A Phase 1/2A Study of the Safety and Efficacy of Modified Stromal Cells (SB623) in Patients With Stable Ischemic Stroke
Phase: PHASE1
Conditions: Chronic Ischemic Stroke
Sponsor: SanBio, Inc.



 
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TABLE OF CONTENTS 
1.0 
PROTOCOL SYNOPSIS ............................................................................................. 6 
2.0 
BACKGROUND ......................................................................................................... 11 
2.1 
MEDICAL NEED ...................................................................................................................... 11 
2.2 
TREATMENT OF ISCHEMIC STROKE ........................................................................................ 11 
2.2.1 
Current Therapies ........................................................................................................... 11 
2.2.2 
Time Course for Stable Stroke ........................................................................................ 11 
2.2.3 
Experimental Cellular Therapies ................................................................................... 11 
2.2.4 
Stereotactic Surgery........................................................................................................ 12 
2.3 
METHODS TO EVALUATE SEVERITY OF STROKE ................................................................... 12 
2.4 
RATIONALE FOR USE OF SB623 CELLS IN STROKE ................................................................ 12 
2.4.1 
Summary of SB623 Cells Properties ............................................................................... 12 
2.4.2 
Summary of Notch-1 Gene Properties ............................................................................ 13 
3.0 
OVERALL EXPERIENCE WITH INVESTIGATIONAL PRODUCT ............... 13 
3.1 
STUDY AGENT ........................................................................................................................ 13 
3.2 
PRECLINICAL PHARMACOLOGY ............................................................................................. 13 
3.2.1 
In Vitro ............................................................................................................................ 13 
3.2.1.1 
Protection from Oxygen/Glucose Deprivation ............................................. 13 
3.2.1.2 
Trophic Factor Secretion ............................................................................. 14 
3.2.1.3 
Extracellular Matrix Secretion..................................................................... 15 
3.2.1.4 
Epigenetic Changes ...................................................................................... 15 
3.2.1.5 
Effects on Osteogenesis and Adipogenesis................................................... 17 
3.2.1.6 
Anti-inflammatory and Immunosuppressive Properties ............................... 17 
3.2.2 
In Vivo Stroke Models ..................................................................................................... 18 
3.2.2.1 
Study N-030 .................................................................................................. 18 
3.2.2.2 
Study N-034 .................................................................................................. 20 
3.2.2.3 
Study N-035 .................................................................................................. 22 
3.3 
MECHANISM OF ACTION ......................................................................................................... 24 
3.4 
ADME .................................................................................................................................... 24 
3.4.1 
PSP021 (N-032) .............................................................................................................. 24 
3.4.2 
MPI 1295-001 ................................................................................................................. 25 
3.4.3 
N-029 .............................................................................................................................. 26 
3.4.4 
N-033 .............................................................................................................................. 26 
3.5 
OVERALL PRECLINICAL PHARMACOLOGY AND ADME SUMMARY ...................................... 27 
3.6 
TOXICOLOGY .......................................................................................................................... 31 
3.6.1 
12-Month Rat Tumorigenicity ......................................................................................... 31 
3.6.2 
4-Month Rat Tumorigenicity Bridging Study .................................................................. 31 
3.6.3 
CsA Dose Selection for Monkey Safety Study ................................................................. 32 
3.6.4 
Study Number MPI-004; MPI Research ......................................................................... 32 
3.6.5 
One-Month Cynomolgus Monkey +-CsA ........................................................................ 32 
3.6.6 
6-Month Toxicity: Cynomolgus monkey ......................................................................... 32 
3.7 
SUMMARY OF PRECLINICAL SAFETY STUDIES ....................................................................... 33 
3.8 
SUMMARY OF KNOWN AND POTENTIAL RISKS AND BENEFITS ............................................. 36 
4.0 
DESCRIPTION AND JUSTIFICATION OF TREATMENT REGIMEN ........... 36 
4.1 
DOSAGES ................................................................................................................................ 36 
4.2 
JUSTIFICATION ....................................................................................................................... 36 
5.0 
NO CYCLOSPORINE A ........................................................................................... 36 

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5.1 
RATIONALE ............................................................................................................................ 36 
5.2 
MONITORING FOR HUMORAL OR CELL-MEDIATED IMMUNE RESPONSE ............................... 37 
6.0 
STUDY PARAMETERS AND OBJECTIVES ........................................................ 37 
6.1 
PARAMETERS ......................................................................................................................... 37 
6.1.1 
Safety .............................................................................................................................. 37 
6.1.2 
Efficacy ........................................................................................................................... 37 
6.2 
OBJECTIVES ............................................................................................................................ 38 
6.2.1 
Primary Objective ........................................................................................................... 38 
6.2.2 
Secondary Objectives...................................................................................................... 38 
7.0 
SURGICAL AND IMPLANTATION PROCEDURES .......................................... 38 
8.0 
PATIENT SELECTION ............................................................................................ 39 
8.1 
INCLUSION CRITERIA ............................................................................................................. 39 
8.2 
EXCLUSION CRITERIA ............................................................................................................ 39 
9.0 
INVESTIGATIONAL PLAN .................................................................................... 40 
9.1 
OVERALL STUDY DESIGN ...................................................................................................... 40 
9.2 
DURATION OF PATIENT PARTICIPATION ................................................................................ 41 
10.0 
STUDY ASSESSMENTS ........................................................................................ 41 
10.1 
SCHEDULE OF STUDY ACTIVITIES ...................................................................................... 41 
10.2 
PRE-STUDY EVALUATION AND BASELINE (PRE-SCREEN, SCR. 1, WEEK -3 AND SCR. 2, 
 
WEEK -1) ............................................................................................................................ 44 
10.2.1 
Pre-Screen (Optional) .................................................................................................... 44 
10.2.2 
Scr. 1, Week -3 ................................................................................................................ 44 
10.2.3 
Scr. 2, Week -1 (±2 Days) ............................................................................................... 45 
10.3 
BASELINE AND ENROLLMENT (DAYS -2 TO 1, NOT INCLUDING WEEKENDS) ..................... 45 
10.3.1 
Baseline (Weekday -1 to -2 ) ........................................................................................... 45 
10.3.2 
Enrollment (Days -1 or 1) ............................................................................................... 45 
10.4 
CELL ADMINISTRATION (DAY 1) ........................................................................................ 46 
10.5 
FOLLOW-UP PERIOD (STUDY DAY 2) ................................................................................. 46 
10.6 
FOLLOW-UP PERIOD (STUDY DAY 8) ................................................................................. 46 
10.7 
FOLLOW-UP PERIOD (END OF MONTHS 1, 2, 3, 4 ± 5 DAYS) .............................................. 47 
10.8 
FOLLOW-UP PERIOD (END OF MONTH 6 ±7 DAYS) ............................................................ 47 
10.9 
FOLLOW-UP PERIOD (MONTHS 9, 12 ±7 DAYS) ................................................................. 47 
10.10 
LAST EVALUATION (END OF MONTH 24 ±14 DAYS OR EARLY WITHDRAWAL) ................ 48 
11.0 
DESCRIPTION OF STUDY TREATMENT........................................................ 48 
11.1 
STUDY DRUG DESCRIPTION ............................................................................................... 48 
11.2 
STUDY DRUG PACKAGING.................................................................................................. 48 
11.3 
STUDY DRUG SHIPMENT AND STORAGE ............................................................................ 48 
11.4 
PREPARATION AND ADMINISTRATION ............................................................................... 49 
11.5 
STUDY DRUG ACCOUNTABILITY PROCEDURES ................................................................. 49 
12.0 
CONCOMITANT MEDICATIONS ...................................................................... 49 
13.0 
STUDY WITHDRAWAL/TERMINATION ........................................................ 49 
13.1 
STUDY TERMINATION ......................................................................................................... 49 
13.2 
SITE TERMINATION ............................................................................................................. 49 
13.3 
PATIENT DISCONTINUATION .............................................................................................. 50 
13.4 
PATIENTS LOST TO FOLLOW UP ......................................................................................... 50 
14.0 
STOPPING RULES ................................................................................................ 50 

 
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15.0 
CLINICAL AND LABORATORY EVALUATIONS AND PROCEDURES ... 50 
15.1 
MEDICAL HISTORY ............................................................................................................. 50 
15.2 
PHYSICAL EXAMINATION AND VITAL SIGNS ..................................................................... 50 
15.3 
SAFETY LABORATORY........................................................................................................ 51 
15.4 
PREGNANCY TEST: SERUM OR URINE β-HCG..................................................................... 51 
15.5 
ANTIBODIES TO HLA ANTIGENS ON SB623 ....................................................................... 51 
15.6 
SERUM ANTIBODIES TO SB623 .......................................................................................... 51 
15.7 
PBMC FUNCTION ............................................................................................................... 51 
15.8 
CLINICAL STROKE EVALUATIONS ...................................................................................... 52 
15.8.1 
European Stroke Scale (ESS) .......................................................................................... 52 
15.8.2 
National Institute of Health (NIH) Stroke Scale ............................................................. 52 
15.8.3 
Modified Rankin Scale (MRS) ........................................................................................ 52 
15.8.4 
Fugl-Meyer Score ........................................................................................................... 52 
15.9 
COGNITIVE QUESTIONNAIRE .............................................................................................. 52 
15.10 
ASSESSMENT OF CELLULAR METABOLISM ........................................................................ 52 
16.0 
ADVERSE EVENTS ............................................................................................... 52 
16.1 
GENERAL INFORMATION .................................................................................................... 52 
16.2 
ADVERSE EVENT REPORTING PERIOD ................................................................................ 53 
16.3 
RECORDING OF AES ........................................................................................................... 54 
16.4 
ASSESSING RELATIONSHIP OF AE TO STUDY DRUG .......................................................... 54 
16.5 
REPORTING SERIOUS OR UNEXPECTED AES ...................................................................... 54 
16.6 
FOLLOW-UP OF ADVERSE EVENTS ..................................................................................... 55 
17.0 
EXTERNAL DATA SAFETY MONITORING BOARD .................................... 55 
18.0 
STATISTICAL METHODS ................................................................................... 55 
18.1 
OVERVIEW OF ANALYSIS ................................................................................................... 55 
18.1.1 
Safety Parameters ........................................................................................................... 55 
18.1.2 
Efficacy Parameters........................................................................................................ 56 
18.1.3 
Efficacy Objectives ......................................................................................................... 56 
18.2 
PATIENTS TO BE INCLUDED IN THE ANALYSES .................................................................. 56 
18.2.1 
Efficacy Population ........................................................................................................ 56 
18.2.2 
Safety Population ............................................................................................................ 56 
18.3 
ANALYSIS OF EFFICACY ..................................................................................................... 56 
18.3.1 
Primary Analysis ............................................................................................................ 56 
18.3.2 
Secondary Analyses ........................................................................................................ 56 
18.4 
ANALYSIS OF SAFETY ......................................................................................................... 57 
18.5 
DETERMINATION OF SAMPLE SIZE ..................................................................................... 57 
18.6 
DEVIATIONS FROM THE PROTOCOL ANALYSIS PLAN ......................................................... 57 
19.0 
ADMINISTRATION OF THE STUDY ................................................................ 57 
19.1 
REGULATORY CONSIDERATIONS ........................................................................................ 57 
19.2 
INDEPENDENT ETHICS COMMITTEE (EC)/INSTITUTIONAL REVIEW BOARD (IRB) ............ 57 
19.3 
PATIENT INFORMATION AND INFORMED CONSENT ............................................................ 58 
19.4 
ADHERENCE TO THE PROTOCOL ......................................................................................... 58 
19.5 
PROTOCOL MODIFICATIONS ............................................................................................... 59 
19.6 
DATA COLLECTION ............................................................................................................ 59 
19.7 
MAINTAINING RECORDS..................................................................................................... 60 
19.8 
MONITORING, AUDITING, INSPECTING ............................................................................... 60 
19.9 
CONFIDENTIALITY .............................................................................................................. 60 
19.10 
PUBLICATION POLICY ......................................................................................................... 61 

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20.0 
APPENDIX A: SAMPLE INFORMED CONSENT ............................................ 62 
21.0 
APPENDIX B: ESSENTIAL STUDY DOCUMENTS......................................... 70 
22.0 
APPENDIX C: WHO STANDARD TOXICITY CRITERIA ............................. 74 
23.0 
APPENDIX D: COGNITIVE FUNCTION TEST BATTERY ........................... 81 
24.0 
REFERENCES ........................................................................................................ 82 
 
LIST OF TABLES 
Table 1 
Summary of Preclinical Pharmacology and ADME Studies ........................................ 28 
Table 2 
Summary of Preclinical Safety Studies .......................................................................... 34 
Table 3 
Dosages, Volumes and Cell Concentrations ................................................................... 36 
Table 4 
Study Procedures Flow Chart ......................................................................................... 42 
Table 5 
Relationship of Adverse Event to the Administration of the Study Drug ................... 54 
Table 6 
WHO (World Health Organization) Toxicity Criteria by Grade ................................ 75 
Table 7 
Cognitive Function Test Battery ..................................................................................... 81 
 
LIST OF FIGURES 
Figure 1 
SB623 co-culture protects primary rat hippocampal slices from OGD ................... 14 
Figure 2 
Trophic Factors Released in Conditioned Medium ................................................... 14 
Figure 3 
SB623 Cells Secrete Beneficial Extracellular Matrix ................................................ 15 
Figure 4 
CpG methylation status of 5 different genes for 3 donors ........................................ 16 
Figure 5 
Differentiation potential of MASC and SB623 ........................................................... 17 
Figure 6 
Elevated Body Swing Test: 1-Month Rat Study ........................................................ 19 
Figure 7 
Bederson Neurologic Exam: 1-Month Rat Study ...................................................... 19 
Figure 8 
Comparison of SB623 and MSC in MCAo Rat Model .............................................. 20 
Figure 9 
Elevated Body Swing Test: 3-Month Rat Study ........................................................ 20 
Figure 10 
Bederson Neurologic Exam: 3-Month Rat Study ...................................................... 21 
Figure 11 
CsA is not Needed for Long-Term Improvement of Stroke Deficits ........................ 23 
Figure 12 
Primate Needle Track ................................................................................................... 25 
Figure 13 
Primate Y-ISH Staining ............................................................................................... 25 

 
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1.0 
PROTOCOL SYNOPSIS 
Protocol #: 
SB-STR01 
Title: 
A Phase 1/2A Study of the Safety and Efficacy of Modified Stromal Cells 
(SB623) in Patients with Stable Ischemic Stroke 
Study 
Objectives: 
Primary: To evaluate the safety and tolerability of intracranial 
administration of SB623 cells.  Safety will be determined during 2 years 
post-implant. 
Secondary: To evaluate clinical and radiographic response to 3 dose levels 
of intracranial administration of SB623 cells.  The major efficacy 
endpoints will be determined at 6 months; measures will also be at 1, 2, 3, 
4, 9, 12, and 24 months. 
Background and 
Rationale 
SB623 cells are adult bone-marrow-derived cells that have been transiently 
transfected with a plasmid construct encoding the intracellular domain of 
human Notch-1.  SB623 cells secrete factors that protect neurons in models 
of ischemic insult.  In a rat occlusion model of stroke to the middle 
cerebral artery region, implantation of SB623 into and around the area of 
the infarct resulted in improvement of neurological behavior. 
The safety of implanted SB623 cells was evaluated in a 6-month primate 
study and in 2 nude rat studies (4 mos. and 12 mos.).  The primates were 
immunosuppressed with cyclosporine and the nude rats further 
immunosuppressed with an anti-NK cell antibody.  There were no SB623-
related clinical, laboratory, or histological abnormalities found. 
The stereotactic surgical delivery of cells to patients with stroke has been 
shown to have an acceptable safety profile in two prior clinical studies with 
another product.  In addition, a retrospective study of over 2,650 patients 
undergoing stereotactic surgery during a 28-year period at one major clinic 
has shown a high degree of safety with the procedure. 
Finally, the European Stroke Scale (ESS), the Modified Rankin Score, the 
National Institute of Health Stroke Scale (NIHSS), the Fugl-Meyer scale 
for motor function, and a neurocognitive battery (e.g., Rey Complex Figure 
Test), have been used and validated, at least for acute stroke.  
Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging 
has shown that changes in metabolic activity relative to baseline in the 
infarct area and surrounding areas correlated with performance on the 
motor subscale of the ESS. 
Study Design 
This is an open-label safety study of stereotactic, intracranial injection of 
SB623 cells in patients with hemiparesis from stable ischemic stroke who 
have remained stable during the prior 3 weeks (based on NIHSS 
assessments at weeks -3 and -1).  While primarily a safety study, efficacy 
parameters will also be evaluated.  Three cohorts will receive escalating 
single doses of SB623, which are to be stereotactically implanted into grey 
or white matter sites adjacent to the infarct region.  One burr-hole 
craniostomy will be created, and cells implanted using 3 needle tracks with 
5 deposits for each track at varying depths around the damaged area.  Cell 

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implantation will be standardized as to volume (20 µL/deposit) and rate (10 
µL/min), with spacing between each implant of approximately 5-6 mm.  
Each deposit is expected to take approximately 2-3 minutes, with each 
needle track being completed within 15 minutes.  Each cohort will consist 
of 6 subjects defined by an increasing total number of cells implanted.  
Safety will be monitored by the Investigator, Principal Monitor, Medical 
Monitor, and an external Data Safety Monitoring Board.  For the first 
cohort, a single patient will first be dosed, then evaluated over a 2 week 
period for safety prior to dosing the next member of the cohort.  This 2-
week interval will continue between each of the remaining members of this 
cohort.  If the safety profile is acceptable for a cohort, and after review by 
the DSMB, the first patient in each subsequent cohort will be dosed, 
beginning 4 weeks after dosing of the last patient of the prior cohort.  For 
the second and third patients in each of the subsequent cohorts, there will 
be an interval of 2 weeks after the prior patients prior to further enrollment. 
Safety will be monitored by clinical symptoms, laboratory findings, and 
MRI brain imaging.  Two or more serious adverse events will trigger a 
review by the DSMB before continuing enrollment.  Possible efficacy will 
be determined based on changes in the clinical measures of stroke through 
standardized assessments and on FDG-PET brain imaging. 
A dose-limiting toxicity will be defined as any grade 3 or 4 event which is 
at least possibly related to study product or administration procedure  If the 
first patient in a cohort has a dose-limiting toxicity attributable to the 
SB623 cells, then no further patients will be dosed in that cohort until a 
comprehensive evaluation has been conducted.  If 2 of 6 patients in a 
cohort have a dose-limiting toxicity attributable to the SB623 cells, then no 
further patients will be dosed in that or higher-dose cohorts.  Each dose-
limiting-toxicity will be evaluated by the DSMB.  The DSMB shall be the 
final arbitrator for attributions. 
Patient 
Population 
Adult patients with hemiparesis from stable ischemic stroke.  Stable stroke 
will be defined as 6-60 mos. post stroke with motor neurological deficit, 
post-physical therapy, and with no more than ±1 point change in clinical 
stroke evaluation (using NIHSS) in the 3 weeks prior to study enrollment.  
The interval of 6-60 months for this patient population is based on a 
number of studies that have shown that over 90% of ischemic stroke 
patients are stable by 90 days post-stroke.  The upper limit of 36 mos. was 
chosen to allow for the possibility of some brain tissue plasticity 
remaining, while mainly to increase the potential patient population. 
Statistical 
Considerations 
Based on the animal data, no dose-limiting toxicity is expected.  However, 
if the true rate of toxicity is 40%, a sample size of 6 patients per cohort 
would result in a < 5% chance of missing a dose-limiting toxicity.  A 
pooled analysis of changes from Baseline for all patients for each of the 
efficacy parameters will be conducted.  In addition, a possible dose-
response will be evaluated. 
No. of Patients 
18 Evaluable 

 
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No. of Study 
Sites 
Up to 8 
Inclusion 
Criteria 
• Age 18-75 years 
• Documented history of completed ischemic stroke in subcortical region 
of MCA or lenticulostriate artery with or without cortical involvement, 
with correlated findings preferably by MRI or by CT if MRI is 
contraindicated 
• Between 6 and 60 months post-stroke, and having a motor neurological 
deficit 
• No significant further improvement with physical therapy/rehabilitation 
(confirmed by no change in NIHSS greater than ±1 within three weeks 
prior to enrollment) 
• Modified Rankin Score of 3 or 4 
• NIH Stroke score of >7 
• Two evaluations during prior 3 weeks with no more than  ±1 point 
change in clinical evaluation using the NIH Stroke Scale 
• Able and willing to undergo computed tomography (CT), magnetic 
resonance imaging (MRI), and positron-emission tomography (PET) 
scans of the head 
• Agree that use of antiplatelet, anti-coagulant, or non-steroidal anti-
inflammatory drugs to be determined by the local medical staff and in 
accordance with the ACCP 2012 guideline “Perioperative Management 
of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of 
Thrombosis, 9th Edition: American College of Chest Physicians 
Evidence-Based Clinical Practice Guidelines”, if applicable1, provided 
that no antiplatelet, anti-coagulant, or non-steroidal anti-inflammatory 
drugs are to be restarted post surgery until after the Day 8 MRI is read 
and are determined to be safe to re-start 
• Normal emotional status; i.e., no disabling psychological deficits 
• Ability of patient or legal authorized representative to understand and 
sign an Informed Consent 
Exclusion 
Criteria 
• History of more than 1 symptomatic stroke 
• History or presence of any other major neurological disease 
• Cerebral infarct size >100 cm3 measured by MRI 
• Myocardial infarction within prior 6 mos. 
• Known presence of any malignancy except squamous or basal cell 
carcinoma of the skin 
• History of CNS malignancy 
• History of seizures or current use of antiepileptic medication 
• Uncontrolled systemic illness, including, but not limited to: 
hypertension (systolic >150 mm Hg or diastolic >95 mm Hg); diabetes; 
renal, hepatic, or cardiac failure 
• Uncontrolled psychiatric illness, including depression (Hamilton Score 
of >14) 
• Total bilirubin >1.5 mg/dL 
• Serum creatinine >1.5 mg/dL 

