A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of OMS721 in Adults With Thrombotic Microangiopathies
Phase: PHASE2
Conditions: Thrombotic Microangiopathies
Sponsor: Omeros Corporation

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1 
 
-
OMEROS CORPORATION 
CLINICAL PROTOCOL 
PROTOCOL NO. OMS721-TMA-001 
Amendment 11.1 
EUDRACT Number: 2014-001032-11 
Investigational New Drug 
OMS721 
PHASE2 
A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the 
Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of 
OMS721 in Adults with Thrombotic Microangiopathies 
01 June 2020 
II<, 
OMEROS 
 
 
 
 
 
 
APPROVED BY: 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol No. OMS721-TMA-001 (A11.1) 
 
1.1. 
Investigator Agreement 
I have read Omeros Protocol No. OMS721-TMA-001 Amendment 11.1 and agree to conduct the 
study, as described in this protocol, and provide the necessary assurances that this study will be 
conducted according to the stipulations of the protocol, including all statements regarding 
confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and International Conference on Harmonisation (ICH) guidelines. 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

3 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
 
1.2. 
Contact Information 
 
Sponsor Medical Monitor 
 
 
 
 
 
 
PSI Medical Monitor 
 
 
 
 
Novotech Medical Monitor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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4 
 
Protocol No. OMS721-TMA-001 (A11.1) 
 
1.3. 
Amendments 
Amendment 
Date 
Abbreviated Summary of Change 
01 
21 Mar 
2014 
• 
Added text that if Grade 3 or higher adverse events occur in any patient 
in a cohort, then safety information will be provided to the United 
States Food and Drug Administration for review prior to proceeding 
with dose escalation 
• 
Added text on how dose selection will occur for Stage 2 
• 
Added text to provide stopping rules for the study 
02 
31 Mar 
2014 
• 
The safety data will be reviewed by a clinical study monitoring team 
• 
Added text that adverse events of Grade 3 or higher will be reviewed 
carefully with respect to number and causality when determining if 
dose escalation is appropriate 
• 
Added text on how dose selection will occur for Stage 2 
• 
Added text to provide stopping rules for the study 
03 
03 Apr 
2014 
• 
Added exclusion criteria of baseline resting heart rate < 45 beats per 
minute or > 100 beats per minute, and baseline QTcF > 470 milliseconds. 
• 
Added electrocardiogram to safety assessments. 
04 
16 Apr 
2014 
• 
Section 7.4 was amended to remove the limitation on the stopping rule to 
“treatment-related” adverse events and now includes all adverse events 
05 
21 Nov 
2014 
• 
Inclusion criteria No. 4 was amended to clarify and re-define 
hematopoietic stem cell transplant-associated thrombotic microangiopathy 
and refractory thrombotic thrombocytopenic criteria 
• 
Exclusion criteria No. 5 was amended to change the upper limit of resting 
heart rate from 100 to 115 beats per minute 
• 
Exclusion criteria No. 11 was amended to change the minimum value of 
abnormal liver function tests from 3 times to 5 times the upper limit of 
normal 
• 
Exclusion criteria No. 14 was added to include hypersensitivity to product 
constituents 
• 
The early termination criteria were amended to remove the requirement to 
discontinue patients who have received a prohibited concomitant therapy 
06 
04 Feb 
2015 
• 
Changed refractory thrombotic thrombocytopenic purpura to thrombotic 
thrombocytopenic purpura and added biopsy-diagnosed post-renal 
transplant thrombotic microangiopathy 
• 
Removed the time requirement in atypical hemolytic uremic syndrome 
screening inclusion criteria 
• 
Added thrombotic thrombocytopenic purpura inclusion criteria for platelet 
count and microangiopathic hemolysis 
• 
Removed inclusion criteria pertaining to failure to attain a treatment 
response 
• 
Added screening criteria of mycobacterial or significant fungal infection 
07 
26 Mar 
2015 
• 
Removed post-renal transplant as a patient population 
• 
Added Standard of Care treatment regimen 
• 
 
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5 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
 
Amendment 
Date 
Abbreviated Summa1·y of Change 
08 
20 Jul 
• 
Added third stage to the study allowing patients with response to therapy 
2015 
to continue on study treatment for an additional 4 weeks or 12 weeks 
depending on the disease type 
• 
Increased the number of study centers from- 
• 
Increased duration of the study from 20 months to 48 months 
• 
Increased the number of patients to be enrolled from 29 to 89 
• 
Increased stage 2 treatment period for atypical hemolytic uremic 
syndrome patients from 4 weeks to 12 weeks 
• 
Added detection of AEs that occur at an incidence of at least 7.5% in the 
separate coho1is 
• 
Removed text around stopping rnles and added periodic review by Data 
Monitoring Committee 
09 
20Apr 
2017 
• 
Note: Amendment 09 was not implemented 
12 Oct 
2018 
• 
Closed enrollment of thrombotic thrombocytopenic pwpura and atypical 
hemolytic uremic syndrome patients 
• 
Changed the dose to 370 mg IV weekly x 4 for HSCT-TMA patients 
• 
Added Amendment Summa1y of Changes 
• 
Updated the nonclinical experience and rationale for selection of dose 
• 
Updated patient enrollment nwnbers for ongoing clinical studies 
11.1 
28May 
2020 
• 
Provided for collection of additional data for patients with hematopoietic 
stem cell transplant-associated thrombotic microangiopathy 
• 
Changed the primary and secondary objectives to focus on hematopoietic 
stem cell transplant-associated thrombotic microangiopathy 
• 
Defined criteria by which to detennine clinical response to treatment 
• 
Changed all reference to individuals with disease from "subject" to 
"patient" 
Note: Amendment 11 was signed but not submitted when an e1TOr in the secondaiy 
objectives was discovered and removed in Amendment 11.1 
11.1 
01 Jun 
2020 
• 
Removed "renal function in patients who had renal dysfunction at 
baseline" from the seconda1y objectives as this was not intended to be 
included in Amendment 11 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol No. OMS721-TMA-001 (A11.1) 
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2. 
SYNOPSIS 
 
Name of Sponsor/Company: Omeros Corporation 
Name of Investigational Product: OMS721 
Name of Active Ingredient: OMS721 (MASP-2 monoclonal antibody) 
Protocol Number: OMS721-TMA-001 
Title of Study: A Phase 2, uncontrolled, three-stage, dose-escalation cohort study to evaluate 
the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of 
OMS721 in adults with thrombotic microangiopathies 
Planned Number of Clinical Study Center(s): 
Expected Duration of Study: Approximately 
48 months (first patient visit to last patient visit) 
Phase of Development: Phase 2 
Objectives: 
The purpose of this Phase 2 study is to evaluate the safety, efficacy, pharmacokinetics (PK), 
pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic 
microangiopathies (TMA). As of Protocol Amendment 11, the primary and secondary 
endpoints are modified to provide for evaluation of response in patients with hematopoietic 
stem cell transplant (HSCT)-associated TMA. 
The co-primary objectives of this study are to: 
• Assess the safety and tolerability of multiple-dose administration of OMS721 in 
patients with TMA (this will be assessed in patients with HSCT-TMA as well as in 
patients with atypical hemolytic uremic syndrome [aHUS] or thrombotic 
thrombocytopenic purpura [TTP]) 
• Evaluate the efficacy of OMS721 in patients with HSCT-TMA by response defined 
as: 
− Improvement in TMA laboratory markers of platelet count and lactate 
dehydrogenase (LDH), and 
− Improvement in clinical status 
Methodology: 
This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1 of 3 
forms of TMA: aHUS, TTP, or HSCT-TMA. 
In Stage 1 of the study, OMS721 was administered to 3 cohorts (Cohorts 1, 2, and 3), with 
dose escalation by cohort to identify the optimal dosing regimen. After enrollment and 
treatment of each cohort, there was a safety review to determine whether dose escalation 
should proceed. In Stage 2, the dose selected in the first stage was administered to expanded 
cohorts initially planned to be 40 patients per cohort with distinct etiologies (aHUS alone in 
1 cohort, and TTP or HSCT-TMA in the other cohort). As of Amendment 10 of this protocol, 
enrollment of aHUS and TTP patients was closed. As of Amendment 11 of this protocol, 

Protocol No. OMS721-TMA-001 (A11.1) 
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enrollment in the study has been completed. Patients completing Stage 2 may be eligible for 
continued treatment in Stage 3 if they have tolerated OMS721 treatment and derived clinical 
benefit. 
OMS721 is to be used in conjunction with standard of care treatments. Standard of care 
treatments are not to be delayed or withheld from patients entering this study. These treatments 
should be initiated according to local standard of care. For example, plasma exchange should 
not be delayed while waiting for initiation of OMS721 treatment if local standard of care is to 
administer plasma exchange. 
OMS721 will be administered by intravenous (IV) infusion. The cohorts and treatments are 
provided below. 
For patients with HSCT-TMA enrolled under Amendment 10 or earlier versions of this 
protocol, additional data will be collected. These data will include supplemental data on 
patient demographics and baseline conditions, donor characteristics, the transplant procedure, 
concomitant medications, TMA-related laboratory measures, transfusions, transplant 
complications, and outcomes. These data will be derived from medical records from the time 
of transplant conditioning through the last available patient contact with the site, or up to 
2 years (104 weeks) following the first dose of OMS721, whichever comes first. These data 
were requested by regulatory authorities because patients who have undergone HSCT typically 
have complicated post-transplant courses, and these additional data will provide the needed 
information to draft patient narratives, including the full patient profile, and allow for better 
understanding of OMS721 response and outcomes. 
As of Amendment 11, enrollment in the study has been completed, and the additional data will 
be collected until a predetermined data cutoff date for those patients who have not reached 
2 years after first OMS721 dose. 
Cohort (Number) 
Stage 
Treatment 
1 (N = 3) 
1 
OMS721 Dose 0.675 mg/kg IV weekly x 4 
2 (N = 3) 
1 
OMS721 Dose 2.0 mg/kg IV weekly x 4 
3 (N = 3) 
1 
OMS721 Dose 4.0 mg/kg IV weekly x 4 
4 (N = 40 aHUS) 
As of Amendment 10, Cohort 4 is closed 
2 
OMS721 Dose 4.0 mg/kg IV weekly x 12 
4 (N ≤ 40 aHUS) 
As of Amendment 10, Cohort 4 is closed 
3 
OMS721 Dose 4.0 mg/kg IV weekly x 12 
5 (N = 40 TTP or HSCT-TMA) 
As of Amendment 10, TTP enrollment is closed 
2 
OMS721 Dose 4.0 mg/kg IV weekly x 4 
As of Amendment 10, the dose is changed to 
370 mg IV weekly x 4 
5 (N ≤ 40 TTP or HSCT-TMA) 
As of Amendment 10, TTP enrollment is closed 
3 
OMS721 Dose 4.0 mg/kg IV weekly x 4 
As of Amendment 10, the dose is changed to 
370 mg IV weekly x 4 
Abbreviations: aHUS = atypical hemolytic uremic syndrome; HSCT-TMA = hematopoietic stem cell transplant- 
associated thrombotic microangiopathy; IV = intravenous; TTP = thrombotic thrombocytopenic purpura. 
The Stage 1 study schedule included 9 visits across 3 periods. Stage 1 is complete. 
Period 1 – Screening (Visit 1, up to 4 weeks) 
Period 2 – Treatment (Visit 2 to Visit 5, 4 weeks) 

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Period 3 – Follow-up (Visit 6 to Visit 9, 8 weeks) 
The length of time for individual patient participation was approximately 12 to 16 weeks. 
The Stage 2 study schedule for the aHUS cohort (Cohort 4) included 17 visits across 
3 periods: 
Period 1 – Screening (Visit 1, up to 4 weeks) 
Period 2 – Treatment (Visit T-1 to Visit T-12, 12 weeks) 
Period 3 (if patient did not continue to Stage 3) – Follow-up (Visit F-1 to Visit F-4, 
6 weeks) 
The length of time for individual aHUS patient participation in Stage 2 was approximately 
18 to 22 weeks, depending on the time from screening to the first dose of OMS721 
administration. Patients entering Stage 3 did not undergo the follow-up visits in Stage 2. The 
Stage 3 study schedule for the aHUS cohort included 16 visits across 2 periods. 
Period 2 (continued from Stage 2) – Treatment (Visit T-13 to Visit T-24, 12 weeks) 
Period 3 – Follow-up (Visit F-1 to Visit F-4, 6 weeks) 
The length of time for individual aHUS patient participation in Stage 3 was approximately 
18 weeks, and the total length of time in Stage 2 and Stage 3 was approximately 30 to 
34 weeks, depending on the time from screening to the first dose of OMS721 administration in 
Period 2. 
As of Amendment 10 of this protocol, Cohort 4 was closed. As of Amendment 11 of this 
protocol, enrollment in the study has been completed. 
The Stage 2 study schedule for the TTP/HSCT-TMA cohort (Cohort 5) includes 9 visits 
across 3 periods: 
Period 1 – Screening (Visit 1, up to 4 weeks) 
Period 2 – Treatment (Visit T-1 to Visit T-4, 4 weeks) 
Period 3 (if patient does not continue to Stage 3) – Follow-up (Visit F-1 to Visit F-4, 
10 weeks) 
The length of time for individual TTP/HSCT-TMA patient participation in Stage 2 (if he or 
she does not continue to Stage 3) will be approximately 14 to 18 weeks, depending on the time 
from screening to the first dose of OMS721 administration. Patients entering Stage 3 will not 
undergo the Follow-up visits in Stage 2. 
The Stage 3 study schedule for the TTP/HSCT-TMA cohort includes 8 visits across 
2 periods: 
Period 2 (continued from Stage 2) – Treatment (Visit T-5 to Visit T-8, 4 weeks) 
Period 3 – Follow-up (Visit F-1 to Visit F-4, 6 weeks) 
The length of time for individual TTP/HSCT-TMA patient participation in Stage 3 will be 
approximately 10 weeks, and the total length of time in Stage 2 and Stage 3 will be 

Protocol No. OMS721-TMA-001 (A11.1) 
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approximately 14 to18 weeks, depending on the time from screening to the first dose of 
OMS721 administration in Period 2. 
As of Amendment 10 of this protocol, TTP enrollment was closed. As of Amendment 11 of 
this protocol, enrollment in the study has been completed. 
The coronavirus associated lockdown situation in various countries has created uncertainty in 
the ability to collect all follow-up data and resolve all queries on a few patients enrolled in the 
study. When adequate data on the primary and secondary endpoints is available, the database 
will be locked for interim analyses and creation of an interim CSR to enable regulatory 
submission for drug approval. Efforts will continue to collect additional follow-up data and 
resolve any outstanding queries. 
Number of Patients (Planned): 
Approximately 60 
Diagnostic Criteria and Main Criteria for Inclusion: 
Patients may be included in the study only if they meet all of the following criteria: 
1. Competent to provide informed consent. 
2. Voluntarily provide informed consent in accordance with local regulations and 
governing ethics committee requirements prior to any procedures or evaluations 
performed specifically for the sole purpose of the study. 
3. Are age ≥ 18 at screening (Visit 1). 
4. Have a diagnosis of one of the following TMAs: 
• 
As of Amendment 10 of this protocol, enrollment of aHUS patients was 
closed. Primary aHUS, diagnosed clinically and having ADAMTS13 
activity > 10% in plasma. Patients are eligible with or without a 
documented complement mutation or anti-complement factor H 
(anti-CFH) antibody. Patients are categorized according to their response 
to plasma therapy (plasma exchange or plasma infusion): 
o Plasma therapy-resistant aHUS patients must have all of the 
following: 1) screening platelet count < 150,000/µL despite at least 
4 plasma therapy treatments prior to screening; 2) evidence of 
microangiopathic hemolysis (presence of schistocytes, serum LDH 
> upper limit of normal [ULN], haptoglobin < lower limit of 
normal [LLN]); and 3) serum creatinine > ULN. 
o Chronic plasma therapy-responsive aHUS patients (plasma therapy- 
sensitive) must require at least once-per-week plasma therapy for 
4 weeks before first dose of OMS721 with serum 
creatinine > ULN. 
• 
As of Amendment 10 of this protocol, enrollment of TTP patients was 
closed. TTP defined as having all of the following: 
o Platelet count < 150,000/µL 
o Evidence of microangiopathic hemolysis (presence of schistocytes, 
serum LDH > ULN, or haptoglobin < LLN) 

Protocol No. OMS721-TMA-001 (A11.1) 
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o ADAMTS13 activity ≤ 10% during the current episode of TTP or 
historically 
• 
Persistent HSCT-associated TMA defined as having all of the following at 
least 2 weeks following modification or discontinuation of calcineurin 
inhibitor treatment or at least 30 days after the transplant: 
o Platelet count < 150,000/µL 
o Evidence of microangiopathic hemolysis (presence of schistocytes, 
serum LDH > ULN, or haptoglobin < LLN) 
o Renal dysfunction (doubling of serum creatinine from 
pre-transplant). 
5. No clinically apparent alternative explanation for thrombocytopenia and anemia. 
6. If sexually active and of childbearing potential, must agree to practice a highly 
effective method of birth control until the end of the study, defined as one which 
results in a low failure rate (i.e., less than 1% per year) when used consistently and 
correctly, such as implants, injectables, combined oral contraceptives, some 
intrauterine devices, sexual abstinence, or vasectomized partner. 

11 
 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
 
Exclusion Criteria: 
Patients will be excluded from the study for any of the following reasons: 
1. Had eculizumab therapy within 3 months prior to screening. 
2. Have Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome. 
3. Have a positive direct Coombs test. 
4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy 
(prophylactic antimicrobial therapy administered as standard of care is allowed). 
5. Baseline resting hea1t rate< 45 beats per minute or> 115 beats per minute. 
6. Baseline QTcF > 470 milliseconds. 
7. Have malignant hype1tension (diastolic blood pressure> 120 1llill Hg with bilateral 
hemonhages or "cotton-wool" exudates on funduscopic examination). 
8. Have a poor prognosis with a life expectancy of less than 3 months in the opinion of 
the Investigator. 
9. Are pregnant or lactating. 
10. Have received treatment with an investigational dmg or device within 4 weeks prior to 
screemng. 
11. Have abno1mal liver ftmction tests defined as alanine aminotransferase or aspaitate 
aminotransferase> 5 times ULN. 
12. Have a positive test for human immunodeficiency vims antibodies. 
13. Are an employee of Omeros, an Investigator, a study staff member, or their illllllediate 
family member. 
14. Have a known hypersensitivity to any constituent of the product. 
15. Presence of any condition that the Investigator believes would put the patient at risk. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Duration of Treatment: 
Stage I -Four weekly doses. As of Amendment 11 of this protocol, Stage 1 is complete. 
Stage 2-Twelve weekly doses for aHUS. As of Amendment 10 of this protocol, aHUS 
emollment was closed. 
 
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Protocol No. OMS721-TMA-001 (A11.1) 
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Stage 2 – Four weekly doses for TTP/HSCT-TMA. As of Amendment 10 of this protocol, TTP 
enrollment was closed. 
Stage 3 – Additional 12 weekly doses for aHUS. As of Amendment 10 of this protocol, aHUS 
enrollment was closed. 
Stage 3 – Additional 4 weekly doses for TTP/HSCT-TMA. As of Amendment 10 of this 
protocol, TTP enrollment was closed. 
As of Amendment 11 of this protocol, enrollment in the study has been completed. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable 
Study Endpoints: 
The co-primary endpoints are: 
• Safety as assessed by adverse events (AEs), vital signs, electrocardiograms (ECGs), 
and clinical laboratory tests (includes patients with HSCT-TMA, aHUS, and TTP) 
• For HSCT-TMA patients, response to OMS721 treatment. A responder is defined 
as a patient with HSCT-TMA who demonstrates improvement in laboratory TMA 
markers (platelet count and LDH) and clinical benefit (either improvement in organ 
function or reduction in transfusion burden). The specific criteria are defined as 
follows: 
− Improvement in laboratory TMA markers: 
 Platelet count: 
• For patients with baseline platelet count ≤ 20,000/μL: 
o  Tripling of baseline platelet count 
and 
o Post baseline platelet count > 30,000/μL 
and 
o No platelet transfusions 2 days before and on the day of 
the platelet count collection 
• For patients with baseline platelet count > 20,000/μL 
o Increase in platelet count ≥ 50% 
and 
o Post baseline platelet count > 75,000/μL 
and 
o No platelet transfusions 2 days before and on the day of 
the platelet count collection 
and 

Protocol No. OMS721-TMA-001 (A11.1) 
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 LDH: 
• LDH < 1.5 x ULN 
and 
− Improvement in clinical status: 
 Improvement in organ function as evidenced by any of the following: 
• Improvement in renal function: 
•  Reduction of creatinine > 40% 
or 
• Creatinine < ULN and reduction of creatinine > 20% 
or 
• Discontinuation of renal replacement therapy (RRT) 
or 
• Improvement in pulmonary function: 
• Extubation and discontinuation of ventilator support 
or 
• Discontinuation of non-invasive mechanical ventilation 
(continuous positive pressure ventilation) 
or 
• Improvement in neurological function: 
• Improvement in reversible neurological conditions (e.g., 
cessation of seizures) 
or 
• Stabilization of irreversible neurological conditions (e.g., 
stability of neurological deficits following stroke without 
further deterioration or subsequent strokes) 
or 
• Improvement in gastrointestinal function (gastrointestinal 
HSCT-TMA will require diagnosis by tissue biopsy): 
• Improvement measured by improvement in the 
gastrointestinal measures in the Mount Sinai Acute 
GVHD International Consortium (MAGIC) criteria 
or 
 Freedom from transfusion (no transfusions for at least 4 weeks from the 
last transfusion except for patients who died within 4 weeks of the last 

Protocol No. OMS721-TMA-001 (A11.1) 
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transfusion; only evaluated in patients who received transfusions within 
the 2 weeks prior to or on the first OMS721 dose date) 
The secondary endpoints of this study are to evaluate the following in patients with HSCT- 
TMA treated with OMS721: 
• 100-day survival, from the date of TMA diagnosis 
• Overall survival, from the date of TMA diagnosis 
• Duration of response defined as the number of days from the first response date to 
the first relapse date 
• Freedom from platelet transfusion defined as no platelet transfusions for at least 
4 weeks following the last platelet transfusion except for patients who died within 
4 weeks of the last platelet transfusion (only evaluated in patients who had platelet 
transfusions within the 2 weeks prior to or on the first OMS721 dose date) 
• Freedom from red blood cell (RBC) transfusion defined as no RBC transfusions for 
at least 4 weeks following the last RBC transfusion except for patients who died 
within 4 weeks of the last RBC transfusion (only evaluated in patients who had 
RBC transfusions within the 2 weeks prior to or on the first OMS721 dose date) 
• Change from baseline in platelet count (post baseline platelet counts without 
platelet transfusions 2 days before and on the day of the platelet count collection 
will be used) over time using central laboratory values 
• Change from baseline in LDH over time using central laboratory values 
• Change from baseline in haptoglobin over time using central laboratory values 
• Change from baseline in hemoglobin (Hgb) (post baseline Hgb without RBC and 
whole blood transfusions 6 days before and on the day of the Hgb collection will be 
used) over time using central laboratory values 
• Change from baseline in creatinine over time using central laboratory values 
• The PK of multiple-dose administration of OMS721 (this will be assessed in 
patients with HSCT-TMA as well as patients with aHUS and TTP) 
• The PD of multiple-dose administration of OMS721 (this will be assessed in 
patients with HSCT-TMA as well as patients with aHUS and TTP) 
• The immunogenicity of multiple-dose administration of OMS721 (this will be 
assessed in patients with HSCT-TMA as well as patients with aHUS and TTP) 
Statistical Methods: 
Sample Size 

Protocol No. OMS721-TMA-001 (A11.1) 
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In Stage 1 of the study, 3 patients per dose-escalation cohort is a common scheme and is 
considered to be sufficient in combination with data from the Phase 1 study to allow selection 
of a dose for Stage 2. 
In Stage 2, the sample size for each cohort (aHUS and HSCT-associated TMA/TTP) is 
determined by comparison to the total sample size of uncontrolled Phase 2 studies that 
provided sufficient data for approval of eculizumab for the treatment of aHUS [Legendre 
2013]. This sample size is considered adequate in these orphan diseases to identify treatment 
effects in uncontrolled studies. 
It is expected that approximately 28 HSCT-TMA patients enrolled before Protocol 
Amendment 11 will be included to support a regulatory approval. The width of the exact 95% 
confidence interval (CI) for the response rate based on 28 HSCT-TMA patients ranges from 
12.3% to 38.7%. If the observed response rate is 50%, the exact 95% CI is 30.6% to 69.4%. 
Efficacy 
A patient is a responder if this patient meets the responder criteria at any time post baseline 
during the study. Analysis of the primary efficacy endpoint will use a non-responder 
imputation to impute missing or incomplete data to evaluate response. The number and 
percentage of responders will be summarized with exact 95% CI (Clopper-Pearson) for the 
Full Analysis Set (FAS) and Per-protocol Analysis Set (PAS) populations. The FAS 
population will include all HSCT-TMA patients who receive any amount of study drug. The 
PAS population will include all HSCT-TMA patients who received at least 4 weeks of study 
treatment (treatment period is greater than or equal to 28 days). Each criteria of the response 
will also be summarized in the same fashion. 
Pharmacokinetic Analyses 
Plasma concentrations of OMS721 and PD measures will be provided in listings. These data 
will be used in integrated population PK/PD analyses across studies. A PK/PD analysis plan 
will document the analyses. 
Anti-Drug Antibody Response 
The number and percentage of patients with anti-drug antibody (ADA) will be summarized by 
disease, dose, Drug Product formulation, and time. Potential effects of ADA on PK and PD 
will be evaluated in integrated population PK/PD analyses, which will be documented in the 
PK/PD analysis plan. 
Pharmacodynamic Analyses 
The PD effect will be assayed ex vivo by quantifying lectin pathway activity and summarized 
by disease, dose, and time. 
Pharmacokinetic/Pharmacodynamic Relationship 
The correlation of serum concentration of OMS721 and PD effect will be evaluated. 
Safety Analyses 
All patients who receive any study drug will be included in the safety analyses. The safety 
data, including AEs, vital signs, laboratory data, and reasons for withdrawal from study, will 

Protocol No. OMS721-TMA-001 (A11.1) 
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16 
 
 
 
 
be descriptively summarized by disease and dose. Adverse events will be coded according to 
preferred term and system/organ class using the Medical Dictionary for Regulatory Activities 
AE coding dictionary. 

