Clinical trial NCT04406623
Conditions: Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma
Sponsor: Shattuck Labs, Inc.
Start date: 2020-06-29; Completion date: 2023-02-02
Enrollment: 27 participants; Allocation: NA; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.

Detailed description:
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an optional dose expansion cohort. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D.

Arms: arm 1: Intravenous administration
Interventions: intervention 1: SL-172154
Intervention descriptions: intervention 1: The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
1 
Protocol Title: Phase 1 Dose Escalation Study of the Agonist Redirected 
Checkpoint, SL-
-Fc-CD40L) Administered Intravenously in 
Subjects with Ovarian Cancer 
Short Title: Phase 1 Study of SL-172154 (SIRP -Fc-CD40L) in Subjects with Ovarian Cancer 
 
Protocol Identifying Number: SL03-OHD-101 
Version Number: v6.0  
Compound Number: SL-172154 
Study Phase: Phase 1   
Investigational New Drug (IND) Sponsor: Shattuck Labs 
Legal Registered Address: 
Shattuck Labs, Inc. 
21 Parmer Way, Suite, 200 
 
Durham, North Carolina 27709 
 
 
Regulatory Agency Identifier Number(s) 
IND: 142568 
EudraCT: 2020-000422-26 
NCT: 04406623 
Approval Date:  24 August 2021  
 
 
 
This document is the confidential property of Shattuck Labs. It contains proprietary information and 
is submitted to the clinical trial site for the sole purpose of reviewing and conduct of the named clinical 
trial. Reproduction, disclosure, or use of the submission or information contained therein in whole or 
part otherwise than for this purpose is prohibited unless Shattuck Labs provides prior written 
authorization for such reproduction, disclosure or use. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
2 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_00 
24 January 2020 
Original 
SL03-OHD-01_01 
03 March 2020 
Amendment No. 1 
Rationale for Amendment Changes 
The protocol is amended to address corrections to instructions and information provided on the 
drug product in Section 5. 
Summary of Changes (new text denoted in italics font) 
1. Investigational Product Description Section 5.1.1 was updated as follows: 
Unit Dose strength(s)/Dose Level(s): SL-172154 10 mg/mL; 1 mL in a 5 mL sized glass vial (Refer 
to Section 3.3 for dose levels) 
Physical Description: SL-172154 10 mg/mL for infusion is 10 mg of SL172154 per single dose vial 
at a concentration of 10 mg/mL in a 5mL glass vial closed with a in a 5 mL glass vial closed with a 
FluroTec® rubber stopper and sealed with a flip-off aluminium seal. See the Study Pharmacy Manual 
(SPM) for additional detail. 
Route/Administration/Duration: Delivered as IV solution via a syringe pump or IV infusion pump. 
See the Study Pharmacy Manual (SPM) for additional details. Duration of infusion depends on the 
dose. See Table 1: SL-172154 Dose Escalation Plan in Section 3.3 of the protocol. 
2. In Section 5.1.2.1: 
a)  Removed text: DO NOT USE a filter for drug preparation. Instructions for preparation of doses 
will be included in the Study Pharmacy Manual.  
b) The dosing solution of SL-172154 can be held up to 24 hours under refrigerated conditions or 8 
hours at room temperature (diluted drug product in bag or syringe) from a stability perspective; 
but should be used as soon as possible as the product does not contain an antimicrobial 
preservative. Preparation (e.g., dilution) and administration of study drug may occur at room 
temperature without protection from light. See the SPM for details. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
3 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_01 
03 March 2020 
Amendment No. 1 
SL03-OHD-01_02 
24 April 2020
Amendment No. 2 
Rationale for Amendment Changes 
The protocol is amended to address comments by the United States FDA during review of the 
IND for SL-172154. 
Summary of Changes (Details outlined in Appendix 16.6) 
1. Homologous recombinant deficiency (HRD) status will be collected for all subjects including 
BRCA status 
2. Inclusion criteria revised to allow enrollment of subjects who fulfill the definitions below: 
a)  all subjects with primary ovarian, peritoneal and fallopian cancers are required to have 
received platinum-based therapies.b)   HRD positive subjects if they have failed prior PARP 
inhibitor therapy given with or without bevacizumab and,  
c)  refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their 
condition. 
3. Treatment beyond progression per iRECIST requires that subjects have no decline in their ECOG 
performance status. 
4. The DLT assessment period for assessment of AEs that inform dose escalation decisions is 28 
days (not 21 days as originally proposed). 
5. Provided further clarification of the intent to monitor subjects for adverse events for 90 days 
after SL-172154 treatment is permanently discontinued. 
6. Revised the DLT criteria to include any deaths that are not clearly due to the underlying disease 
or extraneous causes. 
7. Clarified that subjects eligible for dose escalation must have tolerated SL-172154 therapy well 
and experienced AEs < or = Grade 1 in severity on the most recent cycle of study treatment. 
8. Clarified that all AEs that occur in subjects enrolled in this study will be collected starting from 
the time subject consents to participate until they are discontinued from the study. 
9. Minor Editorial changes 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
4 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_02 
24 April 2020 
Amendment No. 2 
SL03-OHD-01_03 
05 May 2020 
Amendment No. 3 
Rationale for Amendment Changes 
Additional test results now indicate that SL-172154 binds to red cells and may obscure the 
assessment of ABO red blood cell phenotyping. The protocol is amended to address the 
possibility that treatment with SL-172154 may interfere with compatibility tests including the 
antibody screen and crossmatch that are a part of a routine pre-transfusion work up should 
subjects on this study require a blood transfusion for supportive care.  
This amendment also addresses a comment provided by the FDA during review of the IND 
application for SL-172154 on allowable storage condition limits for diluted drug product at room 
temperature and under refrigerated conditions.   
In addition, assessment of C reactive protein will now be collected at baseline during the 
screening and post treatment follow up visits. Minor editorial changes were also made to the 
text. 
The Summary of Changes are outlined in Appendix 16.7    


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
5 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_03 
05 May 2020 
Amendment No. 3 
SL03-OHD-01_04 
28 September 2020 
Amendment No. 4 
Rationale for Changes in Amendment 04 
The protocol is amended to include exploration of a once weekly dosing schedule of SL-172154 
in dose escalation to determine a recommended phase 2 dose for further study. Minor editorial 
changes and clarifications (e.g., NCT number added to the title page) are also included. 
The Summary of Changes are outlined in Appendix 16.8
Administrative Changes (7 October 2020) 
1. Corrected typographical errors replacing SL-279252 with SL-172154 as noted 
a. Evaluation of an Alternative Dosing Schedule Section 3.3 (5th sentence) including 
Summary of Changes in Appendix 16.8 denoting new text in Section 3.3: During dosing on 
Schedule 2, SL 279252 SL-172154 will be administered once weekly (D1, D8, D15, and 
D22) every 28 days. 
b. Schedule of Assessments Table Section 6.2: SL 279252 SL-172154 administrationo
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
6 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_04 
28 September 2020 
Amendment No. 4 
SL03-OHD-01_05 
12 July 2021 
Amendment No. 5 
Rationale for Changes in Amendment 05 
The protocol is amended to include infusion pre-medication instructions (Section 5), and 
additions of a C1D8 pre-dose PK/ADA sample and C1D3 immunophenotyping, receptor 
occupancy and cytokine sample. Minor editorial and clarifying changes were made as well. 
 
 
The Summary of Changes are outlined in Appendix 16.9 
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
7 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_05 
12 July 2021 
Amendment No. 5 
SL03-OHD-01_06 
24 August 2021 
Amendment No. 6 
Rationale for Changes in Amendment 06 
The protocol is amended to revise the eligibility criteria required for study participation. The 
investigational product information in Section 5.1 has been updated to reflect the current 
program level description of SL-172154 (additional details are provided in the Study Pharmacy 
Manual). In addition, a minor editorial change was made to the Schedule of Assessments Table 
for Schedule 1 (Section 6.1) to include weight on C1D1 to reflect this assessment described in 
Section 5.1.4. 
 
The Summary of Changes are outlined in Appendix 16.10


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
8 
TABLE OF CONTENTS
TABLE OF CONTENTS..................................................................................................................................... 8
LIST OF TABLES............................................................................................................................................13
LIST OF FIGURES..........................................................................................................................................13
LIST OF ABBREVIATIONS .............................................................................................................................14
STATEMENT OF COMPLIANCE ....................................................................................................................18
KEY TRIAL CONTACTS..................................................................................................................................19
STUDY SCHEMA...........................................................................................................................................20
PROTOCOL SYNOPSIS..................................................................................................................................21
1.
INTRODUCTION, BACKGROUND AND STUDY RATIONALE..................................................................31
1.1
Background Information.............................................................................................................31
1.2
Investigational Product, SL-172154 ............................................................................................32
1.2.1
Mechanism of Action..........................................................................................................32
1.2.2
In Vitro Pharmacology.........................................................................................................34
1.2.3
In Vivo Pharmacology..........................................................................................................34
SL-172154 anti-tumor activity with anti-CTLA-4, anti-PD-1 or ADCC-competent 
antibodies .......................................................................................................................................34
1.2.4
Toxicology and Toxicokinetics.............................................................................................35
1.3
Rationale for Investigation of SL-172154....................................................................................37
1.4
Potential Risks and Benefits of SL-172154..................................................................................38
1.4.1
Potential Risks.....................................................................................................................38
1.4.2
Potential Benefits................................................................................................................40
2.
STUDY OBJECTIVES AND OUTCOME MEASURES ................................................................................42
3.
STUDY DESIGN.....................................................................................................................................44
3.1
Description of Study Design........................................................................................................44
3.1.1
Selection of the Recommended Phase 2 dose....................................................................45
3.1.2
Sample Size .........................................................................................................................46
3.2
Justification for Starting Dose and Schedule of SL-172154 ........................................................46
3.2.1
Criteria for Decision to Transition from Schedule 1 to Schedule 2.....................................47
3.3
SL-172154 Dose Escalation Plan..................................................................................................48
3.3.1
Intrasubject Dose Escalation...............................................................................................49
3.4
Definition of Dose-Limiting Toxicity............................................................................................50
3.5
Concomitant Medications, Treatments, and Procedures...........................................................51
3.5.1
Prohibited Medications/Treatments ..................................................................................51


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
9 
3.5.2
Medications to be used with Caution.................................................................................51
3.6
Toxicity Management Guidelines Dosing Delays/Dose Modifications .......................................52
3.6.1
Management of Infusion-related Reactions.......................................................................53
Infusion or Hypersensitivity Reactions ...........................................................................................53
Cytokine-release Syndrome............................................................................................................54
3.6.2
Management of Immune-related Reactions.......................................................................56
irAEs - General................................................................................................................................. 56
Hepatotoxicity................................................................................................................................. 57
Anemia............................................................................................................................................58
Thrombocytopenia..........................................................................................................................58
3.6.3
Management of Other AEs Not Specified...........................................................................59
3.7
Discontinuation of Study Therapy ..............................................................................................60
3.8
Antibody Detection and Compatibility Testing for Transfusion .................................................60
3.9
Criteria to Resume Treatment ....................................................................................................61
3.10
Participant Withdrawal of Consent.............................................................................................61
3.11
Lost to Follow-up ........................................................................................................................61
3.12
Premature Termination or Suspension of Study ........................................................................62
3.13
Duration of Treatment................................................................................................................62
3.14
Duration of Follow-Up ................................................................................................................63
3.15
End of Study Definition...............................................................................................................63
4.
STUDY POPULATION ...........................................................................................................................63
4.1
Participant Inclusion Criteria.......................................................................................................63
4.2
Participant Exclusion Criteria......................................................................................................65
4.3
Screen Failures............................................................................................................................66
4.4
Accrual Goal ................................................................................................................................67
5.
PHARMACEUTICAL PRODUCT INFORMATION ....................................................................................67
5.1
Investigational Product (SL-172154)...........................................................................................67
5.1.1
Investigational Product Description....................................................................................67
5.1.2
Preparation/Handling/Administration/Storage of SL-172154/Investigational Product.....68
Preparation .....................................................................................................................68
Handling ..........................................................................................................................68
Administration ................................................................................................................68
Storage............................................................................................................................68


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
10
5.1.3
Investigational Product Accountability...............................................................................69
5.1.4
Dosing and Change in Weight.............................................................................................69
5.1.5
Monitoring Dose Administration ........................................................................................69
5.1.6
Treatment of Investigational Product Overdose ................................................................69
5.2
Drug Accountability and Treatment Compliance........................................................................70
6.
STUDY ASSESSMENTS AND PROCEDURES...........................................................................................70
6.1
SOA Table: Schedule 1 Dose Escalation, Dose Expansion and Pharmacodynamic Cohorts .......72
6.1.1
Supplementary Tables for SL-172154 Phase 1 Cohorts......................................................76
6.1.2
Correlative Sample Time points for SL-172154...................................................................78
6.2
SOA Table: Schedule 2 Dose Escalation, Dose Expansion and Pharmacodynamic Cohorts .......79
6.3
Demographics, Medical History, Screening and Safety Assessments.........................................83
6.3.1
Informed Consent ...............................................................................................................83
6.3.2
Eligibility Criteria.................................................................................................................83
6.3.3
Subject Demographics ........................................................................................................83
6.3.4
Medical History...................................................................................................................83
6.3.5
Concomitant Medications...................................................................................................83
6.4
Safety Evaluations.......................................................................................................................83
6.4.1
Physical Examination...........................................................................................................83
6.4.2
ECOG Performance Status ..................................................................................................83
6.4.3
Pulse Oximetry....................................................................................................................83
6.4.4
Vital Signs............................................................................................................................84
6.4.5
Cardiac Assessments...........................................................................................................84
Electrocardiograms.........................................................................................................84
Echocardiogram ..............................................................................................................84
6.4.6
Laboratory Assessments .....................................................................................................84
Ad Hoc Labs for IRR or CRS AEs.......................................................................................85
Pregnancy Testing...........................................................................................................85
Blood Type and Screen (ABO/Rh) and DAT.....................................................................86
6.5
Pharmacokinetics........................................................................................................................86
6.5.1
Intensive PK Sampling.........................................................................................................86
6.6
Anti-drug Antibody Assessments................................................................................................86
6.7
Pharmacodynamic/Biomarker Assessments ..............................................................................86
6.7.1
Pharmacodynamic Assessments in Blood...........................................................................87


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
11
Cytokine and Chemokine Analysis ..................................................................................87
Receptor Occupancy .......................................................................................................87
SL-172154 Binding to Red Blood Cells ............................................................................87
Immunophenotyping ......................................................................................................87
6.7.2
Pharmacodynamic Assessment of Tumor Tissue................................................................87
Fresh Tumor Biopsies......................................................................................................87
Archival Tumor................................................................................................................88
6.8
Assessment of Anti-tumor Activity .............................................................................................89
6.9
Unscheduled Visit .......................................................................................................................89
7.
SAFETY ASSESSMENTS ........................................................................................................................89
7.1
Definitions for Safety Parameters...............................................................................................89
7.1.1
Events not Qualifying as AEs/SAEs......................................................................................91
7.2
Classification of an Adverse Event..............................................................................................91
7.2.1
Assessment of Severity .......................................................................................................91
7.2.2
Assessment of Causality......................................................................................................92
7.2.3
Expectedness ......................................................................................................................92
7.3
Timing for Event Assessment and Follow-up..............................................................................93
7.4
Procedures for Recording and Reporting of Adverse Events......................................................93
7.5
Reporting of Pregnancy...............................................................................................................94
7.6
Reporting of Overdose................................................................................................................94
7.7
Study Halting Rules .....................................................................................................................94
7.8
Safety Oversight..........................................................................................................................95
8.
ANTI-TUMOR ACTIVITY ASSESSMENTS...............................................................................................95
8.1
Disease Assessment....................................................................................................................95
8.1.1
Assessment of Response.....................................................................................................96
8.2
Criteria for Treatment Beyond Initial Progression......................................................................96
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS........................................................................96
9.1
Study Design and Sample Size Determinations ..........................................................................96
9.2
Statistical Analyses......................................................................................................................98
9.2.1
Analysis Populations ...........................................................................................................98
9.2.2
Interim Analyses..................................................................................................................98
9.2.3
General Data Analysis Consideration..................................................................................99
9.2.4
Safety Analyses ...................................................................................................................99


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
12
9.2.5
Efficacy Analyses...............................................................................................................100
9.2.6
Pharmacokinetic Analysis ................................................................................................. 100
Anti-Drug Antibody Analysis .........................................................................................101
9.2.7
Pharmacodynamics Analyses............................................................................................101
10. CLINICAL MONITORING.....................................................................................................................101
11. SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA AND DOCUMENTS .....................................101
11.1
Source Data...............................................................................................................................101
11.2
Access to Data...........................................................................................................................101
11.3
Data Recording and Record Keeping ........................................................................................102
12. QUALITY ASSURANCE PROCEDURES................................................................................................. 102
13. ETHICS/PROTECTION OF HUMAN SUBJECTS ....................................................................................102
13.1
Ethical Standard........................................................................................................................102
13.2
Institutional Review Board/Institutional Ethics Committee.....................................................102
13.3
Informed Consent Process........................................................................................................102
13.3.1
Consent/Assent and Other Informational Documents Provided to Subjects...................102
13.3.2
Consent Procedures and Documentation.........................................................................103
13.4
Participant and Data Confidentiality.........................................................................................103
13.4.1
Research Use of Stored Human Samples, Specimens, or Specimen Data........................104
13.5
Future Use of Stored Specimens...............................................................................................104
14. DATA HANDLING AND RECORD KEEPING .........................................................................................104
14.1
Communication and Data Dissemination Plan .........................................................................104
14.2
Data Collection and Management Responsibilities..................................................................105
14.3
Study Records Retention...........................................................................................................105
14.4
Protocol Deviations...................................................................................................................106
14.5
Publications and Data Sharing Policy........................................................................................106
15. LITERATURE REFERENCES .................................................................................................................107
16. APPENDICES ......................................................................................................................................110
16.1
mTPI-2 Dose Escalation Scenarios ............................................................................................110
16.2
ECOG Performance Status Criteria............................................................................................112
16.3
Contraception Requirements....................................................................................................113
16.3.1
Pregnancy Status...............................................................................................................114
16.4
Cockcroft-Gault Formula for Creatinine Clearance...................................................................115
16.5
RECIST v1.1 and iRECIST Criteria...............................................................................................116


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
13 
 
16.5.1 
RECIST v1.1 Criteria ........................................................................................................... 116 
16.5.2 
Evaluation of Response ..................................................................................................... 117 
16.5.3 
iRECIST v1.1 Criteria .......................................................................................................... 117 
16.6 
Summary of Changes for Protocol Amendment 02 .................................................................. 121 
16.7 
Summary of Changes for Protocol Amendment 03 .................................................................. 125 
16.8 
Summary of Changes for Protocol Amendment 04 .................................................................. 128 
16.9 
Summary of Changes for Protocol Amendment 05 .................................................................. 135 
16.10 
Summary of Changes for Protocol Amendment 06 .............................................................. 139 
LIST OF TABLES 
Table 1: SL-172154 Dose Escalation Plan in Phase 1 ................................................................................ 49 
Table 2: Phase 1 Serial PK, ADA, Cytokines and RBC Binding (C1/D1 - 48 hrs postdose) ..................... 76 
Table 3: Predose PK, ADA Sample (C1/D8) .............................................................................................. 77 
Table 4: Phase 1 Serial PK, ADA, Cytokines and RBC Binding (C1D15/D16, C2D1/D2, and 
C2D15/D16) ................................................................................................................................................ 77 
Table 5: Phase 1 Serial PK, ADA, Cytokines (C3/D1 and Beyond) .......................................................... 78 
Table 6: Complement, Immunophenotyping, Receptor Occupancy Time Points ....................................... 78 
Table 7. Dose Escalation Decision Rules for Each Dose Level based on mTPI-2 ..................................... 97 
Table 8: Serum SL-172154 PK Parameters .............................................................................................. 100 
LIST OF FIGURES 
Figure 1: Mechanism of Action of SL-172154 Alone or Combined with an ADCC-competent mAb ...... 33 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
14 
 
LIST OF ABBREVIATIONS
Ab 
Antibody
ADA
Anti-drug antibodies 
ADCC
Antibody dependent cell-mediated cytotoxicity
ADCP 
Antibody dependent cellular phagocytosis 
ADL
Activities of daily living 
AE 
Adverse event 
AIMV 
Alstroemeria-Mosaic Virus
ALT
Alanine aminotransferase
AML 
Acute myeloid leukemia 
APTT 
Activated partial thromboplastin time
APC
Antigen presenting cell
AR 
Adverse reaction
ARC
Agonist redirected checkpoint
AST
Aspartate aminotransferase
AUC
Area under the serum concentration time curve 
AUC0-last
Area under the serum concentration time curve, time 0 to the last quantifiable 
concentration 
AUC0-inf
Area under the serum concentration time curve from time 0 extrapolated to infinity 
AUC0-t 
Area under the serum concentration time curve, time 0 to time = t
%AUCext
Percentage of AUC0-inf due to extrapolation from Tlast to infinity 
AUCtau 
The area under the serum concentration time curve, over the dosing interval
-hCG 
Beta- human chorionic gonadotropin 
BP 
Blood pressure
BRCA 
Breast cancer gene
°C 
Degrees Celsius 
CBC
Complete blood count
CBR
Clinical benefit rate 
CD 
Cluster of differentiation
CD40L 
Cluster of differentiation 40 ligand 
C1D1 
Cycle 1, day 1
CFR 
Code of Federal Regulations 
cGAS
Cyclic guanine monophosphate-adenosine monophosphate synthase 
CL
Clearance 
Cm  
Centimeters
Cmax 
Maximum observed concentration 
Cmin 
Minimum observed concentration
CMP
Clinical monitoring plan 
CO2
Bicarbonate
CR 
Complete response 
CrCl
Creatinine clearance
CRF 
Case report form
CRS 
Cytokine release syndrome
CT
Computed tomography
CTCAE
Common terminology criteria for adverse event
CTLA-4
Cytotoxic T cell lymphocyte-associated antigen 4 
CXCL 
Chemokine ligand
CYP450
Cytochrome P450
DAT
Direct antiglobulin test 
DC 
Dendritic cells 
DLT(s) 
Dose-limiting toxicity(ies) 
DOR
Duration of response 
DRF
Dose-range-finding


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
15 
 
EC
Effective concentration
ECD
Extracellular domain
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic Case Report Form
EOI
End of infusion
FCBP
Female of childbearing potential
FDA
Food and Drug Administration
FFPE
Formalin-fixed paraffin-embedded
FIH
First in human
FP
Fusion protein
FSH
Follicle stimulating hormone
GCP
Good Clinical Practice
GITR
Glucocorticoid-induced tumor necrosis factor receptor
GLP
Good Laboratory Practice
H1/H2
Histamine 1/ Histamine 2
HBsAg 
Hepatitis B surface antigen 
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HED
Human equivalent dose 
Hgb 
Hemoglobin 
HNSTD 
Highest non-severely toxic dose
hr (time) 
Hour(s)
HR 
Heart rate
HRD
Homologous recombination deficiency 
HSR(s) 
Hypersensitivity reaction(s)
Hu5F9-G4 
5F9 (i.e., anti-CD47 monoclonal antibody)
IB 
Investigator brochure
ICF 
Informed consent
ICH 
International Conference of Harmonisation 
iCPD 
Immune confirmed progression of disease
iCR
Immune complete response
IEC
Institutional Ethics Committee 
Interferon gamma
Ig 
Immunoglobulin
IHC 
Immunohistochemistry
IL
Interleukin 
IND
Investigational new drug
INR 
International normalized ratio
IP 
Investigational product
iPR 
Immune partial response 
irAE
Immune-related adverse event
IRB 
Institutional Review Board
iRECIST 
Immune response evaluation criteria in solid tumors 
IRR(s) 
Infusion-related reaction(s)
irSAE 
Immune-related serious adverse event
iSD 
Immune stable disease
iUPD
Immune unconfirmed progression of disease 
IV (i.v.)
Intravenous
Kd 
Receptor off-rate constant
Kg 
Kilogram 
LDH
Lactate dehydrogenase


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
16 
 
LLN
Lower limit of normal
LVEF
Left ventricular ejection fraction
m2
Square meter
mAb(s)
Monoclonal antibody(ies)
MABEL
Minimum anticipated biological effect level
MAD
Maximum administered dose 
MDS
Myelodysplastic syndrome
mg
Milligrams
mg/dL
Milligrams per deciliter
mg/kg
Milligrams per kilogram
Min
Minutes
mL
milliliter
mm
millimeter
MMF
Mycophenolate mofetil
Mmol
Millimole
MRI
Magnetic resonance imaging 
MTD
Maximum tolerated dose 
mTPI-2
Modified toxicity probability interval 2
NCI 
National Cancer Institute
NHP
Non-human primate
NF-kB
Nuclear factor kappa B 
Ng 
Nanogram
NK
Natural killer 
NL(s) 
New lesion(s)
NLNT 
New lesions non-target
NLT
New lesions target
nM 
Nanomolar
NOAEL
No observed adverse effect level 
ORR
Objective response rate
PARP 
Polyadenosine diphosphate polymerase  
PBMC
Peripheral blood mononuclear cells
PCR 
Polymerase chain reaction
PD
Progressive Disease 
PD-1
Programmed cell death protein 1 
PD-L1 / PD-L2
Programmed cell death ligand 1 / Programmed cell death ligand 2 
PK
Pharmacokinetic
PK/PD 
Pharmacokinetic/pharmacodynamic 
pM 
Picomolar
PR 
Partial response 
PSPD 
Pseudo-progression of disease
PT 
Prothrombin time
QTc
Corrected QT interval 
RBC
Red blood cell 
RECIST
Response evaluation criteria in solid tumors
RNA
Ribonucleic acid
RP2D
Recommended phase 2 dose
RR 
Respiratory rate
SAE
Serious Adverse Event
SAP
Statistical analysis plan
scFv
Single-chain variable fragment
SD
Stable disease 
SL-172154 
-Fc-CD40L agonist redirected checkpoint 
SLM
Study Lab Manual


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
17 
 
SMC
Safety Monitoring Committee
SOA
Schedule of Assessments
SOI
Start of infusion
SOM
Sum of measurements
SPM
Study Pharmacy Manual
STING
Stimulator of interferon genes
SUSAR
Suspected, unexpected serious adverse reaction
T
Temperature
T4
Thyroxine 4
t½
terminal elimination half-life
Signal regulatory protein alpha
TK
Toxicokinetic 
Tlast
Time of last observed quantifiable concentration
TLS
Tumor lysis syndrome
Tmax
Time of maximum observed concentration
TMDD
Target-mediated drug disposition
TME
Tumor microenvironment
TNF-
Tumor necrosis factor alpha 
TRAF 
TNF receptor associated factor 
TSH
Thyroid stimulating hormone 
TXT
Treatment 
µg
Microgram
ULN
Upper limit of normal
UP
Unanticipated problems
Vz 
Volume of distribution
WBC
White blood cell 
Wk
Week
 
Terminal elimination rate constant 
~
Approximately 
º
Degree 
Trademark Information 
Trademarks of Shattuck Labs, Inc.
Trademarks not owned by Shattuck Labs, Inc.
Agonist Redirected Checkpoint (ARC™) FluroTec®


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
18 
 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the protocol and the International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, and applicable Federal 
Regulations on the Protection of Human Subjects, and consistent with the consensus ethical 
principles derived from international guidelines including the Declaration of Helsinki and Council 
for International Organizations of Medical Sciences International Ethical Guidelines. The 
Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the Sponsor and documented approval from the Institutional Review 
Board (IRB)/Institutional Ethics Committee (IEC), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
have completed Human Subjects Protection Training. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.
Principal Investigator:
 
 
________________________________       ___________________________________ 
Print/Type Name 
 
 
 
Signature 
 
Date: ______________ 
 
 
 




CONFIDENTIAL 
 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
20
 
STUDY SCHEMA
 
 
Abbreviations: D = day; DLT = dose limiting toxicity; IV = intravenous; mTPI-2 = modified toxicity probability interval-2;   
 PD = pharmacodynamic; PK = pharmacokinetics; q2wks = once every 2 weeks; RP2D = recommended phase 2 dose 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
21 
 
PROTOCOL SYNOPSIS
Sponsor
Shattuck Labs
Product Name
SL-172154
Other Names
-Fc-CD40L recombinant fusion glycoprotein
Protocol Title
Phase 1 Dose Escalation Study of the Agonist Redirected 
Checkpoint, SL-
-Fc-CD40L) 
Administered Intravenously in Subjects with Ovarian 
Cancer
Protocol Number
SL03-DEL-101 
Clinical Phase
Phase 1 
Planned Sample Size
Approximately 33-54 subjects
Planned Number of Sites & Countries
Approximately 6-10 clinical sites;
United States  
Recruitment Duration 
25 months (~2 years) 
Study Duration
39 months (~ 3 years)
Background and Rationale 
The investigational product, SL-172154, 
-Fc-CD40L) linked via a human Fc. Fusion of the extracellular domains 
membrane protein, with CD40L, a type 2 membrane protein, generated a single molecule with dual 
specificity that retained individual target avidity. The mechanism of action of SL-172154 is designed to pair 
the increased phagocytic activity of macrophages through CD47-
 with the costimulatory role 
of CD40L in augmenting the antigen cross-presenting ability of dendritic cells. In vitro, SL-172154 was 
shown to bind to its cognate targets, CD47 and CD40, both individually and simultaneously. High binding 
affinity for CD47 and CD40 was noted as well as a slow off-rate (KD values of 0.628 nM and 4.74 nM, 
respectively), indicating a longer on-target resident time. This longer resident time could be of benefit in the 
tumor microenvironment (TME) where CD47 is known to be expressed. CD40-mediated activity by 
SL-172154 was demonstrated in a NFkB reporter system in which CD40-dependent signaling was 
stimulated in the absence of Fc receptor cross-linking, and in cultured human peripheral blood mononuclear 
cells (PBMCs) in which dose-dependent proliferation, an increase in the number of interleukin (IL)-2 
secreting PBMCs, and the secretion of multiple cytokines were observed. 
The anti-
-Fc-CD40L was studied in established syngeneic CT26 colorectal murine 
tumor models. The performance of intraperitoneal adminis
-Fc-CD40L was compared to 
treatment with CD47 blocking antibodies, CD40 agonist antibodies, the combination of the two antibodies 
-Fc-CD40L led to 
higher rates of primary tumor rejection (63%) than either antibody given as monotherapy (anti-CD40, 0% 
and anti-CD47, 0%), or the antibody combination treatment group (33%). To assess the durability of an 
immune response without re-treatment, mice that rejected the initial tumor were re-challenged with a second 
CT26 tumor on the opposite flank on day 40. Of the 2 mice initially cured with the antibody combination, 
-Fc-CD40L group, 3 of 5 (60%) mice rejected the tumor 
re-challenge suggesting that a memory response was generated against the tumor, which led to protection 
against a subsequent tumor challenge.  This memory response correlated with a robust increase in AH1 
tetramer +/CD8+ cells in the spleen and the tumor for both the anti-CD40/CD47 combination and the 
-Fc-CD40L treated mice in comparison to vehicle controls. The preclinical data package 
demonstrates that SL-172154 selectively and specifically binds to its intended targets, CD47 and CD40, 
with high affinity. Furthermore, both targets exhibit functional activity in a variety of in vitro assays and 
anti-tumor models. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
22 
 
Background and Rationale (continued)
In the non-human primate (NHP) studies, dose dependent infusion-related toxicity was observed with repeat 
dosing. The infusion-related reactions (IRRs) are believed to be the result of exacerbated pharmacology of 
SL-172154 in the presence of anti-drug antibodies (ADA). SL-172154 is a pharmacologically active 
molecule: a dose dependent postdose decrease in lymphocyte counts and an increase in a number of serum 
cytokines was observed; with cytokine elevations tending to increase with repeated dosing. The emergence 
of ADA in all animals by Day 15 was expected given that SL-172154 is based on human amino acid 
sequences which have 82% identity to the corresponding cynomolgus sequences. The activation of 
complement was coincident with the emergence of ADA. Overall, the nonclinical safety studies support the 
administration of SL-172154 as an intravenous (IV) infusion in the proposed first-in-human (FIH) clinical 
study SL03-OHD-101.  
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic 
effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future 
development. Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian 
tube, and primary peritoneal cancers. Ovarian and related cancers were selected for investigation in this 
Phase 1 study of SL-172154 due to the fact that a high percentage of tumors have detectable CD47 
expression [Wang, 2015; Brightwell, 2016]. Furthermore, CD47 is a tumor associated antigen in ovarian 
cancer with high levels of expression in epithelial ovarian cancer cells compared with normal ovarian cells 
[Li, 2017]. Finally, tumor-associated macrophages constitute over 50% of cells within the peritoneal TME 
and malignant ascites and are potential targets for therapy [Gupta, 2018]. Given that the antigen-presenting 
cell is hypothesized to be the primary target of SL-172154, the unique immune contexture of ovarian cancers 
makes this histology particularly suitable for investigation. 
Study Objectives 
Primary Objective(s)
Outcome Measures 
To evaluate the safety and tolerability of SL-
172154 and to identify the maximum tolerated 
dose (MTD) or maximum administered dose 
(MAD) of SL-172154 in subjects with 
platinum-ineligible ovarian, fallopian tube, 
and primary peritoneal cancers  
Safety/tolerability outcomes include: incidence of all 
adverse events (AEs) and immune-related adverse 
events (irAE), serious adverse events (SAEs), fatal 
SAEs, dose limiting toxicity (DLT), AEs and irAEs 
leading to discontinuation, and changes in safety 
assessments (e.g., laboratory para-meters, vital signs 
etc.) 
per 
National 
Cancer 
Institute 
Common 
Terminology Criteria for Adverse Events (NCI-CTCAE 
– version 5.0).  
The MTD is defined based on the rate of DLTs and the 
MAD is the highest dose administered 
Secondary Objectives 
Outcome Measures 
To select the recommended Phase 2 dose 
(RP2D) for SL-172154. 
Based on review of all data collected during dose 
escalation, dose expansion, and pharmacodynamic 
cohorts including safety, tolerability, pharmacokinetics 
(PK), anti-tumor activity, and pharmacodynamic effects 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
23 
 
Secondary Objectives 
Outcome Measures 
To assess preliminary evidence of anti-tumor 
activity of SL-172154 
Disease assessment per investigator assessment 
according to Response Evaluation Criteria in Solid 
Tumors version 1.1 (RECIST v1.1). 
 Objective response rate (ORR) (proportion of 
subjects whose best response is a complete response 
[CR] or partial response [PR]) 
 Clinical benefit rate (CBR): proportion of subjects 
whose best overall response is a CR, PR or stable 
 
 Time to response (TTR): time from the first dose until 
the first response (CR or PR, whichever is recorded 
first) that is subsequently confirmed  
 Duration of response (DOR): time between first 
response (CR or PR, whichever is recorded first) that 
is subsequently confirmed and date of disease 
progression 
To evaluate immunogenicity to SL-172154 
during and after treatment. 
Number/proportion of subjects with positive anti-
drug antibody (ADA) titer 
 ADA duration  
Transient vs. persistent ADA 
To characterize the PK of SL-172154. 
Maximum observed concentration (Cmax) and time 
at which the maximum concentration is observed 
(Tmax) and minimum observed concentration 
(Cmin) following single and multiple doses of SL-
172154 
 Area under the serum concentration-time curve 
(AUC) 
 Terminal elimination half-life (t½), Clearance (CL) 
and Volume of Distribution (Vz) 
Exploratory Objectives
Outcome Measures 
To assess target engagement of cluster of 
differentiation 40 (CD40) on peripheral blood 
mononuclear cells (PBMCs) prior to and 
following SL-172154 administration. 
Free/total receptor occupancy of CD40
To assess target engagement of CD47 on red 
blood cells (RBCs) and PBMCs prior to and 
following SL-172154 administration. 
Free/total receptor occupancy of CD47
To assess pharmacodynamic biomarkers in 
blood prior to, on-treatment and following SL-
172154 administration. 
Pharmacodynamic biomarkers in blood: 
 Changes from baseline in cytokine/chemokine levels 
potentially including (but not confined to) interleukin 
(IL)-
), tumor necrosis 
-7, IL-8, IL-15, IL-10, IL-
12p70, chemokine ligand CXCL9, CXCL10 
 Changes from baseline in cell counts and percentages 
of circulating immune cells including T cell subsets, 
B cell subsets, and myeloid cells  
 Circulating immunoglobulin (Ig) levels 
 Complement activation by assessment of SC5b-9 
terminal fragment 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
24 
 
Exploratory Objectives
Outcome Measures 
To assess pharmacodynamic biomarkers in 
tumor tissue prior to, on-treatment and 
following SL-172154 administration. 
Pharmacodynamic 
biomarkers 
in 
tumor 
tissue 
including: 
Changes in T cells subsets, B cell subsets and 
myeloid cells. 
CD47 and CD40 expression 
Programmed cell death ligand 1 (PD-L1) expression
To evaluate binding of SL-172154 to RBCs
Presence of SL-172154 on RBCs
To estimate progression-free survival (PFS) 
and overall survival (OS)   
PFS based on investigator assessment: time from first 
dose to progression by RECIST v1.1 or death, 
whichever comes first  
OS: time from first dose to death 
To evaluate efficacy using immune-related 
response criteria. 
ORR, CBR, TTR, DOR and PFS based on 
investigator assessment per immune Response 
Evaluation Criteria (iRECIST)  
Study Design 
This clinical trial is a FIH, open label, multi-center, dose escalation Phase 1 study of SL-172154 designed 
to evaluate the safety, PK, pharmacodynamic effects, and anti-tumor activity of SL-172154 monotherapy 
administered as an IV infusion. The planned total sample size is approximately 33 -54 subjects.  If only 
Schedule 1 is evaluated, the planned total sample size for dose escalation is 21 subjects. If Schedule 1 
and Schedule 2 are both fully evaluated across 5 dose levels in dose escalation, the maximum planned 
sample size for dose escalation is 42. Approximately 6 subjects may be enrolled in an optional 
pharmacodynamic cohort; and approximately 6 subjects in the dose expansion cohort at the dose and 
schedule selected for further evaluation. Dose escalation will utilize the modified Toxicity Probability 
Interval (mTPI-2) design [Guo, 2017] with a target dose limiting toxicity (DLT) rate of 30% for the 
MTD. Subjects will be enrolled in cohorts of approximately 3 subjects into sequential dose levels of SL-
172154 and evaluated for DLT during the 28-day DLT evaluation period starting from the first dose of 
SL-172154. At each dose level, a minimum 3-day stagger between dosing the first and second subject is 
required.  The planned dose escalation is in half-log increments as outlined in the table below under the 
Treatment Schedules Section. The study may also enroll a pharmacodynamic cohort to obtain additional 
pharmacodynamic data from a total of approximately 6 additional subjects at one or more dose levels 
that have completed evaluation for safety without exceeding the MTD. Subjects enrolled in the 
pharmacodynamic cohort will not inform dose escalation decisions. Approximately 6 subjects may be 
enrolled in a dose expansion cohort to further characterize safety, tolerability, PK, anti-tumor activity, 
and pharmacodynamic data to inform the selection of a RP2D. The goal is to enroll approximately 6-12 
subjects at the potential RP2D, including subjects in dose escalation, pharmacodynamic cohort, and dose 
expansion. 
Treatment Schedules 
 Schedule 1: SL-172154 will be administered IV on days 1, 8, 15 of a 28-day cycle in cycle 1 and then 
 
 Schedule 2: SL-172154 will be administered IV once weekly on days 1, 8, 15, and 22 every 28 days 
in every cycle. The starting dose on schedule 2 would be instituted at a dose level that has completed 
evaluation for safety on schedule 1 and then continue dose escalation as defined by the mTPI-2 design. 
Alternative schedules may be explored if emerging data indicate less frequent dosing of SL-172154 
should be evaluated. In this case, SL-172154 may be administered once every two weeks, once every 
three weeks or once every four weeks. The starting dose on these alternate schedules would be instituted 
at a dose level that has completed evaluation for safety and then continue dose escalation as defined by 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
25 
 
the mTPI-2 design, emerging safety data and as recommended by the Safety Monitoring Committee 
(SMC).
Dose Escalation Scheme – Phase 1 
Dose escalation will begin at the starting dose of 0.1 milligrams per kilogram (mg/kg) as outlined below. 
Intermediate or higher dose levels not shown may be explored based on emerging data (e.g., safety and 
pharmacodynamic data).   
Dose Level
IV Dose of SL-172154 
(mg/kg)a,b,c, d, e 
Duration of Infusiond
Level 1 - starting dose 
0.1
30 minutes (+/- 10 minutes)
Level 2
0.3
30 minutes (+/- 10 minutes)
Level 3 
1.0
30 minutes (+/- 10 minutes)  
Level 4 
3.0
60 minutes (+/- 15 minutes)  
Level 5 
10.0 
60 minutes (+/- 15 minutes)
a) Dosing will begin on Schedule 1 with SL-172154 administered in 28-day cycles on days 1, 8, 
 
b) Dose escalation on Schedule 2 may be tested. If Schedule 2 is opened, SL-172154 may be 
administered once weekly on days 1, 8, 15, and 22 of each 28-day cycle. 
c) Intermediate or higher dose levels may be tested based on emerging safety and 
pharmacodynamic data.  
d) The actual body in kilograms (kg) will be used for dose calculation in all subjects who body 
the same as that calculated for a subject weighing 100 kg. 
e) Infusion time may change based on final drug volume needed for administration, safety and 
tolerability of the infusion for the subject and/or observed safety findings during the study. 
Please refer to the Study Pharmacy Manual (SPM) for details. 
Intrasubject dose escalation(s) may be considered on a case-by-case basis, provided that the subject has 
completed at least 2 cycles at the originally assigned dose, has tolerated treatment well, and experienced 
 Grade 1 toxicity on the most recent cycle of SL-172154 therapy. A subject’s dose may be increased to 
a dose level that has completed evaluation for safety and has not exceeded the MTD. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
26 
 
Definition of Dose Limiting Toxicity  
DLTs are as defined in the bulleted points below. Toxicities will be graded as per National Cancer 
Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5).  The 
determinate period for DLT is the first 28 days of SL-172154 dosing on Schedule 1 or Schedule 2. 
Note: AEs clearly related to disease progression or intercurrent illness are not considered DLTs.  
Inflammatory reactions attributable to local anti-tumor responses (e.g., severe pain) are not considered 
DLTs. 
 
Any death not clearly due to underlying disease or extraneous causes 
 
 
 
Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin: 
o 
A
 
o 
 
o 
nt increase in total 
enrollment as described above. 
 