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• Hemoglobin <10.0 g/dL  
• Absolute neutrophil count <2000 /mm3 
• Lymphocytes <800 /mm3 
• Platelet count <100,000/mm3 
• Liver disease supported by AST (SGOT) or ALT (SGPT) ≥2.5 x 
institutional upper limit of normal 
• Serum calcium >11.5 mg/dl 
• International Normalized Ratio of Prothrombin Time (INR) >1.2 
• Signs and symptoms of intracranial herniation or increased intracranial 
pressure 
• Acute intracranial hemorrhage 
• Use of neuroleptic drugs 
• Unexplained abnormal preoperative test values (blood tests, 
electrocardiogram [ECG], chest X-ray); patients with 
electrocardiographic evidence to suggest a recent myocardial 
infarction, major dysrhythmia, x-ray evidence of infection, atrial 
fibrillation, or congestive heart failure will be excluded 
• Participation in any other investigational trial within 4 weeks of initial 
screening and within 7 weeks of study entry 
• Botulinum toxin injection, phenol injection, intrathecal baclofen, or any 
other interventional treatments for spasticity (except bracing and 
splinting) within the previous 3 mos. 
• Ongoing use of herbal or other non-traditional drugs 
• Ongoing drug or alcohol abuse 
• Contraindications to head CT, MRI, or PET 
• Pregnant or lactating 
• Female patients of childbearing potential unwilling to use an adequate 
birth control method during the first 6 months of the study 
• Presence of serum antibodies to donor SB623 cells with a Luminex 
value of >1000 MFI (Maximum Fluorescence Intensity): HLA Class I 
(HLA-A*23:PWMV, HLA-A*68:CGBR; HLA-B*45:FJH, HLA-
B*53:KJW; or HLA-Bw4, HLA-Bw6; HLA-Cw*04:SSWB, HLA-
Cw*16:01); or Class II (HLA-DRB1 *13:NGUB, HLA-DRB1 *16:02; 
HLA-DQB1*05:CHZY, HLA-DQB1*05:BK; HLA-DQA1*01:DVB, 
HLA-DQA1*X, HLA-DRB3,4,5: 3*03:01, HLA-DRB3,4,5: 5*02:02) 
• Any other condition or situation that the investigator believes may 
interfere with the safety of the subject or the intent and conduct of the 
study 
Dosage, Mode of 
Administration, 
and Treatment 
Duration 
All dosages of cells to be administered stereotactically through one burr-
hole craniostomy within and adjacent to the infarct using 3 needle tracks 
and 5 cell deposits per track at varying depths (20 µL each). 
Cohort 1: 
2.5 X 106 SB623 Cells 
(8.3 X 106 cells/mL) 
Cohort 2: 
5.0 X 106 SB623 Cells 
(17 X 106 cells/mL) 
Cohort 3: 
10 X 106 SB623 Cells  
(33 X 106 cells/mL) 

 
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Duration of 
Patient Study 
Participation 
Two years (except if there is an unresolved Grade 2 adverse event at least 
possibly related to the therapy, in which case the patient will be followed 
until resolved or reduced to Grade 1). 
Cell Storage 
Conditions and 
Reconstitution 
SB623 cells will be kept frozen in vapor phase liquid nitrogen at study sites 
within the shipping container until ready for use, then thawed, washed, and 
re-suspended at one of 3 different concentrations in Plasma-Lyte A® as 
summarized above. 
Efficacy 
Parameters 
• Clinical improvement of stroke symptoms using the European Stroke 
Scale, the NIH Stroke Scale, and the Modified Rankin Scale, 
improvement in motor functions using the Fugl-Meyer scale, and 
improvement in cognitive status using a test battery (including Rey 
Complex Figure Test) 
• Increase in fluorodeoxyglucose (FDG) uptake measured by positron 
emission tomography (PET) 
Safety 
Parameters 
• SB623- and surgical-related adverse events using WHO toxicity 
criteria 
• Adverse changes imaged by head MRI (edema, adverse anatomical 
changes) 
• Serious adverse events (SAEs) using WHO toxicity criteria 
• Serum chemistry and hematology 
Other 
Laboratory 
Parameters 
• Serum levels of antibodies to SB623 cells and PBMC function assay 
• Development of serum antibodies to donor SB623 cells: HLA Class I 
(HLA-A*23:PWMV, HLA-A*68:CGBR; HLA-B*45:FJH, HLA-
B*53:KJW; or HLA-Bw4, HLA-Bw6; HLA-Cw*04:SSWB, HLA-
Cw*16:01); or Class II (HLA-DRB1 *13:NGUB, HLA-DRB1 *16:02; 
HLA-DQB1*05:CHZY, HLA-DQB1*05:BK; HLA-DQA1*01:DVB, 
HLA-DQA1*X, HLA-DRB3,4,5: 3*03:01, HLA-DRB3,4,5: 5*02:02) 

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2.0 
BACKGROUND 
2.1 
Medical Need 
Stroke is the third leading cause of death in the United States, Europe, and most countries in 
the world.2,3,4,5  In 2007, nearly 700,000 new or recurrent strokes and 160,000 stroke-related 
deaths were expected to occur in the United States.6,7  In addition, magnetic resonance 
imaging (MRI) studies reveal that nearly 22 million asymptomatic strokes occur every year.8  
Stroke is also a major cause of prolonged neurologic disability in adults,3,4,6,8,9 with an annual 
economic burden of over $62 billion in the United States.10  In addition to the main risk 
factor of hypertension, diabetes is also recognized as a significant risk factor.11  Thus, 
incidences of stroke-related deaths and disability are expected to rise even higher as the 
population ages,2,4,5,12,13 and as the incidence of diabetes increases.14 
2.2 
Treatment of Ischemic Stroke 
2.2.1 Current Therapies 
For acute ischemic stroke, immediate post-stroke interventions focus on life support through 
respiratory and cardiac control of blood pressure, monitoring oxygen saturation and blood 
glucose level, prevention of metabolic disturbances, maintenance of organ function, and 
management of elevated intracranial pressure.15  The only approved therapies in the U.S. are 
thrombolytic agents, to be given within 3 hrs. of onset of the stroke.  It has been estimated 
that less than 5% of acute ischemic stroke patients receive this therapy, probably due to the 
stringent criteria for thrombolytic intervention, the patient arrival beyond the 3-hour window, 
and lack of adequate facilities at many hospitals.16  As the stroke fully develops, and the 
patient stabilizes, some regimen of physical therapy is almost universally applied. 
2.2.2 Time Course for Stable Stroke 
Acute ischemic stroke is generally accepted to be defined as up to several days, if not hours.  
Longitudinal studies on rates of improvement after ischemic stroke have shown that 90% of 
patients with ischemic stroke achieve no further improvement after about 90 days.17  This 
time period was found to be independent of degree of initial severity regardless of methods 
used to assess by most investigators,17,18,19 while others found that severe and very severe 
cases continued to have slight improvement for 2-3 weeks more using a different method of 
assessment.20 
2.2.3 Experimental Cellular Therapies 
For the stable stroke patient, no proven therapies exist to reverse the damage and improve 
overall motor or cognitive function.  As reviewed recently, a variety of cellular therapies 
have been examined.21,22,23  Clinical trials with these agents have so far been limited, with 
only three trials conducted and reported to date, with only two having used human cells. 
Fetal cells from the porcine lateral ganglionic eminence which had been shown to improve 
deficits in an animal model of Huntington’s disease,24,25 and in an animal model of middle-
cerebral artery occlusion26 were studied in a Phase 1 clinical trial.  Five patients with chronic, 
stable, moderate-sized basal ganglia infarcts received intrastriatal implantation of the cells.  
One of the patients developed a cortical vein occlusion, and the study was terminated by the 
Food and Drug Administration.  Attribution of the adverse event has not been clarified.  
None of the patients showed improvement on the Modified Rankin Scale.23 

 
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Cultured human neurons derived from an embryonal carcinoma cell line that was isolated 
from a teratocarcinoma (LBS-Neurons) which had been shown to improve deficits in an 
animal model of middle-cerebral artery occlusion27 were studied in an open-label Phase 1 
clinical trial.28, Initially, 4 patients with stable stroke received stereotactic implants 2 million 
cells in one needle track into the area of infarction, divided into 3 implants with 20 µL per 
implant..  Subsequently, 8 additional patients were randomized to receive either single-pass 
(2 million cells in 3 implants) or 3-pass (6 million cells in 9 implants) injections into the area 
of infarction.  All patients also received cyclosporine A orally.  The outcomes were that the 
procedures and injections were well tolerated with a mean improvement in all patients by the 
European Stroke Score (ESS) that was statistically significant, and with an improvement in 
FDG-PET scans in half of the patients at 6 months. 
Based on the encouraging results from that Phase 1 study, an open-label, observer-blinded 
Phase 2 study was conducted with LBS-Neurons in 18 patients who were randomized 
between surgery with 5 or 10 million cells implanted (25 implantation sites) plus 
rehabilitation (14 patients), or rehabilitation alone (4 patients), with all surgical patients also 
receiving cyclosporine A orally.29  The patient mix was approximately an equal number with 
ischemic or hemorrhagic stroke.  The outcomes were that both the procedure and the cell 
implants were again well tolerated.  There was no statistically-significant improvement in the 
ESS between groups, although some improvements were found when patients were analyzed 
as their own controls.  Some cognitive improvements were also noted.  Finally, there were 
statistically-significant improvements in some of the Fugl-Meyer assessments, but not on 
overall motor function. 
2.2.4 Stereotactic Surgery 
In addition to the two studies referred to above with LBS Neurons, a retrospective study of 
over 2,650 patients who received stereotactic surgery over a 28-year period at one major 
clinic found an incidence of surgery-related complications to be <1%, establishing the high 
degree of safety for this procedure.  Complications reported included a need for a craniotomy 
for hematoma evacuation (0.36%), perioperative seizures (0.36%), burr hole infections 
(0.08%), and death (0.08%).30 
2.3 
Methods to Evaluate Severity of Stroke 
No one method has been shown to be adequately encompassing to evaluate the severity of 
stroke, since a constellation of symptoms is usually present.  Accordingly, neurologists use 
several methods to score neurological deficits, including standardized stroke scales such as 
the European Stroke Scale (ESS),31 the National Institutes of Health Stroke Scale 
(NIHSS),32,33 the Modified Rankin Scale (MRS),34,35 the Hemispheric Stroke Scale (HSS),36 
the Fugl-Meyer scale for motor deficits,37,38 and a battery of cognitive tests.39  A variety of 
other tests have also been used. 
2.4 
Rationale for Use of SB623 cells in Stroke 
2.4.1 Summary of SB623 Cells Properties 
SB623 cells are human bone marrow-derived cells and are being developed as an allogeneic 
cell therapy for chronic, stable stroke and other neurodegenerative conditions.  SB623 cells 
are generated under GMP conditions by the transient transfection of bone marrow stromal 
cells (MASC) with a plasmid encoding the human Notch-1 intracellular domain.40  This 

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transfection is considered transient because the plasmid rapidly disappears with further 
expansion/passaging of the cells.  Thus, the gene and its products which were initially 
detected at very low levels are not expected to be present at all after a short time post-
implantation. 
Unlike the MASC cells used to produce SB623 cells, the product has limited potential to 
differentiate into bone or adipose cells. 
2.4.2 Summary of Notch-1 Gene Properties 
Notch-1 is involved in the regulation of the development process in many species, including 
humans.  Notch is a heterodimeric transmembrane receptor.  Its natural ligands (Serrate, 
Jagged, Delta) are also integral membrane proteins, revealing a cell-cell or juxtacrine role for 
Notch.  Once stimulated by a ligand, Notch is proteolytically cleaved releasing the Notch 
IntraCellular Domain (NICD) from the plasma membrane.  Once released, the NICD 
migrates to the nucleus where it plays the role of an activating transcription factor for a 
number of genes. 
3.0 
Overall Experience with Investigational Product 
This section includes a brief summary of preclinical data available on SB623.  More detailed 
information can be found in the Investigator’s Drug Brochure for SB623 cells. 
3.1 
Study Agent 
SB623 cells are bone-marrow-derived stromal cells that have been transiently transfected 
with the intercellular domain of the human Notch-1 gene. 
3.2 
Preclinical Pharmacology 
3.2.1 In Vitro 
The in vitro characterization of SB623 cells has included 8 basic areas: fate of SB623 cells, 
protection of primary neurons from Oxygen Glucose Deprivation, the secretion of 
neurotrophic factors, Notch-1 signal transduction, epigenetic changes, osteo- and 
adipogenesis, and anti-inflammatory properties of SB623.  See the Investigator’s Drug 
Brochure for details on these studies. 
3.2.1.1 Protection from Oxygen/Glucose Deprivation 
Figure 1 shows the effects of SB623 co-culture on hippocampal slices.  Similar protection 
was observed using SB623 conditioned medium (not shown) Taken together, these results 
strongly suggest that SB623 cells secrete soluble factors that can protect neurons. 

 
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Figure 1 
SB623 co-culture protects primary rat hippocampal slices from OGD 
 
Data are expressed as fold change over untreated controls.  Measurements were taken at 
24 and 48 hours post OGD.  SB623 cells were produced from 5 different donors. 
 
3.2.1.2 Trophic Factor Secretion 
The starting material for SB623 is bone marrow aspirate, from which are isolated Marrow 
Adherent Stromal Cells (MASC) also known as Marrow Stromal Cells (MSC).  These cells 
have been extensively studied and are known to secrete a wide variety of factors.  
Independent of MSCs, a variety of factors have been shown to be implicated in beneficial 
effects for cerebral ischemia.  Figure 2 shows the list of cytokines that were investigated.  
The ones in blue are secreted by both SB623 and MSC.  The ones underlined are secreted by 
SB623 in much higher concentrations compared to MSC. 
Figure 2 
Trophic Factors Released in Conditioned Medium 
• Custom antibody 
array (RayBiotech)
• 30 cytokines
VEGF
HB-EGF
TNFα
GDNF
TGFβ
GCSF
TGFα
FGF-7
SDF-1
FGF-2
PDGF-AA
Erythropoietin R
NT-3
EGF
MMP-1
DKK-4
MCP-1
DKK-1
LIF
CNTF
IL-8
b-NGF
IL-6
BMP-7
IL-1α
BMP-6
IGF-I
BMP-4
HGF
BDNF
 
The right panel shows the results from a Ray Biotech antibody array. The list on the right 
show factors found in MASC and SB623 conditioned media (blue) and those preferentially 
produced by SB623 (underlined). 
 
0.0
5.0
10.0
15.0
20.0
25.0
30.0
24
48
Time Post-OGD (hours)
Fold Change in LDH Release
 vs. Matched Control
OGD Only
OGD + D1 SB623
OGD + D2 SB623
OGD + D3 SB623
OGD + D4 SB623
OGD + D5 SB623

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3.2.1.3 Extracellular Matrix Secretion 
SB623 cells have been shown to secrete beneficial extracellular matrix in culture with rat 
neural cells, as measured by a increase in growth of intact cells.  This is illustrated in Figure 
3 below. 
Figure 3 
SB623 Cells Secrete Beneficial Extracellular Matrix 
 
0
20
40
60
80
100
120
140
160
180
0
5
10
15
20
25
Days of culture
LDH, mU
MSC-ECM
SB623-ECM
PDL
A
ECM
PDL
B
MASC-ECM
 
Panel A shows cell mass (as Lactate Dehydrogenase) vs. days in culture. Poly-D-lysine 
(PDL) serves as a control. Panel B show a photomicrograph from MASC. SB623 and PDL 
respectively. 
 
In this experiment, culture of MSC or SB623 with poly-D lysine as control resulted in 
secretion of matrix.  When rat neuronal cells, including glia, were allowed to grow on the 
matrices, the rate growth was much faster with SB623 matrix compared to MSC-matrix, as 
measure by the number of intact cells using concentration of LDH after lysing as a surrogate.  
As seen in B of the figure, both SB623 matrix and MSC matrix resulted in rat neurons 
Secretion of Matrix 
 
3.2.1.4 Epigenetic Changes 
SB623 cells are produced by transient transfection of MASC cells.  A stable phenotypic 
change in the absence of a change in the genomic sequence is defined as epigenetic.  There 
are a wide variety of epigenetic marks that can specifically alter gene expression and alter 
cellular behavior.  These include covalent modifications (acetylation, methylation, etc.) of 
the N-terminal “tails” of the histones, creating more or less densely packed chromatin and 
thereby altering the accessibility of RNA polymerase and other components of the 
transcriptional apparatus to their DNA targets.  This is one of the basic mechanisms 
controlling gene expression.  Another form of epigenetic control is accomplished by DNA 
methylation.  The sequence CpG is underrepresented in the genome.  There are enzymes that 
can methylate the 5 position of cytosine de novo and others that complete the methylation of 
hemi-methylated CpG/GpC basepairs, creating a heritable mark.  There are high densities of 

 
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CpGs near the promoters of about half of the genes in the human genome.  These CpG 
“islands” are typically in hypomethylated in undifferentiated cells.  When the CpG island of 
a particular gene becomes hypermethylated, chromatin density increases and down-regulates 
the expression of that gene. 
SB623 cells have an altered developmental potential when compared to the MASC source 
cell.  We reasoned that the pattern of CpG methylation might be different in SB623 vs. 
MASC.  In ongoing work with a contract research laboratory (Epiontis, GmbH, Berlin), we 
performed bisulfite sequencing on CpG islands associated with a collection of candidate 
genes.  The results are shown in Figure 4. 
Figure 4 
CpG methylation status of 5 different genes for 3 donors 
 
Each individual colored bar represents a PCR amplicon within a gene-associated CpG 
island. Multiple amplicons represent each gene. The sequence pre- and post-bisulfite 
conversion repeals the number of methyl-Cs present in the amplicon. The degree of 
methylation is indicated by color (yellow = completely unmethylated, blue = 100% 
methylated. White bars mean no sequence could be obtained. MASC (control) and SB623 
(target) from three different donors were compared. 
 

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Figure 4 reveals that 4 of the 5 genes examined (LRKK1, ROPN1L, IGF2R and SDF4) are 
more methylated in SB623 than in MASC.  One gene (DNMT3b) is less methylated in 
SB623 compared to MASC. 
We are currently looking more globally at DNA methylation.  If this pattern holds, (increase 
methylation in SB623) we can conclude that SB623 cells are more differentiated than 
MASC.  This should also lead to candidate genes to help explain SB623 properties at a 
molecular level. 
3.2.1.5 Effects on Osteogenesis and Adipogenesis 
MASCs are also known as Marrow Stem Cell because of their ability to differentiate into 
tissues derived from the embryonic mesenchyme, specifically bone, cartilage and adipose.  
We compared the osteogenic and adipogenic potential of SB623 to MASC using standard 
differentiation protocols. 
After several weeks of differentiation, the osteogenic cells were stained for bone formation 
with alizarin red and the adipogenic cells stained for fat with Oil Red O.  The results are 
shown below in Figure 5. 
Figure 5 
Differentiation potential of MASC and SB623 
 
Cells were grown in osteogenic and adipogenic media (plus or minus BMP6) for several 
weeks and then stained with Alizarin Red (bone) or Oil Red O (fat). 
 
