A Multicenter, Two Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in Subjects With Chronic Spinal Cord Injury
Phase: PHASE1
Conditions: Chronic Spinal Cord Injury
Sponsor: ReNetX Bio, Inc.

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A Multicenter, Two Part (Open-Label Single-Ascending 
Dose Followed by Double-Blind, Placebo-Controlled Repeat 
Dose) Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Efficacy of AXER-204 in Subjects 
with Chronic Spinal Cord Injury (the RESET* Study) 
*RESET- Chronic SCI Study.  ReNetX Safety Efficacy and Tolerability
of AXER-204 for Chronic SCI 
PROTOCOL RNX-AX204-101 
PHASE 1B/2A 
AXER-204 
IND #: 135648 
Sponsor: 
ReNetX Bio, Inc. 
157 Church St 19th Fl 
New Haven, CT 06510 
www.renetx.com  
Date of Issue:  FINAL V 4.0 October 1, 2020 
This document is confidential and is the sole property of ReNetX Bio, Inc. It is to be distributed 
for review only to investigators, potential investigators, consultants, trial staff, and applicable 
independent ethics committees or institutional review boards. The contents of this document 
shall not be disclosed to others without written authorization from ReNetX Bio, Inc., unless it is 
necessary to obtain informed consent from potential trial subjects. 
NCT03989440

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PROCEDURES IN CASE OF EMERGENCY 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
Email Address and Telephone 
Number 
Study Medical Monitor 
 
 
Study Director 
George Maynard, PhD 
President and CSO 
 
 
24-Hour emergency 
contact 
Primary:   
 
 
Back-up: 
 
 
 
 
 
 
 
 

Digitally signed by George D. 
Maynard 
Date: 2020.10.01 11:02:25 
-04'00'
 
 
 
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PROTOCOL SPONSOR SIGNATURE PAGE 
Title of Study 
A Multicenter, Two Part (Open-Label Single-Ascending Dose followed by 
Double-Blind, Placebo-Controlled Repeat Dose) Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in Subjects with 
Chronic Spinal Cord Injury 
George Maynard, PhD 
President and Chief Scientific 
Officer, ReNetX Bio, Inc. 
Gilbert Block, MD, PhD 
Sponsor 
ReNetX Bio, Inc. 
157 Church St 19th Fl 
New Haven, CT 06510 
www.renetx.com 
 
Signature 
Clinical Consultant to ReNetX. Bio, 
Inc. 
-
 
Study Medical Monitor
 
ReNetX Bio, Inc. 
Signature 
Signature 
3 
Date 
.l Odctv ;;,oar) 
Date 
Date 
Confidential 

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1. 
SYNOPSIS 
Name of Sponsor/Company: 
ReNetX Bio, Inc. 
Name of Investigational Product: 
AXER-204 
Name of Active Ingredient: 
hNgR(310)-Fc 
Title of Study:  
A Multicenter, Two Part (Open-Label Single-Ascending Dose followed by Double-Blind, Placebo-
Controlled Repeat Dose) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy 
of AXER-204 in Subjects with Chronic Spinal Cord Injury   
Study center(s): Approximately 5 study centers in the United States (US) 
Studied period (years):  
Estimated date first subject enrolled: July 2019 (Part 1) 
Estimated date last subject completed: November 2020 (Part 1) 
Estimated date first subject enrolled:  February 2021 (Part 2) 
Estimated date last subject completed: June 2022 (Part 2) 
Phase of development: 1b and 2a 
 
Objectives:  
Study RNX-AX204-101 is a two-part (Part- 1 and 2) study that will be run sequentially.  Part 1 is 
considered a Phase 1b study, while Part 2 is considered a Phase 2a study.  Each part has unique 
objectives.  
Part 1 Single Ascending Dose 
Primary Objectives 
To evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending, single intrathecal lumbar 
slow bolus infusions of AXER-204 in subjects with chronic spinal cord injury (CSCI). 
Part 2 Repeat Dose 
Primary Objectives 
1. To evaluate the safety and tolerability of repeat intrathecal lumbar slow bolus infusions of 
AXER-204 compared to placebo in subjects with CSCI.  
2. To evaluate the pharmacokinetics of repeat doses of AXER-204 in subjects with CSCI 
Secondary Objectives (Part 2 only) 
To assess the efficacy of repeat dose therapy of AXER-204 compared to placebo on function and 
activities of daily living (ADL) measures as assessed by: 
• 
International Standards for Neurological Classification of SCI (ISNCSCI) Upper 
Extremity Motor Score (UEMS). 
• 
Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance 
• 
Version III of the Spinal Cord Independence Measure (SCIM III) self-care  
Exploratory Objectives (Part 2 only) 

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To evaluate the efficacy of repeat dose therapy of AXER-204 compared to placebo as assessed by the 
following:   
• 
ISNCSCI lower extremity motor and sensory scores  
• 
GRASSP strength, sensation and prehension ability scores 
• 
SCIM III mobility scores 
• 
International Standards to document remaining Autonomic Function after Spinal Cord 
Injury (ISAFSCI) 
• 
Patient Reported Outcomes 
− 
CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 
− 
SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 will 
provide data on the subjects' perceived health and well-being over the course of the 
study.   
− 
Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
Patient’s Global Impression of Change (PGIC) – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed   
Methodology:  
Study RNX-AX204-101 is a two-part study that will be run sequentially, with Part 2 planned to start 
after Part 1 has been completed.  Each Part will be conducted at approximately 5 centers in the United 
States.   
Eligible subjects will be ages 18 to 65 years inclusive, male or female, with a traumatic spinal cord 
injury that occurred at least 1 year prior to the screening date.  Subjects must have significant 
neurological impairment of the hands and arms.  Subjects who participated in Part 1 may be evaluated 
for enrollment in Part 2 provided at least 6 months will have elapsed between the dose received in 
Part 1 and the initiation of dosing in Part 2.   
Part 1 
Part 1 is a multicenter, open-label, single ascending dose study in subjects with chronic spinal cord 
injury.  Four cohorts of 6 subjects each are planned, with subjects within each cohort expected to 
receive the same dose of study drug.  Thus, up to 24 subjects will be enrolled in Part 1, and all will 
receive AXER-204.   
Study drug will be administered sequentially, with at least 3 days between subjects being dosed 
within each cohort (following 72-hour safety assessment review by sponsor in conjunction with the 
investigators and medical monitor for each prior subject). 
The study stages for Part 1 are: 
• 
Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, their 
washout period for prohibited concomitant medications. The screening laboratory tests 
must be completed within 28 days prior to Day 1. 
• 
Treatment period:  Check-in Day 1, administration of study drug, 3-night in-clinic stay, 
and discharge on Day 4 following the completion of all scheduled procedures.  

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• 
Follow-up: Subjects will have follow-up visits for up to 29 days post-dose as follows: 
subjects will receive a phone call on Study Days 5, 6, and 7 to inquire about their general 
health and will return to the clinic for visits on Study Day 8 (± 1 day), Study Day 15 (±3 
days), and Study Day 29 or Early Termination (± 4 days).  For each cohort in Part 1, the 
same general procedures will be applied, as follows.   
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI to 
determine spinal cord structure and intrathecal space (Appendix 12); MRIs will be run locally and 
evaluated by a sponsor-arranged expert.  Additional radiological assessments may be performed at the 
discretion of the Principal Investigator, including CT or MRI of the head and X-ray of the lumbar 
spine as additional evaluations to rule out potential contraindications for lumbar puncture.  The 
subject’s demographics, medical and surgical history, and prior and concomitant medications will be 
recorded.  Screening/baseline assessments will be performed, and subjects will undergo blood draws 
where blood, serum collection, viral serology will be obtained, and urine samples will be collected. 
The screening laboratory tests must be completed within 28 days prior to Day 1. 
Subjects will also be presented with a separate biobank ICF for review.  If a subject agrees, samples 
of his/her CSF, blood, MRI scans and data collected in the study, will be stored for future research.  A 
subject does not have to agree or sign the biobank ICF in order to be eligible to participate in this 
main study.   
Prospective subjects must follow dosing restrictions as specified in the protocol for each medication 
listed in Exclusion Criteria. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene). 
Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers may 
be permitted to participate in the trial provided the dosage and frequency of use are not considered 
likely to interfere with evaluation of safety and efficacy endpoints in the trial.  Determination of 
exclusion due to use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician based on 
medical assessment of factors including the dosage, frequency of use, and medical condition being 
treated.    
In the event that a subject is rescreened, the original screening MRI and expert review of the images 
may be used for the rescreening provided the MRI was completed within 6 months of rescreening.  
Similarly, neurological examinations and questionnaires do not need to be repeated provided the 
rescreening occurs within 84 days of the time of data collection. 
In-Clinic Treatment Period: 
Eligible subjects will be admitted to the clinic on the evening prior to or on the day of dosing (Study 
Day 1) dependent on clinical site requirements.  Following final pre-treatment assessments, subjects 
will undergo a lumbar puncture (LP) and receive their single dose of study drug administered via 
intrathecal lumbar slow bolus infusion by the Principal Investigator or a trained and licensed 
designee.  Dosing will be according to Table 2.   
Subjects will remain in-clinic until discharge on Study Day 4 and will undergo daily safety 
assessments and observation.  
Blood and CSF samples will be obtained.  The timing for serum and CSF sample collection may be 
adjusted for subsequent cohorts based on PK data from the preceding cohorts. In addition to 
undergoing PK analysis, serum samples obtained from blood collected at pre-dose and on Study Days 
8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 

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Table 2: 
Treatment by Cohort - Part 1 (Study RNX-AX204-101) 
Cohort 
Treatment 
Number Subjects 
1 
3 mg AXER-204 
6 
2 
30 mg AXER-204 
6 
3 
90 mg AXER-204 
6 
4 
200 mg AXER-204 
6 
Follow-up:  
Sites will contact the subjects via telephone on Study Days 5, 6, and 7 to inquire as to their general 
health status.   
Subjects will return to the Clinic on Study Days 8 (±1d), 15 (±3d), and 29 (±4d).  On Study Days 8 
(±1d) and 29 (±4d), CSF and serum PK samples will be collected.  Blood will be collected for clinical 
laboratory testing and serum for PK on Day 15 (±3d).  Vital signs, AEs, and general health status will 
be assessed at each follow-up visit and end of study assessments will be performed on Study Day 29 
(±4d). 
Dose Escalation in Part 1 
Dose escalation decisions will be made jointly by the investigators, sponsor, and medical monitor.  
The investigators, sponsor, and medical monitor may also make adjustments to the dosing plan, as 
appropriate for reasons of safety and tolerability.   
Data and Safety Monitoring Board (DSMB) 
In order to ensure the utmost safety of subjects, the sponsor will also use an independent Data and 
Safety Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed 
from the DSMB will be required in order for the study to continue (i.e. to resume if stopped or 
ongoing study will be stopped if DSMB does not recommend proceeding).  During Part 1, the DSMB 
will be consulted prior to resuming the study if any of the stopping criteria are met.  The DSMB will 
also be asked to review the safety and tolerability data from Part 1 before starting Part 2.  The DSMB 
will meet during Part 2 after the first subject has completed 3 months of dosing and approximately 
every 3 months thereafter while dosing continues in the study (allowing for potential scheduling 
logistics). In addition to the pre-determined DSMB data review meeting, the DSMB may be engaged 
at any time at the request of an investigator, the sponsor, or medical monitor. A charter will be written 
to describe the DSMB’s objectives, schedule for data reviews, and general responsibilities in respect 
to the study.  All DSMB decisions will be documented in writing, and where required, submitted to 
the institutional review board (IRB) for their review or information.    
Dose Escalation Rules for Part 1 
Dose escalation (for each sequential cohort) will not occur until 6 subjects in the prior cohort have 
completed the initial 3 day in-clinic period AND at least two subjects have completed their Day 29 
post-dose follow-up visit.  Determination of whether to escalate dose in the subsequent cohort will be 
made by the sponsor in conjunction with the investigators and medical monitor after review of all 
clinical and any available PK data.  Review will include adverse events (AEs) and serious AEs 
(SAEs), and specifically the following potential stopping criteria will be evaluated prior to each dose 
escalation.  If the dose is well tolerated in the completed dose group, the sponsor, in conjunction with 
the investigators and medical monitor, will recommend escalation to the next dose level.   
Stopping Rules/Study Interruption/Discontinuation Notice 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing or 
stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 

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occurrence of any individual adverse events which, in the judgment of the investigators and medical 
monitor in conjunction with the sponsor, need further characterization with respect to progression and 
reversibility before further dosing is conducted.  Such adverse events may include non-serious 
unusual events.  If dosing is stopped, review of the data by the investigators and medical monitor in 
conjunction with the sponsor and the DSMB must occur before dosing can be resumed.  Dosing will 
only be resumed with DSMB approval.   
Pharmacokinetic and anti-drug antibody test results will not be required for dose escalation unless it is 
determined to be advisable by the sponsor in conjunction with the investigators and medical monitor 
based on emergent data from the study.  CSF and serum samples will be analyzed for each cohort 
immediately after all subjects have been dosed.  The sponsor may direct earlier analysis of a partially 
completed cohort if completion of the cohort is delayed or partial cohort data is desired to aid in 
interpretation of any emergent clinical data.   
Part 2 
Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in CSCI 
subjects.  Approximately 32 subjects will be randomized (ratio 1:1) to receive AXER-204 or placebo 
(an isotonic phosphate buffered saline formulation).  Subject to review of the safety, tolerability, and 
pharmacokinetic data from Part 1 and DSMB approval, the dose will be 200 mg given once every 3 
weeks for 15 weeks as outlined in the schedule of events.  Subject to DSMB approval, the dose may 
be reduced to 90 mg and the dose interval may be modified based on data from Part 1 but is not 
expected to be less than once every 14 days or more than 28 days.  Subject to DSMB approval, the 
dose and dose frequency may also be adjusted during Part 2 based on emergent safety and tolerability 
data. 
The study stages for Part 2 are: 
• 
Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, their 
washout period for prohibited concomitant medications.  The screening laboratory tests 
must be completed within 28 days prior to Day 1. 
• 
Treatment Period (15 weeks).  Investigational product given approximately every 21 days 
for up to 104 days per subject.  A telephone call to assess status regarding any adverse 
events will be conducted on Study Day 8 (±3 days). 
• 
Follow-up (21 weeks).  Following the last Treatment Period dose of investigational 
product or Early Termination of dosing, a telephone call to assess status regarding any 
adverse events will be conducted on Study Day 137 (± 7 days) and two follow-up visits 
will occur at Study Days 169 (± 7 days) and 253 (± 7 days). 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI to 
determine spinal cord structure and intrathecal space; MRIs will be run locally and evaluated by a 
sponsor-arranged expert. Additional radiological assessments may be performed at the discretion of 
the Principal Investigator, including CT or MRI of the head and X-ray of the lumbar spine as 
additional evaluations to rule out potential contraindications for lumbar puncture. The subject’s 
demographics, medical and surgical history, and prior and concomitant medications will be recorded.  
Screening assessments will be performed, and subjects will undergo blood draws where blood, serum 
collection, viral serology will be obtained, and urine samples will be collected. The screening 
laboratory tests must be completed within 28 days prior to Day 1. 

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Subjects will also be presented with a separate biobank ICF for review. If a subject agrees samples of 
his/her CSF, blood, MRI scans and data collected in the study, will be stored for future research.  A 
subject does not have to agree or sign the biobank ICF in order to be eligible to participate in the main 
study.   
Prospective subjects must follow dosing restrictions as specified in the protocol for each medication 
listed in Exclusion Criteria. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene).  
Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers may 
be permitted to participate in the trial provided the dosage and frequency of use are not considered 
likely to interfere with evaluation of safety and efficacy endpoints in the trial.  Determination of 
exclusion due to use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician based on 
medical assessment of factors including the dosage, frequency of use, and medical condition being 
treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the images 
may be used for the rescreening provided the MRI was completed within 6 months of rescreening.  
Similarly, neurological examinations and questionnaires do not need to be repeated provided the 
rescreening occurs with 84 days of the time of data collection. 
Treatment Period 
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will be 
stratified based on pre-treatment American Spinal Injury Association Impairment Scale (AIS) grade 
(AIS A,B vs. AIS C,D) and prior receipt of study drug in Part 1 (Received AXER-204 in Part 1 vs. 
Did not receive AXER-204 in Part 1).  
Subjects will receive their baseline assessments and assigned (double-blind) treatment on Study Day 
1.  A telephone call to assess status regarding any adverse events will be conducted on Study Day 8 (± 
3 days).  Subjects will then return to the Clinic on Day 21 (± 5 days) for safety, efficacy, and PK 
assessments and their second dose of investigational product.  Thereafter, subjects will return 
approximately every 21 days, at Study Days 42 (± 5 days) (third dose), 63 (± 5 days) (fourth dose), 84 
(± 5 days) (fifth dose), 104 (± 5 days) (sixth dose), for safety, efficacy, and PK assessments (pre-
dose) and investigational product administration.     
Cerebrospinal fluid samples will be collected pre-dose at each treatment (dosing) visit, including 
Study Day 1, during a single LP procedure for collecting and dosing.  Serum for PK and 
immunogenicity (ADA) testing will be collected pre-dose at the timepoints specified in the schedule 
of events within 4 hours prior to investigational product administration.  Serum will also be collected 
for PK at 4 h post-dose at specified visits. 
For dosing visits that include neurological exams and questionnaires (e.g. ISNCSCI, GRASSP, SCIM 
III self-care and mobility), these assessments should be performed prior to dosing. Depending on 
scheduling considerations, subjects may be asked to return the following day for dose administration.  
Under this circumstance, nearby overnight accommodations will be arranged for the subject upon 
request. 
Following dosing, patients will remain under the observation of study personnel in the hospital setting 
(eg, may include infusion center, PACU, recovery suite, observation unit, short stay center) for 4 
hours for safety monitoring. Thereafter, if deemed clinically stable by the Investigator, patients may 
leave the hospital setting.  If further safety observation is directed by the investigator, the subject may 
be directed to remain at a nearby overnight accommodation or home (if within a reasonable distance) 
and report the next morning for examination or to remain in the hospital overnight.  Note that, under 
these circumstances, there is no requirement for an overnight hospital stay; if a decision is made to 

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keep the patient overnight for convenience (e.g. travel issues), this hospitalization should not initiate a 
serious adverse event report (e.g. local alternate accommodations not readily available). 
Follow-Up 
Study personnel will conduct telephone call with subjects on Study Day 137 (± 7 days) to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come to 
the clinic for evaluation.  Subjects will return at Study Days 169 (± 7 days) and 253 (± 7 days) for 
safety and efficacy assessments.   
Stopping Rules/Study Interruption/Discontinuation Notice 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing or 
stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and medical 
monitor in conjunction with the sponsor, need further characterization with respect to progression and 
reversibility before further dosing is conducted.  Such adverse events may include non-serious 
unusual events.  If dosing is stopped, review of the data by the sponsor in conjunction with the 
investigators and medical monitor in conjunction with the sponsor and the Data and Safety 
Monitoring Board (see below regarding DSMB composition and charter) must occur before dosing 
can be resumed.  Dosing will only be resumed with DSMB approval. 
Data and Safety Monitoring Board (DSMB)   
In order to ensure the utmost safety of subjects, the Sponsor will also use a Data and Safety 
Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed from the 
DSMB will be required in order for the study to continue (i.e. to resume if stopped or ongoing study 
will be stopped if DSMB does not recommend proceeding).  The DSMB will review the safety and 
tolerability data from Part 1 before recommending starting Part 2.  In addition to the pre-determined 
DSMB data review meetings, the DSMB may be engaged at any time at the request of an investigator, 
the sponsor, or medical monitor. A charter will be written to describe the DSMB’s objectives, its 
membership, schedule for data reviews, and general responsibilities with respect to the study.  All 
DSMB decisions will be documented in writing, and where required, submitted to the institutional 
review board (IRB) for their review or information.   
Number of Subjects (planned):  
Part 1 will enroll up to 24 subjects in cohorts of 6 subjects each. Part 2 will enroll approximately 32 
subjects, randomized in a 1:1 ratio (and thus approximately 16 subjects per arm) to repeated doses of 
AXER-204 or of matching placebo. 
Diagnosis and main criteria for eligibility:  
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 
1. Men or women between the ages of 18 and 65 years, inclusive 
2. Traumatic spinal cord injury that occurred ≥ 1 year ago  
3. Cervical spinal cord injury with serious neurological deficit as evidenced by 1) bilateral ISNCSCI 
UEMS between 4 and 36 points inclusive, and 2) bilateral GRASSP prehension ability score 
between 4 and 17 points inclusive 
4. Confirmation by MRI of the following: 
a. Chronic SCI (persistent spinal cord lesion) 
b. For AIS grade of A without sensory or motor zone of partial preservation extending at 
least two levels caudal to the level of injury, no apparent transection of the cord  

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c. CSF space spanning the lesion 
5. Read, understood, and provided written informed consent after the nature of the study has been 
fully explained and must be willing to comply with all study requirements and procedures. 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including gunshot 
that did not penetrate the spinal cord 
2. Women who are pregnant or lactating, and women of childbearing potential except those using 
adequate birth control measures. All female subjects must have a negative serum pregnancy test 
at Screening and women of childbearing potential must have a negative urine pregnancy run 
locally at the Randomization/Pre-Dose Visit on Study Day 1.  All subjects (male and female) as 
well as non-study female partners of male subjects, must use adequate birth control measures 
during the course of the study and for at least 10 weeks after the subjects’ last dose of 
investigational product  
• 
Adequate or effective contraception is defined as double barrier contraception (eg, 
condom plus spermicide in combination with a female condom, diaphragm, cervical cap, 
contraceptive sponge, implants, injectables, combined oral contraceptives, sexual 
abstinence (total abstinence from sexual intercourse as the preferred lifestyle of the 
subject; periodic abstinence is not acceptable), or sexual intercourse with only a 
vasectomized partner.  Subjects and/or partners who are surgically sterile or women with 
confirmed postmenopausal status are exempt from this requirement.   
3. History of stroke, cerebrovascular injury, or elevated intracranial pressure 
4. Contraindications for lumbar puncture 
5. Requiring mechanical ventilatory assistance of any type 
6. Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg 
7. Botulinum toxin injection, with the exception of bladder treatments, within 4 months prior to 
study 
8. History of life threatening allergic or immune-mediated reaction to vaccines, or biologic drugs, at 
any time or any life threatening allergic or immune-mediated reaction within the past 12 months. 
9. Systemic use of immunosuppressants within the past 2 months with the exception of 
mineralocorticoids 
10. Significant deformities, contractures (with less than 50% of normal range of motion at affected 
joints), or any issues that limit completion of UEMS with the ISNCSCI exam 
11. Recent changes in anti-spasmodic or anti-spasticity medications.  Anti-spasmodic or anti-
spasticity medication is permitted providing that the subject has been on a stable dose for at least 
12 weeks before the Screening Visit (Visit 1) and agrees to remain on a stable dose throughout 
the course of the study 
12. Any orthopedic injury, recent surgeries, or current diagnosis of any primary diseases affecting 
upper limb function outside of SCI (eg, infection, tumor, congenital malformations, Huntington’s 
disease, Parkinson’s disease) 
13. Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF 