Any AE that requires permanent discontinuation of SL-172154 
 
Any Grade 3 or greater AE except for those listed below: 
o 
 
o Grade 3 anemia 
o Grade 3 or 4 neutropenia not associated with fever that improves to Grade 2 within 7 days.   
o Grade 3 or 4 lymphopenia 
o Grade 3 thrombocytopenia not associated with clinically significant bleeding and does not 
require medical intervention 
o Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms and are 
reversed with appropriate medical intervention 
o Grade 3 laboratory abnormalities that are not deemed clinically significant by the SMC. 
o Indirect/unconjugated hyperbilirubinemia without significant clinical consequences 
o Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
signs/symptoms or findings on imaging consistent with pancreatitis 
o Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate clinical 
management 
o Grade 3 hypertension that can be controlled (i.e., systolic BP < 140 mmHg and diastolic BP < 
90 mmHg) with medical therapy. 
o Grade 3 endocrine disorder (thyroid, pituitary, hyperglycemia and/or adrenal insufficiency) that 
is managed with treatment with resolution of symptoms within 14 days after treatment onset. 
o Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with appropriate 
clinical management 
o Vitiligo or alopecia of any grade 
 
Other AEs may be considered a DLT as determined by the investigator in conjunction with the SMC. 
interruption of SL-172154 for more than 6 weeks or AEs that result in subjects not receiving at least 2 
of the 3 scheduled doses of SL-172154 on Schedule 1 (or at least 2 of the 4 scheduled doses of SL-
172154 on Schedule 2) during the DLT assessment period due to AE(s) may be taken into consideration 
when assessing the totality of the data in determining DLT and the RP2D.   




CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
28 
 
treatment and for 30 days (which is expected to exceed 5 half-lives) after the last dose of IP. FCBP 
must start using acceptable contraception at least 14 days prior to D1 of IP. 
11. Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any 
other anti-
NOTE: Low-grade or controlled toxicities such 
supplementation may be allowed upon agreement by the Sponsor Medical Monitor). 
12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless there is 
excessive risk as determined by the investigator. 
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply: 
1. Prior treatment with an anti-CD47 or anti-
 
2. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of SL-172154. 
Therapy
Washout period
Chemotherapy 
3 weeks
Hormonal therapy 
3 weeks 
PD-1/L1 inhibitor and other immunotherapies not otherwise 
specified  
3 weeks 
Tumor vaccine 
4 weeks 
Cell-based therapy
8 weeks 
Other mAbs or biologic therapies
3 weeks 
Other investigational agents not covered above 
4 weeks or 5 half-lives 
whichever is shorter 
Major surgery 
2 weeks 
Radiation (except palliative intent which does not require 
washout)
2 weeks 
3. Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression therapy for 
cancer treatment is prohibited.  Concurrent use of hormones for non-cancer related conditions is 
acceptable.   
4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of 
SL-172154 treatment with the following exceptions (i.e., the following are allowed with or within 
14 days of D1 of IP): 
o Topical, intranasal, inhaled, ocular, intraarticular corticosteroids 
o Physiological doses of replacement steroid (e.g., for adrenal insufficiency) not to exceed 10 
mg/day of prednisone or equivalent 
o Steroid premedication for reaction to IV contrast 
5. Receipt of live attenuated vaccine within 28 days of D1 of IP. 
6. Active or documented history of autoimmune disease. Exceptions include controlled Type I diabetes, 
vitiligo, alopecia areata or hypo/hyperthyroidism.  
 
 
Exclusion Criteria (continued) 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
29 
 
7. Hypersensitivity to the active drug substance or to any of the excipients for the agent to be 
administered or subjects with known hypersensitivity to Chinese hamster ovary cell products. 
8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).   
9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 
5 days of D1 of IP). 
10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal 
disease associated with diarrhea within 6 months of D1 of IP.
11. Clinically significant or uncontrolled cardiac/thromboembolic disease including any of the 
following: 
o Myocarditis 
o Unstable angina within 6 months from D1 of IP 
o Acute myocardial infarction within 6 months from D1 of IP  
o Uncontrolled hypertension 
o New York Heart Association Class II, III or IV congestive heart failure 
o Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular 
tachycardia, second- or third- degree atrioventricular block without a pacemaker, circulatory 
collapse requiring vasopressor or inotropic support, or arrhythmia that is not stabilized on 
therapy) 
o Clinically symptomatic thromboembolism on stable anticoagulation for less than three months 
12. Untreated central nervous system or leptomeningeal metastases. Subjects with treated central nervous 
prior to D1 of IP and no longer require steroids.  
13. Women who are breast feeding. 
14. Psychiatric illness/social circumstances that would limit compliance with study requirements and 
substantially increase the risk of AEs or compromised ability to provide written informed consent. 
15. Another malignancy that requires active therapy and that in the opinion of the investigator and 
Sponsor would interfere with monitoring of radiologic assessments of response to IP.  
16. Has undergone allogeneic stem cell transplantation or organ transplantation.
17. Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B 
(positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; if HCV antibody (Ab) 
test is positive check for HCV ribonucleic acid [RNA]).  
(NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody positive, but HBsAg 
negative are eligible for enrollment. HCV: Subjects who are HCV Ab positive, but HCV ribonucleic acid 
(RNA) negative are eligible for enrollment). 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
30 
 
Safety Oversight 
During the study while subjects are receiving treatment with SL-172154, SMC meetings will be held to 
review relevant data with the investigators or delegates.  These meetings will be held once a month (or 
more frequently if required) during dose escalation to share safety data and communicate results of 
ongoing analyses. All available safety, PK, pharmacodynamic, and clinical outcome data for all subjects 
at the time of the scheduled SMC Meeting will be reviewed and summarized.  Attendees of SMC 
meetings will include but not be limited to clinical investigators (or designees), the Sponsor Medical 
Monitor and Statistician. The SMC will operate in accordance with the SMC charter which will define 
roles and accountabilities and the process for safety review.   
The Sponsor will remain in constant contact with the clinical sites during the enrollment period to ensure 
that cohort enrollment during the dose escalation of this study is completed as per protocol.  All dose 
escalation or safety decisions made by the SMC will be documented in writing with copies maintained 
at each site and the Trial Master File at the Contract Research Organization.  
Statistical Analyses 
The safety evaluation will be based on the All Treated Population defined as all subjects who received 
at least one dose of study treatment. Frequency tables will be used to describe safety and tolerability 
parameters AEs, irAEs, SAEs, fatal SAEs and AEs leading to discontinuation of SL-172154. Changes 
in toxicity grade for clinical chemistry and hematology will also be summarized. AEs will be mapped to 
a Medical Dictionary for Regulatory Activities preferred term and system organ classification. 
Laboratory abnormalities will be graded according to the NCI CTCTAE v5., if applicable. The DLT 
evaluation will be based on the DLT evaluable population (defined as All Treated subjects enrolled in 
the dose escalation cohorts 
 on 
Schedule 1 (or at least 2 of the 4 scheduled doses of SL-172154 on Schedule 2) and complete the safety 
follow-up through the 28-day DLT evaluation period; or 2) who experience any DLT during the DLT 
evaluation period). DLTs will be summarized by dose level. The MTD will be estimated using isotonic 
regression. 
Anti-tumor activity data will be summarized by dose level and overall in the All Treated population and 
Response Evaluable population (defined as Subjects in the All Treated Population who have a baseline 
disease assessment and have at least one post-baseline disease assessment or have progressed or died 
before the first post-baseline disease assessment). The primary analysis of anti-tumor activity assessment 
is based on RECIST v1.1 and exploratory analysis of anti-tumor activity assessment is based on 
iRECIST.  
The PK serum concentrations and PK parameters will be summarized and analyzed using appropriate 
statistical methods. The pharmacodynamic biomarkers values will be summarized descriptively by dose 
level and visit.     
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
31 
 
1.
INTRODUCTION, BACKGROUND AND STUDY RATIONALE 
1.1
Background Information 
An essential element for increasing the immunogenicity of a tumor involves the processing of 
tumor antigens released from dead or dying tumor cells, and the subsequent presentation of tumor 
antigens on major histocompatibility complex (MHC) molecules expressed by activated antigen 
presenting cells (APCs). Cluster of differentiation (CD)47 is expressed by many somatic and 
hematopoietic tissues and is an important protective mechanism to prevent red blood cell (RBC) 
and platelet destruction by macrophages and splenic CD4+ dendritic cells (DCs) [Oldenborg, 
2000; Blazar, 2001; Yamao, 2002; Olsson, 2005; Yi, 2015]. The anti-phagocytic activity of 
me’ signal which ultimately leads to RBC destruction by splenic dendritic cells (DCs) is dependent 
upon a second activating signal, including CD18 containing integrins [Yi, 2015]. Uncoupling of 
improved regulation for erythrocyte homeostasis and should be considered in the therapeutic 
 
Abundant expression of CD47 in many solid and hematogenous tumors led to investigation of 
whether tumor cells had co-opted this pathway as a protective mechanism against immune 
by macrophages for erythrocyte homeostasis would also explain the observed anti-tumor benefit 
-Fc fusion proteins [Chao, 2012; 
Willingham, 2012; Weiskopf, 2013]. More recent studies, however, have clarified that DCs are 
also an important target o
[Liu, 
2015]
hance 
sensing of phagocytosed tumor mitochondrial deoxyribonucleic acid, which initiates a cyclic 
guanine monophosphate – adenosine monophosphate synthase/stimulator of interferon genes 
(cGAS/STING) mediated type I interferon response that facilitates cross-presentation of tumor 
antigens to CD8+ T cells [Liu, 2015; Xu, 2018]
-clinical 
immunity.   
for anti-tumor immunity [Hildner, 2008]
-tumor immunity 
is due to the specialized ability of these APCs to cross-present exogenous tumor antigens. 
Following phagocytosis, these tumor antigens gain entry to the DC cytosol and then are cross-
presented to CD8+ T cells. CD40 ligation by CD40 ligand (CD40L)
-) DCs, is an important signal for enhancing the antigen cross-presenting activity of 
exogenous antigen by DCs to CD8+ T cells [O'Connell, 2000; Delamarre, 2003; Yasumi, 2004; 
de Silva, 2019]. Interestingly, activation of tumor necrosis factor receptor-associated factor 
(TRAF) signaling downstream of CD40 ligation has also been shown to facilitate a type I 
interferon response via STING activation, but STING activation does not appear to be essential 
for the anti-tumor immune response to CD40 stimulation [Byrne, 2016; Yao, 2016]. Despite the 
potentially context-dependent role of a type I interferon response, anti-tumor immunity to CD40 
agonists remained dependent upon batf3 positive DCs and CD8+ T cells [Byrne, 2016]. These data 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
32 
 
adaptive immunity, however the two pathways appear to have distinct dependence upon a type I 
interferon response. 
-Fc fusion proteins and anti-CD47 antibodies, as well as CD40L-Fc fusion proteins and 
CD40 agonist antibodies are being investigated in clinical trials and have demonstrated 
preliminary evidence of anti-tumor activity [Vonderheide, 2007; Kornbluth, 2012; Ingram, 2017; 
Lin, 2017; Petrova, 2017; R. Advani, 2018; Kauder, 2018; Merz, 2018; Sikic, 2019; Vitale, 2019]. 
immune response 
suggests that the two pathways could be complimentary or synergistic in combination and have 
the potential to improve anti-tumor activity in cancer patients.  
In an attempt to improve upon current paradigms, Shattuck Labs has developed a bifunctional 
fusion protein (FP) platform, capable of simulta
tumor necrosis factor (TNF) receptor superfamily co-stimulators. Shattuck’s Agonist Redirected 
Checkpoint (ARC™) platform adjoins the extracellular domain (ECD) of a select type 1 membrane 
protein to the ECD of a select type 2 membrane protein, via a central Fc domain. Using this 
approach, combination immunotherapy can be achieved by a single fusion protein (FP). Superior 
preclinical activity has been observed compared to the separate administration of two individual 
antibodies against identical targets [de Silva, 2019]. 
-
Fc-CD40L ARC™ fusion protein as a means to target these pathways with a single compound.   
1.2 
Investigational Product, SL-172154 
The investigational product (IP), SL-172154, is a novel FP consisting of human SIRP and CD40L 
(SIRP  -Fc-CD40L) linked via a human Fc. Fusion of the ECDs of SIRP , a type 1 membrane 
protein, with CD40L, a type 2 membrane protein, generated a single molecule with dual specificity 
that retained individual target avidity.  
1.2.1
Mechanism of Action 
The mechanism of action of SL-172154 is designed to pair the costimulatory role of CD40 ligand 
(CD40L) in augmenting the antigen cross-presenting ability of DCs with the increased phagocytic 
activity of macrophages through CD47-SIR
binding (Figure 1A and Figure 1B). Importantly, 
because the ECDs of SIRP  and CD40L are physically linked to one another and localized to the 
tumor microenvironment (TME), APCs and tumor cells receive these signals in a spatiotemporally 
coordinated manner.  
 
 
 
 
 
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
33 
 
Figure 1: Mechanism of Action of SL-172154 Alone or Combined with an ADCC-competent mAb 
(A) Tumor expressed CD47 binds 
 on the APCs and suppresses APC (i.e. macrophages and DCs) activities 
including tumor phagocytosis and cross-presentation to CD8+ T-cells. 
(B) 
-Fc-CD40L directly induces APC activation. The CD40L end of the molecule engages CD40 on the APC 
resulting in APC stimulation and promoting an antigen-specific CD8+ T-cell response. 
the ARC™ blocks CD47 on the tumor cell thus directly enhancing APC-mediated phagocytosis of tumor cells.  
(C) Macrophage-mediated tumor phagocytosis can be further enhanced by combin
-Fc-CD40L with a 
tumor-targeted ADCC competent antibody via engagement of the Fc-receptor on the APC.  
(D) Direct APC activation through CD40L and direct blocking of CD47 do not eat me’ signals enhance tumor 
phagocytosis, increase antigen cross presentation and anti-tumor response when SL-172154 is administered 
alone.  
-Fc-CD40L with checkpoint blocking agents increases CD40 target density 
and may stimulate a more potent and durable anti-tumor response. CD47-SIRP -mediated tumor phagocytosis 
is further enhanced when 
-Fc-CD40L is combined with an ADCC-competent antibody. 
 
SL-172154, or its mouse surrogate, m
-Fc-CD40L, has demonstrated functional activity in 
in vitro and in vivo nonclinical test systems. The nonclinical data supporting the translational study 
of SL-172154 in human subjects with cancer is described in detail in the Investigator’s Brochure 
(IB) [Report_SL2020IB001].  The mechanism of action, information from the nonclinical in vitro 
and in vivo pharmacology, toxicokinetics (TK), and toxicity evaluations and the rationale for 
investigation are briefly summarized.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
34
1.2.2
In Vitro Pharmacology 
In vitro, SL-172154 was shown to bind to its cognate targets, CD47 and CD40, both individually 
and simultaneously. High binding affinity for CD47 and CD40 was noted as well as a slow off-rate 
(KD values of 0.628 nM and 4.74 nM, respectively), indicating a longer on-target resident time. 
This longer resident time could be of benefit in the tumor microenvironment (TME) where CD47 
is known to be expressed. CD40-mediated activity by SL-172154 was demonstrated in a NFkB 
reporter system in which CD40-dependent signaling was stimulated in the absence of Fc receptor 
cross-linking, and in cultured human peripheral blood mononuclear cells (PBMCs) in which dose-
dependent proliferation, an increase in the number of interleukin (IL)-2 secreting PBMCs, and the 
secretion of multiple cytokines were observed. In addition, 
-mediated activity 
was demonstrated by SL-172154 increasing human macrophage-mediated phagocytosis of tumor 
cells in vitro, which was further enhanced when SL-172154 was combined with a tumor-targeted 
ADCP/ADCC-competent antibody (rituximab, cetuximab, or trastuzumab).  
1.2.3
In Vivo Pharmacology 
-Fc-CD40L leads to a significant early and sustained activation 
of murine DCs (CD8+ and CD4+ DC) which matched the duration of activation observed with 
murine CD40 antibodies. This finding confirmed a previous report that CD47 blockade in vivo 
leads to rapid upregulation of CD86 and MHC-II on splenic CD8 + DCs [Yi, 2015]. 
In vivo, the anti-
-Fc-CD40L was studied in established syngeneic CT26 
colorectal murine tumor models. The performance of intraperitoneal administration of
-
Fc-CD40L was compared to treatment with CD47 blocking antibodies, CD40 agonist antibodies, 
the combination of the two antibodies and vehicle control. These experiments demonstrated that 
-Fc-CD40L led to higher rates of primary tumor rejection (63%) than 
either antibody given as monotherapy (anti-CD40, 0% and anti-CD47, 0%), or the antibody 
combination treatment group (33%). To assess the durability of an immune response without re-
treatment, mice that rejected the initial tumor were re-challenged with a second CT26 tumor on 
the opposite flank on day 40. Of the 2 mice initially cured with the antibody combination, 0 mice 
-Fc-CD40L group, 3 of 5 (60%) mice rejected the 
tumor re-challenge suggesting that a memory response was generated against the tumor, which led 
to protection against a subsequent tumor challenge.  This memory response correlated with a robust 
increase in AH1 tetramer +/CD8+ cells in the spleen and the tumor for both the anti-CD40/CD47 
-Fc-CD40L treated mice in comparison to vehicle controls. 
SL-172154 anti-tumor activity with anti-CTLA-4, anti-PD-1 or ADCC-
competent antibodies  
To assess the effect of combining 
-Fc-CD40L with checkpoint inhibitors, mice 
were treated with the following two combinations: 
-Fc-CD40L + murine anti-cytotoxic T 
lymphocyte-associated antigen 4 (CTLA-4) antibody or murine or anti-programmed cell death 1 
(anti-PD1) antibody. In these combination experiments, the baseline tumor volume was increased 
by approximately 2-3-fold compared to the monotherapy studies, in order to create a more stringent 
environment to observe potential synergistic or additive relationships. Both combinations 
improved anti-tumor response and overall tumor rejection in comparison to the monotherapy 
controls.  Anti-CTLA-4 in combination with concurrent 
-Fc-CD40L resulted in a potent 
memory response (57% primary tumor rejection and 100% secondary tumor rejection in 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
35 
 
comparison to 0% primary tumor rejection for the monotherapy controls). Similar results were 
noted with anti-PD-
-Fc-CD40L with 43% primary tumor rejection and 100% 
secondary tumor rejection. These synergistic relationships were noted when anti-PD-1 or anti-
CTLA-4 was administered first or concurren
-Fc-CD40L. The effect was lost 
-Fc-CD40L treatment preceded treatment with anti-CTLA-4 or anti-PD-1.  
Other anti-CD47 agents have demonstrated that tumor phagocytosis is augmented via 
combinations with tumor-targeting antibodies such as rituximab [Chao, 2012]. Rituximab induces 
complement and natural killer (NK) cell–mediated, antibody-dependent, cell-mediated 
cytotoxicity (ADCC) effects by means of its active Fc effector function. In addition, the Fc region 
of rituximab provides a potent prophagocytic signal for macrophages by stimulating antibody-
dependent cellular phagocytosis.  
Since SL-172154 was observed to potentiate the activity of rituximab in vitro, the combination of 
m
-Fc-CD40L with a murine surrogate for rituximab (murine anti-CD20) was investigated 
in two CD20+ mouse tumor models, WEHI3 and A20, that were subcutaneously implanted. In 
both tumor models, similar control of established tumor growth was observed when anti-CD20 
antibodies or m
-Fc-CD40L were tested as monotherapy. In keeping with the in vitro 
phagocytosis data, 
-Fc-CD40L + anti-CD20 resulted in a further 
-Fc-CD40L + anti-
CD20 resulted in 33% of the mice rejecting the tumor, while 17% of mice rejected the tumor when 
treated with anti-CD20 as monotherapy. There was no tumor rejection in the A20 model, 
-Fc-CD40L induced significant anti-
tumor efficacy in both CD20+ hematological tumors models which was enhanced by combination 
with anti-CD20. 
 Collectively, these data demonstrate that SL-172154 has a dual mechanism of action (Figure 1A 
and Figure 1B).  Tumor cells expressing CD47 normally bind SIRP  and suppress APCs including 
macrophages and DCs. One  mechanism of action of SL-172154 is direct enhancement of APC-
ARC™. SL-172154-mediated tumor phagocytosis can be enhanced through combination with a 
targeted ADCC competent antibody (Figure 1C and Figure 1D). A second mechanism of action of 
SL-172154 is induction of APC activation through CD40 which stimulates an antigen-specific 
CD8+ T cell response. Combination treatment of SL-172154 with checkpoint blocking agents 
increases CD40 target density which may stimulate a more potent and durable anti-tumor response.  
1.2.4 Toxicology and Toxicokinetics 
The cynomolgus monkey was selected for the nonclinical toxicology studies due to the cross-
reactivity of SL-172154 binding to the respective targets in this species and in vitro activity. The 
anatomical, physiological, and biochemical similarities of cynomolgus monkeys to humans 
facilitate extrapolation of potential effects to human.  
Two, repeat intravenous (IV) dose studies, utilizing once-weekly administration, of up to 5 weeks 
in duration, have been conducted in cynomolgus monkeys. In both the dose range finding (DRF) 
study and Good Laboratory Practice (GLP) definitive study, the evaluated SL-172154 doses were 
0.1, 1, 10, and 40 mg/kg. The GLP study also included recovery groups to evaluate the 
reversibility, progression, or delayed appearance of any observed findings following a 4-week off-
dose period. Additionally, SL-172154 was evaluated in vitro for potential hemolysis. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
36 
 
In the DRF study, SL-172154 was well tolerated with no incidence of infusion related reactions. 
Generally, dose-proportional postdose decreases in lymphocytes (0.1 to 40 mg/kg) and platelets 
(10 and 40 mg/kg) were observed during the study with both parameters trending toward, or 
returning, to baseline after a 7-day recovery period. A number of serum cytokines were increased
with the elevations being generally dose-dependent and tending to increase with repeated dosing. 
Anti-drug antibodies (ADA) were present in all SL-172154-treated monkeys by Day 15 (Dose 3) 
and may have contributed to reduced serum SL-172154 levels on Day 29. Plasma complement 
split products were increased coincident with the emergence of ADA. In the DRF study, 40 mg/kg 
was designated as the HNSTD and corresponded with mean Cmax and AUC0-last values of 
727,000 ng/mL and 1,670,000 
, respectively, on Day 1 (Dose 1), and 594,000 ng/mL and 
1,060,000 ng h/mL, respectively, on Day 29 (Dose 5). 
In the GLP study, the occurrence of dose-dependent infusion-related reactions (IRRs) at 10 and 40 
mg/kg (Days 15 or 22) resulted in early termination of dosing in these two dose groups with 2 
monkeys in the 40 mg/kg group euthanized in extremis [a female on Day 15 (Dose 3) and a male 
on Da
 mg/kg (Days 16 
and 23) and transient, mild decreases in lymphocytes were seen in the 40 mg/kg group (both sexes 
on Days 2 and 16; 2 of 4 males on Day 23). Dose-dependent increases in splenic weight and 
increased lymphoid cellularity in the spleen and lymph node were noted and attributed to SL-
172154 administration. These findings were reversed after a 4-week recovery period. Assessment 
of pharmacodynamic biomarkers showed that SL-172154 occupied CD40 and CD47 receptors on 
circulating blood cells and caused elevations in a number of serum cytokines. Transient and 
reversible complement activation was coincident with the production of ADA to SL-172154. 
Additionally, the presence of ADA from at least Day 15 (Dose 3) onward likely contributed to low 
or non-quantifiable plasma SL-172154 concentrations on Day 29. At the 1.0 mg/kg dose level, 
there were no clinical observations, abnormalities in clinical pathology parameters, or 
non-reversible pathology findings, thus 1.0 mg/kg was considered to be the no-observed-adverse-
effect level (NOAEL) for intravenous infusion doses of SL-172154. The 1.0 mg/kg dose 
corresponded with mean Cmax and AUC0-last values of 1230 ng/mL and 518 
on Day 1. 
The mean terminal elimination half-
2) on Day 1 was approximately 0.4 hours following a 1 
mg/kg dose and was higher with mean values of approximately 1.1 and 0.9 hours for the 10 mg/kg 
and 40 mg/kg dose groups, respectively. 
In contrast to the DRF study, there was evidence of toxicity in the GLP study that manifested as 
dose-dependent infusion-related reactions. The GLP study was a larger study than the DRF study.  
The GLP study was conducted with study drug that is representative of the Good Manufacturing 
Process used for clinical drug supplies. The acute clinical observations that were noted in the GLP 
study were paleness and decreased activity; the severity of signs and symptoms during dose 
administration resulted in 2 monkeys dosed at 40 mg/kg being euthanized in extremis.
Pharmacodynamic analyses performed on the samples from the cynomolgus monkeys in both the 
DRF and GLP studies demonstrated similar, dose-dependent, on-target pharmacological effects.   
The on-target pharmacological effects that were noted in the DRF and GLP study included post-
dose changes in peripheral blood lymphocytes and elevations in serum cytokines. In the GLP 
study, on Day 1 (Dose 1), SL-172154 readily bound to its intended targets, in a dose-dependent 
% CD40 receptor occupancy on PBMCs and ~80% CD47 receptor 
occupancy on RBCs in the 10 and 40 mg/kg groups. Furthermore, in the GLP study, SL-172154-
mg/kg. Most cytokine increases were 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
37 
 
observed after repeated administration, generally increased with repeated dosing, and were 
coincident with emergence of ADA which may have exacerbated the cytokine response. Cytokine 
levels returned to or were near control levels prior to the next dose. The cytokines with the largest 
increases in the GLP study were: IL-1 receptor antagonist, monocyte chemoattractant protein-1, 
IL-6, CD40-ligand, IL-8, macrophage inflammatory protein-
stromal cell-derived factor-
and vascular endothelial growth factor-A. 
RBC hemolysis was investigated and ultimately ruled out as a potential causal or contributory 
factor to the IRRs. In vitro incubation of SL-172154 with human whole blood did not result in any 
detectable hemolysis. While SL-172154 was shown to bind to CD47 receptors on RBCs in the 
monkey GLP study, there were no changes in erythrocyte count, hemoglobin, or hematocrit in the 
study which were not also observed in control animals. Furthermore, analysis of laboratory values 
from the GLP study, including lactate dehydrogenase, total bilirubin, hemoglobin and hematocrit 
demonstrated no evidence of anemia or hemolysis.  
ADA developed in both the DRF and GLP studies with a similar time course. The emergence of 
ADA in cynomolgus monkeys was not unexpected because SL-172154 is based on human amino 
acid sequences which have 82% identity to the cynomolgus. Across both studies, pretreatment 
samples from all monkeys in the study were negative. In the GLP study, prior to receiving Dose 2 
on Day 8 (168 hours following Dose 1), an ADA response was detected in only 1 animal in each 
of the 10 and 40 mg/kg groups. On Day 15, prior to Dose 3, all animals in the SL-172154 treatment 
groups had a positive ADA titer, and remained positive at subsequent time points, including at 
necropsy of the 10 and 40 mg/kg recovery groups (4 weeks after their last SL-172154 dose). 
Complement activation, as evidenced by increased plasma C5b-9 concentrations, was only noted 
after the emergence of ADA. 
In summary, the repeat IV dose toxicity studies in cynomolgus monkeys demonstrated on-target 
pharmacological activity of SL-172154. The onset of ADA, elevations in serum cytokines, 
activation of complement, and postdose changes in lymphocyte counts were similar between the 
DRF and GLP studies. Dose-dependent, infusion-related toxicity was observed with repeat dosing 
in the GLP study, a finding that is attributable to exaggerated pharmacology and immunogenicity. 
Thus, the IRRs are believed to be the result of exacerbated pharmacology of SL-172154 in the 
presence of ADA. Overall, the nonclinical safety assessment program supports the administration 
of SL-172154 as an intravenous infusion in the first-in-human (FIH) clinical study SL03-OHD-
101.  
1.3 
Rationale for Investigation of SL-172154  
The preclinical data package provided in the IB [Report_SL2020IB001] demonstrates that SL-
172154 selectively and specifically binds to its intended targets, CD47 and CD40, with high 
affinity. Furthermore, both targets exhibit functional activity in a variety of in vitro assays and 
anti-tumor models.  
SL-172154 is designed to pair the costimulatory role of CD40L in augmenting the antigen cross-
presenting ability of DCs with the increased phagocytic activity of macrophages through CD47-
-172154 to CD47 in the tumor for an extended 
period of time may block this important checkpoint axis and provide a larger window of 
opportunity for increased tumor phagocytosis, CD40L co-stimulation, and greater antigen-
processing and presentation. Furthermore, both the CD47/SIRP
the CD40/CD40L axes 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
38 
 
appear capable of bridging innate and adaptive immunity, suggesting that the two pathways could 
be complimentary or synergistic in combination. The data also suggest that the tethering of SIRP
to CD40L using an ARC™ provides a mechanistic advantage over the separate administration of
two antibodies that have different PK properties, distribute separately, and may compete for Fc 
receptor binding. We hypothesize that co-localization and co-stimulation is critical for 
combination immunotherapy and will result in superior clinical activity in comparison to the 
separate administration of two individual antibodies targeting CD40 and CD47. 
SL-172154 overcomes several major functional limitations seen with existing bifunctional 
technologies (i.e., bispecific antibodies or linked single-chain variable fragment [scFv] molecules). 
The active unit of SL-172154 exists as a glycosylated multimer, thereby retaining high target 
avidity, and inducing CD40 receptor clustering and active signaling. The TNF superfamily 
receptors (i.e., CD40, OX40, GITR, 4-1BB) require clustering on a cell membrane and coordinated 
binding of multiple receptors for signal activation. With bispecific antibodies or linked scFv 
molecules, one of the two target binding domains is replaced to bind a second molecule thus 
resulting in a loss of target avidity.  The monovalent binding interaction with each of these two 
targets is incapable of activating receptors that require clustering on a cell membrane. For this 
reason, there is not a current example of a bispecific antibody or linked scFv that is able to 
simultaneously block a checkpoint ligand while stimulating a TNF costimulatory receptor.  
This FIH Phase 1 study will evaluate the safety, tolerability, PK, anti-tumor and pharmacodynamic 
effects of SL-172154 to identify the dose and schedule i.e., recommended Phase 2 dose (RP2D) 
for future development. The trial will enroll patients with platinum-ineligible ovarian, fallopian 
tube, and primary peritoneal cancers (Section 4.1). Ovarian and related cancers were selected for 
investigation in the Phase 1 study of SL-172154 due to the fact that these histologies have a high 
percentage of tumors with detectable CD47 expression  (TCGA data; [Wang, 2015; Brightwell, 
2016].  A tissue microarray of 265 tissues from patients with ovarian, primary peritoneal and 
fallopian tube cancers were analyzed by immunohistochemical analysis for CD47 expression and 
expression was detected in 210 of 265 cases (79%). Furthermore, CD47 is a tumor associated 
antigen in ovarian cancer with high levels of expression in epithelial ovarian cancer cells compared 
with normal ovarian cells [Li, 2017]. Finally, ovarian cancer is characterized by peritoneal 
metastases which are facilitated by a crosstalk between tumor cells and other cells in the TME. 
Tumor-associated macrophages constitute over 50% of cells within the peritoneal TME and 
malignant ascites and are potential targets for therapy [Gupta, 2018]. Given that the APC is 
hypothesized to be the primary target of SL-172154, the unique immune contexture of ovarian 
cancers makes this histology particularly suitable for investigation. These hypotheses are 
supported by the results of a Phase 1 study of an anti-CD47 antibody, Hu5F9-G4, in which 
monotherapy activity was reported in 2 (partial responses) out of 13 patients with ovarian cancer 
[Sikic, 2019].  
1.4
Potential Risks and Benefits of SL-172154 
1.4.1
Potential Risks
Potential risks to subjects are addressed by safety guidelines and vigilant monitoring of participants 
as outlined below. Potential safety concerns are based on preclinical safety toxicology findings in 
cynomolgus monkeys dosed with SL-172154 and other in vivo or in vitro studies of SL-172154 
summarized in the IB, as well as established clinical management guidelines. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
39 
 
SL-172154 is a pharmacologically active molecule [Report_SL2020IB001].  The risks (evaluation 
of safety and tolerability) and potential benefits (evaluation of anti-tumor activity) of SL-172154 
in humans will be assessed for the first time in this Phase 1 clinical trial.  In the absence of data in 
humans, an assessment of potential safety risks is based on (1) the results of nonclinical studies 
with SL-172154 (e.g., non-human primate (NHP) studies in cynomolgus monkeys); and (2) the 
adverse event (AE) profile of other CD40 agonists and CD47-SIRP  targeting agents.  
Based on a thorough review of the totality of the NHP data (including clinical findings, laboratory 
studies, cytokine analysis, TK, immunogenicity studies, complement split product levels, and 
anatomical pathology), the underlying etiology of the SL-172154-related effects is most likely due 
to a combination of both the pharmacologic activity of the molecule and to immunologic reactions 
to SL-172154 administration. The following are potential contributory factors to the dose 
dependent IRRs: (1) elevations in serum cytokines; (2) postdose changes in lymphocyte number; 
(3) development of ADA and downstream complement activation. 
Adverse events that have been observed following administration of other CD40 agonists agents 
include infusion related reactions (most common symptoms associated with infusion related 
reactions are chills, nausea, vomiting, hypotension, pyrexia, pruritus, rash), cytokine release 
syndrome (CRS), fatigue, rash, elevation of hepatic transaminases, lymphopenia, anemia, 
thrombocytopenia, 
neutropenia, 
thromboembolism, 
and 
inflammatory 
eye 
disorders 
(conjunctivitis and ocular hyperemia). Immune mediated events, including dermatitis, colitis, 
hypophysitis and thyroiditis, have not been seen with CD40 antibodies but remain a potential 
concern [Vonderheide, 2001; Calvo, 2019].  
Adverse events that have been observed following administration of agents that target the CD47-
SIRP  
axis 
include 
anemia, 
hemagglutination, 
hyperbilirubinemia, 
lymphopenia, 
thrombocytopenia, neutropenia, elevation of hepatic transaminases, fatigue, headache, fever, and 
infusion related reactions [Ansell, 2016; Chow, 2019; Sikic, 2019]. 
Implications 
for 
monotherapy 
dosing 
of 
SL-172154 
in 
this 
FIH 
clinical 
trial 
[Report_SL2020IB001]: 
1) The data indicate a potential risk for IRRs and CRS in humans. The IRRs that were noted in 
the NHP studies were potentially cytokine-mediated as they demonstrated dose- and time-
dependence. In contrast, antibody-mediated type 1 or type 3 hypersensitivity reactions (HSRs) 
would not be expected to demonstrate dose-dependence. Furthermore, CRS is to be expected 
given the mechanism of action of SL-172154.  The steps taken to minimize these risks include 
low starting dose, decreased dose frequency in comparison to the weekly dosing schedule for 
the NHP studies, administration in an outpatient oncology clinic or inpatient setting, 
management guidelines (e.g., rescue treatments, prophylaxis), and extended monitoring when 
indicated. The steps taken to minimize the risks are outlined in the Toxicity Management 
Guidelines section of the protocol (Section 3.6). This section is based on robust management 
guidelines that are available for managing CRS in the context of treatment with adoptive T-
cell therapies, bispecific antibodies, and agonist antibodies.
2) Immunogenicity Risk and Complement Activation: ADA did emerge in the non-human 
primate studies as expected given that SL-172154 is based on human amino acid sequences 
which have 82% identity to the corresponding cynomolgus sequences. However, SL-172154 
and hence SL-172154 is considered to 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
40 
 
have a low risk of immunogenicity in humans. Subjects in the clinical trial will, nevertheless, 
be monitored starting at baseline and serially for ADA and complement activation. In the event 
of a positive ADA response, antibody titer will be measured, and antibody isotype will be 
characterized. A guideline for monitoring and management of HSRs is included in the protocol 
(Section 3.6.1). 
3) Hemolysis and Anemia: SL-172154 does bind RBCs in vivo but was not shown to cause 
hemolysis in NHPs. The lack of hemolysis is likely due to the fact that the Fc domain of SL-
172154 is inactive [Chow, 2019]. Regardless, subjects will be monitored serially for evidence 
of hemolysis and anemia. Another potential risk is that treatment with SL-172154 may result 
in interference with pre-transfusion testing due to SL-172154 binding of CD47 on RBC and 
platelet membranes [Report_SL2020IB001]. To investigate this possible risk, blood 
phenotyping, type and screen (ABO/Rh), and direct antiglobulin test (DAT) will be performed 
before and following exposure to SL-172154.  
4) Immune-Related Adverse Events (irAEs): As with other checkpoint inhibitors and 
costimulatory molecules, irAEs resulting from a breakdown of self-tolerance remain a 
potential concern associated with SL-172154 administration. As experience using checkpoint 
inhibitor therapies has grown, the list of toxicities has increased, and the types of AEs observed 
span essentially every organ class. Extensive knowledge in managing immune-related 
toxicities has developed over the years and led to the publication of consensus guidelines in 
peer reviewed journals [Haanen, 2017; Puzanov, 2017; Brahmer, 2018].  Moreover, clinical 
trial sites familiar with these therapeutic agents have developed institutional guidelines to 
ensure effective management of these toxicities. Monitoring and management of irAEs as 
outlined in protocol section 3.6 follow these consensus guidelines in this FIH study. 
In summary, this Phase 1 study has taken the following precautions to minimize the potential for 
adverse outcome: (1) the study is being conducted at centers that have extensive experience with 
this class of agents and the management of associated toxicities; (2) the starting dose of SL-172154 
is estimated based on minimum anticipated biological effect level (MABEL) and is 10x lower than 
the NOAEL observed in the NHP studies (Section 3.2). Therefore, the starting dose is expected to 
be lower than doses associated with AEs in humans; (3) staggered enrollment between dose 
cohorts and within cohorts allows for the monitoring of acute toxicities in one subject before 
treating another; (4) administration of SL-172154 in an outpatient oncology treatment 
center/hospital allows for close monitoring of subjects for AEs and for timely action; (5) guidelines 
for management of AEs based on established guidelines [Haanen, 2017; Puzanov, 2017; Rosello, 
2017; Brahmer, 2018; Porter, 2018] are provided in the clinical trial protocol (Section 3.6); (6) a 
Safety Monitoring Committee (SMC) will meet monthly and on an ad hoc basis to review 
emerging toxicities, and assess the impact of these toxicities on study conduct. 
1.4.2 Potential Benefits 
The clinical benefits of SL-172154 are unknown: no clinical trials in human subjects have been 
conducted to date. SL-172154 targets both the CD40/CD40L and the SIRP /CD47 axes. 
Monoclonal antibodies and fusion proteins targeting each of these axes have been extensively 
evaluated in clinical trials [Beatty, 2017; Uger, 2020] but there are no current regulatory approvals 
for agents targeting either axis. There are currently no reported multitargeted agents or trials for 
CD47 inhibitors in combination with CD40 agonists.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
41 
 
Encouraging preliminary anti-tumor activity has been observed in patients with hematologic 
malignancies and solid tumors receiving CD47 blockade alone as well as in combination with 
 me’ signals (rituximab, trastuzumab, azacitidine) and the T-cell 
checkpoint inhibitor pembrolizumab [Uger, 2020]. The most advanced development program is 
for Hu5F9-G4 (5F9), a high affinity humanized IgG4 anti-CD47 antibody, that is administered IV 
with a 1 mg/kg priming dose followed by weekly maintenance doses up to 45 mg/kg [Sikic, 2019]. 
The unique dosing regimen minimizes red blood cell (RBC) toxicity by selectively clearing aging 
RBCs, which results in a mild and transient anemia. Pooled efficacy results from Phase 1b/2 of 
5F9 and rituximab (n = 75) indicate an objective response rate (ORR) of 49% and a complete 
response (CR) rate of 21% [R. Advani, 2018; R. Bartlett Advani, N.L. Smith, S.M. et al. , 2019]. 
These response rates are likely higher than those achievable with rituximab alone in this patient 
population as the majority have previously failed a prior rituximab-containing regimen. 5F9 in 
combination with azacitidine, a demethylating agent that upregulates calreticulin expression on 
tumor cells, is also showing clinical promise, with an ORR of 100% in untreated myelodysplastic 
syndromes (MDS) patients (n = 11, 55% CR rate), and 64% in untreated acute myeloid leukemia 
(AML) patients (n = 14) [Sallman, 2019]. The combination appears to compare favorably with 
historical data from azacitidine monotherapy. As a monotherapy, 5F9 has shown relatively low 
response rates: 10% in relapsed/refractory AML/MDS patients and 5% in solid tumors. 
Several different CD40 agonistic antibodies have been studied in early phase trials [Beatty, 2017]. 
Sporadic responses in solid and hematologic malignancies including renal cell cancer, melanoma, 
diffuse large B cell lymphoma and Hodgkin’s lymphoma have been noted with monotherapy CD40 
agonists. However, a critical component that is believed to mediate the anti-tumor effect is the 
presence of tumor antigen, which is necessary for CD40-activated APCs to induce antigen-specific 
T cell adaptive immunity. This is the hypothesis for several other ongoing clinical trials combining 
CD40 agonists with vaccines and chemotherapy.  
The mechanism of action of SL-172154 is designed to pair the costimulatory role of CD40L in 
augmenting the antigen cross-presenting ability of DCs with the increased phagocytic activity of 
macrophages through CD47-
are physically linked to one another and localized to the TME, APCs and tumor cells receive these 
signals in a spatiotemporally coordinated manner, potentially leading to more potent and durable 
anti-tumor response. This FIH, Phase 1 clinical trial of SL-172154 is designed to evaluate the 
safety and tolerability of SL-172154 monotherapy. Secondary endpoint measures include 
determination of a RP2D and schedule for monotherapy dosing, assessment of the PK and 
pharmacodynamic effects of SL-172154, and a preliminary description of anti-tumor activity.  
Subjects with platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers are 
eligible for enrollment.  
 
 
 








CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
45 
 
For each dose level evaluated on Schedule 1 or Schedule 2, the minimum number of subjects 
evaluable for DLT (see Section 9.2.1 for definition of DLT evaluable subject) will be 3 unless 
unacceptable toxicity is observed prior to enrollment of 3 subjects (e.g., the first 2 subjects 
experience a DLT before the third subject enrolls). The maximum number of subjects evaluable 
for DLT at a dose level will be 12 (e.g., this may be reached by sequential enrollment of 4 cohorts 
of 3 subjects) assuming the dose decision is to stay at the current dose from the first 3 cohorts. If 
the maximum of 12 DLT evaluable subjects at a given dose level is reached, a dose escalation 
a dose de-escalation 
decision will be made if 
   
Note: Example scenarios for dose escalation per mTPI-2 dose decision rules are provided in 
Appendix 16.1. 
During dose escalation, a review of available safety data for all subjects at a given dose level will 
be undertaken by the SMC approximately every four weeks and a decision made regarding the 
safety profile of that dose level.  
Pharmacodynamic Cohorts  
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort to obtain 
additional pharmacodynamic data from a total of approximately 6 additional subjects at one or 
more dose levels that have completed evaluation for safety without exceeding the MTD on the 
selected schedule. Subjects in the pharmacodynamic cohort must have tumor accessible for biopsy 
without excessive safety risk and must consent to providing paired biopsies for translational 
research. Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation 
decisions but the pharmacodynamic information gathered from these additional subjects will 
inform selection of doses for further evaluation and the RP2D determination. Subjects in the 
pharmacodynamic cohort will be followed per the Schedule of Assessment (SOA) table provided 
in Section 6. 
Dose Expansion  
Approximately 6 subjects may be enrolled in the dose expansion cohort on a selected schedule. 
Subjects may be enrolled at one or more dose levels to further characterize safety, tolerability, PK, 
anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D. The number of 
subjects in dose expansion will vary depending on the number of subjects enrolled in both dose 
escalation and the pharmacodynamic cohort at a potential RP2D. The goal is to enroll 
approximately 6-12 subjects at the potential RP2D, including subjects in dose escalation, 
pharmacodynamic cohort, and dose expansion. Subjects enrolled in the dose expansion cohort(s) 
will be followed per the Schedule of Assessment (SOA) table provided in Section 6. 
3.1.1 Selection of the Recommended Phase 2 dose 
Selection of the RP2D and schedule for SL-172154 monotherapy will be based upon the totality 
of the data in subjects treated in dose escalation, dose expansion and pharmacodynamic cohorts.  
Approximately 6-12 subjects (inclusive of the subjects enrolled at this dose in the Dose Escalation, 
Pharmacodynamic cohort, and Dose Expansion) may be treated at the RP2D.     