Protocol No. OMS721-TMA-001 (A11.1) 
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3. 
TABLE OF CONTENTS AND LIST OF TABLES AND FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ............................................................................................................... 1 
1.1. 
Investigator Agreement ................................................................................................ 2 
1.2. 
Contact Information ..................................................................................................... 3 
1.3. 
Amendments ................................................................................................................ 4 
2. 
SYNOPSIS ................................................................................................................... 6 
3. 
TABLE OF CONTENTS AND LIST OF TABLES AND FIGURES ...................... 17 
TABLE OF CONTENTS .............................................................................................................. 17 
LIST OF TABLES ........................................................................................................................ 22 
LIST OF FIGURES ....................................................................................................................... 22 
4. 
LIST OF ABBREVIATIONS .................................................................................... 24 
5. 
INTRODUCTION...................................................................................................... 26 
5.1. 
Background ................................................................................................................ 26 
5.1.1. 
Description of OMS721 ............................................................................................. 26 
5.1.2. 
Indication – Thrombotic Microangiopathies .............................................................. 27 
5.1.2.1. 
Atypical Hemolytic Uremic Syndrome ...................................................................... 28 
5.1.2.2. 
Thrombotic Thrombocytopenic Purpura .................................................................... 28 
5.1.2.3. 
Hematopoietic  Stem  Cell  Transplant-Associated  Thrombotic 
Microangiopathy ........................................................................................................ 29 
5.1.3. 
Scientific Rationale .................................................................................................... 30 
5.2.30 
5.2.1.30 
5.2.2.31 
5.3.32 
5.3.1.32 
5.3.1.1.32 
5.3.1.2.33 
5.3.1.3.34 
5.3.2.34 
6. 
STUDY PURPOSE AND OBJECTIVES .................................................................. 34 
6.1. 
Primary Study Objectives .......................................................................................... 34 

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6.2. 
Secondary Study Objectives ....................................................................................... 35 
6.3. 
Exploratory Objectives................................................................................................ 35 
7. 
STUDY DESIGN AND PROCEDURES ................................................................... 35 
7.1. 
Summary of Study Design .......................................................................................... 35 
7.1.1. 
Stage 1 ......................................................................................................................... 37 
7.1.2. 
Stage 2 and Stage 3 ..................................................................................................... 38 
7.2. 
Study Rationale ........................................................................................................... 40 
7.2.1.41 
7.3. 
Study Endpoints .......................................................................................................... 44 
7.3.1. 
Primary Endpoints ....................................................................................................... 44 
7.3.2. 
Secondary Endpoints ................................................................................................... 45 
7.3.3. 
Exploratory Endpoints ................................................................................................ 46 
7.4. 
Study Extension .......................................................................................................... 46 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS .............................................. 47 
8.1. 
Patient Inclusion Criteria............................................................................................. 47 
8.2. 
Patient Exclusion Criteria ........................................................................................... 48 
8.3. 
Patient Withdrawal Criteria......................................................................................... 49 
8.3.1. 
Early Discontinuation of Study Drug Administration ................................................. 49 
8.3.2. 
Patient Withdrawal from the Study ............................................................................. 49 
8.3.3. 
Notification of Withdrawal ......................................................................................... 50 
9. 
STUDY DRUG AND TREATMENT OF PATIENTS .............................................. 50 
9.1. 
OMS721 Drug Product ............................................................................................... 50 
9.1.1. 
Packaging and Labeling of Drug Product ................................................................... 50 
9.1.2. 
Blinding ....................................................................................................................... 51 
9.1.3. 
Study Drug Dose Preparation ...................................................................................... 51 
9.1.3.1. 
Supplemental Drug Administration for Patients Receiving Plasma Therapy ............. 51 
9.1.4. 
Storage and Handling of Drug Product ....................................................................... 52 
9.1.5. 
Study Drug Accountability.......................................................................................... 52 
9.2. 
Return of Drug Product ............................................................................................... 52 
10. 
STUDY PROCEDURES ............................................................................................ 52 
10.1. 
Study Schedule ............................................................................................................ 52 
10.1.1. 
Stage 1 ......................................................................................................................... 52 

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10.1.1.1. 
Stage 1 Screening Visit (Visit 1, Up to Day –28) ....................................................... 53 
10.1.1.2. 
Stage 1 Baseline Platelet Counts ................................................................................. 54 
10.1.1.3. 
Stage 1 Method of Assigning Patients to Treatment Cohorts ..................................... 54 
10.1.1.4. 
Stage 1 Treatment – Week 1 (Visit 2, Day 1) ............................................................. 54 
10.1.1.5. 
Stage 1 Treatment – Week 2 (Visit 3, Day 8 ± 1) ....................................................... 55 
10.1.1.6. 
Stage 1 Treatment – Week 3 (Visit 4, Day 15 ± 1) ..................................................... 55 
10.1.1.7. 
Stage 1 Treatment – Week 4 (Visit 5, Day 22 ± 1) ..................................................... 56 
10.1.1.8. 
Stage 1 Follow-Up (Visit 6, Day 29 ± 1) .................................................................... 57 
10.1.1.9. 
Stage 1 Follow-Up (Visit 7, Day 36 ± 2) .................................................................... 57 
10.1.1.10. Stage 1 Follow-Up (Visit 8, Day 50 ± 3) .................................................................... 57 
10.1.1.11. Stage 1 Follow-Up End of Study (Visit 9, Day 78 ± 7) .............................................. 58 
10.1.2. 
Stage 2 and Stage 3 ..................................................................................................... 58 
10.1.2.1. 
Stage 2 Screening Visit (Visit 1, Up to Day –28) ....................................................... 58 
10.1.2.2. 
Stage 2 Baseline Platelet Counts ................................................................................. 59 
10.1.2.3. 
Stage 2 and Stage 3 Method of Assigning Patients to Treatment Cohorts ................. 59 
10.1.2.4. 
Stage 2 Treatment – Week 1 (Visit T-1, Day 1) ......................................................... 60 
10.1.2.5. 
Stage 2 and Stage 3 Treatment – Visit T-N (where N is > 1 [the week of 
treatment after the week of the first dose]) ................................................................. 61 
10.1.2.6. 
Stage 2 or Stage 3 Follow-Up – Visit F-N (where N is the number of the 
follow-up visit) ............................................................................................................ 61 
10.1.3. 
Early Termination ....................................................................................................... 61 
10.1.4. 
Unscheduled Visits - Supplemental OMS721 Administration for Patients 
Receiving Plasma Therapy or Adverse Events ........................................................... 62 
10.1.5. 
Timing of Study Procedures ....................................................................................... 62 
10.1.5.1. 
Stage 1 ......................................................................................................................... 62 
10.1.5.2. 
Stage 2 and Stage 3 ..................................................................................................... 63 
10.1.6. 
Timing of Study Visits ................................................................................................ 63 
10.2. 
Concomitant Therapy .................................................................................................. 63 
10.2.1. 
Allowed Concomitant Therapies ................................................................................ 63 
10.2.1.1. 
Plasma Therapy ........................................................................................................... 63 
10.2.1.2. 
Renal Dialysis ............................................................................................................. 63 
10.2.1.3. 
Immunosuppressive Medications ................................................................................ 64 
10.2.1.4. 
Erythrocyte Stimulating Agents .................................................................................. 64 

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10.2.1.5. 
Suspected Infection ..................................................................................................... 64 
10.2.2. 
Prohibited Concomitant Therapies .............................................................................. 64 
10.2.2.1. 
Eculizumab .................................................................................................................. 64 
10.3. 
Treatment Compliance ................................................................................................ 64 
10.3.1. 
Definition of Departure from Protocol ........................................................................ 64 
10.4. 
Safety Monitoring ....................................................................................................... 64 
10.4.1. 
Dose Escalation Review .............................................................................................. 64 
10.4.2. 
Data Monitoring Committee ....................................................................................... 65 
11. 
ASSESSMENT OF EFFICACY ................................................................................. 65 
11.1. 
Primary Efficacy Measures ......................................................................................... 65 
11.2. 
Secondary Efficacy Measures ..................................................................................... 65 
11.3. 
Pharmacokinetics Measures ........................................................................................ 65 
11.4. 
Pharmacodynamics Measures ..................................................................................... 65 
11.5. 
Immunogenicity Measures .......................................................................................... 66 
11.6. 
Exploratory Measures ................................................................................................. 66 
12. 
ASSESSMENT OF SAFETY ..................................................................................... 66 
12.1. 
Safety Parameters ........................................................................................................ 66 
12.1.1. 
Laboratory Tests ......................................................................................................... 66 
12.1.2. 
Other Safety Measures ................................................................................................ 67 
12.2. 
Definition of Adverse Events ...................................................................................... 67 
12.2.1. 
Definition of Adverse Events ...................................................................................... 67 
12.2.2. 
Definitions of Severity ................................................................................................ 68 
12.2.3. 
Relationship to Study Drug ......................................................................................... 68 
12.2.4. 
Assessment of the Clinical Outcome of Adverse Events ............................................ 68 
12.3. 
Reporting Adverse Events .......................................................................................... 69 
12.3.1. 
Adverse Event Reporting ............................................................................................ 69 
12.3.2. 
Serious Adverse Event Reporting ............................................................................... 70 
12.3.3. 
Reporting of Serious Adverse Events to Regulatory Agencies .................................. 70 
12.3.4. 
Pregnancy and Overdose Reporting ............................................................................ 70 
12.4. 
Type and Duration of the Follow-Up of Patients After Adverse Events .................... 71 
12.5. 
Appropriateness of Measurements .............................................................................. 71 
12.5.1. 
Efficacy Measures ....................................................................................................... 71 

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12.5.2. 
Pharmacokinetic Measures.......................................................................................... 71 
12.5.3. 
Pharmacodynamic Measures ....................................................................................... 71 
12.5.4. 
Immunogenicity Measures .......................................................................................... 71 
12.5.5. 
Exploratory Measures ................................................................................................. 71 
12.5.6. 
Safety Measures .......................................................................................................... 71 
13. 
STATISTICS .............................................................................................................. 72 
13.1. 
Determination of Sample Size .................................................................................... 72 
13.2. 
Statistical and Analytical Plans ................................................................................... 72 
13.2.1. 
General Considerations ............................................................................................... 72 
13.2.1.1. 
Handling of Missing Data ........................................................................................... 73 
13.2.1.2. 
Analysis Populations ................................................................................................... 73 
13.2.2. 
Patient Disposition ...................................................................................................... 73 
13.2.3. 
Patient Characteristics ................................................................................................. 73 
13.2.4. 
Treatment Compliance ................................................................................................ 73 
13.2.5. 
Efficacy Analyses ....................................................................................................... 73 
13.2.5.1. 
Analysis of Primary Efficacy Endpoint ...................................................................... 73 
13.2.5.2. 
Analysis of Secondary Efficacy Endpoints ................................................................. 74 
13.2.6. 
Pharmacokinetic Analyses .......................................................................................... 75 
13.2.7. 
Pharmacodynamic Analyses ....................................................................................... 75 
13.2.8. 
Exploratory Analyses .................................................................................................. 75 
13.2.9. 
Safety Analyses ........................................................................................................... 75 
13.2.9.1. 
Extent of Exposure ...................................................................................................... 75 
13.2.9.2. 
Adverse Events ........................................................................................................... 75 
13.2.9.3. 
Clinical Laboratory Results ........................................................................................ 76 
13.2.9.4. 
Vital Signs ................................................................................................................... 76 
13.2.9.5. 
Electrocardiogram ....................................................................................................... 76 
13.2.10. 
Interim Analyses ......................................................................................................... 77 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ......................................... 77 
14.1. 
Study Monitoring ........................................................................................................ 77 
14.2. 
Audits and Inspections ................................................................................................ 77 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................... 78 
15.1. 
Monitoring .................................................................................................................. 78 

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15.2. 
Auditing ...................................................................................................................... 79 
16. 
ETHICS ....................................................................................................................... 79 
16.1. 
Ethics Review ............................................................................................................. 79 
16.2. 
Ethical Conduct of the Study ...................................................................................... 79 
16.2.1. 
Regulatory Considerations .......................................................................................... 79 
16.2.2. 
Investigator Information .............................................................................................. 79 
16.2.3. 
Protocol Amendments and Study Termination. .......................................................... 80 
16.2.4. 
Participant Confidentiality .......................................................................................... 80 
16.2.5. 
Clinical Trial Agreement............................................................................................. 80 
16.3. 
Informed Consent Process .......................................................................................... 80 
16.4. 
Investigator Reports .................................................................................................... 81 
17. 
DATA HANDLING AND RECORDKEEPING ........................................................ 81 
17.1. 
Data Management Responsibilities ............................................................................. 81 
17.2. 
Data Capture Methods ................................................................................................ 81 
17.3. 
Source Documents ...................................................................................................... 81 
17.4. 
Retention of Records ................................................................................................... 82 
18. 
REFERENCES ............................................................................................................ 83 
19. 
APPENDICES ............................................................................................................ 87 
19.1. 
Study Schedule of Events – Stage 1 ........................................................................... 87 
19.2. 
aHUS Cohort: Stages 2 and 3 Study Schedule of Events ........................................... 89 
19.3. 
TTP/HSCT-TMA Cohort: Stages 2 and 3 Study Schedule of Events ........................ 92 
19.4. 
Supplemental Data Collection (HSCT-TMA Patients Enrolled Under 
Amendment 10 or Earlier) .......................................................................................... 95 
19.5. 
Laboratory Measure Schedule .................................................................................. 103 
 
LIST OF TABLES 
Table 1: 
OMS721-TMA-001 Treatment Stages and Cohorts .................................................. 37 
Table 2: 
Additional Data Collection ........................................................................................ 97 
 
LIST OF FIGURES 
Figure 1: 
Stage 1 Study Design Schematic ............................................................................... 38 
Figure 2: 
Stage 2 Study Design Schematic (aHUS Cohort) ....................................................... 38 

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Figure 3: 
Stage 3 Study Design Schematic (aHUS Cohort) ....................................................... 39 
Figure 4: 
Stage 2 Study Design Schematic (HSCT-TMA Cohort) ............................................ 39 
Figure 5: 
Stage 3 Study Design Schematic (HSCT-TMA Cohort) ............................................ 40 
Figure 6: ......................................................................................................................................... 42 
Figure 7: ......................................................................................................................................... 43 
Figure 8: ......................................................................................................................................... 43 
Figure 9: 
Additional Data Collection Schematic ........................................................................ 96 

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4. 
LIST OF ABBREVIATIONS 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviations and Specialist Terms 
 
Abbreviation or Specialist Term 
Explanation 
ADA 
anti-drug antibody 
ADAMTS13 
a disintegrin and metalloproteinase with a thrombospondin type 1 
motif, member 13 
AE 
adverse event 
aHUS 
atypical hemolytic uremic syndrome 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under time-concentration curve 
BIW 
twice weekly 
BP 
blood pressure 
BTD 
Breakthrough Therapy Designation 
C3 
Complement component 3 
C3a 
complement component 3a 
C5a 
complement component 5a 
C5b-9 
complement components 5b-9, also known as the membrane 
attack complex 
CFH 
complement factor H 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum concentration 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAH 
diffuse alveolar hemorrhage 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
EMA 
European Medicines Agency 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GVHD 
graft-versus-host disease 
Hgb 
hemoglobin 
HIPAA 
Health Insurance and Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplant 
HUS 
hemolytic uremic syndrome 
ICH 
International Conference on Harmonisation 
IgAN 
immunoglobulin A nephropathy 
IgG4 
immunoglobulin G4 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 

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Abbreviation or Specialist Term 
Explanation 
IV 
intravenous 
λz 
elimination rate constant 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
LLOQ 
lower limit of quantitation 
mAb 
monoclonal antibody 
MASP 
mannan-binding lectin-associated serine protease 
MBL 
mannan-binding lectin 
MedRA 
Medical Dictionary for Regulatory Activities 
nM 
nanomolar 
NOAEL 
no observed adverse effect level 
OS 
overall survival 
PAS 
Per-protocol Patient Set 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
QW 
once weekly 
RBC 
red blood cell 
RR 
respiratory rate 
RRT 
renal replacement therapy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SOC 
System Organ Class 
STEC 
Shiga toxin-producing E. coli 
t½ 
elimination half-life 
TMA 
thrombotic microangiopathy 
TTP 
thrombotic thrombocytopenic purpura 
ULN 
upper limit of normal 
VOD 
veno-occlusive disease 

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5. 
INTRODUCTION 
5.1. 
Background 
This study was originally designed to provide preliminary information on the safety and potential 
efficacy of OMS721 for the treatment of thrombotic microangiopathies (TMAs). As originally 
designed, this study included 3 types of TMA—hematopoietic stem cell transplant-associated 
TMA (HSCT-TMA), atypical hemolytic uremic syndrome (aHUS), and thrombotic 
thrombocytopenic purpura (TTP)—and included 2 stages: a dose-escalation stage and a cohort 
expansion stage. A separate Phase 3 study has been initiated for patients with aHUS (Study 
OMS721-HUS-002); therefore, patients with aHUS are no longer being enrolled in Study 
OMS721-TMA-001. Patients with TTP are also no longer being enrolled in this study because it 
was difficult to observe a treatment effect over the current standard of care. 
Improvements in laboratory TMA markers have been observed in patients with HSCT-TMA in 
this ongoing study, and marked unexpected improvements were observed in some patients with 
life-threatening disease. In support of an application for Breakthrough Therapy Designation 
(BTD) from the United States Food and Drug Administration (FDA), Omeros Corporation 
(Omeros, Sponsor) compared survival in OMS721-treated patients with a literature-based 
historical control. A substantial survival improvement was observed, and BTD was granted by 
FDA for the treatment of patients with HSCT-TMA who have persistent TMA despite 
modification of immunosuppressive therapy. The Sponsor has had continued discussions with 
regulatory agencies internationally regarding approval of OMS721 for the treatment of HSCT- 
TMA. These discussions have focused on approval based on patients with HSCT-TMA treated in 
this study as well as patients with HSCT-TMA treated under compassionate use or expanded- 
access protocols. Efficacy will be assessed by response to treatment evaluated by organ function 
or transfusion burden and laboratory measures of TMA. 
Amendment 11 of this protocol provides for collection of additional data for OMS721-treated 
patients with HSCT-TMA to determine patient responses and longer-term outcomes and to 
support marketing authorization applications. The additional data to be collected are limited to 
patient demographics and baseline conditions, donor characteristics, the transplant procedure, 
concomitant medications, TMA-related laboratory measures, transfusions, transplant 
complications, and outcomes (see Section 19.4 for additional detail). 
 
5.1.1. 
Description of OMS721 
Omeros Corporation (Omeros, Sponsor) is developing OMS721, a human immunoglobulin G4 
(IgG4) monoclonal antibody (mAb) to mannan-binding lectin-associated serine protease 2 
(MASP-2), for the treatment of lectin complement pathway-mediated diseases. 
The primary function of the complement system is to protect the host against infectious agents 
[Ricklin 2010]. This complex system targets immune and inflammatory responses to surfaces 
that display molecular patterns not usually present on healthy host cells. Activation of the 
complement system initiates a series of proteolytic steps that culminate in the formation of a 
membrane attack complex, which disrupts the membranes of targeted cells causing lysis and cell 
death. In addition, complement activation triggers opsonization and the recruitment of 
phagocytic cells to further engage the infectious agents. 

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Three pathways activate complement in response to distinct initiating events: the classical, lectin, 
and alternative pathways. The classical pathway is triggered by immune complexes and mediates 
important immune effector functions. The lectin pathway can be activated by specific types of 
cell-surface carbohydrate patterns that are usually found on microbes, but not on healthy host 
cell surfaces. These carbohydrate patterns are also found on injured host tissue. Lectin pathway 
activation is initiated by members of the MASP enzyme family. These proteases are synthesized 
as proenzymes that, in blood, form a complex with lectins, such as mannan-binding lectin 
(MBL), ficolins, and collectins. These lectins bind to carbohydrate patterns on foreign or injured 
host cell surfaces, targeting MASPs to their site(s) of action and leading to activation of MASPs. 
There are 3 known MASPs: MASP-1, MASP-2, and MASP-3 [Yongqing 2012]. MASP-2 is 
thought to be the key enzyme responsible for activation of the lectin pathway; upon activation, it 
cleaves its substrates, complement component 2 and complement component 4, both of which 
contribute to the formation of the complement component 3 (C3) convertase, which is a central 
component of complement activation. 
OMS721 blocks the action of MASP-2, thereby inhibiting the lectin pathway of complement 
activation. The alternative pathway, by contrast, is continuously activated at a low level and is 
kept in check by a series of regulatory proteins. The alternative pathway also acts as an 
amplification loop, increasing the host immune response following activation of the classical 
and/or the lectin pathways. While the complement system supports innate host defense against 
pathogens, mutations in the genome or tissue damage can cause inappropriate activation and lead 
to serious disease, e.g., TMA, in which endothelial damage as well as fibrin and platelet-rich 
thrombi in the microvasculature lead to end-organ damage. 
OMS721 is a fully human IgG4 mAb directed against MASP-2. OMS721 avidly binds to 
recombinant MASP-2 (apparent equilibrium dissociation constant approximately 100 picomolar) 
and exhibits greater than 5000-fold selectivity over the homologous proteins complement 
component 1s, complement component 1r, and MASP-1. In functional assays, OMS721 inhibits 
the human lectin pathway with nanomolar (nM) potency (concentration leading to 50% 
inhibition of approximately 3 nM) but has no significant effect on the classical or alternative 
complement pathways. OMS721 administered either by intravenous (IV) or subcutaneous (SC) 
injection to mice, non-human primates, and humans resulted in high plasma concentrations that 
were associated with suppression of lectin pathway activation in an ex vivo assay. OMS721 
treatment reduced complement components 5b-9 (C5b-9, also known as the membrane attack 
complex) deposition and thrombus formation in in vitro models of TMA and inhibited thrombus 
formation in a mouse model of TMA, thus demonstrating that OMS721 is a potential candidate 
for the treatment of diseases that result from inappropriate lectin pathway activation. 
5.1.2. 
Indication – Thrombotic Microangiopathies 
Based on mechanism of action and results of nonclinical studies, OMS721 is in development for 
the treatment of TMA and other diseases potentially mediated by the lectin pathway of 
complement. Thrombotic microangiopathy is a descriptive name for histologic abnormalities 
consisting of thickening of arteriole and capillary walls with endothelial damage, subendothelial 
accumulation of protein and debris, and fibrin and platelet-rich thrombi occluding vessel lumina. 
The disorders that are associated with TMA are characterized by systemic or intrarenal 
aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. 

