A Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy
Phase: PHASE3
Conditions: Chronic Gout
Sponsor: Swedish Orphan Biovitrum

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
15 DEC 2022 
1. 
TITLE PAGE 
STUDY DRUG: SEL-212 (a combination of SEL-037 and SEL-110.36) 
STUDY NUMBER: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE: 15 December 2022 
A RANDOMIZED DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SEL-212 IN 
PATIENTS WITH GOUT REFRACTORY TO CONVENTIONAL THERAPY 
Sponsor Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472, USA 
Tel: 617-923-1400 
Fax: 617-924-3454 
Approvers: 
 
 
Signature: 
Date: 
 
 
 
December 16, 2022
December 16, 2022
NCT #: NCT04596540

PHASE 3 STUDY: SEL-212/302 
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PROPRIETARY AND CONFIDENTIAL 
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SELECTA BIOSCIENCES CLINICAL STUDY PROTOCOL 
A RANDOMIZED DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SEL-212 IN 
PATIENTS WITH GOUT REFRACTORY TO CONVENTIONAL THERAPY 
STUDY NUMBER: SEL-212/302 
 
CONTACT INFORMATION 
Sponsor: Selecta Biosciences 
65 Grove Street  
Watertown, MA 02472 
Tel: 617-923-1400 
Fax: 617-924-3454 
Email: clinicaltrials@selectabio.com  
Clinical Study Leader: 
 
 
Selecta Biosciences 
65 Grove Street 
Watertown, MA 02472 
Tel: 
 
Fax: 
 
Email: 
 
Medical Contact: 
 
 
Parexel International 
10 Shaumyana str., building 1 
Saint-Petersburg, 195027, Russia 
Tel: 
 
Email: 
 
Pharmacovigilance: PAREXEL Safety Services 
Fax Number: +1 781-434-5957 
In case of issues with fax, Email: NorthAmerica_Medical@parexel.com 
 
 
 

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INVESTIGATOR’S AGREEMENT 
I agree: 
• 
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 
 

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PROPRIETARY AND CONFIDENTIAL 
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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 Active Ingredient: 
SEL-037 (pegadricase, recombinant pegylated C. utilis 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 Randomized, Double-Blind, Placebo-controlled Study of SEL-212 in Patients with Gout Refractory 
to Conventional Therapy 
Study Center(s): approximately 50 study centers (North America and Other Global Sites) 
Studied Period:  
18 months 
Phase of Development:  
Phase 3 
Objectives:  
Primary: 
• 
To assess the reduction in serum uric acid (sUA) in patients with gout refractory to 
conventional therapy treated with two different dose levels of SEL-212 compared to placebo  
Secondary: 
• 
To compare the pharmacodynamic (PD) effect on sUA in patients with gout refractory to 
conventional treatment treated with two different dose levels of SEL-212 compared to 
placebo  
• 
To assess change(s) of the following in patients with gout refractory to conventional 
treatment treated with two different dose levels of SEL-212 compared to placebo: 
o Tophus burden 
o Patient Reported Outcomes (PROs) including assessments of: patients’ quality of life 
(QoL) (SF-36), activity limitation (HAQ-DI), and Provider Global Assessment of Disease 
Activity  
o Gout flares 
o Joint tenderness and swelling 
• 
To assess effects on the formation of anti-uricase and anti-pegadricase antibodies  
• 
To assess the safety and tolerability of SEL-212 compared to placebo 

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PROPRIETARY AND CONFIDENTIAL 
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• 
To assess the reduction in serum uric acid (sUA) in patients with gout refractory to 
conventional treatment treated with two different dose levels of SEL-212 compared to 
placebo, amongst those with tophi at baseline 
Exploratory: 
• 
To assess the levels of uricase activity in patients receiving SEL-212 compared to placebo 
• 
To assess the effect on monosodium urate crystal deposits and/or total body monosodium 
urate crystal deposits in patients with gout refractory to conventional treatment treated 
with two different dose levels of SEL-212 compared to placebo (imaging patients only) 
• 
To assess the status of biomarkers related to inflammation and tolerogenic immunologic 
responses in patients with gout refractory to conventional treatment treated with two 
different dose levels of SEL-212 compared to placebo  
• 
To assess the relationship between multiomic markers of gout and treatment effect in 
patients with gout refractory to conventional treatment treated with two different dose 
levels of SEL-212 compared to placebo 
• 
To assess the impact on patient’s self-assessment of gout flares and burden of disease using 
a validated patient diary (weekly) in patients treated with two different dose levels of SEL-
212 compared to placebo 
• 
To assess the correlation between immune tolerance related multiomic markers and anti-
pegadricase antibody formation in patients treated with two different dose levels of SEL-212  
Methodology:  
This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to 
determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. The 
study will randomize approximately 140 patients with chronic refractory gout. Approximately 60% of 
the randomized patients will have tophi at Baseline. Patients, stratified as to the presence or 
absence of tophi, will be randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment 
with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each 
trial (SEL-212/301 and SEL-212/302). These two trials will have identical designs with respect to 
being double-blinded, placebo-controlled as well as identical planned sample sizes, 
inclusion/exclusion criteria, efficacy/safety assessments and timing thereof, but will be distinguished 
by a blinded 6-month extension in SEL-212/301 and that SEL-212/302 will include sites outside of the 
United States. Placebo patients in either SEL-212/301 or SEL-212/302 who complete the study, will 
be offered enrolment in an open-label extension study for treatment with SEL-212 (SEL-212/303). 
Efficacy assessments will be conducted at intervals that are appropriate to determine treatment 
effect with samples for the primary endpoint drawn during Treatment Period 6. Samples will be 
collected at intervals that are appropriate to determine the uricase activity of SEL-212. Safety will be 
monitored throughout the study with an independent data safety monitoring board (DSMB).  

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Screening Phase 
After providing written informed consent, the patient is considered enrolled in the study. Patients 
will be evaluated for inclusion during the Screening Phase. For all patients, the standard Screening 
Phase will be up to 45 days prior to Baseline. The Screening Phase may be initiated by a preliminary 
screening with an abbreviated informed consent focused on COVID-19 testing and serum uric acid 
levels followed by providing study-wide informed consent and the remainder of screening 
assessments if determined to proceed. Of note, if the sUA level obtained during preliminary 
screening meets eligibility requirements (i.e., ≥ 7 mg/dL), the sUA should not be repeated during the 
subsequent complete screening assessment. Concurrently with the Screening Phase, a 
premedication period for potential gout flare with colchicine (or a non-steroidal anti-inflammatory 
drug [NSAID], if colchicine is contraindicated) of at least 7 days prior to Baseline will be required for 
all patients, and a washout period of at least 7 days will be required prior to Baseline for patients on 
any urate-lowering therapy (ULT). Both the ULT washout period and the gout flare prophylaxis 
period may be started earlier than 7 days prior to Baseline. At the discretion of the PI, chronic 
refractory gout patients whose sUA is lower than the eligibility level of ≥ 7 mg/dL on prescreening or 
initial screen, may undergo ULT washout prior to retesting the sUA. Initiation of gout flare 
prophylaxis with colchicine (or non-steroidal anti-inflammatory drug [NSAID], if colchicine is 
contraindicated) can also be considered coincidentally with the ULT washout to prevent a potential 
gout flare. 
Double-Blind Treatment Phase 
The total duration of the double-blind Treatment Phase will be approximately 6 months  
(i.e., 168 days, consisting of six 28-day treatment cycles). 
Eligible patients, stratified according to the presence or absence of tophi, will be randomized in a 
1:1:1 allocation ratio prior to Baseline to receive one of two dose levels of SEL-212 or placebo. The 
SEL-212 doses will differ as to the SEL-110.36 component. Participants will receive SEL-037 
administered at a dose of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving 
SEL-110.36 at a dose of either 0.1 mg/kg (SEL-212A) or 0.15 mg/kg (SEL-212B) via IV infusion. The 
placebo will consist of normal saline that will be administered in the same way that the SEL-212 
components are administered to maintain the integrity of the study blind.  
Patients will complete 6 treatment periods each having a duration of 28 days. Patients will receive 
treatment with study drug or placebo on Day 0 of each treatment period for a total of 6 doses. For 
each treatment cycle, patients in both treatment and placebo groups will receive 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 1 hour for safety 
assessments.  
With each dose, a blood sample will be drawn for assessment of sUA level and uricase activity 
immediately prior to infusion (i.e., Time 0 h) with SEL-212 or placebo and 1 hour after the infusion of 
the second component of SEL-212 or of placebo is completed. Serum uric acid levels will be assessed 
through additional post-infusion blood samples at pre-determined time points by an independent, 
central, unblinded medical monitor.  
Gout flares will be assessed at each study visit during the Treatment Phase using a validated 
definition of flares in patients with established gout (Gaffo 2018). In addition, in an exploratory 
manner, gout flares will be self-assessed by the patient weekly after randomization and in each 
Treatment Period using a weekly flare diary (Poiley 2016). Patient reported outcome measures 

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(PROs), tophus burden, and joint swelling and tenderness will be assessed on Day 0 of Treatment 
Periods 1 and 4, and at the end of Treatment Period 6 or early termination (ET) if a patient 
discontinues the study prior to the end of 6 monthly infusions. Samples for anti-uricase, anti-PEG, 
and anti-pegadricase antibody levels will be obtained (i) prior to administration of study drug dosing 
and at Day 21 for each of the six treatment periods throughout the trial and (ii) at the end of 
Treatment Period 6 or at early termination (ET) if a patient discontinues study treatment prior to end 
of 6 monthly infusions. Exploratory assessments of inflammatory/immunologic biomarkers and 
multiomic analysis will also be assessed. 
Safety laboratory samples, consisting of, but not limited to, complete blood count (CBC) including 
white blood cell count (WBC) and absolute neutrophil count; liver function tests (LFTs) including 
aspartate aminotransferase (AST) and alanine transaminase (ALT); serum lipids (including 
triglycerides and low density lipoprotein (LDL)); analyses of renal function including creatinine, 
urine-albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) will be 
collected on Day 0 and Day 21 of Treatment Period 1, on Day 21 only of each of Treatment Periods 2-
5, and on Day 21 and Day 28 / ET of Treatment Period 6. On Treatment Period 1 Day 0, safety 
laboratory samples will be collected pre-infusion in both the SEL-212 arms and the placebo arm. 
Concomitant medications and procedures and adverse events (AEs) will be monitored continuously 
during the study. Post-Baseline chest X-rays (CXR) will be taken at six months / early termination to 
assess for presence of or changes in interstitial lung disease (ILD) compared to the baseline CXR.  
Follow-Up Phase 
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 at the following times: either (1) at the completion 
of the 6 month Treatment Phase or (2) at early termination if the patient voluntarily withdraws 
consent. Patients who terminate the study prematurely will continue to be followed by having all ET 
assessments performed. Patients who terminate the study prematurely will have all ET assessments 
performed. Patients who terminate the study prematurely who are unable to be on-site for the ET 
visit will be contacted by telephone for safety follow-up.  
If withdrawn from study drug, the patient will continue study visits to the end of Treatment Period 6. 
Data and Safety Monitoring Board (DSMB) 
An independent Data and Safety Monitoring Board (DSMB) 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: 
• sUA level < 2.0 mg/dL, measured 1 hour after the infusion of the second component of study 
drug is completed during Treatment Period 1 
AND 
• 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 
Stopping rules will be assessed by an independent, central, unblinded medical monitor. 

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If withdrawn from study drug, the patient will continue study visits to the end of Treatment Period 6. 
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 a protocol deviation 
occurs where a patient is not able to be dosed within the dosing day window (for example in the 
case of COVID-19 restrictions temporarily preventing dosing) the current treatment period will be 
extended up to a maximum of 90 days without skipping doses for patients with a Day 21 visit sUA 
value ≤ 1.0 mg/dL during Treatment Period 1 or ≤ 6.0 mg/dL during Treatment Periods 2, 3, 4, or 5 in 
the D21 visit window or subsequent up to the rescheduled dosing visit. If a protocol deviation occurs 
in Treatment Period 6 such that the patient was unable to have an EOS visit performed within the 
visit window, then the Treatment Period 6 Day 28 visit should still occur 28 days (+3/-4 days) after 
the Treatment Period 6 dose or as close to the visit window as possible to collect the final primary 
endpoint SUA sample. To maintain the blind, a central group of unblinded pre-specified medical 
personnel will adjudicate the implementation of the 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 ULT 60 days after the 
patient’s last study drug treatment. ULT shall not be SEL-212 or any experimental or marketed 
uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®)), for the remainder of the study.  
Number of Patients (Planned):  
• Planned Enrollment: Approximately 140 patients randomized (total): 
o SEL-212A: approximately 47 patients 
o SEL-212B: approximately 47 patients 
o Placebo: approximately 47 patients 
Approximately 60% of the randomized patients will have tophi at Baseline. 

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Diagnosis and Main Criteria for Inclusion:  
Inclusion Criteria: 
A patient must meet all 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 negative results of an FDA Emergency Use Authorized COVID-19 molecular assay for 
detection of SARS-CoV-2 RNA from a nasal or oropharyngeal specimen; 
4. Has a history of symptomatic gout defined as: 
o 
≥ 3 gout flares within 18 months of Screening or 
o 
Presence of ≥ 1 gout tophus or 
o 
Current diagnosis of gouty arthritis 
5. At the Screening Visit male age 19 – 80 years, inclusive or female of non-childbearing 
potential age 19-80 years, inclusive, where non-childbearing potential is defined as: 
o > 6 weeks after hysterectomy with or without surgical bilateral salpingo-oophorectomy 
or 
o Post-menopausal (> 24 months of natural amenorrhea or in the absence of >24 months 
of amenorrhea, one documented confirmatory FSH measurement) 
6. Has chronic refractory gout defined as having failed to normalize sUA and whose signs and 
symptoms are inadequately controlled with any of the xanthine oxidase inhibitors, either 
allopurinol and/or febuxostat at the medically appropriate dose, or for whom these drugs are 
contraindicated for the patient; 
7. Has at Screening sUA ≥ 7 mg/dL 
8. Has not participated in a clinical trial within 30 days of the Screening Visit and agrees to not 
participate in a clinical trial for the duration of the study; 
9. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative antibodies to 
hepatitis C.  
Exclusion Criteria: 
A patient who meets any of the following criteria will be excluded from this study: 
1. Has a history of anaphylaxis, severe allergic reactions, or severe atopy; 
2. Has a history of any allergy to pegylated products, including, but not limited to pegloticase 
(Krystexxa®), 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®); 
3. Is taking and cannot discontinue known major CYP3A4/P-gp inhibitors or major CYP3A4/P-gp 
inducers at least 14 days before dosing. Patients must remain off these medications for the 
duration of the study, including natural products such as St. John’s Wort or grapefruit juice. 

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4. Is taking drugs known to interact with rapamycin (sirolimus - Rapamune®) such as 
cyclosporine, diltiazem, erythromycin, ketoconazole, posaconazole, voriconazole, 
itraconazole, rifampin, verapamil unless they are stopped 14 days prior to dosing and will not 
be used/prescribed during the trial. 
5. Had major surgery within 3 months of initial screening.  
6. Had a gout flare during Screening that was resolved for less than 1 week prior to first 
treatment with study drug (exclusive of chronic synovitis/arthritis) unless the patient has a 
history of inter-flare intervals of < 1 week. 
7. Has uncontrolled diabetes at Screening with HbA1c ≥ 8.5%; 
8. Has fasting Screening glucose > 240 mg/dL 
9. Has fasting Screening triglyceride > 500 mg/dL; 
10. Has fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; 
11. Has glucose-6-phosphate dehydrogenase (G6PD) deficiency;  
12. Has uncontrolled hypertension defined as blood pressure > 170/100 mmHg at Screening and 
1 week prior to dosing 
13. Individual laboratory values which are exclusionary 
o White blood cell count (WBC) < 3.0 x109/L 
o Serum aspartate aminotransferase (AST) or alanine amino transferase (ALT) 
> 3x upper limit of normal (ULN) in the absence of known active liver disease 
o Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 
o Urine-albumin-creatinine ratio (UACR) > 30 mg/g creatinine (conventional units) or > 3.39 
mg/mmol creatinine (SI units) 
o Hemoglobin (Hgb) < 9 g/dL 
o Serum phosphate < 2.0 mg/dL 
14. Is receiving ongoing treatment for arrhythmia, including placement of an implantable 
defibrillator, unless considered stable and on active treatment; 
15. Has evidence of unstable cardiovascular disease or unstable cerebrovascular disease. This 
includes patients who have had a cardiac/vascular event(s) in the last 3 months including 
heart attack, stroke or vascular bypass surgery or patients who are deemed, by their 
physician or PI, to have active cardiovascular, cerebrovascular, or peripheral vascular 
symptoms/disease inadequately controlled by medication; 
16. Has congestive heart failure, New York Heart Association Class III or IV; 
17. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with evidence 
of clinically significant arrhythmia or other abnormalities that, in the opinion of the 
investigator, are consistent with significant underlying cardiac disease; 
18. History of significant hematological disorders within 5 years or autoimmune disorders, 
and/or patient is currently immunosuppressed or immunocompromised;  
19. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), 
pegloticase (Krystexxa®), pegadricase (SEL-037)) 
20. Patient has received a live vaccine in the previous 6 months.  

