, all patients, 
Investigators, study personnel, and Sponsor personnel involved in the conduct of the study will 


PROPRIETARY AND CONFIDENTIAL 
PAGE 34 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
have access to the randomized treatment assignments. Only the assessments of qualitative 
endpoints (health questionnaires and joint assessment) will be conducted on an assessor-blinded 
basis. The open-label design was selected because of the substantial differences in administration 
of SEL-212 and KRYSTEXXA (Section 10) and the practicality of maintaining the treatment 
blind. The parallel arms involving active treatment will permit adequate statistical comparison of 
the groups for efficacy and safety signal detection. 
KRYSTEXXA was selected as the active comparator because it is approved for this patient 
population and because the exogenous protein carries similar risks to the SEL-037 component of 
SEL-212. 
7.6.2 
Rationale for the Study Population 
The selection of this study population (Section 8) is based primarily on the desired therapeutic 
indication that the Sponsor will seek. Other selection criteria were set in order to maximize the 
ability to detect efficacy signals while minimizing any undue risk to the enrolled patients. 
Therefore, the severity and refractoriness of the patient’s disease and SUA level are key 
Inclusion Criteria (Section 8.1). In order to enhance the safety of patients on treatment, key 
Exclusion Criteria involve history of severe allergies or allergies to products that have similar 
features to the components of SEL-212, medical factors that might be exacerbated while on 
treatment, and prior exposure to experimental or marketed uricase therapies. 
7.6.3 
Rationale for the Selected Dose 
Dose selection for this study was based on safety and efficacy analyses of the clinical 
development program for SEL-212, beginning with a completed Phase 1b study 
(Study SEL-212/101: “A Phase I Single Ascending Dose Safety, Pharmacokinetic and 
Pharmacodynamics Study of SEL-212 in Subjects with Elevated Blood Uric Acid,” 
NCT02648269 ) and a currently ongoing Phase 2 study (Study SEL-212/201: “An Open Label 
Phase II Multiple Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 
Followed by Open Label Administration of SEL-037 in Subjects with Symptomatic Gout and 
Elevated Blood Uric Acid ,” NCT02959918). 
Doses of KRYSTEXXA selected for this study are based on the manufacturer’s approved 
labeling (KRYSTEXXA Prescribing Information 2018). 
7.6.3.1 
Phase 1b Study with SEL-212 
This was a Phase 1b double-blind, sequential, single-ascending-dose study (SEL-110; Cohorts 1, 
3, 5, and 7) combined with an open label, single-ascending-dose study (SEL-212; Cohorts 2, 4, 
6, 10, 12 and 14) to assess the safety, tolerability, and PK of SEL-212 and SEL-110. 
Additionally, the study was to assess the PD (ability to reduce SUA) and immunogenicity 
(ability to prevent ADAs to uricase and pegadricase) of SEL-212. Generally, patients were dosed 
on a cohort basis in an ascending stepwise manner. A control group was dosed with SEL-037 
only. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 35 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
In the Phase 1b study, patients (N = 64) with a serum uric acid level ≥ 6 mg/dL, with or without 
a history of gout, were administered SVP-rapamycin alone, pegadricase alone, or SEL-212 as an 
intravenous infusion. Mitigation of ADAs and a dose-dependent reduction in SUA levels 
occurred from study Day 1 to Day 30 in patients administered SEL-212 (data on file). There was 
no effect of SVP-rapamycin alone on SUA levels, and patients administered pegadricase alone 
developed ADAs that resulted in loss of SUA control by Day 14. SEL-212 was generally well 
tolerated at all dose levels. The maximum tolerated dose of SVP-rapamycin was determined to 
be 0.3 mg/kg. Data from this study were used to select additional dose levels of each component 
of SEL-212 for evaluation in the currently ongoing Phase 2 study SEL-212/201. 
7.6.3.2 
Phase 2 Study with SEL-212 
The Phase 2 study SEL-212/201 was designed as an open-label, multiple-dose clinical study of 
the combination drug, SEL-212, which was combined with an open-label, multiple-dose 
evaluation of pegadricase alone (SEL-037). Part A of the study consisted of three 28-day 
treatment cycles of SEL-212, which was then followed by Part B, which consisted of two 28-day 
treatment cycles of SEL-037 alone, with a primary objective of assessing the safety, tolerability, 
PK, PD of SEL-212 (i.e., the combination of SEL-110 and SEL-037). Part C of the study 
consisted of five 28-day treatment cycles of SEL-212 with a primary objective of assessing the 
safety, tolerability, PK, and PD of SEL-212. Additional assessments include the ability of 
SEL-212 to reduce serum uric acid levels and prevent anti-drug antibodies to uricase, PEG, and 
pegadricase. 
Overall, in the currently ongoing Phase 2 study with SEL-212, SUA levels have remained 
consistently below 6 mg/dL in 70% to 89% of evaluable Part A patients administered SEL-212 
once monthly for 3 months. Similarly, in Part C where SEL-212 was administered once monthly 
for 5 months, SUA levels have remained below 6 mg/dL in 61% to 75% of evaluable patients 
through the end of the fifth treatment period. All evaluable Part C patients who had SUA levels 
below 6 mg/dL at week 12 also had SUA below 6 mg/dL at Week 24. The control of SUA has 
occurred in the context of low incidences of infusion reactions, anaphylaxis, and gout flares as 
well as treatment-emergent adverse events (TEAEs) known to be potentially associated with 
sirolimus (Rapamune®). Data support a once monthly dosing regimen. 
7.6.4 
Rationale for the Primary Efficacy Endpoint 
The incidence of gout increases as circulating uric acid levels increase (Campion 1987) and 
lowering circulating urate levels is a primary means of managing gout. The American College of 
Rheumatology recommends lowering urate levels to a target of less than 6 mg/dL at minimum 
(Khanna 2012a) to improve the signs and symptoms of gout. 
Based on a proposed indication of treatment of chronic gout refractory to conventional therapy, 
the objectives of this study design are to assess the reduction in SUA in cohorts of adult subjects 
treated with SEL-212 compared to KRYSTEXXA. The proposed primary endpoint is 


PROPRIETARY AND CONFIDENTIAL 
PAGE 36 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve and 
maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment Period 3 and 
Treatment Period 6. 
7.6.5 
Rationale for Secondary Efficacy Endpoints 
Secondary endpoints were selected based on symptoms of chronic gout as well as quality of life 
as a consequence of chronic gout. Patients with severe, chronic gout are often refractory to oral 
therapies and often present with swollen or tender joints. Exacerbation of gout (flare) and joint 
tenderness and swelling impact a patients’ ability to maintain physical activity and functioning 
and correspond to quality of life. Several instruments will be used to assess quality of life and 
will include patient-reported outcomes, provider-reported assessments, and generalized 
assessments of overall quality of life. 
7.7 
Benefits and Risks 
Chronic gout refractory to conventional therapy is a rare and serious condition associated with 
increased mortality rate and significantly decreased quality of life and for which there are very 
limited treatment options. Data from the Phase 2 study SEL-212/201 provide preliminary clinical 
evidence demonstrating that SEL-212 is a substantial improvement over available therapy: 
• Substantially increased percentage of patients that maintain control of SUA while on 
therapy 
• Substantially reduced gout flare rate during therapy 
• Substantially reduced risk of infusion reactions 
• More convenient to and greater compliance by patients because of once monthly therapy 
• Acceptable safety at the doses to be studied in this Phase 2 study 
SEL-212 has the potential to be an unprecedented safe and effective treatment option for patients 
for which other treatment options are inadequate. The overall balance between benefits and risks 
appears acceptable for the SEL-202/202 study of SEL-212 in the intended population of patients 
with chronic gout refractory to conventional therapy. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 37 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1 
Patient Inclusion Criteria 
A patient must meet all of the following criteria to be eligible for this study: 
 
1. Has provided written informed consent prior to the conduct of any study specific 
procedures; 
2. Understands and is willing and able to comply with study requirements, including the 
schedule of follow-up visits; 
3. Has a history of symptomatic gout defined as: 
a. ≥ 3 gout flares within 18 months of Screening or 
b. Presence of ≥ 1 tophus or 
c. Current diagnosis of gouty arthritis 
4. At the Screening Visit: male age 21 – 80 years, inclusive, or female of non-childbearing 
potential age 21-80 years, inclusive, where non-childbearing potential is defined as: 
a. > 6 weeks after hysterectomy with or without surgical bilateral salpingo- 
oophorectomy or 
b. Post-menopausal (> 24 months of natural amenorrhea or in the absence of 
> 24 months of amenorrhea, 1 documented confirmatory FSH measurement) 
5. Has at Screening SUA ≥ 7 mg/dL, with chronic refractory gout defined as having failed 
to normalize SUA and whose signs and symptoms are inadequately controlled with 
xanthine oxidase inhibitors at the medically appropriate dose, or these drugs are 
contraindicated for the subject; 
6. Is negative for anti-PEG antibodies at Screening; 
7. Has not participated in a clinical trial within 30 days of the Screening Visit and agrees not 
to participate in a clinical trial for the duration of the study; 
8. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative 
antibodies to hepatitis C; 
9. Has adequate venous access and able to receive IV therapy; 
10. If applicable, has sufficiently recovered from any prior surgery to allow for successful 
completion of study procedures. 
8.2 
Patient Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study: 
 
1. Prior exposure to any experimental or marketed uricase (e.g., pegloticase [Krystexxa®], 
pegadricase [SEL-037], rasburicase [Elitek, Fasturtec]); 
2. History of anaphylaxis or severe allergic reactions to medications; 
3. History of any allergy to pegylated products, including, but not limited to, peginterferon 
alfa-2a (Pegasys®), peginterferon alfa-2b (PegIntron®), pegfilgrastim (Neulasta®), 
pegaptanib (Macugen®), pegaspargase (Oncaspar®), pegademase (Adagen®), peg-epoetin 


PROPRIETARY AND CONFIDENTIAL 
PAGE 38 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
beta (Mircera®), pegvisomant (Somavert®) certolizumab pegol (Cimzia®), naloxegol 
(Movantik®), peginesatide (Omontys®), and doxorubicin liposome (Doxil®); 
4. Known moderate and severe CYP3A4 inhibitors or inducers must be discontinued 
14 days before dosing and patients must remain off the medication for the duration of the 
study, including natural products such as St. John’s Wort or grapefruit juice; 
5. Drugs known to interact with Rapamune® such as cyclosporine, diltiazem, erythromycin, 
ketoconazole (and other antifungals), nicardipine (and other calcium channel blockers), 
rifampin, verapamil unless they are stopped 2 weeks prior to starting the trial and will not 
be used during the trial; 
6. Initiation or change in dose of hormone-replacement therapy for menopausal women less 
than 1 month prior to the Screening Visit or during the Screening Phase would be 
exclusionary. If after being on a stable dose of hormone-replacement therapy for 
1 month the patient may be considered for the study if she continues to meet all other 
inclusion and exclusion criteria; 
7. A gout flare during Screening that was resolved for less than 1 week prior to first 
treatment with study drug (exclusive of synovitis/arthritis), unless the patient has a 
history of inter-flare intervals < 1 week; 
8. Uncontrolled diabetes at Screening with HbA1c ≥ 8%; 
9. Fasting Screening glucose > 240 mg/dL; 
10. Fasting Screening triglyceride > 300 mg/dL; 
11. Fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; 
12. Glucose-6-phosphate dehydrogenase (G6PD) deficiency; 
13. Uncontrolled hypertension defined as blood pressure >170/100 mmHg at both Screening 
and 1 week prior to dosing; 
14. Individual laboratory values which are exclusionary 
o White blood cell count (WBC) < 3.0 x109/L 
o Serum aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) > 3x upper limit of normal (ULN) 
o Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 
o Hemoglobin (Hgb) < 9 g/dL 
o Serum phosphate < 2.0 mg/dL 
15. Patients whose arrhythmia is unstable on current treatment; 
16. History of coronary artery disease, including myocardial infarction or unstable angina, 
within the last 6 months; 
17. Congestive heart failure, New York Heart Association Class III or IV; 
18. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with 
evidence of prior myocardial infarction, clinically significant arrhythmia, or other 
abnormalities that, in the opinion of the investigator, are consistent with significant 
underlying cardiac disease; 


PROPRIETARY AND CONFIDENTIAL 
PAGE 39 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
19. History of significant hematological disorders or autoimmune disorders, and/or subject is 
immunosuppressed or immunocompromised; 
20. Subject is currently taking dabigatran (Pradaxa®), rivaroxaban (Xarelto®), 
edoxaban (Savaysa®), warfarin (Coumadin®), or apixaban (Eliquis®); 
21. Subject has received an inactivated vaccine in the previous 3 months with respect to the 
randomization date or has received a live virus vaccine in the previous 6 months with 
respect to the randomization date. Recombinant vaccines are excluded from this 
exclusion criterium; 
22. Subject is planning to receive any live or attenuated virus vaccination during the study. 
23. History of malignancy within the last 5 years other than basal skin cancer; 
24. Any condition, that in the opinion of the investigator, would be negatively affected by 
rapamycin; 
25. Subjects with a documented history of moderate or severe alcohol or substance use 
disorder within the 12 months prior to randomization; 
26. Subjects who, in the opinion of the investigator, present with a condition that would 
compromise their safety or that would make study completion unlikely. 
8.2.1 
Patient Completion and Withdrawal Criteria 
8.2.1.1 
Screen Failures 
A patient is considered enrolled in the study at the time of ICF signature. Any patient that is 
screened but not dosed will be considered a screen failure and the reason for failure will be 
documented. Within the 45-day screening window, out-of-range laboratory tests may be repeated 
up to 2 times before declaring a screen failure. After the 45-day screening window, patients can 
be re-screened once. 
8.2.1.2 
Patient Completion 
A patient will be considered to have completed the study when the patient has completed Safety 
Follow-up that occurs 30 (+ 4) days after the final dose of study drug. Enrolled patients who 
prematurely discontinue for any reason before completion of the study will be treated as outlined 
below in Section 8.2.1.3.1. 
8.2.1.3 
Enrolled Patient Withdrawal and Discontinuations 
8.2.1.3.1 
Withdrawal Procedures 
Early termination from the study occurs when an enrolled patient withdraws consent or the 
Investigator terminates a patient. The reason for withdrawal will be evaluated and recorded in the 
case report form (CRF) and source documents. Patients that withdraw will not be replaced. 
Patients may withdraw consent at any time. Reason(s) for withdrawal of consent, failure to return 
for the necessary visits, or termination from the study should be documented. All patients that 
withdraw early from the study, upon termination should have the Early Termination visit 


PROPRIETARY AND CONFIDENTIAL 
PAGE 40 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
assessments completed (i.e., End of Study assessments) (Section 20), if the assessments pose no 
risk to the patient and the patient allows such assessments. 
The Investigator should consult with the Sponsor/medical monitor prior to withdrawing any 
patient from the study. Since this is a multiple-dose study, once dosed, patients generally should 
not be terminated by the Investigator and should be followed through the end of Treatment 
Period 6, unless the patient withdraws consent or is lost to follow-up. In situations where 
continued participation in certain aspects of the study pose a risk to the patient, with consultation 
with the medical monitor, the Investigator should discontinue those procedures that pose a risk 
and should continue to collect data and conduct those assessments that do not put the patient at 
risk through the end of Treatment Period 6. Patients with compliance issues or major deviations 
that effect data quality will also continue to be followed through the end of Treatment Period 6 
collecting as much data on the patient as possible, unless otherwise indicated by the Sponsor. 
8.2.1.3.2 
Patients Lost To Follow-Up 
For patients to be considered as lost to follow-up, at least 3 contact attempts must be 
documented, of which the last must be a letter sent by a service that requires a delivery signature 
record (e.g., US Postal Service certified letter or Federal Express/UPS letter that requires 
signature of delivery). If the letter is undeliverable or no response is received within 7 days, the 
patient will be considered terminated due to lost to follow-up. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 41 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
9. 
TREATMENT OF PATIENTS 
9.1 
Description of Study Drug 
SEL-212 is comprised of 2 components: SEL-037 and SEL-110.36 (Table 1). Lyophilized 
SEL-037 supplied as 40 mg SEL-037, with phosphate buffer and mannitol as excipients, in a 
20 mL borosilicate glass vial with a chlorobutyl rubber stopper and an aluminum-plastic 
combination blue cap. SEL-110.36, a lyophilized powder containing synthetic biodegradable 
polymeric nanoparticles encapsulating rapamycin, with sucrose and Tris buffer 
(tris(hydroxymethyl)aminoethane) as excipients in a 20 mL, Type 1 borosilicate glass vial with a 
chlorobutyl rubber stopper and an aluminum-plastic combination white cap. Vials are filled to 
provide 10 mg of SEL-110.36. 
Table 1: 
Investigational Product 
Investigational Product 
Investigational Product 
Product Name: 
SEL-037 
SEL-110.36 
Dosage Form: 
Lyophilized powder for 
solution 
Lyophilized powder for 
suspension 
Unit Strength: 
40 mg SEL-037 per vial 
10 mg SEL-110.36 per vial 
Route of Administration: 
Intravenous infusion 
Intravenous infusion via syringe 
pump 
Physical Description: 
20 mL borosilicate glass vial 
with rubber stopper and 
aluminum-plastic blue 
combination cap 
20 mL borosilicate glass vial 
with rubber stopper and 
aluminum-plastic white 
combination cap 
Manufacturer: 
Manufactured for Selecta 
Biosciences by 3S and 
Emergent BioSolutions 
Manufactured for Selecta 
Biosciences by LSNE Contract 
Manufacturing 
 
9.2 
Concomitant Medications and Therapies 
Concomitant medications are permitted during this study unless otherwise restricted. 
Concomitant medications used in the 3 months prior to screening and during the study will be 
documented. 
9.2.1 
Uric Acid Lowering Therapy 
Uric acid lowering therapy (ULT) including, but not limited to allopurinol, febuxostat (Uloric®), 
probenecid, lesinurad (Zurampic®, Duzallo®), and benzbromarone ULT, are not permitted for 
use during the study. Patients will undergo a ULT washout period prior to dosing with study 
drug according to the schedules described in Section 20. 
Patients cannot have any prior exposure to or be presently be taking any experimental or 
marketed uricase therapy, as defined in Exclusion Criterion 1 (Section 8.2). 


PROPRIETARY AND CONFIDENTIAL 
PAGE 42 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
9.2.2 
Anticoagulants Use 
Anticoagulant use, as defined in Exclusion Criterion 20 (Section 8.2) is prohibited during the 
study. 
9.2.3 
Hormone Replacement Therapy 
Hormone replacement therapy in menopausal women should remain stable throughout the study. 
 
9.2.4 
CYP3A4 Inducers and Inhibitors 
The use of CYP3A4 moderate and severe inducers or inhibitors are prohibited 14 days prior to 
dosing and during the trial. Examples of moderate or severe inducers include, but are not limited 
to carbamazepine-Tegretol®, phenobarbital, phenytoin-Dilantin®, rifampin/rifampicin-Rifadis®, 
rifabutin-Mycobutin®, St. John’s Wort-Hypericum perforatum. Examples of moderate or severe 
inhibitors include, but are not limited to nefazodone-Serazone®, itraconazole-Sporanox®, 
ketoconazole-Nizoral®, voricinazole-Vfend®, atraznavir-Reyataz®, indinavir-Crixvan®, 
nelfinavir-Viracept®, ritonavir-Norvir, saquinavir-Invirase®, clarithromycin-Biaxin®, 
telithomycin-Ketek®, and grapefruit juice. 
9.2.5 
Other Concomitant Medications 
Patients on medications (e.g., antifungals and/or calcium channel blockers) that do not rely on a 
mechanism of action that is known to increase the level or effect of sirolimus (Rapamune®) are 
permitted to continue taking these medications prior to and during the study, and will not be 
noted as a protocol deviation. 
9.3 
Treatment Compliance 
Study drug will be administered in the controlled environment of a clinical research center. 
Direct observation of the administration of the study drug by study staff will ensure compliance. 
The date and time of the start and stop of drug administration and volume infused will be 
recorded. 
9.4 
Randomization and Blinding 
This is a randomized, open-label treatment study. Patients will be randomized 1:1 to receive 
SEL-212 or KRYSTEXXA. Randomization preferably should occur 7 days prior to the first dose 
of study drug (ie, Day -7). The randomization will be stratified for tophus presence (yes/no). 
Assessments of qualitative endpoints will be conducted on an assessor-blinded basis. 
Prior to study drug administration in Treatment Periods 2 through 6, the Investigator will 
determine a patient’s eligibility for treatment with study drug by evaluating the patient’s SUA 
level measured from the blood sample obtained from Day 21 of the most recently completed 
Treatment Period (SEL-212 cohort) or from the previous 2 measurements (KRYSTEXXA 
cohort). 
Study personnel will endeavor to safeguard the integrity of the qualitative endpoint blind to 
minimize bias in the study. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 43 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1 
Study Drug 
This is a randomized, open-label treatment study. The designated site representative will prepare 
study drug on the day of treatment. Prior to study drug administration in Treatment Periods 2 
through 6, the Investigator will determine a patient’s eligibility for treatment with study drug by 
evaluating the patient’s SUA level measured from the blood sample obtained from Day 21 of the 
most recently completed Treatment Period (SEL-212 cohort) or from the previous 2 
measurements (KRYSTEXXA cohort). 
10.1.1 
SEL-212 
SEL-212 is comprised of 2 components: SEL-037 and SEL-110.36. Refer to Section 9.1 for 
complete descriptions of the components. 
The dose level to be investigated in this study will be: 
 
• SEL-212: consisting of 0.15 mg/kg SEL-110.36 and 0.2 mg/kg SEL-037 
10.1.2 
KRYSTEXXA 
KRYSTEXXA (pegloticase injection) will consist of commercially available study drug. 
The dose level to be investigated in this study will be: 
• KRYSTEXXA: 8 mg (uricase protein) (KRYSTEXXA Prescribing Information 2018) 
10.2 
Study Drug Packaging and Labeling 
SEL-212 will be supplied in vials in individual cartons with cartons and vials unassigned to a 
patient. KRYSTEXXA will be packaged according to the manufacturer’s specifications. 
10.3 
Study Drug Storage 
Upon receipt of the SEL-037 vials at the clinical site, the vials should be stored in a secured way 
at 2°C to 8°C within the primary or secondary box container in order to protect the SEL-037 
from long-term light exposure. 
Upon receipt of the SEL-110.36 vials at the clinical site, the vials should be stored in a secured 
way at 2°C to 8°C within the primary or secondary box container in order to protect the 
SEL-110.36 from long-term light exposure. 
 