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Thrombotic microangiopathies may present as a primary condition or in association with other 
diseases. The classification scheme for TMA has evolved as the etiology and pathophysiology of 
distinct patient populations have been established [Besbas 2006]. Thrombotic microangiopathies 
can present with several clinical presentations, including TTP, aHUS, HSCT-TMA, and TMA 
caused by cancer chemotherapy, calcineurin inhibitor administration, and systemic lupus 
erythematosus. 
 
5.1.2.1. 
Atypical Hemolytic Uremic Syndrome 
Hemolytic uremic syndrome (HUS) occurs primarily in children following a diarrheal illness and 
is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal 
failure. A major category of TMA is Shiga toxin-producing Escherichia coli-associated 
hemolytic uremic syndrome (STEC-HUS), which has also been referred to as diarrhea + HUS or 
typical HUS. Another type of HUS is atypical HUS (aHUS), which is a recurrent illness often 
associated with complement dysregulation. 
Atypical HUS is a rare, life-threatening disease that, if left untreated, results in end-stage renal 
disease in 50% of patients within 1 year of diagnosis [Loirat 2011]. Dysregulation of the 
complement system is central to aHUS pathogenesis, and genetic abnormalities in complement 
genes have been identified in more than 60% of all aHUS patients. Certain mutant variants of the 
genes encoding complement factor H, factor I, factor B, and C3 have been identified as major 
risk factors; these alleles lead to increased complement activity. This complement hyperactivity 
is linked, by a mechanism that is not well understood, to a procoagulant phenotype on kidney 
endothelial cells that promotes the formation of microthrombi in the renal microvasculature and 
results in rapidly declining renal function in about half of affected individuals. Familial studies 
have shown that aHUS has incomplete penetrance and that approximately 50% of the carriers of 
the high-risk alleles develop the condition [Sullivan 2010]. It is thought that certain precipitating 
factors are needed to trigger aHUS. Such precipitating factors include infection, malignancies, 
use of endothelium-damaging drugs, transplantation, and pregnancy. Many of these precipitating 
factors are linked to endothelial cell activation, stress, or injury. Atypical HUS is treated with 
plasma therapy (plasma exchange or plasma infusion) or eculizumab, an anti-C5 mAb. 
 
5.1.2.2. 
Thrombotic Thrombocytopenic Purpura 
Thrombotic thrombocytopenic purpura was initially described as a syndrome that occurs 
primarily in adults characterized by a pentad of signs and symptoms consisting of 
thrombocytopenia, microangiopathic hemolytic anemia, neurologic and renal abnormalities, and 
fever. Thrombotic thrombocytopenic purpura is characterized by a severe deficiency of the von 
Willebrand factor-cleaving protease termed ADAMTS13 (a disintegrin and metalloproteinase 
with a thrombospondin type 1 motif, member 13). 
In practice, the clinical distinction between TTP and HUS is not always clear [Moake 2002]. 
Thrombotic thrombocytopenic purpura has many of the same clinical and laboratory features as 
aHUS but is associated with low ADAMTS13 activity (≤ 5% to 10% of normal depending on the 
assay) due to genetic mutations or autoantibodies to the protein [George 2006]. It is typically 
associated with lower platelet counts, which can be severe. Plasma exchange is the standard 
treatment for TTP, with some patients requiring the addition of corticosteroids and/or rituximab 
to achieve an adequate response. 

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5.1.2.3. 
Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy 
Hematopoietic stem cell transplant-associated TMA is a serious multisystem disease affecting 
post-transplant outcomes [Jodele 2015]. The kidney is the most commonly affected organ, but 
the disease also occurs in the lung, central nervous system, gastrointestinal tract, and serosal 
tissues. The reported incidence of HSCT-TMA varies in retrospective and pathological reviews, 
but a prospective study of 100 pediatric patients found an incidence of 39%, 79% of which had 
features portending a poor prognosis [Jodele 2014a]. A recent large retrospective chart review of 
adult patients also reported an incidence of 39% [Postalcioglu 2018]. 
Hematopoietic stem cell transplantation induces substantial endothelial injury [Vion 2015]. This 
injury results from toxic conditioning regimes, immunosuppressive drugs, infections, and 
graft-versus-host disease (GVHD) [Khosla 2017]. This endothelial injury is believed to 
contribute to many serious post-HSCT complications, including veno-occlusive disease (VOD) 
(also known as sinusoidal obstructive syndrome), GVHD, capillary leak syndrome, diffuse 
alveolar hemorrhage (DAH), and TMA [Akil 2015, Carreras 2011, Khosla 2017, Vion 2015]. 
Preconditioning endothelial health and the degree of post-transplant endothelial injury measured 
by serum biomarkers are associated with both the development and severity of post-transplant 
complications [Cooke 2008, Dietrich 2013, Gloude 2017, Lindas 2014]. Suppression of 
tumorigenicity-2, a marker of endothelial injury, has been demonstrated to correlate with the risk 
of GVHD, TMA, and death following HSCT [Abu Zaid 2017, Rotz 2017a, Vander Lugt 2013]. 
The association of TMA and steroid-refractory GVHD has also been observed clinically and 
linked to endothelial injury [Rotz 2017a, Zeisbrich 2017]. Thus, TMA appears to be one 
manifestation of endothelial cell injury associated with HSCT. Limiting endothelial injury would 
be expected to reduce the severity of related clinical syndromes, such as TMA, as well as other 
complications related to endothelial cell injury. 
Endothelial injury activates the lectin pathway of complement on the endothelial cell surface 
[Collard 2000]. Complement activation induces formation of complement component 3a (C3a) 
and complement component 5a (C5a). Preclinically, C3a and C5a have induced endothelial 
activation associated with endothelial injury and pro-inflammatory changes, leukocyte 
recruitment, and endothelial apoptosis [Mahajan 2016, Wu 2016, Zhang 2010]. Complement 
activation further leads to formation of C5b-9 on the cell surface. While membrane-bound, it can 
cause cell lysis. Even when sublytic, C5b-9 causes additional cell injury that induces secretion of 
prothrombotic factors, platelet activation, upregulation of adhesion molecules, and dysfunctional 
morphological changes in the endothelium [Kerr 2012]. These complement-mediated activities 
may amplify endothelial injury and dysfunction, causing or worsening clinical conditions. 
Complement activation has been demonstrated in HSCT-TMA and GVHD [Cherry 2015, Rotz 
2017b]. Eculizumab, a C5 inhibitor, has been reported to improve survival in patients with 
HSCT-TMA having features portending a poor prognosis [Bohl 2017, de Fontbrune 2015, Jodele 
2014b]. Inhibition of the lectin pathway could limit endothelial cell injury by inhibiting both C3a 
and C5a, without increasing infection risk associated with classical pathway inhibition. 
There are no approved products indicated for the treatment of HSCT-TMA. First-line 
management of HSCT-TMA includes modification or cessation of any immunosuppressive 
regimen, appropriate treatment of infections and/or GVHD if present, aggressive control of 
hypertension, and other supportive therapy as deemed appropriate by the treating physician 

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[Khosla 2017]. Plasma therapy is thought to have no utility in this patient population [Khosla 
2017, Rosenthal 2016]. Patients who do not respond to modification of their immunosuppression 
have a poor prognosis. Adult m01iality has been repo1ted to be as high as 100% (4 out of 
4 patients, all of whom died within 69 days from diagnosis) [Worel 2007]. In a larger and more 
recent series, only 17% of adult patients (4 out of 24) who unde1went immunosuppression 
modification and received treatment with plasmapheresis, defibrotide, or rituximab survived 
1 year [Bohl 2017]. Eculizumab has been repo1ied to treat HSCT-TMA effectively with a 90% 
response rate when used off-label in 1 adult study; however, there was a high rate of infection­ 
related m01iality following eculizumab treatment [Bohl 2017]. These data demonstrate that 
HSCT-TMA is a life-threatening condition and, with the lack of effective treatment options, 
represents a significant l1lllnet medical need. 
 
5.1.3. 
Scientific Rationale 
The lectin pathway acts as an innate immune sensor of tissue injmy and has a dominant role in 
activating complement in settings of endothelial cell stress or injmy [Collard 1999]. Therefore, 
the lectin pathway likely plays a key role in initiating and pe1petuating complement activation in 
TMA, and inhibition of the lectin pathway may address both TMA and complement-mediated 
organ injmy related to TMA. 
The role ofMASP-2 activity in promoting TMA following endothelial injmy has been 
conoborated in experimental animal models. Intravital microscopy studies have shown that, 
while lipopolysaccharide-induced microvascular injmy leads to extensive microvascular 
coagulation in the affected blood vessel of wild-type mice, these microthrombi are completely 
absent in MASP-2-deficient mice [Manuel DN et al unpublished obse1vation]. Moreover, 
treatment of no1mal mice with OMS721 reduced microthrombi fo1mation compared to isotype 
controls in a fluorescein isothiocyanate-labeled dextran photo-activation model [described in the 
Investigator's Brochure, Section 4.1.2.1]. Also, in vitro studies have demonstrated that OMS721 
inhibits C5b-9 deposition or thrombus fo1mation on endothelial cells activated with human sera 
from patients having aHUS in both the active and remission states. 

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■ 
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6. 
STUDY PURPOSE AND OBJECTIVES 
The pmpose of this Phase 2 study is to evaluate the safety, efficacy, PK, PD, and 
immunogenicity of OMS72 l in patients with TMA. As of Amendment 11 of this study protocol, 
the prima1y and seconda1y endpoints are modified to provide for evaluation of response in 
patients with HSCT-associated TMA. 
 
6.1. 
Primary Study Objectives 
The co-prima1y objectives of this study are to: 
• 
Assess the safety and tolerability of multiple-dose administration of OMS72 l in 
patients with TMA (this will be assessed in patients with HSCT-TMA as well as in 
patients with aHUS or TTP) 
• 
Evaluate the efficacy of OMS721 in patients with HSCT-TMA by response defined 
as: 
- 
Improvement in TMA laborat01y markers of platelet count and lactate 
dehydrogenase (LDH), and 
- 
Improvement in clinical status 

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6.2. 
Secondary Study Objectives 
The secondary objectives of this study are to evaluate the following in patients with HSCT-TMA 
treated with OMS721: 
• Duration of response 
• 100-day survival 
• Overall survival (OS) 
• Platelet count change from baseline 
• Lactate dehydrogenase change from baseline 
• Haptoglobin change from baseline 
• Hemoglobin (Hgb) change from baseline 
• Creatinine change from baseline in patients who had no reason other than HSCT- 
TMA for creatinine elevation 
• Freedom from platelet transfusion in patients who received at least 1 platelet 
transfusion within 2 weeks of the first OMS721 dose 
• Freedom from red blood cell (RBC) transfusion in patients who received at least 
1 RBC transfusion within 2 weeks of the first OMS721 dose 
• The PK of multiple-dose administration of OMS721 (this will be assessed in patients 
with HSCT-TMA as well as patients with aHUS and TTP) 
• The PD of multiple-dose administration of OMS721(this will be assessed in patients 
with HSCT-TMA as well as patients with aHUS and TTP) 
• The immunogenicity of multiple-dose administration of OMS721 (this will be 
assessed in patients with HSCT-TMA as well as patients with aHUS and TTP) 
 
6.3. 
Exploratory Objectives 
The exploratory objectives of this study are to: 
• Assess the effect of baseline circulating MBL levels on PK and PD measures 
• Assess the effect of baseline circulating MASP-2 levels on PK and PD measures 
• Describe the effect of OMS721 on TMA laboratory markers in patients with aHUS 
and TTP 
 
7. 
STUDY DESIGN AND PROCEDURES 
7.1. 
Summary of Study Design 
This is a Phase 2, uncontrolled, three-stage, ascending-dose-escalation study in patients with 
TMA: aHUS, TTP, or HSCT-TMA. As originally designed, the primary outcomes to be 
measured were safety and clinical activity. The secondary outcomes to be measured were PK, 

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PD, and immunogenicity (i.e., presence of ADA response). Amendment 10 discontinued 
enrollment of patients with aHUS and TTP. Amendment 11 provides for collection of additional 
data from patients with HSCT-TMA, changes the primary and secondary objectives to focus on 
HSCT-TMA, and defines criteria by which to determine clinical response to treatment. 
Amendment 11 also provides for collection of PK and PD measures for analysis within 
integrated population PK and PD analyses across different studies. 
OMS721 is to be used in conjunction with standard of care treatments. Standard of care 
treatments are not to be delayed or withheld from patients entering this study. These treatments 
should be initiated according to local standard of care. For example, plasma exchange should not 
be delayed while waiting for initiation of OMS721 treatment if local standard of care is to 
administer plasma exchange. 
In Stage 1 of the study, OMS721 was administered to 3 cohorts (Cohort 1, Cohort 2, and 
Cohort 3), with dose escalation by cohorts to identify the optimal dosing regimen. After 
enrollment and treatment of each cohort, there was a safety review to determine whether dose 
escalation should proceed. In Stage 2, the dose selected in the first stage was administered to 
expanded cohorts initially planned to be 40 patients per cohort with distinct etiologies (aHUS 
alone in 1 cohort and TTP or HSCT-TMA in the other cohort). As of Amendment 10 of this 
protocol, enrollment of aHUS and TTP patients was closed. As of Amendment 11 of this 
protocol, enrollment in the study has been completed. 
Each patient in Stage 1 received 4 weekly doses of OMS721. Prior to Amendment 10, patients in 
Stage 2 with aHUS received 12 weekly doses, and patients with TTP or HSCT-TMA received 
4 weekly doses. Patients in Stage 2 who demonstrate improvement in TMA signs during their 
initial treatment period may be eligible for Stage 3, which provides continued treatment under 
this protocol. Patients in the aHUS cohort were eligible for an additional 12 weekly doses. 
Patients in the HSCT-TMA cohort may be eligible for an additional 4 weekly doses. The 
patient’s treating Investigator and the Sponsor’s medical monitor will determine eligibility for 
Stage 3 based upon the patient’s response to therapy, safety, and tolerability prior to the last 
scheduled treatment visit in Stage 2 in order to determine the appropriate PK draws following 
that visit. (Note: patients entering Stage 3 will not undergo the Stage 2 follow-up visits.) Follow- 
up visits are planned to allow adequate time for ADA assessment and/or at least 6 weeks of 
follow-up after the last dose to allow adequate time for OMS721 elimination, whichever is 
longer. As of Amendment 10 of this protocol, enrollment of aHUS and TTP patients was closed. 
As of Amendment 11 of this protocol, enrollment in the study has been completed. 
Different treatment durations for the different cohorts in Stage 2 and Stage 3 are provided 
because the natural history and response to treatment of each disease state is different. For 
example, plasma therapy for acute episodes of TTP typically is stopped when remission is 
achieved. Relapses occur, but generally not immediately. Also, HSCT-TMA often resolves 
within a few weeks of calcineurin inhibitor modification. These diseases could be effectively 
treated with relatively short-term treatment. On the other hand, treatment for aHUS is often 
chronic, and relapses are common following discontinuation of treatment. Therefore, the 
treatment duration for the TTP/HSCT-TMA cohort is shorter than the treatment duration of the 
aHUS cohort. 

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OMS721 will be administered by IV infusion. The planned enrollment is up to approximately 
60 patients overall. The stages, cohorts, and treatments are provided in Table 1. 
Table 1: 
OMS721-TMA-001 Treatment Stages and Cohorts 
Stage, 
Cohort 
Number of Patients 
Planned 
OMS721 Dose 
 
 
1, Cohort 1 
3 
0.675 mg/kg IV weekly x 4 
1, Cohort 2 
3 
2.0 mg/kg IV weekly x 4 
1, Cohort 3 
3 
4.0 mg/kg IV weekly x 4 
2, Cohort 4a 
40 (aHUS) 
4.0 mg/kg IV weekly x 12 
3, Cohort 4a 
≤ 40 (aHUS) 
4.0 mg/kg IV weekly x 12 
2b, Cohort 5 
 40 (TTPc/HSCT-TMA) 
4.0 mg/kg or 370 mg IV weekly x 4 
3b, Cohort 5 
≤40 (TTPc/HSCT-TMA) 
4.0 mg/kg or 370 mg IV weekly x 4 
Abbreviations: aHUS = atypical hemolytic uremic syndrome; HSCT-TMA = hematopoietic stem cell transplant- 
thrombotic microangiopathy; IV = intravenous. 
a As of Amendment 10, Cohort 4 was closed. 
b Doses for Stage 2 and Stage 3 were determined from Stage 1 PK, PD, and safety results. After Stage 1, this was 
4 mg/kg. As of Amendment 10 of this protocol, the dose for HSCT-TMA patients was 370 mg IV weekly x 4. Any 
patients in the middle of treatment at the time of this protocol amendment remained on their original dose. 
c As of Amendment 10 of this protocol, enrollment of TTP patients was closed. 
As of Amendment 11 of this protocol, enrollment in the study has been completed. 
For patients with HSCT-TMA enrolled under Amendment 10 or earlier versions of this protocol, 
additional data will be collected. Notification and consent of patients (or legal representatives for 
deceased patients) for this additional data collection are being collected according to local rules 
and regulations. 
These additional data are outlined in this amendment in Section 19.4. These data will include 
supplemental data on patient demographics and baseline conditions, donor characteristics, the 
transplant procedure, concomitant medications, TMA-related laboratory measures, transfusions, 
transplant complications, and outcomes. These data will be derived from medical records from 
the time of transplant conditioning through the last available patient contact with the site or up to 
2 years (104 weeks) after the first OMS721 dose, whichever is earlier. These data were requested 
by regulatory authorities because patients who have undergone HSCT typically have 
complicated post-transplant courses, and these additional data will allow for better understanding 
of OMS721 response and outcomes. As of Amendment 11, enrollment in the study has been 
completed, and the additional data will be collected until a predetermined data cutoff date for 
those patients who have not reached 2 years after first OMS721 dose. 
 
7.1.1. 
Stage 1 
In Stage 1, eligible patients were enrolled to sequential cohorts without regard to etiology of 
TMA. Dose escalation was guided by safety monitoring through at least 1 week after the last 
patient in the cohort had completed treatment. It may have been necessary to change the number 
of cohorts and dose levels based on emerging PK and PD data, which would have been 

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implemented by a protocol amendment. The safety, PK, and PD data from the first stage were 
reviewed to set the dose for the second stage. 
As of Amendment 11 of this protocol, Stage 1 is complete. 
The Stage 1 study design is illustrated in Figure 1. 
Figure 1: 
Stage 1 Study Design Schematic 
 
The Stage 1 study schedule includes 9 visits across 3 periods: 
Period 1 – Screening (Visit 1, up to 4 weeks) 
Period 2 – Treatment (Visit 2 to Visit 5, 4 weeks) 
Period 3 – Follow-up (Visit 6 to Visit 9, 8 weeks) 
The length of time for individual patient participation in Stage 1 was approximately 12 to 
16 weeks, depending on the time from screening to the first dose of OMS721 administration. 
 
7.1.2. 
Stage 2 and Stage 3 
aHUS Cohort 
The Stage 2 and Stage 3 study designs are illustrated in Figure 2 and Figure 3 for the aHUS 
cohorts. As of Amendment 10 of this protocol, enrollment of aHUS patients was closed. 
Figure 2: 
Stage 2 Study Design Schematic (aHUS Cohort) 
 
The Stage 2 study schedule for the aHUS cohort (Cohort 4) includes 17 visits across 3 periods: 
Period 1 – Screening (Visit 1, up to 4 weeks) 
Period 2 – Treatment (Visit T-1 to Visit T-12, 12 weeks) 
Period 3 (if patient does not continue to Stage 3) – Follow-up (Visit F-1 to Visit F-4, 
6 weeks) 
The length of time for individual aHUS patient participation in Stage 2 (if he or she did not 
continue to Stage 3) was approximately 18 to 22 weeks, depending on the time from screening to 

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Continued 
from Stage2 
Dose #18 
(T·18: Day 120) 
Dose #24 
(T-24: Day 162) 
Fo ow-Up F-N 
(4 Visits) 
Da s 169-204 
Treatment Period (T-N) 
Screening 
(Day-28) 
Dose #1 
(T-1: Day 1) 
Dose #2 
(T-2: Day 8) 
Dose#3 
(T-3: Day 15) 
Dose #4 
(T-4: Day 22) 
Continue to Stage 3 
Follow-Up (F•N) 
{4 visits) 
(Days 29-92) 
 
 
the first dose of OMS721 administration. Follow-up visits for patients who did not continue to 
Stage 3 occurred on Day 85, Day 92, Day 106, and Day 120. 
Patients with aHUS who completed Stage 2 treatment may have been eligible for an additional 
12 weeks of treatment if the Investigator believed the patient was at risk for relapse of TMA, the 
patient tolerated OMS721 treatment, and the patient had no conditions that increase the risk of 
OMS721 treatment (e.g., serious active infection). The patient's treating Investigator and the 
Sponsor's medical monitor determined eligibility for Stage 3 based upon the patient's response 
to therapy and safety and tolerability prior to the last scheduled treatment visit in Stage 2 in order 
to dete1mine the appropriate PK draws following that visit. Patients entering Stage 3 did not 
undergo the Follow-up visits in Stage 2. 
Figure 3: 
Stage 3 Study Design Schematic (aHUS Cohort) 
Treatment Period (T-N) 
 
Treatment Period (T-N) 
 
The Stage 3 study schedule for the aHUS cohort (Coho1t 4) includes 16 visits across 2 periods: 
Period 2 (continued from Stage 2)-Treatment (Visit T-13 to Visit T-24, 12 weeks) 
Period 3 - Follow-up (Visit F-1 to Visit F-4, 6 weeks) 
The length of time for individual aHUS patient paiticipation in Stage 3 was approximately 
18 weeks and the total length of time in Stage 2 and Stage 3 was approximately 30 to 34 weeks. 
Follow-up visits occuned on Day 169, Day 176, Day 190, and Day 204. 
The overall study was planned to take approximately 48 months to complete (from first patient 
visit to last patient visit). 
TTP/HSCT-TMA Cohort 
The Stage 2 and Stage 3 study designs are illustrated in Figure 4 and Figure 5 for the HSCT­ 
TMA coho1t. As of Amendment 10 of this protocol, enrollment of TTP patients was closed. As 
of Amendment 11 of this protocol, enrollment in the study has been completed. 
Figure 4: 
Stage 2 Study Design Schematic (HSCT-TMA Cohort) 
 

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Continued 
from Stage 2 
Dose#S 
(T-5: Day 29) 
Dose#6 
(T-6: Day 36) 
Dose#7 
(T-7: Day 43) 
Dose#B 
(T-8: Day SO) 
Follow-Up (F-N) 
(4 visits) 
(Days 57-92) 
 
 
The Stage 2 study schedule for the HSCT-TMA coho1t (Coho1t 5) includes 4 doses with up to 
9 visits across 3 periods: 
Period 1- Screening (Visit 1, up to 4 weeks) 
Period 2-Treatment (Visit T-1 to Visit T-4, 4 weeks) 
Period 3 (if patient does not continue to Stage 3)-Follow-up (Visit F-1 to Visit F-4, 
10 weeks) 
The length of time for individual HSCT-TMA patient paiticipation in Stage 2 (if he or she does 
not continue to Stage 3) was approximately 14 to 18 weeks, depending on the time from 
screening to the first dose of OMS721 administration. Follow-up visits for patients who do not 
continue to Stage 3 will occur on Day 29, Day 36, Day 50, and Day 92. 
Patients with HSCT-TMA who have completed the Stage 2 treatment period may be eligible for 
an additional 4 weeks of treatment if the Investigator believes the patient is at risk for relapse of 
TMA or has not responded to the initial 4 weeks of treatment, the patient tolerated OMS721 
treatment, and the patient has no conditions that increase the risk of OMS721 treatment (e.g., 
serious active infection). The patient's treating Investigator and the Sponsor's medical monitor 
will detennine eligibility for Stage 3 based upon the patient's response to therapy and safety and 
tolerability prior to the last scheduled treatment visit in Stage 2 in order to detennine the 
appropriate PK draws following that visit. Patients entering Stage 3 will not undergo the Follow­ 
up visits in Stage 2. 
Figure 5: 
Stage 3 Study Design Schematic (HSCT-TMA Cohort) 
Treatment Period (T-N) 
 
 
 
The Stage 3 study schedule for the HSCT-TMA coho1t (Coho1t 5) includes 8 visits across 2 
periods: 
Period 2 (continued from Stage 2)- Treatment (Visit T-5 to Visit T-8, 4 weeks) 
Period 3 -Follow-up (Visit F-1 to Visit F-4, 6 weeks) 
Follow-up visits in Stage 3 for the HSCT-TMA cohort will occur on Day 57, Day 64, Day 78, 
and Day 92. The length of time for individual TTP/HSCT-TMA patient paiticipation in Stage 3 
will be approximately 10 weeks, and the total length of time in Stage 2 and Stage 3 will be 
approximately 14 to 18 weeks. 
 
