A Phase I, Open-Label Study to Assess the Effect of Escalating Doses of Cyclophosphamide on the Engraftment of SB-728-T in Aviremic HIV-Infected Subjects on HAART
Phase: PHASE1
Conditions: HIV
Sponsor: Sangamo Therapeutics

Sangamo BioSciences, Inc. 
Protocol SB-728-1101 
Confidential 
 
Page 1 of 70                                                                                   Version: January 30, 2014 
Clinical Study Protocol 
 
A Phase I, Open-Label Study to Assess the Effect of 
Escalating Doses of Cyclophosphamide on the 
Engraftment of SB-728-T in Aviremic HIV-Infected 
Subjects on HAART  
Protocol Number: 
SB-728-1101 
BB-IND: 
14129 
Sponsor: 
Sangamo BioSciences, Inc. 
Point Richmond Tech Center II 
501 Canal Blvd., Suite A100 
Richmond, CA  94804 
Phone:  (510) 970-6000 
Fax:  (510) 970-6009 
Medical Monitor: 
 
Winson Tang, M.D.  
Phone:  (510) 970-7800 
Fax:  (510) 970-6009 
Original Version: 
Amendment 1: 
Amendment 2:  
Amendment 3: 
Amendment 4: 
Amendment 5: 
Amendment 6: 
Amendment 7: 
Amendment 8: 
Amendment 9: 
 
November 15, 2011 
March 14, 2012 
August 3, 2012  
November 9, 2012 
April 18, 2013 
June 21, 2013 
August 22, 2013 
October 04, 2013 
November 18, 2013 
January 30, 2014 
 
 
Confidentiality Statement 
This document contains confidential information. It is intended solely for the use of the principal 
investigator, co-investigators, staff, appropriate institutional review boards or ethical committees, and 
other required regulatory bodies.

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 3 of 70                                                                                   Version: January 30, 2014 
TABLE OF CONTENTS 
1.     INTRODUCTION ................................................................................................... 11 
1.1 
CLINICAL EXPERIENCE WITH SB-728-T ............................................................... 11 
1.2 
CYCLOPHOSPHAMIDE TO ENHANCE SB-728-T ENGRAFTMENT .............................. 12 
1.2.1  Cyclophosphamide and Adaptive Immunotherapy ............................................. 13 
1.2.2  Safety of Cyclophosphamide in Autoimmune Disease ....................................... 13 
1.2.3  Use of Cyclophosphamide in HIV ................................................................... 14 
1.3 
HAART TREATMENT INTERRUPTION ................................................................... 14 
1.4 
RISK BENEFIT ANALYSIS .................................................................................... 15 
1.5 
STUDY HYPOTHESIS .......................................................................................... 16 
2. 
STUDY OBJECTIVES ........................................................................................ 16 
2.1 
PRIMARY OBJECTIVE ......................................................................................... 16 
2.2 
SECONDARY OBJECTIVES .................................................................................. 16 
3. 
STUDY DESIGN ................................................................................................. 16 
3.1 
OVERVIEW ........................................................................................................ 17 
3.2 
NUMBER OF SUBJECTS ...................................................................................... 17 
3.3 
DOSE ESCALATION ............................................................................................ 17 
3.4 
COHORT EXPANSION ......................................................................................... 17 
3.5 
STUDY DURATION .............................................................................................. 17 
3.6 
VISIT SCHEDULE ............................................................................................... 17 
3.7 
STUDY PROCEDURES ........................................................................................ 18 
4. 
SUBJECT SELECTION ..................................................................................... 18 
4.1 
INCLUSION CRITERIA .......................................................................................... 18 
4.2 
EXCLUSION CRITERIA ........................................................................................ 19 
5.  
INFORMED CONSENT ...................................................................................... 20 
6. 
STUDY METHODOLOGY .................................................................................. 20 
6.1 
SCREENING VISIT PROCEDURES ......................................................................... 20 
6.2 
SUBJECT ENROLLMENT PROCEDURES................................................................. 21 
6.3 
PRE- LEUKAPHERESIS AND LEUKAPHERESIS ........................................................ 21 
6.3.1  Pre-Leukapheresis: ......................................................................................... 21 
6.3.2  Leukapheresis: ............................................................................................... 21 
6.4 
BASELINE ASSESSMENTS ................................................................................... 22 
6.4.1  
Baseline for Research Blood Collection: ....................................................... 22 
6.4.2  Baseline: ....................................................................................................... 22 
6.5 
STUDY TREATMENT AND FOLLOW-UP .................................................................. 22 
6.5.1  
Cyclophosphamide Administration ............................................................... 22 
6.5.2  Day 0 – SB-728-T infusion ............................................................................. 24 
6.5.3  Day 1 ............................................................................................................ 24 
6.5.4  Day 5 (- 1 day) (Cohorts 4 and 5 only) ............................................................. 24 
6.5.5  Week 1, Day 12 (-1 day) (Cohorts 4 and 5 only), Week 2, Week 3, and Week 4 (+/- 
2 day) 24 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 4 of 70                                                                                   Version: January 30, 2014 
6.5.6  Weeks 6, 8, 10, 12, 14, 18 and 22: 16-Week HAART Treatment Interruption ....... 25 
6.5.7  Month 7, Month 8, Month 10, Month 12 (+/- 1 week) ........................................ 26 
6.5.8  Long-Term Follow-up .................................................................................... 27 
7.  
INSTRUCTIONS FOR EVALUATIONS ............................................................. 27 
8.  
MEDICATIONS .................................................................................................. 28 
8.1 
SB-728-T ........................................................................................................ 28 
8.1.1   Inventory, Storage, and Handling of the Drug Product ...................................... 28 
8.1.2  SB-728-T Administration ............................................................................... 29 
8.1.3  Precautions .................................................................................................... 29 
8.1.4  Dose Modifications ........................................................................................ 30 
8.2 
CYCLOPHOSPHAMIDE ......................................................................................... 30 
8.3 
HAART ............................................................................................................ 31 
8.3.1  Discontinuation of HAART ............................................................................ 31 
8.3.2  Reinstitution of HAART ................................................................................. 31 
8.4 
CONCOMITANT MEDICATION ............................................................................... 31 
9.  
SAFETY AND POTENTIAL RISKS ................................................................... 32 
9.1 
SB-728-T ........................................................................................................ 32 
9.1.1  Emergence of CXCR4 HIV ............................................................................. 32 
9.1.2  Carcinogenicity ............................................................................................. 32 
9.1.3  Replication Competent Adenovirus (RCA) ....................................................... 33 
9.1.4  Immunogenicity ............................................................................................. 33 
9.2 
CYCLOPHOSPHAMIDE ......................................................................................... 34 
9.3 
HAART TREATMENT INTERRUPTION (TI) ............................................................. 34 
10. 
ADVERSE EVENTS ........................................................................................... 36 
10.1 
ADVERSE EVENT REPORTING PERIOD ................................................................. 36 
10.2 
DEFINITIONS OF AN ADVERSE EVENT .................................................................. 36 
10.3 
RECORDING OF AN ADVERSE EVENT ................................................................... 37 
11. 
SERIOUS ADVERSE EVENT ............................................................................ 38 
11.1 
SERIOUS ADVERSE EVENT REPORTING PERIOD ................................................... 38 
11.2 
DEFINITIONS OF A SERIOUS ADVERSE EVENT ...................................................... 38 
11.3 
RECORDING OF A SERIOUS ADVERSE EVENT ....................................................... 39 
12. 
SUBJECT WITHDRAWAL, DOSE ESCALATION, AND STOPPING RULES .. 39 
12.1 
SUBJECT WITHDRAWAL AND DISCONTINUATION FROM STUDY ............................... 39 
12.2 
DOSE ESCALATION RULES ................................................................................. 39 
12.3 
COHORT EXPANSION ......................................................................................... 40 
12.4 
STOPPING RULES .............................................................................................. 40 
12.4.1 
Stopping Rules for Treatment Interruption .................................................... 40 
12.4.2 
Stopping Rules for Study ............................................................................ 40 
13. 
STATISTICAL ANALYSIS AND DATA ANALYSIS .......................................... 41 
13.1 
SAMPLE SIZE .................................................................................................... 41 
13.2 
STATISTICAL METHODS/DATA ANALYSIS .............................................................. 42 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 5 of 70                                                                                   Version: January 30, 2014 
13.3 
INTENT-TO-TREAT POPULATION .......................................................................... 42 
13.4 
DEMOGRAPHICS ................................................................................................ 42 
13.5 
ENDPOINTS AND ANALYSIS ................................................................................. 42 
13.5.1 
Primary Endpoint ....................................................................................... 42 
13.5.2 
Secondary Endpoints .................................................................................. 43 
14. 
INVESTIGATOR OBLIGATIONS ....................................................................... 43 
14.1 
INFORMED CONSENT ......................................................................................... 43 
14.2 
INSTITUTIONAL REVIEW BOARD AND BIOSAFETY COMMITTEE ................................ 44 
14.2.1. 
Protocol Amendments ................................................................................. 44 
14.2.2. 
Other Reporting Obligations ........................................................................ 44 
14.3 
SUBJECT PRIVACY ............................................................................................. 44 
14.4 
REPORTING OBLIGATIONS .................................................................................. 44 
15. 
ADMINISTRATIVE CONSIDERATIONS ............................................................ 44 
15.1 
STUDY DOCUMENTATION ................................................................................... 44 
15.2 
RECORD RETENTION ......................................................................................... 45 
15.3 
CASE REPORT FORMS ....................................................................................... 45 
15.4 
TERMINATION OF THE STUDY .............................................................................. 45 
15.5 
STUDY MONITORING .......................................................................................... 46 
15.6 
PUBLICATION STATEMENT .................................................................................. 46 
15.7 
STUDY FUNDING ................................................................................................ 47 
REFERENCES .............................................................................................................. 48 
APPENDIX 1:  SCHEDULE OF EVENTS ..................................................................... 50 
APPENDIX II: DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS ................................................. 51 
 
 
 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 6 of 70                                                                                   Version: January 30, 2014 
Protocol SB-728-1101 Synopsis 
Title 
A  Phase I, Open-Label Study to Assess the Effect of Escalating Doses of 
Cyclophosphamide on the Engraftment of  SB-728-T in Aviremic HIV-
Infected Subjects on HAART  
Sponsor 
Sangamo BioSciences, Inc. 
Investigational 
Products 
SB-728-T (Autologous CD4+ T-cells genetically modified at the CCR5 gene 
by Zinc Finger Nucleases SB-728). 
Objectives 
Primary:  
To evaluate the safety and tolerability of escalating doses of 
cyclophosphamide administered up to 3 days prior to SB-728-T infusion. 
Secondary: 
1. Evaluate the effect of escalating doses of cyclophosphamide on SB-728-T 
engraftment 
2. Evaluate the effect of SB-728-T on plasma HIV-1 RNA levels following 
HAART interruption 
3. Evaluate long-term persistence of SB-728-T in peripheral blood as 
measured by pentamer PCR 
4. Evaluate change in CD4+ T-cell counts in peripheral blood after treatment 
with SB-728-T 
5. Evaluate the change in HIV reservoirs as part of exploratory research 
Study Population Up to 40 aviremic HIV-infected subjects on stable HAART may be enrolled 
and treated in 5 dose cohorts.  
Main 
Inclusion 
Criteria 
HIV diagnosed  men and women > 18 years of age on HAART with 
undetectable viral loads for the preceding 3 months and peripheral blood 
CD4+ T-cell counts >500 cells/µL at screening. 
Study Design 
Phase 1, open-label, dose escalation, multi-center study. 
Treatment Plan 
Up to 40 subjects will be enrolled and treated in one of five treatment cohorts: 
Cohort 1: Intravenous cyclophosphamide 200 mg 
Cohort 2: Intravenous cyclophosphamide 0.5 g/m2 
Cohort 3: Intravenous cyclophosphamide 1.0 g/m2 
Cohort 4: Intravenous cyclophosphamide 2.0 g/m2 
Cohort 5: Intravenous cyclophosphamide 1.5 g/m2 
 
Within each cohort, treatment will be staggered so that each subsequent 
subject cannot be infused with cyclophosphamide until at least 2 weeks after 
the preceding subject. Up to 3 days after receiving cyclophosphamide, 
subjects will be infused with 0.5 to 4.0 x 1010 SB-728-T cells. A Safety 
Monitoring Committee will determine if it is safe to dose escalate prior to 
treatment of subsequent cohorts.  
 
 
If one subject within a cohort develops a dose limiting toxicity (DLT) defined 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 7 of 70                                                                                   Version: January 30, 2014 
as a Grade 3 non-hematological adverse event (AE) excluding alopecia or 
Grade 4 hematological AE related to cyclophosphamide, 3 additional subjects 
will be enrolled and treated in that cohort.  
 
If no DLT develops in 3 subjects in Cohort 5 (1.5 g/m2), additional subjects 
may be enrolled into that cohort.  
 
Upon evaluation of data from Cohort 5 (1.5 g/m2), the sponsor may elect to 
enroll  additional subjects into  Cohort 3 (1.0 g/m2). 
 
Subjects with aviremia and CD4 cell counts ≥500 cells/µL will have their anti-
retroviral treatment stopped 6 weeks after SB-728-T infusion. HAART will be 
discontinued for a period of at least 16 weeks.  
During the 16-week treatment interruption, HAART will be reinstituted in 
subjects whose CD4 cell counts drop to <500 cells/µL and/or whose HIV-
RNA increases to >100,000 copies/mL on three consecutive measurements 
tested every 2 weeks. 
At the end of the 16-week treatment interruption:  
• HAART will be reinstituted in subjects with HIV RNA levels >10,000 
copies/mL and/or CD4 <500 cells/µL.  
• Subjects with HIV RNA levels ≤10,000 copies/mL and CD4 count ≥ 
500 cells/µL may elect to remain off HAART and undergo extended 
TI (subjects with HIV RNA levels below limit of detection will remain 
off HAART).  
During extended TI, HAART will be reinstituted in subjects when one or both 
of the following criteria are met: 
• HIV RNA levels > 10,000 copies/mL, confirmed by two additional 
consecutive monthly measurements 
• CD4 count < 500 cells/µL, confirmed by an additional consecutive 
monthly measurement  
 
 
Study Duration 
The duration of study participation will be approximately 15 months for each 
subject divided into approximately 3 months for screening, leukapheresis, and 
SB-728-T production, and 12 months for treatment and study follow-up.   
Sample Size and 
Analyses 
This is a phase 1 study in which three to six evaluable subjects in each cohort 
will be treated to evaluate safety of each cyclophosphamide dose level. A 
cohort can be expanded if there is no DLT in the first 3 subjects treated or no 
more than 1 DLT in 6 subjects treated in that cohort. The primary focus of this 
study is to evaluate the safety of escalating doses of cyclophosphamide 
administered prior to the SB-728-T infusion.  As such, if no adverse events are 
observed in a group of three evaluable subjects, we can be 95% confident that 
the true adverse event rate is less than 70%. Expansion of each cohort to 6 
subjects will decrease the rate to 46%.There will be limited statistical power to 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 8 of 70                                                                                   Version: January 30, 2014 
 
 
 
evaluate efficacy and related biological endpoints. Therefore, analyses will be 
primarily descriptive and exploratory in nature.   

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 9 of 70                                                                                   Version: January 30, 2014 
 
Schema of the Study Visits   
 
 
release
Screen
A
p
h
e
r
e
s
i
s
SB‐728‐T 
Production 
6‐8 weeks
Infusion and Safety Evaluations‐12 months
BL
CTX D0   D1   1    2    3    4    6    8    10    12    14    18    22        7   8   10   12
Week 
Month
CTX1,2
SB‐728‐T INFUSION
Treatment Interruption
L
o
n
g
T
e
r
m
F
o
l
l
o
w
U
p
D5 D12
BL  
BR
1Cohort 1: IV cyclophosphamide 200 mg 
Cohort 2: IV cyclophosphamide 0.5 g/m2 
Cohort 3: IV cyclophosphamide 1.0 g/m2 
Cohort 4: IV cyclophosphamide 2.0 g/m2 
Cohort 5: IV cyclophosphamide 1.5 g/m2  
 
2 Administer CTX up to 3 days prior to Day 0. 
Enrollment of cohorts will be sequential. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 10 of 70                                                                                   Version: January 30, 2014 
ABBREVIATIONS 
AE 
 
adverse event/experience 
AIDS  
acquired immunodeficiency syndrome 
ALP 
 
alkaline phosphatase 
ALT 
 
alanine aminotransferase (SGPT) 
ANC  
absolute neutrophil count 
 
 
AST 
 
aspartate aminotransferase (SGOT) 
CBC  
complete blood count 
CCR2  
chemokine (C-C motif) receptor 2 
CCR5  
chemokine (C-C motif) receptor 5 
CD4 
 
cluster of differentiation 4 
C of A  
Certificate of Analysis 
CRF 
 
case report form 
CTX  
cyclophosphamide 
CXCR4 
chemokine (C-X-C motif) receptor 4 
DLT 
 
dose limiting toxicity 
DMSO  
dimethyl sulfoxide  
DNA  
deoxyribonucleic acid 
ELISA  
enzyme linked immunoassay 
FDA  
Food and Drug Administration 
HAART 
highly active antiretroviral therapy 
HBsAg 
hepatitis B surface antigen 
HCV  
hepatitis C virus 
HIV 
 
human immunodeficiency virus 
IFN 
 
interferon 
INR 
 
immunologic nonresponders 
IR 
 
immunologic responders 
IV 
 
intravenous 
IRB 
 
institutional review board 
NCI 
 
National Cancer Institute 
NNRTI  
non-nucleoside reverse transcriptase inhibitors  
NRTI  
nucleoside reverse transcriptase inhibitors 
NIH 
 
National Institutes of Health 
PBMC  
peripheral blood mononuclear cell 
PCR 
 
polymerase chain reaction 
PI 
 
Principal Investigator 
RCA  
replication-competent adenovirus 
RNA  
ribonucleic acid 
RNAi  
RNA interference  
SAE 
 
serious adverse event 
SB-728-T 
SB-728 modified CD4+ T-cells 
SMC  
Safety Monitoring Committee 
TI 
 
Treatment Interruption 
TIL 
 
tumor infiltrating lymphocytes 
VL 
 
viral load 
ZFN 
 
zinc finger nucleases 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 11 of 70                                                                                   Version: January 30, 2014 
1.     INTRODUCTION 
The advent of potent anti-retroviral agents has changed HIV infection from a nearly universal 
fatal disease to a chronic viral infection. However, in response to selection pressures associated 
with the use of antiretrovirals, the virus is developing resistance to many of these drugs. Thus, 
there is a need for new therapeutic approaches that can eradicate HIV such as T-cell 
immunotherapy. The objectives of this therapy are to augment HIV-specific T-cells and to 
reverse or decrease the progressive destruction of CD4+ T-cells that leads to clinical AIDS. 
However, these CD4+ T-cells remain susceptible to infection with HIV. Sangamo BioSciences, 
Inc. (Sangamo) has developed a process to modify autologous CD4+ T-cells ex vivo at the CCR5 
gene by zinc finger nucleases (ZFN) encoded by SB-728 in a replication deficient adenoviral 
vector. Since CCR5 is an important co-receptor for HIV entry, it is hypothesized that disruption 
of CCR5 in CD4+ T-cells with zinc finger nucleases will offer a survival advantage to these 
cells.  
SB-728-T is the name of the experimental agent that has been administered to subjects infected 
with HIV. SB-728-T consists of autologous enriched CD4+ T-cells that have been transduced ex 
vivo with SB-728 resulting in modification of the CCR5 gene. SB-728 is a replication deficient 
recombinant Ad5/35 viral vector encoding the CCR5 specific ZFNs (SBS8196z and SBS8267) 
which through transient episomal expression delivers these nucleases to transduced cells. The 
two ZFNs bind to a composite 24-bp sequence found specifically in the region encoding the first 
transmembrane domain of the CCR5 gene, just upstream from the naturally occurring CCR5 
delta 32 mutation. Expression of the CCR5-specific ZFNs induces a double stranded break which 
is repaired by the cell leading to random sequence insertions or deletions in ~30% of cells 
transduced with SB-728. These insertions and deletions disrupt the CCR5 coding sequence 
leading to frameshift mutation and termination of CCR5 protein expression. Additional human 
pre-clinical information can be found in the Clinical Investigator’s Brochure for SB-728-T. 
1.1 
Clinical Experience with SB-728-T  
SB-728-T has been administered to over 60 subjects in three ongoing Phase 1 studies to date, one 
sponsored by the University of Pennsylvania (protocol number 806383) and the other two by 
Sangamo (SB-728-0902 and SB-728-1002). SB-728-0902 and the PENN study have enrolled a 
total of 21 aviremic subjects on HAART to date; 6 immunologic responders (IR) with CD4 >450 
cells/µL and 15 immunologic nonresponders (INR) with CD4 <500 cells/uL. Subjects were 
infused with 5 to 30 billion cells. The mean CD4 and SB-728-T count increased by 1533/µL 
(range 216-3025) and 83/µL, respectively, on day 7 in IR and by 820/uL (range 133-4467) and 
19/µL, respectively, in INR from the 2 studies. Increases in CD4 over time correlated with SB-
728-T engraftment (г=0.78, p<0.0001). SB-728-T was detected in the gut mucosa of all 18 
subjects biopsied (median 6%).  
A HAART treatment interruption (TI) was performed 4 weeks after SB-728-T infusion (5-10 
billion cells) in the 6 IRs. HIV-RNA dropped ~0.8-2.1 log from their peak levels in 3 of the 6 
subjects (Figure 1.1-1). In one CCR5 delta 32 heterozygous subject with a viral setpoint of 
165,000 copies/mL, viral load (VL) peaked at 6247 copies/mL during Week 6 of TI and was 
undetectable by Week 12. Similarly, a subject in Sangamo Study SB-728-0902 had a >1-log 
decrease in his HIV-RNA when he underwent a TI one year after the infusion of 10 billion SB-
728-T cells. Furthermore, in SB-728-0902, PBMC HIV proviral DNA was evaluated using a new 
Digital Droplet qPCR method. Samples with previously undetectable levels using traditional 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 12 of 70                                                                                   Version: January 30, 2014 
qPCR now showed measurable proviral DNA. Three of the six subjects with >11 month follow-
up had an ~1-log decrease over time.  
 
