A Phase 2, Multicenter, Multinational, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of ORGN001 (Formerly ALXN1101) in Pediatric Patients With Molybdenum Cofactor Deficiency (MoCD) Type A Currently Treated With Recombinant Escherichia Coli-derived Cyclic Pyranopterin Monophosphate (rcPMP)
Phase: PHASE2
Conditions: Molybdenum Cofactor Deficiency, Type A
Sponsor: Origin Biosciences

 
 
 
 
 
NCT Number: NCT02047461 
 
 
Certain information within this protocol has been redacted (i.e., specific content is masked 
irreversibly from view with a black bar) to protect either personally identifiable information or 
company confidential information. 
 
 
This may include, but is not limited to, redaction of the following: 
 
• Named persons or organizations associated with the study. 
• Proprietary information, such as scales or coding systems. 
• Other information as needed to protect confidentiality of BridgeBio Pharma, Sentynl 
Therapeutics, Inc., or their partners, or to otherwise protect the integrity of the clinical 
study. 

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INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator’s Brochure for ORGN001 (formerly ALXN1101). I 
have read the ALXN1101-MCD-201 study protocol and agree to conduct the study as outlined. I 
agree to maintain the confidentiality of all information received or developed in connection with 
this protocol. I agree to conduct the trial in accordance with ethical principles that have their 
origin in the Declaration of Helsinki and are consistent with the International Council for 
Harmonisation (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements. 
 
 
 
 
 
 
______________________________________________ 
Printed Name of Investigator 
 
 
 
 
 
 
______________________________________________  
_____________ 
Signature of Investigator 
 
 
 
 
 
Date 
 

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SYNOPSIS 
Name of Sponsor/Company: Origin Biosciences, Inc. (Origin); previously; Alexion Pharmaceuticals, Inc. 
(Alexion) 
Name of Investigational Product: ORGN001 (formerly ALXN1101) 
Name of Active Ingredient: Cyclic pyranopterin monophosphate monohydrobromide dihydrate 
Title of Study: A Phase 2, Multicenter, Multinational, Open-Label, Dose-Escalation Study to Evaluate the 
Safety and Efficacy of ORGN001 (formerly ALXN1101) in Pediatric Patients with Molybdenum Cofactor 
Deficiency (MoCD) Type A Currently Treated with Recombinant Escherichia coli-derived Cyclic Pyranopterin 
Monophosphate (rcPMP) 
Study centers: This will be a multicenter, multinational study with approximately 5 investigational study 
centers. 
Principal Investigator: TBD 
Investigators: TBD 
Studied period:  
6-Month Initial Treatment Period, followed by an Extension Period 
Estimated date first patient enrolled: February 2014 
Estimated date last patient completed: The Extension Period is expected to last until 
ORGN001 is commercially available or development is stopped.  
Phase of 
development: 
2/3 
Study Rationale 
Molybdenum cofactor deficiency (MoCD) is a rare, life-threatening, autosomal recessive, inborn error of 
metabolism characterized by disruption of the metabolic pathway for production of molybdenum cofactor 
(MoCo), which is essential for the function of sulfite oxidase (SO), 
 dehydrogenase, and aldehyde 
oxidase. While all 3 enzymes are dependent on MoCo, the loss of SO activity is responsible for the severe and 
rapidly progressive neurologic damage seen in MoCD. 
The incidence of MoCD is estimated to be between 1/100,000 and 1/200,000 newborn babies worldwide 
(Schwahn 2015). Affected individuals usually present as neonates with severe symptoms such as intractable 
seizures, burst-suppression or multifocal electroencephalogram (EEG), exaggerated startle reactions, axial 
hypotonia, limb hypertonia, and feeding difficulties. Neuronal injury is severe and is rapidly progressive as a 
result of accumulation of toxic levels of sulfite in the brain and subsequent formation of S-sulfocysteine (SSC). 
Death commonly occurs in the neonatal period, and patients who survive that period develop a severe static 
encephalopathy and developmental delay due to central nervous system (CNS) injury including subcortical cystic 
cavitation, hydrocephalus, diffuse cortical atrophy, and basal ganglia injury. At present, there is no cure. 
Although there are 3 types of MoCD, two-thirds of MoCD patients have Type A, which is due to a mutation in 
the MOCS1 gene localized on 6p21.3. In MoCD Type A, the first of the 4 synthetic steps in the formation of 
MoCo is interrupted, and guanosine triphosphate (GTP) cannot be converted into cyclic pyranopterin 
monophosphate (cPMP). Diagnosis of MoCD Type A is based on clinical presentation and biochemical 
phenotype (such as elevated urinary sulfite and/or SSC, and low or absent uric acid in the urine or plasma), and 
diagnosis is then confirmed by genetic testing. 
ORGN001 (cyclic pyranopterin monophosphate monohydrobromide dihydrate), provides a therapeutic approach 
for the treatment of MoCD Type A by restoring the MoCo biosynthesis. Results of preclinical pharmacology 
studies with ORGN001 suggest that the metabolic derangement in MoCD Type A could be corrected by 
administration of synthetic cPMP, resulting in restoration of enzymatic activity and thus, correction of the 
metabolic pathways that would otherwise lead to the accumulation of toxic metabolites causing CNS injury. 

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Statistical methods: 
The statistical analysis of all safety and efficacy parameters will be conducted on all patients who receive at least 
1 dose of ORGN001. All data collected in this study will be documented using summary tables, figures and 
patient data listings. For categorical variables, frequencies and percentages will be presented. For continuous 
variables, descriptive statistics (n, mean, median, standard deviation [SD], minimum, and maximum) will be 
presented. 
Safety: 
The incidence of treatment-emergent AEs and SAEs will be summarized by System Organ Class (SOC) and 
Preferred Term overall, by severity, and by relationship to study drug. Changes from baseline in vital signs, 
laboratory assessments (chemistry, hematology, and urinalysis) will be summarized. Shifts from baseline in 
laboratory assessments as well as physical examination findings will be summarized for the different time points. 
Efficacy: 
Changes from baseline in urine and blood SSC levels and percentage changes from baseline to the study time 
points will be summarized. Observed values and changes in Bayley-III cognitive, gross, fine motor scaled scores 
and cognitive and motor composite scores will be summarized. The frequency of seizures will be summarized. 
Shifts from baseline in clinical findings from neurologic examinations and neuroimaging findings will be 
presented for the different time points. Growth parameters (body weight, body length, and head circumference) 
will be converted to age-adjusted z-scores and summarized over time. Graphical displays will be presented as 
appropriate. 
Pharmacokinetics: 
Plasma concentration versus time profiles will be graphically summarized. Noncompartmental PK parameters 
such as Cmax, tmax, AUC, and t½ will be determined if possible, and, dose linearity will be explored. Plasma 
concentration and PK parameter summaries will include descriptive statistics, as appropriate. 
 