7.2. 
Study Rationale 
This is the first study of OMS721 in patients with TMA. In addition to evaluating safety, 
tolerability, PK, PD, and immunogenicity, clinical activity in patients with TMA is to be 
obtained. Results from nonclinical toxicity studies of OMS721, Phase 1 studies in healthy 
volunteers, a Phase 2 study in glomernlonephropathies, and data collected in this study as of the 
time of this amendment indicate that there is a positive benefit/risk ratio to conduct this study at 

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the proposed doses in patients with TMA. Patients previously emolled thus far in this study have 
tolerated OMS721 well. The treatment period is being extended because the non-human primate 
chronic toxicity study has been completed without treatment-related adverse findings, patients 
previously emolled in this study have demonstrated improvement in laborato1y measmes of 
TMA, and continued treatment has been requested. Inclusion of patients in this ongoing protocol 
provides for better safety and efficacy evaluation than expanded access across Investigators. The 
difference in treatment dmations reflects the different courses of the TMA subpopulations 
included in this study. 

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7.3. 
Study Endpoints 
7.3.1. 
Primary Endpoints 
The co-primary endpoints are: 
• Safety as assessed by adverse events (AEs), vital signs, ECGs, and clinical laboratory 
tests (includes patients with HSCT-TMA, aHUS, and TTP) 
• For HSCT-TMA patients, response to OMS721 treatment. A responder is defined as a 
patient with HSCT-TMA who demonstrates improvement in laboratory TMA 
markers (platelet count and LDH) and clinical benefit (either improvement in organ 
function or reduction in transfusion burden). The specific criteria are defined as 
follows: 
− Improvement in laboratory TMA markers: 
 Platelet count: 
• For patients with baseline platelet count ≤ 20,000/μL: 
o  Tripling of baseline platelet count 
and 
o Post baseline platelet count > 30,000/μL 
and 
o No platelet transfusions 2 days before and on the day of the 
platelet count collection 
• For patients with baseline platelet count > 20,000/μL 
o Increase in platelet count ≥ 50% 
and 
o Post baseline platelet count > 75,000/μL 
and 
o No platelet transfusions 2 days before and on the day of the 
platelet count collection 
and 
 LDH: 
• LDH < 1.5 x upper limit of normal (ULN) 
and 
− Improvement in clinical status: 
 Improvement in organ function as evidenced by any of the following: 
• Improvement in renal function: 

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•  Reduction of creatinine > 40% 
or 
• Creatinine < ULN and reduction of creatinine > 20% 
or 
• Discontinuation of renal replacement therapy (RRT) 
or 
• Improvement in pulmonary function: 
• Extubation and discontinuation of ventilator support 
or 
• Discontinuation of non-invasive mechanical ventilation 
(continuous positive pressure ventilation) 
or 
• Improvement in neurological function: 
• Improvement in reversible neurological conditions (e.g., 
cessation of seizures) 
or 
• Stabilization of irreversible neurological conditions (e.g., 
stability of neurological deficits following stroke without 
further deterioration or subsequent strokes) 
or 
• Improvement in gastrointestinal function (gastrointestinal HSCT- 
TMA will require diagnosis by tissue biopsy): 
• Improvement measured by improvement in the 
gastrointestinal measures in the Mount Sinai Acute GVHD 
International Consortium (MAGIC) criteria 
or 
 Freedom from transfusion (no transfusions for at least 4 weeks from the 
last transfusion except for patients who died within 4 weeks of the last 
transfusion, only evaluated in patients who received transfusions within 
the 2 weeks prior to or on the first OMS721 dose date) 
 
7.3.2. 
Secondary Endpoints 
The secondary endpoints are to evaluate the following in patients with HSCT-TMA treated with 
OMS721: 
• Duration of response, defined as the number of days from the first response date to 
the first relapse date 

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• 100-day survival, from the date of TMA diagnosis 
• Overall survival, from the date of TMA diagnosis 
• Freedom from platelet transfusion defined as no platelet transfusions for at least 
4 weeks following the last platelet transfusion except for patients who died within 
4 weeks of the last platelet transfusion (only evaluated in patients who had platelet 
transfusions in the 2 weeks prior to or on the first OMS721 dose date) 
• Freedom from RBC transfusion defined as no RBC transfusions for at least 4 weeks 
following the last RBC transfusion except for patients who died within 4 weeks of the 
last RBC transfusion (only evaluated in patients who had RBC transfusions in the 
2 weeks prior to or on the first OMS721 dose date) 
• Change from baseline in platelet count (post baseline platelet counts without platelet 
transfusions 2 days before and on the day of the platelet count collection will be used) 
over time using central laboratory values 
• Change from baseline in LDH over time using central laboratory values 
• Change from baseline in haptoglobin over time using central laboratory values 
• Change from baseline in Hgb (post baseline Hgb without RBC and whole blood 
transfusions 6 days before and on the day of the Hgb collection will be used) over 
time using central laboratory values 
• Change from baseline in creatinine over time using central laboratory values 
• The PK of multiple-dose administration of OMS721 (this will be assessed in patients 
with HSCT-TMA as well as patients with aHUS and TTP) 
• The PD of multiple-dose administration of OMS721(this will be assessed in patients 
with HSCT-TMA as well as patients with aHUS and TTP) 
• The immunogenicity of multiple-dose administration of OMS721 (this will be 
assessed in patients with HSCT-TMA as well as patients with aHUS and TTP) 
 
7.3.3. 
Exploratory Endpoints 
The exploratory endpoints are: 
• Assess the effect of baseline circulating MBL levels on PK and PD measures in 
patients with HSCT-TMA, aHUS, and TTP 
• Assess the effect of baseline circulating MASP-2 levels on PK and PD measures in 
patients with HSCT-TMA, aHUS, and TTP 
• Describe the effect of OMS721 on TMA laboratory markers in patients with aHUS 
and TTP 
 
7.4. 
Study Extension 
Patients completing the treatment period of Stage 2 may be eligible for continued OMS721 
treatment in Stage 3. Patients may be eligible for extension of their treatment with OMS721 in 

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Stage 3 if they are deriving clinical benefit, have not displayed any signs or symptoms of serious 
toxicity, and the Investigator and Sponsor’s medical monitor agree that the patient may derive 
benefit from continuing treatment in Stage 3. The primary objective of the Stage 3 extension is to 
provide a treatment option that may be better than alternative treatments. A secondary objective 
of this extension is to assess safety and efficacy parameters of OMS721 during extended 
treatment. 
The decision to offer extended treatment will be made on a case-by-case basis and will be 
implemented under the following guidelines: 
• The patient provides informed consent for further treatment. 
• The benefit-to-risk assessment is positive for the patient. 
The patient’s treating Investigator and the Sponsor’s medical monitor will determine eligibility 
for Stage 3 based upon the patient’s response to therapy and safety and tolerability prior to the 
last scheduled treatment visit in Stage 2 in order to determine the appropriate PK draws 
following that visit. 
 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Patient Inclusion Criteria 
Patients may be included in the study only if they meet all of the following criteria: 
1. Competent to provide informed consent. 
2. Voluntarily provide informed consent in accordance with regulations and governing 
ethics committee requirements prior to any procedures or evaluations performed 
specifically for the sole purpose of the study. 
3. Are age ≥ 18 years at screening (Visit 1). 
4. Have a diagnosis of TMA in accordance with one of the following 3 categories: 
• As of Amendment 10 of this protocol, enrollment of aHUS patients was closed. 
Primary aHUS, diagnosed clinically and having ADAMTS13 activity > 10% in 
plasma. Patients are eligible with or without a documented complement mutation or 
anti-complement factor H (anti-CFH) antibody. Patients are categorized according to 
their response to plasma therapy (plasma exchange or plasma infusion): 
o Plasma therapy-resistant aHUS patients must have all of the following: 
 Screening platelet count < 150,000/µL despite at least 4 plasma therapy 
treatments prior to screening 
 Evidence of microangiopathic hemolysis (presence of schistocytes, serum 
LDH > ULN, or haptoglobin < lower limit of normal [LLN]) 
 Serum creatinine > ULN 

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o Chronic plasma therapy-responsive aHUS patients (plasma therapy-sensitive) 
must require at least once-per-week plasma therapy for 4 weeks before first dose 
of OMS721 with serum creatinine > ULN. 
• As of Amendment 10 of this protocol, enrollment of TTP patients was closed. TTP 
defined as having all of the following: 
o Platelet count < 150,000/µL 
o Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH 
> ULN, or haptoglobin < LLN) 
o ADAMTS13 activity ≤ 10% during the current episode of TTP or historically 
• Persistent HSCT-associated TMA defined as having all of the following at least 
2 weeks following modification or discontinuation of calcineurin inhibitor treatment 
or at least 30 days after the transplant: 
o Platelet count < 150,000/µL 
o Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH 
> ULN, or haptoglobin < LLN) 
o Renal dysfunction (doubling of serum creatinine from pre-transplant) 
5. No clinically apparent alternative explanation for thrombocytopenia and anemia. 
6. If sexually active and of childbearing potential, must agree to practice a highly effective 
method of birth control until the end of the study, defined as one that results in a low 
failure rate (i.e., less than 1% per year) when used consistently and correctly, such as 
implants, injectables, combined oral contraceptives, some intrauterine devices, sexual 
abstinence, or vasectomized partner. 
8.2. 
Patient Exclusion Criteria 
Patients will be excluded from the study for any of the following reasons: 
1. Had eculizumab therapy within 3 months prior to screening. 
2. Have STEC-HUS. 
3. Have a positive direct Coombs test. 
4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy 
(prophylactic antimicrobial therapy administered as standard of care is allowed). 
5. Baseline resting heart rate < 45 beats per minute or > 115 beats per minute. 
6. Baseline QTcF > 470 milliseconds. 
7. Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral 
hemorrhages or “cotton-wool” exudates on funduscopic examination). 
8. Have a poor prognosis with a life expectancy of less than 3 months in the opinion of the 
Investigator. 
9. Are pregnant or lactating. 

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10. Have received treatment with an investigational drug or device within 4 weeks prior to 
screening. 
11. Have abnormal liver function tests defined as ALT or aspartate aminotransferase (AST) 
> 5 times ULN. 
12. Have a positive test for human immunodeficiency virus (HIV) antibodies. 
13. Are an employee of Omeros, an Investigator, a study staff member, or their immediate 
family member. 
14. Have a known hypersensitivity to any constituent of the product. 
15. Presence of any condition that the Investigator believes would put the patient at risk. 
 
8.3. 
Patient Withdrawal Criteria 
8.3.1. 
Early Discontinuation of Study Drug Administration 
Patients may voluntarily withdraw from the study at any time for any reason without prejudice to 
further treatment. A patient must permanently discontinue study drug under any of the following 
circumstances: 
• The patient becomes pregnant. Study drug must be discontinued immediately and the 
pregnancy reported to the Sponsor. 
• The patient wishes to discontinue study drug treatment for any reason. 
• The patient experiences a medical emergency that necessitates discontinuing study 
drug treatment. 
• The patient receives a prohibited concomitant therapy. 
• The Investigator, Sponsor, or patient’s primary care physician decides to discontinue 
treatment for medical reasons or due to the patient’s noncompliance with the 
protocol. 
The reason for termination of study drug before study completion must be recorded in the 
patient’s Case Report Form (CRF). The patient should complete all scheduled study Follow-Up 
visits provided written consent to do so has not been withdrawn. Patients who discontinue study 
drug prematurely will not be replaced. 
8.3.2. 
Patient Withdrawal from the Study 
A patient must be withdrawn from the study and discontinue study drug under the following 
circumstances: 
• The patient wishes to withdraw consent to participate in the study. 
• The Investigator or patient’s primary care physician decides that the patient should be 
withdrawn from the study. 
• The Sponsor decides that the patient should be withdrawn or the Sponsor discontinues 
the study for any reason. 

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The reason for withdrawal must be recorded in the patient’s CRF. The patient should complete 
the evaluations scheduled for the last follow-up visit (dependent on the patient’s cohort and 
Stage), provided written consent to do so has not been withdrawn. Patients who are withdrawn 
may be replaced at the discretion of the Sponsor in consultation with the Investigator in order to 
meet study objectives. 
8.3.3. 
Notification of Withdrawal 
When a study participant, voluntarily or involuntarily, is withdrawn from the study , the Sponsor 
and the ethics committee (as applicable, in accordance with Institutional Review Board 
[IRB]/Independent Ethics Committee [IEC] requirements) will be notified and provided with the 
reasons for patient’s withdrawal from this study. 
 
9. 
STUDY DRUG AND TREATMENT OF PATIENTS 
OMS721 is manufactured using current Good Manufacturing Practices for investigational use. 
OMS721 is a human IgG4 mAb directed against MASP-2. Two formulations are available, the 
higher concentration drug product (185 mg/mL) and the lower concentration drug product 
(100 mg/mL), depending on which amendment patients were enrolled under (see Section 9.1.3). 
 
9.1. 
OMS721 Drug Product 
OMS721 100 mg/mL Injection Solution is a clear, colorless to yellow-brown liquid. It consists of 
2 mL OMS721 Drug Substance, formulated in 20 mM sodium acetate, 5% sorbitol, and 0.01% 
polysorbate 80, pH 5.0 ± 0.8, at a concentration of 100 mg/mL, and supplied in a single-use 
5 mL sterile, clear-glass vials. Each vial contains 2 mL of 100 mg/mL Injection Solution. As of 
Amendment 10 of this protocol, the 100 mg/mL formulation will not be used for newly enrolled 
patients. 
Drug Product, OMS721 185 mg/mL is a clear, colorless to yellow-brown liquid. It contains 
OMS721 Drug Substance (nominal concentration of 185 mg/mL), formulated at pH 5.8, in 
citrate (20 mM), arginine (200 mM), and polysorbate 80 (0.01%). The Drug Product is supplied 
in a single-use type I glass 2 mL vial containing 2 mL of solution. 
The OMS721 Drug Product (185 mg/mL) will be further diluted for IV administration in 
accordance with the preparation instructions described below. 
9.1.1. 
Packaging and Labeling of Drug Product 
OMS721 100 mg/mL Injection Solution is packaged in 5 mL clear-glass vials containing 2 mL 
of OMS721. As of Amendment 10 of this protocol, the 100 mg/mL formulation will not be used 
for newly enrolled patients. 
Drug Product, OMS721 185 mg/mL is packaged in 2 mL clear-glass vials containing 2 mL of 
OMS721. This formulation will come packaged in a single vial per single carton. 
The vials and single outer cartons will be labeled in accordance with applicable regulations, 
including, at a minimum, the following information: 

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51 
 
 
 
• Name of the drug product (OMS721 100 mg/mL Injection Solution or Drug Product, 
OMS721 185 mg/mL) 
• Product identification number 
• Regulatory cautionary statement regarding investigational or clinical trial use 
9.1.2. 
Blinding 
No blinding is necessary in this study. 
 
9.1.3. 
Study Drug Dose Preparation 
Prior to preparation, the study drug should be inspected for any particulate matter or 
discoloration. If any particulate matter or discoloration is observed, the vial should not be used. 
As of Amendment 10 of this protocol, only the Drug Product, OMS721 185 mg/mL formulation 
will be used. The refrigerated vials (Drug Product, OMS721 185 mg/mL) must be used within 
4 hours following septum piercing. Do not shake or heat the OMS721. Avoid exposure to direct 
sunlight. 
As of Amendment 10 of this protocol, the dose is changed to a fixed dose of 370 mg. 
For dispensing, Drug Product OMS721 185 mg/mL is removed from refrigerated storage and 
allowed to come to room temperature undisturbed for a minimum of 30 minutes and then used to 
prepare the appropriate dosing solution. 
The appropriate calculated volume of Drug Product, OMS721 185 mg/mL will be withdrawn 
from the vial using polypropylene syringes for dose preparation. 
The measured OMS721 dose will be added to a polyvinyl chloride or polyolefin infusion bag 
containing a minimum of 50 mL D5W or normal saline for injection solution and mixed by 
gentle inversion about 10 times. The infusion preparation should not be shaken. The prepared 
infusion bag should be properly labeled, including the date and time of preparation, and kept at 
room temperature until ready for administration. The infusion bag should be administered within 
4 hours of preparation. If the infusion bag is not used within 4 hours, then it should be discarded 
and the disposition recorded under drug accountability. 
The diluted study drug should be infused intravenously over approximately a 30-minute period. 
 
9.1.3.1. 
Supplemental Drug Administration for Patients Receiving Plasma Therapy 
If the patient is receiving plasma exchange or plasma infusion on the day of study drug 
administration, then the study drug should be started within 3 hours after completion of plasma 
therapy. 
If plasma exchange is performed at any time prior to the next scheduled dose, then a 
supplemental dose of study drug (50% of assigned dose) should be administered within 1 hour 
after completion of each plasma exchange up to 4 supplemental doses per week. The total 
weekly dose should not exceed 300% of the assigned dose. 
If plasma infusion is performed at any time prior to the next scheduled dose, then a supplemental 
dose (50% of assigned dose) should be administered before each plasma infusion up to 

Protocol No. OMS721-TMA-001 (A11.1) 
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52 
 
 
 
 
4 supplemental doses per week. The total weekly dose should not exceed 300% of the assigned 
dose. 
9.1.4. 
Storage and Handling of Drug Product 
OMS721 Drug Product vials are to be stored according to the Investigator’s Brochure. 
• As of Amendment 10 of this protocol, 100 mg/mL Injection Solution will no longer 
be used for newly enrolled patients. Any remaining vials of OMS721 100 mg/mL 
Injection Solution should be returned or destroyed as described in Section 9.1.5 and 
Section 9.2. 
• Drug Product, OMS721 185 mg/mL is stored at 2°C to 8°C. 
Allow Drug Product, OMS721 185 mg/mL to come to room temperature without manipulation 
(i.e., warming up in your hands or putting the vial in hot water is not allowed) for a minimum of 
30 minutes, and then use it to prepare the appropriate dosing solution. The OMS721 Drug 
Product must be used to prepare the appropriate dosing solution within 4 hours after piercing of 
the vial septum. Drug Product that has not been punctured can be at room temperature for 
24 hours. 
 
9.1.5. 
Study Drug Accountability 
In compliance with the US FDA, European Medicines Agency (EMA), and other applicable 
regulations, records will be maintained by the Investigator and/or pharmacist designee for 
OMS721 study Drug Product delivery to the site, the inventory at the site, the use of each vial, 
and the return of used and unused Drug Product, including dates and quantities. The Investigator 
and/or pharmacist designee will maintain the investigative site’s study drug accountability 
documentation. The documentation should include the identification of the Drug Product used, 
Drug Product, OMS721 100 mg/mL Injection Solution or Drug Product, 185 mg/mL. After the 
study has been completed, a copy of the Investigator/pharmacy drug accountability records will 
be provided to the Sponsor. The original drug accountability records will be retained by the site. 
9.2. 
Return of Drug Product 
At the end of the study, the Sponsor will inform the site as to disposition of unused Drug 
Product. If instructed, unused supplies may be destroyed at the site according to local laws, 
regulations, and the institution’s standard operating procedures. 
 
10. 
STUDY PROCEDURES 
The Schedule of Events for each cohort and Stage is summarized in Section 19. 
 
10.1. 
Study Schedule 
10.1.1. 
Stage 1 
As of Amendment 11 of this protocol, Stage 1 is complete. 

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Study procedures were performed at Screening (Visit 1, Day –28 to 0), at each of the dosing days 
during the Treatment Period (Visit 2 to Visit 5, Day 1 to Day 25), and during the Follow-up 
Period (Visit 6 to Visit 9, Day 29 to Day 78). 
 
10.1.1.1. Stage 1 Screening Visit (Visit 1, Up to Day –28) 
Screening evaluations will occur within 28 days prior to dosing (Day 1). Before any of the 
screening evaluations are performed for the specific purpose of this study, the patient must 
provide informed consent for this study in compliance with regulations and governing ethics 
committee requirements. The procedures listed below will be performed and documented to 
determine patient eligibility prior to treatment assignment. 
1. A medical history, including directed questioning regarding prior mycobacterial infection 
or significant fungal infection, will be taken, and demographics will be recorded. 
2. The history of TMA will be recorded, including the following information: 
• Type of TMA (aHUS, TTP, or HSCT-TMA). As of Amendment 10 of this protocol, 
enrollment of aHUS and TTP patients is closed. 
• Date of diagnosis (for HSCT-TMA, interval from time of transplantation) 
• History of previous episodes of TMA (record dates for prior episodes) 
• Family history of TMA 
• History of kidney transplantation for TMA-induced renal failure 
• Symptoms related to current episode of TMA 
• Diagnostic evaluations for TMA, e.g., Shiga toxin testing, complement genetic 
testing, ADAMTS13, Coombs test 
• Description of the type and frequency of plasma therapy during current episode 
• Description of frequency of dialysis during current episode 
• Immune suppressive medications to treat current episode 
• If taking calcineurin inhibitors chronically, changes, if any, to the dose and regimen 
during current episode 
3. Use of prior and concomitant medications will be obtained. 
4. Vital signs will be taken, including BP, pulse rate, respiratory rate (RR), and temperature 
(after at least 5 minutes of rest in the supine position). 
5. A complete physical examination will be performed, including height and weight. If 
diastolic BP is > 120 mm Hg, then a funduscopic examination will be performed to 
exclude malignant hypertension. Rectal or genital examinations are not required, unless 
medically indicated. 
6. A 12-lead ECG will be taken (after at least 5 minutes of rest in the supine position). 
7. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis. 