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14. Uncontrolled medical condition including but not limited to cardiovascular disease, sleep apnea, 
obstructive lung disease, severe neuropathic or severe chronic pain, severe autonomic dysreflexia 
15. Participation in any other investigational drug or device trial within 30 days or within 5 half-lives 
of the investigational drug or any past participation in a SCI cellular therapy trial. 
16. Regular use of the following concomitant medications that might confound efficacy and/or safety 
assessments is prohibited, including, but not limited to, the following:  
a. Antipsychotic drugs with the exception of use of these mood stabilizers for the 
adjunctive treatment of depression provided the subject is on a stable dose for at least 12 
weeks prior to Screening and the dose is not anticipated to change during participation in 
the trial. 
b. Anticoagulants, however, daily low dose aspirin (81mg) therapy is permitted. 
c. Opiates, sedative hypnotics, or tranquilizers unless used to treat anxiety, pain, or sleep 
disorder and the dosage and frequency of use are not considered likely to interfere with 
evaluation of safety and efficacy endpoints in the trial. Determination of exclusion due to 
use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician 
based on medical assessment of factors including the dosage, frequency of use, and 
medical condition being treated.   
d. Use of tumor necrosis factor [TNF] inhibitors 
e. Use of Class 1 antiarrhythmic.  
17. Use of antidepressants (SSRI, SNRI, TCA, buspirone) is PERMITTED but limited to subject 
being on a stable dose for at least 12 weeks 
18. History of severe acute or chronic medical or psychiatric condition or laboratory abnormality that 
could increase the risk associated with trial participation or investigational product administration 
or could interfere with the interpretation of trial results and including but not limited to the 
following:  
• 
human immunodeficiency virus (HIV) infection 
• 
active chronic hepatitis B or hepatitis C infection including hepatitis B surface antigen 
and hepatitis C antigen positive subjects with or without abnormal liver enzymes 
• 
immunosuppressive disease 
• 
chronic renal disease/failure as evidenced by estimated glomerular filtration rate (eGFR) 
of <60 
• 
concurrent neurodegenerative disease 
• 
cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or 
symptomatic congestive heart failure within the past 12 months or serious uncontrolled 
and clinically significant cardiac arrhythmia as determined by the investigator 
• 
dementia or significantly altered mental status including brain injury with ongoing 
cognitive signs and symptoms that would prohibit the understanding or rendering of 
informed consent and compliance with the requirements of the protocol 
19. Evidence or self-report of alcohol or drug abuse within the previous 12 months 

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20. Any conditions that in the judgement of the investigator would make the subject inappropriate for 
entry into the trial 
Investigational product, dosage and mode of administration:  
AXER-204 is a human fusion protein to promote axon growth and recovery of neurological function.  
AXER-204 is administered by intrathecal lumbar slow bolus injection.   
Part 1:  
Dosage will be by cohort, with 4 sequentially-treated cohorts planned.  Intrathecal doses of AXER-
204 below 90 mg will be diluted and delivered as a solution in 10 mL of isotonic phosphate buffered 
saline.  Both the 90 mg dose and 200 mg dose will be dosed with the current study drug 
concentration.  All administration will be given following a removal of an equivalent volume of CSF.  
Intrathecal injections will be given at a rate of 100 mL/hr using a medically approved syringe pump 
(eg, 12 minutes to administer 20 mL) to avoid significant disruption of natural CSF flow and pressure 
and monitored by medical personnel.   
The starting dose of 3 mg is estimated to be below the pharmacologically active dose.  Dose 
escalation will proceed to 30 mg, 90 mg, 200 mg contingent on safety, tolerability, and available PK.  
Thus, dosing volumes will be given as follows: 
• 
Cohort 1:  3 mg, 10 mL 
• 
Cohort 2:  30 mg, 10 mL 
• 
Cohort 3:  90 mg, 9 mL 
• 
Cohort 4:  200 mg, 20 mL 
Part 2 
Subject to review of the safety, tolerability, and pharmacokinetic data from Part 1 and DSMB 
approval, the dose will be 200 mg given once every 3 weeks for 15 weeks as outlined in the schedule 
of events.  Subject to DSMB approval, the dose may be reduced to 90 mg and the dose interval may 
be modified based on data from Part 1 but is not expected to be less than once every 14 days or more 
than 28 days.  Subject to DSMB approval, the dose and dose frequency may also be adjusted during 
Part 2 based on emergent safety and tolerability data. 
The maximum volume of injection by intrathecal lumbar slow bolus injection is limited to 20 mL in 
this study based on published tolerance data from studies with other agents employing the same route 
of administration.  If an injection volume of 20 mL, corresponding to a 200 mg dose of AXER-204, is 
reached in Part 1 dose escalation portion of the study with acceptable safety and tolerance, the 200 mg 
dose will be designated as the dose for Part 2 at the discretion of the Sponsor in conjunction with the 
investigators, DSMB, and medical monitor.   
Duration of treatment:  
Part 1 is a single-dose treatment for each subject.  Subjects will have up to an 84-day screening 
period, a 3-day in-clinic treatment period, and a follow-up period through 29 days post-dose.  Thus, 
study participation for each subject in Part 1 is expected to be approximately up to 16 weeks in 
duration.  
Part 2 Placebo-controlled Repeat Dose Portion.  Subjects will have up to an 84-day screening period, 
a 104-day treatment period with injections given every 21 days through Day 104, and then post 
treatment follow-ups at Study Days 137, 169, and 253.  The follow-up on Study Day 137 will consist 
of a telephone call conducted by study personnel to assess status regarding any adverse events.  Thus, 
study participation for each subject in Part 2 is expected to be up to approximately 337 days in 
duration. 

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Reference therapy, dosage and mode of administration:  
Part 1 does not include placebo. 
Part 2 includes a matching placebo control, to be given at the same intervals and volume as the 
investigational product.  Placebo consists of a phosphate buffered saline formulation.  
At each study site, for each dose to be administered in Part 2, an unblinded pharmacist will prepare 
prefilled syringes for dose administration in order to maintain the blind for study personnel 
administering the investigational product and performing all other study procedures. 
Criteria for evaluation: 
Pharmacokinetics: 
Both serum and cerebrospinal fluid samples will be collected for analyses, as shown in Table 3 and 
Table 4. 
In Part 1, a window relative to the nominal timepoint is allowed for sample collection as follows: 
• 
Blood serum pharmacokinetic samples will be collected at 0 hour (immediately pre-
dose), and 1 h (±10 min), 6 h (±10 min), 12 h (±10 min), and 24 h (±10 min) post-dose, 
as well as at Study Day 4 (72h ± 10 min), 8 (±1d), 15 (±3d), and 29 (±4d).   
• 
Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose), 24 h (±2h) Study Day 4 (72 h ±4h), and Study Days 8 (±1d), and 
29 (±4d).  
The timing for serum and CSF sample collection may be adjusted for subsequent cohorts based on 
pharmacokinetic data from the preceding cohorts.  Serum PK samples collected at pre-dose and on 
Study Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
In Part 2, Visits 3-7 (Study Days 21, 42, 63, 84, 104) will have a window of ±5 days and Visits 8 and 
9 (Study Days 169 and 253) will have a window of ±7 days.  CSF samples will be collected for PK 
analysis pre-dose on Study Days 1, 21, 42, 63, 84, and 104.  The CSF sample collected on Study Day 
253 will also be analyzed for PK.  Serum samples will be collected for PK analysis pre-dose and 4 h 
post-dose on Study Days 1, 21, 42, 63, 84, and 104.  Serum will also be collected for PK analysis on 
Study Days 169 and 253.  Pre-dose serum will be collected for ADA analysis on Study Days 1, 21, 
42, 63, 84, and 104.  Serum will also be collected for ADA analysis on Study Days 169 and 253.  A 
subset of the CSF samples may also be analyzed for ADAs depending on development and presence 
of ADAs in the serum.  Part 2 serum and CSF from subjects receiving placebo will be collected but 
will not be analyzed for PK and ADAs. 
In Part 2 on Study Days 1, 21, 42, 63, 84, and 104 a window relative to the nominal timepoint is 
allowed for sample collection as follows: 
• 
Blood serum pharmacokinetic samples will be collected at 0 hour (within 4 h pre-dose), 
and 4 h (±10 min) post-dose 
• 
Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose) 
Table 3: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Day 1 (Dosing day)  
Day 2 (24 hours 
post-dose) 
Day 4 (72 hours 
post-dose)  
Day 
8 
Day 
15 
Day 
29 
Cerebrospinal 
Fluid  
Pre-Dose 
X 
X 
X 
 
X 

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Serum 
Pre-Dose, and post-dose at 
Hours 1, 6, 12 
X 
X 
X 
X 
X 
Serum aliquot for 
ADA 
X (Pre-Dose) 
 
 
X 
 
X 
Table 4: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
Study Phase 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
Month (M) 
1 
21 
 
42 
 
63 
84 
 
104 
 
169 
M6 
253/ET 
M9 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
Cerebrospinal Fluid  
X 
X 
X 
X 
X 
X 
X 
Serum 
X 
X 
X 
X 
X 
X 
X 
X 
Serum aliquot for 
ADA 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations:  M = month, ET = Early Termination 
 
Efficacy 
Part 1  
Part 1 is focused on safety, tolerability, and pharmacokinetics.  However, a subset of efficacy 
assessments are to be performed including:  
• 
ISNCSCI.  ISNCSCI is a comprehensive clinician-administered neurological exam for 
SCI. It is widely used for research and clinical (neurologic) description to fully assess 
sensory and motor functioning and level of injury in traumatic SCI.  The UEMS will be 
calculated from the ISNCSCI. 
• 
GRASSP.  GRASSP is a clinician administered test that assesses strength in 10 key 
muscles in the upper extremity as well as dexterity and fine motor skills. 
• 
SCIM III self-care and mobility scores.  SCIM III measures functional outcomes in three 
sections:  self-care, respiration and sphincter management, and mobility.  The current 
study will employ the self-care and mobility subscores. 
Part 2 
The primary objective of Part 2 is to evaluate the safety, tolerability, and pharmacokinetics of repeat 
dosing.  In addition, a number of efficacy assessments are included as secondary endpoints.  The key 
secondary efficacy endpoint for Part 2 will be within-subject change from pre-treatment baseline and 
slope for UEMS as compared to placebo.  The same trained raters should be used for a particular 
patient as much as possible.  The assessments will be performed in the order outlined in Section 11.2. 
Additional secondary efficacy endpoints will include within-subject changes from pre-treatment 
baseline and slope for: 
• 
GRASSP prehension performance scores.  GRASSP is a clinician-administered test with 
three subset scores that assesses strength in 10 key muscles in the upper extremity as well 
as dexterity and fine motor skills. 
• 
SCIM III self-care scores.  Although the SCIM III measures functional outcomes in three 
sections:  self-care, respiration and sphincter management, and mobility, the current study 
will employ the self-care and mobility subscores.  The evaluation will be administered by 
interview of the patient by a clinician. 
Exploratory endpoints will include within-subject changes over time from pre-treatment in: 

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• 
ISNCSCI lower extremity motor and sensory scores.  ISNCSCI is a comprehensive 
clinician-administered neurological exam for SCI. It is widely used for research and 
clinical (neurological) description to fully assess sensory and motor functioning and level 
of injury in traumatic SCI.   
• 
GRASSP strength, sensation and prehension ability scores   
• 
SCIM III mobility scores 
• 
ISAFSCI.  The ISAFSCI will be used to document autonomic control of the heart, blood 
pressure, sweating, and temperature regulation.  Lower urinary tract function, bowel 
function, and sexual function will be scored. 
• 
Patient Reported Outcomes 
− 
CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 
− 
SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 will 
provide data on the subjects' perceived health and well-being over the course of the 
study.   
− 
Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
PGIC – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed.  
Safety: 
Safety will be evaluated similarly for both Parts, through the collection of data from: 
• 
Physical examinations 
• 
Vital signs 
• 
12-lead electrocardiograms 
• 
Laboratory parameters (hematology, blood chemistry, and urinalysis).  Analysis of CSF 
for protein, cell count, and glucose. 
• 
Treatment-emergent adverse events (TEAEs).   
− 
TEAEs will be defined as any AE occurring during or after the injection of study 
drug or placebo.   
− 
TEAEs will be limited to those events occurring within 28 days after the last visit. 
Condition-specific safety outcomes will include adverse changes in: 
• 
ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• 
Spasticity (Modified Ashworth Scale).  A clinician administered examination for 
spasticity which measures muscle tone.  A score of 0-4 is assigned to each muscle group 
evaluated.  Note: Testing will exclude fingers and thumb. 
• 
Pain (BPI). A self-administered questionnaire used to assess the severity of a subject's 
pain and the impact of this pain on the subject's daily functioning.  
Statistical Methods 

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A general description is included here for the investigator.  A detailed Statistical Analysis Plan will be 
submitted to the IND prior to unblinding the database for Part 2. 
Sample Size  
The Part 1 sample size was derived empirically from experience with previous single ascending dose 
clinical studies in other disorders and is deemed appropriate to achieve the study objectives. 
The Part 2 sample size was selected to ensure adequate power for detecting treatment-related change 
in bilateral UEMS (Score from 0 to 50). 
A 5-point difference, between the treated and placebo groups, in the change from baseline to 6 
months in bilateral UEMS is considered clinically meaningful. Analysis of historical data for cervical 
SCI patients for the period between ~6-12 months following acute SCI indicates a standard deviation 
of bilateral UEMS change over 6 months to be around 3 to 4 points. 
With a sample size of 12 subjects per active and placebo group, Part 2 of the study has 80% power 
with Type I error of α=0.05 (two sided), assuming a 5-point difference as indicated above, and with a 
common standard deviation within each treatment group of approximately 4 in the change from 
baseline to 6 months in bilateral UEMS.  
Accounting for uncertainties in the assumptions based upon historical data used to extrapolate for 
estimating the sample size in this study and the need for estimation of missing data a sample size of 
approximately 16 subjects per treatment arm (32 total) will be randomized.    
Stages of Analysis 
The analysis for this study will be performed in three stages, with the first analysis performed upon 
completion of the clinical portion of Part 1, the second analysis (including the core efficacy 
assessment) performed upon completion Day 169 of Part 2 (ie, after all subjects have completed 
through Study Day 169), and the final analysis performed upon completion of the post-treatment 
follow-up phase of Part 2 (Day 253).  The methods applied to each analysis will be consistent with 
the objectives of the study.   
The blind will be maintained for all blinded study personnel (including investigators and subjects) 
through the completion of Day 169 of Part 2.  After completion of Day 169, designated sponsor staff 
and external consultants/contractors required to perform the analysis will be unblinded to the 
treatment allocations in order to complete data analysis though Day 169.  The blind will be 
maintained for site investigators and subjects through completion of Day 253 unless the blind must be 
broken sooner for safety or regulatory reasons.   
General Methods 
Data will be tabulated using both descriptive and inferential statistics where specified.   
• 
For Part 1, data will be tabulated by dose cohort as well as pooled (all subjects 
combined), and no inferential statistics are planned. 
• 
For Part 2, data will be tabulated for each treatment group separately (placebo and 
AXER-204) to allow for visual inspection of outcomes between the arms.  Inferential 
statistical comparison of the treatment groups is planned. 
For both Parts, all data collected will be included in by-domain data listings, sorted by subject number 
and time point, or as appropriate. 
No hypothesis testing will be performed for demographics, background, or safety data.  
Continuous data will be summarized by presenting the number of subjects (n), means, mean changes 
from baseline, mean % changes from baseline (where appropriate), standard deviations, minimum, 
First quartile (Q1), median, third quartile (Q3), and maximum values. The number of subjects with 
missing data will be indicated. 

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Categorical data will be summarized by presenting the number of subjects (n), the number of subjects 
with missing data as well as counts and percentages in each of the categories. Percentages will be 
based upon the number of subjects with available data. 
When inferential testing is applied to all efficacy assessments, dichotomous/binary categorical 
efficacy endpoints will be assessed via a 2-sided Fisher’s Exact test or Chi-square test as appropriate.  
Continuous efficacy endpoints will also present least-squares means and p-values from hypothesis 
testing of efficacy endpoints using mixed-effects model for repeated measures (MMRM). 
Additional details will be included in the statistical analysis plan (SAP) which will be finalized prior 
to unblinding Part 2 of the study and any amendments to it made prior to locking the database and 
unblinding the study.   
Handling of Missing Data 
Every attempt will be made to collect all protocol required data at each time point.     
Imputations will only be performed for efficacy data and for missing or partial dates, missing severity 
or relationship to investigational product. Missing AE or CM dates and missing severity or 
relationship to study drug will always use a conservative approach. Details will be included in the 
SAP.  
For subjects who discontinue treatment (for any reason), subjects will continue to be followed and 
key efficacy endpoints and safety data collected where possible. 
Analysis Populations 
Safety Population:  Safety outcomes will be assessed for all subjects who are given at least one dose 
of investigational product.  
Full Analysis Set (FAS) Population:  Efficacy outcomes will be evaluated using the FAS, defined as 
all subjects randomized, treated with at least 1 dose of investigational product, and with at least one 
post-baseline assessment of efficacy. 
Per Protocol Population: The per protocol population will be a subset of FAS and include subjects 
who received at least 80% of study drug and have no major protocol deviations that would impact 
efficacy assessment.  
Alpha Level Considerations 
All inferential testing will be performed using two-sided 5% Type I error (α), and therefore 2-sided p-
values ≤ 0.05 will be considered statistically significant in this study. 
The first hypothesis test will be the key secondary efficacy endpoint of change in bilateral UEMS 
from baseline to Study Day 169 using the MMRM model as detailed below. Additional secondary 
efficacy endpoints tested will be the change in GRASSP prehension performance from baseline and 
slope to Study Day 169 and of change in SCIM self-care from baseline to Study Day 169.  
Efficacy Endpoints 
Changes from pre-treatment to each on-treatment time point will be calculated, with the primary time 
point at Day 169.  Shifts over time in ordinal endpoints will be presented, with comparisons between 
treatment groups assessed using a CMH row mean scores statistic at each time point.  Slope of change 
will also be evaluated. 
Safety Endpoints 
Changes from pre-treatment will be calculated in a similar fashion as for the efficacy endpoints, but 
no inferential statistics will be provided for safety endpoints.  Shifts from baseline in 
electrocardiogram (ECG) will be tabulated for heart rate and QTcF.  Other endpoints will be assessed 
according to the scale of the variable. 
Pharmacokinetic Endpoints 

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Concentration data in both blood serum and in CSF will be assessed descriptively over time.  
Correlation with efficacy and safety outcomes may be performed, as the data warrant. 
Potential Open-Label Extension Study 
The sponsor may, pending data outcomes from this current study, initiate an open-label extension 
study at a later date.  This study would provide subjects who participated in Study RNX-AX204-101, 
during either Part 1 only and those receiving placebo in Part 2, the potential opportunity to participate 
in a repeat-dose study with AXER-204.   
Initiation of the open-label extension study will be contingent on satisfactory results from the current 
clinical study (Part 1 and Part 2) supportive of continued development, funding, and the requisite 
regulatory and IRB approvals. 
 

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Table 5: 
Part 1 Schedule of Events (Study RNX-AX204-101)1 
Study Phase 
Screening 
In-Clinic Treatment 
Post-Treatment Follow-Up 
 
Study Day 
-84 
through -1 
1 
2 
3 
4 
5, 6, 72 
8 
± 1 days 
15 
± 3 days 
29/ET3 
± 4 days 
Pre-Dose 
Post 
Visit Number 
1 
2 
 
 
 
 
Phone 
Call4 
3 
4 
5 
Informed consents (Main & Biobank) 
X 
 
 
Register Subject/Contact EDC/Assign Subject ID  
X 
 
 
 
 
 
 
 
 
 
Inclusion & Exclusion Criteria 
X 
X 
 
 
Instructions for potential washout period for concomitant medications 
and for alcohol use 
X 
 
 
 
 
 
 
 
 
 
Urine sample for drug screen5 
X 
 
 
 
 
 
 
 
 
 
Medical/Disease History 
X 
X 
 
 
Full Physical Examination & Ht/Wt 
X 
 
 
 
 
 
 
 
 
X 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Vital signs (BP, pulse, RR or pulse ox, oral temp)6 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
ECG7 
X 
X 
X 
 
 
X 
 
 
 
 
Serum pregnancy, chorionic gonadotropin  
X 
 
 
MRI8 
X 
 
 
ISNCSCI assessment, including AIS (Clinician Assessed) 
X 
 
 
 
 
 
 
 
 
X 
SCIM III self-care and mobility subscores (Clinician Assessed) 
X 
 
 
X 
GRASSP (Clinician Assessed) 
X 
 
 
X 
Admission/Discharge to/from Clinic 
 
Admit 
 
 
 
Discharge 
 
 
 
 
Physical Examination (abbreviated) 
 
X 
 
 
 
X 
 
 
 
 
CSF collection (for PK assessment)10 
 
X 
 
X 
 
X 
 
X 
 
X 
Dosing of Investigational Product 
 
Dosing 
 
 
 
 
 
 
 
 
Study Drug Accountability 
 
 
X 
 
 
 
 
 
 
 
Serum (for PK and ADA assessment)9 
 
X 
Hr 1, 6, 
12 
X 
 
X 
 
X 
X 
X 
Modified Ashworth Scale (Clinician Assessed) 
X 
 
 
X 
SF-36 v2 Health Survey (Subject Reported) 
X 
 
 
X 
Neuro-QOL v1.0 – Upper Extremity Function (Fine Motor, 
ADL) (Subject Reported) 
X 
 
 
 
 
 
 
 
 
X 
Brief Pain Inventory (Subject Reported) 
X 
 
 
X 
ISAFSCI (Clinician Assessed) 
X 
 
 
X 
Clinical laboratory sample collection10 
X 
X 
X 
X 
X 
 
X 
X 
Viral Serology11 
X 
 
 
X 
Urinalysis  
X 
 
 
X 

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Study Phase 
Screening 
In-Clinic Treatment 
Post-Treatment Follow-Up 
 
Study Day 
-84 
through -1 
1 
2 
3 
4 
5, 6, 72 
8 
± 1 days 
15 
± 3 days 
29/ET3 
± 4 days 
Pre-Dose 
Post 
Visit Number 
1 
2 
 
 
 
 
Phone 
Call4 
3 
4 
5 
Urine pregnancy test12 
 
X 
 
 
 
 
 
 
 
X 
Prior and Concomitant Medications 
Prior 
 
Concomitant (On-going) 
Adverse Events13 
 
 
Treatment-Emergent (On-going) 
Serious Adverse Events 
Pre-
Treatment 
 
Treatment-Emergent (On-going) 
 
1 Abbreviations:  AE = adverse events, ECG = electrocardiogram, EDC = electronic data capture. ET = early termination.  ID = identification, PK = 
pharmacokinetic, SAE = serious adverse event 
2 Note:  Day 7 phone call may be skipped if Day 8 visit actually occurs on Day 7. 
3 ET:  early termination.  Subjects who terminate the treatment prematurely (including those withdrawn from the study) should have all assessments performed 
according to the protocol.  However, subjects who discontinue from the study may only have assessments performed per the ET visit. 
4 Phone calls from the site to the subject will be made each day (Study Days 5, 6, and 7) after discharge from the clinic.  Subjects will be queried for general health. 
5 Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, marijuana, opiates, phencyclidine, barbiturates, 
benzodiazepines, methadone, and propoxyphene).  Patients must abstain from drinking alcohol and using recreational marijuana in US states where marijuana is 
legal, for at least 3 days prior to laboratory screening assessments on nominal Day-28. 
6 Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) will be measured after the patient has been in a sitting or 
recumbent position for 5 minutes. Frequency noted below: 
Screening visit - Once 
Day 1 - Pre-dose, post-dose, then every 3 hours for 1st 24 h following dosing 
Day 2-Day 4 (until discharge from the clinical unit) - Starting at 24 h post-dose, take vitals every 6 hours 
Day 8, 29 - Pre-LP, post-LP, then every 3 hours until subject leaves the unit 
Day 15 - Pre-blood draw 
7 ECGs will be taken in triplicate, 5 minutes apart, will be obtained after the patient has been in a supine (resting) position for at least 5 minutes. At Visit 2, 
triplicate ECGs will be taken twice, pre-and post-dose.  All ECGs will be read locally. 
8 MRIs will be read by a sponsor-arranged expert prior to subject enrollment into the study 
9 Serum samples collected and analyzed for ADA pre-dose and on Study Days 8 and 29 
10 Clinical Laboratory Sample Collection: Sample collected on Study Days 1-4 are to be processed locally.  INR/PTT is required prior to the Day 1 lumbar 
puncture procedure with repeat INR/PTT tests on subsequent Study Days at the direction of the Principal Investigator.   
11 Infectious disease testing at Screening and Visit 5 (Study Day 29/ET) will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, hepatitis C antibody. 
12 Urine Pregnancy Test will be performed locally on site for women of childbearing potential. 
13 Adverse Events are only collected upon the start of study drug.  Events occurring prior to this are to be reported as part of the subject medical history.  
However, SAEs are to be collected from the time of informed consent. 