MASC cells readily differentiated in to bone and adipose as expected.  On the other hand, 
SB623 cells are dramatically attenuated in their ability to differentiate into these tissues.  
This has been demonstrated for multiple lots of SB623 (not shown).  These finding suggest 
that SB623 may be less likely than MASC to form ectopic bone or fat after implantation in 
vivo. 
3.2.1.6 Anti-inflammatory and Immunosuppressive Properties 
Bone marrow stromal cells, also known as mesenchymal stem cells (MSCs) or marrow-
adherent stem cells (MASCs) are known to have anti-inflammatory and immunosuppressive 
properties.  Since SB623 cells are derived from MASCs, the anti-inflammatory and 
immunosuppressive properties of these cells were assessed.  In a Mixed Lymphocyte 

 
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Reaction (MLR), immune cells from two unrelated donors are mixed and immune cell 
activation and proliferation are measured as an indicator of adaptive and innate immune 
activity.  The results from this experiment demonstrated that, in the presence of SB623 cells, 
the activation and proliferation of T cells is attenuated.  In another series of experiments the 
effects of SB623 on dendritic cell formation was measured, since dendritic cells are the 
primary initiators of the T cell response in the MLR.  To assess the impact of SB623 cells on 
dendritic cells, a co-culture assay between immature dendritic cells and SB623 cells was 
performed.  The results demonstrated that SB623 cells reduce the levels of co-stimulatory 
molecules on dendritic cells.  Collectively, these anti-inflammatory and immunosuppressive 
properties may contribute to SB623’s regenerative properties and seem to obviate the need 
for immunosuppressive drugs during SB623 therapy. 
3.2.2 In Vivo Stroke Models 
3.2.2.1 Study N-030 
Therapeutic Benefits of SB623 in Experimental Stroke 
SB623 cells or vehicle were implanted into the striatum of male Sprague-Dawley rats that 
had been stroked with the MCAo procedure in the right hemisphere, and immunosuppressed 
with CsA, 10 mg/kg/day i.p.  At 4 weeks post-stroke, 3 groups of 10 animals each were 
implanted with either 90,000 SB623 cells (low dose), 180,000 SB623 cells (high dose) or an 
equivalent volume of sterile buffer alone (vehicle).  Rats were immunosuppressed throughout 
the planned one-month post-transplantation survival time.  Behavioral measurements were 
made pre-stroke, immediately post-stroke, and at 7 days, 14 days, and 28 days post-stroke. 
At 7 days and up to one month post-transplantation, the animals treated with SB623 cells 
showed significant behavioral improvement (p≤0.00001) with both the elevated body swing 
test and the Bederson score compared to the control group, with the higher dose of SB623 
cells suggesting a trend of improvement compared to the lower dose.41  See Figure 6 and 
Figure 7. 
Histological evaluation of the brain at 28 days using the anti-human nuclear antibody HuNu 
showed 7-9% cell survival.  Staining with MAP2, a neuronal marker along with HuNu 
showed that < 1% of the cells had differentiated along a neural pathway.  Nissl staining 
revealed a significant rescue of the ischemic penumbra, with 45% cell loss in the control 
animals and 20% in the treated animals, regardless of dose (p<0.01). 
Overall, the positive behavioral outcomes and the relatively low number of engrafted cells in 
this study point more to a trophic support mechanism rather than to one of cell replacement. 

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Figure 6 
Elevated Body Swing Test: 1-Month Rat Study 
 
 
The Elevated Body Swing Test shows SB623 cells promote stroke recovery. Pre-stroke the 
animals had no rotational bias after lifting by the tail (50%).  The animals showed typical 
defective movement behavior post-stroke (near 100%) bias.  Low dose (90,000 SB623 cells) 
and high dose (180,000 cells) improved over the course of the 28 day study. 
 
Figure 7 
Bederson Neurologic Exam: 1-Month Rat Study 
 
SB623 cells at both doses caused an improvement in the multicomponent Bederson 
neurological score post-stroke. 
 
50 
60 
70 
80 
90 
100 
110 
Pre Stroke 
Post 
Stroke 
7 Day 
14 Day 
28 Day 
Rotational Bias (%) 
High 
Low 
Vehicle 
0 
0.5 
1 
1.5 
2 
2.5 
3 
3.5 
Pre 
Post 
7 day 
14 day 
28 day 
Bederson Score 
High 
Low 
Vehicle 
Bedrson Score 

 
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Figure 8 
Comparison of SB623 and MSC in MCAo Rat Model 
Balance Beam
Saline
SB
MSC
Saline
SB
MSC
Limb Placing
Morris Water Maze
(Memory Component)
Saline                     SB                     MSC
Mimura et al. (2005) J. Neuropathol. Exp. Neurol. 64:1108-1117
 
A published study comparing MASC (MSC) and rat-derived SB623-like cells shows 
superior benefit in balance beam, limb placing and Morris water maze. 
3.2.2.2 Study N-034 
Therapeutic Benefits of SB-623 in Experimental Stroke41 
SB623 cells were implanted into the striatum of male Sprague-Dawley rats at 4 weeks post-
MCAo stroke with either 90,000 SB623 cells (low dose), 180,000 SB623 cells (high dose) or 
an equivalent volume of sterile buffer alone (vehicle).  Rats were immunosuppressed daily 
with cyclosporine A (CsA, 10 mg/kg, i.p.) throughout the planned three-month post-
transplantation survival time.  Behavior evaluations were conducted monthly through month 
3.  At 1 month and up to three months post-transplantation, the animals treated with SB623 
cells showed significant behavioral improvement compared to the control group, with the 
higher dose of SB623 cells showing a strong trend of improvement compared to the lower 
dose.41  See Figure 9 and Figure 10 below. 
 
Figure 9 
Elevated Body Swing Test: 3-Month Rat Study 
 
SB623 cells show enduring benefit in EBST scores over 3 months. A trend in dose 
response is evident. 
50
60
70
80
90
100
110
Baseline
Post-
stroke
1 Month
2 Months
3 Months
Rotational Bias (%)
Vehicle
Low  Dose
High Dose

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Figure 10 
Bederson Neurologic Exam: 3-Month Rat Study 
 
A similar 3 month benefit is seen in the same animals using the multi-component 
Bederson neurological score. 
The one-hour MCAo stroke surgery produced consistent behavioral impairments at one 
month post-stroke as revealed by significant biased swing activity and neurological deficits 
in EBST and Bederson exam, respectively, compared to pre-stroke performance of the 
animals in both tests.  Pair-wise comparisons between pre-stroke and post-stroke 
performance of the animals revealed significant impairments in both tests (p’s < 0.0001) in 
all stroke animals included in this study. 
Following random assignments of the stroke animals to either vehicle, low dose 90,000 
SB623, or high dose 180,000 SB623, ANOVA revealed significant effects for both tests (p’s 
< 0.0001).  Those that received the high 180k SB623 or low dose 90k SB-623 displayed 
significant attenuation of behavioral deficits in both tests compared to vehicle-treated stroke 
animals (p’s < 0.0001).  This behavioral recovery by SB-623 transplanted stroke animals was 
sustained at 1, 2, and 3 months post-transplantation and showed a trend of a dose-response. 
At each month post-transplantation, each group of animals was euthanized and perfused with 
saline and formalin for immunohistochemistry and histological examination.  Brains were 
removed and post-fixed in formalin in PBS followed by sucrose in phosphate buffer.  
Thereafter, cryostat sectioned tissues were obtained.  Coronal sections from the ischemic 
striatal penumbra in each animal were stained with Nissl, a marker of ischemic cell death.  
Examination revealed that the stroke animals that received vehicle alone exhibited abundant 
ischemic cell death characterized by cells with swollen or damaged cell membrane.  The 
stroke animals that received low or high dose SB-623 cells displayed obviously fewer 
numbers of ischemic cells, indicating reduction in ischemic cell death in these transplanted 
animals.  Free-floating sections were incubated with the antibodies MAP2 (a marker of 
immature neurons) and HuNu (a marker of human cells). Brain sections from each group 
(i.e., months 1, 2, and 3) showed the presence of human cells.  Samples from the higher-dose 
groups showed more double-labeling that those from the lower-dose groups.  A small 
percentage of the HuNu-positive cells also stained positive with NeuN, a maker of mature 
neurons.  None of the HuNu-positive cells stained positive with the glia marker GFAP. 

 
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3.2.2.3 Study N-035 
Therapeutic Benefits of SB-623 in Experimental Stroke with/without CsA: 6-mo. Study42 
SB623 cells were implanted into the striatum of male Sprague-Dawley rats at 4 weeks post-
MCAo stroke with 180,000 SB623 cells or an equivalent volume of sterile buffer alone 
(vehicle), with two control groups.  One group of cell-treated rats and one group of control 
rats were immunosuppressed daily with cyclosporine A (CsA, 10 mg/kg, i.p.) throughout the 
planned six-month post-transplantation survival time.  Similarly, one group of cell-treated 
rats received no CsA and one group of control rats received no CsA.  Behavior evaluations 
were conducted monthly through month 6.  At 1 month and through 6 months post-
transplantation, both groups of animals treated with SB623 cells showed significant 
behavioral improvement on all behavioral measures compared to the control groups, with no 
differences between groups receiving or not receiving CsA.  This is illustrated in Figure 12 
below for the Elevated Body Swing Test.  Similar significant results were also obtained for 
the Forelimb Akinesia, Paw Grasp, and Balance Beam tests.  See the Investigator’s Drug 
Brochure for further details. 
Histological evaluation of the brains of the stroke animals that received SB623 or vehicle, 
with or without immunosuppression displayed no eventful inflammation or immune 
response.  There was no obvious difference between vehicle treatment groups and 
transplanted groups, indicating that such increased immunoreactivity was due to the stroke 
insult and not the transplants.  Further, the intensities of immunoreactivity of the astrocyte 
marker GFAP, the leukocyte marker CD11b, the macrophage/microglia marker Iba1, and the 
T cell marker CD3 were comparable across all treatment groups.  The lack of differences in 
these inflammatory and immune markers across groups clearly indicates that intracerebral 
transplantation of human SB623 cells in stroke rats did not elicit overt host reaction.  
Moreover, these observations also reveal that immunosuppression is not needed to prevent 
inflammatory response of the host tissue following SB623 transplantation. 
SB623 cell grafts did not reduce the extent of core cerebral infarction, the transplants 
significantly enhance the survival of host cells in the peri-infarct area (Figures 7-12).  In view 
of graft survival being sporadic at 6 months post-transplantation (Figures 13-14), the 
plausible mode of action of SB623 grafts in promoting behavioral recovery and histological 
rescue of the peri-infarct area is likely not via cell replacement but due to secretion of growth 
factors by either the transplants or the SB623-stimulated host tissue. 

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Figure 11 
CsA is not Needed for Long-Term Improvement of Stroke Deficits 
Notes: 
• n=10 per treatment group
• Control data from stroke animals that received intrastriatal vehicle infusion and treated with i.p. vehicle or CsA
• Data are means +/- standard deviation
EBST
0
20
40
60
80
100
120
1
2
3
4
5
6
7
8
Time Period
% Biased Swing Activity
Control
SB623+CsA
SB623+Veh
Baseline
Month 3
Month 1
Month 2
Post-
Stroke
Month 6
Month 4
Month 5
 
The conclusions were:42 
For behavioral recovery in stroke animals following SB623 transplants: 
• Recovery of motor and neurologic functions in stroke rats was sustained up to 6 
months post-transplantation, which appeared to improve over time 
• Immunosuppression was confirmed to be not critical in promoting and maintenance 
of behavioral improvement in ischemic stroke rats 
• No overt behavioral or gross physical side effects in any of the rats enrolled in this 
long-term study 
For host tissue inflammatory and immune status following SB623 transplants: 
• There is no observable eventful inflammation or immune response between control 
and transplanted stroke animals, with or without CsA. 
• Overall, the ipsilateral stroke side appears to display slightly higher immunoreactivity 
across all markers compared to the contralateral non stroke side. 
• There is no obvious difference between control groups and transplanted groups, 
indicating that such increased immunoreactivity in inflammatory and immune 
markers in the ipsilateral stroke side is due to the stroke insult and not the vehicle 
infusion or cell transplant.  
For rescue of stroke brain following SB623 transplants: 
• There is no observable difference in the volume of infarction with or without 
transplants, and also with or without CsA.  
• However, when the number of surviving cells is counted within the peri-infarct area, 
transplanted stroke animals displayed significantly higher cell survival than vehicle-
infused stroke animals. 

 
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• The rescue of ischemic peri-infarct area by transplantation of SB623 cells was not 
affected by immunosuppression, in that with or without CsA, the transplants 
increased cell survival in the peri-infarct area.  
For SB623 graft survival in stroke brain: 
• Using human specific antigen antibody, HuNu, we did not detect robust graft survival 
at 6 months post-transplantation.  Only sporadic HuNu positive cells (1-5) in each 
transplanted brain were observed 
• This observed minimal graft survival was not affected by immunosuppression, in that 
with or without CsA, we only detected a few HuNu positive cells in those stroke 
animals that received SB623 transplants. 
3.3 
Mechanism of action 
SB623 cells secrete factors that protect other cells from hypoxic injury, as shown with 
primary neurons and hippocampal slices (see Sections 3.2.1.1 and 3.2.1.2).43  These factors 
may provide trophic support to damaged cells in vivo.  In addition, SB623 cells secrete 
matrix that provides support for neural cell growth.44  Additional investigation into the 
mechanism is ongoing. 
3.4 
ADME 
All available evidence to date indicates that SB623 cells stay within the brain, with no 
evidence for any movement outside the brain.  See below study summary. 
Cells implanted in brains are not detectable beyond 1 month in athymic nude rats (see 
Sections 3.6.1 and 3.6.2) or in immunosuppressed normal Cynomolgus monkeys at 1 month 
(see section 3.6.6).  Studies with SB623 in rat models of stroke found approximately 7-9% of 
implanted cells survived at 1 mo., with < 1% differentiated along a neural pathway (see 
Section 3.2.2).  This is consistent with results also from a study in a rat model of Parkinson’s 
disease,45 in which less than 1% of intrastriatal-implanted SB623 cells survived at 3 weeks 
post-implant.  In another study using the stroke rat, cells were not detectable in the brain at 6 
mos., regardless of whether the animals had been treated with CsA or not. 
3.4.1 PSP021 (N-032) 
A 7 day Study of Lot D-24M2P3 SB623 Cells Implanted into the Brain of an Adult Female 
Immunosuppressed Cynomolgus Monkey 
A short-term study in Cynomolgus monkeys was conducted to determine the location, 
morphology and immunologic response of implanted SB623 cells.46  A total of 5 X 106 
SB623 cells from a male donor were implanted each into the cortical left hemisphere and the 
subcortical right hemisphere of a normal, CsA-treated female Cynomolgus monkey, with 
observations up to 1 week post-implantation.  The injection paradigm was evaluated for 
potential toxicities in preparation for proposed safety studies in the non-human primate.  A 
method of localizing implanted human SB623 cells was also confirmed in this study. 
Histological examination of the brain included using Y-chromosome in situ hybridization (Y-
ISH) staining.  Figure 12 shows staining to indicate the needle track for the injection of the 
cells.  Figure 13 shows the areas that appear with Y-ISH staining, indicating the presence of 
the SB623 cells. 

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The results of this study found that implanted SB623 cells persist for at least 7 days in the 
immunosuppressed non-human primate with minimal evidence of cell death or necrosis of 
the host tissue.  The method of delivery used in this study resulted in no local or systemic 
toxicities at 7 days from either the coordinate placement, volume of infusate injected or the 
rate of infusion.  The Y-chromosome In Situ Hybridization method was used to localize 
human cells implanted to the female non human primate brain in both perfused frozen 
sections and in perfused, thin paraffin sections. 
Figure 12 
Primate Needle Track 
 
Male SB623 cells are localize in the 
female primate brain using Y 
chromosome in-situ hybridization. SB623 
cells show up as brown against a blue 
background. The needle track is shown. 
Figure 13 
Primate Y-ISH Staining 
 
A close-up of Y-ISH staining of SB623 
cells implanted in primate brain.  
 
 
3.4.2 MPI 1295-001 
Implantation of SanBio Cells Into the Brains of Athymic Nude Rats: A Short-Term 
Biodistribution Study 
The purpose of this study was to test the implantation procedure in athymic rats; determine 
the post-implantation survival of SB623 cells and the growth of human HT1080 
fibrosarcoma cells in the brains of athymic nude rats, and to develop a method of detecting 
the implanted SB623 cells. 
Each rat was mounted in a stereotaxic instrument.  Bilateral injections of cell suspensions 
were made into the cortex and striatum.  Four small holes were drilled in the skull at the 
required coordinates47 of both the right and left hemispheres (1 cortex and 1 striatal hole per 
hemisphere).  Nine days after surgery, there were two animals in Group 2 (HT1080 
fibrosarcoma cells) found dead in their cages.  The remaining two animals in this group were 
observed to have impairment that made it necessary for them to be euthanized in extremis.  
All animals in this group were submitted to necropsy in accordance with the protocol.  

 
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Sixteen days after surgery, all four animals in Group 1 (SB623 cells) were submitted to 
necropsy.  No abnormal findings in animals receiving SB623 were observed clinically, 
macroscopically, or microscopically.  No SB623 cells were found in the brain at 16 days 
post-implant. 
3.4.3 N-029 
Survival of SB623 Cells Transplanted to the Naïve Adult Rat 
This study was designed to assess the feasibility of using SB623 cells in subsequent in vivo 
transplantation models.  The endpoints of this study were the acute in vivo survival and 
migratory capacity of SB623 cells transplanted to naïve adult athymic rat brain at 5 hr,, 48 hr, 
and 14 days post implantation. 
A total of 8 rats were used in this study. SB623 cells were stereotaxically implanted into the 
brains of adult male athymic male rats. Rats were transplanted bilaterally into identical sites 
in the dorsolateral striatum with approximately 36,000 to 42,000 SB623 cells in 2 uL of 
modified 1X Dulbecco’s phosphate-buffered saline without calcium or magnesium, (DPBS 
w/o Ca+Mg).  Rats were sacrificed at 5h, 48h and 14d post implantation. Cell survival and 
migratory capacity at the implant site was determined by localizing human derived SB623 
cells in perfused sections using human nuclear antigen immunocytochemistry.  Sections were 
counterstained with Nissl or hemotoxylin eosin. 
Survival, determined by positive human nuclear (HuNu) antigen staining at 5 hr. and 48 hr. 
post-implantation, was 16.7% and 9.6%, respectively.  Survival at 14 days was 8.2%. 
This study confirmed that the SB623 cells transplanted to the striatum of the nude rat have 
the capacity to survive at acute time points.  Furthermore, there was no evidence of extensive 
migration of implanted SB623 cells. 
3.4.4 N-033 
A 2-Day Study SB623 Cells Implanted Into The Brains Of Adult Male Athymic Rats; a 
Comparison of DPBS and Plasma-Lyte A as Formulation Buffers and the Effects of 
Increased Delivery Rates/Volumes 
This study was designed to justify the change from formulation in Dulbecco’s Phosphate 
Buffered Saline (DPBS) to Plasma-Lyte A USP and to determine the impact of doubling the 
dose, volume and implantation rate to determine if these increases can be used in a planned 
rat safety study.  SB623 cells were implanted bilaterally into the striata of adult male athymic 
rats and were assessed histologically at 2 days following transplantation. 
Cells were suspended in DPBS for implantation into the right hemisphere and in Plasma-Lyte 
A for implantation into the left hemisphere.  The cells were infused into a 2-mm column, 
depositing 2 uL of cell suspension at 0.5-mm intervals throughout the dorso-ventral length of 
the column, for a total dose of 230K cells per hemisphere.  SB623 cells were visualized by 
human nuclear antibody immunohistochemistry and showed no significant difference in cell 
survival at 2d post implantation between cells formulated in DPBS versus Plasma-Lyte A.  In 
vitro cell viability and stability at 4 hr. at RT did not differ in either of the two formulation 
buffers. 
Three of the 6 rats injected showed evidence of damage within the striatum.  The larger 
injection volume may have contributed to increased tissue damage and a decreased cell 

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survival seen in this study compared to previous studies.  In addition, the faster rate of cell 
infusion (2 µL/min vs. 1 µL/min) used in the present study may have contributed to apparent 
compression damage in the host tissue. 
We conclude that while doses of 230K cells can be injected into single tracks in the adult rat 
striatum, these volumes and/or injection rates are not optimal for maximum survival of 
SB623 cells in vivo and appear to be associated with host tissue damage. 
The use of DPBS versus Plasma-Lyte A to formulate the cells demonstrated small qualitative 
differences in the morphology of the cells within the graft core.  However; there were no 
demonstrated significant differences in cell survival in vivo or in the in vitro stability of the 
cells following incubation at room temperature for at least 4 hr. 
3.5 
Overall Preclinical Pharmacology and ADME Summary 
Results of all the preclinical pharmacology and ADME studies with SB623 are summarized 
in Table 1 below. 
 

