A Phase 2, Multicenter, Open-label Study to Evaluate the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization
Phase: PHASE2
Conditions: Fetal and Neonatal Alloimmune Thrombocytopenia
Sponsor: Rallybio

A Phase 2, Multicenter, Open-label Study to Evaluate the Pharmacokinetics and Safety of 
RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization. 
 
Unique Protocol ID: IPA2202 
NCT Number:  
NCT06435845 
EudraCT Number: 
2024-512651-20-00 
Date of Protocol: 
14 October 2024 

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TITLE PAGE 
Protocol Title 
A Phase 2, Multicenter, Open-label Study to Evaluate the 
Pharmacokinetics and Safety of RLYB212 in Pregnant Women 
at Higher Risk for HPA-1a Alloimmunization 
Protocol Number 
IPA2202 
Compound 
RLYB212 
Brief Title 
Phase 2 Study on the Pharmacokinetics and Safety of 
RLYB212 in Pregnant Women at Higher Risk for HPA-1a 
Alloimmunization 
Study Phase 
2 
Sponsor Name 
Rallybio IPA, LLC 
Legal Registered 
Address 
 
 
New Haven, CT 06510 
EU Legal 
Representative 
FGK Representative Services BV 
Regulatory Agency 
Identifier Number(s) 
IND: Not available 
EU CT: 2024-512651-20 
NCT: NCT06435845 
WHO: Not available  
EUDRANET: Not available  
Other: Not applicable 
Protocol Date 
Document Version 
Date 
Version 1.0  
11 March 2024 
Version 1.1 
23 August 2024 
Version 2.0 
04 September 2024 
Version 3.0 
25 September 2024 
Version 4.0 
14 October 2024 
CONFIDENTIALITY NOTICE 
The information contained in this protocol and all other information relevant to RLYB212 are 
the confidential and proprietary information of Rallybio IPA, LLC and, except as may be 
required by federal, state, or local laws or regulation, may not be disclosed to others without the 
prior written permission of Rallybio IPA, LLC. 
 
 

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INVESTIGATOR AGREEMENT 
IPA2202: A Phase 2, Multicenter, Open-label Study to Evaluate the Pharmacokinetics and Safety 
of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization. 
I have read the protocol, including all appendices, and I agree that it contains all the necessary 
information for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in compliance with current Good Clinical Practice (GCP) standards as defined 
by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH) Guideline for GCP, all applicable national, state, and local laws and 
regulations, and the applicable Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) and other institutional requirements.  
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Rallybio or specified designees. I will 
discuss the material with them to ensure that they are fully informed about RLYB212, 
understand this study, and are able to comply. 
______________________________ 
__________________________ 
Principal Investigator Name (printed) 
Signature 
______________________________ 
Date 

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TABLE OF CONTENTS 
 
1 
PROTOCOL SUMMARY .....................................................................................................8 
1.1 
Synopsis ...............................................................................................................................8 
1.2 
Schema ..............................................................................................................................16 
1.2.1 
Interventional Study (IPA2202) ...............................................................................16 
1.2.2 
Non-interventional (Observational) Sub-study (IPA2202A) .................................17 
1.3 
Schedule of Activities (SoA) ............................................................................................18 
2 
INTRODUCTION ................................................................................................................24 
2.1 
Study Rationale ................................................................................................................24 
2.2 
Background ......................................................................................................................25 
2.2.1 
Disease Background ...................................................................................................25 
2.2.2 
Investigational Product Background .......................................................................26 
2.3 
Benefit/Risk Assessment ..................................................................................................29 
2.3.1 
Risk Assessment .........................................................................................................29 
2.3.2 
Benefit Assessment .....................................................................................................32 
2.3.3 
Overall Benefit-Risk Conclusion ..............................................................................33 
2.3.4 
Other Risk Minimization Actions/Monitoring ........................................................33 
3 
OBJECTIVES AND ENDPOINTS .....................................................................................34 
3.1 
Interventional ...................................................................................................................34 
3.2 
Non-Interventional (Observational) ...............................................................................35 
4 
STUDY DESIGN ..................................................................................................................36 
4.1 
Overall Design ..................................................................................................................36 
4.2 
Scientific Rationale for Study Design .............................................................................37 
4.3 
Justification for Dose .......................................................................................................37 
4.4 
End of Study Definition ...................................................................................................38 
5 
STUDY POPULATION .......................................................................................................39 
5.1 
Eligibility Criteria for Screening (Part 1) ......................................................................39 
5.1.1 
Inclusion Criteria to be Confirmed at Screening Part 1 ........................................39 
5.1.2 
Exclusion Criteria to be Confirmed for Screening Part 1 ......................................39 
5.2 
Eligibility Criteria for Study Intervention ....................................................................40 
5.2.1 
Inclusion Criteria for Study Drug Administration to be Confirmed at 
Screening Part 2 .........................................................................................................40 
5.2.2 
Exclusion Criteria for Study Drug Administration to be Confirmed at 
Screening Part 2 .........................................................................................................40 
5.3 
Lifestyle Considerations ..................................................................................................41 
5.4 
Screen Failures (Screening Part 2) .................................................................................41 
6 
STUDY INTERVENTION ..................................................................................................42 
6.1 
Study Intervention(s) Administered ...............................................................................42 
6.2 
Preparation/Handling/Storage/Accountability .............................................................42 
6.3 
Measures to Minimize Bias: Randomization and Blinding..........................................43 
6.4 
Study Intervention Compliance ......................................................................................43 
6.5 
Dose Modification ............................................................................................................43 
6.6 
Concomitant Therapy ......................................................................................................43 
6.6.1 
Rescue Medicine .........................................................................................................44 

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6.6.2 
Excluded Treatments, Medical Devices, and/or Procedures During Study 
Period ..........................................................................................................................44 
6.7 
Intervention of Overdose or Dosing Errors...................................................................44 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...........................................................................45 
7.1 
Discontinuation of Study Intervention ...........................................................................45 
7.1.1 
Temporary Discontinuation ......................................................................................45 
7.1.2 
Study Stopping Rules .................................................................................................45 
7.2 
Participant Discontinuation/Withdrawal from the Study ...........................................46 
7.3 
Lost to Follow-up .............................................................................................................46 
7.4 
Non-interventional (Observational) Sub-study – Subject Decision to 
Withdraw ..........................................................................................................................47 
8 
STUDY ASSESSMENTS AND PROCEDURES ...............................................................48 
8.1 
FNAIT Laboratory Screening Assessments ..................................................................48 
8.1.1 
Screening Part 1 .........................................................................................................48 
8.1.2 
Screening Part 2 .........................................................................................................49 
8.2 
Pharmacokinetic Assessments ........................................................................................50 
8.3 
Assessment of Pregnancy and Neonatal Outcomes.......................................................50 
8.3.1 
Obstetric/Fetal Doppler Ultrasound ........................................................................50 
8.3.2 
Visit Assessments for Pregnancy Outcomes that are Live Births .........................51 
8.3.3 
Vital Assessments for Pregnancy Outcomes that are Not Live Births ..................51 
8.3.4 
Neonatal/Infant Assessments ....................................................................................51 
8.4 
Safety Assessments ...........................................................................................................52 
8.4.1 
Physical Examinations ...............................................................................................52 
8.4.2 
Vital Signs ...................................................................................................................53 
8.4.3 
Electrocardiograms....................................................................................................53 
8.4.4 
Clinical Laboratory Assessments .............................................................................53 
8.5 
Adverse Events and Serious Adverse Events ................................................................53 
8.5.1 
Time Period and Frequency for Collecting AE and SAE Information.................54 
8.5.2 
Method of Detecting AEs and SAEs .........................................................................54 
8.5.3 
Follow-up of AEs and SAEs ......................................................................................54 
8.5.4 
Regulatory Reporting Requirements for SAEs .......................................................55 
8.5.5 
Adverse Events of Special Interest ...........................................................................55 
8.6 
Measurement of Anti-HPA-1a Alloantibodies ..............................................................55 
8.7 
Immunogenicity Assessments .........................................................................................55 
8.8 
Efficacy Assessments .......................................................................................................56 
8.9 
Non-interventional (Observational) Sub-study Assessments .......................................56 
8.9.1 
Visit Assessments for Pregnancy Outcomes that are Live Births .........................56 
8.9.2 
Visit Assessments for Pregnancy Outcomes that are Not Live Births ..................56 
8.10 
Independent Data Monitoring Committee ....................................................................57 
9 
STATISTICAL CONSIDERATIONS ................................................................................58 
9.1 
Statistical Hypothesis .......................................................................................................58 
9.2 
Sample Size Determination .............................................................................................58 
9.3 
Analysis Sets/Populations for Analysis ..........................................................................59 
9.4 
Statistical Analyses...........................................................................................................59 
9.4.1 
General Considerations .............................................................................................59 

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9.4.2 
Primary Endpoints.....................................................................................................59 
9.4.3 
Secondary Endpoints .................................................................................................60 
9.4.4 
Tertiary/Exploratory Endpoints...............................................................................61 
9.4.5 
Other Safety Analyses................................................................................................61 
9.5 
Interim Analyses ..............................................................................................................61 
9.6 
Non-interventional (Observational) Sub-study .............................................................62 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................................63 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................63 
10.1.1 
Regulatory and Ethical Considerations ...................................................................63 
10.1.2 
Financial Disclosure ...................................................................................................63 
10.1.3 
Informed Consent Process ........................................................................................64 
10.1.4 
Data Protection...........................................................................................................64 
10.1.5 
Committee Structure .................................................................................................64 
10.1.6 
Dissemination of Clinical Study Data ......................................................................65 
10.1.7 
Data Quality Assurance .............................................................................................65 
10.1.8 
Source Documents ......................................................................................................66 
10.1.9 
Study and Site Start and Closure .............................................................................66 
10.1.10 
Publication Policy.......................................................................................................67 
10.2 
Appendix 2: Clinical Laboratory Tests..........................................................................67 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ...........................................................................69 
10.3.1 
Definition of Adverse Events.....................................................................................69 
10.3.2 
Definition of Serious Adverse Events .......................................................................69 
10.3.3 
Definitions of Pregnancy- and Parturition-specific Adverse Events .....................70 
10.3.4 
Recording and Follow-up of AE and/or SAE ..........................................................71 
10.3.5 
Reporting of SAEs......................................................................................................73 
10.4 
Appendix 4: Abbreviations .............................................................................................74 
10.5 
Appendix 5: Protocol Amendment History ...................................................................77 
11 REFERENCES .....................................................................................................................79 
 
 
 

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TABLE OF TABLES 
Table 1-1 
Anticipated Eligibility Criteria for Sub-study ..................................................15 
Table 1-2 
Schedule of Activities: Screening Part 1 and Screening Part 2 .......................19 
Table 1-3 
Schedule of Activities: Subjects Eligible for RLYB212 Interventional 
Treatment and Postnatal Follow-up...................................................................20 
Table 1-4 
Schedule of Activities: Subjects Eligible for Non-interventional 
(Observational) Sub-study and Follow-up ........................................................23 
Table 2-1 
Risk Assessment of RLYB212 .............................................................................29 
Table 6-1 
Study Intervention(s) Administered ...................................................................42 
Table 8-1 
Screening Test Paradigm ....................................................................................49 
Table 10-1 
Protocol-required Clinical Laboratory Assessments ........................................68 
 
TABLE OF FIGURES 
Figure 1-1 
Overall Study Design (Interventional and Non-interventional 
[Observational]) ...................................................................................................11 

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1 PROTOCOL SUMMARY  
1.1 
Synopsis 
Protocol Title: A Phase 2, Multicenter, Open-label Study to Evaluate the Pharmacokinetics and 
Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization 
Short Title: Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant 
Women at Higher Risk for HPA-1a Alloimmunization 
Rationale: RLYB212 is a human monoclonal anti-human platelet antigen (HPA)-1a 
immunoglobulin G antibody designed to selectively bind to HPA-1a positive fetal derived cells 
or cell fragments present in the maternal circulation. The therapeutic goal of RLYB212 is to 
drive the rapid and complete elimination of HPA-1a positive fetal antigen from the maternal 
circulation in HPA-1b/b pregnant women and prevent maternal HPA-1a alloimmunization.  
A prophylactic dose regimen consisting of a single 0.12 mg subcutaneous (SC) loading dose of 
RLYB212 no later than gestational week (GW) 16 followed by 0.06 mg SC every 4 weeks 
(Q4W) through parturition is proposed for HPA-1b/b pregnant women at risk for HPA-1a 
alloimmunization. This dose regimen is the result of exposure simulations in pregnant women 
using a clinical pharmacology model based on pharmacokinetic (PK) and pharmacodynamic 
(PD) single and multiple dose data from two clinical studies with RLYB212 in HPA-1b/b 
volunteers, a meta-analysis of monoclonal antibody PK parameters, allometric scaling to account 
for demographic differences between study populations (Phase 1/non-pregnant and pregnant), 
and the dynamic physiologic changes that occur during gestation. The dose regimen is intended 
to achieve near steady state RLYB212 concentrations after the first dose and for steady state 
concentrations to be maintained within a target range of ~3 ng/mL to ~10 ng/mL for the duration 
of the pregnancy.  
The target lower boundary is supported by clinical and preclinical data demonstrating that 
concentrations of RLYB212 sufficient to bind ~10% of HPA-1a positive receptors in an antigen 
challenge model are effective to drive rapid elimination of circulating HPA-1a positive antigen 
positive cells. The target upper boundary of ~10 ng/mL is supported by a comprehensive 
toxicology program that demonstrated RLYB212 to have no observed adverse effect level 
(NOAEL) margins of up to 242-fold greater than 10 ng/mL in antigen negative dams bearing 
heterozygous antigen positive offspring (representative of HPA-1b/b women bearing an HPA-1a 
positive fetus and at risk of alloimmunization) and projected exposures well over 10-fold greater 
than 10 ng/mL in antigen positive fetuses and neonates (representative of HPA-1a/b fetuses and 
neonates). The target upper boundary is further informed by an extensive review of available 
literature on clinical assessments of HPA-1a alloimmunization and fetal and neonatal 
alloimmune thrombocytopenia (FNAIT), where a maternal HPA-1a alloantibody level of 
3 IU/mL has been reported as the threshold for the occurrence of anti-HPA-1a 
antibody-mediated fetal/neonatal thrombocytopenia. Using the most conservative estimates for 
binding equivalence in IU for RLYB212, the steady state upper boundary exposure target 
accounts for an additional margin of safety by maintaining RLYB212 concentrations at or below 
~0.5 IU/mL. 

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The purpose of this Phase 2 study is to assess the PK and safety of RLYB212 at the proposed 
therapeutic dose regimen in HPA-1b/b pregnant women at higher risk for HPA-1a 
alloimmunization and FNAIT. Following confirmation of the prophylactic RLYB212 dose 
regimen, it is planned to evaluate the safety and efficacy of RLYB212 in a Phase 3 registration 
trial in pregnant women at higher risk for the occurrence of HPA-1a alloimmunization and 
FNAIT. 
Objectives and Endpoints (Interventional/Study IPA2202) 
Objective 
Endpoint 
Primary 
• 
To evaluate the PK profile of 
RLYB212 during pregnancy following 
repeat SC administration  
• 
Maternal PK parameters, eg,   
○ 
half-life of RLYB212 (t½) 
○ 
maximum RLYB212 concentration (Cmax) 
○ 
time to maximum RLYB212 concentration (tmax) 
○ 
apparent clearance (CL/F) of RLYB212 
○ 
apparent volume of distribution (Vd) 
○ 
area under the RLYB212 concentration versus time curve 
(AUC) 
• 
To assess maternal and fetal safety of 
RLYB212 during pregnancy  
• 
Type, seriousness, and incidence of AEs 
• 
Physical examination findings 
• 
Vital signs 
• 
Maternal clinical laboratory values 
• 
ECG 
• 
Obstetric/fetal doppler ultrasound 
Secondary 
• 
To evaluate RLYB212 exposure in the 
neonate at delivery 
• 
Concentration of RLYB212 in cord blood  
• 
To assess the safety of RLYB212 in the 
HPA-1a positive neonate 
• 
Type, seriousness, and incidence of AEs including 
fetal/neonatal AEs 
• 
Physical examination findings, including APGAR scores 
• 
Vital signs  
• 
To assess the immunogenicity of 
RLYB212  
• 
Development of ADAs  
• 
To assess pregnancy and neonatal 
outcomes following antenatal 
RLYB212 administration  
• 
Number of spontaneous abortions 
• 
Number of elective abortions 
• 
Number of stillbirths 
• 
Number of premature births 
• 
Number of full term births (≥ 37 completed weeks of 
gestation) 
• 
Overall health and development of infants at 4-6 weeks and 
12 months of age 
• 
To assess the occurrence of neonatal 
thrombocytopenia following antenatal 
RLYB212 administration 
• 
Neonatal thrombocytopeniaa and severe neonatal 
thrombocytopenia  
• 
To assess the occurrence of HPA-1a 
alloimmunization 
• 
Presence of maternal anti-HPA-1a alloantibodies at Week 10 
post pregnancyb 
ADA = anti-drug antibody; AE = adverse event; APGAR = Appearance, Pulse, Grimace, Activity, and Respiration; 
ECG = electrocardiogram; HPA-1a = human platelet antigen 1a; PK = pharmacokinetic(s); SC = subcutaneous. 
a Evaluation of neonatal thrombocytopenia will be based on the umbilical cord sample taken at parturition. 
b For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 

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A non-interventional (observational) sub-study (IPA2202A) is planned based on the phased 
approach to participant enrollment that results from the sequential cohort design. Because of the 
rarity of the potential occurrence of HPA-1a alloimmunization, the non-interventional 
(observational) sub-study will serve to augment an ongoing FNAIT Natural History Study 
(NCT05345561), ie, generating natural history data on the occurrence of HPA-1a 
alloimmunization and pregnancy/neonatal outcomes in women at higher FNAIT risk. 
Descriptions of the non-interventional (observational) sub-study design are presented separately 
across this protocol. 
Objectives and Endpoints (Non-interventional [Observational]/Study IPA2202A) 
Objective 
Endpoint 
• 
To inform the frequency of HPA-1a 
alloimmunization among pregnant 
women identified at higher FNAIT risk 
• 
Occurrence of anti-HPA-1a maternal alloimmunization at 
Week 10 postpartuma 
• 
To inform the frequency of pregnancy 
outcomes among pregnant women 
identified at higher FNAIT risk 
• 
Rate of spontaneous abortion, defined as non-deliberate fetal 
death which occurs prior to 19 weeks of gestation 
• 
Rate of elective abortion, defined as deliberate termination of 
pregnancy at any time in gestation 
• 
Rate of stillbirth, defined as non-deliberate fetal death 
anytime in gestation on or after 19 weeks of gestation 
• 
Rate of premature birth, defined as live birth prior to 
37 completed weeks of gestation 
• 
Rate of full term birth (≥ 37 completed weeks of gestation) 
• 
To inform the frequency, where data 
are available, of neonatal 
thrombocytopenia in infants born to 
women who have alloimmunized, as 
determined by detectable anti-HPA-1a 
antibody at Week 10 postpartuma 
• 
Neonatal thrombocytopenia and severe neonatal 
thrombocytopenia, as determined by a platelet count 
< 150 × 109/L and < 50 × 109/L, respectively, where data are 
available 
a For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
Overall Design 
This study is a single-arm, open-label, multicenter study of RLYB212 in HPA-1b/b pregnant 
participants at higher risk for the occurrence of HPA-1a alloimmunization and FNAIT. A 
laboratory testing paradigm will be applied at screening to identify women at higher risk for 
HPA-1a alloimmunization. Study IPA2202 is comprised of three phases: a two-part screening 
phase, an antenatal treatment phase, and a postpartum follow-up phase (Figure 1-1). Study 
duration for each participant is anticipated to be ~44 weeks, inclusive of the screening visits 
through the Week 10 postpartum visit. For each child born during the study, the duration is 
anticipated to be ~12 months. 
For the non-interventional (observational) sub-study (IPA2202A), the same two-part screening 
phase for the intervention, as applicable, is followed by a postpartum/safety follow-up phase. 
The sub-study duration is anticipated to be ~44 weeks, inclusive of the screening visits through 
the Week 10 postpartum visit. 
The overall design of the Phase 2 study, including the non-interventional (observational) 
sub-study, is presented in Figure 1-1. 

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Figure 1-1 
Overall Study Design (Interventional and Non-interventional [Observational]) 
FNAIT = fetal and neonatal alloimmune thrombocytopenia; ICF = informed consent form; PK = pharmacokinetic; SC = subcutaneous. 
For Screening (Part 2)/ICF: Enrollment planned for 8 eligible participants for whom the pregnancy results in a live birth and who are evaluable for PK and safety assessments. 
Pregnancy/neonatal 
outcomes
Informed Consent:
Non-interventional 
Sub-study
10-week post-partum HPA-1a 
alloimmunization
Non-interventional Sub-study
RLYB212 SC
Administration
Parturition
PK/Immunogenicity Sampling/
Study Specified Assessments
Antenatal Treatment Phase
Screening Phase
Screening (Part 1)/ICF: Pregnant 
Individuals at Higher Risk for FNAIT 
(n = 5000)
•
Antenatal Treatment Phase cohort 
enrollment fulfilled (or complete)
•
Results of Screening Part 1 out of 
window (GW 16), or
•
Refusal of consent to Screening Part 2
Consent to Screening (Part 2)/ICF: 
Pregnant Individuals at Higher Risk 
for FNAIT eligible to receive Study 
Intervention (n = 8)
Eligible for Antenatal 
RLYB212
•
Screen failure,
•
Antenatal Treatment Phase cohort 
enrollment fulfilled,
•
Results of Screening Part 2 out of 
window (GW 16), or
•
Withdrawal of consent for Antenatal 
Treatment Phase
Higher Risk
Higher Risk
Next Steps: Continue study per 
protocol/DMC recommendations
Independent Data Monitoring 
Committee
Maternal Safety Follow up through 10 
weeks post partum
Neonate/Infant Safety Follow up at 
4-6 weeks and 12 months of age
Maternal and 
Neonate/Infant 
Safety Follow-up
Post Partum/Safety Follow-up
Review of All 
Available Data

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Screening Phase 
In participants presenting at GW 6 or after who provide informed consent, blood samples will be 
collected at the Screening Part 1 visit to assess for higher risk for the occurrence of HPA-1a 
alloimmunization during their pregnancy. The first test will be a test for maternal HPA-1 
genotype. In participants identified as HPA-1b/b (ie, HPA-1a negative), subsequent tests will be 
performed to confirm the participant has an HLA-DRB3*01:01 positive genotype, is 
anti-HPA-1a alloantibody negative, and is carrying an HPA-1a/b (ie, HPA-1a positive) fetus. 
Participants who meet all eligibility criteria in Screening Part 1 (ie, HPA-1b/b and 
HLA-DRB3*01:01 positive genotype; anti-HPA-1a alloantibody negative; fetal HPA-1a/b 
genotype) and who provide informed consent for Screening Part 2 (Visit 1/schedule of activities 
[SoA], Table 1-3) will be assessed to determine if they meet all eligibility criteria to enter the 
antenatal treatment phase of the study and to receive RLYB212 in accordance with protocol dose 
regimen.  
Antenatal Treatment Phase 
For participants who meet all the eligibility criteria at Screening Part 2 (Visit 2/Table 1-3), 
dosing with RLYB212 will be initiated at Visit 3, which must occur no later than GW 16. If the 
fetal HPA-1 genotype is pending and will not be available by the planned visit at ~GW 16, the 
subject will be dosed with the initial dose of RLYB212 pending the result (of the replicate tests), 
provided all other Screening Part 2 criteria are met. A second dose of RLYB212 will not be 
given if definitive fetal HPA-1a results are not available by Visit 4 (~GW 20). If the fetal 
HPA-1a genotype data are only available after the initial dose of RLYB212 is given and the fetus 
is HPA-1b/b, ie, not at risk for HPA-1a alloimmunization, the participant will be discharged 
from the study to receive normal prenatal care and follow-up by their physician. In this case, the 
participant would have been determined not to be at risk for development of HPA-1a 
alloimmunization and FNAIT. 
Dosing will be continued at the protocol-specified dose regimen during the pregnancy with the 
final dose of RLYB212 administered within 24 hours (±24 hours) of parturition.  
Postpartum/Safety Follow-up 
Upon completion of the antenatal treatment phase, participants will be monitored through 
10 weeks postpartum. Safety follow-up for the neonate/infant will be at 4-6 weeks and 
12 months following parturition. For pregnancies that do not result in a live birth, monitoring 
will be for 10 weeks from the date of the pregnancy terminating event. 
Statistical Considerations 
No statistical hypothesis testing will be performed in this study. No formal interim analyses will 
be conducted. Preliminary data may be used for summary purposes and for communication with 
health authorities. 

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Number of Participants 
It is anticipated that approximately 5,000 participants will be screened to enroll 8 eligible 
participants for whom the pregnancy results in a live birth and who are evaluable for PK and 
safety assessments. Up to 4 participants may be replaced if they were assigned to study drug but 
did not receive the study drug. Participants may be replaced for reasons other than clinical safety, 
including insufficient PK sample collection to characterize pharmacokinetics. 
Eligibility Criteria 
Eligibility for this study will be established using a two-part screening procedure. Screening 
Part 1 will identify those participants who are at higher risk for the occurrence of maternal 
HPA-1a alloimmunization and FNAIT in their pregnancy. Women in their first or subsequent 
pregnancy may be included in the study. If a participant meets eligibility criteria in Screening 
Part 1, they may proceed to Screening Part 2 to determine their eligibility for enrollment and 
subsequent treatment with RLYB212. If a participant is eligible at Screening Part 2 for the 
antenatal treatment phase, but the cohort has been fully enrolled, the participant will be requested 
to consent for enrollment in the non-interventional (observational) sub-study (Table 1-1). 
Inclusion Criteria to be Confirmed at Screening Part 1 
1. Written/signed informed consent (for Screening Part 1) 
2. 18-45 years of age 
3. Pregnant women who present at GW 6 or after and confirmed to be: 
a. HPA-1b/b (HPA-1a negative) 
b. HLA-DRB3*01:01 positive 
c. Anti-HPA-1a alloantibody negative 
d. Carrying an HPA-1a/b (HPA-1a positive) fetus   
Exclusion Criteria to be Confirmed at Screening Part 1 
1. Prior history of HPA-1a-related FNAIT 
2. Prior history of HPA-1a alloimmunization 
3. Prior history of platelet transfusion or other blood transfusions  
4. Body mass index (BMI) ≥ 35 kg/m2  
Eligibility Criteria for Study Intervention 
Participants who meet all eligibility criteria in Screening Part 1 (ie, HPA-1b/b and 
HLA-DRB3*01:01 positive genotype; anti-HPA-1a alloantibody negative; fetal HPA-1a/b 

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genotype) and who provide informed consent for Screening Part 2, will be assessed for eligibility 
to enter the study’s antenatal treatment phase and to receive treatment with RLYB212 provided 
all inclusion and no exclusion criteria are met. 
Inclusion Criteria for Study Drug Administration to be Confirmed at Screening Part 2 
1. Written/signed informed consent (for Screening Part 2) 
2. 18-45 years of age  
3. Pregnancy no later than GW 16 at the time of first study drug administration as determined 
by the principal investigator or qualified staff 
Exclusion Criteria for Study Drug Administration to be Confirmed at Screening Part 2 
Participants are excluded from the study if any of the following criteria apply: 
1. Multiple pregnancy (> 1 fetus) 
2. Known sensitivity and/or immediate hypersensitivity to any components of RLYB212 or its 
formulation 
3. History of hypersensitivity to protein therapeutics 
4. Any participant with a history of past or current intravenous immunoglobulin (IVIG) use for 
an underlying disease (eg, autoimmune disease) 
5. Requires ongoing systemic corticosteroid or systemic immunosuppressive treatment for any 
reason 
6. History of pre-eclampsia in a previous pregnancy  
7. Participants with an in vitro fertilized pregnancy or serving as pregnancy surrogates 
8. Current (or within the last 90 days) participation in another clinical study and have received 
an investigational drug and device within the last 90 days 
9. Participants known or suspected of not being able to comply with this study protocol 
10. History of any connective tissue or autoimmune or autoinflammatory disease, especially 
autoimmune thrombocytopenia 
11. Any co-morbid medical or obstetric condition(s), laboratory abnormality, concomitant 
treatment, or other reason that, in the investigator’s opinion, could adversely affect the safety 
of the participant and/or fetus, impair the assessment of study results, or preclude compliance 
with the study. 

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Non-interventional (Observational) Sub-study (IPA2202A) Eligibility and Population 
It is anticipated that a limited number of participants will be enrolled in the non-interventional 
(observational) sub-study. Criteria for enrollment in the sub-study, with reference to the two-part 
Screening phase, include the following: 
Table 1-1 
Anticipated Eligibility Criteria for Sub-study 
Screening Part 1 
Screening Part 2 
In the Antenatal Treatment Phase, the enrollment for the current sentinel or sequenced cohort has been fulfilled 
Results of Screening are only available after the first study drug administration window (by GW 16) has passed 
Refusal of consent to Screen Part 2 
Screen Failure 
--- 
Withdrawal of consent for Antenatal Treatment Phase 
Intervention Groups and Duration  
All interventional participants will receive SC RLYB212 administered using a vial and syringe. 
RLYB212 treatment will be initiated at the dosing visit (Visit 3) with an initial SC dose of 
0.12 mg no later than GW 16, followed by SC doses of 0.06 mg Q4W and with a final 0.06 mg 
dose administered within 24 hours (±24 hours) of parturition.  
A key goal of the study is to define the RLYB212 dose regimen that achieves the pre-determined 
target exposure range through parturition. Modification of the RLYB212 dose regimen may 
therefore be necessary, to ensure desired steady state concentrations are maintained through 
pregnancy and parturition between a target lower bound of ~3 ng/mL and a target upper bound of 
~10 ng/mL.  
Modification of RLYB212 dose/dose frequency may be made within a cohort or between 
cohorts, based on available PK data from participant(s) with a completed pregnancy. Dose 
modifications are not anticipated during the pregnancy of an individual participant.  
Data Monitoring Committee 
An independent data monitoring committee (DMC) will monitor safety outcomes and study 
conduct and will provide recommendations for consideration by the Sponsor regarding the 
continuation of the study, dosing of further participants in the study, or stopping the study for all 
participants or subgroups of participants in the study. Safety data will include, but not be limited 
to, those outcomes listed as primary and secondary endpoints. 
The Sponsor will propose a detailed mandate to the DMC and review this with the DMC prior to 
the initiation of screening. A detailed DMC charter and operating rules will be prepared and 
signed by DMC members before study start. 

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1.2 
Schema 
1.2.1 
Interventional Study (IPA2202) 
DMC = data monitoring committee; FNAIT = fetal and neonatal alloimmune thrombocytopenia; GW = gestational week; ICF = informed consent form; n (for 
DMC section) = total number of participants receiving the intervention; SC = subcutaneous; W = week. 
For Screening (Part 2)/ICF: Enrollment planned for 8 eligible participants for whom the pregnancy results in a live birth and who are evaluable for PK and safety 
assessments. 
 
Safety Follow-up
Screen (Part 1)  for Higher
FNAIT Risk
GW
16
GW
40
Subcutaneous Administration of RLYB212
Screen (Part 2) for Study 
Intervention Eligibility
End of 
Study
n = 1
Detailed Study Design
Data Monitoring Committee
1st Screening/ICF: Pregnant 
Women at Higher Risk for FNAIT
(n = 5000)
2nd Screening/ICF: Pregnant 
Women at Higher Risk for FNAIT 
to receive Study Intervention
(n = 8)
RLYB212 SC
Administration
Next Scheduled Subjects
Parturition
DMC
DMC
Overall Study Design
Maternal Safety Follow up 
through10 weeks
post partum
Parturition
W10
post parturition
n = 4
n = 8
Neonate/Infant
Safety Follow-up
at 4-6 weeks and
12 months
Neonate/Infant  Safety Follow-up up 
at  4-6 weeks and  12 months
Pharmacokinetic/Immunogenicity Sampling
Next 
Scheduled 
Subjects
Sentinel
Sentinel + Cohort 1
Sentinel + Cohorts 1 and 2

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1.2.2 
Non-interventional (Observational) Sub-study (IPA2202A) 
FNAIT = fetal and neonatal alloimmune thrombocytopenia; GW = gestational week; HPA = human platelet antigen; ICF = informed consent form; W = week. 
* Refer to Section 1.2.1. 
 
Pregnancy/neonatal 
outcomes
Informed Consent:
Non-interventional
Sub-study
10-week post-partum HPA-
1a alloimmunization
Non-InterventionalSub-study
Screening Phase
Screening (Part 1)/ICF: Pregnant 
Individuals at Higher Risk for FNAIT 
(n = 5000)
•
Antenatal Treatment Phase cohort 
enrollment fulfilled or complete
•
Results of Screening Part 1 out of 
window (GW 16), or
•
Refusal of consent to Screening Part 2
Consent to Screening (Part 2)/ICF: 
Pregnant Individuals at Higher Risk 
for FNAIT eligible to receive Study 
Intervention (n = 8)
Eligible for Antenatal 
RLYB212 *
•
Screen failure,
•
Antenatal Treatment Phase cohort 
enrollment fulfilled,
•
Results of Screening Part 2 out of 
window (GW 16), or
•
Withdrawal of consent for Antenatal 
Treatment Phase
Higher Risk
Higher Risk

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1.3 
Schedule of Activities (SoA) 
 
Quick Link 
Table 1-2 
Schedule of Activities: Screening Part 1 and Screening Part 2 
Table 1-3 
Schedule of Activities: Eligibility for Study Intervention, Antenatal Treatment, and Postnatal 
Follow-up 
Table 1-4 
Schedule of Activities: Subjects Eligible for Non-interventional (Observational) Sub-study and 
Follow-up 
 
 
 

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Table 1-2 
Schedule of Activities: Screening Part 1 and Screening Part 2 
Assessments 
Notes 
Screening Part 1 
 
Informed consent (SCR) 
Consent for blood samples to be collected to determine higher risk 
for occurrence of HPA-1a alloimmunization and FNAIT during the 
pregnancy. 
Demographics 
Year of birth, self-characterized race, ethnicity, and obstetric 
history. Gestational age in weeks as estimated by the principal 
investigator or qualified staff. 
Blood samples for FNAIT laboratory 
testing 
Pregnant participant presenting at GW 6 or after the pre-natal visit 
will be determined to be eligible if they are: HPA-1b/b genotype 
(HPA-1a negative), HLA-DRB3*01:01 positive genotype, 
anti-HPA-1a alloantibody negative, and fetal HPA-1a/b genotype 
(ie, HPA-1a positive)a. 
Screening Part 2  
(after Screening Part 1 and by 
~GW 16) 
Consent for further assessments to confirm participants meet all 
inclusion/exclusion criteria and are eligible for treatment with 
RLYB212 and for their pregnancy to be followed according to the 
requirements of the protocol. 
Note: This is the same as “Visit 2” in Table 1-3. 
FNAIT = fetal and neonatal alloimmune thrombocytopenia; GW = gestational week; SCR = screening. 
a Two distinct samples and analyses are performed, per industry practice, to confirm absence of the HPA-1b 
allele in the fetus, with timing between sampling ~2 weeks.  
 