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Table 6: 
Part 2 Schedule of Events (Study RNX-AX204-101)1 
Study Phase 
Screening 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
-84 
through 
-1 
1 
8 
(±3 
days) 
21 
 
42 
 
63 
84 
 
104 
 
137 
Month 5 
169 
Month 6 
253/ET2 
Month 9 
Visit Number 
1 
2 
 
3 
4 
5 
6 
7 
 
8 
9 
Informed consents (Main & Biobank) 
X 
 
 
Register Subject/Contact EDC/Assign Subject ID  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
Instructions for potential washout period for concomitant 
medications and for alcohol use 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical/Disease History 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
MRI2  
X 
 
 
 
 
 
 
 
 
 
 
Telephone call3 
 
 
X 
 
 
 
 
 
X 
 
 
Full Physical Examination & Ht/Wt 
X 
 
 
 
 
 
 
 
 
 
X 
Physical Examination (abbreviated) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
 
Vital Signs (BP, pulse, RR or Pulse Ox, oral temp)4 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
ECG5 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
ISNCSCI assessment including AIS  
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
GRASSP6  
X 
X 
 
X 
X 
X 
X 
SCIM III self-care and mobility subscores 
 
X 
 
 
 
X 
 
X 
 
X 
X 
Modified Ashworth Scale 
 
X 
 
 
 
 
 
 
 
X 
X 
Brief Pain Inventory 
 
X 
 
 
 
 
 
 
 
X 
X 
Neuro-QOL v1.0 – Upper Extremity Function (Fine Motor, ADL)  
 
X 
 
 
 
 
 
 
 
X 
X 
SF-36 v2 Health Survey  
 
X 
 
 
 
 
 
 
 
X 
X 
CUE-Q 
 
X 
 
 
 
 
 
 
 
X 
X 
PGIC Chronic SCI 
 
X 
 
 
 
 
 
 
 
X 
X 
ISAFSCI 
X 
 
 
X 
X 
CSF collection (pre-dose if dosing visit)7 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
Clinical laboratory sample collection (CSF) 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
Dosing of Investigational Product 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Investigational Product Accountability 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Serum collection for PK (pre-dose & 4 h post-dose if dosing visit) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Serum collection for ADA (pre-dose if dosing visit) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Clinical laboratory sample collection8 
X 
X 
 
X 
X 
X 
X 
X 
Viral Serology9 
X 
 
 
X 
X 
Serum pregnancy, chorionic gonadotropin  
X 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test10 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 

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Study Phase 
Screening 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
-84 
through 
-1 
1 
8 
(±3 
days) 
21 
 
42 
 
63 
84 
 
104 
 
137 
Month 5 
169 
Month 6 
253/ET2 
Month 9 
Visit Number 
1 
2 
 
3 
4 
5 
6 
7 
 
8 
9 
Urine sample for drug screen11 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis  
X 
X 
 
X 
X 
X 
X 
X 
Prior and Concomitant Medications 
Prior 
Concomitant (On-going) 
Post-Trt 
Adverse Events12 
 
Treatment-Emergent (On-going) 
Post-Trt 
Serious Adverse Events 
Pre-Trt 
Treatment-Emergent (On-going) 
Post-Trt 
 
1 Abbreviations:  ADA = anti-drug antibody, AE = adverse events, ECG = electrocardiogram, EDC = electronic data capture. ET = early termination.  ID = 
identification, PK = pharmacokinetic, SAE = serious adverse event 
2 MRIs will be run locally and findings read by a sponsor-arranged expert prior to subject enrollment into the study. 
3 Telephone call to inquire about any AEs and determine if subject should come to clinic for evaluation. 
4 Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) will be measured after the patient has been in a sitting or 
recumbent position for 5 minutes.  Vitals will be taken pre-dose, post dose, then every 2 hours until subject leaves the unit 
5 ECGs will be taken in triplicate, 5 minutes apart, and will be obtained after the patient has been in a supine (resting) position for at least 5 minutes. ECGs are 
taken pre-dose at visits where study drug is administered.  ECGs will be read locally. 
6 GRASSP prehension ability and prehension performance testing will be video recorded. 
7 Remove aliquot for CSF labs before processing CSF for pharmacokinetics/biomarkers and biobank samples. 
8 Clinical Laboratory Sample Collection: INR/PTT is required prior to the Day 1 lumbar puncture procedure with repeat INR/PTT tests on subsequent Study 
Days only if directed by the Principal Investigator.  Screening labs must be completed within 28 days of enrollment. 
9 Infectious disease testing at Screening, Visit 8 (Month 6) and Visit 9 (Month 9) will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, hepatitis C 
antibody. 
10 Urine Pregnancy Test will be performed locally on site for women of childbearing potential. 
11 Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, marijuana, opiates, phencyclidine, barbiturates, 
benzodiazepines, methadone, and propoxyphene).   
12 Adverse Events are only collected upon the start of study drug.  Events occurring prior to this are to be reported as part of the subject medical history.  
However, SAEs are to be collected from the time of informed consent. 

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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................4 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............24 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................31 
4. 
INVESTIGATORS AND STUDY PERSONNEL .....................................................33 
5. 
INTRODUCTION ......................................................................................................34 
5.1. 
AXER-204, a Human NoGo Trap Fusion Protein ......................................................34 
5.2. 
Nonclinical Summary .................................................................................................36 
5.3. 
Clinical Experience with AXER-204 and Lumbar Puncture ......................................36 
5.4. 
Rationale for Dose Selection ......................................................................................37 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................39 
6.1. 
Part 1 Single Ascending Dose ....................................................................................39 
6.1.1. 
Primary Objective .......................................................................................................39 
6.2. 
Part 2 Placebo-Controlled Repeat Dose .....................................................................39 
6.2.1. 
Primary Objectives .....................................................................................................39 
6.2.2. 
Secondary Objectives .................................................................................................39 
6.2.3. 
Exploratory Objectives ...............................................................................................39 
7. 
INVESTIGATIONAL PLAN .....................................................................................41 
7.1. 
Overall Study Design ..................................................................................................41 
7.1.1. 
Part 1 ...........................................................................................................................41 
7.1.1.1. 
Screening ....................................................................................................................41 
7.1.1.2. 
In-Clinic Treatment Period .........................................................................................42 
7.1.1.3. 
Follow-Up ...................................................................................................................43 
7.1.2. 
Part 2 ...........................................................................................................................43 
7.1.2.1. 
Screening ....................................................................................................................43 
7.1.2.2. 
Treatment Phase ..........................................................................................................44 
7.1.2.3. 
Follow-Up ...................................................................................................................44 
7.2. 
Number of Subjects ....................................................................................................45 
7.3. 
Treatment Assignment ................................................................................................45 
7.3.1. 
Part 1 ...........................................................................................................................45 

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7.3.2. 
Part 2 ...........................................................................................................................45 
7.3.3. 
Dose Escalation Decisions and Data and Safety Monitoring Board (DSMB) 
Dose Escalation in Part 1 ............................................................................................46 
7.3.3.1. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 1) ..........................46 
7.3.3.2. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 2) ..........................46 
7.3.4. 
Data and Safety Monitoring Board .............................................................................47 
7.4. 
Criteria for Study Termination ...................................................................................47 
8. 
STUDY ENTRY CRITERIA .....................................................................................48 
8.1. 
Subject Inclusion Criteria ...........................................................................................48 
8.2. 
Subject Exclusion Criteria ..........................................................................................48 
9. 
WITHDRAWAL OF SUBJECTS ..............................................................................51 
9.1. 
Subject Withdrawal Criteria .......................................................................................51 
10. 
TREATMENT OF SUBJECTS ..................................................................................52 
10.1. 
Description of Study Drug & Placebo ........................................................................52 
10.2. 
Concomitant Medications ...........................................................................................52 
10.3. 
Treatment Compliance ................................................................................................53 
10.4. 
Randomization and Blinding ......................................................................................54 
10.4.1. 
Part 1 ...........................................................................................................................54 
10.4.2. 
Part 2 ...........................................................................................................................54 
11. 
STUDY PROCEDURES ............................................................................................56 
11.1. 
Part 1 ...........................................................................................................................56 
11.1.1. 
Screening Period, Visit 1 (Study Days -84 through -1) ..............................................56 
11.1.2. 
In-Clinic Treatment, Visit 2 (Study Days 1 to 4 [Pre-Dose and Post-Dose]).............58 
11.1.3. 
Post-Treatment Follow-up Phone Calls, Study Days 5, 6, and 7 ...............................59 
11.1.4. 
Post Treatment Follow-up Visits 3 & 4 (Study Days 8 and 15) .................................59 
11.1.5. 
Post Treatment Follow-up Visit 5 (Study Day 29/ET) ...............................................59 
11.2. 
Part 2 ...........................................................................................................................60 
11.2.1. 
Screening Period, Visit 1 (Study Days -84 through -1) ..............................................61 
11.2.2. 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) .............................62 
11.2.3. 
Follow-up on Study Day 137 ......................................................................................65 
11.2.4. 
Follow-up Visits 8 and 9 (Study Days 169 and 253)..................................................65 
12. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............66 
12.1. 
Study Drug ..................................................................................................................66 

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12.2. 
Investigational Product Packaging and Labeling .......................................................66 
12.3. 
Investigational Product Storage ..................................................................................66 
12.4. 
Investigational Product Preparation ............................................................................67 
12.5. 
Investigational Product Management .........................................................................67 
12.6. 
Investigational Product Accountability ......................................................................67 
12.7. 
Investigational Product Handling and Disposal .........................................................67 
13. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS .............................69 
13.1. 
Efficacy .......................................................................................................................69 
13.1.1. 
Part 1 ...........................................................................................................................69 
13.1.2. 
Part 2 ...........................................................................................................................69 
13.2. 
Pharmacokinetics ........................................................................................................70 
13.2.1. 
Serum ..........................................................................................................................73 
13.2.2. 
Cerebrospinal Fluid ....................................................................................................73 
13.2.3. 
Shipment of Pharmacokinetic Samples ......................................................................73 
14. 
ASSESSMENT OF SAFETY .....................................................................................74 
14.1. 
Safety Parameters .......................................................................................................74 
14.1.1. 
Demographic/Medical History ...................................................................................74 
14.1.2. 
Vital Signs ..................................................................................................................74 
14.1.3. 
Physical Examination .................................................................................................75 
14.1.4. 
Electrocardiogram (ECG) ...........................................................................................75 
14.1.5. 
Laboratory Assessments .............................................................................................75 
14.1.5.1. 
Other Laboratory Tests ...............................................................................................77 
14.1.5.2. 
Virus Serology ............................................................................................................77 
14.1.5.3. 
Drug Screen ................................................................................................................77 
14.2. 
Adverse and Serious Adverse Events .........................................................................77 
14.2.1. 
Definition of Adverse Events .....................................................................................77 
14.2.2. 
Abnormal Test Findings .............................................................................................78 
14.2.3. 
Adverse Events of Special Interest (AESI) ................................................................78 
14.2.4. 
Serious Adverse Event (SAE) ....................................................................................79 
14.2.4.1. 
Hospitalization ............................................................................................................79 
14.2.5. 
Adverse Event Reporting ............................................................................................80 
14.2.5.1. 
Severity Assessment ...................................................................................................81 
14.2.5.2. 
Causality Assessment .................................................................................................81 

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14.2.5.3. 
Exposure in Utero .......................................................................................................82 
14.2.5.4. 
Reporting Requirements .............................................................................................83 
14.2.5.5. 
Non-Serious Adverse Event Reporting Requirements ...............................................83 
14.2.5.6. 
Sponsor Reporting Requirements to Regulatory Authorities .....................................84 
15. 
STATISTICS ..............................................................................................................85 
15.1. 
Sample Size ................................................................................................................85 
15.2. 
Stages of Analysis .......................................................................................................85 
15.3. 
General Methods .........................................................................................................85 
15.4. 
Handling of Missing Data ...........................................................................................86 
15.5. 
Subgroups ...................................................................................................................86 
15.6. 
Analysis Populations ..................................................................................................86 
15.7. 
Alpha Level Considerations .......................................................................................87 
15.8. 
Subject Disposition and Exposure ..............................................................................87 
15.9. 
Demographics and Baseline Characteristics Analyses ...............................................87 
15.10. 
Efficacy Endpoints ......................................................................................................87 
15.10.1. 
Part 2 Efficacy Endpoints ...........................................................................................87 
15.11. 
Safety Endpoints .........................................................................................................88 
15.12. 
Pharmacokinetic Endpoints ........................................................................................90 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................91 
17. 
ETHICS ......................................................................................................................92 
17.1. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..................92 
17.2. 
Ethical Conduct of the Study ......................................................................................92 
17.3. 
Subject Information and Consent ...............................................................................92 
17.4. 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP .........93 
18. 
DATA HANDLING AND RECORDKEEPING .......................................................94 
18.1. 
Case Report Forms .....................................................................................................94 
18.2. 
Record Retention ........................................................................................................94 
19. 
PUBLICATION POLICY ..........................................................................................95 
19.1. 
Publications by Investigators ......................................................................................95 
20. 
LIST OF REFERENCES (ALPHABETICAL) ..........................................................96 
21. 
INVESTIGATORS AGREEMENT ...........................................................................99 
APPENDIX 1. INTERNATIONAL STANDARDS TO DOCUMENT REMAINING 
AUTONOMIC FUNCTION AFTER SPINAL CORD INJURY (ISAFSCI) ..........100 

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APPENDIX 2. CUE-Q SAMPLE SCALE ...............................................................................101 
APPENDIX 3. ISNCSCI SAMPLE FORM (INCLUDES KEY SECONDARY 
EFFICACY SCORE) ................................................................................................105 
APPENDIX 4. GRASSP SAMPLE FORM ..............................................................................107 
APPENDIX 5. MODIFIED ASHWORTH SCALE SAMPLE ................................................109 
APPENDIX 6. SF-36 V2 HEALTH SURVEY ........................................................................112 
APPENDIX 7. NEURO-QOL UPPER EXTREMITY FUNCTION SAMPLE .......................118 
APPENDIX 8. SPINAL CORD INDEPENDENCE MEASURE SAMPLE ............................120 
APPENDIX 9. BRIEF PAIN INVENTORY SAMPLE ...........................................................122 
APPENDIX 10. PATIENT’S GLOBAL IMPRESSION OF CHANGE ..................................124 
APPENDIX 11. AXER-204 AND PLACEBO DOSE ADMINISTRATION 
PROCEDURE...........................................................................................................125 
APPENDIX 12. MAGNETIC RESONANCE IMAGING (MRI) PROCEDURES .................129 
 

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LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................2 
Table 2: 
Treatment by Cohort - Part 1 (Study RNX-AX204-101) .............................................7 
Table 3: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................14 
Table 4: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................15 
Table 5: 
Part 1 Schedule of Events (Study RNX-AX204-101) ................................................20 
Table 6: 
Part 2 Schedule of Events (Study RNX-AX204-101) ................................................22 
Table 7: 
Abbreviations and Specialist Terms (Study RNX-AX204-101) ................................31 
Table 8: 
Treatment by Cohort (Part 1, Study RNX-AX204-101) ............................................42 
Table 9: 
Study Drug and Placebo (Study RNX-AX204-101) ..................................................52 
Table 10: Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................72 
Table 11: Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................72 
Table 12: Laboratory Parameters to be Assessed (Study RNX-AX204-101) ............................76 
Table 13: Moderate and Marked Liver Function Abnormality Thresholds (Study RNX-
AX204-101) ................................................................................................................76 
Table 14: Relatedness Definitions (Study RNX-AX204-101) ...................................................81 
 

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LIST OF FIGURES 
Figure 1: 
Key Components Regulating Axonal Growth in the Adult Mammalian 
Central Nervous System .............................................................................................34 
Figure 2: 
Putative Mechanism of AXER-204 ............................................................................35 
 
  

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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 7: 
Abbreviations and Specialist Terms (Study RNX-AX204-101) 
Abbreviation or Specialist 
Term 
Explanation 
ADA 
Anti-drug antibodies 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse events of special interest 
AIS 
American Spinal Injury Association Impairment Scale 
ANCOVA 
Analysis of Covariance 
BMI 
Body mass index 
BPI 
Brief Pain Inventory 
BUN 
Blood urea nitrogen 
CMH 
Cochran-Mantel-Haenszel 
CNS 
Central nervous system 
CRO 
Contract research organization 
CSCI 
Chronic Spinal Cord Injury 
CSF 
Cerebrospinal fluid 
CTCAE 
Common Terminology Criteria for Adverse Events 
CUE-Q 
Capabilities of Upper Extremity – Questionnaire  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated Glomerular Filtration Rate 
ER 
Emergency room 
ET 
Early termination 
FAS 
Full analysis set population 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GRASSP 
Graded Redefined Assessment of Strength, Sensation and Prehension 
HED 
Human equivalent dose 
HIV 
Human immunodeficiency virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
DSMB 
Data and Safety Monitoring Board 

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Abbreviation or Specialist 
Term 
Explanation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Integrated response technology 
ISAFSCI 
International Standards to document remaining Autonomic Function after 
Spinal Cord Injury 
ISNCSCI 
International Standards for Neurological Classification of SCI 
LP 
Lumbar Puncture 
LSMean 
Least Square Means 
MEP 
Motor Invoked Potentials 
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum Tolerated Dose 
NOAEL 
No Observed Adverse Effect Level 
NOEL 
No Observed Effect Level 
OAE 
Other significant adverse event 
PACU 
Post-Anesthesia Care Unit 
PGIC 
Patient’s Global Impression of Change 
PI 
Principal Investigator   
PK 
Pharmacokinetics 
PRN 
Pro re nata (as needed) 
QoL 
Quality of Life 
QTcF 
QT interval using Fridericia Correction Formula 
SAE 
Serious adverse event 
SCIM III 
Version III of the Spinal Cord Independence Measure 
SF-36 
 Short Form - 36 v2 Health Survey 
SNRI 
serotonin norepinephrine reuptake inhibitor 
SOC 
system organ class 
SSRI 
selective serotonin reuptake inhibitor 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
UEMS 
upper extremity motor score 
UMC 
Uppsala Monitoring Centre 
US 
United States 
WHO 
World Health Organization 

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4. 
INVESTIGATORS AND STUDY PERSONNEL 
This study will be conducted by qualified investigators under the Sponsorship of ReNetX Bio, 
Inc. (the sponsor) at approximately 5 investigational centers in the United States. 
The contact information for the Medical Monitor along with the telephone numbers of the other 
contact persons for the sponsor are listed in Table 1.  Contact information for 
, the 
designated Contract Research Organization, (CRO), and other vendors are listed in the 
Investigator Site File provided to each site. 

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5. 
INTRODUCTION 
5.1. 
AXER-204, a Human NoGo Trap Fusion Protein 
Mammalian brain and spinal cord networks stabilize during development, such that axonal 
growth in the adult CNS is either non-existent or extremely limited. After adult CNS injury, the 
extracellular factors that maintain axonal stability restrict axonal growth and permit only 
severely limited recovery of function. Adult extracellular axonal growth inhibitors include a 
group of proteins from the oligodendrocyte, Nogo-A, MAG, OMgp, and ephrin-B3, which 
interact with axonal receptors, including NgR1, NgR2, PirB, and EphA4 [Liu 2006, Schwab 
2014].  Extracellular proteoglycans, containing chondroitin sulfates, also inhibit axonal sprouting 
in the adult CNS, particularly near sites of astrogliosis and scar formation [Ohtake 2015, Sharma 
2012].  There is substantial molecular cross talk between ligands and receptors.  The key 
inhibitory ligands Nogo, MAG, and OMgp all bind and activate NgR1 on axons to inhibit axonal 
extension.  Likewise, PirB (LILRB2) has been found to bind Nogo, MAG, and OMgp and to 
mediate axonal growth inhibition.  Consistent with partially overlapping roles in axonal 
inhibition, simultaneous genetic deletion of Nogo, MAG, and OMgp has greater impact on 
axonal growth and functional recovery following CNS injury than deletion of a single inhibitor 
[Cafferty 2010].  A representation of the role of Nogo, MAG, and OMgp and other key 
regulators of axonal growth in the adult CNS is presented in Figure 1.  
Figure 1: 
Key Components Regulating Axonal Growth in the Adult Mammalian 
Central Nervous System 
 
Targeting one ligand or one receptor in the inhibitory adult CNS pathways has been shown to 
yield some benefit in certain specific pre-clinical spinal cord injury (SCI) models.  Based on 
these observations, anti-Nogo antibodies are entering clinical trials for new (subacute) SCI. In 
distinction, NoGo Trap (AXER-204, Nogo Receptor decoy, hNgR1(310)ecto-Fc Ala Ala) 

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represents a mechanistically superior approach to promoting axonal growth following injury as it 
binds three key inhibitors, Nogo, MAG, and OMgp, and blocks their interaction with 
endogenous NgR1 and other receptors (Figure 2).  Consistent with this mechanism, NoGo Trap 
has been shown in multiple laboratories to promote axonal growth and recovery of function in a 
variety of pre-clinical models of CNS injury including stroke [Lee 2004], dorsal root crush injury 
[Harvey 2009], acute transection SCI [Li 2004], and acute/sub-acute contusion SCI [Ji 2006, 
Wang 2006, Wang 2014].  Most critically, NoGo Trap supports axonal growth and functional 
recovery in chronic contusion SCI [Wang 2011], while no other blocker of extrinsic signals has 
reported efficacy in this setting.  Recent pre-clinical studies have shown that intrathecal lumbar 
administration results in broad CNS distribution in rat and non-human primate and that 
intermittent intrathecal bolus injection of the protein provides equivalent restoration of function 
in rat contusion SCI in comparison to previously obtained results employing continuous infusion 
[Wang 2014].  AXER-204 promotes corticospinal axon growth and the use of the impaired 
forelimb during spontaneous feeding and the impaired hindlimb during locomotion non-human 
primates with cervical hemisection SCI [Wang 2020]. 
Figure 2: 
Putative Mechanism of AXER-204 
 
 
The present clinical evaluation of AXER-204 is being conducted in subjects with chronic SCI.  
This plan is based on the enhanced feasibility for detecting treatment-related functional 
improvements in subjects with otherwise stable deficits [Fawcett 2007, NSCISC 2018].  The 