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54 
 
 
 
 
8. Serum pregnancy test will be performed in women of childbearing potential. 
9. Serology tests will be performed for HIV antibodies. 
10. Stool will be tested for Shiga toxin if STEC-HUS has not been previously excluded. 
11. Direct Coombs test will be performed if not previously obtained. 
12. Complement genetic testing will be performed in patients with primary aHUS if not 
previously obtained. 
13. ADAMTS13 activity testing will be performed if not previously obtained. 
 
10.1.1.2. Stage 1 Baseline Platelet Counts 
Eligible patients will have the platelet count performed on at least 2 separate days in the week 
prior to the first OMS721 dose (Day 1) to establish the baseline (averaged with the pre-dose 
value on Day 1). In patients who are receiving plasma therapy, the platelet counts should be 
obtained prior to such therapy. 
10.1.1.3. Stage 1 Method of Assigning Patients to Treatment Cohorts 
Eligible patients will be assigned to the current dose cohort in the first stage of the study. 
 
10.1.1.4. Stage 1 Treatment – Week 1 (Visit 2, Day 1) 
This visit is for the first dose of OMS721 administration. The study drug should be requested 
from the site pharmacy and prepared no earlier than 3.5 hours prior to the start of administration. 
Prior to dosing with study drug, the following procedures will be performed: 
1. Review of AEs, presence of TMA symptoms, concomitant medications, and therapies. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position). 
3. ECG will be taken (after at least 5 minutes of rest in the supine position). 
4. Laboratory tests will be performed, including: 
• Hematology, chemistry, LDH, haptoglobin, coagulation, and urinalysis. 
• Serum or urine pregnancy test will be performed in women of childbearing potential. 
If the test result is positive, then the patient will be excluded from the study. 
• Blood samples for future research related to TMA will be taken. The samples will 
enable DNA, RNA, proteins, and cells to be extracted for analyses. 
• Serum PK sample will be taken. 
• Serum PD sample will be taken. 
• Serum ADA sample will be taken. 
OMS721 will be administered by IV infusion over approximately 30 minutes. 
After start of dosing with study drug, the following procedures will be performed: 

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55 
 
 
 
 
1. AEs will be recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: 15 minutes after 
start of dosing, 30 minutes after start of dosing (after end of dosing), 1 hour after start of 
dosing (30 minutes after end of dosing), 2.5 hours after start of dosing (2 hours after end 
of dosing). 
3. ECG will be taken (after at least 5 minutes of rest in the supine position) immediately 
before the 5 minute PK sample. 
4. Serum PK samples will be taken at the following time points after end of dosing: 
5 minutes, 2 hours, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4). 
5. Serum PD sample will be taken 2 hours after end of dosing. 
6. The patient may be discharged after completion of the 2 hours after end-of-dosing 
procedures and arrangements made for the patient to undergo collection of PK samples 
on Day 2, Day 3, and Day 4. 
10.1.1.5. Stage 1 Treatment – Week 2 (Visit 3, Day 8 ± 1) 
This is the second dose of OMS721 administration. The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: prior to dosing and 
at 15 minutes, 30 minutes, 1 hour, and 2.5 hours after start of dosing. 
3. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis (prior to OMS721 administration). 
4. Blood sample for future research related to TMA will be taken (prior to OMS721 
administration). 
5. OMS721 will be administered by IV infusion over approximately 30 minutes. 
6. Serum PK samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
7. Serum PD samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
8. Serum ADA sample will be taken prior to dosing. 
9. AEs during and after the IV infusion will be recorded. 
 
10.1.1.6. Stage 1 Treatment – Week 3 (Visit 4, Day 15 ± 1) 
This is the third dose of OMS721 administration. The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 

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2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: prior to dosing and 
at 15 minutes, 30 minutes, 1 hour, and 2.5 hours after start of dosing. 
3. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis (prior to OMS721 administration). 
4. Blood sample for future research related to TMA will be taken (prior to OMS721 
administration). 
5. OMS721 will be administered by IV infusion over approximately 30 minutes. 
6. Serum PK samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
7. Serum PD samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
8. Serum ADA sample will be taken prior to dosing. 
9. AEs during and after the IV infusion will be recorded. 
 
10.1.1.7. Stage 1 Treatment – Week 4 (Visit 5, Day 22 ± 1) 
This is the fourth and last dose of OMS721 administration. The following procedures will be 
performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: prior to dosing and 
at 15 minutes, 30 minutes, 1 hour, and 2.5 hours after start of dosing. 
3. ECG will be taken (after at least 5 minutes of rest in the supine position) prior to dosing. 
4. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis (prior to OMS721 administration). 
5. Blood sample for future research related to TMA will be taken (prior to OMS721 
administration). 
6. OMS721 will be administered by IV infusion over approximately 30 minutes. 
7. ECG will be taken (after at least 5 minutes of rest in the supine position) immediately 
before the 5 minute PK sample. 
8. Serum PK samples will be taken prior to dosing and at the following time points after end 
of dosing: 5 minutes, 2 hours, 24 hours (Day 23), 48 hours (Day 24), 72 hours (Day 25). 
9. Serum PD samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
10. Serum ADA sample will be taken prior to dosing. 
11. AEs during and after the IV infusion will be recorded. 

Protocol No. OMS721-TMA-001 (A11.1) 
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12. Arrangements should be made for the patient to undergo collection of PK samples on the 
3 days following Visit 4 (Day 23, Day 24, and Day 25 if Visit 4 occurs on Day 22). 
 
10.1.1.8. Stage 1 Follow-Up (Visit 6, Day 29 ± 1) 
The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position). 
3. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
and urinalysis. 
4. Blood sample for future research related to TMA will be taken. 
5. Serum PK sample will be taken. 
6. Serum PD sample will be taken. 
7. Serum ADA sample will be taken. 
 
10.1.1.9. Stage 1 Follow-Up (Visit 7, Day 36 ± 2) 
The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position). 
3. Clinical laboratory tests will be performed for hematology, chemistry, LDH, and 
haptoglobin. 
4. Blood sample for future research related to TMA will be taken. 
5. Serum PK sample will be taken. 
6. Serum PD sample will be taken. 
7. Serum ADA sample will be taken. 
 
10.1.1.10. Stage 1 Follow-Up (Visit 8, Day 50 ± 3) 
The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Clinical laboratory tests will be performed for hematology, chemistry, LDH, and 
haptoglobin. 
3. Blood sample for future research related to TMA will be taken. 
4. Serum PK sample will be taken. 

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5. Serum PD sample will be taken. 
6. Serum ADA sample will be taken. 
 
10.1.1.11. Stage 1 Follow-Up End of Study (Visit 9, Day 78 ± 7) 
The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Clinical laboratory tests will be performed for hematology, chemistry, LDH, and 
haptoglobin. 
3. Serum or urine pregnancy test will be performed in women of childbearing potential. 
4. Blood sample for future research related to TMA will be taken. 
5. Serum PK sample will be taken. 
6. Serum PD sample will be taken. 
7. Serum ADA sample will be taken. 
The patient will complete the study at this visit. 
 
10.1.2. 
Stage 2 and Stage 3 
The study visits in Stage 2 and Stage 3 are described as Treatment (T) visits and Follow-up (F) 
visits. All patients will undergo the same procedures at the Screening, Treatment, and Follow-up 
visits. The number of Treatment and Follow-up visits will vary between stages and cohorts. As 
of Amendment 11, enrollment in the study has been completed. 
 
10.1.2.1. Stage 2 Screening Visit (Visit 1, Up to Day –28) 
Screening evaluations will occur within 28 days prior to dosing (Day 1). Before any of the 
screening evaluations are performed for the specific purpose of this study, the patient must 
provide informed consent for this study in compliance with regulations and governing ethics 
committee requirements. The procedures listed below will be performed and documented to 
determine patient eligibility prior to treatment assignment. 
1. A medical history, including directed questioning regarding prior mycobacterial infection 
or significant fungal infection, will be taken and demographics will be recorded. 
2. The history of TMA will be recorded, including the following information: 
• Type of TMA (aHUS, TTP, or HSCT-TMA). As of Amendment 10 of this protocol, 
enrollment of aHUS and TTP patients is closed. 
• Date of diagnosis (for HSCT-TMA, interval from time of transplantation) 
• History of previous episodes of TMA (record dates for prior episodes) 
• Family history of TMA 
• History of kidney transplantation for TMA-induced renal failure 

Protocol No. OMS721-TMA-001 (A11.1) 
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59 
 
 
 
• Symptoms related to current episode of TMA 
• Diagnostic evaluations for TMA, e.g., Shiga toxin testing, complement genetic 
testing, ADAMTS13, Coombs test 
• Description of the type and frequency of plasma therapy during current episode 
• Description of frequency of dialysis during current episode 
• Immune suppressive medications to treat current episode 
• If taking calcineurin inhibitors chronically, changes, if any, to the dose and regimen 
during current episode 
3. Use of prior and concomitant medications will be obtained. 
4. Vital signs will be taken including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position). 
5. A complete physical examination will be performed, including height and weight. If 
diastolic BP is > 120 mm Hg, then a funduscopic examination will be performed to 
exclude malignant hypertension. Rectal or genital examinations are not required, unless 
medically indicated. 
6. A 12-lead ECG will be taken (after at least 5 minutes of rest in the supine position). 
7. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis. 
8. Serum pregnancy test will be performed in women of childbearing potential. 
9. Serology tests will be performed for HIV antibodies. 
10. Stool will be tested for Shiga toxin if STEC-HUS has not been previously excluded. 
11. Direct Coombs test will be performed if not previously obtained. 
12. Complement genetic testing will be performed in patients with primary aHUS if not 
previously obtained. 
13. ADAMTS13 activity testing will be performed if not previously obtained. 
 
10.1.2.2. Stage 2 Baseline Platelet Counts 
Eligible patients will have the platelet count performed on at least 2 separate days in the week 
prior to the first OMS721 dose (Day 1) to establish the baseline (averaged with the pre-dose 
value on Day 1). In patients who are receiving plasma therapy, the platelet counts should be 
obtained prior to such therapy. 
10.1.2.3. Stage 2 and Stage 3 Method of Assigning Patients to Treatment Cohorts 
Eligible patients will be assigned to the selected dose and relevant disease cohort in the second 
stage of the study. Patients eligible to continue in Stage 3 will remain at the same dose and in the 
same disease cohort as assigned in Stage 2. 

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10.1.2.4. Stage 2 Treatment – Week 1 (Visit T-1, Day 1) 
This visit is for the first dose of OMS721 administration. The study drug should be requested 
from the site pharmacy and prepared no earlier than 3.5 hours prior to the start of administration. 
Prior to dosing with study drug, the following procedures will be performed: 
1. Review of AEs, presence of TMA symptoms, concomitant medications, and therapies. 
2. Vital signs will be taken including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position). 
3. ECG will be taken (after at least 5 minutes of rest in the supine position). 
4. Laboratory tests will be performed, including: 
• Hematology, chemistry, LDH, haptoglobin, coagulation, and urinalysis. 
• Serum or urine pregnancy test will be performed in women of childbearing potential. 
If the test result is positive, then the patient will be excluded from the study. 
• Blood samples for future research related to TMA will be taken. The samples will 
enable DNA, RNA, proteins, and cells to be extracted for analyses. 
• Serum PK sample will be taken. 
• Serum PD sample will be taken. 
• Serum ADA sample will be taken. 
OMS721 will be administered by IV infusion over approximately 30 minutes. 
After start of dosing with study drug, the following procedures will be performed: 
1. AEs will be recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: 15 minutes after 
start of dosing, 30 minutes after start of dosing (after end of dosing), 1 hour after start of 
dosing (30 minutes after end of dosing), 2.5 hours after start of dosing (2 hours after end 
of dosing). 
3. ECG will be taken (after at least 5 minutes of rest in the supine position) immediately 
before the 5-minute PK sample. 
4. Serum PK samples will be taken at the following time points after end of dosing: 
5 minutes, 2 hours, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4). 
5. Serum PD sample will be taken 2 hours after end of dosing. 
6. The patient may be discharged after completion of the 2 hours after end-of-dosing 
procedures and arrangements made for the patient to undergo collection of PK samples 
on Day 2, Day 3, and Day 4. 

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10.1.2.5. Stage 2 and Stage 3 Treatment – Visit T-N (where N is > 1 [the week of 
treatment after the week of the first dose]) 
The following procedures will be performed on the subsequent doses of OMS721: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: prior to dosing and 
at 15 minutes, 30 minutes, 1 hour, and 2.5 hours after start of dosing. 
3. Clinical laboratory tests will be performed for hematology, chemistry, LDH, haptoglobin, 
coagulation, and urinalysis (prior to OMS721 administration). 
4. Blood sample for future research related to TMA will be taken (prior to OMS721 
administration). 
5. Serum PK samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. At the last treatment visit, additional PK samples will also be 
taken at the following timepoints: 24 hours, 48 hours, and 72 hours after the end of the 
last dose. 
6. Serum PD samples will be taken at the following time points: prior to dosing and at 
2 hours after end of dosing. 
7. OMS721 will be administered by IV infusion over approximately 30 minutes. 
8. AEs during and after the IV infusion will be recorded. 
 
10.1.2.6. Stage 2 or Stage 3 Follow-Up – Visit F-N (where N is the number of the follow- 
up visit) 
The following procedures will be performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Clinical laboratory tests will be performed for hematology, chemistry, LDH, and 
haptoglobin. 
3. Blood sample for future research related to TMA will be taken. 
4. Serum PK sample will be taken. 
5. Serum PD sample will be taken. 
6. Serum ADA sample will be taken. 
7. Serum or urine pregnancy test will be performed in women of childbearing potential at 
the last Follow-Up visit only. 
10.1.3. 
Early Termination 
All patients will be encouraged to complete all evaluations. However, patients who prematurely 
discontinue the study will have the assessments for the last Follow-up visit, if possible. 

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10.1.4. 
Unscheduled Visits - Supplemental OMS721 Administration for Patients 
Receiving Plasma Therapy or Adverse Events 
If a patient has a cardiovascular AE, e.g., chest pain, palpitations, presyncope or syncope, hypo- 
or hypertension, an ECG should be taken and a serum PK sample taken immediately after the 
ECG. 
Patients who are receiving plasma therapy (plasma exchange or plasma infusion) will be treated 
with supplemental doses of OMS721 as provided in Section 9.1.3.1. 
If the patient is receiving plasma exchange or plasma infusion on the day of study drug 
administration, then the study drug should be given within 3 hours after completion of plasma 
therapy. 
If plasma exchange is performed at any time prior to the next scheduled dose, then a 
supplemental dose (50% of assigned dose) should be administered within 1 hour after 
completion of each plasma exchange up to 4 supplemental doses per week. The total weekly 
dose should not exceed 300% of the assigned dose. 
If plasma infusion is performed at any time prior to the next scheduled dose, then a supplemental 
dose (50% of assigned dose) should be administered before each plasma infusion up to 
4 supplemental doses per week. The total weekly dose should not exceed 300% of the assigned 
dose. 
On the day of supplemental OMS721 administration, the following procedures will be 
performed: 
1. AEs, presence of TMA symptoms, concomitant medications, and therapies will be 
recorded. 
2. Pre-dose vital signs will be taken, including BP, pulse rate, RR, and temperature (after at 
least 5 minutes of rest in the supine position). 
3. Pre-dose serum PK sample will be taken. 
4. OMS721 will be administered by IV infusion over approximately 30 minutes. 
5. Vital signs will be taken, including BP, pulse rate, RR, and temperature (after at least 
5 minutes of rest in the supine position) at the following time points: 15 minutes after 
start of dosing, 30 minutes after start of dosing (after end of dosing), 1 hour after start of 
dosing (30 minutes after end of dosing), 2.5 hours after start of dosing (2 hours after end 
of dosing). 
6. Serum PK samples will be taken at 5 minutes after end of dosing. 
 
10.1.5. 
Timing of Study Procedures 
 
10.1.5.1. Stage 1 
Procedures with a specified time frame will be considered per protocol if they are performed 
within the following windows: vital signs on dosing days ± 5 minutes in the first hour of start of 
dosing and ± 10 minutes thereafter; PK and PD draws on the day of dosing ± 5 minute; PK 
draws on Day 2, Day 3, Day 4, Day 23, Day 24, and Day 250 ± 2 hours. If multiple procedures 

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are specified at one time point, they should be performed in the following order: blood draw and 
then vital signs, with the blood draw at the exact specified time. 
10.1.5.2. Stage 2 and Stage 3 
Procedures with a specified time frame will be considered per protocol if they are performed 
within the following windows: vital signs on dosing days ±5 minutes in the first hour of start of 
dosing and ± 10 minutes thereafter; PK and PD draws on the day of dosing ± 5 minute; PK 
draws at the 24-, 48-, and 72-hour timepoints following the first and last dose ± 2 hours. If 
multiple procedures are specified at one time point, they should be performed in the following 
order: blood draw and then vital signs, with the blood draw at the exact specified time. 
10.1.6. 
Timing of Study Visits 
Visits outside the specified window will be considered protocol deviations. If OMS721 is not 
able to be administered within the visit window ± 2 days, the Investigator should contact the 
Sponsor Medical Monitor to discuss the course of action and disposition of the patient. 
10.2. 
Concomitant Therapy 
All concomitant medications and therapies will be recorded in the CRF. 
The following guidelines will be used in relation to treatments directed to TMA, underlying 
conditions, and suspected infections. 
10.2.1. 
Allowed Concomitant Therapies 
 
10.2.1.1. Plasma Therapy 
• Plasma therapy-resistant aHUS – plasma therapy during OMS721 treatment is 
allowed if the Investigator considers it medically indicated. 
• Chronic plasma therapy-responsive aHUS – plasma therapy should be continued until 
there is a sign of improvement in TMA, e.g., increase in platelet count, decrease in 
LDH, increase in haptoglobin, increase in hemoglobin, decrease in creatinine, at 
which time the Investigator should consider withholding plasma therapy and 
monitoring TMA parameters to assess whether plasma therapy can be discontinued. 
• TTP – plasma therapy is allowed if the Investigator considers it medically indicated. 
• HSCT-associated TMA – plasma therapy during OMS721 treatment is discouraged 
because there is no evidence that it is efficacious in this setting, and it requires 
supplemental OMS721 dosing. It is allowed if the Investigator considers it medically 
indicated. 
10.2.1.2. Renal Dialysis 
Renal dialysis therapy should be managed according to standard of care. OMS721 is not 
expected to be removed by hemodialysis so no supplemental dosing is planned. 

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10.2.1.3. Immunosuppressive Medications 
Immunosuppressive medications should be managed according to standard of care. 
 
10.2.1.4. Erythrocyte Stimulating Agents 
Erythrocyte-stimulating agents should be managed according to standard of care. 
 
10.2.1.5. Suspected Infection 
Because increased susceptibility to infections is a potential risk of inhibiting MASP-2 activity, 
patients should be closely monitored for symptoms or signs of infection. If the patient is 
suspected to have developed an infection, empiric antimicrobial therapy should be promptly 
initiated along with appropriate microbiological testing to identify the source of infection. 
 
10.2.2. 
Prohibited Concomitant Therapies 
 
10.2.2.1. Eculizumab 
If the Investigator decides to administer eculizumab, the patient should be withdrawn from the 
study. 
10.3. 
Treatment Compliance 
The study drug is to be administered by study personnel. Administration dates and times must be 
recorded in the CRFs. If any portion of a dose of study drug is not administered, an explanation 
must be provided in the source document and on the CRF. 
10.3.1. 
Definition of Departure from Protocol 
The following definitions will apply to the reporting of emergency and non-emergency 
departures from the protocol: 
Protocol Deviation: Any non-adherence to study procedures or schedules, as specified by the 
protocol. 
 
10.4. 
Safety Monitoring 
10.4.1. 
Dose Escalation Review 
The Sponsor’s Medical Monitor will monitor safety data in an ongoing manner throughout the 
study. 
In Stage 1 of the study, after enrollment and completion of dosing for each cohort, there was a 
safety review to determine whether dose escalation should proceed. Data for the safety review 
included AEs and clinically significant abnormalities in laboratory tests. PK and PD data may be 
reviewed to support dose escalation review, but they are not required because the main criteria 
will be safety. The safety data was reviewed by a clinical study monitoring team that consisted of 
the Sponsor Medical Monitor, PSI Medical Monitor, and at least 2 Investigators. The dose 
escalation decision will be guided by using the Common Terminology Criteria for Adverse 
Events (CTCAE) (Version 4.0) [USDHHS 2009] to grade AEs with a focus on Grade 3 or higher 
AEs. The number and causality of Grade 3 or higher AEs will be considered to determine if dose 

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escalation was appropriate. At the end of Stage 1, there was a safety and pharmacology data 
review to select the dose for Stage 2 and Stage 3, which were either the maximally tolerated dose 
or the biologically effective dose, whichever was lower. 
 
10.4.2. 
Data Monitoring Committee 
A DMC will meet (in-person or by telephone) and review cumulative data approximately every 
6 months. The DMC will review all serious adverse events (SAEs) on an ongoing basis as they 
occur. After each meeting (or as needed between meetings), the chairperson of the DMC will 
provide in writing 1 of the following recommendations to the Sponsor: 1) continue the study as 
planned, 2) continue the study under an amended protocol describing the recommended 
amendment, 3) suspend enrollment in the study pending provision of additional information, 4) 
suspend treatment in the study pending provision of additional information, or 5) discontinue the 
study. The DMC recommendation will also include the reasons upon which the recommendation 
is based. The DMC recommendations will be filed in the trial master file and included as an 
appendix in the clinical study report. 
 
11. 
ASSESSMENT OF EFFICACY 
In addition to the safety assessments described in Section 12 , this study evaluates efficacy, PK, 
PD, immunogenicity, and exploratory measures. 
 
11.1. 
Primary Efficacy Measures 
The primary efficacy measure is the proportion of patients who respond to OMS721 treatment 
defined as a patient with HSCT-TMA who demonstrates improvement in laboratory TMA 
markers (platelet count and LDH) and clinical benefit (either improvement in organ function or 
reduction in transfusion burden) as outlined in Section 7.3.1. 
 
11.2. 
Secondary Efficacy Measures 
The secondary efficacy measures are of duration of response, improved survival, organ function, 
or laboratory markers as outlined in Section 7.3.2 . 
11.3. 
Pharmacokinetics Measures 
Serial serum samples will be collected according to the Schedule of Events (Section 19) for 
analysis of OMS721 concentration. The samples will be analyzed by the bioanalytical laboratory 
of PRA in Lenexa, Kansas, using a validated assay method with a lower limit of quantitation 
(LLOQ) of 50 ng/mL. Sample collection and processing procedures will be provided in the study 
laboratory manual. 
11.4. 
Pharmacodynamics Measures 
Serial serum samples will be collected according to the Schedule of Events (Section 19) for 
analysis of the PD measure of inhibition of ex vivo lectin pathway activation. The samples will 
be analyzed by the bioanalytical laboratory of PRA in Assen, The Netherlands, using a validated 

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method. Sample collection and processing procedures will be provided in the study laboratory 
manual. 
11.5. 
Immunogenicity Measures 
Serial serum samples will be collected according to the Schedule of Events (Section 19) for 
analysis of ADA. The samples will be analyzed by the bioanalytical laboratory of PRA in Assen, 
The Netherlands, using a validated assay method. Sample collection and processing procedures 
will be provided in the study laboratory manual. 
 