KRYSTEXXA will be handled and stored according to the manufacturer’s currently approved 
labeling (KRYSTEXXA Prescribing Information 2018). 
10.4 
Study Drug Preparation 
Doses of SEL-212 are calculated on a mg/kg basis according to a patient’s weight. For Treatment 
Period 1, the patient’s Screening weight will be used for dose preparation. For the remaining 


PROPRIETARY AND CONFIDENTIAL 
PAGE 44 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Treatment Periods, the patient’s weight at the Day 21 visit from the preceding Treatment Period 
will be used for dose calculation. Detailed procedures and examples of dose calculations and 
study drug preparation are provided in the Study Operations Manual. 
10.4.1 
SEL-037 Preparation 
Each vial of SEL-037 will be reconstituted with 6.9 mL of sterile water for injection, USP 
(United States Pharmacopeia or equivalent) which forms a 6 mg/mL concentrated solution and 
then the appropriate dose diluted for administration in 100 mL of room temperature 0.9% sodium 
chloride for injection, USP. The full resultant volume of the SEL-037-normal saline solution 
(100 mL saline + required volume of reconstituted SEL-037 + saline bag manufacturing overfill) 
will be administered in the allotted time. Reconstituted SEL-037 is stable at room temperature 
for 18 hours and the diluted SEL-037-normal saline solution for infusing should be used (i.e., 
infusion completed) within 6 hours of dilution. If not administered immediately, store 
refrigerated. The SEL-037 dose administration must be completed within 12 hours of the start of 
reconstitution. 
10.4.2 
SEL-110.36 Preparation 
Each vial of SEL-110.36 will be reconstituted with 4.9 mL of sterile water for injection, USP 
(United States Pharmacopeia or equivalent) which forms a 2 mg/mL suspension before being 
drawn into appropriate size syringe/syringes for IV infusion with syringe pump. Reconstituted 
SEL-110.36 is stable for 24 hours at room temperature at normal light conditions. SEL-110.36 
should be administered on the same day and as soon as possible after reconstitution. If not 
administered immediately, store refrigerated. The SEL-110.36 dose must be completely 
administered within 12 hours of the start of reconstitution. 
10.4.3 
KRYSTEXXA Preparation 
Doses of KRYSTEXXA will be calculated and prepared based on the manufacturer’s currently 
approved labeling (KRYSTEXXA Prescribing Information 2018). 
Under appropriate aseptic technique, 1 mL of KRYSTEXXA will be withdrawn from the vial 
and injected into a single 250 mL bag of 0.9% Sodium Chloride Injection, USP or 0.45% 
Sodium Chloride Injection USP for IV infusion. The solution will not be mixed or diluted with 
other drugs. Thorough mixing will be by inversion, not shaking. The diluted solution may be 
kept for 4 hours at 2°C to 8°C (36°F to 46°F) and at room temperature (20°C to 25°C, 68°F to 
77°F). It is recommended that diluted solutions be stored under refrigeration, not frozen, 
protected from light, and used within 4 hours of dilution. 
Detailed procedures for study drug preparation are provided in the Study Operations Manual. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 45 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
10.5 
Premedication 
10.5.1 
Gout Flares (Prevention and Treatment) 
All patients that meet all inclusion and exclusion criteria will be premedicated for gout flare 
prevention. The regimen will begin at least 7 days prior to the first dosing of study drug and 
continue for as long as the patient is participating in the clinical study. 
Patients not already taking colchicine will receive colchicine 1.2 mg as a single loading dose 
followed by 0.6 mg QD for the remainder of participation in the trial. If the patient cannot 
tolerate the loading dose level of 1.2 mg, then the patient will initiate and maintain colchicine at 
0.6 mg. Patients with a documented medical reason that describes a contraindication to 
colchicine will receive ibuprofen 600 mg TID or an equivalent NSAID unless the patient has a 
contraindication to NSAID. At the discretion of the Investigator, a proton pump inhibitor may be 
prescribed with the NSAID as gastric prophylaxis. Patients with documented medical reasons 
that describe contraindications to both colchicine and NSAIDs will receive no premedication for 
gout flare. 
Patients who began receiving a NSAID as gout flare prevention medication due to a 
contraindication to colchicine should continue to receive the NSAID during study participation. 
These medications will be supplied by the clinic. 
As gout flares are expected to occur despite preventative premedication, incidents of gout flare 
are to be recorded as an AE and treated at the discretion of the Investigator to provide adequate 
patient care. 
10.5.2 
Premedication with Antihistamines and Steroids 
All patients in the study will be pre-medicated with oral antihistamines and steroids as follows 
for prevention of infusion reactions: 
• Prednisone (40 mg) orally approximately 24 (± 12) hours prior to dosing (morning before 
study drug dosing on Day 0) 
• Fexofenadine (180 mg) orally approximately 12 (± 2) hours prior to dosing (evening 
before study drug dosing on Day 0) 
• Fexofenadine (180 mg) orally approximately 2 (± 1) hours prior to dosing (day of study 
drug dosing) 
• Methylprednisolone (40 mg) (or equivalent) IV approximately 1 (± 0.5) hours prior to 
dosing (day of study drug dosing) 
 
Refer to Section 12.2.1.5 for guidance on reducing the risk of infusion reactions and for 
managing infusion reactions. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 46 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
10.6 
Administration 
10.6.1 
SEL-212 
Before administration of SEL-212, patients will be premedicated with antihistamines and 
steroids as described in Section 10.5. 
Patients will receive treatment with SEL-212 on Day 0 of each Treatment Period for a total of 
6 doses of study drug. 
All study drugs should be administered through the same IV access. All blood samples should be 
drawn from an alternative venous access. 
If an infusion reaction occurs, Investigators are permitted to use concomitant medications or 
treatments deemed necessary to provide adequate patient care. Investigators should also utilize 
the infusion reaction lab kit provided in the Study Operations Manual to collect additional blood 
specimens. In the case of a Grade 3 or 4 infusion reactions occurring during an infusion, the 
administration of study drug should be immediately discontinued, and the affected patient should 
be treated according to the clinical trial site’s protocol for infusion reactions (e.g., monitoring, 
administration of antihistamines, corticosteroids, fluids and epinephrine, as clinically indicated). 
The reconstituted SEL-110.36 will be withdrawn from the vial and dosed via IV infusion with a 
syringe infusion pump utilizing an appropriately sized syringe. SEL-110.36 will be infused at a 
rate of 3.0 mL/hr for the first 30 minutes, then a rate adequate to deliver the remaining dose 
volume over a period of 60 minutes concurrently with 125 mL normal saline. Following the 
infusion of SEL-110.36, the main IV line must be flushed with normal saline prior to the start of 
the SEL-037 infusion. Refer to the Study Operations Manual for instructions regarding infusions 
for patients with medical history involving cardiovascular comorbidities. 
SEL-037 infusion will start within 15 minutes after completion of the SEL-110.36 infusion. 
SEL-037 will be infused via infusion pump over a time period of no less than 120 minutes. If an 
infusion reaction occurs during the administration of SEL-037, the infusion may be slowed, or 
stopped and restarted at a slower rate at the discretion of the physician. Following the infusion of 
SEL-037, the main IV line must be flushed with normal saline. 
The Investigator is permitted to modify the infusion parameters (decrease the rate of infusion or 
interrupt the infusion) ONLY if medically warranted in response to an AE. The Investigator will 
notify the unblinded medical monitor of any changes in infusion parameters. Detailed 
instructions for modifying the infusion parameters are included in the Study Operations Manual. 
10.6.2 
KRYSTEXXA 
Before administration of KRYSTEXXA, patients will be premedicated with antihistamines and 
steroids as described in Section 10.5. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 47 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Patients will receive treatment with KRYSTEXXA on Day 0 and Day 14 of each Treatment 
Period for a total of 12 doses of study drug. 
All study drugs should be administered through the same IV access. All blood samples should be 
drawn from an alternative venous access. 
KRYSTEXXA will administered based on the manufacturer’s currently approved labeling 
(KRYSTEXXA Prescribing Information 2018). Detailed instructions for study drug administration 
are provided in the Study Operations Manual. 
Before administration, the diluted solution of KRYSTEXXA should be allowed to reach room 
temperature, but never exposed to artificial heating (eg, hot water, microwave). The diluted 
solution of KRYSTEXXA should be administered by IV infusion via gravity feed, syringe-type 
pump, or infusion pump over no less than 120 minutes. Following the infusion of 
KRYSTEXXA, the main IV line must be flushed with normal saline. 
If an infusion reaction occurs, Investigators are permitted to use concomitant medications or 
treatments deemed necessary to provide adequate patient care. Investigators should also utilize 
the infusion reaction lab kit provided in the Study Operations Manual to collect additional blood 
specimens. In the case of a Grade 3 or 4 infusion reactions occurring during an infusion, the 
administration of study drug should be immediately discontinued, and the affected patient should 
be treated according to the clinical trial site’s protocol for infusion reactions (e.g., monitoring, 
administration of antihistamines, corticosteroids, fluids and epinephrine, as clinically indicated). 
10.7 
Study Drug Accountability 
Study drug will only be used as directed in the protocol. Study personnel will account for all 
vials of study drugs received, dispensed, and used for each patient, and vials returned. The date 
and time of reconstitution and dilution will be recorded. Used vials should be traceable back to 
the patient. The Investigator is responsible for the study drug accountability, reconciliation, and 
record maintenance. Refer to the Study Operations Manual for additional instructions. 
10.8 
Study Drug Handling and Disposal 
Unused, partially used and empty vials will be stored until the Sponsor or Sponsor’s 
representative instructs the site to return or dispose of the vials. Unused supplies will be returned 
or disposed of using appropriate documentation according to International Conference on 
Harmonization-Good Clinical Practice (ICH-GCP), local requirements, applicable Occupational 
Safety and Health Administration and Environmental Protection Agency regulations, and 
applicable study-specific procedures. Refer to the Study Operations Manual for additional 
instructions. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 48 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
11. 
ASSESSMENT OF EFFICACY 
11.1 
Activity Assessment 
11.1.1 
Serum Uric Acid Assessment 
The primary endpoint of this study is the comparison in the percentage of patients on SEL-212 
vs. KRYSTEXXA who achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of 
the time during Treatment Period 3 and Treatment Period 6. 
Serum samples for measurement of SUA will be collected according to the schedules described 
in Section 20. Methods used for processing samples and for measurement of SUA levels are 
described in the Study Operations Manual. 
11.2 
Gout Assessment 
11.2.1 
Gout Flare Assessment 
Gout flare will be assessed as part of TEAE collection with severity determined as described in 
Section 12.2.2.3. 
11.2.2 
Joint Assessment 
Tender and/or swollen joints will be counted. The following joints will be assessed: 
metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the hands; 
the metatarsophalangeal and interphalangeal joints of the feet; shoulder, elbow, wrist, knee, 
ankle, tarsus, sternoclavicular, and acromioclavicular joints. 
11.3 
Health Questionnaires: Patient Reported Outcomes and Quality of Life 
Assessment 
11.3.1 
Health Assessment Questionnaire-Disability Index (HAQ-DI) 
The HAQ-DI will be administered according to the schedules described in Section 20. 
 
The HAQ-DI, which includes the patient global assessment and pain scale, is an instrument that 
assesses fine movements of the upper extremity, locomotor activities of the lower extremity, and 
activities that involve both the upper and lower extremities. Standard scoring takes into account 
the use of aids and devices or assistance from another person. There are 20 items in 8 categories 
that represent a comprehensive set of functional activities: dressing, rising, eating, walking, 
hygiene, reach, grip, and usual activities. The stem of each item assesses a patient’s functional 
ability using their usual equipment during the past week. Each category contains at least 2 
specific sub-category questions. For example, under the category “walking,” patients are asked 
about their ability to walk outdoors on flat ground and to climb up 5 steps. 
11.3.2 
Provider Global Assessment of Disease Activity 
The Provider Global Assessment of Disease Activity (PrGA) will be conducted according to the 
schedules described in Section 20. The PrGA will be administered to assess the severity of the 


PROPRIETARY AND CONFIDENTIAL 
PAGE 49 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
patient’s disease on a scale from 0 (patient feels “very well”) to 100 (patient feels “very poor”). 
Lower scores indicate less severe disease. 
11.3.3 
Short Form Health Survey 36 (SF-36) 
The SF-36 will be administered according to the schedules described in Section 20. 
 
The SF-36 is a 36-item scale constructed to survey health status and quality of life (Ware 1992). 
The SF-36 assesses 8 health concepts: limitations in physical activities because of health 
problems; limitations in social activities because of physical or emotional problems; limitations 
in usual role activities because of physical health problems; bodily pain; general mental health 
(psychological distress and well-being); limitations in usual role activities because of emotional 
problems; vitality (energy and fatigue); and general health perceptions. The standard form of the 
instruments asks for patients to reply to questions according to how they have felt over the 
previous week. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 50 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
12. 
ASSESSMENT OF SAFETY 
12.1 
Safety Parameters 
12.1.1 
Demographic/Medical History 
Demographic and significant medical history will be documented according to the schedules 
described in Section 20. Medical history will be recorded up to the time of dosing. 
12.1.2 
Concomitant Medications and Procedures 
Concomitant medications and procedures will be documented according to the schedules 
described in Section 20. 
12.1.3 
Vital Signs 
Vital signs will be documented according to the schedules described in Section 20. 
 
Vital signs will include systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse 
(beats per minute, bpm), respiratory rate (breaths per minute), and temperature (°C). Blood 
pressure and heart rate will be recorded after at least 5 minutes of rest in a sitting position. 
12.1.4 
Electrocardiogram (ECG) 
A standard 12-lead ECG will be performed according to the schedules described in Section 20. 
 
12.1.5 
Weight and Height 
Weight (kg) and height (cm) will be performed according to the schedules described in 
Section 20. Height will be measured at Screening only. Weight will be used to calculate study 
drug dosage as described in Section 10.4. 
12.1.6 
Physical Examination 
Physical examinations will be conducted according to the schedules described in Section 20. 
Breast, rectal, and urogenital exams are not required unless warranted based on the clinical 
judgment of the patient’s medical history or current medical condition. The physical exam 
should be done by a physician or physician’s assistant or similarly qualified individual. 
12.1.7 
Tophus Assessment 
Assessment of the presence of tophi will be conducted according to the schedules described in 
Section 20. Patients will be stratified according to the presence of tophi (yes/no). 
At the time of tophus assessment (Section 20), selected investigational sites will photograph 
tophi on the hands and feet in a subset of subjects for illustrative purposes. Detailed procedures 
for conducting the photography are provided in the Study Operations Manual. 
12.1.8 
Laboratory Assessments 
All laboratory assessment will be conducted according to the schedules described in Section 20. 
Procedures for processing samples are included in the study operations manual. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 51 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
12.1.8.1 
Hematology 
Hematology assessments will include white blood cells (WBC) count with differential, red blood 
cell (RBC) count, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell 
distribution width (RDW), platelet (Plt) count, mean platelet volume (MPV). 
12.1.8.2 
Blood Chemistry 
Clinical chemistry assessments will include alkaline phosphatase, alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine, 
fibrinogen, glucose (fasting), phosphorous, and electrolytes (sodium, potassium, chloride, 
bi-carbonate, phosphate, and magnesium). 
 
The following clinical laboratory assessments will be conducted only during Screening to 
determine eligibility for study participation: anti-PEG antibodies and G6PD. 
12.1.8.3 
Lipids 
Lipid assessments will include total cholesterol, high-density lipoprotein (HDL), low-density 
lipoprotein (LDL), and triglycerides. 
12.1.8.4 
Coagulation 
Coagulation assessments will include prothrombin time (PT), activated partial thromboplastin 
time (aPTT), international normalized ratio (INR). 
12.1.8.5 
Urinalysis 
Urinalysis will include assessment of urinary protein, albumin, creatinine, pH, specific gravity, 
blood, glucose, ketones, bilirubin, leukocyte, esterase, WBC, RBC, crystals, casts (cast types), 
epithelial cells (renal and nonrenal), bacteria, mucus, and yeast. 
At Screening only, urine will be collected for pregnancy testing (Section 12.1.8.8). 
 
12.1.8.6 
Anti-Drug-Antibodies 
A blood sample for assessment of development of anti-drug-antibodies will be collected for 
possible future analysis. 
12.1.8.7 
Serology 
Serology screening will include human immunodeficiency virus (HIV) antibodies 1 and 2, 
hepatitis-B surface antigen (HBsAg), and hepatitis-C antibody (HCVAb). If HCVAb is positive, 
then HCV virus level will be determined. 
12.1.8.8 
Pregnancy Screen 
Samples for urine pregnancy testing (hCG) will be obtained. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 52 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Female partners of male patients who are of childbearing potential are required to practice an 
acceptable form of birth control to continue in the study and for 30 days after the last study drug 
administration. Male patients of reproductive potential who are having intercourse with female 
partners of childbearing potential must agree to use 2 forms of contraception, 1 of which must be 
a barrier method, during the study and for 90 days after the last study drug administration. 
Acceptable barrier methods include a condom and diaphragm. Acceptable forms of birth control 
for female partners of childbearing potential are non-hormonal and hormonal intrauterine 
devices, hormonal birth control pills, hormonal birth control patches, hormonal birth control 
injections, hormonal birth control implants. Spermicide used alone is not an acceptable method 
and must be used with another acceptable form birth control method. Abstinence is acceptable if 
consistent with the patient’s normal lifestyle. 
If a patient becomes pregnant after she begins taking study drug, the procedures in 
Section 12.2.2.7 should be followed. 
12.1.8.9 
Definition of Childbearing Potential and Acceptable Contraceptive Methods 
A woman is considered of childbearing potential (i.e., fertile), following menarche and until 
becoming post-menopausal unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. 
A postmenopausal state is defined as no menses for > 24 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used 
to confirm a post-menopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of > 24 months of amenorrhea, one confirmatory 
FSH measurement must be obtained or documented. 
For female partners of childbearing potential, the following methods of contraception, when used 
consistently and correctly, are considered reliable for participation in the study: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: oral, intravaginal, or transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, 
injectable or implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal; occlusion 
• Vasectomized partner (provided that partner is the sole sexual partner and that 
vasectomized partner has received medical assessment of the surgical success) 
• Sexual abstinence (refraining from heterosexual intercourse during the entire study 
period; the reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical study and the preferred and usual lifestyle of the patient) 


PROPRIETARY AND CONFIDENTIAL 
PAGE 53 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
12.1.9 
Premedication Regimen 
Refer to Section 10.5 for procedures about premedication regimens to prevent infusion 
associated reactions and gout flare. 
12.2 
Adverse and Serious Adverse Events 
12.2.1 
Definition of Adverse Events 
Definitions in this section are in accordance with 21 CFR 312.32. 
 