 
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Table 1 
Summary of Preclinical Pharmacology and ADME Studies 
Animal Species/Model 
Study Type 
SB623 Dose, Route 
Results 
Study Reference 
Normal Animal 
Athymic nude rat 
8 Animals randomized 
into 2 groups 
16-day pilot study 
Implant procedure, 
survival and safety of 
SB623 cells compared 
to HT1080 
fibrosarcoma cells 
0.5 million SB623 cells 
total dose/animal 
One time administration 
Half into each hemisphere, 
divided into 60% striatum 
and 40% cortex 
No abnormal findings in animals 
receiving SB623 
SB623 cells were found in the brain 
at 16 days post-implant 
HT1080-treated animals died or 
were in extremis by day 9 
MPI 1295-00148 
(SanBio PSP010) 
Athymic male rat 
SB623 in vivo survival 
36-42,000 SB623 cells 
total dose/animal 
One time administration 
Half into each hemisphere 
into striatum 
No abnormal findings in animals 
receiving SB623 
The percentage survival decreased 
from 16.7% to 8.2% over 14d. 
No evidence of extensive migration 
N-029 
(SanBio PSP006) 
Nude rat 
Pilot study to develop 
Y-ish assay 
In vitro assay development 
Y-ish assay is usable for detecting 
SB623 from male human donors in 
either rat or monkey tissue 
N-031 
(SanBio PSP028) 
Athymic male rat 
Rat survival of cell lot 
used in the MPI safety 
study 
233,000 cells/hemisphere 
in either Plasma-Lyte A or 
DPBS into striatum 
Some tissue damage with both 
vehicles, concluded to be due to 
larger injection volume and/or more 
rapid rate of infusion compared to 
other studies 
No differences in cell survival 
between the vehicles in vivo or up to 
4 hr. in vitro 
N-033 
(SanBio PSP005) 
 

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Animal Species/Model 
Study Type 
SB623 Dose, Route 
Results 
Study Reference 
Cynomolgus Monkey 
Immunosuppressed with 
CsA 
Pilot primate safety 
and SB623 survival 
One-time administration 
Total 5.8 million cells per 
hemisphere in 4 needle 
tracks in either cortical or 
subcortical areas) 
Minimal evidence of cell death or 
necrosis of the host tissue 
No local or systemic toxicities at 7d 
SB623 cells persist for at least 7d by 
Y-ish assay 
N-032 
(SanBio PSP021) 
 
Stroke 
Sprague-Dawley Rat 
MCAo Stroke 
Immunosuppressed with 
CsA 
Biodistribution 
180,000 cells 
stereotactically implanted 
into the striatum 
Using qPCR, no SB623 cells were 
found in spleen, lung, heart, liver, 
kidney, and testes of stroked animals 
2 weeks after implant 
Althea 7-RT-
SB0102 
(SanBio PSP034) 
Sprague-Dawley Rat 
MCAo Stroke 
Immunosuppressed with 
CsA 
7-day, 14-day, 28-day 
efficacy and cell 
survival 
Vehicle control 
One-time administration 
90,000 or 180,000 cells, 1 
mo. post-MCAo, 
intrastriatal in right 
hemisphere 
Statistically-significant (p≤0.0001) 
improvement with both doses 
compared to control in both the 
elevated body swing test and 
Bederson score at all time points. 
Cell survival ranged from 5-7% for 
the two dose levels at 28 days, with 
< 1% expressing the neuronal 
marker MAP2. 
Implantation of SB623 cells resulted 
in a significant rescue of the 
ischemic penumbra compared to 
control (p<0.01) regardless of dose. 
N-03041 
(SanBio PSP007) 

 
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Animal Species/Model 
Study Type 
SB623 Dose, Route 
Results 
Study Reference 
Sprague-Dawley Rat 
MCAo Stroke 
Immunosuppressed with 
CsA  
1-mo., 2-mo., and 3-
mo. Efficacy, cell 
survival and safety 
Vehicle control  
One-time administration 
90,000 or 180,000 cells, 1 
mo. post-MCAo, 
intrastriatal in right 
hemisphere 
Statistically-significant (p≤0.0001) 
improvement with both doses 
compared to control in both the 
elevated body swing test and 
Bederson score at all time points. 
N-03441 
(SanBio PSP027) 
Sprague-Dawley Rat 
MCAo Stroke 
Comparison 
with/without CsA 
1-6-mo. Efficacy, cell 
survival and safety 
Vehicle controls 
One-time administration 
180,000 cells, 1 mo. post-
MCAo, intrastriatal in right 
hemisphere 
Statistically-significant (p≤0.0001) 
improvement with both doses 
compared to control in all 
motor/neurological measures at all 
time points. 
No inflammatory response 
attributable to the SB623 cells. 
N-03542 
 
 

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3.6 
Toxicology 
Three GLP safety studies of SB623 cells have been conducted: a 12-mo. tumorigenicity 
study in athymic nude rats, a 4-mo. bridging study in athymic nude rats, and a 6-month study 
in immunosuppressed Cynomolgus monkeys. 
3.6.1 12-Month Rat Tumorigenicity 
(Study number 1295-002; MPI Research) 
The purpose of this GLP study was to assess the possible tumorigenicity of SB623 cells after 
stereotactic implantation into brains of nude rats.  A total of 5 X 105 SB623 cells or vehicle 
were administered into the striatum and cortex of both hemispheres of a total of 120 athymic 
nude male and female rats further immunosuppressed with the rabbit anti-NK cell antibody 
Anti-Asialo GM1 (GM1Ab), with observations up to 12 months post-implantation.  Two 
implantations were done in each hemisphere with 10 µL per hemisphere (20 µL per animal): 
6 µL into the striatum and 4 µL into the cortex.  Animals (15 each per group per sex) were 
sacrificed at 6 mos. and 12 mos. post-implant. 
The endpoints of the study were: clinical observations; clinical pathology at termination; 
histology of major organs (including brain); cellular markers for presence of SB623, 
phenotype expression, and inflammation/immune responses. 
No SB623 cells, as determined from an anti-human mitochondrial antibody, were found at 6 
or 12 months. 
There were no adverse cell-related findings in clinical observations or clinical pathology.  
Histological examination of the brain and other organs and tissues showed no abnormalities 
that could be attributed to SB623 cells.49  Because no cells were found at either time point of 
this study, the biological relevance of these findings may be inconclusive.  Minimal to 
moderate unilateral hydronephrosis was noted in 3 of 13 males from the vehicle group and 6 
of 10 males from the 5 x 105 SB623 cells group.  In addition to the hydronephrosis, infarct 
and/or chronic inflammation was noted in 3 of 10 males at the dose of 5 x 105 SB623 cells.  
Although there was a higher incidence of renal findings in males treated with SB623, these 
observations were unilateral in males receiving SB623.  Therefore, a test article relationship 
was considered unlikely. 
3.6.2 4-Month Rat Tumorigenicity Bridging Study 
(Study number 1295-008; MPI Research) 
The purpose of this GLP study was to assess the possible tumorigenicity and survival of 
SB623 cells after stereotactic implantation into brains of nude rats using identical procedures 
as with study 1295-008 above, except without a control group.  A total of 5 X 105 SB623 
cells were administered into the striatum and cortex of both hemispheres of a total of 30 
athymic nude male and female rats further immunosuppressed with the rabbit anti-NK cell 
antibody Anti-Asialo GM1 (GM1Ab), with observations up to 4 months post-implantation.  
Two implantations were done in each hemisphere with 10 µL per hemisphere (20 µL per 
animal): 6 µL into the striatum and 4 µL into the cortex.  Animals (3 per sex per time point) 
were sacrificed at 2 wks., 1 mo., 2 mos., 3 mos. and 4 mos. post-implant. 
The endpoints of the study are clinical observations, clinical pathology, histology of the 
brain, and cellular markers for presence of SB623 cells at each time point. 

 
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SB623 cells, as determined from an anti-human mitochondrial antibody or qPCR, were found 
at 2 wks., but not at 1 month.50 ,51  Determination of the presence of cells by qPCR showed 
that cells could be detected, but not quantifiable, at 28 days.  Cells could not be detected at 
months 2, 3, or 4. 
There have been no adverse cell-related findings in clinical observations or clinical 
pathology.  Histological examination of the brain has shown no abnormalities that could be 
attributed to SB623 cells.  Since cells were found to be present only at the 2-wk. time point, 
the biological relevance of these findings beyond 2 wks. may be inconclusive. 
3.6.3 CsA Dose Selection for Monkey Safety Study 
The dose of cyclosporine was based on results of a pharmacokinetic study of i.m. 
cyclosporine in Cynomolgus monkeys (see Section 3.6.4 below), and a supporting 
subsequent study also in Cynomolgus monkeys (see Section 3.6.5 also below). 
3.6.4 Study Number MPI-004; MPI Research 
Three male Cynomolgus monkeys were administered cyclosporine i.m. daily at 15 mg/kg for 
4 days.  Blood samples for analysis of cyclosporine levels were taken at 0 hr., 1 hr., 2 hr., 3 
hr., 5 hr., 8 hr. 12 hr., and 24 hrs. on days 1, 2, and 3 at 24 hrs.  Mean trough levels ranged 
from 463 ng/mL (day 1) to 758 ng/mL (day 3).  The conclusion was that a dose of 15 mg/kg 
i.m. in the Cynomolgus monkey would provide adequate blood levels for the planned safety 
study with trough levels remaining relatively constant. 
3.6.5 One-Month Cynomolgus Monkey +-CsA 
(Study number S08-10131, Valley Biosystems and MPI Research)52 
Two groups of 2 animals each were implanted with SB623 at a dose of 5 X 105 cells or 
vehicle.  The striata of the left and right hemispheres of each animal received two injection 
tracts of 100 µL each consisting of five 20-µL implants.  The right hemispheres of each 
animal received the cells, while the left hemisphere received vehicle only.  One group of 
animals also received Cyclosporine A, 15 mg/kg/day I.M. beginning two days prior to 
surgery, while the other group received an equivalent amount of vehicle i.m. with the same 
schedule. 
There were no clinical symptoms in the animals that could be attributed to SB623.  There 
were also no adverse hematology or serum chemistry findings that could be attributed to 
SB623.  The brain histological findings were that no SB623 cells were found at 1 month.  
Further, no histological differences were seen between the brains of any of the animals, or 
between the hemispheres of each animal. 
The conclusions were that immunosuppression in this animal model did not prevent 
clearance of SB623 by one month and that there were no differences in pathology of the 
brains comparing with or without CsA. 
3.6.6 6-Month Toxicity: Cynomolgus monkey 
(Study number 1295-005; MPI Research) 
The purpose of this GLP study was to assess the overall safety of SB623 after stereotactic 
implantation into brains of Cynomolgus monkeys.  A total of 5 X 106 SB623 cells or vehicle 
was implanted each into the cortical left hemisphere and the subcortical right hemisphere in 

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12 normal female Cynomolgus monkeys, immunosuppressed with daily i.m. cyclosporine 15 
mg/kg, with observations up to 6 months post-implantation. 
Each hemisphere received 2 injection tracks, with each track consisting of two sites, each 
receiving 50 µL, for a total of 200 µL per hemisphere (5 million cells or vehicle), using a 
concentration of 25,000 cells/µL or vehicle.  Animals (1 control, 3 cells each) were sacrificed 
at 1 mo., 3 mos., and 6 mos. post-implant. 
The endpoints of the study were: clinical observations; clinical pathology at 2 weeks, 1 mo., 
3 mos., and 6 mos.; histology of major organs (including brain); and cellular markers for 
presence of SB623, phenotype expression, and inflammation/immune responses. 
No SB623 cells, as determined from an anti-human antibody or a Y-ish assay, were found at 
1, 3 or 6 months. 
There were no adverse, cell-related findings in clinical observations or clinical pathology.  
Histological examination of the brain and other organs and tissues showed no abnormalities 
that were attributed to SB623 cells.53  Because no cells were found at any time point of this 
study, the biological relevance of these findings may be inconclusive.  One animal in the 91-
day recovery group and three animals in the 181-day recovery group that received SB623 
cells had an area of necrosis in the external capsule adjacent to the putamen at one or both 
injection sites.  Each area of necrosis measured approximately 1.0 x 0.5 to 3.0 x 0.5 mm in 
size and was characterized by loss of neuropil with associated reactive gliosis and minimal 
mononuclear infiltrate including gitter cells.  The areas of necrosis observed in these animals 
were concluded to be most likely due to the act of injection rather than a direct test article 
effect. 
3.7 
Summary of Preclinical Safety Studies 
See below Table 2 below.

 
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Table 2 
Summary of Preclinical Safety Studies 
Study Reference 
Study Description 
Group Size 
(Species, sex) 
Duration/Dose 
Route of Admin. 
Results/Conclusions 
MPI 1295-002 
(N-007) 
Rat tumorigenicity 
study: 6 mos. and 12 
mos. evaluation; 
athymic nude rat 
receiving anti-asialo 
antibody 
60 males: equal 
control and cells 
60 females: 
equal control and 
cells 
One-time administration 
Total 0.5 million cells per 
animal (0.25 million per 
hemisphere, with 60% in 
striatum and 40% in 
cortex in each 
hemisphere) 
Striatum and cortex 
No tumors at either 6 
mos. or 12 mos. 
No cell-related adverse 
findings during the 
study or at 6 mos. or 
12 mos. 
No SB623 cells were 
seen at 6 mos. 
MPI 1295-008 
Rat tumorigenicity 
bridging study: 1 mo., 
2 mos., 3 mos., and 4 
mos. 
30 animals: 3 per 
sex per time 
point 
One-time administration 
Total 0.5 million cells per 
animal (0.25 million per 
hemisphere, with 60% in 
striatum and 40% in 
cortex in each 
hemisphere) 
Striatum and cortex 
No tumors at any time 
point to date (3 mos.) 
No cell-related adverse 
findings.  
SB623 cells were seen 
at 2 wks. but not at 1 
or 2 mos.. 
S08-10131 
One-month pilot 
primate safety and 
SB623 survival 
comparing 
with/without CsA at 
15 mg/kg/day i.m. 
4 females 
One time administration 
with or without CsA 
Total 5 million cells in the 
right hemisphere striatum 
and vehicle in the left 
hemisphere striatum using 
2 injection tracts each 
with 5 implants. 
Striatum 
No SB623 cells were 
found at 1 month. 
No adverse clinical, 
laboratory, no 
histological findings 
attributable to SB623. 
No histological 
differences in the 
brains or hemispheres 

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Study Reference 
Study Description 
Group Size 
(Species, sex) 
Duration/Dose 
Route of Admin. 
Results/Conclusions 
MPI 1295-005 
(N-018) 
Cynomolgus monkey 
safety study: 1 mo., 3 
mos., and 6 mos. 
evaluation 
CsA at 15 mg/kg i.m. 
daily 
9 females with 
cells 
3 females with 
control vehicle 
One-time administration 
Total 10 million cells per 
animal (5 million cells per 
hemisphere in either 
cortical or subcortical 
areas) 
Subcortical right 
hemisphere or 
cortical left 
hemisphere 
No tumors at 1 mo., 3 
mos., or 6 mos. 
No cell-related adverse 
findings during the 
study or at 1 mo., 3 
mos. or 6 mos. 
No SB623 cells were 
seen at 1 mo., 3 mos., 
or 6 mos. 
 

 
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3.8 
Summary of Known and Potential Risks and Benefits 
No prior clinical studies with SB623 have been conducted.  Based on the available animal 
data, no risks have been identified, but considerable potential benefit in reversing 
neurological deficits has been observed in a rat model of stroke. 
4.0 
DESCRIPTION AND JUSTIFICATION OF TREATMENT REGIMEN 
4.1 
Dosages 
All dosages of cells are to be administered stereotactically through one burr-hole craniostomy 
using 3 needle tracks within and adjacent to the infarct and 5 cell deposits per track at 
varying depths, with 20 µL per deposit.  Concentrations of cell suspensions to be used will 
vary depending on the total dosage required per patient.  See Table 3 below. 
Table 3 
Dosages, Volumes and Cell Concentrations 
 
Total 
SB623 
Cells/Pt. 
Total SB623 
Cells/Deposit 
Total SB623 
Cells/Track 
Concentration 
of SB623 
Cells per 
Injection 
Total Volume 
per Deposit, 
per Track, 
and Total 
Cohort 1 
2.5 X 106 
1.65 X 105 
8.25 X 105 
8.3 X 106 
cells/mL 
20 µL, 100 
µL, and 300 
µL 
Cohort 2: 
5.0 X 106 
3.3 X 105 
16.5 X 105 
17 X 106 
cells/mL 
20 µL, 100 
µL, and 300 
µL 
Cohort 3 
10 X 106 
6.6 X 105 
33 X 105 
33 X 106 
cells/mL 
20 µL, 100 
µL, and 300 
µL 
 
4.2 
Justification 
Based on the animal pharmacology and safety studies (see Sections 3.2 and Section 3.6 
above), particularly the primate study that used 10 million cells/animal, and considering the 
larger brain mass of humans, a maximum dose of 10 X 106 SB623 cells and a deposition 
volume of 20 µL are considered likely to be safe and have a good chance of showing some 
efficacy.  The range of doses, as low as 2.5 X 106 SB623 cells, is considered necessary to 
observe any possible dose-response trends.  The stereotactic surgery procedure to be used 
(see Section 7.0) has been shown to be safe and well tolerated in another similar study29,54, 
and in a retrospective study.30 
The patient population of 6-60 months post-stroke was chosen to allow for stabilization of 
motor deficits, particularly after physical therapy, and to allow a sufficient number of 
patients for reasonable accrual.  The duration of time needed for stabilization will vary by 
patient, with >95% stabilized at 3 mos. post-stroke.30  Entry criteria to this study require 
demonstration of stable motor deficit(s) during the prior 3-week period. 
5.0 
NO CYCLOSPORINE A 
5.1 
Rationale 

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The toxicity properties of CsA are well known and present serious risks to patients, 
particularly older ones.  Although most of the toxicity studies summarized in Section 3.6 
used CsA, this was done to maximize the chances of uncovering any possible tumorigenicity 
properties of SB623.  Subsequently, it was found that the presence of CsA was not relevant 
for the pharmacologic activity of SB623 in the MCAo stroke rat model (see Section 3.2.2).  
Although this is a xeno-transplant model, these findings suggested a need to re-evaluate the 
need for CsA in all future studies, including clinical.  The other animal toxicity studies also 
indicated that even in immunosuppressed models, SB623 did not survive beyond a month or 
so, indicating clearance by means of an innate immune response rather than an adaptive one.  
Finally, an in vitro study has shown that SB623 possesses anti-inflammatory and 
immunosuppressive activity (see Section 3.2.1.6), thus suggesting the possibility that lack of 
use of CsA may not result in an adverse inflammatory response or any adverse cell-mediated 
immune response.  Nevertheless, careful monitoring will be done to unsure safety of the 
patients (see below). 
5.2 
Monitoring for Humoral or Cell-Mediated Immune Response 
In the Ph. 1/2a clinical study, Patients will be evaluated on Day 8 after implantation, monthly 
thereafter through month 4, and then at months 6, 9, 12 and 24 for any symptoms of 
inflammation, humoral immune response, or cell-mediated immune response (see Table 4).  
The parameters to be followed are: vital signs, hematology, serum chemistry, lipid panel, 
cytokine levels (TNF-α, IL-6, IFN-γ), CRP, head MRI, antibodies to SB623, and PBMC 
function (see Section 15.0). 
6.0 
STUDY PARAMETERS AND OBJECTIVES 
The overall objective of the study is to evaluate the safety and efficacy of SB623 cells 
stereotactically implanted in the brains of patients with stable stroke. 
6.1 
Parameters 
6.1.1 Safety 
• Adverse events 
• Serious adverse events (SAE) 
• Periodic head MRI scans 
• Serum chemistry, hematology, SB623 antibodies to SB623, cytokines, and PBMC 
function 
6.1.2 Efficacy 
• Clinical Stroke Evaluations: European Stroke Scale (ESS),31 NIH Stroke Scale 
(NIHSS), Modified Rankin Score (MRS), Fugl-Meyer Score,38 Cognitive Battery (see 
Appendix D, Section 1.0, Table 7). 
• Uptake of fluorodeoxyglucose measured by positron emission tomography (FDG-
PET) 
 
 

 
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6.2 
Objectives 
6.2.1 Primary Objective 
The primary objective is to determine acute and long-term safety of SB623 cells 
administered stereotactically around the infarct region of brains of patients with stable 
ischemic stroke. 
 