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substantially larger chronic SCI patient population compared to acute SCI cases should facilitate 
enrollment of this study and has the potential to translate into benefit for many more individuals. 
5.2. 
Nonclinical Summary 
Nonclinical data are summarized for AXER-204.  In addition, data from nonclinical studies with 
various surrogate proteins, primarily a rat form of the NoGo Trap protein, are included.  AXER-
204 binds to the myelin associated ligands Nogo (measured using Nogo-66 fragment), MAG, 
and OMgp in ELISA format in vitro.  Likewise, binding to MAG and OMgp has been measured 
using a Fluorescence Resonance Energy Transfer (FRET) assay.  Consistent with the binding 
profile, AXER-204 prevents Nogo-22 mediated inhibition of cultured axon growth.  AXER-204 
promotes functional recovery following contusion spinal cord injury in rat with either continuous 
infusion into the cerebrospinal fluid (CSF) via intracerebroventricular cannula or intermitted 
bolus intrathecal administration.  Moreover, the intermittent intrathecal treatment increased the 
growth of raphespinal axons after injury.  
A number of additional evaluations in spinal cord injury models were conducted using the rat 
form of the protein.  Overall, the pharmacological effects include functional recovery and 
enhanced axon growth.  Of particular importance, NoGo Trap was found to enhance functional 
recovery in chronic contusion injury in rat – supporting evaluation in chronic SCI.  In 
pharmacokinetics studies, AXER-204 distributed broadly in the CSF, spinal cord tissue, and 
brain tissue following intrathecal administration.  Tissue half-life was prolonged over the half-
life in CSF.  Daily intrathecal bolus infusions of AXER-204 in non-GLP 14-day range finder 
toxicology studies in rat and monkey did not identify adverse effects from test article (No 
observed adverse effect level [NOAEL] was maximum feasible dose volume for each study). 
CSF and serum exposure were confirmed in each study.  Similarly, no test article-related toxicity 
was observed in GLP toxicology studies with administration of AXER-204 by intrathecal bolus 
infusions every other day in rat for two months and in monkey for up to 108 days. Accordingly, 
the no observed effect level (NOEL) for rat and monkey was equivalent to the maximum feasible 
dose.  Toxicology studies employed frequent bolus infusions in order to maximize the 
cumulative dose evaluated.  
Off-target effects such as toxicity due to systemic exposure are not anticipated with AXER-204 
because the requisite ligands Nogo, MAG, and OMgp are mostly localized in the CNS and 
AXER-204 exposure is predominantly localized to the CNS following intrathecal administration 
in animal studies.  Nonetheless, a one-month GLP rat toxicology study employing intravenous 
dosing was completed and the maximum dose tested was found to be equivalent to the NOAEL. 
Please refer to the AXER-204 Investigator’s Brochure for a more detailed description of 
toxicology investigations. 
5.3. 
Clinical Experience with AXER-204 and Lumbar Puncture 
The present study represents the first evaluation of AXER-204 in humans.   
There is extensive published clinical experience with lumbar puncture (LP) procedures 
representative of those required for administration of AXER-204.  The most common adverse 
events (AEs) associated with LP consist of post-LP back pain and post-LP headache. This 
protocol includes procedures designed to minimize the incidence and severity of AEs associated 

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with LP including optimal choice of spinal needle, removal of an equivalent volume of CSF 
relative to the volume of investigational product injected, and a controlled rate of slow bolus 
injection of investigational product. 
5.4. 
Rationale for Dose Selection 
In Part 1, the initial dose escalation sequence for the study is 3, 30, 90, and 200 mg. The starting 
dose 3 mg was selected to be 30-fold below the estimated human pharmacologically active dose 
of 90 mg.  Adjusting for cross-species scaling by CSF volume, toxicology studies did not 
identify AXER-204 related toxicity when given at equivalent (monkey) or at three-fold higher 
(rat) doses vs. the maximum planned human dose when given every other day by slow bolus 
intrathecal administration for up to 57 days in rat and 108 days in monkey.  Similarly, adjusting 
for cross-species scaling by CSF volume and accounting for the more frequent dosing in the GLP 
toxicology studies, the cumulative doses given in rat and monkey toxicology exceeded the 
maximum feasible human dose by at least 21-fold and 8-fold respectively.  The maximum doses 
in toxicology were the maximum feasible doses based on the tolerable volumes for intrathecal 
administration.  The 3 and 30 mg doses will be diluted from the formulation to provide a 
constant injection volume of 10 mL.  The 90 mg and 200 mg doses will be given without dilution 
resulting in dosing volumes of 9 mL and 20 mL respectively.  The dose volumes were selected 
based on published studies and drug label information for other therapeutics describing safety 
and drug distribution following intrathecal administration. 
A conservative approach was applied in deriving the starting dose in Part 1 in order to enhance 
safety.  For drugs delivered intrathecally, published FDA guidance suggests scaling based on 
compartment volumes and concentrations of the therapeutic [Guidance for Industry, FDA].  
Using compartment volumes, the pharmacologic human equivalent dose (HED) is calculated by 
dividing the rat effective dose by rat CSF volume and multiplying by the CSF volume for 
human. This yields an estimated pharmacologic HED of 90 mg.  The starting dose of 3 mg is 
anticipated to be free of detectable pharmacological effects using the method outlined in the 
Draft Guidance for Industry and Reviewers of November 2005 entitled “Estimating the 
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult healthy 
Volunteers” and incorporates a safety factor of 30 compared to the estimated human 
Pharmacologically Active Dose of 90 mg.  The maximum dose volume of 20 mL represents 
approximately 10-15% of total average CSF volume for adults and roughly 30% of spinal CSF 
volume [Kroin 1992, Thorne 2001, Sakka 2011].  The dose will be introduced immediately 
following collection of an equivalent volume of CSF and at a controlled constant rate of 100 
mL/h (12 min for 20 mL).  The bolus injection rate selected is five times the average time 
required to regenerate the CSF collected (20 mL/h) [Hladky 2014].  The time required to 
regenerate CSF collected by lumbar puncture has been found to approximately equal the time 
needed to normalize CSF pressure [Brinker 2014, Masserman 1934].  Thus, the sequence of CSF 
collection followed by controlled bolus infusion of an equivalent volume of investigational 
product is designed to reduce the impact on CSF pressure and flow.  The controlled bolus 
injection rate selected is slower than the rate of injection specified for several marketed products 
administered intrathecally including:  Omnipaque 10-17 mL injected over 1-2 min, a small 
amount of CSF may be removed prior to injection [OMNIPLAQUE Package Insert]; 
Methotrexate, usually 2-6 mL (up to 10 mL) injected over 1-3 min following removal of an 
equivalent volume of CSF; Spinraza 5 mL injected in children over 1-3 min after removal of 5 

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mL CSF [SPINRAZA Package Insert].  Published results indicate that volumes ranging from 10-
30 mL of CSF can be administered in humans without adverse effects beyond occasional mild 
headache provided an equivalent volume of CSF is first removed [Papisov 2013, Rieselbach 
1962a, Rieselbach 1962b, Rieselbach 1963].  The conservative controlled injection rate of 
AXER-204 following collection of an equivalent volume of CSF is designed to reduce the 
potential for adverse effects arising from disruption of CSF pressure and flow.   
Distribution following bolus intrathecal administration is reported to depend strongly on 
injection volume, with smaller volumes favoring less rapid distribution.  Rapid broad distribution 
to the cisterna magna is reported following bolus intrathecal lumbar administration provided a 
volume over 10% of total CSF is given [Papisov 2013, Rieselbach 1962a].  Estimates of total 
subarachnoid CSF volume in adults generally range between 90-170 mL and 150 mL is 
commonly taken as the volume for dose modeling [Brinker 2014, Kuttler 2010].  Thus, the range 
of AXER-204 dose volumes of 9-20 mL are selected to facilitate rapid and broad distribution 
over the length of the cord.  
To ensure subject safety, dose selection for Part 2 of the study will be based on safety, 
tolerability, and pharmacokinetics data generated in Part 1 and the DSMB will review and 
approve dosing frequency and level before recommending starting Part 2.  The maximum safe 
dose identified in Part 1 will be selected for repeated administration in Part 2.  The frequency of 
dosing in Part 2 will be determined based on analysis of pharmacokinetic data.  In addition, 
biomarkers of target engagement and mechanism engagement are under development with the 
objective of implementing these assays to aid in guiding dose frequency in Part 2.  The dosing 
will be no more frequent than once every two weeks or as long as once every 4 weeks for Part 2. 
As described for Part 1, repeat-dose toxicology studies with much more frequent administration 
in rat and cynomolgus monkey did not identify AXER-204 toxicity. 

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6. 
TRIAL OBJECTIVES AND PURPOSE 
Study RNX-AX204-101 is a two-part (Parts 1 and 2) study that will be run sequentially.  Part 1 
is considered a Phase 1b study, while Part 2 is considered a Phase 2a study.  Each part has 
unique objectives. 
6.1. 
Part 1 Single Ascending Dose 
6.1.1. 
Primary Objective 
To evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending, single intrathecal 
lumbar slow bolus infusions of AXER-204 in subjects with chronic spinal cord injury (CSCI). 
6.2. 
Part 2 Placebo-Controlled Repeat Dose 
6.2.1. 
Primary Objectives 
1. To evaluate the safety and tolerability of repeat intrathecal lumbar slow bolus infusions 
of AXER-204 compared to placebo in subjects with CSCI.  
2. To evaluate the pharmacokinetics of repeat doses of AXER-204 in subjects with CSCI 
6.2.2. 
Secondary Objectives 
To assess the efficacy of repeat dose therapy of AXER-204 compared to placebo on functional 
and activities of daily living (ADL) measures as assessed by: 
• International Standards for Neurological Classification of SCI (ISNCSCI) Upper 
Extremity Motor Score (UEMS) 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance 
• Version III of the Spinal Cord Independence Measure (SCIM III) self-care  
6.2.3. 
Exploratory Objectives 
In Part 2, the efficacy of repeat dose therapy of AXER-204 compared to placebo as assessed by 
the following:  
• ISNCSCI lower extremity motor and sensory scores  
• GRASSP strength, sensation and prehension ability scores 
• SCIM III mobility scores 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 

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− SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 
will provide data on the subjects' perceived health and well-being over the course 
of the study.   
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
PGIC – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed.  

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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
Study RNX-AX204-101 is a two-part study that will be run sequentially, with Part 2 planned to 
start after Part 1 has completed. Each Part will be conducted at approximately 5 centers in the 
United States.   
For each Part, eligible subjects will be ages 18 to 65 years inclusive, male or female, with a 
traumatic spinal cord injury that occurred at least 1 year prior to the screening date.  Subjects 
must have significant neurological impairment of the hands and arms.  Subjects who participated 
in Part 1 may be evaluated for enrollment in Part 2 provided at least 6 months will have elapsed 
between the dose received in Part 1 and the initiation of dosing in Part 2.   
7.1.1. 
Part 1 
Part 1 is a multicenter, open-label, single ascending dose study in subjects with chronic spinal 
cord injury.  Four cohorts of 6 subjects each are planned, with subjects within each cohort 
expected to receive the same dose of study drug.  Thus, up to 24 subjects will be enrolled in Part 
1, and all will receive AXER-204.  
If the Maximum Tolerated Dose (MTD) is reached prior to the fourth cohort, the sponsor may 
enroll the remaining subjects (up to a total enrollment of 24 for the study) to obtain further data 
at the tolerated dose levels.  The sponsor in conjunction with the investigators and medical 
monitor will determine dose escalation according to the methods described in Section 7.3.3. 
Study drug will be administered sequentially, with at least 3 days between subjects being dosed 
within each cohort (following 72-hour safety assessment review by the sponsor in conjunction 
with the investigators and medical monitor for each prior subject). 
The study stages for Part 1 are: 
• Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, 
their washout period for prohibited concomitant medications. The screening 
laboratory tests must be completed within 28 days prior to Day 1. 
• Treatment period:  Check-in Day 1, administration of study drug, 3-night in-clinic 
stay, and discharge on Day 4 following the completion of all scheduled procedures.  
• Follow-up: Subjects will have follow-up visits for up to 29 days post-dose as follows: 
subjects will receive a phone call on Study Days 5, 6, and 7 to inquire about their 
general health and will return to the clinic for visits on Study Day 8 (± 1 day), Study 
Day 15 (±3 days) and Study Day 29 or Early Termination (± 4 days).  See Table 5 for 
the Schedule of Events for Part 1. 
7.1.1.1. 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI 
to determine spinal cord structure and intrathecal space (Appendix 12); MRIs will be run locally 
and evaluated by a sponsor-arranged expert.  Additional radiological assessments may be 

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performed at the discretion of the Principal Investigator, including CT or MRI of the head and X-
ray of the lumbar spine as additional evaluations to rule out potential contraindications for 
lumbar puncture. The subject’s demographics, medical and surgical history, and prior and 
concomitant medications will be recorded.  Screening/baseline assessments will be performed, 
and subjects will undergo blood draws where blood, serum collection, viral serology will be 
obtained, and urine samples will be collected.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
to participate in this main study.   
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the 
images may be used for the rescreening provided the MRI was completed within 6 months of 
rescreening.  Similarly, neurological examinations and questionnaires do not need to be repeated 
provided the rescreening occurs within 84 days of the time of data collection. 
7.1.1.2. 
In-Clinic Treatment Period 
Eligible subjects will be admitted to the clinic on the evening prior to or on the day of dosing 
(Study Day 1) dependent on clinical site requirements.  Following final pre-treatment 
assessments, subjects will undergo a lumbar puncture (LP) and receive their single dose of study 
drug administered via intrathecal lumbar slow bolus infusion by the Principal Investigator or a 
trained and licensed designee.  Dosing will be according to Table 8.  
Subjects will remain in-clinic until discharge on Study Day 4 and will undergo daily safety 
assessments and observation.  
Blood and CSF samples will be obtained.  The timing for serum and CSF sample collection may 
be adjusted for subsequent cohorts based on PK data from the preceding cohorts. In addition to 
undergoing PK analysis, serum samples obtained from blood collected at pre-dose and on Study 
Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
 
Table 8: 
Treatment by Cohort (Part 1, Study RNX-AX204-101) 
Cohort 
Treatment 
Number of Subjects 
1 
3 mg AXER-204 
6 
2 
30 mg AXER-204 
6 

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3 
90 mg AXER-204 
6 
4 
200 mg AXER204 
6 
7.1.1.3. 
Follow-Up 
Sites will contact the subjects via telephone on Study Days 5, 6, and 7 to inquire as to their 
general health status.   
Subjects will return to the Clinic on Study Day 8 (±1d), for CSF and serum PK assessments, on 
Day 15 (±3d) for blood collection (serum PK analysis), and again on Study Day 29 (±4d) (for 
end of study assessments).  Vital signs, concomitant medications, AEs, and general health status 
will be assessed at each visit. 
7.1.2. 
Part 2 
Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in CSCI 
subjects.  Approximately 32 subjects will be randomized (ratio 1:1) to receive AXER-204 or 
placebo (an isotonic phosphate buffered saline formulation).  Subject to review of the safety, 
tolerability, and pharmacokinetic data from Part 1 and DSMB approval, the dose will be 200 mg 
given once every 3 weeks for 15 weeks as outlined in the schedule of events.  Subject to DSMB 
approval, the dose may be reduced to 90 mg and the dose interval may be modified based on data 
from Part 1 but is not expected to be less than once every 14 days or more than 28 days.  Subject 
to DSMB approval, the dose and dose frequency may also be adjusted during Part 2 based on 
emergent safety and tolerability data. 
The study stages for Part 2 are: 
• Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessment and, if needed, their 
washout period for prohibited concomitant medications.  The screening laboratory 
tests must be completed within 28 days prior to Day 1. 
• Treatment Period (15 weeks). Study treatment given every 2-4 weeks for 15 weeks in 
total per subject.   
• Follow-up (21 weeks).  Following the last Treatment Period dose of investigational 
product or Early Termination of dosing, a telephone call to assess status regarding 
any adverse events will be conducted on Study Day 137 (± 7 days) and follow-up 
visits will occur at Study Days 169 (± 7 days) and 253 (± 7 days). 
See Table 6 for the Schedule of Events for Part 2. 
7.1.2.1. 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI 
to determine spinal cord structure and intrathecal space; MRIs will be run locally and evaluated 
by a sponsor-arranged expert.  Additional radiological assessments may be performed at the 
discretion of the Principal Investigator, including CT or MRI of the head and X-ray of the 
lumbar spine as additional evaluations to rule out potential contraindications for lumbar 

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puncture. The subject’s demographics, medical and surgical history, and prior and concomitant 
medications will be recorded.  Screening assessments will be performed, and subjects will 
undergo blood draws where blood, serum collection, viral serology will be obtained, and urine 
samples will be collected.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
to participate in this main study.   
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the 
images may be used for the rescreening provided the MRI was completed within 6 months of 
rescreening.  Similarly, the ISNCSCI and GRASSP do not need to be repeated provided the 
rescreening occurs with 84 days of the time of data collection. 
7.1.2.2. 
Treatment Phase 
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will 
be stratified based on pre-treatment AIS grade (AIS A,B vs. AIS C,D) and prior receipt of study 
drug in Part 1 (Received AXER-204 in Part 1 vs. Did not receive AXER-204 in Part 1). 
Subjects will undergo baseline assessments and receive their assigned (double-blind) treatment 
on Study Day 1.  Study personnel will conduct telephone call with subjects on Study Day 8 (± 3 
days) to assess status regarding any adverse events.  Subjects will then return to the Clinic on 
Day 21 (± 5 days) for safety, efficacy, and PK assessments and their second dose of study 
investigational product.  Thereafter, subjects will return approximately every 21 days, at Study 
Days 42 (± 5 days) (third dose), 63 (± 5 days) (fourth dose), 84 (± 5 days) (fifth dose), 104 (± 5 
days) (sixth dose), for safety, efficacy, and PK assessments (pre-dose) and investigational 
product administration.   
Cerebrospinal fluid samples will be collected pre-dose at each treatment (dosing) visit, including 
Study Day 1, during a single LP procedure for collecting and dosing.  Serum for PK and 
immunogenicity (ADA) testing will be collected pre-dose at specified visits (See Table 11), 
within 4 hours prior to investigational product administration.  Serum will also be collected for 
PK at 4 h post-dose at specified visits. 
7.1.2.3. 
Follow-Up 
Study personnel will conduct telephone call with subjects on Study Day 137 (± 7 days) to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come 

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to the clinic for evaluation. Subjects will return at Study Days 169 (± 7 days), and 253 (± 7 days) 
for safety and efficacy assessments.   
7.2. 
Number of Subjects 
Part 1 will enroll up to 24 subjects in cohorts of 6 subjects each.  
Part 2 will enroll approximately 32 subjects, randomized in a 1:1 ratio (and thus approximately 
16 subjects per arm) to repeated doses of AXER-204 or of matching placebo.   
If the dropout rate is such that the power of the study could be compromised, or that the study 
objectives cannot reliably be achieved, the Sponsor may elect to replace those subjects who 
discontinue prematurely, provided discontinuation is not due to adverse events related to 
investigational product administration. 
7.3. 
Treatment Assignment 
7.3.1. 
Part 1 
Dosage will be by cohort, with 4 sequentially-treated cohorts planned.  Intrathecal doses of 
AXER-204 below 90 mg will be diluted and delivered as a solution in 10 mL of isotonic 
phosphate buffered saline.  Both the 90 mg dose and 200 mg dose will be dosed with the current 
study drug concentration.  All administration will be given following a removal of an equivalent 
volume of CSF. Intrathecal injections will be given at a rate of 100 mL/hr using a medically 
approved syringe pump (eg, 12 minutes to administer 20 mL) to avoid significant disruption of 
natural CSF flow and pressure.   
The starting dose of 3 mg is estimated to be below the pharmacologically active dose.  Dose 
escalation will proceed to 30 mg, 90 mg, 200 mg contingent on safety, tolerability, and available 
PK.  Thus, dosing volumes will be given as follows: 
• Cohort 1:  3 mg, 10 mL 
• Cohort 2:  30 mg, 10 mL 
• Cohort 3:  90 mg, 9 mL 
• Cohort 4:  200 mg, 20 mL 
7.3.2. 
Part 2 
Subject to review of the safety, tolerability, and pharmacokinetic data from Part 1 and DSMB 
approval, the dose will be 200 mg given once every 3 weeks for 15 weeks as outlined in the 
schedule of events.  Subject to DSMB approval, the dose may be reduced to 90 mg and the dose 
interval may be modified based on data from Part 1 but is not expected to be less than once every 
14 days or more than 28 days.  Subject to DSMB approval, the dose and dose frequency may 
also be adjusted during Part 2 based on emergent safety and tolerability data. 
The maximum volume of injection by intrathecal lumbar slow bolus injection is limited in this 
study to approximately 20 mL based on published tolerance data from studies with other agents 
employing the same route of administration.  If an injection volume of 20 mL, corresponding to a 
200 mg dose of AXER-204, is reached in Part 1 dose escalation portion of the study with 

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acceptable safety and tolerance, the 200 mg dose will be designated as the dose for Part 2 at the 
discretion of the Sponsor in conjunction with the investigators, DSMB, and medical monitor.   
7.3.3. 
Dose Escalation Decisions and Data and Safety Monitoring Board (DSMB) Dose 
Escalation in Part 1 
Dose escalation decisions will be made jointly by the investigator, sponsor, and medical monitor.  
The investigator, sponsor, and medical monitor may also make adjustments to the dosing plan, as 
appropriate for reasons of safety and tolerability.  Dose escalation (for each sequential cohort) 
will not occur until 6 subjects in the prior cohort have completed the initial 3 day in-clinic period 
AND at least two subjects have completed their Day 29 post-dose follow-up visit.  
Determination of whether to escalate dose in the subsequent cohort will be made jointly by the 
investigators, sponsor, and medical monitor after review of all clinical and available PK data.  
Review will include AEs and serious AEs (SAEs), and specifically the following potential 
stopping criteria will be evaluated prior to each dose escalation. 
7.3.3.1. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 1) 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing 
or stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and 
medical monitor in conjunction with the sponsor, need further characterization with respect to 
progression and reversibility before further dosing is conducted.  Such adverse events may 
include non-serious unusual events.  If dosing is stopped, review of the data by the investigators 
and medical monitor in conjunction with the sponsor and the DSMB must occur before dosing 
can be resumed.  Dosing will only be resumed with DSMB approval. 
Pharmacokinetic and anti-drug antibody test results will not be required for dose escalation 
unless it is determined advisable by the sponsor in conjunction with the investigators and 
medical monitor based on emergent data from the study.  CSF and serum samples will be 
analyzed for each cohort immediately after all subjects have been dosed.  The sponsor may direct 
earlier analysis of a partially completed cohort if completion of the cohort is delayed or partial 
cohort data is desired to aid in interpretation of any emergent clinical data.   
If the investigators and medical monitor in conjunction with the sponsor determine that the dose 
is well tolerated in the completed dose group, dosing will proceed to the next dose level.   
7.3.3.2. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 2) 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing 
or stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and 
medical monitor in conjunction with the sponsor, need further characterization with respect to 
progression and reversibility before further dosing is conducted.  Such adverse events may 
include non-serious unusual events.  If dosing is stopped, review of the data by the sponsor in 
conjunction with the investigators and medical monitor in conjunction with the sponsor and the 
Data and Safety Monitoring Board (see below regarding DSMB composition and charter) must 
occur before dosing can be resumed.  Dosing will only be resumed with DSMB approval. 

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7.3.4. 
Data and Safety Monitoring Board 
In order to ensure the utmost safety of subjects, the sponsor will also use a Data and Safety 
Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed 
from the DSMB will be required in order for the study to continue (i.e. to resume if stopped or 
ongoing study will be stopped if DSMB does not recommend proceeding).  The DSMB will 
review the safety and tolerability data from Part 1 before recommending starting Part 2 and 
during Part 2 after the first subject has completed 3 months of dosing and approximately every 3 
months thereafter while dosing continues in the study (allowing for potential scheduling 
logistics). In addition to the pre-determined DSMB data review meetings, the DSMB may be 
engaged at any time at the request of an investigator, the sponsor, or medical monitor, or if 
stopping rules are triggered. A charter will be written to describe the DSMB’s objectives, its 
membership, schedule for data reviews, and general responsibilities in respect to the study.  All 
DSMB decisions will be documented in writing, and where required, submitted to the 
institutional review board (IRB) for their review or information.   
7.4. 
Criteria for Study Termination 
If the dosing is stopped during the study due to safety and tolerability concerns, a 
recommendation from the DSMB that it is safe to resume dosing will be required in order to 
continue dosing. 
All decisions will be documented in writing, and where required, submitted to the institutional 
review board/independent ethics committee (IRB/IEC) for their review or information.   