12.2.1.1 
Adverse Event (AE) 
An AE is any untoward medical occurrence associated with the use of a drug (i.e., study drug) in 
humans, whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a drug and does not imply any judgment about causality. An AE can 
arise with use of any drug or medicinal product. A treatment-emergent AE (TEAE) is an AE that 
starts or worsens at any time after initiation of study drug on Day 0 of Treatment Period 1 until 
the End of Study Visit (30 days after completion of the last dose of study drug). 
Patients will be considered enrolled in the study upon signing the ICF. During the Screening 
Phase (from time informed consent is signed to immediately before dosing) any clinically 
significant changes in the patient’s health will be recorded in the patient’s medical history and 
will not be considered as AEs. AEs will be collected from the time the patient is dosed (infusion 
is started) until the end of the End of Study Visit. SAEs will be collected from the time the 
patient signs informed consent until the End of Study Visit. 
12.2.1.2 
Serious Adverse Event (SAE) 
An SAE is any AE that occurs irrespective of study treatment assignment, if it satisfies any of 
these criteria: 
• Results in death; 
• Is life-threatening; 
• Requires inpatient hospitalization ≥ 24 hours or prolongs existing hospitalization; 
• Results in persistent or significant disability or incapacity or substantial disruption of the 
ability to conduct normal life functions; 
• Is a congenital anomaly or birth defect; 
• Is an important medical event that, based upon appropriate medical judgment, may 
jeopardize the patient or patient and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 
 
12.2.1.3 
Suspected Adverse Reaction 
A suspected adverse reaction is an AE for which there is a reasonable possibility that the drug 
caused the AE. For the purposes of IND safety reporting, “reasonable possibility” means there is 
evidence to suggest a causal relationship between the drug and the AE. Suspected adverse 


PROPRIETARY AND CONFIDENTIAL 
PAGE 54 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
reaction implies a lesser degree of certainty about causality than adverse reaction, which means 
any AE caused by a drug. 
12.2.1.4 
Unexpected Adverse Events and Unexpected Suspected Drug Reaction 
An AE or suspected adverse reaction (an AE where there is a reasonable possibility that the drug 
caused the event; suspected drug related) is considered “unexpected” if it is not listed in the 
SEL-212 Investigator’s Brochure or is not listed at the specificity or severity that has been 
observed. 
12.2.1.5 
Infusion Reactions / Adverse Events of Special Interest 
A study drug-related AE that occurs within 24 hours after initiation of study drug infusion will 
be assessed as an infusion reaction. An infusion reaction suspected to be anaphylaxis will be 
assessed according to the clinical criteria for the diagnosis of anaphylaxis based on the National 
Institute of Allergy and Infectious Diseases (NIAID) / Food Allergy & Anaphylaxis Network 
(FAAN) Symposium criteria (Sampson 2006). 
Infusion reactions will be managed and treated as described below. In addition to premedication 
with antihistamines and steroids (Section 10.5.2), the following steps will be implemented in this 
protocol to either reduce the risk of infusion reactions or manage infusion reactions. 
• Patients with immunoreactivity to PEG will be ineligible for the study 
• Patients with prior exposure to uricase therapy will be ineligible 
• Patients with a history of anaphylaxis or severe allergic reactions, angioedema, or 
previous infusion reactions will be excluded from the trial. 
• Study drug will be administered at controlled rates only in a healthcare setting and by 
healthcare providers sufficiently equipped and prepared to manage infusion reactions 
including anaphylaxis. 
• In case of infusion reaction, sites will perform specific assessments as specified in the 
Study Operations Manual. 
• Each patient will be observed for infusion reactions after dosing of study drug in the 
clinic for approximately 1 hour after the end of study drug infusion. Patients will be 
informed about the signs or symptoms of infusion reactions and will be instructed to 
notify the Investigator immediately if they believe they are experiencing a reaction. 
• Each patient shall remain for a minimum of 1 hour after the completion of infusion of 
study drug for a period of safety observation. 
• Only sites with immediate capability to appropriately respond to a reaction of this 
severity will be allowed to participate in the trial to reduce the risk to any patient. 
 
Adverse events of special interest (AESI) will be recorded specifically for occurrences of: gout 
flares, infections, viral infections, interstitial lung disease, stomatitis, infusion-related reactions 
including anaphylaxis, malignancies, renal failure; and the following lab tests, if deemed 


PROPRIETARY AND CONFIDENTIAL 
PAGE 55 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
clinically significant by the PI: hyperlipidemia, worsening of renal function tests, proteinuria, 
and leukopenia. 
12.2.2 
Recording Adverse Events 
Patients will be encouraged to spontaneously report any changes in health from the time of 
signing the ICF through completion of the study. Study staff will also inquire about any changes 
in the patient’s health. 
All AEs will be recorded in the source document and the CRF. It is the responsibility of the 
Investigator to review all documentation (e.g., hospital progress notes, laboratory, and 
diagnostics reports) for the presence of AEs and for a complete evaluation of known AEs. 
At minimum for each AE, the Investigator will evaluate and report the event 
name/term/description, onset (date and time), resolution (date and time), event severity/intensity, 
relationship to study drug, action taken in regard to study drug, whether the event is an SAE, and 
whether or not it caused the patient to discontinue the study. The event time is only required 
while the patient is in the clinic. 
During the Screening Phase (from time informed consent is signed to immediately before 
dosing) any clinically significant changes in the patient’s health will be recorded in the patient’s 
medical history and will not be considered as AEs. 
12.2.2.1 
Adverse Event Term/Name/Description 
The Investigator will attempt to establish a diagnosis of each AE based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis will be the AE term used to 
document the AE/SAE and not the individual signs/symptoms. 
12.2.2.2 
Relationship to Study Drug 
The Investigator is obligated to assess the relationship between study drug and the occurrence of 
each AE. The Investigator will use clinical judgment to determine the relationship. Alternative 
causes, such as natural history of the underlying diseases, concomitant therapy, other risk factors, 
and the temporal relationship of the event to the study drug will be considered and investigated. 
The Investigator will also consult the SEL-212 Investigator’s Brochure and/or Product 
Information for marketed products in the determination of his/her assessment. 
The Investigator will assess causality as to whether the event is related or not related to study 
drug based on the following definitions: 
• Not Related: If no valid reason exists for suggesting a relationship to study drug or the 
AE was more likely explained by causes other than study drug. 
• Unlikely to be Related: Onset of the event has a reasonable temporal relationship to study 
drug administration and although a causal relationship is unlikely, it is biologically 
plausible. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 56 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
• Possibly Related: Onset of the event has a strong temporal relationship to administration 
of the study drug and a causal relationship is biologically plausible 
• Related: The study drug dosing and AE were closely related in time and the AE may be 
explained by exposure to study product: e.g., known pharmacological effect or recurrence 
on re-challenge. 
 
There may be situations, particularly when an SAE has occurred, where the Investigator has 
minimal information to make an assessment in an initial SAE report. However, it is very 
important that the Investigator always makes an assessment of causality for every SAE prior to 
transmission of the SAE report. The Investigator may change his/her opinion of causality in light 
of follow-up information, amending the SAE report accordingly. Any assessment of causality 
made by the Investigator should also be documented in the patient’s source medical record. 
12.2.2.3 
Adverse Event Intensity/Severity Grading 
AEs will be classified according to the Rheumatology Common Toxicity Criteria, version 2.0 
(Woodworth 2007). Additional details of the criteria can be found in the study operations 
manual. 
• Grade 1 (mild): AE that is usually transient of short duration; or involves mild or minor 
symptoms which are of marginal clinical relevance; or is asymptomatic consisting of 
clinical or diagnostic observations alone; no intervention or only minimal treatment with 
non-prescription intervention was required. The event does not generally interfere with 
usual activities of daily living. 
• Grade 2 (moderate): AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living (e.g., shopping, 
laundry, transportation, or ability to conduct finances), causing discomfort but poses no 
significant or permanent risk or harm to the patient. 
• Grade 3 (severe): AE that is medically significant/important but not life-threatening; may 
require brief hospitalization to prevent the event from worsening; interrupts usual 
activities of daily living, or significantly affects clinical status, or may require intensive 
therapeutic intervention. 
• Grade 4 (life-threatening): An AE, and/or its immediate sequelae, which is associated 
with an imminent risk of death or which is associated with physical or mental disabilities 
that affect or limit the ability of a person to perform activities of daily living (eating, 
ambulation, toileting, etc.); disability may be persistent or result in significant disability, 
incapacity or limitation of self-care activities. 
 
For an assessment of anaphylaxis, the clinical criteria for the diagnosis of anaphylaxis will be 
based on the NIAID/FAAN Symposium criteria (Sampson 2006). 
12.2.2.4 
Assessment of Outcome 
The result or conclusion of the AE will be assessed and recorded by the Investigator as: 
• Fatal 


PROPRIETARY AND CONFIDENTIAL 
PAGE 57 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
• Not recovered/not resolved (the AE has not improved or patient has not recuperated). 
• Recovered/resolved (the AE has improved or patient has recuperated) 
• Recovered/resolved with sequelae (recuperated but retained pathological conditions 
resulting from the AE) 
• Recovering/resolving (the patient is improving but the AE has not yet resolved) 
• Unknown (not known, not observed, not recorded, or refused) 
12.2.2.5 
Action Taken with Study Drug 
The action taken with reference to study drug will be assessed by the investigator as: 
• Dose not changed (dose completed) 
• Dose interrupted (IV infusion was temporally modified by temporarily stopping the 
infusion; slowing of the rate of infusion should also be classified as interrupted) 
• Drug withdrawn (IV infusion was modified through termination of the infusion) 
A response option for increasing or decreasing the dose is not an available course of action in 
this study. 
12.2.2.6 
Laboratory and Diagnostic Abnormalities as Adverse Events 
Clinically significant abnormal laboratory findings or other abnormal diagnostic assessments 
(e.g., ECGs, vital signs) that are detected in dosed patients or that significantly worsen relative to 
baseline in dosed patients will be reported as AEs. Clinical significance is based on the 
Investigator’s judgment but will typically include findings that results in study withdrawal, result 
in active management of the patient, or are associated with clinical signs and symptoms. Since 
the study requires patients with elevated or abnormal SUA levels, abnormal SUA levels will 
typically not be an AE unless judged by the Investigator as being more severe than expected for 
the patient. 
12.2.2.7 
Pregnancy 
While pregnancy itself is not considered to be an AE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE and followed. The 
outcome of all pregnancies must be followed up and documented even if the patient is no longer 
a study patient. 
The Investigator, or his/her designee, will collect pregnancy information on every female who 
becomes pregnant while enrolled in this study and on every female partner of a male patient who 
becomes pregnant while the male partner is enrolled in this study. The Investigator will report to 
the Sponsor or Sponsor’s designee within 24 hours of learning of a patient’s or female partner of 
a patient’s pregnancy. In the case of a female partner of a male patient enrolled in the study 
becoming pregnant while the male patient is enrolled in this study, a separate pregnancy partner 
informed consent form will be completed by the patient’s partner. The patient or female partner 


PROPRIETARY AND CONFIDENTIAL 
PAGE 58 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
of a patient must also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the Sponsor or Sponsor Designee, as 
appropriate. Follow-up on the child will be to the first well-child visit. Any premature 
termination of the pregnancy will be reported. 
A spontaneous abortion or congenital abnormalities/birth defects will be considered SAEs and 
will be reported as such. Furthermore, any SAE occurring as a result of a post-study pregnancy 
and is considered reasonably related to the study drug by the Investigator, will be reported to the 
Sponsor. 
12.2.3 
Reporting Adverse Events 
12.2.3.1 
Adverse Event Reporting Period 
The study period during which AEs must be reported is from the time the patient is dosed until 
the 30 days after the last infusion of study drug. During the Screening Phase (from time informed 
consent is signed up to the time of dosing) any clinically significant changes in the patient’s 
health will be recorded in the patient’s medical history and will not be considered as AEs. 
Investigators are not obligated to actively seek AEs or SAEs in former study patients. However, 
if the Investigator learns of any SAE, including a death, at any time after a patient has been 
discharged from the study, and he/she considers the event reasonably related to the study drug, 
the Investigator should promptly notify the Sponsor. 
12.2.3.2 
SAE Reporting Procedures 
If SAEs occur, all Investigators should immediately, but not later than 24 hours of observing or 
learning of the event, complete and fax the SAE form to Syneos Health and Pharmacovigilance. 
Facsimile (for SAE only): 
 
 
Email (for SAE only): 
 
 
The Investigator will complete the SAE form and provide all case information available at the 
time of the initial report. The investigator must include the following mandatory case 
information: 
1. The patient identification number 
2. The event description 
3. The seriousness criteria 
4. The Investigator’s causality assessment 
 
The reporting Investigator must send the written and signed SAE report by facsimile or email, 
within 24 hours of observing, notification of, or learning of the SAE to Syneos Health and 
Pharmacovigilance as described above. Follow-up information regarding an SAE and the 
supporting data, including laboratory findings and discharge summaries, should be sent by 


PROPRIETARY AND CONFIDENTIAL 
PAGE 59 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
facsimile or email to Syneos Health and Pharmacovigilance within 24 hours of receipt of the 
information. 
If the Investigator does not have all information regarding an SAE, the Investigator will not wait 
to receive additional information before completing as much of the form as possible and 
notifying the safety group. The form will be updated when additional information is received. 
The Investigator will always provide at minimum: 1) AE term or event name/description, 
2) patient identifier, 3) an assessment of causality (Section 12.2.2.2). 
 
12.2.3.3 
Regulatory Reporting Requirements for SAEs 
The Sponsor or Sponsor representative will report fatal or life-threatening SAEs that are 
unexpected suspected adverse reactions to the relevant regulatory authorities within 7 calendar 
days, and non-fatal or life-threatening SAEs that are unexpected suspected adverse reactions 
within 15 calendar days as Investigational New Drug (IND) Safety Reports, in accordance with 
21 CFR 312.32. Prompt notification of SAEs by the Investigator to the appropriate project 
contact for SAE receipt is essential so that legal obligations and ethical responsibilities towards 
the safety of other patients are met. 
12.2.3.4 
Reporting Safety Information to the IRB/IEC 
The Investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to the Institutional 
Review Board (IRB)/Ethics Committee (EC). 
All Investigators involved in studies with this drug will receive a copy of each IND Safety 
Report. When an Investigator receives an IND Safety Report or other safety information (e.g., 
revised Clinical Investigator’s Brochure/Investigator’s Brochure), the responsible person 
according to local requirements is required to promptly notify his or her IRB. 
12.2.4 
Follow-up of Adverse Events 
The Investigator is required to proactively follow each patient and provide further information in 
regards to AEs and SAEs. All AEs and SAEs will be followed until 30 days after the last dose of 
study drug, resolution of the event, until the condition stabilizes, until the event is otherwise 
explained, or until the patient is lost to follow-up, whichever occurs earlier. Once resolved, the 
appropriate CRF entries and event reporting forms will be updated, as appropriate. 
All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts. The Investigator will ensure that follow-up includes any 
supplemental investigations as may be indicated to elucidate the nature and/or causality of the 
AE or SAE. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 60 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
The Sponsor or the Sponsor’s designee may request that the Investigator perform or arrange for 
the conduct of supplemental measurements and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the AE or SAE. The Investigator is obligated to assist. If a patient 
dies during participation in the study or during a recognized follow-up period, the Sponsor will 
be provided with a copy of any post-mortem findings, including histopathology. 
New or updated information will be recorded on the originally completed SAE forms, with all 
changes signed and dated by the Investigator. This information will also be entered into the CRF. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 61 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
13. 
STATISTICS 
Details of the statistical methods outlined in the protocol for this study, including the hierarchical 
ordering of the secondary endpoints, will be documented in a Statistical Analysis Plan (SAP) that 
will be finalized prior to first patient randomized. The SAP may add additional exploratory 
analyses; modifications to the planned analyses will be identified as such in the SAP. 
13.1 
Sample Size Determination 
The primary efficacy criterion in this study is defined as the percentage of subjects who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment Period 3 
and Treatment Period 6. 
The percentage of responders according to the above criterion is assumed to be 65% in the 
SEL-212 arm and 44% in the KRYSTEXXA arm. 
Using the Chi-square test for comparison between the SEL-212 arm and the KRYSTEXXA arm, 
and considering a one-sided alpha=5% and the statistical power of 80%, results in 69 subjects per 
treatment group. Taking into account that some subjects may be excluded from the modified 
Intent-to-Treat (mITT) analyses (Section 13.2.4), 75 subjects per treatment group will be 
randomized. For the sample size estimation, Chi-square test, instead of the Cochran-Mantel- 
Haenszel test, is used although the randomization will be stratified for tophus presence (yes/no) 
as there is no valid assumption of the distribution of this stratification variable within the eligible 
subject population. 
Sample size calculations were performed with the software package nQuery Advisor® Sample 
Size Calculator V. 8.2.1.0. 
13.2 
Analysis Populations 
13.2.1 
Screened / Randomized Set 
The Screened Set will include all patients who signed an informed consent. The Randomized Set 
will include all patients randomized. 
13.2.2 
Safety Set (SS) 
The Safety Set will include all patients who were administered any amount of study medication. 
Patients will be analyzed according to treatment received. The SS will be used for all analyses of 
safety endpoints and for the presentation of patients in all patient listings. 
13.2.3 
Intent-to-Treat (ITT) Set 
The Intent-to-Treat (ITT) Set will be used as the primary population for the analysis of efficacy. 
The ITT Set will include all randomized patients. Patients will be analyzed according to 
randomized treatment. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 62 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
13.2.4 
Modified ITT (mITT) Set 
The modified ITT (mITT) Set will include all randomized patients who were administered at 
least one complete dose of study medication and have at least one post-baseline assessment of 
SUA. Patients will be analyzed according to randomized treatment. The mITT will also be used 
for analyses of efficacy endpoints. 
13.2.5 
Per Protocol Set 
The Per Protocol Set (PPS) will include all patients who 1) were administered any amount of 
study medication, and 2) have completed at least 65% of the study dosing visits with or without 
receiving study drug (eg at least 4 of 6 TP Day 0 visits for patients receiving SEL-212 or at least 
8 of 12 TP Day 0 or Day14 visits for patients receiving Krystexxa) unless early termination from 
the study occurred after study drug withdrawal due to meeting stopping rules or due to an 
adverse event, or due to PI discretion (for example where at least one pre-dose SUA was >6 
mg/dL in the Krystexxa arm and patient was discontinued from study treatment), and 3) who 
have no major Protocol deviations (Section 13.3) affecting the primary efficacy assessments. 
Patients will be analyzed according to randomized treatment. 
 
13.3 
Protocol Deviations 
All protocol deviations related to study inclusion or exclusion criteria, conduct of the trial, 
patient management, dosing, and sampling procedures or patient assessment will be listed. The 
list of protocol deviations will be reviewed by the Sponsor, the principal investigator, the study 
statistician and the study pharmacokineticist and finalized before database lock. Determination of 
whether the deviation is major or minor will be based on the biasing impact of the deviation on 
the safety and efficacy data. 
13.4 
Efficacy Analyses 
13.4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is defined as: 
 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment 
Period 3 and Treatment Period 6 
 
The primary estimand will take into consideration the treatment policy strategy, ie, Treatment 
Period 6 (and also Treatment Period 3) assessments will be considered for all subjects in ITT 
independently whether the subject has completed the study treatment or has terminated early the 
study treatment. Additionally, the estimand based on the while-on-treatment strategy for dealing 
with study treatment terminators will be defined. For all used estimands of the primary efficacy, 
the estimator for the comparison between the treatment groups is defined as the difference in the 
proportion of responders between subjects receiving SEL-212 versus those receiving 
KRYSTEXXA during Treatment Periods 3 and 6. The statistical testing will be performed 
confirmatory using the Cochran-Mantel-Haenszel (CMH) test – considering the randomization 


PROPRIETARY AND CONFIDENTIAL 
PAGE 63 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
stratum of tophus presence (yes/no) – with a one-sided type 1 error rate α = 5%. In addition, 90% 
two-sided confidence intervals for the overall treatment difference between SEL-212 and 
KRYSTEXXA treatment groups without stratification will be computed. The analysis of the 
estimands will be carried out based on the ITT primarily. Supportive analyses will be performed 
on the mITT and the PP. For each defined estimand sensitivity analyses will be performed using 
different imputation approaches for missing values. Details of the applied approaches will be 
presented in the Statistical Analysis Plan. 
The SUA time curve will be used to estimate the proportion of time that the SUA level is below 
6 mg/dL. Based on the serum samples collected during Treatment Periods 3 and 6, an estimate of 
the time with SUA < 6 mg/dL can be determined by connecting each two neighboring data points 
with a straight line. If the SUA time curve goes above 6 mg/dL the linear interpolation method 
will be used to estimate the point in time at which the SUA time curve intercepts the line 
between the last SUA value < 6 mg/dL and the first value ≥ 6 mg/dL. 
The proportion of time that the SUA level is < 6 mg/dL will be computed by taking the ratio 
between the time during which the SUA level remains < 6 mg/dL (if necessary, using the linear 
interpolation method) and the entire time interval within Treatment Periods 3 and 6. 
Let T1 be the total time interval in hours for Treatment Period 3 of which W1 hours is the time 
interval during which SUA level is < 6 mg/dL. Similarly, for Treatment Period 6, assume T2 is 
the total time interval in hours of which W2 hours is the time interval during which SUA level is 
< 6 mg/dL. For a subject to be considered a responder, the proportion of time that the SUA level 
is < 6 mg/dL during Treatment Periods 3 and 6 must be at least 80%. The proportion of time that 
the SUA level is < 6 mg/dL, i.e., percentage of non-hyperuricemic time, is calculated using the 
following formula: 
𝑃𝑟𝑜𝑝𝑜𝑟𝑡𝑖𝑜𝑛 = 
 