Figure 1.1-1: Viral Load Following Treatment Interruption in Immunologic Responders 
 
 
The results to date suggest SB-728-T infusion increases CD4 counts that persist over time. SB-
728-T expands rapidly and home to the gut. Preliminary data suggest that SB-728-T may 
decrease proviral DNA. In one subject with the highest level of CCR5 modification, VL was 
controlled (< limit of detection) without HAART. There have been no serious adverse events 
(SAEs), associated with SB-728-T, reported to date. SB-728-T infusions were well tolerated with 
only mild reversible infusion related adverse events (AEs). The most common AEs were a garlic 
odor caused by the DMSO required for cell freezing, and fever and chills.  
1.2 
Cyclophosphamide to Enhance SB-728-T Engraftment 
Cyclophosphamide is a nitrogen mustard alkylating agent that attaches an alkyl group to the 
guanine base of DNA. It is a prodrug that is converted by mixed function oxidase enzymes in the 
liver to the main active metabolite, phosphoramide mustard which forms DNA crosslink between 
and within DNA strands. The unchanged drug has a half-life of 3 to 12 hrs and is eliminated 
primarily in the form of metabolites although 5 to 25% of the drug is excreted unchanged in the 
urine. 
Preclinical studies have shown that cyclophosphamide can deplete T-cells and macrophages with 
rapid repopulation of lymphoid tissues upon discontinuation of the drug. Normal numbers of 
different T-cell populations were fully restored in mice 16 to 30 days after a single dose of 
cyclophosphamide (Kolb, Poupon et al. 1977). In another study, the total lymphocyte count in 
mice nadired at <10% of normal in the thymus, bone marrow, spleen and lymph nodes three days 
Days
0
14
28
42
56
70
84
98
112
126
140
154
168
182
Viral load (Copies/mL)
101
102
103
104
105
106
Viral Setpoint (Copies/mL)
101
102
103
104
105
106
Subjects
201
203
204
205 *
251
253
Treatment Interruption
*CCR5 - Δ32 Heterozygote
Dotted line denotes reinstitution of HAART

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 13 of 70                                                                                   Version: January 30, 2014 
after a single injection of cyclophosphamide (300mg/kg). The repopulation kinetics differed 
markedly within these tissues with the thymus reaching normal numbers by day 14 and twice 
normal by day 21. The bone marrow and spleen were normal by day 7 and 11, respectively but 
the lymph nodes were only at 30% of normal by day 21 (Willers and Sluis, 1975). These data 
demonstrate that the lymphodepleting effects of cyclophosphamide are readily reversible with 
rapid repopulation of lymphoid organs when the drug is discontinued.  
1.2.1 Cyclophosphamide and Adaptive Immunotherapy 
Cyclophosphamide has been shown to have beneficial immunomodulatory effects that may be 
exploited for adaptive immunotherapy. Several mechanisms have been suggested including 1) T-
cell growth factors such as type 1 IFN, 2) dendritic cell expansion and activation with antigen 
driven T cell proliferation, 3) improved homing to lymphoid organs, 4) homeostatic proliferation 
and 5) elimination of regulatory T-cells.  
Lymphodepletive treatment to enhance engraftment of adoptively transferred T-cells has been 
pioneered in the use of autologous T-cells in the treatment of cancer. The T cell populations used 
in these studies consisted of antigen specific or chimeric T cell receptor-transduced autologous 
cells. Recently there has been significant clinical success with this approach, with 
lymphodepletion an important contributing factor. Dudley and Rosenberg at the NCI treated 
melanoma subjects with cyclophosphamide and fludarabine prior to adoptive cell transfer of 
expanded tumor infiltrating lymphocytes and showed a 51% objective clinical response rate of 
tumor shrinkage (Dudley et al., 2005; Dudley and Rosenberg, 2003). More recently, the 
beneficial effect of a non-myeloablative lymphodepleting regimen on adoptive T-cell therapy 
was demonstrated in chronic lymphocytic leukemia patients treated with low doses of chimeric 
antigen receptor CD19 (CART19) transduced autologous T-cells (Porter et al., 2011). These 
results demonstrate that nonmyeloablative lymphodepletion prior to adoptive transfer of T-cells 
results in greatly enhanced in vivo expansion. Furthermore, the expanded cells retain their 
immunologic function.      
1.2.2 Safety of Cyclophosphamide in Autoimmune Disease 
Cyclophosphamide has been successfully deployed as therapy for numerous autoimmune 
diseases including Goodpasture's syndrome, systemic lupus erythematous, rheumatoid arthritis, 
Wegener's granulomatosis, and membranous glomerulonephritis. Adverse effects and toxicities, 
including hemorrhagic cystitis and gonadal dysfunction are dose dependent and are uncommon 
with total cumulative doses below 10 g. The risk of malignancy with oral therapy is proportional 
to the cumulative dose and increases substantially at cumulative doses greater than 30 g. 
Treatment with cumulative doses of 10 g or less has been shown to be associated with incidence 
of malignancy similar to that of a control population (Baker et al., 1987). Importantly, unlike 
other cytoreductive agents, cyclophosphamide has no cumulative bone marrow toxicity. 
Table 1.2.2-1 is reproduced from a paper detailing the side-effects of cyclophosphamide in 
subjects with autoimmune disease (Martin et al, 1997). A total of 329 subjects with a variety of 
autoimmune diseases received intravenous (IV) cyclophosphamide in nine studies. The mean 
cumulative dose ranged from 1.4 g to 16 g. Infection was the most common side effect but most 
of the subjects were also receiving glucocorticoid. Hemorrhagic cystitis was seen in only 2 of the 
studies and may be prevented by adequate fluid intake to induce a diruesis. Only two of the 
studies reported cancer and the total was seven subjects. The cumulative dose of 
cyclophosphamide that was administered in these two studies was 4.7 and 10 grams. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 14 of 70                                                                                   Version: January 30, 2014 
 
Table 1.2.2-1: Literature Review of the Side Effects of Intravenous Cyclophosphamide 
Pulse Therapy in Subjects with Autoimmune Disease 
 
1.2.3 Use of Cyclophosphamide in HIV 
The effect of cyclophosphamide on HIV cellular reservoir in subjects receiving HAART was 
evaluated in Clinical Study ACTG 380 (Bartlett et al., 2002). Ten treatment naïve HIV subjects 
were treated with stavudine, lamivudine and nelfinavir. When the subjects became aviremic on 
two serial tests, they were randomized equally to HAART alone or HAART plus 
cyclophosphamide. Cyclophosphamide was administered every 6 weeks at three escalating dose 
levels (750 mg/m2, 1.2 g/m2 and 1.8 g/m2, or a cumulative dose of 3.75 g/m2 over 12 weeks). 
Total lymphocyte counts decreased by a mean of 709 cells/mm3 (p<0.02 compared with control 
patients), and CD4 counts were not significantly affected. HIV proviral DNA decreased similarly 
in both groups but HIV RNA increased in the cyclophosphamide group, an observation that was 
attributed to non-compliance with HAART. The study demonstrated that the use of 
cyclophosphamide was lymphodepleting, did not significantly reduce total CD4 counts, and was 
adequately tolerated. Toxicity included transient nausea following the infusion; one subject with 
Grade 3 neutropenia and one subject with Grade 2 thrombocytopenia. Additional information on 
the safety of cyclophosphamide is discussed in Section 9.2. 
1.3 
HAART Treatment Interruption 
HAART TI was initially advocated to enhance antiviral immune response in acute HIV infection 
(Paton, 2008) and in the setting of virologic failure and multidrug resistance (Lawrence et al., 
2003). However, studies conducted to date have failed to demonstrate a clinical benefit in either 
setting. In subjects with successfully treated chronic HIV infection, TI is associated with inferior 
clinical outcomes (Oxenius et al, 2002). However, TI has been successfully deployed as an 
analytical method to assess the effectiveness of different immunologic/immune-modulatory 
interventions, especially during vaccine trials. The kinetics of viral rebound are well 
characterized, typically occurring within 2 to 4 weeks following discontinuation of drug, and 
viral replication is routinely re-suppressed with resumption of therapy. Data from the currently 
ongoing U Penn study suggest that TI can be safely performed in the currently proposed study 
(Section 9.3). 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 15 of 70                                                                                   Version: January 30, 2014 
A variety of in-vitro studies may be used to assess HIV-1 specific immune responses following 
the infusion of CCR5 disrupted CD4 cells. However, the correlation of in vitro testing to immune 
protection in vivo is largely unknown (van Lunzen et al, 2007). By comparison, plasma HIV 
RNA level is an excellent biomarker for assessing the antiviral activity of a test agent in patients 
with chronic HIV infection. Therefore, sustained suppression of plasma HIV-1 RNA after the 
discontinuation of HAART and or the protection of CD4 cell loss associated with ongoing viral 
replication would be the most stringent test of an immunologic intervention such as SB-728-T. 
In the current study, only subjects with aviremia and CD4 cell counts ≥500 cells/µL at the 
initiation of the TI will have HAART interrupted. In addition, subjects will be monitored closely 
during the TI period and HAART will be reinstituted in subjects in whom CD4 cell counts drop 
to <500 cells/µL and/or whose HIV-RNA increases to >100,000 copies/mL over a sustained 
period (defined as three consecutive measurements tested every 2 weeks). 
At the end of the 16-week TI: 
• HAART will be reinstituted in subjects with HIV RNA levels >10,000 copies/mL 
and/or CD4 <500 cells/µL.   
• Subjects with HIV RNA levels ≤ 10,000 copies/mL and CD4 count ≥ 500 cells/µL 
may elect to remain off HAART and undergo extended TI (subjects with HIV RNA 
levels below the limit of detection will remain off HAART).  
 
During extended TI, HAART will be reinstituted in subjects when one or both of the following 
criteria are met: 
• HIV RNA levels > 10,000 copies/mL, confirmed by two additional consecutive 
monthly measurements. 
• CD4 count < 500 cells/µL, confirmed by an additional consecutive monthly 
measurement. 
Subjects may have HAART reinstituted at any time at the discretion of the subject and/or PI.  
1.4 
Risk Benefit Analysis 
Following myeloablative conditioning regimens for hematopoietic stem cell transplants, T cell 
proliferation and immunoglobulin production are usually impaired for 6 to 12 months post 
transplant but may persist for as long as 4 to 10 years after autologous stem cell transplantation 
(Nordoy T et al., 2001). Adoptive T-cell therapy has been successfully applied to the rescue of 
chemotherapy induced lymphopenia in the setting of non-Hodgkin’s lymphoma (Laport et al, 
2003), chronic myelogenous leukemia (Rapoport et al, 2004), relapsed acute leukemia (Porter et 
al, 2006) and refractory multiple myeloma by Dr. Carl June and his colleagues at UPENN.  
The kinetics of immune reconstitution with autologous polyclonal CD3/CD28 stimulated T-cells 
(~1x1010 cells) following high dose chemotherapy with busulfan and autologous stem cell 
transplantation in multiple myeloma was evaluated in three successive trials. In the first study, 52 
subjects were randomized to receive a single infusion of CD3/CD28 stimulated T- cells, either 
12 or 100 days after stem cell transplantation (Rapoport et al., 2005). T-cells were infused two 
days after stem cell infusion in the subsequent study (Rapoport et al., 2011 and Stadtmauer et al., 
2011). There was a rapid reconstitution of lymphocytes with normal circulating levels achieved 
by day 5. A lymphocytosis was observed in ~30% of the patients that persisted for up to 8 weeks. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 16 of 70                                                                                   Version: January 30, 2014 
Reconstitution of T cell to normal levels occurs by 5 days post T-cell infusion but the 
lymphocyte count was higher in subjects that received T-cells on day 2 relative to those who 
were infused on day 12 or day 100. These data suggest that T-cell expansion following adoptive 
transfer may be time-dependent with more proliferation occurring when the cells are infused 
early after lymphocyte depletion.  
T-cell infusions in these studies were well tolerated with chills/rigors, nausea and low grade 
fevers the most common AEs. Similarly, cyclophosphamide has been safely administered to 
patients with a variety of conditions including autoimmune diseases and infection with HIV 
(Section 1.2). At the non-myeloablative doses of cyclophosphamide (200 mg to 2.0 g/m2) that 
will be administered in this study, the adverse effects are readily managed by routine medical 
interventions such as antiemetics and adequate hydration (Section 9.2). The top dose of 
cyclophosphamide selected for this study, 2.0 g/m2, is below the total cumulative dose of 3.75 
g/m2 that had been safely administered to HIV infected patients in a previous study (Section 
1.2.3). Collectively, these data suggest that the potential benefit of expanding HIV-1 resistant 
CCR5 modified T-cells may be greater than the potential adverse effects of low dose 
cyclophosphamide. 
1.5 
Study Hypothesis 
The objectives of T-cell immunotherapy in people infected with HIV, are to augment HIV-
specific T-cells and to reverse or decrease the progressive destruction of CD4+ T-cells that leads 
to clinical AIDS. SB-728-T has been safely administered to over 60 HIV-infected subjects in 
three clinical trials conducted to date. The level of engraftment has varied from negligible to 
~10% of the CD4+ T-cells in the vascular compartment. Preliminary analyses of HAART TI in 
the UPENN study suggest that an anti-HIV effect may correlate with the level of SB-728-T 
engraftment. Concurrently, non-myeloablative lymphodepletion with cyclophosphamide has 
been demonstrated to enhance engraftment of adoptively transferred T-cells through a variety of 
mechanisms (Section 1.2). The current study is being undertaken to increase SB-728-T 
engraftment through the administration of low non-myeloablative doses of cyclophosphamide. 
  
2. 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to evaluate the safety and tolerability of escalating doses of 
cyclophosphamide administered up to 3 days prior to SB-728-T infusion. 
2.2 
Secondary Objectives 
The secondary objectives of this study are to evaluate: 
1. Effect of escalating doses of cyclophosphamide on SB-728-T engraftment 
2. Effect of SB-728-T on plasma HIV-1 RNA levels following HAART interruption 
3. Long-term persistence of SB-728-T in peripheral blood as measured by pentamer PCR 
4. Change in CD4+ T-cell counts in peripheral blood after treatment with SB-728-T 
5. Change in HIV reservoirs as part of exploratory research 
 
3. 
STUDY DESIGN 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 17 of 70                                                                                   Version: January 30, 2014 
3.1 
Overview 
This is a Phase 1, open-label, dose-escalation, multi-center study. Subjects who satisfy all 
inclusion/exclusion criteria (Section 4) are eligible to participate in this study. Within each 
cohort, treatment will be staggered so that each subsequent subject cannot be infused with 
cyclophosphamide until at least 2 weeks after the preceding subject. Up to 3 days after receiving 
cyclophosphamide, subjects will be infused with 0.5 to 4.0 x 1010 SB-728-T cells. Subjects who 
are aviremic and have CD4 cell counts ≥500 cells/µL will undergo a minimum 16 week TI 
beginning 6 weeks after infusion of SB-728-T. TI may be extended beyond 16 weeks for subjects 
whose HIV RNA levels ≤ 10,000 copies/mL and CD4 count ≥ 500 cells/µL at the end of the 16-
week TI. Subjects will be followed for 12 months after the infusion. 
Additional research blood collection and/or an optional leukapheraesis may be performed during 
the study upon sponsor request. 
3.2 
Number of Subjects 
Up to 40 aviremic HIV-infected subjects on stable HAART will be enrolled and treated in 5 dose 
cohorts (3-6 subjects/cohort).  
3.3 
Dose Escalation 
The decision to dose escalate to the next cohort will be made by a Safety Monitoring Committee 
(SMC). Safety data through Week 4 from all subjects within a cohort will be reviewed by the 
SMC. If one subject within a cohort develops a dose limiting toxicity (DLT) defined as a Grade 3 
non-hematological AE excluding alopecia or Grade 4 hematological AE (all deemed related to 
cyclophosphamide), 3 additional subjects will be enrolled and treated in that cohort. Dose 
escalation to the next cohort may proceed if there is no more than one DLT in a cohort of 6 
subjects. 
3.4 
Cohort Expansion  
If no DLT develops in 3 subjects in Cohort 5 (1.5 g/m2), additional subjects may be enrolled into 
that cohort.   
 
Upon evaluation of data from Cohort 5 (1.5 g/m2), the sponsor may elect to enroll additional 
subjects into Cohort 3 ( 1.0 g/m2).  
3.5 
Study Duration 
The duration of study participation will be approximately 15 months for each subject divided 
into approximately 3 months for screening, leukapheresis, and SB-728-T production, followed 
by 12 months for treatment and study follow-up.   
3.6 
Visit Schedule 
Subjects will complete all screening procedures then undergo a 10 L leukapheresis to collect 
peripheral blood mononuclear cells for the manufacturing of SB-728-T (approximately 2 
months). Subjects will then receive IV cyclophosphamide up to 3 days prior to the infusion of 
SB-728-T on Day 0 for optimal engraftment. Subjects in Cohorts 4 and 5 will have additional 
testing on Day 5 and Day 12. Subjects will be seen weekly on Weeks 1 through 4. Subjects will 
then begin a minimum 16-week TI beginning on Week 6. Subjects will be evaluated at weeks 8, 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 18 of 70                                                                                   Version: January 30, 2014 
10, 12, 14, 18 and 22 during the TI. After completion of the 16-week TI or during TI extension 
(Section 9.3), subjects will be seen at Month 7, Month 8, Month 10, and Month 12. 
Upon the sponsor’s request, additional blood collection and /or an optional leukapheresis may be 
performed during the study. 
3.7 
Study Procedures 
Subjects will have periodic blood tests to assess safety labs, plasma HIV-1 RNA levels and 
CD4+ T-cell counts; physical exams; AE assessment; and review of medications.  (Appendix I).  
 
4. 
SUBJECT SELECTION 
4.1 
Inclusion Criteria 
1. 
Written informed consent signed and dated by study subject.   
2. 
Male or female, 18 years of age or older. 
3. 
Documented HIV diagnosis.  
4. 
Adequate venous access and no other contraindications for leukapheresis. 
5. 
Absolute neutrophil count (ANC) > 2500/mm3.  
6. 
Hemoglobin level ≥ 13 g/dL (males); > 12 g/dL (females). 
7. 
Platelet count ≥ 200,000/mm3.  
8. 
Serum creatinine < 1.5 mg/dL. 
9. 
AST and ALT ≤ 2.5 times the upper limit of normal.  
10. Must be willing to comply with study-mandated evaluations; including only 
changing antiretroviral regimen when indicated by the study doctor during the 
study period.  
11. Female of childbearing potential must have a negative serum pregnancy test at 
screening and negative urine pregnancy test at the baseline visit prior to infusion. 
A female subject is considered to be of childbearing potential if she is 
postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 2 years 
postmenopausal.   
12. Have no polymorphisms in the CCR5 ZFN target region as determined by Cel 1 
SNP assay at screening.  
13. All subjects must have received at least 6 months of continuous HAART therapy 
and have had undetectable VLs for the preceding 3 months. Subjects who had 
intermittent isolated episodes of detectable low-level viremia <500 copies 
RNA/mL; blips) will remain eligible. 
14. On stable antiretroviral medication (no changes to treatment within 4 weeks of 
screening.  
15. CD4+ T-cell count ≥500 cells/µL.  
16. HIV-1 RNA below the limit of assay detection obtained at screening.  
17. Willing to discontinue current antiretroviral therapy during the treatment 
interruption. 
18. Adenoviral Neutralizing Antibody ≤40 
19. Low innate immune system activation as determined by the sponsor 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 19 of 70                                                                                   Version: January 30, 2014 
4.2 
Exclusion Criteria 
1. 
Acute or chronic hepatitis B or hepatitis C infection.  
2. 
Active or recent (in prior 6 months) AIDS defining complication. 
3. 
CXCR4 tropic or dual tropic HIV virus. 
4. 
Any cancer or malignancy within the past 5 years, with the exception of 
successfully treated basal cell or squamous cell carcinoma of the skin or low 
grade (0 or 1) anal or cervical dysplasia. 
5. 
Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or 
uncontrolled arrhythmias. 
6. 
History or any features on physical examination indicative of a bleeding diathesis. 
7. 
Previous treatment with any HIV experimental vaccine within 6 months prior to 
screening, or any previous gene therapy using an integrating vector. 
NOTE: Subjects treated with placebo in an HIV vaccine or gene therapy study 
will not be excluded if documentation that they received placebo or sham gene 
therapy is provided. 
8. 
Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., 
interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, 
etc.) within 30 days prior to screening. 
NOTE: Use of inhaled or topical steroids is not exclusionary.  
9. 
Breast-feeding, pregnant or unwilling to use acceptable methods of birth control 
for 6 months following the infusion of SB-728-T cells. 
NOTE: The following are acceptable methods of birth control: 
a. Condoms (male or female) with or without a spermicidal agent  
b. Intrauterine device (IUD)  
c. Diaphragm or cervical cap with spermicide 
d. Hormonal-based contraception 
Subjects who become pregnant after SB-728-T infusion must inform the 
investigator of their pregnancy and agree to provide follow-up information at 
time of delivery. 
10. Use of Aspirin, dipyridamole, warfarin or any other medication that is likely to 
affect platelet function or other aspects of blood coagulation during the 2 week 
period prior to leukapheresis.  
11. Active drug or alcohol use or dependence that, in the opinion of the investigator, 
would interfere with adherence to study requirements. 
12. Serious illness requiring systemic treatment and/or hospitalization within 30 days 
prior to study entry. 
13. Elevations of baseline serum bilirubin and amylase ≥3 times the upper limit of 
normal.  
NOTE: Asymptomatic elevations due to HAART medications are not 
exclusionary, when, in the opinion of the investigator, the abnormalities are not 
attributable to intrinsic hepatic disease.   