 
Additional details for statistical analyses will be described in the statistical analysis plan. 

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SUMMARY OF CHANGES 
 
Section 
Description of Change  
1.3 Risk/Benefit Assessment 
Additional text: 
“In vitro and preclinical studies have identified that 
ORGN001 has phototoxic potential. Patients and caregivers 
are instructed to avoid direct sunlight and to use precautions 
when exposed to the sun. Protective measures include 
wearing of sunglasses, a hat, long sleeved shirts, long pants 
and the use of protective sunscreen.” 

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TABLE OF CONTENTS 
ALXN1101-MCD-201 ........................................................................................................1 
SPONSOR SIGNATURE PAGE ......................................................................................2 
INVESTIGATOR’S AGREEMENT ................................................................................3 
PROCEDURES IN CASE OF EMERGENCY ...............................................................4 
SYNOPSIS ..........................................................................................................................5 
SUMMARY OF CHANGES ...........................................................................................10 
TABLE OF CONTENTS ................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..............................15 
1 
INTRODUCTION ....................................................................................................17 
1.1 
Background ..........................................................................................................17 
1.2 
Rationale for the Study ........................................................................................17 
1.3 
Risk/Benefit Assessment ......................................................................................18 
1.4 
Rationale for the Patient Population ..................................................................19 
1.5 
Rationale for Proposed Dosing ...........................................................................19 
1.6 
Rationale for the Overall Design ........................................................................20 
1.7 
Clinical Studies with ORGN001 .........................................................................20 
2 
TRIAL OBJECTIVES AND ENDPOINTS ...........................................................21 
2.1 
Objectives..............................................................................................................21 
2.1.1 
Primary Objective ..........................................................................................21 
2.1.2 
Secondary Objectives.....................................................................................21 
 
 
2.2 
Endpoints ..............................................................................................................21 
2.2.1 
Safety Endpoints ............................................................................................21 
2.2.2 
Efficacy Endpoints .........................................................................................21 
2.2.3 
Pharmacokinetic Endpoint ...........................................................................22 
 
 
3 
INVESTIGATIONAL PLAN ..................................................................................23 
3.1 
Overall Study Design ...........................................................................................23 
3.2 
NUMBER OF PATIENTS ..................................................................................24 
3.3 
Study Treatment and Dose Escalations .............................................................24 
3.4 
SAFETY REVIEW COMMITTEE ...................................................................25 
3.4.1 
Criteria to Hold Dose Escalation ..................................................................25 
3.4.2 
Safety Criteria for Unscheduled Dose Adjustments ...................................26 
3.5 
Criteria for Site or Study Termination ..............................................................26 
4 
SELECTION AND WITHDRAWAL OF PATIENTS .........................................37 
4.1 
Patient Recruitment and Consent ......................................................................37 
4.2 
Patient Inclusion Criteria ....................................................................................37 
4.3 
Patient Exclusion Criteria ...................................................................................37 
4.4 
Patient Withdrawal Criteria ...............................................................................37 
5 
TREATMENT OF PATIENTS ...............................................................................39 
5.1 
Description of Study Drug ..................................................................................39 
5.2 
Prior and Concomitant Medications and Procedures ......................................39 
5.3 
Treatment Compliance ........................................................................................39 
6 
STUDY DRUG MATERIALS AND MANAGEMENT ........................................40 
6.1 
Study Drug ............................................................................................................40 
6.2 
Study Drug Packaging and Labeling .................................................................40 

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6.3 
Study Drug Storage..............................................................................................40 
6.4 
Study Drug Preparation ......................................................................................40 
6.5 
Study Drug Administration ................................................................................40 
7 
STUDY DRUG ACCOUNTABILITY ....................................................................41 
7.1 
Study Drug Handling and Disposal ....................................................................41 
8 
SCREENING ASSESSMENTS ...............................................................................41 
8.1 
Informed Consent ................................................................................................41 
8.2 
Demographic Data and Onset of Disease ...........................................................41 
8.3 
Medical History, Family History, and Genotype ..............................................41 
9 
EFFICACY ASSESSMENTS ..................................................................................41 
9.1 
Neurologic Examinations ....................................................................................42 
9.2 
Bayley Scales of Infant and Toddler Development ...........................................42 
9.3 
THE GROSS MOTOR FUNCTION CLASSIFICATION SYSTEM .............42 
9.4 
Wechsler Preschool and Primary Scale of Intelligence ....................................43 
9.5 
Seizure Diary ........................................................................................................43 
9.6 
Neuroimaging .......................................................................................................43 
9.7 
Growth Parameters .............................................................................................43 
9.8 
Feeding Pattern Assessment................................................................................43 
10 PHARMACODYNAMIC ASSESSMENTS ...........................................................44 
11 PHARMACOKINETIC ASSESSMENTS .............................................................46 
12 SAFETY ASSESSMENTS .......................................................................................48 
12.1 
Vital Signs .............................................................................................................48 
12.1.1 
Additional Blood Pressure Measurements ..................................................48 
12.2 
Physical Examination ..........................................................................................48 
12.3 
Laboratory Assessments ......................................................................................49 
12.3.1 
Hematology .....................................................................................................49 
12.3.2 
Serum Chemistry ...........................................................................................49 
12.3.3 
Coagulation .....................................................................................................50 
12.3.4 
Urinalysis ........................................................................................................50 
12.4 
Electroencephalogram .........................................................................................50 
12.5 
Adverse Event Management ...............................................................................50 
12.5.1 
Definition of an Adverse Event .....................................................................50 
12.5.2 
Definition of a Serious Adverse Event .........................................................51 
12.5.3 
Severity Assessment .......................................................................................52 
12.5.4 
Causality Assessment .....................................................................................52 
12.5.5 
Outcome ..........................................................................................................53 
12.5.6 
Recording Adverse Events ............................................................................53 
12.5.7 
Reporting of Serious Adverse Events to Sponsor .......................................54 
12.5.8 
Reporting Requirements ...............................................................................54 
13 STATISTICAL METHODS AND PLANNED ANALYSES ................................56 
13.1 
General Considerations .......................................................................................56 
13.2 
Determination of Sample Size .............................................................................56 
13.3 
Analysis Population .............................................................................................56 
13.4 
Demographics and Baseline Characteristics .....................................................56 
13.5 
Patient Disposition and Treatment Compliance ...............................................56 
13.6 
Prior and Concomitant Medications ..................................................................56 
13.7 
Efficacy Analyses .................................................................................................56 
13.7.1 
Primary Efficacy Analysis .............................................................................56 

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13.7.2 
Secondary Efficacy Analyses ........................................................................57 
 