𝑊1 + 𝑊2 
𝑇1 + 𝑇2 × 100 
 
A logistic regression model controlling for the distribution of baseline characteristics will be 
performed as supportive analysis. 
Summary tables of the percentage of responder (subjects who achieve and maintain reduction of 
SUA < 6 mg/dL for at least 80% of the time) in each treatment period will be provided by 
treatment group. Additionally, a summary table with the total time a subject has SUA values < 6 
mg/dL will be provided for each treatment period by treatment group. 
Summary tables of the actual values and change from baseline for SUA results will be provided 
for each scheduled sampling time point by treatment group. 
Additionally, mean SUA level, reduction in mean SUA and percent reduction in mean SUA from 
baseline during Treatment Period 3 or Treatment Period 6 will be presented by treatment group. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 64 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
• Mean SUA level is defined as the area under the SUA time curve (computed using the 
linear trapezoidal rule during Treatment Periods 3 and 6) divided by the corresponding 
time interval. 
• Reduction in mean SUA is computed by subtracting baseline SUA level from mean SUA 
during Treatment Period 3 and 6. 
• Percent reduction in the mean SUA from baseline is computed as the mean SUA level 
during Treatment Periods 3 and 6 minus baseline SUA level divided by baseline SUA 
level multiplied by 100 
 
13.4.2 
Secondary Efficacy Endpoints and Analyses 
The secondary endpoints of this study are: 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment 
Period 6 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for 100% of the time during Treatment Period 
6 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment 
Period 3 
• Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA who achieve 
and maintain reduction of SUA < 6 mg/dL for 100% of the time during Treatment Period 
3 
• Comparison between patients on SEL-212 vs. KRYSTEXXA in pre-dose SUA values 
> 6 mg/dL during Treatment Periods 2-6. The pre-dose SUA is collected on the dosing 
day prior to the dosing administration or it is collected at the visit where dosing would 
have occurred had the patient not been previously withdrawn from study drug. 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change in health 
questionnaires 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare incidence per 
3-month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of gout flare frequency per 
3-month period (Treatment Periods 1-3 and Treatment Periods 4-6) 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from 
Baseline to Treatment Period 6 in number of tender joints 
• Comparison between patients on SEL-212 vs. KRYSTEXXA of the change from 
Baseline to Treatment Period 6 in number of swollen joints 
 
All statistical tests in secondary endpoints for the comparison between SEL-212 and 
KRYSTEXXA will be performed using one-sided tests at a type 1 error rate level of α=5%. In 
addition, 90% confidence intervals for treatment differences between SEL-212 and 


PROPRIETARY AND CONFIDENTIAL 
PAGE 65 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
KRYSTEXXA treatment groups will be computed. The efficacy analyses will be carried out 
based on the ITT and PP Sets. mITT analyses will be performed if appropriate. 
Summary table of the number and percentage of subjects who achieve and maintain reduction of 
SUA < 6 mg/dL for at least 80% of the time during Treatment Period 6 will be provided by 
treatment group. The comparison between the treatment groups will be performed similar to the 
primary efficacy endpoint using a CMH-test considering the randomization stratum. 
Summary table of the number and percentage of subjects who achieve and maintain reduction of 
SUA < 6 mg/dL for 100% of the time during Treatment Period 6 will be provided by treatment 
group. The comparison between the treatment groups will be performed similar to the primary 
efficacy endpoint using a CMH-test considering the randomization stratum. 
Summary table of the number and percentage of subjects with pre-dose SUA values > 6 mg/dL 
during Treatment Periods 2-6 will be provided by treatment group. The comparison between the 
treatment groups will be performed similar to the primary efficacy endpoint using a CMH-test 
considering the randomization stratum. 
For the health questionnaires, comparison with regards to change from baseline in health 
questionnaires will be performed using an ANCOVA with the respective change from baseline 
value as dependent variable, treatment group and the randomization stratum as independent fixed 
factors and the baseline value as independent covariate. 
For each health questionnaire, summary tables of total scores or domain scores and subscale 
scores will be provided for each scheduled assessment time by treatment group. Additionally, 
summaries of the changes from baseline will be provided. 
The number and percentage of subjects reporting gout flares per 3-months period and overall, i.e. 
Treatment Periods 1-3 and Treatment Periods 4-6 and Period 1-6, will be summarized by 
treatment group and will be tested using a CMH-test considering the randomization stratum. 
The frequency of gout flares will be summarized per 3-months period and overall and by severity 
for each treatment and will be compared using ANOVA model with presences of tophus and 
treatment as fixed factors. In addition for periods 4-6 and 1-6, poisson regression model will be 
used with number of gout flares as independent variable, treatment and presence of tophus as 
fixed factor, and length of follow-up for each corresponding treatment period as covariate. 
Comparison with regards to change of tender joints from baseline will be performed using an 
ANCOVA with the change from baseline value as dependent variable, treatment group and 
randomization stratum as independent fixed factors and the baseline number of tender joints as 
independent covariate. In case of non-normality the non-parametric Wilcoxon test will be used 
for the comparison between the treatment groups. Summary tables of the number of tender joints 


PROPRIETARY AND CONFIDENTIAL 
PAGE 66 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
for each assessment timepoint and for the change from baseline will be provided by treatment 
group. 
Comparison with regards to change of swollen joints from baseline will be performed using an 
ANCOVA with the change from baseline value as dependent variable, treatment group and 
randomization stratum as independent fixed factors and the baseline number of swollen joints as 
independent covariate. In case of non-normality, the non-parametric Wilcoxon test will be used 
for the comparison between the treatment groups. Summary tables of the number of swollen 
joints for each assessment timepoint and for the change from baseline will be provided by 
treatment group. 
13.4.3 
Subgroup Analyses 
In the event of a prolonged gout flare which is not successfully managed, Investigators will most 
likely treat patients with corticosteroids which will have a downstream effect on the duration of 
flares, swollen/tender joint counts and QOL assessments. In order to better extrapolate the 
results, a subgroup analysis will be conducted for patients who receive “additional gout flare 
treatment” in each arm for these objectives. Details of this subgroup analysis will be provided in 
the SAP. 
13.5 
Safety Analyses 
13.5.1 
Extent of exposure: 
Frequency counts of number of patients who received all doses (i.e., completed study treatment) 
and descriptive statistics of doses and total cumulative doses by treatment group (SEL-212 or 
KRYSTEXXA) will be presented. 
13.5.2 
Adverse Events / Adverse Drug Reactions: 
All AEs will be coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), 
using the most recent MedDRA Version. All AEs will be summarized by SOC and PT. 
An overall summary will be provided of the number and percentage of patients reporting TEAEs, 
serious TEAEs, treatment-related TEAEs, AESIs, TEAEs leading to withdrawal, and TEAEs 
leading to death. 
The number and percentage of patients with TEAEs / serious TEAEs / TEAEs leading to 
withdrawal/treatment-related TEAEs will be summarized by SOC and PT for each treatment 
group (SEL-212 or KRYSTEXXA). AESIs will also be summarized. 
TEAEs will also be summarized by maximum intensity and causality. 
 
13.5.3 
Laboratory Assessments 
Laboratory data will be summarized by the type of laboratory test and will be presented for each 
scheduled visit stratified by treatment group (SEL-212 or KRYSTEXXA). Normal reference 


PROPRIETARY AND CONFIDENTIAL 
PAGE 67 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
ranges and markedly abnormal results will be used in the summary of laboratory data. Data will 
be flagged according to the reference limits (High or Low), if applicable. Changes from baseline 
will be presented for each post-baseline visit. Shift tables of the number of patients with 
low/normal/high values at each scheduled post-baseline visit compared to the low/normal/high 
categorization at baseline will be provided by treatment group (SEL-212 or KRYSTEXXA). 
13.5.4 
Vital Signs 
Summary tables of the actual values and changes from baseline will be provided for each vital 
sign parameter at each scheduled visit by treatment group (SEL-212 or KRYSTEXXA). 
13.5.5 
ECG 
For each 12-lead ECG variable the actual value and the change from baseline will be 
summarized for the scheduled visits by treatment group (SEL-212 or KRYSTEXXA). 
Frequency tables of abnormal clinically significant evaluations as well as the number and 
percentage of patients with noteworthy QTcF/QTcB values (> 450, > 480 and > 500 ms) and of 
patients with noteworthy QTcF/QTcB changes from baseline (≥ 30 but <60; ≥ 60 ms) will be 
provided. 
13.5.6 
Tophus Assessment 
For each tophus assessment variable (including total number, location, palpation and appearance) 
the actual value and the change from baseline will be summarized for the scheduled visits by 
treatment group (SEL-212 or KRYSTEXXA). 


PROPRIETARY AND CONFIDENTIAL 
PAGE 68 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties other than those noted below is prohibited. Upon the 
patient’s permission, medical information may be given to the patient’s personal physician or to 
other appropriate medical personnel responsible for the patient’s welfare. Data generated as a 
result of this study must be made available for inspection upon request by representatives of the 
US FDA, national and local health authorities, the Sponsor or its representatives, and by the 
IRB/EC (or equivalent). 


PROPRIETARY AND CONFIDENTIAL 
PAGE 69 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
15.1 
Study Monitoring 
In accordance with applicable regulations, ICH-GCP and procedures covering the study, a 
monitor will contact the site prior to the subject enrollment to review the protocol and data 
collection procedures with site staff. In addition, the monitor will periodically contact the site, 
including conducting on-site visits at an appropriate frequency to ensure data quality and to 
ensure the safety and rights of subjects are being protected. 
The investigator agrees to allow the monitor direct access to all relevant documents and to 
allocate his/her time and the time of his/her staff to the monitor to discuss findings and any 
relevant issues. 
15.2 
Audits and Inspections 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
quality assurance audits may occur during the study or after the study is complete. Authorized 
representatives of the Sponsor, the CRO conducting the study, a regulatory authority, an IRB 
may visit the site to perform audits or inspections to 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, ICH-GCP, and any applicable 
regulatory requirements. 
If an audit or inspection occurs, the Investigator and institution agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her staff to the auditor/inspector to discuss findings and any relevant issues. The 
Investigator should contact the Sponsor immediately if contacted by a regulatory agency about 
an inspection. 
15.3 
Protocol Modifications 
The initial protocol as well as all protocol amendments must be signed and dated by the 
Investigator and approved by the IRB prior to implementation of the original protocol and any 
amendment. The Principal Investigator must submit all protocol modifications to the IRB, as 
applicable for specific Investigators, or applicable local regulatory authority. The Sponsor or 
designee will submit protocol modifications to the FDA as needed. 
Departures from the protocol will be determined as allowable on a case-by-case basis or in event 
of an emergency involving subject safety. The Investigator or other physician in attendance must 
contact the Medical Monitor as soon as possible to discuss the circumstances of the emergency. 
The Medical Monitor, in concurrence with the Investigator, will decide whether the patient 
should continue to participate in the study. All protocol deviations and the reason for such 
deviations must be noted on the source document and in the CRF, and reported to the IRB as 
appropriate. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 70 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
16. 
ETHICS AND GOOD CLINICAL PRACTICE COMPLIANCE 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording and reporting trials that involve human patients. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
patients are protected, consistent with the principles that have their origin in the Declaration of 
Helsinki (World Medical Association 2013), and that the clinical trial data are credible. 
The study will be conducted under a US IND and all applicable US FDA and local laws and 
regulations and Good Clinical Practice Guidelines. The Investigator agrees to conduct the study 
in compliance with the current version of US Food Drug & Cosmetic Act, Section 21 CFR, 
Part 312, Subpart D (Responsibilities of Sponsor and Investigators), part 50 (Protection of 
Human Subjects), part 56 (Institutional Review Boards), the principles of the Declaration of 
Helsinki, and with the laws and regulations of the country in which the research is conducted in 
order to afford the greatest protection to the individual. The Investigator must fully adhere to the 
principles outlined in the “Guideline for Good Clinical Practice” International Conference on 
Harmonisation (ICH) Tripartite Guideline and, for studies conducted in the EU/European 
Economic Area (EEA) countries, the Investigator will ensure compliance with the EU Clinical 
Trial Directive [2001/20/EC]. 
This study will be conducted in full compliance with the Institutional Review Board (IRB) / 
Ethics Committee (EC) regulations in 21 CFR 56 and applicable local regulatory guidance, in 
accordance with ICH-GCP. IRB/EC approval for the investigation must be obtained before the 
study is initiated. Initial IRB/EC approval, and all materials approved by the IRB/EC for this 
study including the patient consent form and recruitment materials must be maintained by the 
Investigator and made available for inspection. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 71 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
17. 
DATA HANDLING AND RECORDKEEPING 
17.1 
Data Management 
17.1.1 
Case Report Forms 
Data for this study will be recorded via an EDC system using eCRFs. It will be transcribed by 
the site from the paper source documents onto the eCRF. 
The information collected on eCRFs must be identical to the corresponding information 
appearing in original source documents. There are no exceptions to this rule. In general, source 
documentation will be found in a chart maintained by qualified medical personnel in a hospital, 
clinic, or physician’s office. (The eCRF is not considered as source data for this trial). 
Accurate and reliable data collection will be assured by verification and cross check of the 
eCRFs against the Investigator’s records by the study monitor (source document verification), 
and the maintenance of a drug dispensing log by the Investigator. 
As a matter of regulations, the Investigator is responsible for the accuracy and authenticity of all 
clinical and laboratory data entered onto eCRFs. Prior to submission, each completed eCRF must 
be reviewed for accuracy by the Investigator, corrected as necessary, and then approved and e- 
signed. The Investigator’s e-signature serves to attest that the information contained on the 
eCRFs has been reviewed by the Investigator and is true and accurate. 
The eCRFs should be completed by the Investigator or a qualified designee from the site as soon 
as the data are available. Instructions for the completion of eCRFs will be provided. 
The eCRFs will be considered complete when all missing, incorrect, and/or inconsistent data 
have been accounted for. 
17.1.2 
Retention of Records 
An Investigator must maintain adequate records to include the disposition of the study 
medication(s) and adequate and accurate source documentation that record all observations and 
other data pertinent to the investigation on each patient in the study. These records are to include 
the case report forms (CRFs), source documentation, and supporting data, including, for 
example, signed and dated informed consent forms and medical records (including progress 
notes by the physician and/or other qualified medical personnel, the patient’s hospital and clinic 
chart[s], and the nurses’ notes). 
The FDA (21 CFR §312.62[c]) states that the Investigator shall retain the required records: 
 
a. For a period of 2 years following the date a marketing application is approved for the 
drug for the indication for which it is being investigated; or 
b. If no application is to be filed or if the marketing application is not approved for such 
indication, until 2 years after the investigation is discontinued and the FDA is notified. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 72 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
If neither a) nor b) applies, then the Investigator shall retain the required records for a minimum 
of 15 years after the completion or discontinuation of the study. 
For sites outside the US, the Investigator must comply with US FDA regulations and with the 
record retention policies of the relevant national and local health authorities. The Investigator 
must obtain the Sponsor’s written permission before disposing of any records. 
If the Investigator retires, relocates, or for any reason withdraws from the study, then the study 
records may be transferred to an acceptable person or institution with the written approval of the 
Sponsor. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 73 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
18. 
REPORTING STUDY RESULTS AND PUBLICATION POLICY 
Following analysis of the data and upon request by the Investigator, the Sponsor will supply a 
listing of site-specific treatment assignments, tabulated data, and statistical analysis, as 
appropriate. A summary of the study results will be provided to each Investigator following its 
release by the Sponsor. The Investigator will acknowledge receipt of any data listings or study 
results. 
Guidelines concerning publication of the results of this clinical study are contained within the 
formal Clinical Study Agreement associated with this protocol. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 74 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
19. 
LIST OF REFERENCES 
Becker MA, Schumacher HR, Benjamin KL, et al. Quality of life and disability in patients with 
treatment-failure gout. J Rheumatol. 2009;36(5):1041-1048. 
Brook RA, Forsythe A, Smeeding JE, Lawrence Edwards N. Chronic gout: epidemiology, 
disease progression, treatment and disease burden. Curr Med Res Opin. 2010;26(12):2813-2821. 
Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences 
in the Normative Aging Study. Am J Med. 1987 Mar;82(3):421-6. 
Chandratre P, Roddy E, Clarson L, Richardson J, Hider SL, Mallen CD. Health-related quality of 
life in gout: a systematic review. Rheumatology (Oxford). 2013;52(11):2031-2040. 
Choi HK, Mount DB, Reginato AM; American College of Physicians; American Physiological 
Society. Pathogenesis of gout. Ann Intern Med. 2005 Oct 4;143(7):499-516. 
Choi H. Epidemiology of crystal arthropathy. Rheum Dis Clin North Am. 2006 May;32(2):255- 
73, v. 
Dalbeth N, Schauer C, Macdonald P, et al. Methods of tophus assessment in clinical trials of 
chronic gout: a systematic literature review and pictorial reference guide. Ann Rheum Dis. 
2011;70(4):597-604. 
Edwards NL, Sundy JS, Forsythe A, Blume S, Pan F, Becker MA. Work productivity loss due to 
flares in patients with chronic gout refractory to conventional therapy. J Med Econ. 
2011;14(1):10-15. 
 
Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College 
of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and 
pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012a 
Oct;64(10):1431-46. 
Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, et al. 2012 American College 
of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory 
prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012b Oct;64(10):1447-61. 
Krystexxa Prescribing Information. Horizon Pharma. 2018. 
 
Lim SY, Lu N, Oza A, et al. Trends in gout and rheumatoid arthritis hospitalizations in the 
United States, 1993-2011. JAMA. 2016;315(21):2345-2347. 
Luk AJ, Simkin PA. Epidemiology of hyperuricemia and gout. Am J Manag Care. 2005 
Nov;11(15 Suppl):S435-42. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 75 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Mallamaci F, Testa A, Leonardis D, et al. A genetic marker of uric acid level, carotid 
atherosclerosis, and arterial stiffness: a family-based study. Am J Kidney Dis. 2015;65(2):294- 
302. 
Peterson DE, O’Shaughnessy JA, Rugo HS, et al. Oral mucosal injury caused by mammalian 
target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical 
practice. Cancer Medicine. 2016; 5(8):1897-1907. 
Rai SK, Avina-Zubieta JA, McCormick N, et al. Trends in gout and rheumatoid arthritis 
hospitalizations in Canada from 2000-2011. Arthritis Care Res. 2017;69(5):758-762. 
Richette P, Garay R. Novel drug discovery strategies for gout. Expert Opin Drug Discov. 2013 
Feb;8(2):183-9. 
Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev 
Rheumatol. 2013;9(1):13-23. 
Ryan LM. Gout. http://www.merckmanuals.com/professional/musculoskeletal-and-connective- 
tissue-disorders/crystal-induced-arthritides/gout. Accessed July 22, 2016. 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report--Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. 
So A. Developments in the scientific and clinical understanding of gout. Arthritis Res Ther. 
2008;10(5):221. 
Strand V, Khanna D, Singh JA, Forsythe A, Edwards NL. Improved health-related quality of life 
and physical function in patients with refractory chronic gout following treatment with 
pegloticase: evidence from phase III randomized controlled trials. J Rheumatol. 
2012;39(7):1450-1457. 
 