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 20 of 70                                                                                   Version: January 30, 2014 
14. Recent vaccination or intercurrent illness (within 5 weeks prior to SB-728-T 
infusion). 
NOTE: it is recommended that subjects should have completed their routine 
vaccinations (hepatitis A or B, pneumococcus, influenza and tetanus diphtheria 
booster) at least 30 days prior to screening for the study. 
15. Have an allergy or hypersensitivity to study product excipients (human serum 
albumin, DMSO and Dextran 40). 
16. Currently participating in another clinical trial or participation in such a trial 
within 30 days prior to screening visit.  
17. Subjects who are currently taking maraviroc or have received maraviroc within 6 
months prior to screening. 
18. Any other condition that, in the opinion of the clinical investigator or sponsor, 
might compromise any aspect of this trial. 
 
5.  
INFORMED CONSENT 
Prior to entering the study, the investigator or designated personnel will explain to each subject 
the nature of the study, its purpose, the procedures, the expected duration, alternative therapies 
available, and the benefits and risks involved in study participation.  Subjects will be given an 
information and consent document, will have the opportunity to ask questions, and will be 
informed of their right to withdraw from the study at any time without prejudice. After this 
explanation and before any study-specific procedures have been performed, the subject must 
voluntarily sign and date the informed consent document. 
The subject will receive a copy of the signed and dated written informed consent form and any 
other written information required to be provided to the subject. Subjects will be re-consented at 
the time of any informed consent amendment, as applicable, and will be provided a copy of the 
consent form. 
 
6. 
STUDY METHODOLOGY 
Prior to initiation of this study, the study site must have the protocol and subject informed 
consent form approved by the IRB. Subjects must be willing to participate in all study 
procedures in this protocol. The following sections describe all study procedures. See Section 7 
for details of evaluations. Additional detailed instructions will be provided in the Study 
Reference Manual.   
A table of all study procedures is presented in the Schedule of Events (Appendix 1).  
6.1 
Screening Visit Procedures 
The objective of the screening visit is to identify subjects who meet the stated inclusion and 
exclusion criteria and who are willing and able to participate in the study. The following 
screening information and procedures must be completed and results reviewed for eligibility. 
The following will be performed at the screening visit: 
1. Obtain a signed and dated subject informed consent form and authorization 
document to use and disclose medical information prior to performing any study-
specific procedures 
2. Assign a subject number 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 21 of 70                                                                                   Version: January 30, 2014 
3. Review the inclusion and exclusion criteria 
4. A complete medical history including demographic information; access and review 
of concomitant medications. If the subject is not normally seen at the study center, it 
may be necessary to obtain medical records to confirm study eligibility.  
5. Complete Physical Exam  
6. 12-lead ECG 
7. Hepatitis B surface antigen (HBsAG) and hepatitis C antibody (HCV) (not required 
if HBsAG or HCV antibody are negative within 60 days of screen visit) 
8. Serum pregnancy test (female of childbearing potential) 
9. Urinalysis for presence of glucose, protein, bilirubin, blood, pH, and specific gravity 
10. CBC with differential, platelet count, and ANC 
11. Serum chemistry: electrolytes (Na, K, CO2, Cl), creatinine, BUN, glucose, uric acid, 
total bilirubin, ALP, ALT (or SGPT), AST (or SGOT), LDH, albumin, calcium, and 
total protein, phosphorus.  
12. CD4+ T-cell counts and CD4/CD8 ratio 
13. HIV-1 RNA  
14. CCR5 SNP Cel-I assay 
15. Ad and SB-728 Immunogenicity 
16. HIV-1 Co-receptor Tropism 
17. Innate immune system activation 
6.2 
Subject Enrollment Procedures 
Prior to the first leukapheresis, the study site must verify that the subject meets all inclusion and 
none of the exclusion criteria. A subject is considered enrolled after they meet all the entry 
criteria and have undergone the first leukapheresis.   
6.3 
Pre- Leukapheresis and Leukapheresis  
Subjects who meet all the eligibility criteria will be scheduled for leukapheresis. Sangamo 
BioSciences should be contacted by the study center prior to scheduling leukapheresis and 
Sangamo will ensure availability of manufacturing facility.   
6.3.1 Pre-Leukapheresis: 
The following blood tests must be drawn approximately 1 week prior to the leukapheresis 
procedure and results sent to the Apheresis unit and Sangamo.   
1. CBC with differential and platelet count 
2. Electrolytes (Na, K, C02, Cl) 
3. Calcium 
4. Liver function tests (albumin, total protein, alkaline phosphatase, AST, ALT,  total 
bilirubin) 
6.3.2 Leukapheresis: 
From a single 10L volume leukapheresis, at least 10 x 109 white blood cells will be harvested to 
manufacture SB-728-T. The leukapheresis procedure will be conducted according to the facilities 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 22 of 70                                                                                   Version: January 30, 2014 
guideline. The cells from the leukapheresis product will be genetically modified and expanded 
using anti-CD3/CD28 beads. The cell product is expected to be ready for release to the study 
center approximately 6-8 weeks later. If the product from the first leukapheresis does not meet 
cell release criteria or there are insufficient cells for the intended dose, a second leukapheresis 
may be scheduled. The second leukapheresis will be at least three weeks after the first 
leukapheresis. AEs documented during leukapheresis will be entered onto the CRFs. 
6.4 
Baseline Assessments 
6.4.1  Baseline for Research Blood Collection: 
The following blood tests will be drawn between the leukapheresis procedure and 
cyclophosphamide administration:   
1. CBC with differential 
2. CD4+ T-cell count 
3. Research blood 
6.4.2 Baseline: 
Baseline assessments will be performed approximately one week prior to cyclophosphamide 
administration, and the subject should be evaluated. The following tests are performed at the 
baseline visit: 
1. 
Assessment of AEs 
2. 
Review concomitant medications 
3. 
Urine pregnancy test (for females of child bearing potential only) 
4. 
Chemistry 
5. 
CBC with differential, platelet count, and ANC 
6. 
Urinalysis 
7. 
CD4+ T-cell count 
8. 
HIV-1 RNA  
9. 
Height and Weight  
10. 
Research blood (may be performed on the day of cyclophosphamide infusion 
and prior to cyclophosphamide infusion) 
The following may be performed up to 4 weeks prior to the SB-728-T infusion 
11. 
Pentamer assay 
12. 
Ad and SB-728 immunogenicity  
 
6.5 
Study Treatment and Follow-up 
After baseline tests are reviewed, the study center will contact Sangamo BioSciences to schedule 
SB-728-T dosing. Refer to the Study Reference Manual for details. All subjects will be followed 
for a total of 12 months after SB-728-T infusion according to the schedule in Appendix 1. 
6.5.1  Cyclophosphamide Administration 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 23 of 70                                                                                   Version: January 30, 2014 
Cyclophosphamide should be administered up to 3 days prior to SB-728-T infusion. Subjects 
should consume at least 4L of fluids over the 24 hrs prior to receiving cyclophosphamide 
(Cohorts 4 and 5 only). All subjects will remain at the study site after cyclophosphamide 
administration until vital signs are satisfactory and stable. Subject may be released from the 
study site at investigator’s discretion. Subjects in Cohorts 4 and 5 will have additional testing of 
CBC (with differential), platelet count, and ANC on Day 5 and Day 12. Subjects will be 
monitored, as needed, post cyclophosphamide administration.  
1. AE assessment 
2. Assessment of concomitant medications 
3. Vital signs: temperature, pulse, and blood pressure (pre and post cyclophosphamide 
administration) 
Pre-Cyclophosphamide administration: 
4. Chemistry 
5. CBC with differential, platelet count, and ANC 
6. Urinalysis 
7. CD4+ T-cell count 
8. Volume status of subject will be assessed to ensure subject is euvolemic 
9. Euvolemic subjects will be infused IV with 1L of IV fluids over approximately 1-2 
hours. 
10. Antiemetic administration: Subjects may be prescribed with an antiemetic (IV, oral 
or suppository) before, during, and after cyclophosphamide infusion to prevent and 
treat nausea and vomiting. Recommended antiemetic regimen: Palonosetron (Aloxi) 
0.25 mg IV and Aprepitant (Emend) 125 mg by mouth (PO) 60 minutes before 
cyclophosphamide. Other antiemetics may be given at the discretion of the 
investigator and with sponsor consultation if possible. 
Cyclophosphamide Administration: 
11. Cyclophosphamide administration 
Post-Cyclophosphamide Administration: 
12. 1L of IV fluids infused over approximately 1-2 hrs after cyclophosphamide 
administration  
13. Subjects in Cohorts 1-3 should consume at least 4L of fluids over the 24 hrs after 
receiving cyclophosphamide. Subjects in Cohorts 4 and 5 should consume 4L of 
fluids per day over the next 7 days. 
14. Subjects will be sent home with urine dipsticks and are to test their urine twice daily 
(once in the morning and again in the evening) for 7 days following administration 
of cyclophosphamide. Subjects are to call the study center if any hematuria is 
detected. (Cohorts 4 and 5 only) 
15. Recommended antiemetic regimen: Aprepitant (Emend) 80mg PO daily (QD) for the 
following 6 days. Other antiemetics may be given at the discretion of the investigator 
and with sponsor consultation if possible. 
 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 24 of 70                                                                                   Version: January 30, 2014 
Subjects in Cohorts 4 and 5 will have additional testing of CBC (with differential), platelet 
count, and ANC on Day 5 and Day 12. 
 
Post cyclophosphamide administration, if neutrophil count drops to ≤ 750/mm3, 
administration of Filgrastim is recommended. Filgrastim can be discontinued when 
neutrophil count is ≥ 1000/mm3 (Section 8.2). 
6.5.2 Day 0 – SB-728-T infusion 
All subjects will remain at the study site for approximately 2 hours after SB-728-T infusion and 
vital signs are satisfactory and stable. SB-728-T should be infused up to 3 days after completion 
of the cyclophosphamide administration. (Section 8.1) 
1. AE assessment 
2. Assessment of concomitant medications 
3. Vital signs: temperature, pulse, and blood pressure (pre and post SB-728-T infusion) 
Pre-SB-728-T Infusion: 
4. Chemistry 
5. CBC with differential, platelet count, and ANC 
6. Urinalysis 
7. CD4+ T-cell count 
8. Research blood 
SB-728-T Infusion: 
9. SB-728-T infusion (0.5 to 4.0 x 1010 cells) 
6.5.3 Day 1 
1. 
AE assessment  
2. 
Chemistry 
3. 
CBC with differential, platelet count, and ANC  
4. 
Urinalysis 
5. 
CD4+ T-cell count 
6. 
Pentamer assay 
7. 
Research blood 
6.5.4 Day 5 (- 1 day) (Cohorts 4 and 5 only) 
1. CBC with differential, platelet count, and ANC  
6.5.5 Week 1, Day 12 (-1 day) (Cohorts 4 and 5 only), Week 2, Week 3, and Week 4 (+/- 
2 day) 
1. 
AE assessment 
2. 
Review of concomitant medications (weekly visits only) 
3. 
Chemistry (Weeks 1 and 3 only) 
4. 
CBC with differential, platelet count, and ANC 
5. 
Urinalysis (Weeks 1 and 4 only) 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 25 of 70                                                                                   Version: January 30, 2014 
6. 
CD4+ T-cell count (weekly visits only) 
7. 
HIV-1 RNA (weekly visits only) 
8. 
Ad and SB-728 immunogenicity (Weeks 1 and 4 only) 
9. 
Pentamer assay (weekly visits only) 
10. 
Research blood (Week 2 only) 
6.5.6 Weeks 6, 8, 10, 12, 14, 18 and 22: 16-Week HAART Treatment Interruption 
All subjects with aviremia and CD4 cell counts ≥500 cells/µL will undergo a minimum 16-week 
TI. Subjects will be seen every other week (+/- 3 days) for the first 8 weeks (weeks 6, 8, 10, 12, 
14) and then every month (+/- 1 week) for the remaining 8 weeks of the TI (weeks 18 and 22). 
(Section 8.3) 
Subjects will discontinue HAART under the supervision of the principal investigator. Non-
nucleoside reverse transcriptase inhibitors (NNRTI) such as Rescriptor, Sustiva, Intelence, and 
Viramune have been reported to have a longer half life than nucleoside reverse transcriptase 
inhibitors (NRTI). Therefore, to avoid suboptimal drug exposure which may promote drug 
resistance, subjects on a NNRTI containing regimen should discontinue the NNRTI seven days 
before stopping their other antiretrovirals (Taylor et al., 2007). The time of medication 
interruption is noted in medication records and CRFs. The TI begins for an individual subject on 
the day that all antiretrovirals agents have been discontinued.  
The following procedures will be performed at each visit during the TI: 
1. 
Begin TI (discontinue all HAART) (Week 6) 
2. 
AE assessment 
3. 
Assessment of concomitant medications 
4. 
Vital signs (temperature, pulse, blood pressure, and weight) (Weeks 6 and 22 only) 
5. 
Chemistry (Weeks 6, 8, 12, 18, and 22 only) 
6. 
CBC with differential and platelet count  
7. 
CD4+ T-cell (during the initial 16 week TI, test will be repeated every 2 weeks for 
3 consecutive measurements for values <500 cells/µL) 
8. 
HIV-1 RNA (during the initial 16 week TI, test will be repeated every 2 weeks for 
3 consecutive measurements for values >100,000 copies/mL) 
9. 
HIV-1 coreceptor tropism and resistance testing will be performed once if HIV 
RNA exceeds 1,000 copies/mL 
10. 
Pentamer  
11. 
Ad and SB-728 immunogenicity (Week 12 only) 
12. 
Research blood (Weeks 6, 14, and 22 only) 
At the end of the 16-week TI at Week 22: 
• HAART will be reinstituted in subjects with HIV RNA levels >10,000 copies/mL and/or 
CD4 <500 cells/µL.    
• Subjects with HIV RNA levels ≤ 10,000 copies/mL and CD4 count ≥ 500 cells/µL may 
elect to remain off HAART and undergo extended TI beyond 16-weeks (subjects with a 
VL that is below the limit of detection will remain off HAART). (Section 8.3) 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 26 of 70                                                                                   Version: January 30, 2014 
During extended TI, HAART will be reinstituted when one or both of the following criteria are 
met: 
• HIV RNA levels > 10,000 copies/mL, confirmed by two additional consecutive monthly 
measurements (for a total of 3 measurements) 
• CD4 count < 500 cells/µL, confirmed by an additional consecutive monthly measurement 
(for a total of 2 measurements) 
Subjects will not be put back on HAART until all results are available.  
Subjects may have HAART reinstituted at any time at the discretion of the subject and/or PI. 
6.5.7 Month 7, Month 8, Month 10, Month 12 (+/- 1 week) 
1. 
AE assessment 
2. 
Assessment of concomitant medications 
3. 
Complete Physical Exam (Month 12 only) 
4. 
Vital signs (temperature, pulse, blood pressure, and weight) (Month 8 only) 
5. 
Chemistry (Months 7, 10 and 12 only) 
6. 
CBC with differential and platelet count 
7. 
Urinalysis (Months 7 and 12 only) 
8. 
CD4+ T-cell count 
(For subjects in extended TI, test will be repeated monthly for a total of 2 
consecutive measurements if CD4 count <500 cells/µL) 
9. 
HIV-1 RNA 
(For subjects in extended TI, test will be repeated monthly for a total of 3 
consecutive measurements if HIV-1 RNA levels > 10,000 copies/mL) 
10. 
Pentamer (Months 8 and 12 only) 
11. 
Ad and SB-728 immunogenicity (Months 7 and 12 only) 
12. 
Research blood  
 
The following additional study procedures may be performed upon request of sponsor:  
1. Additional Research Blood collection of 80 mL one or two times. The second blood 
collection of 80 mL will be performed only when insufficient cells are obtained from 
the first collection. If any subject agrees to undergo optional leukapheresis in the 
study, this research blood collection of 80 mL will not be performed.  
a. Blood collection for CBC with differential and CD4+ T-cell counts 
b. 80 mL blood collection 
2. Optional leukapheresis  
Subject who agrees to an optional leukapheresis will undergo the following additional 
study procedures:  
• Pre-Leukapheresis Visit: ≤ 7 days prior to the leukapheresis procedure, the 
following blood tests will be performed and results sent to the apheresis facility 
and Sangamo: 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 27 of 70                                                                                   Version: January 30, 2014 
a. CBC with differential, platelet count 
b. Electrolytes (Na, K, C02, Cl) 
c. Calcium 
d. Liver function tests (albumin, total protein, alkaline phosphatase, AST, 
ALT,  total bilirubin) 
e. CD4+ T-cell counts (The test will be performed only if the leukapheresis 
center cannot collect this blood sample) 
• Leukapheresis Procedure Visit: The following will be performed:  
a. CBC with differential and CD4+ T-cell counts (prior to the leukapheresis). 
If the leukapheresis center cannot collect the blood sample, this blood 
collection should be done at the pre-leukapheresis visit.  
b. a 10L volume leukapheresis procedure will be conducted according to the 
apheresis facility guidelines.  
6.5.8 Long-Term Follow-up 
Long term follow-up for this study will be conducted under a separate protocol.  At the time of 
informed consent for this protocol, subjects will be made aware of the long term follow-up 
requirement. 
 
7.  
INSTRUCTIONS FOR EVALUATIONS 
 Complete Physical Exam: a complete physical examination must include at a minimum 
an examination of the skin, head, mouth, and neck; auscultation of the chest; cardiac 
exam; abdomen; examination of the lower extremities for edema; and a breast exam for 
females. The complete physical exam will also include vital signs (temperature, pulse, 
blood pressure)(weight and height at Screen and Baseline Visits). 
 CBC: Hemoglobin, hematocrit, platelet count, red cell count, and white cell count with 
differential count including absolute neutrophil count at screening and baseline.  
 Chemistry: Bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
alkaline phosphatase (ALP), sodium, potassium, chloride, bicarbonate, urea nitrogen, 
creatinine, total protein, albumin, calcium, and phosphorous.  
 Hepatitis B: subjects must have documentation of a negative HBsAg test within 60 days 
prior to study entry.  Subjects who have not previously had the test or subjects who were 
negative more than 60 days prior will have a test at screen prior to leukapheresis. 
 Hepatitis C: subjects must have documentation of a negative HCV antibody test within 
60 days prior to screening. Subjects who have not previously had the test or subjects who 
were negative more than 60 days prior to screening will have a HCV antibody test at 
screening and results must be reviewed prior to leukapheresis.  If the HCV antibody is 
positive, the subject may return for a HCV RNA test.  If the HCV RNA test is negative, 
the subject may undergo leukapheresis.  HCV RNA must be by any RT-PCR or bDNA 
assay performed by a laboratory with a CLIA certification or its equivalent and results 
evaluated prior to leukapheresis. The test is not required if documentation of a negative 
result of a HCV RNA test performed within 60 days prior to screening is provided. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 28 of 70                                                                                   Version: January 30, 2014 
 HIV-1 Co-receptor Tropism and Resistance Testing: the HIV-1 co-receptor tropism assay 
measures whether a patient has CCR5, CXCR4 or dual tropic virus.  The tropism assay 
looks at the surface receptors on HIV to determine the dominant co-receptor. Resistance 
testing will be performed using a highly accurate HIV drug resistance test that provides 
the complete picture of resistance and combines actual phenotype and genotype drug 
resistance data. The report will include drug resistance information for all of the approved 
NRTIs, NNRTIs, and protease inhibitors. 
 