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
46 
 
3.1.2
Sample Size
If only Schedule 1 is evaluated, the planned total sample size is 21 for dose escalation. If Schedule 
1 and Schedule 2 are both fully evaluated in dose escalation, the maximum planned sample size
for dose escalation is 42 This sample size assumes evaluation of approximately 21 subjects across 
5 dose levels in dose escalation on Schedule 1 and 21 subjects across 5 dose levels on Schedule 2. 
Approximately 6 subjects may be enrolled in an optional pharmacodynamic cohort. After a dose 
and schedule are selected, approximately 6 subjects will be included in the dose expansion cohort. 
The number of subjects in dose expansion will vary depending on the number of subjects enrolled 
in both the dose escalation and pharmacodynamic cohorts at a potential RP2D. The goal is to enroll 
approximately 6-12 subjects at the potential RP2D, including subjects in the dose escalation, 
pharmacodynamic, and dose expansion cohorts. Overall, the total sample size estimate for this 
study is 33 subjects assuming only Schedule 1 is evaluated, and 54 subjects if both Schedule 1 and 
Schedule 2 are fully evaluated. See Section 9.1 for more details.  
3.2 
Justification for Starting Dose and Schedule of SL-172154  
Analysis of available data support a starting dose of 0.1 mg/kg for the administration of SL-172154 
to humans via IV infusion. The starting dose for the FIH clinical study of SL-172154 was 
determined based on MABEL principles, taking into account available preclinical pharmacology, 
toxicology, and pharmacokinetic data. The most sensitive in vitro measure of biological activity 
in response to SL-172154 exposure was the PBMC proliferation assay conducted in AIMV 
medium.  Additional key data to support selection of the starting dose for the FIH study is data 
from cynomolgus monkey toxicology studies, including identifying the NOAEL, and the 
pharmacokinetic results.   
The in vitro potency of SL-172154 in human PBMCs was estimated using the AIMV 
(Alstroemeria-Mosaic Virus) proliferation assay. PBMCs from humans and cynomolgus monkeys 
(9 donors/species) were exposed to increasing concentrations of SL-172154 (0 to 100 nM) for 7 
days after which absorbance of each sample was measured at 490 nm as an index of cell 
proliferation. This study demonstrated a dose-dependent increase in proliferation in both humans 
and cynomolgus monkeys PBMCs.  While human PBMCs were overall more sensitive, there was 
similarity in the degree of SL-172154-stimulated proliferation in humans and cynomolgus 
monkeys at both EC20 and EC50. An EC20 value of 5.18 nM was calculated for human PBMC 
proliferation using a baseline Emax model. The human EC20 has been chosen as the target Cmax 
concentration benchmark for systemic exposure, consistent with the conclusion by Saber et al. that 
a starting dose of 10 to 30% pharmacologic activity was acceptable for CD3 targeted bispecific 
constructs [Saber, 2017].
In vivo monkey PK data from the GLP toxicology study [Report_SL2020IB001] were used to 
convert the target Cmax to a human equivalent dose (HED). In the monkey GLP toxicology study, 
a dose of 1 mg/kg was associated with a mean Cmax of 1230 ng/mL (13.96 nM, n=6 monkeys). 
Note that the lowest dose studied in the GLP study was 0.1 mg/kg; however, the Cmax was not 
well characterized as only two animals had measurable concentrations at this dose level. The non-
quantifiable concentrations were likely due to the rapid clearance of SL-172154 from the serum. 
Potential explanations for rapid drug clearance include an antigen sink due to the ubiquitous 
expression of CD47 on peripheral blood cells (i.e., RBC, platelets, PBMC) and target-mediated 
uptake at early time points with trafficking of cells (e.g., PBMC) and bound drug to peripheral 
tissues. From Day 15 onwards, the removal of drug by anti-drug antibodies results in rapid 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
47 
 
clearance. Assuming dose-proportionality, a dose of 0.4 mg/kg in the monkey is predicted to 
achieve the preliminary human target Cmax (5.18 nM). The 0.4 mg/kg dose level in monkeys was 
converted to a HED using a standard conversion factor of 0.32 [FDA, 2005]. The resultant 
preliminary starting dose for IV infusion of SL-172154 in humans is 0.1 mg/kg (0.4 mg/kg x 0.32).
The GLP study concluded that 1.0 mg/kg was considered to be NOAEL for IV infusion doses of 
SL-172154. Thus, the proposed SL-172154 starting dose of 0.1 mg/kg is 1/10th the NOAEL dose 
of 1 mg/kg observed in cynomolgus monkeys and provides an appropriate safety margin for the 
FIH starting dose. 
Justification for Schedule: A weekly dosing schedule for 5 consecutive weeks was implemented 
in the NHP studies.  Toxicity was dose-dependent (only at the higher doses) and occurred at the 
third and subsequent doses.  Receptor occupancy data from Day 1 (Dose 1) demonstrated that SL-
172154 readily bound to its intended target in a dose-
receptor occupancy on PBMCs and ~80% CD47 receptor occupancy on RBCs in the 10 and 40 
mg/kg groups. Maximal occupancy for the CD47 receptor on RBCs was attained by 1 hour post-
infusion and persisted through at least 168 hours. CD40 receptor occupancy was transient, likely 
influenced by endocytosis and migration of CD40+ cells to tissues including the spleen.   
Based upon the durability of binding for SL-172154 to CD47, dosing for the clinical trial will 
begin by incorporating administration of SL-172154 on Schedule 1 on Day 1, 8, 15, and then every 
2 weeks thereafter. The Day 8 dose was retained as no toxicity was observed at this time point, 
minimal pharmacodynamic effects were noted, and this dose may have contributed to the 
pharmacodynamic effect on day 15. In NHPs, multiple factors may have contributed to the onset 
of reactions at Day 15 including ADA, complement activation, margination of lymphocytes and 
cytokine elevations.  It is unknown if these contributing factors would be observed in humans at 
the doses studied.  Therefore, dosing on Day 1, 8, 15 is considered acceptable.  The 2-week 
treatment free interval beyond Day 15 may allow for pharmacodynamic effects to subside between 
subsequent doses and to mitigate toxicity. A more or less intensive dosing schedule may be 
instituted if safety and pharmacodynamic data support more or less frequent dosing of SL-172154 
(e.g., one dose given weekly on Schedule 2 or every two weeks or every 3 weeks or every 
4 weeks). 
3.2.1 Criteria for Decision to Transition from Schedule 1 to Schedule 2
Schedule 1 may be safe and tolerable, but pharmacodynamic effects may not be present or 
detectable, or pharmacokinetic parameters may suggest that a more frequent dosing schedule is 
warranted. In this event an alternative dosing schedule (i.e., Schedule 2; once weekly dosing over 
28 days in each cycle) will be explored in lieu of Schedule 1.  During dose escalation 
pharmacokinetic parameters will be analyzed by dose level and subjects will be monitored for 
pharmacodynamic effects pre- and post-dose. Dynamic changes that are anticipated following 
administration of pharmacologically active doses of SL-172154 include: 
 Changes from baseline in cell counts and percentages of circulating immune cells including 
T cell subsets, B cell subsets, and myeloid cells 
 Increase in cytokines/chemokines 
 Changes in circulating immunoglobulins 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
48 
 
 Free/Total receptor occupancy of CD47 and CD40 
Appearance of activation markers on the surface of CD4 lymphocytes and macrophages in 
the peripheral blood 
The anticipated timing of pharmacodynamic effects based on NHP studies is at cycle 1, day 15 
(C1D15) and beyond, although these effects may be observed as early as C1D1 and C1D8.    
3.3 
SL-172154 Dose Escalation Plan  
Dose escalation will begin on Schedule 1 at the starting dose of 0.1 milligrams per kilogram 
(mg/kg) as outlined in Table 1 below. Intermediate or higher dose levels not shown may be 
explored based on emerging data (e.g., safety and pharmacodynamic data).  Dose escalation of SL-
172154 will not exceed half-log increments. The DLT assessment period is 28 days in length and 
ends 14 days after the last dose is administered in the first cycle on Schedule 1 and 7 days after the 
last dose is administered on Schedule 2. Dose escalation will follow the mTPI-2 decision rules 
outlined in Table 7 in Section 9.1.   
 Schedule 1 administration for SL-172154: Given on days 1, 8, and 15 in cycle 1 over 28 
days and then every two weeks thereafter on days 1 and day 15 in cycles  2 every 28 days. 
 Schedule 2 administration for SL-172154: Given on days 1, 8, 15 and 22 of each 28-day 
cycle
 Cycle length for Schedules 1 and 2: 28 days 
 DLT assessment period for Schedules 1 and 2: 28 days  
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
49 
 
Table 1: SL-172154 Dose Escalation Plan in Phase 1
Dose Level
IV Dose of SL-172154 
(mg/kg)a,b,c,d,e
Duration of Infusiond 
Level 1 - starting dose 
0.1 
30 minutes (+/- 10 minutes)
Level 2
0.3
30 minutes (+/- 10 minutes)
Level 3 
1.0 
30 minutes(+/- 10 minutes) 
Level 4 
3.0 
60 minutes (+/- 15 minutes)
Level 5 
10.0 
60 minutes (+/- 15 minutes)
a)
Dosing will begin on Schedule 1 with SL-172154 administered in 28-day cycles on days 1, 8, and 15 in 
. 
b) 
Dose escalation on Schedule 2 may be tested: If Schedule 2 is opened, SL-172154 may be administered 
once weekly on days 1, 8, 15, and 22 of each 28-day cycle.  
c) 
Intermediate or higher dose levels may be tested based on emerging safety and pharmacodynamic data.  
d) 
The actual body in kilograms (kg) 
calculated for a subject weighing 100 kg (see Section 5.1.4). 
e) 
Infusion time may change based on final drug volume needed for administration, safety and tolerability of 
the infusion for the subject and/or observed safety findings during the study. Please refer to the Study 
Pharmacy Manual (SPM) for details. 
Evaluation 
of 
an 
Alternative 
Dosing 
Schedule: 
Safety, 
pharmacokinetic 
and/or
pharmacodynamic data from the dose escalation cohorts and pharmacodynamic cohorts, if 
available, may support exploration of a more or less intensive dosing schedule for SL-172154. If 
these data from Schedule 1 support exploration of more frequent dosing (see Section 3.2.1 for 
criteria needed to transition to Schedule 2), then cohort enrollment on Schedule 2 will be instituted 
in lieu of Schedule 1. The starting dose on Schedule 2 will be at a dose level that has completed 
evaluation for safety on Schedule 1 as defined by the mTPI-2 design. Dose escalation (or de-
escalation) may then proceed on schedule 2 as shown in Table 1. During dosing on Schedule 2, 
SL-172154 will be administered once weekly (D1, D8, D15, and D22) every 28 days. If less 
frequent dosing is supported by safety, pharmacokinetic and/or pharmacodynamic data, SL-
172154 may be administered once every two weeks, once every three weeks or once every four 
weeks. The starting dose on a less frequent schedule would be instituted at a dose level that has 
completed evaluation for safety as defined by the mTPI-2 design, emerging safety data and as 
recommended by the SMC. 
3.3.1 Intrasubject Dose Escalation 
Intrasubject dose escalation(s) may be considered on a case-by-case basis, provided that the subject 
has completed at least 2 cycles at the originally assigned dose, has tolerated treatment well, and 
experienced 
ity on the most recent cycle of SL-172154 therapy. A subject’s dose 
may be increased to a dose level that has completed evaluation for safety and has not exceeded the 
MTD. Approval for intrasubject dose escalation must be obtained from the Sponsor Medical 
Monitor and must be documented on an Intrasubject Dose Escalation Decision Form provided by 
the Sponsor.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
50 
 
3.4
Definition of Dose-Limiting Toxicity
DLTs are as defined in the bulleted points below. Toxicities will be graded as per National Cancer 
Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5).  The 
determinate period for DLT is the first 28 days of SL-172154 dosing on Schedule 1 or Schedule 2. 
Note: AEs clearly related to disease progression or intercurrent illness are not considered DLTs.  
Inflammatory reactions attributable to local anti-tumor responses (e.g., severe pain) are not 
considered DLTs. 
 Any death not clearly related to underlying disease or extraneous causes 
 Any 
Grade 4 AE 
 Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin: 
o 
AST or ALT el
or 
 
o 
or 
 
o 
crease 
on value at enrollment as described above. 
 Any AE that requires permanent discontinuation of SL-172154 
 Any Grade 3 or greater AE except for those listed below: 
o 
 
o Grade 3 anemia 
o Grade 3 or 4 neutropenia not associated with fever that improves to Grade 2 within 7 
days.   
o Grade 3 or 4 lymphopenia 
o Grade 3 thrombocytopenia not associated with clinically significant bleeding and does 
not require medical intervention 
o Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms 
and are reversed with appropriate medical intervention
o Grade 3 laboratory abnormalities that are not deemed clinically significant by the SMC.
o Indirect/unconjugated hyperbilirubinemia without significant clinical consequences 
o Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
signs/symptoms or findings on imaging consistent with pancreatitis
o Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate 
clinical management
o Grade 3 hypertension that can be controlled (i.e., systolic BP < 140 mmHg and diastolic 
BP < 90 mmHg) with medical therapy. 
o Grade 3 endocrine disorder (thyroid, pituitary, hyperglycemia and/or adrenal 
insufficiency) that is managed with treatment with resolution of symptoms within 14 
days after treatment onset. 
o Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with 
appropriate clinical management 
o Vitiligo or alopecia of any grade 
 Other AEs may be considered a DLT as determined by the investigator in conjunction with the 
SMC. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
51 
 
A 
(s) that occurs beyond the DLT period or Grade 2 events that require continuous 
interruption of SL-172154 for more than 6 weeks or AEs that result in subjects not receiving at 
least 2 of the 3 scheduled doses of SL-172154 on Schedule 1 (or at least 2 of the 4 scheduled doses 
of SL-172154 on Schedule 2) during the DLT assessment period due to AE(s) may be taken into 
consideration when assessing the totality of the data in determining DLT and the RP2D.   
3.5 
Concomitant Medications, Treatments, and Procedures 
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
supportive care except for prohibited medications (see Section 3.5.1).  Best supportive care should 
be provided when necessary for all subjects (including antibiotics, bisphosphonates, receptor 
activator of nuclear factor kappa B ligand (RANKL) inhibitors, nutritional support, correction of 
metabolic disorders, optimal symptom control, and pain management including palliative 
radiotherapy after consultation with the Sponsor Medical Monitor. 
Use of inhaled, topical, intranasal corticosteroids or local steroid injections (e.g., intra-articular 
injection) is permitted. Temporary use of corticosteroids (e.g., prior to computed tomography [CT] 
to prevent contrast allergies) is acceptable after consultation with the Sponsor Medical Monitor.  
3.5.1 Prohibited Medications/Treatments 
Subjects must be instructed not to take any medications, including over-the-counter products 
without first consulting with the investigator.  The following medications are prohibited during 
SL-172154 therapy: 
 Any investigational anti-cancer therapy not described in this protocol 
 Any concurrent chemotherapy, radiotherapy (except palliative radiotherapy after 
consultation with the Sponsor Medical Monitor), hormonal or hormonal suppression
therapy for anti-cancer intent, immunotherapy, or biologic therapy for cancer treatment   
 Immunosuppressive medications for primary prophylaxis against IRRs are not permitted. 
Subjects who require immunosuppressive medications (e.g., corticosteroids) for 
management of irAEs or IRRs should be managed per Toxicity Management Guidelines
in Section 3.6. 
 Live attenuated vaccines during the study through 30 days after the last dose of SL-172154 
3.5.2
Medications to be used with Caution 
SL-172154  is a therapeutic protein that may induce the transient release of cytokines including 
IL-6 which in turn, may inhibit the activity of cytochrome P450 (CYP450) enzymes including 
CYP3A4 activity [Evers, 2013].  Although not tested clinically, a drug-drug interaction may occur 
with the coadministration of medications that are CYP450 substrates. Drugs metabolized by 
CYP450 enzymes may have reduced clearance or an increase in half-life or peak plasma 
concentration and should be used with caution. There may be an increased risk of side effects for 
drugs that are CYP450 substrates. Where possible consider substitutions for these medicinal 
products if therapeutic effects cannot be monitored. 
A complete list of drugs that are CYP450 substrates including CYP3A4 substrates is available at: 
https://drug-interactions.medicine.iu.edu/Main-Table.aspx (Flockhart Table). 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
52 
 
3.6
Toxicity Management Guidelines Dosing Delays/Dose Modifications 
No dose reductions are permitted for SL-172154. The toxicity guidelines provided in this section 
represent general guidance for AEs that are considered by the investigator to be related to treatment 
with SL-172154. All AEs should be assessed using NCI-CTCAE v5.0 criteria. These guidelines 
are not meant to be prescriptive and investigators should always use clinical judgement in the 
determination of dosing. Investigators should always err on the side of caution if treatment-related 
toxicity is suspected. Subjects should be thoroughly evaluated to rule out any alternative etiology 
(e.g., disease progression, concomitant medications, and infections). In the absence of a clear 
alternative etiology, all events should be considered potentially immune related. 
Please see Section 5.1.5 Monitoring Dose Administration for further information on SL-172154.  
NOTE: Hereafter in this section and in subsequent sections, SL-172154 monotherapy may be 
referred to as SL-172154 or as IP.   
Differentiating between IRRs that are due to either the common non-allergic hypersensitivity 
reactions [HSRs (e.g., CRS)] or the rarer allergic HSRs can be challenging due to overlapping 
clinical manifestations. There are no specific clinical features (including symptoms and timing of 
reaction) that can absolutely distinguish between these two entities. General guidance is provided 
below for IRRs secondary to both allergic and non-allergic HSRs e.g., CRS. These guidelines are 
not meant to be prescriptive. Established institutional guidelines should be followed where 
appropriate. At the resolution of the event, the entirety of the data including clinical symptoms, 
response to treatment and laboratory studies should be re-evaluated to determine the final etiology 
of the event. For purposes of standardized reporting, utilize terms based on best medical judgement 
of the AE/SAE and the definition found in NCI-CTCAE v5.0 for IRR, allergic reaction, 
anaphylaxis, and CRS. 
Discretionary use of primary prophylaxis for IRR prevention for subjects enrolled at 3 mg/kg or 
less is permitted. However, as noted in Section 3.6.1, secondary prophylaxis (i.e., prevention of 
IRRs following an initial episode) for these subjects is appropriate and permitted at the discretion 
of the investigator for all dose levels. Primary prophylaxis for IRR prevention is required with 
each SL-172154 administration  for subjects enrolled at 10mg/kg or higher dose levels. See Section 
5.1.2.3 for details regarding the primary prophylaxis medications.  
NOTE:
-site or hospitalized for close 
observation until resolution of symptoms as per Table 3.6.1.


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
53
 
3.6.1
Management of Infusion-related Reactions
Adverse Event
General Guidance for Infusion-related Reactions (IRRs) [Rosello, 2017; Porter, 2018]
 
Infusion or 
Hypersensitivity 
Reactions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute reactions to the IV administration of biologic agents are not uncommon. Reactions are either allergic reactions to foreign proteins or non-immune reactions. The 
term HSR is used to describe objectively reproducible signs or symptoms initiated by exposure to a defined stimulus at dose tolerated by a normal person. Allergy is 
an HSR initiated by specific immunological mechanisms. Anaphylaxis is a severe, life threatening HSR. CRS consists of a non-allergic, cytokine mediated HSR.  
Differentiation between the common non-allergic HSR reactions and the rarer allergic HSR reactions can be challenging due to overlapping clinical manifestations. 
Fever, chills, rigors, headache, arthralgias, back pain, abdominal pain, nausea, vomiting, diarrhea, dyspnea, flushing, pruritus, and changes in heart rate and blood 
pressure are manifestations of common acute infusion reactions. Proinflammatory cytokines such as TNF-
-6 may play a role in these reactions. Symptoms 
more suggestive of allergic HSR include generalized pruritus, urticaria, wheezing, frequent coughing, and anaphylactic symptoms. Subjects must be monitored for 
signs and symptoms of IRRs with prompt institution of treatment.  Subjects should be notified that symptoms may occur during the first infusion and for up to several 
hours afterwards or with subsequent infusions. Instruct subjects to contact their physician if symptoms or signs of an IRR occur. 
Severity
(Symptoms) 
Management
Grade 1 
 Infusion interruption not indicated.  
 Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or until recovery from symptoms 
 Consider pre-medication (antipyretics, histamine (H1 and H2 antihistamines), leukotriene inhibitors, corticosteroids) for subsequent infusions per 
investigator/institutional guidelines if pre-medications are not already required.
Grade 2
Temporarily interrupt 
-172154 or decrease the rate of the infusion by 50%.
Begin IV infusion of normal saline and treat with antipyretics, histamine 1 and 2 (H1 and H2) antihistamines, and leukotriene inhibitor.  
Corticosteroids and/or bronchodilator therapy may also be administered as appropriate. Consider opioids (e.g., meperidine) for rigors. 
 Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or until recovery from symptoms. Consider 
admission to hospital. 
If the infusion is interrupted, then restart the infusion at no more than 50% of the rate at which the reaction symptoms occurred. For subsequent 
infusions, consider starting infusion at 50% rate at which the symptoms occurred and titrate to tolerance. 
 If symptoms recur, then no further 
-172154 will be administered at this visit. 
The following prophylactic pre-medications are recommended for future infusions: antipyretics, antihistamines with/without corticosteroids per 
institutional guidelines 
Grade 3
Immediately discontinue infusion of 
-172154 
Begin IV infusion of normal saline and treat with epinephrine, bronchodilators, diphenhydramine, ranitidine, corticosteroids, oxygen, fluids, 
vasopressors, etc. and consider opioids (e.g., meperidine) for rigors. as indicated and per institutional guidelines. Epinephrine is the drug of choice 
in an anaphylactic reaction and its administration should not be delayed. 
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or until recovery from symptoms. Consider 
admission to hospital. 
Rechallenge should not be attempted in cases of true anaphylaxis. In other cases, once subject has completely recovered, carefully consider if it is 
safe for the subject to receive 
-172154 at the next scheduled dose with pre-medication (e.g., corticosteroids, antihistamines, antipyretics) and 
 
-172154 (after an event of grade 3 event 
of infusion-related reaction) must be administered in an inpatient or outpatient setting with prolonged observation for a minimum of 12 hours after 
the completion of the infusion. Start infusion at 50% rate at which the symptoms occurred.  If no further symptoms, rate may be escalated at 
intervals and increments as clinically appropriate. If symptoms recur, permanently discontinue 
-172154.


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
54
 
 
Severity 
(Symptoms)
Management
Infusion or 
hypersensitivity 
reactions 
(continued from 
previous page) 
Grade 4 
 
 
Permanently discontinue 
-172154.
 Admit to hospital for close observation until resolution of symptoms 
 Manage severe IRRs per institutional standards (e.g., epinephrine, diphenhydramine, ranitidine, corticosteroids, bronchodilators, oxygen, fluids, 
etc. and consider opioids (e.g., meperidine) for rigors.  Epinephrine is the drug of choice in an anaphylactic reaction and its administration should 
not be delayed 
Adverse Event 
General Guidance for Cytokine Release Syndrome (CRS)  [Rosello, 2017; Porter, 2018] 
 
 
 
 
 
 
Cytokine-release 
Syndrome 
 
CRS is a non-antigen specific, systemic inflammatory response that occurs as result of high-level immune activation with concomitant elevations of cytokines (e.g., 
-
-10, TNF-
-2, IFN ). Clinical features of the syndrome include (but are not confined to) fever, flu-like symptoms, rash, nausea, vomiting, diarrhea, 
hypotension, tachypnea, transaminitis, hypofibrinogenemia, elevation in D-dimer, hyperbilirubinemia, azotemia, neurologic manifestations. The syndrome can 
progress to life-threatening capillary leak, hypoxic respiratory failure, vasodilatory shock and end-organ dysfunction. NOTE: CRS may have a similar presentation 
to a type 1 HSR and may be clinically indistinguishable. 
Severity 
(symptoms)
Management
Grade 1
 
-172154 by 50%, until resolution of the event
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or until recovery from symptoms.
 Maintain IV access. Symptomatic treatment with antipyretics, antiemetics, analgesics, histamine 1/histamine 2 (H1/H2) antihistamines as 
needed; monitor fluid balance; assess for infection. Consider opioids (e.g., meperidine) for rigors. Regularly evaluate for signs of further 
deterioration 
For subsequent infusions, consider pre-medication (e.g., antipyretics, antihistamines) per institutional guidelines
Grade 2
-172154 
Start IV infusion with normal saline. Administer oxygen if needed. Treat with antipyretics, H1/H2 antagonists (diphenhydramine 50 mg IV plus 
ranitidine 50 mg IV), and/or methylprednisolone 1-2 mg/kg or equivalent dose of corticosteroid every 6 hours and manage per institutional 
guidelines. Consider opioids (e.g., meperidine) for rigors. Closely monitor cardiac and other organ functions. 
 Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or until recovery from symptoms.
Consider admission to hospital for management of symptoms, organ dysfunction or administration of therapy
 
-172154 (after an event of grade 2 CRS) must be administered in an inpatient or outpatient setting with 
prolonged observation for a minimum of 12 hours after the completion of the infusion. 
 For subsequent infusions, start infusion at 50% rate at which the symptoms occurred and titrate to tolerance. Pre-medicate with dexamethasone 
20 mg, antipyretics, H1/H2 antihistamines, and manage per institutional guidelines. 
Subjects with extensive comorbidities or those of older age should be treated as for Grade 3.  Subjects with worsening symptoms should be 
treated as for Grade 3


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
55
 
 
 
Adverse Event 
Severity 
(Symptoms)
Management
 
Cytokine-release 
Syndrome 
(continued from 
previous page) 
Grade 3 or 4 
 
-172154
 Hospitalization required for management of symptoms related to organ dysfunction: admit to the hospital and potentially the intensive care unit 
or equivalent for close monitoring and management 
 Treat hypotension with IV fluid for blood pressure support and/or pressers.  Administer oxygen for treatment of hypoxia. Cryoprecipitate or fresh 
frozen plasma may be required for coagulopathy. Manage per institutional guidelines. 
 Manage severe IRRs and CRS per institutional standards (e.g., epinephrine, diphenhydramine, ranitidine, corticosteroids, bronchodilators, 
oxygen, fluids, meperidine for rigors, etc.).  Epinephrine is the drug of choice in an anaphylactic reaction and its administration should not be 
delayed 
 Administer tocilizumab at a dose of 8 mg/kg. If clinical improvement does not occur within 24 hours, administer a second dose of tocilizumab.  
 Second-line therapies:  
o 
Methylprednisolone 2 mg/kg/day IV tapered over several days. For subjects with severe neurologic symptoms, consider using 
dexamethasone due to more efficient penetration of the blood-brain barrier.   
o 
anti-TNF-
or soluble TNF-
-1R-based inhibitors (anakinra). 
 For Grade 3 CRS, may consider rechallenge after consultation with medical monitor. If rechallenge is given: 
o 
-172154 (after an event of grade 2 CRS) must be administered in an inpatient or outpatient 
setting with prolonged observation for a minimum of 12 hours after the completion of the infusion. 
o 
Start infusion at 50% rate at which the symptoms occurred.  If no further symptoms, rate may be escalated at intervals and increments 
as clinically appropriate. 
o 
-172154.  
o 
If there is no evidence of CRS with the subsequent infusion, premedication with high dose steroids may be omitted for subsequent 
infusions.  
o 
Any patient that experiences recurrence of Grade 3 CRS following re-treatment must be permanently discontinued from study 
treatment. 
-172154.


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
56
 
3.6.2
Management of Immune-related Reactions
Adverse Event
General Guidance for Management of Immune-related Adverse Events (irAEs) [Haanen, 2017; Puzanov, 2017; 
Brahmer, 2018]
irAEs - General 
 
 
Guidelines for management of irAEs across body systems are outlined in this section.  These guidelines are not meant to be prescriptive. Established institutional 
guidelines should be followed where appropriate. Severity of irAE are categorized according t
-172154 may either be continued, held or permanently discontinued.  
Management relies heavily on corticosteroids and other immunomodulatory agents.  Generally, the decision on IP and institution of immunosuppressive therapy 
(corticosteroid therapy) can be approached as noted below.  However, treatment should be individualized depending on the subject’s medical history, the nature 
and severity of the AE, co-morbidities, and ability to tolerate corticosteroids.  When starting corticosteroid therapy, consider initiating proton pump inhibitors for 
gastrointestinal (GI) toxicity prophylaxis.  Once toxicity has improved t
-week period. Add 
pneumocystis pneumonia prophylaxis (cotrimoxazole or inhaled pentamidine if cotrimoxazole allergy) if more than 3 weeks of immunosuppression expected (>30 
mg prednisone or equivalent).  Consider calcium & vitamin D supplementation as per local guidelines.
Severity (Symptoms) 
Management
Grade 1
-172154 is continued, and treatment with corticosteroids is usually not indicated
Grade 2
 
-172154 may be continued. 
 Depending on the nature of the AE, corticosteroids may be indicated.  
 Start with oral prednisone 0.5-
-172154 is generally held during corticosteroid therapy and until irAE has resolved 
 
If IV therapy is required, use methylprednisolone 0.5 – 1 mg/kg/day.  If no improvement in symptoms, the dose may be increased 
to 2 mg/kg/day.   
Grade 3
-172154.  
Start prednisone 1-2 mg/kg/day (or equivalent dose of methylprednisolone).  
If no improvement, consider adding alternative immune suppressant therapy.
Grade 4
-172154 and start IV methylprednisolone 1-2 mg/kg/day.  
If no improvement, consider adding alternative immunosuppressant.
 
 
 


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
57
 
Adverse Event 
General Guidance for Hepatotoxicity 
 
 
 
 
 
 
 
 
 
Hepatotoxicity 
 
 
 
 
 
 
Monitor signs, symptoms and laboratory evidence of liver dysfunction.  Evaluate alternative etiologies: review medications for hepatotoxic drugs and alcohol 
history; perform liver screen: hepatitis A, B, C serology, hepatitis E PCR, antinuclear antibody (ANA)/smooth muscle antibody/liver kidney microsomal antibodies 
/soluble liver antibody/liver-pancreas antigen/liver cytosol iatrogene antibodies, iron studies. Consider imaging for progressive disease/thrombosis.  Guidelines 
TCAEv5. Discontinue 
-172154 
 
Severity (Symptoms) 
Management 
Grade 1
-172154 with close monitoring. 
Monitor liver function at least weekly; if liver function is stable, reduce frequency of blood tests. 
Grade 2
-172154.  
 Assessments as above; monitor liver function ~every 3 days 
 Consider hepatology consult and liver biopsy is optional.  
 If persistent or rising liver chemistries or significant clinical symptoms and an immune etiology is suspected, start oral prednisone 
0.5-1 mg/kg/day (or equivalent of methylprednisolone) with 4-week taper. 
-
ivalent.  
Grade 3 
-172154. 
 
-172154 for liver function test abnormality that meets following criteria in subjects who enroll with 
or 
 
 Permanently discontinue 
-172154 for liver function test abnormality that meets following criteria in subjects who enroll with 
or total bilirubin > 5 x baseline.   
 If persistent or rising liver chemistries, or significant clinical symptoms and an immune etiology is suspected, start oral prednisone 
0.5-1 mg/kg/day (or equivalent of methylprednisolone) with 4-week taper. Obtain hepatology consult and assessments as above, 
monitor liver function daily; consider liver biopsy. 
Other Grade 3 laboratory abnormalities: re-challenge may be considered only after consultation with hepatologist. 
Grade 4
-172154.
Consider hospitalization; obtain hepatology consult; assessments as above; monitor liver function daily; consider liver biopsy.  
 If an immune etiology is suspected, immediately start methylprednisolone 1-2 mg/kg (start with 2 mg/kg for Grade 4) or equivalent. 
If refractory after 3 days, consider mycophenolate mofetil (MMF). Avoid the use of infliximab in immune mediated hepatitis.
 
 


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
58
 
Adverse Event
General Guidance for Hematologic Toxicity
Anemia 
Subjects with cancer can have multiple causes of cytopenias and thus blood counts must
-172154 does exhibit binding to white blood 
cells (WBCs), red blood cells (RBCs) and platelets in non-human primate studies, but there was no evidence of neutropenia, anemia, hemagglutination, RBC 
destruction or clinically significant thrombocytopenia. However, in the event of anemia, it is important to use physical exams, complete blood counts (CBCs), 
serum chemistries, D-dimer testing and review of peripheral smears to look for evidence of RBC agglutination, microangiopathy, spherocytosis, and evidence 
of RBC destruction (e.g., schistocytosis, fragments).  A hematologic AE needs to be distinguished from transient changes in laboratory values that can occur 
during initiation of an immune response (e.g., lymphopenia, lymphocytosis, eosinophilia, neutrophilia, monocytosis can be observed following treatment). 
Development of persistent or progressive cytopenias should prompt evaluation of potential causes. In cases where an obvious cause cannot be identified, an 
autoimmune cause should be considered and investigated accordingly. Since the CTCAE definition of thrombocytopenia describes absolute platelet levels rather 
than a change in cell number, it is not a reliable tool for evaluating potentially life-threatening cytopenias. Drug binding to CD47 on RBCs may result in interference 
with standard serologic techniques for blood compatibility testing (Section 6.4.6.3).
Severity (Symptoms)
Management
Grade 1 
-172154 with close clinical follow-up and laboratory evaluation
Grade 2
Consider holding 
-172154 until AE has reverted to Grade 1 or baseline.  
Consider hematology consult
 Repeat type and screen and DAT  
 Transfusion per existing guidelines (minimum number of units to relieve symptoms of anemia or to return subject to safe 
hemoglobin (Hgb) range), folic acid supplementation. 
Grade 3 
-172154 until AE has reverted to Grade 1 or baseline.  
Repeat type and screen and DAT
Hematology consult, consider hospitalization, transfusion per existing guidelines (minimum number of units to relieve symptoms of 
anemia or to return subject to safe Hgb range), folic acid supplementation.
Grade 4
-172154. 
If evidence of an immune-mediated etiology, give prednisone 1-2 mg/kg/day; if no improvement on or if worsening on 
corticosteroids or severe symptoms on presentation, initiate other immunosuppressive drugs, such as rituximab, IVIG, 
cyclosporine, infliximab, MMF, anti-thymocyte globulin. 
Hospitalize; hematology consult; transfuse per existing guidelines.
Thrombocytopenia
Severity (Symptoms)
Management
Grade 1
-172154 with close clinical follow-up and laboratory evaluation.
Grade 2
Consider holding
-172154 until AE has reverted to Grade 1 or baseline. 
Consider Hematology Consult


CONFIDENTIAL 
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
59
 
Thrombocytopenia 
(continued from 
previous page) 
Severity (Symptoms) 
Management 
Grade 3 or 4 
Hold 
-172154 until AE has reverted to Grade 1 or baseline. 
Hematology consult.
 If evidence of an immune-mediated etiology, give prednisone 1-2 mg/kg/day or equivalent.   
 IVIG 1 g/kg may be used with corticosteroids when a more rapid increase in platelet count is required.  This dosage may be 
repeated if necessary.  
 If treatment with corticosteroids and/or IVIG has been unsuccessful, subsequent treatment may include rituximab, 
thrombopoietin receptor agonists, or more potent immunosuppression
 
 
 
 
3.6.3 Management of Other AEs Not Specified
Severity (Symptoms)
Dose Modification
Toxicity Management
Any Grade 
Note: Dose modifications are not required for AEs not deemed to be related to 
-172154 
(i.e., events due to underlying disease) or for laboratory abnormalities not deemed to be 
clinically significant. 
Treat accordingly, as per institutional standard
Grade 1
No dose modifications 
 Treat accordingly, as per institutional standard 
Grade 2
Consider holding 
-172154 
Treat accordingly, as per institutional standard
Grade 3
Hold 
-172154 
14 days, resume 
-172154. Otherwise, discontinue 
-172154.  
(Note: For Grade 3 labs, decision to hold should be based on accompanying clinical 
signs/symptoms, the Investigator’s clinical judgment, and consultation with the Sponsor).
Treat accordingly, as per institutional standard
 
Grade 4
Discontinue 
-172154.
(Note: For Grade 4 labs, decision to discontinue should be based on accompanying clinical 
signs/symptoms, the Investigator’s clinical judgment, and consultation with the Sponsor).
Treat accordingly, as per institutional standard
 
(Reference: American Society of Clinical Oncology Educational Book 2015 “Managing Immune Checkpoint Blocking Antibody Side Effects” by Michael Postow MD.)


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
60 
 
3.7
Discontinuation of Study Therapy 
SL-172154 should be discontinued by the investigator when a subject meets one of the conditions 
requiring discontinuation outlined in Section 3.6. The investigator may, however, elect to 
discontinue SL-172154 for an AE, laboratory abnormality, or intercurrent illness which, in the 
judgment of the investigator, presents substantial clinical risk to the subject with continued dosing. 
If study therapy is permanently discontinued for reasons other than progressive disease or 
withdrawal of consent, the subject will remain in the study to be evaluated for disease progression.  
See the SOA in Section 6 for data to be collected at the time of discontinuation of SL-172154.   
3.8 
Antibody Detection and Compatibility Testing for Transfusion   
SL-172154 binds to red cells and may obscure the assessment of ABO red blood cell phenotyping. 
There is also a possibility that treatment with SL-172154 may interfere with compatibility tests, 
including the antibody screen and crossmatch that are part of a routine pre-transfusion work up  
[Report_SL2020IB001].  
At screening, before exposure to SL-172154, all subjects must have: 
 ABO and D group (ABO/Rh) type and antibody screen and antibody identification if 
required 
 Direct antiglobulin test (DAT) 
 Phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and 
MNSs.  
 Inform the blood bank that the subject is to commence SL-172154. 
 
Determining this extended RBC phenotype prior to exposure to SL-172154 will facilitate and 
allow the option of selecting extended antigen-matched RBCs should a blood transfusion be 
warranted, and compatibility not be able to be demonstrated due to drug interference.  
After exposure to SL-172154: 
In subjects who may/do require RBC transfusion after SL-172154 therapy has commenced, it is 
recommended that an ABO/D type, antibody screen, and auto control and/or DAT be performed 
as per routine testing methods.   
Following guidance of the local Transfusion Service Medical Director (or equivalent person) and 
the Transfusion Service standard operating procedures the following considerations may apply if 
interference with testing is seen: 
 If the ABO group cannot be concluded from the forward and reverse typing, a decision 
may be made to transfuse based on the RBC ABO forward type only, provided it is 
concordant with the ABO record pre-therapy, or alternatively group O red cells may be 
used for transfusion. 
 Differential adsorption may allow valid reverse type and antibody screening. 
 Performing an eluate on a DAT+ sample should follow local standard operation procedure. 
 For emergency transfusions, the transfusion laboratory may consider using Group O or 
ABO type specific units if time permits, without consideration of extended phenotype if 
units are not available.


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
61 
 
 For elective red cell transfusions when the crossmatch is incompatible, leukocyte-reduced 
units matched for the extended phenotype of the patient (as described above) will be used, 
i.e. the patient will receive units negative for the antigens that he/she lacks.  
 Where matching for all specified blood groups is not possible (e.g., for MNS), local sites 
will decide on the best matched donor units to be used.  
Plasma therapy will be blood-type specific. Platelets will be blood type compatible
whenever possible, and if not, will have been tested and found not to have high titer anti-A or
anti-B. 
3.9
Criteria to Resume Treatment
A participant may resume SL-172154 as outlined in Section 3.6.  If the criteria to resume treatment 
are met, the subject should restart treatment at the next scheduled time point per protocol.    
3.10 
Participant Withdrawal of Consent 
 A participant may withdraw from the study at any time at his/her own request; or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. 
 At the time of withdrawal of consent, an early discontinuation visit should be conducted, 
as shown in the SOA in Section 6. See SOA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The participant will be permanently discontinued both from the IP and from the study at 
that time.  Every effort must be made to continue follow-up of participants for protocol-
specified safety follow-up procedures to capture AEs, SAEs, and unanticipated problems 
(UPs). 
 If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
 If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
3.11
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
o
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 
o
Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter sent to the participant’s last known mailing 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
62 
 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record.
o Should the participant continue to be unreachable, he/she will be considered as lost 
to follow up and withdrawn from the study. 
3.12
Premature Termination or Suspension of Study
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason. Written notification, documenting the reason for study suspension or termination, will be 
provided by the Sponsor to investigators, the Food and Drug Administration (FDA) and the
European Medicines Agency and other regulatory authorities. If the study is prematurely 
terminated or suspended, the investigator will promptly inform the Institutional Review 
Board/Institutional Ethics Committee (IRB/IEC) and will provide the reason(s) for the termination 
or suspension.  Study sites will be closed upon study completion. A study site is considered closed 
when all required documents and study supplies have been collected or destroyed and a study-site 
closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are not 
limited to: 
 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor's procedures, or GCP guidelines 
 
Inadequate recruitment of participants by the investigator 
 
Discontinuation of further development of the IP 
 
Determination of unexpected, significant, or unacceptable risk to participants  
3.13 
Duration of Treatment 
The planned treatment duration with IP is for a maximum of two years. In the absence of treatment 
delays due to AE(s), treatment may continue until two years or until one of the following criteria 
applies: 
 
Disease progression per RECIST v1.1 NOTE: See Section 8.2 for criteria allowing 
for continuing treatment past initial progression. 
 