11.6. 
Exploratory Measures 
Serial blood samples will be collected according to the Schedule of Events (Section 19) for 
future research (for patients who provide consent for this purpose), which may include analyses 
of DNA, RNA, protein, or cells. The proteins that are planned to be measured include MBL and 
MASP-2 because they are related to the mechanism of action of OMS721. Currently there are no 
plans for analysis of DNA, RNA, cells, or other proteins. The samples are collected in the event 
that emerging data from this study or published data from other research suggest that specific 
analyses may be informative with respect to prognosis, pharmacological response, clinical 
response, or toxicities. 
The change from baseline in TMA laboratory markers are exploratory measures in patients with 
aHUS and TTP. 
 
12. 
ASSESSMENT OF SAFETY 
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting the Sponsor to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient. The Investigator is responsible for appropriate 
medical care of patients during the study. 
Contact information for the Sponsor’s Medical Monitor for this study is provided in Section 1.2. 
 
12.1. 
Safety Parameters 
Safety will be evaluated by assessing AEs, clinical laboratory tests, vital signs, and ECG. Only 
clinically significant (per Investigator opinion) changes in vital signs or laboratory tests 
accompanied by clinical symptoms or those that require medical intervention will be reported as 
AEs. 
12.1.1. 
Laboratory Tests 
For evaluation of some of the laboratory assessments, a central laboratory will be used for all of 
the sites. The name and address of the clinical laboratory are included in the Investigator file. 
The following laboratory assessments will be performed in this study: 
• Chemistry tests include glucose, urea nitrogen, creatinine, total protein, albumin, total 
bilirubin, alkaline phosphatase, ALT, AST, calcium, sodium, potassium, chloride, and 
bicarbonate. 

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• Hematology tests include white blood cell count with automated differential 
(neutrophils, segmented neutrophils, lymphocytes, monocytes, eosinophils and 
basophils), schistocytes per high-powered field, RBC count, Hgb, hematocrit, mean 
corpuscular volume, mean corpuscular Hgb, mean corpuscular hemoglobin 
concentration, red cell distribution width, and platelet count. 
• Coagulation tests include prothrombin time, International Normalised Ratio (INR), 
and activated partial thromboplastin time. 
Urinalysis tests include color, specific gravity, pH, glucose, protein, bilirubin, urobilinogen, 
blood, ketone, nitrite, leukocyte esterase and microscopic if required (RBCs, white blood cells, 
and bacteria). 
12.1.2. 
Other Safety Measures 
• Vital signs include systolic and diastolic BP, pulse rate, RR, and temperature. 
• ECG parameters include heart rate, PR interval, QRS interval, QT interval, and QTc 
interval calculated by Fridericia’s formula (QTcF), along with a clinical interpretation 
by the Investigator. 
12.2. 
Definition of Adverse Events 
12.2.1. 
Definition of Adverse Events 
The following definitions from the International Conference on Harmonisation (ICH) Guideline 
E2A will apply to the reporting of AEs and adverse drug reactions: 
Adverse Event: Any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. 
Adverse Drug Reaction: All noxious and unintended responses to a medicinal product related 
to any dose. 
The phrase, “responses to a medicinal product” means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship 
cannot be ruled out. 
Unexpected Adverse Drug Reaction: An adverse reaction, the nature or severity of which is 
not consistent with the Investigator’s Brochure. 
Serious Adverse Event: Any untoward medical occurrence that at any dose: 
• Results in death 
• Is life-threatening 
− The term “life-threatening” refers to an event in which the patient 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 prolongs existing hospitalization 

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• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
Serious adverse events also include important medical events that may not be immediately life- 
threatening or result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above. Examples of 
such events are 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. 
12.2.2. 
Definitions of Severity 
Adverse events will be graded using the CTCAE v.4.0 [USDHHS 2009]. 
Note that “seriousness” and “severity” are distinct concepts. “Serious” is a term applied to an AE 
that meets specific requirements (refer to Section 12.2.1). “Severity” refers to the AE intensity 
classification. 
 
12.2.3. 
Relationship to Study Drug 
The Investigator will determine the assessment of the causal relationship of the AE to the study 
drug. 
The relationship of AEs to study drug is categorized as probable, possible, unlikely, or not 
related. An alternative etiology must be provided for all AEs for which the relationship to study 
drug is considered “possible,” “unlikely,” or “not related.” 
Definitions of each of these terms are below: 
Probable: The AE has a timely relationship to administration of the study drug and there is no 
apparent, potential alternate etiology. 
Possible: The AE has a timely relationship to administration of the study drug and there is an 
apparent, potential alternate etiology. 
Unlikely: The AE is likely related to an etiology other than administration of study drug. 
Not Related: The AE is related to an etiology other than the study drug. 
An AE with causal relationship not initially determined will require follow-up to assign 
causality. 
12.2.4. 
Assessment of the Clinical Outcome of Adverse Events 
The Investigator (a study physician) will determine the clinical outcome of the AE as follows: 
Recovered Completely: Patient has fully recovered from the event with no residual effects 
observable. 
Recovered with Sequelae: Effects of the event are stabilized and constant. The likelihood of 
these effects changing (improving or worsening) is low. 
Not Yet Recovered: Effects of the event are still present and changing. The event is not 
considered recovered completely or recovered with sequelae. 

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Unknown; Lost to Follow-up: Not known, not observed, not recorded, or refused to provide 
information. 
Died: The event may or may not be the primary cause of death (may or may not be the 
immediate cause of death). 
 
12.3. 
Reporting Adverse Events 
12.3.1. 
Adverse Event Reporting 
Adverse events will be collected from the time informed consent is obtained until the last 
Follow-up visit. 
All AEs will be documented in the source records and will be recorded in the CRFs as 
appropriate. All AEs, whether observed by the Investigator or reported by the patient, and 
whether or not thought to be related to the study drug, will be recorded on the appropriate CRF. 
In describing AEs on the CRF, standard, medically accepted terminology will be used. 
The description of each AE will identify the date of onset, duration, severity (see Section 12.2.2 
for Definitions of Severity), any action taken (including any diagnostic procedures or laboratory 
tests performed and all treatments that were administered), the outcome of the event, and 
relationship to the study drug. 
Any medical condition that is present at the time that the patient is screened should be considered 
as baseline and not recorded as an AE. However, if the medical condition increases in frequency 
or severity during or following administration of the study drug, it will be recorded as an AE on 
the appropriate CRF. 
An AE is defined as any untoward medical occurrence in a patient administered a pharmaceutical 
product and which does not necessarily have to have a causal relationship with this treatment. 
Adverse events may be reported by the patient, discovered by the Investigator and Investigator’s 
staff, or detected through physical examination, laboratory test, or other means. 
Adverse events include: 
• Any unfavorable and unintended sign, medical diagnosis, or symptom that occurs 
between the time of the first administration of study drug and the study duration 
required by the protocol. 
• Any new undesirable medical experience or an unfavorable and unintended change of 
an existing condition that occurs between the time of the first administration of study 
drug and the study duration required by the protocol, whether or not considered 
related to study drug. 
• Abnormal laboratory findings considered by the Investigator to be clinically 
significant, i.e., those that are unusual for the population being studied or individual 
patient. 
Whenever possible, the Investigator should group signs or symptoms that constitute a single 
diagnosis into a single event term. For example, cough, rhinitis, and sneezing might be grouped 
together as upper respiratory tract infection. 

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In cases where the Investigator notices an unanticipated benefit to the patient, study site 
personnel should enter unanticipated benefit with the actual event term (for example, the 
complete actual term may be unanticipated benefit-sleeping longer). 
 
12.3.2. 
Serious Adverse Event Reporting 
All SAEs will be: 
• recorded on the appropriate SAE case report form 
• followed through resolution or at a stable condition by a study physician 
• reviewed by a study physician. 
The investigative site is required to report any SAE directly to the Sponsor’s pharmacovigilance 
designee on the Serious Adverse Event form within 24 hours of becoming aware of the event, 
whether or not the SAE is deemed drug-related (see Section 1.2 for contact information). 
The study physician will complete an Expedited or Serious Adverse Event Form within the 
following timelines: 
• All deaths and immediately life-threatening events, whether related or unrelated to 
study drug, will be recorded on the Expedited or Serious Adverse Event Form and 
faxed/electronically communicated within 24 hours of site awareness. 
Other supporting documentation of the event may be requested by the pharmacovigilance staff 
and should be provided as soon as possible. 
A distinction is drawn between serious and severe events. A severe event is a major experience 
of its type. A severe event does not necessarily need to be serious. For example, nausea that 
persists for several hours may be considered severe nausea, but not a serious adverse experience. 
On the other hand, a stroke that results in only a limited degree of disability may be considered a 
mild stroke, but it would be considered a SAE. 
Death is an outcome of an event and not an event per se (sudden death or death of unexplainable 
causes can be reported, but follow-up will be required until cause of death is determined). 
 
12.3.3. 
Reporting of Serious Adverse Events to Regulatory Agencies 
The Sponsor or its designee will submit the SAEs requiring expedited reporting to regulatory 
agencies. The ethics committee will be notified of SAEs in accordance with federal, national, 
and local laws and regulations. 
 
12.3.4. 
Pregnancy and Overdose Reporting 
Cases of pregnancy must be reported for tracking purposes. If a patient becomes pregnant during 
the study, the Sponsor’s Pharmacovigilance designee must be notified by fax or email within 
24 hours of site awareness and the patient discontinued from study drug. Additional instructions 
for reporting of the pregnancy and outcome will be provided by the Sponsor at the time of 
notification. Pregnancies of partners of male patients will also be followed provided the patient’s 
partner provides informed consent for follow-up of the pregnancy. 

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Occurrences of overdose should be reported to the Sponsor for tracking purposes. Overdose is 
defined as any dosing above the protocol-defined dosing instructions. Additional instructions for 
reporting overdose information will be provided by the Sponsor at the time of notification. 
 
12.4. 
Type and Duration of the Follow-Up of Patients After Adverse 
Events 
All reportable AEs will be followed until satisfactory resolution or until the Investigator deems 
the event to be chronic or the participant to be stable. 
If an SAE persists at the last visit or the time of early termination after study treatment, it will be 
marked as “ongoing” and “not yet recovered” in the CRF. It will be followed by the Investigator 
until such time that it is deemed to be resolved or at a stable condition. Follow-up data for such 
SAEs will be collected in the source documents and reported appropriately. 
12.5. 
Appropriateness of Measurements 
12.5.1. 
Efficacy Measures 
The primary efficacy measure evaluates the proportion of patients who respond to OMS721 
treatment. The response criteria include laboratory measures of TMA activity and clinical status. 
These measures provide an assessment of underlying TMA activity as well as potential clinical 
benefit experienced by patients. Secondary efficacy measures provide population-level support 
for patient-level responses observed. 
12.5.2. 
Pharmacokinetic Measures 
Drug concentrations are standard PK measures. 
 
12.5.3. 
Pharmacodynamic Measures 
Inhibition of ex vivo lectin pathway activation is a relevant PD measure as this is the biological 
target of OMS721. 
12.5.4. 
Immunogenicity Measures 
Anti-drug antibody response is a standard immunogenicity measure for a therapeutic protein. 
 
12.5.5. 
Exploratory Measures 
Mannan-binding lectin and MASP-2 concentrations are being measured to assess whether 
OMS721 administration alters them. Laboratory TMA measures in patients with aHUS and TTP 
are appropriate exploratory evaluations in these populations. 
12.5.6. 
Safety Measures 
The collection of AEs, clinical laboratory tests, vital signs, and ECGs are standard safety 
measures. 

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13. 
STATISTICS 
13.1. 
Determination of Sample Size 
In Stage 1 of the study, 3 patients per dose escalation cohort is a common scheme and is 
considered to be sufficient in combination with data from the Phase 1 study to allow selection of 
a dose for Stage 2. 
In Stage 2, the sample size for each cohort (aHUS and HSCT-TMA/TTP) is determined by 
comparison to the total sample size of uncontrolled Phase 2 studies that provided sufficient data 
for approval of eculizumab for the treatment of aHUS [Legendre 2013]. This sample size is 
considered adequate in these orphan diseases to identify treatment effects in uncontrolled studies. 
It is expected that approximately 28 HSCT-TMA patients enrolled before Protocol Amendment 
11 will be included to support a regulatory approval. The width of the exact 95% confidence 
interval (CI) for the response rate based on 28 HSCT-TMA patients ranges from 12.3% to 
38.7%. If the observed response rate is 50%, the exact 95% CI is 30.6% to 69.4%. 
Because this is an exploratory study, the sample size may be adjusted based on emerging data. If 
the sample size differs markedly from the planned enrollment, the protocol will be amended to 
accommodate the change. 
13.2. 
Statistical and Analytical Plans 
The statistical and analytical plans presented below are an overview of key analysis methods. 
Details of the analysis will be specified in the statistical analysis plan (SAP). A change to the 
data analysis methods described in the protocol will require a protocol amendment only if it 
alters a principal feature of the protocol. The SAP will be finalized prior to interim database lock. 
Any changes to the methods described in the final SAP will be described and justified in the 
clinical study report. 
13.2.1. 
General Considerations 
All data summaries will be descriptive in nature. Summary statistics for continuous variables will 
include number of patients, mean, median, standard deviation, minimum, and maximum. For 
categorical variables, frequencies and percentages will be provided. When required for the 
statistical analysis of a particular variable, the baseline value will be the last recorded value prior 
to the administration of the first dose of study treatment. There are 2 exceptions. The baseline 
platelet count is defined as the average of the 2 predose values. The baseline creatinine is defined 
as the maximum creatinine value between the diagnosis of TMA and 4 weeks after the first dose 
of OMS721. 
Statistical analyses will be focused on the HSCT-TMA patients and will be summarized by 
OMS721 dose (4.0 mg/kg, 370 mg, and both doses combined). Atypical hemolytic uremic 
syndrome and TTP patients will be summarized separately by OMS721 dose. 

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13.2.1.1. Handling of Missing Data 
Non-responder imputation will be used to handle missing data for the binary efficacy endpoints. 
Time-weighted average analysis and repeated measures models will be used to analyze the 
continuous secondary efficacy endpoints over time. 
 
13.2.1.2. Analysis Populations 
Efficacy analyses will be performed for the Full Analysis Set (FAS) population and the Per- 
protocol Patient Set (PAS) population. The FAS population will include all HSCT-TMA patients 
who received any amount of study drug. The PAS population will include all HSCT-TMA 
patients who received at least 4 weeks of study treatment (treatment period is ≥ 28 days). 
Safety analyses will be based on the Safety Analysis Set population, which includes all patients 
(aHUS, TTP, and HSCT-TMA) who received any amount of study drug. 
13.2.2. 
Patient Disposition 
An accounting of study patients by disposition will be tabulated by disease and dose. Patients 
who discontinued study drug prematurely or withdrew from the study will be summarized and 
listed, with reason for early termination/withdrawal. 
 
13.2.3. 
Patient Characteristics 
Demographic, other baseline characteristics, concomitant medications, and therapies (plasma 
therapy or renal dialysis) will be summarized descriptively by disease and dose. 
13.2.4. 
Treatment Compliance 
Because all dosing will be under direct supervision of study personnel, treatment compliance will 
not be analyzed. Dosing information, including supplemental dosing in conjunction with plasma 
therapy, will be listed. 
13.2.5. 
Efficacy Analyses 
 
13.2.5.1. Analysis of Primary Efficacy Endpoint 
A patient is a responder if this patient meets the responder criteria (Section 7.3) at any time post 
baseline during the study. If a patient is not evaluable for a response criterion due to confounding 
factors, the non-evaluable response criterion will not be included in the determination of 
responder. Evaluability of each response criterion will be determined by a clinical review of 
relevant data and will be documented in the clinical study report. For example, potential 
confounding factors include graft failure for platelet count or transfusions and nephrotoxic 
medications for renal function. Furthermore, laboratory values collected from both the local 
laboratories and the central laboratories will be used to determine response status. 
Analysis of the primary efficacy endpoint will use a non-responder imputation to impute missing 
or incomplete data to evaluate response. The number and percent of responders will be 
summarized with exact 95% CI (Clopper-Pearson) by dose and total for the FAS and PAS 
populations. If the lower bound of the exact 95% CI is greater than 15%, there is sufficient 

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evidence to demonstrate efficacy of OMS721 in the target patient population. Each criteria of the 
response will be listed for each patient. 
Sensitivity analyses will include: 
• Subgroup analyses for the FAS population 
• A completer analysis will be performed using the patients with non-missing responses 
only. Exact 95% CI for the completer response rate will be provided for the FAS 
population by dose. 
• Two alternative definitions of response will be analyzed: 
− The first alternative response is defined as achieving an improvement in TMA 
markers and an improvement in renal function as defined in Section 7.3. The 
number and percent of the patients achieving the first alternative response will be 
summarized with exact 95% CI by dose for the FAS population. 
− The second alternative response is defined as the same as the primary endpoint by 
excluding the neurological function defined in Section 7.3. The number and 
percent of patients achieving the second alternative response will be summarized 
with exact 95% CI by dose for the FAS population. 
In addition, individual patient plots of platelet count and LDH over time will be provided. 
 
13.2.5.2. Analysis of Secondary Efficacy Endpoints 
The 100-day survival status will be determined as a binary variable. A patient achieves a 100-day 
survival if the overall survival from the date of HSCT-TMA diagnosis of the patient is ≥ 100 
days. If the 100-day survival status of a patient is unknown (i.e., censored before 100 days), this 
patient will be considered to have died prior to 100 days. The 100-day survival rate will be 
estimated with exact 95% CI by dose for the FAS population. 
Overall survival will be calculated from the date of TMA diagnosis. Overall survival will be 
analyzed using Kaplan-Meier method by dose for the FAS population. Median overall survival 
and its 95% CI will be estimated by dose. 
The duration of response will be estimated for the FAS population. Duration of response is 
defined as the number of days from the first response date to the first relapse date (first relapse 
date – first response date + 1). The first response date is the first date that platelet count and LDH 
response is achieved. Relapse is defined as having a platelet count greater than 50% decrease 
from the maximum platelet count and an LDH greater than 1.5 times the ULN. Relapse will be 
evaluated using the platelet count and the LDH collected within 1 week. Duration of response 
will be censored at the last platelet or LDH collection date if relapse does not occur during the 
study. Kaplan-Meier analysis of the duration of response will be performed for the patients who 
achieve a response by dose for the FAS population. Median duration of response will be 
presented with 95% CI. 
Binary secondary efficacy endpoints will be summarized with exact 95% CI by dose for the FAS 
population. Non-responder imputation will be used to handle missing data. 

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In addition, efficacy laboratory values of platelet count, LDH, creatinine, hemoglobin, and 
haptoglobin will be plotted over time for the HSCT-TMA patients. 
13.2.6. 
Pharmacokinetic Analyses 
Plasma concentrations of OMS721 and PD measures will be provided in listings. These data will 
be used in integrated population PK/PD analyses across studies. A PK/PD analysis plan will 
document the analyses. 
13.2.7. 
Pharmacodynamic Analyses 
The number and percent of patients with ADA will be summarized by disease, dose, Drug 
Product formulation, and time. Potential effects of ADA on PK and PD will be evaluated in 
integrated population PK/PD analyses which will be documented in the PK/PD analysis plan. 
13.2.8. 
Exploratory Analyses 
The concentration of MBL and MASP-2 will be summarized with descriptive statistics by 
disease, dose time, and Drug Product formulation, if appropriate. Thrombotic microangiopathy 
markers will be summarized by disease for aHUS and TTP. 
13.2.9. 
Safety Analyses 
 
13.2.9.1. Extent of Exposure 
Study drug administration and duration of treatment will be summarized by disease and dose. 
 
13.2.9.2. Adverse Events 
Adverse events collected during the study and significant AEs will be combined for analysis. 
They will be labeled as AEs for simplicity. Significant AEs are the AEs that occurred outside the 
protocol-specified reporting period and will be collected for the HSCT-TMA patients only. For 
reporting purposes, AEs will be divided into 2 categories: 
• Those that occurred prior to the start of study treatment (pre-treatment events) and 
• Those that occur or worsen in intensity after the start of study treatment (treatment- 
emergent adverse events). 
Summary of AEs will include the non-serious AEs during the AE evaluation period and all 
reported serious AEs. The AE evaluation period is defined from the time of informed consent to 
37 days after the last study drug administration. 
All AEs will be classified by system organ class and preferred term using the Medical Dictionary 
for Regulatory Activities (MedDRA). An AE is considered treatment-related if the relationship 
to study drug is either probable or possible as assessed by the Investigator. 
Patient incidence of the following AEs will be provided: 
• Pre-treatment AEs by MedDRA System Organ Class (SOC), preferred term, dose, 
and disease 
• Treatment-emergent AEs by MedDRA SOC, preferred term, dose, and disease 

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• Treatment-emergent AEs by MedDRA preferred term, dose, and disease 
• Treatment-related AEs by MedDRA SOC, preferred term, dose, and disease 
• Treatment-emergent AEs by MedDRA preferred term, maximum severity, dose, and 
disease 
• AEs leading to study discontinuation by MedDRA SOC, preferred term, dose, and 
disease 
• Treatment-emergent serious AEs (SAEs) by MedDRA SOC, preferred term, dose, 
and disease 
• Treatment-related SAEs by MedDRA SOC, preferred term, dose, and disease 
• AEs leading to death by MedDRA SOC, preferred term, dose, and disease 
In addition, the following analyses will be performed: 
• Treatment-emergent AEs and treatment-emergent SAEs during the AE evaluation period 
will be summarized separately for patients with and without ADA postdose. 
• Treatment-emergent AEs that started or worsen in intensity after the AE evaluation 
period will be summarized with patient incidence by SOC, preferred term, disease group, 
and dose level. 
• Pre-treatment and treatment-emergent significant infections will be summarized by 
infection type, which will be determined before database lock and will be documented in 
the CSR. 
13.2.9.3. Clinical Laboratory Results 
Statistical analysis of clinical laboratory tests will be based on the results from central 
laboratories only. Results from central and local laboratories will be listed. 
Summary statistics for the actual values and the change from baseline will be tabulated for 
laboratory results by dose, disease, and scheduled visit. Patients with laboratory values outside of 
the normal reference range at any post baseline assessment will be summarized by dose and 
disease. Shift tables comparing the baseline National Cancer Institute (NCI) CTCAE grade to the 
worst post baseline grade will be provided by dose and disease. 
13.2.9.4. Vital Signs 
Summary statistics for actual values and change from baseline will be tabulated for vital signs by 
dose, disease, and scheduled visit. 
 
13.2.9.5. Electrocardiogram 
The ECG parameters (heart rate, PR interval, QRS interval, QT interval, and QTc interval) at 
each time point as well as the change from baseline will be summarized with descriptive 
statistics by dose and disease. These parameters will be determined electronically by the ECG 
machine at the clinical site. QTcF will be calculated using Fridericia’s formula. 

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The overall ECG assessment will be reported as “Normal,” or “Abnormal – not clinically 
significant” or “Abnormal – clinically significant” with respect to relevant abnormalities by the 
Investigator. Shifts from the baseline ECG assessment to the worst post baseline ECG 
assessment will be tabulated by dose and disease. A listing of specific ECG abnormalities will be 
provided. 
13.2.10. 
Interim Analyses 
The coronavirus associated lockdown situation in various countries has created uncertainty in the 
ability to collect all follow-up data and resolve all queries on a few patients enrolled in the study. 
When adequate data on the primary and secondary endpoints is available, the database will be 
locked for interim analyses and creation of an interim CSR to enable regulatory submission for 
drug approval. Efforts will continue to collect additional follow-up data and resolve any 
outstanding queries. 
 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Investigator will maintain appropriate medical and research records for this trial in 
accordance with ethics committee, regulatory, and ICH requirements for the protection of 
confidentiality of patients. The Investigator and his/her study center(s) will permit authorized 
representatives of the Sponsor, the governing ethics committee, competent authority, FDA, 
EMA, and/or other regulatory agencies to examine clinical records for the purposes of assisting 
with data entry, monitoring the study, including verifying the accuracy and completeness of data, 
evaluating study safety, assessing protocol and regulatory adherence and quality assurance 
reviews, audits, and inspections. 
 