8.  
MEDICATIONS 
8.1 
SB-728-T 
SB-728-T is autologous CD4+ T-cells modified at the CCR5 gene by ZFN expressed by SB-728, 
a replication deficient adenoviral vector. Autologous CD4+ T lymphocytes are transduced ex 
vivo with SB-728 adenoviral vector. The final T-cell product, SB-728-T, is generated using 2 
major elements: 1) a replication deficient chimeric Ad5/F35 adenoviral vector SB-728, used as 
an accessory product for gene delivery of CCR5 specific zinc finger nucleases and 2) CCR5 
modified autologous CD4+ T-cells (SB-728-T) that have undergone ex vivo T-cell activation, ex 
vivo genetic modification by the SB-728 vector, expansion and formulation.  The composition of 
the final T-Cell product is:   
Composition of SB-728-T 
Component 
Unit Formula  
SB-728 Treated CD4+ T-cells 
0.5-1.25 x 1010/100 mL 
PlasmaLyte A 
31.25% 
Dextran 40 and 5% Dextrose 
10% 
25% Human Serum Albumin 
20% 
Dimethyl Sulfoxide (DMSO) 
7.5% 
Dextrose 5%/.45% NaCl 
31.25% 
 
The final drug product is tested for identity, cell count, purity, viability, potency, mycoplasma, 
endotoxin, and sterility. Cells that have not met specifications or will not be infused will be 
destroyed by the manufacturer according to their procedures. A copy of the Certificate of 
Analysis (C of A) will accompany each infusion bag.  A copy of the C of A and an addendum to 
the C of A that report the cell viability will be sent with each subsequent lot. 
8.1.1  Inventory, Storage, and Handling of the Drug Product 
SB-728-T is cryopreserved in a 500 mL cryocyte infusion bag at ≤ -130◦C.  The infusion bags 
will contain approximately 50 mL of T-cells (actual volume dependent on number of cells) and 
have a label affixed containing the following information: protocol number, subject study 
number, lot number and “FOR AUTOLOGOUS USE ONLY”. Each bag of cryopreserved 
genetically modified CD4+ T-cells will contain approximately 0.5-1.0 x 1010 cells at a 
concentration of approximately 1 x 108 cells/mL of infusible cryomedia.   
The CCR5 ZFN-modified T-cells are not released from the manufacturer until the release criteria 
for the infused cells are met. Release tests are performed in process, on the pre-harvest cells, and 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 29 of 70                                                                                   Version: January 30, 2014 
on the final cryopreserved product. QC testing will be performed by Sangamo BioSciences, Inc. 
and commercial testing laboratories, prior to administration of cells to the subject. Quality 
control test results and documentation will be reviewed by external Quality Assurance personnel. 
The final release test for cell viability by Trypan Blue will be performed approximately 72 hours 
before the scheduled thaw and infusion. The C of A will include the actual number of cells and 
volume contained within the infusion bag. The T-cell product will be stored frozen at the 
manufacturing facility until ready to be shipped to the clinical study center. The T-cell product 
and the C of A will be shipped frozen either via courier or overnight to the clinical study center 
prior to the scheduled infusion. The T-cell product should remain frozen at the clinical study 
center until successful placement of the IV infusion line into the subject. 
The T-cell product is considered biohazard material therefore if any CCR5 ZFN-modified T-cells 
are not infused, the infusion bag and tubing will be disposed of according to the study center’s 
procedures for safe handling of biological material. 
Accessibility to labeled T-cell product should only be to those individuals authorized by the 
investigator to dispense this study drug. 
The study center is required to maintain complete records of all study products received. 
Inventory will include the description of labeled product received during the course of this study, 
as well as a record of the labeled product that is dispensed. At the conclusion or termination of 
this study, return or destruction of all drug supplies must be coordinated with Sangamo 
BioSciences. Refer to the Study Reference Manual for additional details. 
The investigator agrees not to supply labeled product to any person other than study personnel 
and subjects in this study. 
8.1.2 SB-728-T Administration 
Side effects following SB-728-T cell infusions include transient fever, chills, and/or nausea. It is 
recommended that the subject be pre-medicated with acetaminophen 650 mg by mouth and 
diphenhydramine hydrochloride (Benadryl) 25-50 mg by mouth or IV, prior to the infusion of 
SB-728-T. These medications may be repeated every 3-4 hours as needed. A course of non-
steroidal anti-inflammatory medication may be prescribed if the subject continues to have fever 
not relieved by acetaminophen. It is recommended that subjects not receive systemic 
corticosteroids 
such 
as 
hydrocortisone, 
prednisone, 
prednisolone 
(Solu-Medrol) 
or 
dexamethasone (Decadron) at any time, except in the case of a life-threatening emergency, since 
this may have an adverse effect on T-cells. If corticosteroids are required for an acute infusion 
reaction, an initial dose of hydrocortisone 100 mg is recommended. 
SB-728-T will be shipped to the study site prior to the scheduled infusion. SB-728-T should be 
infused up to 3 days after completion of the cyclophosphamide administration. The study product 
should be thawed just prior to the scheduled infusion. Prior to the infusion, two individuals will 
independently verify all information in the presence of the subject to confirm that the 
information is correctly matched to the subject. The cell product should be infused within 15 
minutes after it is thawed and before the solution becomes warm in the IV bag to ensure viability 
of infused cells.  Detailed instructions for the thaw and infusion of cells are in the Study 
Reference Manual. 
8.1.3 Precautions 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 30 of 70                                                                                   Version: January 30, 2014 
SB-728-T is an investigational product, and there is a possible risk of anaphylaxis. Emergency 
medical equipment will be available during the infusion in case the subject has an allergic 
response, or severe hypotensive crisis, or any other reaction to the infusion. Vital signs 
(temperature, pulse, blood pressure) will be taken before and after infusion, then according to the 
study center procedures for a minimum of two hours. The subject will be asked to remain in the 
study unit until the study staff considers it safe for him/her to leave. 
In the unlikely event that the subject develops sepsis or systemic bacteremia following SB-728-T 
infusion, appropriate cultures and medical management should be initiated. If possible 
contamination of the SB-728-T product is suspected, the product can be retested for sterility 
using archived samples that are stored at the manufacturing facility. 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood and blood products, appropriate blood and secretion precautions 
should be employed by all personnel in the drawing of blood and shipping and handling of 
specimens for this study, as currently recommended by the Centers for Disease Control and 
Prevention and the National Institutes of Health. 
All dangerous goods materials, including diagnostic specimens and infectious substances, must 
be transported according to the instructions detailed in the International Air Transport 
Association (IATA) Dangerous Goods Regulations. 
8.1.4 Dose Modifications 
No dose modifications are possible since this is a single infusion study. 
8.2 
Cyclophosphamide 
Cyclophosphamide is a sterile white powder containing cyclophosphamide monohydrate. It is 
available in vials of 500 mg, 1.0 g and 2.0 g vials for single use only. The vials should be stored 
at 25◦C. Cyclophosphamide should be administered up to 3 days prior to SB-728-T infusion. The 
following doses of cyclophosphamide will be infused IV:  Cohort 1 (200 mg), Cohort 2 (0.5 
g/m2), Cohort 3 (1.0 g/m2), Cohort 4 (2.0 g/m2), and Cohort 5 (1.5 g/m2).   
Subjects may be pre-medicated with acetaminophen 650 mg by mouth and diphenhydramine 
hydrochloride (Benadryl) 25-50 mg by mouth or IV, prior to the infusion of cyclophosphamide. 
These medications may be repeated every 3-4 hours as needed.  
Antiemetics 
Recommended antiemetics such as Aloxi 0.25 mg IV and Emend 125 mg PO should be given 60 
minutes before cyclophosphamide followed by Emend 80mg PO once a day for the following 6 
days. Other antiemetic regimens may be given at the discretion of the investigator and with 
sponsor consultation, if possible.  Subjects may be prescribed with an antiemetic (IV, oral or 
suppository) if nausea and vomiting develops during cyclophosphamide administration.  
Filgrastim 
After cyclophosphamide administration, if neutrophil count drops to ≤ 750/mm3, administration 
of Filgrastim is recommended. Filgrastim can be discontinued when neutrophil count is ≥ 
1000/mm3. 
The adverse effects of cyclophosphamide that occur at a frequency of >10% are discussed in 
Section 9.2. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 31 of 70                                                                                   Version: January 30, 2014 
Please refer to the FDA approved manufacturer’s package insert and the Study Reference 
Manual for additional information. 
8.3 
HAART 
8.3.1 Discontinuation of HAART  
Subjects with aviremia and CD4 cell counts >500 cells/µL at Week 6 will discontinue HAART 
under the supervision of the principal investigator during the TI. NNRTIs such as Rescriptor, 
Sustiva, Intelence, and Viramune have been reported to have a longer half life than NRTIs. 
Therefore, to avoid suboptimal drug exposure which may promote drug resistance, subjects on 
an NNRTI containing regimen should discontinue the NNRTI seven days before stopping their 
other antiretrovirals (Taylor et al., 2007). The time of medication interruption is noted in 
medication records and CRFs. 
8.3.2 Reinstitution of HAART 
During the 16-week TI, tests for HIV-RNA and CD4 count will be repeated in 14 days for values 
>100,000 copies/mL and <500 cells/µL, respectively. HAART therapy will be reinstituted if the 
subject experiences a sustained VL increase to >100,000 copies/mL (on 3 consecutive 
measurements tested every 2 weeks) and/or a sustained drop  in the CD4 count <500 cells/µL (on 
3 consecutive measurements tested every 2 weeks). The drug regimen that the subject will 
receive will be determined by the Principal Investigator in consultation with the subject’s 
primary HIV physician. To guide the selection of therapy, the tropism and sensitivity of the virus 
to antivirals will be determined by HIV-1 coreceptor and resistance testing, respectively. If the 
VL or CD4 drop is not sustained, the subject will be advised not to reinstate HAART until after 
the TI to allow for evaluation of the subject’s VL. 
At the end of the 16-week TI at Week 22: 
• HAART will be reinstituted in subjects with HIV RNA levels >10,000 copies/mL, 
and /or CD4 <500 cells/µL.  
• Subjects with HIV RNA levels ≤10,000 copies/mL and CD4 count ≥ 500 cells/µL 
may elect to remain off HAART and undergo extended TI beyond 16 weeks (subjects 
with HIV RNA levels below the limit of detection will remain off HAART).   
During extended TI, HAART will be reinstituted in subjects when one or both of the following 
criteria are met: 
• HIV RNA levels > 10,000 copies/mL, confirmed by two additional consecutive 
monthly measurements 
• CD4 count < 500 cells/µL, confirmed by an additional consecutive monthly 
measurement 
Subjects will not be put back on HAART until all results are available.  
Subjects may have HAART reinstituted at any time at the discretion of the subject and/or PI. 
8.4 
Concomitant Medication 
The investigator will record all concomitant medications including those given in treatment of 
AEs on the concomitant medication page in the subject’s case report form. Any medication taken 
by the subject from screening throughout the course of the study, including over-the-counter 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 32 of 70                                                                                   Version: January 30, 2014 
medicinal products, dietary supplements, and herbal medications, should be recorded on this 
form. 
Aspirin, dipyridamole, Plavix, warfarin, or any other medications likely to affect platelet 
function or other aspects of blood coagulation are prohibited during the 2-week period prior to 
leukapheresis.  
Oral corticosteroids, hydroxyurea, and immunomodulating agents are prohibited until 
completion of this study. A brief course (< 1 week) of oral corticosteroids is allowed on study. 
Routine vaccines are prohibited for six months following infusion of cells, unless medically 
indicated. 
 
9.  
SAFETY AND POTENTIAL RISKS 
9.1 
SB-728-T 
SB-728-T at doses ranging from 5 to 40 billion cells has been safely administered to 
approximately 60 HIV-infected subjects in four clinical trials to date. The longest duration of 
follow-up has been over 3 years in the first subject infused. There was one SAE to date, cellulitis 
and MRSA-abscess of left arm, grade 3, unrelated to study drug. It occurred approximately 9 
months after the SB-728-T infusion. Most of the AEs have been mild to moderate in severity and 
the majority were related to SB-728-T infusion. These include chills, fever, headache, myalgia, 
sweats, dizziness, fatigue, and a “garlic” body odor. All AEs resolved without sequelae.  
9.1.1 Emergence of CXCR4 HIV 
There is a theoretical possibility that CXCR4 viral variants may emerge following inhibition of 
CCR5. CXCR4 variants are more common in late stage HIV infection. Even if the CCR5 
depleted cells results in relative selection of low levels of CXCR4 variants, the antiretroviral 
treatment regimen will be able to maintain viral suppression therefore it is not expected that this 
will be a problem of clinical significance. Subjects in this study will be tested for presence of 
dual tropic or CXCR4 tropic virus prior to entering into the study and any subjects with evidence 
of dual or CXCR4 tropism will be excluded. During the TI, a sample will be sent for the HIV-1 
coreceptor assay to asses for CXCR4 or dual tropism when the VL increases to > 1,000 
copies/mL. Subjects with a CXCR4 or dual tropic virus will be restarted on HAART. 
9.1.2 Carcinogenicity 
There is a risk that people who receive gene transfer may develop new tumors derived from their 
genetically modified cells. This risk is primarily associated with viral gene transfer vectors that 
integrate into the cellular DNA where they may dysregulate genes controlling proliferation. The 
risk with non-integrating adenoviral DNA gene transfer is extremely low. Extensive preclinical 
safety studies have been carried out and support the safety of SB-728 ZFNs, are briefly 
summarized here and are recently published in Nature Biotechnology (Perez et al, 2008). Deep 
sequencing studies at genome sites chosen by their ability to bind to the SB-728 ZFNs with up to 
2 base mismatches have shown that the SB-728 ZFNs effect cleavage only at the target CCR5 
gene and at approximately one tenth the CCR5 rate at the highly homologous site of the CCR2 
gene.  Extremely low levels of modification are also seen in the intron of a third gene, ABLIM-2 
at an extremely low frequency of <1 in 18,000 genes. This data confirms the specificity of SB-
728 to the CCR5 gene. No SB-728 specific effects on cell growth have been observed, indicating 
that in vitro SB-728 ZFN modification does not appear to affect cell biology and replication.  

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 33 of 70                                                                                   Version: January 30, 2014 
Overall increases in double stranded DNA breaks as visualized by fluorescence microscopy has 
shown a transient increase just after ZFN treatment, which is self limiting, occurs at the time and 
level of expected CCR5 specific ZFN activity and is below the level induced by etoposide, which 
blocks topoisomerase II leading to DNA breaks during cell division. No T cell transformation 
has been detected in a soft agar transformation assay, or in multiple animal biotoxicity studies in 
which each animal received greater than the equivalent of a human dose, and over all animals a 
log equivalent of a human dose was evaluated. Taking this data together, there is currently no 
indication that SB-728 modified T-cells is unsafe and may cause T-cell tumors.  
9.1.3 Replication Competent Adenovirus (RCA) 
The A5/F35 SB-728 vector used in this study is derived from the common cold adenovirus. SB-
728 is tested for presence of RCA and meets FDA specification of less than 1 RCA in 3 x 1010 
vector particles. The tropism of this adenoviral vector is that of Type B adenoviruses, and it is 
more efficient at transducing hematopoietic cells than the more commonly used Type C 
adenovirus (Ad5).  
Previous experience has shown that systemically distributed replication competent adenovirus 
vectors (Ad5) induce elevated liver enzymes at the dose of 6x1012 vector particles and that the 
lethal dose is 1x1014 vector particles when administered systemically (Small et al., 2006a). The 
current protocol will use approximately 6x1012 viral particles to transduce T-cells ex vivo.  
However, at the completion of the ex vivo T-cell culture expansions, there is a significant 
reduction of the level of adenovirus in the T-cells. Preclinical data indicates that during the 8 to 
10 days of culture of the T-cells after transduction with SB-728, there is at least a 4,000-fold 
reduction of detectable adenoviral genomes by PCR at cell harvest.  
Previous studies with the intentional systemic administration of replication competent but 
selective adenovirus has shown circulating virus for up to 29 days at IV doses of  3 x10 12 and 6 
x10 12 vector particles and, with the concomitant development of high levels of  neutralizing anti-
adenoviral antibodies in all subjects by day 28. This was associated with self limited and 
asymptomatic increases in liver function tests (Small et al., 2006b). There has been no evidence 
of hepatitis in the 35 subjects treated to date. Nonetheless, subjects participating in the study will 
be monitored carefully for liver function abnormalities and signs or symptoms of hepatitis.  
Subjects in this study will be evaluated for replication competent adenovirus (by an E1 gene 
PCR assay), as well as adenovirus neutralizing antibody titers. The clearance of any adenovirus 
(whether replication deficient or competent) should be quite rapid since most subjects will have 
preexisting antibodies to the Ad 5 penton base and hexon proteins.  
9.1.4 Immunogenicity 
The Ad5 fiber 35 vector utilizes AD5 hexon and penton capsid proteins and the AD 35 fiber 
capsid protein (Nilsson et al. 2004). Pre-existing neutralizing anti bodies to Ad5, which is the 
most prevalent adenoviral serotype antibody in man, could be reactive to SB-728-T (Aste-
Amezaga et al. 2004). After infusion of SB-728-T, all of the patients tested to date have 
developed elevated neutralizing adenovirus antibodies.  There were no associated AEs.  In 
general, subjects with higher pre-existing antibody titer had a lower level of engraftment of SB-
728-T in peripheral blood as measured by Quantitative PCR for a common CCR5 modification 
(pentamer assay, units = number of copies of pentamer/1e6 genomes) compared to the subjects 
with low pre-existing antibody levels.   

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 34 of 70                                                                                   Version: January 30, 2014 
9.2 
Cyclophosphamide 
Cyclophosphamide is associated with a variety of side effects. The adverse effects that occur at a 
frequency of >10% includes alopecia, infertility, nausea and vomiting, hemorrhagic cystitis and 
bone marrow suppression. Antiemetics will be given prophylactically and as needed for nausea 
and vomiting. Leukopenia is more common than thrombocytopenia and anemia with the onset 7 
days after administration and a nadir at 10 to 14 days followed by recovery at 21 days. Subjects 
in Cohorts 4 and 5 will have additional testing of CBC (with differential), platelet count, and 
ANC on Day 5 and Day 12. After cyclophosphamide administration, if neutrophil count drops to 
≤ 750/mm3, administration of Filgrastim is recommended. Filgrastim can be discontinued when 
neutrophil count is ≥ 1000/mm3. Subjects will be monitored, as needed, post cyclophosphamide 
administration. The majority of the adverse effects require the administration of high cumulative 
doses of cyclophosphamide (Section 1.2.2). 
Hemorrhagic cystitis is a potential untoward effect of cyclophosphamide therapy with the 
metabolite acrolein implicated as the major urothelial toxin. The incidence of hemorrhagic 
cystitis was reported to be 6% among subjects who received cyclophosphamide (1.0-1.2 g/m2) 
for ovarian cancer. At these low doses, the American Society of Clinical Oncology recommends 
administering fluids to induce a diuresis. In this study, subjects in Cohorts 1-3 will be hydrated 
with 1 liter of IV fluids prior to cyclophosphamide administration and with another liter prior to 
discharge from the study center. Subjects are instructed to drink 4L of fluids over the next 24 hrs 
to insure adequate diuresis. Subjects in Cohorts 4 and 5 will be instructed to drink 4L of fluids 
over the 24 hrs prior to receiving cyclophosphamide and will receive 1L of fluids administered 
IV over 1-2 hrs immediately prior to cyclophosphamide infusion. At discharge from the study 
center, subjects will be instructed to drink 4L of fluids per day for 7 days following 
cyclophosphamide administration to insure adequate diuresis. Subjects will be instructed to test 
their urine twice daily for microscopic hematuria with urine dipsticks and to contact the study 
center immediately if hematuria (either micro or macro) is detected.  
Cyclophosphamide is a carcinogen and has been associated with malignancies. The risk depends 
upon the dose administered, other co-administered chemotherapy, use of radiotherapy, treatment 
intensity and duration of therapy. Cumulative doses totaling 10 g or less has been shown to be 
associated with an incidence of malignancy that is similar to that of the normal untreated 
population (Baker et al., 1987). Therefore, the low doses (200 mg to 2.0 g/m2) that will be 
administered in this study are unlikely to be carcinogenic. 
9.3 
HAART Treatment Interruption (TI) 
The efficacy and safety of HAART interruption for HIV patients has been reviewed by Paton 
(Paton, 2008). Data indicates that there is no clinical benefit to patients with acute HIV infection 
or those with virologic failure due to multidrug resistance. Indeed, TI may be harmful in patients 
with chronic successfully treated infections. Therefore, TI is currently only recommended in the 
context of clinical trials. 
The safety of TI has been demonstrated by unpublished data from the Penn study. In that study, 
six subjects had HAART interrupted beginning 4 weeks after receiving SB-728-T (Table 9.3-1). 
Five of the subjects have completed the TI. HIV-RNA which was below the limit of detection at 
the time of the TI became detectable at 2 to 6 weeks, peaking at 6 to 8 weeks and then declined 
at 12 weeks. In subjects 1, 2 and 6, the VL dropped 0.5- to 2-log within 4 to 6 weeks and 
declined after reinstituting HAART. The TI was halted in Subjects 3 and 4 as per the stopping 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 35 of 70                                                                                   Version: January 30, 2014 
rules. In Subject 3, HAART was reinitiated because the HIV-RNA increased to >100,000 
copies/mL on three consecutive measurements while Subject 4 was found to be infected with 
dual-tropic HIV. Subject 5 became aviremic 12 weeks following initiation of the TI; this subject 
was subsequently found to be a CCR5 delta-32 heterozygote by genotyping. 
 
Table 9.3-1: Plasma HIV-1 RNA (copies/mL) during TI 
 
      TI  
 
 
 
 
   
 
 
HAART 
Subject 
0 
2 wks 
4 wks 
6 wks 
8 wks 
12 wks 
16 wks 
1 
<48 
<48 
<48 
359 
33,885 
9,596 
358 
2 
<40 
103 
4991 
100,635 
12,149 
8,248 
<40 
3 
<40  
353 
119,855  
189,054 
Halted 
1131 
473 
4 
<48 
<20 
84 
57643 
163,837 
Halted 
86 
5 
<40 
<40 
<40 
6247 
4020 
<40 
--- 
6 
<48 
24,604 
13,288 
80,658 
28,628 
12,871 
--- 
 
Several precautions have been instituted in this protocol to insure subject safety. Subjects will be 
monitored closely during the TI period with study visits every 2 weeks for the first 8 weeks and 
monthly for the remaining 8 weeks. If the HIV RNA increases to >100,000 copies/mL and/or the 
CD4 count drops to <500 cells/µL, the tests will be repeated every 2 weeks for a total of 3 
consecutive measurements. HAART will be reinstituted in subjects whose CD4 cell counts drop 
to <500 cells/µL and/or whose HIV-RNA increases to >100,000 on three consecutive 
measurements. During extended TI, additional monitoring will be performed as needed for 
safety.  CD4 T-cell count will be repeated monthly for a total of 2 consecutive measurements if 
CD4 count <500 cells/µL and HIV-1 RNA will be repeated monthly for a total of 3 consecutive 
measurements if HIV-1 RNA levels > 10,000 copies/mL. In addition, all subjects infected with a 
CXCR4 virus will resume HAART. The effectiveness of these stopping rules is demonstrated by 
the reinstitution of HAART in Subjects 3 and 4 in the PENN study cited above. 
It is possible that some patients could experience symptoms compatible with retroviral rebound 
syndrome, or rarely, other clinical events that occur before use of HAART (e.g. immune 
thrombocytopenia). The kinetics of viral rebound are well characterized, typically occurring 
within 2 to 4 weeks following discontinuation of drug, and viral replication is routinely re-
suppressed with resumption of therapy. 
The psychological risks associated with TI appear to be minimal. In a survey reported at the 
2002 International AIDS Conference in Barcelona, study investigators quizzed enrollees about 
their experience in the Spanish Swiss Intermittent Treatment Trial, and found that the majority 
"viewed their experience positively." Only two stated they would not participate in a similar TI 
trial, compared to 72 that said they definitely would and 25 who answered that they would 
consider it. In terms of any problems taking HAART after interruptions, 73 reported that that it 
was no different, 10 said it felt easier while 17 found it more difficult. Furthermore, fewer side 
effects were reported upon restarting HAART than when therapy was first initiated (Le Braz et 
al., 2002). 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 36 of 70                                                                                   Version: January 30, 2014 
10. 
ADVERSE EVENTS 
10.1 
Adverse Event Reporting Period 
During both the treatment and follow-up periods, subjects will be queried and events will be 
assessed at each clinic visit.  Subjects will be reminded to immediately report any SAE to the 
investigator.  Any study procedure related AEs that occur from enrollment to initiation of 
treatment will also be recorded. 
10.2 
Definitions of an Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. The term “adverse event” could include any of the following 
events which develop or increase in severity during the course of the study. Examples include: 
• Any sign, symptom, or physical examination finding that worsens in nature, severity, or 
frequency compared to baseline. Whether thought to be related or unrelated to the 
condition under study 
• Any clinically significant laboratory abnormality or laboratory abnormality that requires 
medication or hospitalization 
• All reactions from study drug, including those occurring as a result of an overdose, abuse, 
withdrawal phenomena, sensitivity, or toxicity to study drug 
• Concurrent illness 
• Injury or accident 
A pre-existing condition is one that is present prior to or at the start of the study and is to be 
reported as part of the subject’s medical history.  It should be reported as an AE only if the 
frequency, intensity, or the character of the condition worsens during study treatment. 
The term AE also applies to laboratory findings or results of other diagnostic procedures that are 
considered to be clinically relevant (e.g., that required unscheduled diagnostic procedures or 
treatment measures, or resulted in withdrawal from the study). 
 