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21. Patient is planning to receive any live vaccine during the study. Of note, inactivated vaccines 
are permitted but, study drug may affect response to vaccination; therefore, during study 
drug treatment, vaccination with inactivated vaccines may be less effective. Consider high-
dose influenza vaccine to increase the likelihood of developing a protective immune 
response. 
22. History of malignancy within the last 5 years other than basal skin cancer; 
23. Any condition, that in the opinion of the investigator, would be negatively affected by 
rapamycin.  
24. Patients with a documented history of moderate or severe alcohol or substance use disorder 
within the 12 months prior to randomization. 
25. History of or evidence of clinically severe interstitial lung disease 
26. Immunocompromised state, regardless of etiology 
27. Patients who, in the opinion of the investigator, present with a condition that would 
compromise their safety or that would make study completion unlikely 
 
Investigational Product and Placebo, Dosage and Mode of Administration:  
Investigational Product 
• 
SEL-212 is comprised of 2 components: SEL-110.36 and SEL-037 
• 
SEL-110.36: nanoparticle composed of PLA and PLA-PEG encapsulating rapamycin. 
• 
SEL-037: pegadricase, a recombinant pegylated C. utilis urate oxidase. 
Dosage of Investigational Product 
SEL-212A: 
• 
SEL-110.36: 0.1 mg/kg based on patient’s body weight 
• 
SEL-037: 0.2 mg/kg based on patient’s body weight 
SEL-212B: 
• 
SEL-110.36: 0.15 mg/kg based on patient’s body weight 
• 
SEL-037: 0.2 mg/kg based on patient’s body weight 
Mode of Administration 
• 
Gout flare prophylaxis 
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 0.6 mg daily as tolerated. 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 per day. If the patient cannot tolerate the loading dose level of 0.6 mg, then 
the patient will initiate and maintain colchicine at 0.3 mg per day. 
• 
Premedication (prior to study drug administration on Day 0 of each treatment period) 
o Prednisone (40 mg) oral (PO) approximately 24 (± 12) hours prior to dosing 

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o Fexofenadine 180 mg oral (PO) approximately 12 (± 2) hours prior to dosing  
o Fexofenadine 180 mg oral (PO) approximately 2 (± 1) hours prior to dosing 
o Methylprednisolone 100 mg (or equivalent) up to 125 mg, depending on patient weight, 
IV approximately 1 (± 0.5) hours prior to dosing 
• 
SEL-110.36 
o Blinded IV infusion with a syringe infusion pump at steady rate of 1.5 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 normal saline. If an infusion reaction occurs during the 
administration of SEL-110.36, the infusion may be slowed, or stopped and then restarted 
at a slower rate at the discretion of the Investigator.  
• 
SEL-037 
o Blinded administration up to 30 minutes after completion of the SEL-110.36 infusion.  
o Blinded administration via infusion pump over no less than 120 minutes. If an infusion 
reaction occurs during the administration of SEL-037, the infusion may be slowed, or 
stopped and then restarted at a slower rate at the discretion of the Investigator. 
Placebo 
Placebo will consist of normal saline. Normal saline will be administered sequentially in the same 
way that the SEL-212 components are administered to maintain the integrity of the study blind. All 
premedications will be given prior to placebo as well, to maintain the blind. 
Duration of Treatment:  
All patients are planned to receive study drug during a 168-day double-blind treatment phase 
consisting of six 28-day treatment cycles. Patients will receive study drug on Day 0 of each of the 6 
treatment periods.  
The total duration of participation in the study will range from approximately 26 to 31 weeks (184 to 
215 days) as follows: 
• Screening and/or washout and premedication period: up to 45 days (up to 6.5 weeks) 
• Treatment Phase: 168 days (24 weeks) 
• Safety Follow-Up: 30 days after last infusion  

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Criteria for Evaluation: 
Efficacy:  
The confirmatory analysis of efficacy will be performed at Day 28 of Treatment Period 6.  
Primary Efficacy Endpoint: 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with 
regards to the following primary efficacy endpoint: 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for at 
least 80% of the time during Treatment Period 6 by Day 28 
The main estimand for the primary efficacy endpoint considers, for the comparison between each 
SEL-212 treatment group versus placebo, the difference in the percentage of treatment responders 
whereby a responder is defined as a subject who has sUA < 6 mg/dL for at least 80% of the time 
during Treatment Period 6. For this primary estimand, intercurrent events which lead to a 
discontinuation of study treatment due to lack of efficacy (includes meeting the stopping criteria), 
treatment-related or non-treatment related AE, patients with a positive COVID-19 test result along 
with severe or critical symptoms of COVID-19,  used a prohibited medication that significantly lowers 
sUA, or death will be considered as treatment failures following the composite strategy, for all other 
intercurrent events such as use of a prohibited medication that does not lower sUA the treatment-
policy strategy will be used. 
Key Secondary Efficacy Endpoints: 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with 
regards to the following key secondary efficacy endpoints. Respective estimands of interest are 
defined. 
• 
Reduction of mean sUA as computed by subtracting the Baseline sUA level from the mean 
sUA (area under the sUA time curve) during Treatment Period 6 
• 
Percent reduction of mean sUA as computed by subtracting the Baseline sUA level from the 
mean sUA (area under the sUA time curve) during Treatment Period 6 
• 
The change from Baseline to Day 28 of Treatment Period 6 in the physical summary score of 
the Short Form Health Survey (SF-36) 
• 
In patients with tophi at Baseline, the percentage of patients with at least partial response 
(PR) (as best response) in overall tophus response evaluation until Day 28 of Treatment 
Period 6 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for at 
least 80% of the time during Treatment Period 6 in subset of patients with tophi at baseline 
• 
The change from Baseline to Day 28 of Treatment Period 6 in number of tender joints  
• 
The change from Baseline to Day 28 of Treatment Period 6 in the total score of the Health 
Assessment Questionnaire (HAQ-DI) 
• 
Gout flare incidence during Treatment Periods 1-6 
• 
Gout flare incidence during Treatment Periods 1-3  

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Additional Secondary Efficacy Endpoints: 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with 
regards to the following additional secondary efficacy endpoints: 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for 100% 
of the time during Treatment Period 6  
• 
 
• 
Percentage of pre-dose sUA values < 6 mg/dL during Treatment Periods 2-6 for each patient  
• 
Pre-treatment anti-pegadricase and anti-uricase antibody formation and levels in each 
treatment period in the SEL-212 active treatment arms during Treatment Periods 1-6 
• 
Percentage of patients with development of new tophi until Day 28 of Treatment Period 6 in 
the subgroups of tophaceous patients and in non-tophaceous patients at Baseline  
• 
In patients with tophi at Baseline, the percentage of patients with at least PR (as best 
response) in overall tophus response evaluation until Day 0 of Treatment Period 4 
• 
Change from Baseline to Day 28 of Treatment Period 6 in subscales of Health Assessment 
Questionnaire (HAQ-DI), in Provider Global Assessment of Disease Activity, and in subscales 
of Short Form Health Survey (SF-36)  
• 
The percentage of patients with at least 1 gout flare during Treatment Periods 1-3 
• 
The percentage of patients with at least 1 gout flare during Treatment Periods 1-6 
• 
Change from Baseline to Treatment Period 6 in number of swollen joints  
• 
Length of time patients are anti-uricase antibody free or before induction of anti-uricase 
antibody levels above baseline in patients receiving SEL-212  
• 
Length of time patients are anti-pegadricase antibody free or before induction of 
anti-pegadricase antibody levels above baseline in patients receiving SEL-212  
Exploratory Endpoints: 
• 
Levels of uricase activity in patients receiving SEL-212 
• 
Levels of monosodium urate crystal deposits and/or total body monosodium urate crystal 
deposits (imaging patients only) 
• 
Levels of inflammatory and tolerogenic biomarkers  
• 
Changes in antibody production (anti-uricase and anti-pegadricase) in patients in the SEL-
212 groups 
• 
Gout flare incidence during Treatment Periods 4-6  
• 
Gout flare incidence during Treatment Periods 1-3 based on self-reported weekly gout flare 
diary 
• 
Gout flare incidence during Treatment Periods 1-6 based on self-reported weekly gout flare 
diary 

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• 
Gout flare incidence during Treatment Periods 4-6 based on self-reported weekly gout flare 
diary 
• 
Assessment of association between multiomic markers of gout and treatment effect in 
patients treated with SEL-212 
• 
Comparison of immune tolerance related multiomic markers in patients on SEL-212 who 
developed anti-uricase and anti-pegadricase antibodies vs. those patients on SEL-212 that 
did not develop anti-uricase and anti-pegadricase antibodies 
Safety: 
Safety Endpoints: 
• 
Safety and tolerability of SEL-212 compared to placebo as assessed by AEs, adverse event of 
special interest (AESI), 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; eGFR, UACR, vital signs; 
immunogenicity analyses; 12-lead ECGs; and physical examination findings. 
Statistical Methods 
Details of the statistical methods outlined in the protocol for this study will be documented in a 
Statistical Analysis Plan (SAP), which will be finalized prior to database lock. The SAP may add 
additional exploratory analyses; modifications to the planned analyses will be identified as such in 
the final SAP. 
Analysis Populations 
• 
Screened / Randomized Set: The Screened Set will include all patients who signed an informed 
consent. The Randomized Set will include all patients randomized and will be used for the 
presentation in all patient listings. Randomized but not treated patients will be replaced. 
• 
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. 
• 
Intent-to-Treat (ITT) Set: The Intent-to-Treat (ITT) Set will include all randomized and treated 
patients. Patients will be analyzed according to randomized treatment group assignment. The 
ITT will be used as primary population for analyses of efficacy endpoints. 
• 
A number of modified ITT (mITT) populations will be defined, as a result of either the COVID-19 
pandemic or the conflict in Ukraine.  
o mITT1: will include all randomized patients who were dosed, except those who 
discontinue treatment due to a COVID-19 infection as defined in section 12.1.8.7 or 
do not have at least two SUA measurements 7 days apart in TP6 due to a/multiple 
missed visits due to a COVID-19 infection or subsequent complications as defined in 
section 12.1.8.7.  
o mITT2: will include all randomized patients who were dosed, except those who were 
recruited in sites from Ukraine or Russia where the data quality are compromised 
due to logistical issues, defined as: 

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1. Those who received fewer than 6 treatment doses due to logistical issues, for 
example a patient who is unable to receive one or more doses within the 90 day 
window due to lack of IMP or site closure due to the conflict. 
2. Those who have limited laboratory safety data available/reportable after 
February 24, 2022, for example missing data that result in major protocol 
deviations 
3. Those whose data were not able to be monitored after February 24, 2022  
o mITT3: will include all randomized patients who were dosed, except those who were 
recruited in sites from Ukraine or Russia. 
Patients will be analyzed according to randomized treatment.  
• 
Per Protocol Set: The Per Protocol Set (PPS) will include all patients who were administered at 
least one complete dose of study medication, who have at least one post-baseline assessment 
of sUA, who have sufficient data to assess the primary efficacy endpoint, and who have no 
major Protocol deviations affecting the primary efficacy assessments. Patients will be analyzed 
according to randomized treatment. Criteria for exclusion from the PPS will be provided in the 
Statistical Analysis Plan.  
• 
All Randomized Set: The all randomized set will include all patients who were randomized. 
Patients will be analyzed according to randomized treatment group assignment. 
Efficacy Analyses 
Primary Efficacy Analysis 
The primary efficacy endpoint is the percentage of patients on SEL-212 versus placebo who achieve 
and maintain reduction of sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6.  
The main estimand for the primary efficacy endpoint will consider a binary variable indicating the 
treatment response when having completed 6 cycles of study treatment, whereby a responder is 
defined as a subject who has sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6. 
For this primary estimand, intercurrent events which lead to a discontinuation of study treatment 
due to lack of efficacy (includes meeting the stopping criteria), treatment-related or 
non-treatment-related AE, patients with a positive COVID-19 test result along with severe or critical 
symptoms of COVID-19, used a prohibited medication that lowers sUA, or death will be considered 
as treatment failures following the composite strategy, for all other intercurrent events such as use 
of a prohibited medication that does not lower sUA  the treatment-policy strategy will be used. The 
population-level summary is defined as the difference in the percentage of treatment responders of 
each SEL-212 treatment group versus placebo. Missing response will be multiple imputed. The 
statistical testing of each SEL-212 treatment group versus placebo will be performed using the 
Mantel-Haenszel (MH) estimate and test for common risk difference considering the randomization 
stratum of tophus presence (yes/no) with a two-sided type 1 error rate α = 2.5% to adjust for the 
two comparisons against placebo.  
Further estimands will be defined in the SAP. However, only the test results of the main estimand 
will be considered as confirmatory. Sensitivity analysis will be performed using the tipping-point 
analysis.  

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The analysis of the estimands will be carried out based on the ITT population primarily. Supportive 
analyses will be performed on the mITT, all randomized and the PP populations. 
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 Period 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 
Period 6. For a patient to be considered a responder in Treatment Period 6, the proportion of time 
that the sUA level is < 6 mg/dL (i.e., percentage of nonhyperuricemic time) during Treatment Period 
6 must be at least 80%. A frequency table of the percentage of responder will be provided by 
treatment group.  
Additionally, a summary table with the total time a patient has sUA values ≤ 6 mg/dL in Treatment 
Period 6 will be provided by treatment group.  
Summary table 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 6 will be 
presented by treatment group. 
• 
Mean sUA level is defined as the area under the sUA time curve (computed using the linear 
trapezoidal rule during Treatment Period 6) divided by the corresponding time interval.  
• 
Reduction in mean sUA is computed by subtracting baseline sUA level from mean sUA during 
Treatment Period 6.  
• 
Percent reduction in the mean sUA from baseline is computed as the mean sUA level during 
Treatment Period 6 minus baseline sUA level divided by baseline sUA level multiplied by 100% 
Key Secondary Efficacy Analysis 
If the superiority of both (one) SEL-212 treatment group(s) against placebo for the main estimand of 
the primary efficacy is shown with a p-value ≤ 0.025, the hierarchical testing approach will continue 
to the testing of the main estimands of the key secondary efficacy comparing pairwise both (one) 
SEL-212 treatments against placebo. Only the main estimands of the key secondary efficacy will be 
tested in the successive order. The test result of the nth key secondary efficacy estimand will be 
considered as confirmatory if the p-value of the two-sided test of the previous estimand resulted in a 
value less or equal 0.025.  
Most main estimands with a continuous or numerical endpoint will be tested between each SEL-212 
treatment group versus placebo using the mixed model for repeated measures (MMRM) with the 
change from baseline in the respective variable as dependent variable, and treatment, treatment-by-
period interaction, randomization stratum and baseline value of the respective variable as fixed 
effect variables. The Least Square (LS) Mean difference between each SEL-212 and placebo 
treatments groups will be estimated on the treatment-by-visit interaction at the Day 28 visit of 
Treatment Period 6, along with its 97.5% confidence interval, and 2-sided p-values. 
The main estimands defined for binary or response variables will be tested between each SEL-212 
treatment group versus placebo using the Mantel-Haenszel (MH) estimate and test for common risk 

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difference considering the randomization stratum of tophus presence (yes/no) or Chi-square test 
with continuity correction (when comparing the subgroup of patients with tophus at Baseline), as 
appropriate. The difference of proportions between each SEL-212 and placebo treatments groups 
will be presented along with its 97.5% confidence interval, and 2-sided p-values.  
Descriptive summaries will be provided for all endpoints by treatment group and period, if 
appropriate. 
Further Secondary Efficacy Endpoints and Analyses 
Additional secondary efficacy endpoints will be summarized by treatment group using descriptive 
statistics for the ITT population and will be compared between each SEL-212 treatment group and 
placebo using MH or Chi-square tests, as appropriate, in case of binary endpoints or using ANCOVA 
or MMRM, as appropriate, in case of continuous or numerical endpoints. Exploratory p-values of 
two-sided tests with 95% confidence intervals for treatment differences between each SEL-212 
treatment group and placebo will be presented.  
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 with the number and percentage of patients reporting TEAEs, serious TEAEs, treatment-
related TEAEs, 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 and 
TEAEs of special interest will be summarized by SOC and PT for each treatment group, and overall. 
TEAEs will also be summarized by maximum intensity and relationship to study drug. Event rates by 
treatment group and overall will be provided for patients with at least one related TEAE, at least one 
SAE, and at least one TEAE of special interest. Additionally, the rate difference with 95% confidence 
interval comparing each SEL-212 treatment group to placebo as well as comparing the integrated 
SEL-212 arms to placebo will be provided.  
Laboratory data will be summarized by the type of laboratory test and will be presented for each 
scheduled visit stratified by treatment group and overall. Shift tables of the number of patients with 
low/normal/high (or abnormal/normal) values at each scheduled post-baseline visit compared to the 
low/normal/high (or abnormal/normal) categorization at Baseline will be provided by treatment 
group, and overall. Summary tables of actual values and changes from baseline will be provided for 
each continuous laboratory parameter at each scheduled visit by treatment group and overall. 
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, and overall. 
For each 12-lead ECG variable the actual value and the change from baseline will be summarized for 
the scheduled visits by treatment group, and overall. A shift table of the number and percentage of 
subjects with normal and abnormal, and clinically significant abnormal values at each scheduled 
post-baseline visit compared to respective categorization at baseline will be provided by treatment 
group for the overall ECG interpretation. 
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. 

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Sample Size Determination 
The primary efficacy criterion in this study is defined as the rate of the patients who achieve and 
maintain reduction of sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6. The 
responder rate for the primary estimand in all randomized and dosed patients is assumed to be 45% 
in SEL-212 and 5% in placebo. Considering a randomization ratio of 1:1:1 for SEL-212A and SEL-212B 
against placebo, a statistical power of 90%, a two-sided alpha-level of 2.5% in each pairwise test 
against placebo, and using the Chi-square test with continuity correction, 32:32:32 randomized and 
dosed patients will be required for the following respective groups: SEL-212A, SEL-212B and placebo. 
Considering the potential that some randomized patients will terminate early (approx. 8%), the 
number of the patients required to be randomized (and not replaced) in total was 105 (i.e., 
35:35:35) to demonstrate efficacy. The randomized but not dosed patients will be replaced. 
An additional 15 patients have been added to the study sample size to account for potential 
treatment discontinuations that may occur due to the ongoing COVID-19 pandemic as a result of the 
emergence of COVID-19 variants which were not accounted for in the sample size calculations. 
Furthermore, an additional 20 patients have been added to the study sample size to account for 
treatment discontinuations/lost to follow-up that may occur due to the conflict between Ukraine 
and Russia in both countries. This results in approximately 140 patients (i.e. approximately 47 per 
group) to be randomized and dosed to demonstrate efficacy. 
 