Terkeltaub R. Gout. Novel therapies for treatment of gout and hyperuricemia. Arthritis Res Ther. 
2009;11(4):236. 
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual 
framework and item selection. Med Care. 1992 Jun;30(6):473-83. 
Woodworth T, Furst DE, Alten R, Bingham CO 3rd, Yocum D, Sloan V, et al. Standardizing 
assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology 
Common Toxicity Criteria v.2.0. J Rheumatol. 2007 Jun;34(6):1401-14. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 76 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Wortmann RL Gout and hyperuricemia. In Kelley’s Textbook of Rheumatology, 8th ed.; 
Firestein, G.S; Budd, R.C.; Harris, E.D.; McInnes, I.B; Ruddy, S.; Sergent, J.S. Eds.; Elsevier: 
Philadelphia, 2008; pp 1481-1506. 
Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general 
population: NHANES 2007-2008. Am J Med. 2012;125(7):679-687.e671. 
World Medical Association. World Medical Association Declaration of Helsinki: ethical 
principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 77 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
20. 
APPENDICES 


APPENDIX A 
SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO SEL-212 
PROPRIETARY AND CONFIDENTIAL 
PAGE 78 OF 84 
 
 
 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D04 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D2820 
Informed Consent 
X 
Demographics 
X 
Inclusion/Exclusion 
X 
Medical History 
X 
Physical Examinations 
X5 
X6 
X6 
X6 
X6 
X6 
X6 
X5 
X5 
Vital Signs 
X 
X 
X7 
X7 
X7 
X7 
X7 
X7 
X 
X 
X 
Weight and Height8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tophus Assessment 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
Screening Labs9 
X 
Screening Lab: Anti-PEG-Ab 
X 
Urine Pregnancy Test 
X 
Washout: ULTs 
X10 
Patients will abstain from ULT use after the ULT washout period 
Document ULTs Discontinued 
X 
Dispense Premedication: Gout 
Flare and Infusion Reaction 
X 
Premedication: Gout Flare 
X11 
Continuously 
Premedication: Infusion 
Reaction 
X12 
X12 
X12 
X12 
X12 
X12 
Safety Labs: Chemistry13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Hematology14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Coagulation15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Lipids16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Urinalysis17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Anti-drug-Ab 
X 
X 
Gout Flare Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Joint Assessment (tenderness, 
swelling) 
X 
X 
X 
X 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 


Appendix A SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO SEL-212, CONTINUED 
PROPRIETARY AND CONFIDENTIAL 
PAGE 79 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D04 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D2820 
Health Questionnaires18 
X 
X 
X 
X 
Collect Sample for SUA 
X 
Refer to Schedule of Assessments in Appendix B for SUA Sample Collection during Treatment Period 
X 
Study Drug Administration 
Refer to Schedule of Assessments in Appendix B for Study Drug Administration during the Treatment Period 
Concomitant Medications / 
Procedures 
Continuously 
X 
X 
AE/SAE Collection 
X19 
X19 
Continuously 
X 
X 
1. Phone call at 30 (+ 4) days after the last study drug infusion for assessment of concomitant medications/procedures, AEs, and SAEs. 
2. Visit window at Day 21 of each Treatment Period is -2 days to +1 day. 
3. Visit window is -2 days. 
4. Study drug dosing to occur 28 days from the previous dose with a window of -4 days to +3 days of the intended dosing day. 
5. Full physical exam 
6. Directed physical exam 
7. Assess vital signs on Day 0 at Time 0 (pre-dose), within + 5 minutes after completion of infusion of the first component of study drug, and 1 hour (+ 5 minutes) after completion of 
infusion of the second component of study drug. 
8. Height measured once during Screening only. 
9. Screening labs to include: SUA, anti-PEG-antibodies, hepatitis B and C antibodies, human immunodeficiency virus 1/2 (HIV1/2), hemoglobin-A1c (HbA1c), glucose, triglycerides, LDL, 
glucose-6-phosphate dehydrogenase (G6PD), WBC, AST, ALT, Hgb, serum creatinine, and serum phosphate, urinalysis 
10. Begin ULT washout at least 7 days prior to Day 0 of Treatment Period 1. 
11. Begin colchicine 0.6 mg QD premedication at least 7 days prior to Day 0 of Treatment Period 1. Patients not already taking colchicine will receive colchicine 1.2 mg as a single loading 
dose followed by the 0.6 mg every day regimen. If the patient cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate and maintain colchicine at 0.6 mg. 
12. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (± 12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to 
study medication. 
13. Chemistry labs to include: Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine, fibrinogen, 
glucose (fasting), phosphorous, electrolytes (sodium, potassium, chloride, bi-carbonate, phosphate and magnesium). 
14. Hematology labs to include: white blood cells (WBC) count with differential, red blood cell (RBC) count, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet (Plt) count, mean platelet volume (MPV) 
15. Coagulation labs to include: prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR) 
16. Lipid labs to include: total cholesterol, HDL, LDL, triglycerides 
17. Urinalysis to include: urinary protein, albumin, creatinine, pH, specific gravity, blood, glucose, ketones, bilirubin, leukocyte, esterase, WBC, RBC, crystals, casts (cast types), epithelial 
cells (renal and nonrenal), bacteria, mucus, and yeast. 
18. Refer to Section 11.3 for Health Questionnaires. 
19. During Screening, SAE collection begins at time of signing informed consent. Non-serious AE will not be collected during Screening. 
20. Visit window is -2 days to +6 days 
Abbreviations: Ab: antibody; D (d): day; ECG: electrocardiogram; EOS: end of study; ET: early termination; h: hour; RCTC: Rheumatology Common Toxicity Criteria; Scr: 
Screening Period; SUA: serum uric acid; TP: treatment period; ULT: urate lowering therapy 


APPENDIX B 
SCHEDULE OF ASSESSMENTS: SEL-212 DOSING AND SUA DURING THE TREATMENT PERIOD 
PROPRIETARY AND CONFIDENTIAL 
PAGE 80 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Assessments 
Day 
Timepoint 
Treatment Periods: 1, 2, 4, and 5 
Treatment Periods 3 and 6 
D01 
D21 
D01 
D7 
D14 
D21 
D282 
0h 
~1.5h 
~3.5h 
~4.5h 
0h 
~1.5h 
~3.5 
~4.5h 
Premedicate: Infusion Reaction 
X3 
X 
Blood Sample: SUA 
X4 
X5 
X 
X4 
X5 
X 
X 
X 
X 
Study Drug Infusion (Component 1)6 
X ----------- 7 
X ------------ 7 
Study Drug Infusion (Component 2)8 
X7 ------------- X 
X7 ------------- X 
1. Study drug dosing to occur 28 days from the previous dose with a window of -4 days to +3 days of the intended dosing day. 
2. Treatment Period 6 only. 
3. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (± 12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) 
hours prior to study medication. 
4. Obtain sample prior to study drug infusion. 
5. Obtain sample 1 (± 0.25) hour after completion of infusion of Component 2. 
6. Component 1 will be SEL-110.36 for patients randomized to treatment with SEL-212. 
7. Before starting infusion with Component 2, a period of up to 15 minutes is permitted after completion of infusion of Component 1. 
8. Component 2 will be SEL-037 for patients randomized to treatment with SEL-212. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 81 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
APPENDIX C 
SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO KRYSTEXXA 
 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D04 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D2820 
Informed Consent 
X 
Demographics 
X 
Inclusion/Exclusion 
X 
Medical History 
X 
Physical Examinations 
X5 
X6 
X6 
X6 
X6 
X6 
X6 
X5 
X5 
Vital Signs 
X 
X 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
X 
X 
X 
Weight and Height8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tophus Assessment 
X 
X 
X 
12-Lead ECG 
X 
X 
X 
Screening Labs9 
X 
Screening Lab: Anti-PEG-Ab 
X 
Urine Pregnancy Test 
X 
Washout: ULTs 
X10 
Patients will abstain from ULT use after the ULT washout period 
Document ULTs Discontinued 
X 
Dispense Premedication: Gout 
Flare and Infusion Reaction 
X 
Premedication: Gout Flare 
X11 
Continuously 
Premedication: Infusion 
Reaction 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
X12 
Safety Labs: Chemistry13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Hematology14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Coagulation15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Lipids16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Urinalysis17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Labs: Anti-drug-Ab 
X 
X 
Gout Flare Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Joint Assessment (tenderness, 
swelling) 
X 
X 
X 
X 
Health Questionnaires18 
X 
X 
X 
X 


PROPRIETARY AND CONFIDENTIAL 
PAGE 82 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Appendix C, SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO KRYSTEXXA, CONTINUED 
 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D04 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D2820 
Collect Sample for SUA 
X 
Refer to Schedule of Assessments in Appendix D for SUA Sample Collection during Treatment Period 
X 
Study Drug Administration 
Refer to Schedule of Assessments in Appendix D for Study Drug Administration during the Treatment Period 
Concomitant Medications / 
Procedures 
Continuously 
X 
X 
AE/SAE Collection 
X19 
X19 
Continuously 
X 
X 
 
1. Phone call at 30 (+ 4) days after the last study drug infusion for assessment of concomitant medications/procedures, AEs, and SAEs. 
2. Visit window at Day 14 of each Treatment Period is -2 days to +3 days; visit window at Day 7 and 21 of TP3 and TP6 is -2 days to +3 days. 
3. Visit window is -2 days. 
4. Study drug dosing to occur 14 days from the previous dose with a window of -2 days to +3 days of the intended dosing day. 
5. Full physical exam 
6. Directed physical exam 
7. Assess vital signs on Day 0 and 14 at Time 0 (pre-dose), and 1 hour (+ 5 minutes) after completion of infusion. 
8. Height measured once during Screening only. 
9. Screening labs to include: SUA, anti-PEG-antibodies, hepatitis B and C antibodies, human immunodeficiency virus 1/2 (HIV1/2), hemoglobin-A1c (HbA1c), glucose, triglycerides, LDL, 
glucose-6-phosphate dehydrogenase (G6PD), WBC, AST, ALT, Hgb, serum creatinine, and serum phosphate 
10. Begin ULT washout at least 7 days prior to Day 0 of Treatment Period 1. 
11. Begin colchicine 0.6 mg QD premedication at least 7 days prior to Day 0 of Treatment Period 1. Patients not already taking colchicine will receive colchicine 1.2 mg as a single loading 
dose followed by the 0.6 mg every day regimen. If the patient cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate and maintain colchicine at 0.6 mg. 
12. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (± 12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to 
study medication. 
13. Chemistry labs to include: Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine, fibrinogen, 
glucose (fasting), phosphorous, electrolytes (sodium, potassium, chloride, bi-carbonate, phosphate and magnesium). 
14. Hematology labs to include: white blood cells (WBC) count with differential, red blood cell (RBC) count, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet (Plt) count, mean platelet volume (MPV) 
15. Coagulation labs to include: prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR) 
16. Lipid labs to include: total cholesterol, HDL, LDL, triglycerides 
17. Urinalysis to include: urinary protein, albumin, creatinine, pH, specific gravity, blood, glucose, ketones, bilirubin, leukocyte, esterase, WBC, RBC, crystals, casts (cast types), epithelial 
cells (renal and nonrenal), bacteria, mucus, and yeast. 
18. Refer to Section 11.3 for Health Questionnaires. 
19. During Screening, SAE collection begins at time of signing informed consent. Non-serious AE will not be collected during Screening. 
20. Visit window is -2 days to +6 days 
Abbreviations: Ab: antibody; D (d): day; ECG: electrocardiogram; EOS: end of study; ET: early termination; h: hour; RCTC: Rheumatology Common Toxicity Criteria; Scr: 
Screening Period; SUA: serum uric acid; TP: treatment period; ULT: urate lowering therapy 


PROPRIETARY AND CONFIDENTIAL 
PAGE 83 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
 
 
APPENDIX D 
SCHEDULE OF ASSESSMENTS: KRYSTEXXA DOSING AND SUA DURING THE TREATMENT 
PERIOD 
 
Assessments 
Day 
Timepoint 
Treatment Periods: 1, 2, 4, and 5 
Treatment Periods 3 and 6 
D01 
D14 
D01 
D7 
D14 
D21 
D282 
0h 
~2.0h 
~3.0h 
0h 
~2.0h 
~3.0h 
0h 
~2.0h 
~3.0h 
0h 
~2.0h 
~3.0h 
Premedicate: Infusion Reaction 
X3 
X3 
X 
X3 
 
Blood Sample: SUA 
X4 
X5 
X4 
X5 
X4 
X5 
X 
X4 
 
X5 
X 
X 
Study Drug Infusion 
X --------- X 
X --------- X 
X ---------- X 
X --------- X 
1. Study drug dosing to occur 14 days from the previous dose with a window of -2 days to +3 days of the intended dosing day. 
2. Treatment Period 6 only. 
3. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (± 12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) 
hours prior to study medication. 
4. Obtain sample prior to study drug infusion. 
5. Obtain sample 1 (± 0.25) hour after completion of infusion. 


PROPRIETARY AND CONFIDENTIAL 
PAGE 84 OF 84 
 
 
STUDY: SEL-212/202 
VERSION: 3.0 
EFFECTIVE DATE 
08 JUN 2020 
 
Revision History 
 
Version 
Reason for Change 
Date 
1.1 
• Clarifications, administrative corrections 
12 APR 2019 
2.0 
• Clarifications, administrative corrections 
• Updated study personnel information 
• Reduced Screening threshold SUA to 7 mg/dL to allow 
for enrollment of all patients with serum uric acid above 
the limit of solubility 
14 MAY 2019 
2.1 
• Clarifications, administrative corrections 
• Updated study personnel information 
• Added oral steroid premedication 24hr prior to dose 
03 FEB 2020 
3.0 
• Clarifications, administrative corrections 
• Updated study personnel information and sponsor address 
• Updated secondary endpoints 
• Updated statistical analysis population definitions 
• Updated primary efficacy population to be ITT 
• Updated statistical analysis approach for gout flare 
endpoint 
• Clarification of visit windows 
08 JUN 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

SAP_001.pdf: 
This document is confidential. 
SAP Version: 4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 1 of 41 
Statistical Analysis Plan 
Sponsor Name: Selecta Biosciences 
Protocol Number: SEL-212/202 
Protocol Title: A STUDY TO COMPARE THE EFFICACY OF SEL-212 TO KRYSTEXXA® IN GOUT 
PATIENTS REFRACTORY TO CONVENTIONAL THERAPY 
Protocol Version and Date: 1.0, 24 January 2019 
Protocol Version and Date: 2.0, 14 May 2019 
 Protocol Version and Date: 2.1, 03 Feb 2020 
Protocol Version and Date: 3.0, 15 Jun 2020 
Syneos Health Project Code: 7000459 
Author: 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Selecta Biosciences.  Acceptance 
of this document constitutes agreement by the recipient that no information contained herein will be 
published or disclosed without prior written authorization from an official of Selecta Biosciences.  However, 
this document may be disclosed to appropriate Institutional Review Board and Ethics Committees or duly 
authorized representatives of a national regulatory authority under the condition that they are requested 
to keep it confidential. In the event of an actual or suspected breach of this obligation, Syneos Health 
should be notified promptly. 
NCT #: NCT03905512


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 2 of 41 
Revision History 
Version # 
Date 
(DD-Mmm-YYYY) 
Document Owner 
Revision Summary 
1.0 
17-Apr-2019 
 
First Signed Version  
2.0 
16-Dec-2019 
 
• 
Added clarification of unblinding for Selecta 
during interim analysis  
• 
Added specified rules for primary response 
calculation, TEAE definition and Summary for 
tophus 
• 
Incorporated some edits per Selecta review 
comments including summarie for period 3 
SUA response 
 
2.1 
18-Apr-2020 
 
• 
Updated per protocol 2.1 
• 
Incorporated comments and requested  
additional analyses due to COVID-19 Pandemic  
2.2 
22-May-2020 
 
• 
Redefined primary efficacy population as ITT set 
and modified imputation for primary endpoint  
• 
Added clarification for PP population and major 
protocol deviation affecting efficacy  
3.0 
09-Jun-2020 
 
• 
Updated per protocol 3.0 and Incorporated 
some edits per Selecta review comments 
3.1 
04-Sep-2020 
 
• 
Added secondary efficacy endpoints related to 
mean SUA (sections 4.2, 7.2.1) 
• 
Added some clarification for PD (section 5.6) 
• 
Add missing data listing due to Covid-19 
(section 5.9) 
• 
Add log-rank test for subgroup patients with 
present and absence of tophus (section 6.1) 
4.0 
08-Sep-2020 
 
• 
Updated signature page by replacing 
 
 with 
 
 




Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 4 of 41 
Table of Contents 
Revision History ............................................................................................................................ 2 
Approvals .................................................................................................................................... 3 
 
Glossary of Abbreviations .................................................................................................... 7 
 
Purpose ................................................................................................................................ 9 
 
Study Objectives ................................................................................................................ 10 
 
Endpoints ........................................................................................................................... 20 
 
Analysis Sets ...................................................................................................................... 22 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 5 of 41 
 
Demographic, Other Baseline Characteristics and Medication .......................................... 24 
 
Efficacy ............................................................................................................................... 26 
 
Safety ................................................................................................................................. 32 
 
DSMC and Interim Analyses .............................................................................................. 34 
 
Reference List .................................................................................................................... 35 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 6 of 41 
 
Programming Considerations ............................................................................................. 36 
 
Quality Control ................................................................................................................... 41 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 7 of 41 
 
Glossary of Abbreviations 
Abbreviation 
Description 
Ab 
Antibody 
AE 
Adverse event 
AESIs 
Adverse events of special interest 
aPTT 
Activated partial thromboplastin time 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
eCRF 
Electronic Case report form 
CMH 
Cochran-Mantel-Haenszel 
CYP3A4 
Cytochrome P450, family 3, subfamily A 
d 
Day, Study day 
dL 
Deciliter 
DSMC 
Data and Safety Monitoring Committee 
ECG 
Electrocardiogram 
EOS 
End of Study 
ET 
Early Termination 
g 
gram 
G6PD 
Glucose-6-phosphate dehydrogenase  
GFR 
Glomerular Filtration Rate  
h 
Hour 
HAQ-DI 
Health Assessment Questionnaire-Disability Index 
Hct 
Hematocrit 
HDL 
High-density Lipoprotein 
Hgb 
Hemoglobin  
HIV  
Human immunodeficiency virus 
HbA1c 
Hemoglobin-A1c  
ICF 
Informed consent form 
LDL 
Low-density Lipoprotein 
INR 
International normalized ratio 
ITT 
Intent-to-Treat 
kg 
Kilograms 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligrams 
mITT  
Modified Intent-to-Treat 
ml 
Milliliters 
MPV 
Mean Platelet Volume 
NIAID 
National Institute of Allergy and Infectious Diseases 
PEG 
Polyethylene glycol 
Plt 
Platelet 
PrGA 
The Provider Global Assessment of Disease Activity 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 8 of 41 
Abbreviation 
Description 
PP 
Per Protocol 
PT 
Preferred Term 
QD 
Once Daily 
QoL 
Quality of life 
RBC 
Red Blood Cell 
RCTC 
Rheumatology Common Toxicity Criteria 
RDW 
Red Cell Distribution Width 
SAE  
Serious adverse event 
SAP 
Statistical Analysis Plan 
Scr 
Screening Period 
SF-36 
Short Form Health Survey 36 
SUA 
Serum Uric Acid 
SOC 
System Organ Class 
SS 
Safety Set 
TEAE 
Treatment-emergent adverse events 
TLFs 
Tables, Listings and Figures 
TP 
Treatment Period 
ULN 
Upper limit of normal 
ULT 
Uric acid lowering therapy 
WHO-DD 
World Health Organization Drug Dictionary 
WBC 
White Blood Cell 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 9 of 41 
 
Purpose 
The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary tables and 
figures which will be produced, and the statistical methodologies that will be used, are complete and 
appropriate to allow valid conclusions regarding the study objectives. 
 
Responsibilities 
Syneos Health will perform the statistical analyses and are responsible for the production and quality control 
of all tables, figures and listings.   
 
Timings of Analyses 
The primary analysis of safety and efficacy is planned after all patients complete the final study visit or 
terminate early from the study. 
An interim analysis will be conducted when 100% of patients are scheduled to have completed 3 months 
of study treatment (ie. scheduled to have completed Treatment Period (TP) 4 Day 0 visit). Since this is an 
open label study, unblinding of Syneos personel is not applicable when performing interim analyses. 
Selecta is blinded to all post dose serum uric acid (SUA) values and the primary endpoint throughout the 
study except that Selecta will be unblinded to the primary endpoint results at delivery of the interim 
analysis. As such, the interim analysis will be performed so that the study data will be collected once the 
timepoint criteria above is met, but the study data will be held by Syneos as a mitigation against 
significant COVID-19 pandemic disruption in the dataset.  The primary and secondary endpoints will not 
be calculated nor the interim analysis results delivered to Selecta until requested by Selecta due to 
significant disruption in the study or due to the last patient dosing having occurred in the study. Selecta 
will remain blinded to individual subject SUA data until the final analysis. Syneos’s biostats and 
programming study team will prepare all report summaries for the interim analyses. The purpose of the 
interim analysis is for business planning and so a protocol update including sample size adjustment is not 
applicable. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 10 of 41 
 
Study Objectives 
 
Primary Objective 
The primary objective is to assess the reduction of SUA in patients treated with SEL-212 compared to 
KRYSTEXXA®. 
 