Suspected Adverse Reaction is any AE for which there is a reasonable possibility that the drug 
caused the AE. “Reasonable possibility” means there is evidence to suggest a causal relationship 
between the drug and the AE. Suspected adverse reaction implies a lesser degree of certainty 
about causality than adverse reaction, which means any AE caused by a drug. 
Unexpected AE or Unexpected Suspected Adverse Reaction:  An AE or suspected adverse 
reaction is considered “unexpected” if it is not listed in the investigator brochure or is not listed 
at the specificity or severity that has been observed; or, if an investigator brochure is not required 
or available, is not consistent with the risk information described in the general investigational 
plan or elsewhere in the current application, as amended.  For example, under this definition, 
hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator brochure 
referred only to elevated hepatic enzymes or hepatitis.  Similarly, cerebral thromboembolism and 
cerebral vasculitis would be unexpected (by virtue of greater specificity) if the investigator 
brochure listed only cerebral vascular accidents.  “Unexpected,” as used in this definition, also 
refers to AEs or suspected adverse reactions that are mentioned in the investigator brochure as 
occurring with a class of drugs or as anticipated from the pharmacological properties of the drug, 
but are not specifically mentioned as occurring with the particular drug under investigation. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 37 of 70                                                                                   Version: January 30, 2014 
10.3 
Recording of an Adverse Event 
The principal investigator is responsible for evaluating all AEs, obtaining supporting documents, 
and determining that documentation of the event is adequate. He/she is responsible for 
determining the severity and relationship to the investigational drug.  The principal investigator 
may delegate these duties to sub-investigators and must assure that these sub-investigators are 
qualified to perform these duties under the supervision of the principal investigator. 
All AEs will be recorded in the subject's case report form (CRF).  The detailed description of the 
event will include appropriately graded severity of the AE and its relationship to the study drug. 
Severity will be categorized by toxicity grade according to the Division of AIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), 
Version 1.0, December 2004, Clarification 1.0, August 2009 with the exception of the following: 
nausea or vomiting will be a Grade 3 non-hematological AE if IV fluids are required for more 
than 24 hours. 
 
AEs not listed in the DAIDS Clinical Trial Toxicity Criteria with the exception of noninfective 
cystitis will be evaluated by using the following criteria:  
• Grade 1, Mild: Symptoms causing no or minimal interference with usual social & 
functional activities  
• Grade 2, Moderate:  Symptoms causing greater than minimal interference with usual 
social & functional activities  
• Grade 3, Severe:  Symptoms causing inability to perform usual social & functional 
activities 
• Grade 4, Potentially Life-threatening: Symptoms causing inability to perform basic self-
care functions OR medical or operative intervention indicated to prevent permanent 
impairment, persistent disability, or death  
• Grade 5: For any AE where the outcome is death. 
Noninfective cystitis will be graded according to the Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.03 with the following criteria:  
• Grade 1: Microscopic hematuria; minimal increase in frequency, urgency, dysuria, or 
nocturia; new onset of incontinence   
• Grade 2:  Moderate hematuria; moderate increase in frequency, urgency, dysuria, 
nocturia or incontinence; urinary catheter placement or bladder irrigation indicated; 
limiting instrumental activities of daily living (ADL) 
• Grade 3:  Gross hematuria; transfusion, IV medications or hospitalization indicated; 
elective endoscopic, radiologic or operative intervention indicated  
• Grade 4: Life-threatening consequences; urgent radiologic or operative intervention 
indicated 
• Grade 5: Death 
The relationship of the AE to the investigational drug will be determined by the principal 
investigator and will be categorized as:  
• Not Related: Any AE that does not meet the definition of a suspected AE reaction. 
 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 38 of 70                                                                                   Version: January 30, 2014 
All grade 3 and 4 clinical laboratory results that represent an increase in severity from baseline 
will be reported as AEs if it is not associated with a diagnosis already reported on the case report 
form.  A grade 1 or 2 clinical laboratory abnormality should be reported as an AE only if it is 
considered clinically significant by the investigator. 
In the event of death, the cause of death should be recorded as the AE and reported as an SAE.  
“Death” is not the AE; “death” is an outcome.  If an autopsy is performed, a copy of the autopsy 
report should be obtained if possible. 
 
11. 
SERIOUS ADVERSE EVENT 
11.1 
Serious Adverse Event Reporting Period 
SAEs, whether or not unexpected or considered to be associated with the use of the labeled 
product, must be communicated to Sangamo BioSciences upon discovery of the event, either by 
telephone or fax within 24 hours. 
Medical Monitor: 
Winson Tang, M.D. 
Phone Number: 
Office : (510) 970-7800 
 
Mobile: (310) 497-7038  
Assistant to Dr. Tang: 
Vivian Tran 
Phone Number: 
(510)-970-6000, extension 200 
Fax Number: 
(510) 970-6009 
The investigator is responsible for promptly notifying the Institutional Review Board (IRB) in 
accordance with local regulations, of all SAEs. The National Institutes of Health (NIH) requires 
that all investigators participating in gene transfer research report all serious AEs immediately to 
the FDA, NIH, and Institutional Biosafety Committee. Sangamo BioSciences will assume the 
responsibility for reporting SAEs to the FDA. 
All “serious” events must be followed with appropriate medical management until resolved or 
stabilized.   
11.2 
Definitions of a Serious Adverse Event 
Any AE or suspected adverse reaction is considered “serious” ” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening AE 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect in the offspring of an exposed patient 
 
An AE or suspected adverse reaction is considered “life-threatening” if, in the view of either the 
investigator, or sponsor, its occurrence places the patient or subject at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death). 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 39 of 70                                                                                   Version: January 30, 2014 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
With regard to results obtained from tests in laboratory animals or in vitro testing, whether or not 
conducted by the sponsor, a SAE includes any event suggesting significant risk to human 
subjects. 
 
11.3 
Recording of a Serious Adverse Event 
SAEs reported by telephone must be recorded on a written SAE Report Form, provided by 
Sangamo BioSciences.  The SAE report form must be faxed to Sangamo BioSciences within 24 
hours. 
The medical monitor will then advise the investigator regarding the nature of any further 
information or documentation that is required.  Follow-up reports must be submitted in a timely 
fashion as additional information becomes available. 
 
12. 
SUBJECT WITHDRAWAL, DOSE ESCALATION, AND STOPPING RULES   
12.1 
Subject Withdrawal and Discontinuation from Study  
Subjects should be discontinued from study for any of the following reasons: 
 
Request by the subject to withdraw. 
 
Request of the sponsor or primary care provider if he or she thinks the study is no 
longer in the best interest of the subject. 
 
Pregnancy prior to SB-728-T infusion. 
 
Subject judged by the investigator to be at significant risk of failing to comply with 
the provisions of the protocol as to cause harm to self or seriously interfere with the 
validity of the study results. 
 
At the discretion of the IRB, Office for Human Research (OHR), Food and Drug 
Administration (FDA), investigator, or Sangamo. 
Subjects will be strongly encouraged to continue with follow-up safety evaluations if they 
withdraw consent. If a subject discontinues from the study a conference between the investigator 
and medical monitor will take place to ensure that all subjects will comply with the follow-up 
safety evaluations of the protocol. Subjects will be assessed for treatment-related AEs and 
disease status. 
12.2 
Dose Escalation Rules 
A SMC will determine if it is safe to dose escalate to the next cohort. If one subject within 
Cohorts 1-5 experiences a DLT defined as a Grade 3 non-hematological AE excluding alopecia 
or Grade 4 hematological AE (all deemed related to cyclophosphamide), 3 additional subjects 
will be enrolled and treated in that cohort. Dose escalation to the next cohort may proceed if 
there is not more than one DLT (all deemed related to cyclophosphamide) in a cohort of 6 
subjects.  Safety data including AEs, clinical laboratory results (chemistry, hematology, CD4 T-

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 40 of 70                                                                                   Version: January 30, 2014 
cell counts and VL) through Week 4 from all subjects within a cohort will be reviewed by this 
group to determine if it is safe to proceed with SB-728-T infusion.  
Treatment of subjects will be staggered at least 2 weeks apart. 
12.3 
Cohort Expansion  
If no DLT develops in 3 subjects in Cohort 5 (1.5 g/m2), additional subjects may be enrolled into 
that cohort.  
Upon evaluation of data from Cohort 5 (1.5 g/m2), the sponsor may elect to enroll additional 
subjects into Cohort 3 (1.0 g/m2).  
12.4 
Stopping Rules  
12.4.1 Stopping Rules for Treatment Interruption 
The TI will be stopped if the subject experiences a sustained VL increase to >100,000 copies/mL 
(at least 3 consecutive measurements tested every 2 weeks) and/or a sustained drop (at least 3 
consecutive measurements tested every 2 weeks) in the CD4 count <500 cells/µL during the 
initial 16 weeks of TI. HAART will be reinstituted in these subjects. The drug regimen that the 
subject will receive will be determined by the Principal Investigator in consultation with the 
subject’s primary HIV physician. To guide the selection of therapy, the tropism and sensitivity of 
the virus to antivirals will be determined.  
At the end of the 16-week TI: 
• 
HAART will be reinstituted in subjects with HIV RNA levels >10,000 copies/mL, and 
/or CD4 <500 cells/µL. 
• Subjects with HIV RNA levels ≤10,000 copies/mL and CD4 count ≥ 500 cells/µL may 
elect to remain off HAART and undergo extended TI beyond 16 weeks (subjects with 
HIV RNA levels below the limit of detection will remain off HAART).   
 
HAART will be reinstituted in subjects, whose TI is extended beyond 16 weeks, when one or 
both of the following criteria are met: 
• HIV RNA levels >10,000 copies/mL, confirmed by two additional consecutive monthly 
measurements.  
• CD4 count <500 cells/µL, confirmed by an additional consecutive monthly measurement.  
Subjects may have HAART reinstituted at any time at the discretion of the subject and/or PI. 
12.4.2 Stopping Rules for Study  
Safety data for subjects in each cohort will be evaluated for consideration of dose escalation by a 
SMC one month after the last SB-728-T infusion in the cohort. Safety data including AEs, 
clinical laboratory results (chemistry, hematology, CD4 T-cell counts and VL) will be evaluated. 
Subjects in the subsequent cohort may be screened and enrolled prior to the safety review. 
However they will not be infused until the SMC has reviewed the data and approved for dose 
escalation of that cohort. The SMC will convene at any time, as needed.  
The study will be paused if: 
 
There are excessive or unexpected toxicities associated with the protocol. Specifically, 
the study will be paused if it is determined that two subjects in a cohort (Cohorts 1-5) 
have a non-hematological Grade 3 toxicity excluding alopecia and/or hematological 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 41 of 70                                                                                   Version: January 30, 2014 
Grade 4 toxicity, or if one subject has Grade 5 toxicity as determined by the DAIDS 
Clinical Trial Toxicity Criteria of December 2004, Clarification 1.0, August 2009 and 
judged to be related to the study treatment.  The study will be paused and available data 
will be evaluated by the SMC.  
 
A subject experiences an absolute lymphocyte count greater than 10,000 uL, until the 
evaluation of the nature of the lymphocyte increase is determined. If it is found not to be 
related to the study treatment, then the study will resume. 
 
Confirmed CXCR4 or CXCR4 and CCR5 dual tropic virus: if at least two subjects 
develop a VL that can be assessed for tropism (>1,000 copies/mL) and they are both 
either CXCR4 or dual tropic, the study will be paused and available data will be 
evaluated by the SMC.  
The study will be stopped if: 
 
The Investigator, Sponsor, SMC, independent safety monitor or regulatory body decides 
for any reason that subject safety may be compromised by continuing the study.   
 
The Sponsor decides to discontinue the development of the intervention to be used in this 
study. 
 
An analysis of clonal outgrowth of T-cells determines that it is a result of SB-728-
mediated oncogenesis. 
 
Sustained (confirmed) virologic failure without an alternative explanation: If any subject 
develops an increase in HIV-1 RNA of > 5000 copies/mL when not undergoing TI, the 
test will be repeated once a week for an additional 2 weeks. If the VL remains > 5000 
copies/mL for at least 3 weeks, and has no alternative explanation (such as non-
compliance) other than the study treatment, the study will be stopped. 
 
13. 
STATISTICAL ANALYSIS AND DATA ANALYSIS 
This is an exploratory study and thus, there will be limited statistical power to evaluate efficacy 
and related biological endpoints. Therefore, analyses will be primarily descriptive and 
exploratory in nature.  
13.1 
Sample Size 
This is a phase 1 study in which three to six evaluable subjects in each cohort will be treated to 
evaluate safety of each cyclophosphamide dose level. A cohort can be expanded if there is no 
DLT in 3 subjects treated or no more than 1 DTL in 6 subjects treated in that cohort. In order to 
have an evaluable sample size, subjects who prematurely discontinue the study prior to the 
conclusion of the TI will be replaced with another subject. Safety will be evaluated after each 
cohort before treating the next dose cohort. Table 13.1-1 provides the probability of failing to 
observe an AE in a sample size of three or six evaluable subjects, for various underlying true AE 
rates. Thus, only AEs that occur at least 60% of the time are likely to be detected in a cohort of 
three subjects. 
 
Table 13.1-1 
 
 
  
Probability of Failing to Observe an 
Adverse Event 
True Adverse 
Event Rate 
 
N=3 
 
N=6 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 42 of 70                                                                                   Version: January 30, 2014 
5% 
86% 
74% 
10% 
73% 
53% 
20% 
51% 
26% 
30% 
34% 
12% 
40% 
22% 
5% 
50% 
13% 
2% 
60% 
6% 
<1% 
70% 
3% 
<1% 
 
Table 13.1-2 shows the exact 95% confidence intervals for possible number of observed safety 
outcomes in three or six subjects. For example, if no AEs are observed in a group of six 
evaluable subjects, we can be 95% confident that the true AE rate is less than 46%. 
 
Table 13.1-2 
 
Exact 95% Confidence Interval 
# Observed 
Adverse Events 
 
N=3 
 
N=6 
0 
(  0.0%,   70.1%) 
(  0.0%,   45.9%) 
1 
(  8.4%,   90.6%) 
(  0.4%,   64.1%) 
2 
(  9.4%,   99.2%) 
(  4.3%,   77.7%) 
3 
(29.2%, 100.0%) 
(11.8%,   88.2%) 
4 
– 
(22.3%,   95.7%) 
5 
– 
(35.9%,   99.6%) 
6 
– 
(54.1%, 100.0%) 
 
 
13.2 
Statistical Methods/Data Analysis 
All tables, listings, and data summaries will be performed in SAS version 9.2 or later. 
13.3 
Intent-to-Treat Population 
All subjects enrolled in this study who receive any portion of the SB-728-T infusion will be 
included in the intent-to-treat population. 
13.4 
Demographics 
Demographic and baseline characteristics will be summarized by treatment cohorts.   
13.5 
Endpoints and Analysis 
Since this is a dose ranging study to evaluate safety, efficacy analyses will be descriptive and 
exploratory in nature. Continuous variables will be summarized by means, standard deviations, 
medians and ranges by cohort. Categorical variables will be summarized with counts and 
percentages per category by cohort.  
13.5.1 Primary Endpoint 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 43 of 70                                                                                   Version: January 30, 2014 
Safety assessment will occur on all subjects who received cyclophosphamide. All reported AEs 
will be coded to a standard set of terms using the Medical Dictionary for Regulatory Activities 
(MedDRA) AE dictionary. The frequency of each event will be summarized by severity and by 
relatedness to the study treatment. 
Terminations, premature withdrawals, AEs, concomitant medications, and laboratory data will be 
tabulated. Laboratory data will be summarized for each time-point that specimens are collected. 
Change-from-baseline values may be calculated for selected laboratory parameters. Shift-tables 
(change-from-baseline relative to the normal range) may be constructed for selected laboratory 
parameters. 
13.5.2 Secondary Endpoints 
The secondary endpoints of this study are exploratory in nature and will assess if 
cyclophosphamide increases SB-728-T engraftment as well as provide evidence of anti-viral 
activity. These exploratory endpoints may help to define the primary endpoints for future studies. 
1. Effect of escalating doses of cyclophosphamide on SB-728-T engraftment 
2. Effect of SB-728-T on plasma HIV-1 RNA levels following HAART interruption 
3. Long-term persistence of SB-728-T in peripheral blood as measured by pentamer PCR 
4. Change in total number of CD4+ T-cells in peripheral blood after treatment with SB-728-
T 
5. Change in HIV reservoirs as part of exploratory research 
 
14. 
INVESTIGATOR OBLIGATIONS 
The investigator will ensure that the study is conducted in compliance with the protocol, the 
Declaration of Helsinki and according to ICH Guidelines for Good Clinical Practice (E6) and all 
regulatory and institutional requirements, including those for subject privacy, informed consent, 
Institutional Review Board or Ethics Committee approval and record retention. 
14.1 
Informed Consent 
According to 21 CFR Part 50.20, no investigator may involve a human being as a subject in 
research covered by these regulations unless the investigator has obtained the legally effective 
informed consent of the subject or the subject’s legally authorized representative. An investigator 
shall seek such consent only under circumstances that provide the prospective subject sufficient 
opportunity to consider whether or not to participate and that minimize the possibility of 
coercion or undue influence. The information that is given to the subject or the representative 
shall be in language understandable to the subject or the representative. 
Sangamo will provide the investigator with a template for the consent form.  State and local laws 
and/or institutional requirements may require the disclosure of additional information in the 
informed consent. The proposed consent form must be submitted to Sangamo prior to submission 
to the IRB or IEC to ensure that it meets Sangamo standards for consent forms. 
The IRB or IEC must approve the consent form. A copy of the approved form must be submitted 
to Sangamo.  
Prior to the initiation of any procedures relating to the study, informed consent shall be 
documented by the use of a written consent form approved by the IRB and signed and dated by 
the subject at the time of consent. A copy of the signed informed consent will be given to the 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 44 of 70                                                                                   Version: January 30, 2014 
person signing the form. The investigator must keep each subject’s signed consent form on file 
for inspection by a regulatory authority at any time. 
14.2 
Institutional Review Board and BioSafety Committee 
This protocol, informed consent document, and relevant substantive data are to be submitted to 
the appropriate Institutional Review Board (IRB) and BioSafety Committee (BSC) for review 
and approval before the initiation of the study. Amendments to the protocol will also be 
submitted to the IRB and BSC (as appropriate) prior to implementation of the change. A letter 
documenting the IRB/BSC’s approval must be received by the Sponsor prior to initiation of the 
study.  
14.2.1. Protocol Amendments 
Any changes to this protocol will be initiated by Sangamo in writing as a protocol amendment. 
The amendment must be submitted to the IRB together with a revised informed consent form, if 
applicable. Written documentation of IRB approval must be received before the amendment may 
take effect. 
14.2.2. Other Reporting Obligations 
The Principal Investigator is also responsible for informing their IRB of the progress of the study 
and for obtaining annual IRB renewal. The IRB must be informed at the time of completion of 
the study. The Principal Investigator should provide their IRB (if required by the institution) with 
a summary of the results of the study. 
14.3 
Subject Privacy 
Subject medical information obtained for the purposes of this trial is confidential, and disclosure 
to third parties, other than those noted below, is prohibited. Upon the subject’s request and 
written permission, medical information may be given to his/her personal physician or other 
appropriate medical personnel responsible for the subject’s welfare. Data generated for this study 
must be available for inspection on request to representatives of the FDA, other national or local 
health authorities, Sangamo, and the associated IRB/IEC. 
Release of research results or data that reveal subject names or other identifiers, such as 
photographs, audio or videotapes, must be carried out in accordance with Department of Health 
and Human Services Standards for Privacy of Individual Health information, 45 CFR 164.508. 
Written authorization must be obtained from the subject and IRB/IEC prior to the release of such 
information. Identifiable subject data may not be used for purposes of promoting the study drug. 
14.4 
Reporting Obligations 
Sangamo BioSciences, Inc., the sponsor of this IND, is required to report to the FDA annually on 
the status of the trial. Status reports must be filed by the Principal Investigator with their IRB on 
an annual basis. 
 