 
 

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Table 1-3 
Schedule of Activities: Subjects Eligible for RLYB212 Interventional 
Treatment and Postnatal Follow-up 
Study Period 
Eligibility, Treatment, and Follow-up Perioda 
Notes 
 
SV 
Pt 1 
SV 
Pt 2 
(B) 
Initial 
Dose 
 
Dose 
2 
Dose 
3 
 
Dose 
4 
 
Dose 
5 
 
Dose 
6 
 
Dose 
7 
 
EOS Infant 
EOS 
Gestational Week 
presented for 
Screening Visits, 
Parturition and 
Postpartum. 
Weeks since Initial 
Dose presented for 
subsequent dosing 
and PK sampling; 
visit window for 
Visits 4-13 are 
±3 days; and ±7 for 
Visits 15-16 
Gestational 
Week <14 <16 by 16 ~18 ~20 
~24 ~26 ~28 ~30 ~32 ~34 ~36 ~38 
Pb 
PP4 PP10  
Week Since 
Initial Dose 
 
 
0 
2 
4 
8 
10 
12 
14 
16 
18 
20 
22 
 
 
 
 
Visit 
Number 1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
 
General and Safety Assessments 
Informed 
consent, 
eligibility 
confirmation, 
demographics, 
and medical 
history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Including obstetric 
history. Gestational 
age in weeks is 
confirmed by the 
principal 
investigator or 
qualified staff 
Brief physical 
exam  
(height, weight, 
BMI) 
X 
X* 
 
 
X 
X 
 
 
X 
 
 
 
X 
X* 
X 
X* 
 
X* = full physical 
exam  
Should be 
symptom directed  
Vital signs 
 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
 
12-lead ECG 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
ECG to be 
performed pre-
dose, where 
applicable 
AE/SAE 
review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant 
medication 
review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Obstetric and 
fetal doppler 
ultrasound 
 
X 
 
 
X 
X 
 
X 
 
X 
 
X 
Y 
X 
 
 
 
Y = Week 38 is for 
high-risk 
pregnancies as 
assessed by the PI 
Laboratory Assessments 
Viral serology 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, hepatitis B 
and C 
Hematology, 
chemistry, 
coagulation, 
CRP 
 
X* 
 
 
X* 
 
 
X* 
 
X* 
 
 
 
X* 
X 
X 
 
X*: Collection of 
sample up to 
1 hour prior to 
study drug 
administration  
Urinalysis 
 
X* 
 
 
X* 
 
 
X* 
 
X* 
 
 
 
X* 
X 
X 
 
X*: Collection of 
sample up to 
1 hour prior to 
study drug 
administration  

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Study Period 
Eligibility, Treatment, and Follow-up Perioda 
Notes 
 
SV 
Pt 1 
SV 
Pt 2 
(B) 
Initial 
Dose 
 
Dose 
2 
Dose 
3 
 
Dose 
4 
 
Dose 
5 
 
Dose 
6 
 
Dose 
7 
 
EOS Infant 
EOS 
Gestational Week 
presented for 
Screening Visits, 
Parturition and 
Postpartum. 
Weeks since Initial 
Dose presented for 
subsequent dosing 
and PK sampling; 
visit window for 
Visits 4-13 are 
±3 days; and ±7 for 
Visits 15-16 
Gestational 
Week <14 <16 by 16 ~18 ~20 
~24 ~26 ~28 ~30 ~32 ~34 ~36 ~38 
Pb 
PP4 PP10  
Week Since 
Initial Dose 
 
 
0 
2 
4 
8 
10 
12 
14 
16 
18 
20 
22 
 
 
 
 
Visit 
Number 1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
 
RLYB212 PK 
 
 
X* 
Y 
X* 
X* 
Y 
X* 
Y 
X* 
Y 
X* 
Y 
X* 
X 
 
 
X*: Collection of 
sample up to 
1 hour prior to 
study drug 
administration. 
Y: Sample window 
of ±7 days 
ADA 
 
 
X* 
 
X* 
X* 
 
X* 
 
X* 
 
X* 
 
X* 
X 
 
 
X*: Collection of 
sample up to 
1 hour prior to 
study drug 
administration 
Study Intervention 
Study drug 
administration 
 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X* 
 
 
 
Proposed dosing 
window of ±3 days 
X*: Dosing within 
24 hours 
(±24 hours) of 
parturition 
Other Assessments 
HPA-1a 
alloantibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Pregnancy 
outcome 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Cord blood 
samplec 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Platelet and 
hematocrit, 
hemoglobin, 
reticulocytes, total 
bilirubin, 
RLYB212 
concentration 
If neonatal 
thrombocytopenia 
is present, follow-
up to resolution is 
required through 
normalization of 
platelet count as 
per standard of 
care 
Newborn 
general statusd 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 

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Study Period 
Eligibility, Treatment, and Follow-up Perioda 
Notes 
 
SV 
Pt 1 
SV 
Pt 2 
(B) 
Initial 
Dose 
 
Dose 
2 
Dose 
3 
 
Dose 
4 
 
Dose 
5 
 
Dose 
6 
 
Dose 
7 
 
EOS Infant 
EOS 
Gestational Week 
presented for 
Screening Visits, 
Parturition and 
Postpartum. 
Weeks since Initial 
Dose presented for 
subsequent dosing 
and PK sampling; 
visit window for 
Visits 4-13 are 
±3 days; and ±7 for 
Visits 15-16 
Gestational 
Week <14 <16 by 16 ~18 ~20 
~24 ~26 ~28 ~30 ~32 ~34 ~36 ~38 
Pb 
PP4 PP10  
Week Since 
Initial Dose 
 
 
0 
2 
4 
8 
10 
12 
14 
16 
18 
20 
22 
 
 
 
 
Visit 
Number 1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
 
Infant general 
status 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X* 
 
Y 
X*: if infant 
present at 
4-6 weeks.  
Y: 12 months 
(±2 weeks)  
After Visit 3, windows for administering RLYB212 and other maternal assessments are ±3 days, with the exception of PK assessments at 
Weeks 30 and 38 which are ±7 days. The last dose of RLYB212 is to be administered within 24 hours (±24 hours) of parturition. 
ADA = anti-drug antibody; AE = adverse event; BMI = body mass index; CRP = C-reactive protein; D = day; ECG = electrocardiogram; 
EOS = end of study; GW = gestational week; h = hour; HPA = human platelet antigen; m = minute; P = Parturition; PI = principal investigator; 
PK = pharmacokinetic(s); PP = postpartum; SAE = serious adverse event; SV = study visit; Tx = treatment.  
a Screening Part 1 (presenting at GW 6 or after) women will consent to screening blood tests for HPA-1a genotyping and, if have an HPA-1b/b 
genotype, testing for HLA-DRB3*01:01, anti-HPA-1a alloantibody negative, and confirmation of fetal HPA-1a/b genotype via two distinct 
samples/analyses (as outlined in Table 1-2). At Screening Part 2, targeted after the Screening Part 1 visit, and by ~GW 16, those participants who 
are HPA-1b/b and HLA-DRB3*01:01 positive genotype, anti-HPA-1a alloantibody negative, and fetal HPA-1a/b genotype will be consented to 
further assessments to confirm they meet all inclusion/exclusion criteria and are eligible for treatment with RLYB212 and for their pregnancy to 
be followed according to the requirements of the protocol.  
b Assumption is that the full term birth is at 40 weeks. If this occurs earlier than 40 weeks, the assessments planned for Week 40 will be 
conducted at parturition. 
c Evaluation of neonatal thrombocytopenia will be based on the umbilical cord sample taken at parturition. 
d Newborn general status to include Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The APGAR score is to be captured 
twice: once at 1 minute after birth and again at 5 minutes after birth. The physical examination of the newborn is the routine clinical examination 
performed at birth.  
 

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Table 1-4 
Schedule of Activities: Subjects Eligible for Non-interventional 
(Observational) Sub-study and Follow-up 
Study Period 
Eligibility and Follow-up Perioda 
Notes 
 
SV 
Pt 1 
SV 
Pt 2,  
if applicableb 
EOS 
 
Gestational Week 
<14 
<16 
PP10c 
General Assessments 
Informed consent, 
eligibility 
confirmation, 
demographics, and 
obstetric history 
Xδ 
X 
 
Gestational age in weeks is 
confirmed by the principal 
investigator or qualified staff 
Other Assessments 
HPA-1a 
alloantibodies 
X 
 
X 
 
Pregnancy 
outcomed 
 
 
X 
Based on medical records, ie, 
neonatal thrombocytopenia to 
be sourced from the neonate’s 
medical records 
BMI = body mass index; D = day; EOS = end of study; GW = gestational week; HPA = human platelet antigen; m = minute; 
PI = principal investigator; PP = postpartum; SV = study visit.  
δ As defined in Table 1-2. 
a Screening Part 1 (presenting at GW 6 or after) women will consent to screening blood tests for HPA-1a genotyping and, if have 
an HPA-1b/b genotype, testing for HLA-DRB3*01:01, anti-HPA-1a alloantibody negative, and confirmation of fetal HPA-1a/b 
genotype via two distinct samples/analyses (as outlined in Table 1-2). At Screening Part 2 targeted after the Screening Part 1 
visit, and by ~GW 16, those participants who are HPA-1b/b and HLA-DRB3*01:01 positive genotype, anti-HPA-1a alloantibody 
negative, and fetal HPA-1a/b genotype, will be consented to further assessments to confirm they meet all inclusion/exclusion 
criteria and are eligible for treatment with RLYB212 and for their pregnancy to be followed according to the requirements of the 
protocol.  
b In some cases, enrollment into the non-interventional (observational) sub-study will occur following SV1; therefore SV2 would 
not be applicable. SV2 presented for completeness. 
c Assumption is that the live birth is at 40 weeks. If this occurs earlier than 40 weeks, the assessments planned for Week 40 will 
be conducted at parturition. 
d For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the date of the 
pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth).  
 

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2 INTRODUCTION 
RLYB212 is a recombinant human monoclonal anti-human platelet antigen (HPA)-1a 
immunoglobulin G (IgG)1κ antibody designed to selectively bind to HPA-1a positive 
fetal-derived cells or cell fragments present in the maternal circulation. The therapeutic goal of 
RLYB212 is to drive rapid and complete elimination of HPA-1a positive fetal antigen from the 
maternal circulation in HPA-1b/b pregnant women and prevent maternal HPA-1a 
alloimmunization (Section 2.1). 
2.1 
Study Rationale 
A prophylactic dose regimen consisting of a single 0.12 mg subcutaneous (SC) loading dose of 
RLYB212 no later than gestational week (GW) 16 followed by 0.06 mg SC every 4 weeks 
through parturition is proposed for HPA-1b/b pregnant women at risk for HPA-1a 
alloimmunization. This dose regimen is the result of exposure simulations in pregnant women 
using a clinical pharmacology model based on pharmacokinetic (PK) and pharmacodynamic 
(PD) data from two clinical studies with RLYB212 in HPA-1b/b volunteers, a meta-analysis of 
monoclonal antibody PK parameters, allometric scaling to account for demographic differences 
between study populations, and the dynamic physiologic changes that occur during gestation. 
The dose regimen is intended to achieve near steady state RLYB212 concentrations after the first 
dose and to maintain RLYB212 concentrations within a target range of ~3 ng/mL to ~10 ng/mL.  
The target lower boundary is supported by clinical and preclinical data demonstrating that 
concentrations of RLYB212 sufficient to bind ~10% of HPA-1a positive receptors in an antigen 
challenge model are effective to drive rapid elimination of circulating HPA-1a positive antigen 
positive cells. The target upper boundary of ~10 ng/mL is supported by a comprehensive 
toxicology program that demonstrates RLYB212 to have no observed adverse effect level 
(NOAEL) margins of up to 242-fold greater than 10 ng/mL in antigen negative dams bearing 
heterozygous antigen positive offspring (representative of HPA-1b/b women at risk of 
alloimmunization) and projected exposures well over 10-fold greater than 10 ng/mL in antigen 
positive fetuses and neonates (representative of HPA-1a/b fetuses and neonates). The target 
upper boundary is further informed by an extensive review of available literature on clinical 
assessments of alloimmunization rates and FNAIT, where maternal HPA-1a alloantibody levels 
of 3 IU/mL, measured at GW 28 or 34, has been reported as the threshold for the occurrence of 
anti-HPA-1a antibody-mediated fetal/neonatal thrombocytopenia [1, 2]. Using the most 
conservative estimates for binding equivalence in IU for RLYB212, the steady state exposure 
target accounts for an additional margin of safety by maintaining RLYB212 concentrations at or 
below ~0.5 IU/mL.  
The purpose of this Phase 2 study is to assess the PK and safety of RLYB212 at the proposed 
therapeutic dose regimen in HPA-1b/b pregnant women at higher risk for HPA-1a 
alloimmunization and FNAIT.  
Following confirmation of the prophylactic RLYB212 dose regimen, it is planned to evaluate the 
safety and efficacy of RLYB212 in a Phase 3 registration trial in pregnant women at higher risk 
for the occurrence of HPA-1a alloimmunization and FNAIT. 

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2.2 
Background 
2.2.1 
Disease Background 
FNAIT is a rare and potentially life-threatening disorder that can cause uncontrolled bleeding in 
the fetus and neonate due to maternal alloantibody-mediated destruction of fetal/neonatal 
platelets. It is estimated to occur in approximately 1 in 1,000 pregnancies and can result in 
potentially severe consequences, including fetal and neonatal intracranial hemorrhage (ICH) that 
can cause death of the fetus or newborn or irreversible brain damage that results in lifelong 
neurologic disability. ICH due to HPA-1a alloimmunization is estimated to occur in 
approximately 1 in 10,000 pregnancies, which translates to approximately 1,000 annual cases of 
ICH in Europe and North America [3].   
Maternal alloimmunization to fetal platelet antigen is the prerequisite event leading to FNAIT. A 
fetal-maternal mismatch in HPA-1 is the most common cause of maternal alloimmunization 
leading to FNAIT, accounting for approximately 75% to 80% of FNAIT cases [4-7]. The HPA-1 
alleles arise from a single nucleotide polymorphism that results in either a leucine (HPA-1a) or a 
proline (HPA-1b) at residue 33 of integrin β3 [8]. If the woman is negative for the HPA-1a 
antigen (HPA-1b homozygous), fetal platelets or cell fragments that are positive for paternally 
inherited HPA-1a antigen and which enters the maternal circulation can induce production of 
maternal HPA-1a alloantibodies. The maternal anti-HPA-1a alloantibodies can then traverse the 
placenta and destroy the fetal platelets, resulting in FNAIT [9]. Furthermore, in women who are 
positive for the HLA-DRB3*01:01 allele, the risk to become HPA-1a alloimmunized is 
approximately 25 times higher than in women who do not carry this allele [10]. 
There are currently no available treatments for the prevention of HPA-1a alloimmunization in 
pregnant women at risk for the occurrence of FNAIT. At present, most treatment modalities for 
pregnant women at risk for FNAIT are generally administered post factum, after it has been 
determined that the woman had a prior child born with FNAIT, and maternal alloimmunization 
had already occurred.  
Available data suggest FNAIT has a similar pathophysiology to that of hemolytic disease of the 
fetus and newborn (HDFN) [11]. In the case of HDFN, a Rhesus D (RhD)-negative pregnant 
woman may develop alloantibodies to RhD antigens that have been inherited from the father and 
expressed on fetal red blood cells (RBCs). The maternal antibodies can traverse the placenta and 
destroy the fetal RBCs, leading to anemia and potentially hydrops fetalis, and/or death of the 
fetus. 
Following the introduction of anti-RhD over 50 years ago [12], prophylactic administration of 
anti-RhD antibodies to prevent maternal RhD alloimmunization has been used with great success 
in the prevention of HDFN, which now rarely occurs. The anti-RhD antibody preparation 
(eg, WinRho SDF®; RhoPhylac®) is an IgG fraction containing a standardized antibody dose to 
the RhD antigen, which is administered by intramuscular injection as a prophylactic treatment to 
an RhD-negative pregnant woman during pregnancy at GW 27 to 28 and within 72 hours of 
parturition.  

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Since hemolytic disease of the fetus and newborn (HDFN) and FNAIT share a common 
alloimmune basis, administration of a prophylactic treatment is seen as the optimal approach to 
managing the risk of FNAIT, where passive transfer of the disease-causing agent itself 
(ie, anti-RhD antibodies in HDFN and anti-HPA-1a antibodies in FNAIT) can safely and 
effectively prevent maternal alloimmunization at concentrations well below the threshold 
associated with adverse clinical sequelae in the fetus or neonate. It is anticipated that RLYB212 
has the potential to provide comparable efficacy for preventing HPA-1a alloimmunization and 
the occurrence of FNAIT, as has been established for anti-RhD products in preventing RhD 
alloimmunization and occurrence of HDFN. 
2.2.2 
Investigational Product Background 
RLYB212 is a recombinant human monoclonal anti-HPA-1a IgG1κ antibody designed to 
selectively bind to HPA-1a positive fetal-derived cells or cell fragments present in the maternal 
circulation. 
2.2.2.1 
Nonclinical Studies 
In vitro binding and activity assessments were consistent with RLYB212 being highly selective 
for the HPA-1a isoform of integrin β3 and having full IgG1 effector function capability. It is 
anticipated that RLYB212 will display no pharmacologic activity in the absence of HPA-1a and 
is capable of selectively opsonizing fetal-derived HPA-1a positive cells and cell fragments 
present in maternal circulation. 
The bi-allelic nature of an HPA-1a negative pregnant woman bearing a heterozygous HPA-1a 
positive fetus can only be replicated in a transgenic animal model. Nonclinical efficacy and 
safety studies were therefore performed using a bi-allelic transgenic mouse model of FNAIT, 
where the gene encoding murine integrin β3 was “humanized” to reconstitute the human HPA-1a 
epitope by replacing 5 amino acids with their human counterparts (referred to as the APLDQ 
model for the amino acid substitutions made) [13]. 
Efficacy was assessed using an HPA-1a alloimmune challenge model where female HPA-1a 
negative wild-type (WT) mice received a transfusion of HPA-1a positive transgenic (APLDQ) 
murine platelets. Prophylactic administration of RLYB212 at doses estimated to saturate ~10% 
of HPA-1a platelet antigen was both necessary and sufficient to drive rapid and complete 
elimination of HPA-1a positive platelets in a dose-dependent manner and prevent HPA-1a 
alloimmunization [14]. 
To assess safety, general toxicology studies were conducted in WT mice to mimic dosing in 
antigen-negative women and in heterozygous APLDQ mice to assess exposure risks in the 
antigen positive fetus and neonate (with an emphasis on hematology).  
A 4-week, repeat-dose, Good Laboratory Practice (GLP) toxicity study was conducted to 
evaluate the potential toxicity, the toxicokinetic (TK) properties, and the immunogenicity of 
RLYB212 in antigen negative mice. Groups of male and female C57BL/6 mice received 
RLYB212 SC injections at doses up to 0.125 mg/kg/dose, every 3 days for 4 weeks. RLYB212 
was well tolerated with no associated toxicity, with average maximum serum concentration 
(Cmax) exposures up to 532-fold higher than the target upper boundary in IPA2202. 

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A second 4-week repeat-dose GLP toxicity study of SC administration was conducted to 
evaluate the potential toxicity, the TK properties, and the potential reversibility of RLYB212 in 
heterozygous antigen positive mice. Groups of male and female heterozygous APLDQ mice 
received RLYB212 SC injections at 0.025 mg/kg once weekly. It is noted that the assay used to 
measure RLYB212 in circulation detects only free drug, which limits the ability to accurately 
assess exposure levels in antigen positive animals; therefore, a parallel TK control arm in WT 
mice was included for estimation of RLYB212 exposures. RLYB212 was well tolerated with 
average Cmax exposure margins up to 12.5-fold over the target upper boundary in IPA2202 after 
the first dose and 47-fold over the target upper boundary after the last dose, with no drug-related 
clinical signs or effects on body weights or body weight gains. Observed effects on hematology 
in both antigen positive and negative animals (increase in lymphocytes, neutrophils, and total 
white blood cells) were considered non-adverse and were reversible.  
Reproductive toxicology studies were conducted in female WT mice bred to transgenic APLDQ 
sires, to mimic the population of HPA-1b/b women bearing an HPA-1a positive fetus. Parallel 
control dose groups in pregnant mice bearing antigen-negative litters were utilized to confirm the 
relative ratio of maternal to fetal/neonatal exposures after dosing with RLYB212 during 
gestation and lactation. An additional study was also conducted in pregnant mice bearing 
antigen-positive litters to evaluate histopathology of heterozygous HPA-1a antigen-positive 
fetal-derived tissues (placenta, fetus, and neonate).  
Over the series of reproductive toxicology studies that were performed, RLYB212 did not cause 
any adverse effects on mice during reproduction or embryo-fetal developmental (EFD) studies, 
ie, there were no effects on gestation, parturition, lactation, or maternal behavior in the dams and 
no effects on mortality, growth, or sexual maturation in their offspring. Minimal findings were 
noted from one study only, which included slightly increased post-implantation losses and 
slightly decreased fetal bodyweights in the 0.125 mg/kg dose group. Post-implantation losses in 
this study were variable and included several individual dams across all dose groups with losses 
which exceeded twice the standard deviation. Individual animal data included one dam each in 
the control and low dose group which were excluded due to early delivery. Decrease in fetal 
bodyweight was mild in the high dose group. While anti-drug antibodies (ADAs) were not 
measured in this study, immunogenicity could be related to these findings as RLYB212 
concentrations varied and were undetectable in several animals.   
This evaluation, taken together with the overall developmental and reproductive toxicity (DART) 
package including four other studies where no increase in post-implantation losses or decrease in 
pup fetal bodyweight was noted, led to an overall assessment of low risk for reproductive 
toxicity. Exposure margins from the reproductive toxicity package of studies ranged from 
average Cmax margins in pregnant dams of up to 65-fold at gestation day 18 and 242-fold at 
lactation day 5. While direct measurement of RLYB212 exposure in heterozygous antigen 
positive offspring was not possible, antigen negative control groups demonstrated RLYB212 
fetal exposures in utero at gestation day 18 of ~1-3 fold greater than those measured in the dams. 
Extrapolation of maternal:fetal/neonatal exposure ratios in control groups in combination with 
direct measurement of RLYB212 in antigen negative dams bearing antigen positive offspring 
enable projected exposure margins in antigen positive fetuses and neonates well over 10-fold 
greater than the target upper boundary of ~10 ng/mL in IPA2202. A tissue cross reactivity (TCR) 
study was conducted consisting of a panel of 37 adult human tissues; RLYB212 staining to the 

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plasma membrane of cells was generally consistent with reported expression of integrin β3 
(platelets, bone marrow megakaryocytes, placental trophoblasts, and epithelial, mesothelial, and 
mononuclear cells). In a second TCR study evaluating fetal human tissue, RLYB212 staining 
was consistent with that expected, ie, endothelial cells, various epithelial cells, nerves, and 
mononuclear leukocytes. The remainder of binding in the fetal human tissues was cytoplasmic in 
nature and judged of little to no toxicologic concern due to the limited accessibility of the 
cytoplasmic compartment to monoclonal antibodies in vivo. Overall, the TCR studies show no 
significant toxicological concerns. 
The nonclinical pharmacology and toxicology data support clinical investigation of RLYB212 to 
HPA-1b/b women bearing an HPA-1a positive fetus who are at risk for the occurrence of 
HPA-1a alloimmunization and FNAIT, with broad safety margins and no significant drug related 
toxicologic effects. Refer to the Investigational Brochure for additional nonclinical background 
information. 
2.2.2.2 
Early Clinical Development Studies 
Clinical experience with RLYB212 is based on data from a Phase 1 single- and multiple-dose 
first-in-human study in HPA-1b/b male and female participants (IPA2001) and data from a 
Phase 1b single dose, prospective proof-of-mechanism (PoM)/proof-of-concept (PoC) study in 
HPA-1b/b males (IPA2003). 
Study IPA2001 assessed the safety and PK of SC administered RLYB212 following single dose 
administration (0.21 mg) and multiple dose administration (0.29 mg on Day 1 followed by 
0.1 mg every 2 weeks for an additional 10 weeks). RLYB212 was well tolerated in both cohorts 
of the study. The majority of treatment emergent adverse events (TEAEs) were reported as mild 
and no severe TEAEs, serious adverse events (SAEs) or TEAEs leading to withdrawal from 
study treatment were reported. Six possibly related TEAEs were reported in 3 participants 
(18.8%), all of whom received RLYB212 in the multiple dose cohort. The most common of the 
possibly related TEAEs was headache (2 events in 2 participants) and two of the possibly related 
TEAEs were of moderate severity (headache and muscle spasms). There were no clinically 
meaningful findings related to clinical laboratory evaluations. There were no clinically 
meaningful findings related to vital signs, electrocardiograms (ECGs), or physical examinations. 
RLYB212 displayed a PK profile consistent with an SC-administered monoclonal antibody, with 
a median tmax that ranged from 7 to 14 days, followed by a mono-exponential decline with a 
mean serum half-life of ~25 days. Two RLYB212 participants showed positive results for ADAs 
against RLYB212 (1 transient in Cohort 1 and 1 persistent with low titer in Cohort 2). No 
clinical findings attributable to ADAs were observed in these 2 participants and based on the 
similarity in PK profiles between participants with ADA positive and ADA negative results, the 
development of anti-RLYB212 antibodies had no clinically significant effect on the PK of 
RLYB212.  
In Study IPA2003, a Phase 1b PoM/PoC study, the ability of RLYB212 to rapidly eliminate 
HPA-1a positive platelets in HPA-1b/b participants was confirmed. In this study, participants 
received a single SC dose of RLYB212 (0.09 or 0.29 mg) or placebo on Day 1, followed by a 
transfusion of HPA-1a positive platelets on Day 8. Assessments of HPA-1a positive platelet 
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continued through Day 85. RLYB212 was shown to produce rapid and complete elimination of 
transfused HPA-1a positive platelets in HPA-1b/b participants that was dose dependent, with a 
reduction in mean platelet elimination half-life of ≥ 90% in both dose groups that met the 
prospective PoC criteria. In both dose groups, RLYB212 was well tolerated and no SAEs, severe 
TEAEs, or TEAEs considered related or possibly related were reported. There were no clinically 
meaningful findings related to clinical laboratory evaluations (including alloimmune response to 
HPA-1a positive platelets), vital signs, ECGs, or physical examinations. A single participant in 
the 0.29 mg RLYB212 group was reported to have ADA positive results on Days 15 and 29, and 
at the final study visit on Day 85. The ADA titer was low at each timepoint. Based on 
examination of the PK profiles, and PK parameter values for this single ADA positive participant 
remaining within the range of parameter values in the ADA negative participant at the 0.29 mg 
RLYB212 dose, development of anti-RLYB212 antibodies had no significant effect on the PK of 
RLYB212. 
2.3 
Benefit/Risk Assessment 
2.3.1 
Risk Assessment 
Refer to the Investigational Brochure for detailed information on the potential benefits, risks, and 
reasonably expected adverse events (AEs) of RLYB212.   
Table 2-1 
Risk Assessment of RLYB212 
Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy   
Study Intervention (RLYB212) 
Maternal Risks 
Immune 
reactions, 
including ADA 
formation 
• 
Since the primary sequence of RLYB212 
is a native human IgG, the likelihood of 
immune reaction in humans is expected 
to be low. 
• 
RLYB212 is not predicted to have any 
inherent pharmacologic activity against 
host tissues in HPA-1b/b pregnant 
women, as these individuals do not carry 
the HPA-1a antigen. 
• 
Off-target, nonspecific risks of any 
biologic or monoclonal antibody such as 
hypersensitivity reactions may be 
observed. 
• 
Clinical manifestation of hypersensitivity 
reactions may range from immediate 
onset findings such as rash, urticaria, and 
in more severe cases, anaphylaxis, to 
delayed onset finding such as influenza-
like symptoms (pyrexia, sore throat). 
• 
Measures implemented to monitor the risk 
of immune reactions: 
○ 
Monitoring of participant safety (eg, 
occurrence of TEAEs). 
○ 
Participants observed in clinic for 
1 hour after SC administration of 
RLYB212. 
○ 
ADA monitored per SoA (Section 1.3 
and Section 8.7). 
• 
Impact of ADAs on the PK of RLYB212 
will be evaluated. 
• 
Excipients used in the RLYB212 drug 
product are commonly used with mAbs;  
○ 
The PS 80 concentration is less than 
chronically used drug products such as 
adalimumab and rituximab,  
○ 
Additionally, precautions are made in 
the protocol to dose at the investigative 
site, with post-dose observation for 
1 hour. 

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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy   
• 
ADA may develop after administration of 
RLYB212. ADAs have been reported in 
three participants in Phase 1 studies 
(IPA2001 and IPA2003), two participants 
after single dose and one participant after 
multiple dose administration. The 
development of anti-RLYB212 
antibodies had no clinically significant 
effect on the PK of RLYB212.  
• 
Repeat administration of polysorbate 
(PS) 80 containing drug may induce 
anaphylaxis, which causes uterine 
contractions or malperfusion of the uterus 
with fetal outcomes. 
Injection site 
reaction 
• 
Smaller SC injection volume of 
RLYB212 may reduce likelihood of 
injection site reactions. 
• 
Symptoms of injection site reaction may 
include pain, swelling, erythema, 
pruritus, and rash around the site of 
injection. 
• 
SC injection will be administered by the 
investigator or designee. 
• 
Participants will be observed in clinic for 
1 hour after administration of RLYB212. 
• 
Injection site rotation may be considered to 
help avoid soreness at previous SC 
injection site(s).  
• 
Participant safety will be monitored 
throughout the study. 
Study Participation 
Risks related to 
study 
procedures 
• 
Study specific procedures are those used 
in obstetric care. Some assessments (eg, 
blood draws or obstetrical doppler 
ultrasounds) may be more frequent. 
• 
Participants will be monitored per obstetric 
standard of care 
Fetal and Neonatal Risks  
Fetal 
• 
Occurrence of fetal thrombocytopenia 
due to presence of high circulating fetal 
levels of RLYB212. 
• 
Potential adverse fetal outcomes 
including spontaneous abortion, preterm 
delivery, intrauterine growth retardation, 
and hemorrhage. 
• 
Placental inflammation or compromise 
from RLYB212 binding to fetal antigen 
on placenta. 
• 
Exposure of an HPA-1b/b fetus to 
RLYB212 
• 
The safety of the RLYB212 SC dose 
regimen is supported by general toxicology 
studies and developmental and reproductive 
toxicology studies (including histological 
examination). Across studies, projected 
exposure margins in antigen positive 
fetuses and neonates (representative of 
HPA-1a/b fetuses and neonates) were well 
over 10-fold greater than the target upper 
boundary of 10 ng/mL).  
• 
The target upper boundary for RLYB212 
exposure (~10 ng/mL) is ~6-fold below the 
safety threshold for anti-HPA-1a 
alloantibody titers associated with clinical 
sequelae of FNAIT, as reported by 
Killie et al [1]. 

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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy   
• 
Cell-free fetal DNA collected for fetal 
genotyping is at low levels before GW 10 
(<3% of total maternal circulating 
cfDNA and gradually increases by about 
1% by Week 20). [15] Due to these low 
levels of fetal DNA prior to GW 16, 
confirmation of fetal HPA-1 genotype 
may come after initial dose of RLYB212 
at GW 16. (Section 8.1.1 and 
Section 8.1.2). Consequently, some 
participants carrying a potentially 
HPA-1b/b fetus will be exposed to the 
loading dose of RLYB212 despite not 
being at risk for alloimmunization. 
• 
The Phase 2 study (IPA2202) employs 
sentinel subject dosing through pregnancy 
followed by two sequential, sequenced 
cohorts. Modification of the RLYB212 
dose regimen may be performed during the 
study based on available PK data from 
participant(s) with a completed pregnancy, 
to ensure desired steady state 
concentrations are maintained through 
pregnancy and parturition between a target 
lower bound of ~3 ng/mL and a target 
upper bound of ~10 ng/mL. 
• 
For women receiving RLYB212 loading 
dose (0.12 mg) before the fetal genotype is 
definitively determined, there is a ~85% 
chance that the fetus will be HPA-1a/b and 
hence express the antigen (due to the 
prevalence of the HPA-1b gene and 
application of the Hardy-Weinberg 
principle in the case of unknown paternal 
genotype). In that case, all aspects to 
mitigate fetal/placental harm noted above 
will be in place and the loading dose will 
have been administered appropriately. 
There remains a roughly 15% chance, 
however, that the fetus will be determined 
to be HPA-1b/b, consistent with the 
maternal genotype. In this case, RLYB212 
administration will be stopped, and the 
pregnancy will be followed for an 
additional 4 weeks for safety and PK 
assessment. Since RLYB212 is directed 
against the HPA-1a epitope, which neither 
mother nor fetus express, the antibody will 
not bind to maternal or fetal tissues. 
Therefore, RLYB212 is expected to pose no 
risk other than that of any exogenous 
monoclonal antibody, as outlined under 
“Maternal Risks” within this table. 
• 
Fetal doppler ultrasound monitoring will be 
performed at regular intervals during the 
study and consistent with obstetric standard 
of care, to detect any evidence of placental 
structural abnormality, organ pathology, 
hemorrhage, or delayed growth in the fetus.  
• 
A cord blood sample will be collected at 
delivery to evaluate fetal exposure to 
RLYB212.  

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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy   
• 
The study design employs sentinel subject 
dosing through pregnancy followed by 
2 sequential, sequenced cohorts. Maternal 
PK at the end of pregnancy will be 
evaluated before initiating dosing in the 
subsequent cohort (Section 4.1).  
• 
An independent DMC will monitor safety 
data at regular intervals throughout the 
duration of the study according to a study 
specific DMC charter (Section 2.3.4 and 
Section 10.1.5 (Appendix 1).  
Neonate/infant 
• 
Potential risks related to continued 
presence of circulating RLYB212 in 
neonatal/infant circulation or breast milk. 
• 
It is expected that transient levels of 
RLYB212 will be present during the first 
few weeks of breast feeding.  
• 
Based on experience in individuals with 
FNAIT, breast feeding has not affected 
the rapid recovery of platelet counts after 
birth (unlike the situation with ITP) [16] 
and hence due to its benefits, breast 
feeding is recommended by the ICTMG 
FNAIT patient information leaflet. 
• 
Levels of anti-HPA-1 activity transmitted 
by breast milk during the peripartum 
period in the case of RLYB212 are 
anticipated to be considerably less than 
those transmitted to infants with active 
FNAIT.  
• 
A cord blood sample will be collected at 
delivery to assess for possible occurrence of 
neonatal thrombocytopenia.  
• 
Safety of the neonate/infant up to 4-6 weeks 
postpartum will be assessed by neonatal 
infant standard of care practices including 
neonatal/infant general status examination, 
measurement of APGAR score (at birth). 
• 
The benefit of breast feeding outweighs the 
potential risk; breast feeding will be 
permitted, therefore no mitigation is 
required.  
ADA = anti-drug antibody; AGPAR = Appearance, Pulse, Grimace, Activity, and Respiration Cmax = maximum 
serum concentration; DMC = data monitoring committee; FNAIT = fetal and neonatal alloimmune 
thrombocytopenia; HPA = human platelet antigen; ICTMG = International Collaboration for Transfusion Medicine 
Guidelines; IgG = immunoglobulin G; ITP = immune thrombocytopenia; mAb = monoclonal antibody; 
PK = pharmacokinetic; SC = subcutaneous; SoA = schedule of activities; TEAE = treatment-emergent adverse 
events. 
2.3.2 
Benefit Assessment 
The target population for prophylactic antenatal administration of RLYB212 is pregnant women 
who are at higher risk for the occurrence of HPA-1a alloimmunization and FNAIT in their 
pregnancy. There is currently no available prophylactic treatment to prevent HPA-1a 
alloimmunization. While the ability of RLYB212 to prevent HPA-1a alloimmunization will be 
assessed in a planned Phase 3 registration trial, available nonclinical and clinical data support 
potential therapeutic benefit, based on:  
• A similar condition, HDFN, is effectively prevented by prophylactic treatment with small 
doses of antigen specific IgG (ie, anti-RhD antibody preparations). 

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• RLYB212 prevents HPA-1a alloimmunization at the same doses that produce accelerated 
elimination of HPA-1a positive platelets in the bi-allelic APLDQ murine model of FNAIT.  
• It is noted that the effective concentrations shown to prevent alloimmunization are well 
below the NOAEL for RLYB212 in the general and reproductive toxicology studies. 
• RLYB212 has demonstrated rapid and complete elimination of HPA-1a/b platelets 
exogenously administered to participants with an HPA-1b/b genotype. 
• Clinical data support a favorable tolerability profile of RLYB212 at exposures in HPA-1b/b 
non-pregnant volunteers that exceed the ~10 ng/mL target upper boundary by ~2-fold, while 
the target upper boundary is expected to provide a 6-fold safety margin for the fetus. 
2.3.3 
Overall Benefit-Risk Conclusion 
The benefit-risk of RLYB212 is assessed in the context of the target population of pregnant 
women who are at higher risk for the occurrence of HPA-1a alloimmunization in their pregnancy 
and for which no prophylactic therapeutic presently exists. The intended dose regimen is 
projected to maintain steady state concentrations of RLYB212 that are well below those 
evaluated in relevant nonclinical investigations including maternal-fetal toxicology data and the 
threshold level of native HPA-1a alloantibodies associated with risk of fetal/neonatal 
thrombocytopenia reported by Killie et al. [1] (Section 4.3). The RLYB212 dose regimen may 
also be modified during the study based on available PK data from participant(s) with a 
completed pregnancy, to ensure desired steady state concentrations are maintained through 
pregnancy and parturition between the target lower bound of ~3 ng/mL and the target upper 
bound of ~10 ng/mL. 
In considering all measures to be implemented to closely monitor and manage potential risks 
identified in association with RLYB212, it is the Sponsor’s assessment that the benefit/risk for 
administration of RLYB212 to pregnant women is favorable and supports inclusion of eligible 
participants in accordance with the protocol-defined eligibility requirements. 
2.3.4 
Other Risk Minimization Actions/Monitoring  
An independent data monitoring committee (DMC) will monitor safety outcomes and study 
conduct and will provide recommendations for consideration by the Sponsor regarding the 
continuation of the study, dosing of further participants in the study, or stopping the study for all 
participants or subgroups of participants in the study. Safety data will include, but not be limited 
to, those outcomes listed as primary and secondary endpoints. 
A detailed DMC charter and operating rules will be prepared and signed by DMC members 
before study start. Additional information on the DMC is provided in Section 10.1.5 
(Appendix 1). 
 