6.2.2 Secondary Objectives 
• To estimate clinical improvement of patients primarily with the ESS and secondarily 
with the NIHSS, the MRS, the Fugl-Meyer Score and Cognitive Tests 
• To estimate metabolic improvement in and around the infarct region using FDG-PET 
7.0 
SURGICAL AND IMPLANTATION PROCEDURES 
The surgical procedure is a modification of one used earlier with another cell product,29,54 
and which has been shown to have a high degree of safety in a retrospective study of over 
2,600 patients undergoing stereotactic surgery over the course of 28 years at one major 
clinic.30  On the morning of surgery, a standard stereotactic coordinate frame (Leksell 
Stereotactic System®, manufactured by Elekta55) is to be applied to the head under local 
anesthesia and mild sedation.  Either a head CT scan overlaid on the Baseline MRI or a head  
MRI scan alone is to be performed for stereotactic targeting.  The MRI scans are to use 
insulated posts an RIF transmitter head, and 1.5 tesla.  A safe trajectory is to be defined to 
enter a cortical gyrus, sparing a sulcus.  Points are to be determined in the basal ganglia 
inferior to the stroke and beyond the stroke.  Three needle tracks are to be determined with 
trajectories in the same paramedian plane spaced by 5-6 mm at the target 
One burr-hole craniostomy (1-1.5 cm) is to be fashioned under local anesthesia.  The dura is 
to be opened and a 1.8-mm outer-diameter, 15-cm long stabilizing cannula containing a 
removable solid stylet is to be inserted to a point just proximal to the penumbra of the stroke 
area.  The solid stylet is then to be removed, followed by insertion into the stabilizing 
cannula of a 0.9-mm outer diameter, 19-cm. long, 20-µL volume Pittsburgh Implantation 
Cannula  (previously qualified for product stability and delivery and provided by the 
Sponsor) down to the deepest target point for the first implantation.  A total volume of 100 
µL of cell suspension is to be aspirated into a 100-µL syringe through the implant cannula.  
The implantation cannula is then to be filled with cell suspension.  Five 20-µL volumes of 
cells are to be injected slowly (approximately 10 µL/min.) into 5 implantation sites, slowly 
withdrawing the stabilizing needle probe so that the implantations are spaced as equally as 
possible (intervals of 4-5 mm) with 2-3 implants within the penumbra distal to the stroke area 
and 2-3 implants within the penumbra proximal to the stroke area.  The target locations will 
be selected by the site neurosurgeon and neurologist to be closest to the motor pathway based 
on the patient’s own neuroanatomy.  This procedure is to be repeated with 2 other needle 
tracks with different trajectories, inserted through the same burr-hole craniostomy. 
After completion of the procedure, the patient will receive a CT scan and be admitted to a 
neurosurgical patient ward for 24 hour observation, during which it is recommended that the 
patient be on a flat bed with optimal hydration and keeping the subject's head as flat as 
possible for the next 24 hours.  The patient will be discharged on the first post-operative day 

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unless complications require a longer stay.  An MRI is to be done on the first post-operative 
day (Day 2; see Section 10.5) to insure there are no significant bleeding risks. 
8.0 
PATIENT SELECTION 
8.1 
Inclusion Criteria 
1. Age 18-75 years 
2. Documented history of completed ischemic stroke in subcortical region of MCA or 
lenticulostriate artery with or without cortical involvement, with correlated findings 
preferably by MRI or by CT if MRI is contraindicated 
3. Between 6 and 60 months post-stroke, and having a motor neurological deficit 
4. No significant further improvement with physical therapy/rehabilitation (confirmed 
by no change in NIHSS greater than ±1 within three weeks prior to enrollment) 
5. Modified Rankin Score of 3 or 4 
6. NIH Stroke Scale score of >7 
7. Two evaluations during prior 3 weeks with no more than  ±1 point change in clinical 
evaluation using the NIH Stroke Scale 
8. Able and willing to undergo computed tomography (CT), magnetic resonance 
imaging (MRI), and positron-emission tomography (PET) scans of the head 
9. Agree that use of antiplatelet, anti-coagulant, or non-steroidal anti-inflammatory 
drugs to be determined by the local medical staff and in accordance with the 
ACCP 2012 guideline “Perioperative Management of Antithrombotic Therapy: 
Antithrombotic Therapy and Prevention of Thrombosis, 9th Edition: American 
College of Chest Physicians Evidence-Based Clinical Practice Guidelines”, if 
applicable1, provided that no antiplatelet, anti-coagulant, or non-steroidal anti-
inflammatory drugs are to be restarted after surgery until after the Day 8 MRI is read 
and determined to be safe to re-start 
10. Normal emotional status; i.e., no disabling psychological deficits 
11. Ability of patient or legal authorized representative to understand and sign an 
Informed Consent 
8.2 
Exclusion Criteria 
1. History of more than 1 symptomatic stroke 
2. History or presence of any other major neurological disease 
3. Cerebral infarct size >100 cm3 measured by MRI 
4. Myocardial infarction within prior 6 mos 
5. Known presence of any malignancy except squamous or basal cell carcinoma of the 
skin 
6. History of CNS malignancy 
7. History of seizures or current use of antiepileptic medication 
8. Uncontrolled systemic illness, including, but not limited to: hypertension (systolic 
>150 mm Hg or diastolic >95); diabetes; renal, hepatic, or cardiac failure 
9. Uncontrolled psychiatric illness, including depression (Hamilton Score >14) 

 
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10. Total bilirubin >1.5 mg/dL 
11. Serum creatinine >1.5 mg/dL 
12. Hemoglobin <10.0 g/dL  
13. Absolute neutrophil count <2000 /mm3 
14. Lymphocytes <800 /mm3 
15. Platelet count <100,000/mm3 
16. Liver disease supported by AST (SGOT) or ALT (SGPT) ≥2.5 x institutional upper 
limit of normal 
17. Serum calcium >11.5 mg/dl 
18. International Normalized Ratio of Prothrombin Time (INR) >1.2 
19. Signs and symptoms of intracranial herniation or increased intracranial pressure 
20. Acute intracranial hemorrhage 
21. Use of neuroleptic drugs 
22. Unexplained abnormal preoperative test values (blood tests, electrocardiogram 
[ECG], chest X-ray); patients with electrocardiographic evidence to suggest a recent 
myocardial infarction, major dysrhythmia, x-ray evidence of infection, atrial 
fibrillation, or congestive heart failure will be excluded 
23. Participation in any other investigational trial within 4 weeks of initial screening and 
within 7 weeks of study entry 
24. Botulinum toxin injection, phenol injection, intrathecal baclofen, or any other 
interventional treatments for spasticity (except bracing and splinting) within the 
previous 3 mos. 
25. Ongoing use of herbal or other non-traditional drugs 
26. Ongoing drug or alcohol abuse 
27. Contraindications to head CT, MRI, or PET 
28. Pregnant or lactating 
29. Female patients of childbearing potential unwilling to use an adequate birth control 
method during the first 6 months of the study 
30. Presence of serum antibodies to donor SB623 cells with a Luminex value of >1000 
MFI (Maximum Fluorescence Intensity): HLA Class I (HLA-A*23:PWMV, HLA-
A*68:CGBR; HLA-B*45:FJH, HLA-B*53:KJW; or HLA-Bw4, HLA-Bw6; HLA-
Cw*04:SSWB, HLA-Cw*16:01); or Class II (HLA-DRB1 *13:NGUB, HLA-DRB1 
*16:02; HLA-DQB1*05:CHZY, HLA-DQB1*05:BK; HLA-DQA1*01:DVB, HLA-
DQA1*X, HLA-DRB3,4,5: 3*03:01, HLA-DRB3,4,5: 5*02:02) 
31. Any other condition or situation that the investigator believes may interfere with the 
safety of the subject or the intent and conduct of the study 
9.0 
INVESTIGATIONAL PLAN 
9.1 
Overall Study Design 
This is an open-label study of stereotactic, intracranial injection of SB623 cells (SB623 cells) 
in patients with hemiparesis from stable ischemic stroke who have remained stable during the 

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prior 3 weeks (as documented by NIHSS assessments at weeks -3 and -1).  Three cohorts will 
receive escalating singe doses of SB623, which are to be stereotactically implanted into grey 
or white matter sites adjacent to the infarct region.  One burr-hole craniostomy will be 
created, and cells implanted using 3 needle tracks with 5 cell deposits for each track at 
varying depths.  Cell implantation will be standardized as to volume (20 µL/deposit) and rate 
(10 µL/min), with spacing between each implant of approximately 5-6 mm.  Each deposit is 
expected to take approximately 2-3 minutes, with each needle track being completed within 
15 minutes.  Each cohort will consist of 6 subjects defined by an increasing total number of 
cells implanted.  Safety will be monitored by the Investigator, Principal Monitor, Medical 
Monitor, and an external Data Safety Monitoring Board (DSMB).  For the first cohort, a 
single patient will first be dosed, then evaluated over a 2 week period for safety prior to 
dosing the next member of this cohort.  This 2-week interval will continue between each of 
the remaining members of the cohort.  If the safety profile is acceptable for a cohort, and 
after review by the DSMB, the first patient in each subsequent, sequential cohort will be 
dosed, beginning 4 weeks after dosing of the last patient of the prior cohort.  For the second 
and third patients in each of the subsequent cohorts, there will be an interval of 2 weeks after 
the prior patients prior to further enrollment. 
Safety will be monitored by clinical symptoms, laboratory findings, and MRI brain imaging.  
Efficacy will be determined based on changes in the clinical measures of stroke and on FDG-
PET brain imaging. 
A dose-limiting toxicity will be defined as any grade 3 or 4 events which are at least possibly 
related to study product or administration procedure.  If the first patient in a cohort has a 
dose-limiting toxicity attributable to the SB623 cells, then no further patients will be dosed in 
that cohort until a comprehensive evaluation has been conducted.  If 2 of 6 patients in a 
cohort have a dose-limiting toxicity attributable to the SB623 cells, then no further patients 
will be dosed in that or other higher-dose cohorts.  Each dose-limiting-toxicity will be 
evaluated by the DSMB.  The DSMB shall be the final arbitrator for attributions. 
9.2 
Duration of Patient Participation 
Two years (except if there is an unresolved Grade 2 adverse event at least possibly related to 
the therapy, in which case the patient will be followed until resolved or reduced to Grade 1). 
10.0 STUDY ASSESSMENTS 
10.1 Schedule of Study Activities 
Table 4 below lists the procedures to be followed throughout the course of the study. 
 

 
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Table 4 
Study Procedures Flow Chart 
 
Scr. 1 
Scr. 2 
Baseline1 
Enroll2 
Cell 
Admin 
Follow-Up Period 
Last 
Eval. 
Study Day 
 
 
-2 to-1 
-1 to 1 
1 
2 
8 
 
 
 
 
 
 
Study Week 
-3 
-1 
1 
1 
1 
1 
2 
 
 
 
 
 
 
Study Month 
 
 
 
 
 
 
 
End of 1 
and 2 
End of 3 
and 4 
End 
of 6 
End 
of 9 
End 
of 12 
End 
of 24 
Informed Consent 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X4 
X5 
X6 
 
 
 
 
 
 
 
 
 
Medication History 
X 
X4 
X5 
X6 
 
 
 
 
 
 
 
 
 
Signs & Symptoms 
X 
X4 
X5 
X6 
 
 
 
 
 
 
 
 
 
Pregnancy Test7 
X8 
 
X 
 
 
 
 
 
 
 
 
 
 
Physical Exam. 
X 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Vital Signs 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Chest X-Ray and ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology (Section 15.3) 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Serum Chemistry (Sect. 15.3) 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
INR 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Occult Malig. (Sect. 10.2.2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid Panel (Section 15.3) 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Cytokines (Section 15.3) 
 
 
X 
 
 
 
X 
X (mo. 2) 
X (mo. 4) 
X 
X 
X 
X 
Blood for HLA antibodies 
X9 
 
 
 
 
 
 
 
 
 
 
 
 
Head CT 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Imaging--Head FDG-PET 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
Imaging--Head MRI 
X10 
 
X 
 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
                                                 
1 Only after documentation of stable stroke by two evaluations within 3 weeks prior to study entry using the NIH Stroke Scale (no more than ±1 point) 
2 Enrollment only after all inclusion and exclusion criteria are verified and the patient qualifies for the study 
3 Prior to any study-related procedures 
4 Only changes since Screen 1 
5 Only changes since Screen 2 
6 Only changes since Baseline 
7 Only for women of childbearing potential 
8 Serum β-HCG at Screening; serum or urine β-HCG at Baseline 
9 May also be done at a pre-Screen visit 
10 May instead be done at a pre-Screen visit 
11 Or CT overlaid with MRI from Baseline 

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Scr. 1 
Scr. 2 
Baseline1 
Enroll2 
Cell 
Admin 
Follow-Up Period 
Last 
Eval. 
Study Day 
 
 
-2 to-1 
-1 to 1 
1 
2 
8 
 
 
 
 
 
 
Study Week 
-3 
-1 
1 
1 
1 
1 
2 
 
 
 
 
 
 
Study Month 
 
 
 
 
 
 
 
End of 1 
and 2 
End of 3 
and 4 
End 
of 6 
End 
of 9 
End 
of 12 
End 
of 24 
Clinical Stroke Evaluations 
X12 
X12 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
Cognitive Questionnaire 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
Blood for antibodies to 
SB623 and for PBMCs 
 
 
X 
 
 
 
X 
X (mo. 2) 
X (mo. 4) 
X 
X 
X 
X 
Serum Antibod. (see Sect. 
15.6 for assay schedule) 
 
 
 
 
 
 
 
 
 
 
 
 
 
PBMC Function (see Sect. 
15.7 for assay schedule) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
                                                 
12 NIHSS and Modified Rankin at Scr. 1 and only NIHSS at Scr. 2 

 
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10.2 Pre-study Evaluation and Baseline (Pre-Screen, Scr. 1, Week -3 and Scr. 2, 
Week -1) 
The following will be done prior to performing any study-specific procedures: 
• Informed Consent Signed: study-related details will be carefully discussed with the 
patient.  The patient will sign an Informed Consent Form approved by the local Ethics 
Committee. 
10.2.1 Pre-Screen (Optional) 
• Blood sample for determination of presence of antibodies to donor SB623 cells with a 
Luminex value of >1000 MFI (Maximum Fluorescence Intensity): HLA Class I 
(HLA-A*23:PWMV, HLA-A*68:CGBR; HLA-B*45:FJH, HLA-B*53:KJW; or 
HLA-Bw4, HLA-Bw6; HLA-Cw*04:SSWB, HLA-Cw*16:01); or Class II (HLA-
DRB1 *13:NGUB, HLA-DRB1 *16:02; HLA-DQB1*05:CHZY, HLA-
DQB1*05:BK; HLA-DQA1*01:DVB, HLA-DQA1*X, HLA-DRB3,4,5: 3*03:01, 
HLA-DRB3,4,5: 5*02:02) 
• Head MRI 
10.2.2 Scr. 1, Week -3 
• Inclusion/Exclusion Criteria 
• Demographics 
• Medical History 
• Medication History 
• Signs & Symptoms 
• Pregnancy Test (serum β-hCG) 
• Physical Exam. 
• Vital Signs Including Weight 
• Chest X-Ray and ECG 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• INR 
• Determination of occult malignancy by occult blood in stools (hemocult test), finding 
on chest x-ray, carcinoembryonic antigen, prostate-specific antigen (males only), 
cancer antigen 125 (females only), α-fetoprotein, and β-hCG 
• Blood sample for determination of presence of serum antibodies to donor SB623 cells 
with a Luminex value of >1000 MFI (Maximum Fluorescence Intensity): HLA Class 
I (HLA-A*23:PWMV, HLA-A*68:CGBR; HLA-B*45:FJH, HLA-B*53:KJW; or 
HLA-Bw4, HLA-Bw6; HLA-Cw*04:SSWB, HLA-Cw*16:01); or Class II (HLA-
DRB1 *13:NGUB, HLA-DRB1 *16:02; HLA-DQB1*05:CHZY, HLA-
DQB1*05:BK; HLA-DQA1*01:DVB, HLA-DQA1*X, HLA-DRB3,4,5: 3*03:01, 
HLA-DRB3,4,5: 5*02:02) 
• Imaging (head MRI: only if not done at a pre-screen visit) 

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• Clinical Stroke Evaluations (NIHSS and Modified Rankin only) 
10.2.3 Scr. 2, Week -1 (±2 Days) 
The following will be performed: 
• Medical History (only changes since Scr. 1) 
• Medication History (only changes since Scr. 1) 
• Signs & Symptoms (only changes since Scr. 1) 
• Vital Signs 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Clinical Stroke Evaluations (NIHSS only) 
10.3 Baseline and Enrollment (Days -2 to 1, not including weekends) 
10.3.1 Baseline (Weekday -1 to -2 ) 
The following will be performed at Baseline: 
• Inclusion/Exclusion 
• Medical History (only changes since Screen 2) 
• Medication History (only changes since Screen 2) 
• Signs & Symptoms (only changes since Screen 2) 
• Pregnancy Test (serum or urine β-hCG) 
• Physical Exam. 
• Vital Signs 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• INR 
• Lipid Panel (Section 15.3) 
• Cytokines (Section 15.3) 
• Imaging (head MRI & FDG-PET) 
• Clinical Stroke Evaluations 
• Cognitive Questionnaire (Section 23.0, Table 7) 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Section 15.7) 
• Luminex assay for antibodies to SB623 
 
10.3.2 Enrollment (Days -1 or 1) 
Enrollment can only occur after performing all assessments and verifying that the patient 
meets the inclusion and exclusion criteria for the study. 
 
 

 
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10.4 Cell Administration (Day 1) 
Prior to any procedures, the patient will be queried on the use of any changes in medication 
since Baseline. 
Prior to cell implantation, either a head CT overlaid with the Baseline head MRI or a head 
MRI alone will be done to determine the exact locations for the implants. 
Using the procedures in Section 6.0, surgical and implantation Procedures and Section 10.4, 
Preparation and Administration, one burr hole will be made in the skull of the patient in a 
location that will allow ready access to the infarct region.  Cells will be implanted using 3 
needle tracks with 5 cell deposits for each track at varying depths.  Cell implantation will be 
standardized as to volume (20 µL/deposit) and rate (10 µL /min), with spacing between each 
implant of approximately 5-6 mm. 
After cell implantation, the following will be performed: 
• Imaging (head CT only) 
• Adverse Events 
• Concomitant medications 
10.5 Follow-Up Period (Study Day 2) 
The following will be performed: 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
• Head MRI (MRI must be read before re-starting any antiplatelet, anticoagulant, or 
non-steroidal anti-inflammatory agents) 
10.6 Follow-Up Period (Study Day 8) 
The following will be performed: 
• Vital Signs 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Lipid Panel (Section 15.3) 
• Cytokines (Section 15.3) 
• Head MRI 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Section 15.7) 
• Luminex assay for antibodies to SB623 and PBMC function assay 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
 
 

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10.7 Follow-Up Period (End of Months 1, 2, 3, 4 ± 5 Days) 
• Vital Signs 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Lipid Panel (Section 15.3) 
• Plasma Cytokines (months 2, 4 only) (Section 15.3) 
• Imaging (head MRI) 
• Clinical Stroke Evaluations 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Months 2, 4 only) (Section 15.7) 
• Luminex assay for antibodies to SB623 and PBMC function assay (Months 2, 4 only) 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
10.8 Follow-Up Period (End of Month 6 ±7 Days) 
• Vital Signs 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Lipid Panel (Section 15.3) 
• Plasma Cytokines (Section 15.3) 
• Imaging (head MRI & PET) 
• Clinical Stroke Evaluations 
• Cognitive Questionnaire (Section 23.0, Table 7) 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Section 15.7) 
• Luminex assay for antibodies to SB623 and PBMC function assay 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
10.9 Follow-Up Period (Months 9, 12 ±7 Days) 
• Physical Exam. (Month 12 only) 
• Vital Signs (Including Weight for Mo. 12 only) 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Lipid Panel 
• Plasma Cytokines (Section 15.3) 
• Imaging--Head MRI 
• Imaging—FDG PET (mo. 12 only) 

 
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• Clinical Stroke Evaluations 
• Cognitive Questionnaire (Month 12 only) (Section 23.0, Table 7) 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Month 12 only) 
• Luminex assay for antibodies to SB623 and PBMC function assay 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
10.10 Last Evaluation (End of Month 24 ±14 Days or Early Withdrawal) 
• Physical Exam. 
• Vital Signs Including Weight 
• Hematology (Section 15.3) 
• Serum Chemistry (Section 15.3) 
• Lipid Panel 
• Plasma Cytokines (Section 15.3) 
• Imaging (head MRI & PET) 
• Clinical Stroke Evaluations 
• Cognitive Questionnaire (Section 23.0, Table 7) 
• Blood for antibodies to SB623 and peripheral blood mononuclear cells (PBMC) 
function assays and for storage of PBMCs (Section 15.7) 
• Luminex assay for antibodies to SB623 and PBMC function assay 
• Adverse Events 
• Concomitant Medications (see Section 12.0) 
11.0 DESCRIPTION OF STUDY TREATMENT 
11.1 Study Drug Description 
SB623 cells are provided as a 1-mL sterile cell suspension, containing ≥5 X 106 cells/mL, 
cryopreserved in CryoStore™ freezing media. 
11.2 Study Drug Packaging 
Individual 1.5-mL Nalgene™ cryovials. 
11.3 Study Drug Shipment and Storage 
The cryovials containing the frozen cell suspensions are shipped in a dry nitrogen shipper 
and should be stored in the vapor phase within the shipping container provided by the 
Sponsor until transferred at the site to a GMP-compliant liquid nitrogen container. 
The Sponsor will arrange for Study Drug to be shipped to the clinical site. 
 
 
 

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11.4 Preparation and Administration 
Details for preparation of the cell suspension for administration will be provided by the 
Sponsor.  Clinical sites will be provided necessary materials for reconstitution of the cells 
and will be trained by the Sponsor.  The cryopreserved cells will be thawed, washed, 
centrifuged, and re-suspended in Plasma-Lyte A at varying concentrations (see Section 4.1) 
for administration to the patient within approximately 3 hours of re-suspension.  Prior to 
administration, a gram stain and a test for endotoxin will be done and a sterility test initiated 
on the last cell wash to insure continued sterility.  If the endotoxin level is > 5 EU/mL or the 
gram stain is positive, implantation will not occur.  If the sterility test is positive, an 
investigation will be conducted to determine the source of the contamination.  In addition, 
identification of the pathogen and sensitivity will be done and the patient treated with an 
appropriate antibiotic.  In this event, the patient will be followed closely for adverse events 
associated with a possible infection and response to antimicrobial therapy, including frequent 
clinic visits until any infection is cleared. 
This Investigational Product may not be used for any purpose other than this clinical study. 
11.5 Study Drug Accountability Procedures 
The Investigator will be responsible for maintaining inventory and accounting for all Study 
Drug received from the Sponsor on a drug accountability log.  After reconciliation has been 
completed, all Study Drug vials received by the Investigator (used and unused) will be 
collected, and the used vials destroyed at the site under supervision of the monitor per 
institutional standard operating procedure.  Unopened vials will be kept frozen until returned 
to the Sponsor. 
12.0 CONCOMITANT MEDICATIONS 
All concomitant medications including prescription and over-the-counter drugs taken during 
the 14 days prior to enrollment or used anytime during the study through 2 years post Study 
Drug will be documented.  Documentation (through month 9 only) will include changes from 
the prior visit, start and stop dates, dose, and reasons for the medication use. 
Investigational drugs or devices for any other indication are not allowed during the study. 
13.0 STUDY WITHDRAWAL/TERMINATION 
13.1 Study Termination 
The protocol may be terminated at anytime by the Sponsor in the event of significant Study-
Drug-related adverse effects. 
13.2 Site Termination 
The study site will be closed if there is evidence of fraud, other unethical conduct, or 
significant non-compliance to the protocol or to Good Clinical Practices (GCPs).  Should 
patient enrollment be unsatisfactory, or data recording be inaccurate and/or incomplete, the 
Sponsor may terminate the study and remove all study materials from the study site. 
 