15. 
ADMINISTRATIVE CONSIDERATIONS 
15.1 
Study Documentation 
The Investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system containing all study-related documentation. These files must be suitable for 
inspection by the Sponsor or the FDA at any time and should consist of the following elements: 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 45 of 70                                                                                   Version: January 30, 2014 
a) 
Subject files containing the completed medical records, supporting source 
documentation, electronic case report forms and the IRB approved Informed 
Consent signed by subjects. 
b) 
Study files containing all version of the IRB approved protocol with all 
amendments, IRB approved informed consent forms, copies of all pre-study 
documentation, Form FDA 1572 and all correspondence to and from the IRB and 
the Sponsor. 
c) 
The investigator should maintain a list of appropriately qualified persons who are 
delegated to perform significant study-related studies. In addition, the investigator 
should maintain a signature sheet to document signatures and initials of all 
persons authorized to make entries and/or corrections on the source documents 
and electronic case report forms. 
15.2 
Record Retention 
According to 21 CFR 312.62(c), the investigator shall retain records required to be maintained 
under this part for a period of 2 years following the date a marketing application is approved for 
the drug for the indication for which it is being investigated. If no application is to be filed or if 
the application is not approved for such indication, the investigator shall retain these records 
until 2 years after the investigation is discontinued and the FDA is notified. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with Sangamo BioSciences. It is the responsibility of Sangamo 
BioSciences to inform the investigator as to when these documents no longer need to be retained. 
15.3 
Case Report Forms 
The investigator is responsible for the quality of the data recorded on the case report form. The 
data recorded should be a complete and accurate account of the subject’s record collected during 
the study 
Clinical data will be recorded on case report forms (CRFs) provided by Sangamo. All forms 
must be legible and complete. The investigator must review all entries for completeness and 
correctness. When changes or corrections are made on any case report form, an audit trail will be 
generated to record date and time when a change is made, who made the change, and reason for 
the change as needed. The original entry should not be obscured. 
The investigator agrees to complete and sign case report forms in a timely fashion, after 
completion of each subject, and make them available to the Sangamo study monitor for full 
inspection. In addition, all data queries should be resolved promptly. 
15.4 
Termination of the Study 
Sangamo retains the right to terminate the study and remove all the study materials from the 
study site at any time. Specific instances that may precipitate such termination are as follows: 
• 
Completion of the study at an investigational site 
• 
Investigator withdrawal from participation in study 
• 
Termination of this study by Sangamo 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 46 of 70                                                                                   Version: January 30, 2014 
15.5 
Study Monitoring  
Sangamo BioSciences, as sponsor of this study, is responsible to regulatory authorities for 
ensuring the proper conduct of the study as regards protocol adherence and validity of the data 
recorded on the case report forms presented to the regulatory authorities.  Sangamo BioSciences 
has therefore assigned a clinical monitor and a medical monitor to this study. Their duties are to 
aid the investigator and, at the same time, Sangamo BioSciences in the maintenance of complete, 
legible, well-organized, and easily retrievable data. In addition, a Sangamo BioSciences study 
monitor will ensure an understanding of the protocol, reporting responsibilities, and the validity 
of the data.   
Individual study sites will be monitored by a Sangamo representative at appropriate intervals to 
assure satisfactory consenting process, data recording, and protocol adherence. In order to 
perform their roles well, the Sangamo BioSciences monitors must be given direct access to 
primary subject data (source documents) that support data entered onto the case report forms. 
The investigator and staff are expected to cooperate and provide all relevant study 
documentation in detail at each site visit on request for review. Each study center will also be 
routinely monitored by telephone to keep abreast of subject status and to answer questions. 
Regulatory authorities, the IRB, and/or the sponsor’s clinical quality assurance group may 
request access to all source documents, case report forms, and other study documentation for on-
site audit, or inspection. Direct access to these documents must be guaranteed by the 
investigator, who must provide support at all times for these activities. 
The investigator or designated person should agree, as a minimum requirement, to record the 
following information in the subject notes: 
• Protocol identification number, brief description or title of study 
• Date and statement that subject has given written informed consent 
• All study follow-up visit dates 
• AEs as described in Sections 10.0 and 11.0 of this protocol 
Entries in the subject notes must contain the signature or initials of the person making the entries. 
The clinical study monitor will perform source data verification at each monitoring visit. 
15.6 
Publication Statement 
The results of this clinical trial may be used by Sangamo in registration documents for regulatory 
authorities in the U.S. or abroad, or for public dissemination in the form of papers, abstracts, 
posters, or other informational materials to be presented at scientific meetings, or published in 
professional journals, or as a part of an academic thesis by an investigator. 
All proposed publications, papers, abstracts, or other written materials related to the study, or an 
outline of any proposed oral presentations, shall be submitted to Sangamo for approval at least 
45 days prior to (1) submission of such written materials for publication or (2) any proposed oral 
disclosure to a third party. Sangamo shall have the right to review and comment on such written 
material or outline, and to confirm the accuracy of the data described therein by comparison with 
that collected during the course of this study. In the event that Sangamo determines that an 
enabling description of patentable subject matter is contained in such written material or outline, 
it shall notify the clinical site(s) within 1 month after receipt by Sangamo and Sangamo will have 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 47 of 70                                                                                   Version: January 30, 2014 
an additional 90 days for review. 
In the event of publication using multi-center data, the number of subjects enrolled by each 
investigator will usually determine the order of participation, unless otherwise agreed upon by 
the investigators and Sangamo. 
15.7 
Study Funding 
The costs necessary to perform the study will be agreed to by the investigator and/or the 
management of the study facility and will be documented in a separate financial agreement. All 
financial agreements will be signed by the investigator and Sangamo BioSciences. 
 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 48 of 70                                                                                   Version: January 30, 2014 
REFERENCES 
Aste-Amezaga, M et al. Quantative adenovirus neutralization assays based on the secreted 
alkaline phosphatase reporter gene: application in epidemiologic studies and in the design of 
adenovector vaccines.  Human Gene Therapy 15: 293-304 (2004) 
Baker GL, Kahl LE, et al.: Malignancy following treatment of rheumatoid arthritis with 
cyclophosphamide. Long-term case-control follow-up study. Am J Med 83: 1-9, 1987. 
Bartlett JA, Miralles GD, et al.: Addition of cyclophosphamide to antiretroviral therapy does not 
diminish the cellular reservoir in HIV-infected persons.  AIDS Rsrch and Human Retroviruses 
18:535-43, 2002 
Dudley ME, Wunderlich JR, et al: Adoptive cell transfer therapy following non-myeloablative 
but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic 
melanoma. J Clin Onc 23:2346-57, 2005.  
Dudley ME, Rosenberg SA: Adoptive cell-transfer for the treatment of patients with cancer. Nat 
Rev Cancer, 3:666-75, 2003. 
Hensley ML, et al.: American Society of Clinical Oncology 2008 Clinical Practice Guideline 
Update: Use of Chemotherapy and Radiation Therapy Protectants. J Clin Onc 27:127-145, 2009 
Kolb, JP, Poupon MF, et al.: Splenic modifications induced by cyclophosphamide in C3H/He, 
nude, and "B" mice." J Immunol 118: 1595-99, 1977. 
Laport GG, Levine BL, et al. Adoptive transfer of costimulated T cells induces lymphocytosis in 
patients with relapsed/refractory non-Hodgkin's lymphoma following CD34-selected 
hematopoietic cell transplantation. Blood 102: 2004-13, 2003. 
Lawrence J, Mayers DL, et al.: Structured treatment interruption in patients with multidrug 
resistant human immunodeficiency virus. New Engl J Med 349:837-46, 2003. 
LeBraz MLB, Fagard CF, et al.: Physical and psychological impacts of structured treatment 
interruptions. Poster presentation: The XIV International AIDS Conference: Abstract no. 
ThPpB2134. 
Martin F, Lauwerys B, et al: Side-effects of intravenous cyclophosphamide pulse therapy. Lupus 
6:254-57, 1997. 
Nilsson, M et al. Development of adenoviral vector system with adenovirus serotype 35 tropism; 
efficient transient gene transfer into primary malignant hematopoietic cells.  Journal Gene 
Medicine (6): 631-641(2004) 
Nordoy, T et al.: Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 
years after high-dose therapy with ABMT. Serological responses to revaccination according to 
EBMT guidelines. Bone Marrow Transplant. 28:681-87, 2001. 
Oxenius A, Price DA, et al.: Stimulation of HIV-specific cellular immunity by structured 
treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci 
USA 99:13747-52, 2002. 
Patton, NI: Treatment Interruption strategies: how great are the risks? Curr Opin Infect Dis 
21:25-30, 2008. 

Sangamo BioSciences, Inc.  
Protocol SB-728-1101                                                                                                                 Confidential 
Page 49 of 70                                                                                   Version: January 30, 2014 
Perez et al.: Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-
finger nucleases.  Nature Biotechnology 26, 808 - 816 (2008)  
Porter DL, Levine BL, et al.: A phase I trial of donor lymphocyte infusions expanded and 
activated ex-vivo via CD3/CD28 co-stimulation. Blood 107: 1325-31, 2006. 
Porter DL, Levine BL, et al.: Chimeric antigen receptor-modified T cells in chronic lymphoid 
leukemia. New Engl J Med 365:725-33, 2011. 
Rapoport AP, Levine BL, et al.: Molecular remission of CML after autotransplantation followed 
by adoptive transfer of costimulated autologous T cells. Bone Marrow Transplant. 33:53-60, 
2004. 
Rapoport AP, Stadtmauer EA, et al.: Restoration of immunity in lymphopenic individuals with 
cancer by vaccination and adoptive T-cell transfer. Nat Med 11: 1230-1237, 2005. 
Rapoport AP, Aqui NA, et al.: Combination immunotherapy using adoptive T-cell transfer and 
tumor antigen vaccination based on hTERT and survivin following ASCT for myeloma. Blood 
117: 788-97, 2011. 
Small, E.J et al. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific 
antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic 
prostate cancer. Molecular Therapy 14, 107-117 (2006b) 
Stadtmauer E A, Vogl DT, et al.: Transfer of Influenza Vaccine-Primed Co-stimulated 
Autologous T-Cells after Stem Cell Transplantation for Multiple Myeloma Leads to 
Reconstitution of Influenza Immunity: Results of a Randomized Clinical Trial. Blood 117: 63-
71, 2011. 
Taylor S, Boffito M, et al.: Stopping antiretroviral therapy. AIDS 21:1673-82, 2007. 
Van Lunzen J, Glaunsinger T, et al.: Transfer of autologous gene-modified T cells in HIV-
infected patients with advanced immunodeficiency and drug-resistant virus. Molecular Therapy 
15:1024-33, 2007. 
Willers JM, Sluis E: The influence of cyclophosphamide on antibody formation in the mouse." 
Ann Immunol (Paris) 126: 267-79, 1975. 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 50 of 70                                                                                   Version: January 30, 2014 
APPENDIX 1:  SCHEDULE OF EVENTS  
Procedure 
Screen 
 
Pre‐Leukapheresis 
(1 wk prior to 
leukapheresis) 
Leukapheresisa 
Baseline 
for 
Research 
Blood 
(between 
Leuk and 
CTX) 
Baseline  
(~1 wk 
prior to 
CTX) 
CTX 
Day 0 
Day 
1 
Day 5 
(‐1 day) 
Cohorts 4 
& 5 only 
Wk 1 
(+2 
days) 
Day 12 
(‐1 day) 
Cohorts 
4 & 5 
only 
Wk 2 
(+2 
days) 
Wk 3 
(+2 
days) 
Wk 4 
(+2 
days) 
Wk 6 
(+3 
days) 
‐‐‐‐‐‐‐‐‐ 
Start TI 
Wk 8 
(+3 days) 
Wk 10 
(+3 days) 
Wk 12 
(+3 
days) 
Wk 14 
(+3 days) 
Wk 18 
(+1 wk) 
Wk 22  
(+1 wk)  
_____ 
Evaluate 
TIm 
M 7, M 8,  
M 10, M 12 
(+1 wk) 
Inclusion Exclusion / 
Informed  Consentb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
M12 only 
Vital Signsc 
 
 
 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
M8 only 
12‐lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Leukapheresis 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide 
Administration 
 
 
 
 
 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SB‐728‐T infusion 
 
 
 
 
 
 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events 
 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
 
 
 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hepatitis B and Cf 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testg 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry 
X 
Xh 
 
 
X 
X 
X 
X 
 
X 
 
 
X 
 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
M7, M10, M12 
only 
CBC w diff / platelets(ANC 
at Screen through Week 
4) 
X 
X 
 
X 
(CBC 
w/diff 
only) 
X 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
 
 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
X 
M7, M12 only 
CD4+ T‐cell counts 
X 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
Xi 
Xi 
Xi 
Xi 
Xi 
Xi 
Xi 
X 
HIV‐1 RNA (Viral Load) 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
X 
X 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
X 
CCR5 SNP CEL‐1 assay 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ad and SB‐728 
immunogenicity 
X 
 
 
 
Xk 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
M7, M12 only 
Pentamer 
 
 
 
 
Xk 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Month 8 and 
12 only 
HIV‐1 Coreceptor and 
resistance test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xm 
 
Research Blood 
X 
 
 
X 
Xl 
 
X 
X 
 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
Upon request of sponsor: Additional 80 mL research blood collection, CBC with differential, and CD4+ T‐cell Count:  One to 2 times during the study. If subject agrees to participate in the optional leukapheresis procedure, this additional blood collection will not be 
performed. 
 
 
a If second leukapheresis is required, it must be > 3 weeks after the first leukapheresis.  
b Inform subjects of Long‐term, Follow‐up study 
c Ht and wt at BL,  Vital signs on CTX and Day 0 (temp., pulse,  BP) and on Wks 6, 22 and M8 and M12 (temp, pulse, BP and weight) 
d Cyclophosphamide should be administered up to 3 days prior to the SB‐728‐T infusion. Refer to Protocol Sections 6.5.1 and 8.2 and the Study Reference 
Manual for further details 
e Refer to Protocol Sections 6.5.2 and 8.1 and the Study Reference Manual for further details 
f Not required if negative results within 60 days of screening visit 
g Serum pregnancy test at Screen and urine pregnancy test at Baseline  
h Electrolytes (Na, K, C02, Cl), calcium, liver function tests (albumin, total protein, alkaline phosphatase, AST, ALT, total bilirubin)
iCD4 test will be repeated every 2 weeks for 3 consecutive measurements for values <500 cells/µL 
j HIV‐1 RNA test will be repeated every  2 weeks for 3 consecutive measurements for values >100,000 
copies/mL  
k May be performed up to 4 weeks prior to the SB‐728‐T infusion, Day 0.  
lResearch blood may be drawn on day of and prior to cyclophosphamide infusion. 
m HIV‐1 coreceptor and resistance testing will be performed once if HIV RNA exceeds 1,000 copies/mL 
during TI. Refer to protocol sections 6.5, 8.3, and 9.3

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 51 of 70                                                                                   Version: January 30, 2014 
 
APPENDIX II: DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS 
 
Version 1.0, December, 2004; clarification August 2009 
 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(“DAIDS AE Grading Table”) is a descriptive terminology which can be utilized for Adverse 
Event (AE) reporting. A grading (severity) scale is provided for each AE term. 
 
This clarification of the DAIDS Table for Grading the Severity of Adult and Pediatric AE’s 
provides additional explanation of the DAIDS AE Grading Table and clarifies some of the 
parameters.  
 
I. 
INSTRUCTIONS AND CLARIFICATIONS 
 
Grading Adult and Pediatric AEs 
The DAIDS AE Grading Table includes parameters for grading both Adult and Pediatric AEs.  
When a single set of parameters is not appropriate for grading specific types of AEs for both 
Adult and Pediatric populations, separate sets of parameters for Adult and/or Pediatric 
populations (with specified respective age ranges) are given in the Table.  If there is no 
distinction in the Table between Adult and Pediatric values for a type of AE, then the single set 
of parameters listed is to be used for grading the severity of both Adult and Pediatric events of 
that type.   
Note: In the classification of adverse events, the term “severe” is not the same as 
“serious.” Severity is an indication of the intensity of a specific event (as in mild, 
moderate, or severe chest pain).  The term “serious” relates to a participant/event 
outcome or action criteria, usually associated with events that pose a threat to a 
participant’s life or functioning.  
 
Addenda 1-3 Grading Tables for Microbicide Studies 
For protocols involving topical application of products to the female genital tract, male genital 
area or rectum, strong consideration should be given to using Appendices I-III as the primary 
grading scales for these areas. The protocol would need to specifically state that one or more of 
the Appendices would be primary (and thus take precedence over the main Grading Table) for 
items that are listed in both the Appendix and the main Grading Table. 
Addendum 1 - Female Genital Grading Table for Use in Microbicide Studies - PDF 
Addendum 2 - Male Genital Grading Table for Use in Microbicide Studies - PDF  
Addendum 3 - Rectal Grading Table for Use in Microbicide Studies - PDF  
 
Grade 5 
For any AE where the outcome is death, the severity of the AE is classified as Grade 5.  
 
Estimating Severity Grade for Parameters Not Identified in the Table 
In order to grade a clinical AE that is not identified in the DAIDS AE grading table, use the 
category “Estimating Severity Grade” located on Page 3. 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 52 of 70                                                                                   Version: January 30, 2014 
 
 
Determining Severity Grade for Parameters “Between Grades” 
If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an 
AE could be either Grade 2 or Grade 3), select the higher of the two grades for the AE. If a 
laboratory value that is graded as a multiple of the ULN or LLN falls between two grades, select 
the higher of the two grades for the AE. For example, Grade 1 is 2.5 x ULN and Grade 2 is 2.6 x 
ULN for a parameter. If the lab value is 2.53 x ULN (which is between the two grades), the 
severity of this AE would be Grade 2, the higher of the two grades. 
 
Values Below Grade 1 
Any laboratory value that is between either the LLN or ULN and Grade 1 should not be graded. 
 
Determining Severity Grade when Local Laboratory Normal Values Overlap with Grade 1 
Ranges  
In these situations, the severity grading is based on the ranges in the DAIDS AE Grading Table, 
even when there is a reference to the local lab LLN. 
 
For example: Phosphate, Serum, Low, Adult and Pediatric > 14 years Grade 1 range is 2.50 
mg/dL - < LLN. A particular laboratory’s normal range for Phosphate is 2.1 – 3.8 mg/dL. A 
participant’s actual lab value is 2.5.   In this case, the value of 2.5 exceeds the LLN for the local 
lab, but will be graded as Grade 1 per DAIDS AE Grading Table. 
 
II. 
DEFINITIONS OF TERMS USED IN THE TABLE: 
 
Basic Self-care Functions 
Adult 
Activities such as bathing, dressing, toileting, 
transfer/movement, continence, and feeding. 
Young Children 
Activities that are age and culturally appropriate (e.g., feeding 
self with culturally appropriate eating implement). 
LLN 
Lower limit of normal 
 
Medical Intervention 
Use of pharmacologic or biologic agent(s) for treatment of an 
AE. 
NA 
Not Applicable 
Operative Intervention 
Surgical OR other invasive mechanical procedures. 
ULN 
Upper limit of normal 
Usual Social & Functional 
Activities 
Adult 
Adaptive tasks and desirable activities, such as going to work, 
shopping, cooking, use of transportation, pursuing a hobby, etc. 
Young Children 
Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 53 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
ESTIMATING SEVERITY GRADE 
Clinical adverse event 
NOT identified 
elsewhere in this 
DAIDS AE Grading 
Table  
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Symptoms causing 
inability to perform usual 
social & functional 
activities 
Symptoms causing 
inability to perform basic 
self-care functions OR 
Medical or operative 
intervention indicated to 
prevent permanent 
impairment, persistent 
disability, or death  
SYSTEMIC 
Acute systemic 
allergic reaction  
Localized urticaria 
(wheals) with no 
medical intervention 
indicated 
Localized urticaria with 
medical intervention 
indicated OR Mild 
angioedema with no 
medical intervention 
indicated 
Generalized urticaria 
OR Angioedema with 
medical intervention 
indicated OR 
Symptomatic mild 
bronchospasm 
Acute anaphylaxis OR 
Life-threatening 
bronchospasm OR 
laryngeal edema 
Chills 
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Symptoms causing 
inability to perform usual 
social & functional 
activities 
NA 
Fatigue 
Malaise 
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Symptoms causing 
inability to perform usual 
social & functional 
activities 
Incapacitating fatigue/ 
malaise symptoms 
causing inability to 
perform basic self-care 
functions 
Fever (nonaxillary) 
37.7 – 38.6°C 
38.7 – 39.3°C 
39.4 – 40.5°C 
> 40.5°C  
Pain (indicate body 
site) 
DO NOT use for pain 
due to injection (See 
Injection Site 
Reactions: Injection 
site pain) 
See also Headache, 
Arthralgia, and 
Myalgia 
Pain causing no or 
minimal interference 
with usual social & 
functional activities 
Pain causing greater 
than minimal 
interference with usual 
social & functional 
activities 
Pain causing inability to 
perform usual social & 
functional activities 
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other 
than emergency room 
visit) indicated 
 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 54 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Unintentional weight 
loss 
NA 
5 – 9% loss in body 
weight from baseline 
10 – 19% loss in body 
weight from baseline 
≥ 20% loss in body 
weight from baseline OR  
Aggressive intervention 
indicated [e.g., tube 
feeding or total 
parenteral nutrition 
(TPN)] 
INFECTION 
Infection (any other 
than HIV infection) 
Localized, no 
systemic antimicrobial 
treatment indicated 
AND Symptoms 
causing no or minimal 
interference with 
usual social & 
functional activities 
Systemic antimicrobial 
treatment indicated 
OR Symptoms 
causing greater than 
minimal interference 
with usual social & 
functional activities 
Systemic antimicrobial 
treatment indicated 
AND Symptoms causing 
inability to perform usual 
social & functional 
activities OR Operative 
intervention (other than 
simple incision and 
drainage) indicated 
Life-threatening 
consequences (e.g., 
septic shock) 
INJECTION SITE REACTIONS 
Injection site pain 
(pain without touching) 
Or 
Tenderness (pain 
when area is touched)  
Pain/tenderness 
causing no or minimal 
limitation of use of 
limb 
Pain/tenderness 
limiting use of limb OR 
Pain/tenderness 
causing greater than 
minimal interference 
with usual social & 
functional activities 
 
Pain/tenderness 
causing inability to 
perform usual social & 
functional activities 
 
Pain/tenderness causing 
inability to perform basic 
self-care function OR 
Hospitalization (other 
than emergency room 
visit) indicated for 
management of 
pain/tenderness 
Injection site reaction (localized) 
Adult > 15 years 
 
Erythema OR 
Induration 
of 5x5 cm – 9x9 cm 
(or 25 cm2 – 81cm2) 
Erythema OR 
Induration OR Edema 
> 9 cm any diameter 
(or > 81 cm2) 
Ulceration OR 
Secondary infection OR 
Phlebitis OR Sterile 
abscess OR Drainage 
Necrosis (involving 
dermis and deeper 
tissue) 
 