14.1. 
Study Monitoring 
The Investigator and his/her study center(s) agree to allow the Sponsor or its representative to 
have direct access to all study-related source data/documents (as noted above) during monitoring 
visits. The monitoring visits provide the Sponsor with the opportunity to evaluate the progress of 
the study, to verify the accuracy and completeness of CRFs, to resolve any inconsistencies in the 
study records, as well as assuring that all protocol requirements, applicable regulations, and 
Investigator's obligations are being fulfilled. 
The study monitor will record the date of each visit together with a summary of the status and 
progress of the study. Proposed actions will be confirmed with the Investigator. 
14.2. 
Audits and Inspections 
The study center will allow representatives of the Sponsor to periodically audit, at mutually 
convenient times, during and after the study all CRFs and corresponding source documents for 
each patient. CRFs will be reviewed by the Sponsor or its representative for adherence to 
protocol, completeness, and acceptability. Portions of the patient's medical and hospital records 
pertinent to the study will be reviewed at the study center to assure accuracy. It is important that 
the Investigator and/or other staff are available at these visits. 

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Additionally, during the course of this study or after it has been completed, representatives of 
FDA or other regulatory agency and the Investigator’s ethics committee may inspect the study 
and review all study documents and reports, including CRFs, each patient’s medical records, and 
other source documents. The Investigator agrees to make all study records, reports, and 
correspondence available to representatives of a regulatory agency or ethics committee. It is 
important that the Investigator and/or other staff are available at these visits. If contacted by a 
regulatory agency for an inspection, please call the Sponsor’s study monitor immediately. 
Contact information for the Sponsor’s study monitor is included in the Investigator file. 
 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following standard operating procedures, monitors will verify that the clinical trial is conducted 
and that data are generated, documented (recorded), and reported in compliance with the 
protocol, Good Clinical Practice (GCP), and applicable regulatory requirements. 
The investigational site should have standard operating procedures for quality management and 
will provide direct access to all trial-related sites, source data/documents, and reports for the 
purpose of monitoring and auditing by the Sponsor and inspection by local and regulatory 
authorities. 
Data management will implement quality-control procedures beginning with the data entry 
system and generate data-quality checks that will be run on the database. Any missing data or 
data anomalies will be communicated to the site(s) for clarification/resolution. The site will be 
obligated to resolve the clarification of data in a timely manner. 
 
15.1. 
Monitoring 
Standards for GCP, as outlined by the ICH and FDA, will be applied to all study-based 
procedures. 
To ensure accurate, complete, and reliable data, the Sponsor or its representatives will do the 
following: 
• Provide instructional material to the study sites, as appropriate. 
• Provide start-up training and continuing training (if applicable) to the Investigator and 
study personnel on the protocol, the completion of the CRFs, and study procedures. 
• Make periodic monitoring visits to the investigational site. 
• Be available for consultation and stay in contact with the investigational site 
personnel by mail, telephone, electronic mail, and/or fax. 
• Monitor the patient data recorded in the CRF against source documents at the 
investigational site. 
• Review and evaluate CRF data and use standard criteria to detect potential errors in 
data collection and forward them to the Investigator for resolution. 

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15.2. 
Auditing 
The study may be audited periodically by the Sponsor or its representatives at any time. 
 
16. 
ETHICS 
16.1. 
Ethics Review 
Each participating institution must provide for the review and approval of this protocol, the 
associated informed consent documents, and any patient-directed materials by a properly 
constituted, IEC, or IRB. Any amendments to the protocol, consent, or patient-directed materials 
must also be approved prior to implementation. The Investigator will provide the Sponsor or its 
designee with documentation of the IRB or IEC approval of the protocol, informed consent 
document, and patient-directed materials before the study may begin at the investigative site(s). 
In addition, the Investigator will submit for review to the investigative site’s IRB/IEC: 
• Clinical Investigator’s Brochure and updates 
• Required safety and SAE reports 
• Deviations from the protocol and applicable FDA regulations (as required by the 
IRB/IEC) 
• Any additional submissions (e.g., continuing review reports or new information) 
required by the site’s IRB/IEC 
The IRB/IEC will provide initial and continuing review. The continuing review will be 
performed at least once per year. 
The Investigator must provide the Sponsor or its designee all IRB/IEC related submission 
decisions, approvals, and/or acknowledgement of receipts, as appropriate. 
16.2. 
Ethical Conduct of the Study 
16.2.1. 
Regulatory Considerations 
This study will be conducted in accordance with the protocol and ethical principles stated in the 
Declaration of Helsinki, GCP, and all other applicable national, state, and local laws, rules, and 
regulations. 
After reading the protocol, the Investigator will sign the Investigator Agreement and return it to 
the Sponsor or its designee. 
16.2.2. 
Investigator Information 
The contact information and qualifications of the Investigators and name and address of the 
research facilities are included in the Investigator file. 

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16.2.3. 
Protocol Amendments and Study Termination 
Any Investigator-initiated changes to the protocol (with the exception of changes to eliminate an 
immediate hazard to a study patient) must be approved by the Sponsor prior to seeking approval 
from the IRB/IEC and prior to implementing. The Investigator is responsible for enrolling 
patients who have met protocol eligibility criteria. Protocol deviations must be reported to the 
Sponsor and to the local IRB/IEC in accordance with IRB/IEC policies. 
The Sponsor may terminate the study at any time. The IRB/IEC must be advised in writing of 
study completion or early termination. 
 
16.2.4. 
Participant Confidentiality 
All reports and communications relating to patients in the study will identify each patient only by 
the patient’s initials and/or patient number. 
 
16.2.5. 
Clinical Trial Agreement 
Payments by the Sponsor to Investigators and institutions conducting the trial, requirements for 
Investigators’ insurance, the publication policy for clinical trial data, and other requirements are 
specified in the Clinical Trial Agreement. 
 
16.3. 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continuing throughout the individual’s study participation. Any procedures 
specifically for the study cannot be started until the informed consent form is signed by the 
patient and the person conducting the consent. Discussion of risks and possible benefits of this 
therapy will be provided to the patients. Consent forms describing in detail the Study 
Agent(s)/Intervention(s) study procedures and risks are given to the patient, and written 
documentation of informed consent is required prior to starting study agent/intervention. Consent 
forms will be IRB/IEC-approved, and the patient will be asked to read and review the document. 
Upon reviewing the document, the Investigator or appropriate designee will explain the research 
study to the patient and answer any questions that may arise. The patients should have sufficient 
opportunity to discuss the study and process the information in the consent process prior to 
agreeing to participate. The patients may withdraw consent at any time throughout the course of 
the trial. A copy of the informed consent document will be given to the patients for their records. 
The rights and welfare of the patients will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this study. 
In addition, patients will provide written permission for use and disclosure of protected health 
information collected in connection with participation in this study through an authorization that 
satisfies the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule (see 45 
CFR 164.508). The authorization will be provided to patients in accordance with IRB 
procedures. The authorization may either be combined with the informed consent or provided as 
a separate document. 
When a patient who may be enrolled in the trial only with the consent of the patient’s legally 
acceptable representative (e.g., minors or participants with severe dementia), the patient should 
be informed about the trial to the extent compatible with the patient’s understanding. If capable, 

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the patient should assent and sign and personally date the written consent form. A separate 
IRB/IEC-approved assent form, describing (in simplified terms) the details of the Study 
Agent(s)/ Intervention(s), study procedures, and risks may be used. Assent forms do not 
substitute for the consent form signed by the patient’s legally acceptable representative. 
Data or records provided to Omeros will be coded, redacted, and de-identified to protect patient 
anonymity. All personal identifying data from this study will be treated in accordance with 
national and local data protection laws. 
 
16.4. 
Investigator Reports 
During the conduct of the study and at its completion, the Investigator will report to the IRB/IEC 
as required by the applicable IRB/IEC requirement and regulations. In addition, the Investigator 
will report to the Sponsor in accordance with regulation 21 CFR 312.64. 
 
17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the Investigator’s site staff to 
ensure that the documents are accurate and complete. Adverse events must be graded, assessed 
for severity and causality, and reviewed by the Investigator. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the Investigator. During the study, the Investigator must maintain complete and accurate 
documentation for the study. 
 
17.2. 
Data Capture Methods 
Case Report Forms are used to transmit the information collected in the performance of this 
study to the Sponsor and FDA. The original CRFs will be retained by the Sponsor, and the 
Investigator will retain copies of the CRFs with the other records for this study. 
The Investigator and study personnel will ensure that proper data for the clinical study are 
collected and accurately documented in the appropriate sections of the CRFs. The Investigator 
will review each CRF for completeness and accuracy and sign and date the forms where 
indicated. In addition, it will be the Investigator's responsibility to provide signatures where 
requested indicating concurrence with data in the CRF. 
Case Report Forms will be reviewed by monitors from the Sponsor or its representative for 
adherence to protocol, completeness, and acceptability. Portions of the patient’s medical and 
hospital records pertinent to the study will be reviewed at the study center to assure accuracy. 
 
17.3. 
Source Documents 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH-GCP, regulatory, and institutional requirements, for the protection of 
confidentiality of participants. 

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Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Examples 
of these original documents and data records include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, participants’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, and participant files and records 
kept at the pharmacy, at the laboratories, and medico-technical departments involved in the 
clinical trial. Food and Drug Administration regulations require that the Investigator prepares 
and maintains adequate and accurate records for each patient treated with study drug. 
 
17.4. 
Retention of Records 
Government agency regulations and directives require that all study documentation pertaining to 
the conduct of a clinical trial must be retained by the Investigator until notified by the Sponsor in 
writing that retention is no longer necessary. 
Case Report Forms are used to transmit the information collected in the performance of this 
study to the Sponsor and regulatory agencies. The original CRFs will be retained by the Sponsor, 
and the Investigator will retain copies of the CRFs with the other records for this study. 
Food and Drug Administration regulations require that the Investigator prepares and maintains 
adequate and accurate records for each patient treated with study drug. Source documents, such 
as hospital, clinic or office charts, laboratory reports, ECGs, operative reports, anesthesia 
records, consultation reports, history and physical examination reports, study worksheets, and the 
signed informed consent, will be included in the Investigator's files with the patient’s study 
records. 
Records containing patient medical information must be handled in accordance with the 
requirements of the HIPAA Privacy Rule (US) or applicable privacy regulations in the relevant 
countries and consistent with the terms of the patient authorization contained in the informed 
consent document for the study (the authorization). Care should be taken to ensure that such 
records are not shared with any person or for any purpose not contemplated by the authorization. 
Furthermore, CRFs and other documents to be transferred to the Sponsor should be completed in 
strict accordance with the instructions provided by the Sponsor, including the instructions 
regarding the coding of patient identities. 
No study document should be destroyed without prior written agreement between the Sponsor 
and the Investigator. Should the Investigator wish to assign the study records to another party or 
move them to another location, written agreement must be obtained from the Sponsor. 

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18. 
REFERENCES 
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for HSCT-associated thrombotic microangiopathy: a study in children and young adults. Blood. 
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Jodele S, Fukuda T, Vinks A, Mizuno K, Laskin BL, Goebel J, et al. Eculizumab Therapy in 
Children with Severe Hematopoietic Stem Cell Transplantation-Associated Thrombotic 
Microangiopathy. Biol Blood Marrow Transplant. 2014b. 
Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM, et al. A new paradigm: 
Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system 
endothelial injury. Blood Rev. 2015;29(3):191-204. 
Kenawy HI, Ali YM, Rajakumar K, Lynch NJ, Kadioglu A, Stover CM, et al. Absence of the 
lectin activation pathway of complement does not increase susceptibility to Pseudomonas 
aeruginosa infections. Immunobiology. 2012;217(2):272-80. 
Kerr H, Richards A. Complement-mediated injury and protection of endothelium: lessons from 
atypical haemolytic uraemic syndrome. Immunobiology. 2012;217(2):195-203. 
Khosla J, Yeh AC, Spitzer TR, Dey BR. Hematopoietic stem cell transplant-associated 
thrombotic microangiopathy: current paradigm and novel therapies. Bone Marrow Transplant. 
2017;53(2):129. 
Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, et al. Terminal 
complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 
2013;368(23):2169-81. 
Lindas R, Tvedt THA, Hatfield KJ, Reikvam H, Bruserud O. Preconditioning Serum Levels of 
Endothelial Cell-Derived Molecules and the Risk of Posttransplant Complications in Patients 
Treated with Allogeneic Stem Cell Transplantation. Journal of Transplantation. 2014;2014:9. 

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85 
 
 
 
 
Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 
2011;6:60. 
Mahajan SD, Tutino VM, Redae Y, Meng H, Siddiqui A, Woodruff TM, et al. C5a induces 
caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus. 
Immunology. 2016;148(4):407-19. 
Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002;347(8):589-600. 
Olesen HV, Jensenius JC, Steffensen R, Thiel S, Schiotz PO. The mannan-binding lectin 
pathway and lung disease in cystic fibrosis--disfunction of mannan-binding lectin-associated 
serine protease 2 (MASP-2) may be a major modifier. Clin Immunol. 2006;121(3):324-31. 
Postalcioglu M, Kim HT, Obut F, Yilmam OA, Yang J, Byun BC, et al. Impact of Thrombotic 
Microangiopathy on Renal Outcomes and Survival after Hematopoietic Stem Cell 
Transplantation. Biol Blood Marrow Transplant. 2018. 
Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune 
surveillance and homeostasis. Nat Immunol. 2010;11(9):785-97. 
Rosenthal J. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review 
of pathophysiology, diagnosis, and treatment. J Blood Med. 2016;7:181-6. 
Rotz SJ, Dandoy CE, Davies SM. ST2 and Endothelial Injury as a Link between GVHD and 
Microangiopathy. N Engl J Med. 2017a;376(12):1189-90. 
Rotz SJ, Luebbering N, Dixon BP, Gavriilaki E, Brodsky RA, Dandoy CE, et al. In vitro 
evidence of complement activation in transplantation-associated thrombotic microangiopathy. 
Blood advances. 2017b;1(20):1632-4. 
Schlapbach LJ, Aebi C, Otth M, Leibundgut K, Hirt A, Ammann RA. Deficiency of mannose- 
binding lectin-associated serine protease-2 associated with increased risk of fever and 
neutropenia in pediatric cancer patients. Pediatr Infect Dis J. 2007;26(11):989-94. 
St Swierzko A, Cedzynski M, Domzalska-Popadiuk I, Macdonald SL, Borkowska-Klos M, 
Atkinson AP, et al. Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large 
cohort of neonates and its clinical associations. Mol Immunol. 2009;46(8-9):1696-701. 
Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, et al. 
Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 
2003;349(6):554-60. 
Sullivan M, Erlic Z, Hoffmann MM, Arbeiter K, Patzer L, Budde K, et al. Epidemiological 
approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. Ann 
Hum Genet. 2010;74(1):17-26. 
Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, et al. Deficiency of mannan- 
binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 
2007;8(2):154-63. 
USDHHS. Common Terminology Criteria for Adverse Events (CTCAE). 2009 5/28/2009. 
Report No.: V4. 

Protocol No. OMS721-TMA-001 (A11.1) 
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86 
 
 
 
 
Vander Lugt MT, Braun TM, Hanash S, Ritz J, Ho VT, Antin JH, et al. ST2 as a marker for risk 
of therapy-resistant graft-versus-host disease and death. N Engl J Med. 2013;369(6):529-39. 
Vion AC, Rautou PE, Durand F, Boulanger CM, Valla DC. Interplay of Inflammation and 
Endothelial Dysfunction in Bone Marrow Transplantation: Focus on Hepatic Veno-Occlusive 
Disease. Semin Thromb Hemost. 2015;41(6):629-43. 
Worel N, Greinix HT, Leitner G, Mitterbauer M, Rabitsch W, Rosenmayr A, et al. ABO- 
incompatible allogeneic hematopoietic stem cell transplantation following reduced-intensity 
conditioning: close association with transplant-associated microangiopathy. Transfus Apher Sci. 
2007;36(3):297-304. 
Wu F, Zou Q, Ding X, Shi D, Zhu X, Hu W, et al. Complement component C3a plays a critical 
role in endothelial activation and leukocyte recruitment into the brain. J Neuroinflammation. 
2016;13:23. 
Yongqing T, Drentin N, Duncan RC, Wijeyewickrema LC, Pike RN. Mannose-binding lectin 
serine proteases and associated proteins of the lectin pathway of complement: two genes, five 
proteins and many functions? Biochim Biophys Acta. 2012;1824(1):253-62. 
Zeisbrich M, Becker N, Benner A, Radujkovic A, Schmitt K, Beimler J, et al. Transplant- 
associated thrombotic microangiopathy is an endothelial complication associated with 
refractoriness of acute GvHD. Bone Marrow Transplant. 2017. 
Zhang J, Defelice AF, Hanig JP, Colatsky T. Biomarkers of endothelial cell activation serve as 
potential surrogate markers for drug-induced vascular injury. Toxicol Pathol. 2010;38(6):856-71. 

Protocol No. OMS721-TMA-001 (A11.1) 
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No use, disclosure or reproduction outside of Omeros without prior written authorization 
87 
 
 
 
 
 
19. 
APPENDICES 
19.1. 
Study Schedule of Events – Stage 1 
Period 
SCR 
Treatment 
Follow-Up 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Day 
Up to 
–28 
1 
2 
3 
4 
8 
15 
22 
23 
24 
25 
29 
36 
50 
78 
Informed Consent, Medical History, and 
Physical Examination 
X 
Vital Signs 
X 
X4 
X4 
X4 
X4 
X 
X 
ECG 
X 
X5 
X5 
Chemistry and Hematology 
X 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Platelet Count 
X1 
X6, 11 
X6, 11 
X6, 11 
X6, 11 
X11 
X11 
X11 
X11 
LDH and Haptoglobin 
X 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Coagulation 
X 
X6 
X6 
X6 
X6 
HIV Serology 
X 
Urinalysis 
X 
X6 
X6 
X6 
X6 
X 
Pregnancy Test 
X12 
X6 
X 
Complement Genetics 
X2 
ADAMTS13, STEC, and Coombs Test 
X3 
Research Sampling 
X6,7 
X10 
X10 
X10 
X10 
X10 
X10 
X10 
Study Drug Administration 
X 
X 
X 
X 
PK Sampling – serum 
X8 
X8 
X8 
X8 
X9 
X9 
X8 
X8 
X8 
X8 
X 
X 
X 
X 
PD Sampling – serum 
X9 
X9 
X9 
X9 
X 
X 
X 
X 
ADA Sampling 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
ConMeds and Therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical 
hemolytic uremic syndrome; ConMeds = concomitant medications; ECG = electrocardiogram; h = hour; HIV = human immunodeficiency virus; LDH = lactate 
dehydrogenase; min = minutes; PD = pharmacodynamics; PK = pharmacokinetics; SCR = screening; STEC = Shiga toxin-producing E. coli. 
1 at least 2 values on separate days obtained in the week prior to Day 1 to establish baseline. 
2 aHUS population only, if not performed previously. 
3 if not previously performed for Coombs and ADAMTS13, if not previously excluded for STEC. 
4 predose; post start of dosing: 15 min, 30 min, 1 h, 2.5 h. 
5 predose; post dose obtained immediately before the 5-minute PK sample. 

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
88 
 
 
 
 
6 pre dose. 
7 DNA, RNA, protein, cells. 
8 predose; post end of dosing: 5 min, 2 h, 24 h, 48 h, 72 h. 
9 predose; post end of dosing: 2 h. 
10 protein, cells. 
11 included as part of hematology. 
12 Serum pregnancy test is required at screening; serum or urine pregnancy test for all other time points. 

CONFIDENTIAL 
No use, disdosure or reproduction outside of Omeros without p1ior wl'itten authorization 
89 
 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
19.2. 
aHUS C0 hort. Sta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA= anti-diug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical 
hemolytic uremic syndi·ome; ConMeds = concomitant medications; ECG = electrocardiogram; h = hour; HIV = human immunodeficiency virus; LDH = lactate 
dehydrogenase; min = minutes; PD = pharmacodynamics; PK = pharmacokinetics; SCR = screening; STEC = Shiga toxin-producing E. coli. 
1 at least 2 values on separate days obtained in the week prior to Day 1 to establish baseline. 
2 aHUS population only, if not perfonned previously. 
ges 2 and 3 StU dIY SChedueIo fEvents 
Sta2e 2: aHUS Coho1·t 
Petiod 
SCR 
Treatment 
Follow-Up 
Visit 
1 
T-1 
T-N 
T-12 
F-1 
F-2 
F-3 
F-4 
Days 
Upto 
-28 
I 
2 
3 
4 
8-77 
78 
.
-;.
:.
... 
I:.!) 
.5 
-0 
t') ε 
G> -0 
I:.!) 
.! - 
0-
0 
·
,,, 
0 ·;-
; 
C  ;> 
0  - 
I:.!) .c 
·.
C-..
-
 
0 E c. 
VJ  E 
·- 0 
- 
<.J 
.C - 0 
--
C 
Q.:: 
:= 
.c 
.
V.
J. 
0 
.c 
79 
80 
81 
85 
92 
106 
120 
lnfo1med Consent, Medical History, 
and Phvsical Examination 
X 
Vital Signs 
X 
x4 
x4 
x4 
ECG 
X 
x5 
Chemistry and Hematology 
X 
x6 
x6 
x6 
X 
X 
X 
X 
Platelet Count 
XI 
X6,ll
X6,ll
X6,ll
x11 
x11 
XII 
x11 
..,DH 
X 
x6 
x6 
x6 
X 
X 
X 
X 
Haptoglobin 
X 
x6 
x6 
x6 
X 
X 
X 
X 
Coagulation 
X 
x6 
x6 
x6 
HIV Serology 
X 
Urinalysis 
X 
x6 
x6 
x6 
Pregnancy Test 
x14 
x6 
X 
Complement Genetics 
x2 
ADAMTS13, STEC, and Coombs Test 
x3 
Research Sampling 
x6,1 
x6,10
x6,10 
xio 
xio 
xto 
xio 
Study Dmg Administrntion 
X 
X 
X 
PK Sampling - semm 
xs 
xs xs xs 
x9 
x9,12 
x12 x12 x12 
X 
X 
X 
X 
PD Sampling - sernm 
x9 
x9 
x9 
X 
X 
X 
X 
ADA Sampling 
x6 
x6 
x6 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
ConMeds and Therapy 
X 
X 
X 
X 
X 
X 
X 
X 
Stage 3 Assessment and Info1med 
=:'.011Sent 
x!3

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
90 
 
 
 
 
3 if not previously performed for Coombs and ADAMTS13, if not previously excluded for STEC. 
4 predose; post start of dosing: 15 min, 30 min, 1 h, 2.5 h. 
5 predose; post dose obtained immediately before the 5-minute PK sample. 
6 pre dose. 
7 DNA, RNA, protein, cells. 
8 predose; post end of dosing: 5 min, 2 h, 24 h, 48 h, 72 h. 
9 predose; post end of dosing: 2 h. 
10 protein, cells. 
11 included as part of hematology. 
12 performed if this is the last day of dosing – predose, post end of dosing: 2 h, 24 h, 48 h, 72 h. 
13 The patient’s treating Investigator and the Sponsor’s medical monitor will determine eligibility for Stage 3 based upon the patient’s response to therapy and 
safety and tolerability prior to the last scheduled treatment visit in Stage 2 in order to determine the appropriate PK draws following that visit. 
14 Serum pregnancy test is required at screening; serum or urine pregnancy test for all other time points. 
 
 
Stage 3: aHUS Cohort 
Period 
Treatment 
Follow-Up 
Visit 
T-13 
T-14 to T- 
23 
T-24 
F-1 
F-2 
F-3 
F-4 
Days 
85 
92 – 155 
162 
163 
164 
165 
169 
176 
190 
204 
Informed Consent, Medical History, and 
Physical Examination 
Vital Signs 
X4 
X4 
X4 
ECG 
Chemistry 
X6 
X6 
X6 
X 
X 
X 
X 
Hematology 
X6 
X6 
X6 
X 
X 
X 
X 
Platelet Count 
X6, 11 
X6, 11 
X6, 11 
X11 
X11 
X11 
X11 
LDH 
X6 
X6 
X6 
X 
X 
X 
X 
Haptoglobin 
X6 
X6 
X6 
X 
X 
X 
X 
Coagulation 
X6 
X6 
X6 
HIV Serology 
Urinalysis 
X6 
X6 
X6 
Pregnancy Test 
X 
Complement Genetics 
ADAMTS13, STEC, and Coombs Test 
Research Sampling 
X6, 10 
X6, 10 
X6, 10 
X10 
X10 
X10 
X10 

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
91 
 
 
 
 
Stage 3: aHUS Cohort 
Period 
Treatment 
Follow-Up 
Visit 
T-13 
T-14 to T- 
23 
T-24 
F-1 
F-2 
F-3 
F-4 
Days 
85 
92 – 155 
162 
163 
164 
165 
169 
176 
190 
204 
Study Drug Administration 
X 
X 
X 
PK Sampling – serum 
X9 
X9 
X8 
X8 
X8 
X8 
X 
X 
X 
X 
PD Sampling – serum 
X9 
X9 
X9 
X 
X 
X 
X 
ADA Sampling 
X6 
X6 
X6 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
ConMeds and Therapy 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical 
hemolytic uremic syndrome; ConMeds = concomitant medications; ECG = electrocardiogram; h = hour; HIV = human immunodeficiency virus; LDH = lactate 
dehydrogenase; min = minutes; PD = pharmacodynamics; PK = pharmacokinetics; STEC = Shiga toxin-producing E. coli. 
1 at least 2 values on separate days obtained in the week prior to Day 1 to establish baseline. 
2 aHUS population only, if not performed previously. 
3 if not previously performed for Coombs and ADAMTS13, if not previously excluded for STEC. 
4 predose; post start of dosing: 15 min, 30 min, 1 h, 2.5 h. 
5 predose; post dose obtained immediately before the 5-minute PK sample. 
6 pre dose. 
7 DNA, RNA, protein, cells. 
8 predose; post end of dosing: 5 min, 2 h, 24 h, 48 h, 72 h. 
9 predose; post end of dosing: 2 h. 
10 protein, cells. 
11 included as part of hematology. 

CONFIDENTIAL 
No use, disdosure or reproduction outside of Omeros without p1ior wl"itten authorization 
92 
 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
 
19.3. 
TTP/HSCT-TMA Cohort: Stages 2 and 3 Study Schedule of Events 
Stage 2: TTP/HSCT-TMA 
Period 
SCR 
Treatment 
Follow-Up 
Visit 
1 
T-1 
T-2 
T-3 
T-4 
F-1 
F-2 
F-3 
F-4 
Days 
Up 
to -28 
1 
2 
3 
4 
8 
15 
22 
..;.. 
... 
= 
M "'O 
-
01) 
"c
'Oo: 
1 - 
.-
.c 
00 ""' ' 
0 ·
·;-
; 
= ... 
0 
..5-=-: 
0.. e Q.
·-
"' E 
=
- 0"" -
-- 
0- 
= 
:
0::
.::
..c 
"..'. 
0 
..c 
23 
24 
25 
29 
36 
50 
92 
Info1med Consent, Medical History, 
and Physical Examination 
X 
Vital Si!ms 
X 
x4 
x4 x4 
x4 
ECG 
X 
xs 
Chemistiy 
X 
x6 
x6 
x6 
x6 
X 
X 
X 
X 
Hematology 
X 
x6 
x6 
x6 
x6 
X 
X 
X 
X 
Platelet Count 
xi x6,11 
X6,l lx6,
x6,1 
x11 x11 x11 x11 
LDH 
X 
x6 
x6 
x6 
x6 
X 
X 
X 
X 
Haptoglobin 
X 
x6 
x6 
x6 
x6 
X 
X 
X 
X 
Coagulation 
X 
x6 
x6 
x6 
x6 
HIV Seroloev 
X 
Urinalysis 
X 
x6 
x6 
x6 
x6 
Pre!mancy Test 
x14 x6 
X 
Complement Genetics 
ADAMTS13, STEC, and Coombs Test 
x3 
Research Sampling 
x6,1 
xio xio 
xio 
xio 
xio 
xio 
xrn 
Study Dmg Administration 
X 
X 
X 
X 
PK Sampling - serum 
xs xs xs xs x9 
x9 
x9,12 
x12 x12 x12 
X 
X 
X 
X 
PD Sampling - serum 
x9 
x9 
x9 
x9 
X 
X 
X 
X 
ADA Sampling 
x6 
x6 
x6 
x6 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
ConMeds and Theraov 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Stage 3 Assessment and Info1med Consent 
x13
Abbreviations: ADA= anti-diug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; 
ConMeds = concomitant medications; ECG = electrocardiogram; HIV = human immunodeficiency vims; LDH = lactate dehydrogenase; 
PD = pha1macodynamics; PK = phannacokinetics; SCR = screening; STEC = Shiga toxin-producing E. coli; TTP/HSCT-TMA = thrombotic 
thrombocytopenic purpw-a/hematopoietic stem cell transplant-thrombotic microangiopathies. 

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
93 
 
 
 
Stage 3: TTP/HSCT-TMA Cohort 
Period 
Treatment 
Follow-Up 
Visit 
T-5 
T-N 
T-8 
F-1 
F-2 
F-3 
F-4 
Days 
29 
36 
43 
50 
51 
52 
53 
57 
64 
78 
92 
Informed Consent, Medical History, and 
Physical Examination 
Vital Signs 
X4 
X4 
X4 
X4 
ECG 
Chemistry 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Hematology 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Platelet Count 
X6, 11 
X6, 11 
X6, 11 
X6, 11 
X11 
X11 
X11 
X11 
LDH 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Haptoglobin 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Coagulation 
X6 
X6 
X6 
X6 
HIV Serology 
Urinalysis 
X6 
X6 
X6 
X6 
Pregnancy Test 
X 
Complement Genetics 
ADAMTS13, STEC, and Coombs Test 
Research Sampling 
X10 
X10 
X10 
X10 
X10 
X10 
X10 
X10 
Study Drug Administration 
X 
X 
X 
X 
PK Sampling – serum 
X9 
X9 
X9 
X8 
X8 
X8 
X8 
X 
X 
X 
X 
PD Sampling – serum 
X9 
X9 
X9 
X9 
X 
X 
X 
X 
ADA Sampling 
X6 
X6 
X6 
X6 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
ConMeds and Therapy 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; 
ConMeds = concomitant medications; ECG = electrocardiogram; h = hour; HIV = human immunodeficiency virus; LDH = lactate dehydrogenase; 
m = minutes; PD = pharmacodynamics; PK = pharmacokinetics; STEC = Shiga toxin-producing E. coli; TTP/HSCT-TMA = thrombotic thrombocytopenic 
purpura/hematopoietic stem cell transplant-thrombotic microangiopathies. 
1 at least 2 values on separate days obtained in the week prior to Day 1 to establish baseline. 
2 aHUS population only, if not performed previously. 
3 if not previously performed for Coombs and ADAMTS13, if not previously excluded for STEC. 
4 predose; post start of dosing: 15 min, 30 min, 1 h, 2.5 h. 
5 predose; post dose obtained immediately before the 5-minute PK sample. 

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
94 
 
 
 
 
6 pre dose. 
7 DNA, RNA, protein, cells. 
8 predose; post end of dosing: 5 min, 2 h, 24 h, 48 h, 72 h. 
9 predose; post end of dosing: 2 h. 
10 protein, cells. 
11 included as part of hematology. 
12 performed if this is the last day of dosing – predose, post end of dosing: 2 h, 24 h, 48 h, 72 h. 
13 The patient’s treating Investigator and the Sponsor’s medical monitor will determine eligibility for Stage 3 based upon the patient’s response to therapy and 
safety and tolerability prior to the last scheduled treatment visit in Stage 2 in order to determine the appropriate PK draws following that visit. 
14 Serum pregnancy test is required at screening; serum or urine pregnancy test for all other time points. 

Protocol No. OMS721-TMA-001 (A11.1) 
CONFIDENTIAL 
No use, disclosure or reproduction outside of Omeros without prior written authorization 
95 
 
 
 
19.4. 
Supplemental Data Collection (HSCT-TMA Patients Enrolled Under Amendment 10 or Earlier) 
For patients with hematopoietic stem cell transplant-associated thrombotic microangiopathies (HSCT-TMA) enrolled under 
Amendment 10 or earlier versions of this protocol, additional data will be collected. These data will include supplemental data on 
patient demographics and baseline conditions, donor characteristics, the transplant procedure, concomitant medications, TMA-related 
laboratory measures, transfusions, transplant complications, and outcomes. These data will be derived from medical records from the 
time of transplant conditioning through the last available patient contact with the site or up to 2 years (104 weeks) following the first 
dose of OMS721, whichever comes first. 
Figure 9 below shows the periods for which additional data are to be collected and summarizes the data types. Details of the data to be 
collected are described in Table 2. 

CONFIDENTIAL 
No use, disdosure or reproduction outside of Omeros without p1ior wl'itten authorization 
96 
 
 
Protocol No. OMS721-TMA-001 (Al 1.1) 
 
 
Figure 9: 
Additional Data Collection Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
• 
Adverse events 
• 
Significant adverse events 
• 
Subject baseline characteristics 
• 
Laboratory measures (central lab) 
• 
Laboratory measures (local lab) 
• 
Subject medical history 
• 
Laboratory measures (local lab) 
• 
Selected medications 
• 
Donor characteristics 
• 
ECGs 
• 
HSCT complications 
• 
Conditioning regime 
• 
All concomitant medications 
• 
Vital status 
• 
Transplant characteristics 
• 
OMS721 administrationdata 
• 
Underlying disease status 
• 
Laboratory measures (local lab} 
• 
PK/PO measures 
• 
Transfusions 
• 
Selected medications 
• 
Clinical Course 
• 
RRT 
• 
TMA history and treatment 
• 
Underlying disease status 
• 
HospitaIizations 
• 
Other HSCT complications 
• 
Transfusions 
• 
Other resource utilization 
• 
Underlying disease status 
• 
RRT 
• 
Transfusions 
• 
Hospitalizations 
• 
RRT 
• 
Other resource utilization 
• 
HospitaIizations 
• 
Other resource utilization 
 
 
Abbreviations: ECG= electrocardiogram; HSCT = hematopoietic stem cell transplant; PD = phannacodynamics; PK= phannacoki11etics; RRT = renal 
replacement therapy; TMA = thrombotic microangiopathies 

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Table 2: 
Additional Data Collection 
 
Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
Patient Baseline Data 
Blood type (ABO and Rh) 
Pre-transplant, once 
Pre-transplant blood type will be collected from the clinical chart and is required for interpretation of the effects 
of post-transplant blood transfusions. 
HLA type 
Pre-transplant, once 
Data will be collected on at least both alleles of A, B, C, and DRB1 loci. Both alleles of the DQB1 and DPB1 
loci will also be collected, if available. These data will be used to determine the degree of transplant match. 
CMV antibody status 
Pre-transplant, once 
Values are positive, negative, and unknown. 
Underlying disease 
Pre-transplant, once 
The disease for which the patient is receiving HSCT 
Underlying disease status 
Pre-transplant, once and at 
every assessment of status 
Collect for underlying malignant diseases only. The categories are primary induction failure, complete 
remission, and relapse. If available, minimal residual disease will be collected. If the patient has had more than 
1 complete response, each will be recorded. 
Prior HSCT 
Pre-transplant, once 
Collect type (e.g., autologous or allogeneic), underlying disease, HLA match, donor relatedness, and cell source 
(bone marrow, peripheral blood stem cells, or cord blood). 
Donor(s) Data 
Age 
Pre-transplant, once 
Required to evaluate outcomes because prognosis is better with younger donors. 
Sex 
Pre-transplant, once 
Required to understand potential risks of female-to-male transplants. 
Race 
Pre-transplant, once 
Collect as “American Indian or Alaska Native,” “Asian,” “Black or African American,” “Native Hawaiian or 
Other Pacific Islander,” “White,” or “Other” (Clinical Data Interchange Standards Consortium compliant terms). 
Blood type (ABO and Rh) 
Pre-transplant, once 
Required for interpretation of the effects of post-transplant blood transfusions. 
HLA type 
Pre-transplant, once 
For example, the HLA data from each donor will be required for a double cord transplant. Data will be collected 
on at least both alleles of A, B, C, and DRB1 loci. Both alleles of the DQB1 and DPB1 loci will also be 
collected, if available. These data will be used to determine the degree of transplant match. 
Relatedness to patient 
Pre-transplant, -once 
Collect as related with relationship (parent, sibling, identical twin, or other) or unrelated. These data impact 
expected outcomes. 
CMV antibody status 
Pre-transplant, once 
Values are positive, negative, and unknown. These data impact expected clinical course. 
Transplant-Related Data 
Cell source 
Pre-transplant, once 
Collect as bone marrow, peripheral blood stem cells, or cord blood. Note the number of units if cord blood is the 
cell source. 
Conditioning regimen 
Pre-transplant, once 
Collect all drugs used in conditioning with dosing regimen (dose level, frequency, and number). If radiation is 
used, collect radiation parameters including the total dose and whether total body irradiation or site-specific. 
 

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Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
Transplant date 
Transplant, once 
The transplant date will be collected from the chart and used to measure survival duration. The day of transplant 
will be Day 0 in the survival calculation. 
Neutrophil engraftment date 
Post-transplant, once 
This is defined as the first date on which the neutrophil count is ≥ 0.5 x 109/L for at least 3 consecutive measures 
on different days. This date is generally noted in the chart as the date of neutrophil engraftment. The chart-noted 
date will be used to define the engraftment date. 
Platelet engraftment date 
Post-transplant, once 
Collect from clinical chart. This is defined as the first date on which the platelet count is 20 x 109/L for at least 
3 consecutive measures on different days with no platelet transfusions in previous 7 days. This date is generally 
noted in the chart as the date of platelet engraftment. The chart-noted date will be used to define the engraftment 
date. 
Chimerism with dates 
Post-transplant, each 
instance 
The percent chimerism will be collected with the corresponding cell type (for each cell type measured – RBC, 
CD34+ cells, mononuclear cells, T-cells, B-cells, granulocytes, and natural killer cells as reported). 
Graft failure 
Post-transplant 
The diagnosis of graft failure with the date will be noted as such and may be qualified as primary or secondary. 
If noted in the chart, the primary or secondary nature should be noted. 
GVHD prophylaxis 
At time of transplant and 
ongoing throughout the 
study 
Prophylaxis for GVHD will generally be provided with immunosuppressive medications. Each medication, dose, 
and dates of administration will be collected. Changes in the medications or decreases in dose will provide 
support for the requirement that patients have persistent HSCT-TMA despite modification of 
immunosuppression. The modification may occur prior to the chart diagnosis of HSCT-TMA because physicians 
react to changes in some measures (e.g., increasing LDH) while another measure (e.g., platelet count) has not 
become abnormal, delaying the diagnosis of HSCT-TMA. 
Patient Status (with dates) 
Vital status 
Last patient follow-up, 
once 
Collect as the latest of 1) the last clinic visit or telephone contact with the patient at which the patient was alive 
or 2) the date of death. 
Cause of death 
Last patient follow-up, 
once 
Collect for patients who have died. If no cause of death is recorded, the cause will be reported as unknown. 
Date of death 
Last patient follow-up, 
once 
Collect for the patients who die. 
Patient Relapse Status (with 
dates) 
Relapse 
Each instance of relapse of 
the primary disease 
Collect (with the date) and record as relapse. Minimal residual disease will be collected, if available. 
Transplant Complications/ 
Interventions 
Acute GVHD 
Each instance at onset 
Collect with the date of diagnosis. 
Chronic GVHD 
At onset 
Collect with the date of diagnosis. 

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Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
VOD 
At onset 
Collect with the date of diagnosis. 
IPS 
Each instance at onset 
Collect with the date of diagnosis. The presence of this syndrome will also be evidence of end-organ 
dysfunction. Idiopathic pneumonia syndrome will include DAH, acute interstitial pneumonitis, adult respiratory 
distress syndrome, peri-engraftment respiratory distress syndrome, non-cardiogenic capillary leak syndrome, and 
cryptogenic organizing pneumonia/bronchiolitis obliterans. 
Capillary leak syndrome 
At onset 
Collect with the first date of diagnosis. 
Posterior reversible 
encephalopathy syndrome 
At onset 
Collect with the first date of diagnosis. 
Bacterial infection 
Each instance at onset 
Collect with the first date of diagnosis and affected organs. The organism will be collected. 
Viral infection 
Each instance at onset 
Collect with the first date of diagnosis and affected organs. The identified virus will be collected. 
Fungal infection 
Each instance at onset 
Collect with the first date of diagnosis and affected organs. The organism will be collected. 
Parasitic infection 
Each instance at onset 
Collect with the first date of diagnosis and affected organs. The organism will be collected. 
Suspected infection 
Each instance at onset 
If noted, collect with the first date of diagnosis and affected organs. If a suspected infection is later identified as 
caused by a specific organism, the event will be collected as an infection caused by the specific organism and not 
as a suspected infection. 
Acute kidney injury 
Each instance at onset 
Collect with the date of first notation if noted in the clinical chart. 
Chronic kidney disease 
At onset 
Collect with the date of first notation if noted in the clinical chart. 
Renal replacement therapy 
Each instance at onset 
Defined as hemodialysis, peritoneal dialysis, and hemofiltration. Collect each instance and the date. 
Stroke 
At onset 
Collect with the first date of diagnosis. 
Confusion/Cognitive 
impairment 
Each instance at onset 
Collect with the first date of diagnosis. 
Seizures 
Each instance at onset 
Collect with the first date of diagnosis. 
Hallucinations 
Each instance at onset 
Collect with the first date of diagnosis. 
Other central nervous system 
Each instance at onset 
Other neurological signs and symptoms will be collected with the first date of diagnosis from the clinical chart. 
Engraftment syndrome 
At onset 
Collect with dates. 
Hypoxia 
Each instance at onset 
Collect with dates. 
Pulmonary arterial 
Hypertension 
At onset 
Collect with dates. 
Continuous positive airway 
pressure 
Each instance at onset 
Collect with dates. 

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Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
Mechanical ventilation/ 
extracorporeal membrane 
oxygenation 
Each instance at onset 
Collect with dates from the clinical chart. 
Tissue biopsy 
Each instance at onset 
Collect with dates and findings from the clinical chart. 
Transfusions (date, number 
of units, ABO, and Rh type) 
Red blood cell 
Each instance 
Collect the number of units with date. ABO and Rh group of each unit will also be collected. 
Whole blood 
Each instance 
Collect the number of units with date. ABO and Rh group of each unit will also be collected. 
Platelets 
Each instance 
Collect the number of units with date. ABO will be collected for each instance. 
Intravenous immunoglobulin 
Each instance 
Collect the number of units with date. 
Plasma therapy 
Each instance 
Plasma therapy is defined as plasma exchange or plasma infusion. Collect each instance of plasma therapy with 
the date. 
TMA Event 
Date of diagnosis 
Each instance 
HSCT-TMA is required for inclusion in the study. The date of diagnosis is the first day that a diagnosis of 
HSCT-TMA was recorded in the clinical chart. 
Date of onset 
Each instance 
HSCT-TMA is required for inclusion in the study. 
TMA treatment 
Each instance 
This will be determined by review of concomitant medications and episodes of plasma therapy. 
Hospital Resource 
Utilization 
Hospitalization time 
Following TMA diagnosis 
Collect all dates of hospital admission and discharge. 
Intensive care unit time 
Following TMA diagnosis 
Collect all dates of intensive care unit admission and discharge. 
Significant Adverse Events 
Each instance 
Collect events (with dates) requiring hospitalization or intervention with medication or procedures. 
Concomitant Medications 
All immunosuppressives and 
changes 
Each instance at onset 
Collect the dates of initiation and discontinuation with each dose per administration. Collect changes in the dose 
per administration and frequency with dates. 
All anti-infectives and 
changes 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
All cytotoxics 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
All targeted therapies 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
All growth factors 
Each instance at onset 
Collect the dates of initiation and discontinuation. 

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101 
 
 
 
 
Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
Eculizumab 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
Defibrotide 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
Investigational agents 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
Total parenteral nutrition 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
Ursodeoxycholic acid 
Each instance at onset 
Collect the dates of initiation and discontinuation. 
Heparin 
Each instance at onset only 
for VOD prophylaxis 
Collect the dates of initiation and discontinuation. 
Laboratory Measures 
Platelet count 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Hemoglobin 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
White blood cell 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Absolute neutrophil count 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Lactate dehydrogenase 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Haptoglobin 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Creatinine 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Bilirubin 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Aspartate aminotransferase 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Alanine aminotransferase 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Alkaline phosphatase 
See laboratory measure 
schedule1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Coombs 
Each instance 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 

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Variables 
Timing/Periodicity of 
Data Collection 
Data Collection Rules/Definitions 
Schistocytes 
See laboratory measure 
schedule 1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Others abnormal 
See laboratory measure 
schedule 1 
Collect from the clinical chart. Overlapping data will also be available from the central laboratory on some dates. 
Abbreviations: CMV = cytomegalovirus; DAH = diffuse alveolar hemorrhage; GVHD = graft-versus-host disease; HLA = human leukocyte antigen; 
HSCT = hematopoietic stem cell transplant; IPS = idiopathic pneumonia syndrome; LDH = lactate dehydrogenase; RBC = red blood cell; TMA = thrombotic 
microangiopathy; VOD = veno-occlusive disease. 
1 Laboratory measure schedule: Laboratory measures will be collected according to the schedule as outlined below. 

Protocol No. OMS721-TMA-001 (A11.1) 
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19.5. 
Laboratory Measure Schedule 
As available, local laboratory measures of platelet count, Hgb, white blood cell count, absolute neutrophil 
count, LDH, haptoglobin, creatinine, bilirubin, AST, ALT, alkaline phosphatase, and schistocytes will be 
collected according to the following schedule: 
Pre-TMA period: 
• Once immediately prior to conditioning 
• On Day –1 or 0 prior to transplant (the measure closest to the transplant). (Day 0 is the day of 
transplant) 
• On Days +2, +4, +6, +8, +10, +14, +21, +28 following transplant and weekly thereafter until 
28 days prior to the diagnosis of TMA 
TMA period: 
• Daily from 28 days prior to the diagnosis of TMA to the later of 12 weeks following the diagnosis 
of TMA or 4 weeks following resolution of TMA 
Post-TMA period: 
• Once weekly following the TMA period for 4 weeks, then once every 2 weeks for 4 weeks, and then 
once monthly ± 3 days until up to 2 years following the first dose of OMS721 
Platelet count should be recorded immediately before and after each platelet transfusion. 
Hemoglobin levels should be recorded immediately before and after each RBC transfusion. 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; Hgb = hemoglobin; LDH = lactate dehydrogenase; RBC = red blood cell; 
TMA = TMA = thrombotic microangiopathy.