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8. 
STUDY ENTRY CRITERIA 
8.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Men or women between the ages of 18 and 65 years, inclusive  
2. Traumatic spinal cord injury that occurred ≥ 1 year ago  
3. Cervical spinal cord injury with serious neurological deficit as evidenced by 1) bilateral 
ISNCSCI UEMS between 4 and 36 points inclusive, and 2) bilateral GRASSP prehension 
ability score between 4 and 17 points inclusive 
4. Confirmation by MRI of the following: 
a. Chronic SCI (persistent spinal cord lesion) 
b. For AIS grade of A without sensory or motor zone of partial preservation 
extending at least two levels caudal to the level of injury, no apparent transection 
of the cord  
c. CSF space spanning the lesion 
5. Read, understood, and provided written informed consent after the nature of the study has 
been fully explained and must be willing to comply with all study requirements and 
procedures. 
8.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including 
gunshot that did not penetrate the spinal cord 
2. Women who are pregnant or lactating, and women of childbearing potential except those 
using adequate birth control measures. All female subjects must have a negative serum 
pregnancy test at Screening and women of childbearing potential must have a negative 
urine pregnancy at the Randomization/Pre-Dose Visit on Study Day 1. All subjects (male 
and female) as well as non-study female partners of male subjects, must use adequate 
birth control measures during the course of the study and for at least 10 weeks after the 
subjects’ last dose of investigational product  
• Adequate or effective contraception is defined as double barrier contraception (eg, 
condom plus spermicide in combination with a female condom, diaphragm, cervical 
cap, contraceptive sponge, implants, injectables, combined oral contraceptives, sexual 
abstinence (total abstinence from sexual intercourse as the preferred lifestyle of the 
subject; periodic abstinence is not acceptable), or sexual intercourse with only a 
vasectomized partner.  Subjects and/or partners who are surgically sterile or women 
with confirmed postmenopausal status are exempt from this requirement.   
3. Contraindications for lumbar puncture 
4. History of stroke, cerebrovascular injury, or elevated intracranial pressure 

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5. Requiring mechanical ventilatory assistance of any type 
6. Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg 
7. Botulinum toxin injection, with the exception of bladder treatments, within 4 months 
prior to study 
8. History of life threatening allergic or immune-mediated reaction to vaccines, or biologic 
drugs, at any time or any life threatening allergic or immune-mediated reaction within the 
past 12 months. 
9. Systemic use of immunosuppressants within the past 2 months with the exception of 
mineralocorticoids 
10. Significant deformities, contractures (with less than 50% of normal range of motion at 
affected joints), or any issues that limit completion of UEMS with the ISNCSCI exam 
11. Recent changes in anti-spasmodic or anti-spasticity medications.  Anti-spasmodic or anti-
spasticity medication is permitted providing that the subject has been on a stable dose for 
at least 12 weeks before the Screening Visit (Visit 1) and agrees to remain on a stable 
dose throughout the course of the study 
12. Any orthopedic injury, recent surgeries, or current diagnosis of any primary diseases 
affecting upper limb function outside of SCI (eg, infection, tumor, congenital 
malformations, Huntington’s disease, Parkinson’s disease) 
13. Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF 
14. Presence of a self-reported uncontrolled medical condition including but not limited to 
cardiovascular disease, sleep apnea, obstructive lung disease, severe neuropathic or 
severe chronic pain, severe autonomic dysreflexia 
15. Participation in any other investigational drug or device trial within 30 days or within 5 
half-lives of the investigational drug or any past participation in a SCI cellular therapy 
trial 
16. Regular use of the following concomitant medications that might confound efficacy 
and/or safety assessments is prohibited, including, but not limited to, the following:  
a. Antipsychotic drugs with the exception of use of these mood stabilizers for the 
adjunctive treatment of depression at least 12 weeks prior to Screening and the dose is 
not anticipated to change during participation in the trial. 
b. Anticoagulants, however, daily low dose aspirin (81 mg) therapy is permitted. 
c. Opiates, sedative hypnotics, or tranquilizers unless used to treat anxiety, pain, or 
sleep disorder and the dosage and frequency of use are not considered likely to 
interfere with evaluation of safety and efficacy endpoints in the trial. Determination 
of exclusion due to use of a specific medication from these classes of medications 
will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, 
frequency of use, and medical condition being treated.   
d. Tumor necrosis factor (TNF) inhibitors 
e. Use of Class 1 antiarrhythmic. 

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17. Use of antidepressants (SSRI, SNRI, TCA, buspirone) is PERMITTED but limited to 
subject being on a stable dose for at least 12 weeks 
18. History of severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that could increase the risk associated with trial participation or 
investigational product administration or could interfere with the interpretation of trial 
results and including but not limited to the following:  
• human immunodeficiency virus (HIV) infection 
• active chronic hepatitis B or hepatitis C infection including hepatitis B surface 
antigen and hepatitis C antigen positive subjects with or without abnormal liver 
enzymes 
• immunosuppressive disease 
• chronic renal disease/failure as evidenced by estimated glomerular filtration rate 
(eGFR) of <60 
• concurrent neurodegenerative disease 
• cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or 
symptomatic congestive heart failure within the past 12 months or serious 
uncontrolled and clinically significant cardiac arrhythmia as determined by the 
investigator 
• dementia or significantly altered mental status including brain injury with ongoing 
cognitive signs and symptoms that would prohibit the understanding or rendering of 
informed consent and compliance with the requirements of the protocol 
19. Evidence or self-report of alcohol or drug abuse within the previous 12 months 
20. Any conditions that in the judgement of the investigator would make the subject 
inappropriate for entry into the trial 
Note:  GFR will be estimated using the Cockcroft-Gault equation [Cockcroft and Gault 1976]. 

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9. 
WITHDRAWAL OF SUBJECTS 
9.1. 
Subject Withdrawal Criteria 
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, or 
administrative reasons.  The reason for a subject discontinuing from the study will be recorded in 
the source documents and electronic case report form (eCRF).  A discontinuation occurs when an 
enrolled subject ceases participation in the study, regardless of the circumstances, prior to 
completion of the protocol.  If a subject does not return for a scheduled visit, every effort should 
be made to contact the subject.  A subject will be considered lost-to-follow-up after 3 failed 
attempts to contact subject are made.  Efforts should be documented on the subject’s record.  In 
any circumstance, every effort should be made to document subject outcome, if possible.  The 
Site Principal Investigator must determine the primary reason for discontinuation.  Withdrawal 
due to adverse event should be distinguished from withdrawal due to insufficient response 
according to the definition of adverse event noted earlier.  A discontinuation must be reported 
immediately to the sponsor if it is due to a serious adverse event.  The final evaluation required 
by the protocol will be performed (as per the early termination assessments).  The Site Principal 
Investigator will record the reason for study discontinuation, provide or arrange for appropriate 
follow-up (if required) for such subjects, and document the course of the subject’s condition. 
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
If the dropout rate is such that the power of the study could be compromised, or that the study 
objectives cannot reliably be achieved, the sponsor may elect to replace those subjects who 
discontinue prematurely. 

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10. 
TREATMENT OF SUBJECTS 
Part 1 is a single-dose treatment for each subject.  Subjects will have an approximate 84-day 
screening period, a 3-day in-clinic treatment period, and a follow-up through 28 days post-dose.  
Thus, study participation for each subject in Part 1 is expected to be approximately 16 weeks in 
duration. 
Part 2 includes a repeat dose injection regimen.  Subjects will have an approximate 84-day 
screening period, a 104-day treatment period (with injections given approximately every 21 days 
through Day 104) and then post treatment follow-ups at Study Days 137, 169, and 253.  Thus, 
study participation for each subject in Part 2 is expected to be up to approximately 337 days in 
duration. 
10.1. 
Description of Study Drug & Placebo 
Investigational product will be packaged in single use identical vials containing 5 mL.  Each vial 
contains placebo or 50 mg of AXER-204.  Vials will be packaged appropriately for shipment.   
Study drug and placebo will be distributed to the clinical site from a designated distribution 
center.  The sponsor will provide the investigator with adequate quantities of study drug, 
placebo, and supplies to dose each subject. Specific details regarding study drug, placebo, dose 
preparation, and accountability will be described in a pharmacy manual at the clinic. 
Table 9: 
Study Drug and Placebo (Study RNX-AX204-101) 
 
Study Drug & Placebo 
Product Name: 
Placebo (Part 2 and used in 
preparing low doses in Part 1) 
AXER-204 
Route of Administration 
Intrathecal injection 
Intrathecal injection 
Physical Description 
Colorless solution 
Colorless solution, may 
contain white or translucent 
particles * 
Manufacturer 
 
 
* AXER-204 drug product may contain inherent proteinaceous particles.  These are removed by 
filtration during dose preparation.  Studies have been completed confirming the potency, purity, 
and safety of AXER-204 after filtration. 
10.2. 
Concomitant Medications 
All concomitant medications, whether prescription, over-the-counter, herbal treatments, or other 
therapy, taken or used by the patient within 28 days of screening through end of study 
assessments will be recorded in the subject’s medical record and in the Concomitant Medications 
eCRF.  

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Regular use of medications which, in the assessment of the Principal Investigator, may confound 
efficacy and/or safety assessments is prohibited.  Such medications may include but are not 
limited to: 
• Anticoagulants 
• antipsychotic drugs 
• marijuana 
• opiates 
• sedative hypnotics 
• tranquilizers.  
Daily low dose aspirin (81 mg) therapy is permitted. 
Antipsychotic drugs used as mood stabilizers for the adjunctive treatment of depression as well 
as antidepressants (SSRI, SNRI, TCA, buspirone) are permitted provided the subject is on a 
stable dose for at least 12 weeks prior to Screening and the dose is not anticipated to change 
during participation in the trial. 
Marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers are permitted 
only if the dosage and frequency of use are not considered likely to interfere with evaluation of 
safety and efficacy endpoints in the trial.  As needed (PRN) use of nonsteroidal anti-
inflammatories and acetaminophen is permitted. 
Prospective subjects who at the time of screening are taking medications that the Principal 
Investigator judges may confound efficacy and/or safety assessments (listed in Exclusion 
Criteria, Section 8.2) must stop them, after signing Informed Consent and receiving instructions 
on the discontinuation of these medications, two weeks or five half-lives –whichever is longer- 
prior to investigational product administration. The prospective subject must be willing to 
discontinue treatment and the Investigator must deem this feasible. The prospective subject 
taking prohibited medication at the time of screening will be considered eligible at the time of 
investigational product administration (Visit 2, Study Day 1) provided no reintroduction of the 
prohibited medication is being considered, the appropriate time window since last administration 
has elapsed, and the subject continues to meet other eligibility criteria.  Subjects must remain off 
prohibited medications until all assessments are completed in the study. Determination of 
exclusion due to use of a specific medication from these classes of prohibited medications will 
be made by the Principal Investigator in conjunction with the Medical Monitor based on medical 
assessment of factors including the dosage, frequency of use, and medical condition being 
treated.   
Concomitant medications will be coded using the World Health Organization (WHO Drug) 
Dictionary.  
10.3. 
Treatment Compliance 
Treatment compliance with investigational product during the treatment periods is expected to be 
high, as subjects will be dosed directly in the clinic under well-controlled conditions.  The date, 
start and stop time of investigational product administration, dose and quantity of investigational 

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product administered will be recorded on the source documents and eCRF.  Non-compliance 
with other aspects of the study protocol (eg, use of prohibited medications, missed study visits) 
will be documented on the subject’s source document and on the eCRF.  
10.4. 
Randomization and Blinding 
10.4.1. 
Part 1 
Part 1 does not include placebo, is open-label, and there is no randomization.  Subjects will be 
enrolled and treated sequentially, with at least 3 days (72 hours) between dosing of consecutive 
patients.  This wait-period will allow for a review of safety data collected during the in-clinic 
treatment phase prior to each new subjects’ dosing.   
10.4.2. 
Part 2 
Central randomization will be implemented in the study.  At the pre-dose visit (Visit 2) Study 
Day 1, eligible subjects will be randomly assigned in a 1:1 ratio to one of two treatment groups 
based on a randomization schedule prepared prior to study start by a statistician.  To enroll the 
patient on Study Day 1, the investigator or designee will enter the subject identification number 
that was assigned at Screening Visit on the enrollment page in the electronic data capture (EDC) 
system. The EDC will assign a unique treatment code, which will be linked to the appropriate 
treatment group as assigned by the randomization schema.    
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will 
be stratified based on pre-treatment AIS grade (AIS A,B vs. AIS C,D) and prior receipt of study 
drug in Part 1 (Received AXER-204 in Part 1 vs. Did not receive AXER-204 in Part 1). 
The blind will be maintained for all blinded study personnel (including investigators and 
subjects) through the completion of Day 169 of Part 2, and thus only designated Sponsor staff, 
members of the DSMB, and other designated unblinded personnel will have access to unblinded 
information prior to database lock for the Day 169 analysis.  At each study site, an unblinded 
pharmacist will prepare prefilled syringes for dose administration in order to maintain the blind 
for study personnel administering the investigational product and performing all other study 
procedures.  After completion of Day 169, designated sponsor staff and external 
consultants/contractors required to perform the analysis will be unblinded to the treatment 
allocations in order to complete data analysis though Day 169.  The blind will be maintained for 
site investigators and subjects through completion of Day 253 unless the blind must be broken 
sooner for safety or regulatory reasons. 
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind.  A formal unblinding process will be used to ensure security and maintenance of the blind.  
However, the investigator should contact the sponsor before breaking the blind.  When the blind 
has been broken for a subject, the reason must be fully documented and entered on the source 
document and eCRF for that subject. 
Data that may potentially unblind the treatment assignment (eg, PK samples) will be handled 
such that the integrity of the blind is maintained and the potential for bias minimized.  This may 
include making special provisions such as segregating the data in question from view by the 
investigator and site study staff, sponsor clinical team, and others as appropriate. 

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The bioanalytical laboratory personnel will be open to the randomization codes in order to 
facilitate PK analytical work and ADA testing.  Personnel are not to communicate or imply in 
any manner, information associated with this to others at the clinical site, the sponsor, its 
consultants, designated CRO, or other vendors. 
A formal analysis of the data will be performed once all subjects have completed their treatment 
period and follow-up assessments through Day 169.  This efficacy analysis will be performed as 
the primary assessment of efficacy in the study; the study will continue through the follow-up 
period to Study Day 253.  A second efficacy analysis will be conducted at Study Day 253. 

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11. 
STUDY PROCEDURES 
11.1. 
Part 1  
Each investigator will be assigned a unique site code. This site code will be concatenated with 
the screening number to assure that each subject will be uniquely identified in the clinical 
database. Site numbering will begin with 01 preceded by the number 1, and screening numbers 
will begin with 001. As subjects are screened, the next subject qualified chronologically at a site 
will be assigned the next number in ascending numerical order.  Thus, the subject identification 
number for the first subject enrolled in Cohort 1 at the first site activated will be 101-001.  The 
first subject enrolled in Cohort 1 at the second site activated will be 102-001 and so on. 
Subjects will participate in the study for a total duration of up to 16 weeks.  Visits will be 
scheduled at: 
• Screening Visit 1 (Study Days -84 to -1) 
• In-Clinic Treatment Visit 2 (Study Days 1 through 4) 
• Post Treatment Follow-up  
− Phone calls on Study Days 5, 6, and 7 
− Visits 3 and 5 (Study Days 8 and 29/early termination [ET]) 
− Visit 4 (Study Day 15) 
− Refer to the Schedule of Events (Table 5) for all the procedures and assessments 
to be performed during Part 1. The following sections provide important details of 
the procedures to be completed for each period. 
11.1.1. 
Screening Period, Visit 1 (Study Days -84 through -1) 
Subjects will sign an ICF before any screening-related procedures are performed. The Screening 
Visit (Visit 1) should occur between Study Days -84 to -1 and screening procedures completed 
during this time period.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
participate in the main study.   
Once the subject has consented to participate in the study (including having blood samples drawn 
and CSF and serum collection for PK assessment), the subject should be registered in the EDC 
system and a 6-digit subject identification number assigned by the designated study site 
personnel.  This number will be used to identify each subject throughout the study and will be 
entered on all study-related documentation and subject medical chart.   
• Note: At either Screening (Visit 1) or Pre-Dose (Visit 2), if a subject is a screen 
failure, not eligible to receive study drug, or if the subject withdraws or is 
discontinued from the study, his/her subject identification number cannot be reissued 
or assigned to another subject. 

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The inclusion and exclusion criteria should be carefully assessed.  The subject’s demographics, 
medical and surgical history, and prior and concomitant medications will be recorded.  
Each subject will undergo a full physical examination including height and weight. The physical 
examination may be performed by the investigator, a sub-investigator who is a medical doctor, or 
a qualified nurse practitioner or physician’s assistant in accordance with the site’s current 
practice and in accordance with local requirements as applicable.  
Blood samples will be obtained for biochemistry, hematology laboratory tests, and viral 
serology.  A urine sample for urinalysis will be collected. 
A serum pregnancy test will be obtained on all female subjects.  
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene). Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained after the subject has been in a sitting (or recumbent) position for 5 
minutes.  A 12-lead ECG will be taken in triplicate, 5 minutes apart, after the patient has been in 
a supine (resting) position for at least 5 minutes. 
Subjects will have several scales administered by a clinician who is trained to administer these.  
Where possible, the order for evaluating these scales should be followed as defined in Section 
11.2.  These include the full ISNCSCI scale, SCIM III self-care and mobility scale, GRASSP, 
Modified Ashworth Scale, and autonomic evaluations as per ISAFSCI.  Subjects will also be 
administered several questionnaires at this visit, including: 
• BPI (Appendix 9) 
• SF-36 v2 (Appendix 6) 
• Neuro-QOL (Appendix 7). 
A magnetic resonance imaging scan will be obtained as described (Appendix 12).  The MRI 
must be completed and results known and made available to the principal investigator prior to 
the subject’s admittance to the clinic on Visit 2 (Pre-Dose).  Results from the MRI will be read 
by a sponsor-arranged expert. 
Subjects who fail to meet any entry criterion that can be assessed at that time are considered to 
be screen failures and are not required to return for additional visits (although a subject can be 
seen at any time for safety reasons).  Subjects who are screen failed due to lab values can be re-
screened as determined by the principal investigator in consultation with the study medical 
monitor.  Subjects who rescreen will be assigned a new screening number. 
Serious AEs will be recorded and monitored starting at the time of subject signing the ICF. 

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Upon completion of the Screening Visit (Visit 1), subjects will be given an appointment 
reminder card that contains the date and time for their next visit.  
See the schedule of events (Table 5) for details on the assessments on each Study Day. 
11.1.2. 
In-Clinic Treatment, Visit 2 (Study Days 1 to 4 [Pre-Dose and Post-Dose]) 
Eligible subjects will be admitted to the clinical site on the evening prior to or morning of the 
scheduled dosing depending on site’s requirements. If during this visit and prior to dosing a 
subject is determined to no longer be eligible to continue in the study, the appropriate Screening 
eCRFs will be completed and the subject deemed a Screen Failure and will not be required to 
return for additional visits (although a subject can be seen at any time for safety reasons.) 
All inclusion and exclusion criteria, medical and surgical history, and prior medications will be 
reviewed for a second time to confirm eligibility.  New SAEs and concomitant medications 
reported by the subject since the Screening Visit (Visit 1) will be recorded on the eCRF.  A urine 
pregnancy test will be performed on all women of childbearing potential.  
Results obtained during the Screening Visit (Visit 1) including the results of the MRI scan must 
be reviewed by the investigator prior to subject treatment with study drug to ensure subject 
remains eligible for the study.  
Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained after the patient has been in a sitting position for 5 minutes. 12-
lead pre- and post-dose ECG will be taken in triplicate, 5 minutes apart, after the patient has been 
in a supine (resting) position for at least 5 minutes.  An abbreviated physical exam should be 
performed. 
If the subject remains eligible for study participation, the EDC will be accessed to enroll the 
subject, visit information will be entered, and the required eCRFs completed.  The research 
pharmacist will be contacted regarding the subject’s enrollment and for specifics about the 
timing of the scheduled lumbar puncture as well as preparation and availability of study drug 
necessary for the intrathecal administration of AXER-204.  
During the lumbar puncture, an amount of CSF approximately equivalent to the amount of study 
drug to be injected into the intrathecal space (~9-20 mL) will be obtained pre-dose for CSF/PK 
assessment, spinal cord injury biobanking, and potentially biomarker analysis.  For the 20 mL 
maximum dose, at least 15 mL of CSF should be collected immediately prior to administration. 
If at least 15 mL cannot be collected, the principal investigator may elect to discontinue the 
subject from the trial or to ask the subject to return on the following day for a second attempt 
after additional hydration.  In this situation, the subject may be directed to remain at a nearby 
overnight accommodation or home (if within a reasonable distance) and report the next morning 
for examination or to remain in the hospital overnight.  Note that, under these circumstances, 
there is no requirement for an overnight hospital stay; if a decision is made to keep the patient 
overnight for convenience (e.g. travel issues), this hospitalization should not initiate a serious 
adverse event report (e.g. local alternate accommodations not readily available).  Study Drug 
AXER-204 will be administered via slow bolus infusion intrathecal administration.  Details 
including dose and quantity administered, physician administering the study drug, and date and 
time of administration will be recorded on the eCRF and in the subject’s record.  Post lumbar 
puncture and post-dose subjects are to be monitored for any adverse events.   

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If a lumbar puncture fails to return CSF after two attempts, it is recommended that fluoroscopy 
be scheduled to assist in achieving successful LP.  Likewise, it is recommended that the lumbar 
puncture procedure be suspended if the CSF sample is bloody or turbid.  Decisions regarding the 
lumbar puncture procedure are at the discretion of the site principal investigator.  
The subject is to be confined to the clinic on Study Days 2, and 3, and discharged on Study Day 
4 after all required assessments have been completed.  See the schedule of events (Table 5) for 
details on the assessments on each Study Day. 
Prior to discharge from the clinical unit on Study Day 4, subjects will be given an appointment 
reminder card that contains the date and time of their next visit.  
11.1.3. 
Post-Treatment Follow-up Phone Calls, Study Days 5, 6, and 7 
Subjects do not have to visit the clinic for Post-treatment follow-up on Days 5, 6, and 7 unless 
necessary to follow-up on adverse events.  Subjects will receive a telephone call from study site 
personnel inquiring as to their general health.  Any reported adverse events experienced by a 
subject will be documented in the subject’s records and on the eCRF.  Subjects will also be 
reminded about their next visit to the study site. 
11.1.4. 
Post Treatment Follow-up Visits 3 & 4 (Study Days 8 and 15) 
At Visit 3, Study Day 8, subjects’ vital signs (BP, pulse, respiratory rate or pulse oximetry, and 
oral body temperature) will be obtained. Subjects will undergo a lumbar puncture and will have 
CSF collected for PK assessments.  Blood samples will be collected and serum samples for PK 
assessments and presence of ADA will be obtained.  Information on changes or newly 
administered concomitant medications as well as any new or ongoing AEs will be collected.    
Subjects will be given instructions to return to the study site for the next visit and provided an 
appointment reminder card. 
During Visit 4, Study Day 15, blood samples will be collected for clinical laboratory testing and 
serum samples obtained for PK analysis.  Information on changes to ongoing and any new 
concomitant medication as well as any new or ongoing AEs will be recorded on the eCRF and in 
the patient’s record.   
At the completion of the visit, subjects will be given an appointment reminder card that contains 
the date and time of their next visit to the study site. 
11.1.5. 
Post Treatment Follow-up Visit 5 (Study Day 29/ET) 
Visit 5 (Study Day 29/ET) is to be conducted on subjects who will be completing the study as 
well as those who terminate early or are withdrawn from the study.   
At this visit, a full physical exam will be performed.  The subject will be weighed and weight 
recorded on the eCRF.  Vital signs (BP, pulse, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained.  A urine pregnancy test will be obtained on all females of 
childbearing potential. 
Subjects will undergo lumbar puncture for CSF collection for PK assessments.  Blood sampling 
for laboratory testing including viral serology will also be obtained. Serum for PK and the 
presence of ADA will be analyzed.  Urine sample will be obtained for urinalysis.   