Pediatric ≤ 15 years 
Erythema OR 
Induration OR Edema 
present but ≤ 2.5 cm 
diameter 
Erythema OR 
Induration OR Edema 
> 2.5 cm diameter but 
< 50% surface area of 
the extremity segment 
(e.g., upper arm/thigh) 
Erythema OR Induration 
OR Edema involving  
≥ 50% surface area of 
the extremity segment 
(e.g., upper arm/thigh) 
OR Ulceration OR 
Secondary infection OR 
Phlebitis OR Sterile 
abscess OR Drainage 
Necrosis (involving 
dermis and deeper 
tissue) 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 55 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Pruritis associated 
with injection  
See also Skin: Pruritis 
(itching - no skin 
lesions) 
Itching localized to 
injection site AND 
Relieved 
spontaneously or with 
< 48 hours treatment  
Itching beyond the 
injection site but not 
generalized OR 
Itching localized to 
injection site requiring 
≥ 48 hours treatment  
Generalized itching 
causing inability to 
perform usual social & 
functional activities 
NA 
SKIN – DERMATOLOGICAL 
Alopecia 
Thinning detectable 
by study participant 
(or by caregiver for 
young children and 
disabled adults) 
Thinning or patchy 
hair loss detectable by 
health care provider 
Complete hair loss 
NA 
Cutaneous reaction – 
rash 
Localized macular 
rash  
Diffuse macular, 
maculopapular, or 
morbilliform rash OR 
Target lesions  
Diffuse macular, 
maculopapular, or 
morbilliform rash with 
vesicles or limited 
number of bullae OR 
Superficial ulcerations 
of mucous membrane 
limited to one site 
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson 
syndrome OR Ulceration 
of mucous membrane 
involving two or more 
distinct mucosal sites 
OR Toxic epidermal 
necrolysis (TEN) 
Hyperpigmentation 
Slight or localized 
Marked or generalized 
NA 
NA 
Hypopigmentation 
Slight or localized  
Marked or generalized 
NA 
NA 
Pruritis (itching – no 
skin lesions)  
(See also Injection 
Site Reactions: 
Pruritis associated 
with injection) 
Itching causing no or 
minimal interference 
with usual social & 
functional activities 
Itching causing greater 
than minimal 
interference with usual 
social & functional 
activities 
Itching causing inability 
to perform usual social 
& functional activities  
NA 
 
CARDIOVASCULAR 
Cardiac arrhythmia 
(general) 
(By ECG or physical 
exam) 
Asymptomatic AND 
No intervention 
indicated 
Asymptomatic AND 
Non-urgent medical 
intervention indicated 
Symptomatic, non-life-
threatening AND Non-
urgent medical 
intervention indicated  
Life-threatening 
arrhythmia OR Urgent 
intervention indicated 
Cardiac-
ischemia/infarction 
NA 
NA 
Symptomatic ischemia 
(stable angina) OR 
Testing consistent with 
ischemia  
Unstable angina OR 
Acute myocardial 
infarction 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 56 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Hemorrhage (significant 
acute blood loss) 
NA 
Symptomatic AND No 
transfusion indicated 
Symptomatic AND 
Transfusion of ≤ 2 units 
packed RBCs (for children 
≤ 10 cc/kg) indicated  
Life-threatening 
hypotension OR 
Transfusion of > 2 units 
packed RBCs (for children > 
10 cc/kg) indicated 
Hypertension 
Adult > 17 years 
(with repeat testing at 
same visit) 
140 – 159 mmHg 
systolic 
OR 
90 – 99 mmHg diastolic 
160 – 179 mmHg systolic 
OR 
100 – 109 mmHg 
diastolic 
≥ 180 mmHg systolic 
OR 
≥ 110 mmHg diastolic 
 
Life-threatening 
consequences (e.g., 
malignant hypertension) 
OR Hospitalization 
indicated (other than 
emergency room visit) 
Correction: in Grade 2 to 160 - 179 from > 160-179 (systolic) and to ≥ 100 -109 from > 100-109 (diastolic) and in Grade 3 to ≥ 180 from > 180 
(systolic) and to  ≥ 110  from > 110 (diastolic). 
Pediatric ≤ 17 years 
(with repeat testing at 
same visit) 
 
NA 
91
st –  94
th percentile 
adjusted for age, height, 
and gender (systolic 
and/or diastolic) 
≥ 95
th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic) 
Life-threatening 
consequences (e.g., 
malignant hypertension) 
OR Hospitalization 
indicated (other than 
emergency room visit) 
Hypotension 
NA 
Symptomatic, 
corrected with oral 
fluid replacement 
Symptomatic, IV fluids 
indicated 
Shock requiring use of 
vasopressors or 
mechanical assistance 
to maintain blood 
pressure 
Pericardial effusion 
Asymptomatic, small 
effusion requiring no 
intervention 
Asymptomatic, 
moderate or larger 
effusion requiring no 
intervention 
Effusion with non-life 
threatening physiologic 
consequences OR 
Effusion with non-urgent 
intervention indicated 
Life-threatening 
consequences (e.g., 
tamponade) OR Urgent 
intervention indicated 
Prolonged PR interval 
Adult > 16 years 
PR interval  
0.21 – 0.25 sec 
PR interval 
> 0.25 sec 
Type II 2nd degree AV 
block OR Ventricular 
pause > 3.0 sec 
Complete AV block 
Pediatric ≤ 16 years 
1st degree AV block 
(PR > normal for age 
and rate) 
Type I 2nd degree AV 
block  
Type II 2nd degree AV 
block  
Complete AV block 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 57 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Prolonged QTc 
Adult > 16 years 
 
Asymptomatic, QTc 
interval 0.45 – 0.47 
sec OR Increase 
interval < 0.03 sec 
above baseline 
Asymptomatic, QTc 
interval 0.48 – 0.49 
sec OR Increase in 
interval 0.03 – 0.05 
sec above baseline 
Asymptomatic, QTc 
interval ≥ 0.50 sec OR 
Increase in interval  
≥ 0.06 sec above baseline 
Life-threatening 
consequences, e.g. 
Torsade de pointes or 
other associated serious 
ventricular dysrhythmia 
Pediatric ≤ 16 years 
Asymptomatic, QTc 
interval 0.450 –  
0.464 sec  
Asymptomatic, QTc 
interval 0.465 –  
0.479 sec  
Asymptomatic, QTc 
interval ≥ 0.480 sec  
Life-threatening 
consequences, e.g.  
Torsade de pointes  or 
other associated serious 
ventricular dysrhythmia 
Thrombosis/embolism 
NA 
Deep vein thrombosis 
AND No intervention 
indicated (e.g., 
anticoagulation, lysis 
filter, invasive 
procedure)  
Deep vein thrombosis 
AND Intervention 
indicated (e.g., 
anticoagulation, lysis 
filter, invasive 
procedure)  
Embolic event (e.g., 
pulmonary embolism, 
life-threatening 
thrombus)  
Vasovagal episode 
(associated with a 
procedure of any kind) 
Present without loss 
of consciousness  
Present with transient 
loss of consciousness 
NA  
NA 
Ventricular 
dysfunction 
(congestive heart 
failure) 
NA 
Asymptomatic 
diagnostic finding AND 
intervention indicated 
New onset with 
symptoms OR Worsening 
symptomatic congestive 
heart failure 
Life-threatening 
congestive heart failure 
GASTROINTESTINAL 
Anorexia 
Loss of appetite 
without decreased 
oral intake 
Loss of appetite 
associated with 
decreased oral intake 
without significant 
weight loss 
Loss of appetite 
associated with 
significant weight loss 
Life-threatening 
consequences OR 
Aggressive intervention 
indicated [e.g., tube 
feeding or total parenteral 
nutrition (TPN)] 
Comment: Please note that, while the grading scale provided for Unintentional Weight Loss may be used as a guideline when 
grading anorexia, this is not a requirement and should not be used as a substitute for clinical judgment.  
Ascites 
Asymptomatic 
Symptomatic AND 
Intervention indicated 
(e.g., diuretics or 
therapeutic 
paracentesis) 
Symptomatic despite 
intervention 
Life-threatening 
consequences 
 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 58 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Cholecystitis 
NA 
Symptomatic AND 
Medical intervention 
indicated 
Radiologic, endoscopic, 
or operative intervention 
indicated 
Life-threatening 
consequences (e.g., 
sepsis or perforation)  
Constipation  
NA 
Persistent constipation 
requiring regular use 
of dietary 
modifications, 
laxatives, or enemas  
Obstipation with manual 
evacuation indicated 
Life-threatening 
consequences (e.g., 
obstruction) 
Diarrhea 
Adult and Pediatric 
≥ 1 year 
Transient or 
intermittent episodes 
of unformed stools 
OR Increase of ≤ 3 
stools over baseline 
per 24-hour period 
Persistent episodes of 
unformed to watery 
stools OR Increase of 
4 – 6 stools over 
baseline per 24-hour 
period 
Bloody diarrhea OR 
Increase of ≥ 7 stools 
per 24-hour period OR 
IV fluid replacement 
indicated 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
Pediatric < 1 year 
Liquid stools (more 
unformed than usual) 
but usual number of 
stools 
Liquid stools with 
increased number of 
stools OR Mild 
dehydration 
Liquid stools with 
moderate dehydration 
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR 
Hypotensive shock 
Dysphagia-
Odynophagia  
Symptomatic but able 
to eat usual diet 
Symptoms causing 
altered dietary intake 
without medical 
intervention indicated 
Symptoms causing 
severely altered dietary 
intake with medical 
intervention indicated 
Life-threatening 
reduction in oral intake 
Mucositis/stomatitis  
(clinical exam) 
Indicate site (e.g., 
larynx, oral) 
See Genitourinary for 
Vulvovaginitis  
See also Dysphagia-
Odynophagia and 
Proctitis 
Erythema of the 
mucosa 
Patchy 
pseudomembranes or 
ulcerations  
Confluent 
pseudomembranes or 
ulcerations OR Mucosal 
bleeding with minor 
trauma 
Tissue necrosis OR 
Diffuse spontaneous 
mucosal bleeding OR 
Life-threatening 
consequences (e.g., 
aspiration, choking) 
Nausea  
Transient (< 24 hours) 
or intermittent nausea 
with no or minimal 
interference with oral 
intake 
Persistent nausea 
resulting in decreased 
oral intake for 24 – 48 
hours 
Persistent nausea 
resulting in minimal oral 
intake for > 48 hours 
OR Aggressive 
rehydration indicated 
(e.g., IV fluids) 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 59 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Pancreatitis 
NA 
Symptomatic AND 
Hospitalization not 
indicated (other than 
emergency room visit) 
Symptomatic AND 
Hospitalization indicated 
(other than emergency 
room visit) 
Life-threatening 
consequences (e.g., 
circulatory failure, 
hemorrhage, sepsis) 
Proctitis (functional- 
symptomatic) 
Also see 
Mucositis/stomatitis  
for clinical exam 
Rectal discomfort 
AND No intervention 
indicated 
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities OR Medical 
intervention indicated  
Symptoms causing 
inability to perform usual 
social & functional 
activities OR Operative 
intervention indicated  
Life-threatening 
consequences (e.g., 
perforation) 
 
Vomiting 
Transient or 
intermittent vomiting 
with no or minimal 
interference with oral 
intake 
Frequent episodes of 
vomiting with no or 
mild dehydration 
Persistent vomiting 
resulting in orthostatic 
hypotension OR 
Aggressive rehydration 
indicated (e.g., IV fluids) 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
NEUROLOGIC 
Alteration in 
personality-behavior 
or in mood (e.g., 
agitation, anxiety, 
depression, mania, 
psychosis) 
Alteration causing no 
or minimal 
interference with 
usual social & 
functional activities  
Alteration causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Alteration causing 
inability to perform usual 
social & functional 
activities  
Behavior potentially 
harmful to self or others 
(e.g., suicidal and 
homicidal ideation or 
attempt, acute 
psychosis) OR Causing 
inability to perform basic 
self-care functions  
Altered Mental Status  
For Dementia, see 
Cognitive and 
behavioral/attentional 
disturbance (including 
dementia and 
attention deficit 
disorder) 
Changes causing no 
or minimal 
interference with 
usual social & 
functional activities 
Mild lethargy or 
somnolence causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Confusion, memory 
impairment, lethargy, or 
somnolence causing 
inability to perform usual 
social & functional 
activities 
Delirium OR 
obtundation, OR coma 
Ataxia  
Asymptomatic ataxia 
detectable on exam 
OR Minimal ataxia 
causing no or minimal 
interference with 
usual social & 
functional activities 
Symptomatic ataxia 
causing greater than 
minimal interference 
with usual social & 
functional activities 
Symptomatic ataxia 
causing inability to 
perform usual social & 
functional activities  
Disabling ataxia causing 
inability to perform basic 
self-care functions 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 60 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Cognitive and 
behavioral/attentional 
disturbance (including 
dementia and 
attention deficit 
disorder)  
Disability causing no 
or minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources not 
indicated 
Disability causing 
greater than minimal 
interference with usual 
social & functional 
activities OR 
Specialized resources 
on part-time basis 
indicated 
Disability causing 
inability to perform usual 
social & functional 
activities OR 
Specialized resources 
on a full-time basis 
indicated 
Disability causing 
inability to perform basic 
self-care functions OR 
Institutionalization 
indicated 
CNS ischemia 
(acute) 
NA 
NA 
Transient ischemic 
attack 
Cerebral vascular 
accident (CVA, stroke) 
with neurological deficit  
Developmental delay 
– Pediatric ≤ 16 
years 
Mild developmental 
delay, either motor or 
cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting  
Moderate 
developmental delay,  
either motor or 
cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting  
Severe developmental 
delay, either motor or 
cognitive, as determined 
by comparison with a 
developmental 
screening tool 
appropriate for the 
setting  
Developmental 
regression, either motor 
or cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting 
Headache  
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Symptoms causing 
inability to perform usual 
social & functional 
activities 
Symptoms causing 
inability to perform basic 
self-care functions OR 
Hospitalization indicated 
(other than emergency 
room visit) OR 
Headache with 
significant impairment of 
alertness or other 
neurologic function  
Insomnia 
NA 
Difficulty sleeping 
causing greater than 
minimal interference 
with usual social & 
functional activities 
Difficulty sleeping 
causing inability to 
perform usual social & 
functional activities 
Disabling insomnia 
causing inability to 
perform basic self-care 
functions 
Neuromuscular 
weakness  
(including myopathy & 
neuropathy)  
Asymptomatic with 
decreased strength 
on exam OR Minimal 
muscle weakness 
causing no or minimal 
interference with 
usual social & 
functional activities 
Muscle weakness 
causing greater than 
minimal interference 
with usual social & 
functional activities 
Muscle weakness 
causing inability to 
perform usual social & 
functional activities  
Disabling muscle 
weakness causing 
inability to perform basic 
self-care functions OR 
Respiratory muscle 
weakness impairing 
ventilation 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 61 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Neurosensory 
alteration (including 
paresthesia and 
painful neuropathy) 
Asymptomatic with 
sensory alteration on 
exam or minimal 
paresthesia causing 
no or minimal 
interference with 
usual social & 
functional activities  
Sensory alteration or 
paresthesia causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Sensory alteration or 
paresthesia causing 
inability to perform usual 
social & functional 
activities 
Disabling sensory 
alteration or paresthesia 
causing inability to 
perform basic self-care 
functions 
 
Seizure: (new onset)  
– Adult ≥ 18 years 
See also Seizure: 
(known pre-existing 
seizure disorder) 
NA 
1 seizure  
2 – 4 seizures  
Seizures of any kind 
which are prolonged, 
repetitive (e.g., status 
epilepticus), or difficult to 
control (e.g., refractory 
epilepsy) 
Seizure: (known pre-
existing seizure 
disorder)  
– Adult ≥ 18 years 
For worsening of 
existing epilepsy the 
grades should be 
based on an increase 
from previous level of 
control to any of these 
levels. 
NA 
Increased frequency 
of pre-existing 
seizures (non-
repetitive) without 
change in seizure 
character OR 
Infrequent break-
through seizures while 
on stable medication 
in a previously 
controlled seizure 
disorder 
Change in seizure 
character from baseline 
either in duration or 
quality (e.g., severity or  
focality)  
Seizures of any kind 
which are prolonged, 
repetitive (e.g., status 
epilepticus), or difficult to 
control (e.g., refractory 
epilepsy) 
Seizure  
– Pediatric < 18 
years 
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting 
< 5 minutes with < 24 
hours post ictal state 
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting 
5 – 20 minutes with  
< 24 hours post ictal 
state 
Seizure, generalized 
onset with or without 
secondary 
generalization, lasting  
> 20 minutes  
Seizure, generalized 
onset with or without 
secondary 
generalization, requiring 
intubation and sedation 
Syncope (not 
associated with a 
procedure) 
NA 
Present 
NA 
NA 
Vertigo 
Vertigo causing no or 
minimal interference 
with usual social & 
functional activities 
Vertigo causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Vertigo causing inability 
to perform usual social 
& functional activities 
Disabling vertigo 
causing inability to 
perform basic self-care 
functions 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 62 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
RESPIRATORY 
Bronchospasm (acute) 
FEV1 or peak flow 
reduced to  
70 – 80% 
FEV1 or peak flow  
50 – 69% 
FEV1 or peak flow  
25 – 49%  
Cyanosis OR FEV1 or 
peak flow < 25% OR 
Intubation 
Dyspnea or respiratory distress 
Adult ≥ 14 years 
Dyspnea on exertion 
with no or minimal 
interference with 
usual social & 
functional activities  
Dyspnea on exertion 
causing greater than 
minimal interference 
with usual social & 
functional activities  
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities  
Respiratory failure with 
ventilatory support 
indicated 
Pediatric < 14 years 
Wheezing OR 
minimal increase in 
respiratory rate for 
age 
Nasal flaring OR 
Intercostal retractions 
OR Pulse oximetry 90 
– 95% 
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities OR Pulse 
oximetry < 90% 
Respiratory failure with 
ventilatory support 
indicated 
MUSCULOSKELETAL 
Arthralgia 
See also Arthritis 
Joint pain causing no 
or minimal 
interference with 
usual social & 
functional activities 
Joint pain causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Joint pain causing 
inability to perform usual 
social & functional 
activities 
Disabling joint pain 
causing inability to 
perform basic self-care 
functions 
Arthritis 
See also Arthralgia 
Stiffness or joint 
swelling causing no or 
minimal interference 
with usual social & 
functional activities 
Stiffness or joint 
swelling causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Stiffness or joint 
swelling causing 
inability to perform usual 
social & functional 
activities 
Disabling joint stiffness 
or swelling causing 
inability to perform basic 
self-care functions  
Bone Mineral Loss 
Adult ≥ 21 years 
BMD t-score  
-2.5 to -1.0  
BMD t-score < -2.5 
Pathological fracture 
(including loss of 
vertebral height) 
Pathologic fracture 
causing life-threatening 
consequences  
Pediatric < 21 years 
BMD z-score  
-2.5 to -1.0 
BMD z-score < -2.5 
Pathological fracture 
(including loss of 
vertebral height) 
Pathologic fracture 
causing life-threatening 
consequences  
Myalgia 
(non-injection site) 
Muscle pain causing 
no or minimal 
interference with 
usual social & 
functional activities 
Muscle pain causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Muscle pain causing 
inability to perform usual 
social & functional 
activities 
Disabling muscle pain 
causing inability to 
perform basic self-care 
functions 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally appropriate 
eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, cooking, use of 
transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social interactions, play 
activities, learning tasks, etc.). 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 63 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Osteonecrosis 
NA 
Asymptomatic with 
radiographic findings 
AND No operative 
intervention indicated 
Symptomatic bone pain 
with radiographic 
findings OR Operative 
intervention indicated 
Disabling bone pain with 
radiographic findings 
causing inability to 
perform basic self-care 
functions 
GENITOURINARY 
Cervicitis  
(symptoms) 
(For use in studies 
evaluating topical  
study agents)  
For other cervicitis see 
Infection: Infection 
(any other than HIV 
infection)  
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities  
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Symptoms causing 
inability to perform usual 
social & functional 
activities  
 
Symptoms causing 
inability to perform basic 
self-care functions  
Cervicitis  
(clinical exam) 
(For use in studies 
evaluating topical  
study agents)  
For other cervicitis see 
Infection: Infection 
(any other than HIV 
infection)  
Minimal cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial 
disruption  
< 25% of total surface 
Moderate cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial 
disruption of 25 – 49% 
total surface 
Severe cervical 
abnormalities on 
examination (erythema, 
mucopurulent 
discharge, or friability) 
OR Epithelial disruption  
50 – 75% total surface 
Epithelial disruption  
> 75% total surface 
Inter-menstrual 
bleeding (IMB) 
Spotting observed by 
participant OR 
Minimal blood 
observed during 
clinical or colposcopic 
examination 
Inter-menstrual 
bleeding not greater in 
duration or amount 
than usual menstrual 
cycle 
Inter-menstrual bleeding 
greater in duration or 
amount than usual 
menstrual cycle 
Hemorrhage with life-
threatening hypotension 
OR Operative 
intervention indicated 
Urinary tract 
obstruction (e.g., 
stone) 
NA 
Signs or symptoms of 
urinary tract 
obstruction without  
hydronephrosis or 
renal dysfunction 
Signs or symptoms of 
urinary tract obstruction 
with hydronephrosis or 
renal dysfunction 
Obstruction causing life-
threatening 
consequences 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 64 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Vulvovaginitis  
(symptoms) 
(Use in studies 
evaluating topical 
study agents)  
For other 
vulvovaginitis see 
Infection: Infection 
(any other than HIV 
infection) 
Symptoms causing no 
or minimal 
interference with 
usual social & 
functional activities  
Symptoms causing 
greater than minimal 
interference with usual 
social & functional 
activities  
Symptoms causing 
inability to perform usual 
social & functional 
activities  
 