Death 
 
Intercurrent illness that prevents further administration of treatment 
 
Unacceptable AE(s) 
 
Participant decides to withdraw from the study 
 
General or specific changes in the participant's condition that render the participant 
unacceptable for further treatment in the judgment of the investigator 
 
Participant non-compliance 
 
Pregnancy 
 
Termination of the study by Sponsor 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
63 
 
All women of childbearing potential should be instructed to contact the investigator immediately 
if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during 
study participation.  The investigator should immediately notify PrimeVigilance upon knowledge 
of pregnancy (Section 7.5). 
Subjects with confirmed CR may elect to discontinue treatment after a minimum of 48 weeks of 
treatment and continue with all relevant study assessments including disease assessments until 
disease progression or start of another anticancer therapy.  
Subjects may be eligible for treatment past progression if they meet criteria as outlined in Section 
8.2.   
Impact of formation of ADA on clinical efficacy (non-response or loss of response to the IP) and 
safety (product specific immunogenicity risk) will be evaluated on an on-going basis.  If a subject 
develops ADA, the Sponsor and investigator may take into consideration these factors in assessing 
the duration of the therapy.   
3.14
Duration of Follow-Up 
Subjects who are withdrawn from study for unacceptable AE(s) will be followed until resolution 
or stabilization of the AE.  Participants who permanently discontinue IP for reasons other than 
progression will continue with disease assessments until progression or start of another anti-cancer
therapy.  Participants who discontinue IP for any reason other than withdrawal of consent will be 
followed for survival for approximately 18 months post treatment discontinuation or until death or 
the end of the study, whichever occurs first. During survival follow-up, the date of the first 
anticancer therapy will also be collected.  
3.15
End of Study Definition 
End of Study is defined as approximately 2 years after the last subject is dosed on cycle 1, day 1 
(C1D1) or the date the study is closed by the sponsor, whichever occurs first. 
4. 
STUDY POPULATION  
Participants may be considered for enrollment in the study if they meet all the eligibility criteria 
stated in Sections 4.1 and 4.2.  Prospective approval of protocol deviations to recruitment and 
enrollment criteria, also known as protocol waivers or exemptions, is not permitted.   
4.1
Participant Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply. 
1. Subject has voluntarily agreed to participate by giving written informed consent in 
accordance with ICH/GCP guidelines and applicable local regulations. 
2. Subject must have a histologically confirmed diagnosis of an unresectable, locally 
advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube 
cancer. 
3. Subjects must be refractory or intolerant to existing therapy(ies) known to provide clinical 
benefit for their condition. Subject must have received platinum-based therapies, and 
should not be eligible for further platinum therapy, or should be intolerant to such therapy. 
Subjects with known HRD positive disease may participate if they have received prior 




CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
65 
 
12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless 
there is excessive risk as determined by the investigator. 
4.2
Participant Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Prior treatment with an anti-CD47 or anti-SIRP  targeting agent or a CD40 agonist. 
2. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of 
SL-172154. 
Therapy 
Washout period 
Chemotherapy 
3 weeks
Hormonal therapy
3 weeks 
PD-1/L1 inhibitor and other immunotherapies not otherwise 
specified 
3 weeks 
Tumor vaccine 
4 weeks 
Cell-based therapy 
8 weeks 
Other mAbs or biologic therapies
3 weeks 
Other investigational agents not covered above 
4 weeks or 5 half-lives 
whichever is shorter
Major surgery 
2 weeks 
Radiation (except palliative intent which does not require 
washout) 
2 weeks  
3. Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression 
therapy for cancer treatment is prohibited.  Concurrent use of hormones for non-cancer 
related conditions is acceptable.   
4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days 
of D1 of SL-172154 treatment with the following exceptions (i.e., the following are 
allowed with or within 14 days of D1 of IP): 
o Topical, intranasal, inhaled, ocular, intraarticular corticosteroids 
o Physiological doses of replacement steroid (e.g., for adrenal insufficiency) not to 
exceed 10 mg/day of prednisone or equivalent 
o Steroid premedication for reaction to IV contrast 
5. Receipt of live attenuated vaccine within 28 days of D1 of IP. 
6. Active or documented history of autoimmune disease. Exceptions include controlled Type 
I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.  
7. Hypersensitivity to the active drug substance or to any of the excipients for the agent to be 
administered or subjects with known hypersensitivity to Chinese hamster ovary cell 
products. 
8. Active pneumonitis (i.e., drug-induced, idiopathic pulmonary fibrosis, radiation-induced, 
etc.).   


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
66 
 
9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of 
infection within 5 days of D1 of IP). 
10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious 
gastrointestinal disease associated with diarrhea within 6 months of D1 of IP. 
11. Clinically significant or uncontrolled cardiac/thromboembolic disease including any of the 
following: 
o Myocarditis 
o Unstable angina within 6 months from D1 of IP 
o Acute myocardial infarction within 6 months from D1 of IP  
o Uncontrolled hypertension 
o New York Heart Association Class II, III or IV congestive heart failure 
o Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular 
tachycardia, second- or third- degree atrioventricular block without a pacemaker, 
circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that is 
not stabilized on therapy) 
o Clinically symptomatic thromboembolism on stable anticoagulation for less than 
three months 
12. Untreated central nervous system or leptomeningeal metastases. Subjects with treated 
central nervous system metastases must have completed definitive treatment (radiotherapy 
 of IP and no longer require steroids.  
13. Women who are breast feeding. 
14. Psychiatric illness/social circumstances that would limit compliance with study 
requirements and substantially increase the risk of AEs or compromised ability to provide 
written informed consent. 
15. Another malignancy that requires active therapy and that in the opinion of the investigator 
and Sponsor would interfere with monitoring of radiologic assessments of response to IP.  
16. Has undergone allogeneic stem cell transplantation or organ transplantation. 
17. Known history or positive test for human immunodeficiency virus, or positive test for 
hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; 
if HCV antibody (Ab) test is positive check for HCV ribonucleic acid [RNA]).  
(NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody positive, but 
HBsAg negative are eligible for enrollment. HCV: Subjects who are HCV Ab positive, but 
HCV ribonucleic acid (RNA) negative are eligible for enrollment). 
4.3 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently treated in the study.  A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities.  




CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
68
5.1.2
Preparation/Handling/Administration/Storage of SL-172154/Investigational 
Product
Preparation
Standard aseptic technique including preparation of doses in a laminar flow hood is required.  
SL-172154 solution, 10 mg/mL, is supplied as a frozen liquid.  Before use, thaw each vial of SL-
172154 solution, 10 mg/mL, overnight under refrigerated conditions, protected from light, or at 
room temperature, until completely thawed.  Following thawing, gently swirl the vial to ensure 
uniformity. Only sterile normal saline (0.9%) should be used to dilute SL-172154. See the SPM 
for further details on the preparation of SL-172154. 
Handling
Under normal conditions of handling and administration, IP is not expected to pose significant 
safety risks to site staff.  A Safety Data Sheet (describing the occupational hazards and
recommended handling precautions) will be provided to site staff if required by local laws or will 
otherwise be available from the Sponsor upon request. 
In the case of unintentional occupational exposure notify the Sponsor and consult the SPM. 
Refer to the SPM for detailed procedures for the disposal and/or return of unused IP. 
Administration
Doses of SL-172154 are to be administered as an IV infusion via an infusion pump or syringe 
pump that can ensure precision within at least 0.1 mL/min. DO NOT USE an in-line filter for 
administration of SL-172154.  
Premedication for IRR prophylaxis is required with each 10mg/kg or higher dose and is at the 
investigator’s discretion for doses less than 10mg/kg. The following premedication is to be 
administered approximately 30 minutes prior to the start of each SL-172154 administration:  
acetaminophen (650 to 1000 mg PO)
diphenhydramine (25-50 mg, or equivalent, PO or IV)
ranitidine (50 mg IV or equivalent).
Infusion rate: The duration of infusion stipulated for each dose is outlined in Table 1: SL-172154 
Dose Escalation Plan in Section 3.3.  
NOTE: A physician must be present at the site or immediately available to respond to emergencies 
during all administrations of IP.  A fully functional resuscitation facility must be available. IP
must not be administered via IV push or bolus but as an IV infusion using an infusion or syringe
pump.  
Storage 
SL-172154 must be stored in a secure area under the appropriate physical conditions for the 
product.  Access to and administration of SL-172154 drug product will be limited to the 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
69 
 
investigator and authorized site staff.  SL-172154 must be dispensed or administered only to 
subjects enrolled in the study and in accordance with the protocol.   
SL-172154 drug product vials are to be stored frozen at a temperature minus (-) 60 C (-60 C to 
-90 C).  Maintenance of a temperature log is required. The drug product should be stored protected
from light.
The expiry date will be on the single vial carton label, if required. 
5.1.3 Investigational Product Accountability 
In accordance with local regulatory requirements, the investigator or designated site staff must 
document the amount of IP dispensed and/or administered to study subjects, relevant dates, 
dilution amounts, SL-172154 lot or batch numbers as on the label, and the amount received from 
the Sponsor, when applicable.  Product accountability records must be maintained throughout the 
course of the study.  Refer to the SPM for further detailed instructions on product accountability. 
5.1.4 Dosing and Change in Weight 
The actual body weight in kg will be used for SL-172154 dose calculation in all subjects whose 
body weight
 is 
should be the same as that calculated for a subject weighing 100 kg.  The subject should be dosed 
according to their C1D1 weight throughout the study (mg/kg) if there is no significant change in 
their weight from the weight recorded at the C1D1 visit.  A change in weight (i.e., increase or 
decrease) of the subject by 10% OR greater will require re-calculation of dose (mg/kg).  
per the institutional standard but no less precise than rounded to a 
whole number prior to calculating the dose to be administered (e.g., 72.5 kg should be rounded up 
to 73 kg, 72.4 kg should be rounded down to 72 kg). 
5.1.5 Monitoring Dose Administration  
SL-172154 must be administered in an outpatient oncology treatment center or inpatient unit to 
enable close monitoring of subjects and proactive management of AEs. The risks associated with 
administration of SL-172154 include infusion reactions and cytokine release syndrome as 
mentioned in Section 3.6. Therefore, appropriate drugs and medical equipment to treat acute HSRs 
and monitoring and management of CRS must be immediately available, and study personnel must 
be trained to recognize and treat these toxicities.  Subjects will be monitored prior to, during, and 
after infusion of SL-172154.  Vital signs will be measured as outlined in the SOA in Section 6 and 
as needed.   
5.1.6 Treatment of Investigational Product Overdose 
In the event of an overdose (defined as administration of a dose and/or schedule greater than the 
dose and/or schedule that had been studied to date) of SL-172154, the investigator should: 
 Contact the Sponsor immediately 
 Closely monitor the subject for AEs/SAEs and laboratory abnormalities for at least 2 weeks 
following the infusion. The appropriate AE management guideline should be followed 
(Section 3.6). Pharmacologic effect could persist even after the IP is no longer detectable 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
70 
 
in the serum.  Subject should have recovered from toxicities that occurred because of the 
excess dose before the next scheduled dose is administered. 
 Obtain a serum sample for PK analysis within 24 hours of the event if requested by the 
Sponsor (determined on a case-by-case basis)
 Document the quantity of the excess dose as well as the duration of the overdosing in the 
electronic case report form (eCRF)
 If a SAE related to overdose of the IP occurs, it should be documented and reported 
accordingly (Section 7.4) 
Decisions regarding dose interruptions for overdose of IP will be made by the investigator in 
consultation with the Sponsor Medical Monitor based on the clinical evaluation of the subject. 
5.2
Drug Accountability and Treatment Compliance 
The investigator or designee is responsible for keeping accurate records of all study drug supplies 
received from the Sponsor, the amount of SL-172154 dispensed for administration to the subjects 
and the amount of unused or partially used drug remaining at the conclusion of the trial. An 
accurate and current accounting of IP administered to each subject must be maintained on an 
ongoing basis by a member of the study site staff in the Drug Accountability Record.  Treatment 
compliance will be monitored by drug accountability as well as the subject’s medical record and 
eCRF. 
Handling and Disposal: Local requirements for disposal of hazardous drugs should be followed 
at each participating clinical site. It is the Investigator’s responsibility to arrange for disposal of all 
partially used or empty containers, provided that procedures for proper disposal have been 
established according to applicable federal, state, local and institutional guidelines and procedures, 
and provided that appropriate records of disposal are kept.  
Prior to the return or destruction of IP, the Sponsor Study Monitor must have performed a complete 
reconciliation of all drugs ensuring accountability records are complete and accurate and are 
retained in the Investigator Site file or pharmacy file. IP that is returned to the IP supplier or 
destroyed on site must be documented in the accountability documentation.  Arrangements for the 
return of SL-172154 will be made by the responsible Study Monitor. 
Refer to the SPM for SL-172154 for further instructions on requirements for the IP under study. 
6.
STUDY ASSESSMENTS AND PROCEDURES  
 Study procedures and their timing are summarized in the SOA. Protocol waivers or exemptions 
are not allowed. 
 Assessments throughout the study are calendar based starting from the first day of dosing (day 
1) in the first treatment cycle. Dose interruptions should not alter the assessment schedule for 
any subsequent treatment period. 
 Adherence to the study design requirements, including those specified in the SOA, is essential 
and required for study conduct. 
 All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 
all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable.


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
71 
 
 Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
count) and obtained before signing of the informed consent (ICF) may be utilized for screening 
or baseline purposes provided the procedures met the protocol-specified criteria and were 
performed within the timeframe defined in the SOA. 
 Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the subject should continue or discontinue SL-172154. 






CONFIDENTIAL 
 
 
 
 
 
SL03-OHD-101 
Compound: SL-172154 
 
 
 
 
 
Version no: 6.0  
74 
f.
Hematology/Clinical Chemistry/Haptoglobin/Ferritin/C reactive protein: will be performed at local laboratories according to the laboratory’s normal 
procedures.  See Section 6.4.6 for list of laboratory test required. 
 
g. Coagulation Tests: prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen, d-dimer will be 
performed at local laboratories according to the laboratory’s normal procedures. 
h. Blood phenotyping (ABO/Rh), and DAT: These tests should be performed at local laboratories according to the laboratory’s normal procedures. 
1) At screening: The following testing should be performed 1) ABO and D group (ABO/Rh) type and antibody screen and antibody identification if required; 2) 
DAT; 3) Phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and MNSs.  
2)
C1/D2: only need to perform blood phenotyping (ABO/Rh) and DAT.
i. 
Thyroid Function Test: Thyroid stimulating hormone (TSH), and free thyroxine 4 (T4) tests will be performed at local laboratories according to the 
laboratory’s normal procedures. 
j. 
Antiviral Testing: Please see exclusion criterion 17 in Section 4.2. These tests will be performed at local laboratories according to the laboratory’s normal 
procedures. 
k. Cardiac Assessments (obtain within 28 days of first dose): 1) Electrocardiagram (ECG):  12-lead ECG reading must be performed at screening to serve 
as a baseline for comparison in the event of a cardiac AE/SAE. 2) ECHO: An ECHO must be performed at screening to serve as a baseline for comparison 
in the event of a cardiac AE/SAE. 
l.
Tumor Assessment and CA-125: Tumor assessments are required for all subjects within 28 days prior to the first dose of SL-172154. CA-125 should also 
be obtained at screening within 21 days of first dose of SL-172154. Baseline and on-treatment tumor assessments for all tumor types by RECIST v1.1 and 
iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan, positron emission 
tomography (PET)/CT, and/or MRI should be performed only if clinically indicated.  Please refer to Section 8 for requirements regarding disease assessment. 
Tumor assessments must be performed at screening and at the following intervals until disease progression: approximately every 8 weeks through week 24 
(e.g., C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 22, 25, 28 and 31), and then every 24 weeks (prior to cycles 37, cycle 
43, etc.) up to conclusion of the study. Confirmatory scans should be performed at least 4 
after initial documentation of an objective 
response or progressive disease. Subjects who discontinue study treatment for reasons other than disease progression (e.g., AE or withdrawal of consent) will 
be monitored for radiologic response until start of another anti-cancer therapy, or disease progression, withdrawal of consent or death. CA-125 should be 
measured to coincide with each scheduled tumor assessment as outlined above with the last required sample for CA-125 obtained at the post treatment visit 
which occurs within 30 days of the last dose of SL-172154. 
m. PK/immunogenicity (i.e., ADA), cytokines and SL-172154 binding to red blood cells (RBCs): Blood sample collection timings for PK, ADA, cytokines 
and measurement of RBC binding are outlined in Section 6.1.1 in supplementary Tables 2, 3, 4 and 5.  PK/ADA/cytokine/RBC binding sample collection 
times on C1D1 through 48 hours postdose are provided in Table 2. PK/ADA/cytokine/RBC binding sample collection times in C2D1, C2D2, C2D15 and 
C2D16 are detailed in Table 4. PK/ADA sample collection times in C1D8 and cycles 3 and beyond are outlined in Table 3 and  Table 5, respectively. Blood 
volumes required are provided in the SLM. PK, ADA, cytokine and RBC binding samples should not be collected from infusion port for drug 
delivery i.e., recommend having a separate line in the opposite arm for sample collection.  
1) If subject has positive ADA test on D1 of cycle 13 or ADA results are not known, then follow up predose samples for PK/ADA should be collected 
every 3 cycles on D1 of subsequent treatment cycles (i.e., cycles 16, 19, 21 and 24) until ADA resolves to baseline OR until the last PK/ADA 
sample is collected within 105-125 days after the last dose of SL-172154. 
2) A PK/ADA sample is collected within 7 to 30 days after the subject discontinues SL-172154 therapy.   


CONFIDENTIAL 
 
 
 
 
 
SL03-OHD-101 
Compound: SL-172154 
 
 
 
 
 
Version no: 6.0  
75 
3)
If subject has positive ADA tests during treatment or ADA results are not known a final PK/ADA sample is collected within 105-125 days after 
the last dose of SL-172154.  
4) Cytokines will be collected in cycle 2 on days 15 and 16 as depicted in Table 4 and on day 1 of cycle 3 as depicted in Table 5. 
n. Correlative laboratory studies:  Refer to supplementary Table 6 for details in Section 6.1.2 plus see the SLM for amount of blood needed and sample 
shipment details. 
 
Complement, Immunophenotyping and Receptor Occupancy  
o. SL-172154 administration: Subjects with confirmed CR who have had a minimum of 48 weeks of treatment may elect to discontinue SL-172154 and 
continue with all relevant study assessments including disease assessments. SL-172154 should be administered on D1, D8, and D15 according to the 
prescribed dosing schedule without deviation in cycle 1 to align with the safety DLT assessment and sample (PK, ADA, etc.) collection schedules. 
Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing days for drug administration.    
p. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of SL-172154. After a subject is 
discontinued from SL-172154 or study therapy due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or 
return to baseline) and documented in the eCRF. If another anti-cancer agent is started within 90 days after the last dose of SL-172154, only SAEs and AEs 
that occur prior to the start of the new anticancer therapy should be recorded.  In the event of a continuing SAE or a non-serious irAE, the subject will be 
asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing indefinitely. AEs will be characterized per NCI-CTCAE 
criteria v5.0 and events recorded in the eCRF.  
 
Ad hoc blood samples for clinical safety labs should be collected for SAE related to IRR or CRS events as noted in Section 6.4.6.1 and the SLM. 
q. Archival tumor tissue (from a recent biopsy): Archival tissue, if available, will be collected from all subjects. If an inadequate amount of archived tissue 
is available, the subject may still participate in the study if they meet eligibility criteria for the study. Moreover, archival tissue may be accepted in lieu of 
the pre-treatment tumor biopsy if the subject has not undergone treatment since time of specimen collection and if the sample was collected via core needle 
biopsy. Please notify the sponsor if archival tissue will be used in lieu of a pre-treatment fresh biopsy Provide formalin-fixed-paraffin-embedded (FFPE) 
tissue on slides (recommended minimum of 10 slides) or a block of FFPE tissue (the latter is preferred). Refer to Section 6.7.2.2 and the SLM for details.  
r.
Tumor Biopsy: Paired biopsies are required (pre- and on-treatment) obtained in subjects who have tumor accessible to core-needle biopsy and there is an 
acceptable level of risk as per investigator assessment.  Biopsies will be obtained at baseline (to evaluate the immune status of the tumor before SL-172154 
treatment) and following the first dose in cycle 2 on or between D2-D6 of cycle 2. In the event that a biopsy cannot be performed at cycle 2, please contact 
the medical monitor to discuss obtaining an on-treatment biopsy following the first dose on or between D2-D6 of a subsequent cycle. Biopsy at the time of 
progressive disease will be optional.  Please refer to Section 6.7.2.1 and SLM for details regarding biopsy. 
s.
Homologous recombinant deficiency (HRD) status: Collection of HRD status (including BRCA status) is requested for all subjects during the screening 
period. Results from standard of care testing should be used. An HRD status that is unknown, not done, or unavailable at baseline will not preclude the 
subject from study participation.  
t. 
Post-Treatment: A Post-Treatment visit will be conducted within 30 days (±3 days) after the last dose of SL-172154, or prior to the start of a new therapy, 
or at the end of study, or if the subject's participation is terminated early.  See AE monitoring footnote above.      
u. Follow-Up: All subjects will be contacted after discontinuing study therapy to collect survival status. Subjects should be contacted every 3 months (+/- 14 
days) until approximately 18 months of follow up, death, withdrawal of consent, lost to follow-up or end of study. Contact may include clinic visit, telephone 
contact, email or mail to document survival status. 
 












CONFIDENTIAL 
 
 
 
 
 
SL03-OHD-101 
Compound: SL-172154 
 
 
 
 
 
Version no: 6.0  
81 
1)
At screening: The following testing should be performed 1) ABO and D group (ABO/Rh) type and antibody screen and antibody identification if required; 2) 
DAT; 3) Phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and MNSs. 
2) C1/D2: only need to perform blood phenotyping (ABO/Rh) and DAT. 
i. 
Thyroid Function Test: Thyroid stimulating hormone (TSH), and free thyroxine 4 (T4) tests will be performed at local laboratories according to the 
laboratory’s normal procedures. 
j. 
Antiviral Testing: Please see exclusion criterion 17 in Section 4.2. These tests will be performed at local laboratories according to the laboratory’s normal 
procedures. 
k. Cardiac Assessments (obtain within 28 days of first dose): 1) Electrocardiagram (ECG):  12-lead ECG reading must be performed at screening to serve 
as a baseline for comparison in the event of a cardiac AE/SAE. 2) ECHO: An ECHO must be performed at screening to serve as a baseline for comparison 
in the event of a cardiac AE/SAE.
l. 
Tumor Assessment and CA-125: Tumor assessments are required for all subjects within 28 days prior to the first dose of SL-172154. CA-125 should also 
be obtained at screening within 21 days of first dose of SL-172154. Baseline and on-treatment tumor assessments for all tumor types by RECIST v1.1 and 
iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan, positron emission 
tomography (PET)/CT, and/or MRI should be performed only if clinically indicated.  Please refer to Section 8 for requirements regarding disease assessment. 
Tumor assessments must be performed at screening and at the following intervals until disease progression: approximately every 8 weeks through week 24 
(e.g., C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 22, 25, 28 and 31), and then every 24 weeks (prior to cycles 37, cycle 
43, etc.) up to conclusion of the study.  
response or progressive disease. Subjects who discontinue study treatment for reasons other than disease progression (e.g., AE or withdrawal of consent) will 
be monitored for radiologic response until start of another anti-cancer therapy, or disease progression, withdrawal of consent or death. CA-125 should be 
measured to coincide with each scheduled tumor assessment as outlined above with the last required sample for CA-125 obtained at the post treatment visit 
which occurs within 30 days of the last dose of SL-172154. 
m. PK/immunogenicity (i.e., ADA), cytokines and SL-172154 binding to red blood cells (RBCs): Blood sample collection timings for PK, ADA, cytokines 
and measurement of RBC binding are outlined in Section 6.1.1 in supplementary Tables 2, 3, 4 and 5.  PK/ADA/cytokine/RBC binding sample collection 
times on C1D1 through 48 hours postdose are provided in Table 2. PK/ADA/cytokine/RBC binding sample collection times in C2D1, C2D2, C2D15 and 
C2D16 are detailed in Table 4. PK/ADA sample collection times in C1/D8 and cycles 3 and beyond are outlined in Table 3 and Table 5, respectively. Blood 
volumes required are provided in the SLM. PK, ADA, cytokine and RBC binding samples should not be collected from infusion port for drug 
delivery i.e., recommend having a separate line in the opposite arm for sample collection.  
1) 
If subject has positive ADA test on D1 of cycle 13 or ADA results are not known, then follow up predose samples for PK/ADA should be collected 
every 3 cycles on D1 of subsequent treatment cycles (i.e., cycles 16, 19, 21 and 24) until ADA resolves to baseline OR until the last PK/ADA 
sample is collected within 105-125 days after the last dose of SL-172154. 
2) 
A PK/ADA sample is collected within 7 to 30 days after the subject discontinues SL-172154 therapy.   
3) 
If subject has positive ADA tests during treatment or ADA results are not known a final PK/ADA sample is collected within 105-125 days after 
the last dose of SL-172154.  
4) 
Cytokines will be collected in cycle 2 on days 15 and 16 as depicted in Table 4 and on day 1 of cycle 3 as depicted in Table 5. 
 
n. Correlative laboratory studies:  Refer to supplementary Table 6 for details in Section 6.1.2 plus see the SLM for amount of blood needed and sample 
shipment details. 


CONFIDENTIAL 
 
 
 
 
 
SL03-OHD-101 
Compound: SL-172154 
 
 
 
 
 
Version no: 6.0  
82 
 
Complement, Immunophenotyping and Receptor Occupancy  
 
o. SL-172154 administration: Subjects with confirmed CR who have had a minimum of 48 weeks of treatment may elect to discontinue SL-172154 and 
continue with all relevant study assessments including disease assessments. SL-172154 should be administered on D1, D8, D15 and D22 according to the 
prescribed dosing schedule without deviation in cycle 1 to align with the safety DLT assessment and sample (PK, ADA, etc.) collection schedules. 
Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing days for drug administration.    
p. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of SL-172154. After a subject is 
discontinued from SL-172154 or study therapy due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or 
return to baseline) and documented in the eCRF. If another anti-cancer agent is started within 90 days after the last dose of SL-172154, only SAEs and AEs 
that occur prior to the start of the new anticancer therapy should be recorded.  In the event of a continuing SAE or a non-serious irAE, the subject will be 
asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing indefinitely. AEs will be characterized per NCI-CTCAE 
criteria v5.0 and events recorded in the eCRF.  
 
Ad hoc blood samples for clinical safety labs should be collected for SAE related to IRR or CRS events as noted in Section 6.4.6.1 and the SLM. 
q. Archival tumor tissue (from a recent biopsy): Archival tissue, if available, will be collected from all subjects. If an inadequate amount of archived tissue 
is available, the subject may still participate in the study if they meet eligibility criteria for the study. Moreover, archival tissue may be accepted in lieu of 
the pre-treatment tumor biopsy if the subject has not undergone treatment since time of specimen collection and if the sample was collected via core needle 
biopsy. Please notify the sponsor if archival tissue will be used in lieu of a pre-treatment fresh biopsy Provide formalin-fixed-paraffin-embedded (FFPE) 
tissue on slides (recommended minimum of 10 slides) or a block of FFPE tissue (the latter is preferred). Refer to Section 6.7.2.2 and the SLM for details.  
r. 
Tumor Biopsy: Paired biopsies are required (pre- and on-treatment) obtained in subjects who have tumor accessible to core-needle biopsy and there is an 
acceptable level of risk as per investigator assessment.  Biopsies will be obtained at baseline (to evaluate the immune status of the tumor before SL-172154 
treatment) and following the first dose in cycle 2 on or between D2-D6 of cycle 2. In the event that a biopsy cannot be performed at cycle 2, please contact 
the medical monitor to discuss obtaining an on-treatment biopsy following the first dose on or between D2-D6 of a subsequent cycle. Biopsy at the time of 
progressive disease will be optional.  Please refer to Section 6.7.2.1 and SLM for details regarding biopsy. 
s.
Homologous recombinant deficiency (HRD) status: Collection of HRD status (including BRCA status) is requested for all subjects during the screening 
period. Results from standard of care testing should be used. An HRD status that is unknown, not done, or unavailable at baseline will not preclude the 
subject from study participation.  
t. 
Post-Treatment: A Post-Treatment visit will be conducted within 30 days (±3 days) after the last dose of SL-172154, or prior to the start of a new therapy, 
or at the end of study, or if the subject's participation is terminated early.  See AE monitoring footnote above.      
u. Follow-Up: All subjects will be contacted after discontinuing study therapy to collect survival status. Subjects should be contacted every 3 months (+/- 14 
days) until approximately 18 months of follow up, death, withdrawal of consent, lost to follow-up or end of study. Contact may include clinic visit, telephone 
contact, email or mail to document survival status. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
83 
6.3
Demographics, Medical History, Screening and Safety Assessments 
6.3.1 Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent 
form before any trial specific procedures are performed and prior to starting treatment with SL-
172154. Refer to Section 13.3. 
6.3.2 Eligibility Criteria  
Subjects must meet all the eligibility criteria outlined in the protocol to be eligible for participation.   
6.3.3
Subject Demographics
The age, year of birth, sex, race, and ethnicity of each subject will be recorded during Screening. 
6.3.4
Medical History
A complete medical history will be taken during the Screening period. The history will include the 
background and progress of the participant’s malignancy and a description of prior therapies 
received to treat the disease under study and the response to these therapies.  
6.3.5 Concomitant Medications 
Concomitant medications and procedures will be recorded during the Screening period and 
throughout the study as specified in the SOA.
 
6.4 
Safety Evaluations 
6.4.1 Physical Examination 
A complete physical examination should be performed at screening and at the post-treatment visit 
by a qualified physician or their designee.  The exam will include, at a minimum, assessments of 
the head and neck, eyes, ears, nose throat, skin, thyroid, cardiovascular, respiratory, 
gastrointestinal and neurological systems, lymph nodes and extremities. Height (at screening) and 
weight will also be measured and recorded.  Investigators should pay special attention to clinical 
signs related to previous serious illnesses. Physical exams should be performed per standard of 
care during the on-treatment period. 
6.4.2 ECOG Performance Status 
Participant’s performance status will be assessed using the ECOG performance status tool (see 
Appendix Section 16.2). 
6.4.3 Pulse Oximetry 
Oxygen saturation will be measured with a pulse oximeter at room air without supplementation.
Refer to footnote “d” in the SOA tables for details on when to collect pulse oximetry. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
84
6.4.4
Vital Signs
Vital signs will be assessed in a semi-supine position at rest and will include temperature (T), 
systolic and diastolic blood pressure (BP), heart rate (HR), and respiratory rate (RR). BP and RR
measurements should be preceded by at least 5 min of rest for the participant in a quiet setting 
without distractions. Refer to footnote “d” in the SOA tables for details on when to collect vital 
signs. 
6.4.5
Cardiac Assessments
Electrocardiograms
A single, screening 12-lead ECG will be obtained as outlined in the SOA using an onsite standard 
of care ECG machine that automatically calculates HR and measures PR, QRS, QT, and corrected 
QTc (QTc) intervals.  ECGs should be performed as clinically indicated during the conduct of the 
study.  Any treatment emergent abnormalities of clinical consequence should be reported as AEs.  
Echocardiogram 
A screening ECHO will be obtained as outlined in the SOA to assess left ventricular ejection 
fraction. ECHOs should be performed as clinically indicated during the conduct of the study. Any 
treatment emergent abnormalities of clinical consequence should be reported as AEs.
6.4.6
Laboratory Assessments 
Refer to the SOA in Section 6 for the timing and frequency of tests performed. 
Local Clinical Labs
Hematology
Clinical Chemistry 
Hemoglobin
Blood urea nitrogen 
Magnesium
Hematocrit
Creatinine
Phosphorus
Platelet Count
Glucose
Total Protein
Red Blood Cell Count 
Sodium
Albumin
White Blood Cell Count 
Potassium
Lactate dehydrogenase
Automated WBC Differential
Calcium
Bicarbonate 
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Haptoglobin
Ferritin 
C reactive protein
Liver Panel
Total and direct bilirubin
Aspartate aminotransferase 
Alanine aminotransferase 
Alkaline phosphatase
Blood Type and Screen
Serum/Urine Pregnancy Test
ABO/Rh               Duffy, MNS
-human chorionic gonadotropin
D, C, E                    Antibody screen
Kell, Kidd     
Direct antiglobulin test            
Coagulation 
Thyroid
Antiviral Testing
Prothrombin time and International-
normalized ratio 
Activated partial thromboplastin time 
Fibrinogen
D-Dimer
Thyroid stimulating 
hormone 
Free thyroxine 4 
Hepatitis B: HBsAg / HBV core Ab
Hepatitis C: HCV Ab / HCV RNA viral 
load


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
85
Refer to SOA and supplementary tables provided in Section 6 for the timing and frequency of 
central laboratory tests.
Central Laboratory Testsa
Cytokines and Chemokines
Complement (SC5b-9 test)
Binding of SL-172154 to RBCs
PK/Immunogenicitya
Pharmacokinetics (SL-172154 serum concentration)
Anti-drug antibodies 
Flow Cytometrya
Receptor Occupancy Panels 
Immunophenotyping Panels
Tumor IHCa
PD-L1 expression
CD47 and CD40 expression 
Changes in T cell subsets, B cells, and macrophages
a) Samples in this table will be analyzed at a Central Lab. Refer to the SLM for details for sample collection 
procedures, handling, storage and shipment instructions. 
Ad Hoc Labs for IRR or CRS AEs
Ad hoc labs should be collected as noted if IRR/CRS occurs. The samples to be collected are 
provided below. 
Ad Hoc Labsa,b 
Required Local Clinical Labs
Required Central Labs
Complete blood count with differential
Chemistry Panel
D-Dimer
Coagulation panel
C reactive protein
Ferritin
Pharmacokinetics (SL-172154 serum concentration)
Anti-drug antibodies
Complement (SC5b-9)
Cytokines and Chemokines
Immunophenotyping Panels
a)
Refer to the SLM for sample collection procedures, handling, storage and shipment instructions.  PK will be 
measured with each corresponding ADA sample.
b)
Specific biomarker, PK, ADA, and local clinical samples will be collected as soon as possible if an AE related 
to CRS or IRR to SL-172154 occurs.  
All protocol-required central laboratory assessments must be conducted in accordance with 
the SLM.  
Pregnancy Testing
All FCBP subjects must have a negative pregnancy test (serum or urine) at Screening. A separate 
assessment is required if a negative Screening pregnancy test is obtained more than 72 hours before 
the first dose of SL-172154. Subjects with a positive pregnancy test must be excluded from the 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
86
study. Subjects with a negative pregnancy test result must agree to use an effective contraception 
method as described in Appendix Section 16.3.  
In the rare event that -hCG is elevated as a tumor marker, please see guidance in Appendix 
Section 16.3.1.
Blood Type and Screen (ABO/Rh) and DAT
SL-172154 does bind RBCs but has not been shown to cause hemolysis in NHPs. However, 
treatment with SL-172154 may make phenotyping difficult due to expected coating of the RBC 
membrane. Thus, blood phenotyping, type and screen (ABO/Rh), and DAT should be performed 
at screening before exposure to SL-172154. At screening the following testing should be 
performed: 1) ABO and D group (ABO/Rh) type and antibody screen and antibody identification 
if required; 2) DAT; 3) phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, 
Jk, Fy and MNSs. At cycle 1/day 2, testing should only include ABO/Rh type and DAT testing as 
outlined in the SOA tables in Section 6. 
6.5
Pharmacokinetics
6.5.1
Intensive PK Sampling  
Intensive serial PK samples will be collected for all subjects enrolled in dose escalation cohorts. 
Actual dose administration and PK sampling times will be documented in the subject’s medical 
record.  In the first cycle starting on Day 1, samples will be collected as outlined in the SOA and 
supplementary tables provided. Beyond cycle 3 day 1, only predose samples will be collected for 
ADA and PK analyses. Refer to supplementary tables provided in Section 6.1.1 for details.
6.6
Anti-drug Antibody Assessments
Predose blood samples will be collected from all subjects enrolled in the study for determination 
of ADA starting on day 1 and periodically throughout the course of therapy (Refer to 
supplementary tables provided in Section 6.1.1 for details). If subject has a positive ADA test on 
D1 of cycle 13 or if ADA results are unknown, then predose samples for ADA should continue to
be collected every 3 cycles on D1 of subsequent treatment cycles until ADA becomes negative or 
until a final ADA sample is collected within 105 – 125 days after permanently stopping treatment 
with SL-172154.  
6.7
Pharmacodynamic/Biomarker Assessments
Blood samples and tumor tissue (where available) will be collected from all subjects in this study 
for pharmacodynamic/biomarker research as specified in the SOA and supplementary tables 
(Sections 6.1.1 and 6.1.2). Below is an overview of the Pharmacodynamic/Biomarker plan, the 
sample requirements, supporting analytics, and intended goal of performing the proposed assays.  
A separate SLM detailing the preparation, storage, and shipping requirements for blood or fresh 
and archival tumor tissue collection during the study will be provided. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
87
6.7.1
Pharmacodynamic Assessments in Blood
Cytokine and Chemokine Analysis  
The levels of serum proteins such as cytokines and chemokines will be measured as noted in
Section 6.4.6.  Levels of serum cytokines/chemokines may provide context to AEs observed in 
subjects following infusion of SL-172154 and may act as pharmacodynamic markers of activity.  
Receptor Occupancy
Receptor occupancy of SL-172154 on CD47 and CD40 will be measured by flow cytometry. This 
analysis will provide evidence that SL-172154 is engaging its expected targets and allows receptor 
occupancy (free and total) to be calculated and assessed across dose groups. 
SL-172154 Binding to Red Blood Cells 
Blood samples will be collected from all subjects enrolled in the study for determination of SL-
172154 binding to RBCs starting on day 1 and periodically throughout the course of Cycles 1 
and 2.  
Immunophenotyping 
Protein expression of phenotypic markers, proliferation markers, and activation markers will be 
assessed by flow cytometry. Changes in the composition of T cells, B cells and myeloid cells in 
the peripheral blood may provide insights into the mechanism of action of SL-172154 and serve 
as biomarkers for immune response.  
6.7.2
Pharmacodynamic Assessment of Tumor Tissue
Fresh Tumor Biopsies
The efficacy of cancer immunotherapy is conditioned by the infiltration of tumors by activated 
tumor-specific T cells. The activity of these T cells will be affected by the immunosuppressive 
environment in the tumor (e.g., T-regulatory cells, and suppressive myeloid cells such as myeloid-
derived suppressor cells and M2 macrophages). Therefore, the direct evaluation of the “immune 
landscape” inside the tumor is of great value for understanding the mechanism of action of SL-
172154 and optimizing cancer immunotherapy. Immunohistochemistry (IHC) analyses will be 
performed on the fresh tumor samples. The immune infiltrate of the tumor will be assessed by 
visualizing and assessing the phenotype of cells in the tumor micro-environment by IHC.  
Additionally, the spatial distribution and redistribution upon treatment of immune cells within the 
TME has also been found to be linked to the response to immunotherapies and can be evaluated 
by these procedures. The immune profile of the tumor could be used to predict clinical response 
or validate the mechanism of the immune response to SL-172154. On-treatment biopsies of 
progressing lesions will be obtained for further characterization of the changes in the TME.  For 
each time point, three core needle biopsies should be obtained for research studies (see SLM for 
details). 
Baseline and on-treatment biopsies (to evaluate the immune status of the tumor before and on SL-
172154 treatment) are required for all subjects for whom the biopsy has minimal risk. A 
Screening/Baseline biopsy and an on-treatment biopsy at Cycle 2 on or between day 2 through day 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
88
6 (the expected time of an immune response to SL-172154 therapy) must be obtained.  Biopsy at 
the time of progressive disease will be optional. The time interval for the on-treatment biopsy may 
be changed by the Sponsor if pharmacodynamic data from the ongoing study indicates that a 
different time point would be more suitable.  
It is strongly recommended that the biopsies are obtained from non-target and measurable lesions. 
If such a lesion is not present, a biopsy may be obtained from a target lesion that is 2 centimeters 
(cm) or more. The same lesion should be biopsied pre-and post- treatment, and measurement of 
the lesion that is biopsied should be documented. Where possible lymph node biopsies should be
avoided in subjects with solid tumors as reliable measure of tumor infiltrating lymphocytes (or 
their activation) in a background of (non-tumor) lymphoid tissue is challenging. If feasible, biopsy 
material should be collected after disease progression has been confirmed and documented, ideally 
on lesions that have progressed. 
Biopsy Collection Safety Considerations and Procedure
For a given subject, 3 core needle biopsies of the selected tumor lesion should be obtained at the 
time points noted in the SOA. Biopsies should be fixed in formalin and paraffin embedded. The 
entire block must be submitted. Please refer to the SLM for further instructions.  
Only percutaneous biopsies will be performed on subjects with solid tumors. Mediastinal, open 
surgical or laparoscopic, gastrointestinal, peritoneal or bronchial endoscopic biopsies are permitted 
ONLY when obtained incidentally to a clinically necessary procedure and not for the sole purpose 
of the clinical trial.  No laparoscopic, or endoscopic or open surgical procedure will be performed 
solely to obtain a biopsy for this protocol.  However, excisional biopsy or endoscopic biopsy is
allowed if medically indicated and can be used for analysis.  Biopsies will be sent for analyses as
defined in the protocol.  
Contraindications to percutaneous biopsy:
Significant coagulopathy or anticoagulation treatment that cannot be adequately corrected. 
Severely compromised cardiopulmonary function or hemodynamic instability. 
Lack of a safe pathway to the lesion.  
Inability of the subject to cooperate with, or to be positioned for, the procedure. 
If a lesion is deemed appropriate for biopsy with minimal risk (no more than 2% risk of serious 
complication requiring hospitalization) to the participant by agreement between the investigators 
and Interventional Radiology, an attempt at biopsy should be made.  
The use of imaging to facilitate biopsies will be decided by members of the Interventional 
Radiology team at the clinical site and may include ultrasound, CT scan, or MRI.  Should CT scan 
be needed for biopsy, the number of scans for each procedure will be limited to the minimum 
number needed to safely obtain a biopsy.  Tumor biopsies and local anesthesia will be performed 
only if they are of low risk (<2% major complication rate) to the participant as determined by the 
investigators and interventional radiologist. 
Archival Tumor 
Archival tissue, if available, will be collected from all subjects. Archival tumor tissue (1 block 
preferred or a minimum of 10 unstained slides of FFPE tissue; see SLM for details) that is 
representative of current disease status (e.g., metastatic disease) is requested. If an inadequate 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
89 
amount of archived tissue is available, the subject may still participate in the study if they meet 
eligibility criteria for the study.  
Archival tissue may be accepted in lieu of the screening/baseline fresh tumor biopsy if the subject 
has not undergone anti-cancer treatment since time of specimen collection and if the sample was 
collected via core needle biopsy. Please notify the sponsor if archival tissue will be used in lieu of 
the baseline fresh tumor biopsy.  
6.8
Assessment of Anti-tumor Activity
The primary analysis of anti-tumor activity is according to RECIST v1.1 for solid tumors. 
Treatment beyond progression is permitted provided the subject meets protocol specified criteria
(see Section 8.2).  Disease assessment will be performed at baseline and at the following intervals 
until disease progression is confirmed: every 8 weeks through week 24, and every 12 weeks 
thereafter until year 2, and every 24 weeks until study conclusion. Refer to Section 8 for additional 
details. All subjects will be followed up for survival unless they withdraw consent.  
6.9
Unscheduled Visit  
In the event of an unscheduled visit, the subject should undergo safety screening to include a 
physical exam, vital signs (HR, BP, T, and RR) and pulse oximetry.  Clinical hematology and 
chemistry labs may be collected if considered necessary for subject assessment. The reason for the 
unscheduled visit should be documented in the eCRF. All AEs or SAEs reported by the subject or 
observed by the investigator should be documented and reported; this includes relevant medical 
information gathered during the unscheduled visit related to clinical assessment of AEs or SAEs
(Section 7.4). 
7.
SAFETY ASSESSMENTS  
Subjects will be followed continuously for all AEs starting when a subject has signed the ICF, 
throughout the course of treatment and for 90 days after the last dose of IP. After a subject is 
discontinued from SL-172154 due to progressive disease or for other reasons, any ongoing AEs 
should be followed until resolution (or return to baseline) and documented in the eCRF. If another 
anti-cancer agent is started within 90 days after the last dose of SL-172154, only SAEs and AEs 
that occur prior to starting the new anticancer therapy should be recorded. All observed or 
volunteered AEs (serious or non-serious) and abnormal laboratory test findings, if applicable, 
whether suspected to have a causal relationship to SL-172154 or not will be recorded in the subject 
medical record and in the eCRF. AEs will be graded according to NCI-CTCAE v5.0.  For all AEs, 
sufficient information will be pursued and/or obtained to permit an adequate determination of 
seriousness and outcome of the event (i.e., whether it should be classified as a SAE or not) and an 
assessment of the causal relationship between the AE and SL-172154.  AEs will be followed until 
resolution (or return to baseline) or stabilization.  Refer to Section 7.4 for documentation and 
reporting of AEs. 
7.1 
Definitions for Safety Parameters 
Event
Definition 
Adverse Event (AE)
The AE observation period starts at the time of signing informed consent and includes 
baseline or washout periods, even if no study treatment has been administered.  
An AE is defined as any untoward medical occurrence in a subject to whom the IP has 
been administered, regardless of whether the event is considered related to that product.