 
13.8 
Safety Analyses .....................................................................................................57 
13.8.1 
Adverse Events ...............................................................................................57 
13.8.2 
Laboratory Parameters .................................................................................58 
13.8.3 
Physical Examinations and Vital Signs ........................................................58 
13.8.4 
Electroencephalograms .................................................................................58 
13.9 
Pharmacokinetic Analysis ...................................................................................58 
13.10 Other Statistical Issues ........................................................................................58 
13.10.1 
Missing or Invalid Data .................................................................................58 
13.10.2 
Computing Environment...............................................................................58 
14 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ....................................59 
14.1 
Study Monitoring .................................................................................................59 
14.2 
Audits and Inspections ........................................................................................59 
14.3 
Institutional Review Board .................................................................................59 
15 QUALITY CONTROL AND QUALITY ASSURANCE ......................................60 
16 ETHICS .....................................................................................................................60 
16.1 
Ethics Review .......................................................................................................60 
16.2 
Data Monitoring Committee Review .................................................................60 
16.3 
Written Informed Consent ..................................................................................61 
16.4 
Patient Data Protection .......................................................................................61 
17 DATA HANDLING AND RECORDKEEPING....................................................62 
17.1 
Inspection of Records ..........................................................................................62 
17.2 
Retention of Records............................................................................................62 
17.3 
Retention of Biological Samples .........................................................................62 
17.4 
Data Privacy .........................................................................................................63 
18 PUBLICATION POLICY ........................................................................................63 
19 LIST OF REFERENCES .........................................................................................64 
20 APPENDICES ...........................................................................................................65 
APPENDIX A. 
BLOOD SAMPLING VOLUMES ...................................................66 
APPENDIX B. 
BLOOD SAMPLING VOLUMES TABLE (SCREENING 
THROUGH MONTH 6) ...........................................................................................67 
APPENDIX C. 
--BLOOD SAMPLING VOLUMES (EXTENSION PERIOD AND 
SAFETY FOLLOW-UP VISIT) ..............................................................................69 
APPENDIX D. 
BLOOD SAMPLING VOLUMES FOR UNSCHEDULED DOSE 
ADJUSTMENT .........................................................................................................70 
 

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LIST OF TABLES 
Table 1: 
Emergency Contact Information ..............................................................4 
Table 2: 
Abbreviations and Specialist Terms.......................................................15 
Table 3: 
Schedule of Assessments (Screening and Month 1 of the 6-Month Initial 
Treatment Period) ....................................................................................28 
Table 4: 
Schedule of Assessments (Months 2 through 6 of the 6-Month Initial 
Treatment Period) ....................................................................................31 
Table 5: 
Schedule of Assessments for an Unscheduled Dose Adjustment .........34 
Table 6: 
Schedule of Assessments (Extension Period and Safety Follow-Up) ...35 
Table 7: 
ORGN001 Description .............................................................................39 
Table 8: 
Pharmacokinetic Sampling Schedule .....................................................46 
Table 9: 
Criteria for Child-Pugh Classification ...................................................48 
Table 10: 
Blood Sampling Volumes (Screening Through Month 6) ....................67 
Table 11: 
Sample Volume Collection During the Extension Period and Safety 
Follow--Up Visit .......................................................................................69 
Table 12: 
Sample Volume Collection for an Unscheduled Dose Adjustment .....70 
 
LIST OF FIGURES 
Figure 1: 
ALXN1101-MCD-201 Study Design ......................................................27 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
1H NMR 
Proton nuclear magnetic resonance spectroscopy 
13C NMR 
Carbon nuclear magnetic resonance spectroscopy 
31P NMR 
Phosphorous nuclear magnetic resonance spectroscopy 
AE 
Adverse event 
Alexion 
Alexion Pharma GmbH 
AUC 
Area under the plasma concentration-time curve 
BP 
Blood pressure 
Bayley-III 
Bayley Scales of Infant and Toddler Development-Third Edition 
°C 
Degrees Celsius 
Cmax 
Maximum observed plasma concentration 
CNS 
Central nervous system 
Colbourne 
Colbourne Pharmaceuticals GmbH 
cPMP 
Cyclic pyranopterin monophosphate 
CRF 
Case Report Form 
CT 
Computed tomography 
CYP 450 
Cytochrome P450 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
E. coli 
Escherichia coli 
eCRF 
Electronic Case Report Form 
EEG 
Electroencephalogram 
EMLA 
Eutectic mixture of local anesthetics 
EOI 
End of infusion 
EOS 
End of study 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GMFCS 
Gross Motor Function Classification System 
GMP 
Good Manufacturing Practice 
GTP 
Guanosine triphosphate 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
LC-MS/MS 
Liquid chromatography with tandem mass spectrometric detection 
MoCD 
Molybdenum cofactor deficiency 
MedDRA 
Medical Dictionary for Regulatory Activities 
MoCo 
Molybdenum cofactor 
MPT 
Molybdopterin 
MRI 
Magnetic resonance imaging 
MS 
Mass spectroscopy 
MSDS 
Material Safety Data Sheet 
N 
Normal 
NOAEL 
No observed adverse effect level 
Origin 
Origin Biosciences, Inc. 
PD 
Pharmacodynamics 

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PI 
Principal Investigator 
PK 
Pharmacokinetics 
PT 
Prothrombin time 
RBC 
Red blood cell 
rcPMP 
Recombinant E. coli-derived cPMP 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SO 
Sulfite oxidase 
SOC 
System Organ Class 
SRC 
Safety Review Committee 
SSC 
S-sulfocysteine 
t1/2 
Terminal half-life 
tmax 
Time to maximum observed plasma concentration 
UK 
United Kingdom 
US 
United States (of America) 
UV 
Ultraviolet (spectroscopy) 
WBC 
White blood cell 
WHODrug 
World Health Organization Drug Dictionary 
WPPSI 
Wechsler Preschool and Primary Scale of Intelligence 