 

 
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13.3 Patient Discontinuation 
Patients will be free to discontinue from the study at any time without giving a reason(s).  
Patients will be considered discontinued from the study in the event of any of the following 
reasons: 
• 
Withdrawal of the patient’s consent for any reason  
• 
Investigator’s discretion due to patient’s medical condition 
If patient withdrawal occurs during the study period, the Last Evaluation visit should be 
performed, whenever possible, at the time of patient withdrawal or as soon as possible (see 
Section 10.8).  The Investigator should continue to evaluate the medical condition of any 
patient who has withdrawn for 2 years post-implant. 
In the event a patient withdraws from the study for any reason, the Investigator must 
notify the Principal Monitor by telephone within 24 hours of withdrawal. 
13.4 Patients Lost to Follow Up 
Patients who cannot be reached after at least three attempts will be categorized as lost to 
follow up.  The attempts to reach the patients must be documented, with at least one of the 
attempts written and sent to the patient via certified mail.  Patients lost to follow up will still 
be included in the analysis of the study. 
14.0 STOPPING RULES 
A dose-limiting toxicity will be defined as any grade 3 or 4 events which are at least possibly 
related to study product or administration procedure.  If the first patient in a cohort has a 
dose-limiting toxicity attributable to the SB623 cells, then no further patients will be dosed in 
that cohort until a comprehensive evaluation has been conducted.  If 2 of 6 patients in a 
cohort have a dose-limiting toxicity attributable to the SB623 cells, then no further patients 
will be dosed in that or higher-dose cohorts.  Each dose-limiting-toxicity will be evaluated by 
the DSMB. 
In addition, adverse events attributable to the surgical procedure, such as intracranial 
infection, intracranial bleeding, or seizures, shall be subject to review by the DSMB 
The DSMB shall be the final arbitrator for attributions. 
15.0 CLINICAL AND LABORATORY EVALUATIONS AND PROCEDURES 
15.1 Medical History 
Medical history will include significant medical conditions and surgical history, medications 
taken within 2 weeks prior to signing the Informed Consent, and signs and symptoms 
occurring within 3 weeks after signing the Informed Consent. 
15.2 Physical Examination and Vital Signs 
A complete physical examination will be performed (including a genital/rectal exam if 
clinically indicated). 
Vital signs will include oral temperature, blood pressure at rest, heart rate, and respiratory 
rate (and Weight for Weeks -3, and Mos. 12, 24). 

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15.3 Safety Laboratory 
All safety laboratory evaluations will be conducted at the laboratories located at or associated 
with the clinical site.  At every sampling time point, approximately 5 mL of blood will be 
drawn for each of the hematology and serum chemistry panels. 
The following laboratory evaluations will be performed: 
• Hematology Panel: hematocrit, hemoglobin, WBC, platelet count, lymphocyte count, 
neutrophil count 
• Serum Chemistry Panel: sodium, chloride, calcium, potassium, magnesium, 
bicarbonate, lactate, C-reactive protein, glucose, creatinine, BUN, AST, ALT, 
alkaline phosphatase, and total bilirubin 
• Lipid Panel: total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides 
• Cytokines: Plasma TNF-α, Plasma IL-6, and Plasma IFN-γ 
• INR 
15.4 Pregnancy Test: Serum or urine β-hCG 
• Serum β-hCG at Screening 1 (using same blood draw as for serum chemistry) 
• Urine β-hCG at Baseline 
15.5 Antibodies to HLA Antigens on SB623 
• A serum sample, taken at initial screening (and optionally at a Pre-Screening visit) 
will be used to determine the presence of antibodies to donor SB623 cells with a 
Luminex value of >1000 MFI (Maximum Fluorescence Intensity): HLA Class I 
(HLA-A*23:PWMV, HLA-A*68:CGBR; HLA-B*45:FJH, HLA-B*53:KJW; or 
HLA-Bw4, HLA-Bw6; HLA-Cw*04:SSWB, HLA-Cw*16:01); or Class II (HLA-
DRB1 *13:NGUB, HLA-DRB1 *16:02; HLA-DQB1*05:CHZY, HLA-
DQB1*05:BK; HLA-DQA1*01:DVB, HLA-DQA1*X, HLA-DRB3,4,5: 3*03:01, 
HLA-DRB3,4,5: 5*02:02) 
15.6 Serum Antibodies to SB623 
Serum antibody measurements will be made to monitor a possible humoral-mediated 
immune response.  Blood samples (approximately 10 mL) will also be taken at the intervals 
indicated in Table 4 for measurements of serum antibodies to SB623 using the Luminex 
assay.  Assays may be done bimonthly on pooled samples. 
15.7 PBMC Function 
PBMC function will be evaluated to monitor any possible cell-mediated immune responses, 
including inflammation. 
Blood samples (approximately 20 mL) will also be taken at the intervals indicated in Table 4.  
PBMCs from Baseline Samples will be aliquoted into approximately 20 tubes to provide at 
least 600,000 cells per tube, then kept frozen in vapor phase of liquid nitrogen until needed as 
controls for subsequent time-point assays.  For all other time points, PBMCs will be isolated 
and the sample split into multiple vials of equal portions (A and B) containing at least 
600,000 cells each, then similarly frozen until time to assay PBMC function.  PBMC 
function during the study will be determined on the A portions by stimulation with 

 
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PMA/ionomycin/SB623, evaluating any changes from baseline in cytokine secretion.  These 
evaluations on batched samples of PBMCs will be approximately at bimonthly intervals 
during the first 6 months, quarterly thereafter through the first year, then at 2 years. 
B portions of PBMCs will be stored in the vapor phase of liquid nitrogen until requested by 
the Sponsor for any subsequent determination of PBMC function if needed for further safety 
follow up. 
15.8 Clinical Stroke Evaluations 
15.8.1 European Stroke Scale (ESS) 
Specific information on scoring using the ESS31 can be found in the publicatin. 
15.8.2 National Institute of Health (NIH) Stroke Scale 
Specific information on scoring using the NIH Stroke Scale56 can be found in the 
publication. 
15.8.3 Modified Rankin Scale (MRS) 
Specific information on scoring using the MRS34,35 can be found in the publications. 
15.8.4 Fugl-Meyer Score 
Specific information on scoring using the Fugl-Meyer Scale38 can be found in the 
publication. 
15.9 Cognitive Questionnaire 
A battery of tests will be used to evaluate cognitive function.  These are summarized in Table 
7, Appendix D, Section 23.0.  Additional details will be provided by the Sponsor. 
15.10 Assessment of Cellular Metabolism 
Functional assessment of cells within and around the infarct will be determined by use of 
18F-fluorodeoxyglucose uptake measured by positron emission tomography (PET). 
16.0 ADVERSE EVENTS 
16.1 General Information 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and that does not necessarily 
have a causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of an investigational 
product, whether or not considered related to the investigational product.  This includes any 
side effects, injury, toxicity, or sensitivity reaction, and may include a single symptom or 
sign, a set of related symptoms or signs, or a disease.  An adverse event is also any laboratory 
abnormality judged to be clinically significant by the Investigator or Sub-investigator(s) that 
worsened compared to Baseline. 
Throughout the course of the study, every effort should be made to remain alert to possible 
adverse experiences.  Patients should be encouraged to report adverse events spontaneously 
or in response to general, non-directed questioning. 

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With the occurrence of an adverse event, the primary concern is the safety of the patient.  If 
necessary, appropriate medical intervention should be provided, and the investigational drug 
discontinued. 
An AE does not include: 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion); the condition that leads to the procedure is an adverse event 
• 
Pre-existing diseases or conditions present or detected at the start of the study that do 
not worsen in severity or frequency 
• 
Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions) 
• 
Overdose of either Study Drug or concomitant medication without any signs or 
symptoms 
A Serious Adverse Event (SAE) is any adverse event that results in any of the following: 
• 
death, 
• 
life-threatening event, 
• 
hospitalization or prolongation of hospitalization, 
• 
a persistent or significant disability/incapacity, 
• 
congenital anomaly/birth defect, or 
• 
an event that may require intervention to prevent any one of the other outcomes listed 
above (based on medical judgment) 
An Unexpected Adverse Event is any AE that is not identified in nature, severity, or 
frequency in the current Investigator’s Drug Brochure or product information.  For this study, 
an unexpected adverse event also includes neurological deterioration, procedural 
complications, seizures, benign and malignant tumors and pregnancy, and will be submitted 
as expedited reports. 
An Unexpected Adverse Drug Reaction (ADR) is an adverse reaction, the nature or 
severity of which is not consistent with the applicable product information (e.g., 
Investigator’s Brochure for an unapproved investigational medicinal product).  All noxious 
and unintended responses to a medicinal product related to any dose should be considered 
ADRs.  All serious and unexpected ADRs will have expedited reporting to the FDA. 
16.2 Adverse Event Reporting Period 
The adverse event reporting period for this trial begins upon receiving the first dose of Study 
Drug and ends 24 weeks after the administration of SB623. 
All AEs (both serious and non-serious) must be followed until resolution or until a stable 
clinical endpoint is reached.  All measures required for AE management and the ultimate 
outcome of the AE must be recorded in the source document and reported to the Sponsor. 
 
 

 
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16.3 Recording of AEs 
All AEs, regardless of severity, seriousness, or presumed relationship to Study Drug, must be 
recorded using medical terminology in the source document and on the CRF.  Events will be 
recorded at all study sites using standard terminology provided by the Sponsor or designate 
(e.g., CRO), such as COSTART terminology. 
The WHO (World Health Organization) Standard Toxicity Criteria (STC) will be used to 
assist in categorizing and grading adverse events.  A copy of the WHO STC will be provided 
in the study documents.  Whenever possible, a diagnosis should be given when signs and 
symptoms are due to common etiology (e.g., cough, runny nose, sneezing, sore throat, and 
head congestion should be reported as “upper respiratory infection”). 
16.4 Assessing Relationship of AE to Study Drug 
The Investigator must record his/her opinion concerning the relationship of the AE to study 
therapy on the Adverse Event CRF.  Table 5 below provides guidance for assigning 
relationship to Study Drug. 
Table 5 
Relationship of Adverse Event to the Administration of the Study Drug 
Unrelated 
There is not a temporal relationship to study drug administration (e.g., too early, 
too late, or study drug not taken), or there is a reasonable causal relationship 
between another drug, concurrent disease, or circumstance and the AE. 
Unlikely  
There is a temporal relationship to study drug administration, but there is not a 
reasonable causal relationship between the study drug and the AE (i.e., the AE 
is doubtfully related to study drug) 
Possibly 
There is a reasonable causal relationship between the study drug and the AE.  
Information related to withdrawal of study drug is lacking or unclear 
Probably 
There is a reasonable causal relationship between the study drug and the AE.  
The event responds to withdrawal of study drug.  Re-challenge is not required 
Definitely  There is a reasonable causal relationship between the study drug and the AE.  
The event responds to withdrawal of study drug, and recurs with re-challenge, 
when clinically feasible 
 
16.5 Reporting Serious or Unexpected AEs 
Any Serious Adverse Event, including death that occurs during this study (from the first dose 
of Study Drug up to and including 4 weeks following the last dose of Study Drug), whether 
or not the event is considered to be related to the study treatment, must be reported 
immediately (within 24 hours after the site becomes aware of the event) to the Principal 
Monitor. 
The contact information for reporting SAEs is as follows: 
Ernest Yankee, Ph.D. 
Phone: 650-625-8965 ext 44 
Cell: 650-892-4448 
Email: ernest.yankee@san-bio.com 
 
 

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The Investigator is encouraged to discuss with the Principal Monitor any adverse experiences 
for which the issue of reportability is unclear or questioned. 
A verbal or faxed Serious Adverse Event Report must be followed by a written report signed 
by the Investigator within 48 hours.  Written notification must include SAE start and stop 
dates, Study Drug dosage and treatment history, description of SAE with applicable 
laboratory test results, list of concomitant medications, relationship of Study Drug to SAE, 
autopsy report (if applicable), and any other relevant information such as medical history, 
hospital discharge summary, etc.  The report should be as complete as possible without 
delaying Sponsor notification. 
An SAE Report should be prepared containing as much available information concerning the 
event as possible so that a written report can be filed with the appropriate regulatory 
authorities.  Any SAE follow-up information requested by the Sponsor or the Sponsor’s 
designee should be provided in a timely manner. 
Upon receipt of notification of any Serious Adverse Event, the Sponsor will immediately 
conduct an evaluation of the event and take action indicated by the results of the evaluation.  
This may include notification of the FDA, other Investigators, IRBs and/or the suspension or 
termination of the study.  The Investigator is required to report Serious Adverse Events and 
Unexpected Adverse Events to the local Ethics Committee (EC) or Institutional Review 
Board (IRB) in accordance with the EC/IRB bylaws. 
All additional follow-up evaluations of the SAE must be reported to the Sponsor.  These data 
should be faxed to the Principal Monitor at 650-625-8472 as soon as they are available. 
16.6 Follow-up of Adverse Events 
All AEs (both serious and non-serious) should be followed until resolution or until a stable 
clinical endpoint is reached.  All measures required for AE management and the ultimate 
outcome of the AE must be recorded in the source document and reported to the Sponsor. 
17.0 EXTERNAL DATA SAFETY MONITORING BOARD 
An External Data Safety Monitoring Board (DSMB) will continuously evaluate toxicity and 
mortality rates, and recommend appropriate actions, according to the DSMB Charter. 
18.0 STATISTICAL METHODS  
18.1 Overview of Analysis 
18.1.1 Safety Parameters 
• Adverse events related to the surgical procedure 
• SB623-related adverse events 
• Adverse changes imaged by head MRI (edema, adverse anatomical changes) 
• Serious adverse events (SAEs) 
• Serum chemistry and hematology 
 
 

 
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18.1.2 Efficacy Parameters 
• Clinical improvement of stroke symptoms using the European Stroke Scale, the NIH 
Stroke Scale, and the Modified Rankin Scale; improvement in motor functions using 
the Fugl-Meyer scale, and improvement in cognitive status using a test battery 
(including Rey Complex Figure Test; see Appendix D) 
• Increase in fluorodeoxyglucose (FDG) uptake measured by PET 
18.1.3 Efficacy Objectives 
Primary: 
• To evaluate clinical (ESS) and radiographic (FDG-PET) response to 3 dose 
levels of intracranial administration of SB623 cells at 6 months 
Secondary: 
• To evaluate clinical (NIHSS, MRS, Fugl-Meyer, Cognitive Tests) response to 3 
dose levels of intracranial administration  of SB623 cells at 6 months 
• To evaluate clinical (ESS, NIHSS), MRS, and Fugl-Meyer response to 3 dose 
levels of intracranial administration of SB623 cells at 1, 2, 3, 4, 9, 12, and 24 
months; also to evaluate changes from Baseline in cognitive function at 6, 12, 
and 24 mos., and changes from Baseline in radiographic (DFG-PET) responses at 
6, 12, and 24 mos. 
18.2 Patients to be Included in the Analyses 
18.2.1 Efficacy Population 
The intent-to-treat (ITT) population will include all enrolled patients, including those who 
were discontinued from the study or withdrawn for any reason.  The Evaluable population 
will be defined in the Statistical Analysis Plan. 
18.2.2 Safety Population 
The safety analyses will include all enrolled patients who have received Study Drug and who 
have any post-Baseline data. 
18.3 Analysis of Efficacy 
18.3.1 Primary Analysis 
The primary analysis will be a pooled analysis of changes at 6 months from Baseline for all 
patients for ESS and FDG-PET parameters.  Categorical variables will be summarized by 
frequency and percent.  Continuous variable data will be summarized, including mean, 
median, standard deviation and range.  Statistics will be done on changes in scores, and will 
be based on Wilcoxon Signed Rank test unless otherwise specified in the Statistical Analysis 
Plan. 
18.3.2 Secondary Analyses 
The secondary analyses will be pooled analyses of changes from Baseline at 1, 2, 3, 4, 6, 9, 
12, and 24 months for all patients for ESS, NIHSS, MRS, and Fugl-Meyer.  Evaluation of 
changes from Baseline for Cognitive Tests, and FDG-PET parameters will be done at months 
6, 12, and 24.  In addition, possible dose-response will be determined.  Statistics will be done 
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18.4 Analysis of Safety 
Adverse events, clinical laboratory data, and vital signs will be analyzed to evaluate the 
safety of SB623 for all patients in the Safety population through 2 years after the dose of 
Study Drug. 
A treatment-emergent adverse event will be defined as any event not present prior to the 
initiation of treatment or any event already present that worsens in either intensity or 
frequency following exposure to study treatment. 
All adverse event data will be listed per patient including severity, relationship to Study 
Drug, and action taken.  Frequency within each treatment group of each type of adverse 
event will be summarized using an acceptable coding dictionary. 
Laboratory data and vital signs will be listed by patient.  Laboratory data values above and 
below normal ranges which are considered clinically significant will be indicated on the 
listing.  Descriptive statistics will be displayed for each laboratory parameter and vital sign 
assessment at each time point.  The mean change from baseline in each of these continuous 
variables will also be described.   
18.5 Determination of Sample Size 
The sample size of 6 patients per cohort was determined based on safety considerations.  
Based on the animal safety studies, no dose-limiting toxicity is anticipated.  However, if the 
true rate is 40%, a sample size of 6 patients per cohort would result in a < 5% chance of 
missing a dose-limiting toxicity. 
18.6 Deviations from the Protocol Analysis Plan 
Any deviations from the original planned analysis as described in the protocol will be 
detailed in the final integrated clinical report with an explanation of the alternative methods 
employed. 
19.0 ADMINISTRATION OF THE STUDY 
19.1 Regulatory Considerations 
This study will be conducted in compliance with the protocol, ICH Good Clinical Practice 
Guidelines (GCPs), and the applicable local regulatory requirements.  This study will be 
conducted in accordance with the ethical principles that originate in the Declaration of 
Helsinki and ICH Guidelines for Good Clinical Practices (GCPs). 
Study protocols and Informed Consent Forms will be approved by the appropriate Ethics 
Committee or Institutional Review Board (and governmental authorities, as needed) prior to 
initiation of the study at a particular site.  All patients will sign an Informed Consent Form 
prior to any study-specific procedures.  Performance during the study will be routinely 
monitored by a study monitor selected by the Sponsor. 
19.2 Independent Ethics Committee (EC)/Institutional Review Board (IRB) 
The Investigator must submit the final protocol and proposed informed consent document to 
an Independent Ethics Committee (EC) or Institutional Review Board (IRB) that complies 
with the ICH Guideline for Good Clinical Practice.  The EC/IRB will provide the 
Investigator with a written decision regarding the conduct of the study at that site and a copy 

 
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of the document will be forwarded to the Project Manager.  The study will not be initiated 
and patients will not be enrolled until the appropriate documentation of EC/IRB approval of 
the study protocol and the informed consent has been received. 
Substantive modifications to the protocol will be submitted to the EC/IRB for approval.  
These modifications may be implemented only after EC/IRB written approval has been 
received and forwarded to the Project Manager.  Administrative changes to the protocol such 
as a change that has no effect on the conduct of the study or risk to the patient should be 
submitted to the EC/IRB for review, but formal approval is not required. 
The Investigator must also submit any other written information that will be given to the 
study patients as well as any advertisements for patient recruitment, if used, to the EC/IRB 
for approval prior to implementing these documents. 
The Investigator will make appropriate and timely reports to the EC/IRB as required by 
applicable government regulations and EC/IRB policy.  In addition to progress reports, all 
known information regarding serious adverse events, whether observed at their clinical site 
or at another site participating in a clinical investigation with the Study Drug, will be 
reported to the EC/IRB.  It is the Sponsor and/or its designee’s responsibility to inform the 
Investigator of serious adverse events observed at other investigational sites. 
It is the Investigator's obligation to provide the Sponsor and/or its designees with copies of 
all study-related correspondence with the EC/IRB in a timely fashion and to retain originals 
in a file.  This EC/IRB correspondence file will be made available as requested to appropriate 
designees for monitoring or quality assurance review and to governmental regulatory 
representatives during site audits. 
19.3 Patient Information and Informed Consent 
Written informed consent must be obtained from each patient after the nature of the study has 
been fully explained in accordance with the ICH Guideline for Good Clinical Practice.  
Informed consent must be obtained prior to performing any study-specific procedures.  The 
consent form that is used must be approved by both the reviewing EC/IRB and by the 
Sponsor. 
The patient (or surrogate) and the individual explaining the study will sign the current 
EC/IRB-approved version of the consent form.  A copy of the signed consent form will be 
given to the patient.  The date that consent was obtained will be recorded on the case report 
form as well as in the patient's chart. 
A copy of the EC/IRB-approved version of the consent form will be provided to the Sponsor.  
Original signed consent form must be maintained at the site and be made available for 
inspection, as appropriate. 
A sample consent form is provided in Appendix A. 
19.4 Adherence to the Protocol 
The study shall be conducted as described in this protocol except for an emergency situation 
in which proper care of the patient requires immediate alternative intervention.  This protocol 
refers to the protocol as provided by the Sponsor and approved by both the IRB and the FDA.  
All of these versions of the protocol must be the same.  While FDA regulations permit the 
protocol to be amended, this must be done in accordance with the provisions agreed upon on 

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Section 19.5.  Any deviation from the design of the study as set forth in this document must 
be recorded as a protocol deviation and be explained in detail as it occurs and/or is detected. 
19.5 Protocol Modifications 
Neither the Investigators nor the Sponsor will modify this protocol without obtaining the 
concurrence of the other.  All protocol amendments will be issued by the Sponsor, and must 
be signed and dated by the Investigator prior to implementation of the amendment.  The 
Sponsor will submit protocol modifications to Regulatory Agencies as required.  The 
Investigator is responsible for notifying the EC/IRB of changes.  Substantive changes will 
require EC/IRB approval, such as changes in experimental procedures that affect patient 
safety, changes in dosage or study treatment, changes in assessment parameters, or changes 
in patient eligibility criteria.  The EC/IRB may require the Informed Consent Form to be 
altered in the event of protocol changes or new safety information. 
In situations requiring a departure from the protocol, the Investigator or other physician in 
attendance will contact the Sponsor or designee by fax or telephone.  If possible, this contact 
will occur before implementing any departure from protocol.  In all cases, contact with the 
Sponsor or designee must be made as soon as possible in order to discuss the situation and 
agree on an appropriate course of action.  The CRF and source document must describe any 
departure from the protocol and the circumstances. 
19.6 Data Collection 
Patient screening/enrollment will be documented in a study-specific log at the study site.  
This log will capture the following information: patient number, initials, patient personal 
identification number or medical record number, date of screen/enrollment, reason for not 
enrolling (if applicable), and any comments. 
A CRF (Case Report Form) will be provided for each study patient.  Data collected through 
the completion of experimental procedures required by this protocol will be recorded in the 
patient's chart as source documentation.  This data will then be transcribed onto the CRF. 
All required study data, including results of an autopsy if the patient dies during the study, 
will be entered into the Case Report Forms (CRFs) provided by the Sponsor.  All information 
in the CRFs must be supported by original data in the patient’s medical records.  All medical 
records, laboratory printouts, notes made by the physician, and other materials such as x-rays 
will be considered source data and must be available for inspection by the Sponsor and/or 
delegates, or governmental representatives. 
All entries to the CRF must be made in indelible black ink.  All corrections must be made by 
drawing a single line through the error and entering the correct data as close as possible to 
the original entry without obscuring data.  The correction must be initialed and dated by the 
person making the correction.  The Investigator remains responsible for the accuracy and 
adequacy of all data entered on CRFs. 
Data will be monitored as described in Section 19.8.  Under direction of the clinical monitor, 
CRFs will be pulled and further processed for data entry and analysis.  A copy of each CRF 
page must remain at the investigative site in the appropriate patient's CRF binder. 