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Information on changes or newly administered concomitant medications as well as any new or 
ongoing AEs will be recorded on the eCRF.  
All scales should, if possible, be administered by the same clinician who administered the scales 
during the Screening period.  These shall be completed in the order as noted in 11.2 and include 
the full ISNCSCI scale, SCIM III self-care and mobility scale, GRASSP, Modified Ashworth 
Scale, and autonomic evaluations as per ISAFSCI.  Subjects will also be administered several 
questionnaires at this visit, including:  
• BPI (Appendix 9) 
• SF-36 v2 (Appendix 6) 
• Neuro-QOL (Appendix 7) 
Subjects’ completion or termination from the study (in the case of subjects who terminate early 
from the study or who are withdrawn) will be recorded on the eCRF and in the subjects’ record. 
11.2. 
Part 2 
Each investigator will be assigned a unique site code. This site code will be concatenated with 
the screening number to assure that each subject will be uniquely identified in the clinical 
database. Site numbering will begin with 01 preceded by the number 2, and screening numbers 
will begin with 001. As subjects are screened, the next subject qualified chronologically at a site 
will be assigned the next number in ascending numerical order.  Thus, the subject identification 
number for the first subject screened at the first site will be 201-001.  The first subject enrolled at 
the second site will be 202-001 and so on. 
Subjects will participate in the study for a total duration of up to approximately 337 days.  Visits 
will be scheduled at Screening Visit 1 (Study Days -84 to -1), Treatment Phase with Visit 2 
occurring on Study Day 1 and subsequent dosing visits occurring approximately every 21 days 
encompassing Visits 3-7 (Study Days 21 through 104).  There will be telephone calls to assess 
status regarding any adverse events on Study Day 8 and Study Day 137.  Post-treatment follow-
up visits will occur at Visits 8 and 9 (Study Days 169 and 253). 
Refer to the Schedule of Events (Table 6) for all the procedures and assessments performed 
during the study.  The following sections provide important details of the procedures.  Where 
possible, the order that the key measures are to be performed is as follows.   
• ISNCSCI 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
Note: GRASSP prehension ability and prehension performance testing will be video 
recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 
• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
• SF-36 v2 

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• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
11.2.1. 
Screening Period, Visit 1 (Study Days -84 through -1) 
Subjects will sign an ICF before any screening-related procedures are performed. The Screening 
Visit (Visit 1) should occur between Study Days -84 to -1.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
participate in this main study.   
Once the subject has consented to participate in the study (including PK and CSF sampling) and 
has signed the ICF, the subject should be registered in the EDC system and a 6-digit subject 
identification number will be assigned.  This number will be used to identify each subject 
throughout the study and will be entered on all documentation for a subject and into the EDC.   
• Note: At any time during Visit 1 or Visit 2, if a subject is not eligible to receive 
investigational product, or if the subject withdraws or is discontinued from the study, 
their subject identification number cannot be reissued or assigned to another subject. 
The inclusion and exclusion criteria should be carefully assessed. The subject’s demographics, 
medical and disease history, and prior and concomitant medications will be recorded.  
Each subject will undergo a full physical examination including height and weight. The physical 
examination may be performed by the investigator, a sub-investigator who is a medical doctor, or 
a qualified nurse practitioner or physician’s assistant in accordance with the site’s current 
practice and in accordance with local requirements as applicable.  
Blood samples will be obtained for biochemistry, hematology laboratory tests, and viral 
serology. A urine sample for urinalysis will be collected.  A serum pregnancy test will be 
obtained on all female subjects. (Section 8).  Note:  The screening laboratory assessments must 
be completed within 28 days of enrollment. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
Vital signs (blood pressure, pulse rate, pulse oximetry, and oral body temperature) will be 
obtained after the patient has been in a sitting position for 5 minutes. A 12-lead pre-dose ECG 

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will be taken in triplicate, 5 minutes apart, after the patient has been in a supine (resting) position 
for at least 5 minutes.  
Subjects will be assessed by ISNCSCI and GRASSP and their UEMS and GRASSP prehension 
ability scores will be used to assess eligibility. 
An MRI scan will be scheduled and must be completed and results known and made available to 
the Principal Investigator prior to the subject check in to the clinic on Visit 2 (Pre-Dose).  Results 
from the MRI scan will be run locally and findings read by sponsor arranged expert. 
Subjects who fail to meet any entry criterion that can be assessed at that time are considered to 
be screen failures and are not required to return for additional visits (although a subject can be 
seen at any time for safety reasons).  Subjects may be re-screened as determined by the Principal 
Investigator in consultation with the Study Medical Monitor. 
Serious AEs will be recorded and monitored starting at the time of subject signing the ICF. 
Upon completion of the Screening Visit (Visit 1), subjects will be given an appointment 
reminder card that contains the date and time for their next visit.   
11.2.2. 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) 
At Visit 2, Study Day 1, eligible subjects will visit the clinical site to undergo the scheduled 
lumbar puncture. Subject will be randomized in the EDC at this visit.  
If prior to randomization during this visit a subject is determined to no longer be eligible to 
continue in the study, the appropriate Screening eCRFs will be completed and the subject 
deemed a Screen Failure. 
All inclusion and exclusion criteria, medical and surgical history, and prior medications will be 
reviewed for a second time. New SAEs and concomitant medications reported by the subject 
since the Screening Visit (Visit 1) will be recorded on the eCRF. A urine pregnancy test will be 
performed on all women of childbearing potential. 
Results obtained during the Screening Visit (Visit 1) including the results of the MRI scan must 
be reviewed by the investigator prior to subject treatment with investigational product to ensure 
subject remains eligible for the study. Subjects who do not continue to be eligible to participate 
in the study are screen failures and are not required to return for additional visits (although a 
subject can be seen at any time for safety reasons). 
At Visit 2, Study Day 1 the following baseline assessments will be performed in the following 
order prior to dosing: 
• ISNCSCI 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP).  
Note: GRASSP prehension ability and prehension performance testing will be video 
recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 

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• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
• SF-36 v2 Health Survey 
• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
Note:  Baseline ISNCSCI UEMS and GRASSP prehension ability scores may fall outside of the 
lower and upper bounds of the inclusion criteria for these measures by up to 3 points without 
impacting eligibility (i.e. bilateral UEMS must be 1-39 and bilateral GRASSP prehension ability 
may be 1-20 at baseline).  Subjects with scores at baseline (Visit 2, Study Day 1) that fall outside 
of the UEMS and GRASSP prehension ability inclusion criteria by more than 3 points will not be 
eligible to continue in the study.    
Vitals will be taken pre-dose, post dose, then every 2 hours until subject leaves the unit.  Vital 
signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) 
will be obtained after the patient has been in a sitting position for 5 minutes. A 12-lead pre-dose 
ECG will be taken in triplicate, 5 minutes apart, after the patient has been in a supine (resting) 
position for at least 5 minutes. The ECG will be read locally.  An abbreviated physical exam will 
be performed. 
The randomization page in the EDC will be accessed to randomize the subject, visit information 
will be entered, and the required eCRFs completed.  The research pharmacist will be contacted 
regarding the subject’s randomization and for specifics about the timing of the scheduled lumbar 
puncture and preparation and availability of study drug or placebo necessary for the intrathecal 
administration of investigational product.   
Serum will be collected for PK and ADA analysis as detailed in Section 13.2.  
If a lumbar puncture fails to return CSF after two attempts, it is recommended that fluoroscopy 
be scheduled to assist in achieving successful LP.  Likewise, it is recommended that the lumbar 
puncture procedure be suspended if the CSF sample is bloody or turbid.  Decisions regarding the 
lumbar puncture procedure are at the discretion of the site principal investigator.  Additionally, 
investigators may make an assessment based on a given patient that all LPs will be conducted 
under fluoroscopy.  
During the lumbar puncture, an amount of CSF approximately equivalent to the amount of 
investigational product to be injected into the intrathecal space (~9-20 mL) will be obtained pre-
dose for CSF/PK assessment, spinal cord injury biobanking, and potentially biomarker analysis.  
For the 20 mL maximum dose, at least 15 mL of CSF should be collected immediately prior to 
administration. If at least 15 mL cannot be collected, the principal investigator may elect to skip 
dosing for the visit or to ask the subject to return on the following day for a second attempt after 
additional hydration.  In this situation, the subject may be directed to remain at a nearby 
overnight accommodation or home (if within a reasonable distance) and report the next morning 
for examination or to remain in the hospital overnight.  Note that, under these circumstances, 
there is no requirement for an overnight hospital stay; if a decision is made to keep the patient 
overnight for convenience (e.g. travel issues), this hospitalization should not initiate a serious 

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adverse event report (e.g. local alternate accommodations not readily available).  Investigational 
product will be administered via slow bolus infusion intrathecal administration.  Details 
including dose and quantity administered, physician administering the investigational product, 
and date and time of administration will be recorded on the eCRF and in the subject’s record.  
Post lumbar puncture and post-dose subjects are to be monitored for any adverse events.   
The Site Principal Investigator may discontinue a subject from the study due to unsuccessful 
collection of CSF to allow for isovolumetric dose administration if the subject has not received 
any doses and they consider it unlikely that further dosing attempts will be successful.  Subjects 
who received at least one dose of investigational product should complete the remaining visits to 
monitor for safety and efficacy as per the schedule of events. Under this circumstance, further 
per-protocol LP attempts should not be made.  Conducting all LPs under fluoroscopy should be 
considered if difficulties in obtaining adequate CSF collection is encountered.  
For dosing visits that include neurological exams and questionnaires (e.g. ISNCSCI, GRASSP, 
SCIM III self-care and mobility), these assessments should be performed prior to dosing. 
Depending on scheduling considerations, subjects may be asked to return the following day for 
dose administration.  Under this circumstance, nearby overnight accommodations will be 
arranged for the subject upon request. 
Following dosing, patients will remain under the observation of study personnel in the hospital 
setting (eg, may include infusion center, PACU, recovery suite, observation unit, short stay 
center) for 4 hours for safety monitoring. Thereafter, if deemed clinically stable by the 
Investigator, patients may leave the hospital setting.  If further safety observation is directed by 
the investigator, the subject may be directed to remain at a nearby overnight accommodation or 
home (if within a reasonable distance) and report the next morning for examination or to remain 
in the hospital overnight.  Note that, under these circumstances, there is no requirement for an 
overnight hospital stay; if a decision is made to keep the patient overnight for convenience (e.g. 
travel issues), this hospitalization should not initiate a serious adverse event report (e.g. local 
alternate accommodations not readily available).  Upon completion of the visit, subjects will be 
given an appointment reminder card that contains the date and time of the follow-up telephone 
call and for their next visit.  
A telephone call to assess status regarding any adverse events will be conducted on Study Day 8.   
At Study Visits 3 through 7 (Study Days 21 through 104), subjects will receive either AXER-204 
or placebo via slow bolus infusion intrathecal administration.   
At Study Visits 3 through 7, (Study Days 21 through 104), 12-Lead ECGs, abbreviated physical 
examinations vitals will be obtained.  Vitals will be taken pre-dose, post dose, then every 2 hours 
until subject leaves the unit.  Serum collection for PK will be obtained pre-dose and 4 hours post-
dose, CSF will be collected pre-dose (as part of the dosing procedure), urine pregnancy tests will 
be administered on all women of childbearing potential.  Changes to concomitant medication 
will be assessed and recorded as well as adverse events and serious adverse events.   
At Visit 3 (Study Day 21) the following efficacy assessments will be performed prior to dosing: 
• ISNCSCI 
At Visits 5 and 7 (Study Days 63 and 104), the following efficacy assessments will be performed 
prior to dosing in the order listed: 

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• ISNCSCI 
• GRASSP. Note: GRASSP prehension ability and prehension performance testing will 
be video recorded.   
• SCIM III self-care and mobility subscores 
Upon completion of the visit, subjects will be given an appointment reminder card that contains 
the date and time when they will receive a telephone call and the date and time of their next visit.   
11.2.3. 
Follow-up on Study Day 137 
Study Day 137 will consist of a telephone Study personnel will conduct telephone call to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come 
to the clinic for evaluation. 
11.2.4. 
Follow-up Visits 8 and 9 (Study Days 169 and 253) 
At Visits 8 and 9 (Study Days 169 and 253), 12-Lead ECGs, physical examinations (abbreviated 
at Visit 8; full exam at Visit 9, with height/weight), vitals will be performed. Serum samples will 
be collected for PK and ADA analysis as detailed in Section 13.2.  Blood will be collected for 
laboratory testing and viral serology, and urine collected for urinalysis.  Urine pregnancy tests 
will be conducted for women of childbearing potential.  Changes to concomitant medication will 
be assessed and recorded as well as AEs and SAEs.  CSF will be collected at Visit 9 (Study Day 
253). 
In Study Visits 8 and 9, subjects will have all efficacy and QoL assessments performed (see the 
Schedule of Events for specifics, Table 6), in the following order: 
• ISNCSCI 
• GRASSP.  Note: GRASSP prehension ability and prehension performance testing 
will be video recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 
• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL)  
• SF-36 v2 Health Survey 
• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
GRASSP prehension ability and prehension performance testing will be video recorded.  
 

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12. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
Investigational product will be provided to the clinical sites. 
12.1. 
Study Drug 
Single-use vials with labels and an outer fiberboard carton with a single panel label will have the 
following information: 
• LEI - hNgR(310)-Fc Drug Product 
• Concentration: 10 mg/mL  
• Volume: 5 mL 
• Storage: ≤ - 65° C 
• Caution: Filter Before Use - New Drug-Limited by United States Law to 
Investigation Use Only 
• Manufactured by 
 
The clinical trial supply label will be in accordance with ICH GCP and local requirements for 
investigational product labelling. 
12.2. 
Investigational Product Packaging and Labeling 
Investigational products are for investigational use only and the products supplied for this study 
are intended for use only within the context of this study.  The investigational product supplied 
for this study should be stored in a secure, temperature controlled, locked place with restricted 
access, maintained under adequate security until dispensed for subject use or returned to the 
sponsor.   
For all shipments of study drug, site study personnel shall note a 6-month use limit date based on 
the date of thaw of the vials.  A label will be supplied to record the thaw date and storage use 
limit date on the box containing the vials.  Placebo expiry shall be defined in a memo included 
with the shipment and will be extended as warranted via memo when new stability data becomes 
available.  A label will be supplied to record the expiry date on the box containing the vials.  The 
label shall be updated if the expiry is extended before the placebo in the box is fully depleted.   
12.3. 
Investigational Product Storage 
AXER-204 is formulated as an isotonic solution in Phosphate Buffered Saline and is provided in 
5 mL vials. It will be shipped to sites frozen at -80 °C (on dry ice).  Upon receipt it shall be 
placed in the refrigerator at 2-8 °C in a secure location and allowed to thaw for a minimum of 16 
hours prior to use in dose preparation.  Once thawed, AXER-204 shall be kept stored in the 
refrigerator at 2-8 °C for up to 6 months prior to use.  After thawing, the vials containing AXER-
204 should NOT be shaken or vigorously agitated as this may result in generation of foam and 
particles.  Contact the sponsor for instructions in the event there is a deviation from the required 
storage conditions. 

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Placebo consists of Phosphate Buffered Saline and is provided in 5 mL vials.  It will be shipped 
to sites at a temperature of 2-8 °C.  Upon receipt it shall be placed in the refrigerator at 2-8 °C.   
12.4. 
Investigational Product Preparation 
Refer to the dose preparation appendix in the Pharmacy Manual describing the details regarding 
dose preparation.  
12.5. 
Investigational Product Management 
The pharmacist or their designee will verify that investigational product supplies are received 
intact and in the correct amounts by signing and dating the investigational product receipt section 
at the bottom of the packing list.  The person receiving the supplies must verify that the shipment 
contains all the items noted in the shipment inventory.  Any damaged or unusable investigational 
product in a given shipment will be documented in the study files.  The pharmacist must notify 
the sponsor or designee of any damaged or unusable investigational product supplied to the site. 
The site will maintain a Study Drug and Placebo Inventory Log (includes, but not limited to, the 
following: lot number, number of units received, expiry date, and number of vials and syringes 
dispensed.  The site will also maintain patient-specific investigational product dispensing logs. 
An overall accountability of investigational product will be performed and verified throughout 
the study and at the site closeout visit.  Upon completion of the study, copies of the 
investigational product accountability records will be returned to the sponsor.  All used and 
unused study investigational product supplies will be inventoried and accounted, and any used or 
unused supplies which have not been destroyed locally shall be returned to the sponsor or 
designee at the end of the study.  By signing the Investigator Agreement page of this protocol, 
the investigator agrees not to supply investigational product to any person(s) not enrolled in the 
study. 
12.6. 
Investigational Product Accountability 
Subjects will be treated at the clinical site, in-patient clinical unit, or other approved location and 
therefore the Pharmacist or other investigational staff via documentation of receipt of the 
investigational product and dosing/treatment given will perform/maintain accountability.   
12.7. 
Investigational Product Handling and Disposal 
Records of receipt, dispensing records and inventory forms, as applicable, will be examined and 
reconciled during and at the end of the study.  Both the investigational product that is used 
during the study, as well as any remaining unused investigational product, must be accounted for 
on study drug and placebo accountability records provided to the PI by the sponsor or their 
designee or documented per site SOPs.   
At the end of the study or when instructed by the sponsor or designee, all used and unused 
investigational product vials, accompanied by a packing slip, must be returned to the designated 
clinical supplies vendor for disposal or destroyed per site SOPs.  If used investigational product 
vials and/or unused but expired investigational product vials were destroyed locally per site 
policies or procedures, destruction should be documented on the accountability log. 

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In addition, a copy of all completed investigational product accountability records must be 
retained in the Investigators’ Study Files, with a copy sent to the sponsor or their designee. 
The product is to be stored in a safe place (locked facility) at the appropriate temperature. 

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13. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS 
13.1. 
Efficacy 
Site personnel will be trained and certified to perform the efficacy assessments.  The same raters 
will be used for evaluation of a given subject insofar as possible.  Raters will be blinded to 
treatment for Part 2 of the trial. 
13.1.1. 
Part 1 
Part 1 is focused on safety, tolerability, and pharmacokinetics.  However, a subset of efficacy 
assessments are included, as follows: 
• ISNCSCI.  ISNCSCI is a comprehensive clinician-administered neurological exam 
for SCI. It is widely used for research and clinical (neurologic) description to fully 
assess sensory and motor functioning and level of injury in traumatic SCI.  The 
UEMS will be calculated from the full ISNCSCI and evaluated separately. 
• GRASSP [Kalsi-Ryan 2012a, Kalsi-Ryan 2012b].  GRASSP is a clinician 
administered test with three subset scores that assesses strength in 10 key muscles in 
the upper extremity as well as dexterity and fine motor skills. 
• SCIM III self-care and mobility scores [Catz 2007, Itzkovich 2007].  SCIM III 
measures functional outcomes in three sections:  self-care, respiration and sphincter 
management, and mobility.  The current study will employ the self-care and mobility 
subscores. 
13.1.2. 
Part 2 
The primary objective of Part 2 is to evaluate the safety, tolerability, and pharmacokinetics of 
repeat dosing.  In addition, a number of efficacy assessments are included as secondary 
endpoints.  The key secondary efficacy endpoint for Part 2 will be within-subject change from 
pre-treatment baseline and slope for UEMS as compared to placebo.  The UEMS is collected as 
part of the ISNCSCI (Appendix 3). 
Additional secondary efficacy endpoints will include changes from pre-treatment baseline and 
slope for: 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance scores.  GRASSP is a clinician administered test with three 
subset scores that assesses strength in 10 key muscles in the upper extremity as well 
as dexterity and fine motor skills (Appendix 4). 
• Version III of the Spinal Cord Independence Measure (SCIM III) self-care.  SCIM III 
measures functional outcomes in three sections:  self-care, respiration and sphincter 
management, and mobility.  The current study will employ the self-care and mobility 
subscores.  The evaluation will be administered by a clinician (Appendix 8). 
Exploratory functional endpoints will include within-subject changes from pre-treatment 
baseline and slope for: 
• ISNCSCI lower extremity motor and sensory scores  

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• GRASSP strength, sensation and prehension ability scores 
• SCIM III mobility scores 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q) [Marino 2012, Marino 2015].  Assesses subject-
reported upper limb function (Appendix 2). 
− SF-36 v2 - Provides an investigator-evaluated Quality of Life (QoL) assessment 
for subjects.  SF-36 will provide data on the subjects' perceived health and well-
being over the course of the study (Appendix 6). 
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) - 
(Appendix 7). 
− PGIC – Chronic SCI (Appendix 10) – Provides a patient-reported global 
impression of change in the symptoms, activity limitations, emotions and overall 
quality of life with chronic spinal cord injury since beginning the trial. 
• ISAFSCI [Krassioukov 2012].  The ISAFSCI will be used to document autonomic 
control of the heart, blood pressure, sweating and temperature regulation.  Lower 
urinary tract function, bowel function, and sexual function will be scored 
(Appendix 1). 
Exploratory biomarkers of target engagement and axonal growth may be assessed.   
Since the mechanism of action entails enhanced axonal growth and plasticity, changes attained 
through Study Day 169 are anticipated to be most relevant to assessing on-target effects of 
therapy.   
13.2. 
Pharmacokinetics 
Both serum and cerebrospinal fluid samples will be collected for analysis, as shown in Table 10 
and Table 11.   
In Part 1, a window relative to the nominal timepoint is allowed for sample collection as follows: 
• Blood serum pharmacokinetic samples will be collected at 0 hour (immediately pre-
dose), and 1 h (±10 min), 6 h (±10 min), 12 h (±10 min), and 24 h (±10 min) post-
dose, as well as at Study Day 4 (72h ± 10 min), 8 (±1d), 15 (±3d), and 29 (±4d).   
• Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose), 24 h (±2h) Study Day 4 (72 h ±4h), and Study Days 8 (±1d), 
and 29 (±4d).  
The timing for serum and CSF sample collection may be adjusted for subsequent cohorts based 
on pharmacokinetic data from the preceding cohorts.  Serum PK samples collected at pre-dose 
and on Study Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
In Part 2 , Visits 3-7 (Study Days 21, 42, 63, 84, 104) will have a window of ±5 days and Visits 
8 and 9 (Study Days 169 and 253) will have a window of ±7 days.  CSF samples will be 
collected for PK analysis pre-dose on Study Days 1, 21, 42, 63, 84, and 104.  The CSF sample 
collected on Study Day 253 will also be analyzed for PK.  Serum samples will be collected for 

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PK analysis pre-dose and 4 h post-dose on Study Days 1, 21, 42, 63, 84, and 104.  Serum will 
also be collected for PK analysis on Study Days 169 and 253.  Pre-dose serum will be collected 
for ADA analysis on Study Days 1, 21, 42, 63, 84, and 104.  Serum will also be collected for 
ADA analysis on Study Days 169 and 253.  A subset of the CSF samples may also be analyzed 
for ADAs depending on development and presence of ADAs in the serum.  Part 2 serum and 
CSF from subjects receiving placebo will be collected but will not be analyzed for PK and 
ADAs. 
In Part 2 on Study Days 1, 21, 42, 63, 84, and 104 a window relative to the nominal timepoint is 
allowed for sample collection as follows: 
• Serum pharmacokinetic samples will be collected at 0 hour (within 4 h pre-dose), and 
4 h (±10 min) post-dose 
• Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose) 

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Table 10: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Day 1 (Dosing day)  
Day 2 (24 hours post-
dose) 
Day 4 (72 hours post-
dose)  
Day 
8 
Day 
15 
Day 
29 
Cerebrospinal Fluid  
Pre-Dose 
X 
X 
X 
 
X 
Serum  
Pre-Dose, and post-dose at Hours 1, 6, 
12 
X 
X 
X 
X 
X 
Serum aliquot for ADA 
testing 
X (Pre-dose) 
 
 
X 
 
X 
Table 11: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Study Phase 
Treatment Phase 
Window at Visits  3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
Month 
1 
21 
 
42 
63 
 
84 
 
104 
 
169 
Month 6 
253/ET 
Month 9 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
Cerebrospinal Fluid 
X 
X 
X 
X 
X 
X 
X 
Serum  
X 
X 
X 
X 
X 
X 
X 
X 
Serum aliquot for ADA 
testing 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations:  M = month, ET = Early Termination.  
 