 

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3 OBJECTIVES AND ENDPOINTS 
3.1 
Interventional 
Objective 
Endpoint 
Primary 
 
• 
To evaluate the PK profile of RLYB212 
during pregnancy following repeat SC 
administration  
• 
Maternal PK parameters, eg,   
○ 
half-life of RLYB212 (t½) 
○ 
maximum RLYB212 concentration (Cmax) 
○ 
time to maximum RLYB212 concentration (tmax) 
○ 
apparent clearance (CL/F) of RLYB212 
○ 
apparent volume of distribution (Vd) 
○ 
area under the RLYB212 concentration versus time 
curve (AUC) 
• 
To assess maternal and fetal safety of 
RLYB212 during pregnancy  
• 
Type, seriousness, and incidence of AEs 
• 
Physical examination findings 
• 
Vital signs 
• 
Maternal clinical laboratory values  
• 
ECG 
• 
Obstetric/fetal doppler ultrasound 
Secondary 
 
• 
To evaluate RLYB212 exposure in the 
neonate at delivery 
• 
Concentration of RLYB212 in cord blood  
• 
To assess the safety of RLYB212 in the 
HPA-1a positive neonate 
• 
Type, seriousness, and incidence of AEs including 
fetal/neonatal AEs 
• 
Physical examination findings, including APGAR scores 
• 
Vital signs  
• 
To assess the immunogenicity of RLYB212  • 
Development of ADAs 
• 
To assess pregnancy and neonatal outcomes 
following antenatal RLYB212 
administration  
• 
Number of spontaneous abortions 
• 
Number of elective abortions 
• 
Number of stillbirths 
• 
Number of premature births 
• 
Number of full term births (≥ 37 completed weeks of 
gestation) 
• 
Overall health and development of infants at 4-6 weeks 
and 12 months of age 
• 
To assess the occurrence of neonatal 
thrombocytopenia following antenatal 
RLYB212 administration 
• 
Neonatal thrombocytopeniaa and severe neonatal 
thrombocytopenia 
• 
To assess the occurrence of HPA-1a 
alloimmunization 
• 
Presence of maternal anti-HPA-1a alloantibodies at 
Week 10 post pregnancyb 
ADA = anti-drug antibody; AE = adverse event; APGAR = Appearance, Pulse, Grimace, Activity, and Respiration; 
ECG = electrocardiogram; HPA-1a = human platelet antigen 1a; PK = pharmacokinetic(s); SC = subcutaneous. 
a Evaluation of neonatal thrombocytopenia will be based on the umbilical cord sample taken at parturition. 
b For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from the 
date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
 
 

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3.2 
Non-Interventional (Observational) 
Objective 
Endpoint 
• 
To inform the frequency of HPA-1a 
alloimmunization among pregnant women 
identified at higher FNAIT risk 
• 
Occurrence of anti-HPA-1a maternal alloimmunization at 
Week 10 postpartuma 
• 
To inform the frequency of pregnancy 
outcomes among pregnant women 
identified at higher FNAIT risk 
• 
Rate of spontaneous abortion, defined as non-deliberate 
fetal death which occurs prior to 19 weeks of gestation 
• 
Rate of elective abortion, defined as deliberate 
termination of pregnancy at any time in gestation 
• 
Rate of stillbirth, defined as non-deliberate fetal death 
anytime in gestation on or after 19 weeks of gestation 
• 
Rate of premature birth, defined as live birth prior to 
37 completed weeks of gestation 
• 
Rate of full term birth (≥ 37 completed weeks of 
gestation) 
• 
To inform the frequency, where data are 
available, of neonatal thrombocytopenia in 
infants born to women who have 
alloimmunized, as determined by detectable 
anti-HPA-1a antibody at Week 10 
postpartuma 
• 
Neonatal thrombocytopenia and severe neonatal 
thrombocytopenia, as determined by a platelet count 
< 150 × 109/L and < 50 × 109/L, respectively, where data 
are available 
a For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 10 weeks from 
the date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
 
 
 

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4 STUDY DESIGN 
4.1 
Overall Design 
This study is a single-arm, open-label, multicenter study of RLYB212 in HPA-1b/b pregnant 
women who are at higher risk for the occurrence of HPA-1a alloimmunization and FNAIT. A 
laboratory testing paradigm will be applied at screening to identify women at higher risk for 
HPA-1a alloimmunization. 
The study is comprised of three phases: a two-part screening phase, an antenatal treatment phase, 
and a postpartum follow-up phase. An overview of the study design is provided in Figure 1-1 
and Section 1.2. There will be a non-interventional (observational) sub-study for those 
participants who do not receive RLYB212 (Figure 1-1). 
An independent DMC will monitor safety data at regular intervals throughout the duration of the 
study according to a study specific DMC charter. Study duration for each participant is 
anticipated to be ~44 weeks, inclusive of the screening visits through the Week 10 postpartum 
visit. For each child born during the study, the duration is ~12 months. 
The study has been designed to enroll an initial sentinel participant followed by staged 
enrollment of participants to two sequential cohorts. The single sentinel participant will be 
enrolled and receive SC administered RLYB212 for the scheduled duration of their pregnancy. 
The DMC will review all available data through parturition for this sentinel participant, together 
with RLYB212 exposure data and available safety data in the neonate. This review will be 
performed before commencing dosing in subsequent participants. Upon completion of the DMC 
review for that sentinel participant, a cohort of up to 3 additional participants will be enrolled 
and receive SC administration of RLYB212. Following DMC review of all available data 
through parturition for the additional 3 participants, together with RLYB212 exposure data and 
safety data in the neonates, a second cohort of the final 4 participants will be enrolled. 
Modification of the RLYB212 dose regimen may be necessary to ensure steady state 
concentrations are maintained through pregnancy and parturition between a target lower bound 
of ~3 ng/mL and a target upper bound of ~10 ng/mL. Adjustment of the RLYB212 dose/dose 
frequency may be made within a cohort or between cohorts, based on available PK data from 
participant(s) with a completed pregnancy. If the Sponsor determines it is necessary to adjust the 
RLYB212 dose regimen for future participants, the Sponsor will communicate this to the 
investigator and study staff. Dose modifications are not anticipated during the treatment period 
of an individual participant. 
A non-interventional (observational) sub-study (IPA2202A) is planned based on the phased 
approach to participant enrollment that results from the sequential cohort design. Because of the 
rarity of the potential occurrence of HPA-1 alloimmunization, the non-interventional 
(observational) sub-study will serve to augment an ongoing FNAIT Natural History Study 
(NCT05345561), ie, generating natural history data on the occurrence of HPA-1a 
alloimmunization and pregnancy/neonatal outcomes in women at higher FNAIT risk. 

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No formal interim analyses will be conducted for this study. Preliminary data may be used for 
summary purposes and for communication with health authorities.  
4.2 
Scientific Rationale for Study Design 
The dose regimen to achieve therapeutic exposure levels of RLYB212 is informed by a clinical 
pharmacology model that incorporates PK data from a first-in-human safety and PK study 
(IPA2001) in HPA-1b/b participants, and PK and PD data from a Phase 1b platelet elimination 
PoM/PoC study (IPA2003) in HPA-1b/b participants. The clinical pharmacology model also 
incorporates projected PK parameters from a meta-analysis of monoclonal antibodies, allometric 
scaling to account for demographic differences between study populations, and the dynamic 
physiologic changes that occur during gestation. The purpose of this Phase 2 study is to assess 
the PK and safety of RLYB212 at the proposed therapeutic dose regimen in HPA-1b/b pregnant 
women at higher risk for HPA-1a alloimmunization and FNAIT and to guide appropriate dosing 
for a planned Phase 3 safety and efficacy registration trial.  
To achieve the study’s objective, a single arm, open-label design is utilized with all participants 
receiving RLYB212. The enrolled study participants represent the target population for 
RLYB212 ie, HPA-1b/b pregnant women bearing an HPA-1a positive fetus, who are at higher 
risk for the occurrence of HPA-1a alloimmunization and FNAIT. It is planned to follow 
8 participants for whom the pregnancy results in a live birth to enable the PK and preliminary 
safety profile of RLYB212 to be evaluated during pregnancy and to guide appropriate dosing for 
the planned Phase 3 registration trial.  
4.3 
Justification for Dose 
Prophylactic treatment with SC dosing of RLYB212 is designed to drive rapid and complete 
elimination of HPA-1a positive fetal-derived cells and cell fragments from the maternal 
circulation, thereby preventing HPA-1a maternal alloimmunization, by maintaining the highest 
safe exposure of RLYB212 throughout the entire second and third trimesters and immediately 
following parturition. Additionally, by administering RLYB212 via SC doses, peak to trough 
fluctuations are minimized and incorporating an initial 2 × loading dose is projected to achieve 
near steady state concentrations after the first dose, thereby enabling a more consistent PK 
profile over the entire treatment period.  
A prophylactic dose regimen consisting of a single 0.12 mg SC loading dose of RLYB212 
followed by 0.06 mg SC Q4W is proposed as the initial dose for HPA-1b/b pregnant women at 
risk for HPA-1a alloimmunization. The dose regimen is intended to achieve near steady state 
RLYB212 concentrations after the first dose and maintain them within a target range of 
~3 ng/mL to ~10 ng/mL The dose regimen will be adjusted empirically as additional subjects are 
enrolled to achieve the target range. It is possible that additional RLYB212 will be necessary due 
to target mediated drug disposition (TMDD), ie, RLYB212 binding to the HPA-1a epitope 
expressed on placental proteins. 
The target lower boundary is supported by clinical and preclinical data demonstrating that 
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challenge model are effective to drive rapid elimination of circulating HPA-1a positive antigen 
positive cells.  
The target upper boundary of ~10 ng/mL is supported by a comprehensive toxicology program 
that demonstrates RLYB212 to have NOAEL margins of up to 242-fold greater than 10 ng/mL in 
antigen negative dams bearing heterozygous antigen positive offspring (representative of 
HPA-1b/b women at risk of alloimmunization) and projected exposures well over 10-fold greater 
than ~10 ng/mL in antigen positive fetuses and neonates (representative of HPA-1a/b fetuses and 
neonates). The target upper boundary is further informed by an extensive review of available 
literature on clinical assessments of alloimmunization rates and FNAIT, where maternal HPA-1a 
alloantibody levels of 3 IU/mL, measured at GW 28 or 34, has been reported as the threshold for 
the occurrence of anti-HPA-1a antibody-mediated fetal/neonatal thrombocytopenia [1, 2]. These 
data have been used as a basis for our selection of an anti-HPA-1a value of 3 IU/mL as an 
empirically supported maximum threshold for calculating a margin of safe exposure during 
pregnancy, with a negative predictive value of 95% (95% CI: 86-98%) in the prevention of 
anti-HPA-1a antibody mediated fetal/neonatal thrombocytopenia, as reported in Killie et al. [1]. 
Using the most conservative estimates for binding equivalence in IU for RLYB212, the steady 
state exposure target accounts for an additional margin of safety by maintaining RLYB212 
concentrations at or below ~0.5 IU/mL.  
Based on the NOAEL exposure margins in the RLYB212 non-clinical safety toxicology program 
and by adopting the most conservative estimate of RLYB212 binding equivalence in IU as it 
compares to the World Health Organization standard for anti-HPA-1a antibodies, it is estimated 
that the proposed dosing regimen would be well within safe limits for the developing fetus while 
maintaining the capacity to drive rapid and complete elimination of fetal antigen positive cells or 
cell fragments entering into the maternal vascular compartment. 
Refer to the Investigational Brochure for additional background information. 
4.4 
End of Study Definition 
An interventional participant is considered to have completed the study if they have completed 
all phases of the study, including the visit at 10 weeks postpartum or at 10 weeks from the date 
of the pregnancy terminating event (ie, abortion [spontaneous/elective] or stillbirth). A child born 
during the study will have completed after the 12-month visit has been completed. 
A non-interventional (observational) sub-study participant is considered to have completed the 
study if they have completed all phases of the study, including the visit at 10 weeks postpartum 
or at 10 weeks from the date of the pregnancy terminating event (ie, abortion 
[spontaneous/elective] or stillbirth).  
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the schedule of activities (SoA [Section 1.3]) for the last 
participant in the trial (globally). 
 
 

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5 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
Eligibility for this study will be established using a two-part screening procedure. Screening 
Part 1 will identify those participants who are at higher risk for the occurrence of maternal 
HPA-1a alloimmunization and FNAIT in their pregnancy. If a participant meets eligibility 
criteria in Screening Part 1, they may proceed to Screening Part 2 to determine their eligibility 
for enrollment and subsequent treatment with RLYB212. 
Eligibility criteria are provided in Section 5.1 and Section 5.2. 
Approximately 5,000 participants will be screened to identify 8 pregnant individuals who meet 
the study-specific blood test results required for study inclusion and for whom the pregnancy 
results in a live birth and who are evaluable for PK and safety assessments. Women in their first 
or subsequent pregnancy may be included in the study. These participants will be HPA-1b/b and 
HLA-DRB3*01:01 positive genotype, anti-HPA-1a alloantibody negative, and fetal HPA-1a/b 
positive.  
5.1 
Eligibility Criteria for Screening (Part 1) 
The following criteria will be assessed. 
5.1.1 
Inclusion Criteria to be Confirmed at Screening Part 1  
1. Written/signed informed consent (for Screening Part 1) 
2. 18-45 years of age 
3. Pregnant women who present at GW 6 or after and confirmed to be: 
a. HPA-1b/b (HPA-1a negative) 
b. HLA-DRB3*01:01 positive 
c. Anti-HPA-1a alloantibody negative 
d. Carrying an HPA-1a/b (HPA-1a positive) fetus   
5.1.2 
Exclusion Criteria to be Confirmed for Screening Part 1 
1. Prior history of HPA-1a-related FNAIT 
2. Prior history of HPA-1a alloimmunization 
3. Prior history of platelet transfusion or other blood transfusions 
4. BMI ≥ 35 kg/m2  

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5.2 
Eligibility Criteria for Study Intervention 
Participants who meet all eligibility criteria in Screening Part 1 (ie, HPA-1b/b, 
HLA-DRB3*01:01 positive genotype; anti-HPA-1a alloantibody negative; fetal HPA-1a/b 
genotype) and who provide informed consent for Screening Part 2, will be assessed for eligibility 
to enter the study’s antenatal treatment phase and to receive treatment with RLYB212 provided 
all inclusion and no exclusion criteria are met. If a participant is eligible for the intervention 
(Screening Part 2), but the current cohort has been fully enrolled, the participant will be 
requested to consent for enrollment in the non-interventional (observational) sub-study. 
5.2.1 
Inclusion Criteria for Study Drug Administration to be Confirmed at Screening 
Part 2 
1. Written/signed informed consent (for Screening Part 2) 
2. 18-45 years of age  
3. Pregnancy no later than GW 16 at the time of first study drug administration as determined 
by the principal investigator or qualified staff 
5.2.2 
Exclusion Criteria for Study Drug Administration to be Confirmed at Screening 
Part 2 
Participants are excluded from the study if any of the following criteria apply: 
1. Multiple pregnancy (>1 fetus) 
2. Known sensitivity and/or immediate hypersensitivity to any components of RLYB212 or its 
formulation 
3. History of hypersensitivity to protein therapeutics 
4. Any participant with a history of past or current intravenous immunoglobulin (IVIG) use for 
an underlying disease (eg, autoimmune disease) 
5. Requires ongoing systemic corticosteroid or systemic immunosuppressive treatment for any 
reason 
6. History of pre-eclampsia in a previous pregnancy 
7. Participants with an in vitro fertilized pregnancy or serving as pregnancy surrogates 
8. Current (or within the last 90 days) participation in another clinical study and have received 
an investigational drug and device within the last 90 days 
9. Participants known or suspected of not being able to comply with this study protocol 
10. History of any connective tissue or autoimmune or autoinflammatory disease, especially 
autoimmune thrombocytopenia  

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11. Any co-morbid medical or obstetric condition(s), laboratory abnormality, concomitant 
treatment, or other reason that, in the investigator’s opinion, could adversely affect the safety 
of the participant and/or fetus, impair the assessment of study results, or preclude compliance 
with the study 
5.3 
Lifestyle Considerations 
No dietary or lifestyle restrictions are required. 
5.4 
Screen Failures (Screening Part 2) 
Screen failures are defined as participants who consent to participate in the clinical study but do 
not subsequently receive the study intervention. A minimal set of screen failure information for 
those failing to meet criteria at Screening Part 1 and Screening Part 2 is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, assessment of 
eligibility prior to enrollment, and any SAEs. 
Pregnant individuals who do not meet the eligibility criteria for RLYB212 administration may 
not be rescreened during their current pregnancy. However, these individuals will be requested to 
consent for the non-interventional (observational) sub-study (Figure 1-1 and Table 1-1). 

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6 STUDY INTERVENTION 
The study intervention, RLYB212, will be administered to participants in accordance with the 
study protocol. 
Refer to the Pharmacy Manual for detailed information regarding the storage, preparation, 
administration, and destruction of RLYB212. 
6.1 
Study Intervention(s) Administered  
Dose, formulation, and administration instructions for RLYB212 are provided in Table 6-1. 
Reference is made to Section 6.5 regarding the approach to dose modification within or between 
cohorts. 
Table 6-1 
Study Intervention(s) Administered 
 
RLYB212 
Dosage formulation 
Vials, each containing 1 mL of RLYB212 (0.2 mg/mL) solution for SC 
injection 
Unit dose strength(s)/dosage 
level(s) and dosage 
frequencya 
RLYB212 is to be administered at an initial (loading) dose of 0.12 mg no 
later than GW 16 followed by maintenance (repeat) doses of 0.06 mg Q4W 
throughout the pregnancy and with a final 0.06 mg dose within 24 hours 
(±24 hours) of parturition.  
Route of administration 
SC injection using vial and syringe 
Dosing instructions 
Refer to Pharmacy Manual for details.  
The participant will be carefully observed during the injection and observed 
for 1 hour after the administration. 
Storage 
2 °C to 8 °C (do not freeze) 
GW = gestational week; Q4W = every 4 weeks; SC = subcutaneous. 
a Refer to Section 4.3 for justification of dose/dosing frequency. 
6.2 
Preparation/Handling/Storage/Accountability 
The investigator or designee must confirm appropriate temperature and other storage conditions 
have been maintained during transit for all study materials received and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized site 
staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). Further guidance and information for 
the final disposition of unused study interventions are provided in the Pharmacy Manual. 

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6.3 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study and there is no randomization or blinding.  
6.4 
Study Intervention Compliance 
Participants will be dosed at the site and receive RLYB212 directly from the investigator or 
designee and will be observed for 1 hour after dosing by the investigator/site staff. The date and 
time of each dose administered in the clinic will be recorded in the source documents and 
recorded in the case report form (CRF). The dose of RLYB212 and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study intervention. 
6.5 
Dose Modification 
Modification of the RLYB212 dose regimen may be necessary to ensure steady state 
concentrations are maintained through pregnancy and parturition between a target lower bound 
of ~3 ng/mL and a target upper bound of ~10 ng/mL. 
Modification of RLYB212 dose/dose frequency may be made within a cohort or between 
cohorts, based on available PK data from participant(s) with a completed pregnancy. If the 
Sponsor determines it is necessary to adjust the RLYB212 dose regimen for future participants, 
the Sponsor will communicate this to the Investigator and study staff. 
Dose modifications are not anticipated during the treatment period of an individual participant. 
6.6 
Concomitant Therapy 
Standard treatments given during obstetric care are allowed. Routine vaccines, given at 
recommended times during or immediately after pregnancy, will be allowed in the study.  
Any medication (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) or other specific categories of interest that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Concomitant medications may be considered on a case-by-case basis by the investigator in 
consultation with the medical monitor. 

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6.6.1 
Rescue Medicine 
There are no rescue medications defined in the protocol. 
6.6.2 
Excluded Treatments, Medical Devices, and/or Procedures During Study Period 
Broad spectrum immunosuppressant agents and IVIG are not allowed as concomitant 
medications with RLYB212 administration. If such treatments are required, RLYB212 will be 
discontinued but the participant will continue to be followed as described in Section 7.1. 
6.7 
Intervention of Overdose or Dosing Errors 
In the event of an error in dosing, including overdose, the investigator should contact the medical 
monitor/Sponsor immediately and closely monitor the participant for any AE/SAE and 
laboratory abnormalities. Where available, the quantity of the excess dose as well as the duration 
of the overdose should be documented. The Sponsor will determine when and if further dosing 
will be given, and what dose. 

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7 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If study intervention is definitively discontinued, the 
participant will remain in the study to be evaluated for pregnancy outcomes and postnatal 
follow-up in the event of live birth, and for anti-HPA-1a antibody determination. If treatment is 
discontinued because a delayed cell-free fetal DNA determination reveals the fetus is HPA-1b/b, 
the subject will also return 4 weeks after RLYB212 dosing for a safety visit, the context of which 
will the same as Visit 5 in the SoA (Section 1.3). Participants withdrawing consent to be in the 
study or administrative reasons for discontinuation should proceed directly to the end of study 
(EOS) visit (Week 10 postpartum), if possible. 
Refer to the SoA (Section 1.3) for details of the data to be collected at the time of discontinuation 
of RLYB212, follow-up, and for any further evaluations that need to be completed. Permanent 
discontinuation of RLYB212 for safety-related reasons will not be followed by a rechallenge. 
Information on the study assessments and procedures is provided in Section 8. 
7.1.1 
Temporary Discontinuation 
In the event of temporary discontinuation of study intervention, the investigator should contact 
the medical monitor/Sponsor immediately. Further course of action will be decided upon by 
discussion between investigator, Sponsor, and with the DMC, as needed. 
7.1.2 
Study Stopping Rules 
In the event of maternal death1, treatment will be withheld for all study participants, pending 
Sponsor evaluation and DMC recommendation. 
Following occurrence of a maternal/fetal/neonatal common terminology criteria for adverse 
events (CTCAE) Grade 41 or Grade 5 event as specifically described by Spencer et al [17] or any 
of the fetal/neonatal AEs specified in Section 10.3.3 (Appendix 1), treatment with RLYB212 will 
not be initiated in any new study participants pending Sponsor evaluation and DMC 
recommendation. Reference is made to Section 10.3.3 (Appendix 1) for guidance on using the 
maternal and fetal AE severity grading criteria. 
If one or more fetus or neonate in the study has evidence of severe thrombocytopenia or 
hemorrhage, RLYB212 administration will be withheld for all participants pending Sponsor 
evaluation and DMC recommendations. 
 
1 Events that are definitely not related to study treatment (eg, accidents or other external causes) will not trigger 
study-stopping rules. 

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If 2 study participants have stopped RLYB212 administration for any safety-related reason, 
RLYB212 administration will be withheld for all participants pending Sponsor evaluation and 
DMC recommendation. 
In all cases in which dosing of RLYB212 is suspended (for an individual participant or for all 
participants), the Sponsor and DMC will complete an evaluation and decide on further dosing 
promptly. This is so that dosing can be resumed, if appropriate, without serious disruption of 
RLYB212 coverage. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at their own request or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
Participants for whom treatment is withdrawn but who retain consent to continue in the study 
should be followed through all activities in the study SoA (Section 1.3). Those who withdraw 
consent should have EOS (Week 10 postpartum) procedures performed as their end of study 
visit. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
Any participants discontinuing the study early for reasons unrelated to pregnancy outcomes or 
safety will be replaced. 
Up to 4 participants may be replaced if they were assigned to study drug but did not receive the 
study drug. Participants may also be replaced for reasons other than clinical safety, including but 
not limited to insufficient PK sample collection to evaluate the PK profile of RLYB212 during 
pregnancy.  
In addition, where the outcome of the pregnancy is not a live birth, these participants may be 
replaced. Any decision regarding the replacement of participants will be discussed with the DMC 
prior to additional enrollment of participants into the study. 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 

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• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the participant’s medical record. 
• Should the participant continue to be unreachable, she will be considered to have withdrawn 
from the study.  
Discontinuation of specific sites or of the study as a whole are addressed in Section 10.1 
(Appendix 1). 
7.4 
Non-interventional (Observational) Sub-study – Subject Decision to Withdraw 
Participants have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution. Withdrawal of 
consent for a study means that the participant does not wish to or is unable to continue further 
study participation. Participant data up to withdrawal of consent will be included in the analysis 
of the study and, where permitted, publicly available data can be included after withdrawal of 
consent. The investigator is to discuss with the subject appropriate steps for withdrawal of their 
consent from the study. 
 
 

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8 STUDY ASSESSMENTS AND PROCEDURES 
Interventional study procedures and their timing are summarized in the SoA (Section 1.3, 
Table 1-3). Non-interventional (observational) sub-study procedures and their timing are 
summarized in the SoA (Section 1.3, Table 1-4). Protocol waivers or exemptions are not 
allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA (Section 1.3), 
is essential and required for integrity of study conduct. 
Information on how samples are to be stored, processed, and shipped is provided in the 
Laboratory Manual. 
8.1 
FNAIT Laboratory Screening Assessments 
In participants presenting at GW 6 or after who provide informed consent, blood samples will be 
collected at the Screening Part 1 visit to assess for higher risk for the occurrence of HPA-1a 
alloimmunization and FNAIT during their pregnancy.  
The first test will be a test for maternal HPA-1 genotype. In participants identified as HPA-1b/b 
(ie, HPA-1a negative), subsequent tests will be performed to confirm the participant has an 
HLA-DRB3*01:01 positive genotype, is anti-HPA-1a alloantibody negative, and is carrying an 
HPA-1a/b (ie, HPA-1a positive) fetus. 
8.1.1 
Screening Part 1 
The screening test paradigm is provided in Table 8-1. 
 
 

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Table 8-1 
Screening Test Paradigm 
Test 
No. 
Test 
Description 
 
 
Result 
Screening Specific 
Action 
1 
Maternal HPA-1 
genotype 
Test will identify women who are 
HPA-1b/b, indicating risk for 
HPA-1a sensitization and 
occurrence of FNAIT 
1a 
HPA-1b/b 
(HPA-1a negative) 
Perform Test 2 and 3 
1b 
HPA-1a/b; HPA-1a/a 
None – no further 
testing (ineligible) 
2 
Maternal 
HLA-DRB3*01:01 
genotype δ 
Test will identify women who are 
HLA-DRB3*01:01 positive, 
indicating a higher 
alloimmunization risk; performed 
concurrently with Test 3 
2/3a 
HLA-DRB3*01:01 
positive, Anti-HPA-1a 
antibody negative 
Perform Test 4  
3 
Maternal 
anti-HPA-1a 
antibody δ 
Test will establish women who 
have no detectable anti-HPA-1a 
antibody; performed concurrently 
with Test 2 
2/3b 
HLA-DRB3*01:01 
positive, Anti-HPA-1a 
antibody positive 
None – no further 
testing (ineligible) 
2/3c 
HLA-DRB3*01:01 
negative, Anti-HPA-1a 
antibody negative 
None – no further 
testing (ineligible) 
4 
Fetal HPA-1 
genotype 
A cffDNA test to inform on the 
presence of the antigenic stimulus 
for maternal alloimmunization 
4a 
HPA-1a/b 
Treat with SC 
RLYB212 and 
follow up for final 
assessments 
4b 
HPA-1b/b 
None – no further 
testing (ineligible) 
cffDNA = cell-free fetal DNA; FNAIT = fetal and neonatal alloimmune thrombocytopenia; HPA = human 
platelet antigen 
δ Note: for operational efficiency, Test 2 and Test 3 are performed simultaneously 
Screening Part 1 is an initial visit that includes the informed consent, demographic questioning 
(including obstetric history), and the collection of a blood sample for FNAIT testing (Table 1-2). 
This visit is to take place no earlier than GW 6. Individuals will consent to HPA-1 genotyping 
(Test 1) and, if HPA-1b/b, subsequent screening for HLA-DRB3*01:01 (Test 2), anti-HPA-1a 
antibodies (Test 3), and confirmation of fetal HPA-1a genotype (Test 4), as required. 
Two distinct samples and analyses are performed, per industry practice, to confirm absence of 
the HPA-1b allele in the fetus, with timing between sampling ~2 weeks.   
8.1.2 
Screening Part 2 
Participants who meet all eligibility criteria in Screening Part 1 (SoA, Table 1-3, ie, HPA-1b/b 
and HLA-DRB3*01:01 positive genotype; anti-HPA-1a alloantibody negative; fetal HPA-1a/b 
genotype) and who provide informed consent for Screening Part 2 (SoA, Table 1-3) will be 
assessed to determine if they meet all eligibility criteria to enter the antenatal treatment phase 
and to receive treatment with RLYB212 according to the protocol.  
Dosing with RLYB212 will be initiated at Visit 3, which must occur no later than GW 16. That 
is, if the fetal HPA-1 genotype is pending and will not be available by the planned baseline visit 
at GW 16, the subject will be dosed with the initial dose of RLYB212 pending the result (of the 

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replicate tests), provided all other Screening Part 2 criteria are met. A second dose of RLYB212 
will not be given if definitive fetal HPA-1a results are not available by Visit 4 (~GW 20). If the 
fetal HPA-1a genotype data become available after the initial dose of RLYB212 is given and the 
fetus is HPA-1b/b, ie, not at risk for HPA-1a alloimmunization, the participant will be 
discontinued from treatment, followed at a safety visit 4 weeks later and then discharged from 
the study to receive normal prenatal care and follow-up by their physician. In this case, the 
participant would have been determined not to be at risk for development of HPA-1a 
alloimmunization and FNAIT. 
The study has been designed with multiple sequential cohorts (Section 1.2.1). Therefore, if a 
participant has been determined to be eligible for RLYB212, but the cohort has been fully 
enrolled, the participant will be requested to consent for the non-interventional (observational) 
sub-study.  
Eligibility for the non-interventional (observational) sub-study is presented in Table 1-1.  
8.2 
Pharmacokinetic Assessments 
Serum samples will be collected for measurement of concentrations of study drug as specified in 
the SoA (Section 1.3).  
The timing of sampling may be altered during the study based on emergent data (eg, to obtain 
data closer to the time of peak serum concentrations) to ensure appropriate monitoring.  
A cord blood sample will be collected at parturition to inform neonate exposure to RLYB212. 
8.3 
Assessment of Pregnancy and Neonatal Outcomes 
8.3.1 
Obstetric/Fetal Doppler Ultrasound 
Obstetric/fetal doppler ultrasound monitoring will be performed as outlined in the SoA 
(Section 1.3) and at regular intervals during the study and consistent with local obstetric standard 
of care, to detect any evidence of placental structural abnormality, organ pathology, hemorrhage, 
or delayed growth in the fetus, or any doppler velocimetry effects indicative of placental 
insufficiency or fetal anemia. These assessments will be performed in the second trimester and in 
the third trimester taking into consideration applicable guidelines, ie, International Society of 
Ultrasound in Obstetrics & Gynecology (ISUOG) [18-21], local guidelines and other resources 
(eg, ACOG, CADTH Health Technology Review). Suggested obstetric/fetal doppler ultrasound 
assessments from these resources include biometry, eg, head circumference, femur length, fetal 
anatomy (reported as normal OR abnormal [with details] OR not seen, with explanation), 
placenta, eg, position; fetal cardiac activity, hemorrhage in pregnancy, fetal growth 
abnormalities, eg, small-for-gestational age/fetal growth restriction, large-for-gestational 
age/macrosomia; assessment of amniotic fluid volume. Planned doppler assessments include 
velocimetry of the fetal middle cerebral artery, umbilical and uterine arteries as well as fetal 
venous waveforms. 
Because many of these measurements (particularly doppler vascular measurements) can be done 
by different techniques (ultrasound modality, transvaginal vs transabdominal, proximal vs distal 

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umbilical artery), and because multiple indices exist to assess some of the raw ultrasound 
findings, no attempt will be made to standardize techniques in this small study, so long as all 
investigators adhere to recommended practices. 
8.3.2 
Visit Assessments for Pregnancy Outcomes that are Live Births 
For pregnancies that result in a live birth, the assessment of alloimmunization at 10 weeks 
postpartum will include: 
• A blood sample collected for the assessment of maternal alloimmunization (refer to the study 
Laboratory Manual for details), as determined by the presence of detectable anti-HPA-1a 
alloantibodies. 
Other assessments at delivery/parturition will include: 
• Pregnancy outcome (Section 3): full term birth, premature birth, mode of delivery, including 
the date. 
• A cord blood sample will be collected at delivery to assess for the possible occurrence of 
neonatal thrombocytopenia and severe neonatal thrombocytopenia, as determined by a cord 
blood platelet count < 150 × 109/L and < 50 × 109/L, respectively. 
In the event of neonatal thrombocytopenia, the management and treatment of the event will be 
recorded in the CRF. 
8.3.3 
Vital Assessments for Pregnancy Outcomes that are Not Live Births 
For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 
10 weeks from the date of the pregnancy-terminating event (ie, abortion [either spontaneous or 
elective] or stillbirth). This will include: 
• A blood sample collected for the assessment of maternal alloimmunization (refer to the study 
Laboratory Manual for details), as determined by the presence of detectable anti-HPA-1a 
antibodies. 
Other assessments at the pregnancy-terminating event will include: 
• Pregnancy outcome: spontaneous abortion, elective abortion, stillbirth, including the date. 
8.3.4 
Neonatal/Infant Assessments 
8.3.4.1 
Parturition 
• Collect Appearance, Pulse, Grimace, Activity, and Respiration(APGAR) scores at birth, 
gender, weight, head circumference, and length. 

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• Collect cord blood sample for: 
o Platelet count 
o Hematocrit, hemoglobin, reticulocytes, total bilirubin 
o Concentration of RLYB212 
• Record any AEs, eg, fetal/neonatal bleeding (Section 10.3.3) [17] 
• Record any concomitant therapy. 
8.3.4.2 
4-6 Weeks Postpartum Visit 
• Weight, head circumference, and length 
• General health and overall status (absolute values and percentiles) 
• Infant behavior 
• Record any AEs 
• Record any concomitant therapy. 
8.3.4.3 
12 Months Postpartum Visit 
• Weight, head circumference, and height 
• General health and overall status (absolute values and percentiles) 
• Infant behavior 
• Record any AEs 
• Record any concomitant therapy 
• Assess using a formal, reliable, screening tool that measures sensory, motor, and perception 
developmental domains against published norms, eg, Ages & Stages Questionnaires®, Third 
Edition (ASQ®-3). 
8.4 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.4.1 
Physical Examinations 
A complete physical examination will include the following observations/measurements: height, 
weight, general appearance, skin, head, eyes, ears, nose, and throat, lymph nodes, heart, lungs, 

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abdomen, extremities/joints, neurological, and mental status. Any significant abnormalities 
observed at screening will be recorded as medical history. 
A brief physical and obstetric examination (heart, lungs, abdomen) will also be performed 
throughout pregnancy and the postpartum period per the SoA (Section 1.3).  
8.4.2 
Vital Signs 
Systolic and diastolic blood pressures (mmHg), heart rate (beats/minute), and temperature (°C) 
will be recorded in supine position. Any clinically significant abnormal findings will be recorded 
as AEs except events identified at the Screening Part 2 visit. 
8.4.3 
Electrocardiograms 
Prior to dosing, a 12-lead ECG will be obtained using an ECG machine that automatically 
calculates the heart rate and measures PR, QRS, QT, and QTc intervals. A review by a 
cardiologist of the resultant cardiogram is not required prior to dosing. 
8.4.4 
Clinical Laboratory Assessments 
Maternal clinical laboratory assessments will be obtained during the study as summarized in 
Section 10.2 (Appendix 2).  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents.  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified, and the Sponsor notified. 
All protocol-required laboratory assessments as defined in Section 10.2 (Appendix 2) must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the CRF. 
8.5 
Adverse Events and Serious Adverse Events 
AEs will be spontaneously reported by the participant in response to general questions of how 
they are feeling. Specific new AEs will not be solicited, although follow-up questions about prior 
AEs should be asked if not volunteered spontaneously by the participant.  

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The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study or study intervention (Section 10.3 [Appendix 3]).  
The definitions of pregnancy-related and fetal AEs can be found in Section 10.3 (Appendix 3) 
[17]. 
8.5.1 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the Screening Part 2 visit until the end of study visit (10 weeks 
postpartum for the maternal participant, and 4-6 weeks and 12 months of age for the 
neonate/infant) at the time points specified in the SoA (Section 1.3). 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the CRF, 
not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee immediately, and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3 (Appendix 3). The 
investigator will submit any updated SAE data to the Sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
Sponsor. 
8.5.2 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs, and the 
procedures for completing and transmitting SAE reports, are provided in Section 10.3 
(Appendix 3). 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.5.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
or fetus/neonate at subsequent visits/contacts. All SAEs for the participant, fetus, or 
neonate/infant will be followed until resolution, stabilization, the event is otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is provided in Section 10.3 (Appendix 3). 

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8.5.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. 
For all studies except those utilizing medical devices, investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions (SUSAR) according to local 
regulatory requirements and Sponsor policy, and forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.5.5 
Adverse Events of Special Interest 
There are no AEs of special interest specified in this protocol. Fetal and neonatal outcomes, 
many of which are AEs, are the focus of this study, as outlined in Section 8.3. 
8.6 
Measurement of Anti-HPA-1a Alloantibodies 
Serum samples will be tested by the Sponsor or Sponsor’s designee to assess for the presence of 
anti-HPA-1a alloantibodies.  
An initial anti-HPA-1a alloantibody test will be performed at screening to establish the absence 
of detectable alloantibodies (ie, lack of existing HPA-1a alloimmunization). An assessment of 
alloimmunization at the Week 10 postpartum timepoint will inform on the occurrence of HPA-1a 
alloimmunization in the pregnancy.  
The selection of the 10-week postpartum point provides sufficient time since parturition for any 
potential alloantibody response to fetal HPA-1a exposure during the birth, while also minimizing 
interference from residual RLYB212 levels in the samples. 
Measurement of anti-HPA-1a alloantibody will use the same laboratory test at both the baseline 
and the Week 10 postpartum time point (Section 1.3). 
8.7 
Immunogenicity Assessments 
Development of ADAs against RLYB212 will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). To ensure a meaningful interpretation of 
antibody data, all collected ADA samples will have concurrently RLYB212 serum concentration 
samples. Serum samples should also be collected at the final visit from participants who 

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discontinue study intervention or are withdrawn from the study. These samples may be tested by 
the Sponsor or Sponsor’s designee. 
The detection and characterization of ADAs against RLYB212 will be performed using a 
validated assay method by or under the supervision of the Sponsor. The titer of confirmed 
positive samples will be reported as well as the presence of neutralizing antibodies. Other 
analyses may be performed to verify the stability of antibodies to RLYB212, and/or further 
characterize the immunogenicity of RLYB212.  
If positive ADA is detected during the study, the PK profiles from participants who were ADA 
negative and positive will be compared to assess the impact of ADAs on RLYB212 PK. 
8.8 
Efficacy Assessments 
There are no formal efficacy objectives in this study. 
8.9 
Non-interventional (Observational) Sub-study Assessments 
8.9.1 
Visit Assessments for Pregnancy Outcomes that are Live Births 
For pregnancies that result in a live birth, the assessment of alloimmunization will be at 
10 weeks postpartum as defined in Section 8.6. 
• A blood sample will be collected for the assessment of maternal alloimmunization (refer to 
the study Laboratory Manual for details), as determined by the presence of detectable 
anti-HPA-1a antibodies. 
• Pregnancy outcome: full term birth, premature birth, mode of delivery, including the date 
(based on medical records). 
• Occurrence of neonatal thrombocytopenia and severe neonatal thrombocytopenia, as 
determined by a platelet count < 150 × 109/L and < 50 × 109/L, respectively, where data are 
available (based on medical records). 
• Interventions used: eg, intravenous immune globulin (IVIG), steroids, fetal platelet 
transfusions, newborn platelet transfusions. 
8.9.2 
Visit Assessments for Pregnancy Outcomes that are Not Live Births 
For pregnancies that do not result in a live birth, the assessment of alloimmunization will be at 
10 weeks from the date of the pregnancy-terminating event (ie, abortion [spontaneous/elective] 
or stillbirth). 
• A blood sample will be collected for the assessment of maternal alloimmunization (refer to 
the study Laboratory Manual for details), as determined by the presence of detectable 
anti-HPA-1a antibodies. 

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• Pregnancy outcome: spontaneous abortion, elective abortion, stillbirth, including the date 
(based on medical records) 
• Interventions used: eg, IVIG, steroids 
8.10 
Independent Data Monitoring Committee 
A DMC will monitor safety outcomes and study conduct and will provide recommendations for 
consideration by the Sponsor regarding the continuation of the study, dosing of further 
participants in the study or stopping the study for all participants or subgroups of participants all 
along the study.  
Additional details are provided in Section 10.1.5 (Appendix 1).  

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9 STATISTICAL CONSIDERATIONS 
The statistical analysis plan (SAP) will be finalized prior to database lock and will include a 
technical and detailed description of the statistical analyses described in this section. This section 
(Section 9.1 through Section 9.5, inclusive) is a summary of the planned statistical analyses of 
primary and key secondary endpoints with this interventional study. 
9.1 
Statistical Hypothesis 
This study will be descriptive in nature and no hypothesis testing is proposed. 
9.2 
Sample Size Determination 
The primary objectives of the study are to characterize the safety and PK of RLYB212 in 
HPA-1b/b pregnant women at risk of HPA-1a alloimmunization. Empiric PK data from this 
study will be used to supplement the parameters for the current clinical pharmacology model, 
including the impact of target-mediated drug disposition, if necessary. The PK characterization 
of RLYB212 in this study is intended to be exploratory, rather than to meet a pre-specified 
statistical objective. The proposed sample size of 8 is consistent with other studies reported in 
literature intended to characterize the PK of monoclonal antibodies in an exploratory manner and 
has been determined to be adequate from a PK perspective based on the following: 
• Low to moderate variability observed in RLYB212 PK: In Study IPA2001 (Section 2.2.2.2), 
after a single SC dose of 0.21 mg RLYB212 (n = 6), the CV% for RLYB212 exposure in 
HPA-1b/b volunteers was 32.2% for Cmax and 26% for AUClast. After repeat SC dosing in 
Study IPA2001 (0.29 mg of RLYB212 or placebo on Day 1 followed by 0.1 mg on Days 15, 
29, 43, 57, and 71; n = 6), observed CV% were reduced to 18.6% for Cmax and 18% for 
AUCtau, respectively, on Day 71. In Study IPA2003 (Section 2.2.2.2), in HPA-1b/b 
volunteers who received an HPA-1a positive platelet challenge after single SC doses of 
0.09 mg (n = 4) or 0.29 mg (n = 5) RLYB212, the CV% for RLYB212 exposure ranged from 
16.5 and 27.2% for Cmax and from 16 and 24% for AUClast, respectively. Given the low 
inter-individual variability in RLYB212 PK observed across 4 distinct dose regimens in 
21 HPA-1b/b volunteers at dose levels relevant to those proposed in Study IPA2202, 
including in volunteers receiving antigen-positive platelet challenge, the proposed sample 
size of n = 8 is adequate for the stated purpose of an exploratory characterization of 
RLYB212 PK in HPA-1b/b pregnant women at risk of HPA-1a alloimmunization.  
• Antibody PK in pregnancy: While physiological changes during pregnancy such as increases 
in body weight and blood volume are well characterized, published data on maternal 
exposure to therapeutic mAbs throughout the second and third trimesters are available for 
only a limited number of mAbs to date. [22, 23] While the effect of pregnancy on exposure 
parameters is mAb-specific, the variability in the reported PK parameters of individual mAbs 
is modest through all three trimesters of pregnancy.  
• Conservative dose selection approach: The modeling and simulation analyses that supported 
the RLYB212 dose selection for this study incorporated conservative assumptions that 
minimize the risk of maternal serum RLYB212 concentrations exceeding the ~10 ng/mL 

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(0.067 nM) target upper boundary concentration (Section 2.1), which is believed to be well 
below the threshold that could cause harm to the developing fetus. A larger sample size is, 
therefore, not expected to be informative for the purpose of characterizing PK excursions 
outside of this upper threshold. PK data from Study IPA2202 will be used to update the 
modeling and simulation analyses in an iterative manner to inform the dose for the planned 
Phase 3 study. 
It is anticipated that approximately 5,000 participants will be screened to identify 8 pregnant 
women who both meet the study-specific screening test requirements (ie, genotype HPA-1b/b, 
genotype HLA-DRB3*01:01 positive, anti-HPA-1a antibody negative, and carrying an HPA-1a 
positive fetus) and who meet all other inclusion/exclusion criteria to be eligible to receive the 
study intervention (RLYB212). Women in their first or subsequent pregnancy may be included 
in this study. Replacement of participants is permitted to achieve 8 participants for whom the 
pregnancy results in a live birth and who are evaluable for PK and safety assessments 
(Section 7.2). 
9.3 
Analysis Sets/Populations for Analysis 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Safety Analysis Set 
All participants in the study who received one or more doses of RLYB212 
RLYB212 PK Analysis 
Set 
All participants for whom at least one concentration above LLOQ is available for 
RLYB212 will be included in the RLYB212-PK data set for analysis.  
Alloimmunization 
Analysis Set 
All participants who had at least one screening (Screening Part 1 or 2) or baseline 
(Visit 2) determination of anti-HPA-1a activity and a subsequent determination of 
anti-HPA-1a activity postpartum. 
HPA = human platelet antigen; LLOQ = lower limit of quantification; PK = pharmacokinetic. 
9.4 
Statistical Analyses 
The SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses including 
primary and key secondary endpoints. 
9.4.1 
General Considerations 
For continuous variables, descriptive statistics including number of participants, mean, standard 
deviation, median, minimum, and maximum will be presented. For categorical variables, the 
number and percentage of participants will be presented. 
Data analysis and presentation will be performed by SAS version 9.4 or later. 
9.4.2 
Primary Endpoints 
The PK profile of RLYB212 during pregnancy will be modelled via a compartmental population 
PK model with 3 primary parameters, eg, volume of distribution (Vd), clearance (CL), 
absorption rate constant (ka) and derived parameters: Cmax, time to maximum serum 

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concentration (tmax), area under the curve (AUCinf), terminal half-life (t½), and elimination rate 
constant, and a secondary model will provide the following parameters, eg: 
PK Parameter 
Definition 
AUC0-inf 
area under the RLYB212 concentration-time curve from time zero extrapolated to infinity 
AUCtau 
area under the RLYB212 concentration-time curve over the dosing interval 
Cmax 
maximum RLYB212 concentration 
tmax 
time to maximum RLYB212 concentration 
CL/F 
apparent clearance 
t½ 
half-life 
Safety assessment (Section 9.4.3) comprises the second primary endpoint. No formal 
pre-specified analysis is specified in the SAP. 
9.4.3 
Secondary Endpoints 
RLYB212 exposure in the neonate will be evaluated by cord blood concentration of RLYB212, 
which will be a single measurement, and neonatal thrombocytopenia will likewise be evaluated 
by cord blood platelets. 
Other aspects of safety of RLYB212 exposure in the neonate will be evaluated during the 
postpartum follow-up period in terms of type and seriousness and incidence of AEs, physical 
examination findings including APGAR scores, vital signs and cord blood levels for platelets, 
hematocrit, hemoglobin, reticulocytes, total bilirubin, and any additional safety testing done on 
the neonate on an ad hoc basis. 
RLYB212 immunogenicity data and the presence of ADA, and whether there is a neutralizing 
response, will be determined.  
Pregnancy and neonatal outcomes following antenatal RLYB212 administration will include: 
• Number of spontaneous abortions, defined as non‑deliberate fetal death which occurs prior to 
GW 19. 
• Number of elective abortions, defined as deliberate termination of pregnancy at any time in 
gestation. 
• Number of stillbirths, defined as non-deliberate fetal death anytime in gestation on or after 
GW 19. 
• Number of premature births, defined as live birth prior to GW 37.  
• Number of full term births (≥ GW 37).  
• Overall health and development of infants at 4‑6 weeks and 12 months of age.  

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• Neonatal thrombocytopenia and severe neonatal thrombocytopenia, as defined by a platelet 
count < 150 × 109/L and < 50 × 109/L, respectively, collected as a part of the cord blood 
sample. 
Maternal alloimmunization to HPA-1a will be determined by a measurement of maternal 
circulating anti-HPA antibodies at 10 weeks postpartum or 10 weeks from the date of the 
pregnancy-terminating event (ie, abortion [spontaneous/elective] or stillbirth). 
Where possible, data will be summarized using descriptive statistics and listed. 
9.4.4 
Tertiary/Exploratory Endpoints 
Not applicable. 
9.4.5 
Other Safety Analyses 
All routine safety analyses will be performed on the Safety Analysis Set. Data will be presented 
separately for maternal participants and neonates/infants. 
Safety will be evaluated by presenting summaries of AEs and SAEs, maternal clinical laboratory 
evaluations (hematology, serum chemistry, coagulation, and urinalysis [Section 10.2 
(Appendix 2)]), physical examination, ECGs, vital signs, and RLYB212 immunogenicity data 
(ADA and neutralizing antibody response). Safety variables will be tabulated for the safety 
population. AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) supplemented with additional information for pregnancy and parturition-related AEs 
from Spencer et al [17]. 
A TEAE is defined as an AE that occurs after study treatment is first administered through the 
end of the follow-up period. The incidence of TEAEs will be presented by system organ class 
(SOC) and preferred term, by relationship to study drug, and severity. In addition, the incidence 
of serious TEAEs will be presented by system organ class (SOC) and preferred term (PT), 
including obstetric TEAEs as outlined in Section 10.3 (Appendix 3), which will be categorized 
via a dictionary extension specific for these events. Descriptive statistics for clinical laboratory 
test results, ECGs, and vital signs, including changes from baseline, will be presented by time 
point. Incidences of potentially clinically significant clinical laboratory results, ECGs, and vital 
signs, as defined in the SAP, will also be summarized by time point. Frequency and percentages 
of physical exam findings will be summarized. 
Regular obstetric/fetal doppler ultrasounds as scheduled by the protocol will be included in the 
safety evaluation. 
9.5 
Interim Analyses 
No formal interim analyses will be conducted. Preliminary data may be used for summary 
purposes and for communication with health authorities. 

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9.6 
Non-interventional (Observational) Sub-study 
This sub-study is intended to be descriptive in nature; no hypothesis will be tested in this 
sub-study. Demographic and baseline characteristics will be summarized. Discrete variables will 
be summarized using numbers and percentages; continuous variables will be summarized using 
means and SD or medians and IQRs, as appropriate. Administrative tabulated summaries of 
study variables will be generated periodically. Data obtained from the non-interventional 
(observational) sub-study will be pooled with those acquired from study IPA2002 
(NCT05345561) for analysis of natural history variables of the higher risk FNAIT population.   

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines. 
• Applicable ICH Good Clinical Practice (GCP) Guidelines. 
• Applicable laws and regulations. 
• The protocol, protocol amendments, informed consent form (ICF), investigational brochure, 
and other relevant documents (eg, advertisements) must be submitted to an independent 
review board (IRB)/independent ethics committee (IEC) by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC. 
• Notifying the IRB/IEC of serious adverse events (SAEs) or other significant safety findings 
as required by IRB/IEC procedures. 
• Providing oversight of the conduct of the study at the site and adherence to requirements of 
Code of Federal Regulations Title 21 (21 CFR), ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 

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10.1.3 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant 
and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary and will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants will complete an ICF for the initial screening (Screening Part 1) in the study prior to 
assessing eligibility. Participants who are then determined to be eligible for study treatment at 
the subsequent screening (Screening Part 2) are required to sign a new ICF. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of all ICFs (plus any ICFs updated while the participant is enrolled in the study) must be 
provided to the participant. 
10.1.4 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 
The participant must be informed that their personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. 
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5 
Committee Structure 
In this study, an independent data monitoring committee (DMC) will monitor safety outcomes 
and study conduct and will provide recommendations for consideration by the Sponsor regarding 
continuation of the study, dosing of further participants in the study, or stopping the study for all 
participants or subgroups of participants in the study. Safety data will include, but not be limited 
to, those outcomes listed as primary and secondary endpoints. 

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The DMC is a multidisciplinary group composed of experts, physicians experienced in the 
treatment of the disease under investigation, FNAIT. 
The Sponsor will propose a detailed mandate and review this with the DMC, from the outset (a 
detailed DMC charter and operating rules will be prepared and signed by DMC members before 
study start). 
The DMC will review study data at regular intervals as described in the DMC charter. These 
sessions could be regular sessions or ad-hoc sessions. Ad-hoc sessions can be requested by the 
Sponsor or the DMC as needed and at any time during the study. 
10.1.6 
Dissemination of Clinical Study Data 
The Sponsor will register and/or disclose the existence of and the clinical study data as required 
by local laws and regulations. 
10.1.7 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRFs unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities, and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the Monitoring Plan. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (eg, CROs). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents, that the safety and rights of participants are being protected, and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 

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retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
10.1.8 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
Definition of what constitutes source data can be found in the Location of Source Data form 
provided to the site prior to the start of the study. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.9 
Study and Site Start and Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study intervention development. 

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10.1.10 
Publication Policy 
The Sponsor and the investigator(s) will comply with the requirements for publication of study 
results. In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of the sites’ study results following publication of the multicenter study 
results in their entirety. The Sponsor expects that a coordinating investigator will be designated 
to oversee publication of the multicenter study results. Authorship will be determined in line 
with International Committee of Medical Journal Editors authorship requirements. 
If the investigator is authorized to publish individual site data, the investigator agrees to submit 
all manuscripts, publications, or abstracts to the Sponsor before submission. This approach 
allows the Sponsor to protect proprietary information. 
10.2 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 10-1 will be performed by central laboratories and local laboratories.  
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Investigators must document their review of each laboratory safety report. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 

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Table 10-1 
Protocol-required Clinical Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
RBC indices: 
• 
MCV 
• 
MCH 
• 
MCHC 
• 
% reticulocytes 
Platelet count 
WBC count with 
differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry 
Urea 
Potassium 
 
Total bilirubin (and direct 
and indirect bilirubina) 
Albumin 
Sodium 
ALT/SGPT 
Total protein 
Creatinine 
Calcium 
AST/SGOT 
Alkaline phosphatase 
Glucose (nonfasting) 
C-reactive protein 
GGT 
 
Coagulation 
Prothrombin time 
International normalized ratio 
Activated partial thromboplastin time 
Viral Serology 
Hepatitis C virus antibody; Hepatitis B surface antigen (HBsAg); HIV antibody 
Routine 
Urinalysis 
Specific gravity 
Dipstick for glucose, pH, nitrate, occult blood, ketones, bilirubin, urobilinogen, nitrite, and 
leukocyte esterase 
Microscopic examination (if blood or protein is abnormal) 
FNAIT Testing δ 
FNAIT laboratory screening tests for maternal HPA-1a genotype, maternal HLA-
DRB3*01:01 genotype, and maternal HPA-1 alloantibodyb, fetal HPA-1a genotype/cffDNA 
RLYB212 
Specific δ 
Immunogenicity data (ADA response and presence of neutralizing antibody) 
PK 
ADA = anti-drug antibody; ALT = alanine aminotransferase; AST = aspartate aminotransferase; cffDNA = cell-free 
DNA; FNAIT = fetal and neonatal alloimmune thrombocytopenia; GGT = gamma glutamyl transferase; 
HBV = hepatitis B virus; HCV = hepatitis C virus; MCH = mean corpuscular hemoglobin; MCHC = mean 
corpuscular hemoglobin concentration; MCV = mean corpuscular volume; PK = pharmacokinetics; RBC = red 
blood cell; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase; 
WBC = white blood cell. 
a Direct and indirect bilirubin will only be assessed if total bilirubin is elevated. 
b If a positive test result is observed for anti-HPA-1a maternal alloantibody test, the results should be discussed with 
the Sponsor (Section 8.4.4). 
δ FNAIT testing and RLYB212 specific tests are performed in central laboratories; all other tests are performed 
locally. 
 
 

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10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting 
10.3.1 
Definition of Adverse Events 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated 
with the use of study intervention, whether or not considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator (ie, not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency 
and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration even though it may have been 
present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae. 
• 
For efficacy studies, “lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they 
fulfil the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder being 
studied, unless more severe than expected for the participant’s condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the procedure is 
the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience admission to a 
hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or conditions(s) present or detected at the start 
of the study that do not worsen. 
10.3.2 
Definition of Serious Adverse Events 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 

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A SAE is defined as any untoward medical occurrence that, at any dose: 
Results in death 
Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the participant was at risk of 
death at the time of the event. It does not refer to an event, which hypothetically might have caused death, if it 
were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
Results in persistent disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life functions. 
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle) which 
may interfere with or prevent everyday life functions but do not constitute a substantial disruption. 
Is a congenital anomaly/birth defect 
Other situations: 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate in other 
situations such as important medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive intervention in an emergency room or 
at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency room or at 
home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
10.3.3 
Definitions of Pregnancy- and Parturition-specific Adverse Events 
Maternal and Fetal Adverse Events  
Maternal AEs: 
• 
Haemorrhage in pregnancy 
• 
Preterm premature rupture of membranes 
• 
Chorioamnionitis 
• 
Anaemia of pregnancy 
• 
Gestational hypertension 
• 
Pre-eclampsia 
• 
Eclampsia 
• 
Premature labour 
• 
Puerperal infection 
• 
Postpartum haemorrhage (primary) 
• 
Retained placenta or membranes 
• 
Amniotic fluid embolism 

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Fetal AEs: 
• 
Haemorrhage in pregnancy 
• 
Preterm premature rupture of membranes 
• 
Chorioamnionitis 
• 
Anaemia of pregnancy 
• 
Fetal fluid collectiona 
• 
Fetal bradycardia: non-laboura 
• 
Fetal tachyarrhythmiaa  
• 
Cardiac function abnormalitiesa 
• 
Fetal brain scan abnormala 
• 
Fetal gastrointestinal tract imaging abnormala  
• 
Fetal musculoskeletal imaging abnormala 
• 
Fetal renal imaging abnormala 
• 
Fetal movement disordersa  
• 
Fetal neoplasm  
• 
Fetal structural abnormalities: not otherwise classifieda  
• 
Abnormal fetal growtha  
• 
Fetal intraoperative injurya  
• 
Procedure haemorrhagea  
• 
Post-procedural haemorrhagea  
a Added to the list of terms in the MedDRA. 
Source: [17]. 
 
Maternal and Fetal AE Definitions and Severity Grading Criteria 
Guidance on the use of these severity grading criteria: 
• 
If an adverse event fulfils the criteria for more than one grade of severity, the highest applicable grade should 
be used. 
• 
Death resulting from any of the adverse events is classified as grade 5. 
• 
A semicolon indicates ‘or’ within the description of a grade. 
• 
Maternal procedural complications, such as pain and infection, should be identified by the appropriate 
MedDRA preferred term and graded according to CTCAE criteria. 
• 
Maternal thromboembolic events during pregnancy and the puerperium should be identified by the 
appropriate MedDRA preferred term (‘venous thrombosis in pregnancy’, ‘postpartum venous thrombosis’, or 
‘obstetrical pulmonary embolism’) and graded according to the CTCAE criteria ‘thromboembolic event’. 
Source: [17]. 
10.3.4 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation (eg, hospital 
progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records to the 
pharmacovigilance CRO in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by the regulatory 
authorities. In this case, all participant identifiers, with the exception of the participant number, will be 
redacted on the copies of the medical records before submission. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or other 
clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be 
documented as the AE/SAE. 

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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the study and assign 
it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort, and not interfering 
with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be 
confused with a SAE. Severe is a category utilized for rating the intensity of an event; and both AEs and 
SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the definition 
of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention and each occurrence of 
each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or arguments to 
suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and investigated. 
• 
The investigator will also consult the IB and/or Product Information, for marketed products, in his/her 
assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has minimal information to 
include in the initial report to the pharmacovigilance CRO. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial transmission of 
the SAE data to the pharmacovigilance CRO. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and send a SAE 
follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting requirements. 
 
Follow-up of AEs and SAEs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements and/or 
evaluations as medically indicated or as requested by the pharmacovigilance CRO to elucidate the nature 
and/or causality of the AE or SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care professionals. 
• 
After the initial AE/SAE report, the investigator is required to proactively follow each participant or 
fetus/neonate at subsequent visits/contacts.  
• 
All SAEs reported for the participant, fetus, or neonate/infant will be followed until resolution, stabilization, 
the event is otherwise explained, or the participant is lost to follow-up.  
• 
If a participant dies during participation in the study or during a recognized follow-up period, the investigator 
will provide the pharmacovigilance CRO with a copy of any postmortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to the pharmacovigilance CRO within 24 hours of receipt 
of the information. 

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10.3.5 
Reporting of SAEs 
SAE Reporting to the Pharmacovigilance CRO via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to the pharmacovigilance CRO will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool to report the 
event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off-line to 
prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a previously 
reported SAE after the electronic data collection tool has been taken off-line, then the site can report this 
information on a paper SAE form or to the pharmacovigilance CRO by telephone. 
 
 

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10.4 
Appendix 4: Abbreviations 
Abbreviation 
Definition for Term 
21 CFR 
Code of Federal Regulations Title 21 
ADA 
anti-drug antibody 
AE 
adverse event 
ALT 
alanine aminotransferase 
APGAR 
Appearance, Pulse, Grimace, Activity, and Respiration 
AST 
aspartate aminotransferase 
AUC 
area under the (RLYB212) concentration versus time curve 
AUC0-inf 
area under the concentration-time curve from time zero extrapolated to infinity 
cffDNA 
cell-free fetal DNA 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
clearance 
CL/F 
apparent clearance 
Cmax 
maximum serum concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CTCAE 
common terminology criteria for adverse events 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
EOS 
end of study 
FNAIT 
fetal and neonatal alloimmune thrombocytopenia 
GCP 
Good Clinical Practice  
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practice 
GW 
Gestational Week 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDFN 
hemolytic disease of the fetus and newborn 
HIPAA 
Health Insurance Portability and Accountability Act 
HLA 
human leukocyte antigen 
HPA 
human platelet antigen 
HPLC 
high performance liquid chromatography 
ICF 
informed consent form 

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Abbreviation 
Definition for Term 
ICH 
intracranial hemorrhage 
ICTMG 
International Collaboration for Transfusion Medicine Guidelines 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IRB 
Institutional Review Board 
ISUOG 
International Society of Ultrasound in Obstetrics & Gynecology 
ITP 
immune thrombocytopenia 
IVIG 
intravenous immunoglobulin 
ka 
absorption rate constant 
LDH 
lactate dehydrogenase 
LLOQ 
lower limit of quantification 
mAb 
monoclonal antibody 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PoM/PoC 
proof of mechanism/proof of concept 
PT 
preferred term 
Q4W 
every 4 weeks 
RBC 
red blood cell 
RhD 
Rhesus D 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous(ly) 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SoA 
schedule of activities 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
half-life 
TCR 
tissue cross reactivity 
TEAE 
treatment-emergent adverse event 

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Abbreviation 
Definition for Term 
TK 
toxicokinetic(s) 
tmax 
time to maximum (RLYB212) concentration 
ULN 
upper limit of normal 
Vd 
volume of distribution 
WBC 
white blood cell 
WT 
wild-type 
 
 

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10.5 
Appendix 5: Protocol Amendment History 
Version 4.0 (14 October 2024) superseding Version 3.0 (25 September 2024) 
Rationale: 
The SoA was updated to indicate that samples for hematology, chemistry, coagulation, and CRP 
assessments will be collected at Screening Part 2, Visit 2. 
Version 3.0 (25 September 2024) superseding Version 2.0 (04 September 2024) 
Rationale: 
The following changes were made based on feedback received from the European Medicines 
Agency (EMA): 
• Follow-up of the infant to 12 months of age; modifications were incorporated in the 
Synopsis, Schema/SoA, Objectives/Endpoints, End of Study Definition and Study 
Assessments and Procedures. 
In addition, corrected EU CT number (removal of submission number). 
Version 2.0 (04 September 2024) superseding Version 1.1 (23 August 2024). 
Rationale: 
The following changes were made based on feedback received from the European Medicines 
Agency (EMA): 
• Included clarification that the occurrence of neonatal thrombocytopenia following antenatal 
RLYB212 administration will be evaluated based on the umbilical cord sample taken at 
parturition. 
•  Updated Exclusion Criteria at Screening Part 2: 
o Revised exclusion criterion 4 to: “Any participant with a history of past or current 
intravenous immunoglobulin (IVIG) use for an underlying disease (eg, autoimmune 
disease)” 
o Replaced exclusion criterion 7 with new criterion: “Participants with an in vitro fertilized 
pregnancy or serving as pregnancy surrogates” 
• Clarified that broad spectrum immunosuppressant agents and IVIG are not allowed as 
concomitant medications with RLYB212 administration. If such treatments are required, 
RLYB212 will be discontinued but the participant will continue to be followed in the study. 

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• Replaced statement that vaccinations are not allowed within 30 days of screening until 30 
days after the last dose of study drug, with “Routine vaccines, given at recommended times 
during or immediately after pregnancy, will be allowed in the study.” 
• Clarified that up to 4 participants may be replaced if assigned to study drug but did not 
receive the study drug. 
• Removed statements that samples collected as part of the screening and monitoring 
procedures may be retained for the purposes of analytical method validation, or for optional 
exploratory research. 
In addition: 
• The description of the sub-study was changed to “non-interventional (observational)”. 
• For clarity, reference to “live birth” was revised to “full term birth”, where applicable. 
• Updated the window for the last dose of RLYB212 to be administered from “within 72 hours 
of parturition” to “within 24 hours (±24 hours) of parturition”. 
• Included additional explanatory notes to the SoAs; removed “drug testing” from the SoA 
(Table 1-3); and removed “neonatal platelet count” from the SoA (Table 1-3), as it is 
addressed by the “cord blood sample” assessment. 
• Paragraph on Lifestyle Considerations was simplified.  
• Removed references to a Study Reference Manual (not applicable to the study). 
• Removed appendix on liver safety (as this was addressed in Phase 1 studies). 
Version 1.1 (23 August 2024) superseding Version 1.0 (11 March 2024). 
Rationale: 
The following changes were made based on feedback received from the United Kingdom 
Medicines and Healthcare product Regulatory Agency (MHRA), in addition to including the 
NCT number on the title page: 
• Included a description in the protocol of the composition of the independent data monitoring 
committee that will be overseeing the safety of study participants. 
• Included the requirement that after an initial AE/SAE report, the investigator must 
proactively follow each participant or fetus/neonate/infant at subsequent visits/contacts. All 
SAEs for the participant or fetus/neonate/infant will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
 
 

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11 REFERENCES 
1. 
Killie M, Husebekk A, Kjeldsen-Kragh J, Skogen B. A prospective study of maternal 
anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in 
the newborn. Haematologica. 2008;93(6):870-7. 
2. 
Bertrand G, Martageix C, Jallu V, Vitry F, Kaplan C. Predictive value of sequential 
maternal anti-HPA-1a antibody concentrations for the severity of fetal alloimmune 
thrombocytopenia. J Thromb Haemost. 2006;4(3):628-37. 
3. 
Kamphuis MM, Paridaans NP, Porcelijn L, Lopriore E, Oepkes D. Incidence and 
consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics. 
2014;133(4):715-21. 
4. 
Ghevaert C, Campbell K, Walton J, Smith G, Allen D, Williamson L, et al. Management 
and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion. 
2007;47(5):901-10. 
5. 
Davoren A, Curtis B, Aster R, McFarland J. Human platelet antigen-specific 
alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. 
Transfusion. 2004;44(8):1220-5. 
6. 
Spencer J, Burrows R. Feto-maternal alloimmune thrombocytopenia: a literature review 
and statistical analysis. Aust N Z J Obstet Gynaecol. 2001;41(1):45-55. 
7. 
Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S, et al. 348 
cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 1989;1(8634):363-6. 
8. 
Newman P, Derbes R, Aster R. The human platelet alloantigens, PlA1 and PlA2, are 
associated with a leucine33/proline33 amino acid polymorphism in membrane 
glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest. 
1989;83(5):1778-81. 
9. 
Bussel J. Diagnosis and management of the fetus and neonate with alloimmune 
thrombocytopenia. J Thromb Haemost. 2009;7 Suppl 1:253-7. 
10. 
Kjeldsen-Kragh J, Olsen K. Risk of HPA-1a-immunization in HPA-1a-negative women 
after giving birth to an HPA-1a-positive child. Transfusion. 2019;59(4):1344-52. 
11. 
Kjeldsen-Kragh J, Ni H, Skogen B. Towards a prophylactic treatment of HPA-related 
foetal and neonatal alloimmune thrombocytopenia. Curr Opin Hematol. 2012;19(6):469-
74. 
12. 
Kjeldsen-Kragh J, Skogen B. Mechanisms and prevention of alloimmunization in 
pregnancy. Obstet Gynecol Surv. 2013;68(7):526-32. 
13. 
Zhi H, Ahlen M, Rasmussen T, Skogen B, Newman P. An Authentic Murine Model of 
Fetal/Neonatal Alloimmune Thrombocytopenia. Blood. 2019;134(Supplement_1):97-. 

Protocol IPA2202 
Version 4.0, 14 October 2024
RLYB212 
Page 80 of 80
 
 
Rallybio IPA, LLC - Confidential 
 
 
14. 
Zhi H, Sheridan D, Newman D, Newman P. Prophylactic administration of HPA-1a-
specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice. Blood. 
2022;140(20):2146-53. 
15. 
Wienzek-Lischka S, Bachmann S, Froehner V, Bein G. Potential of Next-Generation 
Sequencing in Noninvasive Fetal Molecular Blood Group Genotyping. Transfus Med 
Hemother. 2020;47(1):14-22. 
16. 
Lewin S, Bussel J. Review of fetal and neonatal immune cytopenias. Clin Adv Hematol 
Oncol. 2015;13(1):35-43. 
17. 
Spencer R, Hecher K, Norman G, Marsal K, Deprest J, Flake A, et al. Development of 
standard definitions and grading for Maternal and Fetal Adverse Event Terminology. 
Prenat Diagn. 2022;42(1):15-26. 
18. 
Salomon L, Alfirevic Z, Berghella V, Bilardo C, Chalouhi G, Da Silva Costa F, et al. 
ISUOG Practice Guidelines (updated): performance of the routine mid-trimester fetal 
ultrasound scan. Ultrasound Obstet Gynecol. 2022;59(6):840-56. 
19. 
Salomon L, Alfirevic Z, Da Silva Costa F, Deter R, Figueras F, Ghi T, et al. ISUOG 
Practice Guidelines: ultrasound assessment of fetal biometry and growth. Ultrasound 
Obstet Gynecol. 2019;53(6):715-23. 
20. 
Bhide A, Acharya G, Baschat A, Bilardo C, Brezinka C, Cafici D, et al. ISUOG Practice 
Guidelines (updated): use of Doppler velocimetry in obstetrics. Ultrasound Obstet 
Gynecol. 2021;58(2):331-9. 
21. 
Khalil A, Sotiriadis A, D'Antonio F, Da Silva Costa F, Odibo A, Prefumo F, et al. 
ISUOG Practice Guidelines: performance of third-trimester obstetric ultrasound scan. 
Ultrasound Obstet Gynecol. 2024;63(1):131-47. 
22. 
Seow C, Leung Y, Vande Casteele N, Ehteshami Afshar E, Tanyingoh D, Bindra G, et al. 
The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in 
inflammatory bowel disease. Aliment Pharmacol Ther. 2017;45(10):1329-38. 
23. 
Flanagan E, Gibson P, Wright E, Moore G, Sparrow M, Connell W, et al. Infliximab, 
adalimumab and vedolizumab concentrations across pregnancy and vedolizumab 
concentrations in infants following intrauterine exposure. Aliment Pharmacol Ther. 
2020;52(10):1551-62. 
24. 
James L, Letzig L, Simpson P, Capparelli E, Roberts D, Hinson J, et al. Pharmacokinetics 
of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver 
failure. Drug Metab Dispos. 2009;37(8):1779-84.