 
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Upon further data processing, queries may be generated and sent to the Investigator for 
clarification or correction.  The Investigator will address any queries and forward resolutions 
as directed by the site monitor. 
19.7 Maintaining Records 
A study binder must be maintained at the investigative site and must contain the documents 
identified in Appendix B, including a signed Investigator Agreement.  The Sponsor, or its 
designee, will provide a Study Binder to the site. 
According to U.S. Federal Regulations (21 CFR 312), all records related to this clinical trial 
must be retained by the Investigator for at least 2 years after the last approval of a marketing 
application and until there are no pending or contemplated marketing applications OR until at 
least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product.  The Sponsor will inform the Investigator as to when these 
documents no longer need to be retained.  These documents must be stored in a safe location 
and be available in the event of a regulatory audit. 
Study records that must be retained include, but are not necessarily limited to: patient charts, 
case report forms, product disposition records, essential documents identified in Appendix B, 
and study reports. 
19.8 Monitoring, Auditing, Inspecting 
The Sponsor or designee (e.g., clinical research organization [CRO]) will assure the accuracy 
of data, the selection of qualified Investigators, appropriate study centers and review protocol 
procedures with the Investigators and associated personnel prior to the study and during 
periodic monitoring visits.  The Sponsor or a designee will review CRFs for accuracy and 
completeness during on-site monitoring visits and after their return from the clinical site.  
Discrepancies will be resolved with the Investigator as appropriate. 
The Sponsor or its designees will monitor the study using the following methods: 
• frequent telephone contacts 
• periodic site visits 
• review of original patient records, case report forms, drug accountability and 
storage, and general study documentation 
So that the study may be adequately monitored, the Investigator will cooperate in providing 
the Sponsor’s designees with all study documents (e.g., patient charts and study files) and 
responding to inquiries that may arise as a result of the document review. 
Review of these documents will usually occur during a routine monitoring visit, but may also 
be required during a visit by a quality assurance auditor.  The Investigator will also provide 
access to these records to regulatory representatives if and when requested.  The Sponsor 
reserves the right to terminate the study site if access to source documentation of work 
performed in this study is denied to the Sponsor or regulatory representatives. 
19.9 Confidentiality 
The anonymity of patients participating in this study must be maintained.  Patients will be 
identified by their assigned patient number and their initials in all written communications 
between the Investigator and Sponsor.  Documents that are not submitted to the Sponsor and 

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that identify the patient (e.g., signed informed consent; source documents/charts) will be 
made available to the Sponsor or regulatory authorities for inspections, but will be 
maintained in confidence. 
All study related information provided by the Sponsor to the Investigator and not previously 
published, including but not limited to the active study agent identity, the investigator's 
brochure, the study protocol, verbal and written communication, case report forms, assay 
methods and scientific data, will be considered confidential.  In addition, all information 
developed during the conduct of the clinical investigation of the study agent is also 
considered confidential.  Neither the Investigator nor any of his/her employees or agents shall 
disclose or use this information for any purpose other than the performance of the clinical 
study.  Such information shall remain the confidential and proprietary property of the 
Sponsor, and disclosure to others will be limited to other physicians who are conducting 
studies with the same active study agent, the Ethics Committee/IRB and the applicable 
regulatory authorities except by prior written permission of the Sponsor or its agents.  At 
such time that information becomes widely and publicly available through no fault of the 
Investigator, the obligation of nondisclosure toward that particular information will cease. 
19.10 Publication Policy 
Publication of the results of this study may be appropriate.  At least 30 days prior to expected 
submission to the intended publisher or meeting committee, the Investigator must submit a 
copy of the desired presentation (oral or written) or publication manuscript to the Sponsor.  
This review period may be shortened upon mutual consent where circumstances require 
expeditious review.  The Sponsor reserves the right to suggest modification of any 
publication, presentation or use by the Investigator if such activity may jeopardize a patent 
application, an existing patent, or other proprietary rights. 

 
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20.0 APPENDIX A: SAMPLE INFORMED CONSENT 
(Final version to follow institutional standards) 
 
 
Patient 
Initials 
____ ____ ____ 
 
 
 
 
 
Date 
___ / ___ / ___ 
 
 
AUTHORIZATION TO PARTICIPATE IN A RESEARCH PROJECT 
TITLE OF STUDY: 
A Phase 1/2A Study of the Safety and Efficacy of Modified Stromal Cells (SB623) in 
Patients with Stable Ischemic Stroke 
 
SPONSOR:  
 
 
SanBio, Inc. 
231 S. Whisman Rd. 
 
 
 
 
 
Mountain View, CA  94041 
 
PROTOCOL NO.:  
 
SB-STR01 
INVESTIGATOR:  
 
 
TELEPHONE: 
 
 
 
STUDY SITE LOCATION: 
 
INTRODUCTION: 
You are being invited to take part in a research study that will last approximately 24 months 
for you.  Approximately 18 patients will participate in this study.  It is important that you 
read and understand several general principles that apply to all study participants:  
1. Taking part in the study is entirely voluntary 
2. You do not have to be in any research study offered to you by your doctor.  When 
you are deciding if you should join the study, you may want to talk with someone not 
part of the study about your questions and feelings about joining.  This could be a 
family member, friend, or another health provider 
3. Personal benefit to you (improvement in your stroke symptoms) may or may not 
result from taking part in the study.  Knowledge will be gained from your 
participation that may benefit other patients. 
4. You may withdraw from the study at any time without penalty or loss of any benefits 
to which you are otherwise entitled. 

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The nature of the study, the benefits, risks, discomforts and other information about the study 
are discussed below.  There may be information in this consent form that you do not 
understand.  Any questions you have should be discussed with the staff members.  They will 
explain it to you. 
NOTE: If you are not completely truthful with your study doctor regarding your health 
history, you may harm yourself by participating in this study. 
THE NATURE AND PURPOSE OF THIS STUDY: 
You have been diagnosed with stable ischemic stroke, and have had physical therapy for 
your stroke-related conditions.  Your stroke was caused by a blood clot in a blood vessel in 
your brain and this happened at least 6 months ago, but not more than 60 months ago.  This 
study is being conducted primarily to determine the safety of a cell suspension of SB623 
cells administered by injection into your brain around the area of the stroke.  In addition, 
information will be obtained to determine if there might be any improvement in the severity 
of your stroke.  All the usual standard of care procedures and drugs will also be used. 
SB623 cells are modified cells derived from bone marrow of other adult humans.  From the 
bone marrow, cells are isolated and then modified using recombinant DNA methods to make 
cells that have been shown to secrete agents that may be helpful to dying tissue.  The product 
that you will be using is an investigational drug (not approved by any governmental 
regulatory authorities). 
EXPLANATION OF PROCEDURES TO BE FOLLOWED:  
After you sign the consent form and before you begin treatment, you will be asked questions 
about your medical history, medications you are taking, and how you feel.  You will also 
have a complete physical examination.  The doctor will check your pulse, blood pressure, 
respiratory rate and temperature. 
Approximately 25 mL (a little less than one ounce or two tablespoons) of blood will be 
drawn and a urine sample will be requested for monitoring your health status and to confirm 
that you are eligible to participate in the study.  If you are a woman capable of bearing a 
child, the blood sample will also be used for a pregnancy test. 
You will be evaluated for your stroke symptoms by a variety of methods, such as asking you 
questions and requesting you to make certain movements while you are being videotaped.  
This will be done twice prior to implantation of the SB623 cells, over a three week period.  
This is to confirm that your stroke symptoms are stable. 
You will also be asked to undergo magnetic resonance imaging (MRI) of your head at your 
first screening visit.  The purpose of the MRI is to determine the precise location and size of 
your stroke and to ensure there are no other abnormalities.  MRI machines only use a 
magnetic field.  In addition, the PET scan will require that you be injected with an agent that 
contains a radioactive tag so that the wellness of the cells in and around your stroke area can 
be evaluated. 
 
 

 
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Surgical Procedure and Administration of the Cells: 
The SB623 cells are to be implanted directly into your brain in and around the area of the 
stroke.  To do this, you will have a small hole drilled into your skull.  This will be done under 
local anesthesia.  The exact position of the hole to be made will be determined by having you 
undergo MRI scanning.  MRI (Magnetic Resonance Imaging) is a special procedure using an 
instrument with a very strong magnet.  A special apparatus will be used on your head to 
make sure the hole is positioned such that the implantation of the cells will be precisely into 
the stroke region, at location also determined by MRI.  A needle will be inserted through the 
hole into your brain extending into and slightly beyond the main stroke region.  Cells will be 
implanted at 5 sites through this one needle injection.  Two additional needle insertions with 
5 more implantation sites each will also be done at slightly different angles. 
There will be 3 groups of patients enrolled in this study.  Your assignment to a particular 
group by the study doctor will depend on when you enter the study.  Six patients will be 
studied in group 1 before proceeding to 6 patients in group 2, who in turn will be studied 
before proceeding to 6 patients in group 3.  The total amount of cells you will receive will 
depend on which group you are in.  Group 1 patients will receive 2.5 million cells; group 2 
patients will receive 5 million cells; and group 3 patients will receive 10 million cells.  All 
patients will receive a total of 300 µL of fluid (about 1/3rd of mL, or less than 1/10th of a 
teaspoon or about 6 drops from a standard dropper). 
Study Procedures: 
You will be asked to provide blood samples throughout the study in addition to any samples 
required for your normal care.  Approximately 25 mL (a little less than one ounce or two 
tablespoons) of blood will be drawn at total of 11 times, including the screening and baseline 
samples.  These will be used to monitor safety and to assess certain markers related to the 
cells. 
After completion of the surgical and cell injection procedures, you will be given CT scan (a 
type of imaging procedure using a contrast agent and X-rays) to determine that you have no 
complications, and then will be admitted to a neurosurgical patient ward for 24 hour 
observation.  You will be discharged on the first post-operative day. 
Periodically, you will also receive a PET scan.  PET stands for Positron Emission 
Tomography.  In this procedure, a marker similar to glucose (a sugar) containing an atom 
that emits radiation (positron) will be injected into your blood stream.  A machine that 
measures this radiation will determine if your brain cells are behaving in the usual manner in 
absorbing the glucose marker. 
You will be asked to periodically undergo additional MRI scans to assess your progress and 
to evaluate safety.  You will also be asked standardized questions about your stroke 
symptoms and be asked to make certain movements as you did during your screening. 
REQUEST FOR AUTOPSY: 
In the event of your death during the study from any cause, the study doctor will ask your 
family for permission to perform an autopsy.  The evaluation of organs and tissues after 
death is a very valuable method to learn more about any effects of the study agent.  You 
should talk about the possibility of an autopsy with your family and health provider, and 
advise them of your wishes.  The study sponsor will pay all costs of the autopsy. 

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POSSIBLE RISKS AND DISCOMFORTS: 
This is the first time that SB623 cells have been administered to people, so possible side 
effects are not known, except that mild, post-surgical headache that resolved within 1 week 
has been reported by all 6 of the first cohort of subjects..  It has been administered to animals 
(rats and monkeys) with no negative cell-related effects observed.  Since the cells did not 
survive longer than 3 months in rats, possible later cell effects could not be determined. 
Studies with SB623 cells to determine its capability to cause harm to an unborn child have 
not been performed.  Therefore, if you are pregnant, or think you might be, you will not be 
allowed to participate in this study.  If you are a woman of childbearing potential, you will be 
tested for pregnancy at the beginning of the study. 
Because you will be receiving a CT scan, you will be exposed to a low level of radiation.  
The risks of the contrast material used with the CT scan include rare allergic reactions, 
nausea, flushing, low blood pressure, asthma, stroke and organ damage.  The PET scans will 
also expose you to a low level of radiation from the injected radioactive agent (FDG). 
Although animal studies up to 12 months have shown no evidence of any tumor formation, 
there is the theoretical possibility that SB623 may induce formation of tumors, as has been 
seen with embryonic stem cells.  While this is believed to be very unlikely to occur with 
SB623, periodic MRI measurements will be carried out to provide an early indication if this 
should happen. 
All of the animal safety studies have used animal models that were highly 
immunosuppressed to uncover any possible tumor formation.  However, you will not be 
given any immunosuppressant during this study since other studies have suggested that 
SB623 is itself an immunosuppressant.  Nevertheless, there is a possibility that implantation 
of SB623 could cause local inflammation or a systemic immune response.  This will be 
monitored carefully during the study by making measurements of your blood that include 
standard laboratory tests and by periodic MRI scans as indicated earlier. 
The surgical procedure that you will receive has been associated with a small risk of bleeding 
and infection.  This was documented by studying the records of over 2,650 patients who had 
undergone this surgical procedure over a period of 28 years.  Headaches are a normal and 
expected symptom following surgery for cell implantation, as is mild pain at the site of the 
incision.  These symptoms may last for several days following your operation.  So far, this 
study has demonstrated a small risk of a special bleeding problem, so-called subacute 
subdural hematoma, which is a bleed deep in the brain where the needle was inserted.  
Should this occur, it will be managed by the current standard of care, which may necessitate 
another surgical procedure to remove the blood.  There may also be a small amount of 
cerebral spinal fluid associated with this, which may also require surgical removal.  One 
subject has also had seizure that was readily treated.  This was categorized as possibly related 
to the surgery, and unrelated to the Study Drug. 
Significant new information that becomes known during the course of the research that may 
affect your willingness to continue participation in the study will be provided to you. 
 
 

 
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If you experience more than minimal discomfort after completing the implantation 
procedure, you should: 
1. 
Call the study doctor at once at telephone number: (xxx) xxx-xxxx 
2. 
If necessary, go to the nearest emergency room 
During this study, you will receive the standard care for your condition (including antibiotics, 
pain medicine, cardiovascular support, ventilator support, and hospitalization) as required. 
PREGNANCY/ BIRTH CONTROL: 
If you are pregnant or nursing a child, you cannot take part in this study since there is no 
known information about potential harm to unborn children.  If you are a woman who has 
had a tubal ligation, hysterectomy, or are post-menopausal, you may be eligible to take part 
in this study.  If you are a woman of child-bearing potential you must practice acceptable 
methods of birth control (oral, implantable, or injectable contraceptives; spermicide in 
conjunction with a barrier such as a condom or diaphragm; intrauterine device or IUD) for at 
least the first 6 months of the study. 
ALTERNATIVES TO PARTICIPATION: 
There are no approved therapies for your stroke-related condition.  The study doctor has 
discussed any other options available to you, including non-participation in this study.  If you 
decide not to take part in this study, it will not affect your future treatment. 
POSSIBLE BENEFITS: 
Although it is hoped that participation in this trial may lead to some improvement in your 
condition, the primary goal of this study is to establish safety of the approach rather than to 
maximize the chance for improvement.  Accordingly, you should not expect to receive 
benefit from participation in this study.  However, the knowledge obtained from this research 
may help the health care professionals caring for you to better treat other patients undergoing 
treatment for a condition similar to yours. 
COMPENSATION FOR PARTICIPATION: 
There is no additional cost to you for participation in this research study beyond the costs 
normally associated with your treatment.  The SB623 cells will be provided free of charge to 
you by the Sponsor.  The physician visits and associated tests related to the study will also be 
provided at no cost.  You will be reimbursed any out-of-pocket expenses relating to 
participation in this research study. 
MEDICAL CARE FOR INJURY RELATED TO THIS STUDY: 
In the event of injury resulting from your participation in this research, medical care will be 
provided to you by the study doctor.  The care will be free of charge to you.  The Sponsor of 
the Study is insured in the event you are injured through participation in the study. 
CONFIDENTIALITY AND RELEASE OF MEDICAL RECORDS: 
The study doctor will provide information about your treatment to the Sponsor (SanBio 
Incorporated) and/or its representative.  You have the right to privacy, and all information 
obtained in this study that can identify you individually will remain confidential to the extent 
possible within the state and federal laws.  Only your patient number and initials will be 

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recorded on study documents and reports.  Your name will not be revealed in any reports or 
publications resulting from this study.  Other information, including your gender, age, and 
ethnicity, will be recorded on study documents for the purposes of analyses of the study 
outcome.  Nothing in the study documents will provide any identification of you.  
Governmental and institutional regulatory authorities and the Sponsor and/or its designee 
(the site monitor), may inspect and copy your records pertaining to this study.  The results of 
the study will be reported to governmental agencies. 
In the rare instances for which regulatory authorities may require patient names, the 
regulatory authorities will treat such information as confidential, but disclosure to third 
parties may be required on rare occasions.  Therefore, absolute protection of confidentiality 
by regulatory authorities cannot be promised or implied. 
Because this study involves genetically-modified cells, safety information must be reported 
to the Recombinant DNA Advisory Committee of the National Institutes of Health.  This 
information is available to the public.  However, no information by which participants can be 
identified will be reported with the safety information.  We will try to keep your identity and 
other information collected in this study confidential.  There may be some exceptions when 
the law requires disclosure.  Representatives of [study site], and/or the Food and Drug 
Administration, and/or the National Institutes of Health, or other regulatory agencies outside 
[study site] may ask to review the data collected from this study.  These groups can have 
access to your name and medical records. 
It is possible that the media may want to find out about you because you took part in this 
study.  We will take every precaution to protect your privacy and that of your family.  We 
will also maintain the confidentiality of the research data.  To lower the chance that your 
identity will be made public, all requests for information will be directed to the [study site] 
Public Relations Office.  Despite these efforts, reporters may try to find out who you are 
without the approval of the [study site].  If the media succeed, they might ask to interview 
you and your privacy may be invaded.  Every effort will be made to protect your privacy but 
it may not be possible to do so. 
VOLUNTARY PARTICIPATION AND WITHDRAWAL: 
Your participation in this study is voluntary and you are free to withdraw at anytime.  Any 
new information developed during this research that may be related to your willingness to 
continue participation will be provided to you.  Participation or withdrawal will involve no 
penalties or loss of benefits to which you are otherwise entitled, and will not affect your 
future medical care. 
Your participation in this study may be discontinued without your consent for the following 
reasons: 
• if treatment appears to be medically harmful to you 
• if you fail to follow directions for participation in the study 
• if it is discovered you do not meet the eligibility requirements 
• if the study is canceled 

 
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If you withdraw from, or must be discontinued from the study prior to its completion, you 
will be asked to have a final close out visit to protect your health status. 
POSSIBLE CONFLICTS OF INTEREST: 
The study doctor is a researcher in this study.  As a researcher, he is interested not only in our 
health and well being, but also in the results of this study.  It is possible that sometimes these 
two goals may conflict with one another.  Researchers protect the rights and interests of 
participants by carefully following the rules of the study. 
This research is sponsored by SanBio, Inc.  This means that SanBio is paying the research 
team for the costs of doing the study.  The researchers do not have a financial stake in the 
results of the study. 
 