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
90 
Event
Definition
An AE is also defined as an undesirable medical condition due to a study-related 
procedure.  
Adverse Reaction (AR)
AR is an untoward and unintended response in a subject to an IP. A causal relationship 
between a trial medication and an AE is at least a reasonable possibility, i.e. the 
relationship cannot be ruled out.
Serious Adverse 
Event (SAE) or Serious 
Adverse Reaction 
(SAR) 
An AE or suspected AR that is considered "serious" if, in the view of either the 
investigator or Sponsor, it results in any of the following outcomes:  
 Death (Note: death is an outcome not an event) 
 A life-threatening AE (an event in which the subject was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe) 
 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.  
 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 participant 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. 
Laboratory test(s) that 
meet definition of an 
AE or SAE: 
Any laboratory test result that meets the definition of an AE or SAE or requires 
holding or discontinuation of IP or requires corrective therapy, must be documented 
appropriately. 
 
Ad hoc labs should be collected as noted in Section 6.4.6.1 above if IRR/CRS 
occurs. 
The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the subject’s medical 
record and recorded in the AE section of the eCRF.  The laboratory reports must be filed 
with the source documents. Clinically significant abnormal laboratory findings are those 
which are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
All laboratory tests with clinically significant abnormal values during participation in 
the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator. 
If such values do not return to normal/baseline within a period judged reasonable by the 
investigator, the etiology should be identified, and the Sponsor notified.  
If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in subject management or are 
considered clinically significant by the investigator (e.g., AE, SAE or dose 
interruption), then the results must be recorded in the eCRF. 
Unexpected Adverse 
Reaction 
An adverse reaction (causality related Adverse Event), the nature, severity or outcome 
of which is not consistent with the reference safety information section of the SL-
172154 IB. Product reference safety information is contained in the current Guidance 
for Investigators in Section  6.0 of the Investigator’s Brochure provided to the 
Investigator by the Sponsor.
Suspected Unexpected 
Serious Adverse 
Reaction (SUSAR) 
Suspected Adverse Reaction (causality related AE) that is serious and unexpected. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
91 
7.1.1
Events not Qualifying as AEs/SAEs
Because attribution of AEs is difficult in a FIH study, any toxicity experienced by subjects in this 
study should be recorded as AEs unless otherwise specified. The following are not considered to 
be AEs or SAEs:
 Medical or surgical procedures (e.g., endoscopy, appendectomy). The condition that leads 
to the procedure is considered the AE. 
 Elective procedures, planned hospitalizations, and procedures for treatment of conditions 
noted in the subject’s medical history (present prior to signing the ICF) that have not 
worsened are not considered AEs.  
 Situations where an untoward medical occurrence did not occur (i.e., admission to hospital 
for social circumstances). 
 Anticipated day-to-day fluctuations of pre-existing medical conditions that were present at 
start of study. These conditions are considered part of the subject’s medical history and 
must be adequately documented on the appropriate page of the CRF. 
 Clear progression of disease under study should not be reported as an AE or SAE (unless 
the investigator considers the progression of underlying neoplasia to be atypical in its 
nature, presentation or severity from the normal course of the disease in a particular 
subject). Signs and symptoms that are clearly consistent with the expected progression of 
the underlying cancer should not be reported as an adverse event, and hospitalizations due 
to the progression of cancer do not necessarily qualify for an SAE. If there is any 
uncertainty about an AE being due only to the disease under study, it should be reported as 
an AE or SAE.
 In the case where the medical condition is known when the participant enters the trial, only 
worsening (increased frequency or intensity of the episodes or attacks) will be documented 
as an AE. If the disease is detected during the trial, and if repeated episodes enable 
diagnosis of a chronic disease, the episodes will be grouped together in the CRF, and the 
diagnosis will be clearly described. 
 Laboratory abnormalities: An isolated, out-of-range laboratory result in the absence of 
any associated, clinical finding may or may not be considered an AE, the Investigator’s 
evaluation should be based on a consideration of the overall clinical context. 
 
7.2 
Classification of an Adverse Event 
7.2.1 Assessment of Severity  
The descriptions and grading scales found in the revised NCI-CTCAE version 5.0 will be utilized 
for AE reporting. A copy of these criteria can be downloaded from the website: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. 
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
 Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age 
appropriate 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
92 
 Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
 Grade 5: Death related to AE 
activities of daily living (ADL) refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
For AEs not included in the NCI-CTCAE v5.0 grading system, the following guidelines will be 
used to describe severity. 
 Mild – Events require minimal or no treatment and do not interfere with the subject’s daily 
activities.  
 Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
 Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events may be potentially life-threatening or 
incapacitating. 
NOTE: A distinction should be drawn between serious and severe AEs. Severity is an estimate or 
measure of the intensity of an AE, while the criteria for serious AEs are indications of adverse 
subject outcomes for regulatory reporting purposes. A severe AE need not necessarily be 
considered serious and a serious AE need not be considered severe. 
7.2.2 Assessment of Causality  
The clinician’s assessment of an AE's relationship to SL-172154 is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any 
doubt as to whether a clinical observation is an AE, the event should be reported. All AEs must 
have their relationship to SL-172154 assessed. In a clinical trial, the IP must always be suspect. 
To help assess causality, the following guidelines are used.  
 Related – The AE is known to occur with the IP, there is a reasonable possibility that the 
IP caused the AE, or there is a temporal relationship between the IP and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between the IP and 
the AE.   
 Not Related – There is not a reasonable possibility that the administration of IP caused the 
event, there is no temporal relationship between IP and event onset, or an alternate etiology 
has been established.   
7.2.3 Expectedness 
The Sponsor will be responsible for determining whether an AE is expected or unexpected.  
 Unexpected - An AE will be considered unexpected if the nature, severity, or frequency 
of the event is not consistent with the safety information section 6.0 (Guidance for 
Investigators) of the IB [Report_SL2020IB001] for the IP.  "Unexpected," as used in this 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
93 
definition, also refers to AEs or ARs that are mentioned in the IB as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug not specifically 
mentioned as occurring with the IP under investigation.   
Expected - AEs that are common and known to occur for the IP being studied.  
Expectedness refers to the awareness of AEs previously observed, not on what might be 
anticipated from the properties of the IP. 
7.3
Timing for Event Assessment and Follow-up
All AEs occurring while on study must be documented appropriately regardless of relationship. 
All AEs will be followed to adequate resolution.  The occurrence of an AE or SAE may come to 
the attention of study personnel during study visits and interviews of a study subject presenting for 
medical care, or upon review by a study monitor.  
Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the pre-existing condition deteriorates at any time 
after the subject signs the main study ICF, it will be recorded as an AE. Unanticipated problems 
will be recorded in the data collection system throughout the study.  
AEs characterized as intermittent require documentation of onset and duration of each episode.  
7.4 
Procedures for Recording and Reporting of Adverse Events 
Event
Reporting Procedures 
Adverse Event
Subjects will be followed continuously for AEs during the study and for 90 days after the last 
dose of IP. After a subject is discontinued from IP due to progressive disease or for other reasons, 
any ongoing AE should be followed until resolution (or return to baseline) and documented in 
the eCRF, regardless of whether the event(s) is attributed to trial medication. If another anti-
cancer agent is started within 90 days of the last dose of SL-172154, only SAEs and irAEs that 
occur before the new anticancer therapy should be recorded. The following information will be 
recorded: description, date of onset and end date, severity, assessment of relatedness to trial 
medication, and action taken.  Follow-up information should be provided as necessary.  AEs 
will be followed either until resolution, or the event is considered stable. 
 
It will be left to the Investigator’s clinical judgment to decide whether an AE is of sufficient 
severity to require the subject’s removal from treatment.  A subject may also voluntarily 
withdraw from treatment due to what he or she perceives as an intolerable AE.  If either of these 
occurs, the subject must undergo an end of trial assessment and be given appropriate care under 
medical supervision until symptoms cease, or the condition becomes stable. 
 
Serious 
Adverse Event 
The study clinician will complete a SAE Form within the following timelines:  
 
All deaths and immediately life-threatening events meeting the SAE criteria (as 
outlined in section 7.1), whether related or unrelated, will be recorded on the SAE Form 
and submitted to the study Sponsor or designee within 24 hours of site awareness.  
 
Other SAEs regardless of relationship, will be submitted to the study Sponsor or 
designee within 24 hours of site awareness.  
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the 
event to be chronic or the adherence to be stable. Other supporting documentation of the event 
may be requested by the Sponsor and should be provided as soon as possible. The Sponsor will 
be responsible for notifying Regulatory Authorities of any unexpected fatal or life-threatening 
suspected adverse reaction (AR) as soon as possible but in no case later than 7 calendar days 
after the Sponsor's initial receipt of the information. The Sponsor will be responsible for 




CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
95 
7.8
Safety Oversight 
An SMC will be implemented in this study and will consist of investigators and Sponsor 
representatives. SMC meetings will be conducted monthly (or more frequently if required) during 
dose escalation provided subjects have been enrolled and data are available to be reviewed.  The 
SMC will operate in accordance with the SMC charter which will define roles and accountabilities 
and the process for safety review. Throughout the conduct of the study, safety data will be reviewed 
for each subject on an ongoing basis. Based on the AE profile, severity of the DLTs, indicators of 
potential anti-tumor activity, and other factors, a recommendation on whether to modify the dose 
and/or study design; or continue enrollment will be made by the Sponsor collaboratively with input 
from the SMC. Regulatory authorities and IRBs/IECs will be notified of any decisions to 
prematurely halt the study or subject enrollment. (See section 14.1 for details on safety meetings).
8. 
ANTI-TUMOR ACTIVITY ASSESSMENTS 
Although the clinical benefit of SL-172154 has not yet been established, the intent of offering this 
IP is to provide a possible therapeutic benefit, and thus the participant will be carefully monitored 
for tumor response and symptom relief in addition to safety and tolerability. For the purposes of 
this study, participants should be evaluated for response as outlined in the SOA. Confirmatory 
scans should be performed at least 4 weeks 
 after initial documentation of an objective 
response or progressive disease.  All participants who underwent the first post baseline disease 
assessment at the 8-week time point or progress or die before to the first post baseline disease 
assessment will be considered evaluable for response.   
Assessments must be performed on a calendar schedule and should not be affected by dose 
interruptions or delays. Refer to the SOA (Section 6) for the schedule of disease assessments. More 
frequent disease assessments may be performed at the discretion of the investigator. For subjects 
whose disease may be followed by well-characterized tumor markers (i.e., CA-125), disease 
assessments should include results of tumor marker assessments. If study treatment is withdrawn 
for reasons other than disease progression, radiographic disease assessments should continue as 
per the SOA until documented disease progression, the start of new anti-cancer therapy, 
withdrawal of consent or death. See Sections 8.2 for criteria for continuing treatment past disease 
progression. 
8.1 
Disease Assessment  
Imaging studies, preferable by contrasted computed tomography scan for disease assessment of 
chest, abdomen and pelvis and all other sites of known disease will be performed at baseline and 
at the following intervals until disease progression: every 8 weeks until week 24 and every 12 
weeks thereafter until year 2 and every 6 months until study conclusion. PET-CT, MRI, and/or 
bone scan should be performed as clinically indicated. The same imaging modality used at baseline 
should be employed subsequently. Confirmatory scans should be perform
days) after initial documentation of an objective response or progressive disease.  Contrast 
enhanced imaging is required unless the subject is precluded from receiving contrast (e.g., 
hypersensitivity, renal impairment).  
Treatment beyond progression will be permitted provided the subject meets protocol specified 
criteria in Section 8.2. If subjects discontinue investigational therapy prior to progressive disease, 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
96 
they should continue to be followed with radiologic assessments until disease progression, start of 
a new anti-cancer therapy, withdrawal of consent or death.  
8.1.1
Assessment of Response  
Investigator-assessed response and progression will be evaluated in this study using RECIST v1.1 
[Eisenhauer, 2009] and iRECIST [Seymour, 2017]. The RECIST v1.1 guideline and iRECIST 
guideline are included in this document (Section 16.5).   
8.2
Criteria for Treatment Beyond Initial Progression 
Subjects will be permitted to continue IP beyond initial progressive disease provided the subject 
does not have clinical symptoms of progression, is tolerating IP, has experienced no decline in 
their  ECOG performance status and is gaining clinical benefit as assessed by the investigator.  The 
subject must be made aware of the potential benefits and risks of continuing the IP in the setting 
of progressive disease by signing a separate written informed consent.   
The subject may continue to be treated until one of the following criteria is met: 
 Meets any of the criteria for discontinuation of IP (see Section 3.7) 
 Develops clinical symptoms or signs such that the benefit-risk ratio of continuing therapy 
is no longer justified 
 Experiences rapid progressive disease with risk to vital organs or critical anatomical sites 
requiring urgent medical intervention  
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
9.1
Study Design and Sample Size Determinations
The dose escalation will utilize a mTPI-2 design [Guo, 2017] with target DLT rate of 30% for the 
MTD. The DLT evaluable population is defined in section 9.2.1.  
The mTPI-2 design employs a simple Beta-Binomial Bayesian model with decision rules based on 
the unit probability mass from the posterior probability of DLT rate. With the target DLT rate of
30%, the posterior probability of DLT rate unit interval (0, 1) is divided into subintervals with 
equal length of 0.1 that correspond to different dose escalation decisions: subinterval of (0.25, 
0.35) is to stay at the current dose, subintervals below 0.25 is to escalate to next higher dose, and 
subintervals above 0.35 is to de-escalate to the next lower dose. Subjects will be enrolled in cohorts 
of approximately 3 subjects during the dose escalation. After each cohort of approximately 3 
subjects, the posterior unit probability for subintervals will be calculated based on a 
noninformative prior distribution for the DLT rate (Beta (1,1)) and the total number of subjects 
with DLTs and DLT evaluable subjects for the current dose. A dose escalation/stay/de-escalation 
decision that corresponds to the subinterval with the highest unit probability mass will be selected. 
A minimum of 3 DLT evaluable subjects will be enrolled to a dose level and evaluated for DLT 
before a dose escalation/stay/de-escalation decision can be made unless unacceptable toxicity is 
observed prior to the enrollment of 3 subjects e.g., two subjects experience DLT before the third 
subject enrolls. A dose level will be considered unsafe, with unacceptable toxicity and no 
additional subjects enrolled at that dose level and above, if it has an estimated 95% or more 
probability of exceeding the target DLT rate of 30%. The maximum number of subjects evaluated 
for DLT for each dose level will be 12 subjects (about 4 cohorts of 3 subjects) if the dose escalation 




CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
98 
dose escalation cohorts for each schedule 1 and schedule 2, assessment of approximately 6 subjects 
in an optional pharmacodynamic cohort and assessment of approximately 6 subjects in dose 
expansion. Overall, approximately 6-12 subjects are to be treated at the RP2D for SL-172154. In 
dose escalation cohorts, subject may be replaced if not DLT evaluable.  
NOTE: The planned sample sizes may be revised if additional dose levels are evaluated or if more 
subjects (i.e., 4 subjects dosed in a cohort to ensure that at least 3 subjects are DLT evaluable) are 
enrolled. The Sponsor, in consultation with the SMC, may also elect to add subjects to the dose 
escalation if additional data are needed for RP2D determination. 
9.2
Statistical Analyses 
Complete details of the statistical analysis will be provided in the Statistical Analysis Plan (SAP). 
Any deviations from, or additions to, the original analysis plan described in this protocol will be 
documented in the SAP and final study report. 
9.2.1
Analysis Populations  
For the analysis, the following populations are defined: 
Population 
Description 
Enrolled 
All subjects who have signed the main study inform consent form (ICF).
Screen Failures 
All subjects who have signed the main study ICF but have not received 
any study treatment.  
All Treated
All subjects who have received at least one dose of IP. Safety data will be 
evaluated based on this population.  
DLT Evaluable 
All treated subjects 1) who have received 2 of the 3 scheduled doses of 
IP on schedule 1 or who have received 
4 scheduled doses of IP 
on schedule 2 during cycle 1 and complete the safety follow-up through 
the 28-day DLT evaluation period; or 2) who experience any DLT during 
the DLT evaluation period. DLT evaluable subjects will be used to guide 
dose escalation and to determine the MTD or MAD.
Response 
Evaluable 
Subjects in the All Treated Population who have a baseline disease 
assessment and have at least one post-baseline disease assessment or have 
progressed or died before the first post-baseline disease assessment. 
Pharmacokinetic
Subjects in All Treated Population from whom at least one PK sample is 
obtained and analyzed. The PK population will be used for the PK 
analysis.  
Pharmacodynamic 
Subjects in the All Treated Population for whom at least one 
pharmacodynamic 
sample 
is 
obtained 
and 
analyzed. 
The 
pharmacodynamic population will be used for the pharmacodynamic data 
analysis.  
 
9.2.2
Interim Analyses 
During the dose escalation, the number of subjects with DLTs will be determined after each cohort 
of approximately 3 subjects has been evaluated for DLT. The summary of DLTs for each dose 
level will be based on the number of subjects with DLTs from all subjects dosed and evaluated at 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
99 
the corresponding dose level who meet the definition of the DLT Evaluable Population. Selected 
AE summary tables and listings may be provided during dose escalation to support dose escalation 
decisions.  
9.2.3
General Data Analysis Consideration 
Tabular summaries will be presented by dose levels/schedule/cohorts and total number of subjects 
in the corresponding population. Categorical data will be summarized by the number and 
percentage of subjects in each category. Continuous variables will be summarized by descriptive 
statistics.  
As it is anticipated that accrual will be spread thinly across centers and summaries of data by center 
would be unlikely to provide valuable information, data from all participating centers will be 
pooled prior to analysis. 
All data up to the time of study completion/withdrawal from study will be included in the analysis
for each subject, regardless of duration of treatment. 
9.2.4 Safety Analyses 
The safety evaluation will be based on the All Treated Population and the DLT evaluation will be 
based on the DLT evaluable population.  
DLTs will be summarized by dose level. Frequency tables will be used to describe safety and 
tolerability parameters AEs, irAEs, SAEs, fatal SAEs and AEs leading to discontinuation of SL-
172154. Graphs may also be presented where appropriate. AEs will be mapped to a Medical 
Dictionary for Regulatory Activities (MedDRA) preferred term and system organ classification. 
Laboratory abnormalities will be graded according to the NCI CTCTAE v5., if applicable. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary.  
MTD: The MTD will be estimated using isotonic regression (based on the DLTs observed in DLT 
evaluable subjects). Specifically, the MTD is the dose for which the isotonic estimate of the DLT 
rate is closest to the target DLT rate of 30%. If two or more doses tie for the smallest difference, 
perform the following rules: 
 If the estimated DLT rate < 30% for all doses, then select the higher dose among the tied 
doses; 
 
 
then select the higher dose among the tied doses; 
 
doses 
NOTE: For subjects who undergo intra-subject dose escalation, DLTs will only be assessed during
the DLT period applicable on the subject’s initial dose level.  
A MAD will be reported if the observed DLT rate is <25% among all dose levels.   Otherwise, an 
MTD will be reported.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
100 
9.2.5
Efficacy Analyses 
Anti-tumor activity data will be summarized by dose level/schedule and overall in the All Treated 
population and Response Evaluable population.  
The primary analysis of anti-tumor activity assessment is based on RECIST v1.1 and exploratory 
analysis of anti-tumor activity assessment is based on iRECIST.  
The ORR and CBR will be estimated along with a 95% confidence interval using the exact 
probability method. Change from baseline sum of diameters for target lesions will be provided for 
each subject.  DOR and TTP will be evaluated, using the Kaplan-Meier method, for the subgroup 
of subjects with a confirmed response. The Kaplan-Meier method will be used to estimate the 
PFS/OS curve and PFS/OS rate at time of point of interest.   
9.2.6
Pharmacokinetic Analysis
The PK analysis will be based on the PK population. Serum concentrations for SL-172154 will be 
summarized using tabular and graphical format.  SL-172154 PK parameters will be summarized 
and analyzed using appropriate statistical methods. The Pharmacokinetics of SL-172154 will be 
described using the PK parameters listed in Table 8, as data permit. 
Table 8: Serum SL-172154 PK Parameters 
Cmax
Maximum observed concentration
Tmax
Time of maximum observed concentration 
AUC0-last
The area under the serum concentration time curve, from time 0 to the last 
quantifiable concentration, calculated by a combination of linear and 
logarithmic trapezoidal methods (Linear up/log down method). 
AUC0-t 
The area under the serum concentration time curve, from time 0 to time=t, 
calculated by a combination of linear and logarithmic trapezoidal methods 
(Linear up/log down method). 
AUC0-inf 
Area under the serum concentration time curve from time 0 extrapolated to 
infinity, calculated as AUClast + Clast
z). 
Reliability of AUC0-inf values is contingent on the percent of the total area 
obtained by extrapolation: 
AUC0-inf values with <20% of the total area coming from Clast
z are 
considered acceptable.  
Any exceptions to the above procedures will be clearly documented/justified 
in the PK report. 
AUCtau
The area under the serum concentration time curve, over the dosing interval 
logarithmic trapezoidal methods (Linear up/log down method). 
%AUCext
Percentage of AUC0-inf due to extrapolation from Tlast to infinity 
t½
Terminal elimination half-
z]
CL
Clearance; calculated as Dose/AUC0-inf
Vz 
z
0-inf)


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
Version no: 6.0  
101
Anti-Drug Antibody Analysis 
Individual subject ADA titer and status (positive, negative, inconclusive) vs. nominal time will be 
reported and summarized by dose level.  Onset, duration and persistence of ADA by subject will 
also be summarized by dose level.  ADA isotype may be reported, if supported by the data.  
9.2.7
Pharmacodynamics Analyses   
The
pharmacodynamic analysis
will be based on the pharmacodynamic population. 
Pharmacodynamic biomarkers values will be summarized descriptively by dose level, schedule
and visit.     
10.
CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial complies with the currently approved protocol/amendment(s), with GCP, and with 
applicable regulatory requirement(s).  
Monitoring for this study will be performed by Sponsor or its designees  
Details of clinical site monitoring are documented in a Clinical Monitoring Plan (CMP). 
The CMP describes in detail who will conduct the monitoring, at what frequency 
monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports.  
Independent audits will be conducted by the Sponsor or designee of the Sponsor to ensure 
GCP and monitoring practices are performed consistently across all participating sites and 
that monitors are following the CMP.  
11.
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA AND DOCUMENTS
11.1
Source Data
Source documents are where data are first recorded, and from which subjects’ eCRF data are 
obtained. These include, but are not limited to, hospital records (from which medical history and 
previous and concurrent medication may be summarised into the eCRF), clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
11.2
Access to Data
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB/IEC
or regulatory authorities may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy 
records for the participants in this study. The clinical study site will permit access to such records 
to permit trial-related monitoring, audits and inspections.  
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by local IRB/IEC and Institutional regulations.  
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored by the Sponsor. This will not include the subject’s contact or 
identifying information. Rather, individual subject’s and their research data will be identified by a 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
102 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by Sponsor research staff will be secured and password protected. At the end of 
the study, all study databases will be de-identified and archived by the Sponsor.  
11.3
Data Recording and Record Keeping 
All trial data will be entered on electronic data entry systems that are validated and are maintained 
in accordance with Standard Operating Procedures. The subjects will be identified by a unique 
trial specific number and/or code in any database.  The name and any other identifying detail will 
NOT be included in any trial data electronic file. 
12.
QUALITY ASSURANCE PROCEDURES
The trial will be conducted in accordance with the current approved protocol, GCP, relevant 
regulations and standard operating procedures. Regular monitoring will be performed according 
to GCP. Data will be evaluated for compliance with the protocol, GCP, and accuracy in relation to 
source documents. Following written standard operating procedures, the monitors will verify that 
the conduct of the clinical trial and data generated, are documented and reported in compliance 
with the protocol, GCP and the applicable regulatory requirements. 
13.
ETHICS/PROTECTION OF HUMAN SUBJECTS
13.1
Ethical Standard
The investigator will ensure that this study is conducted in full conformity with Regulations for 
the Protection of Human Subjects of Research codified in 45 Code of Federal Regulations (CFR) 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the International Conference of Harmonisation 
(ICH) E6 and consistent with the consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines for Biomedical Research Involving Human Subjects 
(2002), or ethical policy statement specific to the country, whichever provides the most protection 
to human subjects. 
13.2 
Institutional Review Board/Institutional Ethics Committee 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB/IEC for review and approval. Approval of both the protocol and the consent 
form must be obtained before any subject is screened and enrolled. Any amendment to the protocol 
will require review and approval by the IRB/IEC before the changes are implemented to the study. 
All changes to the consent form will be IRB/IEC approved; a determination will be made regarding 
whether previously consented subjects need to be re-consented. 
13.3 
Informed Consent Process 
13.3.1 Consent/Assent and Other Informational Documents Provided to Subjects 
The investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorized representative and answer all questions regarding the study. Subjects 
will be required to sign and date a study consent form prior to any study-related procedures are 
performed if they meet eligibility requirements of the protocol and wish to participate in the trial. 
If applicable, it will be provided in a certified translation of the local language.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
103 
 Subjects must be informed that their participation is voluntary. Subjects  or their legally 
authorized representative [defined as an individual or judicial or other body authorized 
under applicable law to consent on behalf of a prospective subject to the subject's 
participation in the procedure(s) involved in the research] will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
 Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
 A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative. 
 Subjects who are rescreened are required to sign a new ICF. 
The ICF may contain a separate section or a separate ICF may be used for optional exploratory 
research. The investigator or authorized designee will explain to each subject the objectives of the 
exploratory research. Subjects will be informed that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the study period. Subjects who 
decline to participate in this optional research will not provide this separate signature. 
13.3.2 Consent Procedures and Documentation
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks 
and possible benefits of participation will be provided to the participants and their families. 
Consent forms will be IRB/IEC approved and the participant and/or the legally authorized 
representative will be asked to read and review the document. The investigator and/or his/her 
authorized designee will explain the research study to the participant and answer any questions 
that may arise. All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants should have the opportunity to discuss 
the study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign and date the informed consent document prior to any procedures being done specifically for 
the study. The participants may withdraw consent at any time throughout the course of the trial. A 
copy of the informed consent document will be given to the participants for their records. The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of 
their medical care will not be adversely affected if they decline to participate in this study. 
13.4 
Participant and Data Confidentiality  
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the Sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
samples in addition to the clinical information relating to participants. Therefore, the study 
protocol, study documentation, data, and all other study-related information generated will be held 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
104 
in strict confidence. No information concerning the study, or the data will be released to any 
unauthorized third party without prior written approval of the Sponsor.   
The study monitor, auditors, other authorized representatives of the Sponsor including the contract 
research organization (CRO), if applicable, representatives of the IRB/IEC or the Sponsor 
supplying study product, the Federal government or its designee and applicable regulatory 
authorities will be granted direct access to the study participants’ original medical records 
(including but not limited to office, clinic, hospital, or pharmacy records), all documents required 
to be maintained by the investigator, for verification of clinical trial procedures and/or data, 
without violating the confidentiality of the participants, to the extent permitted by the law and 
regulations.   
All documents will be stored safely in a secure location to protect confidentiality. On all trial-
specific documents, other than the signed consent, the participant will be referred to by the trial 
participant identification number/code, not by name. At the end of the study, all records will 
continue to be kept in a secure location for as long a period as dictated by local IRB/IEC and 
Institutional regulations.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored a Sponsor location. This will not include the participant’s contact 
or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used 
by research staff at the clinical sites and by authorized representatives of the Sponsor will be 
secured and password protected. At the end of the study, all study databases will be de-identified 
and archived at a Sponsor location. 
13.4.1 Research Use of Stored Human Samples, Specimens, or Specimen Data  
 Intended Use: Samples and data collected under this protocol may be used to study the 
effects of the investigational drug on how one’s immune system reacts and how the body 
responds to this type of treatment in treating different types of cancers.  
 Storage: Access to stored samples will be limited to specified study personnel/vendor 
personnel. Samples will be identified by unique subject identification codes. Samples and 
data will be stored using subject ID assigned by the Sponsor and investigators.   
13.5 
Future Use of Stored Specimens 
Specimens collected for this study will be analysed and stored at the Sponsor Data Repository or 
Sponsor-approved vendor.  
During the conduct of the study, an individual subject can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent related to bio-
sample storage, will not be possible after the study is completed.  
14. 
DATA HANDLING AND RECORD KEEPING 
14.1 
Communication and Data Dissemination Plan 
During the study while subjects are receiving treatment with SL-172154, SMC meetings will be 
held to review relevant data with the investigators or delegates.  These meetings will be held once 
a month (or more frequently if required) to share safety data and communicate results of ongoing 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
105 
analyses. All available safety, PK, pharmacodynamic, and clinical outcome data for all subjects at 
the time of the scheduled SMC Meeting will be reviewed and summarized.  Attendees of SMC
meetings will include but not be limited to clinical investigators (or designees), the Sponsor 
Medical Monitor and Statistician. The SMC will operate in accordance with the SMC charter 
which will define roles and accountabilities and the process for safety review.  
The Sponsor will remain in constant contact with the clinical sites during the enrollment period to 
ensure that cohort enrollment during the dose escalation of this study is completed as per protocol.  
All dose escalation or safety decisions made by the SMC will be documented in writing with copies 
maintained at each site and the Trial Master File at the Contract Research Organization.  
14.2 
Data Collection and Management Responsibilities 
An eCRF will be used to record all subject data specified by this protocol. The eCRF must be 
completed by designated and trained study personnel.  The eCRF will be electronically signed by 
the Principal Investigator or a Sub-investigator listed on the Form FDA 1572.  Data collection is 
the responsibility of the clinical trial staff at the site under the supervision of the site investigator. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported.  All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.  Source documents may include but are not limited to, study 
progress notes, e-mail correspondence, computer printouts, laboratory data, and drug 
accountability records.    
Data reported in the eCRF derived from source documents should be consistent with the source 
documents or the discrepancies should be explained and captured in a progress note and 
maintained in the subject’s official electronic study record.  
Clinical data (including but not limited to AEs, concomitant medications, and expected ARs data) 
and clinical laboratory data will be entered into the study database, a 21 CFR Part 11-compliant 
data capture system provided by the Sponsor. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered into an electronic data capture system 
directly from the source documents.  
Study data will be entered into eCRFs at the study site.  Prior to database lock, programmed 
computer edit checks and manual checks will be performed to check for discrepancies and 
reasonableness of the data.  All issues resulting from the computer-generated checks are to be 
resolved as quickly as possible with clarification from study sites. 
14.3 
Study Records Retention 
The Sponsor follows US regulations and ICH guidelines in its retention policy. 
US IND regulations (21CFR 312.62c) require that records and documents pertaining to the conduct 
of this study and the distribution of investigational drug(s) including eCRFs, consent forms, 
laboratory test results, and medication inventory records be kept on file by the Principal 
Investigator for 2 years following the date a marketing application is approved for the drug for the 
indication for which it is being studied.  If no application is to be filed or if the application is not 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
106 
approved for such indication, these records must be kept until 2 years after the investigation has 
been discontinued and regulatory authorities (i.e., FDA, European Medicines Agency, etc.) have 
been notified.  ICH guidelines indicate that study documents should be retained until at least 2 
years after the last approval of a marketing application in an ICH region and until there are no 
pending or contemplated marketing applications in an ICH region, or at least 2 years have elapsed 
since the formal discontinuation of clinical development of the IP. If there is a country or 
institutional policy that specific records and documents be retained for a longer period than 
described above, the applicable sites must comply with those policies in addition to US and ICH 
policies.   
No study records should be destroyed without prior authorization from The Sponsor, the written 
consent of the Sponsor, if applicable. It is the responsibility of the Sponsor to inform the 
investigator when these documents no longer need to be retained. 
14.4 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or GCP requirements.  
The noncompliance may be either on the part of the subject, the investigator, or the study site staff.  
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly.  
It is the responsibility of the site to use continuous vigilance to identify and report deviations to 
the Sponsor Medical Monitor or designee as soon as protocol deviation is identified.  All 
documentation regarding protocol deviations will be maintained in the regulatory file. All 
deviations must be addressed in study source documents and reported to Sponsor. Protocol 
deviations must be sent to the local IRB/IEC per their guidelines. The site Principal Investigator 
is responsible for ensuring all study staff understands the local IRB/IEC reporting guidelines and 
adhere to all related requirements and documentation.  
14.5 
Publications and Data Sharing Policy 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a coordinating 
investigator will be designated by mutual agreement. Authorship will be determined by mutual 
agreement and in line with the International Committee of Medical Journal Editors authorship 
requirements. 
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
107 
15.
LITERATURE REFERENCES
Advani R, Flinn I, Popplewell L, et al. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's 
Lymphoma. N Engl J Med 2018;379:1711-21. 
Advani RB, N.L. Smith, S.M. et al. . The First in-class anti-CD47 antibody HU5F9-G4 + rituximab induces 
responses in relapses/refractory DLBCL and indolent lymphoma: interim phase 1B/2 results. Hematol 
Oncol 2019;37. 
Ansell S, Chen RW, Flinn IW, et al. A Phase 1 Study of TTI-621, a Novel Immune Checkpoint Inhibitor 
Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies. Blood 
2016;128:1812. 
Beatty GL, Li Y, Long KB. Cancer immunotherapy: activating innate and adaptive immunity through CD40 
agonists. Expert Rev Anticancer Ther 2017;17:175-86. 
Blazar BR, Lindberg FP, Ingulli E, et al. CD47 (integrin-associated protein) engagement of dendritic cell 
and macrophage counterreceptors is required to prevent the clearance of donor lymphohematopoietic cells. 
J Exp Med 2001;194:541-9. 
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients 
Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical 
Practice Guideline. J Clin Oncol 2018;36:1714-68. 
Brightwell RM, Grzankowski KS, Lele S, et al. The CD47 "don't eat me signal" is highly expressed in 
human ovarian cancer. Gynecol Oncol 2016;143:393-7. 
Byrne KT, Vonderheide RH. CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in 
Cancer. Cell Rep 2016;15:2719-32. 
Calvo E, Moreno V, Perets R, et al. A phase I study to assess safety, pharmacokinetics (PK), and 
pharmacodynamics (PD) of JNJ-64457107, a CD40 agonistic monoclonal antibody, in patients (pts) with 
advanced solid tumors. J Clin Oncol 2019;37:2527-. 
Chao MP, Weissman IL, Majeti R. The CD47-SIRPalpha pathway in cancer immune evasion and potential 
therapeutic implications. Curr Opin Immunol 2012;24:225-32. 
Chow LQM, Gainor JF, Lakhani NJ, et al. A phase I study of ALX148, a CD47 blocker, in combination 
with established anticancer antibodies in patients with advanced malignancy. J Clin Oncol 2019;37:2514-. 
de Silva S, Fromm G, Shuptrine CW, et al. CD40 Enhances Type I Interferon Responses Downstream of 
CD47 Blockade, Bridging Innate and Adaptive Immunity. Cancer Immunology Research 
2019:canimm.0493.2019. 
Delamarre L, Holcombe H, Mellman I. Presentation of exogenous antigens on major histocompatibility 
complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell 
maturation. J Exp Med 2003;198:111-22. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
Evers R, Dallas S, Dickmann LJ, et al. Critical review of preclinical approaches to investigate cytochrome 
p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white 
paper. Drug Metab Dispos 2013;41:1598-609. 
FDA. Guidance Document: Estimating the maximum safe starting dose in initial clinical trials for 
therapeutics in adult healthy volunteers.  July 6, 2005. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
108 
Guo W, Wang SJ, Yang S, Lynn H, Ji Y. A Bayesian interval dose-finding design addressingOckham's 
razor: mTPI-2. Contemp Clin Trials 2017;58:23-33. 
Gupta V, Yull F, Khabele D. Bipolar Tumor-Associated Macrophages in Ovarian Cancer as Targets for 
Therapy. Cancers (Basel) 2018;10. 
Haanen J, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical 
Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv119-iv42. 
Hildner K, Edelson BT, Purtha WE, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic 
cells in cytotoxic T cell immunity. Science 2008;322:1097-100. 
Ingram JR, Blomberg OS, Sockolosky JT, et al. Localized CD47 blockade enhances immunotherapy for 
murine melanoma. Proc Natl Acad Sci U S A 2017;114:10184-9. 
Kauder SE, Kuo TC, Harrabi O, et al. ALX148 blocks CD47 and enhances innate and adaptive antitumor 
immunity with a favorable safety profile. PLoS One 2018;13:e0201832. 
Kornbluth RS, Stempniak M, Stone GW. Design of CD40 agonists and their use in growing B cells for 
cancer immunotherapy. Int Rev Immunol 2012;31:279-88. 
Li Y, Lu S, Xu Y, et al. Overexpression of CD47 predicts poor prognosis and promotes cancer cell invasion 
in high-grade serous ovarian carcinoma. American journal of translational research 2017;9:2901-10. 
Lin GHY, Chai V, Lee V, et al. TTI-621 (SIRPalphaFc), a CD47-blocking cancer immunotherapeutic, 
triggers phagocytosis of lymphoma cells by multiple polarized macrophage subsets. PLoS One 
2017;12:e0187262. 
Liu K, Yang K, Wu B, et al. Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric 
Cancer. Medicine (Baltimore) 2015;94:e1631. 
Merz C, Sykora J, Marschall V, et al. The Hexavalent CD40 Agonist HERA-CD40L Induces T-Cell-
mediated Antitumor Immune Response Through Activation of Antigen-presenting Cells. J Immunother 
2018;41:385-98. 
O'Connell PJ, Morelli AE, Logar AJ, Thomson AW. Phenotypic and functional characterization of mouse 
hepatic CD8 alpha+ lymphoid-related dendritic cells. J Immunol 2000;165:795-803. 
Oldenborg PA, Zheleznyak A, Fang YF, Lagenaur CF, Gresham HD, Lindberg FP. Role of CD47 as a 
marker of self on red blood cells. Science 2000;288:2051-4. 
Olsson M, Bruhns P, Frazier WA, Ravetch JV, Oldenborg PA. Platelet homeostasis is regulated by platelet 
expression of CD47 under normal conditions and in passive immune thrombocytopenia. Blood 
2005;105:3577-82. 
Petrova PS, Viller NN, Wong M, et al. TTI-621 (SIRPalphaFc): A CD47-Blocking Innate Immune 
Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin Cancer Res 
2017;23:1068-79. 
Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with 
the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 2018;11:35. 
Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: 
consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management 
Working Group. J Immunother Cancer 2017;5:95. 
Report_SL2020IB001. SL-
-Fc-CD40L) Investigator's Brochure. Shattuck Labs. 
Rosello S, Blasco I, Garcia Fabregat L, Cervantes A, Jordan K. Management of infusion reactions to 
systemic anticancer therapy: ESMO Clinical Practice Guidelines. Ann Oncol 2017;28:iv100-iv18. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
109 
Saber H, Del Valle P, Ricks TK, Leighton JK. An FDA oncology analysis of CD3 bispecific constructs and 
first-in-human dose selection. Regul Toxicol Pharmacol 2017;90:144-52. 
Sallman DA, Donnellan WB, Asch AS, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and 
well tolerated alone or with azacitidine in AML and MDS patients: Initial phase 1b results. J Clin Oncol 
2019;37:7009-. 
Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing 
immunotherapeutics. Lancet Oncol 2017;18:e143-e52. 
Sikic BI, Lakhani N, Patnaik A, et al. First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 
Antibody Hu5F9-G4 in Patients With Advanced Cancers. J Clin Oncol 2019;37:946-53. 
Uger R, Johnson L. Blockade of the CD47-SIRPalpha axis: a promising approach for cancer 
immunotherapy. Expert Opin Biol Ther 2020;20:5-8. 
Vitale LA, Thomas LJ, He LZ, et al. Development of CDX-1140, an agonist CD40 antibody for cancer 
immunotherapy. Cancer Immunol Immunother 2019;68:233-45. 
Vonderheide RH, Dutcher JP, Anderson JE, et al. Phase I study of recombinant human CD40 ligand in 
cancer patients. J Clin Oncol 2001;19:3280-7. 
Vonderheide RH, Flaherty KT, Khalil M, et al. Clinical activity and immune modulation in cancer patients 
treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol 2007;25:876-83. 
Wang H, Tan M, Zhang S, et al. Expression and significance of CD44, CD47 and c-met in ovarian clear 
cell carcinoma. Int J Mol Sci 2015;16:3391-404. 
Weiskopf K, Ring AM, Ho CC, et al. Engineered SIRPalpha variants as immunotherapeutic adjuvants to 
anticancer antibodies. Science 2013;341:88-91. 
Willingham SB, Volkmer JP, Gentles AJ, et al. The CD47-signal regulatory protein alpha (SIRPa) 
interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A 2012;109:6662-7. 
Xu M, Wang X, Banan B, et al. Anti-CD47 monoclonal antibody therapy reduces ischemia-reperfusion 
injury of renal allografts in a porcine model of donation after cardiac death. Am J Transplant 2018;18:855-
67. 
Yamao T, Noguchi T, Takeuchi O, et al. Negative regulation of platelet clearance and of the macrophage 
phagocytic response by the transmembrane glycoprotein SHPS-1. J Biol Chem 2002;277:39833-9. 
Yao X, Wu J, Lin M, et al. Increased CD40 Expression Enhances Early STING-Mediated Type I Interferon 
Response and Host Survival in a Rodent Malaria Model. PLoS Pathog 2016;12:e1005930. 
Yasumi T, Katamura K, Yoshioka T, et al. Differential requirement for the CD40-CD154 costimulatory 
pathway during Th cell priming by CD8 alpha+ and CD8 alpha- murine dendritic cell subsets. J Immunol 
2004;172:4826-33. 
Yi T, Li J, Chen H, et al. Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger 
Adaptive Immune Responses. Immunity 2015;43:764-75. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
110 
16.
APPENDICES 
 
16.1 
mTPI-2 Dose Escalation Scenarios 
See Table 7 in Section 9.1 for dose escalation decision rules based on the total number of subjects 
evaluable for DLT and the number of DLTs observed.   
For each dose level, subjects will be enrolled in cohorts of approximately 3 to evaluate DLT and 
make a dose escalation/stay/de-escalation decision based on decision rules in table 6 in section 9.1 
as the following steps: 
Step 1:  The first cohort of at least 3 subjects will be enrolled and evaluated for DLT, and 
dose escalation/stay/de-escalation decision will be made among at least 3 DLT evaluable 
subjects.  Assuming 3 subjects are DLT evaluable in cohort #1, the following decisions 
will be made based on the number of subjects with a DLT among the 3 DLT evaluable 
subjects: 
o If no subject with a DLT, dose escalate to the next higher dose level; 
o If 1/3 subject with a DLT, stay at the current dose level and move to step 2;  
o If 2/3 subjects with a DLT, dose de-escalate to next lower dose level;  
o If 3/3 subjects with a DLT, dose de-escalate to next lower dose level and the current 
dose level will never to be used; 
o If the first 2 subjects experience a DLT before the third subject enrolls, then de-
escalate to the next lower dose level and the current dose level will never be used.  
 
Step 2:  As there is 1 subject with DLT among 3 DLT evaluable subjects in cohort #1, 
approximately 3 subjects will be enrolled and evaluated for DLT at the current dose in 
cohort #2.  Assuming 3 DLT evaluable subjects in cohort #2, the following decisions will 
be made based on the number of subjects with DLT among the 6 DLT evaluable subjects 
from cohort #1 and cohort #2: 
o If 1/6 subjects with a DLT (no subject with a DLT in cohort #2), then dose escalate 
to the next higher dose level;  
o If 2/6 subjects with a DLT (1 subject with a DLT in cohort #2), stay at the current 
dose level and move to step 3;  
o If 3/6 subjects with a DLT (2 subjects with a DLT in cohort #2), dose de-escalate 
to next lower dose level;  
o If 4/6 subjects with a DLT (3 subjects with a DLT in cohort #2), dose de-escalate 
to next lower dose level and the current dose level will never be used.  
 
Step 3:  As there are 2 subjects with DLT among 6 DLT evaluable subjects in cohort #1 
and #2, approximately 3 subjects will be enrolled and evaluated for DLT at the current dose 
in cohort #3.  Assuming 3 DLT evaluable subjects in cohort #3, the following decisions 
will be made based on the number of subjects with DLT among the 9 DLT evaluable 
subjects from cohort #1, cohort #2 and cohort #3: 
o If 2/9 subjects with a DLT (no subject with a DLT in cohort #3), then dose escalate 
to the next higher dose level;  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
111 
o If 3/9 subjects with a DLT (1 subject with a DLT in cohort #3), stay at the current 
dose level and move to step 4;  
o If 4/9 subjects with a DLT (2 subjects with a DLT in cohort #3), dose de-escalate 
to next lower dose level;  
o If 5/9 subjects with a DLT (3 subjects with a DLT in cohort #3), dose de-escalate 
to next lower dose level and the current dose level will never be used.  
 Step 4:  As there are 3 subjects with DLT among 9 DLT evaluable subjects in the first 3 
cohorts, approximately 3 subjects will be enrolled and evaluated for DLT at the current 
dose in cohort #4.  Assuming 3 DLT evaluable subjects in cohort #4, the following 
decisions will be made based on the number of subjects with DLT among the 12 DLT 
evaluable subjects from all 4 cohorts:  
o
If 3/12 subjects with a DLT (no subject with a DLT in cohort #4) with 25% DLT 
rate, then dose escalate to the next higher dose level;  
o
If 4-6 subjects with a DLT (1-3 subjects with a DLT in cohort #4) with 33% to 50% 
DLT rate, dose de-escalate to next lower dose level.  


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
112 
16.2
ECOG Performance Status Criteria
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease performance 
without restriction
1 
Symptoms but ambulatory. Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., 
light housework, office work) 
2 
In bed < 50% of the time. Ambulatory and capable of all self-care, but unable 
to carry out any work activities. Up and about more than 50% of waking 
hours. 
3 
limited self-care, confined to bed 
or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair. 
5 
Dead.
Source: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET al. Toxicity and response 
criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 (6):649-55. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
113 
16.3
Contraception Requirements
Females of reproductive potential must agree to avoid becoming pregnant. Female of reproductive 
potential are required to use adequate methods of birth control from the time of screening (i.e., at 
least 14 days prior to D1 of SL-172154) through at least 30 days after the last dose of SL-172154.  
Definition of Female of Childbearing Potential: 
A female subject who is not sterile due to surgery (i.e., from bilateral tubal ligation/occlusion, 
bilateral oophorectomy, bilateral salpingectomy or complete hysterectomy) or who does not have 
a congenital or acquired condition that prevents childbearing or who is not naturally post-
menopausal for at least 12 consecutive months.  
Definition of Female of Non-Reproductive Potential: 
Female subjects will be considered of non-reproductive potential if they:  
1. Are post-menopausal if defined as amenorrhoeic for 12 consecutive months without 
an alternative medical cause. In women < 45 years of age a high follicle stimulating 
hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy. In the absence of 12 consecutive months of amenorrhea, a 
single FSH measurement is insufficient; 
OR 
2. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy 
or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; 
OR 
3. Have a congenital or acquired condition that prevents childbearing. 
Definition of Male of Non-Reproductive Potential: 
Male partners will be considered of non-reproductive potential if they have azoospermia (whether 
due to having had a vasectomy or due to an underlying medical condition).   
Highly Effective Methods of Contraception (<1% failure rate): 
For contraception, subjects should comply with one of the following: 
1. Practice abstinence† from heterosexual activity;  
OR
2. Use (or have their partner use) acceptable contraception during heterosexual activity.   
Acceptable methods of contraception are‡: 
 Single method (one of the following is acceptable): 
intrauterine device 
vasectomy of a female subject’s male partner 
contraceptive rod implanted into the skin 
 Combination Methods 
o Female Subjects: The following hormonal contraceptives may be used by 
female subjects and requires use of a male condom for the male partner: 
 oral contraceptive pill (estrogen/progestin pill or progestin-only pill)
 contraceptive skin patch 
 vaginal contraceptive ring 
 subcutaneous contraceptive injection 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
114 
†Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if 
it is consistently employed as the subject’s preferred and usual lifestyle and if considered 
acceptable by local regulatory agencies and IRBs/Independent IECs. Periodic abstinence (e.g., 
calendar, ovulation, sympto-thermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception.  
‡If a contraceptive method listed above is restricted by local regulations/guidelines, then it does 
not qualify as an acceptable method of contraception for subjects participating at sites in this 
country/region. 
Subjects should be informed that taking the study medication may involve unknown risks to the 
fetus (unborn baby) if pregnancy were to occur during the study.  To participate in the study, 
subjects of childbearing potential must adhere to the contraception requirement (described above) 
from the time of screening and at least 14 days prior to D1 of SL-172154 through at least 30 days 
after the last dose of SL-172154.   
16.3.1 Pregnancy Status 
In the rare event that -hCG is elevated as a tumor marker, pregnancy should be excluded. At 
minimum, this requires obstetrics evaluation, serial -hCG measurements and ultrasound to 
exclude pregnancy. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
115 
16.4
Cockcroft-Gault Formula for Creatinine Clearance 
Creatinine clearance (mL/min)1 =  Q x (140 – age [yr]) x ideal body weight [kg]2 
 
 
 
 
 
72 x serum creatinine [mg/dL] 
Q = 0.85 for females 
Q = 1.0 for males 
OR 
Creatinine clearance (mL/min)2 =  K x (140 – age [yr]) x ideal body weight [kg]1 
serum creatinine [µmol/L] 
K = 1.0 for females 
K = 1.23 for males 
1. Creatinine clearance has a maximum value of 125 mL/min.  
2. 
% of IBW. Otherwise, use bodyweight 
 
 
Calculation of IBW using the Devine Formula [Devine, 1974]: 
 
Males = 50.0 kg + (2.3 x each inch over 5 ft) or 50.0 kg + (0.906 kg x each cm over 152.4 cm) 
Females = 45.5 kg + (2.3 x each inch over 5 ft) or 45.5 kg + (0.906 kg x each cm over 152.4 cm) 
 
Example: 
Male, actual body weight = 90.0 kg; height = 68 inches; IBW = 50 + (2.3) (68 – 60) = 68.4 kg 
be used in calculating the estimated creatinine clearance 
 
References: 
Devine BJ. Case Number 25 Gentamicin Therapy: Clinical Pharmacy Case Studies. Drug Intell. Clin Pharm. 
1974;8:650-655. 
Levey, A.S., J. Coresh, T. Greene, et al. (2006).  Using standardized serum creatinine values in the modification of 
diet in renal disease study equation for estimating glomerular filtration rate.  Ann Intern Med.  145:247-254. 
Levey, A.S., L.A. Stevens, C.H. Schmid, et al. (2009).  A new equation to estimate glomerular filtration rate.  Ann 
Inter Med.  150:604-612. 
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
116 
16.5
RECIST v1.1 and iRECIST Criteria 
16.5.1 RECIST v1.1 Criteria
Measurable disease:  Measurable tumor lesions (nodal, subcutaneous, lung parenchyma, solid 
organ metastases) are defined as those that can be accurately measured in at least one dimension 
millimeter (mm) with CT scan or clinical examination.  
Bone lesions are considered measurable only if assessed by CT scan and have an identifiable soft 
tissue component th
short axis will be measured and followed. All tumor measurements must be recorded in mm (or 
decimal fractions of cm). Previously irradiated lesions are not considered measurable unless 
progression has been documented in the lesion. 
CT scan and only the short axis of these nodes will contribute to the baseline sum. All other 
-target 
lesions. Nodes that have a short axis <10 mm are considered non-pathological and should not be 
recorded or followed. 
Non-measurable disease:  All other lesions (or sites of disease), including small lesions (longest 
axis), are considered non-measurable disease.  Bone lesions without a measurable soft tissue 
component, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis, 
inflammatory breast disease, lymphangitic involvement of lung or skin, and abdominal masses 
followed by clinical exam are all non-measurable.  Lesions in previously irradiated areas are non-
measurable, unless progression has been demonstrated. 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
they meet the definition of measurability described above. However, if non-cystic lesions are 
present in the same participant, these are preferred for selection as target lesions. 
Target lesions:  When more than one measurable tumor lesion is present at baseline all lesions up 
to a maximum of 5 lesions in total (and a maximum of 2 lesions per organ), representative of all 
involved organs, should be identified as target lesions and recorded and measured at baseline.  
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements.  It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.  A sum of the diameters (longest for non-nodal 
lesions, short axis for nodal lesions) for all target lesions will be calculated and reported as the 
baseline sum diameters.  If lymph nodes are to be included in the sum, then only the short axis is 
added into the sum.  At baseline, the sum of the target lesions (longest diameter of tumor lesions 
plus short axis of lymph nodes: overall maximum of 5) is to be recorded.   


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
117 
After baseline, a value should be provided on the eCRF for all identified target lesions for each 
assessment, even if very small. If extremely small and faint lesions cannot be accurately measured 
but are deemed to be present, a default value of 5 mm may be used. If lesions are too small to 
measure and indeed are believed to be absent, a default value of 0 mm may be used. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
Non-target lesions: All non-measurable lesions (or sites of disease) plus any measurable lesions 
over and above those listed as target lesions are considered non-target lesions and should also be 
recorded at baseline.  Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up.  
16.5.2 Evaluation of Response 
Complete Response (CR): Disappearance of target and non-target lesions and normalization of 
tumor markers.  Pathological lymph nodes must have short axis measures <10 mm (Note: continue 
to record the measurement even if <10 mm and considered CR).  Residual lesions (other than 
nodes <10 mm) thought to be non-malignant should be further investigated (by cytology, 
specialized imaging or other techniques as appropriate for individual cases) before CR can be 
he scan showing 
CR. 
Partial Response (PR): At least a 30% decrease in the sum of the measures (longest diameters 
for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the 
baseline sum of diameters.  Non-target lesions must be non-progressive disease.  Response should 
 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for progressive disease, taking as reference the smallest sum diameters while on study.  
eeks from baseline. 
Progressive Disease (PD):  At least a 20% increase in the sum of diameters of measured lesions 
taking as references the smallest sum of diameters recorded on study (including baseline) AND an 
sease 
(including lesions in previously unassessed areas). In exceptional circumstances, unequivocal 
progression of non-target disease may be accepted as evidence of disease progression, where the 
overall tumor burden has increased sufficiently to merit discontinuation of treatment or where the 
tumor burden appears to have increased by at least 73% in volume. Modest increases in the size 
of one or more non-target lesions are NOT considered unequivocal progression. If the evidence of 
progressive disease is equivocal (target or non-target), treatment may continue until the next 
assessment, but if confirmed, the earlier date must be used. 
16.5.3 iRECIST v1.1 Criteria 
When using iRECIST, the definitions of measurable and non-measurable lesions still follow 
RECIST v1.1. The principles used to establish an objective tumor response when using iRECIST 
are largely unchanged from RECIST v1.1, however, responses assigned using iRECIST have a 
prefix of “i” (e.g., “immune” complete response [iCR]) to differentiate them from responses 
assigned using RECIST v1.1. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
118 
The major change is the concept of resetting the bar if RECIST v1.1 progression is followed at the 
next assessment by tumor shrinkage. This adaptation accounts for instances where an increase in 
tumor burden, or the appearance of new lesions, does not reflect true tumor progression. Therefore, 
iRECIST requires confirmation of progression. 
Confirming Progression: iRECIST requires the confirmation of progression and uses the terms 
iUPD (unconfirmed progression) and iCPD (confirmed progression). Confirmatory scans should 
be performed at least 4 weeks, but no longer than 8 weeks after iUPD.  iCPD is confirmed if further 
increase in tumor burden, compared to the last assessment, is seen as evidenced by one or more of 
the following criteria: 
 
Continued increase in tumor burden (from iUPD) where RECIST v1.1 definitions of progression 
had been met (from nadir) in target, non-target disease or new lesions. 
o Progression in target disease worsens with an increase of at least 5 mm in the absolute 
value of the sum 
o Continued unequivocal progression in non-target disease with an increase in tumor burden 
o Increase in size of previously identified new lesion (s) (an increase of at least 5 mm in the 
absolute value of the sum of those considered to be target new lesions) or additional new 
lesions 
 
RECIST v1.1 criteria are met in lesions types (target or non-target or new lesions) where 
progression was not previously identified, including the appearance of additional new lesions. 
 
If iUPD is not confirmed at the next assessment, then the appropriate response will be assigned 
(iUPD if the criteria are still met, but no worsening, or iSD, iPR or iCR if those criteria are met 
compared to baseline).  
New Lesions:  New lesions (NL) should be assessed and measured as they appear using RECIST 
v1.1 criteria (maximum of 5 lesions, no more than 2 per site, at least 10 mm in long axis (or 15 
mm in short axis for nodal lesions) and recorded as New Lesions-Target (NLT) and New Lesion-
Non-Target (NLNT) to allow clear differentiation from baseline target and non-target lesions.  
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or iCPD). However, the 
measurements of target lesions should NOT be included in the sum of measures of original target 
lesions identified at baseline. Rather, these measurements will be collected on a separate table in 
the eCRF.  
Progressive disease is confirmed in the New Lesion category if the next imaging assessment, 
conducted at least 4 weeks (but not more than 8 weeks) after iUPD confirms further progression 
from iUPD with either an increase of at least 5 mm in the absolute value of the sum of NLT OR 
an increase (but not necessarily unequivocal increase) in the size of NLNT lesions OR the 
appearance of additional new lesions. 
iRECIST Time Point Response Table  
Target Lesions 
Non-Target 
Lesions 
New Lesions 
Time Point Response 
No prior 
iUPD
Prior iUPD 
iCR
iCR 
No
iCR
iCR 
iCR
Non-iCR/Non-
iUPD 
No
iPR 
iPR 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
119 
Target Lesions
Non-Target 
Lesions 
New Lesions 
Time Point Response 
No prior 
iUPD
Prior iUPD 
iPR 
Non-iCR/Non-
iUPD
No
iPR 
iPR
iSD
Non-iCR/Non-
iUPD 
No
iSD
iSD 
iUPD with no 
change OR 
decrease from last 
TP 
iUPD with no 
change OR 
decrease from 
last TP 
Yes
NA
NLs confirms iCPD if NL were previously 
SOM for NLT or any increase for NLNT) 
or number.  If no change in NLs (size or 
number) from last TP, remains iUPD 
iSD
iUPD
No
iUPD
Remains iUPD unless iCPD confirmed 
based in further increase in size of NT 
disease (need not meet RECIST v1.1 
criteria for unequivocal PD) 
iUPD
iUPD 
No
iUPD 
Remains iUPD unless iCPD confirmed 
based on further increase in SOM of at 
least 5 mm, otherwise remains iUPD 
iUPD
iUPD 
No
iUPD 
Remains iUPD unless iCPD confirmed 
based on further increase in previously 
and/or NT lesion iUPD (prior assessment 
need not be unequivocal PD) 
iUPD
iUPD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed 
based on further increase in:  
 previously identified T lesion iUPD 
 
 previously identified NT lesion iUPD 
(prior assessment need not be 
unequivocal PD) 
 size or number of new lesions previously 
identified 
Non-iUPD/PD 
Non-iUPD/PD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed 
based on:  
 
increase in size or number of new 
lesions previously identified 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
120 
Target Lesions
Non-Target 
Lesions 
New Lesions 
Time Point Response 
No prior 
iUPD
Prior iUPD 
RECIST v1.1 principles. If no pseudo-progression of disease (PSPD) occurs, RECIST v1.1 and iRECIST 
assessment immediately prior to this TP. 
PD = progressive disease; SOM = sum of measurements 
Note:  Participants with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic deterioration.”
Every effort should be made to document the objective progression even after discontinuation of treatment. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
121 
16.6
Summary of Changes for Protocol Amendment 02 
Minor Editorial Changes: 
 
Title Page and all page headers have edits to denote version number/date of Amendment 02  
 
Updated TOC and List of Abbreviations  
 
Removed United Kingdom as a country for location of clinical sites from Synopsis section 
(Planned Number of Sites and Countries section) 
 
In Section 3.5.1 clarified that medications are prohibited during SL-172154 therapy (removed 
study) 
Text deleted from footnote m to SOA table in 6.1: CA-125 should be measured to coincide with each 
scheduled tumor assessment as outlined above with the last required sample obtained at the post treatment 
visit which occurs within 30 days of last dose of SL-172154Table 4 
Section 6.1.1 Table 4 title heading added new text: and RBC Binding
 
In Section 7.3 removed first sentence in last paragraph of this section: Changes in the severity of 
an AE will be documented to allow an assessment of the duration of the event at each level of 
severity. 
Changes Made to Address FDA Concerns:
1. Homologous recombinant deficiency (HRD) status will be collected for all subjects including 
BRCA status 
 
Section 6.1 SOA Table and footnotes 
 
Revised to include collection of HRD information during screening and footnote S provided 
new text provided in italics as follows: Homologous recombinant deficiency (HRD) status: 
Collection of HRD status (including BRCA status) is required for all subjects during the 
screening period. Results from standard of care testing will be used. 
 
Footnotes T and U are now associated with Post Treatment and Follow up visits, respectively 
 
2. Inclusion criteria revised to allow enrollment of subjects who fulfill the definitions below: 
a)  all subjects with primary ovarian, peritoneal and fallopian cancers are required to have received 
platinum-based therapies. 
b)   HRD positive subjects if they have failed prior PARP inhibitor therapy given with or without 
bevacizumab and,  
c)  refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their 
condition. 
 
Section 4.1 inclusion criterion #3 revised as follows: 
3.  New Text provided in italics: Subjects should not be eligible for further platinum therapy. 
Subjects must be refractory or intolerant to existing therapy(ies) known to provide clinical 
benefit for their condition. Subject must have received platinum-based therapies, and should 
not be eligible for further platinum therapy, or should be intolerant to such therapy. Subjects 
with HRD positive disease may participate if they have received prior polyadenosine 
diphosphate ribose polymerase (PARP) inhibitor therapy given alone or with bevacizumab.
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
122 
3. Treatment beyond progression per iRECIST requires that subjects have no decline in their ECOG 
performance status. 
 
Section 8.2 provided new text in the 1st paragraph of this section as indicated (new text in 
italics): 
 
Subjects will be permitted to continue IP beyond initial progressive disease provided the 
subject does not have clinical symptoms of progression, is tolerating IP, has experienced 
no decline in  ECOG performance status and is gaining clinical benefit as assessed by the 
investigator.  The subject must be made aware of the potential benefits and risks of 
continuing the IP in the setting of progressive disease by signing a separate written 
informed consent.   
4. The DLT assessment period for assessment of AEs that inform dose escalation decisions is 28 days 
(not 21 days as originally proposed). 
 
Study Schema revised to note 28-day DLT assessment period 
 
Synopsis Sections that include revisions indicating 28-day DLT assessment period:
 
Study Design, Definition of DLT, and Statistical Analysis Sections  
 
Protocol sections revised that include text revisions indicating 28-day DLT 
assessment period (replacing 21-day period) 
 
 
Section 3.1 Description of Study Design 
 
Section 3.3 Description of Dose Escalation Plan 
 
Section 3.4 Definition of Dose Limiting Toxicity  
 
Section 9.2.1 Analysis Populations (revised DLT evaluable population definition) 
 
 
5. Provided further clarification of the intent to monitor subjects for 90 days after SL-172154 
treatment is permanently discontinued. 
 
Protocol sections with text revisions providing clarification of 90-day follow up post last dose 
of study therapy 
 
Section 6.1 SOA table footnote p revised as follows (new text in italics): 
 
p. AE Monitoring: Subjects will be followed continuously for AEs during the study and 
for 90 days after the last dose of SL-172154. After a subject is discontinued from SL-
172154 or study therapy due to progressive disease or for other reasons, any ongoing 
AE should be followed until resolution (or return to baseline) and documented in the 
eCRF. If another anti-cancer agent is started within 90 days after the last dose of SL-
172154, only SAEs and AEs that occur prior to the start of the new anticancer therapy 
within 30 days from last dose of SL 172154 should be recorded. In the event of a 
continuing SAE or a non-serious irAE, the subject will be asked to return for follow-
up until the SAE or AE has resolved or is deemed to be continuing indefinitely. AEs 
will be characterized per NCI-CTCAE criteria v5.0 and events recorded in the eCRF. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
123 
 
Section 7 text revision (new text in italics) 
 
Subjects will be followed continuously for allny AEs starting when a subject has signed 
the ICF, throughout the course of treatment and for 90 days after the last dose of IP. After 
a subject is discontinued from SL-172154 due to progressive disease or for other reasons, 
any ongoing AEs should be followed until resolution (or return to baseline) and 
documented in the eCRF. If another anti-cancer agent is started within 90 days after the 
last dose of SL-172154, only SAEs and irAEs that occur prior to starting the new 
anticancer therapy within 30 days from last dose of SL 172154 should be recorded. All 
observed or volunteered AEs (serious or non-serious) and abnormal laboratory test 
findings, if applicable, whether suspected to have a causal relationship to SL-172154 or 
not will be recorded in the subject medical record and in the eCRF.  AEs will be graded 
according to NCI-CTCAE v5.0.  For all AEs, sufficient information will be pursued and/or 
obtained to permit an adequate determination of seriousness and outcome of the event (i.e., 
whether it should be classified as a SAE or not) and an assessment of the causal relationship 
between the AE and SL-172154.  AEs will be followed until resolution (or return to 
baseline) or stabilization.  Refer to Section 7.4 for documentation and reporting of AEs. 
 
Section 7.4 AE Reporting procedures (new text in italics) 
Subjects will be followed continuously for AEs during the study and for 90 days after the 
last dose of IP. After a subject is discontinued from IP due to progressive disease or for 
other reasons, any ongoing AE should be followed until resolution (or return to baseline) 
and documented in the eCRF, regardless of whether the event(s) is attributed to trial 
medication. If another anti-cancer agent is started within 90 days of the last dose of SL-
172154, only SAEs and irAEs that occur before the new anticancer therapy  within 30 
days from last dose of SL 172154 should be recorded. The following information will 
be recorded: description, date of onset and end date, severity, assessment of relatedness to 
trial medication, and action taken.  Follow-up information should be provided as necessary.  
AEs will be followed either until resolution, or the event is considered stable.
 
6. Revised the DLT criteria to include any deaths that are not clearly due to the underlying disease or 
extraneous causes. 
 
Section 3.4 Definition of Dose Limiting Toxicity and Corresponding Section in Synopsis 
 
New Text: Any death not clearly related to underlying disease or extraneous causes 
 
7. Clarified that subjects eligible for dose escalation must have tolerated SL-172154 therapy well and 
experienced AEs < or = Grade 1 in severity on the most recent cycle of study treatment. 
 
Section 3.3.1 Intrasubject Dose Escalation (and in Synopsis) revised to include new text in 
italics 
 
Intrasubject dose escalation(s) may be considered on a case-by-case basis, provided that 
the subject has completed at least 2 cycles at the originally assigned dose, has tolerated 
treatment well,  and did not experience Grade 3 or higher toxicity, and experienced Grade 
1 toxicity on the most recent cycle of SL-172154 therapy.


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
124 
8. Clarified that all AEs that occur in subjects enrolled in this study will be collected starting from the 
time subject consents to participate until they are discontinued from the study. 
 
Section 7.1.1 Events not Qualifying as AEs/SAEs 
 
New text added: Because attribution of AEs is difficult in a FIH study, any toxicity 
experienced by subjects in this study should be recorded as AEs unless otherwise specified. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
125 
16.7
Summary of Changes for Protocol Amendment 03 
Minor Editorial Changes: 
 
Title Page and all page headers have edits to denote version number/date of Amendment 03 
 
Reference to Investigator’s Brochure (IB) for SL-172154 updated and IB now cited in section 
1.4.1 point #3 Hemolysis and Anemia  
 
Updated TOC 
 
Updated document numbers denoted for Amendments 1 and 2 as shown below 
Shattuck Labs Document Number 
Date 
Version 
SL03-OHD-01_0100 
03 March 2020 
Amendment No. 1 
SL03-OHD-01_0201 
24 April 2020 
Amendment No. 2 
Section 1.2.4 last sentence of 2nd paragraph text removed: Additionally, SL-172154 was 
evaluated in vitro for potential binding to erythrocytes and hemolysis 
Section 1.2.4 second sentence of 7th paragraph new text added (shown in italics) and text 
removed: In vitro incubation of SL-172154 with erythrocytes from cynomolgus monkeys or 
humans whole blood did not result in any detectable hemolysis. 
 
Section 1.2.4 the last sentence of the last paragraph had text removed: Overall, the nonclinical 
safety assessment program supports the administration of SL-172154 as an intravenous infusion 
in the proposed first-in-human (FIH) clinical study SL03-OHD-101. 
 
New text added to footnote l to SOA table in section 6.1 as shown in italics. This new text is last 
sentence in the footnote: CA-125 should be measured to coincide with each scheduled tumor 
assessment as outlined above with the last required sample for CA-125 obtained at the post 
treatment visit which occurs within 30 days of the last dose of SL-172154. 
1. The protocol is amended to address the possibility that treatment with SL-172154 may interfere 
with compatibility tests including the antibody screen and crossmatch that are a part of a 
routine pre-transfusion work up should subjects on this study require a blood transfusion for 
supportive care. 
New Section 3.8 added entitled: Antibody Detection and Compatibility Testing for 
Transfusion   
 
New Text in section provides guidance on antibody detection and compatibility testing of 
subjects on SL-172154 therapy who need a transfusion as supportive care. 
 
Sections following the new section 3.8 and text are as follows: 
o Section 3.9 (previously 3.8) entitled Criteria to Resume Treatment 
o Section 3.10 (previously 3.9) entitled Participant Withdrawal of Consent 
o Section 3.11 (previously 3.10) entitled Lost to Follow-up 
o Section 3.12 (previously 3.11) entitled Premature Termination or Suspension of 
Study 
o Section 3.1.3 (previously 3.12) entitled Duration of Treatment 
o Section 3.14 (previously 3.13) entitled Duration of Follow-up 
o Section 3.15 (previously 3.14) entitled End of Study Definition 
Section 6.1 SOA Table footnote h1 
 
Footnote h1 revised with new text added (shown in italics) and old text removed as follows: 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
126 
1) At screening: The following testing should be performed 1) ABO and D group (ABO/Rh) type and 
antibody screen and antibody identification if required; 2) DAT; 3) Phenotype/genotype for, at a 
minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and MNSs. Full phenotyping should be 
performed to include ABO, Rh, D, C, E, Kell, Kidd, Duffy, MNS, and antibody screen 
2)
C1/D2: only need to perform blood phenotyping (ABO/Rh) and DAT.
Section 6.4.6.3 Blood Type and Screen (ABO/Rh) and DAT 
 
Paragraph revised with new text added (shown in italics) and old text removed as follows: 
SL-172154 does bind RBCs but has not been shown to cause hemolysis in NHPs. However, 
treatment with SL-172154 may make phenotyping difficult due to expected coating of the RBC 
membrane. Thus, blood phenotyping, type and screen (ABO/Rh), and DAT should be 
performed at screening before exposure to SL-172154. At screening the following testing 
should be performed: 1) full phenotyping should include ABO and D group (ABO/Rh) type 
and antibody screen and antibody identification if required; 2) DAT; 3) phenotype/genotype 
for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and MNSs D, C, E, Kell, Kidd, 
Duffy, MNS, and antibody screen should be performed. Subsequent assessment At cycle 1/day 
2, testing should only include (ABO/rRh type)  and DAT testing as outlined in the SOA table 
in Section  6.1.
 
 
2. This amendment also addresses a comment provided by the FDA during review of the IND application 
for SL-172154 on allowable storage condition limits for diluted drug product at room temperature and 
under refrigerated conditions.   
Section 5.1.2.1 Preparation  
 
Removed text and new text (in italics) added to this section as shown below. Microbial 
growth testing of drug product at room temperature and under refrigerated conditions is 
ongoing and this information will be provided in the Study Pharmacy Manual prior to 
enrollment of subjects.    
 
Standard aseptic technique including preparation of doses in a laminar flow hood is required.  
SL-172154 solution 10 mg, 1 mL is supplied as a frozen liquid.  Before use, thaw each vial of SL-
172154 solution, 10 mg/mL, 1 mL overnight under refrigerated conditions, protected from light, or 
thaw each vial at room temperature, until the entire solution is no longer frozen (e.g., within 1 
hour).  Following thawing, gently swirl the vial to ensure uniformity. Only sterile normal saline 
(0.9%) should be used to dilute SL-172154. 
 
The dosing solution of SL 172154 can be held up to 24 hours under refrigerated conditions or 
8 hours at room temperature (diluted drug product in bag or syringe) from a stability perspective; 
but should be used as soon as possible as the product does not contain an antimicrobial preservative. 
Preparation (e.g., dilution) and administration of study drug may occur at room temperature without 
protection from light. See the SPM for further details on the preparation of SL-172154. 
 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
127 
3. C reactive protein will be collected at the baseline screening and post treatment follow up visits. 
 
Section 6.1 SOA Table 
New text (shown in italics) added to Schedule of Assessments/Procedures column for screening 
visit  
 
In the row for ferritin new text added as shown in italics: Ferritin/C reactive protein 
 
Section 6.4.6  
 
C reactive protein was added to the Local Clinical Labs Table under Clinical Chemistry 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
128 
16.8
Summary of Changes for Protocol Amendment 04 
Minor Editorial Changes 
Title Page and all page headers have edits to denote version number/date of Amendment 04 
 
Title Page: NCT number added   
 
Updated TOC and List of Abbreviations (Study Reference Manual (SRM) removed from list) 
 
Minor formatting changes were made throughout document 
 
Key Trial Contacts Sponsor Signatory page deleted text: Study Reference Manual replaced 
with new text (italics) Study Contact List 
 
Inclusion Criterion #3 in Synopsis and Section 4.1 added new text (italics): Subjects must be 
refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their condition. 
Subject must have received platinum-based therapies, and should not be eligible for further 
platinum therapy, or should be intolerant to such therapy. Subjects with known HRD positive 
disease may participate if they have received prior polyadenosine diphosphate ribose polymerase 
(PARP) inhibitor therapy given alone or with bevacizumab. NOTE: HRD testing is not required 
per protocol. 
 
Synopsis Safety Oversight Section new text (italics added): During the study while subjects are 
receiving treatment with SL-172154, SMC meetings will be held to review relevant data with the 
investigators or delegates.  These meetings will be held once a month (or more frequently if 
required) during dose escalation to share safety data and communicate results of ongoing analyses. 
 
Intrasubject Dose Escalation Section 3.3.1 (last two sentences of paragraph):  Approval for 
intrasubject dose escalation must be obtained from the Sponsor Medical Monitor and must be .  
Dose escalation decisions will be documented on an Intrasubject Dose Escalation Decision Form 
provided by the Sponsor (see the Study Reference Manual; SRM). 
 
Section 5.1.4 
per the 
institutional standard but no less precise than rounded to a whole number prior to calculating the 
dose to be administered (e.g., 72.5 kg should be rounded up to 73 kg, 72.4 kg should be rounded 
down to 72 kg). 
 
SOA Table 6.1: New text (italics) added to Title: Schedule 1 Dose Escalation, Dose Expansion 
and Pharmacodynamic Cohorts 
o Cross references to protocol sections updated and footnote letters updated 
o Footnote a: new text added (italics): Screening Period extends from Day -21 to Day -1.  The 
following screening assessments must be performed within 72 hours of the first dose of SL-
172154: hematology profile, chemistry profile, coagulation profile, ECOG score, physical exam, 
and pregnancy test.
 
Section 6.7.1.4 Text removed from Title: PBMCs for Immunophenotyping 
 
Section 7 Safety Assessments: Subjects will be followed continuously for all AEs starting when a 
subject has signed the ICF, throughout the course of treatment and for 90 days after the last dose 
of IP. After a subject is discontinued from SL-172154 due to progressive disease or for other 
reasons, any ongoing AEs should be followed until resolution (or return to baseline) and 
documented in the eCRF. If another anti-cancer agent is started within 90 days after the last dose 
of SL-172154, only SAEs and irAEs that occur prior to starting the new anticancer therapy should 
be recorded. 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
129 
 
Section 7.5 Pregnancy Reporting (first sentence, new text underlined): Although not an AE in 
and of itself, pregnancy as well as its outcome must be documented via the Pregnancy Report 
Form provided by the Sponsor in the SRM.   
 
Section 14.1 Data Handling and Record Keeping: Second paragraph revised as shown: It is the 
responsibility of the site to use continuous vigilance to identify and report deviations by completing 
the Sponsor Protocol Deviation Form to the Sponsor Medical Monitor or designee as soon as 
protocol deviation is identified.  A completed copy of the Sponsor Protocol Deviation Form All 
documentation regarding protocol deviations will be maintained in the regulatory file. All 
deviations must be addressed in study source documents and, reported to Sponsor. Protocol 
deviations must be sent to the local IRB/IEC per their guidelines. The site Principal Investigator is 
responsible for ensuring all study staff understands the local IRB/IEC reporting guidelines and 
adhere to all related requirements and documentation. Further details about the handling of protocol 
deviations will be included in the study reference manual. 
The protocol is amended to include exploration of a once weekly dosing schedule of SL-
172154 in dose escalation to determine a recommended phase 2 dose for further study. (new 
text provided in italics) 
 
 
Study Schema revised to included schedule 2 in sample size estimate (33 to 54 subjects)
 
Synopsis sections updated to accommodate addition of Schedule 2 
o Planned Sample Size: Approximately to 33 to 54 subjects 
o Recruitment Duration: 25 18 months (< ~ 2 years) 
o Study Duration: 39 32 months (< ~3 years) 
o Study Design: This clinical trial is a FIH, open label, multi-center, dose escalation Phase 
1 study of SL-172154 designed to evaluate the safety, PK, pharmacodynamic effects, and 
anti-tumor activity of SL-172154 monotherapy administered as an IV infusion. The 
planned total sample size is approximately 33 - 54 subjects.  If only Schedule 1 is evaluated, 
the planned total sample size for dose escalation is 21 subjects. If Schedule 1 and Schedule 
2 are both fully evaluated across 5 dose levels in dose escalation, the maximum planned 
sample size for dose escalation is 42. assuming evaluation of approximately 21 subjects 
across 5 dose levels in dose escalation; a Approximately 6 subjects may be enrolled in an 
optional pharmacodynamic cohort; and approximately 6 subjects in the dose expansion 
cohort at the dose and schedule selected for further evaluation. 
o Treatment Schedule:  
 
Schedule 1: SL-172154 will be administered IV on days 1, 8, 15 of a 28-day cycle 
in cycle 1 and then every 2 weeks thereafter (on days 1 and 15 in cycles 
 
 
Schedule 2: SL-172154 will be administered IV once weekly on days 1, 8, 15, and 
22 every 28 days in every cycle. The starting dose on schedule 2 would be instituted 
at the current dose level that has completed evaluation for safety on schedule 1 
and then continue dose escalation as defined by the mTPI-2 design.  
Alternative schedules may be explored if emerging data indicate less frequent dosing of 
SL-172154 should be evaluated. In this case, SL-172154 may be administered once every 
two weeks, once every three weeks or once every four weeks. The starting dose on these 
alternate schedules would be instituted at the current dose level that has completed 
evaluation for safety and then continue dose escalation as defined by the mTPI-2 design, 
emerging safety data and as recommended by the Safety Monitoring Committee (SMC). 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
130 
The starting dose on this altered schedule would be instituted at the current dose level (for 
a less intensive dose schedule) or a lower dose level (e.g., for a weekly dose as noted for  
sSchedule 2) as defined by the mTPI 2 design, emerging safety data and as recommended 
by the Safety Monitoring Committee (SMC). 
o Statistical Analysis: The safety evaluation will be based on the All Treated Population 
defined as all subjects who received at least one dose of study treatment. Frequency tables 
will be used to describe safety and tolerability parameters AEs, irAEs, SAEs, fatal SAEs 
and AEs leading to discontinuation of SL-172154. Changes in toxicity grade for clinical 
chemistry and hematology will also be summarized. AEs will be mapped to a Medical 
Dictionary for Regulatory Activities preferred term and system organ classification. 
Laboratory abnormalities will be graded according to the NCI CTCTAE v5., if applicable. 
The DLT evaluation will be based on the DLT evaluable population (defined as All Treated 
ed 
doses of IP during cycle 1 on Schedule 1 (or at least 2 of the 4 scheduled doses of SL-
172154 on Schedule 2) and complete the safety follow-up through the 28-day DLT 
evaluation period; or 2) who experience any DLT during the DLT evaluation period). DLTs 
will be summarized by dose level. The MTD will be estimated using isotonic regression. 
 
 
Protocol sections updated to accommodate addition of Schedule 2 
o Section 3.1 second paragraph: This Phase 1 trial is designed to evaluate the safety, PK, 
pharmacodynamic effects, and anti-tumor activity of SL-172154 monotherapy 
administered IV on days 1, 8, 15 of a 28 day cycle in cycle 1 and then every 2 weeks 
thereafter (on days 
 Subjects with platinum-ineligible ovarian, 
fallopian tube, and primary peritoneal cancers (Section 4.1) are eligible for treatment. 
o Dose Escalation Section 3.1 
Dose escalation will utilize the modified Toxicity Probability Interval (mTPI-2) design 
[Guo, 2017] with target DLT rate of 30% for the MTD. The dose escalation decision rules 
are outlined in Table 7 in Section 9.1.  Subjects will be enrolled in cohorts of approximately 
3 subjects into sequential dose levels of SL-172154 and evaluated for DLT (see Section 
3.4 for Definition of DLT) during the 28-day DLT evaluation period starting from the first 
dose of SL-172154. At each dose level, a minimum 3-day stagger between dosing the first 
and second subject is required.  The planned dose escalation is in half-log increments as 
outlined in Table 1 and Section 3.3. During dose escalation, two possible schedules 
(Schedule 1 and Schedule 2) for administration of SL-172154 may be explored as outlined 
in Section 3.3. Schedule 1 will be evaluated first. A transition to Schedule 2 may be 
implemented for reasons outlined in Section 3.2.1. If Schedule 2 is opened for enrollment, 
then enrollment on Schedule 1 will be halted. If Schedule 2 is opened, the Sponsor may 
also elect to stop enrollment in Schedule 2 early (e.g., based on safety) and resume 
enrollment in Schedule 1.  The MTD or MAD may be determined for either Schedule 1 or 
Schedule 2. Alternatively, a less intensive dosing schedule may be instituted if safety, 
pharmacokinetic and/or pharmacodynamic data on Schedule 1 support less frequent 
dosing of SL-172154. 
 
For each dose level evaluated on Schedule 1 or Schedule 2, the minimum number of 
subjects evaluable for DLT (see Section 9.2.1 for definition of DLT evaluable subject) will 
be 3 unless unacceptable toxicity is observed prior to enrollment of 3 subjects (e.g., the 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
131 
first 2 subjects experience a DLT before the third subject enrolls). The maximum number 
of subjects evaluable for DLT at a dose level will be 12 (e.g., this may be reached by 
sequential enrollment of 4 cohorts of 3 subjects) assuming the dose decision is to stay at 
the current dose from the first 3 cohorts. After enrollment of If reach the maximum of 12 
DLT evaluable subjects at a given dose level is reached, a dose escalation decision will be 
-escalation decision 
  
o
Pharmacodynamic Cohorts Section 3.1 (first sentence)
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort 
to obtain additional pharmacodynamic data from a total of approximately 6 additional 
subjects at one or more dose levels that have completed evaluation for safety without 
exceeding the MTD on the selected schedule.  
o Dose Expansion Section 3.1 (first sentence) 
Approximately 6 subjects may be enrolled in the dose expansion cohort on a selected 
schedule. 
o Sample Size Section 3.1.2 
If only Schedule 1 is evaluated, Tthe planned total sample size is 21 for dose escalation. If 
Schedule 1 and Schedule 2 are both fully evaluated in dose escalation, the maximum 
planned sample size for dose escalation is 36. 42. for this study is approximately 33 
subjects. This sample size assumes evaluation of approximately 21 subjects across 5 dose 
levels in dose escalation on Schedule 1 and 21 subjects across 5 dose levels on Schedule 
2. Approximately 6 subjects  may be enrolled in an optional pharmacodynamic cohort. 
After a dose and schedule are selected, and approximately 6 subjects will be included in 
the dose expansion cohort. The number of subjects in dose expansion will vary depending 
on the number of subjects enrolled in both the dose escalation and pharmacodynamic 
cohorts at a potential RP2D. The goal is to enroll approximately 12 subjects at the potential 
RP2D, including subjects in the dose escalation, pharmacodynamic cohort, and dose 
expansion cohorts. Overall, the total sample size estimate for this study is 33 subjects, 
assuming only Schedule 1 is evaluated, and 12 potential subjects are enrolled at the RP2D 
and 54 subjects if both Schedule 1 and Schedule 2 are fully evaluated. See Section 9.1 for 
more details. 
o New Section 3.2.1 Criteria for Decision to Transition from Schedule 1 to Schedule 2  
New text provided in this section. 
o Section 3.3 Dose Escalation Plan 
Dose escalation will begin on Schedule 1 at the starting dose of 0.1 milligrams per kilogram 
(mg/kg) as outlined in Table 1 below. Intermediate or higher dose levels not shown may 
be explored based on emerging data (e.g., safety and pharmacodynamic data).  Dose 
escalation of SL-172154 will not exceed half-log increments. The DLT assessment period 
is 28 days in length and ends 14 days after the last dose is administered in the first cycle 
on Schedule 1 and 7 days after the last dose is administered on Schedule 2. Dose escalation 
will follow the mTPI-2 decision rules outlined in Table 7 in Section 9.1.   
 
• 
Schedule 1of administration for SL-172154: Given on days 1, 8, and 15 in cycle 1 over 
28 days. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
132 
• 
Schedule 2 administration for SL-172154: Given on days 1, 8, 15 and 22 of each 28-
day cycle 
•   Cycle length for Schedules 1 and 2: 28 days 
• 
DLT assessment period for Schedules 1 and 2: 28 days 
 
o Dose Escalation Plan Table depicted in Synopsis and in Section 3.3 as Table 1: 
Revisions made to as shown below: New text inserted as footnote b and previous text b, c, 
and d footnotes in table 1 are now c, d, and e respectively. 
 
(+/-10 minutes) or (+/- 15 minutes) window added to duration of infusion times 
 
Modified wording in the new footnote e 
Dose Level 
IV Dose of SL-172154 
(mg/kg)a,b,c,d,e 
Duration of Infusiond
 
Level 1 - starting dose 
0.1 
30 minutes (+/- 10 minutes)
Level 2 
0.3 
30 minutes (+/- 10 minutes)
Level 3 
1.0 
30 minutes (+/- 10 minutes)
Level 4 
3.0 
60 minutes(+/- 15 minutes)
Level 5 
10.0 
60 minutes (+/- 15 minutes)
a) 
Dosing will begin on Schedule 1 with SL-172154 administered in 28-day cycles on days 1, 8, and 15 in 
 
b) 
Dose escalation on Schedule 2 may be tested: If Schedule 2 is opened, SL-172154 may be administered 
once weekly on days 1, 8, 15, and 22 of each 28-day cycle.  
c) 
Intermediate or higher dose levels may be tested based on emerging safety and pharmacodynamic data.  
d) 
g, the dose to be administered should be the same as that 
calculated for a subject weighing 100 kg (see Section 5.1.4). 
e) 
Infusion time may change based on final drug volume needed for administration or observed safety and 
tolerability of the infusion for the subject and/or observed safety findings during the study. Please refer to 
the Study Pharmacy Manual (SPM) for details. 
 
o Evaluation of an Alternative Dosing Schedule in Section 3.3: Safety, pharmacokinetic 
and/or and pharmacodynamic data from the dose escalation cohorts and pharmacodynamic 
cohorts, if available, may support exploration of a more or less intensive dosing schedule 
for SL-172154. If safety and pharmacodynamic these data from Schedule 1 support 
exploration of more frequent dosing then cohort enrollment on Schedule 2 will be instituted 
in lieu of Schedule 1. The starting dose on Schedule 2 will be at at dose level that has 
completed evaluation for safety on Schedule 1 as defined by the mTPI-2 design. Dose 
escalation (or de-escalation) may then proceed on schedule 2 as shown in Table 1. During 
dosing on Schedule 2, SL-172154 will be administered once weekly (D1, D8, D15, and 
D22) every 28 days. If less frequent dosing is supported by safety, pharmacokinetic and/or 
pharmacodynamic data, SL-172154  may be administered weekly, once every two weeks, 
once every three weeks or once every four weeks. The starting dose on a less frequent this 
altered schedule would be instituted at a the current dose level that has completed 
evaluation for safety (for a less intensive dose schedule) or a lower dose level (for a weekly 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
133 
dose schedule) as defined by the mTPI-2 design, emerging safety data and as recommended 
by the SMC. 
o Definition of Dose-Limiting Toxicity Section 3.4 (second sentence 1st paragraph in 
this section): The determinate period for DLT is the first 28 days of SL-172154 dosing 
on Schedule 1 or Schedule 2. 
o Definition of Dose-Limiting Toxicity Section 3.4 (last paragraph in this section): 
continuous interruption of SL-172154 for more than 6 weeks or AEs that result in subjects 
not receiving at least 2 of the 3 scheduled doses of SL-172154 on Schedule 1 (or at least 2 
of the 4 scheduled doses of SL-172154 on Schedule 2) during the DLT assessment period 
due to AE(s) may be taken into consideration when assessing the totality of the data in 
determining DLT and the RP2D.   
o Accrual Goal in Section 4.4: The total sample size expected to complete this study is 
approximately 33 to 54 subjects (see Section 9.1).  Approximately 5 clinical sites may 
participate in SL03-OHD-101.  Overall, the study may complete accrual within 
approximately 2518 months (< ~ 2 years). 
o New SOA Table in Section 6.2 and footnotes 
 
Subsequent Numbering in Section 6 reordered according to addition of new SOA 
Table in 6.2 
 
e.g., Demographics and Medical History Screening and Safety Assessments is 
now Section 6.3 (instead of 6.2) etc. for subsequent sections and subsections that 
follow as noted below 
 
Safety Evaluations now Section 6.4 not 6.3 
 
Pharmacokinetics now Section 6.5 not 6.4 
 
Anti-drug Antibodies now Section 6.6 not 6.5 
 
Pharmacodynamic/Biomarker Assessments now 6.7 not 6.6 
 
Assessment of Anti-Tumor Activity now 6.8 not 6.7 
 
Unscheduled Visits now 6.9 not 6.8. 
 
o Sample Size Determination in Section 9.1: The planned sample size is approximately 33-
54 subjects. If only Schedule 1 is evaluated, the planned total sample size is 21 for dose 
escalation. If Schedule 1 and Schedule 2 are both fully evaluated in dose escalation, the 
maximum planned sample size for dose escalation is 42.  This sample size assumes 
evaluation of five dose levels with approximately 21 subjects treated in the dose escalation 
cohorts for each schedule 1 and schedule 2, assessment of approximately 6 subjects in an 
optional pharmacodynamic cohort and assessment of approximately 6 subjects in dose 
expansion. Overall, approximately 12 subjects are to be treated at the RP2D for SL-172154. 
In dose escalation cohorts, subject may be replaced if not DLT evaluable. 
o Definition of DLT Evaluable Population in Section 9.2.1: All treated subjects 1) who 
cycle 1 on schedule 1 or who have 
 and complete the 
safety follow-up through the 28-day DLT evaluation period; or 2) who experience any DLT 
during the DLT evaluation period. DLT evaluable subjects will be used to guide dose 
escalation and to determine the MTD or MAD. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
134 
o Section 9.2.3 General Data Analysis Consideration (first sentence): Tabular summaries 
will be presented by dose levels/schedule/cohorts and total number of subjects in the 
corresponding population. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
135 
16.9
Summary of Changes for Protocol Amendment 05 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 05 of protocol 
Title page 
 
Approval date changed to 12 July 2021; protocol version number changed to version 05 
Rational for Global Amendment 05 added  
Table of Contents  
 
Updated to include new Appendix Section 16.9 
Page numbers revised 
 
List of Tables 
 
 
Revised Table numbers due to addition of new Table to add C1D8 predose PK sample 
 
1. The protocol is amended to include infusion pre-medication instructions (Section 5) 
 
Section 3.6 3rd paragraph revised as shown below (new text in italics): 
Primary Discretionary use of primary prophylaxis against for IRRs prevention is not permitted 
for subjects enrolled at 3.0 mg/kg or less is permitted to avoid obscuring a potential safety 
signal. However, as noted in Section 3.6.1, secondary prophylaxis (i.e., prevention of IRRs 
following an initial episode) for these subjects is appropriate and permitted at the discretion 
of the investigator for all dose levels. Primary prophylaxis for IRR prevention is required with 
each SL-172154 administration and to enable an assessment of whether pre medications should 
be required for all subjects for subjects enrolled at 10mg/kg or higher dose levels. See Section 
5.1.2.3 for details regarding the primary prophylaxis medications. However, as noted in the 
guidance below, secondary prophylaxis (i.e., prevention of IRRs following an initial episode) 
is appropriate and permitted at the discretion of the investigator. 
 
Section 3.6.1 AE: Infusion or Hypersensitivity Reactions (new text in italics): 
o Grade 1 Management 3rd bullet: Consider pre-medication (antipyretics, histamine (H1 and 
H2 antihistamines), leukotriene inhibitors, corticosteroids) for subsequent infusions per 
investigator/institutional guidelines if pre-medications are not already required. 
o Grade 2 Management 4th bullet: If the infusion is interrupted, then restart the infusion at 
no more than 50% of the rate at which the reaction symptoms occurred. For subsequent 
infusions, consider starting infusion at 50% rate at which the symptoms occurred and 
titrate to tolerance. 
o Grade 3 Management 2nd bullet: Begin IV infusion of normal saline and treat with 
epinephrine, bronchodilators, diphenhydramine, ranitidine, corticosteroids, oxygen, fluids, 
vasopressors, etc. and , consider opioids (e.g., meperidine) for rigors, etc. as indicated and 
per institutional guidelines. 
o Grade 3 Management 4th bullet: Rechallenge should not be attempted in cases of true 
anaphylaxis. In other cases, once subject has completely recovered, carefully consider if it 
is safe for the subject to receive SL-172154 at the next scheduled dose with pre-medication 
which the reaction occurred). The next two subsequent infusions of SL-172154 (after an 
event of grade 3 event of infusion-related reaction) must be administered in an inpatient or 
outpatient setting with prolonged observation for a minimum of 12 hours after the 
completion of the infusion. Start infusion at 50% rate at which the symptoms occurred.  If 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
136 
no further symptoms, rate may be escalated at intervals and increments as clinically 
appropriate. If symptoms recur, permanently discontinue SL-172154. 
o Grade 4 Management 3rd bullet: Manage severe IRRs per institutional standards (e.g., 
epinephrine, diphenhydramine, ranitidine, corticosteroids, bronchodilators, oxygen, fluids, 
etc. and consider opioids (e.g., meperidine) for rigors, etc.).  Epinephrine is the drug of 
choice in an anaphylactic reaction and its administration should not be delayed 
 
Section 3.6.1 AE: Cytokine-release Syndrome (new text in italics): 
o Grade 1 Management 3rd bullet: Maintain IV access. Symptomatic treatment with 
antipyretics, antiemetics, analgesics, histamine 1/histamine 2 (H1/H2) antihistamines as 
needed; monitor fluid balance; assess for infection. Consider opioids (e.g., meperidine) for 
rigors. Regularly evaluate for signs of further deterioration 
o Grade 2 Management 2nd bullet: Start IV infusion with normal saline. Administer oxygen 
if needed. Treat with antipyretics, H1/H2 antagonists (diphenhydramine 50 mg IV plus 
ranitidine 50 mg IV), and/or methylprednisolone 1-2 mg/kg or equivalent dose of 
corticosteroid every 6 hours and manage per institutional guidelines. Consider opioids 
(e.g., meperidine) for rigors. Closely monitor cardiac and other organ functions. 
o Grade 3 or 4 Management 3rd bullet: Manage severe IRRs and CRS per institutional 
standards (e.g., epinephrine, diphenhydramine, ranitidine, corticosteroids, 
bronchodilators, oxygen, fluids, meperidine for rigors, etc.).  Epinephrine is the drug of 
choice in an anaphylactic reaction and its administration should not be delayed 
o Grade 3 or 4 Management; for Grade 3 CRS, may consider rechallenge after consultation 
with medical monitor. If rechallenge is given: New sub-bullet #2 as follows Start infusion 
at 50% rate at which the symptoms occurred.  If no further symptoms, rate may be 
escalated at intervals and increments as clinically appropriate. 
 
Section 5.1.2.3 Administration (new text in italics) as shown below:  
Doses of SL-172154 are to be administered as an IV infusion via an infusion pump or syringe 
pump that can ensure precision within at least 0.1 mL/min. DO NOT USE an in-line filter for 
administration of SL-172154. 
Premedication for IRR prophylaxis is required with each 10mg/kg or higher dose and is at the 
investigator’s discretion for doses less than 10mg/kg. The following premedication is to be 
administered approximately 30 minutes prior to the start of each SL-172154 administration:  
 acetaminophen (650 to 1000 mg PO) 
 diphenhydramine (25-50 mg, or equivalent, PO or IV) 
 ranitidine (50 mg IV or equivalent). 
 
2. The protocol is amended to include collection of a PK/ADA predose sample on C1/D8 and 
immunophenotyping, receptor occupancy and cytokine samples on C1D3. 
 
SOA Tables in Sections 6.1 and  6.2 added X to column on C1/D8 to identify assessment of 
PK/ADA sample collection on this study visit. 
o Footnote m in both SOA tables updated to denote collection of C1/D8 PK/ADA sample 
as shown below (new text in italics):  
PK/immunogenicity (i.e., ADA), cytokines and SL-172154 binding to red blood cells 
(RBCs): Blood sample collection timings for PK, ADA, cytokines and measurement of 
RBC binding are outlined in Section 6.1.1 in supplementary Tables 2, 3,  and 4 and 5.  
PK/ADA/cytokine/RBC binding sample collection times on C1D1 through 48 hours 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
137 
postdose are provided in Table 2. PK/ADA/cytokine/RBC binding sample collection times 
in C2D1, C2D2, C2D15 and C2D16 are detailed in Table 4. PK/ADA sample collection 
times in C1D8 and cycles 3 and beyond are outlined in Table 3 and Table 5 4, respectively. 
Blood volumes required are provided in the SLM. PK, ADA, cytokine and RBC 
binding samples should not be collected from infusion port for drug delivery i.e., 
recommend having a separate line in the opposite arm for sample collection.  
 
In Section 6.1.1 new table and caption added at links provided i.e., Table 3: Predose PK, ADA 
Sample (C1/D8) for PK/ADA predose sample on C1D8 
 
SOA Tables in Sections 6.1 and  6.2 added X to column on C1/D3 to identify assessment of  
immunophenotyping, receptor occupancy and cytokine samples on this study visit 
 
In Section 6.1.1 an X was added to Table 2 for collection of a cytokine sample in cycle 1 at the 
48 hr (± 2 hr) post EOI time point. 
 
In Section 6.1.2 a new column was added to Table 6 to collect an immunophenotyping and 
receptor occupancy samples on C1D3 i.e., at the 48 hr (± 2 hr) post EOI time point 
3. Minor editorial changes and clarification edits to text 
 
6-10 clinical sites may participate as denoted in Section 4.4 Accrual Goal (new text in italics). 
The total sample size expected to complete this study is approximately 33 to 54 subjects (see 
Section 9.1).  Approximately 6-10 5 clinical sites may participate in SL03-OHD-101.  
Overall, the study may complete accrual within approximately 25 months (~ 2 years). 
o Planned number of Sites and Countries in Synopsis changed from 5 to 6-10 sites 
 
Section 5.1.2 Title change (new text in italics): Preparation/Handling/Administration/Storage 
of SL-172154/Investigational Product 
 
Section 3.1.1 text change to 1st paragraph second sentence to reflect 6 to 12 subjects may be 
treated at RP2D instead of 12 (new text in italics): Approximately 6-12 subjects (inclusive of the 
subjects enrolled at this dose in the Dose Escalation, Pharmacodynamic cohort, and Dose 
Expansion) may be treated at the RP2D.  
 
Section 3.1.2 text change to second to last sentence to reflect 6 to 12 subjects may be treated at 
RP2D instead of 12 (new text in italics): The goal is to enroll approximately 6-12 subjects at the 
potential RP2D, including subjects in the dose escalation, pharmacodynamic, and dose expansion 
cohorts. Overall, the total sample size estimate for this study is 33 subjects assuming only 
Schedule 1 is evaluated, and 54 subjects if both Schedule 1 and Schedule 2 are fully evaluated. 
See Section 9.1 for more details. 
 
In Tables 2, 3, 4, and 5 in Section 6.1.1: For predose PK, ADA, Cytokine and RBC binding  
samples collected approximately 30 min before dosing, the window for sample collection was 
increased from ±5 min to ±25 min 
 
In Table 6 in Section 6.1.2: For predose complement, immunophenotyping or receptor occupancy 
samples collected before SL-172154 is given, the predose window for sample collection is now 
(- 90 to -530 min)  
 
SOA tables in Sections 6.1 and 6.2 Footnote n text modified as shown (new text in italics): 
Correlative laboratory studies:  Refer to supplementary Table 56 for details in Section 6.1.2 plus 
see the SLM for amount of blood needed and sample shipment details. 
 
Text changes (next text in italics) to title of  Section 6.4.6.1 Ad Hoc Labs for IRR or CRS SAEs  
 
Text changes made in Section 6.4.6.1: Ad hoc labs should be collected as noted if IRR/CRS or an 
immune related serious adverse event (irSAE) occurs. The samples to be collected are provided 
below. 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
138 
 
Table in Section 7.1 Laboratory test(s) that meet definition of an AE or SAE text changed in 
definition of 2nd bullet as shown: Ad hoc labs should be collected as noted in Section 6.4.6.1
above if IRR/CRS or an irSAE occurs. 
 
Section 7.1.1 next text in italics added to bullet #5 as shown: Clear progression of disease under 
study should not be reported as an AE or SAE (unless the investigator considers the progression 
of underlying neoplasia to be atypical in its nature, presentation or severity from the normal 
course of the disease in a particular subject). Signs and symptoms that are clearly consistent with 
the expected progression of the underlying cancer should not be reported as an adverse event, and 
hospitalizations due to the progression of cancer do not necessarily qualify for an SAE. If there is 
any uncertainty about an AE being due only to the disease under study, it should be reported as 
an AE or SAE. 
 
In Section 7.6 the following text changes were made as shown (new text in italics): 
The following events should also be reported to the Sponsor within 24 hours of 
knowledge of the event: The following events should also be reported to the Sponsor and 
PrimeVigilance within 24 hours: 
• 
Overdose: An overdose of SL-172154 should be reported within 24 hours to the 
Sponsor 
• 
Suspected transmission of an infectious agent due to contamination of drug product 
• 
Other events related to misuse of IP 
 


CONFIDENTIAL
SL03-OHD-101 
Compound: SL-172154 
 
Version no: 6.0  
139 
16.10 Summary of Changes for Protocol Amendment 06 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 06 of protocol 
Title page 
Approval date changed to 24 August 2021; protocol version number changed to version 06 
Rationale for Global Amendment 06 added  
Table of Contents  
 
Updated to include new Appendix Section 16.10 
Page numbers revised 
 
 
1. The protocol is amended to remove the Absolute Lymphocyte Count eligibility criteria 
 
Protocol Synopsis: removed ALC eligibility criteria from laboratory parameters required for 
study enrollment 
 
Section 4.1: removed ALC eligibility criteria from laboratory parameters required for study 
enrollment 
2. The protocol is amended to update the investigational product information to reflect the 
current program-level description of SL-172154. 
 
Formulation description in Section 5.1.1 has been updated: 
Solution containing SL-172154 10 mg/ml formulated in 40nM histidine, 150 mM NaCl, at 
pH 7.3. Refer to the Study Pharmacy Manual (SPM) for further description of the drug 
product. 
 
Physical description in Section 5.1.1 has been updated: 
SL-172154 solution, 10 mg/ml in a 5ml glass vial closed with a FluroTec® rubber stopper 
and sealed with a flip-off aluminum seal.
 
Preparation of SL-172154 language has been updated in Section 5.1.2.1 (new text in italics): 
Standard aseptic technique including preparation of doses in a laminar flow hood is 
required. SL-172154 solution, 10 mg/mL, 1 mL is supplied as a frozen liquid.  Before use, 
thaw each vial of SL-172154 solution 10 mg/mL, 1 mL overnight under refrigerated 
conditions, protected from light, or thaw each vial at room temperature, until completely 
thawed the entire solution is no longer frozen (e.g., within 1 hour). 
3. The protocol is amended to update the Schedule of Assessments for Schedule 1 
  
 
Section 6.1: added weight assessment to C1D1 to correctly reflect language in Section 5.1.4 

SAP_001.pdf: 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
2 
 
TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS ....................................................................................................... 4 
1. 
INTRODUCTION .................................................................................................................. 6 
2. 
STUDY OBJECTIVES AND OUTCOME MEASURES ................................................... 6 
3. 
STUDY DESIGN .................................................................................................................... 8 
3.1 
STUDY DESIGN ............................................................................................................... 8 
3.2 
STATISTICAL DESIGN FOR DOSE ESCALATION ............................................................ 11 
3.3 
SAMPLE SIZE ................................................................................................................ 13 
3.4 
DURATION OF STUDY TREATMENT .............................................................................. 13 
3.5 
DURATION OF FOLLOW-UP .......................................................................................... 13 
3.6 
END OF STUDY ............................................................................................................. 14 
3.7 
STUDY ASSESSMENTS AND PROCEDURES .................................................................... 14 
4. 
ANALYSIS POPULATIONS .............................................................................................. 14 
5. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................. 15 
5.1 
INTERIM ANALYSES ..................................................................................................... 15 
5.2 
REPORTING CONVENTIONS .......................................................................................... 15 
5.3 
DATA HANDLING ......................................................................................................... 16 
5.3.1 
Premature Withdrawal and Missing Data ....................................................... 16 
5.3.2 
Baseline and Change from Baseline ............................................................... 16 
5.3.3 
Study Day, Duration, and Time from Event ................................................... 17 
5.3.4 
Imputation of Partial Date .............................................................................. 17 
6. 
STUDY POPULATION....................................................................................................... 18 
6.1 
SUBJECT DISPOSITION .................................................................................................. 18 
6.2 
PROTOCOL DEVIATIONS .............................................................................................. 18 
6.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ..................................................... 18 
6.4 
STUDY CANCER HISTORY ............................................................................................ 18 
6.5 
GENERAL MEDICAL AND SURGICAL HISTORY ............................................................ 18 
6.6 
PRIOR ANTI-CANCER TREATMENT .............................................................................. 19 
6.7 
STUDY DRUG EXPOSURE ............................................................................................. 19 
6.8 
PRIOR AND CONCOMITANT MEDICATIONS .................................................................. 20 
6.9 
CONCOMITANT PROCEDURE ........................................................................................ 20 
7. 
EFFICACY ANALYSES ..................................................................................................... 20 
7.1 
OBJECTIVE RESPONSE RATE ........................................................................................ 20 
7.2      CLINICAL BENEFIT RATE.............................................................................................. 22 
7.3 
TIME TO RESPONSE ...................................................................................................... 23 
7.4 
DURATION OF RESPONSE ............................................................................................. 23 
7.5 
PROGRESSION FREE SURVIVAL .................................................................................... 23 
7.6 
OVERALL SURVIVAL .................................................................................................... 24 
7.7 
EXPLORATORY ANALYSIS ........................................................................................... 24 
7.8 
CA-125 ........................................................................................................................ 26 
8. 
SAFETY ANALYSES .......................................................................................................... 26 
8.1 
MAXIMUM TOLERATED DOSE EVALUATION ............................................................... 26 
8.2 
ADVERSE EVENTS ........................................................................................................ 27 
8.3 
CLINICAL LABORATORY EVALUATION ....................................................................... 28 
8.4 
DEATH .......................................................................................................................... 29 
8.5 
VITAL SIGNS AND PULSE OXIMETRY ........................................................................... 29 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
3 
 
8.6
CARDIAC ASSESSMENTS.............................................................................................. 29
8.7 
ECOG PERFORMANCE STATUS ................................................................................... 29 
8.8 
BLOOD PHENOTYPE AND DIRECT ANTIGLOBULIN TEST ............................................. 29 
8.9 
TRANSFUSION .............................................................................................................. 29 
9. 
PHARMACOKINETIC ANALYSES ................................................................................ 29 
9.1 
DATA HANDLING ......................................................................................................... 30 
9.2 
SL-172154 CONCENTRATION MEASURES ................................................................... 31 
9.3 
PK PARAMETERS ......................................................................................................... 31 
9.4 
ASSESSMENT OF DOSE PROPORTIONALITY ................................................................. 32 
10. PHARMACODYNAMIC AND BIOMARKER ANALYSES .......................................... 33 
11. CHANGE FROM PROTOCOL-SPECIFIED ANALYSES ............................................ 33 
12. LITERATURE REFERENCES ......................................................................................... 33 
13. APPENDIX: LIST OF TABLES, FIGURES AND LISTINGS ....................................... 34 
13.1 LIST OF TABLES ........................................................................................................... 34 
13.2 LIST OF FIGURES .......................................................................................................... 36 
13.3 LIST OF DATA LISTINGS ............................................................................................... 36 
 
 
 
 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
4 
 
LIST OF ABBREVIATIONS 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under the serum concentration time curve 
BLQ 
Below the limit of quantification 
C1D1 
Cycle 1 day 1 
CBR 
Clinical benefit rate 
CD40 
Cluster of differentiation 40 
CD40L 
Cluster of differentiation 40 ligand 
CI 
Confidence interval 
CL 
Clearance 
Cmax 
Maximum observed concentration 
Cmin 
Minimum observed concentration 
CR 
Complete response 
CV 
Coefficient of variation 
CTCAE 
Common terminology criteria for adverse event 
DAT 
Direct antiglobulin test 
DLT(s) 
Dose-limiting toxicity(ies) 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EOI 
End of infusion 
FIH 
First in human 
HRD 
Homologous recombination deficiency 
iBOR 
Best overall response based on iRECIST 
ICH 
International Conference of Harmonisation 
iCPD 
Immune confirmed progression of disease 
iCR 
Immune complete response 
iPR 
Immune partial response 
irAE 
Immune-related adverse event 
iRECIST 
Immune response evaluation criteria in solid tumors 
iSD 
Immune stable disease 
iUPD 
Immune unconfirmed progression of disease 
Kg 
Kilogram 
MAD 
Maximum administered dose  
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligrams 
mg/kg 
Milligrams per kilogram 
MTD 
Maximum tolerated dose  
mTPI-2 
Modified toxicity probability interval 2 
NCA 
Non-compartmental analysis 
NCI 
National Cancer Institute 
NE 
Not evaluable 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PD 
Progressive Disease 










Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
9 
 
primary peritoneal cancers are eligible for treatment. This study includes dose escalation, 
pharmacodynamic, and dose expansion cohorts (see Schema below).  
 
 
 
Dose Escalation Cohorts 
 
During dose escalation, two possible schedules (Schedule 1 and Schedule 2) for administration of 
SL-172154 may be explored as outlined below: 
 Schedule 1: SL-172154 is given on days 1, 8 and 15 in cycle 1 (28 days for each cycle) 
and then every 2 weeks thereafter on days 1 and 15 in cycles >=2 
 Schedule 2: SL-172154 is given on days 1, 8, 15 and 22 each 28-day cycle  
 
Dose escalation for Schedule 1 and Schedule 2 will utilize the modified Toxicity Probability 
Interval (mTPI-2) design as described by Guo et al. with target DLT rate of 30% for the MTD. 
Subjects will be enrolled in cohorts of approximately 3 subjects into sequential dose levels of SL-
172154 and evaluated for DLT during the 28-day DLT evaluation period starting from the first 
dose of SL-172154. At each dose level, a minimum 3-day stagger between dosing the first and 
second subject is required.   
 
Schedule 1 will be evaluated first. A transition to Schedule 2 may be implemented if 
pharmacodynamic effects are not present or detectable in Schedule 1, or pharmacokinetic 
parameters from Schedule 1 may suggest that a more frequent dosing schedule is warranted. If 
Schedule 2 is opened for enrollment, the enrollment on Schedule 1 will be paused. Schedule 2 may 
stop enrollment earlier (e.g., based on safety) and enrollment in Schedule 1 may be resumed. The 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
10 
 
MTD or MAD may be determined for either Schedule 1 or Schedule 2. Alternatively, a less 
intensive dosing schedule may be instituted if safety, pharmacokinetic and/or pharmacodynamic 
data on Schedule 1 support less frequent dosing of SL-172154.   
 
The planned dose escalation is in half-log increments as outlined in Table 1. 
 
Table 1: SL-172154 Dose Escalation Plan in Phase 1 
Dose Level 
IV Dose of SL-172154 
(mg/kg)a,b,c,d 
Duration of Infusione 
Level 1 - starting dose 
0.1 
30 minutes (+/- 10 minutes) 
Level 2 
0.3 
30 minutes (+/- 10 minutes) 
Level 3 
1.0 
30 minutes (+/- 10 minutes) 
Level 4 
3.0 
60 minutes (+/- 15 minutes) 
Level 5 
10.0 
60 minutes (+/- 15 minutes) 
a)
Dosing will begin on Schedule 1 with SL-172154 administered in 28-day cycles on days 1, 8, and 15 in cycle 
 
b) Dose escalation on Schedule 2 may be tested. If Schedule 2 is opened, SL-172154 may be administered once 
weekly on days 1, 8, 15 and 22 of each 28-day cycle.  
c) Intermediate or higher dose levels may be tested based on emerging safety and pharmacodynamic data.  
d) The actual body weight in kilograms (kg) will be used for dose calculation in all subjects whose body weight 
calculated for a subject weighing 100 kg.  
e) Infusion time may change based on final drug volume needed for administration, safety and tolerability of the 
infusion for the subject and/or observed safety findings during the study. Protocol Clarification Memo dated 
on 04MAR2022 clarified that the duration of infusion was to be increased from 60 minutes to 120 minutes (± 
20 minutes) for 10 mg/kg dose level. Protocol Clarification Memo dated on 3JUN2022 clarified that the 
duration of infusion was to be increased from 60 minutes to 120 minutes (± 15 minutes) for 3 mg/kg dose 
level. 
 
For each dose level evaluated at Schedule 1 or Schedule 2, the minimum number of subjects 
evaluable for DLT (see Section 4 for definition of DLT evaluable subject) will be 3 unless 
unacceptable toxicity is observed prior to enrollment of 3 subjects (e.g., the first 2 subjects 
experience a DLT before the third subject enrolls). The maximum number of subjects evaluable 
for DLT at a dose level will be 12 (e.g., this may be reached by sequential enrollment of 4 cohorts 
of 3 subjects) assuming the dose decision is to stay at the current dose from the first 3 cohorts. 
Section 3.2 details the statistical design and rules for dose escalation.   
 
During dose escalation, a review of available safety data for all subjects will be undertaken by the 
Safety Monitoring Committee (SMC) approximately every four weeks and a decision made 
regarding the safety profile of the current and prior dose levels.  
 
Intrasubject dose escalation(s) may be considered on a case-by-case basis, provided that the subject 
has completed at least 2 cycles at the originally assigned dose, has tolerated treatment well, and 
experienced Grade 1 toxicity on the most recent cycle of SL-172154 treatment. 
may be increased to a dose level that has completed evaluation for safety and has not exceeded the 
MTD.  


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
11 
 
 
Pharmacodynamic Cohorts  
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort to obtain 
additional pharmacodynamic data from a total of approximately 6 additional subjects at one or 
more dose levels or one or more dosing schedules that have completed evaluation for safety 
without exceeding the MTD on the selected schedule. Subjects in the pharmacodynamic cohort 
must have tumor accessible for biopsy without excessive safety risk and must consent to providing 
paired biopsies for translational research. Subjects enrolled in the pharmacodynamic cohort will 
not inform dose escalation decisions but the pharmacodynamic information gathered from these 
additional subjects will inform selection of doses for further evaluation and the RP2D 
determination.  
 
Dose Expansion Cohort 
Approximately 6 subjects will be enrolled in the dose expansion cohort on a selected schedule. 
Subjects may be enrolled at one or more dose levels to further characterize safety, tolerability, PK, 
anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D. The number of 
subjects in dose expansion will vary depending on the number of subjects enrolled in both dose 
escalation and the pharmacodynamic cohort at a potential RP2D. The goal is to enroll 
approximately 6-12 subjects at the potential RP2D, including subjects in dose escalation, 
pharmacodynamic cohort, and dose expansion.  
 
Selection of the Recommended Phase 2 Dose 
Selection of the RP2D and schedule for SL-172154 monotherapy will be based upon the totality 
of the data in subjects treated in dose escalation, dose expansion and pharmacodynamic cohorts.  
Approximately 6-12 subjects (inclusive of the subjects enrolled at this dose in the Dose Escalation, 
Pharmacodynamic cohort, and Dose Expansion) may be treated at the RP2D.     
 
3.2 Statistical Design for Dose Escalation 
The dose escalation will utilize a mTPI-2 design with target DLT rate of 30% for the MTD. The 
mTPI-2 design employs a simple Beta-Binomial Bayesian model with decision rules based on the 
unit probability mass from the posterior probability of DLT rate. With the target DLT rate of 30%, 
the posterior probability of DLT rate unit interval (0, 1) is divided into subintervals with equal 
length of 0.1 that correspond to different dose escalation decisions: subinterval of (0.25, 0.35) is 
to stay at the current dose, subintervals below 0.25 is to escalate to next higher dose, and 
subintervals above 0.35 is to de-escalate to the next lower dose. Subjects will be enrolled in cohorts 
of approximately 3 subjects during the dose escalation. After each cohort of approximately 3 
subjects, the posterior unit probability for subintervals will be calculated based on a 
noninformative prior distribution for the DLT rate (Beta(1,1)) and the total number of subjects 
with DLTs and  DLT evaluable subjects for the current dose. A dose escalation/stay/de-escalation 
decision that corresponds to the subinterval with the highest unit probability mass will be selected. 
A minimum of 3 DLT evaluable subjects will be enrolled to a dose level and evaluated for DLT 
before a dose escalation/stay/de-escalation decision can be made unless unacceptable toxicity is 
observed prior to the enrollment of 3 subjects e.g., two subjects experience DLT before the third 
subject enrolls. A dose level will be considered unsafe, with unacceptable toxicity and no 




Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
13 
 
3.3 Sample Size  
If only Schedule 1 is evaluated, the planned total sample size is 21 for dose escalation. If Schedule 
1 and Schedule 2 are both fully evaluated in dose escalation, the maximum planned sample size 
for dose escalation is 42. This sample size assumes evaluation of approximately 21 subjects across 
5 dose levels in dose escalation on Schedule 1 and approximately 21 subjects across 5 dose levels 
on Schedule 2. Approximately 6 subjects may be enrolled in an optional pharmacodynamic cohort. 
After a dose and schedule are selected, approximately 6 subjects will be included in the dose 
expansion cohort. The number of subjects in dose expansion will vary depending on the number 
of subjects enrolled in both the dose escalation and pharmacodynamic cohorts at a potential RP2D. 
The goal is to enroll approximately 6-12 subjects at the potential RP2D, including subjects in the 
dose escalation, pharmacodynamic, and dose expansion cohorts. Overall, the total sample size 
estimate for this study is 33 subjects assuming only Schedule 1 is evaluated, and 54 subjects if 
both Schedule 1 and Schedule 2 are fully evaluated.  
3.4 Duration of Study Treatment  
The planned treatment duration with IP is for a maximum of two years. In the absence of treatment 
delays due to AE(s), treatment may continue until two years or until one of the following criteria 
applies: 
 
Disease progression per RECISTv1.1 (unless eligible for treatment beyond 
progression). 
 
Death 
 
Intercurrent illness that prevents further administration of treatment 
 
Unacceptable AE(s) 
 
Participant decides to withdraw from the study 
 
General or specific changes in the participant's condition that render the participant 
unacceptable for further treatment in the judgment of the investigator 
 
Participant non-compliance 
 
Pregnancy 
 
Termination of the study by Sponsor 
Subjects with confirmed CR may elect to discontinue treatment after a minimum of 48 weeks of 
treatment and continue with all relevant study assessments including disease assessments until 
disease progression or start of another anticancer therapy.  
 
Subjects who permanently discontinue study treatment for reasons other than progression will 
continue with disease assessments until progression or start of another anti-cancer therapy.   
 
3.5 Duration of Follow-up  
Subjects who are withdrawn from study for unacceptable AE(s) will be followed until resolution 
or stabilization of the AE.  Participants who permanently discontinue study treatment for reasons 
other than progression will continue with disease assessments until progression or start of another 
anti-cancer therapy. Subjects who discontinue study treatment for any reason other than 




Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
15 
 
5. GENERAL ANALYSIS CONSIDERATIONS 
5.1 
Interim Analyses 
During the dose escalation, the number of subjects with DLTs will be determined after each cohort 
of approximately 3 subjects has been evaluated for DLT. The summary of DLTs for each dose 
level in Schedule 1 and Schedule 2 will be based on the number of subjects with DLTs from all 
subjects dosed and evaluated at the corresponding dose level who meet the definition of the DLT 
Evaluable Population. Select AE summary tables and listings may be provided during dose 
escalation to support dose escalation decisions.  
5.2 
Reporting Conventions 
The statistical analyses will be reported using summary tables, figures, and data listings. The 
International Conference on Harmonisation (ICH) numbering convention will be used for tables, 
listings, and figures.  
Data from all participating sites will be pooled prior to data summary or analysis. It is anticipated 
that subject accrual will be spread thinly across sites and summaries of data by site will not be 
informative and therefore, will not be provided.   
Unless specified otherwise, all summary tables will be presented by dose schedule/level for all 
subjects in the analysis population, and subjects from dose escalation, pharmacodynamic and dose 
expansion cohorts will be pooled. Summaries will also be provided for subjects at the same dose 
level pooled across schedules. Select safety summary tables may be provided for the dose 
escalation cohorts.  
All individual subject data listings will be presented by dose level, dose schedule and subject, 
unless specified otherwise. Data from all assessments, whether scheduled or unscheduled, will be 
included in the listings. Listings will present the data in their original format (without any 
imputation), unless specified otherwise.  
Summaries by planned time point will include data from scheduled assessments and all data will 
be reported according to the nominal visit for which it will be recorded (i.e., no visit windows will 
be applied). Unscheduled data, when summarized, will be included only in calculation of the 
maximum or minimum value over time such as worst-case post-baseline. If multiple assessments 
are reported on the same date for the same scheduled planned time, the worst-case result will be 
analyzed.  
Continuous variables will be summarized with means, standard deviations, medians, minimums, 
and maximums. The precision of the original measurements will be maintained in summaries and 
listings, when possible. Generally, means and medians will be presented to one more decimal place 
than the raw data, and the standard deviations will be presented to two more decimal places than 
the raw data. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
16 
 
Categorical variables will be summarized by counts and by percentages of subjects in the 
corresponding categories. Percentages are routinely based on the total number of the specified 
population N if not otherwise specified. For frequency counts, categories whose counts are zero 
will be displayed for the sake of completeness. For example, if none of the subjects discontinue 
t to follow-
with zero counts will not have zero percentages displayed.  
All confidence intervals (CIs) will be constructed at the 95% confidence level, unless specified 
otherwise. 
All analyses and tabulations will be performed using SAS  v9.4 or above.  
5.3 
Data Handling 
The following sections provide a general description of the derived and transformed variables 
used to describe and analyze the data.  
5.3.1 Premature Withdrawal and Missing Data  
Subjects who prematurely withdraw from the study will be included in analyses up to the time of 
withdrawal, regardless of the duration of treatment and survival follow-up.  
Missing data occurs when any requested data is not provided, leading to blank field on the 
, 
, etc. are not considered 
to be missing data and should be displayed as such.  
For the time to event endpoints including DOR, PFS and OS, the missing data handling method 
will be censoring. Censoring mechanisms for these endpoints are described in Section 7.   
The length of study treatment for each subject will depend on the safety, tolerability and efficacy 
of the treatment, so the duration of treatment will vary across subjects. Similarly, the duration of 
follow up for survival will also vary.  All time to event endpoints will be analyzed using suitable 
statistical methods. 
In the event that the study is prematurely discontinued, the study team will review the data to 
assess which statistical analyses are still considered appropriate. 
5.3.2 Baseline and Change from Baseline 
Unless otherwise specified, the baseline value is defined as the last value obtained on or before the 
date and time of the first SL-172154 dose on Cycle 1 Day (C1D1). Post-baseline values are defined 
as value obtained after the first dose of SL-172154.  
Change from baseline is calculated as: 
 Post-baseline value - baseline value 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
17 
 
The percent change from baseline is calculated as: 
 (Post-baseline value - baseline value)*100/baseline value  
If either baseline or post-baseline value is missing, the change from baseline and percent change 
from baseline will be missing.  
5.3.3 Study Day, Duration, and Time from Event  
The reference date for age calculation is the date of consent form signed as age is an eligibility 
requirement. The reference date for safety, efficacy and other data analyses is the date of the first 
dose.  
 
 Study Day  Study Day 1 is defined as the date of the first dose; the day before the first 
dose is defined as Study Day -1. There is no study day 0. For a given event date, Study Day 
is calculated relative to the date of first dose of study drug. 
Study Day = [Event Date  First Dose Date] (in days) + 1 day,  
 
where the event date is on or after the first dose date. 
Study Day = [Event Date  First Dose Date] (in days),  
 
where the event date is before the first dose date. 
 Duration (Days)  A duration is calculated as the stop date minus the start date plus one. 
Duration (days) = [Stop Date  Start Date] (in days) + 1 day. 
 Time since an event -Time since an event (e.g. time since initial diagnosis) is calculated 
as the reference date minus the event date. For time since initial diagnosis, the reference 
date is the first dose of study treatment.  
 Time to an event- Time to an event (e.g. time to response, PFS, OS) is calculated as the 
event date minus the reference date+1. For time to response, PFS and OS, the first dose of 
study treatment is the reference date.  
 