 
 

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13.2.1. 
Serum 
Serum samples will be prepared for shipment according to the detailed procedure supplied. For 
research subjects that provided consent, the required quantity will be removed and processed into 
aliquots for inclusion in the spinal cord injury biobank.  Study personnel are required to verify 
that a subject provided the required separate biobank informed consent permitting sample 
inclusion in the biobank before a portion of the serum is removed and processed for this purpose. 
13.2.2. 
Cerebrospinal Fluid 
Cerebrospinal fluid samples will be prepared for shipment according to the detailed procedure 
supplied.  For research subjects that provided consent, from 9 to 20 mL will be removed and 
processed into aliquots for inclusion in the spinal cord injury biobank.  Study personnel are 
required to verify that a subject provided the required biobank separate informed consent 
permitting sample inclusion in the biobank before a portion of the serum is removed and 
processed for this purpose. 
13.2.3. 
Shipment of Pharmacokinetic Samples 
Serum and CSF samples will be packed on dry ice and shipped to the designated lab for 
processing at pre-determined intervals.  Specific instructions will be given to the site personnel. 

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14. 
ASSESSMENT OF SAFETY 
The Schedule of Events for Part 1 given in Table 5, and for Part 2 in Table 6 provide the timing 
for assessments starting with the Screening Visits. 
14.1. 
Safety Parameters 
Safety will be evaluated similarly for both Parts, through the collection of data from: 
• Physical examinations 
• Vital signs 
• 12-lead electrocardiograms 
• Laboratory parameters (hematology, blood chemistry, and urinalysis) 
• Treatment-emergent adverse events (TEAEs).   
− TEAEs will be defined as any AE occurring during or after the injection of 
investigational product.   
− TEAEs will be limited to those events occurring within 28 days after the last visit. 
Condition-specific safety outcomes will include: 
• 
ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• Spasticity (Modified Ashworth Scale) [Pandyan 1999].  A clinician administered 
examination for spasticity which measures muscle tone changes.  A score of 0-4 is 
assigned to each muscle group evaluated (Appendix 5).  Notes: Testing will exclude 
fingers and thumb.  Scores are to be recorded for left and right sides for each muscle 
group tested. 
• Pain (BPI) [Cleeland 1994].  A self-administered questionnaire used to assess the 
severity of a subject's pain and the impact of this pain on the subject's daily 
functioning.  
14.1.1. 
Demographic/Medical History 
Demographic information and medical history will be collected at Screening for determination of 
eligibility. 
14.1.2. 
Vital Signs 
Vital signs, including blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature, will be measured after the patient has been in a sitting/recumbent position for 5 
minutes.   
Height and weight will be captured as per the Schedule of Events.  BMI will be derived. 

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14.1.3. 
Physical Examination 
Physical examinations will be conducted and abnormalities will be described.  At certain visits, 
as indicated in the Schedule of Events, only symptom-driven examinations (abbreviated physical 
examinations) will be performed.   
Clinically significant changes, in the judgment of the investigator, in physical examination 
findings (abnormalities) will be recorded as adverse events. 
14.1.4. 
Electrocardiogram (ECG) 
A 12-lead ECG will be obtained on all subjects.  The electrocardiogram will precede other 
evaluations in the sequence of operations at each timepoint as scheduled.   
The screening ECG will be evaluated by a physician for the presence of abnormalities.  Subjects 
with clinically significant abnormalities may not enter the study.  The timing of these evaluations 
may be adjusted and additional evaluation times may be added, if indicated.   
The 12-lead ECGs will be taken in triplicate.  To minimize variability, patients should be in a 
supine (resting) position for at least 5 minutes prior to each ECG recording, 5 minutes between 
each ECG. If findings from the ECG performed at the Screening Visit (Visit 1) are clinically 
significant and would potentially prevent the subject from safely participating in the study 
(taking into account the patient’s overall status, as well as the medication profile), the patient 
should not be enrolled (or randomized) and should be withdrawn from the study.  
Triplicate ECGs will be performed twice during the Treatment/In-Clinic Visit (Visit 2) just prior 
to the lumbar puncture and within 60 minutes following administration of investigational product 
(and, for Part 2, at each subsequent dosing time point). Clinically significant abnormalities noted 
after investigational product administration are to be recorded as AEs.  All ECGs will be read 
locally by appropriately trained staff. 
14.1.5. 
Laboratory Assessments 
The results of all laboratory tests required by the protocol will be recorded in the subject's eCRF.  
All clinically important abnormal laboratory tests occurring during the study will be repeated at 
appropriate intervals until they return either to baseline or to a level deemed acceptable by the 
Site Principal Investigator and the sponsor, or until a diagnosis that explains them is made.  
Abnormal laboratory test results that result in a change in study drug dosage or in 
discontinuation of the drug, or require intervention or diagnostic evaluation to assess the risk to 
the patient/subject, should be recorded as adverse events in the case report form.  Investigators 
should review the CTCAE toxicity criteria that can be found at the following URL:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
All laboratory assessments will be collected as per the schedule of events (Table 5, Table 6). 
The clinical laboratory tests analyzed in this study are provided in Table 12.  The INRPTT, urine 
pregnancy testing and in-clinic safety laboratory tests requiring stat analysis will be processed 
locally.  In addition, laboratory samples taken during Study Days 1-4 will be processed locally.  
All other laboratory tests will be analyzed by a central laboratory, 
.  All 
CSF, blood, and urine samples will be collected and sent to the central laboratory on the day of 

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collection unless otherwise instructed.  INR/PTT is required prior to the Day 1 lumbar puncture 
procedure with repeat INR/PTT tests on subsequent Study Days only if directed by the Principal 
Investigator.  Clinical laboratory results will be reviewed by the study investigator when results 
are known prior to enrollment/randomization, and results available for each collection during the 
study including prior to discharge from the in-patient clinic in Part 1 of the study.  During the 
course of the study, abnormal laboratory values should be repeated and subjects interviewed for 
evidence of clinical signs and symptoms consistent with the laboratory abnormality. Subjects 
with abnormal laboratories at screening can be rescreened (ie, lab repeated) for inclusion into the 
study within the 28-day screening window specified for labs.  A Laboratory Manual will be 
provided separately for processing and shipping procedures.  
Table 12: 
Laboratory Parameters to be Assessed (Study RNX-AX204-101) 
Hematology 
Serum Chemistry 
Hemoglobin 
Glucose 
Albumin 
Hematocrit 
Blood urea nitrogen 
 
Platelet count (or estimate) 
Creatinine 
Creatine kinase 
White blood cell count including 
differential (absolute values only) 
Total bilirubin 
Calcium 
Alkaline phosphatase 
Total Cholesterol 
Alanine transaminase (ALT) 
 
Red blood cell (RBC) count 
Aspartate transaminase (AST) 
Direct bilirubin 
Mean corpuscular volume (MCV)  
RBC morphology 
MCH 
MCHC 
RDW 
 
Sodium 
Total protein 
 
Phosphorous 
Triglycerides 
Urinalysis 
Potassium 
Uric acid 
pH 
Chloride 
 
Specific gravity 
Bicarbonate 
 
Blood 
Lactate dehydrogenase 
 
Glucose 
 
 
Protein 
Coagulation 
 
Ketones 
Prothrombin time (PT) 
 
Urine Bilirubin  
Activated partial thromboplastin time 
(PTT) 
 
International normalized ratio (INR) 
 
CSF Analysis 
 
 
Cell counts 
Pregnancy tests 
 
Total protein 
Serum pregnancy 
 
Glucose 
Urine pregnancy 
 
Table 13: 
Moderate and Marked Liver Function Abnormality Thresholds (Study 
RNX-AX204-101) 
 
AST/ALT 
Alkaline Phosphatase  Total Bilirubin 

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Moderate 
≥1.5 x ULN 
≥1.2 x ULN 
≥1.5 x ULN 
Marked 
≥3 x ULN 
≥3 x ULN 
≥2 x ULN 
ULN is defined as the upper limit of normal if the pretreatment Baseline was normal, or the 
pretreatment baseline if it was abnormal.   
Moderate abnormal liver function tests should be repeated within 1 to 2 days.  If they are 
confirmed, they should be repeated at intervals determined in consultation with the sponsor and 
medical monitor until they resolve. 
Subjects with an AST/ALT elevation between >3x and 5x ULN must have this test repeated 
upon receipt of this value and the sponsor notified.  If repeat analysis cannot be performed within 
24 hours or if an AST/ALT value >3x ULN is confirmed, the subject must discontinue treatment 
immediately and the sponsor must be notified.  The abnormal tests should be repeated within 48 
hours of receipt of this value and then at 3 to 7-day interval until they resolve.  In consultation 
with the sponsor, additional evaluation of the subject may be arranged.  The additional 
evaluation may include GI consultation and additional laboratory tests (eg, HBV, HAV, and 
CMV serology, CPK, reticulocyte count). 
14.1.5.1. Other Laboratory Tests 
A serum pregnancy test will be performed at scheduled time points (see the Schedules of Events) 
on all women in both Parts 1 and 2.  Serum tests are required at the Screening Visit (Visit 1) for 
Part 1 and Part 2.  Urine pregnancy tests are required at the Dose Visits for Part 1 and Part 2 for 
women of childbearing potential and for Visits 8 and 9 for Part 2.  
14.1.5.2. Virus Serology 
Infectious disease testing will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, 
hepatitis C antibody. 
14.1.5.3. Drug Screen 
A urine sample for drug screening will minimally include amphetamines, cocaine, marijuana, 
opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene. 
14.2. 
Adverse and Serious Adverse Events 
14.2.1. 
Definition of Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage. Examples of AEs include but are not limited to:   
• clinically significant symptoms and signs 
• abnormal test findings 
• changes in physical examination findings 
• hypersensitivity 
• progression/worsening of underlying disease 

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Additionally, AEs may include the signs or symptoms resulting from: 
• drug overdose 
• drug misuse 
• drug interactions 
• exposure in utero 
Diagnostic and therapeutic non-invasive and invasive procedures should not be reported as AEs. 
For example, an acute appendicitis that begins during the AE reporting period should be reported 
as the AE, and the resulting appendectomy should be recorded as treatment of the AE. 
14.2.2. 
Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
AE are as follows:  
• test result is associated with accompanying symptoms, and/or 
• test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
• test result leads to a discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy, and/or 
• test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
14.2.3. 
Adverse Events of Special Interest (AESI) 
Adverse Events of Special Interest (AESI) for this study include possible allergic/immune 
reactions to administration of a protein therapeutic, AEs generally associated with lumbar 
puncture, and theoretical AEs arising from axon growth.  No AESI have been identified from 
non-clinical toxicology studies with AXER-204.  The following are considered AEs of Special 
Interest for this study: 
• Immune/Allergic reactions:  fever, rash, arthralgia, myalgia, hematuria, proteinuria, 
serositis, central nervous system complications, and hemolytic anemia.  Injection site 
reactions may occur 
• Events relating to the lumbar puncture procedure: infection, postdural puncture 
headache, bleeding, brainstem herniation, meningitis, back pain, excessive CSF 
leakage requiring blood patch 
• Complicating infections: discitis and vertebral osteomyelitis 
• Neurological symptoms or injuries: low back pain, radicular injury, abducens palsy 
• Other: late onset of epidermoid tumors of the thecal sac, increased pain, increased 
spasticity 

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14.2.4. 
Serious Adverse Event (SAE) 
An SAE or serious adverse drug reaction is any untoward medical occurrence that at any dose: 
• results in death 
• is life-threatening (immediate risk of death) 
• requires inpatient hospitalization or prolongation of existing hospitalization, except 
overnight hospital stays as outlined in Section 11.2.2 Treatment Phase, Visits 2 
through 7 (Study Days 1 through 104) whereby a decision is made to keep the patient 
overnight for convenience (e.g. travel issues, local alternate accommodations not 
readily available). 
• results in persistent or significant disability/incapacity, or 
• results in congenital anomaly/birth defect. 
Medical and scientific judgment should be exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life-threatening 
and/or result in death or hospitalization. However, if it is determined that the event may 
jeopardize the subject and/or may require intervention to prevent one of the other AE outcomes, 
the important medical event should be reported as serious. 
14.2.4.1. Hospitalization 
Adverse events associated with hospitalization or prolongations of hospitalization are considered 
serious. Any initial admission (even if less than 24 hours) to a healthcare facility meets these 
criteria. Admission also includes transfer within the hospital to an acute/intensive care unit (eg, 
from the psychiatric wing to a medical floor, medical floor to a coronary care unit, neurological 
floor to a tuberculosis unit).  Exception: overnight hospital stays as outlined in Section 11.2.2 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) whereby a decision is made to 
keep the patient overnight for convenience (e.g. travel issues, local alternate accommodations not 
readily available). 
Hospitalization does not include the following: 
• rehabilitation facilities 
• hospice facilities 
• respite care (eg, caregiver relief) 
• skilled nursing facilities 
• nursing homes 
• routine emergency room admissions 
• same day surgeries (as out-subject/same day/ambulatory procedures). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not in itself an SAE. Examples include:  

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• admission for treatment of a preexisting condition not associated with the 
development of a new adverse event or with a worsening of the preexisting condition 
(eg, for work-up of persistent pre-treatment lab abnormality) 
• social admission (eg, subject has no place to sleep) 
• administrative admission (eg, for yearly physical exam) 
• protocol-specified admission during a study (eg, for a procedure required by the study 
protocol) 
• optional admission not associated with a precipitating clinical adverse event (eg, for 
elective cosmetic surgery) 
• preplanned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject. 
14.2.5. 
Adverse Event Reporting 
The investigator is to record all directly observed AEs and all AEs spontaneously reported by the 
subject in the source documents and eCRFs. 
All observed or volunteered AEs regardless of treatment arm or suspected causal relationship to 
the investigational product(s) will be reported as described in the following sections.  
For all AEs, the investigator must pursue and obtain information adequate both to determine the 
outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to the sponsor or its designated representative. For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE. The investigator is required to assess causality.  For AEs with a causal relationship to the 
investigational product, follow-up by the investigator is required until the event or its sequelae 
resolve or stabilize at a level acceptable to the investigator, and the sponsor concurs with that 
assessment.   
In order to ascertain if headaches are secondary to the lumbar puncture per se, the clinical 
characteristics of the headache, including positional exacerbations will be assessed and reported.  
For Part 1, adverse events should be recorded and monitored from the time of first dose through 
subject completion of the study up to 28 days post-dose, or until the investigator deems the AE 
as resolved or stable (unchanging).  Serious AEs should be recorded and monitored from the 
time of signing of the informed consent form (ICF) through subject completion of the study up to 
28 days after completion of the study, or until investigator deems the SAE as resolved or stable 
(unchanging). 
For Part 2, adverse events should be recorded and monitored from the time of first dose up to 28 
days after completion of the study (28 days after Month 9 visit or ET), or until the investigator 
deems the AE as resolved or stable (unchanging).  Serious AEs should be recorded and 
monitored from the time of signing of the informed consent form (ICF) through subject 
completion of the study (28 days after Month 9 visit or ET), or until investigator deems the SAE 
as resolved or stable (unchanging). 

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14.2.5.1. Severity Assessment 
The investigator will use the Common Terminology Criteria for Adverse Events (CTCAE) to 
determine the toxicity grade of AEs, found at the following URL:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily a serious event. For example, a headache may be severe (interferes significantly with 
subject's usual function) but would not be classified as serious unless it met one of the criteria for 
SAEs, listed above. 
14.2.5.2. Causality Assessment 
For all collected AEs, the investigator will determine each AE’s causality based on temporal 
relationship and his/her clinical judgement.  For each AE, relatedness will be assessed with 
respect to 1) investigational product and 2) the LP procedure.  The degree of certainty about 
causality will be graded using the categories below and the investigator must record the causal 
relationship on the eCRF, as appropriate, and report such an assessment in accordance with the 
SAE reporting requirements if applicable. 
Table 14: 
Relatedness Definitions (Study RNX-AX204-101) 
Definitely related 
There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out.  The clinical event, 
including an abnormal laboratory test result, occurs in a plausible 
time relationship to study product intake and cannot be explained 
by concurrent disease or other drugs or chemicals.  The response 
to withdrawal of the study product (dechallenge) should be 
clinically plausible. 
Probably related 
There is evidence to suggest a causal relationship, and the 
influence of other factors is unlikely.  The clinical event, 
including an abnormal laboratory test result, occurs within a 
reasonable time after intake of the study product, is unlikely to be 
attributed to concurrent disease or other drugs or chemicals and 
follows a clinically reasonable response on withdrawal 
(dechallenge). 
Possibly related 
There is some evidence to suggest a causal relationship (eg, the 
event occurred within a reasonable time after intake of the study 
product).  However, other factors may have contributed to the 
event (eg, the subject’s clinical condition, other concomitant 
events).  Although an AE may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
Unlikely to be related 
A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study product makes a causal 
relationship improbable (eg, the event did not occur within a 
reasonable time after intake of the study product) and in which 
other drugs, or chemicals, or underlying diseases provide 

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plausible explanations (eg, the subject’s clinical condition, other 
concomitant treatments). 
Not Related 
The AE is completely independent of study product intake, and/or 
evidence exists that the event is definitely related to another 
etiology.   
14.2.5.3. Exposure in Utero 
An exposure in-utero occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been 
directly exposed to (eg, environmental exposure) the investigational product, or the 
female becomes, or is found to be, pregnant after being directly exposed to the 
investigational product (maternal exposure). 
2. A male has been exposed, either due to treatment or environmental, to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy (paternal exposure). 
If any subject becomes or is found to be pregnant during the study subject’s treatment with the 
investigational product, the investigator must submit this information to the sponsor on an 
Exposure in Utero Form.  In addition, the investigator must submit information regarding 
environmental exposure to the sponsor’s product in a pregnant woman (eg, a nurse reports that 
she is pregnant and has been exposed to the investigational product by contact or spillage) using 
the Exposure in Utero Form.  This must be done irrespective of whether an adverse event has 
occurred and within 24 hours of awareness of the pregnancy.  The information submitted should 
include the anticipated date of delivery (see below for information related to induced termination 
of pregnancy). 
Follow-up is conducted to obtain pregnancy outcome information on all Exposure in Utero 
reports with an unknown outcome.  The investigator will follow the pregnancy until completion 
or until pregnancy termination (ie, induced abortion) and then notify the sponsor of the outcome. 
The investigator will provide this information as a follow-up to the initial Exposure in Utero 
Form.  The reason(s) for an induced abortion should be specified. An Exposure in Utero report is 
not created when an ectopic pregnancy report is received since this pregnancy is not usually 
viable.  Rather, a SAE case is created with the event of ectopic pregnancy. 
If the outcome of the pregnancy meets the criteria for immediate classification as a SAE (ie, 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth or neonatal death]), the investigator should follow the procedures for 
reporting SAEs. 
In the case of a live birth, the “normality” of the newborn can be assessed at the time of birth (ie, 
no minimum follow-up period of a presumably normal infant is required before an Exposure in 
Utero Form can be completed).  The “normality” of an aborted fetus can be assessed by gross 
visual inspection, unless pre-abortion test findings are suggestive of a congenital anomaly. 
Additional information regarding the exposure in utero may be requested by the investigator. 
Further follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 

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investigator must obtain permission from the subject’s partner in order to conduct any follow-up 
or collect any information. 
14.2.5.4. Reporting Requirements 
14.2.5.4.1. Serious Adverse Reporting Requirements 
Each AE is to be assessed to determine if it meets the criteria for an SAE. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.  
If an SAE occurs, the sponsor is to be notified within 24 hours of awareness of the event by the 
investigator.  In particular, if the SAE is fatal or life-threatening, notification to the sponsor must 
be made immediately, irrespective of the extent of available AE information.  This timeframe 
also applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of Exposure in Utero cases (Section 14.2.5.3). 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time of 
his/her first awareness of the AE.  
To report the SAE, complete the SAE form electronically in the eCRF for the study. When the 
form is completed, 
 will be notified electronically and will retrieve the 
form.  If the event meets serious criteria and it is not possible for you to access the internet, fax a 
paper copy to 
.  As soon as internet service has been restored, send an email to 
 at 
.  
 Safety personnel are available for 
SAE reporting on a 24-hour basis. Incoming reports are reviewed during normal business hours.”  
For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the timeframes for reporting specified above.  In addition, an investigator may 
be requested by the sponsor to obtain specific additional follow-up information in an expedited 
fashion.  This information may be more detailed than that captured on the AE page of the eCRF.  
In general, this will include a description of the AE in sufficient detail to allow for a complete 
medical assessment of the case and independent determination of possible causality. Information 
on other possible causes of the event, such as concomitant medications and illnesses must be 
provided. In the case of a patient death, a summary of available autopsy findings must be 
submitted as soon as possible to the sponsor or its designated representative. 
14.2.5.5. Non-Serious Adverse Event Reporting Requirements 
All AEs will be reported on the Adverse Event page(s) of the eCRF. It should be noted that the 
form for collection of SAE information is not the same as the Adverse Event eCRF.  Where the 
same data are collected, the forms must be completed in a consistent manner.  For example, the 
same AE term should be used on both forms.  Adverse events should be reported using concise 
medical terminology on the eCRFs as well as on the form for collection of SAE information. 
A non-serious AESI will be promptly entered in the eCRF and reported on expedited basis 
(within 24 hours) to the sponsor (or designee) to facilitate real-time review of patterns of 
toxicity. Investigators are to report AESIs in accordance with the SAE reporting process noted in 

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Section 14.2.5.4.1 within 24 hours of becoming aware of all AEs of Special Interest.  All AESIs 
must be promptly assessed by the Medical Monitor within 24 hours of receipt. 
14.2.5.6. Sponsor Reporting Requirements to Regulatory Authorities 
Adverse events reporting, including serious unexpected serious adverse reactions (SUSAR), will 
be carried out in accordance with applicable local regulations. 

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15. 
STATISTICS 
15.1. 
Sample Size 
The Part 1 sample size was derived empirically from experience with previous single ascending 
dose clinical studies in other disorders and is deemed appropriate to achieve the study objectives. 
The Part 2 sample size was selected to ensure adequate power for detecting treatment-related 
change in bilateral UEMS (Score from 0 to 50). 
A 5-point difference, between the treated and placebo groups, in the change from baseline to 6 
months in bilateral UEMS is considered clinically meaningful. Analysis of historical data for 
cervical SCI patients for the period between ~6-12 months following acute SCI indicates a 
standard deviation of bilateral UEMS change over 6 months to be around 3 to 4 points. 
With a sample size of 12 subjects per active and placebo group, Part 2 of the study has 80% 
power with Type I error of α=0.05 (two sided), assuming a 5-point difference as indicated above, 
and with a common standard deviation within each treatment group of approximately 4 in the 
change from baseline to 6 months in bilateral UEMS.  
Accounting for uncertainties in the assumptions based upon historical data used to extrapolate 
for estimating the sample size in this study and the need for estimation of missing data a sample 
size of approximately 16 subjects per treatment arm (32 total) will be randomized.    
15.2. 
Stages of Analysis 
The analysis for this study will be performed in three stages, with the first analysis performed 
upon completion of the clinical portion of Part 1, the second analysis (including the core efficacy 
assessment) performed upon completion Day 169 of Part 2 (ie, after all subjects have completed 
through Study Day 169), and the final analysis performed upon completion of the post-treatment 
follow-up phase of Part 2 (Day 253).  The methods applied to each analysis will be consistent 
with the objectives of the study.   
The blind will be maintained for all blinded study personnel (including investigators and 
subjects) through the completion of Day 169 of Part 2. After completion of Day 169, designated 
sponsor staff and external consultants/contractors required to perform the analysis will be 
unblinded to the treatment allocations in order to complete data analysis though Day 169. The 
blind will be maintained for site investigators and subjects through completion of Day 253 unless 
the blind must be broken sooner for safety or regulatory reasons. 
15.3. 
General Methods 
Data will be tabulated using both descriptive and inferential statistics where specified.   
• For Part 1, data will be tabulated by dosing cohort as well as pooled (all subjects 
combined), and no inferential statistics are planned. 
• For Part 2, data will be tabulated for each treatment group separately (placebo and 
AXER-204) to allow for visual inspection of outcomes between the arms.  Inferential 
comparison of the treatment groups is planned. 
For both Parts, all data collected will be included in by-domain data listings, sorted by subject 
number and time point, or as appropriate. 