Secondary Objective(s) 
Secondary objectives are to assess improvement of the following parameters in patients treated with 
SEL-212 compared to KRYSTEXXA®: 
• 
Gout flares 
• 
SUA control 
• 
Joint tenderness and swelling 
• 
Quality of life (QoL) 
 
 
Overall Study Design 
This study is a randomized, open-label, parallel-arm study to compare the safety and efficacy profiles of 
SEL-212 and KRYSTEXXA®. Approximately 150 patients will be randomized 1:1 prior to Baseline to 
receive treatment with SEL-212 or KRYSTEXXA® for 6 months. Efficacy assessments, as measured by 
SUA levels, will be conducted at intervals that are appropriate to determine treatment effect differences, 
including at month 3 and month 6. Assessments of qualitative endpoints will be conducted on an 
assessor-blinded basis. Safety will be monitored throughout the study. 
The study will be divided into 3 study periods: Screening, Treatment, and Follow-up, described below. 
The study is depicted schematically in the figure below: 
The total duration of participation in the study will range from approximately 26 to 31 weeks (184 to 219 
days) for patients randomized to SEL-212 and approximately 28 to 33 weeks (198 to 233 days) for 
patients randomized to KRYSTEXXA® as follows: 
• 
Screening and/or washout and premedication period: up to 45 days (up to 6.5 weeks) 
• 
Treatment: 168 days (24 weeks) for SEL-212 KRYSTEXXA® 
• 
Safety Follow-Up: 30 (+ 4) days after the date of last infusion  
o 
SEL-212: Last scheduled infusion on Study Day 140 
o 
KRYSTEXXA®: Last scheduled infusion on Study Day 154 
 
Patient Selection 
Approximately 150 patients will be selected to participate the study. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 11 of 41 
 
 
Inclusion Criteria 
A patient must meet all of the following criteria to be eligible for this study: 
1. Has provided written informed consent prior to the conduct of any study specific procedures; 
2. Understands and is willing and able to comply with study requirements, including the schedule of 
follow-up visits; 
3. Has a history of symptomatic gout defined as: 
a. ≥ 3 gout flares within 18 months of Screening or 
b. Presence of ≥ 1 tophus or 
c. Current diagnosis of gouty arthritis 
4. At the Screening Visit: male age 21 – 80 years, inclusive, or female of non-childbearing potential 
age 21-80 years, inclusive, where non-childbearing potential is defined as: 
a. > 6 weeks after hysterectomy with or without surgical bilateral salpingo-ooporectomy or 
b. Postmenopausal (> 24 months of natural amenorrhea or in the absence of > 24 months of 
amenorrhea, 1 documented confirmatory FSH measurement) 
5. Has at the Screening Visit SUA ≥ 7 mg/dL, with chronic refractory gout defined as having failed to 
normalize SUA and whose signs and symptoms are inadequately controlled with xanthine 
oxidase inhibitors at the medically appropriate dose or these drugs are contraindicated for the 
subject 
6. Is negative for anti-PEG antibodies at Screening; 
7. Has not participated in a clinical trial within 30 days of the Screening Visit and agrees not to 
participate in a clinical trial for the duration of the study; 
8. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative antibodies to 
hepatitis C; 
9. Has adequate venous access and able to receive IV therapy; 
10. If applicable, has sufficiently recovered from any prior surgery to allow for successful completion 
of study procedures. 
 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study: 
1. Prior exposure to any experimental or marketed uricase (e.g., pegloticase [Krystexxa®], 
pegadricase [SEL-037], rasburicase [Elitek, Fasturtec]) 
2. History of anaphylaxis or severe allergic reactions to medications; 
3. History of any allergy to pegylated products, including but not limited to, peginterferon alfa-2a 
(Pegasys®), peginterferon alfa-2b (PegIntron®), pegfilgrastim (Neulasta®), pegaptanib 
(Macugen®), pegaspargase (Oncaspar®), pegademase (Adagen®), peg-epoetin beta (Mircera®), 
pegvisomant (Somavert®) certolizumab pegol (Cimzia®), naloxegol (Movantik®), peginesatide 
(Omontys®), and doxorubicin liposome (Doxil®); 
4. Known moderate and severe CYP3A4 inhibitors or inducers must be discontinued 14 days before 
dosing and patients must remain off the medication for the duration of the study, including natural 
products such as St. John’s Wort or grapefruit juice. 
5. Drugs known to interact with Rapamune® such as cyclosporine, diltiazem, erythromycin, 
ketoconazole (and other antifungals), nicardipine (and other calcium channel blockers), rifampin, 
verapamil unless they are stopped 2 weeks prior to starting the trial and will not be used during 
the trial. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 12 of 41 
6. Initiation or change in dose of hormone-replacement therapy for menopausal women less than 1 
month prior to the Screening Visit or during the Screening Phase would be exclusionary.  If after 
being on a stable dose of hormone-replacement therapy for 1 month the patient may be 
considered for the study if she continues to meet all other inclusion and exclusion criteria. 
7. A gout flare during Screening that was resolved for less than 1 week prior to first treatment with 
study drug (exclusive of synovitis/arthritis), unless the patient has a history of inter-flare intervals 
< 1 week. 
8. Uncontrolled diabetes at Screening with HbA1c ≥ 8%; 
9. Fasting Screening glucose > 240 mg/dL 
10. Fasting Screening triglyceride > 300 mg/dL; 
11. Fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; 
12. Glucose-6-phosphate dehydrogenase (G6PD) deficiency;  
13. Uncontrolled hypertension defined as blood pressure >170/100 mmHg at both Screening and 1 
week prior to dosing 
14. Individual laboratory values which are exclusionary 
o 
White blood cell count (WBC) < 3.0 x109/L 
o 
Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x upper limit 
of normal (ULN) 
o 
Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 
o 
Hemoglobin (Hgb) < 9 g/dL 
o 
Serum phosphate < 2.0 mg/dL 
15. Patients whose arrhythmia is unstable on current treatment; 
16. History of coronary artery disease, including myocardial infarction or unstable angina, within the 
last 6 months; 
17. Congestive heart failure, New York Heart Association Class III or IV; 
18. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with evidence of 
prior myocardial infarction, clinically significant arrhythmia, or other abnormalities that, in the 
opinion of the investigator, are consistent with significant underlying cardiac disease; 
19. History of significant hematological disorders or autoimmune disorders, and/or subject is 
immunosuppressed or immunocompromised;  
20. Patient is currently taking dabigatran (Pradaxa®), rivaroxaban (Xarelto®), edoxaban (Savaysa®), 
warfarin (Coumadin®), or apixaban (Eliquis®); 
21. Subject has received an inactivated vaccine in the previous 3 months with respect to the 
randomization date or has received a live virus vaccine in the previous 6 months with respect to 
the randomization date. Recombinant vaccines are excluded from this exclusion criterium;  
22. Subject is planning to receive any live or attenuated virus vaccination during the study; 
23. History of malignancy within the last 5 years other than basal skin cancer; 
24. Any condition, that in the opinion of the investigator, would be negatively affected by rapamycin.  
25. Patients with a documented history of moderate or severe alcohol or substance use disorder 
within the 12 months prior to randomization. 
26. Patients who, in the opinion of the investigator, present with a condition that would compromise 
their safety or that would make study completion unlikely. 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 13 of 41 
 
Determination of Sample Size 
The primary efficacy criterion in this study is defined as the percentage of patients who achieve and 
maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment Period 3 and 
Treatment Period 6. The percentage of responders according to the above criterion is assumed to be 
65% in the SEL-212 arm and 44% in the KRYSTEXXA® arm. Using the Chi-square test for comparison 
between the SEL-212 arm and the KRYSTEXXA® arm, and considering a one-sided α=5% and the 
statistical power of 80%, results in 69 patients per treatment group. Taking into account that some 
patients may be excluded from the mITT analyses, 75 patients per treatment group will be randomized. 
For the sample size estimation, Chi-square test, instead of the Cochran-Mantel-Haenszel test, is used 
although the randomization will be stratified for tophus presence (yes/no) as there is no valid assumption 
of the distribution of this stratification variable within the eligible patient population. 
 
Treatment Assignment & Blinding 
This is a randomized, open-label treatment study. Patients will be randomized 1:1 to receive SEL-212 or 
KRYSTEXXA®. Randomization preferably should occur 7 days prior to the first dose of study drug (ie. Day 
-7).  The randomization will be stratified for tophus presence (yes/no). Assessments of qualitative 
endpoints will be conducted on an assessor-blinded basis. 
SEL-212 is comprised of 2 components: SEL-037 and SEL-110.36 with dose level 0.15 mg/kg and 0.2 
mg/kg respectively based on patient’s weight. The dose level for KRYSTEXXA® is 8 mg (uricase protein). 
Study personnel will endeavor to safeguard the integrity of the qualitative endpoint blind to minimize bias 
in the study. 
 
Administration of Study Medication 
The designated site representative will prepare study drug on the day of treatment. For Treatment Period 
1, patient’s weight at screening will be used to determine actual dose level for  SEL-212 cohort.  Prior to 
study drug administration in Treatment Periods 2 through 6, the Investigator will determine a patient’s 
eligibility for treatment with study drug by evaluating the patient’s SUA level measured from the blood 
sample obtained from Day 21 of the most recently completed Treatment Period (SEL-212 cohort) or from 
the previous 2 pre-dose measurements (KRYSTEXXA® cohort). 
Before administration of SEL-212 or KRYSTEXXA®, patients will be premedicated with antihistamines and 
steroids for prevention of infusion reactions. Patients in the SEL-212 cohort will receive treatment with 
SEL-212 on Day 0 of each Treatment Period for a total of 6 doses of study drug. Patients in the 
KRYSTEXXA®  cohort will receive treatment with KRYSTEXXA® on Day 0 and Day 14 of each Treatment 
Period for a total of 12 doses of study drug. 
All study drugs should be administered through the same IV access. All blood samples should be drawn 
from an alternative venous access. 
 
Study Procedures and Flowchart 
Scheduled assessment are presented by the following 4 tables on next a few pages: 
• 
Table A:  schedule of assessment for patients randomized to SEL-212 
• 
Table B:  schedule of assessments: SEL-212 dosing and SUA during the treatment period 
• 
Table C:  schedule of assessment for patients randomized to KRYSTEXXA® 
• 
Table D:  schedule of assessments: KRYSTEXXA® dosing and SUA during the treatment period  


 
 
 
 
 
This document is confidential. 
SAP Version: 4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 14 of 41 
TABLE A  SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO SEL-212 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D04 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D2820 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examinations 
X5 
 
X6 
 
X6 
 
X6 
 
 
 
X6 
 
X6 
 
X6 
 
 
 
X5 
 
X5 
Vital Signs 
X 
X 
X7 
 
X7 
 
X7 
 
 
 
X7 
 
X7 
 
X7 
 
 
X 
X 
 
X 
Weight and Height8 
X 
X 
 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Tophus Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Screening Labs9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Lab: Anti-PEG-Ab 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Washout: ULTs 
 
X10 
Patients will abstain from ULT use after the ULT washout period 
 
 
 
Document ULTs Discontinued 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense Premedication: Gout 
Flare and Infusion Reaction 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Premedication: Gout Flare 
 
X11 
Continuously 
 
 
 
Premedication: Infusion 
Reaction 
 
 
X12 
 
X12 
 
X12 
 
 
 
X12 
 
X12 
 
X12 
 
 
 
 
 
 
Safety Labs: Chemistry13 
X 
 
X 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Hematology14 
X 
 
X 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Coagulation15 
X 
 
X 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Lipids16 
X 
 
X 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Urinalysis17 
X 
 
X 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Anti-drug-Ab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Gout Flare Assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Joint Assessment (tenderness, 
swelling) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
 


 
 
 
 
 
This document is confidential. 
SAP Version: 4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 15 of 41 
Table A 
 SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO SEL-212, CONTINUED 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D04 
D21 
D04 
D21 
D04 
D7 
D14 
D21 
D2820 
 
 
Health Questionnaires18 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Collect Sample for SUA 
X 
 
Refer to Schedule of Assessments in Table B for SUA Sample Collection during Treatment Period 
 
X 
Study Drug Administration 
 
 
Refer to Schedule of Assessments in Table B for Study Drug Administration during the Treatment Period 
 
 
Concomitant Medications / 
Procedures 
 
 
Continuously 
X 
X 
AE/SAE Collection 
X19 
X19 
Continuously 
X 
X 
1. Phone call at 30 (+ 4) days after the last study drug infusion for assessment of concomitant medications/procedures, AEs, and SAEs. 
2. Visit window at Day 21 of each Treatment Period is -2 days to +1 day. 
3. Visit window is -2 days. 
4. Study drug dosing to occur 28 days from the previous dose with a window of -4 days to +3 day of the intended dosing day.  
5. Full physical exam 
6. Directed physical exam 
7. Assess vital signs on Day 0 at Time 0 (pre-dose), within + 5 minutes after completion of infusion of the first component of study drug, and 1 hour (+ 5 minutes) after completion of infusion of the 
second component of study drug. 
8. Height measured once during screening only. 
9. Screening labs to include: SUA, anti-PEG-antibodies, hepatitis B and C antibodies, human immunodeficiency virus 1/2 (HIV1/2), hemoglobin-A1c (HbA1c), glucose, triglycerides, LDL, 
glucose-6-phosphate dehydrogenase (G6PD), WBC, AST, ALT, Hgb, serum creatinine, and serum phosphate, urinalysis 
10. Begin ULT washout at least 7 days prior to Day 0 of Treatment Period 1. 
11. Begin colchicine 0.6 mg QD premedication 7 days prior to Day 0 of Treatment Period 1. Patients not already taking colchicine will receive colchicine 1.2 mg as a single loading dose followed by the 
0.6 mg every day regimen. If the patient cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate and maintain colchicine at 0.6 mg. 
12. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (±12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to study 
medication. 
13. Chemistry labs to include: Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine, fibrinogen, glucose 
(fasting), phosphorous, electrolytes (sodium, potassium, chloride, bi-carbonate, phosphate and magnesium). 
14. Hematology labs to include: white blood cells (WBC) count with differential, red blood cell (RBC) count, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular 
hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet (Plt) count, mean platelet volume (MPV) 
15. Coagulation labs to include: prothrombin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR) 
16. Lipid labs to include: total cholesterol, HDL, LDL, triglycerides 
17. Urinalysis to include: urinary protein, albumin, creatinine, pH, specific gravity, blood, glucose, ketones, bilirubin, leukocyte, esterase, WBC, RBC, crystals, casts (cast types), epithelial cells (renal 
and nonrenal), bacteria, mucus, and yeast. 
18. Refer to protocol section 11.3 for Health Questionnaires. 
19. During Screening, SAE collection begins at time of signing informed consent. Non-serious AE will not be collected during Screening. 
20. Visit window is -2 days to +6 days 
Abbreviations: Ab: antibody; D (d): day; ECG: electrocardiogram; EOS: end of study; ET: early termination; h: hour; RCTC: Rheumatology Common Toxicity Criteria; Scr: Screening Period; SUA: 
serum uric acid; TP: treatment period; ULT: urate lowering therapy 
 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 16 of 41 
TABLE B 
SCHEDULE OF ASSESSMENTS: SEL-212 DOSING AND SUA DURING THE TREATMENT PERIOD 
Assessments 
Day 
Timepoint 
Treatment Periods: 1, 2, 4, and 5 
Treatment Periods 3 and 6 
D01 
D21 
D01 
D7 
D14 
D21 
D282 
0h 
~1.5h 
~3.5h 
~4.5h 
 
0h 
~1.5h 
~3.5 
~4.5h 
 
 
 
 
Premedicate: Infusion Reaction 
X3 
 
 
 
 
X 
 
 
 
 
 
 
 
Blood Sample: SUA 
X4 
 
 
X5 
X 
X4 
 
 
X5 
X 
X 
X 
X 
Study Drug Infusion (Component 1)6 
X----------X7 
 
 
 
X----------X7 
 
 
 
 
 
 
Study Drug Infusion (Component 2)8 
 
X7---------X 
 
 
 
X7---------X 
 
 
 
 
 
1. Study drug dosing to occur 28 days from the previous dose with a window of -4 days to +3 days of the intended dosing day.  
2. Treatment Period 6 only. 
3. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (±12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) 
hours prior to  
study medication. 
4. Obtain sample prior to study drug infusion. 
5. Obtain sample 1 (± 0.25) hour after completion of infusion of Component 2. 
6. Component 1 will be SEL-110.36 for patients randomized to treatment with SEL-212. 
7. Before starting infusion with Component 2, a period of up to 15 minutes is permitted after completion of infusion of Component 1. 
8. Component 2 will be SEL-037 for patients randomized to treatment with SEL-212. 
 
 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 17 of 41 
TABLE C  
SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO KRYSTEXXA® 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D04 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D2820 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examinations 
X5 
 
X6 
 
X6 
 
X6 
 
 
 
X6 
 
X6 
 
X6 
 
 
 
X5 
 
X5 
Vital Signs 
X 
X 
X7 
X7 
X7 
X7 
X7 
 
X7 
 
X7 
X7 
X7 
X7 
X7 
 
X7 
X 
X 
 
X 
Weight and Height8 
X 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Tophus Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Screening Labs9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Lab: Anti-PEG-Ab 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Washout: ULTs 
 
X10 
Patients will abstain from ULT use after the ULT washout period 
 
 
 
Document ULTs Discontinued 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense Premedication: Gout 
Flare and Infusion Reaction 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Premedication: Gout Flare 
 
X11 
Continuously 
 
 
 
Premedication: Infusion 
Reaction 
 
 
X12 
X12 
X12 
X12 
X12 
 
X12 
 
X12 
X12 
X12 
X12 
X12 
 
X12 
 
 
 
 
Safety Labs: Chemistry13 
X 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Safety Labs: Hematology14 
X 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Safety Labs: Coagulation15 
X 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Safety Labs: Lipids16 
X 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Safety Labs: Urinalysis17 
X 
 
X 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Safety Labs: Anti-drug-Ab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Gout Flare Assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Joint Assessment (tenderness, 
swelling) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Health Questionnaires18 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 18 of 41 
  TABLE C 
 SCHEDULE OF ASSESSMENTS FOR PATIENTS RANDOMIZED TO KRYSTEXXA®, CONTINUED 
Assessment 
Scr. 
Treatment Period (TP) 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
- 45 d 
-7 d3 
D0 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D04 
D14 
D04 
D14 
D04 
D7 
D14 
D21 
D2820 
 
 
Collect Sample for SUA 
X 
 
Refer to Schedule of Assessments in Table D for SUA Sample Collection during Treatment Period 
 
X 
Study Drug Administration 
 
 
Refer to Schedule of Assessments in Table D for Study Drug Administration during the Treatment Period 
 
 
Concomitant Medications / 
Procedures 
 
 
Continuously 
X 
X 
AE/SAE Collection 
X19 
X19 
Continuously 
X 
X 
1. Phone call at 30 (+ 4) days after the last study drug infusion for assessment of concomitant medications/procedures, AEs, and SAEs. 
2. Visit window at Day 14 of each Treatment Period is -2 days to +3 days; visit window at Day 7 and 21 of TP3 and TP6 is -2 days to +3 days. 
3. Visit window is -2 days. 
4. Study drug dosing to occur 14 days from the previous dose with a window of -2 days to +3 days of the intended dosing day. 
5. Full physical exam 
6. Directed physical exam 
7. Assess vital signs on Day 0 and Day 14 at Time 0 (pre-dose), and 1 hour (+ 5 minutes) after completion of infusion. 
8. Height measured once during Screening only. 
9. Screening labs to include: SUA, anti-PEG-antibodies, hepatitis B and C antibodies, human immunodeficiency virus 1/2 (HIV1/2), hemoglobin-A1c (HbA1c), glucose, triglycerides, LDL, 
glucose-6-phosphate dehydrogenase (G6PD), WBC, AST, ALT, Hgb, serum creatinine, and serum phosphate 
10. Begin ULT washout at least 7 days prior to Day 0 of Treatment Period 1. 
11. Begin colchicine 0.6 mg QD premedication 7 days prior to Day 0 of Treatment Period 1. Patients not already taking colchicine will receive colchicine 1.2 mg as a single loading dose 
followed by the 0.6 mg every day regimen. If the patient cannot tolerate the loading dose level of 1.2 mg, then the patient will initiate and maintain colchicine at 0.6 mg. 
12. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (±12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to  
study medication. 
13. Chemistry labs to include: Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine, fibrinogen, 
glucose (fasting), phosphorous, electrolytes (sodium, potassium, chloride, bi-carbonate, phosphate and magnesium).  
14. Hematology labs to include: white blood cells (WBC) count with differential, red blood cell (RBC) count, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet (Plt) count, mean platelet volume (MPV) 
15. Coagulation labs to include: prothrombin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR) 
16. Lipid labs to include: total cholesterol, HDL, LDL, triglycerides 
17. Urinalysis to include: urinary protein, albumin, creatinine, pH, specific gravity, blood, glucose, ketones, bilirubin, leukocyte, esterase, WBC, RBC, crystals, casts (cast types), epithelial 
cells (renal and nonrenal), bacteria, mucus, and yeast. 
18. Refer to protocol section 11.3 for Health Questionnaires. 
19. During Screening, SAE collection begins at time of signing informed consent. Non-serious AE will not be collected during Screening. 
20. Visit window is -2 days to +6 days 
Abbreviations: Ab: antibody; D (d): day; ECG: electrocardiogram; EOS: end of study; ET: early termination; h: hour; RCTC: Rheumatology Common Toxicity Criteria; Scr: 
Screening Period; SUA: serum uric acid; TP: treatment period; ULT: urate lowering therapy 
 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 19 of 41 
TABLE D  
SCHEDULE OF ASSESSMENTS: KRYSTEXXA DOSING AND SUA DURING THE TREATMENT 
PERIOD 
Assessments 
Day 
Timepoint 
Treatment Periods: 1, 2, 4, and 5 
Treatment Periods 3 and 6 
D01 
D14 
D01 
D7 
D14 
D21 
D282 
0h 
~2.0h 
~3.0h 
0h 
~2.0h 
~3.0h 
0h 
~2.0h 
~3.0h 
 
0h 
~2.0h 
~3.0h 
 
 
Premedicate: Infusion Reaction 
X3 
 
 
X3 
 
 
X 
 
 
 
X3 
 
 
 
 
Blood Sample: SUA 
X4 
 
X5 
X4 
 
X5 
X4 
 
X5 
X 
X4 
 
X5 
X 
X 
Study Drug Infusion 
X----------X 
 
X----------X 
 
X----------X 
 
 
X----------X 
 
 
 
1. Study drug dosing to occur 14 days from the previous dose with a window of -2 days to +3 days of the intended dosing day. 
2. Treatment Period 6 only. 
3. Pretreatment to minimize potential infusion reactions: oral steroids at 24 (±12) hours and oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) 
hours prior to  
study medication. 
4. Obtain sample prior to study drug infusion. 
5. Obtain sample 1 (± 0.25) hour after completion of infusion. 


 
 
 
 
 
This document is confidential. 
SAP Version: 4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 20 of 41 
 
Endpoints 
 
Primary Efficacy Endpoint 
Primary Endpoint: 
• 
Percentage of patients on SEL-212 vs. KRYSTEXXA® who achieve and maintain reduction of 
SUA < 6 mg/dL for at least 80% of the time during Treatment Period 3 and Treatment Period 6.   
Serum samples for measurement of SUA will be collected according to the schedules described in 
section 3.8 tables B and D.  
 