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1 
INTRODUCTION 
1.1 
Background 
Molybdenum cofactor deficiency (MoCD) is a rare, life-threatening, autosomal recessive, inborn 
error of metabolism characterized by disruption of the metabolic pathway for production of 
molybdenum cofactor (MoCo), which is essential for the function of sulfite oxidase (SO), 
xanthine dehydrogenase, and aldehyde oxidase. While all 3 enzymes are dependent on MoCo, 
the loss of SO activity is responsible for the severe and rapidly progressive neurologic damage 
seen in MoCD. 
The incidence of MoCD is estimated to be between 1/100,000 and 1/200,000 newborn babies 
worldwide (Schwahn 2015). Affected individuals usually present in the neonatal period with 
intractable seizures, burst--suppression or multifocal epileptic electroencephalogram (EEG), 
exaggerated startle reactions, axial hypotonia, limb hypertonia, and feeding difficulties (Johnson 
and Duran 2001; Kikuchi et al, 2012; Vijayakumr et al, 2011). Neuronal injury is severe and is 
rapidly progressive as a result of accumulation of toxic levels of sulfite in the brain and 
subsequent formation of S-sulfocysteine (SSC). Death commonly occurs in the neonatal period, 
and patients who survive that period develop a severe static encephalopathy and developmental 
delay due to central nervous system (CNS) injury including subcortical cystic cavitation, 
hydrocephalus, diffuse cortical atrophy, and basal ganglia injury (Johnson and Duran 2001; 
Johnson et al, 1980). 
Three types of MoCD have been described based on the genetic defect. Two-thirds of MoCD 
patients have Type A, which is due to a mutation in the MOCS1 gene localized on 6p21.3 and 
results in the interruption of the first of the 4 synthetic steps in the formation of MoCo; 
guanosine triphosphate (GTP) cannot be converted into cyclic pyranopterin monophosphate 
(cPMP). Diagnosis of MoCD Type A is based on clinical presentation (encephalopathy, seizures) 
and biochemical phenotype (elevated urinary sulfite and SSC, and low or absent uric acid in the 
urine or plasma). The diagnosis is then confirmed by genetic testing. At present, there is no 
approved therapy available and no cure. 
A treatment targeting MoCo biosynthesis represents a possible therapeutic strategy to treat 
MoCD Type A. A cPMP substitution therapy is expected to reconstitute MoCo biosynthesis and 
restore SO levels, thereby reducing the levels of the neurotoxic compounds, sulfite and SSC. 
1.2 
Rationale for the Study 
The previous sponsor, Alexion Pharma GmbH (Alexion) developed ORGN001 (formerly 
ALXN1101), a synthetic form of cPMP, which is a precursor molecule to MoCo, as a treatment 
for MoCD Type A.  Responsibility for the development of ORGN001 for the treatment of MoCD 
Type A has been assumed by Origin Biosciences, Inc.  ORGN001 provides a therapeutic 
approach for the treatment of MoCD Type A that is intended to restore MoCo biosynthesis. 
Results of preclinical pharmacology studies with ORGN001 suggest that the metabolic 
derangement in MoCD Type A could be corrected by administration of synthetic cPMP, 
resulting in restoration of enzymatic activity and thereby correction of the metabolic pathways 
that lead to the accumulation of toxic metabolites causing CNS injury. 
In vitro, ORGN001 increased molybdopterin (MPT) synthesis and restored SO activity 
(Clinch et al, 2013). Additionally, in a mouse model of MoCD Type A (Lee et al, 2002), 
ORGN001 effectively rescued MOCS1-/- mice from premature death and effectively decreased 
the plasma SSC level.  In 
 repeat dose-toxicity studies in adult rats and dogs, ORGN001 

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3.4.2 
Safety Criteria for Unscheduled Dose Adjustments 
Doses may be adjusted based on the occurrence of drug-related AEs and changes in clinical 
parameters, as assessed by the SRC. The SRC chair will also convene the DMC if a dose 
escalation is being considered or will notify the DMC if the dose is decreased. If a patient has 
significant clinical worsening related to ORGN001 dosing, the dose may be decreased based 
on the clinical status of the patient and, if available, exposure data. If this occurs within the 
first 2 months, the target dose reduction would be approximately 25% of the starting dose 
 or to a level that is 
expected to result in exposure that is below the NOAEL AUC. If an unscheduled dose 
adjustment is necessary during Months 2 through 6 of the study, the patient’s dose will be 
reduced to the last tolerated dose. Alternatively, after dose escalation is complete, the patient 
can be returned to a prior dose based on the patient’s clinical status at the discretion of the 
treating physician after consultation with the SRC. 
3.5 
Criteria for Site or Study Termination 
For reasonable cause, the Investigator, Institutional Review Board (IRB)/Ethics Committee (EC), 
or Sponsor may terminate the study at a given center, in which case, the care of the patients at 
the site would be transferred to a different Investigator, or all centers, in which case, patients 
would return to the care of their treating physician. Conditions that may warrant termination of 
the study or investigational sites participating in this study include, but are not limited to: 
• Discovery of an unexpected, serious, or unacceptable risk to patients enrolled in 
the study 
• Decision on the part of the Sponsor to suspend or discontinue testing, 
evaluation, or development of the study drug 
• Failure of the Investigator to comply with the approved protocol, pertinent 
guidelines, and/or regulations 
• Submission of knowingly false information from the Investigator to the 
Sponsor and/or regulatory authorities 
The end of the study will be defined as the date of the last patient’s last visit.

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Table 3: 
Schedule of Assessments (Screening and Month 1 of the 6-Month Initial Treatment Period) 
Assessment 
Screening/ 
Baseline Period1,2 
Month 1 of the 6-Month Initial Treatment Period 
Study Day 
Month 
Visit Window (Days) 
Informed consent 
Eligibility 
Demographic data and onset of disease5 
Genotype7 
Family history8 
Medical history9 
Physical examination25 
Vital signs12,25 
Additional BP measurements 
Serum chemistry and hematology13, 25 
Coagulation14 
Urinalysis15, 25 
Growth parameters16 
Feeding pattern17 
Neurologic examination25 
GMFCS 
Bayley-III (age-appropriate test)19 
WPPSI20 
Record seizure diary data21, 25 
Neuroimaging22 
EEG23 
PD sampling, urine24,25 

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medications; MoCD = molybdenum cofactor deficiency; MRI = magnetic resonance imaging; PD = pharmacodynamics; PI = principal investigator; PK = 
pharmacokinetics; rcPMP = recombinant E. coli-derived cPMP; SRC = Safety Review Committee; SSC = S-sulfocysteine; WPPSI = Wechsler Preschool and 
Primary Scale of Intelligence. 
 

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22 Daily IV infusion of ORGN001 (24 hours ± 3 hours apart) can occur at home or while in-clinic 
23 Changes in seizure medications, including the reason for the change, will be recorded. 
24 Assessed only if the patient is seen in-clinic. An in-clinic visit is not required for blood and urine collection on this day. 
Abbreviations: AEs = adverse events; Bayley-III = Bayley Scales of Infant and Toddler Development-Third Edition; CRF = case report form; 
EEG = electroencephalogram; eCRF = electronic case report form; EOI = end of infusion; GMFCS = Gross Motor Function Classification System; 
meds = medications; MRI = magnetic resonance imaging; PD = pharmacodynamics; PK = pharmacokinetics; rcPMP = recombinant E. coli-derived cPMP; SRC 
= Safety Review Committee; SSC = S-sulfocysteine; WPPSI = Wechsler Preschool and Primary Scale of Intelligence. 
 

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All patients who discontinue or are withdrawn from the study will be encouraged to complete the 
Safety Follow-up Visit 
. 
The reasons for premature study withdrawal must be recorded in the patient’s case report form 
(CRF)/electronic case report form (eCRF) and in the source records. 
For patients who are prematurely withdrawn from the study due to clinical safety concerns (eg, 
intolerable AEs), the Investigator must immediately notify the Medical Monitor. In these 
patients, AEs leading to premature withdrawal must be followed until resolution or the patient is 
determined to be medically stable, in the opinion of the Investigator. Patients who withdraw from 
the study will not be replaced. 

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9.1 
Neurologic Examinations 
Neurologic examinations will be performed 
. The 
Day 1 assessment must be performed within 2 hours prior to the first infusion. Neurologic 
examinations are also performed if patients have unscheduled dose adjustments 
 
. Neurologic examination includes, but is not limited to, 
assessment of mental status, cranial nerves, motor strength and tone, sensory examination, deep 
tendon reflexes and primitive reflexes, if present. 
9.2 
Bayley Scales of Infant and Toddler Development 
The Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) will be 
administered 
 to assess changes in gross motor, fine 
motor, language, and cognitive development. The Bayley-III will be administered to children 
less than 3 years of age. Additionally, for patients over 3 years of age with severe developmental 
delay, the Bayley-III may be more appropriate than the WPPSI and may therefore be 
administered instead. 
The Bayley-III is a standardized and norm-referenced instrument that assesses changes in gross 
motor, fine motor, language, and cognitive development. It is administered in infants and 
children 1 month to 42 months of age. 
The Bayley-III consists of a core battery of the following 5 scales, 3 of which are administered 
by a trained qualified professional with child interaction: the Cognitive Scale, the Language 
Scale (including the Receptive Communication and Expressive Communication subtests), and 
the Motor Scale (including the Fine Motor and Gross Motor subtests). The Social-Emotional 
Scale and Adaptive Behavior Scale together form the Social-Emotional and Adaptive Behavior 
Questionnaire, which is completed by the parent, legal guardian, or primary caregiver. This 
caregiver-administered portion of the Bayley-III will not be administered as part of this study. 
The Bayley-III assessments must be performed in the order specified in the Bayley-III Manual. 
The Language Scale will be administered only to native English speakers in English-speaking 
countries. 
From raw scores, scaled scores, developmental age equivalents, and growth scores can be 
calculated for the Cognitive, Receptive and Expressive Communication, Fine Motor, and Gross 
Motor subtests. Scaled scores also can be used to calculate the Cognitive, Language, and Motor 
composite scores, percentile ranks, and confidence intervals. 
A qualified professional will administer the Bayley-III and determine the appropriateness of each 
assessment. 
9.3 
THE GROSS MOTOR FUNCTION CLASSIFICATION SYSTEM 
Gross motor function using the GMFCS will be assessed 
 
. 
The GMFCS is a 5-level classification system that describes the gross motor function of children 
and youth (up to 18 years of age) on the basis of their self-initiated movement with particular 
emphasis on sitting, walking, and wheeled mobility for children with impaired motor skills. 
Distinctions between levels are based on functional abilities, the need for assistive technology, 
including hand-held mobility devices (walkers, crutches, or canes) or wheeled mobility, and to a 
much lesser extent, quality of movement. 
Children who have motor functions similar to those classified in "Level I" can generally walk 
without restrictions but tend to be limited in some of the more advanced motor skills. Children 

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• Leads to a change in study dosing outside of the protocol defined 
dosing or discontinuation from the study; 
• Requires significant additional treatment; 
• Does not meet any of the conditions above; however, the Investigator or 
Sponsor considers the result as clinically significant or meeting the definition 
of an AE. 
This definition also includes the signs or symptoms resulting from: 
• Drug overdose 
• Drug withdrawal 
• Drug misuse 
• Drug interactions 
• Extravasation 
• Medication error 
• Occupational exposure 
An AE does not necessarily include the following: 
• Medical or surgical procedures (eg, surgery, endoscopies, tooth extraction, 
transfusion); the condition that leads to the procedure is the AE (eg, 
laparoscopic cholecystectomy is the procedure or treatment for an SAE of 
necrotic gall bladder); 
• Pre-existing diseases or conditions present or detected prior to the 
Screening evaluation that do not worsen; 
• Situations where an untoward medical occurrence has not occurred (eg, 
hospitalization for elective surgery if planned prior to the start of the study, 
social and/or convenience admissions). 
12.5.2 
Definition of a Serious Adverse Event 
Any AE that fulfills any one of the criteria listed below must be recorded as an SAE. An SAE is 
described as any untoward medical occurrence that at any dose: 
Results in death 
Is life-threatening 
Requires hospitalization or prolongation of hospitalizationb  
Hospitalization does not necessarily include the following: 
• Rehabilitation/hospice/nursing facility 
• Emergency Room/Department visit less than 24 hours 
• Elective or preplanned admission/surgery/Day surgery 
• Protocol-specified admission 
• Admission for a pre-existing condition not associated with either a new AE or 
with worsening of a pre-existing AE 
Results in persistent or significant disability/incapacity 

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Is a congenital anomaly/birth defect 
Is an important medical eventc 
a. The term "life-threatening" in the definition of "serious" 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. 
b. Hospitalization requires inpatient or prolongation of an existing hospitalization. AEs that 
are associated with hospitalization or prolongation of hospitalization are considered SAEs. 
c. Important Medical Event: Medical and scientific judgment should be exercised in deciding 
whether expedited reporting is appropriate in other situations, such as important medical 
events that may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the patient or may require intervention to prevent one of the other 
outcomes listed in the definition above. These should also usually be considered serious. 
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. 
Severity and seriousness must be differentiated. Severity describes the intensity of an AE while 
the term seriousness refers to an AE that has met the criteria for an SAE as described above. 
12.5.3 
Severity Assessment 
An assessment of severity will be made by the Investigator using the following criteria: 
• Mild: events require minimal or no treatment and do not interfere with the 
patient’s daily activities. 
• Moderate: events result in a low level of inconvenience or concerns with 
the therapeutic measures. Moderate events may cause some interference 
with functioning. 
• Severe: events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
Change in severity of an AE should be documented based on specific guidance in the eCRF 
Completion Guidelines. 
Severity and seriousness must be differentiated: severity describes the intensity of an AE while 
seriousness refers to an AE that has met the criteria for an SAE. 
12.5.4 
Causality Assessment 
An Investigator causality assessment must be provided for all AEs (both nonserious and serious). 
This assessment must be recorded on the CRF/eCRF and any additional forms as appropriate. 
The definitions for the causality assessments are as follows: 
• Not related (unrelated): This relationship suggests that there is no association 
between the study drug and the reported event. 
• Unlikely related: This relationship suggests that the clinical picture is highly 
consistent with a cause other than the study drug, but attribution cannot be made 
with absolute certainty and a relationship between the study drug and AE cannot 
be excluded with complete confidence. 
• Possibly related: This relationship suggests that treatment with the study drug 
may have caused or contributed to the AE, ie, the event follows a reasonable 

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temporal sequence from the time of drug administration and/or follows a 
known response pattern to the study drug but could also have been produced by 
other factors. 
• Probably related: This relationship suggests that a reasonable temporal sequence 
of the event with the study drug administration exists and the likely association of 
the event with the study drug. This will be based upon the known pharmacological 
action of the study drug, known or previously reported adverse reactions to the 
study drug or class of drugs, or judgment based on the Principal Investigator’s 
clinical experience. 
• Definitely related: Temporal relationship to the study drug. Other conditions 
(concurrent illness, concurrent medication reaction, or 
progression/expression of disease state) do not appear to explain event, 
corresponds with the known pharmaceutical profile, improvement on 
discontinuation, re-appearance on re- challenge. 
12.5.5 
Outcome 
For all AEs, regardless of causal relationships, the Investigator must follow-up on the outcome of 
the event until the event or sequelae either resolves or stabilizes. 
If a patient experiences a SAE with an outcome of death: 
• The SAE resulting in death should have an outcome documented as death/fatal with an end 
date being the date of death. 
• If the patient had additional AEs/SAEs that were ongoing at the time of death, these events 
would be documented as ongoing with no end date. 
• Only 1 event should have an outcome of death/fatal unless an autopsy report or Investigator 
states otherwise. 
12.5.6 
Recording Adverse Events 
All observed or volunteered AEs regardless of causal relationship must be reported as described 
in Section 12.5.4. 
For all AEs, the Investigator must obtain adequate information for the following: 
1. determine the outcome of the AE; 
2. determine if the event meets criteria for an SAE; 
3. assess the severity of the AE; 
4. determine the causality of the AE. 
Adverse events must be documented in clear, unambiguous medical term. Study personnel are 
advised not to use abbreviations or acronyms. 
For each AE, record only the diagnosis on the AE page of the CRF/eCRF. Do not report the 
characteristic signs and symptoms of the diagnosis as additional AEs. 
If a diagnosis is not available, record each sign and symptom as an AE. When a diagnosis 
becomes available, study personnel are to update the source document and the AE page of the 
CRF/eCRF with relevant diagnosis only. 

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For medical or surgical procedures (eg, surgery, endoscopies, tooth extraction, transfusion), the 
condition/diagnosis that leads to the procedure should be recorded as the AE (eg, laparoscopic 
cholecystectomy is the procedure or treatment for an SAE of necrotic gall bladder). 
All AEs that later increase in the frequency and/or severity (medical and scientific judgment 
should be exercised by the Investigator) will be considered new AEs and will be recorded on a 
new line in source and the CRF/eCRF. 
Withdrawal due to an AE or SAE must be clearly differentiated from withdrawal due to other 
reasons. 
12.5.7 
Reporting of Serious Adverse Events to Sponsor 
All AEs must be assessed by the Investigator to determine if they meet criteria for an SAE. All 
SAEs must be reported to the Sponsor or designee immediately or within 24 hours of the 
Investigator or their staff becoming aware of them regardless of the presumed relationship to the 
study drug. 
The Investigator must complete, sign, and date the SAE pages, verify the accuracy of the 
information recorded on the SAE pages with the corresponding source documents, and send a 
copy via email or fax to the contact information provided 
 
 
When further information becomes available, the SAE Form should be updated with the new 
information and reported immediately via the same contact information. 
Additional follow-up information, if required or available, should be entered into the CRF/eCRF 
and sent to the Sponsor within 24 hours of the Investigator site or their staff becoming aware of 
this additional information via the reporting process outlined above. These reporting timelines 
need to be followed for all initial SAE cases and follow-up versions of the initial cases. 
For all SAEs the Investigator must provide the following: 
• Clear identification of the Investigator/Reporter with full contact information, country and 
site number 
• Subject identification details (subject’s unique study identification number) 
• Investigational Medicinal Product(s) administration details (dose and dates) Seriousness 
criteria 
• Appropriate and requested follow-up information in the time frame detailed above 
• Causality of the serious events 
• Outcome of the serious events 
• Medical records and laboratory / diagnostic information 
12.5.8 
Reporting Requirements 
This protocol will use the current IB as the Reference Safety Document. The expectedness and 
reporting criteria of an SAE will be determined by the Sponsor from the Reference Safety 
Document. 
12.5.8.1 
Sponsor Reporting Requirements 
The Sponsor or its legal representative is responsible for notifying the relevant 
regulatory authorities of SAEs meeting the reporting criteria. 

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12.5.8.2 
Investigator Reporting Requirements 
The Investigator must fulfill all local regulatory obligations required for the study Investigators. 
It is the PI’s responsibility to notify the IRB or Independent Ethics Committee (IEC) of all SAEs 
that occur at his or her site. Investigators will also be notified of all unexpected, serious, 
drug--related events (7/15 Day Safety Reports) that occur during the clinical study. Each site is 
responsible for notifying its IRB or IEC (if local) of these additional SAEs. Investigators will 
receive blinded information unless unblinded information is judged necessary for safety reasons. 

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13 
STATISTICAL METHODS AND PLANNED ANALYSES 
13.1 
General Considerations 
Data collected during the study will be presented in summary tables, figures, or by-patient data 
listings. Continuous variables will be summarized using mean, standard deviation (SD), median, 
minimum, and maximum. Categorical variables will be summarized using percentages and 
frequency distributions. No formal hypothesis testing will be performed. 
13.2 
Determination of Sample Size 
At least 4 MoCD Type A patients will be enrolled in the study. The actual sample size 
will depend on the number of eligible patients currently being treated with rcPMP. 
13.3 
Analysis Population 
Efficacy analyses will be performed on the Full Analysis Set (FAS). Due to the small number of 
patients, a Per-Protocol Population will not be utilized for this study. The FAS will include all 
patients who receive at least 1 dose of ORGN001. 
Safety analyses will be performed on the Safety Set, defined as all patients who receive at least 1 
dose of ORGN001. 
13.4 
Demographics and Baseline Characteristics 
All demographic and baseline characteristics information will be summarized for all patients. 
For categorical variables, frequencies and percentages will be presented. Continuous variables 
will be summarized using descriptive statistics (mean, median, SD, and minimum and 
maximum). 
13.5 
Patient Disposition and Treatment Compliance 
The number of patients screened, treated, completing the 6-Month Initial Treatment Period, and 
included in the safety and efficacy analysis sets will be tabulated by counts and percentage of 
patients. Reasons for any patient withdrawals will be provided. 
Treatment compliance with ORGN001 will be presented for all patients. 
13.6 
Prior and Concomitant Medications 
Prior and concomitant medications will be summarized using the Safety Set. Listings of prior 
and concomitant medications will be produced as will listings of seizure medications. 
Medications will be coded using the World Health Organization Drug Dictionary (WHODrug) 
version 01 September 2013 or higher. Medication summaries will be presented by WHODrug 
Anatomical Therapeutic Chemical (ATC) and by WHODrug generic name. 
13.7 
Efficacy Analyses 
Efficacy analyses will be performed on the FAS. 
13.7.1 
Primary Efficacy Analysis 
There is no prespecified primary efficacy endpoint in this study. Secondary efficacy analyses are 
described in Section 13.7.2 
. 