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No hypothesis testing will be performed for demographics, background, or safety data.  
Continuous data will be summarized by presenting the number of subjects (n), means, mean 
changes from baseline, mean % changes from baseline (where appropriate), standard deviations, 
minimum, First quartile (Q1), median, third quartile (Q3), and maximum values. The number of 
subjects with missing data will be indicated. 
Categorical data will be summarized by presenting the number of subjects (n), the number of 
subjects with missing data as well as counts and percentages in each of the categories. 
Percentages will be based upon the number of subjects with available data. 
When inferential testing is applied to all efficacy assessments, dichotomous/binary categorical 
efficacy endpoints will be assessed via a 2-sided Fisher’s Exact test or Chi-square test as 
appropriate.  Continuous efficacy endpoints will also present least-squares means and p-values 
from hypothesis testing of efficacy endpoints using mixed-effects model for repeated measures 
(MMRM). 
Additional details will be included in the statistical analysis plan (SAP) which will be finalized 
prior to unblinding Part 2 of the study and any amendments to it made prior to locking the 
database and unblinding the study.   
15.4. 
Handling of Missing Data 
Every attempt will be made to collect all protocol required data at each time point.     
Imputations will only be performed for efficacy data and for missing or partial dates, missing 
severity or relationship to investigational product. Missing AE or CM dates and missing severity 
or relationship to investigational product will always use a conservative approach. Details will be 
included in the SAP.  
For subjects who discontinue treatment (for any reason), subjects will continue to be followed 
and key efficacy endpoints and safety data collected where possible. 
The primary analyses for change in bilateral UEMS will use a mixed model repeated measures 
which automatically accounts for the missing data based upon the covariate structure assumed. 
To evaluate robustness of results, sensitivity analyses will be performed with imputation 
methods for missing data. 
15.5. 
Subgroups 
The sample size precludes analysis by-subgroup.  However, exploratory assessment of any trends 
among subgroups (eg, by pre-treatment AIS grade) may be performed, after initial review if the 
data warrant. 
15.6. 
Analysis Populations 
Safety Population:  Safety outcomes will be assessed for all subjects who are given at least one 
dose of investigational product.  
Full Analysis Set (FAS) Population:  Efficacy outcomes will be evaluated using the FAS, 
defined as all subjects randomized, treated with at least 1 dose of investigational product, and 
with at least one post-baseline assessment of efficacy. 

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Per Protocol Population: The per protocol population will be a subset of FAS and include 
subjects who received at least 80% of study drug and have no major protocol deviations that 
would impact efficacy assessment.  
15.7. 
Alpha Level Considerations 
All inferential testing will be performed using two-sided 5% Type I error (α), and therefore 2-
sided p-values ≤ 0.05 will be considered statistically significant in this study. 
The first hypothesis test will be the key secondary efficacy endpoint of change in bilateral 
UEMS from baseline to Study Day 169 using the MMRM model as detailed below. Additional 
secondary efficacy endpoints tested will be the change in GRASSP prehension performance from 
baseline to Study Day 169 and of change in SCIM self-care from baseline to Study Day 169.  
15.8. 
Subject Disposition and Exposure 
The numbers of subjects randomized (Part 2 only), completing or withdrawing, along with 
reasons for withdrawal, will be summarized by dose (Part 1) and treatment group (Part 2).  
Tabulation of the number of doses of investigational product, duration of treatment as well as 
total dose given will be provided. 
15.9. 
Demographics and Baseline Characteristics Analyses 
Demographic variables (age, sex, race, and ethnicity) as well as height (cm), weight (kg), Body 
Mass Index (BMI), temperature, heart rate, blood pressure and respiratory rate or pulse oximetry 
(from the vital signs) at baseline will be summarized using descriptive statistics.  All 
demographic data will be provided in a data listing. 
15.10. 
Efficacy Endpoints 
For Part 1 efficacy, outcomes will be presented by each dosing cohort, with no inferential 
assessments among cohorts planned.  Thus, for Part 1, efficacy will be presented only 
descriptively. 
For Part 2, changes from pre-treatment to each on-treatment time point will be calculated, with 
the primary time point at Day 169.  Shifts over time in ordinal endpoints will be presented, with 
comparisons between treatment groups assessed using a CMH row mean scores statistic at each 
time point.  Slope of change will also be evaluated.  Part 2 efficacy analysis is described in the 
following sections. 
15.10.1. 
Part 2 Efficacy Endpoints 
 Change in bilateral UEMS from baseline to Day 169 will be evaluated as a key secondary 
endpoint for the trial. 
Baseline bilateral UEMS is defined as the last non-missing bilateral UEMS prior to first 
treatment in Part 2. 
The null and alternative hypothesis for this study are as follows: 
H0: μA= μP 
HA: μA≠ μP 

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Where H0 and HA refer to the Null and alternative hypothesis to be tested in this study, μA and μP 
refers to the mean change in bilateral UEMS from baseline to Study Day 169 for subjects 
randomized to AXER-204 and Placebo groups respectively.  
Analysis to compare the change in bilateral UEMS from baseline to each post baseline visit will 
be based upon a mixed-effects model for repeated measures (MMRM) for the double-blind 
period using the FAS population. 
Additional secondary efficacy endpoints will include change from baseline to Day 169 in the 
total GRASSP prehension performance score and change from baseline to Day 169 in SCIM III 
self-care score. The analyses for these scores will be handled the same way as the key secondary 
endpoint. 
Exploratory efficacy endpoints will include changes from baseline to each post baseline value in 
each of the following endpoints. 
• Change from baseline to each post baseline value for bilateral UEMS, GRASSP 
prehension performance, and SCIM III self-care scores. 
• Bilateral ISNCSCI sensory and lower extremity motor scores 
• Bilateral GRASSP strength, sensation and prehension ability scores 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q) 
− PGIC – Chronic SCI 
− SF-36 v2 Health Survey 
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL)  
• ISAFSCI.  The ISAFSCI will be used to document autonomic control of the heart, 
blood pressure, sweating and temperature regulation.  Lower urinary tract function, 
bowel function, and sexual function will be scored. 
Responder analyses may be performed to compare the proportion of responders in each treatment 
group. Details of responder analyses with thresholds used to define clinically meaningful 
improvements will be defined in the SAP.  
Sensitivity analyses of the secondary and exploratory endpoints may be performed if the 
outcomes warrant further analysis. 
15.11. 
Safety Endpoints 
The safety analysis will be descriptive in nature.  All safety data will be listed, and data will be 
tabulated by dose (Part 1) and treatment group (Part 2) where the data warrant.  Safety data 
include: 
• AEs, including assessment of lumbar infusion site  
− Events occurring prior to the first dose of investigational product or placebo will 
be defined as pre-treatment events. 

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− For Part 1, TEAEs will be defined as any AE occurring during or after the 
injection of study drug.  This will therefore include all events occurring through 
Day 29/ET. 
− For Part 2, TEAEs will be limited to those events occurring within 28 days after 
the last visit.   
Incidence of AEs will be summarized for each treatment group/cohort by MedDRA system 
organ class (SOC) and preferred term, sorted in descending frequency by SOC, and then by 
preferred term within SOC.  These summaries will be given by treatment in separate tables for 
each of the following TEAE event sets: 
• All events 
• Treatment related events (defined by a relationship to study drug of possible, 
probable, or definite). 
• Serious adverse events 
• Events leading to premature discontinuation from study 
• Events by maximum severity 
• AEs of Special Interest, ie, events relating to the lumbar puncture procedure (eg, 
infection, headache, back pain, excessive CSF leakage requiring blood patch). 
Other safety outcomes will include: 
• Clinical laboratory tests, including hematology, chemistry, metabolic, and urinalysis.  
Changes over time will be presented.  Potentially clinically significant (PCS) ranges 
will be defined and used to determine the incidence of subjects experiencing new-
onset PCS laboratory values, where new-onset is defined as a PCS value for a subject 
following initiation of study treatment for which the subject did NOT have a PCS 
value for that analyte PRIOR to initiation of study treatment. 
• Vital signs including: respiratory rate or pulse oximetry, heart rate, temperature, and 
blood pressure, as per the schedule of events.  BMI will be assessed, with height 
collected only at screening.   
• Physical examination  
• 12-lead ECG.  ECG parameters will be analyzed in a fashion similar to that of clinical 
laboratory parameters. 
Condition-specific safety outcomes will include: 
• ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• Spasticity (Modified Ashworth Scale).  A clinician administered examination for 
spasticity which measures muscle tone.  A score of 0-4 is assigned to each muscle 
group evaluated. Note: Testing will exclude fingers and thumb. 
• Pain (BPI).  A self-administered questionnaire used to assess the severity of a 
subject's pain and the impact of this pain on the subject's daily functioning. 

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Concomitant treatments will be assessed according to the timing of their start/stop dates as they 
relate to the study drug treatment, as follows: 
• Prior.  Medications with start AND stop date before date of first dose of study drug or 
placebo. 
• Concomitant.  Medications with subject exposure that includes at least one dose of 
study drug or placebo. 
• New-onset medications.  Concomitant medications with a start date AFTER the first 
dose of study drug or placebo.  New-onset medications are a subset of the full set of 
concomitant medications. 
• Post-treatment medications.  Medications with a start date at least 28 days AFTER the 
last dose of study drug or placebo. 
Changes from pre-treatment will be calculated in a similar fashion as for the efficacy endpoints, 
but no inferential statistics will be provided for safety endpoints.  Shifts from baseline in ECG 
will be tabulated for heart rate and QTcF.  Other endpoints will be assessed according to the 
scale of the variable. 
15.12. 
Pharmacokinetic Endpoints 
Concentration data in both blood serum and in cerebrospinal fluid will be assessed descriptively 
over time.  Correlation with efficacy and safety outcomes may be performed, as the data warrant. 

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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
During study conduct, the sponsor or its agent will conduct periodic monitoring visits to ensure 
that the protocol and good clinical practices (GCPs) are being followed. The monitors will 
review source documents to confirm that the data recorded on eCRFs are accurate. The 
investigator and institution will allow the sponsor monitors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. 
The study site may be subject to review by IRB/IEC, and/or to quality assurance audits 
performed by the sponsor, or companies working with or on behalf of the sponsor, and/or to 
inspection by appropriate regulatory authorities. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 

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17. 
ETHICS 
17.1. 
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, ICFs, and other relevant documents, eg, subject instructions, recruitment 
advertisements, if applicable, from the IRB/IEC. All correspondence with the IRB/IEC should be 
retained in the Investigator Site File. Copies of IRB/IEC approvals should be forwarded to the 
sponsor. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In that 
event, the investigator must notify the IRB/IEC and the sponsor in writing immediately after the 
implementation. 
17.2. 
Ethical Conduct of the Study 
The study will be conducted in accordance with the Declaration of Helsinki on Ethical Principles 
for Medical Research Involving Human Subjects, adopted by the General Assembly of the World 
Medical Association (2008). 
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonisation (ICH) guideline on Good Clinical Practice (GCP), and applicable 
local regulatory requirements and laws. 
17.3. 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names on 
any sponsor forms, reports, publications, or in any other disclosures, except where required by 
laws. In case of data transfer, the sponsor will maintain high standards of confidentiality and 
protection of subject personal data. 
The ICF must be in compliance with ICH GCP, local regulatory requirements, and legal 
requirements. 
The ICF used in this study, and any changes made during the course of the study, must be 
prospectively approved by both the IRB/IEC and the sponsor before use. 
The investigator must ensure that each study subject, or his/her legally acceptable representative, 
is fully informed about the nature and objectives of the study and possible risks associated with 
participation.  The investigator, or a person designated by the investigator, will obtain written 
informed consent from each subject or the subject's legally acceptable representative before any 
study-specific activity is performed.  The investigator will retain the original of each subject's 
signed ICF and a copy provided to each subject. 

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17.4. 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, the sponsor should be informed immediately.   
In addition, the investigator will inform the sponsor immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 

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18. 
DATA HANDLING AND RECORDKEEPING 
18.1. 
Case Report Forms 
As used in this protocol, the term eCRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
An eCRF is required and should be completed for each included subject.  The completed original 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of the sponsor or appropriate regulatory authorities, 
without written permission from the sponsor. 
The investigator has ultimate responsibility for the accuracy, authenticity, and timely collection 
and reporting of all clinical, safety, laboratory data entered on the eCRFs and any other data 
collection forms.  The eCRFs must be signed by the investigator to attest that the data contained 
on the eCRFs is true.  Any corrections to entries made on the eCRFs must be dated, initialed, and 
explained (if necessary) and should not obscure the original entry. 
In most cases, the source documents are the hospital's or the physician's subject chart. In these 
cases, data collected on the eCRFs must match the data in those charts.  
In some cases, the eCRF, or part of the eCRF, may also serve as source documents. In these 
cases, a document should be available at the investigator’s site as well as at the sponsor and 
clearly identify those data that will be recorded on the eCRF, and for which the eCRF will stand 
as the source document. 
18.2. 
Record Retention 
To enable evaluations and/or audits from regulatory authorities or the sponsor, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient information 
to link records, eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, 
SAE forms, source documents, and detailed records of treatment disposition, and adequate 
documentation of relevant correspondence (eg, letters, meeting minutes, telephone calls reports). 
The records should be retained by the investigator according to ICH, local regulations, or as 
specified in the Clinical Study Agreement, whichever is longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), the sponsor should be prospectively notified. The 
study records must be transferred to a designee acceptable to the sponsor, such as another 
investigator, another institution, or to the sponsor.  The investigator must obtain the sponsor's 
written permission before disposing of any records, even if retention requirements have been 
met. 

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19. 
PUBLICATION POLICY 
Publication of study results is discussed in the Clinical Study Agreement. 
19.1. 
Publications by Investigators 
All information concerning the product, as well as any matter concerning the operation of the 
sponsor or its delegate, such as clinical indications for the drug, its formula, methods of 
manufacture, and other scientific data relating to it, that have been provided by the sponsor or its 
delegate and are unpublished, are confidential and must remain the sole property of the sponsor 
or its delegate.  The Investigator will agree to use the information only for the purposes of 
carrying out this study and for no other purpose unless prior written permission from the sponsor 
or its delegate is obtained.  The sponsor has full ownership of the eCRFs completed as part of the 
study. 
All publications and presentations of the results of the Study are governed by the applicable 
provisions of the Clinical Trial Agreement between the sponsor (or its delegate) and the 
institution.  By signing the study protocol, the investigator agrees that the results of the study 
may be used for the purposes of national and international registration, publication, and 
information for medical and pharmaceutical professionals by the sponsor or its delegate.  If 
necessary, the authorities will be notified of the Investigator’s name, address, qualifications, and 
extent of involvement.  The Investigator may not publish or present any information on this 
study without the express written approval of the sponsor or its delegate.  Additionally, the 
sponsor or its delegate may, for any reason, withhold approval for publication or 
presentation.  Such manuscript or materials should be provided for sponsor/delegate review only 
after the final database, is available. 
 

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20. 
LIST OF REFERENCES (ALPHABETICAL) 
AXER-204 [Investigator’s Brochure] Version #2.0. New Haven, CT: ReNetX Bio, Inc. 2020 
Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids 
Barriers CNS. 2014;11:10. 
Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp synergize with Nogo-A to 
restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci. 
2010;30(20):6825–6837. 
Catz A, Itzkovich M, Tesio L, et al. A multicenter international study on the Spinal Cord 
Independence Measure, version III: Rasch psychometric validation. Spinal Cord. 
2007;45(4):275–291. 
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med 
Singapore. 1994;23(2):129–38. 
Cockcroft DW, Gault H. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16(1): 31-41. 
Fawcett JW, Curt A, Steeves JD, et al. Guidelines for the conduct of clinical trials for spinal cord 
injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and 
statistical power needed for therapeutic clinical trials. Spinal Cord. 2007;45(3):190–205. 
Guidance for industry on estimating the maximum safe starting dose in initial clinical trials for 
therapeutics in adult healthy volunteers. US Department of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research Web site. 
https://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf%23search=%27guidekines+
for+industry+sfe+starting%27 Updated July 2005. Accessed Aug 10, 2018.  
Harvey PA, Lee DHS, Qian F, Weinreb PH, Frank E. Blockade of Nogo receptor ligands 
promotes functional regeneration of sensory axons after dorsal root crush. J Neurosci. 
2009;29(19):6285–6295. 
Hladky SB, Barrand MA. Mechanisms of fluid movement into, through and out of the brain: 
evaluation of the evidence. Fluids Barriers CNS. 2014;11(1):26. 
Itzkovich M, Gelernter I, Biering-Sorensen F, et al., The Spinal Cord Independence Measure 
(SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 
2007;29(24):1926–1933. 
Ji B, Li M, Budel S, et al. Effect of combined treatment with methylprednisolone and soluble 
Nogo-66 receptor after rat spinal cord injury. Eur J Neurosci. 2005;22(3):587–594. 
Kalsi-Ryan S, Beaton D, Curt A, et al. The Graded Redefined Assessment of Strength Sensibility 
and Prehension: reliability and validity. J Neurotrauma. 2012;29(5):905–1014. 
Kalsi-Ryan S, Curt A, Verrier MC, Fehlings MG. Development of the Graded Redefined 
Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific 
to the upper limb in tetraplegia. J Neurosurg Spine. 2012;17(1 Suppl):65–76. 
Krassioukov A, Biering-Sørensen F, Donovan W, et al., International standards to document 
remaining autonomic function after spinal cord injury. J Spinal Cord Med. 2012;35(4):201–310. 

Protocol RNX-AX204-101 
 
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Kroin JS. Intrathecal drug administration. Present use and future trends. Clin Pharmacokinet. 
1992;22(5):319–326. 
Kuttler A, Dimke T, Kern S, Helmlinger G, Stanski D, Finelli LA. Understanding 
pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug 
distribution within the CSF space for intrathecal drugs. J Pharmacokinet Pharmacodyn. 
2010;37(6):629–644. 
Lee JK, Kim JE, Sivula M, Strittmatter SM. Nogo receptor antagonism promotes stroke recovery 
by enhancing axonal plasticity. J Neurosci. 2004;24(27):6209–6217. 
Li S, Liu BP, Budel S, et al. Blockade of Nogo-66, myelin-associated glycoprotein, and 
oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting 
and recovery after spinal injury. J Neurosci. 2004;24(46):10511–10520. 
Liu BP, Cafferty WBJ, Budel SO, Strittmatter SM. Extracellular regulators of axonal growth in 
the adult central nervous system. Philos Trans R Soc Lond B Biol Sci. 
2006;361(1473):1593-1610. 
Marino RJ, Kern SB, Leiby B, Schmidt-Read M, Mulcahey MJ. Reliability and validity of the 
capabilities of upper extremity test (CUE-T) in subjects with chronic spinal cord injury. J Spinal 
Cord Med. 2015;38(4):498–504. 
Marino RJ, Patrick M, Albright W, et al., Development of an objective test of upper-limb 
function in tetraplegia: the capabilities of upper extremity test. Am J Phys Med Rehabil. 
2012;91(6):478–486. 
Masserman JH. Cerebrospinal hydrodynamics: IV. clinical experimental studies. Arch Neur 
Psych. 1934;32(3):523–553. 
NSCISC Spinal Cord Injury, Facts and Figures at a Glance. National Spinal Cord Injury 
Statistical Center Web site. https://www.nscisc.uab.edu/Public/Facts%20and%20Figures%20-
%202018.pdf Accessed Aug 10, 2018.  
Ohtake Y, Li S. Molecular mechanisms of scar-sourced axon growth inhibitors. Brain Res. 
2015:1619:22–35. 
OMNIPAQUE™ (iohexol) Injection Drug Approval Package. US Department of Health and 
Human Services, Food and Drug Administration Web site. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/018956s095,020608s031lbl.pdf. 
Updated July 1993. Accessed Aug 10, 2018.  
Pandyan AD, Johnson GR, Price CI, Curless RH, Barnes MP, Rodgers H. A review of the 
properties and limitations of the Ashworth and modified Ashworth Scales as measures of 
spasticity. Clin Rehabil. 1999;13(5):373–383. 
Papisov MI, Belov VV, Gannon KS. Physiology of the intrathecal bolus: the leptomeningeal 
route for macromolecule and particle delivery to CNS. Mol Pharm. 2013;10(5):1522–1532. 
https://www.rand.org/health/surveys_tools/mos/36-item-short-form.html Updated 2018. 
Accessed Aug 10, 2018.  
Rieselbach RE, Di Chiro G, Freireich EJ, Rall DP. Subarachnoid distribution of drugs after 
lumbar injection. N Engl J Med. 1962;267:1273–1278. PubMed PMID:  13973811 

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Rieselbach RE, Morse EE, Rall DP, Frei E 3rd, Freireich EJ. Treatment of Meningeal leukemia 
with intrathecal aminopterin. Cancer Chemother Rep. 1962 Feb;16:191-6. PubMed PMID: 
14492194. 
Rieselbach RE, Morse EE, Rall DP, Frei E 3rd, Freireich EJ. Intrathecal aminopterin therapy of 
meningeal leukemia. Arch Intern Med. 1963 May;111:620-30.  PubMed PMID: 13973810. 
Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann 
Otorhinolaryngol Head Neck Dis. 2011;128(6):309–316. 
Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Curr Opin 
Neurobiol. 2014;27:53–60. 
Sharma K, Selzer ME, Li S. Scar-mediated inhibition and CSPG receptors in the CNS. Exp 
Neurol. 2012;237(2):370–378. 
SPINRAZATM (nusinersen) injection, for intrathecal use. US Department of Health and Human 
Services, Food and Drug Administration Web site. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209531lbl.pdf, Updated 2016. 
Accessed Aug 10, 2018.  
Thorne RG, Frey WH 2nd. Delivery of neurotrophic factors to the central nervous system: 
pharmacokinetic considerations. Clin Pharmacokinet. 2001;40(12):907–946. 
Wang X, Baughman KW, Basso DM, Strittmatter SM. Delayed Nogo receptor therapy improves 
recovery from spinal cord contusion. Ann Neurol. 2006;60(5):540–549. 
Wang X, Duffy P, McGee AW, et al., Recovery from chronic spinal cord contusion after Nogo 
receptor intervention. Ann Neurol. 2011;70(5):805–821. 
Wang X, Yigitkanli K, Kim CY, et al. Human NgR-Fc decoy protein via lumbar intrathecal 
bolus administration enhances recovery from rat spinal cord contusion. J Neurotrauma. 
2014;31(24):1955–1966. 
Wang X, Zhou T, Maynard GD, et al. Nogo receptor decoy promotes recovery and corticospinal 
growth in non-human primate spinal cord injury. Brain. 2020 Jun 1;143(6):1697-1713. 
 

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21. 
INVESTIGATORS AGREEMENT 
 
I have read the protocol, RNX-AX204-101 and agree to conduct this trial in accordance with all 
stipulations of the protocol and in accordance with International Conference on Harmonisation 
(ICH) and all applicable local Good Clinical Practice (GCP) guidelines, including the 
Declaration of Helsinki.  I agree to maintain the confidentiality of all information received or 
developed in connection with this protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Institution 
 
 
 
 
 
 
 
 
Date