Secondary Efficacy Endpoints 
Secondary Endpoints: 
• 
Reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed by subtracting 
baseline SUA level from the mean SUA (area under the SUA time curve) during Treatment Period 
3 and Treatment Period 6 
• 
Percent reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed as the 
mean SUA level during treatment period (area under the SUA time curve) minus baseline SUA 
level divided by baseline SUA level multiplied by 100 during Treatment Period 3 and Treatment 
Period 6 
• 
Percentage of patients on SEL-212 vs. KRYSTEXXA® who achieve and maintain reduction of 
SUA < 6 mg/dL for at least 80% of the time during Treatment Period 6 
• 
Percentage of patients on SEL-212 vs. KRYSTEXXA® who achieve and maintain reduction of 
SUA < 6 mg/dL for 100% of the time during Treatment Period 6 
• 
Reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed by subtracting 
baseline SUA level from the mean SUA (area under the SUA time curve) during Treatment Period 
6 
• 
Percent reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed as the 
mean SUA level during treatment period (area under the SUA time curve) minus baseline SUA 
level divided by baseline SUA level multiplied by 100 during Treatment Period 6 
• 
Percentage of patients who achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of 
the time during Treatment Period 3  
• 
A summary table of the number and percentage of patients who achieve and maintain reduction 
of SUA < 6 mg/dL for 100% of the time during Treatment Period 3 will be provided by treatment 
group. 
• 
Reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed by subtracting 
baseline SUA level from the mean SUA (area under the SUA time curve) during Treatment Period 
3 
• 
Percent reduction of mean SUA in patients on SEL-212 vs. KRYSTEXXA® as computed as the 
mean SUA level during treatment period (area under the SUA time curve) minus baseline SUA 
level divided by baseline SUA level multiplied by 100 during Treatment Period 3 
• 
Percent of patients on SEL-212 vs. KRYSTEXXA® in pre-dose SUA values > 6 mg/dL during 
Treatment Periods 2-6. The pre-dose SUA is collected on the dosing day prior to the dosing 
administration or it is collected at the visit where dosing would have occurred had the patient not 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 21 of 41 
been previously withdrawn from study drug for those patients who have been withdrawn from 
study drug.  
• 
Change in health questionnaires to end of treatment period 3 and 6: 
o 
Health Assessment Questionnaire-Disability Index (HAQ-DI) 
o 
The Provider Global Assessment of Disease Activity (PrGA)   
o 
Short Form Health Survey 36 (SF-36) 
• 
Percent of patients on SEL-212 vs. KRYSTEXXA® of gout flare incidence per 3-month period 
(Treatment Periods 1-3 and Treatment Periods 4-6) 
• 
Percent of patients on SEL-212 vs. KRYSTEXXA® of gout flare frequency per 3-month period 
(Treatment Periods 1-3 and Treatment Periods 4-6)  
• 
Change from Baseline to Treatment Period 6 in number of tender joints 
• 
Change from Baseline to Treatment Period 6 in number of swollen joints 
 
 
Safety Endpoints 
Safety Endpoints: 
• 
Safety and tolerability of SEL-212 compared to KRYSTEXXA® as assessed by AEs, serious AEs 
(SAEs), deaths, and discontinuations due to AEs 
Additional safety assessments will include review and evaluation of laboratory testing including 
hematology, coagulation, chemistry, urinalysis; vital signs; 12-lead ECGs; and physical examination 
findings. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 22 of 41 
 
Analysis Sets 
 
Screened / Randomized Set 
The Screened Set will include all patients who signed an informed consent. The Randomized Set will 
include all patients who were randomized. 
 
Safety Set 
The Safety Set (SS) will include all patients who were administered any amount of study medication. 
Patients will be analyzed according to treatment received.  The SS will be used for all analyses of safety 
endpoints and for the presentation of patients in all patient listings.  
 
Intent-to-Treat Set   
The Intent–to-Treat (ITT) Set will be used as the primary population for the analysis of efficacy. The ITT 
Set will include all randomized patients. Patients will be analyzed according to randomized treatment.  ITT 
set is same as randomized set by its definition and will be referred as so in this SAP. 
 
Modified Intent-to-Treat  
The modified ITT (mITT) Set will include all randomized patients who were administered at least one 
complete dose of study medication and have at least one post-baseline assessment of SUA. Patients will 
be analyzed according to randomized treatment. The mITT will also be used for analyses of efficacy 
endpoints. 
 
Per Protocol Set  
The Per Protocol (PP) Set will include all patients who 1) were administered any amount of study 
medication, and 2) have completed at least 65% of the study dosing visits with or without receiving study 
drug (eg at least 4 of 6 TP Day 0 visits for patients receiving SEL-212 or at least 8 of 12 TP Day 0 or Day14 
visits for for patients receiving Krystexxa) unless early termination from the study occurred after study drug 
withdrawal due to meeting stopping rules or due to an adverse event, or due to PI discretion (for example 
where at least one pre-dose SUA was >6 mg/dL in the Krystexxa arm and patient was discontinued from 
study treatment), and 3) who have no major Protocol deviations affecting the primary efficacy assessments. 
Patients will be analyzed according to randomized treatment. 
 
Protocol Deviations 
All protocol deviations related to study inclusion or exclusion criteria, conduct of the trial, patient 
management, dosing, and sampling procedures or patient assessment will be listed. The list of protocol 
deviations will be reviewed by the Sponsor, the principal investigator, the study statistician and the study 
pharmacokineticist and finalized before database lock. Determination of whether the deviation is major or 
minor, or has impacts on primary efficacy assessment will be based on the biasing impact of the deviation 
on the safety and efficacy data. Major protocol deviations affecting the primary efficacy assessments 
include: 1) major protocol deviations that lead to premature study drug discontinuation; 2) major protocol 
deviations that lead to patients receiving study drug treatment in treatment periods 3 or 6 that they would 
not otherwise have received (such as incorrect application of the protocol stopping rules that allow a 
patient to continue dosing despite having met the stopping criteria); and 3) protocol deviations that involve 
out of window sampling of SUA due to a) visits occurring outside of the protocol visit window for dosing 
days (where dosing days refer to dosing visits of patients still on study drug who have not previously been 
withdrawn from study drug) in Treatment period 3 and 6, b) visits occurring outside of the protocol visit 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 23 of 41 
window for visits within TP3 or TP6 scheduled 1 week prior to the dosing days, c) visits occurring outside 
of the protocol visit window for TP6 D21 for patients who have not been withdrawn from study drug and 
for dosing day TP4D0, or d) visits occurring 35 days or more beyond TP6D0 for the TP6D28 visit for 
patients who have not been withdrawn from study drug, where the protocol visit window above refers to 
the current protocol window allowed at the time of analysis.  Major protocol deviations affecting the 
primary efficacy assessments will be reviewed and determined periodically during clinical and medical 
review of protocol deviations during the study. 
Protocol deviations related to Covid-19 will be identified and flagged. 
 
General Methods 
SAS® version 9.4 or higher will be used for all statistical analyses and tabulations. 
In general, summaries will present data by treatment group and assessment time where appropriate.  
Unless stated otherwise, descriptive summaries will include n, mean, standard deviation, median, 
minimum and maximum for continuous variables, and n and percent for categorical variables. If there are 
multiple assessments collected on the same scheduled time within the visit windows defined for each 
assessment, the average of these assessments will be used.  For tabulated safety summaries, only the 
scheduled assessments will be included in the summary tables. 
Data collected at unscheduled visits will be included in the data listings but will not be included in the 
analyses or by treatment summaries. 
Adverse events and medical history will be coded according to the most recent version of Medical 
Dictionary for Regulatory Activities (MedDRA). Prior and concomitant medications will be coded using the 
most recent WHO Drug Dictionary version. The actual version of MedDRA and WHO drug used will be 
noted on the corresponding actual output. 
 
Key Definitions 
Baseline is defined as the last non-missing value prior to the start of infusion of SEL-212 or 
KRYSTEXXA®.  
 
Day 0 of Treatment Period 1 is defined as the first date of study drug administration. 
 
Study day within each treatment period will be calculated as date of event/collection – first dose date at 
each treatment period to be consistent with protocol defined day 0. 
 
Overall study day will be calculated as date of event/collection – first dose date of the study.  
 
 
Missing Data 
Missing data will not be imputed unless specified otherwise.  Missing eCRF data due to Covid-19 will be 
listed. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 24 of 41 
 
Demographic, Other Baseline Characteristics and Medication 
 
Patient Disposition and Withdrawals 
Patient disposition data will be listed. Summary tables reflecting the number of patients for the following will 
be presented:  
- 
Screened (or Enrolled) patients 
- 
ITT, SS, mITT, and PP patients 
- 
Patients who complete the study treatment 
- 
Patients who early terminate the study treatment and reasons for early termination  
- 
Patients who early terminate the study and reasons for early termination  
Screen Failure patients will be listed. 
Kaplan-Meier (KM) figures of the time to early termination of the study by treatment group and by presence 
of tophus will be provided.  
Kaplan-Meier (KM) figures of the time to early termination of the study due to adverse event by treatment 
group and by presence of tophus will be provided. 
Kaplan-Meier (KM) figures of the time to early study treatment discontinuation by treatment group and by 
presence of tophus will be provided. 
Kaplan-Meier (KM) figures of the time to early study treatment discontinuation due to stopping rules by 
treatment group and by presence of tophus will be provided.  
Kaplan-Meier (KM) figures of the time to early study treatment discontinuation due to stopping rules or due 
to Infusion-related reactions including infusion reaction, allergic reaction to pre-med or one of drug 
components and anaphylaxis, by treatment group and by presence of tophus will be provided. 
In addition, stratified Log-rank test will be used to test treatment difference with presence of tophus as 
stratification factor for those time to event endpoint mentioned above. Unstratified Log-rank test will be used 
to test treatment difference for patients with presence of tophus and for patients with absence of tophus. 
 
Demographic and Other Baseline Characteristics 
Demographic characteristics such as gender, age, race and ethnicity will be summarized for all ITT patients, 
by treatment and overall.  Demographic characteristics will be also summarized using MITT and PP set 
patients. 
Age will be calculated based on date of signed informed consent as below: 
(Date of informed consent - date of birth) / 365.25 and truncated to complete years 
 
Medical History  
No summaries will be provided. Medical history will be coded using current version of Medical Dictionary 
for Regulatory Activities (MedDRA®). The version number will be noted on the actual data listing for medical 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 25 of 41 
history. Medical history will be listed by treatment and patient including coded terms for system organ class 
and preferred term. 
 
Concomitant Medication and Therapy 
Concomitant medications are permitted during this study unless otherwise restricted. Medications used in 
the 3 months prior to screening and during the study will be recorded on the Concomitant Medications 
electronic case report form (eCRF). The reported medications will be reviewed and evaluated by the 
investigator or designee to determine if they affect a patient’s eligibility to participate or continue to 
participate in the study.  
 
Prior Medication 
Prior medication is defined as any medication which has an end date prior to the date of first dose of 
study drug administration.  
Prior medication will be listed.   
 
Concomitant Medication 
Concomitant medication is defined as any medication which has an end date after the date of first dose of 
study drug administration or missing. 
The original verbatim terms collected in the eCRF for prior and concomitant medications will be coded using 
the World Health Organization Drug Dictionary (WHO-DD current version) into drug class (Anatomical 
Therapeutic Classification [ATC] level 4) and preferred term. 
Concomitant medication will be summarized by treatment, ATC4 and preferred term for SS patients and 
will be listed for all SS patients.    


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 26 of 41 
 
Efficacy 
 
Primary Efficacy Endpoint Analysis 
The primary efficacy endpoint is defined as: 
• 
Comparison in the percentage of patients on SEL-212 vs. KRYSTEXXA® who achieve and 
maintain reduction of SUA < 6 mg/dL for at least 80% of the time during Treatment Period 3 and 
Treatment Period 6 
The SUA time curve will be used to estimate the proportion of time that the SUA level is below 6 mg/dL. 
Based on the serum samples collected during Treatment Periods 3 and 6, an estimate of the time with 
SUA < 6 mg/dL can be determined by connecting each two neighboring data points with a straight line. 
SUA values collected at unscheduled visits within period 3 and period 6 will be included for the SUA time 
curve.  If the SUA time curve goes above 6 mg/dL the linear interpolation method will be used to estimate 
the point in time at which the SUA time curve intercepts the line between the last SUA value < 6 mg/dL 
and the first value ≥ 6 mg/dL. 
The proportion of time that the SUA level is < 6 mg/dL will be computed by taking the ratio between the 
time during which the SUA level remains < 6 mg/dL (if necessary, using the linear interpolation method) 
and the entire time interval within Treatment Periods 3 and 6. For period 3, entire time interval is between 
time of day 0 SUV assessment for period 3 and period 4.  For Period 6, the entire time interval is between 
time of day 0 and day 28 assessment.  
Let T1 be the total time interval in hours for Treatment Period 3 of which W1 hours is the time interval 
during which SUA level is < 6 mg/dL. Similarly, for Treatment Period 6, assume T2 is the total time 
interval in hours of which W2 hours is the time interval during which SUA level is < 6 mg/dL. For a patient 
to be considered a responder, the proportion of time that the SUA level is < 6 mg/dL during Treatment 
Periods 3 and 6 must be at least 80%. The proportion of time that the SUA level is < 6 mg/dL, i.e., 
percentage (p) of non-hyperuricemic time, is calculated using the following formula: 
𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 (𝑝𝑝) = 𝑊𝑊1 + 𝑊𝑊2
𝑇𝑇1 + 𝑇𝑇2 × 100 
 
Missing scheduled assessments of SUA will be imputed as follows: If SUA is missing at day 0 (predose) 
for periods 3, 4 and 6 and day 28 for period 6 in the SEL-212 cohort, baseline SUA will be used for 
calculation. If SUA is missing at day 0 (predose) for periods 3, 4 and 6 and day 28 for period 6 or day 14 
(pre-dose) for treatment periods 3 and 6 in the Krystexxa cohort, baseline SUA will be used for 
calculation. Day 0 predose time point is the same as day 28 of previous treatment period. For example, 
period 4 predose is same as period 3 day 28. If SUA is missing at the post-dose timepoint on dosing days 
(ie post-treatment on Day 0 in SEL-212 cohort or post-treatment on either D0 or D14 in Krystexxa cohort)  
in either Treatment period 3 or 6 or is missing at Day 21 of treatment period 3 or 6 for the SEL-212 cohort 
for a patient, it will be imputed by the mean of the available assessments at the respective time from the 
prior Treatment Periods (ie from Treatment periods 1 and 2 for missing data in TP3 and from Treatment 
periods 1 to 5 for missing data in TP6) of this patient.  Missing SUA assessments at Day 7 and Day 14 in 
the SEL-212 cohort and missing SUA assessments at Day 7 and 21 in the Krystexxa cohort will not be 
imputed, but SUA time curve will be determined by interpolation. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 27 of 41 
If the duration of the Treatment Period 3 or 6 has been extended by more than 6 days beyond its nominal 
28 day duration due to study visits occurring beyond their protocol windows, the corresponding TP4 day 0 
(predose) or TP6 day 28 value will be imputed by the baseline value for the patient at the timepoint of 28 
days after the previous Day 0 timepoint (TP3 or TP6) and only those SUA values drawn within 28 days of 
the respective day 0 (ie. TP3 or TP6) will be used in calculating the proportion of time that the SUA level 
is below 6 mg/dL.   
The primary estimand will take into consideration the treatment policy strategy, ie, Treatment Period 3 
and 6 assessments will be considered for all patients in ITT independently whether the patient has 
completed the study treatment or has terminated the study treatment early. If a subject withdraws from 
study before completing period 6 or is put back on ULTs, the subject will be considered as a non-
responder for the primary efficacy endpoint. The return of ULTs is a confounding factor for subsequent 
SUA efficacy.  
The estimator for the comparison between the treatment groups is defined as the difference in the 
proportion of responders between patients receiving SEL-212 versus those receiving KRYSTEXXA® 
during Treatment Periods 3 and 6. The statistical testing will be performed confirmatory using the 
Cochran-Mantel-Haenszel (CMH) test – considering the randomization stratum of tophus presence 
(yes/no) – with a one-sided type 1 error rate α = 5%. In addition, 90% two-sided confidence intervals for 
the overall treatment difference between SEL-212 and KRYSTEXXA® treatment groups without 
stratification will be computed. The analysis of the estimands will be carried out based on the ITT 
primarily. Supportive analyses will be performed on the mITT and the PP.  
A logistic regression model to compare treatment difference controlling for presence of tophus will be 
performed as supportive analysis. 
In addition, a sensitivity analysis will be performed as below for the primary endpoint: 
• 
If a subject withdraws from study treatment before completing period 6 due to stopping rules met 
for treatment, the subject will be considered as a non-responder for the primary efficacy endpoint.  
• 
If a subject withdraws from the study  before completing period 6 or the study terminates prior to 
a subject completing period 6, the primary efficacy endpoint is based on SUA assessment for 
period 3 where T1 be the total time interval in hours for Treatment Period 3 of which W1 hours is 
the time interval during which SUA level is < 6 mg/dL:  
  
𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 (𝑝𝑝) = 𝑊𝑊1
𝑇𝑇1 × 100 
 
Summary tables of the percentage of responders (patients who achieve and maintain reduction of SUA < 
6 mg/dL for at least 80% of the time) will be provided by treatment group. Additionally, a summary table 
with the total time a patient has SUA values < 6 mg/dL will be provided for treatment period 3 and 
treatment period 6 by treatment group. 
Summary tables of the actual values and change from baseline for SUA results will be provided for each 
scheduled sampling time point by treatment group. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 28 of 41 
Additionally, mean SUA level, reduction in mean SUA and percent reduction in mean SUA from baseline 
during Treatment Periods 3 and 6,  during Treatment 3,  and  during Treatment Period 6 will be 
summarized by treatment group respectively and will be compared for treatment difference using ANOVA 
model with presence of tophus and treatment group as fixed factors 
• 
Mean SUA level is defined as the area under the SUA time curve (computed using the linear 
trapezoidal rule during Treatment Periods 3 and 6) divided by the corresponding time interval.   
• 
Reduction in mean SUA is computed by subtracting baseline SUA level from mean SUA during 
Treatment Period 3 and 6.  
• 
Percent reduction in the mean SUA from baseline is computed as the mean SUA level during 
Treatment Periods 3 and 6 minus baseline SUA level divided by baseline SUA level multiplied by 
100 
 
Secondary Efficacy Endpoint Analyses 
There is no hierarchical ordering of the secondary endpoints.  All secondary endpoint will be included for 
analyses as described. 
 
Secondary Efficacy Endpoints based on SUA  
For the following secondary endpoints, the comparison between SEL-212 and KRYSREXXA® will be 
done similar to the primary efficacy endpoint using a CMH-test considering the randomization stratum of 
tophus presence (yes/no) with one-sided type 1 error rate level of α=5%. In addition, 90% confidence 
intervals for treatment differences between SEL-212 and KRYSTEXXA® treatment groups will be 
computed. The efficacy analyses will be carried out based on the ITT and PP Sets. mITT analyses will be 
performed as supportive.  
• 
percentage of patients who achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of 
the time during Treatment Period 3  
• 
percentage of patients who achieve and maintain reduction of SUA < 6 mg/dL for at least 80% of 
the time during Treatment Period 6 
• 
percentage of patients who achieve and maintain reduction of SUA < 6 mg/dL for 100% of the 
time during Treatment Period 6 
• 
percent of patients whose pre-dose SUA values > 6 mg/dL during Treatment Periods 2-6 
 
A summary table of the number and percentage of patients who achieve and maintain reduction of SUA < 
6 mg/dL for at least 80% of the time during Treatment Period 6 will be provided by treatment group.  
A summary table of the number and percentage of patients who achieve and maintain reduction of SUA < 
6 mg/dL for at least 80% of the time during Treatment Period 3 will be provided by treatment group. 
A summary table of the number and percentage of patients who achieve and maintain reduction of SUA < 
6 mg/dL for 100% of the time during Treatment Period 6 will be provided by treatment group.  
A summary table of the number and percentage of patients who achieve and maintain reduction of SUA < 
6 mg/dL for 100% of the time during Treatment Period 3 will be provided by treatment group. 
A summary table of the number and percentage of patients with pre-dose SUA values > 6 mg/dL during 
Treatment Periods 2-6 will be provided by treatment group.  


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 29 of 41 
 
Change from baseline in HAQ-DI Total Score 
The HAQ-DI, which includes the patient global assessment and pain scale, is an instrument that 
assesses fine movements of the upper extremity, locomotor activities of the lower extremity, and activities 
that involve both the upper and lower extremities. Standard scoring takes into account the use of aids and 
devices or assistance from another person. There are 20 items in 8 categories that represent a 
comprehensive set of functional activities: dressing, rising, eating, walking, hygiene, reach, grip, and 
usual activities. The stem of each item assesses a patient’s functional ability using their usual equipment 
during the past week. Each category contains at least 2 specific sub-category questions. For example, 
under the category “walking,” patients are asked about their ability to walk outdoors on flat ground and to 
climb up 5 steps.  
Eight (8) categories will be assessed by the HAQ-DI: 1) dressing and grooming, 2) arising, 3) eating, 4) 
walking, 5) hygiene, 6) reaching, 7) gripping, and 8) common daily activities. There are 2 or 3 questions 
for each section. Scoring within each section is on a 4-point Likert scale from 0 (without any difficulty) to 3 
(unable to do). The score given to each section is the worst (highest) score within the section (ie, if one 
question is scored 1 and another 2, then the score for the section is 2). In addition, if an aid or device is 
used or if help is required from another individual, then the minimum score for that section is 2. If the 
section score is already 2 or more then no modification is made. The sum of the 8 scores of the 8 
sections will be divided by 8 to obtain the HAQ-DI total score. In the event that one section is not 
completed by a subject then the summed score would be divided by 7. The HAQ-DI total score will be 
calculated if 6 or more sections are available. 
Comparison with regards to change from baseline will be performed using an ANCOVA with the 
respective change from baseline value as dependent variable, treatment group and the randomization 
stratum as independent fixed factors and the baseline value as independent covariate.  
Summary tables of total scores will be provided for each scheduled assessment time by treatment group. 
Additionally, summaries of the changes from baseline will be provided. 
 
Provider Global Assessment of Disease Activity (PrGA)   
The PrGA will be administered to assess the severity of the patient’s disease on a scale from 0 (patient 
feels “very well”) to 100 (patient feels “very poor”). Lower scores indicate less severe disease. 
Comparison with regards to change from baseline in PrGA will be performed using an ANCOVA with the 
respective change from baseline value as dependent variable, treatment group and the randomization 
stratum as independent fixed factors and the baseline value as independent covariate.  
Summary tables of PrGA will be provided for each scheduled assessment time by treatment group. 
Additionally, summaries of the changes from baseline will be provided. 
 
Short Form Health Survey 36 (SF-36) 
The SF-36 is a 36-item scale constructed to survey health status and quality of life (Ware 1992). The SF-
36 assesses 8 health concepts: limitations in physical activities because of health problems; limitations in 
social activities because of physical or emotional problems; limitations in usual role activities because of 
physical health problems; bodily pain; general mental health (psychological distress and well-being); 
limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and 
general health perceptions. The standard form of the instruments asks for patients to reply to questions 
according to how they have felt over the previous week.   


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 30 of 41 
The SF-36 consists of 8 scaled domain scores with range 0-100 with higher score indicating better health 
and 2 component scores (physical component and mental component). The 8 domains are: 
• 
Vitality 
• 
Physical functioning 
• 
Bodily Pain 
• 
General Health Perceptions 
• 
Physical Role Functioning 
• 
Emotional Role Functioning 
• 
Social Role Functioning 
• 
Mental Health 
 
All domain scores and component scores will be derived and collected on eCRF. 
For each domain and component scores, comparison with regards to change from baseline will be 
performed using an ANCOVA with the respective change from baseline value as dependent variable, 
treatment group and the randomization stratum as independent fixed factors and the baseline value as 
independent covariate.  
Summary tables of each domain and component score will be provided for each scheduled assessment 
time by treatment group. Additionally, summaries of the changes from baseline will be provided. 
 
Gout Flares Incidence and Frequency 
The number and percentage of patients reporting gout flares per 3-months period and overall, i.e. 
Treatment Periods 1-3,  Treatment Periods 4-6 and Periods 1-6, will be summarized by treatment group 
and will be tested using a CMH-test considering the randomization stratum.  The same analysis will also 
be performed by patient’s maximum severity of gout flare experienced within each 3-months period. 
The frequency of gout flares will be summarized per 3-months period and overall and by severity for each 
treatment group and will be compared using ANOVA model with presence of tophus and treatment group 
as fixed factors.  In addition for periods 4-6 and 1-6, poisson regression model will be used with number 
of gout flares as independent variable, treatment and presence of tophus as fixed factor, and length of 
follow-up for each corresponding treatment period as covariate.   
 
Change from Baseline to Treatment Period 6 in Number of Tender and Swollen Joints 
Comparison with regards to change in number of tender joints from baseline to end of treatment period 3 
(day 0 period 4)  and  period 6 will be performed using an ANCOVA with the change from baseline value 
as dependent variable, treatment group and randomization stratum as independent fixed factors and the 
baseline number of tender joints as independent covariate. In case of non-normality the non-parametric 
Wilcoxon test will be used for the comparison between the treatment groups. Summary tables of the 
number of tender joints for each assessment time point and for the change from baseline will be provided 
by treatment group. 
Comparison with regards to change of swollen joints from baseline to end of treatment period 3 (day 0 
period 4) and 6 will be performed using an ANCOVA with the change from baseline value as dependent 
variable, treatment group and randomization stratum as independent fixed factors and the baseline 
number of swollen joints as independent covariate. In case of non-normality, the non-parametric Wilcoxon 
test will be used for the comparison between the treatment groups. Summary tables of the number of 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 31 of 41 
swollen joints for each assessment time point and for the change from baseline will be provided by 
treatment group.  
 
Subgroup Analyses 
In the event of a prolonged gout flare which is not successfully managed, Investigators will most likely 
treat patients with corticosteroids which will have a downstream effect on the duration of flares, 
swollen/tender joint counts and QOL assessments. In order to better extrapolate the results, a subgroup 
analysis may be conducted for patients who receive “additional gout flare treatment”.  The statistical 
analysis and summaries described in sections 7.2.2 through 7.2.6 may be repeated for the subgroup of 
patients who receive “additional gout flare treatment” as well as by primary efficacy endpoint (responder 
vs. non-responder).   
 
Deviation from Analyses Planned in Protocol 
 
Additional analyses  
The following analyses are added even though they are not included in the protocol: 
• 
Interim analysis.   
• 
Subgroup analyses on the secondary endpoint by patient’s primary efficacy endpoint 
(responder vs. non-responder).   
The following analyses have been added as a result of the impact of Covid-19 on the study which may 
result in a larger anticipated number of subjects not completing the study and therefore not undergoing 
the assessments required for the primary efficacy endpoint or the study being stopped prematurely by 
sponsor decision. This is in line with FDA Guidance on Conduct of Clinical Trials of Medical Products 
during COVID-19 Pandemic Guidance for Industry, Investigators, and Institutional Review Boards. 
 
• 
Additional analyses suggested to primary endpoint as sensitivity analyses to determine if 
the impact that these have on the conclusions of the study and to describe the impact of 
Covid-19 on the study performance. 
• 
A sensitivity analysis which limited the analysis to results processed in the central 
laboratory to determine if this resulted in different conclusions to those found from the full 
analysis to determine consistency in laboratory testing between central and local 
laboratories. 
• 
Kaplan-Meier analysis of withdrawal from study by treatment arm and presence of tophus 
to determine if subjects withdraw from the study in different proportions and at different 
rates within the treatment groups and depending on the presence of tophus. 
• 
Kaplan-Meier analysis of withdrawal from study due to an adverse event by treatment arm 
and presence of tophus to determine if subjects experience adverse events in different 
proportions and at different rates within the treatment groups and depending on the 
presence of tophus. 
• 
Poisson regression with number of gout flares experienced during treatment periods 1-6 as 
the dependent variable, treatment and the presence of tophus as independent variables 
and length of follow up as a covariate. The ITT population would be used to conduct this 
analysis. Similar analysis is done for periods 4-6. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 32 of 41 
 
Safety 
The population used for safety analyses will be the Safety Set (SS).  Safety will be assessed on the basis 
of adverse event (AE), clinical laboratory data, ECG parameters, physical examinations, and vital signs.  
 
Extent of Exposure 
Frequency counts of number of patients who received all doses (i.e., completed study treatment) and 
descriptive statistics of doses and total cumulative doses by treatment group (SEL-212 or KRYSTEXXA®) 
will be presented. 
Number and percentage of patients who met stopping rules will be summarized by treatment group and 
treatment period. The percentage will be plotted versus treatment period by treatment.  The comparison 
between the treatment groups will be tested using CMH-test stratified by tophus presence (Yes/No). 
 
Treatment Compliance  
Treatment compliance is defined as patients receiving study drug as planned.   
Compliance = 100% x (total volume infused) \ (total volume planned) 
For patient who has received SEL-202, compliance will be calculated for SEL-110.36 and SEL-037.  
For patient who has received KRYSTEXXA®, compliance will be calculated for KRYSTEXXA®.  
Total duration of infusion as well as total time duration between start of infusion and stop of infusion 
will be descriptively summarized by study drug and dosing time point.  
The date and time of the start and stop of drug administration, total infusion duration and volume infused 
will be listed. 
 
Adverse Events / Adverse Drug Reactions 
All AEs will be coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), using the 
most recent MedDRA Version. All AEs will be summarized by treatment, SOC and PT. A treatment-
emergent AE (TEAE) is an AE that starts or worsens at any time after initiation of study drug on Day 0 of 
Treatment Period 1 until the End of Study Visit (30 days after completion of the last dose of study drug).  
An overall summary will be provided of the number and percentage of patients reporting TEAEs, serious 
TEAEs, treatment-related (possibly related and related) TEAEs, Adverse events of special interest 
(AESIs), TEAEs leading to study drug withdrawal, and TEAEs leading to death.   AESIs will be defined by 
medical monitor prior to database lock.  
The number and percentage of patients with TEAEs / serious TEAEs / TEAEs leading to study drug 
withdrawal/treatment-related TEAEs will be summarized by SOC and PT for each treatment group (SEL-
212 or KRYSTEXXA®). AESIs will also be summarized. 
TEAEs will also be summarized by maximum intensity and causality.   
 
Laboratory Evaluations 
Laboratory data will be summarized by the type of laboratory test and will be presented for each scheduled 
visit by treatment group (SEL-212 or KRYSTEXXA®). Normal reference ranges and markedly abnormal 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 33 of 41 
results will be used in the summary of laboratory data. Data will be flagged according to the reference limits 
(High or Low), if applicable. Changes from baseline will be presented for each post-baseline visit. Shift 
tables of the number of patients with low/normal/high values at each scheduled post-baseline visit 
compared to the low/normal/high categorization at baseline will be provided by treatment group (SEL-212 
or KRYSTEXXA®). 
 
Vital Signs  
Summary tables of the actual values and changes from baseline will be provided for each vital sign 
parameter at each scheduled visit by treatment group (SEL-212 or KRYSTEXXA®). 
 
ECG 
For each 12-lead ECG variable the actual value and the change from baseline will be summarized for the 
scheduled visits by treatment group (SEL-212 or KRYSTEXXA®).  
Frequency tables of abnormal clinically significant evaluations as well as the number and percentage of 
patients with noteworthy QTcF/QTcB values (> 450, > 480 and > 500 ms) and of patients with noteworthy 
QTcF/QTcB changes from baseline (≥ 30 but <60; ≥ 60 ms) will be provided. 
 
Tophus Assessment 
For each tophus assessment variable (including total number, location, palpation and appearance) the 
actual value and the change from baseline will be summarized for the scheduled visits by treatment group 
(SEL-212 or KRYSTEXXA). 
 
Physical Examination 
A full physical examination will be performed at Screening, end of treatment period 6 or early termination 
visit and directed physical examinations will be collected at the beginning of each treatment period cycle. 
Physical examination results will be presented in data listings. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 34 of 41 
 
DSMC and Interim Analyses 
An independent Data and Safety Monitoring Committee (DSMC) will be formed by charter in a separate 
document to assist in reviewing safety data and provide recommendations to the Sponsor regarding study 
drug dose adjustment or study termination as needed. 
 
As discussed in section 2.2, An interim analysis will be conducted when 100% of patients are scheduled 
to have completed 3 months of study treatment (ie scheduled to have completed Treatment Period 4 Day 
0 visit). 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 35 of 41 
 Reference List 
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual 
framework and item selection. Med Care. 1992 Jun;30(6):473-83. 
 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 36 of 41 
 Programming Considerations 
All tables, data listings, figures (TLFs), and statistical analyses will be generated using SAS® for 
Windows, Release 9.4 (SAS® Institute Inc., Cary, NC, USA). Computer-generated table, listing and figure 
output will adhere to the following specifications.   
 
General Considerations 
• 
Each output will be stored in a separate file. 
• 
Output files will be delivered in Rich Text Format. 
• 
Numbering of TFLs will follow ICH E3 guidance 
 
Table, Listing, and Figure Format 
 
General 
• 
All TLFs will be produced in landscape format, unless otherwise specified. 
• 
All TLFs will be produced using the Courier New font, size 8  
• 
The data displays for all TLFs will have a minimum 1-inch margin on all 4 sides. 
• 
Headers and footers for figures will be in Courier New font, size 8. 
• 
Legends will be used for all figures with more than 1 variable, group, or item displayed. 
• 
TLFs will be in black and white (no color), unless otherwise specified 
• 
Specialized text styles, such as bolding, italics, borders, shading, and superscripted and subscripted 
text, will not be used in the TLFs, unless otherwise specified. On some occasions, superscripts 1, 2, 
or 3 may be used (see below). 
• 
Only standard keyboard characters will be used in the TLFs. Special characters, such as non-
printable control characters, printer-specific, or font-specific characters, will not be used. 
Hexadecimal-derived characters will be used, where possible, if they are appropriate to help display 
math symbols (e.g., μ). Certain subscripts and superscripts (e.g., cm2, Cmax) will be employed on a 
case-by-case basis. 
• 
Mixed case will be used for all titles, footnotes, column headers, and programmer-supplied formats, 
as appropriate. 
 
Headers 
• All output should have the following header at the top left of each page: 
  SELECTA Biosciences 
        Protocol SEL – 212/202 
     Draft/Final Run <date> 
• All output should have Page n of N at the top or bottom right corner of each page. TFLs are 
internally paginated in relation to the total length (i.e., the page number should appear sequentially 
as page n of N, where N is the total number of pages in the table). 
• The date output was generated should appear along with the program name as a footer on each 
page. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 37 of 41 
 
Display Titles 
• Each TFL is identified by the designation and a numeral. (i.e., Table 14.1.1). ICH E3 numbering is 
strongly recommended, but sponsor preferences are obtained before final determination A decimal 
system (x.y and x.y.z) are used to identify TFLs with related contents. The title is centered. The 
analysis set are identified on the line immediately following the title. The title and table designation 
are single spaced. A solid line spanning the margins will separate the display titles from the 
•  Column headers. There will be 1 blank line between the last title and the solid line. 
Table x.y.z 
First Line of Title 
Second Line of Title if Needed 
(ITT Analysis Set) 
 
 
Column Headers 
• Column headings are displayed immediately below the solid line described above in initial upper-
case characters  
• In the case of efficacy tables, the variable (or characteristic) column will be on the far left followed 
by the treatment group columns and total column (if applicable). P-values may be presented under 
the total column or in separate p-value column (if applicable). Within-treatment comparisons may 
have p-values presented in a row beneath the summary statistics for that treatment. 
• For numeric variables, include “unit” in column or row heading when appropriate. 
• Analysis set sizes will be presented for each treatment group in the column heading as (N=xx) (or 
in the row headings, if applicable). This is distinct from the ‘n’ used for the descriptive statistics 
representing the number of patients in the analysis set. 
• The order of treatments in the tables and listings will be Placebo first in the case of placebo 
controlled studies and Active comparators first in the case of active comparator trials, followed by a 
total column (if applicable). 
 
Body of the Data Display 
11.2.5.1. 
General Conventions 
Data in columns of a table or listing are formatted as follows: 
• Alphanumeric values are left-justified; 
• Whole numbers (e.g., counts) are right-justified; and 
• Numbers containing fractional portions are decimal aligned. 
11.2.5.2. 
Table Conventions 
• Units will be included where available 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 38 of 41 
• If the categories of a parameter are ordered, then all categories between the maximum and 
minimum category are presented in the table, even if n=0 for all treatment groups in a given 
category that is between the minimum and maximum level for that parameter. For example, the 
frequency distribution for symptom severity would appear as: 
Severity 
Rating 
N 
severe 
0 
moderate 
8 
mild 
3 
 
Where percentages are presented in these tables, zero percentages will not be presented and so counts 
of 0 will be presented as 0 and not as 0 (0%). 
• If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation from the 
Study, etc.), then only those categories for which there is at least 1 patient represented in 1 or 
more groups are included. 
• An Unknown or Missing category are added to each parameter for which information is not 
available for 1 or more patients.  
• Unless otherwise specified, the estimated mean and median for a set of values are printed out to 1 
more significant digit than the original values, and standard deviations are printed out to 2 more 
significant digits than the original values. The minimum and maximum should report the same 
significant digits as the original values. For example, for systolic blood pressure: 
N 
  XX 
Mean 
XXX.X 
Std Dev 
     X.XX 
Median 
XXX.X 
Minimum 
XXX 
Maximum 
XXX 
 
• P-values are output in the format: “0.xxx”, where xxx is the value rounded to 3 decimal places. 
Everyp-value less than 0.001 will be presented as <0.001. If the p-value are less than 0.0001, then 
present as <0.0001. If the p-value is returned as >0.999, then present as >0.999 
• Percentage values are printed to one decimal place, in parentheses with no spaces, one space 
after the count (e.g., 7 (12.8%), 13 (5.4%)). Pre-determine how to display values that round down 
to 0.0.  A common convention is to display as '<0.1', or as appropriate with additional decimal 
places. Unless otherwise noted, for all percentages, the number of patients in the analysis set for 
the treatment group who have an observation will be the denominator. Percentages after zero 
counts should not be displayed and percentages equating to 100% are presented as 100%, without 
decimal places.  
• Tabular display of data for medical history, prior/concomitant medications, and all tabular displays 
of adverse event data are presented by the body system, treatment class, or SOC with the highest 
occurrence in the active treatment group in decreasing order, assuming all terms are coded. Within 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 39 of 41 
the body system, drug class and SOC, medical history (by preferred term), drugs (by ATC1 code), 
and adverse events (by preferred term) are displayed in decreasing order. If incidence for more 
than 1 term is identical, they should then be sorted alphabetically. Missing descriptive statistics or 
p-values which cannot be estimated are reported as “-”. 
• The percentage of patients is normally calculated as a proportion of the number of patients 
assessed in the relevant treatment group (or overall) for the analysis set presented. However, 
careful consideration is required in many instances due to the complicated nature of selecting the 
denominator, usually the appropriate number of patients exposed. Describe details of this in 
footnotes or programming notes. 
• For categorical summaries (number and percentage of patients) where a patient can be included in 
more than one category, describe in a footnote or programming note if the patient are included in 
the summary statistics for all relevant categories or just 1 category and the criteria for selecting the 
criteria. 
• Where a category with a subheading (such as system organ class) has to be split over more than 
one page, output the subheading followed by “(cont)” at the top of each subsequent page.  The 
overall summary statistics for the subheading should only be output on the first relevant page. 
11.2.5.3. 
Listing Conventions 
• Listings will be sorted for presentation in order of treatment groups as above, patient number, 
visit/collection day, and visit/collection time. 
• Missing data are represented on patient listings as either a hyphen (“-”) with a corresponding 
footnote (“- = unknown or not evaluated”), or as “N/A”, with the footnote “N/A = not applicable”, 
whichever is appropriate. 
• Dates are printed in SAS DATE9.format (“ddMMMyyyy”: 01JUL2000). Missing portions of dates are 
represented on patient listings as dashes (--JUL2000). Dates that are missing because they are not 
applicable for the patient are output as “N/A”, unless otherwise specified. 
• All observed time values are to be presented using a 24-hour clock HH:MM or HH:MM:SS format 
(e.g., 11:26:45, or 11:26). Time will only be reported if it was measured as part of the study. 
• Units will be included where available 
11.2.5.4. 
Figure Conventions 
• Unless otherwise specified, for all figures, study visits will be displayed on the X-axis and endpoint 
(e.g., treatment mean change from Baseline) values will be displayed on the Y-axis. 
 
Footnotes 
• A solid line spanning the margins will separate the body of the data display from the footnotes.  
• All footnotes will be left justified with single-line spacing immediately below the solid line 
underneath the data display. 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 40 of 41 
• Footnotes should always begin with “Note:” if an informational footnote, or 1, 2, 3, etc. if a 
reference footnote. Each new footnote should start on a new line, where possible. 
• Patient specific footnotes are avoided, where possible. 
• Footnotes will be used sparingly and add value to the table, figure, or listing. If more than six lines 
of footnotes are planned, then a cover page is strongly recommended to be used to display 
footnotes, and only those essential to comprehension of the data will be repeated on each page.  
• The last line of the footnote section will be a standard source line that indicates the name of the 
program used to produce the data display, date the program was run, and the listing source (i.e., 
‘Program : myprogram.sas    Listing source: 16.x.y.z’). 


Statistical Analysis Plan  
Sponsor: Selecta Biosciences  
Protocol No.: SEL-212/202 
 
 
This document is confidential. 
SAP Version:  4.0, 08-Sep-2020 
Controlled Document ID: 3903A.01, Effective Date 29-Oct-2018 
Filing requirements: TMF 
Page 41 of 41 
 Quality Control 
SAS programs are developed to produce output such as analysis data sets, summary tables, data listings, 
figures or statistical analyses. An overview of the development of programs is detailed in Syneos Health 
SOP Developing Statistical Programs (3907)  . 
Syneos Health SOPs Developing Statistical Programs (3907) and  Conducting the Transfer of Biostatistical 
Deliverables (3908) describes the quality control procedures that are performed for all SAS programs and 
output. Quality control is defined here as the operational techniques and activities undertaken to verify that 
the SAS programs produce the output by checking for their logic, efficiency and commenting and by review 
of the produced output.