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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 ..................................................... 20 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS............................................................... 25 
5. 
INTRODUCTION ........................................................................................................................ 28 
5.1 
Gout and Refractory Gout ..................................................................................................... 28 
5.2 
Symptoms of Gout ................................................................................................................. 28 
5.3 
Gout and Hyperuricemia: Exacerbation of Existing Comorbidities ....................................... 29 
5.4 
Impact on Quality of Life ....................................................................................................... 29 
5.5 
Approved Therapies for Chronic Gout Refractory to Conventional Therapy ........................ 30 
5.6 
Unmet Medical Need ............................................................................................................. 31 
6. 
STUDY OBJECTIVES AND ENDPOINTS......................................................................................... 32 
6.1 
Study Objectives .................................................................................................................... 32 
6.1.1 
Primary Objective ............................................................................................... 32 
6.1.2 
Secondary Objectives ......................................................................................... 32 
6.1.3 
Exploratory Objectives ....................................................................................... 32 
6.2 
Study Endpoints ..................................................................................................................... 33 
6.2.1 
Primary Efficacy Endpoint .................................................................................. 33 
6.2.2 
Secondary Efficacy Endpoints ............................................................................ 33 
6.2.2.1 
Key Secondary Efficacy Endpoints ............................................. 33 
6.2.2.2 
Additional Secondary Efficacy Endpoints .................................. 33 
6.2.3 
Exploratory Endpoints ........................................................................................ 34 
6.2.4 
Safety Endpoints ................................................................................................ 34 
7. 
INVESTIGATIONAL PLAN ........................................................................................................... 35 
7.1 
Overall Study Design .............................................................................................................. 35 
7.1.1 
Screening Phase ................................................................................................. 35 
7.1.2 
Double Blind Treatment Phase .......................................................................... 36 
7.1.3 
Follow-Up Phase ................................................................................................. 37 
7.2 
Number of Patients ................................................................................................................ 37 
7.3 
Treatment Assignment .......................................................................................................... 37 
7.4 
Dose Adjustment Criteria ...................................................................................................... 37 
7.4.1 
Safety Criteria for Adjustment or Stopping Doses ............................................. 38 
7.4.1.1 
SEL-212 or Placebo .................................................................... 38 
7.4.2 
Criteria for Adjustment or Stopping Doses ........................................................ 39 
7.5 
Criteria for Study Termination ............................................................................................... 39 
7.6 
Study Rationale ...................................................................................................................... 39 
7.6.1 
Rationale for the Study Design ........................................................................... 39 
7.6.2 
Rationale for the Study Population .................................................................... 40 
7.6.3 
Rationale for the Selected Dose ......................................................................... 41 
7.6.3.1 
Phase 1b Study with SEL-212 ..................................................... 41 
7.6.3.2 
Phase 2 Studies with SEL-212 .................................................... 41 
7.6.4 
Rationale for the Primary Efficacy Endpoint ...................................................... 44 
7.6.5 
Rationale for Secondary Efficacy Endpoints....................................................... 44 
7.6.6 
Rationale for Other Assessments of Clinical Benefit .......................................... 45 

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7.7 
Benefits and Risks .................................................................................................................. 45 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ............................................................................ 46 
8.1 
Patient Inclusion Criteria ....................................................................................................... 46 
8.2 
Patient Exclusion Criteria ....................................................................................................... 46 
8.3 
Patient Completion and Withdrawal Criteria ........................................................................ 48 
8.3.1 
Screen Failures and Replaced Subjects .............................................................. 48 
8.3.2 
Patient Completion ............................................................................................ 48 
8.3.3 
Enrolled Patient Withdrawal and Discontinuations ........................................... 48 
8.3.3.1 
Withdrawal Procedures ............................................................. 48 
8.3.3.2 
Patients Lost to Follow-Up ........................................................ 49 
9. 
TREATMENT OF PATIENTS......................................................................................................... 50 
9.1 
Description of Study Drug ...................................................................................................... 50 
9.2 
Concomitant Medications and Therapies .............................................................................. 50 
9.2.1 
Urate Lowering Therapy ..................................................................................... 50 
9.2.2 
CYP3A4/P-gp Inducers and Inhibitors ................................................................ 51 
9.2.3 
Other Concomitant Medications........................................................................ 51 
9.3 
Treatment Compliance .......................................................................................................... 51 
9.4 
Randomization and Blinding .................................................................................................. 51 
9.4.1 
Procedures for Breaking the Blind Prior to Study Completion .......................... 52 
9.4.2 
Revealing Randomization ................................................................................... 52 
10. STUDY DRUG MATERIALS AND MANAGEMENT ......................................................................... 53 
10.1 
Study Drug ............................................................................................................................. 53 
10.1.1 
SEL-212 ............................................................................................................... 53 
10.1.2 
Placebo ............................................................................................................... 53 
10.2 
Study Drug Packaging and Labeling ....................................................................................... 53 
10.3 
Study Drug Storage ................................................................................................................ 53 
10.4 
Study Drug Preparation ......................................................................................................... 53 
10.4.1 
SEL-037 Preparation ........................................................................................... 54 
10.4.2 
SEL-110.36 Preparation ...................................................................................... 54 
10.4.3 
Placebo Preparation ........................................................................................... 54 
10.5 
Urate-Lowering Therapy Wash-out ....................................................................................... 54 
10.6 
Premedication ........................................................................................................................ 55 
10.6.1 
Gout Flares (Prophylaxis and Treatment) .......................................................... 55 
10.6.2 
Premedication with Antihistamines and Steroids .............................................. 55 
10.7 
Administration ....................................................................................................................... 55 
10.8 
Study Drug Accountability ..................................................................................................... 56 
10.9 
Study Drug Handling and Disposal ......................................................................................... 57 
11. ASSESSMENT OF EFFICACY ........................................................................................................ 58 
11.1 
Activity Assessment ............................................................................................................... 58 
11.1.1 
Serum Uric Acid Assessment .............................................................................. 58 
11.1.2 
Uricase Activity ................................................................................................... 58 
11.2 
Gout Assessment ................................................................................................................... 58 
11.2.1 
Tophus Assessment ............................................................................................ 58 
11.2.2 
Gout Flare Assessment ....................................................................................... 59 
11.2.3 
Joint Assessment ................................................................................................ 60 
11.3 
Health Questionnaires: Patient Reported Outcomes and Quality of Life 
Assessment ............................................................................................................................ 60 

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11.3.1 
Health Assessment Questionnaire-Disability Index (HAQ-DI) ............................ 60 
11.3.2 
Provider Global Assessment of Disease Activity ................................................ 60 
11.3.3 
Short Form Health Survey 36 (SF-36) ................................................................. 60 
11.4 
Inflammation Biomarker and Multiomic Assessments .......................................................... 60 
11.4.1 
Inflammation Biomarkers of Gout ..................................................................... 60 
11.4.2 
Multiomic Markers of Gout ................................................................................ 61 
11.4.3 
Biomarkers of Immune Tolerance ...................................................................... 61 
11.4.4 
Multiomic Markers Related to Immune Tolerance ............................................ 61 
11.4.5 
Human Leukocyte Antigen (HLA) Typing ............................................................ 61 
11.4.6 
Imaging Assessments ......................................................................................... 61 
12. ASSESSMENT OF SAFETY ........................................................................................................... 62 
12.1 
Safety Parameters.................................................................................................................. 62 
12.1.1 
Demographic/Medical History ........................................................................... 62 
12.1.2 
Concomitant Medications and Procedures ........................................................ 62 
12.1.3 
Vital Signs ........................................................................................................... 62 
12.1.4 
Electrocardiogram (ECG) .................................................................................... 62 
12.1.5 
Weight and Height ............................................................................................. 62 
12.1.6 
Physical Examination .......................................................................................... 62 
12.1.7 
Chest X-ray ......................................................................................................... 62 
12.1.8 
Laboratory Assessments .................................................................................... 62 
12.1.8.1 
Hematology ............................................................................... 63 
12.1.8.2 
Blood Chemistry ........................................................................ 63 
12.1.8.3 
Glomerular Filtration Rate (GFR) ............................................... 63 
12.1.8.4 
Lipids .......................................................................................... 63 
12.1.8.5 
Coagulation ................................................................................ 63 
12.1.8.6 
Antibody Assessments ............................................................... 63 
12.1.8.7 
COVID-19 Testing ....................................................................... 63 
12.1.8.8 
Serology ..................................................................................... 65 
12.1.8.9 
Drug Screen ............................................................................... 65 
12.1.8.10 
Pregnancy Screen ...................................................................... 65 
12.1.8.11 
Definition of Childbearing Potential and Acceptable 
Contraceptive Methods ............................................................. 65 
12.1.9 
Premedication Regimen ..................................................................................... 66 
12.2 
Adverse and Serious Adverse Events ..................................................................................... 66 
12.2.1 
Definition of Adverse Events .............................................................................. 66 
12.2.1.1 
Adverse Event (AE) .................................................................... 66 
12.2.1.2 
Serious Adverse Event (SAE) ...................................................... 67 
12.2.1.3 
Suspected Adverse Reaction ..................................................... 67 
12.2.1.4 
Unexpected Adverse Events and Unexpected 
Suspected Drug Reaction .......................................................... 67 
12.2.1.5 
Infusion Reactions / Adverse Events of Special 
Interest ...................................................................................... 67 
12.2.2 
Recording Adverse Events .................................................................................. 68 
12.2.2.1 
Adverse Event Term/Name/Description ................................... 69 
12.2.2.2 
Relationship to Study Drug ........................................................ 69 
12.2.2.3 
Adverse Event Intensity/Severity Grading ................................ 69 
12.2.2.4 
Assessment of Outcome ............................................................ 70 

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12.2.2.5 
Action Taken with Study Drug ................................................... 70 
12.2.2.6 
Laboratory and Diagnostic Abnormalities as 
Adverse Events .......................................................................... 70 
12.2.2.7 
Pregnancy .................................................................................. 71 
12.2.3 
Reporting Adverse Events .................................................................................. 71 
12.2.3.1 
Adverse Event Reporting Period ............................................... 71 
12.2.3.2 
SAE Reporting Procedures ......................................................... 71 
12.2.3.3 
Regulatory Reporting Requirements for SAEs ........................... 72 
12.2.3.4 
Reporting Safety Information to the IRB/IEC ............................ 73 
12.2.4 
Follow-up of Adverse Events .............................................................................. 73 
13. STATISTICS ............................................................................................................................... 74 
13.1 
Sample Size Determination.................................................................................................... 74 
13.2 
Analysis Populations .............................................................................................................. 75 
13.2.1 
Screened / Randomized Set ............................................................................... 75 
13.2.2 
Safety Set (SS)..................................................................................................... 75 
13.2.3 
Intent-to-Treat (ITT) Set ..................................................................................... 75 
13.2.4 
Modified ITT ....................................................................................................... 75 
13.2.5 
Per Protocol Set .................................................................................................. 76 
13.3 
Protocol Deviations ................................................................................................................ 76 
13.4 
Efficacy Analyses .................................................................................................................... 76 
13.4.1 
Primary Efficacy .................................................................................................. 76 
13.4.2 
Key Secondary Efficacy ....................................................................................... 79 
13.4.3 
Further Secondary Efficacy Endpoints and Analyses ......................................... 82 
13.4.4 
Exploratory Endpoints and Analyses .................................................................. 83 
13.5 
Safety Analyses ...................................................................................................................... 83 
13.5.1 
Extent of Exposure ............................................................................................. 83 
13.5.2 
Adverse Events / Adverse Drug Reactions ......................................................... 83 
13.5.3 
Laboratory Assessments .................................................................................... 83 
13.5.4 
Vital Signs ........................................................................................................... 84 
13.5.5 
ECG ..................................................................................................................... 84 
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS........................................................................ 85 
15. QUALITY CONTROL AND QUALITY ASSURANCE .......................................................................... 86 
15.1 
Study Monitoring ................................................................................................................... 86 
15.2 
Audits and Inspections ........................................................................................................... 86 
15.3 
Protocol Modifications .......................................................................................................... 86 
16. ETHICS AND GOOD CLINICAL PRACTICE COMPLIANCE ................................................................ 87 
17. DATA HANDLING AND RECORDKEEPING.................................................................................... 88 
17.1 
Data Management ................................................................................................................. 88 
17.1.1 
Case Report Forms ............................................................................................. 88 
17.1.2 
Retention of Records .......................................................................................... 88 
18. REPORTING STUDY RESULTS AND PUBLICATION POLICY ............................................................ 90 
19. LIST OF REFERENCES ................................................................................................................. 91 
20. APPENDICES ............................................................................................................................. 94 
APPENDIX A 
SCHEDULE OF ASSESSMENTS ...................................................................... 95 
APPENDIX B 
SCHEDULE OF ASSESSMENTS: DOSING, SUA, AND URICASE 
ACTIVITY DURING THE TREATMENT PHASE ............................................................................... 99 

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APPENDIX C 
DOSING, SERUM URIC ACID, AND URICASE ACTIVITY 
ASSESSMENT SCHEDULE (TREATMENT PERIODS 1, 2, 3, 4, AND 5) ............................................ 100 
APPENDIX D 
DOSING, SERUM URIC ACID, AND URICASE ACTIVITY 
ASSESSMENT SCHEDULE (TREATMENT PERIOD 6) .................................................................... 100 
 
LIST OF IN-TEXT TABLES 
Table 1: 
Investigational Product .......................................................................................... 50 
Table 2: 
Individual Tophus Assessment Categories (by Central Reader) ............................ 59 
Table 3: 
Overall Tophus Response Categories .................................................................... 59 
 
 
LIST OF IN-TEXT FIGURES 
Figure 1: 
Study Schematic .................................................................................................... 37 
 
 

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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or Specialist Term 
Definition or Explanation 
AE 
adverse event 
AESI 
adverse event of special interest 
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 
COVID-19 
SARS-CoV-2 corona virus infection 
CR 
Complete Response 
CRF 
case report form 
CRO 
contract research organization 
CT 
computed tomography 
CXR 
chest x-ray 
CYP3A4 
Cytochrome P450, family 3, subfamily A 
d 
Day 
dL 
Deciliter 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EEA 
European Economic Area 
eGFR 
estimated glomerular filtration rate 
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 

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Abbreviation or Specialist Term 
Definition or Explanation 
hCG 
human chorionic gonadotropin 
Hct 
Hematocrit 
HCVAb 
hepatitis-C antibody 
HDL 
high density lipoprotein 
Hgb 
Hemoglobin 
HIV 
human immunodeficiency virus 
I 
Improved 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent 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 
mg 
Milligram 
MH 
Mantel-Haenszel 
mmHg 
millimeters of mercury 
MMRM 
mixed model for repeated measures 
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 
PrGA 
Provider Global Assessment of Disease Activity 
PLA 
poly [D,L-lactide] 
Plt 
Platelet 
PPS 
Per Protocol Set 
PR 
Partial Response 
PT 
Preferred Term 

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Abbreviation or Specialist Term 
Definition or Explanation 
PT 
prothrombin time 
QD 
once daily  
RA 
rheumatoid arthritis 
RBC 
red blood cell 
RCTC 
Rheumatology Common Toxicity Criteria 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
Scr 
Screening Phase 
SD 
Stable Disease 
SF-36 
Short Form Health Survey 
SOC 
System Organ Class 
SS 
Safety Set 
sUA 
serum uric acid 
TEAE 
treatment-emergent adverse event 
TID 
three times daily 
UACR 
urine-albumin-creatine ratio 
UE 
Unable to Evaluate 
ULN 
upper limit of normal 
ULT 
urate lowering therapy 
US FDA 
United States Food and Drug Administration 
USP 
United States Pharmacopeia 
WBC 
white blood cell 

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5. 
INTRODUCTION 
5.1 
Gout and Refractory Gout 
Gout is a chronic inflammatory condition with intermittent episodes of acute 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 160,000 patients in the United States and 
is characterized by uric acid levels that are not adequately controlled by conventional therapies. 
5.2 
Symptoms of Gout 
The symptoms and clinical signs of gout have a broad spectrum of severity. Most symptoms present as 
intermittent attacks or flares while others present as more severe, refractory disease have monosodium 
urate crystal deposition with a constellation of severe manifestations including gout flares, multiple 
joints with chronic gouty arthritis and subcutaneous tophus (Bursill 2019). In tophaceous 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 cells of the innate and adaptive immune response are usually present in 
tophi, which suggest a state of chronic monosodium urate-crystal-stimulated inflammation (Dalbeth 
2010). 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 2008). Additional complications 
include obstruction of the joint and infection as well as urolithiasis with uric acid stones or calcium 
oxalate stones (Ryan 2016). Tophaceous gout is associated with more frequent flares, which may be so 
painful and debilitating that they lead to joint replacement or surgical excision. Over time, flares become 
polyarticular, additive, and increase in severity (Brook 2010). 

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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 experienced worse physical functioning (Strand 2012).  
There is also evidence that gout affects workplace productivity, as studies in patients with chronic, 
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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 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 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 ~>200,000 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 (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 (Richette 2016). 
There are 2 uricase products currently used to treat hyperuricemia, albeit under different 
circumstances: rasburicase (ELITEK®) used for treating hyperuricemia in patients receiving anticancer 
therapy expected to result in tumor lysis and pegloticase (Krystexxa®) indicated for the treatment of 
chronic gout refractory to conventional therapy. 
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® 

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Prescribing Information 2014). 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 (89%) develop anti-pegloticase antibodies (Lipsky 2014). 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 (Sundy 2011). 
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 are potential drawbacks 
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 ImmTOR technology 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 
(ImmTOR) 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 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. 

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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 with gout refractory to 
conventional therapy treated with two different dose levels of SEL-212 compared to placebo.  
6.1.2 
Secondary Objectives 
The secondary objectives of this study are:  
• 
To compare the pharmacodynamic (PD) effect on sUA in patients with gout refractory to 
conventional treatment treated with two different dose levels of SEL-212 compared to placebo  
• 
To assess change of the following in patients with gout refractory to conventional treatment 
treated with two different dose levels of SEL-212 compared to placebo: 
o Tophus burden 
o Patient Reported Outcomes (PROs) including assessments of: patients’ quality of life (QoL) 
(SF-36); activity limitation (HAQ-DI); and Provider Global Assessment of Disease Activity 
o Gout flares 
o Joint tenderness and swelling 
• 
To assess effects on the formation of anti-uricase and anti-pegadricase antibodies 
• 
To assess the safety and tolerability of SEL-212 compared to placebo 
• 
To assess the reduction in serum uric acid (sUA) in patients with gout refractory to conventional 
treatment treated with two different dose levels of SEL-212 compared to placebo, amongst 
those with tophi at baseline 
6.1.3 
Exploratory Objectives 
The exploratory objectives of this study are: 
• 
To assess the levels of uricase activity in patients receiving SEL-212 compared to placebo 
• 
To assess the effect on monosodium urate crystal deposits and/or total body monosodium urate 
crystal deposits in patients with gout refractory to conventional treatment treated with two 
different dose levels of SEL-212 compared to placebo (imaging patients only) 
• 
To assess the status of biomarkers related to inflammation and tolerogenic immunologic 
responses in patients with gout refractory to conventional treatment treated with two different 
dose levels of SEL-212 compared to placebo  
• 
To assess the relationship between multiomic markers of gout and treatment effect in patients 
with gout refractory to conventional treatment treated with SEL-212 compared to placebo 
• 
To assess the impact on patient’s self-assessment of gout flares and burden of disease using a 
validated patient diary (weekly) in patients treated with two different dose levels of SEL-212 
compared to placebo 
• 
To assess the correlation between immune tolerance related multiomic markers and 
anti pegadricase antibody formation in patients treated with two different dose levels of 
SEL-212  

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6.2 
Study Endpoints 
The confirmatory analysis of efficacy will be performed at Day 28 of Treatment Period 6.  
6.2.1 
Primary Efficacy Endpoint 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with regards 
to the following primary endpoint: 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for at least 
80% of the time during Treatment Period 6 by Day 28. 
6.2.2 
Secondary Efficacy Endpoints 
6.2.2.1 
Key Secondary Efficacy Endpoints 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with regards 
to the following key secondary endpoints: 
• 
Reduction of mean sUA as computed by subtracting the Baseline sUA level from the mean sUA 
(area under the sUA time curve) during Treatment Period 6 
• 
Percent reduction of mean sUA as computed by subtracting the Baseline sUA level from the 
mean sUA (area under the sUA time curve) during Treatment Period 6 
• 
The change from Baseline to Day 28 of Treatment Period 6 in the physical summary score of the 
Short Form Health Survey (SF-36) 
• 
In patients with tophi at Baseline, the percentage of patients with at least partial response (PR) 
(as best response) in overall tophus response evaluation until Day 28 of Treatment Period 6 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for at least 
80% of the time during Treatment Period 6 in the subset of patients with tophi at baseline 
• 
The change from Baseline to Day 28 of Treatment Period 6 in number of tender joints 
• 
The change from Baseline to Day 28 of Treatment Period 6 in the total score of the Health 
Assessment Questionnaire (HAQ-DI)  
• 
Gout flare incidence during Treatment Periods 1-6 
• 
Gout flare incidence during Treatment Periods 1-3 
6.2.2.2 
Additional Secondary Efficacy Endpoints 
Each of the two active treatment groups, SEL-212A and SEL-212B, are compared to placebo with regards 
to the following additional secondary efficacy endpoints: 
• 
The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for 100% of 
the time during Treatment Period 6  
• 
 
• 
Percentage of pre-dose sUA values ≤ 6 mg/dL during Treatment Periods 2-6 for each patient 
• 
Pre-treatment anti-pegadricase and anti-uricase antibody formation and levels in each 
treatment period in the SEL-212 active treatment arms during Treatment Periods 1-6 
• 
Percentage of patients with development of new tophi in the subgroups of tophaceous patients 
and in non-tophaceous patients at Baseline during Treatment Periods 1-6 

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• 
In patients with tophi at Baseline, the percentage of patients with at least PR (as best response) 
in overall tophus response evaluation until Day 0 of Treatment Period 4 
• 
Change from Baseline to Day 28 of Treatment Period 6 in the subscales of Health Assessment 
Questionnaire (HAQ-DI), in Provider Global Assessment of Disease Activity, and in subscales of 
Short Form Health Survey (SF-36) 
• 
The percentage of patients with at least 1 gout flare during Treatment Periods 1-3 
• 
The percentage of patients with at least 1 gout flare during Treatment Periods 1-6 
• 
Change from Baseline to Treatment Period 6 in number of swollen joints 
• 
Length of time patients are anti-uricase antibody free or before induction of anti-uricase 
antibody levels above baseline in patients receiving SEL-212  
• 
Length of time patients are anti-pegadricase antibody free or before induction of 
anti-pegadricase antibody levels above baseline in patients receiving SEL-212  
6.2.3 
Exploratory Endpoints 
The exploratory endpoints of this study are: 
• 
Levels of uricase activity in patients receiving SEL-212 
• 
Levels of monosodium urate crystal deposits and/or total body monosodium urate crystal 
deposits (imaging patients only) 
• 
Levels of inflammatory and tolerogenic biomarkers  
• 
Changes in antibody production (anti-uricase and anti-pegadricase) in patients in the SEL-212 
groups 
• 
Gout flare incidence during Treatment Periods 4-6 
• 
Gout flare incidence during Treatment Periods 1-3 based on self-reported weekly gout flare 
diary  
• 
Gout flare incidence during Treatment Periods 1-6 based on self-reported weekly gout flare 
diary 
• 
Gout flare incidence in the Treatment Periods 4-6 based on self-reported weekly gout flare diary  
• 
Assessment of association between multiomic markers of gout and treatment effect in patients 
treated with SEL-212 
• 
Comparison of immune tolerance related multiomic markers in patients on SEL-212 who 
developed anti-uricase and anti-pegadricase antibodies vs. those patients on SEL-212 that did 
not develop anti-uricase and anti-pegadricase antibodies 
6.2.4 
Safety Endpoints 
The safety endpoints of this study are: 
• 
Safety and tolerability of SEL-212 compared to placebo as assessed by AEs, AESI, 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; eGFR; UACR; vital signs; immunogenicity 
analyses; 12-lead ECGs; and physical examination findings. 

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7. 
INVESTIGATIONAL PLAN 
7.1 
Overall Study Design 
This study is one of two randomized, double-blind, placebo-controlled, parallel-arm trials to determine 
the safety and efficacy of two different dose levels of SEL-212 compared to placebo. The study will 
randomize approximately 140 patients with chronic refractory gout. Approximately 60% of the 
randomized patients will have tophi at Baseline. Patients, stratified as to the presence or absence of 
tophi, will be randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of 
two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial 
(SEL212/301 and SEL-212/302). These two trials will have identical designs with respect to being double-
blinded, placebo-controlled as well as identical sample sizes, inclusion/exclusion criteria, efficacy/safety 
assessments and timing thereof, but will be distinguished by a blinded 6-month extension in SEL-
212/301 and that SEL-212/302 will include sites outside of the United States. Placebo patients in either 
SEL-212/301 or SEL-212/302 who complete the study, will be offered enrolment in an open-label 
extension study for treatment with SEL-212 (SEL-212/303). Efficacy assessments will be conducted at 
intervals that are appropriate to determine treatment effect with samples for the primary endpoint 
drawn during Treatment Period 6. Samples will be collected at intervals that are appropriate to 
determine the uricase activity of SEL-212. Safety will be monitored throughout the study with an 
independent data safety monitoring board (DSMB).  
The study will be divided into 3 study phases: 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 
215 days) as follows: 
• 
Screening and/or washout and premedication Phase: up to 45 days (up to 6.5 weeks) 
• 
Treatment Phase: 168 days (24 weeks) 
• 
Safety Follow-Up: 30 days after last infusion  
7.1.1 
Screening Phase 
After providing written informed consent, the patient is considered enrolled in the study. Patients will 
be evaluated for inclusion during the Screening Phase. For all patients, the standard Screening Phase will 
be up to 45 days prior to Baseline. The Screening Phase may be initiated by a preliminary screening with 
an abbreviated informed consent focused on COVID-19 testing and serum uric acid levels followed by 
providing study-wide informed consent and the remainder of screening assessments if determined to 
proceed. Of note, if the sUA level obtained during preliminary screening meets eligibility requirements 
(i.e., ≥ 7 mg/dL), the sUA should not be repeated during the subsequent complete screening 
assessment. Concurrently with the Screening Phase, a premedication period for potential gout flare with 
colchicine (or non-steroidal anti-inflammatory drug [NSAID], if colchicine is contraindicated) of at least 7 
days prior to Baseline will be required for all patients, and a washout period of at least 7 days will be 
required prior to Baseline for patients on any urate-lowering therapy (ULT). Both the ULT washout 

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period and the gout flare prophylaxis period may be started earlier than 7 days prior to Baseline. At 
the discretion of the PI, chronic refractory gout patients whose sUA is lower than the eligibility level 
of ≥7 mg/dL on prescreening or initial screen, may undergo ULT washout prior to retesting the sUA. 
Initiation of gout flare prophylaxis with colchicine (or non-steroidal anti-inflammatory drug [NSAID], if 
colchicine is contraindicated) can also be considered coincidentally with the ULT washout to prevent a 
potential gout flare. 
7.1.2 
Double Blind Treatment Phase 
The total duration of the double-blind Treatment Phase will be approximately 6 months (i.e., 168 days, 
consisting of six 28-day treatment cycles). 
Eligible patients, stratified as to the presence or absence of tophi, will be randomized in a 
1:1:1 allocation ratio prior to Baseline to receive one of two dose levels of SEL-212 or placebo. The SEL-
212 doses will differ as to the SEL-110.36 component. Participants will receive SEL-037 administered at a 
dose level of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving SEL-110.36 at a dose 
level of either 0.1 mg/kg (SEL-212A) or 0.15 mg/kg (SEL-212B) via IV infusion. The placebo will consist of 
normal saline that will be administered in the same way that the SEL-212 components are administered 
to maintain the integrity of the study blind. Refer to Section 10 for details about study drug 
administration.  
Patients will complete 6 treatment periods each having a duration of 28 days. Patients will receive 
treatment with study drug or placebo on Day 0 of each treatment period for a total of 6 doses. For each 
treatment cycle, patients in both treatment and placebo groups will receive premedication to minimize 
the potential for infusion reactions during study drug administration. After completing the study drug 
infusions, participants will remain at the investigational site for 1 hour for safety assessments.  
With each dose, a blood sample will be drawn for assessment of sUA level and uricase activity 
immediately prior to infusion (i.e., Time 0 h) with SEL-212 or placebo and 1 hour after the infusion of the 
second component of SEL-212 or of placebo is completed. Serum uric acid levels will be assessed 
through additional post-infusion blood samples at pre-determined time points by an independent, 
central, unblinded medical monitor.  
Gout flares will be assessed at each study visit during the Treatment Phase using a validated definition of 
flares in patients with established gout (Gaffo 2018). In addition, in an exploratory manner, gout flares 
will be self-assessed by the patient weekly after randomization and in each Treatment Period using a 
weekly flare diary (Poiley 2016). Patient reported outcome measures (PROs), tophus burden and joint 
swelling and tenderness will be assessed on Day 0 of Treatment Periods 1 and 4, and at the end of 
Treatment Period 6 or early termination (ET) if a patient discontinues the study prior to the end of 6 
monthly infusions. Samples for anti-uricase, anti-PEG, and anti-pegadricase antibody levels will be taken 
(i) prior to administration of study drug dosing and at Day 21 for each of the six treatment periods 
throughout the trial and (ii) at the end of Treatment Period 6 or at ET. Exploratory assessments of 
inflammatory/immunologic biomarkers and multiomic analysis will also be assessed. 

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Safety laboratory samples, consisting of, but not limited to, complete blood count (CBC) including white 
blood cell count (WBC) and absolute neutrophil count; liver function tests (LFTs) including aspartate 
aminotransferase (AST) and alanine transaminase (ALT); serum lipids (including triglycerides and low 
density lipoprotein (LDL)), analyses of renal function including creatinine, urine albumin creatinine ratio 
(UACR), and estimated glomerular filtration rate (eGFR) will be collected on Day 0 and Day 21 of 
Treatment Period 1, on Day 21 only of each of Treatment Periods 2-5, and on Day 21 and Day 28 / ET of 
Treatment Period 6. On Treatment Period 1 Day 0, safety laboratory samples will be collected pre-
infusion in both the SEL-212 arm and the placebo arm. Concomitant medications and procedures and 
adverse events (AEs) will be monitored continuously during the study. Post-Baseline chest X-rays (CXR) 
will be taken at at six months / ET to assess for presence of or changes in interstitial lung disease (ILD) 
compared to baseline CXR.  
7.1.3 
Follow-Up Phase 
Patients will be followed for safety monitoring (30 + 4 days) after their final study drug infusion and will 
have an End of Study visit by telephone at the following times: either (1) at the completion of the 6 
month Treatment Phase or (2) at early termination if the patient voluntarily withdraws consent.  
Patients who terminate the study prematurely will continue to be followed by having 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.  
If withdrawn from study drug, regardless of reason, the patient will continue study visits to the end of 
Treatment Period 6. 
Figure 1: 
Study Schematic 
 
7.2 
Number of Patients 
The study will randomize approximately 140 patients with chronic refractory gout. Approximately 60% 
of the randomized patients will have tophi at Baseline. 
7.3 
Treatment Assignment 
Patients will be randomized in a double-blind way with an allocation ratio of 1:1:1 to receive treatment 
with two different dose levels of SEL-212 or placebo. Randomization will be stratified by 
presence/absence of tophi. 
7.4 
Dose Adjustment Criteria 
Unless otherwise specified, study drug will be administered as described in Section 9 and Section 10. 

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7.4.1 
Safety Criteria for Adjustment or Stopping Doses 
7.4.1.1 
SEL-212 or Placebo 
A patient will be withdrawn from study drug for meeting the following stopping rule: 
• 
sUA level < 2.0 mg/dL, measured 1 hour after the infusion of the second component of study 
drug is completed during Treatment Period 1 
AND 
• 
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 
Stopping rules will be assessed by an independent, central, unblinded medical monitor. 
If withdrawn from study drug, the patient will continue study visits to the end of Treatment Period 6. 
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 will 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 a protocol deviation occurs where a 
patient is not able to be dosed within the dosing day window (for example in the case of COVID-19 
restrictions temporarily preventing dosing) the current treatment period will be extended up to a 
maximum of 90 days without skipping doses for patients with a Day 21 visit sUA value ≤ 1.0 mg/dL 
during Treatment Period 1 or ≤ 6.0 mg/dL during Treatment Periods 2, 3, 4, or 5 in the D21 visit window 
or subsequent up to the rescheduled dosing visit. If a protocol deviation occurs in Treatment Period 6 
such that the patient was unable to have an EOS visit performed within the visit window, then the 
Treatment Period 6 Day 28 visit should still occur 28 days (+3/-4 days) after the Treatment Period 6 dose 
or as close to the visit window as possible to collect the final primary endpoint sUA sample. 
To maintain the blind, a central group of unblinded pre-specified medical personnel will adjudicate the 
implementation of the 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 ULT 60 days after the 
patient’s last study drug treatment. ULT shall not be SEL-212 or any experimental or marketed uricase 
(e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®)), for the remainder of the study. 

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7.4.2 
Criteria for Adjustment or Stopping Doses 
An independent Data and Safety Monitoring Board (DSMB) 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 (Appendix A) 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/IEC, Sponsor or designee, or regulatory 
authorities. 
7.6 
Study Rationale 
7.6.1 
Rationale for the Study Design 
Refractory gout is a serious condition affecting approximately >200,000 patients in the United States 
and is characterized by uric acid levels that are not adequately controlled by xanthine oxidase inhibitors, 
such as allopurinol or febuxostat, or for whom such drugs are contraindicated. About 5% to 10% of gout 
patients are not treated effectively with allopurinol and thus continue to have acute flares and may 
experience destructive joint damage and tophus formation (Edwards 2008, Fels 2008). Additionally, 
approximately 2% of gout patients exposed develop hypersensitivity to allopurinol which can lead to 
very serious complications and even death (Markel 2005). 
Pegloticase (Krystexxa®), a pegylated uricase, was approved by the United States Food and Drug 
Administration (FDA) in 2010 for the treatment of chronic gout in patients refractory to conventional 
therapy. Pegloticase is effective in lowering serum uric acid after a single dose. However, >58% of 
subjects treated with pegloticase experience loss of efficacy within 6 months with the vast majority 
experiencing loss of efficacy within 3 months due to the formation of anti-drug antibodies (ADAs) with 
the possibility of infusion reactions, sometimes severe.  
SEL-212 is a combination drug product consisting of SEL-037 and SEL-110.36. SEL-037 (pegadricase, 
pegylated recombinant Candida utilis urate oxidase) is an investigational biological therapeutic product 
presented as a lyophilized pegylated recombinant uricase for intravenous injection. SEL-110.36 is 
designed to inhibit the formation of ADAs when concomitantly administered with a biologic, specifically, 
the uricase, pegadricase or SEL-037.  

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The overall development of SEL-212 remains focused on mitigating the formation of ADAs with the goal 
of providing a product with better efficacy and safety profiles in patients than the only approved 
available therapy. 
Study SEL-212/302 is a randomized, double-blind, placebo-controlled, parallel-arm study to determine 
the safety and efficacy of multiple doses of SEL-212 compared to placebo.  
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 blinding scheme in this study will be applied to all patients, Investigators, study personnel, and 
Sponsor personnel involved in the conduct of the study, except for a designated unblinded statistician 
who will generate and have access to the randomization codes, a designated unblinded site 
representative (e.g., pharmacist) who will prepare study drug on the day of treatment, an unblinded 
infusion nurse who will be responsible for dosing the patient, a designated unblinded medical monitor 
for assessing the treatment stopping rules, and unblinded drug supply personnel. Blinding and 
randomization will reduce the potential for treatment bias and will improve the veracity of detected 
efficacy and safety signals, particularly in the use of patient-reported quality of life assessments. The 
parallel arms involving active treatment and placebo will permit adequate statistical comparison of the 
groups for efficacy and safety signal detection.  
Placebo (normal saline) rather than an active control will be employed in this study for ethical and 
practical considerations. The approved therapeutic for patients with gout refractory to conventional 
therapy (pegloticase) and the uricase product currently used to treat hyperuricemia (rasburicase) 
include exogenous enzymes that are highly immunogenic (Section 5.5) and that would expose patients 
randomized to an active control group to unnecessary risk. The dosing regimens of the approved 
enzymes are substantially different from the dosing regimen of SEL-212 and would defeat the steps 
taken to blind the study. The use of multiple doses of SEL-212 will help determine optimal efficacy: 
safety profile in a heterogenous population of patients with significant co-morbidities.  
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. 

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7.6.3 
Rationale for the Selected Dose 
Dose selection for this Phase 3 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 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).  
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. 
In the Phase 1b study (SEL-212/101), patients (N = 64) with a serum uric acid level ≥ 6 mg/dL, with or 
without a history of gout, were administered SEL-110 alone, SEL-037 (pegadricase) alone, or SEL-212 
(SEL-037 + SEL-110) 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 SEL-110 alone on sUA levels, and patients administered SEL-037 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 SEL-110 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 Phase 2 study 
SEL-212/201. 
7.6.3.2 
Phase 2 Studies with SEL-212 
7.6.3.2.1 
Phase 2 Study SEL-212/201 
The Phase 2 study SEL-212/201 was designed as an open-label, ascending multiple-dose study of the 
combination drug, SEL-212, combined with an open-label, multiple-dose evaluation of SEL-037 
(pegadricase) alone in patients with symptomatic gout and elevated blood uric acid. 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). Additional 
assessments include the ability of SEL-212 to reduce serum uric acid levels and prevent anti-drug 
antibodies to uricase and pegadricase. Part C of the study consisted of 5 monthly doses of SEL-212. 
In Study SEL-212/201 with SEL-212, sUA levels remained consistently below 6 mg/dL in 70% to 89% of 
evaluable Part A patients administered SEL-212 once monthly for 3 months. The control of sUA 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 rapamycin (sirolimus - 

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Rapamune®). Data support a once monthly dosing regimen. For cohorts 7-12 with SEL-110 doses of 0.1 
mg/kg or higher, 46% of evaluable patients had sUA <6 mg/dL at week 20. 
In Part C cohorts receiving 5 monthly doses of SEL-212, 61%, 71%, and 67% of eligible patients in Cohorts 
13, 15, and 17, respectively, maintained sUA control (sUA, <6 mg/dL) at week 12 without the 
development of ADAs. All 21 patients in cohorts 13, 15 and 17 who had sUA < 6 mg/dL at week 12, 
maintained sUA control through the end of treatment period 5 and had sUA < 6 mg/dL at week 20. 
The efficacy signal of SEL-212 in SEL-212/201 persists across multiple treatment cycles in all cohorts and 
through all 5 treatment cycles when SEL-212 is given at each treatment, as demonstrated by dose-
dependent reductions in sUA levels below 6 mg/dL and ADA suppression in conjunction with increasing 
SEL-110 dose levels up to 0.15 mg/kg. 
Cohorts 7,11, 13 and 17 represent the dose regimens that will be evaluated in the Phase 3 program (0.1 
or 0.15 mg/kg SEL-110 and 0.2 mg/kg SEL-037). Part C cohorts 13, 15, and 17 received 5 once monthly 
doses of SEL-212, and patients in the proposed Phase 3 program will receive a total of 6 or 12 once 
monthly doses of SEL-212. 
Across cohorts 1 to 17, 28 SAEs have been reported in 20 of 152 (13.2%) patients. They include 9 
infusion reactions reported as related or possibly related to SEL-212. Of these 9 infusion reactions, only 
3 occurred during repeat dosing of SEL-212 in cohorts 7, 13 and 17; 4 occurred in cohorts that received 
SEL-037 alone or SEL-037 with the lowest dose of SEL-110 (0.05 mg/mL); and 2 were due to dosing 
errors. All SAEs were successfully treated without complication. No study drug related SAEs or 
discontinuations involving gout flares, metabolic disorders, hypophosphatemia, or changes in lipid levels 
have been reported in the Phase 2 study SEL-212/201.  
Leukopenia can be seen in patients taking high doses of rapamycin for extended periods of time. 
Leukopenia was reported by investigators in 11 (7.2%) and neutropenia in 6 (3.9%) of patients. One 
patient’s neutropenia was reported as severe but not identified with a TEAE of infection. No SAEs or 
study drug discontinuations involving leukopenia or neutropenia have been reported. 
Another TEAE seen in patients taking oral rapamycin is stomatitis (mTor Inhibitor associated stomatitis-
mIAS) and was observed in the SEL-212 Phase 2 trial at a lesser rate than seen in previous clinical trials 
(Peterson 2016). Stomatitis or aphthous ulcers were reported in 19 (12.5%) of patients; all were mild or 
moderate in severity. The TEAEs categorized as stomatitis or oral lesions did not result in any SAEs, study 
drug discontinuations, or withdrawals. All resolved with minimal topical oral treatment of 
corticosteroids. 
Additional TEAEs of particular interest for rapamycin are hyperglycemia, hypophosphatemia, and 
hypertriglyceridemia. These were reported in 5.9%, 3.9% and 17.8% of patients in the SEL-212 Phase 2 
trial, respectively. These TEAEs resolved without any medical intervention, their duration was transient, 
and they did not result in any SAEs, study drug discontinuations, or withdrawals. 

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7.6.3.2.2 
Phase 2 Study SEL-212/202 
Study SEL-212/202 is a Phase 2 randomized, open-label, parallel-arm study to compare the safety and 
efficacy of IV infusions of SEL-212 compared to KRYSTEXXA for 6 months. The study has completed 
enrollment but is ongoing in the treatment phase. Data presented are based upon a data cutoff of 19 
March 2020. 
Subjects in the SEL-212 arm received study drug (SEL-110.36, 0.15 mg/kg + SEL-037, 0.2 mg/kg) every 28 
days (Day 0 of each treatment period) for a total of 6 infusions. Subjects in the KRYSTEXXA arm received 
study drug (8 mg) every 14 days (per manufacturer’s prescribing information, Day 0 and Day 14 of each 
treatment period) for a total of 12 infusions.  
The planned enrollment was 150 subjects. Actual enrollment was 170 subjects and included 83 subjects 
in the SEL-212 arm and 87 subjects in the KRYSTEXXA arm.  
Subjects ranged in age from 29 to 79 years with 163 males (95.9%) and 7 females (4.1%). Twenty-seven 
(27) subjects (15.8%) have completed the study and 22 subjects (12.9%) discontinued from the study. 
Primary reasons for early discontinuation from the study were withdrawal of consent in 13 (7.6%) 
subjects, adverse event in 3 (1.8%) subjects, lost to follow-up in 3 (1.8%) subjects; and “other” in 3 
(1.8%) subjects. 
Overall, 135 of the 169 (79.9%) subjects enrolled have experienced TEAEs: 71 of the 83 (85.5%) subjects 
who received SEL-212, and 64 of the 86 (74.4%) subjects who received KRYSTEXXA. Overall, 74 of the 
169 (43.8%) subjects enrolled have experienced a TEAE that was considered by the investigator to be 
related or possibly related to study drug (i.e., drug-related): 41 of the 83 (49.4%) subjects who received 
SEL-212, and 33 of the 86 (38.4%) subjects who received KRYSTEXXA.  
In the study, the following TEAEs were identified as Adverse Events of Special Interest (AESIs): infusion-
related reactions, stomatitis and related terms, gout flares, infections, interstitial lung disease, 
malignancies, renal failure, and clinically significant laboratory tests demonstrating hyperlipidemia, 
worsening of renal function tests, proteinuria, and leukopenia. Subjects with at least 1 TEAE of special 
interest included 24 (27.9%) subjects who received KRYSTEXXA and 33 (39.8%) subjects who received 
SEL-212.  
Overall, most TEAEs have been mild or moderate in severity. Eight (8) of the 83 (9.6%) subjects who 
received SEL-212 experienced a total of 14 severe TEAEs. Four (4) subjects experienced a single severe 
TEAE including anemia, gout, rotator cuff syndrome, and deep vein thrombosis (DVT); 2 subjects 
experienced 2 severe TEAEs including gastrointestinal haemorrhage and gout; and pulmonary embolism 
and DVT; and 2 subjects experienced 3 severe TEAEs including: arthralgia, joint swelling, and ligament 
pain; and presyncope and 2 gout attacks. In addition, 2 subjects who received SEL-212 each experienced 
a life-threatening TEAE, both anaphylactic reactions.  
A total of 6 of the 86 (7.0%) subjects who received KRYSTEXXA experienced a total of 6 severe TEAEs. 
Subjects experienced a single severe TEAE including: 2 gout, an anaphylactic reaction, drug 

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hypersensitivity, gastroenteritis, and an infusion-related reaction. In addition, 2 subjects who received 
KRYSTEXXA each experienced a life-threatening TEAE of cerebrovascular accident and hypertensive 
emergency, respectively. There have been no concerning trends in laboratory values, vital signs, or 
physical examination findings (data not shown). 
Twelve (12) of the 169 (7.1%) subjects enrolled have experienced a total of 14 SAEs. Six (6) of the 83 
(7.2%) subjects who received SEL-212 experienced a total of 7 SAEs and 6 of the 86 (7.0%) subjects who 
received KRYSTEXXA experienced a total of 7 SAEs. Two (2) of the SEL-212 SAEs were considered related 
or possibly related to SEL-212 and 3 of the KRYSTEXXA SAEs were considered related or possibly related 
to KRYSTEXXA by the investigator. 
No deaths have been reported during the study. 
In summary, the safety profile of SEL-212 in the ongoing Phase 2 clinical trial has not demonstrated any 
unexpected TEAEs. In the dose ranging Phase 2 Study SEL-212/201, in general, TEAEs were most 
frequently observed after the first treatment cycle and diminished with successive treatment cycles. 
Therefore, the potential risk of TEAEs did not appear to increase with repeated exposure to SEL-212. 
Cohorts 7, 11, 13, and 17 from Phase 2 Study SEL-212/201 represent the dose regimens that will be 
evaluated in the Phase 3 program; and the dose administered in the Phase 2 study SEL-212/202 (SEL-
110.36, 0.15 mg/kg + SEL-037, 0.2 mg/kg) represents the high dose planned in the Phase 3 program. 
Data from these two Phase 2 studies support the doses to be administered in Phase 3 and efficacy data 
from Phase 2 Study SEL-212/201 support monthly dosing with SEL-212. 
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 adult patients treated with SEL-212 
compared to placebo. The proposed primary endpoint is comparison in the percentage of participants 
treated with two different dose levels of SEL-212 compared to placebo who achieve and maintain 
reduction of sUA <6 mg/dL for at least 80% of the time during Treatment Period 6. 
7.6.5 
Rationale for Secondary Efficacy Endpoints 
Secondary endpoints were selected based on the long term symptoms of gout as well as quality of life as 
a consequence of severe gout. Patients with severe gout are often refractory to oral therapies and often 
present with visible tophi that cause debilitating pain, corresponding to significantly reduced quality of 
life. Exacerbation of gout (flare) and joint tenderness and swelling impact a patients’ ability to maintain 
physical activity and functioning and adversely affect quality of life. Several instruments will be used to 

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assess quality of life and will include patient-reported outcomes, provider-reported assessments, and 
generalized assessments of overall quality of life. 
7.6.6 
Rationale for Other Assessments of Clinical Benefit 
Exploratory assessments will be used to characterize the effect of SEL-212 on biomarkers of 
inflammation related to gout and multiomic markers of gout.  
Genome wide association studies have identified multiple genetic markers in regulating urate 
metabolism. These markers may explain some of the variation observed in the control of sUA levels in 
patients on SEL-212.  
Recombinant uricases are highly immunogenic and formation of anti-drug antibodies can adversely 
affect durability of efficacy. Anti-uricase and anti-pegadricase antibodies will be assessed and correlated 
with response to SEL-212. 
SEL-110 induces durable antigen-specific immune tolerance in preclinical models. Correlation of the 
mitigation of anti-drug antibodies with biomarkers related to immune tolerance would support the 
induction of antigen-specific immune tolerance against SEL-037. 
Finally, visualization of the effect of SEL-212 on joint surfaces will use multiple imaging modalities, 
depending on the investigational site. 
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 dose to be studied in this Phase 3 study 
• 
Potential to re-treat patients after a gap in therapy (> 1 month) because of the mechanism of 
action of SEL-212 
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 Phase 3 study of SEL-212 in the intended population of patients with chronic gout 
refractory to conventional therapy.  

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8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1 
Patient Inclusion Criteria 
A patient must meet all 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 negative results of an FDA Emergency Use Authorized COVID-19 molecular assay for 
detection of SARS-CoV-2 RNA from a nasal or oropharyngeal specimen; 
4. Has a history of symptomatic gout defined as: 
o ≥ 3 gout flares within 18 months of Screening or 
o Presence of ≥ 1 gout tophus or 
o Current diagnosis of gouty arthritis 
5. At the Screening Visit male age 19 – 80 years, inclusive or female of non-childbearing potential 
age 19-80 years, inclusive, where non-childbearing potential is defined as: 
o > 6 weeks after hysterectomy with or without surgical bilateral salpingo-oophorectomy or 
o Post-menopausal (> 24 months of natural amenorrhea or in the absence of >24 months of 
amenorrhea, 1 documented confirmatory FSH measurement) 
6. Has chronic refractory gout defined as having failed to normalize sUA and whose signs and 
symptoms are inadequately controlled with any of the xanthine oxidase inhibitors, either 
allopurinol and/or febuxostat, at the medically appropriate dose, or for whom these drugs are 
contraindicated for the patient 
7. Has at Screening sUA ≥ 7 mg/dL 
8. Has not participated in a clinical trial within 30 days of the Screening Visit and agrees to not 
participate in a clinical trial for the duration of the study; 
9. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative antibodies to 
hepatitis C;  
8.2 
Patient Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study: 
1. Has a history of anaphylaxis, severe allergic reactions, or severe atopy; 
2. Has a history of any allergy to pegylated products, including, but not limited to pegloticase 
(Krystexxa®), 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®); 
3. Is taking and cannot discontinue known major CYP3A4/P-gp inhibitors or major CYP3A4/P-gp 
inducers at least 14 days before dosing. Patients must remain off these medications for the 
duration of the study, including natural products such as St. John’s Wort or grapefruit juice. 

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4. Is taking drugs known to interact with rapamycin (sirolimus - Rapamune®) such as cyclosporine, 
diltiazem, erythromycin, ketoconazole, posaconazole, voriconazole, itraconazole, rifampin, 
verapamil unless they are stopped 14 days prior to dosing and will not be used/prescribed 
during the trial. 
5. Had major surgery within 3 months of initial screening. 
6. Had a gout flare during Screening that was resolved for less than 1 week prior to first treatment 
with study drug (exclusive of chronic synovitis/arthritis) unless the patient has a history of inter-
flare intervals of < 1 week. 
7. Has uncontrolled diabetes at Screening with HbA1c ≥ 8.5%; 
8. Has fasting Screening glucose > 240 mg/dL 
9. Has fasting Screening triglyceride > 500 mg/dL; 
10. Has fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; 
11. Has glucose-6-phosphate dehydrogenase (G6PD) deficiency;  
12. Has uncontrolled hypertension defined as blood pressure > 170/100 mmHg at Screening and 1 
week prior to dosing 
13. Individual laboratory values which are exclusionary 
o White blood cell count (WBC) < 3.0 x109/L 
o Serum aspartate aminotransferase (AST) or alanine amino transferase (ALT)  
> 3x upper limit of normal (ULN) in the absence of known active liver disease 
o Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 
o Urine-albumin-creatinine ratio (UACR) > 30 mg/g creatinine (conventional units) or > 3.39 
mg/mmol creatinine (SI units) 
o Hemoglobin (Hgb) < 9 g/dL 
o Serum phosphate < 2.0 mg/dL 
14. Is receiving ongoing treatment for arrhythmia, including placement of an implantable 
defibrillator, unless considered stable and on active treatment; 
15. Has evidence of unstable cardiovascular disease or unstable cerebrovascular disease. This 
includes patients who have had a cardiac/vascular event(s) in the last 3 months including heart 
attack, stroke or vascular bypass surgery prior to dosing or patients who are deemed, by their 
physician or PI, to have active cardiovascular, cerebrovascular, or peripheral vascular 
symptoms/disease inadequately controlled by medication; 
16. Has congestive heart failure, New York Heart Association Class III or IV; 
17. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with evidence of 
clinically significant arrhythmia or other abnormalities that, in the opinion of the investigator, 
are consistent with significant underlying cardiac disease; 
18. History of significant hematological disorders within 5 years or autoimmune disorders, and/or 
patient is currently immunosuppressed or immunocompromised;  
19. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), 
pegloticase (Krystexxa®), pegadricase (SEL-037)) 
20. Patient has received a live vaccine in the previous 6 months.  

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21. Patient is planning to receive any live vaccine during the study. Of note, inactivated vaccines are 
permitted but, study drug may affect response to vaccination; therefore, during study drug 
treatment vaccination with inactivated vaccines may be less effective. Consider high-dose 
influenza vaccine to increase the likelihood of developing a protective immune response. 
22. History of malignancy within the last 5 years other than basal skin cancer; 
23. Any condition, that in the opinion of the investigator, would be negatively affected by 
rapamycin.  
24. Patients with a documented history of moderate or severe alcohol or substance use disorder 
within the 12 months prior to randomization. 
25. History of or evidence of clinically severe interstitial lung disease 
26. Immunocompromised state, regardless of etiology 
27. Patients who, in the opinion of the investigator, present with a condition that would 
compromise their safety or that would make study completion unlikely 
8.3 
Patient Completion and Withdrawal Criteria 
8.3.1 
Screen Failures and Replaced Subjects 
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. Any 
patient that is randomized but not dosed will be replaced and not included in the ITT population, and 
the reason for not being dosed 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 (except for COVID-19 testing as described in Section 12.1.8.7). 
After the 45-day screening window, patients can be re-screened once.  
8.3.2 
Patient Completion 
A patient will be considered to have completed the study when the patient has completed the Safety 
Follow-up visit that occurs 30 days (+ 4 day) after the Treatment Period 6 Day 0 visit. Enrolled patients 
who prematurely discontinue for any reason before completion of the study will be treated as outlined 
below in Section 8.3.3.1. 
8.3.3 
Enrolled Patient Withdrawal and Discontinuations 
8.3.3.1 
Withdrawal Procedures 
Early termination from the study occurs when an enrolled patient withdraws consent or is lost to follow-
up. The reason for withdrawal will be evaluated and recorded in the case report form (CRF) and source 
documents.  
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 upon termination should have the Early Termination visit assessments completed (i.e., End of 
Study assessments) (Appendix A), if the assessments pose no risk to the patient and the patient allows 
such assessments.  

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The Investigator should consult with the Sponsor/medical monitor prior to withdrawing study drug from 
any patient in the study. Since this is a multiple-dose study, once dosed, patients generally should not be 
terminated by the Investigator. The patient 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.  
8.3.3.2 
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. Additional efforts, will be implemented to encourage overall continued trial 
participation including: 1) weekly phone calls to establish patients overall satisfaction with engagement 
in the trial and participation; 2) use of NSAIDs and/or colchicine as rescue medication for patients with 
breakthrough symptoms; and 3) access to disease related educational material for implementation of 
life-style/dietary changes related to amelioration of the disease process.  

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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 
Urate Lowering Therapy 
Urate lowering therapy (ULT) including, but not limited to allopurinol, febuxostat (Uloric®), probenecid, 
lesinurad (Zurampic®, Duzallo®), losartan, pegloticase (Krystexxa®) 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 schedule described in Appendix A. Patients on a stable long term dose of 
losartan may be allowed to continue in the study without changing to another angiotensin II receptor 
blocker. 
Patients cannot have any prior exposure to or be presently taking any experimental or marketed uricase 
therapy, as defined in Exclusion Criterion 19 (Section 8.2).  

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9.2.2 
CYP3A4/P-gp Inducers and Inhibitors 
The use of CYP3A4/P-gp major inducers or major inhibitors are prohibited 14 days prior to dosing and 
during the trial. Examples of major inducers include, but are not limited to carbamazepine-Tegretol®, 
phenobarbital, phenytoin-Dilantin®, rifampin/rifampicin-Rifadis®, St. John’s Wort-Hypericum perforatum. 
Examples of major 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.  
9.2.3 
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 rapamycin (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 one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to 
determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. The 
study will randomize approximately 140 patients with chronic refractory gout. Approximately 60% of the 
randomized patients will have tophi at Baseline. Patients, stratified as to the presence or absence of 
tophi, will be randomized in a 1:1:1 allocation ratio prior to Baseline to receive one of two dose levels of 
SEL-212 or placebo every 28 days for approximately 6 months in each trial (SEL-212/301 and SEL-
212/302). The SEL-212 doses will differ as to the SEL-110.36 component. Participants will receive 
SEL-037 administered at a dose of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving 
SEL-110.36 at a dose of either 0.1 mg/kg (SEL-212A) or 0.15 mg/kg (SEL-212B) via IV infusion. The 
placebo will consist of normal saline that will be administered in the same way that the SEL-212 
components are administered to maintain the integrity of the study blind. Prior to randomization, to 
ensure balance among the treatment groups with regard to the presence or absence of tophi, a 
stratified randomization algorithm will be incorporated into the IVR system, based on the presence or 
absence of prevalent tophi. All patients, Investigators, study personnel, and Sponsor personnel involved 
in the conduct of the study will be blinded to patient treatment assignment, except for a designated 
unblinded statistician who will generate and have access to the randomization codes, a designated 
unblinded site representative (e.g., pharmacist) who will prepare study drug on the day of treatment, an 
unblinded infusion nurse who will be responsible for dosing the patient, a designated unblinded medical 
monitor for assessing the treatment stopping rules, and unblinded drug supply personnel. Prior to study 
drug administration in Treatment Periods 2 through 6, the unblinded medical monitor will determine a 

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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. The 
unblinded statistician and medical monitor will not otherwise participate in any study procedures or 
data analysis prior to unblinding of the data.  
Central and site laboratory vendors will also be blinded to treatment assignment. 
Certain post-dose laboratory results can be unblinding. Therefore, the results of such laboratory tests 
will be communicated only to unblinded personnel. 
Study personnel will endeavor to safeguard the integrity of the study blind to minimize bias in the 
conduct of the study. 
9.4.1 
Procedures for Breaking the Blind Prior to Study Completion 
Breaking the blind is expressly forbidden except in the event of a medical emergency where the identity 
of the treatment assignment must be known in order to properly treat the patient. If breaking the blind 
is required because of a medical emergency, the treatment identity for the unblinded patient only will 
be revealed by the qualified designee with approval from the Sponsor’s medical monitor or designee. 
In all cases where the code is broken, the Investigator must record the date and reason for code 
breaking. The unblinding should be noted in the participant’s CRF.  
9.4.2 
Revealing Randomization 
In the absence of a medical emergency, the blinded randomization for this study will not be revealed 
until all data are entered in the database, edits checks are performed, queries closed, CRFs are signed by 
the Investigator at each site, and the database is officially locked. 

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10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1 
Study Drug 
This is a randomized, double-blind study. The designated site representative (e.g., pharmacist) will be 
unblinded to enable preparation of study drug on the day of treatment. The site representative will take 
appropriate steps during study drug preparation to maintain the integrity of the study blind. Prior to 
study drug administration in Treatment Periods 2 through 6, the unblinded medical monitor 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 prior treatment period. 
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.  
Two dose levels of SEL-212 will be investigated in this study: 
SEL-212A: 
• 
SEL-110.36: 0.1 mg/kg based on patient’s body weight 
• 
SEL-037: 0.2 mg/kg based on patient’s body weight 
SEL-212B: 
• 
SEL-110.36: 0.15 mg/kg based on patient’s body weight 
• 
SEL-037: 0.2 mg/kg based on patient’s body weight 
10.1.2 
Placebo 
Placebo will consist of normal saline. Normal saline will be administered sequentially in the same way 
that the SEL-212 components are administered to maintain the integrity of the study blind. 
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. 
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. 
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 treatment 

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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 United States 
Pharmacopeia (USP) or equivalent to a 6 mg/mL solution and then the appropriate volume of 
reconstituted solution will be diluted in 100 mL of room temperature 0.9% sodium chloride for injection, 
USP for administration. The detailed reconstitution procedure, including the time for vials to rest 
undisturbed and the number of gentle vial inversions to perform, is provided in the Study Operations 
Manual. 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. The SEL-037-normal saline solution infusion must be completed within 12 hours of the start of vial 
reconstitution. The infusion of SEL-037-normal saline solution must be completed within 6 hours of 
dilution. If not administered immediately, store refrigerated and use within the time specified above.  
SEL-037 should be administered on the same day and as soon as possible after 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 United States 
Pharmacopeia (USP) or equivalent, to a 2 mg/mL suspension before being drawn into appropriately 
sized syringe/syringes for IV infusion with a syringe pump. The detailed reconstitution procedure, 
including the time for vials to rest undisturbed and the number of gentle vial inversions to perform, is 
provided in the Study Operations Manual. The SEL-110.36 dose must be completely administered within 
12 hours of the start of vial reconstitution. SEL-110.36 should be administered on the same day and as 
soon as possible after reconstitution. If not administered immediately, store refrigerated and use within 
the time specified above.  
10.4.3 
Placebo Preparation 
Placebo will consist of normal saline. An unblinded designated site representative (e.g., pharmacist) will 
prepare placebo infusions in a manner that maintains the integrity of the study blind. 
10.5 
Urate-Lowering Therapy Wash-out 
Chronic refractory gout patients may elect to undergo wash-out of urate-lowering therapy at any point 
during Screening but must begin at least 7 days prior to the first dosing of study drug. Patients must 
continue to remain off ULT for as long as they participate in the clinical study. 

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10.6 
Premedication 
10.6.1 
Gout Flares (Prophylaxis and Treatment) 
All patients that are expected to be randomized 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 per day. If the patient 
cannot tolerate the loading dose level of 0.6 mg, then the patient will initiate and maintain colchicine at 
0.3 mg per day.  
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.  
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. 
10.6.2 
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) oral (PO) approximately 24 (± 12) hours prior to dosing 
• 
Fexofenadine (180 mg) oral (PO) approximately 12 (± 2) hours prior to dosing  
• 
Fexofenadine (180 mg) oral (PO) approximately 2 (± 1) hours prior to dosing  
• 
Methylprednisolone (100 mg) (or equivalent) up to 125 mg, depending on patient weight, IV 
approximately 1 (± 0.5) hours prior to dosing  
Refer to Section 12.2.1.5 for guidance on reducing the risk of infusion reactions and for managing 
infusion reactions.  
10.7 
Administration 
Before administration of study drug, patients will be premedicated with antihistamines and steroids as 
described in Section 10.6. The timing of premedication and study drug administration are presented 
graphically in Appendix C and Appendix D. 

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Patients will receive treatment with study drug 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. 
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 1.5 mL/hr 
for the first 30 minutes, then at a rate adequate to deliver the remaining dose volume over a period of 
60 minutes concurrently with 125 mL normal saline. If an infusion reaction occurs during the 
administration of SEL-110.36, the infusion may be slowed, or stopped and then restarted at a slower 
rate at the discretion of the Investigator. 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 up to 30 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 then restarted at a 
slower rate at the discretion of the Investigator. 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) 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. 
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 (samples for: chemistry, hematology, coagulation, histamine, serum tryptase, and 
anti-uricase) provided in the Study Operations Manual to collect additional blood specimens. In the case 
of a Grade 3 or 4 infusion reaction 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 patient should be withdrawn from subsequent study 
drug treatment.  
10.8 
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.  

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10.9 
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. 

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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 treated with two 
different dose levels of SEL-212 compared to placebo who achieve and maintain reduction of sUA < 6 
mg/dL for at least 80% of the time during Treatment Period 6. 
Serum samples for measurement of sUA will be collected according to the schedule described in 
Appendix A. Methods used for processing samples and for measurement of sUA levels are described in 
the Study Operations Manual. 
11.1.2 
Uricase Activity 
Serum samples for measurement of uricase activity will be collected according to the schedule described 
in Appendix A. Validated methods will be used for processing samples and for measurement of uricase 
activity as described in the Study Operations Manual. 
11.2 
Gout Assessment 
11.2.1 
Tophus Assessment 
Assessment of tophi will be performed according to the schedule described in Appendix A. 
Baseline photographs of the hands and feet of each patient will be obtained using a standardized 
method in all patients (whether or not a prevalent tophus was identified by the Investigator at Baseline), 
together with photographs of up to two other representative sites of tophaceous disease. The baseline 
photographs will be assessed by a Central Reader to prospectively identify sites of tophaceous disease 
present at the start of treatment. The Central Reader will be blinded to patient treatment assignment 
and to the Investigator’s identification (or lack of identification) of a tophus to control for potential bias. 
Up to five tophi in the photographs will be chosen by the Central Reader for measurement over the 
course of therapy. The Central Reader will assess the photographs for size of each target tophus using 
the image analysis software. To be considered measurable, tophi are required to be ≥ 5 mm in the 
longest dimension at Baseline and to have borders distinguishable to the Central Reader. Up to two 
tophi (approximately > 10 mm in the longest dimension at Baseline) representative of the patient’s 
tophus burden but unable to be accurately measured (e.g., due to location, shape, or other factors), may 
also be evaluated at the Central Reader’s discretion. Once the Central Reader completes the assessment 
of photographs from a patient’s study visit, the Central Reader will not be permitted to change the 
evaluation. 
Individual response for measurable and unmeasured tophi will be assessed by the Central Reader by 
comparing the tophus area (approximated for unmeasured) to its baseline measurement using 
assessment categories described in Table 2. 

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Table 2: 
Individual Tophus Assessment Categories (by Central Reader) 
Assessment 
Measurable Tophus 
Unmeasured Tophus 
Complete Response (CR) 
A 100% decrease in the area of 
the tophus 
The disappearance of the tophus 
Marked Response (MR) 
At least a 75% decrease in the 
area of the tophus 
Improved (I) 
An approximate 50% or more 
reduction from baseline in the size 
of the tophus 
Partial Response (PR) 
At least a 50% decrease in the 
area of the tophus 
Stable Disease (SD) 
Neither a 50% decrease nor a 
25% increase in the area of the 
tophus can be demonstrated 
Neither improvement nor 
progression from baseline can be 
determined. 
Progressive Disease (PD) 
A 25% or more increase in the 
area of the tophus 
An approximate 50% or more 
increase from baseline in the area 
of the tophus 
Unable to Evaluate (UE) 
The tophus cannot be accurately 
measured for any reason at any 
given post-baseline time point 
The tophus cannot be assessed for 
any reason at any given post- 
baseline time point 
 
The overall categorical tophus responses of CR, PR, SD, or PD will be based on the best response 
reported among all tophi (measurable and unmeasured) for an individual patient, as described in 
Table 3. For the principal analysis of tophus assessments, if any one tophus shows complete response 
(CR), the overall response will be reported as CR if there is no evidence of progressive disease (PD). 
Table 3: 
Overall Tophus Response Categories 
Overall Assessment 
How to determine overall assessment: 
Complete Response (CR) 
If CR (no PD) for either measurable or unmeasured tophus 
Partial Response (PR) 
If MR or PR (no CR, PD) for measurable or Improved (I) for unmeasured tophus 
Stable Disease (SD) 
If SD (no CR, PR, PD) for either measurable or unmeasured tophus 
Progressive Disease (PD) 
If PD for any measurable or unmeasured tophus, or if any new tophus appears 
during the study 
Unable to Evaluate (UE) 
If UE for all measurable or unmeasured tophus 
 
11.2.2 
Gout Flare Assessment 
Gout flare will be assessed as part of AE collection with severity determined as described in Section 
12.2.2.3. Gout flares will be assessed at each study visit during the Treatment Phase using a validated 
definition of flares in patients with established gout (Gaffo 2018). In addition, in an exploratory manner, 
gout flares will be self-assessed weekly by the patient after randomization and in each Treatment Period 
using a weekly flare diary (Poiley 2016). 

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11.2.3 
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 schedule described in Appendix A.  
The HAQ-DI 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. The HAQ-DI includes a patient global assessment 
of disease and a visual analog scale for pain assessment. 
11.3.2 
Provider Global Assessment of Disease Activity 
The Provider Global Assessment of Disease Activity (PrGA) will be conducted according to the schedule 
described in Appendix A. The PrGA will be administered to assess the severity of the patient’s disease on 
a scale from 0 (patients 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 schedule described in Appendix A.  
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.  
11.4 
Inflammation Biomarker and Multiomic Assessments 
11.4.1 
Inflammation Biomarkers of Gout 
Blood samples will be drawn according to the schedule described in Appendix A for assessment of 
inflammation biomarkers. Validated methods will be used for processing samples and for measurement 
of inflammation biomarkers as described in the Study Operations Manual. 

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11.4.2 
Multiomic Markers of Gout 
A blood sample will be drawn according to the schedule described in Appendix A for determination of 
correlations between multiomic markers of gout and observed treatment effect of study drug. Validated 
methods will be used for processing samples and for measurement of multiomic markers as described in 
the Study Operations Manual. 
11.4.3 
Biomarkers of Immune Tolerance 
Blood samples will be drawn according to the schedule described in Appendix A for assessment of 
inflammation biomarkers. Validated methods will be used for processing samples and for measurement 
of inflammation biomarkers as described in the Study Operations Manual. 
11.4.4 
Multiomic Markers Related to Immune Tolerance 
A blood sample will be drawn according to the schedule in (Appendix A for determination of correlations 
between multiomic markers of gout and observed treatment effect of study drug. Validated methods 
will be used for processing samples and for measurement of multiomic markers as described in the 
Study Operations Manual. 
11.4.5 
Human Leukocyte Antigen (HLA) Typing  
A blood sample will be drawn according to the schedule described in Appendix A for determination of 
human leukocyte antigen (HLA). If the sampling timepoint has passed, then the sample for HLA typing 
should be drawn at the next scheduled study visit. Validated methods will be used for processing 
samples and for measurement of human leukocyte antigen as described in the Study Operations 
Manual. 
11.4.6 
Imaging Assessments 
Multi-energy computed tomography (CT) scans will be performed at selected investigational sites as an 
exploratory measure to visualize monosodium urate crystal deposits and/or total body monosodium 
urate crystal deposits. Imaging will be conducted according to the schedule described in Appendix A. 
The Screening assessment should be performed after preliminary determination of eligibility (Section 8) 
and prior to the first study drug dose on Day 0 of Treatment Period 1. Procedures for the multi-energy 
CT scan and analysis can be found in the Study Operations Manual.  
 

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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 schedule described in 
Appendix A. 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 schedule described in 
Appendix A.  
12.1.3 
Vital Signs 
Vital signs will be documented according to the schedule described in Appendix A.  
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. The blood pressure 
measurement should be repeated after at least 30 seconds and the average of the 2 readings calculated 
and recorded. 
12.1.4 
Electrocardiogram (ECG) 
A standard 12-lead ECG will be performed according to the schedule described in Appendix A. 
12.1.5 
Weight and Height 
Weight (kg) and height (cm) will be performed according to the schedule described in  
Appendix A. 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 schedule described in Appendix A. 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. At some visits a Directed Physical Examination 
will be performed. These exams will be focused on assessment of any patient complaints and concerns. 
12.1.7 
Chest X-ray 
Chest X-rays (CXR) will be performed according to the schedule described in Appendix A. Post-baseline 
CXRs will be taken to assess for presence of or changes in interstitial lung disease (ILD) compared to 
baseline CXR. 
12.1.8 
Laboratory Assessments 
All laboratory assessment will be conducted according to the schedule described in Appendix A. 
Procedures for processing samples are included in the Study Operations Manual. 

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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), and platelet (Plt) count. 
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), and electrolytes (sodium, potassium, chloride, bicarbonate, phosphate, and 
magnesium), and urine for urine-albumin-creatinine ratio (UACR). If the UACR cannot be calculated due 
to the microalbumin analysis being below the limit of quantification for the analytical method (eg. <12 
mg/dL), the low microalbumin can be used as a surrogate for an acceptable UACR. 
12.1.8.3 
Glomerular Filtration Rate (GFR) 
Estimated glomerular filtration rate (eGFR) will be calculated according to the Study Operations Manual. 
12.1.8.4 
Lipids 
Fasting lipid assessments will include total cholesterol, high-density lipoprotein (HDL), low-density 
lipoprotein (LDL), and triglycerides. 
12.1.8.5 
Coagulation 
Coagulation assessments will include prothrombin time (PT), activated partial thromboplastin time 
(aPTT), international normalized ratio (INR). 
12.1.8.6 
Antibody Assessments 
Blood samples will be collected for assessment of antibody development to pegadricase and uricase and 
for neutralizing antibodies and anti-pegadricase point of service validation. All blood samples for 
assessment of antibody development are required to be collected prior to study drug dosing. Antibody 
samples collected after the screening period will be assessed only in patients in active treatment arms. 
12.1.8.7 
COVID-19 Testing 
Patients with COVID-19 infection can experience a range of clinical manifestations, from no symptoms to 
critical illness.  
Screening Visit: 
During Screening, all patients should be tested for COVID-19 by an FDA Emergency Use Authorized 
COVID-19 molecular assay for detection of SARS-CoV-2 RNA. A patient with a positive test result is 
permitted to request re-testing. A patient who requests re-testing should wait at least 10 days after the 
date of the first positive COVID-19 diagnostic test, as long as no symptoms have developed. If the 
second test is positive for COVID-19, then the patient will be excluded from enrollment. If the second 
test is negative for COVID-19, then the patient must be tested a third time at least 24 hours after the 
second test to confirm the negative result. 

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On Study: 
Once a patient is enrolled in the study, the investigational site will manage the patient according to its 
institutional standards and procedures established for COVID-19. During the study, a patient presenting 
with both symptoms (only severe and critical illness as per definitions below) of COVID-19 and positive 
COVID-19 test results will be discontinued from study treatment. The patient will be permitted to 
resume study visits for continued assessments (but not treatment with SEL-212 or placebo) according to 
the institutional standards and/or procedures of the investigational site. 
Patients with mild-moderate COVID-19 illness (as per definitions below) will be allowed to resume study 
visits (on treatment with SEL-212 or placebo) after resolution of acute symptoms of clinical disease 
(except for loss of smell and taste) and meeting quarantine requirements so long as their subsequent 
dose occurs ≤90 days from their prior dosing day as per section 7.4.1.1. Patients with mild-moderate 
COVID-19 illness can continue non-dosing study visits as per protocol mandated visit window prior to 
resolution of acute symptoms according to the institutional standards and/or procedures of the 
investigational site. 
Enrolled patients in the study with mild-moderate COVID-19 illness can be treated with anti-SARS-CoV-2 
monoclonal antibodies.  These patients will be allowed to resume study visits (on treatment with SEL- 
212 or placebo) after 2 weeks of receiving monoclonal antibodies, and confirmation of resolution of 
acute symptoms of clinical disease (except for loss of smell and taste), and meeting quarantine 
requirements so long as their subsequent dose occurs ≤90 days from their prior dosing day as per 
section 7.4.1.1. 
Regardless of COVID-19 disease severity, enrolled patients in the study who are treated for COVID-19 
with anti-viral therapy (including Remdesivir), anti-cytokine therapies (including anti-IL-6 or anti-IL-1 
therapy), or JAK-inhibitors will be discontinued from study treatment. These patients will be permitted 
to resume study visits for continued assessments (but not treatment with SEL-212 nor placebo) 
according to the institutional standards and/or procedures of the investigational site. 
The categories of severity of illness (description and criteria) for COVID-19 are noted below as a 
reference: 
Asymptomatic or Pre-symptomatic Infection: Individuals who test positive for COVID-19 but who have 
no symptoms that are consistent with COVID-19. 
Mild Illness: Individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, 
sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but 
who do not have shortness of breath, dyspnea, or abnormal chest imaging. 
Moderate Illness: Individuals who show evidence of lower respiratory disease during clinical assessment 
or imaging and who have an oxygen saturation (SpO2) ≥94% on room air at sea level. 

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Severe Illness: Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial 
pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 
breaths/min, or lung infiltrates >50%. 
Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction. 
The Investigator will report a patient’s positive test results for COVID-19 according to institutional 
standards and/or procedures. 
12.1.8.8 
Serology 
Serology screening will include human immunodeficiency virus (HIV) antibodies 1 and 2, hepatitis-B 
surface antigen (HBsAg), and hepatitis-C antibody (HCVAb). 
12.1.8.9 
Drug Screen 
Urine drug screen will include amphetamines, barbiturates, benzodiazepines, cocaine, and opiates. 
12.1.8.10 
Pregnancy Screen 
Samples for urine pregnancy testing (hCG) will be obtained.  
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 4 months 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. 
Female patients are required to have negative hCG test results throughout the study. If a female patient 
becomes pregnant after she begins taking study drug, the procedures in Section 12.2.2.7 should be 
followed.  
In addition, for any reported case of delayed menstrual period (over 1 month between menstruations) 
and for those women with infrequent or irregular menstrual cycles, confirmation of absence of 
pregnancy should occur. 
12.1.8.11 
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. 

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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 of male patients 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) 
12.1.9 
Premedication Regimen 
Refer to Section 10.6 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 
(and thus SAEs) will be collected from the time the patient is dosed (infusion is started) until the end of 
the End of Study Visit.  

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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 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 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 10.6.2), the following steps will be implemented in this protocol to 
either reduce the risk of infusion reactions or manage infusion reactions. 
• 
Patients with prior exposure to uricase therapy will be ineligible  
• 
Patients with a history of anaphylaxis or severe allergic reactions, history of severe atopy, 
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.  

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• 
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 4.5 hours from the start 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. 
• 
All patients will be contacted approximately 24 hours after infusion to determine whether any 
infusion reaction AEs occurred. 
• 
Patients who experience an infusion reaction will be contacted approximately 24 hours after the 
event as follow-up. 
• 
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. 
• 
Infusion Reactions (an AESI) will be reported to Parexel Safety in the same manner as SAEs using 
the same form but ticking the AESI box rather than the SAE box. 
Adverse events of special interest (AESI) will be recorded specifically for occurrences of: gout flares, 
infections, malignancies, viral infections, interstitial lung disease, stomatitis, infusion-related reactions 
including anaphylaxis, thrombosis (e.g., deep venous thrombosis, pulmonary embolism), and the 
following laboratory tests, if deemed 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 regards 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. 

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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. 
• 
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).  
• 
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, 

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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 
• 
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 regarding 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. 

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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 participant 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 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 (± 
1) 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 
On discovery, all SAEs should be immediately reported (latest within 24 hours of knowledge of the 
event) to PAREXEL Safety Services by: 
Completing the SAE report form and faxing the documents to PAREXEL Safety Services, using the 
appropriate regional PAREXEL SAE fax numbers below: 
                                                                             NA (Billerica): +1 781 434 5957 
   or 

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Completing the SAE report form and submitting it to PAREXEL Safety Services via email utilizing the 
address (es) below: 
                                                                    NA: NorthAmerica_Medical@parexel.com 
In the event that the site is unable to complete the SAE form to report the event within 24 hours of their 
knowledge of the event, the investigators may report the SAE over the telephone via the SAE answering 
service, and then provide the completed SAE form via fax or email. If questions arise regarding the 
reporting procedures or the specifics of the reporting of an event, sites may call utilizing the following 
numbers: 
                                                                         NA (Billerica): +1 781 434 5010 
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 PAREXEL Safety Services as described above. 
Follow-up information regarding an SAE and the supporting data, including laboratory findings and 
discharge summaries, should be sent by facsimile or email to PAREXEL Safety Services 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.  

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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)/Independent Ethics Committee (IEC). 
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/IEC. 
12.2.4 
Follow-up of Adverse Events  
The Investigator is required to proactively follow each patient and provide further information regarding 
AEs and SAEs. All AEs and SAEs will be followed until 30 (+4) 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.  
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.  

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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), which will 
be finalized prior to database lock. The SAP may add additional exploratory analyses; modifications to 
the planned analyses will be identified as such in the final SAP. 
13.1 
Sample Size Determination 
The primary efficacy criterion in this study is defined as the percentage of the patients who achieve and 
maintain reduction of sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6 by Day 28.  
The sample size estimation is based on the main estimand for the primary efficacy criterion from version 
5.0 of the protocol. This estimand considered all patients who discontinue study treatment due to lack 
of efficacy (e.g., meeting stopping rule), due to treatment-related or non-treatment related AE as 
treatment failures, as well as initiating prohibited medication that lowers sUA, withdrawal of consent or 
lost to follow up for reasons other than COVID-19. 
Based on the results in the Phase 2 study (SEL-212/201) with SEL-212, the responder rate in all 
randomized and dosed patients is assumed to be 45% in SEL-212. For placebo, a responder rate of 5% is 
assumed. Considering a randomization ratio of 1:1:1 for SEL 212A and SEL-212B against placebo, a 
statistical power of 90%, a two-sided alpha-level of 2.5% and using the Chi-square test with continuity 
correction for the 2 pairwise comparisons of each SEL-212 dose group against placebo, 32:32:32 
randomized and dosed patients will be required for each treatment group. Considering the potential 
that some randomized patients will terminate early (approx. 8%), the number of the patients required to 
be randomized and dosed in total is 105 (i.e., 35:35:35) to demonstrate efficacy. For the sample size 
estimation, the Chi-square test is used instead of the Mantel-Haenszel test, 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. 
From an amendment in version 6.0 of the protocol, the main estimand for the primary efficacy criterion 
was updated to include patients who present a positive COVID-19 test along with severe or critical 
symptoms of COVID-19, and patients who missed all assessments of sUA during Treatment Period 6, as 
treatment failures. In addition, the ongoing conflict between Ukraine and Russia may lead to treatment 
discontinuations and/or loss to follow-up in both countries; under the main estimand for the primary 
endpoint, these may be considered as treatment failures. As both these factors are expected to be 
unrelated to the treatment then assuming that the number of additional treatment failures to each arm 
would be roughly equal, the difference in response rates can still be assumed to be 40%, unless the 
treatment failure rate due to positive COVID-19 tests along with severe or critical symptoms of COVID-
19 and treatment discontinuation/loss to follow-up due to the conflict between Ukraine and Russia is 
sufficiently high that a difference of 40% cannot be observed (I.e. the treatment failure rate in the active 
arms is >60%, so even if the responder rate for the placebo group is 0%, a difference of 40% cannot be 
observed). 

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To mitigate this risk, an additional 15 patients have been added to the study sample size to account for 
potential treatment discontinuations that may occur due to the ongoing COVID-19 pandemic as a result 
of the emergence of COVID-19 variants which were not accounted for in the sample size calculations. 
Furthermore, an additional 20 patients have been added to the original study sample size to account for 
the treatment discontinuations/loss to follow-up due to the conflict between Ukraine and Russia. These 
two additions to the sample size from the original sample size calculation results in approximately 140 
patients (i.e., approximately 47 per group) to be randomized and dosed to demonstrate efficacy. This 
controls the power of each comparison vs. placebo at approximately 90%, even if the placebo arm were 
to be unaffected with respect to response probability by the conflict between Ukraine and Russia, with a 
response percentage of 5%, and the active treatment arm response percentage were to drop to 37%. 
Sample size calculations were performed with the software package nQuery 8, Version 8.5.0.0 and 
updated using R software version 4.0.4. 
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 and will be used for the presentation of patients in all patient listings. 
Randomized but not treated subjects will be replaced. 
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. 
13.2.3 
Intent-to-Treat (ITT) Set 
The Intent-to-Treat (ITT) Set will include all randomized and dosed patients. Replaced subjects will not 
be included in the ITT. Patients will be analyzed according to randomized treatment. The ITT will be used 
as primary population for analyses of efficacy endpoints. 
13.2.4 
Modified ITT 
A number of modified ITT (mITT) populations will be defined, as a result of either the COVID-19 
pandemic or the conflict in Ukraine. 
mITT1: will include all randomized patients who were dosed, except those who discontinue treatment 
due to a COVID-19 infection as defined in section 12.1.8.7 or do not have at least two SUA 
measurements 7 days apart in TP6 due to a/multiple missed visits due to a COVID-19 infection or 
subsequent complications as defined in section 12.1.8.7.  
mITT2 will include all randomized patients who were dosed, except those who were recruited in sites from 
Ukraine or Russia where the data quality are compromised due to logistical issues, defined as: 

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4. Those who received fewer than 6 treatment doses due to logistical issues, for example 
a patient who is unable to receive one or more doses within the 90 day window due 
to lack of IMP or site closure due to the conflict. 
5. Those who have limited laboratory safety data available/reportable after February 
24, 2022, for example missing data that result in major protocol deviations 
6. Those whose data were not able to be monitored after February 24, 2022  
mITT3: will include all randomized patients who were dosed, except those who were recruited in sites 
from Ukraine or Russia. 
Patients will be analyzed according to randomized treatment.  
13.2.5 
Per Protocol Set  
The Per Protocol Set (PPS) will include all patients who were administered at least one complete dose of 
study medication, who have at least one post-baseline assessment of sUA, who have sufficient data to 
assess the primary efficacy endpoint, and who have no major Protocol deviations affecting the primary 
efficacy assessments. Patients will be analyzed according to randomized treatment. Criteria for exclusion 
from the PPS will be provided in the Statistical Analysis Plan.  
13.2.6 
All randomized Set 
The all randomized set will include all patients who were randomized. Patients will be analyzed 
according to randomized treatment group assignment 
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 finalized 
before database lock. 
13.4 
Efficacy Analyses 
13.4.1 
Primary Efficacy  
The primary efficacy endpoint is defined as: 
• 
Percentage of patients on SEL-212 versus placebo who achieve and maintain reduction of sUA < 
6 mg/dL for at least 80% of the time during Treatment Period 6 by Day 28 
The main estimand for the primary efficacy endpoint is defined as follows: 
• 
Targeted population: Of all patients with gout refractory to conventional treatment defined by 
the study inclusion / exclusion criteria, the analysis population will include patients who were 
randomized to study treatment and who were dosed (ITT population). 

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• 
Variable: Binary variable indicating the treatment response status, whereby a responder is 
defined as a patient has sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6. 
• 
Intercurrent events:  
o Intercurrent events which lead to a discontinuation of study treatment due to lack 
of efficacy (includes meeting the stopping criteria) will be defined as treatment 
failures according to the composite strategy. 
o Premature stopping of study treatment due to treatment-related or 
non-treatment-related AE, with the exception of a positive COVID-19 test result 
along with severe or critical symptoms of COVID-19 will be defined as treatment 
failures according to the composite strategy. 
o Premature stopping of study treatment due to a positive COVID-19 test result along 
with severe or critical symptoms of COVID-19 will be defined as treatment failures 
according to the composite strategy. 
o Death will be considered as treatment failures according to the composite strategy. 
o Use of prohibited medication that lower sUA levels will be considered as treatment 
failures according to the composite strategy. 
o All other intercurrent events (e.g. use of prohibited medication that do not lower 
sUA levels but are classified as a major protocol deviation) will be treated using the 
treatment policy strategy i.e. the assessment of the sUA in TP6 up to Day 28 will be 
used.. 
• 
Population-level summary: Difference in the percentage of treatment responders of each SEL-
212 treatment group versus placebo. 
Further estimands of interest for the primary efficacy will be provided in the SAP. 
Frequency table of the treatment responders for the main primary efficacy estimand and further 
estimands of interest will be provided by treatment group, and the difference between each SEL-212 
treatment group and placebo will be presented together with 97.5% confidence intervals. 
The statistical testing of each SEL-212 treatment group versus placebo in all estimands of primary 
efficacy will be performed using the Mantel-Haenszel (MH) estimate and test for common risk difference 
considering the randomization stratum of tophus presence (yes/no) with a two-sided type 1 error rate α 
= 2.5% to adjust for the two comparisons against placebo. Only the test results of the main estimand will 
be considered as confirmatory.  
 
All above described analyses will be repeated on each of the defined mITT populations, all randomized 
population and on the PP population as a supportive analysis. 

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The sUA time curve with assessments at Day 0 pre-treatment (0 h), Day 0 post-treatment (4.5 h), Day 7, 
Day 14, Day 21, and Day 28 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 Period 6, an estimate of the time with 
sUA < 6 mg/dL by Day 28 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 Period 6 
by Day 28, or the last available assessment before Day 28. Actual times will be plotted on the time 
curve, but only the interpolation of actual times up to Day 28 will be used. If a point at Day 28 is not 
available on the curve (possibly due to an extension of TP6 for reasons such as presenting mild-
moderate COVID-19 symptoms), then the next available assessment between Day 28 and up to, and 
including EOS will be used to interpolate the curve up to Day 28. This can include the use of unscheduled 
sUA assessments. If there are no such assessments available, but the use of unscheduled assessments 
allows the extension of the time curve from the last scheduled assessment prior to Day 28 then these 
can also be used. If only 2 or fewer assessments are available (allowing for the use of assessments after 
Day 28 up to, and including EOS, and further unscheduled assessments prior to Day 28), and the first and 
last attended assessments are less than 7 actual days apart, then the response evaluation of Treatment 
Period 6 will be missing. Otherwise, the response evaluation will be derived from the available data 
points. 
The proportion of time that the sUA level is < 6 mg/dL, i.e., percentage of non-hyperuricemic time, 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 Period 6 
by Day 28 (or last available assessment prior to Day 28 if no assessments are available from Day 28 up 
to, and including EOS). 
For a patient who has completed Treatment Period 6 to be considered a responder, the proportion of 
time that the sUA level is < 6 mg/dL (i.e., percentage of non-hyperuricemic time) during Treatment 
Period 6 by Day 28 must be at least 80%. 
Frequency table of the percentage of responder in Treatment Period 6 (patients who achieve and 
maintain reduction of sUA < 6 mg/dL for at least 80% of the time in Treatment Period 6) will be provided 
by treatment group. Additionally, a summary table with the total time a patient has sUA values < 6 
mg/dL in Treatment Period 6 will be provided by treatment group. 
Summary table 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 6 will be presented by treatment group.  

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• 
Mean sUA level is defined as the area under the sUA time curve (computed using the linear 
trapezoidal rule during Treatment Period 6) divided by the corresponding time interval.  
• 
Reduction in mean sUA is computed by subtracting baseline sUA level from mean sUA during 
Treatment Period 6.  
• 
Percent reduction in the mean sUA from baseline is computed as the mean sUA level during 
Treatment Period 6 minus baseline sUA level divided by baseline sUA level multiplied by 100%. 
13.4.2 
Key Secondary Efficacy  
Hierarchical testing of key efficacy: 
If the superiority of both (one) SEL-212 treatment group(s) against placebo for the main estimand of the 
primary efficacy is shown with a p-value ≤ 0.025, the hierarchical testing approach will continue to the 
testing of the main estimands of the key secondary efficacy comparing pairwise both (one) SEL-212 
treatments against placebo. Only the main estimands of the key secondary efficacy will be tested in the 
successive order of the key secondary efficacy endpoints listed below. The test result of the nth key 
secondary efficacy estimand will be considered as confirmatory if the p-value of the two-sided test of 
the previous estimand resulted in a value less or equal 0.025. 
Key secondary efficacy endpoints: 
1. Reduction of mean sUA as computed by subtracting the Baseline sUA level from the mean sUA 
(area under the sUA time curve) during Treatment Period 6 
2. Percent reduction of mean sUA as computed by subtracting the Baseline sUA level from the 
mean sUA (area under the sUA time curve) during Treatment Period 6 
3. The change from Baseline to Day 28 of Treatment Period 6 in the physical summary score of the 
Short Form Health Survey (SF-36) 
4. In patients with tophi at Baseline, the percentage of patients at least PR (as best response) in 
overall tophus response evaluation until Day 28 of Treatment Period TP6 
5. The percentage of patients who achieve and maintain reduction of sUA < 6 mg/dL for at least 
80% of the time during Treatment Period TP6 by Day 28 in the subset of patients with tophi at 
baseline 
6. The change from Baseline to Treatment Period 6 in number of tender joints 
7. The change from Baseline to Treatment Period 6 in the total score of Health Assessment 
Questionnaire (HAQ-DI)  
8. Gout flare incidence during Treatment Periods 1-6 
9. Gout flare incidence during Treatment Periods 1-3 
The targeted population for all estimands of the key secondary efficacy endpoints numbered as 1, 2, 3, 
6, 7, 8, and 9 is the same population as for the primary efficacy. In case of the key secondary efficacy 
endpoints numbered 4 and 5, the targeted population is additionally restricted to patients with tophi at 
baseline. 

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The main estimand for the key secondary efficacy endpoint ‘Reduction of mean sUA as computed by 
subtracting the Baseline sUA level from the mean sUA (area under the sUA time curve) during 
Treatment Period 6’ considers as variables of interest ‘absolute difference between mean sUA value 
recorded in TP6 and the baseline sUA value’, whereby the handling of all intercurrent events except 
death will be according to the treatment policy strategy. For deaths, the last available value will be used 
(while-on-treatment strategy). The population-level summary is the difference in mean between each 
SEL-212 treatment group vs. placebo. 
The main estimand for the key secondary efficacy endpoint ‘Percent reduction of mean sUA as 
computed by subtracting the Baseline sUA level from the mean sUA (area under the sUA time curve) 
during Treatment Period 6’ considers as variables of interest ‘mean TP6 sUA value – baseline sUA value) 
 baseline sUA value 100’, whereby the handling of all intercurrent events except death will be 
according to the treatment policy strategy. For deaths,  the last available value will be used (while-on-
treatment strategy). The population-level summary is the difference in mean between each SEL-212 
treatment group vs. placebo. 
The main estimand for the key secondary efficacy endpoint ‘Change from Baseline to Day 28 of 
Treatment Period 6 of the Physical Summary Score of SF-36’ consider as variable of interest ‘Change 
from Baseline to 6 months after start of study treatment (Day 28 of Month 6)’, whereby the handling of 
all intercurrent events except death will be according to the treatment-policy strategy. For deaths,  the 
last available value will be used (while-on-treatment strategy). The population-level summary is the 
difference between each SEL-212 treatment group versus placebo in the change from baseline in 
Physical Summary score of SF-36. 
The main estimand for the key secondary efficacy endpoint ‘percentage of patients with at least PR (as 
best response) in overall tophus response evaluation until Day 28 of Treatment Period 6’ in patients with 
tophi at baseline considers as variable of interest the ‘binary variable indicating whether the patient had 
experienced at least a PR or not in overall tophus response evaluation until Day 28 of Treatment Period 
6’, whereby the handling of all intercurrent events except death will be according to the treatment-
policy strategy. For deaths, best response until the last available response evaluation will be used (while-
on-treatment strategy). The population-level summary is the difference in the percentage of patients 
with at least PR in overall tophus response (best response) between each SEL-212 treatment group 
versus placebo. 
The main estimand for the key secondary efficacy endpoint ‘percentage of patients who achieve and 
maintain a reduction of sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6 in a subset 
of patients with tophi at baseline’ considers as variable of interest the ‘Binary variable indicating the 
treatment response when having completed 6 cycles of study treatment, whereby a responder is 
defined as a patient who has sUA < 6 mg/dL for at least 80% of the time during Treatment Period 6’. All 
intercurrent events which lead to a discontinuation of study treatment due to lack of efficacy (includes 
meeting the stopping criteria) treatment-related or non-treatment-related AE, present a positive COVID-
19 test result along with severe or critical symptoms of COVID-19, used a prohibited medication that 

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significantly lowers sUA, or death, will be considered as treatment failures following the composite 
strategy. All other intercurrent events (e.g., use of a prohibited medication that does not lower sUA) will 
be treated using the treatment-policy strategy. The population-level summary is the difference in the 
percentage of treatment responders of each SEL-212 treatment group versus placebo. 
The main estimand for the key secondary efficacy endpoint ‘change from Baseline to Day 28 of 
Treatment Period 6 in number of tender joints’ considers as variable of interest the ‘absolute change in 
number of tender joints from Baseline to 6 months after start of study treatment (Day 28 of Month 6)’, 
whereby the handling of all intercurrent events except death will be according to the treatment-policy 
strategy. For deaths,  the last available value will be used (while-on-treatment strategy). The population-
level summary is the difference in the change from baseline in number of tender joints between each 
SEL-212 treatment group versus placebo. 
The main estimand for the key secondary efficacy endpoint  ‘Change from Baseline to Day 28 of 
Treatment Period 6 of the Total Score of HAQ-DI’ consider as variable of interest ‘Change from Baseline 
to 6 months after start of study treatment (Day 28 of Month 6)’, whereby the handling of all intercurrent 
events except death will be according to the treatment-policy strategy. For deaths,  the last available 
value will be used (while-on-treatment strategy). The population-level summary is the difference 
between each SEL-212 treatment group versus placebo in the change from baseline in the Total Score of 
HAQ-DI. 
The main estimand for the key secondary efficacy endpoint ‘gout flare incidence in Treatment Period 1 
to Treatment Period 6’ and ‘gout flare incidence in Treatment Period 1 to Treatment Period 3’ considers 
as variable of interest ‘Incidence of gout flare during the whole treatment period from start of 
treatment until end of month 6’. and ‘incidence of gout flare during the first 3 months of treatment’. 
Gout flare incidence is defined as the total number of gout flares a patient experiences in respective 
time period divided by the length of observation of the patient in this time period. The handling of all 
intercurrent events except death will be according to the treatment-policy strategy. For deaths, the 
while-on-treatment strategy will be used. The population-level summary is the difference in the gout 
flare incidences between each SEL-212 treatment group versus placebo for the whole treatment period 
(start of treatment until end of month 6) and for the first 3 months of treatment. The analysis will be 
performed separately for the whole treatment (Treatment Period 1 to Treatment Period 6) and for the 
first 3 months (Treatment Period 1 to Treatment Period 3). whereby the confirmatory statistical 
comparison will be performed first for the whole treatment, then for the first 3 months.  
Further estimands for the key secondary efficacy will be defined in the SAP. 
For the above defined estimands, the key secondary efficacy endpoints which are numbered 1, 2, 8 and 
9 will be tested between each SEL-212 treatment group versus placebo using an ANCOVA, adjusting for 
treatment, randomization stratum and baseline value of the respective variable. The Least Square (LS) 
Mean difference between each SEL-212 and placebo treatments groups will be estimated along with its 
97.5% confidence interval, and 2-sided p-values. 

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For the above defined estimands, the key secondary efficacy endpoints which are numbered as 3, 6 and 
7 above - will be tested between each SEL-212 treatment group versus placebo using the mixed model 
for repeated measures (MMRM) with the change to baseline in the respective variable as dependent 
variable, and treatment, treatment-by-period interaction, randomization stratum and baseline value of 
the respective variable as fixed effect variables. The Least Square (LS) Mean difference between each 
SEL-212 and placebo treatments groups will be estimated on the treatment-by-period interaction at 
Treatment Period 6, along with its 97.5% confidence interval, and 2-sided p-values. 
For the above defined estimands, the key secondary endpoints numbered as 4 and 5 will be tested 
between each SEL-212 treatment group versus placebo using the Chi-square test with continuity 
correction.  
The analysis of the estimands will be carried out based on the ITT population with multiple imputation 
of missing values.  
The number of tender joints at scheduled visits and the change from baseline will be summarized by 
treatment group on the ITT, mITT, all randomized and PP populations. 
Frequency table of tophaceous patients at baseline with / without tophus reduction will be provided by 
visit and treatment group on the ITT, mITT, all randomized and PP populations. Additionally, the time 
until the first tophus reduction (i.e., the first time CR or PR is assessed in overall tophus response) will be 
summarized using descriptive statistics by treatment group on the ITT, mITT, all randomized and PP 
populations. 
The HAQ-DI total score and the SF-36 summary score at scheduled visits and the change from baseline 
will be summarized by treatment group on the ITT, mITT, all randomized and PP populations. 
Frequency table of the number and percentage of patients reporting gout flares per 3-months period, 
will be summarized by period and treatment group on the ITT, mITT, all randomized and PP populations. 
Additionally, a frequency table of the number and percentage of patients reporting gout flares per 3-
month period by severity (life-threatening / severe / moderate /mild) and treatment group will be 
provided. The number and percentage of patients with at least one life-threatening or severe versus the 
number and percentage of patients with only mild or moderate gout flares per 3 month period will be 
presented for each treatment group. 
Further supportive analyses for key secondary efficacy variables will be defined in the SAP. 
13.4.3 
Further Secondary Efficacy Endpoints and Analyses 
Additional secondary efficacy endpoints will be summarized by treatment group using descriptive 
statistics on the ITT population and will be compared between each SEL-212 treatment group and 
placebo using MH considering the randomization stratum tophus presence (yes/no) in case of binary 
endpoints or using, or using continuity corrected Chi-square test in case of binary endpoints within 
subgroups with/without tophi at baseline. In case of continuous or numerical endpoints treatment 
groups will be compared by ANCOVA, or MMRM as appropriate. All tests – except the tests within 

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subgroups of tophus yes/no at Baseline - will adjust for the randomization stratum and will present 
exploratory p-values of two-sided tests. In addition, 95% confidence intervals for treatment differences 
between each SEL-212 treatment group and placebo will be computed. Details will be provided in the 
SAP. 
13.4.4 
Exploratory Endpoints and Analyses 
The summary of exploratory endpoints will be performed using descriptive summary statistics. 
Association between multiomic markers of gout and the treatment effect in patients with SEL-212 will 
be investigated. 
13.5 
Safety Analyses 
13.5.1 
Extent of Exposure 
Frequency tables of number and percentage of patients who received all doses and descriptive statistics 
of doses and total cumulative doses by treatment group 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.  
Summaries by each treatment group will be provided on the Safety Set overall and by SOC and PT with 
the number and percentage of patients reporting TEAEs, serious TEAEs, treatment-related TEAEs, AEs of 
special interest (AESIs), infusion reactions (this is a study drug-related AE that occurs within 24 hours 
after initiation of study drug infusion), TEAEs leading to withdrawal and TEAEs leading to death. 
Additional analysis will be performed on a subset of infusion reactions (this is a study drug-related AE 
that occurs within 1 hour after completion of study drug infusion) that fulfil the criteria of an Allergic 
Reaction/Hypersensitivity according to the Rheumatology Common Toxicity Criteria, version 2.0. In the 
overall summary, additionally, the number and percentage of patients with at least one severe TEAE, 
with at least one moderate TEAE but no severe TEAE and with only mild TEAEs will be provided.  
The number and percentage of patients with TEAEs / serious TEAEs treatment-related TEAEs / TEAEs of 
special interest and TEAEs leading to withdrawal will be summarized by SOC and PT for each treatment 
group and overall on the Safety Set.  
Event rates by treatment group and overall will be provided for patients with at least one related TEAE, 
at least one SAE, and at least one TEAE of special interest. Additionally, the relative risk with 95% 
confidence interval comparing each SEL-212 treatment group to placebo as well as comparing the 
integrated SEL-212 arms to placebo will be provided. 
TEAEs will also be summarized by maximum intensity and relationship to study drug.  
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 and overall. Shift tables of the number of patients with 

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low/normal/high (or normal/abnormal, as appropriate) values at each scheduled post-baseline visit 
compared to the low/normal/high (or normal/abnormal, as appropriate) categorization at baseline will 
be provided by treatment group and overall. Summary tables of actual values and changes from baseline 
will be provided for each continuous laboratory parameter at each scheduled visit by treatment group 
and overall. 
13.5.4 
Vital Signs  
Summary tables of the actual values and changes from baseline will be provided for each vital signs 
parameter at each scheduled visit by treatment group and overall. 
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 and overall. A shift table of the number and percentage of patients 
with normal and abnormal, and clinically significant abnormal values at each scheduled post-baseline 
visit compared to the normal / abnormal /clinically significant abnormal categorization at baseline will 
be provided by treatment group for the overall interpretation. 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. 

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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/IEC (or equivalent). 
 

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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 patient 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 patients 
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/IEC 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/IEC prior to implementation of the original protocol and any amendment. The 
Principal Investigator must submit all protocol modifications to the IRB/IEC, 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 patient 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/IEC as appropriate. 

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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) / Independent 
Ethics Committee (IEC) regulations in 21 CFR 56 and applicable local regulatory guidance, in accordance 
with ICH-GCP. IRB/IEC approval for the investigation must be obtained before the study is initiated. 
Initial IRB/IEC approval, and all materials approved by the IRB/IEC for this study including the patient 
consent form and recruitment materials must be maintained by the Investigator and made available for 
inspection. 
 

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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. 
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. 

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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. 
 

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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. 

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19. 
LIST OF REFERENCES 
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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. 
Bursill D, Taylor WJ, Terkeltaub R, et al. Gout, hyperuricaemia and crystal-associated disease network (G-
CAN) consensus statement regarding labels and definitions of disease states of gout. Ann Rheum Dis. 
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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, Smith T, Gray S, et al. Cellular characterization of magnetic resonance imaging bone oedema 
in rheumatoid arthritis; implications for pathogenisis of erosive disease. Ann Rheum Dis. 2009;68(2):279-
82 
Dalbeth N, Pool B, Gamble G, et al. Cellular characterization of the gouty tophus: a quantitative analysis. 
Arthritis Rheum. 2010;62(5):1549-56. 
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. 
Gaffo AL, Dalbeth N, Saag KG, Singh JA, Rahn EJ, et al. Validation of a definition of flare in patients with 
established gout. Arthritis & Rheumatology, 2018;70(3):462-467. 
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 
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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, 2012. Krystexxa® Prescribing Information. L8-1MPI.00 ed2014. 
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. 
Lipsky PE, Calabrese LH, Kavanaugh A, Sundy JS, Wright D, et al. Pegloticase immunogenicity: the 
relationship between efficacy and antibody development in patients treated for refractory chronic gout. 
Arthritis Res Ther. 2014;16(2):R60 
Luk AJ, Simkin PA. Epidemiology of hyperuricemia and gout. Am J Manag Care. 2005 Nov;11(15 
Suppl):S435-42. 
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. 
Poiley J, Steinberg AS, Choi YJ, Davis CS, Martin RL, et al. A randomized, double-blind, active- and 
placebo- controlled efficacy and safety study of Arhalofenate for reducing flare in patients with gout. 
Arthritis & Rheumatology 2016;68(8):2027-2034 
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, Doherty M, Pascual E, et al. Ann Rheum Dis. 2017:76:29-42 
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. 
Schumacher HR. J Rheumatol 2009;36:2342–5; doi:10.3899/jrheum.090370 

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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. 
Sundy JS, Baraf HS, Yood RA, Edwards NL et al. Efficacy and tolerability of pegloticase for the treatment 
of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. 
JAMA. 2011;306(7):711-720 
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. 
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. 

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20. 
APPENDICES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX A 
SCHEDULE OF ASSESSMENTS 
Assessment 
Scr. 
- 45 d to D0 
(Pre-dose)3 
Treatment Phase 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
D0 
D214 
D05 
D214 
D05 
D214 
D05 
D214 
D05 
D214 
D05 
D74 
D144 
D214 
D28 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Multi-energy CT6  
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Physical Examinations 
X7 
X8 
 
X8 
 
X8 
 
X8 
 
X8 
 
X8 
 
 
 
X7 
 
X7 
Vital Signs 
X 
X9 
 
X9 
 
X9 
 
X9 
 
X9 
 
X9 
 
 
X 
X 
 
X 
Weight and Height10 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Screening Labs11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 Testing 
X 
As clinically indicated. Refer to Section 12.1.8.7 
 
 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Washout: ULTs 
X13 
Patients will abstain from ULT use after the ULT washout period 
 
 
 
Document ULTs Discontinued 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense Premedication: Gout Flare 
and Infusion Reaction12 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
Premedication: Gout Flare 
X14 
Continuously 
 
 
 
Randomization 
 
X15 <-------> X15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Premedication: Infusion Reaction 
 
X16 
 
X16 
 
X16 
 
X16 
 
X16 
 
X16 
 
 
 
 
 
 
Safety Labs: Chemistry17 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Hematology18 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Coagulation19 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: Lipids20 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Safety Labs: eGFR17 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
X 
 
X 
Blood Sample for Anti-Pegadricase21 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
Blood Sample for nAbs21 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
Blood Sample for Anti-Pegadricase 
POC Validation21 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
Blood Sample for Anti-Uricase21 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
Blood Sample for Biomarkers6 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
X 
 
 
X 
 
X 
Blood Sample for Multiomic Markers 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 
X 
 
X 

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
15 DEC 2022 
 
 
PROPRIETARY AND CONFIDENTIAL 
PAGE 96 OF 100 
Blood Sample for HLA Typing 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Sample for T Cell Analysis 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
X 
 
X 

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
15 DEC 2022 
 
 
PROPRIETARY AND CONFIDENTIAL 
PAGE 97 OF 100 
Appendix A Schedule of Assessments, continued 
Assessment 
Scr. 
- 45 d to D0 
(Pre-dose)3 
Treatment Phase 
EOS1 
ET 
TP12 
TP22 
TP32 
TP42 
TP52 
TP62 
Day 
D0 
D21 
D05 
D21 
D05 
D21 
D05 
D21 
D05 
D21 
D05 
D74 
D144 
D214 
D28 
 
 
Tophus Assessment/Photography 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Gout Flare Assessment22 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Gout Flare Weekly Diary 
 
Continuously on Weekly Basis23 
 
X 
Joint Assessment (tenderness, 
swelling) 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Health Questionnaires24 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Collect Sample for sUA 
X 
Refer to Schedule of Assessments (Appendix B) for sUA Sample Collection during Treatment Phase 
 
X 
PD/Uricase Activity Assessment 
 
Refer to Schedule of Assessments (Appendix B) for PD/Uricase Activity Assessments during Treatment Phase 
 
X 
Study Drug Administration 
 
Refer to Schedule of Assessments in Appendix B for Study Drug Administration during the Treatment Phase 
 
 
Infusion Reaction Follow-up 
 
Refer to Section 12.2.1.5 
 
 
Concomitant Medications / 
Procedures 
 
Continuously 
X 
X 
AE Collection 
 
Continuously 
X 
X 
SAE Collection  
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/-1 days; visit window at Day 7 and Day 14 of Treatment Period 6 is +2/-1 days; visit window at Day 28 of Treatment 
Period 6 is +3/-4 days. 
3. Visit window is -2 days. 
4. Assessments at this visit are permitted to be performed remotely (inclusive of collecting applicable lab draws and assessments per protocol visit windows). 
5. 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. If a protocol deviation occurs where a patient is 
not able to be dosed within the dosing day window, for example in the case of COVID-19 restrictions temporarily preventing dosing, the current treatment period will be 
extended up to a maximum of 90 days without skipping doses for patients with a Day 21 visit sUA value ≤ 1.0 mg/dL during Treatment Period 1 or ≤ 6.0 mg/dL during 
Treatment Periods 2, 3, 4, or 5 in the D21 visit window or subsequent up to the rescheduled dosing visit. If a protocol deviation occurs in Treatment Period 6 such that the 
patient was unable to have an EOS visit performed within the visit window, then the Treatment Period 6 Day 28 visit should still occur 28 days (+3/-4 days) after the 
Treatment Period 6 dose or as close to the visit window as possible to collect the final primary endpoint SUA sample. 
6. Assessment performed at select sites only 
7. Full physical exam 
8. Directed physical exam 
9. 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. 
10. Height measured once during Screening only. 
11. Screening labs to include: calcium, total complement, hemoglobin-A1c (HbA1c), hepatitis C antibody, hepatitis B surface antigen, human immunodeficiency virus 1/2 
(HIV1/2), urinalysis, glucose-6-phosphate dehydrogenase (G6PD) 

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
15 DEC 2022 
 
 
PROPRIETARY AND CONFIDENTIAL 
PAGE 98 OF 100 
12. Dispense gout flare medication at Screening and as needed during the study. Dispense infusion reaction medication at Screening and at Day 21 of Treatment Periods 1-5. 
13. Begin at least 7 days prior to Day 0 of Treatment Period 1. 
14. Begin at least 7 days prior to Day 0 of Treatment Period 1. 
15. Randomization is permitted at any time between Day -7 to Day 0 (prior to SEL-212 administration). 
16. Premedication to minimize potential infusion reactions: oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to study medication. 
17. Chemistry labs to include: Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total Bilirubin, blood urea nitrogen (BUN), Creatinine, 
UACR, eGFR, Fibrinogen, Glucose (fasting), Electrolytes (sodium, potassium, chloride, bi-carbonate, phosphate, and magnesium) 
18. Hematology labs to include: white blood cells (WBC) count with differential, Red blood cell (RBC) count, Hematocrit (Hct), Hemoglobin (Hgb), Platelet (Plt) count, and 
absolute neutrophil count (Abneu) 
19. Coagulation labs to include: prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR) 
20. Fasting lipid labs to include: total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides 
21. Collect samples prior to study drug dosing. 
22. Gout flares assessed based on validated gout flare definition (Gaffo 2018) 
23. Start gout flare diary at Day 0 of Treatment Period 1. 
24. Refer to Section 11.3 for Health Questionnaires. 
Abbreviations: CT: computed tomography; D (d): day; ECG: electrocardiogram; eGFR: estimated glomerular filtration rate; EOS: end of study; ET: early termination; h: hour; 
nAbs: neutralizing antibodies; PD: pharmacodynamic; RCTC: Rheumatology Common Toxicity Criteria; Scr: Screening Phase; sUA: serum uric acid; TP: treatment period; UACR: 
urine-albumin-creatinine ratio; ULT: urate lowering therapy 
 
 

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
15 DEC 2022 
 
 
PROPRIETARY AND CONFIDENTIAL 
PAGE 99 OF 100 
APPENDIX B 
SCHEDULE OF ASSESSMENTS: DOSING, SUA, AND URICASE ACTIVITY DURING THE TREATMENT PHASE 
Assessments 
Day 
Timepoint 
Treatment Periods: 1, 2, 3, 4, and 5 
Treatment Period 6 
D01 
D212 
D01 
D72 
D142 
D212 
D283 
0h 
~1.5h 
~3.5h 
~4.5h 
 
0h 
~1.5h 
~3.5 
~4.5h 
 
 
 
 
Premedicate: Infusion Reaction 
X4 
 
 
 
 
X 
 
 
 
 
 
 
 
Blood Sample Uricase Activity 
X5 
 
 
X6 
X 
X5 
 
 
X6 
X 
X 
X 
X 
Blood Sample: sUA 
X5 
 
 
X6 
X 
X5 
 
 
X6 
X 
X 
X 
X 
Study Drug Infusion (Component 1)7 
X----------X8 
 
 
 
X----------X8 
 
 
 
 
 
 
Study Drug Infusion (Component 2)9 
 
X8---------X 
 
 
 
X8---------X 
 
 
 
 
 
1. 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.  
2. Assessments at this visit are permitted to be performed remotely (inclusive of collecting applicable lab draws and assessments per protocol visit windows). 
3. Treatment Period 6 only. 
4. Premedication to minimize potential infusion reactions: oral antihistamines at 12 (± 2) hours and 2 (± 1) hours and IV steroids at 1 (± 0.5) hours prior to  
study medication. 
5. Obtain sample prior to study drug infusion. 
6. Obtain sample 1 hour (+15/-0 min) after completion of infusion of Component 2. If a patient is withdrawn from study drug, the post-dose uricase activity and post-dose sUA 
samples do not need to be collected. 
7. Component 1 will be SEL-110.36 at 0.1 mg/kg for patients randomized to SEL-212A and SEL-110.36 at 0.15 mg/kg for patients randomized to SEL-212B or will be placebo. 
8. Before starting infusion with Component 2, a period of up to 30 minutes is permitted after completion of infusion of Component 1. 
9. Component 2 will be SEL-037 for patients randomized to either SEL-212A or to SEL-212B or will be placebo for patients randomized to placebo. 
 
 

PHASE 3 STUDY: SEL-212/302 
VERSION: 7.1 
EFFECTIVE DATE 
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PROPRIETARY AND CONFIDENTIAL 
PAGE 100 OF 100 
APPENDIX C 
DOSING, SERUM URIC ACID, AND URICASE ACTIVITY ASSESSMENT SCHEDULE (TREATMENT PERIODS 1, 2, 3, 4, AND 5) 
 
 
APPENDIX D 
DOSING, SERUM URIC ACID, AND URICASE ACTIVITY ASSESSMENT SCHEDULE (TREATMENT PERIOD 6)