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Treatment-emergent AEs are AEs that begin after the start of ORGN001. Treatment-emergent 
AEs will be summarized by incidence, Preferred Term, System Organ Class (SOC), seriousness, 
severity, relationship to treatment. 
All AEs will be summarized by both event counts and patient counts. For patient counts, if a 
patient has more than one occurrence of an AE for a specific Preferred Term or SOC, the patient 
will be counted only once for that Preferred Term or SOC. The most severe occurrence of an AE 
as well as the most extreme relationship of the AE will be indicated in cases of multiple 
occurrences of the same AE at onset of the AE. 
13.8.2 
Laboratory Parameters 
Changes from Baseline in laboratory assessments (chemistry and hematology) will be 
summarized by visit, and shift tables (L [low], N [normal], H [high]) by visit will be produced 
for clinical laboratory tests. 
13.8.3 
Physical Examinations and Vital Signs 
Physical examinations and Child-Pugh scores (A [a score of 5 to 6], B [a score of 7 to 9], C [a 
score of 10 or above]) will be summarized by visit. Vital signs (systolic and diastolic BP, 
temperature, heart rate, and respiratory rate) and changes from baseline in vital signs will be 
summarized by visit. 
13.8.4 
Electroencephalograms 
The number and percentage of patients with EEG findings will be summarized by visit. 
13.9 
Pharmacokinetic Analysis 
Plasma concentration versus time profiles will be graphically summarized. Non-compartmental 
PK parameters such as Cmax, tmax, AUC, and t½ will be determined if possible, and dose linearity 
will be explored. Plasma concentration and PK parameter summaries will include descriptive 
statistics, as appropriate. Details of PK analyses will be presented in an analysis plan. 
13.10 Other Statistical Issues 
13.10.1 
Missing or Invalid Data 
If a date of a measurement or an event has a missing or an unknown day, the missing or 
unknown Day will be substituted by 15 for the calculation of other variables such as age at which 
the measurement was taken, or the age at the occurrence of an event. If the month or the year of a 
date is missing, no imputation will take place. In general, other missing or invalid observations 
will not be replaced or imputed unless otherwise specified in the SAP. 
13.10.2 
Computing Environment 
Efficacy and safety analyses will be performed using SAS for windows, Version 9.2 or higher 
(SAS Institute Inc., Cary, NC, USA). 
PK analyses will be performed using Phoenix WinNonlin version 6.3 or higher (Pharsight, Cary, 
NC, USA). 

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14 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1 
Study Monitoring 
A representative of the Sponsor or designee may visit the investigational study site to: 
• Determine the adequacy of the facilities and equipment 
• Discuss with the Investigators and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of the Sponsor or its representatives. This will be 
documented in a Clinical Study Agreement between the Sponsor and the Investigator. 
During the study, a representative of the Sponsor or designee will have regular contact with 
the investigational site, for the following: 
• Provide information and support to the Investigators 
• Confirm that facilities and equipment remain acceptable 
• Confirm that all patients have been properly consented 
• Confirm drug accountability 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the CRFs/eCRFs, and that study drug accountability checks are being 
performed 
• Perform source data verification. This includes a comparison of the data in the CRFs/eCRFs 
with the patient’s medical records at the hospital or practice, and other records relevant to the 
study. This will require direct access to all original records for each patient (eg, clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor. 
• Confirm AEs and SAEs have been properly documented on CRFs/eCRFs and confirm any 
SAEs have been forwarded to the Sponsor and those SAEs that met criteria for reporting 
have been forwarded to the IRB. 
The monitor will be available between visits if the Investigators or other staff needs 
information or advice. 
14.2 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an IEC or an IRB may visit the 
site to perform audits or inspections, including source data verification. The purpose of an audit 
or inspection by the Sponsor is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, Good Clinical Practice 
(GCP) guidelines of the International Council for Harmonisation (ICH), and any applicable 
regulatory requirements. The Investigator should contact the Sponsor immediately if contacted 
by a regulatory agency about an inspection. 
14.3 
Institutional Review Board 
The PI must obtain IRB/IEC approval for the investigation. All IRB/IEC approvals, including 
initial and continued review, and all materials approved by the IRB/IEC for this study including 
the patient consent form and recruitment materials must be maintained by the Investigator and 
made available for inspection. 

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15 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor or 
designee may conduct quality assurance audits (Section 14.2). 
16 
ETHICS 
This study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH GCP guidelines. 
Investigators and other study personnel must comply with all instructions and regulations 
specified in this protocol and applicable ICH GCP guidelines and must conduct this study in 
accordance with all local, federal, and regulatory agency regulations. 
In accordance to ICH guidelines, pediatric participation in these studies should occur in qualified 
pediatric centers, with personnel who are properly trained and experienced in studying the 
pediatric population and in evaluating and managing potential pediatric AEs. Site personnel 
should be knowledgeable and skilled in dealing with the pediatric population and its 
age- appropriate needs and be encouraged to use measures that minimize discomfort of 
procedures (e.g., topical anesthesia to place IV catheters, use of indwelling catheters instead of 
repeated venipunctures for blood sampling, and collection of some protocol-specified blood 
samples when routine clinical samples are obtained). 
16.1 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate. The Investigator must submit 
written approval to the Sponsor before he or she can enroll any patient into the study. 
No modifications to the protocol should be made without the approval of both the Investigator 
and the Sponsor. Changes that significantly affect patient safety, the scope of investigation, or 
the scientific validity of the study will require IRB/IEC notification prior to implementation, 
except where the modification is necessary to eliminate an apparent immediate hazard to 
patients. Any deviations from protocol must be fully documented. The PI is responsible for 
informing the IRB or IEC of any amendment to the protocol in accordance with local 
requirements. In addition, the IRB or IEC must approve all advertising used to recruit patients 
for the study. The protocol must be re-approved by the IRB or IEC upon receipt of amendments 
and annually, as local regulations require. 
The PI is also responsible for providing the IRB with reports of any reportable serious adverse 
drug reactions from any other study conducted with the study drug. The Sponsor will provide 
this information to the PI. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
16.2 
Data Monitoring Committee Review 
An independent DMC will be appointed by the Sponsor 
 
 who have no direct relationship with the 
study. 
Prior to each scheduled dose escalation, the SRC chair will convene the DMC to review 
laboratory and clinical data in conjunction with the SRC to determine if dose escalation is 
appropriate (Section 3.4). 

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Final decisions regarding the conduct of the study will be made by the Sponsor after consultation 
with the DMC. All appropriate regulatory authorities and ECs will be notified of any significant 
action. 
The DMC may be asked to provide medical and ethical guidance related to the conduct of the 
study as described above. The DMC will review study information as outlined in the DMC 
charter, which is maintained separately from the study protocol. 
Each member of the DMC will be required to sign a contract agreement, which includes a 
confidentiality and financial disclosure statement, assuring no conflicts of interest as a condition 
for membership on the board. 
16.3 
Written Informed Consent 
The PIs at each center will ensure that the patient's parent or legal guardian is given full and 
adequate oral and written information about the nature, purpose, possible risk and benefit of the 
study. The patient's parent or legal guardian must also be notified that they are free to 
discontinue their child from the study at any time. The parent or legal guardian should be given 
the opportunity to ask questions and allowed time to consider the information provided. 
The signed and dated ICF must be obtained before conducting any study procedures. 
The PIs must maintain the original, signed ICF. A copy of the signed ICF must be given to the 
patient's parent or legal guardian. 
Should new information become available during the conduct of the study that might impact 
parent or legal guardian willingness to continue participation in the study, the parent or legal 
guardian will be notified in a timely manner about the new information and asked to sign a new 
ICF. 
16.4 
Patient Data Protection 
Prior to the performance of any study-related procedures, the patient’s parent or legal guardian 
must authorize the release and use of protected health information as required by local, federal 
and regulatory agency law. 
CRFs/eCRFs will be completed at the site either on paper or in the electronic data capture 
system. Copies of pertinent records in connection with the study, including patient charts and 
laboratory data, will be made available to the Sponsor or designee on request in a timely manner 
throughout the course of the study, with due precaution toward protecting patient privacy. 

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17.4 
Data Privacy 
The Sponsor will make every effort to protect patient privacy. For all study data collection, 
patients will be identified by a unique patient number and date of birth in regions where 
permitted. The results from this study may be presented at meetings or in articles. However, 
patient name or initials that could identify a patient will not be used in any such meetings or 
articles. 
18 
PUBLICATION POLICY 
The full terms for publication are outlined in the Clinical Study Agreement, Statement of 
Agreement, or Master Clinical Study Agreement. Publication terms permit publication only after 
publication of multicenter results and require that any data to be submitted for publication 
including abstract submissions or presentations, be submitted to the Sponsor for review at least 
30 days prior to submission. 

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19 
LIST OF REFERENCES 
Clinch K, Watt DK, Dixon RA, Baars SM, Gainsford GJ, Tiwari A, et al. Synthesis of cyclic 
pyranopterin monophosphate, a biosynthetic intermediate in the molybdenum cofactor pathway. 
J.Med.Chem. 2013 Feb 28;56(4):1730-8. 
European Commission Ethical Considerations for Clinical Trials on Medicinal Products 
Conducted with the Paediatric Population: Recommendations of the ad hoc group for the 
development of implementing guidelines for Directive 2001/20/EC relating to good clinical 
practice in the conduct of clinical trials on medicinal products for human use. 2008 European 
Commission. 2008. 
Committee for Medicinal Products for Human Use (CHMP) and Paediatric Committee (PDCO), 
Guideline on the Investigation of Medicinal Products in the Term and Preterm Neonate. 
European Medicines Agency (EMA) London, 2009 European Medicines Agency (EMA). 2009. 
Hitzert MM, Bos AF, Bergman KA, Veldman A, Schwarz G, Santamaria- Araujo JA, et al. 
Favorable outcome in a newborn with molybdenum cofactor type A deficiency treated with 
cPMP. Pediatrics. 2012 Oct;130(4):e1005-e1010. 
Johnson JL, Duran M. The Metabolic and Molecular Bases of Inherited Disease, Chapter 128, 
Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency. 8 ed. McGraw-Hill; 
2001.3163-77 p. 
Johnson JL, Waud WR, Rajagopalan KV, Duran M, Beemer F, Wadman S. Inborn errors of 
molybdenum metabolism: Combined deficiencies of sulfite oxidase and xanthine dehydrogenase 
in a patient lacking the molybdenum cofactor. Proc Natl Acad Sci. 1980 Jun;77(6):3715-9. 
Kikuchi K, Hamano S, Mochizuki H, Ichida K, Ida H. Molybdenum Cofactor Deficiency Mimics 
Cerebral Palsy: Differentiating Factors for Diagnosis. 
Pediatric Neurology. 2012 Apr 16;47:147-9. 
Lee HJ, Adham IM, Schwarz G, Kneussel M, Sass J, Engel W, et al. Molybdenum 
cofactor-deficient mice resemble the phenotype of human patients. Human Molecular Genetics. 
2002 Dec 15;11(26):3309-17. 
Schwahn BC, Galloway P, Bowhay S, Veldman A, Belaidi A, Santamaria- Araujo J, et al. 
Follow-up of two infants with molybdenum cofactor deficiency (MOCD) group A, on long-term 
treatment with cyclic pyranopterin monophosphate (cPMP). J Inherit Metab Dis. 2011;34(suppl 
3):S84. 
Schwahn BC, Spronsen FJ, Balaidi AA, Bowhay S, Christodoulou J, Derks TG, et al. Efficacy 
and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor 
deficiency type A: a prospective cohort study. Lancet. 2015 Nov 14;386(10007):1955-63. 
Veldman A, Santamaria-Araujo JA, Sollazzo S, Pitt J, Gianello R, Yapalito-Lee J, et al. 
Successful Treatment of Molybdenum Cofactor Deficiency Type A With cPMP. Pediatrics. 2010 
May;125(5):e1249-e1254. 
Veldman A, Schwahn B, Galloway P, van Spronsen FBK, Weis I, et al. Efficacy and safety of 
cyclic pyranopterin monophosphate in the treatment of six newborn babies with molybdenum 
cofactor deficiency type A. J Inherit Metab Dis. 2011;34(suppl 3):S84. 
Vijayakumr K, Gunny R, Grunewald S, Carr L, Chong K, DeVile C, et al. Clinical 
Neuroimaging Features and Outcome in Molybdenum Cofactor Deficiency. Pediatric Neurology. 
2011;45:246-52. 
 

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20 
APPENDICES 
• Appendix A 
Blood Sampling Volumes (European Commission2008; European 
Medicines Agency (EMA) 2009) 
• Appendix B 
Blood Sampling Volumes Table (Screening Through Month 6) 
• Appendix C 
Blood Sampling Volumes Table (Extension Period and Safety Follow- Up 
Visit) 
• Appendix D 
Blood Sampling Volumes for Unscheduled Dose Adjustment