 

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OFFER TO ANSWER QUESTIONS ABOUT THIS STUDY: 
If you have questions about this study, your condition and/or treatment, or if you experience 
a research-related injury or illness, you should contact Insert Name of PI, MD at: (xxx) 
xxx-xxxx 
If you have questions about your rights as a research patient, you may contact a 
representative of the Ethics Committee for this institution at (xxx) xxx-xxxx.   
CONSENT TO PARTICIPATE IN THIS STUDY: 
Your consent to participate in research should be voluntary and informed.  By signing this 
form, you acknowledge that you have read this information (or had it read to you), been 
given an opportunity to ask questions about the information provided in this form, and 
understand the potential risks and benefits.  By signing this form you indicate that you wish 
to participate in the study at this time. 
Having consented, you still have the right to withdraw at any time without jeopardy to your 
care.  If you wish to withdraw, you should notify the study doctor or study coordinator; you 
do not have to give a reason if you do not wish to.  You will not lose any legal rights as a 
research patient by signing this form. 
You will be given a signed copy of this form to keep and refer to as needed. 
 
 
 
 
Signature of Study Patient 
 
Date 
 
 
 
 
 
Printed Name of Study Patient 
 
 
 
 
 
 
 
Signature of Person Explaining Informed Consent 
 
Date 
 
 
 
 
 
Title of Person Explaining Informed Consent 
 
 
 
 

 
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21.0 APPENDIX B: ESSENTIAL STUDY DOCUMENTS 
 
 
 
DOCUMENT 
LOCATION 
COLLECTION TIME 
The following documents will be obtained for 
the regulatory files at the indicated times during 
the trial 
Sponsor 
Site 
Pre-
Study 
During 
Post-
Study 
Investigator’s Drug Brochure 
X 
X 
X 
 
 
Signed protocol and amendments, if any 
X 
X 
X 
 
 
Sample Case-Report Form (CRF) 
X 
X 
X 
 
 
Informed-Consent Form 
X 
X 
X 
 
 
Any other written information given to trial 
patients 
X 
X 
X 
 
 
Advertisement for patient recruitment, if used 
 
X 
X 
 
 
Financial aspects of the trial  
X 
X 
X 
 
 
Insurance statement, where required 
X 
X 
X 
 
 
Signed agreement between: 
• Investigator/institution and Sponsor 
• Investigator/institution and CRO, where 
required 
• Sponsor and CRO 
• Investigator/institution and authority(ies), 
where required 
X 
X 
X 
 
 
Dated, documented approval/favorable opinion 
of IRB/IEC for:  
• Protocol and any amendments 
• CRF, if applicable 
• Informed-Consent Form 
• Any other written information to be 
provided to the patient(s) 
• Advertisements for patient recruitment, if 
used 
• Subject compensation, if any 
• Any other documents given 
approval/favorable opinion 
X 
X 
X 
 
 
IRB/IEC committee composition 
X* 
X 
X 
 
 
Regulatory authority(ies) 
authorization/approval/ notification of protocol, 
where required 
X* 
X* 
X 
 
 
Curriculum vitae and/or other relevant 
documents evidencing qualifications of 
Investigator(s) and Sub-investigators 
X 
X 
X 
 
 

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DOCUMENT 
LOCATION 
COLLECTION TIME 
The following documents will be obtained for 
the regulatory files at the indicated times during 
the trial 
Sponsor 
Site 
Pre-
Study 
During 
Post-
Study 
Normal value(s)/range(s) for 
medical/laboratory/technical procedure(s) 
and/or test(s) included in the protocol 
X 
X 
X 
X 
 
Medical/laboratory, technical procedures/tests 
• Certification or  
• Accreditation or  
• Established quality control and/or external 
quality assessment or  
• Other validation, where required  
X 
X* 
X 
 
 
Sample of label(s) attached to investigational 
product container(s) 
X 
X 
X 
 
 
Instructions for handling of investigational 
product(s) and trial-related materials, if not 
included in the protocol or Investigator’s 
Brochure 
X 
X 
X 
 
 
Shipping records for investigational product(s) 
and trial-related materials 
X 
X 
X 
 
 
Decoding procedures for blinded trials 
X† 
X 
X 
 
 
Investigator’s Brochure updates 
X 
X 
 
X 
 
Revisions to: 
• Protocol/amendment(s)  
• CRF(s) 
• Informed Consent Form(s) 
• Any other written information provided to 
patients 
• Advertisements for patient recruitment, if 
used 
X 
X 
 
X 
 
Dated, documented approval/favorable opinion 
of IRB/IEC for: 
• Protocol amendments 
• Revisions to Informed-Consent Form 
• Revisions to any other written information 
to be provided to the patient 
• Advertisements for patient recruitment, if 
used 
• Any other documents given 
approval/favorable opinion  
• Continuing review of trial 
X 
X 
 
X 
 

 
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DOCUMENT 
LOCATION 
COLLECTION TIME 
The following documents will be obtained for 
the regulatory files at the indicated times during 
the trial 
Sponsor 
Site 
Pre-
Study 
During 
Post-
Study 
Regulatory authority(ies) 
authorizations/approval/ notifications for 
protocol amendment(s) and other documents 
X 
X* 
 
X 
 
Curriculum vitae for new Investigator(s) and/or 
Sub-investigators 
X 
X 
 
X 
 
Updates to normal value(s)/range(s) for medical 
laboratory/technical procedure(s)/test(s) 
included in the protocol 
X 
X 
 
X 
 
Updates of medical/laboratory/technical 
procedures/test 
• Certification or 
• Accreditation or 
• Established quality control and/or external 
quality assessment or 
• Other validation, where required 
X 
X* 
 
X 
 
Documentation of investigational product(s) and 
trial-related materials shipment 
X 
X 
 
X 
 
Relevant communications other than site visits 
• Letters 
• Meeting notes 
• Notes of telephone calls 
X 
X 
 
X 
 
Signed Original Informed-Consent Form 
 
X 
 
 
 
Signed Informed-Consent Form--Copy 
X 
 
 
X 
 
Source documents 
 
X 
 
X 
 
Signed, dated, and completed CRFs 
X‡ 
X§ 
 
X 
 
Documentation of CRF corrections 
X‡ 
X§ 
 
X 
 
Notification by originating Investigator to 
Sponsor of serious adverse events and related 
reports 
X 
X 
 
X 
 
Notification by Sponsor and/or Investigator, 
where applicable, to regulatory authority(ies) 
and IRB(s)/IEC(s) of unexpected serious 
adverse drug reactions and of other safety 
information 
X 
X* 
 
X 
 
Notification by Sponsor to Investigators of 
safety information 
X 
X 
 
X 
 
Interim or annual reports to IRB/IEC and 
authority(ies) 
X* 
X 
 
X 
 
Subject screening log 
X* 
X 
 
X 
 
Subject identification code list 
 
X 
 
X 
 

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DOCUMENT 
LOCATION 
COLLECTION TIME 
The following documents will be obtained for 
the regulatory files at the indicated times during 
the trial 
Sponsor 
Site 
Pre-
Study 
During 
Post-
Study 
Subject enrollment log-original 
 
X 
 
 
 
Subject enrollment log-copy 
X 
 
 
X 
 
Investigational product(s) accountability at the 
site 
X 
X 
 
X 
X 
Record of retained body fluids/tissue samples, if 
any 
X 
X 
 
X 
X 
Documentation of investigational product(s) 
destruction 
X 
X║ 
 
X 
X 
Completed patient identification code list 
 
X 
 
 
X 
Final report by Investigator/institution to 
IRB/IEC where required, and where applicable, 
to the regulatory authority(ies) 
X 
X 
 
 
X 
Clinical study report 
X 
X¶ 
 
 
X 
 
*  Where required 
†  Third party if applicable 
‡  Original   § Copy 
║ If destroyed at site 
¶  If applicable 

 
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22.0 APPENDIX C: WHO STANDARD TOXICITY CRITERIA 
The WHO Standard Toxicity Criteria is tabulated below in Table 6. 
Copies of this document will also be provided to each site as part of the study documents. 
 
For abnormalities not found elsewhere in the WHO table, use the following scale to assign 
grade or severity: 
 
 
Grade 1 
Mild 
Transient of mild discomfort; no limitation in 
activity; no medical intervention/therapy required. 
Grade 2 
Moderate 
Mild-to-moderate limitation in activity; some 
assistance may be need.  No or minimal medial 
intervention/therapy required. 
Grade 3 
Severe 
Marked limitation in activity, some assistance 
usually required; medical intervention/therapy 
required; hospitalization or prolongation of current 
hospitalization possible. 
Grade 4 
Life-threatening 
Extreme limitation in activity, significant 
assistance required; significant medial 
intervention/therapy required; hospitalization or 
prolongation of current hospitalization or hospice 
care probable. 

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Table 6 
WHO (World Health Organization) Toxicity Criteria by Grade 
Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Haematology  
WBC (x103/l)  
4  
3.0 - 3.9  
2.0 - 2.9  
1.0 - 1.9  
< 1.0  
Haematology  
Platelets (x103/l)  WNL  
75.0 - normal  
50.0 - 74.9  
25.0 - 49.9  
< 25.0  
Haematology  
Haemoglobin 
(g/dl)  
WNL  
10.0 - normal  
8.0 - 9.9  
6.5 - 7.9  
< 6.5  
Haematology  
Granulocytes/ 
Bands (x103/l)  
2  
1.5 - 1.9  
1.0 - 1.4  
0.5 - 0.9  
< 0.5  
Haematology  
Lymphocytes 
(x103/l)  
2  
1.5 - 1.9  
1.0 - 1.4  
0.5 - 0.9  
< 0.5  
Haematology  
Haemorrhage  
none  
mild, no  
gross, 1 - 2 units 
transfusion per 
episode  
gross, 3 - 4 units 
transfusion per 
episode  
massive, > 4 units 
transfusion per episode  
Coagulation 
Fibrinogen  
WNL  
0.99 - 0.75 x N  
0.74 - 0.50 x N  
0.49 - 0.25 x N  
< 0.25 x N  
Coagulation 
Prothrombin 
time(Quick)  
WNL  
1.01 - 1.25 x N  
1.26 - 1.50 x N  
1.51 - 2.00 x N  
> 2.00 x N  
Coagulation 
Partial 
thromboplastin 
time  
WNL  
1.01 - 1.66 x N  
1.67 - 2.33 x N  
2.34 - 3.00 x N  
> 3.00 x N  
Metabolic  
Hyperglycaemia 
(mg/dl)  
< 116  
116 - 160  
161 - 250  
251 - 500  
> 500 or ketoacidosis  
Metabolic  
Hypoglycaemia 
(mg/dl)  
> 64  
55 - 64  
40 - 54  
30 - 39  
< 30  
Metabolic  
Amylase  
WNL  
< 1.5 x N  
1.5 - 2.0 x N  
2.1 - 5.0 N  
> 5.0 x N  
Metabolic  
Hypercalcaemia 
(mg/dl)  
< 10.6  
10.6 - 11.5  
11.6 - 12.5  
12.6 - 13.4  
13.5  
Metabolic  
Hypocalcaemia 
(mg/dl)  
> 8.4  
8.4 - 7.8  
7.7 - 7.0  
6.9 - 6.1  
6  

 
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Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Metabolic  
Hypomagnesaemia 
(mg/dl)  
> 1.4  
1.4 - 1.2  
1.1 - 0.9  
0.8 - 0.6  
0.5  
Gastrointestinal Nausea  
none  
able to eat 
reasonable intake  
intake significantly 
decreased but can eat 
no significant 
intake  
__  
Gastrointestinal Vomiting  
none  
1 episode in 24 hrs  2 - 5 episodes in 24 
hrs  
6 - 10 episodes in 
24 hrs  
> 10 episodes in 24 hrs 
or requiring parenteral 
support  
Gastrointestinal Diarrhoea  
none  
increase of 2 - 3 
stools / day over 
pre-Rx  
increase of 4 - 6 
stools / day, or 
nocturnal stools, or 
moderate cramping  
increase of 7 - 9 
stools / day, or 
incontinence, or 
severe cramping  
increase of > 10 stools / 
day or grossly bloody 
diarrhoea, or need for 
parenteral support  
Gastrointestinal Stomatitis  
none  
painless ulcers, 
erythema, or mild 
soreness  
painful erythema, 
oedema, or ulcers but 
can eat solids  
painful erythema, 
oedema, or ulcers 
and cannot eat 
solids  
requires parenteral or 
enteral support for 
alimentation  
Liver  
Bilirubin (N = 17 
µmol/L)  
WNL  
-----  
< 1.5 x N  
1.5 - 3.0 x N  
> 3.0 x N  
Liver  
Transaminase 
(SGOT, SGPT)  
WNL  
2.5 x N  
2.6 - 5.0 x N  
5.1 - 20.0 x N  
> 20.0 x N  
Liver  
Alk Phos or 5 
nucleotidase  
WNL  
< 2.5 x N  
2.6 - 5.0 x N  
5.1 - 20.0 x N  
> 20.0 x N  
Liver  
Liver- clinical  
No change 
from baseline  -----  
-----  
precoma  
hepatic coma  
Kidney, bladder Creatinine  
WNL  
< 1.5 x N  
1.5 - 3.0 x N  
3.1 - 6.0 x N  
> 6.0 x N  
Kidney, bladder Proteinuria  
No change  
1 (+) or < 0.3 g% 
or 3 g/L  
2 - 3 (+) or 0.3 - 1.0 
g% or 3 - 10 g/L  
4 (+) or > 1.0 g% 
or > 10g/L  
nephrotic syndrome  
Kidney, bladder Haematuria  
Negative  
microscopic only  
gross, no clots no Rx 
needed  
gross and clots 
bladder irrigation  
requires transfusion or 
cystectomy  

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Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Kidney, bladder Weight gain/ loss  < 5.0 %  
5.0 - 9.9 %  
10.0 - 19.9 %  
20.00%  
-----  
Pulmonary  
Pulmonary  
none or no 
change  
asymptomatic, with 
abnormality in 
PFTs  
dyspnoea on 
significant exertion  
dyspnoea at 
normal level of 
activity  
dyspnoea at rest  
Cardiac  
Cardiac 
arrhythmias  
none  
asymptomatic, 
transient, requiring 
no therapy  
recurrent or 
persistent, no therapy 
required  
requires 
treatment  
requires monitoring; or 
hypotension, or 
ventricular tachycardia 
or fibrillation  
Cardiac  
Cardiac function  
none  
asymptomatic, 
decline of resting 
ejection fraction by 
less than 20 % of 
baseline value  
asymptomatic, 
decline of resting 
ejection fraction by 
more than 20 % of 
baseline value  
mild CHF, 
responsive to 
therapy  
severe of refractory 
CHF  
Cardiac  
Cardiac ischaemia  none  
non-specific T- 
wave flattening  
asymptomatic, ST 
and T wave changes 
suggesting ischaemia 
angina without 
evidence of 
infraction  
acute myocardial 
infarction  
Cardiac  
Cardiac- 
pericardial  
none  
asymptomatic 
effusion, no 
intervention 
required  
pericarditis (rub, 
chest pain, ECG 
changes)  
symptomatic 
effusion; 
drainage required 
tamponade; drainage 
urgently required  
Cardiac  
Hypertension  
none or no 
change  
asymptomatic, 
transient increase 
by greater than 20 
mm Hg (D) or to > 
150 / 100 if 
previously WNL. 
No treatment 
required.  
recurrent or 
persistent increase by 
greater than 20 mm 
HG (D) or to > 150 / 
100 if previously 
WNL. No treatment 
required.  
requires therapy  hypertensive crisis  

 
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Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cardiac  
Hypotension  
none or no 
change  
changes requiring 
no therapy 
(including transient 
orthostatic hypo-
tension)  
requires fluid 
replacement or other 
therapy but not 
hospitalisation  
requires therapy 
and 
hospitalisation; 
resolves within 
48 hours of 
stopping the 
agent  
requires therapy and 
hospitalisation for > 48 
hrs after stopping the 
agent  
Neurologic  
Neuro: sensory  
none or no 
change  
mild paraesthesias; 
loss of deep tendon 
reflexes  
mild or moderate 
objective sensory 
loss moderate 
paraesthesias  
severe objective 
sensory loss or 
paraesthesias that 
interfere with 
function  
-----  
Neurologic  
Neuro: motor  
none or no 
change  
subjective 
weakness; no 
objective findings  
mild objective 
weakness without 
significant 
impairment of 
function  
objective 
weakness with 
impairment of 
function  
paralysis  
Neurologic  
Neuro: cortical  
none  
mild somnolence or 
agitation  
moderate 
somnolence or 
agitation  
severe 
somnolence, (>50 
% waking hours), 
agitation, 
confusion, 
disorientation or 
hallucinations  
coma, seizures, toxic 
psychosis  
Neurologic  
Neuro: cerebellar  none  
slight 
incoordination, 
dysdiadochokinesia 
intention tremor, 
dysmetria, slurred 
speech, nystagmus  
locomotor ataxia  cerebellar necrosis  
Neurologic  
Neuro: mood  
no change  
mild anxiety or 
depression  
moderate anxiety or 
depression  
severe anxiety or 
depression  
suicidal ideation  

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Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Neurologic  
Neuro: headache  none  
mild  
moderate or severe 
but transient  
unrelenting and 
severe  
-----  
Neurologic  
Neuro: 
constipation  
none or no 
change  
mild  
moderate  
severe  
ileus > 96 hrs  
Neurologic  
Neuro: hearing  
none or no 
change  
asymptomatic, 
hearing loss on 
audiometry only  
tinnitus  
hearing loss 
interfering with 
function but 
correctable with 
hearing aid  
deafness not 
correctable  
Neurologic  
Neuro: vision  
none or no 
change  
-----  
-----  
symptomatic 
subtotal loss of 
vision  
blindness  
Pain  
Pain  
none  
mild  
moderate  
severe  
reg. narcotics  
Skin  
Skin  
none or no 
change  
scattered macular 
or papular eruption 
or erythema that is 
asymptomatic  
scattered macular or 
papular eruption or 
erythema with 
pruritus or other 
associated symptoms  
generalised 
symptomatic 
macular, papular 
or vesicular 
eruption  
exfoliative dermatitis or 
ulcerating dermatitis  
Alopecia  
Alopecia  
no loss  
mild hair loss  
pronounced or total 
hair loss  
-----  
-----  
Allergy  
Allergy  
none  
transient rash, drug 
fever < 38o C 
(100.4o F)  
urticaria, drug fever 
38o C (100.4o F), 
mild bronchospasm  
serum sickness, 
bronchospasm 
requiring 
parenteral 
medication  
anaphylaxis  
Local  
Local  
none  
pain  
pain and swelling 
with inflammation or 
phlebitis  
ulceration  
plastic surgery 
indicated  

 
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Category 
Toxicity 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever of 
unknown origin 
Fever of unknown 
origin  
none  
37.1 - 38.0o C 
98.7o - 100.4o F  
38.1 - 40.0o C 100.5 - 
104o F  
> 40.0o C > 
104.0o F for less 
than 24 hrs  
> 40.0o C (>104o F) for 
more than 24 hrs or 
accompanied by 
hypotension  
Infection  
Infection  
none  
mild  
moderate  
severe  
life-threatening  
Additional 
events  
Asthenia  
Analogous to 
Karnofsky 
index (WHO 
grading)  
   
   
   
   
Additional 
events  
Chills  
Analogous to 
fever  
   
   
   
   
Additional 
events  
Peripheral oedema  analogous to 
weight gain  
   
   
   
   
Additional 
events  
Anorexia  
analogous to 
weight loss  
   
   
   
   
 

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23.0 APPENDIX D: COGNITIVE FUNCTION TEST BATTERY 
Table 7 
Cognitive Function Test Battery 
Estimated Intelligence 
 
*Wechsler Abbreviated Scale of Intelligence (WASI) 2 Test 
Language 
 
Controlled Oral Word Association Category 
 
Vocabulary (WASI) 
Attention 
 
Trails A Time 
 
Digit Vigilance Accuracy 
Learning and Memory 
 
Rey Auditory Learning Test 
 
Rey Complex Figure – immediate & delayed recall 
 
Logical Memory – WMS-III 
Working Memory 
 
Trails B Time and Errors 
 
Letter-Number Sequencing- WMS-III 
Visuospatial/Constructional Ability 
 
Rey Complex Figure Copy 
 
Matrix Reasoning—WASI 
Psychomotor Efficiency 
 
Digit Vigilance Time 
 
Trails A Errors 
 
Digit Symbol Substitution Test -WAIS-III 
 
Grooved Pegboard 
Executive Function (reasoning, mental manipulation) 
 
Stroop Interference 
 
Controlled Oral Word Association—FAS 
Mood State and Quality of Life  
 
Beck Depression Inventory, 2nd Ed. 
 
Beck Anxiety Inventory 
 
 
* Baseline only 

 
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24.0 REFERENCES 
                                                 
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45  Bohn M. Northwestern University. 2007. Unpublished data. 
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49  Study Number 1295-002. Implantation of SanBio SB623 Cells into the Brains of Male 
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50  Study Number 1295-008: Implantation of SanBio SB623 Cells into the Brains of Male 
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51  qPCR data provided by Althea Technologies. 
52  Study conducted for SanBio by Valley Biosystems and MPI Research. 

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53  Study Number 1295-005. A 6-Month GLP Safety Evaluation of SB623 Cells Implanted 
into the Brain of the Monkey. MPI Research, 2007. 
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