To convert days to months, divide the number of days by 30.4375 (365.24/12) and round to one 
decimal place.   
5.3.4 Imputation of Partial Date 
In general, imputed partial dates will not be used to derive study day or duration variables, unless 
otherwise specified. In addition, imputed partial dates are not used for time to event endpoint 
analysis. However, partial dates may be imputed for exploratory analysis. The imputed partial data 
will be flagged in the dataset to indicate the level of imputation. Imputed dates will not be displayed 
in the data listings. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
18 
 
6. STUDY POPULATION 
Unless specified otherwise, all summary tables and data listings for this section will be based on 
the All Treated Population.  
6.1 Subject Disposition 
Summaries of study population and subject disposition will include the number of subjects in each 
analysis population and the primary reason for end of study participation. Study population and 
subject disposition information will be presented in a data listing. Both summary table and listing 
will be based on the Screened population.  
Summaries of study treatment status will include the number of subjects by treatment status, and 
the primary reason for study treatment discontinuation. Subject treatment discontinuation 
information will be presented in a data listing. 
6.2 Protocol Deviations 
Number of subjects for each protocol deviation type and subtype will be summarized for key 
deviations, non-key deviations, and all deviations, respectively. A listing with deviation details 
will be provided for all protocol deviations. A separate listing will be provided for subjects with 
inclusion and exclusion criteria deviation. Other select categories of protocol deviations including 
but not limited to COVID-19 related deviations may be listed or summarized.  
6.3 Demographic and Baseline Characteristics  
Demographic variables include age, sex, ethnicity, race, weight and height. Descriptive statistics 
will be presented for age, weight, and height. Frequency counts and percentages will be presented 
for age groups (18-<65 years, 65-<75 years and 75 years), sex, ethnicity, race, and baseline 
Eastern Cooperative Oncology Group (ECOG) score (0 or 1). All demographic and baseline 
characteristics data will be presented in data listings for All Treated and Screen Failure population, 
respectively.  
6.4 Study Cancer History  
Study cancer history including the type of cancer, FIGO stage at study entry, grade, World Health 
Organization (WHO) histologic classification of cancer, BRCA mutation status and homologous 
recombination deficiency (HRD) status will be summarized in a table. Time since initial diagnosis 
will also be summarized.  All study cancer history data will be presented in a data listing. 
6.5 General Medical and Surgical History 
General medical history and surgical history along with start/end date and ongoing status at study 
entry will be presented in a data listing. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
19 
 
6.6 Prior Anti-Cancer Treatment  
Prior study cancer systemic treatment drugs will be coded using the WHO Drug Dictionary. Prior 
study cancer systemic treatment including regimen number, drug name, start/end date, intent, 
regimen best response, and data of progression will be presented in a data listing. Time since 
progression on the most recent regimen, and number of prior systemic regimens will be included 
in the summary table.  
Prior anti-cancer surgical treatment including the date and intent of procedure will be presented in 
a data listing.  
Prior anti-cancer radiotherapy including start/end date and intent of radiotherapy will be presented 
in a data listing.  
6.7 
Study Drug Exposure 
The individual subject SL-172154 administration including total dose administered, infusion 
concentration, infusion volume, rate of infusion, start and end time, duration of infusion, and 
infusion outcome for each infusion will be presented in a data listing.  
 
Total number of doses received, duration of treatment, average dose received, and dose compliance 
will be summarized. 
 
Subject average dose is calculated as the cumulative dose (mg) that a subject received divided by 
the total number of doses received.   
 
Duration of SL-172154 treatment is defined as: 
 Minimum of (date of death plus 1 day, data cutoff date plus 1 day, and date of last dose + 
14 days if last dose is C1D15 or beyond or + 7 days if last dose is C1D1 or C1D8) minus 
date of first study drug administration for subjects in Schedule 1. 
 Minimum of (date of death plus 1 day, data cutoff date plus 1 day, and date of last dose + 
7 days) minus date of first study drug administration for subjects in Schedule 2. 
In addition to mean, median, minimum and maximum, duration on treatment will also be 
summarized in the following categories: <= 4 weeks, > 4 - 8 weeks, > 8 - 12 weeks, > 12 - 16 
weeks, > 16 weeks.  
Dose compliance is defined as the total mg of SL-172154 infused divided by the total mg of SL-
172154 assigned, expressed as a percentage.   
Duration of SL-172154 treatment will be plotted by subject using a horizontal bar graph with 
information regarding the time of first PR/CR and the first progressive disease (PD), dose level, 
best response (RECIST 1.1) and treatment discontinuation information for each subject.  


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
20 
 
6.8 Prior and Concomitant Medications 
Prior and concomitant medications will be coded to Anatomical Therapeutic Chemical (ATC) 
class and Generic Drug Names using the WHO Drug Dictionary.  
Prior medications are defined as medications that end prior to the date of the first dose of study 
treatment. Concomitant medications are defined as medications taken at any time on or after the 
date of the first dose of study drug. Medications that start prior to the date of the first dose but 
continue beyond the date of first dose will be categorized as concomitant medications. Prior and 
concomitant medications along with dose, route, start/end date, and indication for each medication 
will be presented in a data listing. If both the start and end dates are completely missing, the 
medication will be considered concomitant.  
6.9 Concomitant Procedure  
Concomitant procedures include cancer-related or treatment-related procedure or palliative 
radiotherapy.  Concomitant procedures along with start/end date, and indication for the procedure 
will be presented in a data listing.  
7. EFFICACY ANALYSES 
The efficacy endpoints include ORR, CBR, TTR, DOR, PFS, and OS. The efficacy endpoints 
ORR, CBR, TTR, DOR, and PFS will be based on the investigator disease assessment per RECIST 
1.1. Exploratory analyses of these endpoints will be based on the investigator disease assessment 
per iRECIST (iORR, iCBR, iTTR, iDOR and iPFS).  
 
The efficacy analyses will be based on the All Treated population and/or Response Evaluable 
population, as appropriate. Subjects who do not have any post-baseline disease assessment will be 
considered as non-responders in the calculation of response rate. 
 
Disease response will be evaluated and documented in CRF based on RECIST 1.1 until the first 
PD per RECIST 1.1, and then will be evaluated and documented in CRF based on iRECIST. 
Disease assessment will be performed at baseline (screening visit) and at the following intervals 
until disease progression: every 8 weeks until week 24 and every 12 weeks thereafter until year 2 
and every 6 months until study conclusion. Confirmatory scans should be performed at least 4 
weeks (>28 days) after initial documentation of an objective response. If subjects discontinue study 
treatment prior to progressive disease, they should continue to be followed with radiologic disease 
assessments until disease progression, start of a new anti-cancer therapy, withdrawal of consent or 
death, whichever is earliest.  
7.1 Objective Response Rate  
The ORR is defined as the proportion of subjects whose best overall response is a confirmed CR 
or confirmed PR based on investigator assessment according to RECIST 1.1.  The ORR will be 
estimated with a 95% CI using the exact probability method. The number and percent of subjects 
with the best overall response of CR, PR, SD, PD and not evaluable (NE) will be summarized. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
21 
 
Summary of objective response will be provided for the All Treated population and Response 
Evaluable population, respectively.  
 
The best overall response based on RECIST 1.1 is defined as the best overall response among all 
post-baseline time point assessments until the first PD per RECIST 1.1 or start of new anti-cancer 
therapy, whichever is earlier.  For subjects who have not met the criteria for PD per RECIST1.1 
or have not started a new anti-cancer therapy, the best overall response is defined as the best overall 
response among all post-baseline timepoint assessments.  
 
Based on the investigator assessment of overall response per RECIST 1.1 at post-baseline 
assessments, the best overall response will be determined programmatically as the following and 
Table 3: 
 CR > PR > SD > PD > NE 
 CR = at least two determinations of CR with at least 4 weeks apart before progression. 
 PR = at least two determinations of PR or better with at least 4 weeks apart before 
progression (and not qualifying for CR). 
 
49 days after the first dose and before progression (and 
not qualifying for a CR or PR). The minimum interval from the first dose date for the best 
response of SD is 8 weeks minus 7 days to allow for visit windows of ± 7 days (49 days). 
 If the minimum interval for SD is not met, the best response will depend on the subsequent 
assessments.  See table below for details.  
 PD is considered the best overall response when PD is documented and a best overall 
response of CR, PR, or SD could not be established before documentation of PD. Clinical 
deterioration will not be considered as documented disease progression in the 
determination of the best overall response. 
 NE is considered the best overall response when PD has not been documented and a best 
response of CR, PR or SD could not be established.  
 
Table 3. Best overall response when confirmation of CR and PR required. 
Overall response  
First time point 
Overall response 
Subsequent time 
point 
BEST overall response 
CR 
CR 
CR 
CR 
PR 
SD, PD or PRa 
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD, provided minimum criteria for SD duration met, otherwise, PD 




Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
23 
 
7.3 Time to Response  
The TTR based on RECIST 1.1 is defined as the time from the first dose until the first 
documentation of a subsequently confirmed objective response (confirmed CR or confirmed PR). 
Only subjects who have achieved confirmed objective response will be evaluated for TTR, and 
individual TTR will be presented in a data listing. If data warrants, TTR will be summarized 
descriptively and graphically using Kaplan-Meier methods. The Kaplan-Meier estimate for the 
median TTR along with 95% confidence intervals and the first and third quartiles will be 
determined. Brookmeyer-Crowley method will be used for the confidence interval calculation. 
Kaplan-Meier estimate of TTR rate at 8 weeks, 16 weeks, and other timepoints of interest will be 
included in the summary table.  
7.4    Duration of Response  
The DOR based on RECIST 1.1 is defined as the time from the date of the first CR or PR 
(confirmed at least 28 days later) to the date of first documented disease progression per RECIST 
1.1 or death, whichever occurs first. Only subjects who have achieved a confirmed CR or 
confirmed PR will be evaluated for DOR, and individual DOR will be presented in a data listing. 
 
If a disease progression does not occur, DOR will be censored as of the date of the last evaluable 
disease assessment. The evaluable disease assessment is defined as an assessment for which the 
overall response can be determined. The censoring guidance and the date of PD/death or censoring 
are same as those for PFS in Section 7.5.  If data warrants, DOR will be summarized descriptively 
and graphically using Kaplan-Meier methods. The Kaplan-Meier estimate for the median DOR 
along with 95% confidence intervals and the first and third quartiles will be determined. 
Brookmeyer-Crowley method will be used for the confidence interval calculation. Kaplan-Meier 
estimate of DOR rate at 8 weeks, 16 weeks, and other timepoints of interest will be included in the 
summary table.  
7.5    Progression Free Survival 
The PFS based on RECIST 1.1 is defined as time from the first day of treatment to the first 
documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first. 
Subjects who have not progressed at the time of analysis will be censored at the date of their last 
evaluable disease assessment. Subjects who start new anticancer therapy prior to the documented 
PD will be censored at the last evaluable disease assessment prior to the start of new anticancer 
therapy. The censoring guidance and the date of PD/death or censoring are given in the Table 4 
below.  
 




Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
25 
 
Disease response will be evaluated and documented in CRF based on RECIST 1.1 until the first 
PD per RECIST 1.1, and then will be evaluated and documented in CRF based on iRECIST. The 
iRECIST responses at the timepoint assessments before and on the assessment of first PD per 
RECIST 1.1 are derived based on RECIST 1.1 assessment as in Table 5.  
Table 5. Derivation of iRECIST response for assessments before or on PD per RECIST 1.1   
Timepoint response per RECIST 
Timepoint response per iRECIST 
CR 
iCR 
PR 
iPR 
SD 
iSD 
PD 
iUPD 
NE 
iNE 
 
If data warrants, analysis of iORR, iCBR, iTTR, iDoR, and iPFS based on iRECIST will be 
performed similarly as those based on RECIST 1.1 (Section 7.1, 7.2, 7.4 and 7.5) except the 
following:   
 The best overall response based on iRECIST (iBOR) is defined as the best overall response 
among all post-baseline timepoint assessments until the first confirmed PD per iRECIST 
(iCPD) or the last disease assessment if an iCPD has not been observed.  
 The TTR based on RECIST 1.1 (iTTR) is defined as the time from the first dose until the 
first documentation of a subsequently confirmed objective response per iRECIST (iCR or 
iPR). Only subjects who have achieved objective response (iCR or iPR) will be evaluated 
for iTTR.   
 The DOR based on iRECIST (iDOR) is defined as time from the date of the first iCR or 
iPR (confirmed at least 28 days later) to the date of the first documented iUPD that was 
subsequently confirmed as CPD or death due to any cause, whichever occurs first. Only 
subjects who have achieved objective response (iCR or iPR) will be evaluated for iDOR.  
 PFS based on iRECIST (iPFS) is defined as time from the first day of treatment to the first 
documented iUPD that was subsequently confirmed as iCPD or death due to any cause, 
whichever occurs first.  
 The following will be applied for both iPFS and iDOR: 
o If an unconfirmed PD per iRECIST (iUPD) occurs but is disregarded because of 
later iSD, iPR or iCR, then the iUPD date should not be used as the progression 
event for iPFS/iDOR.  
o If an iUPD is not confirmed and there is no subsequent iSD, iPR or iCR, then the 
iUPD date should still be used as progression event for iPFS/iDOR.  
o If an iUPD is not confirmed and the next timepoint responses are iUPDs but are not 
confirmed, then the last iUPD of the sequential iUPDs will be used as progression 
event for iPFS/iDOR.  
o Subjects who have not progressed at the time of analysis will be censored at their 
last evaluable iRECIST assessment.  
 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
26 
 
7.8 CA-125 
The CA-125 at baseline and post-baseline assessments, and maximum changes in CA-125 from 
baseline among all post baseline assessments will be summarized. Number of subjects with 
>=50%, >=75% and 100% decreases or increase from baseline will be summarized. The percent 
change from baseline in CA-125 for all post-baseline assessments will be plotted by subject. The 
CA-125 test results along with change from baseline will be presented in a data listing. 
8. SAFETY ANALYSES 
Unless specified otherwise, all safety data summaries will be presented by dose schedule/level, 
and all subjects based on the All Treated population. Summaries will also be provided for pooled 
subjects at the same dose level. safety summary will be provided for DLT evaluable populations.   
8.1 Maximum Tolerated Dose Evaluation 
The MTD evaluation will be based on the DLT Evaluable Population. The number and percentage 
of subjects with DLT will be presented by dose schedule and level for dose escalation cohorts. The 
MTD level will be indicated in the summary.  
 
The MTD will be estimated using isotonic regression (based on the DLTs observed in the DLT 
evaluable subjects). A MAD will be reported if the DLT rate never reaches 25%.  Otherwise, an 
MTD will be reported. Isotonic regression is a way to estimate the MTD under the assumption that 
toxicity increases with dose. When using isotonic regression, the first step is to identify the doses 
where the dose-toxicity monotonicity assumption is violated. The DLT estimate is then adjusted 
for the violators such that the final estimate of the DLT rate increases with the dose. The target 
DLT rate is then used to select the MTD. For example, suppose that when the trial is completed, 
the observed DLT rates [# subjects who experienced DLT]/[# evaluable subjects] at five dose 
levels are (0/3, 1/3, 0/3, 4/15, 2/4). In this example the observed DLT rate at Dose Level 2 (i.e., 
1/3=33%) is higher than the observed DLT rate at Dose Level 3 (i.e., 0/3=0%). To adjust for this 
violation, the DLT estimates are replaced with their average, i.e., (1/3+0/3)/2=1/6, resulting in the 
isotonic regression DLT estimates (0/3, 1/6, 1/6, 4/15, 2/4) = (0%, 16.7%, 16.7%, 26.7%, 50%), 
which monotonically increases with the dose level. Based on this isotonic estimate, assuming that 
the trial goal is to find the dose with the DLT rate of 30%, Dose Level 4 will be selected as the 
MTD. If there are no violators of the dose-toxicity monotonicity assumption, isotonic regression 
directly uses the observed DLT rates as the final estimates for MTD selection. For subjects who 
undergo intra-
initial dose level the assignment will be used for MTD determination. 
 
In the case of dose levels with estimated toxicity of equal distance (tied dose levels) from the target 
toxicity of 30%, the following approach will be used: among all tied dose levels the highest dose 
vels have estimated toxicity 
> 30%, in which case the lowest dose level will be selected. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
27 
 
8.2 
Adverse Events 
The AE terms on the eCRFs will be mapped to the preferred terms (PT) and system organ classes 
(SOC) using the Medical Dictionary for Regulatory Activities (MedDRA). Drug-related AEs are 
defined as AEs with relationship to study treatment being related or possible related. A worst-case 
scenario approach will be taken to handle missing data, i.e. AEs with the relationship to study 
treatment as missing will be treated as drug-related AEs.  
All AEs with onset dates on or after the first dose of study treatment are defined as treatment-
emergent adverse events (TEAEs). Only TEAEs will be included in AE tables.  
An overview summary of TEAEs will be produced to include counts and percentages of subjects 
with any TEAE, drug-related TEAEs, DLT, serious TEAEs, drug-related serious TEAEs, fatal 
TEAEs, immune related TEAEs, infusion related reaction AEs, Grade 3 or 4 TEAEs, and TEAEs 
leading to drug withdrawn, drug interrupted, dose not given/held, and infusion interrupted. 
The TEAE by maximum toxicity grade summary tables will use the following algorithms for 
counting subjects: 
 
PT rows: each subject is counted once within each unique PT at the maximum grade.  
For example, if a subject has two headaches, the subject is counted only once under the 
PT 
TEAE PT several times with different 
grades will only be counted once with the maximum grade. 
 
Any event row: each subject with at least one TEAE will be counted only once at the 
maximum grade no matter how many events they have. 
All TEAEs and drug-related TEAEs will be summarized by MedDRA PT and maximum toxicity 
grade. The PT will be ordered by descending order of the subject incidence based on all subjects 
in the analysis population. A table of all TEAEs by SOC and PT will also be provided. 
The following summary tables will be presented by MedDRA PT, in which the PT will be sorted 
by descending order of subject incidence of PT based on all subjects in the analysis population: 
 Summary of all TEAEs.  
 Summary of drug-related TEAEs.  
 Summary of Grade 3 or 4 TEAEs. 
 Summary of DLT.  
 Summary of TEAEs leading to drug interrupted, dose not given/held, infusion 
interrupted, and drug withdrawn. 
 Summary of serious TEAEs. 
 Summary of drug-related serious TEAEs. 
 Summary of immune related TEAEs. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
28 
 
Additional summaries for drug-related IRR AE (toxicity grade, seriousness, number of events, 
action taken) at event-level, at subject-level, and number of subjects with IRR at each dosing 
visit among the first two cycles and during all subsequent cycles combined will be provided. 
All AEs, immune related AEs, drug-related AEs, Grade 3 or 4 AEs, drug-related Grade 3 or 4 
AEs, DLTs, SAEs, fatal AEs, AEs leading to dose not given/held, infusion interruption, dose 
increased or dose reduced, and drug withdrawal, and infusion related reaction signs and 
symptoms will be presented in data listings.  Pretreatment AE, defined as AEs that start prior to 
the first dose of the study treatment, will be flagged in relevant listings. All AEs for the Screen 
Failures population will also be presented in a data listing.  
8.3 
 Clinical Laboratory Evaluation 
The clinical laboratory evaluation includes the following: 
 
Hematology: hemoglobin, hematocrit, platelet count, red blood cell count, white 
blood cell count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.  
 
Clinical chemistry: blood urea nitrogen, creatinine, glucose, sodium, potassium, 
calcium, magnesium, phosphorus, total protein, albumin, lactate dehydrogenase, 
bicarbonate, haptoglobin, ferritin, C reactive protein and liver panel [alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, 
and alkaline phosphatase (ALP)].  
 
Coagulation: prothrombin time, international normalized ratio, activated partial 
thromboplastin time, fibrinogen, and D-dimer.  
 
Thyroid: thyroid stimulating hormone and free thyroxine 4.  
The clinical laboratory grades will be reported using the CTCAE v5.0. Separate listings will be 
provided for hematology, clinical chemistry, coagulation and thyroid tests. For each listing, 
baseline value will be specified for each subject.  
Clinical laboratory results (hematology, clinical chemistry, coagulation, thyroid) will be 
summarized for worst case shift from baseline toxicity grade. Frequencies of maximum observed 
Grade 0-4 toxicity, as defined by the NCI CTCAE v5.0, will be presented for each laboratory 
parameter. The determination of the maximum grade post-baseline takes into account both planned 
and unscheduled assessments.  Separate summaries indicating hyper- and hypo- directionality of 
change will be produced, where appropriate. 
For those laboratory parameters that do not 
have NCI CTCAE v5.0 grading criteria, worst case shift from baseline to post-baseline will be 
summarized. If a subject has worst case 
, the subject will be counted 
in both categories.  
Subjects with elevated worst post-baseline ALT, AST, total bilirubin, or ALP values that fall into 
the following categories will be identified and summarized: 
 ALT in the categories of <=1x upper limit of normal range (ULN), >1x ULN, >3x ULN;  


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
29 
 
 AST in the categories of <=1x ULN, >1x ULN, >3x ULN; 
 total bilirubin in the categories of <=1x ULN, >1x ULN, >2x ULN 
 ALP in the categories of <=1x ULN, >1x ULN, >1.5x ULN, >2x ULN  
 P
-dose total bilirubin > 2 x ULN 
occurred at the same day or after the first incidence date of ALT or AST > 3 x ULN post 
treatment. 
 
Additionally, C1D2 change from C1D1, C1D16 change from C1D15, C2D2 change from C2D1, 
and C2D16 change from C2D15 will be summarized for select laboratory tests (hemoglobin, 
platelet, lymphocytes, neutrophil).  
All laboratory results will be presented by subject in data listings.  
8.4 
Death  
All death records will be presented in a data listing.  Subject incidence of deaths within and outside 
of 30 days of last dose and the cause of death will be summarized.  
8.5 
Vital Signs and Pulse Oximetry 
Vital signs (blood pressure, heart rate, respiration rate, temperature), body weight (with percent 
change from baseline) and pulse oximetry will be presented in a data listing. 
8.6 
Cardiac Assessments  
Cardiac assessments including electrocardiogram (ECG) and echocardiogram (ECHO) assessment 
date and results along with clinically significance will be presented in data listings.hriv  
8.7 
ECOG Performance Status 
ECOG performance status scores will be summarized for baseline, and worst-case shift from 
baseline in a table and presented in a data listing. 
8.8 
Blood Phenotype and Direct Antiglobulin Test  
Blood phenotype and direct antiglobulin test (DAT) assessment date and result will be presented 
in a data listing. 
8.9 
Transfusion 
Transfusions data will be presented in a data listing. 
9.   PHARMACOKINETIC ANALYSES 
The merge of SL-172154 serum concentration with CRF data will be performed after database 
lock by Shattuck Labs to generate a dataset with actual PK sampling times, actual time relative to 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
30 
 
the start of infusion, and SL-172154 concentrations. Derivation of PK parameters will be 
performed by 
 using Phoenix WinNonlin (Version 8.2 or higher).  
Unless otherwise specified, all PK data analysis will be based on the PK population and 
summarized by dose levels regardless of dosing schedules. Subjects who have infusion outcome 
normalized concentration and PK parameter but will be excluded from other summary by dose 
level for the corresponding PK sample collection day.  
9.1 
Data Handling 
The nominal time relative to the start of infusion will be calculated as the planned time relative 
to the end of infusion plus the planned infusion duration. The actual time relative to the start of 
infusion will be calculated as the actual sampling time relative to the start of infusion (SOI) or 
the SOI of the first infusion period if with infusion interruption(s). Missing PK sampling time 
will be handled as the following when calculating the actual time relative to SOI: 
 If a sampling time is missing and no infusion interruption, the actual time relative to SOI 
will be calculated as time from SOI to end of infusion (EOI) plus planned time relative 
EOI. 
 If a sampling time is missing and there is interruption(s) during the infusion, the actual 
time relative to SOI will be calculated as time from the SOI of first infusion period to the 
EOI of the last infusion period plus planned infusion time relative to EOI.  
 
Concentration values that are below the limit of quantification (BLQ) will be handled as the 
following:  
 If a BLQ value occurs at the predose, the BLQ value will be assigned as zero 
concentration. If one or more BLQ values occur in a profile after infusion but before the 
first measurable concentration, the BLQ values will be assigned a value of zero 
concentration. For linear plots, zero concentration value(s) will be included in the plot. 
For log-linear plots, zero concentration value(s) will be assigned a missing value. 
 If a BLQ value occurs after a measurable concentration in a profile and is followed by a 
measurable concentration, then the BLQ will be set as missing.  
 If a BLQ value occurs after the last measurable concentration in a profile, then the BLQ 
values will be set as missing.  
 If two or more BLQ values occur in succession after a measurable concentration, the 
profile will be deemed to have terminated at the first BLQ value (BLQ values will be set 
to missing) and any subsequent concentration will be set as missing. 
 BLQ values that are set to be missing will be omitted from PK parameter generation, 
concentration summary, and the individual PK profile plots. 
 For the time point that all concentrations are BLQ and all BLQ results are imputed to be 
zero, then the mean/median concentration will be reported as zero.  
 For the time point that only some concentrations are BLQ and BLQ values are imputed to 
be zero, the mean/median will be reported unless the mean/median value is below the 
LLQ (10 ng/ml), in which case the value will be assigned as BLQ.  


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
31 
 
9.2 
SL-172154 Concentration Measures 
SL-172154 concentration values will be sorted by dose level, dosing schedule, sample collection 
day, and nominal time points in the listing. All SL-172154 concentration values including BLQ 
will be listed in the same precision as the source data.  
 
SL-172154 concentration will be summarized by dose level for each nominal time point relative 
to the EOI.  Standard summary statistics will be calculated (i.e., mean, standard deviation [SD], 
median, minimum, maximum, coefficient of variation (CV%), geometric mean, geometric 
CV%).  
 
Individual subject concentration-time profiles and median/mean profiles by dose level will be 
plotted for C1D1, C1D15 and C2D1, using the actual time from SOI for individual plots and the 
nominal time from EOI for medina/mean profiles. Each of the figures will contain one plot on 
the untransformed scale (i.e. linear plot) and one plot on the log transformed scale (i.e. semi-log 
plot). For mean concentration profile plot, mean+/- SD for each dose level will be plotted. For 
median concentration profile plot, median along with minimum and maximum for each dose 
level will be plotted. Individual subject concentration-time profiles using actual time from SOI 
(semi-log plot) will also be plotted along with infusion actual start and end time (including any 
interruptions) for each dose level at C1D1, C1D15 and C2D1.  
 
Dose normalized concentration will be calculated by dividing total administered dose (mg).  
Mean (SD) dose normalized concentration time profile will be plotted for each dose level at 
C1D1, C1D15 and C2D1. 
9.3 
PK Parameters  
The PK parameters will be derived from the concentration-time data using the actual collection 
time from SOI. The PK parameters will be calculated by standard non-compartmental analysis 
(NCA) as data permits. At least one post-dose concentration is required for Cmax calculation, and 
at least three consecutive post-dose concentrations are required for AUC parameter calculation.  
 
Table 6  SL-172154 PK Parameters 
Cmax  
Maximum observed concentration over a dosing interval   
Ctrough 
Observed concentration at the end of a dosing interval. 
Tmax  
Time of maximum observed concentration  
AUC0-last  
The area under the serum concentration time curve, from time 0 to the last 
quantifiable concentration, calculated by a combination of linear and 
logarithmic trapezoidal methods (Linear up/log down method).  
AUC0-inf  
Area under the serum concentration time curve from time 0 extrapolated to 
infinity, calculated as AUClast + Clast
z). 
Reliability of AUC0-inf values is contingent on the percent of the total area 
obtained by extrapolation: AUC0-inf values with <20% of the total area 
coming from Clast
z are considered acceptable. Any exceptions to the above 
procedures will be clearly documented/justified in the PK report.  




Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
33 
 
 
Dose normalized PK parameters will be calculated by dividing total administered dose (mg) for 
AUC0-inf, AUC0-last, AUCtau, Cmax, and Ctrough. Additional dose normalized PK parameters may be 
calculated, if appropriate and as data permit. Dose proportionality will be evaluated graphically 
using box plots of dose normalized PK parameters (AUC0-inf, AUC0-last, AUCtau, Cmax, and Ctrough) 
by dose level for C1D1, C1D15 and C2D1.  
Dose proportionality will also be evaluated for the AUC0-inf, AUC0-last, AUCtau, Cmax, and Ctrough 
using the power model as data permit. A statistical linear relationship between the ln-transformed 
PK parameters and the ln-transformed actual dose received in mg will be fitted by using a mixed 
effect model with ln-transformed dose as a fixed effect and subject as random effect. Additional 
predictors may be included in the model. The general form of the power mode is described as: 
Ln(Y) = 0 +  Ln (Dose) +  
dose proportionality.   
10.    PHARMACODYNAMIC AND BIOMARKER ANALYSES 
The analysis plan for pharmacodynamic and biomarker data will be provided in a separate analysis 
plan.   
11.    CHANGE FROM PROTOCOL-SPECIFIED ANALYSES 
There are four changes from protocol-specified analyses: 
1. Protocol Section 9.2.3 states that tabular summaries will be presented by dose 
levels/schedule/cohorts. Due to the limited enrollment, data from different cohorts will be pooled 
and summarized by schedule/dose level. 
2. It is clarified in SAP Section 4 that the DLT Evaluable Population derivation is for the 
subjects enrolled in the dose escalation cohorts. 
3. It is clarified in SAP Section 4 that all subjects who have signed the main study inform 
consent form are defined as Screened population, instead of Enrolled population. 
 
12.    LITERATURE REFERENCES 
1. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, NCI, NIH, 
DHHS, November 27, 2017. 
2. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
3. Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in 
trials testing immunotherapeutics. Lancet Oncol 2017;18:e143-e52. 
4. Brookmeyer, R. and Crowley, J. (1982). A confidence interval for the median survival time. 
Biometrics 38 29-41. 
5. Guo W, Wang SJ, Yang S, Lynn H, Ji Y. A Bayesian interval dose-finding design addressing 
Ockham's razor: mTPI-2. Contemp Clin Trials 2017;58:23-33. 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
34 
 
13.    APPENDIX: LIST OF TABLES, FIGURES AND LISTINGS 
13.1   List of Tables  
ICH 
Heading 
Table 
Number 
Table Description 
Analysis 
Population  
14.1 
 
Demographics 
 
 
14.1.1 
Study Populations and Subject Disposition 
All Screened 
 
14.1.2 
Study Treatment Status 
All Treated 
 
14.1.3 
Protocol Deviations 
All Treated 
 
14.1.4 
Demographic and Baseline Characteristics 
All Treated 
 
14.1.5 
Study Cancer History 
All Treated 
 
14.1.6 
Prior Anti-Cancer Treatment 
All Treated 
14.2 
 
Efficacy 
 
 
14.2.1 
Objective Response with Confirmation Based on RECIST 
1.1  
All Treated 
 
14.2.2 
Objective Response with Confirmation Based on RECIST1.1 
Response 
Evaluable 
 
14.2.3 
Objective Response with Confirmation Based on iRECIST  
All Treated 
 
14.2.4 
Time to Response and Duration of Response Based on 
RECIST 1.1 
Response 
Evaluable 
 
14.2.5 
Time to Response and Duration of Response Based on 
iRECIST  
Response 
Evaluable 
 
14.2.6 
Progression-Free Survival Based on RECIST 1.1  
All Treated 
 
14.2.7 
Progression-Free Survival Based on iRECIST 
All Treated 
 
14.2.8 
Overall Survival  
All Treated 
 
14.2.9 
Tumor Assessment at Baseline 
All Treated 
 
14.2.10 
CA-125  
All Treated 
14.3 
 
Safety 
 
14.3.1 
 
Study drug exposure/adverse event  
 
 
14.3.1.1 
Study Drug Exposure  
All Treated 
 
14.3.1.2 
Overall Summary of Treatment-Emergent Adverse Events  
All Treated 
 
14.3.1.3 
All Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term  
All Treated 
 
14.3.1.4 
All Treatment-Emergent Adverse Events by Preferred Term 
and Maximum Toxicity Grade  
All Treated 
 
14.3.1.5 
Drug-Related Treatment-Emergent Adverse Events by 
Preferred Term and Maximum Toxicity Grade  
All Treated 
 
14.3.1.6 
All Treatment-Emergent Adverse Events by Preferred Term  
All Treated 
 
14.3.1.7 
Serious Treatment-Emergent Adverse Events by Preferred 
Term  
All Treated 
 
14.3.1.8 
Immune Related Treatment-Emergent Adverse Events by 
Preferred Term  
All Treated 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
35 
 
ICH
Heading 
Table
Number 
Table Description 
Analysis 
Population  
 
14.3.1.9 
Drug-Related Treatment-Emergent Adverse Events by 
Preferred Term  
All Treated 
 
14.3.1.10 
Drug-Related Serious Treatment-Emergent Adverse Events 
by Preferred Term  
All Treated 
 
14.3.1.11 
Treatment-Emergent Adverse Events with Toxicity Grade 3 
or 4 by Preferred Term 
All Treated 
 
14.3.1.12 
Dose Limiting Toxicities  
DLT Evaluable 
 
14.3.1.13.1 
Treatment-Emergent Adverse Events leading to Infusion 
Interrupted by Preferred Term  
All Treated 
 
14.3.1.13.2 
Treatment-Emergent Adverse Events Leading to Dose Not 
Given/Held by Preferred Term 
All Treated 
 
14.3.1.13.3 
Treatment-Emergent Adverse Events Leading to Drug 
Interrupted by Preferred Term 
All Treated 
 
14.3.1.14 
Treatment-Emergent Adverse Events leading to Drug 
Withdrawn by Preferred Term  
All Treated 
 
14.3.1.15 
Summary of Drug-Related Infusion Related Reaction at 
Subject Level 
All Treated 
 
14.3.1.16 
Summary of Drug-Related Infusion Related Reaction at 
Event Level 
All Treated 
 
14.3.1.17 
Summary of Drug-Related Infusion Related Reaction by 
Dosing Visit 
All Treated 
 
14.3.1.18 
Deaths  
 
14.3.5 
 
Laboratory 
 
 
14.3.5.1 
Hematology  Maximum CTCAE Grade Shift from Baseline 
All Treated 
 
14.3.5.2 
Chemistry  Maximum CTCAE Grade Shift from Baseline  
All Treated 
 
14.3.5.3 
Coagulation and Thyroid Function Test  Maximum CTCAE 
Grade Shift from Baseline  
All Treated 
 
14.3.5.4 
Laboratory Tests without CTCAE - Maximum Shift from 
Baseline with Respect to Normal Range  
All Treated 
 
14.3.5.5 
Post-Baseline Potential Serious Hepatoxicity 
All Treated 
 
14.3.5.6 
Summary of Change for Select Laboratory Tests 
All Treated 
14.3.6 
 
Other Safety Data 
 
 
14.3.6.1 
ECOG Performance Status  Maximum Shift from Baseline 
All Treated 
14.3.7 
 
PK 
 
 
14.3.7.1 
SL-172154 Serum Concentration-Time Data   
PK 
 
14.3.7.2 
SL-172154 PK Parameters  
PK 
 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
36 
 
13.2   List of Figures  
 
13.3   List of Data Listings   
ICH 
Heading 
Listing 
Number 
Listing Description 
Analysis 
Population  
16.2 
 
SUBJECT DATA LISTINGS 
 
ICH 
Heading
Figure 
Number 
Figure Description 
Analysis 
Population  
14.2 
14.2.1 
Horizontal Bar Plot of Duration on Treatment by Response  
All Treated 
 
14.2.2 
Waterfall Plot of Target Lesions Maximum Reduction in Sum of 
Lesion Diameters 
All Treated 
 
14.2.3 
Plot of Target Lesions Percent Change from Baseline Sum of Lesion 
Diameters Over Time  
All Treated 
 
14.2.4 
Kaplan-Meier Plot of Time to Response Based on RECIST 1.1 and 
iRECIST 
Response 
Evaluable 
 
14.2.5 
Kaplan-Meier Plot of Duration of Response Based on RECIST1.1 and 
iRECIST  
Response 
Evaluable 
 
14.2.6 
Kaplan-Meier Plot of Progression-Free Survival Based on RECIST1.1 
and iRECIST  
All Treated 
 
14.2.7 
Kaplan-Meier Plot of Overall Survival  
All Treated 
 
14.2.8 
Plot of Percent Change from Baseline for CA-125 Over Time  
All Treated 
14.3 
14.3.7.1 
Plot of Individual SL-172154 Concentration-time Profiles by Dose 
Level (Linear and Semi-log) 
PK 
 
14.3.7.2 
Plot of Individual SL-172154 Concentration-time Profiles with 
Infusion Time by Dose Level (Semi-log) 
PK 
 
14.3.7.3 
Plot of Mean (+/-SD) SL-172154 Concentration-time Profile by Dose 
Level (Linear and Semi-log) 
PK 
 
14.3.7.4 
Plot of Median (Min-Max) SL-172154 Concentration-time Profile by 
Dose Level (Linear and Semi-log) 
PK 
 
14.3.7.5 
Plot of Mean (+/-SD) Dose Normalized SL-172154 Concentration-time 
Profile by Dose Level (Linear and Semi-log) 
PK 
 
14.3.7.6 
Box Plot of Cmax by Dose Level  
PK 
 
14.3.7.7 
Box Plot of Dose Normalized Cmax versus Dose Level  
PK 
 
14.3.7.8 
Box Plot of AUC0-last versus Dose Level  
PK 
 
14.3.7.9 
Box Plot of Dose Normalized AUC0-last versus Dose Level  
PK 
 
14.3.7.10 
Box Plot of Cmax versus Visit for Each Dose Level  
PK 
 
14.3.7.11 
Box Plot of AUC0-last versus Visit for Each Dose Level 
PK 
 
14.3.7.12 
Box Plot of Dose Normalized AUC0-inf versus Dose Level  
PK 
 
14.3.7.13 
Box Plot of Dose Normalized AUCtau versus Dose Level  
PK 
 
14.3.7.14 
Box Plot of Dose Normalized Ctrough versus Dose Level  
PK 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
37 
 
ICH 
Heading 
Listing 
Number 
Listing Description 
Analysis 
Population  
16.2.1 
 
Discontinued subjects 
 
 
16.2.1.1 
Study Population and Subject Disposition 
All Screened 
 
16.2.1.2 
Study Treatment Discontinuation  
All Treated 
 
16.2.1.3 
Informed Consent and Protocol Amendment Re-Consent 
All Treated 
16.2.2 
 
Protocol deviations 
 
 
16.2.2.1 
Protocol Deviations 
All Treated 
 
16.2.2.2 
COVID-19 Related Protocol Deviations 
All Treated 
 
16.2.2.3 
Inclusion and Exclusion Criteria Deviation  
All Treated  
16.2.4 
 
Demographics  
 
 
16.2.4.1 
Demographic and Baseline Characteristics 
All Treated 
 
16.2.4.2 
Medical and Surgical History 
All Treated 
 
16.2.4.3 
Study Cancer History 
All Treated 
 
16.2.4.4 
Prior Anti-Cancer Systemic Treatment 
All Treated 
 
16.2.4.5 
Prior Radiotherapy 
All Treated 
 
16.2.4.6 
Prior Surgery Treatment 
All Treated 
 
16.2.4.7 
Prior and Concomitant Medications 
All Treated 
 
16.2.4.8 
Concomitant Procedures 
All Treated 
 
16.2.4.9 
Demographic and Baseline Characteristics for Screen Failure 
Subjects  
Screen Failure  
16.2.5 
 
Study Drug Exposure 
 
 
16.2.5.1 
Study Drug Administration 
All Treated 
 
16.2.5.2 
SL-172154 Serum Concentration-Time Data 
PK 
 
16.2.5.3 
SL-172154 PK Parameters  
PK 
16.2.6 
 
Individual efficacy response data 
 
 
16.2.6.1 
Tumor Assessment: Target Lesions  
All Treated 
 
16.2.6.2 
Tumor Assessment: Non-Target Lesions  
All Treated 
 
16.2.6.3 
Tumor Assessment: New Lesions  
All Treated 
 
16.2.6.4.1 
Tumor Responses Based on RECIST 1.1  
All Treated 
 
16.2.6.4.2 
Tumor Responses Based on iRECIST 
All Treated 
 
16.2.6.5 
Time to Response and Duration of Response Based on 
RECIST 1.1 and iRECIST  
Response 
Evaluable 
 
16.2.6.6.1 
Progression-Free Survival Based on RECIST 1.1  
All Treated 
 
16.2.6.6.2 
Progression-Free Survival Based on iRECIST  
All Treated 
 
16.2.6.7 
Overall Survival  
All Treated 
 
16.2.6.8 
Summary of CA-125 
All Treated 


Statistical Analysis Plan for SL03-OHD-101  
SL-172154                                                                                                                       
17January2023
38 
 
ICH 
Heading 
Listing 
Number 
Listing Description 
Analysis 
Population  
16.2.7 
 
Adverse Event Listings 
 
 
16.2.7.1 
All Adverse Events 
All Treated 
 
16.2.7.2 
Dose Limiting Toxicities  
DLT evaluable 
 
16.2.7.3 
Drug-Related Adverse Events 
All Treated 
 
16.2.7.4 
Adverse Events with Toxicity Grade 3 or 4 
All Treated 
 
16.2.7.5 
Drug-Related Adverse Events with Toxicity Grade 3 or 4 
All Treated 
 
16.2.7.6 
Fatal Adverse Event 
All Treated 
 
16.2.7.7 
Serious Adverse Events 
All Treated 
 
16.2.7.8 
Immune Related Adverse Events 
All Treated 
 
16.2.7.9 
Infusion Related Reaction Adverse Events 
All Treated 
 
16.2.7.10 
Adverse Events Leading to Infusion Interrupted 
All Treated 
 
16.2.7.11 
Adverse Events Leading to Dose Increased or Dose Reduced  
All Treated 
 
16.2.7.12 
Adverse Events Leading to Dose not given/Held 
All Treated 
 
16.2.7.13 
Adverse Events Leading to Drug Withdrawn  
All Treated 
 
16.2.7.14 
Infusion Reaction Signs and Symptoms 
All Treated 
 
16.2.7.15 
Death  
All Treated 
 
16.2.7.16 
All Adverse Events for Screen Failure Subjects  
Screen Failure 
16.2.8 
 
Individual Laboratory Measurements 
 
 
16.2.8.1 
Hematology  
All Treated 
 
16.2.8.2 
Clinical Chemistry (including ferritin and haptoglobin) 
All Treated 
 
16.2.8.3 
Coagulation and Thyroid Function 
All Treated 
16.2.9 
 
Listing of other safety data  
 
 
16.2.9.1 
Vital Signs and Pulse Oximetry  
All Treated 
 
16.2.9.2 
ECOG Performance Status 
All Treated 
 
16.2.9.3 
Cardiac Assessments: ECG  
All Treated 
 
16.2.9.4 
Cardiac Assessments: ECHO 
All Treated 
 
16.2.9.5 
Blood Phenotyping and Direct Antiglobulin Test  
All Treated 
 
16.2.9.6 
Transfusions 
All Treated