Symptoms causing 
inability to perform basic 
self-care functions  
Vulvovaginitis  
(clinical exam) 
(Use in studies 
evaluating topical study 
agents)  
For other vulvovaginitis 
see Infection: Infection 
(any other than HIV 
infection) 
Minimal vaginal 
abnormalities on 
examination OR 
Epithelial disruption  
< 25% of total surface 
Moderate vaginal 
abnormalities on 
examination OR 
Epithelial disruption of 
25 - 49% total surface 
Severe vaginal 
abnormalities on 
examination OR Epithelial 
disruption  
50 - 75% total surface 
Vaginal perforation OR 
Epithelial disruption 
> 75% total surface 
OCULAR/VISUAL 
Uveitis 
Asymptomatic but 
detectable on exam 
Symptomatic anterior 
uveitis OR Medical 
intervention indicated 
Posterior or pan-uveitis 
OR Operative 
intervention indicated 
Disabling visual loss in 
affected eye(s)  
Visual changes (from 
baseline) 
Visual changes 
causing no or minimal 
interference with usual 
social & functional 
activities 
Visual changes causing 
greater than minimal 
interference with usual 
social & functional 
activities 
Visual changes causing 
inability to perform usual 
social & functional 
activities 
Disabling visual loss in 
affected eye(s) 
ENDOCRINE/METABOLIC 
Abnormal fat 
accumulation 
(e.g., back of neck, 
breasts, abdomen) 
Detectable by study 
participant (or by 
caregiver for young 
children and disabled 
adults) 
Detectable on physical 
exam by health care 
provider 
Disfiguring OR Obvious 
changes on casual visual 
inspection 
NA 
Diabetes mellitus 
NA 
New onset without need 
to initiate medication 
OR Modification of 
current medications to 
regain glucose control 
New onset with initiation 
of medication indicated 
OR Diabetes uncontrolled 
despite treatment 
modification 
Life-threatening 
consequences (e.g., 
ketoacidosis, 
hyperosmolar non-ketotic 
coma)  
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 65 of 70                                                                                   Version: January 30, 2014 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Gynecomastia 
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults) 
Detectable on physical 
exam by health care 
provider 
Disfiguring OR Obvious 
on casual visual 
inspection 
NA 
Hyperthyroidism  
Asymptomatic 
 
Symptomatic causing 
greater than minimal 
interference with usual 
social & functional 
activities OR Thyroid 
suppression therapy 
indicated 
Symptoms causing 
inability to perform usual 
social & functional 
activities OR Uncontrolled 
despite treatment 
modification  
Life-threatening 
consequences (e.g., 
thyroid storm) 
Children: Activities that are age and culturally appropriate (e.g., social interactions, play activities, learning tasks, etc.). 
Hypothyroidism 
Asymptomatic 
Symptomatic causing 
greater than minimal 
interference with usual 
social & functional 
activities OR Thyroid 
replacement therapy 
indicated 
Symptoms causing 
inability to perform usual 
social & functional 
activities OR 
Uncontrolled despite 
treatment modification  
Life-threatening 
consequences (e.g., 
myxedema coma) 
Lipoatrophy 
(e.g., fat loss from the 
face, extremities, 
buttocks) 
Detectable by study 
participant (or by 
caregiver for young 
children and disabled 
adults) 
Detectable on physical 
exam by health care 
provider 
Disfiguring OR Obvious 
on casual visual 
inspection 
NA 
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding. 
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally 
appropriate eating implement). 
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social 
interactions, play activities, learning tasks, etc.). 
 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 66 of 70                                                                                   Version: January 30, 2014 
 
 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
HEMATOLOGY 
Standard International Units are listed in italics 
Absolute CD4+ count  
– Adult and Pediatric  
> 13 years 
(HIV NEGATIVE ONLY) 
300 – 400/mm3 
300 – 400/µL 
200 –  299/mm3 
200 – 299/µL 
100 – 199/mm3 
100 – 199/µL 
< 100/mm3 
< 100/µL 
Absolute lymphocyte 
count  
– Adult and Pediatric  
> 13 years 
(HIV NEGATIVE ONLY) 
600 – 650/mm3 
0.600 x 109 – 
0.650 x 109/L 
500 – 599/mm3 
0.500 x 109 –  
0.599 x 109/L 
350 – 499/mm3 
0.350 x 109 –   
0.499 x 109/L 
< 350/mm3 
< 0.350 x 109/L 
Comment:  Values in children ≤ 13 years are not given for the two parameters above because the absolute counts are variable. 
Absolute neutrophil count (ANC)  
Adult and Pediatric,  
> 7 days 
1,000 – 1,300/mm3 
1.000 x 109 – 
1.300 x 109/L 
750 – 999/mm3 
0.750  x 109 –  
0.999 x 109/L 
500 – 749/mm3 
0.500  x 109 –  
0.749 x 109/L   
< 500/mm3 
< 0.500 x 109/L 
Infant∗†, 2 – ≤ 7 days 
1,250 – 1,500/mm3 
1.250  x 109 –  
1.500 x 109/L 
1,000 – 1,249/mm3 
1.000 x 109 –  
1.249 x 109/L 
750 – 999/mm3 
0.750  x 109 –  
0.999  x 109/L 
< 750/mm3 
< 0.750 x 109/L 
Infant∗†, ≤1 day 
4,000 – 5,000/mm3 
4.000 x 109 –  
5.000 x 109/L 
3,000 – 3,999/mm3 
3.000 x 109 –  
3.999 x109/L 
1,500 – 2,999/mm3 
1.500 x 109 –  
2.999 x 109/L 
< 1,500/mm3 
< 1.500 x 109/L 
Comment:  Parameter changed from “Infant, < 1 day” to “Infant, ≤1 day” 
Fibrinogen, decreased 
100 – 200 mg/dL 
1.00 – 2.00 g/L 
OR 
0.75 – 0.99 x LLN 
75 – 99 mg/dL 
0.75 – 0.99 g/L 
OR 
0.50 – 0.74 x LLN 
50 – 74 mg/dL 
0.50 – 0.74 g/L 
OR 
0.25 – 0.49 x LLN 
< 50 mg/dL  
< 0.50 g/L 
OR 
< 0.25 x LLN 
OR  
Associated with gross 
bleeding  
∗ Values are for term infants.  Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin). 
 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 67 of 70                                                                                   Version: January 30, 2014 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Hemoglobin (Hgb) 
Comment:  The Hgb values in mmol/L have changed because the conversion factor used to convert g/dL to mmol/L has been 
changed from 0.155 to 0.6206 (the most commonly used conversion factor).  For grading Hgb results obtained by an analytic 
method with a conversion factor other than 0.6206, the result must be converted to g/dL using the appropriate conversion factor 
for that lab. 
Adult and Pediatric 
≥ 57 days 
 
(HIV POSITIVE ONLY) 
8.5 – 10.0 g/dL 
5.24 – 6.23 mmol/L 
 
7.5 – 8.4 g/dL 
4.62–5.23 mmol/L 
 
6.50 – 7.4 g/dL 
4.03–4.61 mmol/L 
 
< 6.5 g/dL 
< 4.03 mmol/L 
 
Adult and Pediatric  
≥ 57 days  
(HIV NEGATIVE ONLY)  
10.0 – 10.9 g/dL 
6.18 – 6.79 mmol/L 
OR 
Any decrease  
2.5 – 3.4 g/dL 
1.58 – 2.13 mmol/L 
9.0 – 9.9 g/dL 
5.55 - 6.17 mmol/L 
OR 
Any decrease  
3.5 – 4.4 g/dL 
2.14 – 2.78 mmol/L 
7.0 – 8.9 g/dL 
4.34 - 5.54 mmol/L 
OR 
Any decrease  
≥ 4.5 g/dL 
> 2.79 mmol/L
< 7.0 g/dL 
< 4.34 mmol/L 
 
Comment:  The decrease is a decrease from baseline 
Infant∗†, 36 – 56 days 
(HIV POSITIVE OR 
NEGATIVE) 
8.5 – 9.4 g/dL 
5.24 – 5.86 mmol/L 
7.0 –  8.4 g/dL 
4.31 – 5.23 mmol/L 
6.0 – 6.9 g/dL 
3.72 – 4.30 mmol/L 
< 6.00 g/dL 
< 3.72 mmol/L 
Infant∗†, 22 – 35 days 
(HIV POSITIVE OR 
NEGATIVE) 
9.5 – 10.5 g/dL 
5.87 - 6.54 mmol/L 
8.0 – 9.4 g/dL 
4.93 – 5.86 mmol/L 
7.0 – 7.9 g/dL 
4.34 – 4.92 mmol/L 
< 7.00 g/dL 
< 4.34 mmol/L 
Infant∗†, ≤ 21 days 
(HIV POSITIVE OR 
NEGATIVE) 
12.0 – 13.0 g/dL 
7.42 – 8.09 mmol/L 
10.0 – 11.9 g/dL 
6.18 – 7.41 mmol/L 
9.0 – 9.9 g/dL 
5.59- 6.17 mmol/L 
< 9.0 g/dL 
< 5.59 mmol/L 
Correction:  Parameter changed from “Infant < 21 days” to “Infant ≤ 21 days” 
International Normalized 
Ratio of prothrombin time 
(INR) 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 3.0 x ULN 
> 3.0 x ULN 
Methemoglobin 
5.0 – 10.0% 
10.1 – 15.0% 
15.1 – 20.0% 
> 20.0% 
Prothrombin Time (PT) 
1.1 – 1.25 x ULN 
1.26 – 1.50 x ULN 
1.51 – 3.00 x ULN 
> 3.00 x ULN 
Partial Thromboplastin 
Time (PTT) 
1.1 – 1.66 x ULN 
1.67 – 2.33 x ULN 
2.34 – 3.00 x ULN 
> 3.00 x ULN 
Platelets, decreased 
100,000 –  
124,999/mm3 
100.000 x 109 – 
124.999 x 109/L 
50,000 –  
99,999/mm3 
50.000 x 109 – 
99.999 x 109/L 
25,000 –  
49,999/mm3 
25.000 x 109 – 
49.999 x 109/L 
< 25,000/mm3 
< 25.000 x 109/L 
WBC, decreased 
2,000 – 2,500/mm3 
2.000 x 109 –  
2.500 x 109/L 
1,500 – 1,999/mm3 
1.500 x 109 –  
1.999 x 109/L 
1,000 – 1,499/mm3 
1.000 x 109 –  
1.499 x 109/L 
< 1,000/mm3 
< 1.000 x 109/L 
∗ Values are for term infants.  Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin). 
 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 68 of 70                                                                                   Version: January 30, 2014 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
CHEMISTRIES 
 
Standard International Units are listed in italics  
Acidosis 
NA 
pH < normal, but ≥ 7.3 
pH < 7.3 without life-
threatening 
consequences 
pH < 7.3 with life-
threatening 
consequences 
Albumin, serum, low 
3.0 g/dL – < LLN 
30 g/L – < LLN 
2.0 – 2.9 g/dL 
20 – 29 g/L 
< 2.0 g/dL 
< 20 g/L 
NA 
Alkaline Phosphatase 
1.25 – 2.5 x ULN† 
2.6 – 5.0 x ULN† 
5.1 – 10.0 x ULN† 
> 10.0 x ULN† 
Alkalosis 
NA 
pH > normal, but ≤ 7.5 
pH > 7.5 without life-
threatening 
consequences 
pH > 7.5 with life-
threatening 
consequences  
ALT (SGPT) 
1.25 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10.0 x ULN 
> 10.0 x ULN 
AST (SGOT) 
1.25 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10.0 x ULN 
> 10.0 x ULN 
Bicarbonate, serum, low 
16.0 mEq/L – < LLN 
16.0 mmol/L – < LLN 
11.0 – 15.9 mEq/L 
11.0 – 15.9 mmol/L 
8.0 – 10.9 mEq/L 
8.0 – 10.9 mmol/L 
< 8.0 mEq/L 
< 8.0 mmol/L 
Comment:  Some laboratories will report this value as Bicarbonate (HCO3) and others as Total Carbon Dioxide (CO2).  These 
are the same tests; values should be graded according to the ranges for Bicarbonate as listed above. 
Bilirubin (Total) 
Adult and Pediatric > 
14 days 
1.1 – 1.5 x ULN 
1.6 – 2.5 x ULN 
2.6 – 5.0 x ULN 
> 5.0 x ULN 
Infant∗†, ≤ 14 days 
(non-hemolytic) 
NA 
20.0 – 25.0 mg/dL 
342 – 428 µmol/L 
25.1 – 30.0 mg/dL 
429 – 513 µmol/L 
> 30.0 mg/dL 
> 513.0 µmol/L 
Infant∗†, ≤ 14 days 
(hemolytic) 
NA 
NA 
20.0 – 25.0 mg/dL 
342 – 428 µmol/L 
> 25.0 mg/dL 
> 428 µmol/L 
Calcium, serum, high 
Adult and Pediatric  
≥ 7 days 
10.6  – 11.5 mg/dL 
2.65 – 2.88 mmol/L 
11.6  – 12.5 mg/dL 
2.89 – 3.13 mmol/L 
12.6  – 13.5 mg/dL 
3.14 – 3.38 mmol/L 
> 13.5 mg/dL 
> 3.38 mmol/L 
Infant∗†, < 7 days 
11.5 – 12.4 mg/dL 
2.88 – 3.10 mmol/L 
12.5 – 12.9 mg/dL 
3.11 – 3.23 mmol/L 
13.0 – 13.5 mg/dL 
3.245 – 3.38 mmol/L 
> 13.5 mg/dL 
> 3.38 mmol/L 
Calcium, serum, low  
Adult and Pediatric  
≥ 7 days  
7.8  – 8.4 mg/dL 
1.95 – 2.10 mmol/L 
7.0  – 7.7 mg/dL 
1.75 – 1.94 mmol/L 
6.1  – 6.9 mg/dL 
1.53 – 1.74 mmol/L 
< 6.1 mg/dL 
< 1.53 mmol/L 
Infant∗†, < 7 days 
6.5 – 7.5 mg/dL 
1.63 – 1.88 mmol/L 
6.0 – 6.4 mg/dL 
1.50 – 1.62 mmol/L 
5.50 – 5.90 mg/dL 
1.38 – 1.51 mmol/L 
< 5.50 mg/dL 
< 1.38 mmol/L 
Comment:  Do not adjust Calcium, serum, low or Calcium, serum, high for albumin 
∗ Values are for term infants.  Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 69 of 70                                                                                   Version: January 30, 2014 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Cardiac troponin I (cTnI) 
NA 
NA 
NA 
Levels consistent with 
myocardial infarction or 
unstable angina as 
defined by the 
manufacturer 
Adult ≥ 18 years 
200 – 239 mg/dL 
5.18 – 6.19 mmol/L 
240 – 300 mg/dL 
6.20 – 7.77 mmol/L 
> 300 mg/dL 
> 7.77 mmol/L 
NA 
Pediatric < 18 years 
170 – 199 mg/dL 
4.40 – 5.15 mmol/L 
200 – 300 mg/dL 
5.16 – 7.77 mmol/L 
> 300 mg/dL 
> 7.77 mmol/L 
NA 
Creatine Kinase 
3.0 – 5.9 x ULN† 
6.0 – 9.9 x ULN† 
10.0 – 19.9 x ULN† 
≥ 20.0 x ULN† 
Creatinine 
1.1 – 1.3 x ULN† 
1.4 – 1.8 x ULN† 
1.9 – 3.4 x ULN† 
≥ 3.5 x ULN† 
 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Glucose, serum, high  
Nonfasting 
116 – 160 mg/dL 
6.44 – 8.88 mmol/L 
161 – 250 mg/dL 
8.89 – 13.88 mmol/L 
251 – 500 mg/dL 
13.89 – 27.75 mmol/L 
> 500 mg/dL 
> 27.75 mmol/L 
     
Fasting 
110 – 125 mg/dL 
6.11 – 6.94 mmol/L 
126 – 250 mg/dL 
6.95 – 13.88 mmol/L 
251 – 500 mg/dL 
13.89 – 27.75 mmol/L 
> 500 mg/dL 
> 27.75 mmol/L 
Adult and Pediatric  
≥ 1 month 
55 – 64 mg/dL 
3.05 – 3.55 mmol/L 
40 – 54 mg/dL 
2.22 – 3.06 mmol/L 
30 – 39 mg/dL 
1.67 – 2.23 mmol/L 
< 30 mg/dL 
< 1.67 mmol/L 
Infant∗†, < 1 month 
50 – 54 mg/dL 
2.78 – 3.00 mmol/L 
40 – 49 mg/dL 
2.22 – 2.77 mmol/L 
30 – 39 mg/dL 
1.67 – 2.21 mmol/L 
< 30 mg/dL 
< 1.67 mmol/L 
Lactate 
ULN - < 2.0 x ULN 
without acidosis 
≥ 2.0 x ULN without 
acidosis 
Increased lactate with 
pH < 7.3 without life-
threatening 
consequences  
Increased lactate with 
pH < 7.3 with life-
threatening 
consequences  
Comment: Added ULN to Grade 1 parameter  
LDL cholesterol (fasting) 
Adult ≥ 18 years 
130 – 159 mg/dL 
3.37 – 4.12 mmol/L 
160 – 190 mg/dL 
4.13 – 4.90 mmol/L 
≥ 190 mg/dL 
≥ 4.91 mmol/L 
NA 
Pediatric > 2 - < 18 
years 
110 – 129 mg/dL  
2.85 – 3.34 mmol/L 
130 – 189 mg/dL 
3.35 – 4.90 mmol/L 
≥ 190 mg/dL 
≥ 4.91 mmol/L 
NA 
Lipase 
1.1 – 1.5 x ULN 
1.6 – 3.0 x ULN 
3.1 – 5.0 x ULN 
> 5.0 x ULN 
Magnesium, serum, low 
1.2  – 1.4 mEq/L 
0.60 – 0.70 mmol/L 
0.9 – 1.1 mEq/L 
0.45 – 0.59 mmol/L 
0.6 – 0.8 mEq/L 
0.30 – 0.44 mmol/L 
< 0.60 mEq/L 
< 0.30 mmol/L 
∗ Values are for term infants.  Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin). 
 

Sangamo BioSciences, Inc. 
Phase 1 Protocol SB-728-1101  
Confidential 
 
Page 70 of 70                                                                                   Version: January 30, 2014 
 
LABORATORY 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-THREATENING 
Pancreatic amylase 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 5.0 x ULN 
> 5.0 x ULN 
Phosphate, serum, low 
Adult and Pediatric  
> 14 years 
2.5 mg/dL – < LLN 
0.81 mmol/L – < LLN 
2.0 – 2.4 mg/dL 
0.65 – 0.80 mmol/L 
1.0 – 1.9 mg/dL 
0.32 – 0.64 mmol/L 
< 1.00 mg/dL 
< 0.32 mmol/L 
Pediatric 1 year – 14 
years  
3.0 – 3.5 mg/dL 
0.97 – 1.13 mmol/L 
2.5 – 2.9 mg/dL 
0.81 – 0.96 mmol/L 
1.5 – 2.4 mg/dL 
0.48 – 0.80 mmol/L 
< 1.50 mg/dL 
< 0.48 mmol/L 
Pediatric < 1 year 
3.5 – 4.5 mg/dL 
1.13 – 1.45 mmol/L 
2.5 – 3.4 mg/dL 
0.81 – 1.12 mmol/L 
1.5 – 2.4 mg/dL 
0.48 – 0.80 mmol/L 
< 1.50 mg/dL 
< 0.48 mmol/L 
Potassium, serum, high 
5.6 – 6.0 mEq/L 
5.6 – 6.0 mmol/L 
6.1 – 6.5 mEq/L 
6.1 – 6.5 mmol/L 
6.6 – 7.0 mEq/L 
6.6 – 7.0 mmol/L 
> 7.0 mEq/L 
> 7.0 mmol/L 
Potassium, serum, low 
3.0 – 3.4 mEq/L 
3.0 – 3.4 mmol/L 
2.5 – 2.9 mEq/L 
2.5 – 2.9 mmol/L 
2.0 – 2.4 mEq/L 
2.0 – 2.4 mmol/L 
< 2.0 mEq/L 
< 2.0 mmol/L 
Sodium, serum, high 
146 – 150 mEq/L 
146 – 150 mmol/L 
151 – 154 mEq/L 
151 – 154 mmol/L 
155 – 159 mEq/L 
155 – 159 mmol/L 
≥ 160 mEq/L 
≥ 160 mmol/L 
Sodium, serum, low 
130 – 135 mEq/L 
130 – 135 mmol/L 
125 – 129 mEq/L 
125 – 129 mmol/L 
121 – 124 mEq/L 
121 – 124 mmol/L 
≤ 120 mEq/L 
≤ 120 mmol/L 
Triglycerides (fasting) 
NA 
500 – 750 mg/dL 
5.65 – 8.48 mmol/L 
751 – 1,200 mg/dL 
8.49 – 13.56 mmol/L 
> 1,200 mg/dL 
> 13.56 mmol/L 
Uric acid 
7.5 – 10.0 mg/dL 
0.45 – 0.59 mmol/L 
10.1 – 12.0 mg/dL 
0.60 – 0.71 mmol/L 
12.1 – 15.0 mg/dL 
0.72 – 0.89 mmol/L 
> 15.0 mg/dL 
> 0.89 mmol/L 
URINALYSIS 
 
Standard International Units are listed in italics 
Hematuria (microscopic) 
 6 – 10 RBC/HPF 
> 10 RBC/HPF 
Gross, with or without 
clots OR with RBC 
casts 
Transfusion indicated 
Proteinuria, random 
collection 
1 + 
2 – 3 + 
4 + 
NA 
Proteinuria, 24 hour collection 
Adult and Pediatric  
≥ 10 years 
200 – 999 mg/24 h 
0.200 – 0.999 g/d 
1,000 – 1,999 mg/24 h
1.000 – 1.999 g/d 
2,000 – 3,500 mg/24 h 
2.000 – 3.500 g/d 
> 3,500 mg/24 h 
> 3.500 g/d 
Pediatric > 3 mo -  
< 10 years 
201 – 499 mg/m2/24 h
0.201 – 0.499 g/d 
500 – 799 mg/m2/24 h
0.500 – 0.799 g/d 
800 – 1,000  
mg/m2/24 h 
0.800 – 1.000 g/d 
> 1,000 mg/ m2/24 h 
> 1.000 g/d 
∗ Values are for term infants.  Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin).