Clinical trial NCT03604692
Conditions: Chronic Graft-versus-host-disease
Keywords: cGVHD
Sponsor: Syndax Pharmaceuticals
Start date: 2018-11-01; Completion date: 2024-10-18
Enrollment: 41 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 1/2, Open-label, Dose Escalation study to investigate axatilimab in participants with active chronic graft versus host disease (cGVHD).

Detailed description:
This is a dose escalation and dose expansion study in participants with active cGVHD who have received at least 2 lines of prior therapy.

Arms: arm 1: Escalating dose levels of axatilimab to establish the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D).

Intravenous (IV) infusion; axatilimab at a dose of 0.15 milligrams (mg)/kilogram (kg) to 3 mg/kg. arm 2: Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample size.

IV infusion; axatilimab at a dose of 1 mg/kg.
Interventions: intervention 1: axatilimab
Intervention descriptions: intervention 1: axatilimab is a high affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD.

Protocol documents:
Prot_000.pdf: 
Product: SNDX-6352 
Protocol Number: SNDX-6352-0503 
Date: 12 April 2022, Version 10.0 
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Confidentiality Notice 
This document contains confidential information of Syndax Pharmaceuticals, Inc., the contents 
of which must not be disclosed to anyone other than the study staff and members of the 
respective Institutional Review Board/Ethics Committee. 
The information in this document cannot be used for any purpose other than the evaluation or 
conduct of the clinical investigation without the prior written consent of Syndax 
Pharmaceuticals, Inc. 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 1/2, Open-Label, Dose Escalation and Dose Expansion 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, 
Pharmacodynamic Activity, and Efficacy of SNDX-6352 in 
Subjects with Active Chronic Graft Versus Host Disease who have 
Received at least 2 Lines of Prior Therapy 
Protocol Number: 
SNDX-6352-0503 
Compound Number: 
SNDX-6352 
Compound Name: 
axatilimab 
Study Phase: 
Phase 1/2 
Sponsor Name: 
Syndax Pharmaceuticals, Inc. 
Legal Registered 
Address: 
35 Gatehouse Drive 
Building D, Floor 3 
Waltham, MA 02451 
Regulatory Agency 
Identifier Number(s): 
IND: 139,019 
Approval Date: 
Version 10.0, 12 April 2022 
NCT #: NCT03604692


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SIGNATURE PAGE 
 
 
Sponsor Signatory: 
 
 
Electronically signed 
by: 
 
Reason: I am an 
approver. 
Date: Apr 12, 2022 
14:25 MDT 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Monitor Name and Contact Information: 
 
Tel: 
 
Email: 
 


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INVESTIGATOR’S AGREEMENT 
I have read the attached protocol (SNDX-6352-0503) entitled “A Phase 1/2, Open-Label, Dose 
Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamic Activity, and Efficacy of SNDX- 6352 in Subjects 
with Active Chronic Graft Versus Host Disease who have Received at least 2 Lines of Prior 
Therapy”, dated 12 June 2020, Version 8.0 and agree to abide by all provisions set forth therein. 
I agree to comply with the International Council for Harmonisation Tripartite E6 Guideline on 
Good Clinical Practice applicable regulations of the Food and Drug Administration and other 
applicable regulations. 
I agree to ensure that Financial Disclosure Statements will be completed by: 
• me 
• my sub-investigators 
at the start of the study, at study completion, and for up to 1 year after the study is completed, if 
there are changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of Syndax. 
 
 
 
 
Signature 
Name of Principal Investigator 
Date 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
 
DOCUMENT HISTORY 
Document 
Date 
Protocol V10, Amendment 10 (Site and FDA) 
12 April 2022 
Protocol V9, Amendment 9 (Site and FDA) 
17 December 2020 
Protocol V8, Amendment 8 (Site and FDA) 
12 June 2020 
Protocol V7, Amendment 7 (Site and FDA) 
19 December 2019 
Protocol V6, Amendment 6 (Site and FDA) 
29 August 2019 
Protocol V5, Amendment 5 (Site and FDA) 
23 July 2019 
Protocol V4, Amendment 4 (Site and FDA) 
18 December 2018 
Protocol V3, Amendment 3 (Site and FDA) 
11 July 2018 
Protocol V2.1, Amendment 2 (FDA only) 
21 June 2018 
Protocol V2, Amendment 1 (FDA only) 
18 June 2018 
Original Protocol V1 (Site and FDA) 
15 May 2018 
Amendment 10, 12 April 2022 
Overall Rationale for the Amendment 
Syndax has introduced the following modification to protocol V9.0; these changes are presented 
in order of importance: 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
6.7 Dose 
Modification 
Subsection 6.7.1, Axatilimab Taper, was added 
to define the option of axatilimab taper as an 
alternative to immediate drug discontinuation. 
Taper of cGVHD therapies is a common 
medical practice that may mitigate risk of 
cGVHD flare during discontinuation. 
Measured discontinuation may limit 
occurrence of cGVHD flares. Data 
collected during this period may provide 
additional information on durability of 
axatilimab benefit. 


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TABLE OF CONTENTS 
SIGNATURE PAGE ........................................................................................................................ 2 
INVESTIGATOR’S AGREEMENT................................................................................................ 3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................. 4 
1. 
PROTOCOL SUMMARY .......................................................................................... 10 
1.1. 
Synopsis ...................................................................................................................... 10 
1.2. 
Schedule of Activities (SoA) ...................................................................................... 15 
2. 
INTRODUCTION....................................................................................................... 18 
2.1. 
Study Rationale ........................................................................................................... 18 
2.2. 
Background ................................................................................................................. 20 
2.3. 
Benefit/Risk Assessment ............................................................................................. 20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................. 22 
3.1. 
Phase 1 Dose Escalation .............................................................................................. 22 
3.2. 
Phase 2 Dose Expansion ............................................................................................. 24 
4. 
STUDY DESIGN ........................................................................................................ 26 
4.1. 
Overall Design ............................................................................................................ 26 
4.2. 
Rationale for Study Design ......................................................................................... 30 
4.3. 
Justification for Dose................................................................................................... 30 
4.4. 
End of Study Definition .............................................................................................. 31 
5. 
STUDY POPULATION ............................................................................................. 32 
5.1. 
Inclusion Criteria ......................................................................................................... 32 
5.2. 
Exclusion Criteria........................................................................................................ 34 
5.3. 
Screen Failures ............................................................................................................ 35 
6. 
STUDY INTERVENTION ......................................................................................... 36 
6.1. 
Study Intervention(s) Administered ............................................................................ 36 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................. 37 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ......................................... 37 
6.4. 
Study Intervention Compliance ................................................................................... 37 
6.5. 
Dose Limiting Toxicity Criteria .................................................................................. 38 
6.6. 
Concomitant Therapy .................................................................................................. 39 
6.6.1. 
Prohibited Medications ............................................................................................... 40 


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6.7. 
Dose Modification .......................................................................................................40 
6.7.1. 
Axatilimab Taper ........................................................................................................41 
6.7.2. 
Guidelines for Toxicity Management .........................................................................42 
6.7.2.1. 
AST, ALT, Bilirubin, CK, Amylase and Lipase elevation .........................................42 
6.7.2.2. 
Other Non-hematologic Toxicity ................................................................................44 
6.7.2.3. 
Hematologic Toxicity..................................................................................................44 
6.7.2.4. 
SNDX-6352 Infusion-Related Reaction ......................................................................45 
6.7.2.5. 
Immune-related Adverse Events for SNDX-6352 ......................................................46 
6.8. 
Intervention after the End of the Study .......................................................................51 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ...................................................................52 
7.1. 
Discontinuation of Study Intervention ........................................................................52 
7.1.1. 
Temporary Discontinuation .........................................................................................52 
7.2. 
Subject Discontinuation/Withdrawal from the Study .................................................52 
7.3. 
Lost to Follow up ........................................................................................................53 
8. 
STUDY ASSESSMENTS AND PROCEDURES.......................................................54 
8.1. 
Safety Assessments .....................................................................................................54 
8.1.1. 
Physical Examinations ................................................................................................54 
8.1.2. 
Neurological Examinations .........................................................................................54 
8.1.3. 
Vital Signs ...................................................................................................................55 
8.1.4. 
Electrocardiograms ......................................................................................................55 
8.1.5. 
Karnofsky/Lansky Performance Status Scale ..............................................................55 
8.1.6. 
Clinical Safety Laboratory Assessments .....................................................................56 
8.2. 
Efficacy Assessments ..................................................................................................57 
8.2.1. 
Response Determination according to 2014 NIH Consensus definitions ...................57 
8.2.2. 
Physician-Reported Global and Organ Specific cGVHD Activity 
Assessment ..................................................................................................................59 
8.2.3. 
Patient-Reported cGVHD Activity Assessment..........................................................59 
8.3. 
Adverse Events and Serious Adverse Events ..............................................................59 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information ........................59 
8.3.2. 
Method of Detecting AEs and SAEs ...........................................................................60 


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8.3.3. 
Follow-up of AEs and SAEs .......................................................................................60 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................61 
8.3.5. 
Pregnancy ....................................................................................................................61 
8.3.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs ...............................................................................................................61 
8.4. 
Treatment of Overdose ................................................................................................62 
8.5. 
Pharmacokinetics ........................................................................................................62 
8.6. 
Pharmacodynamics and Exploratory endpoints ..........................................................63 
8.7. 
Biomarkers ..................................................................................................................64 
8.7.1. 
Immunogenicity Assessments .....................................................................................64 
9. 
STATISTICAL CONSIDERATIONS ........................................................................66 
9.1. 
Statistical Hypotheses .................................................................................................66 
9.2. 
Sample Size Determination .........................................................................................66 
9.3. 
Populations for Analyses .............................................................................................67 
9.4. 
Statistical Analyses .....................................................................................................67 
9.4.1. 
OBD Analyses: Phase 1 ..............................................................................................67 
9.4.2. 
Safety Analyses: Phase 1 and Phase 2.........................................................................67 
9.4.3. 
Efficacy Analyses: Phase 1 and Phase 2 .....................................................................69 
9.4.4. 
Other Analyses: Phase 1 and Phase 2..........................................................................70 
9.5. 
Interim Analyses .........................................................................................................70 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................71 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations .....................71 
10.1.1. 
Regulatory and Ethical Considerations .......................................................................71 
10.1.2. 
Informed Consent Process ..........................................................................................71 
10.1.3. 
Data Protection ............................................................................................................72 
10.1.4. 
Safety Review Committee (SRC) ...............................................................................72 
10.1.5. 
Dissemination of Clinical Study Data .........................................................................73 
10.1.6. 
Data Quality Assurance ...............................................................................................73 
10.1.7. 
Source Documents ......................................................................................................74 
10.1.8. 
Study and Site Closure ................................................................................................74 


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10.1.9. 
Publication Policy ....................................................................................................... 75 
10.2. 
Appendix 2: Clinical Laboratory Tests ....................................................................... 76 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................ 78 
10.3.1. 
Definition of AE.......................................................................................................... 78 
10.3.2. 
Definition of SAE ....................................................................................................... 79 
10.3.3. 
Definition of Adverse Events of Special Interest (AESI) ........................................... 80 
10.3.4. 
Definition of Suspected and Unexpected Adverse Reaction ....................................... 80 
10.3.5. 
Recording and Follow-Up of AE and/or SAE ............................................................ 80 
10.3.6. 
Reporting of SAEs and AESI ...................................................................................... 83 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................. 84 
10.5. 
Appendix 5: Rating Scales .......................................................................................... 87 
10.5.1. 
Global cGVHD Activity Assessment – Physician Report .......................................... 87 
10.5.2. 
cGVHD Lee Symptom Scale ...................................................................................... 90 
10.6. 
Appendix 6: Abbreviations ......................................................................................... 91 
10.7. 
Appendix 7: Protocol Amendment History................................................................. 94 
11. 
REFERENCES .......................................................................................................... 107 
 
List of Tables 
Table 1: 
Phase 1 Dose Escalation Scheme ................................................................................27 
Table 2: 
Study Intervention .......................................................................................................36 
Table 3: 
Axatilimab Taper Schedule and Duration for Each Dose Level .................................41 
Table 4: 
AST, ALT Bilirubin, CK, Amylase and Lipase: Dose Modification 
Guidelines for SNDX-6352 ......................................................................................... 43 
Table 5: 
Other Non-hematologic Toxicity: Dose Modification Guidelines for 
SNDX-6352 ................................................................................................................. 44 
Table 6: 
Hematologic Toxicity: Dose Modification Guidelines for SNDX-6352 .................... 45 
Table 7: 
Infusion-related Reactions for SNDX-6352 ................................................................ 46 
Table 8: 
Management of Immune-related Adverse Events for SNDX-6352 ............................ 47 
Table 9: 
Karnofsky and Lansky Performance Status ................................................................ 56 


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Table 10: 
Response Determination for Chronic GVHD Clinical Studies based on 
Clinician Assessments .................................................................................................58 
Table 11: 
Adverse Event Observation Periods ............................................................................60 
Table 12: 
Efficacy Endpoints Definition and Statistical Analysis Method (Phase 1 and 
Phase 2) .......................................................................................................................69 
Table 13: 
Protocol-Required Safety Laboratory Assessments ....................................................76 
Table 14: 
Highly Effective methods of contraception (<1% failure rate) ...................................85 
List of Figures 
Figure 1: 
Phase 1 Dose Escalation Decision Tree ......................................................................29 
Figure 2: 
Phase 2 1 mg/kg Dose Expansion ...............................................................................30 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 1/2, Open-Label, Dose Escalation and Dose Expansion Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic Activity, and Efficacy of 
SNDX-6352 in Subjects with Active Chronic Graft Versus Host Disease who have Received at 
least 2 Lines of Prior Therapy. 
Rationale 
Chronic graft-versus-host disease (cGVHD) remains the major cause of morbidity and non- 
relapse mortality after allogeneic hematopoietic stem cell transplantation (HSCT). cGVHD 
typically manifests with multiorgan pathology which often occurs during the first year 
post-HSCT but can also develop beyond the first year post-HSCT (Jagasia, et al 2015). 
Treatment of cGVHD is currently based on steroid administration and although many other 
approaches, including additional immune suppressants, ultraviolet B (UVB) phototherapy, and 
extracorporeal photopheresis (ECP) are commonly used, none have proven clearly effective. 
Targeting macrophages by preventing differentiation and survival in tissue through the inhibition 
of colony stimulating factor 1 receptor (CSF-1R) has proven highly effective in animal systems. 
SNDX-6352 is a humanized IgG4 monoclonal antibody (mAb) directed against CSF-1R with the 
potential to treat cGVHD through blockade of macrophage activity. 
Objectives and Endpoints - Phase 1 
 
Objectives 
Endpoints 
Primary 
• To characterize the optimal biologic dose 
(OBD) and identify recommended Phase 2 
dose(s) (RP2D) of SNDX-6352 in subjects 
with cGVHD 
• OBD and RP2D(s) of SNDX-6352 
Secondary 
• To evaluate the safety and tolerability of 
SNDX-6352 in subjects with cGVHD 
• Frequency and severity of adverse events 
(AEs) and serious adverse events (SAEs) 
• To assess the plasma pharmacokinetics 
(PK) profile of SNDX-6352 in subjects 
with cGVHD 
• Plasma PK of SNDX-6352 
• To assess the pharmacodynamic (PD) 
profile of SNDX-6352 
• Changes from baseline in colony 
stimulating factor 1 (CSF-1) and 
interleukin (IL)-34 levels and their 
association with cGVHD response 


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Objectives 
Endpoints 
• Changes from baseline in circulating 
monocyte number (CD14/16) 
• To evaluate changes in biomarkers 
following SNDX-6352 administration 
• Changes from baseline in inflammation 
biomarkers that may include monocyte 
chemoattractant protein 1 (MCP1), 
Chemokine (C-C motif) ligand 3 (CCL3) 
and CCL5 expression 
• To assess the immunogenicity of 
SNDX-6352 
• Presence of anti-drug antibodies (ADA) 
Objectives and Endpoints - Phase 2 Expansion Cohort(s) 
For definition of efficacy endpoints, please refer to Table 12 in Section 9.4.3. 
 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of SNDX-6352 in 
subjects with cGVHD 
• Proportion of subjects with complete 
response (CR) or partial response (PR) 
(Overall Response Rate [ORR]) at Cycle 
7 Day 1 (Day 168) 
Secondary 
• To evaluate the safety and tolerability of 
SNDX-6352 in subjects with cGVHD 
• Frequency and severity of AEs and SAEs 
• Secondary efficacy endpoints 
• Best overall response rate (BOR) 
• Failure free survival (FFS) 
• Duration of response (DOR) 
• Sustained response rate (SRR) (CR or PR 
≥ 20 weeks) 
• Organ-specific response rate based on 
2014 National Institute of Health (NIH) 
Consensus Development Project on 
Criteria for Clinical Trials in cGVHD 
• Joints and fascia response based on 
refined NIH response algorithm for 
cGVHD (Inamoto, et al 2020) 


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Objectives 
Endpoints 
• To assess patient-reported outcomes 
(PROs) in subjects with cGVHD treated 
with SNDX-6352 
• To assess changes in subject-reported 
symptom activity using the Lee cGVHD 
symptom scale. 
• Proportion of subjects with a ≥7-point 
improvement in normalized score 
• To evaluate corticosteroid or calcineurin 
inhibitor use 
• Percent reduction in average daily dose 
(or equivalent) or discontinuation of 
corticosteroid use after study entry 
• Percent reduction in average daily dose 
(or equivalent) or discontinuation of 
calcineurin inhibitor use, after study 
entry 
Overall Design 
This is a Phase 1/2, open-label dose escalation and dose expansion study to evaluate the safety, 
tolerability, PK/PD activity, OBD/RP2D(s) and efficacy of SNDX-6352 in subjects with active 
cGVHD who have failed at least 2 prior lines of therapy due to progression of disease, 
intolerability or toxicity. Subjects ≥18 years of age with active cGVHD who have erythematous 
rash involving >25% body surface area or a NIH mouth score of >4 must have received prior 
ibrutinib (IMBRUVICA®) therapy. The study will consist of a Screening period, a Treatment 
period, and a Safety Follow-up period. 
In both study phases, study intervention will be given via intravenous (IV) infusion every 
2 weeks (Q2W) until disease progression or unacceptable toxicity occurs for a maximum of 
6 cycles. Subjects may receive study intervention in either an inpatient or outpatient setting. 
After 6 cycles of biweekly treatment, in subjects without cGVHD progression, the study 
intervention may be administered either biweekly or every 4 weeks (Q4W) at the Investigator’s 
discretion in discussion with the Sponsor. 
In both study phases, response criteria will be assessed every 28 days, and at the end of treatment 
visit or discontinuation of the study intervention using 2014 NIH Consensus Development 
Project on Criteria for Clinical Trials in cGVHD: CR, PR, lack of response (unchanged, mixed or 
progression). Window periods of ±1 day for Cycle 1 and ±3 days for each subsequent cycle will 
be allowed for response assessments. 
Phase 1 Dose-Escalation Cohorts 
Eligible subjects will be enrolled sequentially to evaluate escalating doses of SNDX-6352 as 
depicted below (for more information refer to Section 4.1 and Figure 1). For all cohorts, dose 
limiting toxicity (DLT) assessment window is 28 days from initiation of treatment with 
SNDX-6352 or administration of third dose (C2D1), whichever is later. For DLT criteria see 
Section 6.5. Decision to dose escalate will be made by the Safety Review Committee (SRC). 
Based on emerging data and the evaluation of the safety and tolerability data as a whole, it may 


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also be decided that accrual will take place at an intermediate dose level and/or alternative 
dosing schedule (e.g., 3 mg/kg Q4W or 4 mg/kg Q4W). The OBD is defined as the lowest safe 
dose with the highest rate of biologic activity. Biologic activity is determined by 100% reduction 
of non-classical monocytes at the time of dose interval and plateaued increase of circulating 
CSF-1 levels that persist for an entire dosing level. 
Dose Escalation Scheme 
 
Dose cohort 
Dose levels of SNDX-6352 
Dosing schedule**** 
1* 
0.15 mg/kg (starting dose) 
Q2W up to 12 cycles.*** 
2* 
0.5 mg /kg 
3** 
1 mg/kg 
4** 
3 mg/kg 
4a** 
2 mg/kg 
Q2W = every 2 weeks; Q4W = every 4 weeks 
* Single subject cohort which can be expanded to 3+3 design depending on toxicity 
** 3+3 design, 3 subjects per cohort which can be expanded to 6 subjects depending on dose limiting toxicity (DLT) 
***If no progression, treatment may be continued after 6 cycles at Q2W or Q4W at investigator’s discretion in 
discussion with Sponsor. 
**** Based on emerging data, intermediate dose levels and/or alternative dosing schedules may be used 
Phase 2 Dose-Expansion Cohort(s) 
1 mg/kg Cohort 
PK, PD, clinical response and safety data indicate that 1 mg/kg of SNDX-6352 is biologically 
active, induces organ specific responses and symptom improvement with no significant adverse 
events. This expansion cohort is designed to evaluate the preliminary efficacy of SNDX-6352 at 
1 mg/kg. The dose-expansion phase will be conducted concurrently with the dose-escalation 
phase; however, subjects will be enrolled preferentially in the Phase 1 dose-escalation cohorts. 
Subjects may only be enrolled in this expansion cohort if enrollment in the current dose- 
escalation cohort is complete or assessment of DLTs and the recommendation for enrollment of 
the next dose escalation cohort by the SRC are pending. Intra-subject dose escalation to the 
3 mg/kg dose is allowed after the dose has been cleared by the SRC in Phase 1 and after 
Investigator consultation with the Sponsor (for more information refer to Section 4.1 and 
Figure 2). 
Disclosure Statement: 
• The dose-escalation phase is a sequential group (dose-escalating) treatment study 
with up to 5 cohorts that is open-label. 
• The dose-expansion phase is a parallel group treatment study with open-label cohorts. 


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Number of Subjects: 
• In the dose-escalation phase, up to 30 subjects will be enrolled. 
• In the dose-expansion phase, up to 22 subjects will be enrolled per cohort. 
Intervention Groups and Duration: 
The total study duration for each subject will be 16 months as follows: 
 
Screening period: 
Up to 28 days (1 month) prior to the first dose of study 
intervention 
Treatment period: 
Up to 365 days (12 months) 
Safety Follow-up period: 
Up to 90 days (3 months) after the last administration of 
study intervention 
 
Safety Review Committee: Yes 


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1.2. 
Schedule of Activities (SoA) 
 
Study Procedure 
Screening 
Treatment Period 
Safety Follow-Up 
Cycle (each cycle consists of 28-days) 
Days post last dose ±7 
days 
Cycle 1 
Cycles 2 to 6 
Cycles 7+ 
Day in Cycle 
-28 to 0 
1 
8 
15 
22 
1 
15 
1 
+301 
+60 
+90 
Visit Window 
NA 
NA 
±1D 
±1D 
±1D 
±3D 
±3D 
±3D 
±7D 
±7D 
±7D 
Informed consent 
X 
Demographics2 
X 
Eligibility criteria 
X 
Medical & disease history3 & prior 
medications 
X 
Karnofsky/Lansky Performance 
Scale4 
X 
X 
X 
X 
X 
X 
X 
Complete physical examination 
X 
X5 
X 
X 
X 
Height 
X 
Symptoms-directed physical exam 
X 
X 
X 
X 
X 
X 
Vital signs6 and weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Neurological examination 
X 
X 
X 
X 
X 
X 
X 
12-Lead Electrocardiogram 
X 
X7 
X 
 
 
 
 
1 In case of early discontinuation, this visit (30 days after last dose of study intervention) will serve as end of study visit 
2 Includes age, race, and ethnicity 
3 A complete medical history will be documented and updated prior to the administration of the first dose of study intervention. The medical history will include cancer history, 
including date of and stage at diagnosis, method of diagnosis, all previous treatments and response to such treatment, and any medical condition that might complicate the subject’s 
disease or affect the treatment outcome. 
4 The Karnofsky Scale will be used for subjects aged 16 years and older, and the Lansky Scale will be used for subjects less than 16 years old 
5 If the Screening complete physical exam was performed within 7 days before C1D1, a symptom-directed physical exam may be performed at enrollment. 
6 Vital signs should also be obtained during or after the infusion, if clinically indicated 
7 Pre-dose 


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Study Procedure 
Screening 
Treatment Period 
Safety Follow-Up 
Cycle (each cycle consists of 28-days) 
Days post last dose ±7 
days 
Cycle 1 
Cycles 2 to 6 
Cycles 7+ 
Day in Cycle 
-28 to 0 
1 
8 
15 
22 
1 
15 
1 
+301 
+60 
+90 
Visit Window 
NA 
NA 
±1D 
±1D 
±1D 
±3D 
±3D 
±3D 
±7D 
±7D 
±7D 
Safety Laboratory (hematology, & 
biochemistry)8 
X 
X 
X 
X 
X9 
As clinically indicated 
X 
X 
Coagulation factors 
X 
X10 
Bone markers (BAP, CTX) 
X 
X11 
HCV RNA12 
X 
Urinalysis 
X 
X13 
As clinically indicated 
Pregnancy testing14 
X 
X 
X15 
X 
X 
SNDX-6352 administration 
X 
X 
X 
X 
X 
DLT/toxicity assessment16 
X17 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
8 Refer to Appendix 2 (Section 10.2) for full list of clinical laboratory tests 
9 For the 3 mg/kg Q4W cohort only, the Cycle 1 Day 22 safety laboratory sample is not required unless clinically indicated 
10 On Cycle 3 Day 1 only, before skin biopsy 
11 Bone turnover markers (bone alkaline phosphatase [BAP], C-terminal telopeptide [CTX]) will be collected pre-dose on C3D1 
12 Polymerase chain reaction is required and must be negative for HCV RNA in subjects positive for HCV antibody 
13 Performed only if Screening laboratory tests performed >7 days prior to C1D1 
14 For female subjects of child-bearing potential, a serum pregnancy test is required to be performed during screening and within 3 days before the first study intervention dose if 
the screening pregnancy test is performed more than 3 days before the first study intervention dose. A serum pregnancy is also required at the end of study. During the study, 
either urine or serum pregnancy tests are performed. 
15 Pregnancy testing is to be repeated every 2 cycles (8 weeks), on Day 1 of Cycles 3, 5,7, 9 and 11 
16 DLT/toxicity assessments will be done up to Cycle 2 Day 1, inclusive 
17 DLT assessment window is 28 days from initiation of treatment with SNDX-6352 or administration of third dose (C2D1), whichever is later 


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Study Procedure 
Screening 
Treatment Period 
Safety Follow-Up 
Cycle (each cycle consists of 28-days) 
Days post last dose ±7 
days 
Cycle 1 
Cycles 2 to 6 
Cycles 7+ 
Day in Cycle 
-28 to 0 
1 
8 
15 
22 
1 
15 
1 
+301 
+60 
+90 
Visit Window 
NA 
NA 
±1D 
±1D 
±1D 
±3D 
±3D 
±3D 
±7D 
±7D 
±7D 
cGVHD response determination18, 19, 
20 
X 
X 
X 
Physician-reported global cGVHD 
activity assessment21,18, 19 
X 
X 
X 
Lee cGVHD Symptom Scale 
X 
X 
X 
Pharmacokinetics22 
X 
X 
X 
X23 
X24 
X 
Pharmacodynamics25 
X 
X 
X 
X26 
X 
Anti-drug antibody27 
X 
X 
X 
X 
X 
Tissue biopsy28 
X 
X29 
BAP = bone alkaline phosphatase; cGVHD = chronic graft versus host disease; CTX = C-terminal telopeptide; D = day; DLT = dose limiting toxicity; 
HCV RNA = hepatitis C virus ribonucleic acid; NA = not applicable 
 
18 Response evaluation will be according to 2014 NIH Consensus definitions; Window periods of ±3 days will be allowed for each response assessment 
19 It is preferred that all cGVHD assessments be done by the same health care provider who completed the C1D1 assessment. At minimum, the C7D1 assessment should be 
performed by the same health care provider who performed the C1D1 assessment. In addition, any assessments leading to changes in cGVHD therapy must be confirmed by the PI 
or primary treating physician. 
20 cGVHD assessments may be done every 12 weeks starting at Cycle 13 
21 Pulmonary Function Tests (PFTs) performed C1D1 prior to dosing, if PFTs have not been completed within 4 weeks of scheduled first dose. Frequency beyond C1 will be 
performed per standard of care 
22 PK sampling will occur at Cycle 1: predose, at 30 min (end of infusion), and at 1 hour (± 5 min), 8 hours (± 10 min) on Day 1 and Day 15; and at 168 hours (±24 hours) on 
Day 8. SNDX-6352 levels in plasma samples will be determined using a validated enzyme-linked immunosorbent assay (ELISA). 
23 For the 3 mg/kg Q4W cohort only, collect PK samples anytime on Cycle 1 Day 22 
24 PK samples will be collected predose on C2D1 and D1 of every cycle thereafter. Further PK sample collection will stop once axatilimab taper (Section 6.7.1.) commences. 
25 Plasma levels of a cytokine panel (may include CSF-1, IL-34, MCP-1, CCL3 and CCL5) and circulating monocyte number (CD14/16) will be collected on C1D1-predose, 
C1D8, C1D15-predose, C2D1-predose, C4D1-predose and end of treatment 
26 For the 3 mg/kg Q4W cohort only, collect a PD sample for circulating monocytes (CD14/16) anytime on Cycle 1 Day 22 
27 ADA will be captured at predose on C1D1, C1D15, C3D1, Day 1 of each following cycle, End of Treatment and 30-day follow up visit. 
28 Skin biopsy is only applicable for subjects with skin cGVHD 
29 Biopsy will be done on C3D1; skin biopsy only in subjects with skin cGVHD; lung biopsy only in subjects with transbronchial lung cGVHD 


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2. 
INTRODUCTION 
2.1. 
Study Rationale 
SNDX-6352 is a humanized IgG4 monoclonal antibody (mAb) with high affinity against colony 
stimulating factor-1 receptor (CSF-1R) under investigation for the treatment of advanced solid 
tumors and chronic graft vs. host disease (cGVHD). SNDX-6352 clinical development includes a 
completed Phase 1 study in healthy volunteers (SNDX-6352-0001) and an ongoing multiple 
ascending repeat dose study in patients with solid tumors (SNDX-6352-0502). 
CSF-1R is expressed on cells of the mononuclear phagocyte lineage including 
immunosuppressive macrophages that accumulate within the tumor microenvironment. These 
tumor-associated macrophages (TAMs) are believed to play a key role in inhibiting anti-tumor 
T cell immune responses while promoting tumor progression. High levels of TAMs have been 
shown to correlate with poor prognosis for certain cancers and nonclinical studies have 
demonstrated that inhibition of TAMs can enhance anti-tumor immune responses. By binding to 
CSF-1R and blocking activation by its two known ligands, colony stimulating factor-1 (CSF-1) 
and interleukin-34 (IL-34), SNDX-6352 may affect the migration, proliferation, differentiation, 
and survival of TAMs. By targeting this key cellular player in the pathogenesis of cancer, 
CSF-1R blockade has the potential to slow disease progression and increase the clinical benefit 
of anti-tumor immunotherapeutic approaches [reviewed in (Cannarile, et al 2017; Quail and 
Joyce 2017)]. 
Nonclinical pharmacology studies with an anti-CSF-1R antibody have been completed in mouse 
models of IL-17 dependent skin and lung GVHD (Alexander, et al 2014). These studies 
established that donor bone marrow derived macrophages (F4/80+CSF-1R+CD206+iNOS–) were 
responsible for generating the fibrotic disease symptoms of cGVHD and that blockade of CSF-1 
dependent monocyte recruitment, differentiation and proliferation ameliorated and prevented the 
development of cGVHD. Neither CCL2/CCR2 nor GM-CSF/GM-CSFR signaling pathways 
were required for macrophage infiltration or development of cGVHD. Importantly, in both 
models, depletion of macrophages using an anti-CSF-1R mAb markedly reduced cutaneous and 
pulmonary cGVHD. Taken together, these data support a key role for donor-derived 
macrophages in the development of cGVHD and suggest that targeting CSF-1 signaling after 
transplantation may prevent and treat cGVHD (reviewed in (MacDonald, et al 2017)). 
The standard of care for cGVHD has long consisted of steroid administration to relieve 
symptoms and delay disease progression, however this approach is associated with significant 
toxicity and emergence of resistance. Based on recent insight into the molecular mechanism 
involved in the disease related inflammatory process, interventions targeting kinases involved in 
these signaling pathways such as BTK, JAK1/2, and Syk have shown promising results in 
nonclinical and patient sample correlative studies (MacDonald, et al 2017) and of these, BTK 
inhibition has shown evidence of efficacy in Phase 2 clinical studies (Miklos, et al 2017). 
Therapies that directly target the donor derived, disease promoting macrophage have not yet 
been tested clinically. Targeting macrophages by preventing differentiation and survival in tissue 


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through the inhibition of CSF-1R has proven highly effective in animal systems (Alexander, et al 
2014). Therefore, mAbs that are targeted to CSF-1R on the surface of macrophages, such as 
SNDX-6352, have potential as immunotherapeutic approaches to treat cGVHD. 
Clinical data with CSF-1R targeted therapies in cancer patients have been reported for several 
agents including the small molecule PLX3397 and antibodies RG7155, JNJ-4036527, AMG820 
and FPA008. These agents generally have been tolerated well with emerging class effects of 
periorbital edema, pruritus and elevated liver enzymes that may be related to on-target effects of 
CSF-1/CSF-1R blockade in Kupffer cells, a type of macrophage found in the liver, which are 
important for clearance of liver enzymes. Currently there are no safety data available for other 
CSF-1R targeted therapies in cGVHD as these agents have not yet been tested in this indication. 
See the IB for further details. 
In vitro studies have demonstrated that SNDX-6352 binds to human CSF-1R (KD 4-8pM, 
Fc-tagged construct) and cross-reacts with cynomolgus monkey CSF-1R but not rodent CSF-1R. 
SNDX-6352 has been shown to inhibit potently both CSF-1 and IL-34 induced MCP-1 release 
from human monocytes (IC50, 270pM and 100pM respectively) and completely inhibits the 
viability of macrophages during the CSF-1-mediated differentiation process in vitro (IC50 
455pM). A ligand (both CSF-1 and IL-34) blocking surrogate rodent antibody, Ab535, has been 
generated for preclinical studies in mice and inhibits tumor growth in models of colon (MC38), 
breast (MCF-7, MDA-MB-231) and prostate (PC-3) cancer and enhances activity of immune 
checkpoint blockade in the syngeneic MC38 tumor model. 
Based on nonclinical data demonstrating that targeting CSF-1/CSF-1R prevents and treats 
cGVHD through depletion of donor derived macrophages, the Phase 1 study will evaluate the 
safety, tolerability, pharmacokinetics and pharmacodynamics activity of SNDX-6352 in subjects 
with active cGVHD who have failed two prior therapies due to progression of disease, 
intolerability or toxicity. Up to 30 subjects are anticipated to participate. 
SNDX-6352 PK and PD data from healthy subjects and solid tumor subjects indicate that all 
doses tested at Q2W, ranging from 0.15 mg/kg to 6 mg/kg have demonstrated evidence of 
biologic activity. Measurement of circulating non-classical monocytes levels, CSF-1 and IL-34 
levels and receptor occupancy indicate a dose dependent effect of SNDX-6352 on these markers 
that correlate well with drug concentrations. Increased dosing effects the magnitude of change as 
well as duration of effect. At 1 mg/kg in both healthy subjects and solid tumor patients, depletion 
of non-classical monocytes is prolonged through approximately Day 10 of a 14-day dosing 
interval with recovery to baseline by the next dose. Doses higher than 1 mg/kg deplete 
monocytes for the full 14-day interval. 
Preliminary data from the Phase 1 portion of this study indicate that both the PK and monocyte 
depletion effects at 1mg/kg are consistent with the data from the prior studies demonstrating that 
dose dependent biologic activity is conserved across healthy subjects, solid tumor and cGVHD 
subjects. These data justify 1 mg/kg as a potentially optimal biologic dose with early evidence of 
clinical benefit in cGVHD subjects treated at this dose level. The Phase 2 expansion phase will 
further evaluate preliminary efficacy of SNDX-6352 at 1 mg/kg in subjects with active cGVHD 


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who have failed two prior therapies due to progression of disease, intolerability or toxicity. Up to 
22 subjects are anticipated to participate. 
 
2.2. 
Background 
cGVHD is an immune-mediated serious and life-threatening complication after allogeneic 
hematopoietic cell transplantation (HSCT), occurring in 30% to 70% of patients (Jagasia, et al 
2015; Merkel, et al 2016). Most cases are diagnosed within the first year at a median of 4 to 6 
months after HSCT, but 5-10% of cases are initially diagnosed beyond the first post-transplant 
year. cGVHD most often involves the skin and mouth, but almost any other organ system can be 
involved (Merkel, et al 2016); it may be restricted to a single organ or site or may be widespread, 
with profound impact on quality of life. The pathophysiology of the cGVHD may involve 
inflammation, cell-mediated immunity, humoral immunity, and fibrosis (Jagasia, et al 2015). 
Treatment of cGVHD is currently based on steroids administration; systemic treatment begins 
with prednisone at 0.5 to 1 mg/kg per day, followed by a taper to reach an alternate-day regimen 
(Flowers and Martin 2015; MacDonald, et al 2017). Corticosteroids are typically administered 
for a median of 2 to 3 years, leading to substantial morbidity. An effort to decrease corticosteroid 
doses has led to their use in combination with other immunosuppressants, such as cyclosporine, 
tacrolimus, and sirolimus, in frontline or second-line settings, despite a lack of clinical evidence 
supporting additional efficacy after combining these agents with corticosteroids (Miklos, et al 
2017). Approximately 50% to 60% of patients with cGVHD require secondary treatment within 
2 years after initial systemic treatment; however, no consensus has been reached regarding the 
optimal choice of secondary agents (such as rituximab or imatinib) (Flowers and Martin 2015). 
Recently, the U.S. Food and Drug Administration (FDA) expanded the approval of Imbruvica® 
(ibrutinib, a kinase inhibitor) for the treatment of adult patients with (cGVHD) after failure of 
one or more treatments (Miklos, et al 2017). 
As described in the study rationale above (Section 2.1), SNDX-6352, a humanized IgG4 mAb 
that blocks CSF-1R on the surface of macrophages, has potential as an immunotherapeutic 
approach to treat cGVHD. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of SNDX-6352 is 
provided in its Investigator’s Brochure. 
 
2.3. 
Benefit/Risk Assessment 
The available nonclinical data and safety clinical data with SNDX-6352 to date support clinical 
investigation in subjects with cGVHD. Please refer to the SNDX-6352 IB for the available 
clinical and safety information of SNDX-6352. 
Expected adverse events (AEs) that may be predicted to occur based on the pharmacological and 
toxicology properties of SNDX-6352, even if not yet observed with SNDX-6352 include 
periorbital edema, facial swelling, infusion reactions and pruritus. 
Due to SNDX-6352 mechanism of action (pharmacological inhibition of CSF-1R), SNDX-6352 
may induce dose-dependent and reversible increases in circulating levels of creatine kinase (CK), 


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aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase 
(GLDH), amylase and lipase (see IB for details). Kupffer cells in the liver (which are involved in 
the clearance of these enzymes) are in the macrophage lineage and susceptible to SNDX-6352 
inhibition of CSR-1R. The expected increases in these enzyme levels are related to decreased 
clearance from the blood, rather than from drug-induced liver injury and are not associated with 
any histopathological change. Laboratory assessments (i.e., clinical chemistries, including tests 
for liver function) will be performed as specified in protocol to monitor subject’s safety. 
A priori mechanistic considerations highlight a number of potential risks, which will be 
monitored in a clinical study setting. On the basis of the information currently available, the risk- 
benefit of SNDX-6352 is considered acceptable for cGVHD. 
Given the underlying scientific basis for testing CSF-1R targeted therapy in cGVHD, the lack of 
treatment options in this cGVHD population, the conservative initial dose escalation and 
preliminary PK, PD, safety and preliminary evidence of clinical activity seen in the Phase 1 
portion of this study , the risk of SNDX-6352 in the proposed patient population is justified. 
Refer to the SNDX-6352 IB for additional information about the known and expected benefits 
and risks and reasonably expected adverse events of SNDX-6352. 


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3. 
OBJECTIVES AND ENDPOINTS 
For definition of efficacy endpoints for Phase 1 (exploratory) and Phase 2 (primary and 
secondary), please refer to Table 12 in Section 9.4.3. 
3.1. 
Phase 1 Dose Escalation 
 
Objectives 
Endpoints 
Primary 
• To characterize the OBD and identify 
RP2D(s) of SNDX-6352 in subjects 
with cGVHD 
• OBD and RP2D(s) of SNDX-6352 
Secondary 
• To evaluate the safety and tolerability 
of SNDX-6352 in subjects with 
cGVHD 
• Frequency and severity of AEs and SAEs 
• To assess the plasma PK profile of 
SNDX-6352 in subjects with cGVHD 
• Plasma PK of SNDX-6352 
• To assess the PD profile of SNDX-6352 
• Changes from baseline in CSF-1 and IL-34 
levels and their association with cGVHD 
response 
• Changes from baseline in circulating 
monocyte number (CD14/16) 
• To evaluate changes in biomarkers 
following SNDX-6352 administration 
• Changes from baseline in inflammation 
biomarkers that may include MCP1, CCL3 
and CCL5 expression 
• To assess the immunogenicity of 
SNDX-6352 
• Presence of ADA 
Exploratory and Pharmacodynamic 


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Objectives 
Endpoints 


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3.2. 
Phase 2 Dose Expansion 
 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of SNDX-6352 
in subjects with cGVHD 
• Proportion of subjects with CR or PR 
(ORR) at Cycle 7 Day 1 (Day 168) 
Secondary 
• To evaluate the safety and tolerability of 
SNDX-6352 in subjects with cGVHD 
• Frequency and severity of AEs and SAEs 
• Secondary efficacy endpoints 
• BOR 
• FFS 
• DOR 
• SRR (CR or PR ≥ 20 weeks) 
• Organ-specific response based on 2014 
NIH Consensus Development Project on 
Criteria for Clinical Trials in cGVHD 
• Joints and fascia response based on 
refined NIH response algorithm for 
cGVHD (Inamoto, et al 2020) 
• To assess PROs in subjects with cGVHD 
treated with SNDX-6352 
• To assess changes in subject-reported 
symptom activity using the Lee cGVHD 
symptom scale 
• Proportion of subjects with a ≥7-point 
improvement in normalized score 
• To evaluate corticosteroid or calcineurin 
inhibitor use 
• Percent reduction in average daily dose 
(or equivalent) of corticosteroids. 
• Proportion of patients who discontinue 
corticosteroid use after study entry 
• Percent reduction in average daily dose 
(or equivalent) of calcineurin inhibitor 
• Proportion of patients who discontinue 
calcineurin inhibitor use, after study 
entry 


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Objectives 
Endpoints 
Exploratory and Pharmacodynamic 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 1/2, open-label, dose escalation and dose expansion study to evaluate the safety, 
tolerability, PK/PD, RP2D(s)/OBD and efficacy of SNDX-6352 in subjects with active cGVHD 
who have failed at least 2 prior lines of therapy due to progression of disease, intolerability or 
toxicity. Subjects ≥18 years of age with active cGVHD who have erythematous rash involving 
>25% body surface area or a NIH mouth score of >4 must have received prior ibrutinib therapy. 
The study will consist of a Screening period, a Treatment period, and a Safety Follow-up period. 
In both study phases, study intervention will be given via IV infusion Q2W until disease 
progression or unacceptable toxicity occurs for a maximum of 6 cycles. Subjects may receive 
study intervention in either an inpatient or outpatient setting. After 6 cycles of biweekly 
treatment, in subjects without cGVHD progression, the study intervention may be administered 
either Q2W or Q4W, at the Investigator’s discretion in discussion with the Sponsor. 
In both study phases, response criteria will be assessed every 4 weeks and at the end of treatment 
visit or discontinuation of the study intervention using 2014 NIH Consensus Development 
Project on Criteria for Clinical Trials in cGVHD: CR, PR, lack of response (unchanged, mixed or 
progression). Window periods of ±1 day for Cycle 1 and ±3 days for each subsequent cycle will 
be allowed for response assessments. 
At each study visit subjects will undergo assessments as specified in the Schedule of Activities 
(Section 1.2). 
Dose Escalation 
Eligible subjects will be enrolled sequentially to evaluate escalating doses SNDX-6352 as 
depicted in Table 1 and Figure 1. For all cohorts, DLT assessment window is 28 days from 
initiation of treatment with SNDX-6352 or administration of third dose (C2D1), whichever is 
later. For DLT criteria see Section 6.5. Decision to dose escalate will be made by the SRC. 
Based on emerging data and the evaluation of the safety and tolerability data as a whole, it may 
also be decided that accrual will take place at an intermediate dose level and/or alternative 
dosing schedule (e.g., 3 mg/kg Q4W or 4 mg/kg Q4W). The OBD is defined as the lowest safe 
dose with the highest rate of biologic activity. Biologic activity is determined by 100% reduction 
of non-classical monocytes at the time of dose interval and plateaued increase of circulating 
CSF-1 levels that persist for an entire dosing level. 


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Table 1: 
Phase 1 Dose Escalation Scheme 
 
Dose cohort 
Dose levels of SNDX-6352 
Dosing schedule**** 
1* 
0.15 mg/kg (starting dose) 
Q2W up to 12 cycles.*** 
2* 
0.5 mg /kg 
3** 
1 mg/kg 
4** 
3 mg/kg 
4a** 
2 mg/kg 
* Single subject cohort which can be expanded to 3+3 design depending on toxicity 
** 3+3 design, 3 subjects per cohort which can be expanded to 6 subjects depending on DLT 
*** If no progression, treatment may be continued after 6 cycles at Q2W or Q4W at investigator’s discretion in 
discussion with Sponsor. 
**** Based on emerging data, intermediate dose levels and/or alternative dosing schedules may be used 
 
The 2 lowest dose cohorts, 0.15 mg/kg and 0.5 mg/kg, will initially be a single-subject cohort. If 
the first subject enrolled into the 0.15 mg/kg cohort does not experience ≥ Grade 2 toxicity 
(non-DLT) during toxicity assessment window, the next enrolled subject will receive 0.5 mg/kg 
and if that subject treated at 0.5 mg/kg does not experience ≥ Grade 2 toxicity (non-DLT) during 
toxicity assessment window, enrollment to Cohort 3 (1 mg/kg) will be initiated utilizing 3+3 
design. However, if the first subject in Cohort 1 (0.15 mg/kg) experiences ≥ Grade 2 toxicity 
(non-DLT) during toxicity assessment window, a 3+3 design will be utilized beginning with that 
dose and 2 additional subjects will be enrolled into Cohort 1 (total of 3 subjects); if any of these 
3 subjects experience DLT, then 3 additional subjects will be enrolled (total of 6 subjects). If 
none of these 3 subjects experience DLT, enrollment will proceed to Cohort 2 and the same 
escalation rules will apply prior to proceeding to Cohort 3. 
For Cohort 3 (1 mg/kg), initially 3 subjects will be enrolled. If no DLT observed from these 3 
subjects, enrollment will proceed to Cohort 4 (3 mg/kg). However, if 1 of these 3 subjects at 
1 mg/kg experiences a DLT during toxicity assessment window, 3 additional subjects will be 
enrolled into Cohort 3 (total of 6). If 1 out of 6 subjects in Cohort 3 experiences a DLT, 
enrollment will proceed to Cohort 4a (2 mg/kg), instead of Cohort 4 (3 mg/kg). If 2 out of 6 
subjects at 1 mg/kg experience a DLT, dose will be de-escalated to a lower dose. 
For Cohort 4a (2 mg/kg), if enrollment continues directly from Cohort 3 (1 mg/kg), then 3 
subjects will initially be enrolled, if no DLT observed from these 3 subjects at 2 mg/kg, 
enrollment will proceed to Cohort 4 (3 mg/kg). However, if 1 of these 3 subjects experiences a 
DLT, 3 additional subjects will be enrolled into Cohort 4a at 2 mg/kg (total of 6). If 1 out of 6 
subjects experiences a DLT, dose escalation will proceed to Cohort 4 (3 mg/kg). If 2 out of 6 
subjects experience a DLT, dose will be de-escalated to a lower dose 
For Cohort 4 (3 mg/kg), 3 subjects will initially be enrolled. If no DLT observed from these 3 
subjects, then 3 additional subjects will be enrolled into Cohort 4 (total of 6). If 0 or 1 of these 6 
subjects at 3 mg/kg experiences a DLT, this dose will be considered the maximum tolerated dose 


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(MTD) and aRP2D. If 2 out of 6 subjects at 3 mg/kg experience a DLT, dose will be de-escalated 
to Cohort 4a if less than 6 subjects are enrolled in Cohort 4a and enroll up to a total of 6 subjects. 
If 0 or 1 of these 6 subjects at 2 mg/kg experiences a DLT, this dose will be considered the MTD 
and a RP2D. Under both scenarios, if 2 out of 6 subjects experience a DLT, dose will be de- 
escalated to a lower dose. 
The MTD is defined as the highest dose level at which no more than 1 of 6 subjects experienced 
a DLT. However, the OBD/RP2D may be a dose that is lower than MTD. 
For subjects who are enrolled into dose cohort of 0.15 mg/kg, and 0.5 mg/kg, if they have 
tolerated the originally assigned dose without ≥Grade 2 study intervention related AE for 2 
cycles, at Investigator’s discretion, their dose may be subsequently escalated to higher dose that 
has been evaluated by SRC to have an acceptable safety profile. However, they will be included 
in the DLT evaluation only for the dose cohort to which they were originally assigned. 


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Figure 1: 
Phase 1 Dose Escalation Decision Tree 
 


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Figure 2: 
Phase 2 1 mg/kg Dose Expansion 
 
 
4.2. 
Rationale for Study Design 
Phase 1 is a modified dose escalation 3+3 design, which is a well-accepted design in cancer 
studies (Jaki, et al 2013). As a precautionary measure, the initial 2 cohorts (sub-optimal doses of 
SNDX-6352, 0.15 mg/kg and 0.5 mg/kg) are single subject cohorts, prior to starting with 
1 mg/kg. The study also allows expediting dose escalation from 1 mg/kg to 3 mg/kg without 
compromising subject’s safety. Intermediary doses may also be investigated, depending on 
outcome. For subjects who start with the 2 lower doses (0.15 mg/kg and 0.5 mg/kg), intra-subject 
dose escalation is allowed to enable them to benefit from a therapeutic dose. The dose levels, i.e., 
0.15, 0.5, 1, 2 (if required), and 3 mg/kg, are expected to be sufficient for evaluation of the 
safety, PK and PD profile, OBD, and early indications of clinical activity. The PK and extent of 
target binding will be closely monitored during this clinical study. 
Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample 
size based on preliminary PK, PD, safety and preliminary evidence of clinical activity observed 
in Phase 1. 
4.3. 
Justification for Dose 
For Phase 1, the SNDX-6352 starting dose of 0.15 mg/kg is planned with ascending dose levels 
of 0.5, 1, 2 (if required), and 3 mg/kg. The starting dose of 0.15 mg/kg was selected based on 
available clinical data (PK and safety) in healthy volunteers (SNDX-6352-0001) and the 
preliminary data from the multiple ascending dose study SNDX-6352-0502 Phase 1a. This was 
determined by taking both the no-observed-adverse-effect-level (NOAEL) and minimum 
anticipated biological effect level (MABEL) for SNDX-6352 into consideration. 


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In SNDX-6352-0001, 3 cohorts of healthy volunteer subjects have received a single dose of 
either 0.15 mg/kg, 1 mg/kg, or 3 mg/kg and completed the PK sampling and safety assessments 
for each of those dose levels. Based on the data from the 1 mg/kg cohort, the average maximum 
concentrations were approximately 22500 ng/mL and were achieved by approximately 1 hour. 
The AUC0-last estimates (over 7 days) were determined to be 1289 µg/*hr/mL. The half-life of 
SNDX-6352 was determined to be approximately 56 hours. There were no DLTs that would 
prevent dosing the higher dose cohorts. Mild to moderate eyelid swelling lasting for up to 
approximately 4 weeks has been observed in the majority of subjects dosed at 3 mg/kg, which 
precluded further dose escalation in healthy volunteers. 
SNDX-6352 PK and PD data from healthy subjects and solid tumor patients indicate that all 
doses tested at Q2W, ranging from 0.15 mg/kg to 6 mg/kg have demonstrated evidence of 
biologic activity. Measurement of circulating non-classical monocytes levels, CSF-1 and IL-34 
levels and receptor occupancy indicate a dose dependent effect of SNDX-6352 on these markers 
that correlate well with drug concentrations. Increased dosing effects the magnitude of change as 
well as duration of effect. At 1 mg/kg in both healthy subjects and solid tumor patients, depletion 
of non-classical monocytes is prolonged through approximately Day 10 of a 14-day dosing 
interval with recovery to baseline by the next dose. Doses higher than 1 mg/kg deplete 
monocytes for the full 14-day interval. 
Preliminary data from the Phase 1 portion of this study indicate that both the PK and monocyte 
depletion effects at 1mg/kg are consistent with the data from the prior studies demonstrating that 
dose dependent biologic activity is conserved across healthy subjects, solid tumor and cGVHD 
subjects. These data justify 1 mg/kg as a potential optimal biologic dose with early evidence of 
clinical benefit in cGVHD subjects treated at this dose level. The Phase 2 expansion phase will 
further evaluate preliminary efficacy of SNDX-6352 at 1 mg/kg in subjects with active cGVHD 
who have failed two prior therapies due to progression of disease, intolerability or toxicity. Up to 
22 subjects are anticipated to participate. 
Please refer to SNDX-6352 IB for more details. For dose modifications criteria, please refer to 
Section 6.7. 
4.4. 
End of Study Definition 
A subject is considered to have completed the study if he/she has completed post-study follow- 
up assessments which are at 90 days after termination of study intervention or the last scheduled 
procedure shown in the Schedule of Activities. 
The end of the study is defined as the date of the last post-study assessment (90 days after the 
study intervention termination) of the last subject in the study. 


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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Subjects are eligible to be included in the study, in either Phase 1 or Phase 2, only if all the 
following criteria apply: 
Age 
1. Subject must be 6 years of age or older, at the time of signing the informed consent. 
Type of Subject and Disease Characteristics 
2. Subjects who are allogeneic HSCT recipients with cGVHD requiring systemic immune 
suppression. 
3. Subjects with active cGVHD who have received at least 2 lines of therapy. Subjects ≥18 
years of age with active cGVHD who have erythematous rash involving >25% body 
surface area or a NIH mouth score of >4 must have received prior ibrutinib therapy. 
Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 
NIH Consensus Development Project on Criteria for Clinical trials in cGVHD (Jagasia, et 
al 2015). 
4. Subjects may have persistent active acute and cGVHD manifestations (overlap 
syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for 
Clinical trials in cGVHD. 
Diagnostics assessments 
5. Karnofsky Performance Scale of ≥60 with a life expectancy of at least 3 months (if aged 
16 years or older); Lansky Performance Score of ≥60 (if aged <16 years). 
6. Adequate organ and bone marrow functions evaluated during the 14 days prior to 
enrollment as follows: 
a. Absolute neutrophil count ≥1.5 × 109/L without growth factors within 1 week of 
study entry); 
b. Platelet count ≥50 × 109/L (without transfusion within 2 weeks of study entry); 
c. Total bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase 
(AST) ≤ upper limit of normal (ULN); 
d. For subjects with suspected liver cGVHD, ALT and AST ≤3  ULN and total 
bilirubin ≤ULN; 
e. Creatinine clearance (CrCl) ≥50 mL/min/1.73 m2 or a serum creatinine ≤1.5 mg/dL 
based on the Cockcroft-Gault formula. 


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Sex 
7. Male and/or female. 
Contraceptive use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
8. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be 
sexually active with a female partner of childbearing potential must use a male condom 
plus spermicide from the time of screening throughout the total duration of the study 
intervention treatment period and 90 days after the last dose of study intervention. 
However, periodic abstinence, the rhythm method, and the withdrawal method are not 
acceptable methods of contraception. Male subjects should refrain from sperm donation 
throughout this period. 
9. Female subjects: Evidence of post-menopausal status or negative urinary or serum 
pregnancy test for female pre-menopausal subjects. Women will be considered post- 
menopausal if they have been amenorrheic for 12 months without an alternative medical 
cause. The following age-specific requirements apply: 
− Women <50 years of age would be considered post-menopausal if they have been 
amenorrheic for 12 months or more following cessation of exogenous hormonal 
treatments and if they have luteinizing hormone and follicle-stimulating hormone 
levels in the post-menopausal range for the institution or underwent surgical 
sterilization (bilateral oophorectomy or hysterectomy). 
− Women ≥50 years of age would be considered post-menopausal if they have been 
amenorrheic for 12 months or more following cessation of all exogenous 
hormonal treatments, had radiation-induced menopause with last menses >1 year 
ago, had chemotherapy-induced menopause with last menses >1 year ago, or 
underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy). 
− Female subjects of childbearing potential who are not abstinent and intend to be 
sexually active with a non-sterilized male partner must use at least 1 highly 
effective method of contraception (Table 14) from the time of screening 
throughout the total duration of the study intervention treatment period and 90 
days after the last dose of study intervention. Non-sterilized male partners of a 
female subject of childbearing potential must use male condom plus spermicide 
throughout this period. Cessation of birth control after this point should be 
discussed with a responsible physician. Periodic abstinence, the rhythm method, 
and the withdrawal method are not acceptable methods of birth control. Female 
subjects should also refrain from breastfeeding throughout this period. 


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Informed Consent 
10. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1.2) 
which includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
5.2. 
Exclusion Criteria 
Subjects are excluded from the study, in both Phase 1 and Phase 2, if any of the following 
criteria apply: 
Medical Conditions 
1. Has acute GVHD without manifestations of cGVHD. 
2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of 
the underlying cancer or post-transplant lymphoproliferative disease at the time of 
screening. 
3. History or other evidence of severe illness, uncontrolled infection or any other conditions 
that would make the subject, in the opinion of the Investigator, unsuitable for the study 
4. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus 
(HCV) or hepatitis B virus (HBV). 
5. Diagnosed with another malignancy (other than malignancy for which transplant was 
performed) within 3 years of enrollment, unless previously treated with curative intent 
and must be approved by Sponsor medical monitor (e.g., completely resected basal cell or 
squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast 
ductal carcinoma in situ, or low-risk prostate cancer after curative resection). 
6. Female subjects who is pregnant or breastfeeding. 
Prior/Concomitant Therapy 
7. Previous exposure to study intervention or known allergy/sensitivity to study 
intervention. 
8. Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for 
treatment of cGVHD (This does not include agents being prescribed expressly for the 
treatment of acute GVHD). 
To be eligible, at study enrollment, subjects must have been on stable dose of 
corticosteroids and CNI for at least 2 weeks. 
For approved or commonly used agents, a washout of 2 weeks or 5 half-lives, whichever 
is shorter, is required at study enrollment. 
Prior/Concurrent Clinical Study Experience 
9. Receiving an investigational treatment within 28 days of study entry. 


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5.3. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) maybe 
rescreened. Rescreened subjects should be assigned the same subject number as for the initial 
screening. 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study subject according to the 
study protocol. 
 
6.1. 
Study Intervention(s) Administered 
Table 2: 
Study Intervention 
 
Intervention Name 
SNDX-6352 
Type 
Biologic 
Dose Formulation 
Solution for infusion 
Unit Dose Strength(s) 
mg/kg 
Dosage Level(s) 
0.15, 0.5, 1, 3, 2 mg/kg and other intermediary doses and/or alternative 
dosing schedules based on emerging data. 
Frequency: Every 2 weeks (Day 1 and 15 of each 4-week cycle) up to 6 
months, if no progression, either Q2W or Q4W up to Month 12, at the 
Investigator’s discretion in discussion with the Sponsor. 
Route of 
Administration 
IV infusion over 30 minutes; time windows of -5 minutes to +10 minutes are 
permitted (i.e., infusion time is 25 to 40 minutes). The exact duration of 
infusion should be recorded in both source documents and eCRFs. 
IMP definition 
A new drug or biological drug that is used in a clinical investigation (FDA) 
Sourcing 
SNDX-6352 is manufactured by Nova Laboratories Ltd (Leicestershire UK) 
for UCB Pharma S.A. (Braine-l’Alleud Belgium). 
Study intervention will be provided to the site centrally by the Sponsor or 
designated representative. 
Packaging and 
Labeling 
SNDX-6352 is supplied as a 1.3 mL (1.0 mL extractable volume) sterile, 
preservative free solution in 2 mL, colorless, Type I glass vials closed with a 
rubber stopper and sealed with an aluminum overseal and flip-off cap. The 
vials are single use only and contain no preservatives. 
Label text for the SNDX-6352 vial will at a minimum include the protocol 
number, the contents of the vial (e.g., SNDX-6352 50 mg/mL), lot number, 
storage conditions, and Sponsor name and address. Labels comply with 
regulatory requirements for investigational products. 
Former Name(s) or 
Alias(es)] 
UCB-6352 


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6.2. 
Preparation/Handling/Storage/Accountability 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
2. Only subjects enrolled in the study may receive study intervention and only authorized 
site staff may supply or administer study intervention. All study intervention must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area 
in accordance with the labeled storage conditions with access limited to the Investigator 
and authorized site staff. 
3. SNDX-6352 drug product must be diluted to 50 mL with 0.9% saline solution (sodium 
chloride injection) supplied in an infusion bag. No other drugs should be added to the 
solution for infusion containing SNDX-6352. 
4. The dose amount required to prepare the SNDX-6352 infusion solution will be based on 
the subject’s weight in kilograms (kg). All subjects should be weighed within 3 days 
prior to dosing. If the subject experiences either a weight loss or gain >10% compared to 
the weight used for the last dose calculation, the amount of study intervention must be 
recalculated. For weight change < 10%, the decision to recalculate the SNDX-6352 dose 
can be in accordance with institutional practice. 
5. The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
6. Further guidance and information for the final disposition of unused study interventions 
are provided in the Pharmacy Manual. 
 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable. The study is open-label. 
 
6.4. 
Study Intervention Compliance 
Administration of SNDX-6352 will be supervised by the Investigator or sub-Investigator. Any 
delegation of this responsibility must follow the standard procedures. Records of treatment 
administration for each subject will be kept during the study. Clinical research associates will 
review study intervention administration records and verify compliance with the Pharmacy 
Manual during site visits and at the completion of the study. Deviation(s) from the prescribed 
dosage regimen should be recorded in the eCRF. 
A mandatory 2-hour observation period after each SNDX-6352 infusion (for potential infusion- 
related reactions) is required following the first 4 SNDX-6352 infusions. If no infusion reaction 
occurs in relation to the first 4 infusions, the post-infusion observation period may be 
discontinued at investigator’s discretion. Patients who experience an infusion-related reaction at 
any point must continue to undergo the mandatory observation after each infusion. 


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6.5. 
Dose Limiting Toxicity Criteria 
DLTs will be assessed during a DLT assessment window, which is the first 28 days from the first 
dose of SNDX-6352 or administration of the third dose (C2D1), whichever is later (from C1D1 
to C2D1). All DLTs will be reported in the Sponsor’s electronic data capture (EDC) system 
within 24 hours. 
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that 
occurs within the DLT assessment window (defined above), meets any of the criteria below, is 
assessed by the Investigator as not being definitely attributable to underlying disease, disease 
progression, inter-current illness, concomitant medications or any other alternative cause. 
Hematological toxicities 
• Neutropenia 
− Grade 4 neutropenia (absolute neutrophil count [ANC] <500/μL) 
− Any grade febrile neutropenia [i.e., ANC <1000 per mm3 and associated with 
fever (oral temperature ≥38ºC) requiring antibiotic therapy] 
• Thrombocytopenia 
− Grade 4 thrombocytopenia (i.e., platelet <25,000 per mm3) 
− Grade 3 thrombocytopenia (i.e., platelets <50,000 per mm3) with clinically 
significant bleeding 
• Grade 4 anemia 
Non-hematological toxicities: 
• Any Grade 3 or Grade 4 non-hematological, non-hepatic toxicity 
• Criteria meeting Hy’s Law: elevation of ALT/AST ≥3  ULN and concurrent total 
bilirubin ≥2  ULN in the absence of cholestasis (elevation of alkaline phosphatase 
(ALP) and GGT > 2.5  ULN) 
• ≥ Grade 3 ALT/AST elevation 
• Isolated Grade ≥2 ALT or AST (> 3 to 5  ULN) in the absence of cholestasis 
(elevation of ALP and gamma glutamyl transferase (GGT) > 2.5  ULN). 
Exceptions: 
− 
Asymptomatic Grade 2 AST (> 3 to 5  ULN) that is accompanied by 
≤ Grade 1 ALT (> ULN to 3  ULN) and ≤ Grade 1 total bilirubin (> ULN 
to 1.5  ULN), will not be considered DLT 
• For Q4W dosing only, any asymptomatic ≥Grade 3 lipase or amylase if there is end 
organ damage or if it lasts for ≥4 weeks. 


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• ≥ Grade 3 creatine kinase (CK) increase with clinical symptoms and/or evidence of 
end organ damage (i.e., increased serum or urine myoglobin) 
Exception: 
− 
In the absence of any clinical symptoms and no evidence of end organ 
damage, ≥ Grade 3 will NOT be considered a DLT (subjects will undergo 
an assessment for end organ damage to exclude the possibility of toxicity) 
• Other Grade 3 laboratories abnormalities 
Exception: 
− 
Isolated Grade 3 electrolyte abnormalities persisting for >72 hours despite 
maximal medical intervention will be considered a DLT unless they are 
considered to be part of a syndrome in which the grading of the syndrome 
would itself determine whether the finding was a DLT 
• Grade 3 infusion reaction 
• ≥ Grade 3 periorbital edema 
• Subjects who require delay in therapy for ≥2 weeks for any CTCAE grade toxicity 
during the DLT assessment period. Additionally, toxicity resulting in subject 
receiving < 70% of planned dose intensity within the first 6 weeks; note the 6-week 
time frame accounts for dose delays with the intention being to dose at least 3 times 
within 6 weeks including C2D1. 
Subjects who receive <90% of the SNDX-6352 infusion in Cycle 1 (i.e., because the infusion 
had to be discontinued due to an infusion reaction) and do not experience a DLT will not be 
considered evaluable in the assessment of the overall DLT rate for the particular dose level 
cohort and will be replaced. 
Subjects who withdraw or are withdrawn from study treatment prior to completing the DLT 
assessment window for any reason other than a study intervention-related toxicity through 
Cycle 1, will not be considered evaluable for DLTs and will be replaced. 
If a subject experiences a DLT in Cycle 1, the study intervention will be held until recovery to 
Grade 1 or baseline, and if the Investigator considers it in the subject’s best interest to continue 
on study treatment, with the approval by the Sponsor medical monitor, study intervention 
administration may be resumed at a reduced dose. 
 
6.6. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving at the time of enrollment or receives 
during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 


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• Dosage information including dose and frequency 
All treatments that the Investigator considers necessary for a subject’s plan of care may be 
administered concomitantly with SNDX-6352 at the Investigator’s discretion per standard of 
care. Other supportive medications in accordance with standard clinical practice (such as for 
prophylaxis for encapsulated bacteria, viral and fungal infections) are permitted per institutional 
policy. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
 
6.6.1. 
Prohibited Medications 
• Only 1 systemic corticosteroid and 1 CNI are allowed at the time of enrollment; any 
other immune suppressive agents for treatment of chronic GVHD are not permitted. 
− This does not include agents for treatment of acute GVHD and prophylaxis for 
chronic GVHD. 
− At study enrollment, subjects must have been on stable dose of corticosteroids for 
at least 2 weeks. 
− Corticosteroids may be tapered, per local institutional guidelines, after the first 4 
weeks of study intervention administration at the discretion of the Investigator. 
One re-escalation of corticosteroids (up to a dose of 1 mg/kg daily of prednisone 
or equivalent) up to 5 months from start of SNDX-6352 is allowed at the 
discretion of Investigator. 
• Live virus vaccinations 
• Antineoplastic systemic chemotherapy or biological therapy except when used as 
maintenance therapy (e.g., FLT3 inhibitors or TKIs started prior to enrollment into 
this study) to prevent relapse. 
• Investigational agents other than SNDX-6352 
• Radiation therapy: Administration of palliative radiation therapy will be considered 
relapse or progression of the primary disease. 
• Traditional herbal medicines: these therapies are not fully studied, and it is unknown 
whether their use may result in unanticipated drug-drug-interactions that may cause 
or confound the assessment of toxicity. 
 
6.7. 
Dose Modification 
For the first 3 doses, dose delays, but not dose reduction, will be allowed for SNDX-6352. Any 
dose delay or modification during the first 2 cycles in Phase 1 should be discussed with the 
Sponsor’s Medical Monitor. 


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In subjects who have a DLT-type AE (Section 6.5), study intervention treatment will be held 
until resolution of toxicity to Grade 0-1. 
After the first 3 doses, both dose delays and dose reductions will be allowed as described below. 
Subjects who do not tolerate therapy after 1 dose level reduction from starting dose must 
withdraw from the study. Once the SNDX-6352 dose is reduced, it cannot be re-escalated. Dose 
interruptions for reason(s) other than toxicity, such as surgical procedures, may be allowed with 
Sponsor approval. The acceptable length of interruption will depend on agreement between the 
Investigator and the Sponsor. 
All dose modifications should be based on toxicity described in the sections below and should be 
properly documented in source documents. Investigators may take a more conservative approach 
than the guidelines outlined in the protocol on the basis of clinical judgment that is in the best 
interest of the subject. Such instances should be reported to the Medical Monitor. 
6.7.1. 
Axatilimab Taper 
 
If after 12 months of treatment, axatilimab treatment is to be stopped, an axatilimab taper 
followed by discontinuation may be pursued as an alternative to immediate agent 
discontinuation. Table 3 provides dose taper guidance. 
 
Table 3: 
Axatilimab Taper Schedule and Duration for Each Dose Level 
 
Last dose 
administered 
Taper 1 
(8 weeks) 
Taper 2 
(8 weeks) 
Taper 3 
(8 weeks) 
Taper 4 
(8 weeks) 
3 mg/kg Q2W 
3 mg/kg Q4W 
(2 doses) 
2 mg/kg Q4W 
(2 doses) 
1 mg/kg Q4W 
(2 doses) 
1 mg/kg Q8W 
(1 dose) 
End 
3 mg/kg Q4W 
2 mg/kg Q4W 
(2 doses) 
1 mg/kg Q4W 
(2 doses) 
1 mg/kg Q8W 
(1 dose) 
End 
2 mg/kg Q4W 
1 mg/kg Q4W 
(2 doses) 
1 mg/kg Q8W 
(1 dose) 
End 
1 mg/kg Q2W 
1 mg/kg Q4W 
(2 doses) 
1 mg/kg Q8W 
(1 dose) 
End 
Q2W = every 2 weeks; Q4W = every 4 weeks 
For doses not listed, consultation with the Sponsor is required before taper initiation. 
Patients completing the taper schedule will continue undergoing study-specific assessment every 
28 days, with the final treatment period evaluation occurring 28 days after the last dose. Thirty 
(± 7) days after the last evaluation in the treatment period, patients will initiate the Safety 
Follow-up period of the study. 
Should progression of cGVHD be recorded at any point after taper initiation, axatilimab use on 
the protocol may not be restarted. 


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6.7.2. 
Guidelines for Toxicity Management 
The guidelines for the management of toxicities are outlined as follows with toxicities graded by 
the Investigator according to the NCI CTCAE, version 5.0. 
6.7.2.1. 
AST, ALT, Bilirubin, CK, Amylase and Lipase elevation 
Dose modification guidelines for SNDX-6352 due to AST, ALT, bilirubin, CK, amylase or 
lipase elevation are specified in Table 4. 


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Table 4: 
AST, ALT Bilirubin, CK, Amylase and Lipase: Dose Modification Guidelines 
for SNDX-6352 
 
Toxicity 
Dose modifications 
Asymptomatic Grade 2 AST (>3 to 
5  ULN), with ≤Grade 1 ALT and 
≤Grade 1 total bilirubin, no change 
from baseline of ALT and total 
bilirubin 
Continue SNDX-6352 without dose delay or reduction with 
agreement from both Investigator and Sponsor Medical 
Monitor 
Grade 2 ALT (>3 to 5  ULN) with 
total bilirubin ≤Grade 1 
Hold SNDX-6352 dose until recovery to Grade 1 (> ULN to 
3  ULN) or baseline, then resume SNDX-6352 at the same 
dose 
Grade 3 AST or ALT (> 5 to 
20  ULN) with total bilirubin 
≤Grade 1 
Hold SNDX-6352 dose until recovery to Grade 1 (> ULN to 
3  ULN) or baseline, then resume SNDX-6352 at a reduced 
dose (if this will be the 4th planned dose or onward) 
Concurrent ALT or AST ≥3  ULN 
and total bilirubin ≥2  ULN in the 
absence of cholestasis (elevation of 
ALP and gamma glutamyl 
transferase (GGT) >2.5  ULN) 
Permanently discontinue SNDX-6352 
Grade 4 AST or ALT (>20  ULN) 
Permanently discontinue SNDX-6352 
Grade 2 total bilirubin 
Hold SNDX-6352 dose, rule out hemolysis and cholestasis, 
until recovery to Grade 1 or baseline, then resume SNDX-6352 
at the same dose 
Grade 3 total bilirubin 
Hold SNDX-6352 dose, rule out hemolysis and cholestasis, 
until recovery to Grade 1 or baseline, then resume SNDX-6352 
at a reduced dose (if this will be the 4th planned dose or 
onward) 
≥ Grade 3 CK, amylase or lipase in 
the absence of any clinical symptoms 
• 
Before administering axatilimab, conduct diagnostic 
evaluation, eg, serum and urine myoglobin, or CPK-MB, 
BUN, creatinine, ECG, troponin (I or T). 
• 
If results show no evidence of end organ damage, continue 
axatilimab without dose reduction, with agreement from 
both Investigator and Sponsor Medical Monitor. 
If the results show evidence of end organ damage, axatilimab 
should be discontinued. 
Symptomatic Grade 3 CK, amylase 
or lipase 
Permanently discontinue SNDX-6352 with agreement from 
both Investigator and Sponsor Medical Monitor 
SNDX-6352 can cause modulation of Kupffer cells in the liver, which may lead to elevation of liver 
enzymes (ALT and AST). Serum bilirubin, alkaline phosphatase (ALP) and gamma glutamyl 
transferase (GGT) will need to be monitored along with ALT and AST for assessment of liver toxicity. 


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6.7.2.2. 
Other Non-hematologic Toxicity 
The rules for the management of other non-hematologic toxicities are outlined as follows in 
Table 5 with toxicities graded by the Investigator according to the NCI CTCAE, version 5.0. 
Table 5: 
Other Non-hematologic Toxicity: Dose Modification Guidelines for 
SNDX-6352 
 
Toxicity 
Dose modifications 
Grade 4 
Administer symptomatic remedies/start prophylaxis. 
Any Grade 4 events require permanent treatment discontinuation from 
SNDX-6352. 
Grade 3 
Administer symptomatic remedies/ start prophylaxis. Hold SNDX- 
6352 dose until recovery to Grade 1 or baseline under the following 
directions: 
1. If recovered within 4 weeks, resume SNDX-6352 at a reduced 
dose (if this will be the 4th dose or onward). 
2. If the SNDX-6352 dose is held for more than 4 consecutive 
weeks, permanently discontinue SNDX-6352. 
Grade 2 
Administer symptomatic remedies / start prophylaxis. 
Hold SNDX-6352 dose until recovery to Grade 1 or baseline, resume 
SNDX-6352 at the same dose. 
 
6.7.2.3. 
Hematologic Toxicity 
The guidelines in Table 6 will be followed for determining the dose modifications based on 
hematologic status at the time of planned dosing. 


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Table 6: 
Hematologic Toxicity: Dose Modification Guidelines for SNDX-6352 
 
Toxicity 
Dose modifications 
Grade 3 to 4 neutropenia, 
Febrile neutropenia or 
neutropenic infection 
Grade 3 to 4 
uncomplicated 
thrombocytopenia, or 
Grade 2 complicated 
thrombocytopenia 
Hold SNDX-6352 dose until recovery to Grade 1 or study baseline under 
the following directions. 
1. If recovered within 4 weeks, resume SNDX-6352 at next lower 
dose (if this will be the 4th dose or onward) 
2. If the SNDX-6352 dose is held for more than 4 consecutive weeks, 
permanently discontinue SNDX-6352. 
Recurrence of the same 
hematologic toxicity 
If the same hematologic toxicity recurs: 
1. Administer symptomatic remedies/ start prophylaxis. Hold SNDX- 
6352 dose until recovery to Grade 1 or baseline. 
2. If recovered within 7 days, resume SNDX-6352 at next lower 
dose. 
3. If the episode is not recovered within 14 days despite SNDX-6352 
dose reduction to next lower dose, as described above, 
permanently discontinue SNDX-6352. 
4. If the 3rd episode, permanently discontinue SNDX-6352. 
 
6.7.2.4. 
SNDX-6352 Infusion-Related Reaction 
If a subject experiences an SNDX-6352 infusion-related reaction, they may continue on study 
intervention treatment per guidance presented in Table 7. Subjects who previously experienced 
an infusion-related reaction will receive a premedication regimen of 25 to 50 mg IV or oral 
equivalent diphenhydramine and 650 mg IV or oral equivalent acetaminophen/paracetamol 
approximately 30 to 60 minutes prior to each subsequent dose of SNDX-6352. 
Treatment modifications for SNDX-6352 infusion-related reactions are outlined in Table 7. 


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Table 7: 
Infusion-related Reactions for SNDX-6352 
 
NCI-CTCAE Grade 
Treatment Modification for SNDX-6352 
Grade 1 – mild 
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
Decrease SNDX-6352 infusion rate by 50% being 
given at the time of event onset and monitor closely 
for any worsening. 
Grade 2 – moderate 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(e.g., antihistamines, nonsteroidal anti- 
inflammatory drug [NSAIDs], narcotics, IV 
fluids); prophylactic medications indicated for ≤ 
24 hours. 
Temporarily discontinue SNDX-6352 infusion. 
Resume infusion at 50% of previous rate once 
infusion-related reaction has resolved or decreased 
to at least Grade 1 in severity and monitor closely 
for any worsening. At next cycle, administer oral 
premedication with antihistamine and anti-pyretic 
and monitor closely for infusion reaction. 
Grade 3 or Grade 4 – severe or life- 
threatening Grade 3: Prolonged (e.g., not 
rapidly responsive to symptomatic medication 
and/or brief interruption of infusion); recurrence 
of symptoms following initial improvement; 
hospitalization indicated for clinical sequelae 
Grade 4: Life-threatening consequences – urgent 
intervention is indicated. 
Stop the SNDX-6352 infusion immediately and 
disconnect infusion tubing from the subject. 
Subjects have to be withdrawn immediately from 
SNDX-6352 treatment and must not receive any 
further SNDX-6352 treatment. 
NSAIDs = nonsteroidal anti-inflammatory drugs 
If a Grade 2 infusion-related reaction does not improve or worsens after implementation of the 
modifications indicated in Table 7 (including reducing the infusion rate by 50%), the Investigator 
may consider treatment with corticosteroids, and the infusion should be stopped for that day. At 
the next cycle, administration of oral premedication with antihistamine and anti-pyretic is 
required. Prophylactic steroids are NOT permitted. If the subject has a second infusion-related 
reaction of Grade 2 or higher on the slower 50% infusion rate, with or without the addition of 
further medication to the mandatory premedication, the infusion should be stopped, and the 
subject removed from SNDX-6352 treatment. 
 
6.7.2.5. 
Immune-related Adverse Events for SNDX-6352 
Because inhibition of CSF-1/IL-34 signaling pathway may stimulate the immune system, 
immune-related adverse events (irAEs) may occur. General guidance includes the following: 
• Grades 1 to 2: Treat symptomatically or with moderate dose steroids, more frequent 
monitoring. 
• Grades 1 to 2 (persistent for >5-7 days): Manage similarly to high-grade adverse 
events (Grades 3 to 4). 
• Grades 3 to 4: Treat with high-dose corticosteroids. 
Please refer to Table 8 for management of irAEs. 


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Table 8: 
Management of Immune-related Adverse Events for SNDX-6352 
 
Gastrointestinal Immune-related Adverse Events 
Severity of 
Diarrhea/Colitis 
(NCI CTCAE v5.0) 
Management* 
Follow-up* 
Grade 1 
Diarrhea: < 4 stools/day 
over baseline 
Colitis: asymptomatic 
Continue SNDX-6352 therapy with symptomatic 
treatment (e.g., loperamide) after ruling out infectious 
etiology. 
Close monitoring for worsening symptoms. Educate 
subject to report worsening immediately. If worsens, 
treat as Grade 2 or Grade 3 to 4. 
Grade 2 
Diarrhea: 4 to 6 stools/day 
over baseline; IV fluids 
indicated < 24 hours; not 
interfering with activity of 
daily living (ADL) 
Colitis: abdominal pain; 
blood in stool 
Delay SNDX-6352 therapy; symptomatic treatment. 
Consider lower GI endoscopy and biopsy to evaluate 
for acute GVHD 
If improves to Grade 1, resume SNDX-6352 therapy. If 
persists > 5 to 7 days or recurs, give 0.5 to 
1.0 mg/kg/day oral methyl-prednisolone or equivalent. 
When symptoms improve to Grade 1, taper steroids 
over at least 1 month, and resume SNDX-6352 therapy 
per protocol. If worsens or persists > 3 to 5 days with 
oral steroids, treat as Grade 3 to 4 
Grade 3 to 4 
Diarrhea (Grade 3): 
≥ 7 stools/day over baseline; 
incontinence; IV fluids 
≥ 24 hours; interfering with 
ADL. 
Colitis (Grade 3): severe 
abdominal pain; medical 
intervention indicated; 
peritoneal signs 
Grade 4: life-threatening, 
perforation 
Discontinue SNDX-6352 therapy per protocol; give 
1 to 2 mg/kg/day methylprednisolone IV or 
equivalent. 
Consider lower GI endoscopy and biopsy to evaluate 
for acute GVHD 
If improves, continue steroids until Grade 1, then taper 
over at least 1 month. If persists > 3 to 5 days, or recurs 
after improvement, add infliximab 5 mg/kg (if no 
contra-indication). 
Note: Infliximab should not be used in cases of 
perforation or sepsis. 


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Dermatological Immune-related Adverse Events 
Grade of Rash (NCI 
CTCAE v5.0) 
Management* 
Follow-up* 
Grades 1 to 2 
Covering ≤ 30% body 
surface area 
Symptomatic therapy (for example, antihistamines, 
topical steroids). Continue SNDX-6352 therapy. 
If persists > 1 to 2 weeks or recurs: consider skin 
biopsy; delay SNDX-6352 therapy. Consider 0.5 to 
1.0 mg/kg/day methylprednisolone IV or oral 
equivalent. Once improving, taper steroids over at least 
1 month, and resume SNDX-6352 therapy. If worsens, 
treat as Grade 3 to 4. 
Grades 3 to 4 
Covering >30% body 
surface area; life-threatening 
consequences 
Delay or discontinue SNDX-6352 therapy; consider 
skin biopsy and dermatology consult; give 1.0 to 
2.0 mg/kg/day methyl-prednisolone IV or IV 
equivalent. 
If improves to Grade 1, taper steroids over at least 
1 month. Resume SNDX-6352 therapy. 
Pulmonary Immune-related Adverse Events 
Grade of pneumonitis 
(NCI CTCAE v5.0) 
Management* 
Follow-up* 
Grade 1 
Radiographic changes only 
Consider delay of SNDX-6352 therapy; monitor for 
symptoms every 2 to 3 days; consider Pulmonary and 
Infectious Disease consults. 
Re-image at least every 3 weeks. If worsens, treat as 
Grade 2 or Grade 3 to 4. 
Grade 2 
Mild to moderate new 
symptoms 
Delay SNDX-6352 therapy; Pulmonary and 
Infectious Disease consults; monitor symptoms daily, 
consider hospitalization; give 1.0 mg/kg/day 
methylprednisolone IV or oral equivalent; consider 
bronchoscopy, lung biopsy. 
Re-image every 1 to 3 days. If improves, when 
symptoms return to near baseline, taper steroids over at 
least 1 month, then resume SNDX-6352 therapy. If not 
improving after 2 weeks or worsening, treat as Grade 3 
to 4. 
Grades 3 to 4 
Severe new symptoms; New 
or worsening hypoxia; life- 
threatening 
Discontinue SNDX-6352 therapy; hospitalize; 
Pulmonary and Infectious Disease consults; give 2 to 
4 mg/kg/day methylprednisolone IV or IV equivalent. 
Consider bronchoscopy, lung biopsy. 
If improves to baseline, taper steroids over at least 6 
weeks. If not improving after 48 hours or worsening, 
add additional immunosuppression (e.g., infliximab, 
cyclophosphamide, IV immunoglobulin, or 
mycophenolate mofetil). 


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Hepatic Immune-related Adverse Events 
Grade of liver test 
elevation 
(NCI CTCAE v5.0) 
Management* 
Follow-up* 
Grade 2 Total bilirubin >1.5 
to ≤3  ULN 
Delay SNDX-6352 therapy; increase frequency of 
monitoring to every 3 days. 
If returns to baseline, resume routine monitoring; 
resume SNDX-6352 therapy. If elevations persist > 5 to 
7 days or worsen, give 0.5 to 1 mg/kg/day methyl- 
prednisolone or oral equivalent. When liver function 
test (LFT) returns to Grade 1 or baseline, taper steroids 
over at least 1 month. Resume SNDX-6352 therapy. 
Concurrent AST or ALT 
>3  ULN and total 
bilirubin >2  ULN 
Discontinue SNDX-6352 therapy; increase frequency 
of monitoring to every 1 to 2 days. Give 1.0 to 2.0 
mg/kg/day methyl-prednisolone IV or IV equivalent. 
Consult gastroenterologist. Consider obtaining 
MRI/CT scan of liver and liver biopsy if clinically 
warranted. 
If returns to Grade 2, taper steroids over at least 1 
month. If does not improve in > 3 to 5 days, worsens or 
rebounds, add mycophenolate mofetil 1 g twice daily. If 
no response within an additional 3 to 5 days, consider 
other immunosuppressants per local guidelines. 
AST or ALT >5  ULN 
with total bilirubin 
≤1.5  ULN 
Delay SNDX-6352 therapy; increase frequency of 
monitoring to every 1 to 2 days. Give 1.0 to 2.0 
mg/kg/day methyl-prednisolone IV or IV equivalent. 
Consult gastroenterologist Consider obtaining 
MRI/CT scan of liver and liver biopsy if clinically 
warranted. 
Asymptomatic; delay dose until resolves to Grade ≤ 1, 
then resume SNDX-6352 at a reduced dose (if this will 
be the 4th planned dose or onward) 
Exception: 
Asymptomatic, isolated 
Grade 2 AST with Grade 1 
ALT and TB) 
Continue study treatment without dose delay or 
reduction with agreement from both Investigator and 
Sponsor medical monitor 
Symptomatic; hold dose until resolves to Grade ≤ 1, 
permanently discontinue SNDX-6352 dosing. 


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Endocrine Immune-related Adverse Event 
Endocrine Disorder 
Management* 
Follow-up* 
Asymptomatic TSH 
abnormality 
Continue SNDX-6352 therapy. If TSH < 0.5  LLN, or TSH > 2  ULN, or consistently out of range in 2 
subsequent measurements, include T4 at subsequent cycles as clinically indicated. Consider endocrinology 
consult. 
Symptomatic 
endocrinopathy 
Evaluate endocrine function. Consider pituitary scan. 
If symptomatic with abnormal lab/pituitary scan, 
delay SNDX-6352 therapy; give 1 to 2 mg/kg/day 
methyl-prednisolone IV or oral equivalent. Initiate 
appropriate hormone therapy. If no abnormal 
lab/pituitary MRI scan but symptoms persist, repeat 
labs in 1 to 3 weeks/MRI in 1 month. 
If improves (with or without hormone replacement), 
taper steroids over at least 1 month. Resume 
SNDX-6352 therapy. Subjects with adrenal 
insufficiency may need to continue steroids with 
mineralocorticoid component. 
Suspicion of adrenal crisis 
(e.g., severe dehydration, 
hypotension, shock out of 
proportion to current illness) 
Delay or discontinue SNDX-6352 therapy; rule out sepsis. Stress dose of IV steroids with mineralocorticoid 
activity; give IV fluids. Consult endocrinologist. If adrenal crisis ruled out, then treat as above for symptomatic 
endocrinopathy. 
* A delay of SNDX-6352 for up to 6 weeks from the day they were scheduled to receive their next dose is acceptable for subjects who are actively receiving 
steroid treatment for the management of immune-related adverse events 


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6.8. 
Intervention after the End of the Study 
No formal open-label extension is planned after the end of the study (12 months of treatment). 
Subjects who are deriving benefit may be allowed to continue at present or reduced dose based 
on Investigator’s discretion and in consultation with the Sponsor. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
It may be necessary for a subject to permanently discontinue study intervention prior to planned 
completion of treatment regimen (see Section 6.7 for dose modification and toxicity 
management). If study intervention is permanently discontinued, the subject will remain in the 
study to be evaluated for up to 90 days post last dose of study intervention. See the Schedule of 
Activities (Section 1.2) for data to be collected at the time of discontinuation of study 
intervention (30 days post last dose of study intervention). 
7.1.1. 
Temporary Discontinuation 
See Section 6.7 for dose modification and toxicity management. 
 
7.2. 
Subject Discontinuation/Withdrawal from the Study 
Subjects have the right to withdraw partially or fully from the study at any time and for any 
reason without prejudice to their future medical care by the physician or at the institution. 
Partial withdrawal of consent means that the subject does not wish to take study intervention any 
longer but is still willing to collaborate in providing further data by continuing on study (e.g., 
participate in all subsequent study visits or procedures or follow-up contact). Full withdrawal of 
consent for a study means that the subject does not wish to receive further investigational 
treatment and does not wish to, or is unable to, continue further study participation. Any subject 
may fully or partially withdraw consent to participate in the study at any time during the study. 
The level of study withdrawal is to be noted in the source documentation. 
In the event of discontinuation of all treatment or full withdrawal from the study, the Investigator 
will complete the End of Treatment form and indicate the date and the appropriate reason. To the 
greatest extent possible, the Investigator will attempt to complete protocol-required all tests and 
evaluations listed for the End of Treatment visit and Safety Follow-up visits. If a subject fails to 
return for the necessary visits, every effort must be made to contact the subject and determine the 
reason(s); this should be recorded on the eCRF. 
Reasons for permanently discontinuing study therapy and/or observation might include: 
• Withdrawal of consent 
• Progressive disease or exacerbation of any of the signs or symptoms of the disease 
assessed by Investigator 
• Administrative decision by the Investigator or Sponsor 
• Pregnancy 
• Significant protocol deviation or subject noncompliance 
• Unacceptable toxicity 


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• A study treatment delay >4 weeks due to AEs 
• Need for intervention or therapy determined by the Investigator to be medically 
necessary that is precluded by protocol. 
• The Investigator believes it is no longer in the subject’s best interest to continue study 
therapy 
In addition, the Sponsor may decide to discontinue the trial prematurely for any reason. 
 
7.3. 
Lost to Follow up 
A subject 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 subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 
• Before a subject is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1 in 
Section 10.1. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing for Phase 1 and Phase 2 are summarized in the 
Phase 1 SoA (Section 1.2). Immediate safety concerns should be discussed with the 
Sponsor immediately upon occurrence or awareness to determine if the subject should 
continue or discontinue study intervention. 
• 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. 
• Procedures conducted as part of the subject’s routine clinical management (e.g., blood 
count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA. 
• The maximum amount of blood collected from each subject over the duration of the 
study (12 treatment cycles), including any extra assessments that may be required, 
will not exceed 200 mL (~14 tablespoons). Repeat or unscheduled samples may be 
taken for safety reasons or for technical issues with the samples. 
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.2). 
 
8.1.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
head, ears, eyes, nose and throat (HEENT), dermatological, respiratory, 
cardiovascular, gastrointestinal, neurological, and lymphatic, and musculoskeletal 
systems. Height will also be measured and recorded. 
• Symptom-directed physical examination will be conducted as clinically indicated. 
• Weight will be measured when complete or symptom-directed physical examinations 
are performed. 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.1.2. 
Neurological Examinations 
A neurological examination will include general appearance, posture and gate, motor activity, 
assessment of mental status, cranial nerves, sensory and neuromuscular function, and reflexes. 


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Investigators will be instructed to counsel subjects not to operate or drive heavy, complex 
machinery until 30 days after the last dose of SNDX-6352. 
 
8.1.3. 
Vital Signs 
• Vital signs, systolic and diastolic blood pressure (mmHg), pulse rate (beats per 
minute), respiration rate (breaths per minute), and temperature (°F or C; oral or 
axillary), will be measured as per standard practice. If initial blood pressure 
measurement is abnormal, repeat blood pressure measurement while the subject is in 
a semi-supine position after resting 5 minutes. 
• The same units and mode should be used for a subject across all measurements. 
8.1.4. 
Electrocardiograms 
• Triplicate 12-lead ECG will be obtained as outlined in the SoA (see Section 1.2 using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, 
QT, and QTc intervals). 
• At each time point at which triplicate ECG are required, 3 individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. The full set of triplicates should be completed in less than 4 minutes. 
• ECGs will be recorded after the subject has rested in a supine position for at least 
10 minutes. 
• If a clinically significant abnormal ECG (Grade 3 or above by CTCAE v5.0) is 
reported, the ECG needs to be reviewed by a cardiologist. 
• An ECG may be repeated anytime, as clinically indicated. 
8.1.5. 
Karnofsky/Lansky Performance Status Scale 
The Karnofsky/Lansky Performance Status allows subjects to be classified as to their functional 
impairment on a scale from 0 to 100. The lower the score, the worse the survival for most serious 
illnesses. The score can be used to compare effectiveness of different therapies and to assess the 
prognosis in individual subjects. The Karnofsky Scale is designed for subjects aged 16 years and 
older, and the Lansky Scale is designed for subjects less than 16 years old (Lansky, et al 1987). 
The Karnofsky scale is widely used validated tool in oncology settings, especially HSCT 
(Crooks, et al 1991; O'Toole and Golden 1991; Schag, et al 1984). 
The Karnofsky/Lansky performance status scales is presented in Table 9. 


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Table 9: 
Karnofsky and Lansky Performance Status 
 
Score Karnofsky (for subjects ≥16 years) 
Lansky (for subjects < 16 years) 
Able to carry on normal activity; no special 
care is needed 
Able to carry on normal activity; no 
special care is needed 
100 
Normal, no complaints, no evidence of disease 
Fully active 
90 
Able to carry on normal activity, minor signs or 
symptoms of disease. 
Minor restriction in physically strenuous 
play 
80 
Normal activity with effort, some signs or 
symptoms of disease 
Restricted in strenuous play, tires more 
easily, otherwise active 
Unable to work, able to live at home, cares for 
most personal needs, a varying amount of 
assistance is needed 
Mild to moderate restriction 
70 
Cares for self, unable to carry on normal activity 
or do active work 
Both greater restrictions of, and less time 
spent in active play 
60 
Requires occasional assistance, but is able to 
care for most of his/her needs 
Ambulatory up to 50% of time, limited 
active play with assistance/supervision 
50 
Requires considerable assistance and frequent 
medical care 
Considerable assistance required for any 
active play, fully able to engage in quiet 
play 
Unable to care for self, requires equivalent of 
institutional or hospital care, disease may be 
progressing rapidly 
Moderate to severe restriction 
40 
Disabled, requires special care and assistance 
Able to initiate quite activities 
30 
Severely disabled, hospitalization indicated; 
Death not imminent 
Needs considerable assistance for quiet 
activity 
20 
Very sick, hospital indicated, death not 
imminent 
Limited to very passive activity initiated by 
others (e.g., TV) 
10 
Moribund, fatal processes progressing rapidly 
Completely disabled, not even passive play 
0 
Death 
Death 
 
8.1.6. 
Clinical Safety Laboratory Assessments 
• See Section 10.2 (Appendix 2) for the list of clinical laboratory tests to be performed 
and see the SoA for the timing and frequency. 
• The Investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study 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 


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underlying disease, unless judged by the Investigator to be more severe than expected 
for the subject's condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 30 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or medical monitor. 
− If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified, and the Sponsor 
notified. 
− All protocol-required laboratory assessments, as defined in Section 10.2 
(Appendix 2), must be conducted in accordance with the laboratory manual and 
the SoA. 
− 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., SAE 
or AE or dose modification), then the results must be recorded in the CRF. 
8.2. 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.2). 
It is preferred that all cGVHD assessments be done by the same health care provider who 
completed the C1D1 assessment. At minimum, the C7D1 assessment should be performed by the 
same health care provider who performed the C1D1 assessment. In addition, any assessments 
leading to changes in cGVHD therapy must be confirmed by the PI or primary treating 
physician. 
8.2.1. 
Response Determination according to 2014 NIH Consensus definitions 
Response evaluation will be an exploratory endpoint in Phase 1 and the primary endpoint in 
Phase 2. Overall physician-assessed responses will be evaluated at C7D1 as defined by the 2014 
NIH Consensus Development Project on Criteria for Clinical trials in cGVHD (Lee, et al 2015). 
CR is defined as resolution of all manifestations in each organ or site, and PR is defined as 
improvement in at least 1 organ or site without progression in any other organ or site. 
Table 10 contains the Working Group proposed consensus definitions of CR, PR and progression 
for assessment of organ specific responses as well as a global response determination. 


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Table 10: 
Response Determination for Chronic GVHD Clinical Studies based on 
Clinician Assessments 
 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin Score 
by 1 or more points 
Increase in NIH Skin Score 
by 1 or more points, except 
0 to 1 
Eyes 
NIH Eye Score 0 after 
previous involvement 
Decrease in NIH Eye Score 
by 1 or more points 
Increase in NIH Eye Score 
by 1 or more points, except 
0 to 1 
Mouth 
NIH Modified OMRS 0 
after previous involvement 
Decrease in NIH Modified 
OMRS of 2 or more points 
Increase in NIH Modified 
OMRS of 2 or more points 
Esophagus 
NIH Esophagus Score 0 
after previous involvement 
Decrease in NIH Esophagus 
Score by 1 or more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 
after previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI 
Score by 1 or more points, 
except 0 to 1 
Lower GI 
NIH Lower GI Score 0 
after previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI 
Score by 1 or more points, 
except from 0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and Total 
bilirubin after previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2 ULN 
Lungs 
Normal %FEV1 after 
previous involvement 
If PFTs not available, NIH 
Lung Symptom Score 0 
after previous involvement 
Increase by 10% predicted 
absolute value of %FEV1 
If PFTs not available, 
decrease in NIH Lung 
Symptom Score by 1 or 
more points 
Decrease by 10% predicted 
absolute value of %FEV1 
If PFTs not available, 
increase in NIH Lung 
Symptom Score by 1 or 
more points, except 0 to 1 
Joints and 
fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 
25 after previous 
involvement by at least 1 
measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in P- 
ROM score by 1 point for 
any site 
Increase in NIH Joint and 
Fascia Score by 1 or more 
points or decrease in P- 
ROM score by 1 point for 
any site 
Global 
Clinician overall severity 
score 0 
Clinician overall severity 
score decreases by 2 or 
more points on a 0-10 scale 
Clinician overall severity 
score increases by 2 or more 
points on a 0-10 scale 
ULN = upper limit of normal. 
Source: (Lee, et al 2015) 


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8.2.2. 
Physician-Reported Global and Organ Specific cGVHD Activity Assessment 
Physician-reported global and organ specific cGVHD activity assessment is an exploratory 
endpoint in Phase 1 and a secondary endpoint in Phase 2. 
Changes in cGVHD severity as defined by the NIH 2014 Consensus Criteria will be evaluated 
using physician reported global and organ specific cGVHD activity assessment form 
(Section 10.5.1). The clinicians will provide a subjective assessment of current overall chronic 
GVHD severity on a 4-point scale (no chronic GVHD, mild, moderate, severe) independent of 
the recorded NIH global severity score (Table 10, last line), and their evaluations of cGVHD 
changes since the last assessment scored on a 7-point scale. Key organ assessments include skin, 
mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia (Jagasia, et al 2015; Lee, 
et al 2015). 
8.2.3. 
Patient-Reported cGVHD Activity Assessment 
Patient-reported cGVHD activity assessment (Section 10.5.2) is an exploratory endpoint in Phase 
1 and a secondary endpoint in Phase 2. 
Changes in patient-reported symptom activity will be evaluated using the cGVHD Lee symptom 
scale (Lee, et al 2002).which has been recommended for use by the 2005 and 2014 National 
Institutes of Health (NIH) Consensus Conferences to capture cGVHD symptoms. 
The Lee cGVHD symptom questionnaire asks subjects to indicate the degree of “bother” that 
they experienced during the past 7 days due to symptoms in 7 domains potentially affected by 
chronic GVHD (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, 
energy, emotional distress) (Lee, et al 2002). Published evidence supports its validity, reliability, 
and sensitivity to cGVHD severity (Lee, et al 2015; Merkel, et al 2016). 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3 (Section 10.3). 
AE will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the subject to discontinue the study intervention and/or the study (see Section 7). 
 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected at the time points specified in the SoA (Section 1.2). 
Table 11 below summarizes the different observation periods for AEs, SAEs, and adverse event 
of special interest (AESI). 


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Table 11: 
Adverse Event Observation Periods 
 
Type of 
Event 
Adverse Event 
Serious Adverse Event 
AESI with study intervention 
Reporting 
period 
From consent 
until 30 days 
after the end of 
treatment 
From consent until 90 days after 
the last dose of study treatment 
for all SAEs, and any time after 
the end of study for SAEs 
believed to be related to study 
intervention 
From consent until 90 days after 
the last dose of study treatment, 
or 30 days after the initiation of a 
new anti-cancer therapy or any 
new therapy for GVHD, 
whichever is earlier 
Reporting 
Timelines to 
the Sponsor 
Entered into the 
clinical 
database on an 
ongoing basis 
Within 24 hours 
Within 24 hours 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the 
eCRF not the AE section. 
The Investigator is responsible for ensuring that all AEs observed by the Investigator or reported 
by subjects are properly captured in the subject’s medical records and reported in the eCRF. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the Investigator must promptly notify the 
Sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in 
Section 10.3.3), will be followed until resolution, stabilization, the event is otherwise explained, 
or the subject is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 3 (Section 10.3). 


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8.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of a SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of subject and the 
safety of a study intervention under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy 
and forwarded to investigators, as necessary. 
• An Investigator who receives an Investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
 
8.3.5. 
Pregnancy 
• Details of all pregnancies in female subjects, and female partners of a male subject, 
will be collected after the start of study intervention and until 90 days after the last 
dose of study intervention. 
• If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4 
(Section 10.4). 
• All female subjects, and female partners of male subjects, becoming pregnant must be 
followed to completion/termination of the pregnancy. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
The following disease related events (DREs) are common in subjects with cGVHD and can be 
serious/life threatening: 
• Disease progression: if disease progression occurs, record the date first documented 
in the EOT visit eCRF. Signs and symptoms related to PD should be reported in the 
appropriate eCRF as an AE or as an SAE if the event in question meets the criteria for 
seriousness. 


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Because these events are typically associated with the disease under study, they will not be 
reported according to the standard process for expedited reporting of SAEs even though the 
event may meet the definition of a SAE. These events will be recorded on the corresponding 
eCRF page in the subject’s CRF within the appropriate time frame. 
In addition, the following will not be considered AEs 
• Worsening of a pre-existing medical condition, (i.e., diabetes, migraine headaches, 
gout) should be considered an AE if there is either an increase in severity, frequency, 
or duration of the condition or an association with significantly worse outcomes. 
• Interventions for pretreatment conditions (i.e., elective cosmetic surgery) or medical 
procedures that were planned before study enrollment are not considered AEs. 
NOTE: However, if either of the following conditions applies, then the event must be recorded 
and reported as an SAE (instead of a DRE): 
• The event is, in the Investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual subject. 
OR 
• The Investigator considers that there is a reasonable possibility that the event was 
related to study intervention. 
 
8.4. 
Treatment of Overdose 
Any overdose or incorrect administration of study intervention should be noted on the 
Study Drug Administration eCRF (including quantity of the excess dose and the duration of the 
overdose). AEs associated with an overdose or incorrect administration of study intervention 
should be recorded on the AE eCRF. 
For this study, a study intervention overdose will be defined as a dose exceeding the dose 
prescribed in the protocol by 20%. No specific information is available on the treatment of 
overdose of SNDX-6352. 
The overdose will not be considered an SAE unless the outcome of the overdose meets 
seriousness criteria. All reports of overdose with and without an adverse experience must be 
reported within 24 hours to one of the individuals listed on the Sponsor contact information page 
found in the Administrative Binder. The subject should be carefully monitored for potential 
adverse reactions and symptomatic treatment instituted as per institutional standards of care. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
 
8.5. 
Pharmacokinetics 
• Whole blood samples of approximately 3.5 mL will be collected for measurement of 
serum concentrations of SNDX-6352 as specified in the SoA (Section 1.2). 
Instructions for the collection and handling of biological samples will be provided by 


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the Sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Samples will be used to evaluate the PK of SNDX-6352. Samples collected for 
analyses of SNDX-6352 serum concentration may also be used to evaluate safety, 
efficacy and/or pharmacodynamic aspects related to concerns or questions arising 
during or after the study. 
• Any genetic analyses performed on these serum samples will be consistent with 
consent given for the skin punch biopsy. Subject confidentiality will be maintained. 
At visits during which blood samples for the determination of PK, ADA and PD 
related to SNDX-6352 will be taken, 1 sample of sufficient volume can be used. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the Sponsor 
and site study files but will not constitute a protocol amendment. The IRB/IEC will be informed 
of any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
8.6. 
Pharmacodynamics and Exploratory endpoints 
 
 
 
 
 
 
• 
 
 
 
• 
 
 
 
 
• 
 
 
• 
 
 
 
 
 
 
 


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8.7. 
Biomarkers 
Collection of samples for other biomarker research is also part of this study. The following blood 
samples for immune correlate analyses biomarker research may be performed and will be 
collected from all subjects in this study as specified in the SoA (Section 1.2): 
• Levels of blood immune parameters that may include CSF-1, IL-34, IFN-gamma, 
IL-1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha, 
and sCD163, CD204/206 and change from baseline compared to PK, safety 
endpoints. 
• Levels of Circulating classical and non-classical monocytes and change from baseline 
compared to PK, safety endpoints. 
• Analysis of numbers of circulating immune cell subsets including CD8+ T cells, 
CD4+ T cells, B cells, natural killer (NK) cells and change from baseline compared to 
PK and safety endpoints. 
Refer to the Study Laboratory Manual for instructions on sample collection and shipment to the 
central laboratories. 
Samples will be tested for SNDX-6352 related activities to evaluate their association with the 
observed clinical responses. 
• In addition, samples will be stored, and analysis may be performed on biomarker 
variants thought to play a role in immune-modulation including, but not limited to, 
emergent candidate genes/genome-wide analysis for RNA, serum analytes, or tissue 
biomarkers to evaluate their association with observed clinical responses to 
SNDX-6352. 
• Refer to the Study Laboratory Manual for instructions on sample collection and 
shipment to the central laboratories. 
Other samples may be used for research to develop methods, assays, prognostics and/or 
companion diagnostics related to immune modulation, disease processes and pathways 
associated with disease state, and/or mechanism of action of SNDX-6352. 
Samples may be stored for a maximum of 10 years (or according to local regulations) following 
the last subject’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses to SNDX-6352. 
8.7.1. 
Immunogenicity Assessments 
Antibodies to SNDX-6352 will be evaluated in serum samples collected from all subjects 
according to the SoA. Additionally, serum samples should also be collected at the final visit from 
subjects who discontinued SNDX-6352 or were withdrawn from the study. These samples will 
be tested by the Sponsor or Sponsor's designee. 


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Serum samples will be screened for antibodies binding to SNDX-6352 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to SNDX-6352 and/or further characterize the immunogenicity of SNDX-6352. 
The detection and characterization of antibodies to SNDX-6352 will be performed using a 
validated assay method by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to SNDX-6352 will also have matching samples evaluated for 
SNDX-6352 serum concentration to enable interpretation of the antibody data. Antibodies may 
be further characterized and/or evaluated for their ability to neutralize the activity of the study 
intervention(s). Samples may be stored for a maximum of 10 years (or according to local 
regulations) following the last subject’s last visit for the study at a facility selected by the 
Sponsor to enable further analysis of immune responses to SNDX-6352. 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
In Phase 1, statistical analyses will be descriptive and graphical in nature and no formal 
hypothesis testing will be performed. 
Assuming a true DLT rate of 5% or less, there would be a 3% chance that dose escalation would 
be halted in a given cohort (i.e., observing 2 or more patients with DLT). If a true DLT rate of 
50% is assumed, then there would be an 83% chance that dose escalation would be halted in a 
given cohort. It is anticipated that approximately 30 evaluable patients will be enrolled. 
 
9.2. 
Sample Size Determination 
Phase 1 Dose Escalation: Up to 30 subjects will be enrolled in this study. 
Phase 2 Dose Expansion: A maximum of 22 subjects will be enrolled. A true ORR of 60% is 
hypothesized. A response rate greater than 30% is considered the lower threshold. The number of 
responders needed to declare the study a success was based on single proportion binomial test 
with 91% power and 1-sided significance level of 5%. Ninety percent 2-sided confidence interval 
of the observed one sample proportion will be calculated. The trial will be considered a success 
if the lower limit of 90% confidence interval is greater than 30%. Eleven responders out of 22 
subjects will provide the lower limit of 90% confidence interval of 31.1% (90% CI [31.1%, 
68.9%]). 


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9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
 
Population 
Description 
Enrolled (intent 
to treat [ITT] set) 
All subjects who sign the ICF and were enrolled into the study. 
Evaluable 
Subjects who have received at least 1 cycle of treatment and have at least 
one post-baseline response assessment. 
Full analysis set 
(FAS) 
The FAS is a subset of all enrolled subjects, with subjects excluded for 
the following reasons: 
• Failure to receive at least one dose of SNDX-6352 
• Lack of baseline data for those analyses that require baseline data 
Safety set 
All subjects who received at least 1 dose of study intervention. 
PK/PD set 
All subjects who received SNDX-6352 and who have evaluable PK /PD 
serum samples available at baseline and during at least 2 cycles of 
treatment. 
For skin biopsy and lung biopsy specimens, subjects with baseline and 
after 2 cycles will be evaluated. 
 
9.4. 
Statistical Analyses 
The statistical analysis plan will be developed and finalized before database lock and will 
describe the subject populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical analyses 
of the primary and secondary endpoints. 
The analysis of safety will be performed on the Safety set while efficacy evaluation will be 
performed on the ITT, FAS, Evaluable set. 
 
9.4.1. 
OBD Analyses: Phase 1 
OBD will be determined after a review of the safety, tolerability, depletion of circulating non- 
classical monocytes and increasing concentrations of circulating CSF-1. The OBD is defined as 
the lowest safe dose with the highest rate of biologic activity. Biologic activity is determined by 
100% reduction of non-classical monocytes at the time of dose interval and plateaued increase of 
circulating CSF-1 levels that persist for an entire dosing level. 
9.4.2. 
Safety Analyses: Phase 1 and Phase 2 
Safety will be assessed by clinical review of all relevant parameters including vital signs 
measurements, Karnofsky/Lansky performance scale, AEs, SAEs, physical and neurological 
examination findings, ECG results, and laboratory values. 


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Summary tables and listings will be provided for all reported treatment-emergent adverse events 
(TEAEs), defined as AEs that start on or after the first administration of study treatment. The 
reported AE term will be assigned a standardized preferred term using the current version of the 
Medical Dictionary for Regulatory Activities (MedDRA). 
Treatment-emergent adverse event will be summarized based on the number and percentage of 
patients experiencing the event by MedDRA system organ class and preferred term. In the event 
a patient experiences repeat episodes of the same AE, then the event with the highest severity 
grade and strongest causal relationship to study treatment will be used for purposes of incidence 
tabulations. 
Tabular summaries will be provided for the following: 
• DLTs 
• All treatment-emergent adverse events 
• Treatment-emergent adverse events by relationship to study drug treatment and 
maximum severity grade 
• Treatment-emergent adverse events with action of study drug treatment 
delayed/interrupted or dose reduced 
• Treatment-emergent adverse events with action of study treatment discontinued 
• SAEs 
• Neurological examination 
• Changes in Karnofsky/Lansky performance status scale 
• Changes in chemistry and hematology parameters 
• Changes in vital signs, weight and ECGs 
The observed DLT rate in each dose cohort will be calculated by the crude proportion of patients 
who experienced DLT with a 2-sided 95% exact binomial CI. 


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9.4.3. 
Efficacy Analyses: Phase 1 and Phase 2 
Table 12: 
Efficacy Endpoints Definition and Statistical Analysis Method (Phase 1 and 
Phase 2) 
 
Definitions and Statistical Analysis Method 
Phase 1 
Phase 2 
The proportion of subjects with CR or PR (ORR) at Cycle 7 Day 1 
(Day 168) is defined by the 2014 NIH Consensus Development Project 
on Criteria for Clinical Trials in cGVHD. 
Exact 95% confidence intervals will be calculated for the true ORR. 
Exploratory 
Primary 
The BOR is defined by the 2104 NIH Consensus Development Project 
on Criteria for Clinical Trials in cGVHD. 
The proportion of subjects with BOR and 95% CI will be calculated 
- 
Secondary 
Organ-specific response rate (CR or PR) will be assessed based on the 
2014 NIH Consensus Development Project on Criteria for Clinical 
Trials in cGVHD 
Exploratory 
Secondary 
Failure free survival (FFS) will be defined as the time from first dose 
of study intervention to unequivocal progression of cGVHD or relapse 
of underlying malignancy or addition of another systemic immune 
suppressive therapy or discontinuation of study treatment due to 
toxicity or death for any reason. 
FFS will be summarized descriptively using the Kaplan-Meier method 
Exploratory 
Secondary 
The DOR is defined as the time of initial response until documented 
progression or start of another systemic treatment. 
DOR will be summarized descriptively using the Kaplan-Meier 
method 
Exploratory 
Secondary 
The SSR of CR/PR ≥20 weeks is defined as rate of CR/PR lasting for 
at least 20 weeks from the time of initial response. 
The proportion of subjects with SRR and 95% confidence intervals 
will be calculated. 
Exploratory 
Secondary 
Changes in subject-reported symptom activity will be assessed using 
the Lee cGVHD Symptom Scale. 
Exploratory 
- 
Changes in subject-reported symptom activity will be assessed using 
the Lee cGVHD Symptom Scale. 
The proportion of subjects with a ≥ 7-point improvement in 
normalized score and 95% CI will be calculated. 
- 
Secondary 
Joints and fascia response based on refined NIH response algorithm for 
cGVHD (Inamoto, et al 2020) 
- 
Secondary 


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9.4.4. 
Other Analyses: Phase 1 and Phase 2 
Pharmacokinetic and other correlative studies will be summarized and displayed graphically. 
Trends in levels will be evaluated from before to Cycle 7 Day 1 (Day 168) after starting study 
intervention. Additional details for PK, PD, and biomarker exploratory analyses will be 
described in the statistical analysis plan finalized before database lock. The population PK 
analysis and pharmacodynamic analyses will be presented separately from the main clinical 
study report (CSR). 
 
Other Endpoints and Statistical Analyses 
Phase 1 
Phase 2 
Percent reduction in average daily dose (or equivalent) or 
discontinuation of corticosteroid use after study entry 
Percent reduction in average daily dose (or equivalent) or 
discontinuation of calcineurin inhibitor use, after study entry 
Exploratory 
Secondary 
 
9.5. 
Interim Analyses 
No formal interim analysis is planned in either Phase 1 or Phase 2. 
Following determination of the OBD and RP2D(s), the SRC will conduct a formal review of PK, 
PD, safety and tolerability assessments. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
−  Applicable ICH Good Clinical Practice (GCP) Guidelines 
−  Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the 
Investigator and reviewed and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study subjects. 
• The Investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
 
10.1.2. 
Informed Consent Process 
• 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 must be informed that their participation is voluntary. Subjects or their 
legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 


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Health Insurance Portability and Accountability Act (HIPAA) 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. 
A subject who is rescreened is not required to sign another ICF if the rescreening occurs within 
(28) days from the previous ICF signature date. 
The ICF will contain a separate section that addresses the use of blood samples for optional 
future research. The Investigator or authorized designee will explain to each subject the 
objectives of the future research. Subjects will be told that they are free to refuse to participate 
and may withdraw their consent at any time and for any reason during the storage period. A 
separate signature will be required to document a subject's agreement to allow any remaining 
specimens to be used for future research. Subjects who decline to participate in this optional 
research will not provide this separate signature. 
 
10.1.3. 
Data Protection 
• Subjects will be assigned a unique identifier by the Sponsor. Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred. 
• The subject must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the Subject. 
• The subject must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
 
10.1.4. 
Safety Review Committee (SRC) 
The SRC, consisting of investigators and Sponsor, will review safety parameters of each cohort 
as specified in the SRC charter. In Phase 1, the SRC will be convened after each dose cohort to 
determine whether the dose should be expanded, escalated or de-escalated. In addition, the SRC 
will recommend the OBD and RP2D(s) for further evaluation as specified in the SRC charter. 
The SRC will continue to meet on an ad hoc basis to evaluate emerging safety data from Phase 2. 


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The SRC may recommend stopping the study if at any time during the study there are 
unacceptable AEs or safety concerns as described in the protocol stopping rules defined in the 
SRC charter. 
For each SRC meeting, pre-specified reports will be provided by the data management group. In 
addition, the SRC Chair will be provided with or have access to periodical safety and efficacy 
reports as specified in the SRC charter. The SRC Chair may share these reports with the SRC or 
convene additional meetings of the SRC at his/her discretion. The SRC Chair may request 
additional safety and efficacy data based on the review of study data. 
Further details regarding data safety monitoring guidelines will be included in the SRC Charter, 
which is the governing document that supersedes this section of the protocol. 
10.1.5. 
Dissemination of Clinical Study Data 
A clinical study report will be developed by the Sponsor at completion of data analysis. This 
report will be a clinical and statistical integrated report, according to the ICH E3 guidelines. 
Sponsor will register the study and post study results regardless of outcome on a publicly 
accessible website in accordance with the applicable laws and regulations. 
10.1.6. 
Data Quality Assurance 
• All subject data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). 
The Investigator is responsible for verifying that data entries are accurate and correct 
by physically or electronically signing the CRF. 
• The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk- 
Based Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
• The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 


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protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator per ICH-GCP and local regulations or 
institutional policies. No records may be destroyed during the retention period 
without the written approval of the Sponsor. No records may be transferred to another 
location or party without written notification to the Sponsor. 
10.1.7. 
Source Documents 
• Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s 
site. 
• Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available. 
• Source documents are original documents, data, and records from which the subject’s 
eCRF data are obtained. These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 
10.1.8. 
Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected 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 subjects by the Investigator 
• Discontinuation of further study intervention development 


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10.1.9. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this 
is foreseen, the Investigator agrees to submit all manuscripts or abstracts to the 
Sponsor before submission. This allows the Sponsor to protect proprietary 
information and to provide comments. 
• 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 International 
Committee of Medical Journal Editors authorship requirements. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 13 will be performed by the local laboratory. 
• In addition to the scheduled assessments (specified in SoA), clinical laboratory 
evaluations may be repeated during the treatment period per the Investigator’s clinical 
judgment. 
• Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5 of the protocol. 
• Laboratory assessments will be done as specified in SoA (Section 1.2). Additional 
laboratory assessments may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
Table 13: 
Protocol-Required Safety Laboratory Assessments 
 
Hematology 
White blood cell count (WBC) with differential 
(Neutrophils, Lymphocytes, Monocytes, 
Eosinophils, Basophils) 
Red blood cell (RBC) 
Hemoglobin 
Hematocrit 
Platelet count 
Coagulation factors, including PT or INR and 
aPTT (Screening only) 
Clinical Chemistriesa 
Alanine Aminotransferase (ALT) 
Aspartate Aminotransferase (AST) 
Alkaline phosphatase 
Gamma-glutamyl transferase (GGT) 
Total bilirubin (fractionated) 
Albumin 
Calcium 
Blood urea nitrogen (BUN) 
Sodium 
Creatinine 
Chloride 
Potassium 
Glucose 
Bicarbonate 
Phosphorus/phosphates 
Lactic dehydrogenase 
Uric acid 
Total protein 
Amylase 
Magnesium (Screening only, unless clinically 
indicated) 
Lipase 
Creatine Kinase 


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Urinalysis 
Basic Urinalysis (dipstick, including macroscopic 
appearance, bilirubin, blood, color, glucose, 
ketones, leukocyte esterase, nitrite, pH, protein, 
specific gravity, urobilinogen; prior to each 
administration of study intervention treatment 
after C1 if clinically indicated). 
Full urinalysis (dipstick plus microscopic 
evaluation) to be performed only at the Screening 
and End of Treatment visits). 
Other Laboratory Assessments 
SNDX-6352 ADA (to be evaluated by central 
laboratory) 
Bone turnover markers (to be evaluated by central 
laboratory): 
• 
Bone alkaline phosphatase (BAP) 
• 
C-terminal telopeptide (CTX) 
Coagulation studies, including PT or INR and 
aPTT 
Human chorionic gonadotropin (hCG) pregnancy 
test (as needed for women of childbearing 
potentialb 
HCV RNAc 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 6.5 (DLT) and Section 6.7 (dose modification). 
b For female subjects of child-bearing potential, a serum pregnancy test is required to be performed during screening 
and within 3 days before the first study intervention dose if the screening pregnancy test is performed more than 3 
days before the first study intervention dose. A serum pregnancy is also required at the end of study. During the 
study, either urine or serum pregnancy tests are performed. Pregnancy testing is to be repeated every 2 cycles (8 
weeks) 
c Polymerase chain reaction is required and must be negative for HCV RNA in subjects positive for HCV antibody 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
 
AE Definition 
• 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment (ICH E6:1.2). 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (i.e., not related to progression of underlying disease). 
• 
Worsening of a pre-existing medical condition, (i.e., diabetes, migraine headaches, gout) should be 
considered an AE if there is either an increase in severity, frequency, or duration of the condition or 
an association with significantly worse outcomes. 
• 
New conditions detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which 
are associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 


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10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
 
A SAE is defined as any untoward medical occurrence that, at any dose: 
1.  Results in death 
2.  Is life-threatening (i.e., places the subject at immediate risk of death) 
The term 'life-threatening' in the definition of 'serious' refers to 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. 
3.  Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
4. Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
5.  Is a congenital anomaly/birth defect 
6. Is an important medical event that although may not result in death, be life-threatening, or require 
hospitalization, may be considered a serious adverse drug experience when, based upon appropriate 
medical judgment, may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
• 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization, or development of drug dependency or drug abuse. 


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10.3.3. 
Definition of Adverse Events of Special Interest (AESI) 
 
Adverse Events of Special Interest for SNDX-6352 are by the Sponsor defined as: 
• 
DLTs 
• 
Infusion-related reactions including hypersensitivity reactions 
• 
irAEs 
• 
Infections 
 
10.3.4. 
Definition of Suspected and Unexpected Adverse Reaction 
 
Suspected adverse reactions are defined as: 
• 
any AE for which there is a reasonable possibility that the study intervention caused the AE. For 
the purposes of Sponsor regulatory safety reporting, “reasonable possibility” means there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
Unexpected Adverse events are defined as: 
• 
AE which is not listed in the reference safety information of the IB of the study intervention or is 
not listed at the specificity or severity that has been observed. 
 
10.3.5. 
Recording and Follow-Up of AE and/or SAE 
 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF/SAE form. 
• 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to the 
Medical Monitor/Syndax in lieu of completion of the AE/SAE CRF/SAE form. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
Medical Monitor/Syndax. In this case, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records before submission. The Investigator 
will attempt to establish a diagnosis of the event based on signs, symptoms, and/or other clinical 
information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be 
documented as the AE/SAE. 


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Assessment of Intensity 
AE severity will be evaluated by the Investigator in accordance with the NCI CTCAE v5.0. For AEs 
that are not adequately addressed in the NCI CTCAE, the Investigator should classify the intensity of 
the AE using the following guidelines: 
• 
Grade 1: Mild: Aware of sign or symptom, but easily tolerated; no intervention needed 
• 
Grade 2: Moderate: Discomfort enough to cause interference with usual activity, minimal non- 
invasive intervention indicated (e.g., short course of antibiotics) 
• 
Grade 3: Severe: Medically significant but not immediately life-threatening; incapacitation 
with inability to work or do usual activity 
• 
Grade 4: Life-threatening: Refers to an event in which the subject was at risk of death at the 
time of the event, as judged by the Investigator; urgent/emergent intervention indicated. This 
category should not be used for an event that hypothetically might have caused death if it were 
more severe. 
• 
Grade 5: Fatal outcome. 
It will be left to the Investigator’s clinical judgment to determine whether an AE is of sufficient 
severity to require the subject’s removal from treatment or from the study. A subject may also 
voluntarily withdraw consent from treatment due to what she/he perceives as an intolerable AE. If 
either of these situations arises, the subject should be strongly encouraged to undergo an end-of-study 
assessment and be under medical supervision until symptoms cease or the condition becomes stable. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
The Investigator must make a judgment regarding whether or not the AE was related to the study drug. 
The Investigator will also review laboratory test results and determine whether an abnormal value in an 
individual subject represents a clinically significant change from baseline and whether or not the 
change is related to study intervention. Guidelines for assessing relationship to study intervention are 
as follows: 
The study intervention relationship will be assessed by means of the question: “Is there a reasonable 
possibility that the event may have been caused by study intervention?” The causal relationship 
between an AE and the study intervention will be determined by the following definitions: 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to study intervention administration and cannot be explained by 
concurrent disease or other drugs or chemicals. The response to withdrawal of the study intervention 
(dechallenge) should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge procedure if necessary. 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study intervention, is unlikely to be attributed to concurrent 
disease or other drugs or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge information is not required to fulfill this definition. 


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Assessment of Causality 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, other factors may have 
contributed to the event (e.g., the participant’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or “definitely related”, as appropriate. 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to study intervention administration makes a causal relationship improbable (e.g., the event 
did not occur within a reasonable time after administration of the study intervention) and in which 
other drugs or chemicals or underlying disease provides plausible explanations (e.g., the participant’s 
clinical condition, other concomitant treatments). 
Not Related - The AE is completely independent of study intervention administration, and/or evidence 
exists that the event is definitely related to another etiology. There must be an alternative, definitive 
etiology documented by the clinician. 
When assessing the relationship between administration of the study drugs and the AE, the following 
should be considered: 
• 
Follows a temporal sequence from administration of investigational product 
• 
Is a known response to the investigational product based on clinical or preclinical data 
• 
Could not be explained by the known characteristics of the subject’s clinical state, 
environmental or toxic factors, or other therapy administered to the subject 
• 
Disappears or decreases upon cessation or reduction of dose of investigational product 
• 
Reappears or worsens when investigational product is reinstated 
The Investigator must continue to follow all AEs until resolution or the Investigator assesses them as 
chronic or stable. This follow-up may extend after the end of the study. The Investigator must promptly 
report to his or her IRB/EC all unanticipated problems involving risks to subjects, per institutional 
requirements. This includes death from any cause and all SAEs reasonably or possibly associated with 
the use of study drug according to IRB/EC procedures. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Medical 
Monitor/Syndax to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
• 
[If a subject dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide Medical Monitor/Syndax with a copy of any post-mortem findings 
including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt of 
the information. 


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10.3.6. 
Reporting of SAEs and AESI 
 
SAE/AESI Reporting to Syndax via email or facsimile 
• 
On discovery, all SAEs and AESI should be immediately reported (latest within 24 hours of 
knowledge of the event) to Syndax by completing the SAE report. AESI, regardless of 
seriousness, are reported via an SAE report form. If the AESI does not meet the criteria for 
seriousness, the form should be completed, but no criteria for seriousness should be checked on 
the SAE form. The completed SAE form and supporting documents should be emailed to: 
 
Please note that this email address is for the reporting of SAE, AESI, and pregnancy information 
only. 
Back-up reporting method: 
• 
Back-up reporting method to Syndax is fax of SAE form to 
 
• 
Contacts for SAE reporting can be found in Investigational Site File 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete 
hysterectomy). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
Women will be considered postmenopausal if they have been amenorrheic for 12 months without 
an alternative medical cause. The following age-specific requirements apply: 
• Women <50 years of age would be considered post-menopausal if they have been 
amenorrheic for 12 months or more following cessation of exogenous hormonal 
treatments and if they have luteinizing hormone and follicle-stimulating hormone 
levels in the post-menopausal range for the institution. 
• Women ≥50 years of age would be considered post-menopausal if they have been 
amenorrheic for 12 months or more following cessation of all exogenous hormonal 
treatments, had radiation-induced menopause with last menses >1 year ago, had 
chemotherapy-induced menopause with last menses >1 year ago. 
Note: Females on hormone replacement therapy (HRT) and whose menopausal status is 
in doubt will be required to use one of the non-estrogen hormonal highly effective 
contraception methods if they wish to continue their HRT during the study. Otherwise, 
they must discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
Other conditions: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternative medical cause other than 
the above (e.g., Mullerian agenesis, androgen insensitivity), Investigator discretion 
should be applied to determining study entry. 


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Note: Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
Contraception Guidance: 
Female subjects of childbearing potential should be informed that taking study intervention may 
involve unknown risks to the fetus (unborn baby) if a pregnancy were to occur during the study. 
Specifically, the study intervention may have adverse effects on a fetus in utero. 
See inclusion criteria 9 in Section 5.1 for study requirements for female and male subjects. 
Subjects with childbearing potential should use highly effective methods of contraception, 
defined as one that results in a low failure rate (i.e., less than 1% per year) when used 
consistently and correctly are described in Table 14. These contraceptive methods must be used 
for at least 90 days after the last dose of study intervention. Subjects must adhere to the 
contraception requirement for the duration of the study and during the follow-up period to 
participate in the study. If there is any question that a subject will not reliably comply with the 
requirements for contraception, that subject should not be entered into the study. 
Note that some contraception methods are not considered highly effective (e.g., male or female 
condom with or without spermicide; female cap, diaphragm, or sponge with or without 
spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal 
contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding 
Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral 
contraceptive pills). 
Table 14: 
Highly Effective methods of contraception (<1% failure rate) 
 
Barrier/Intrauterine methods 
Hormonal Methods 
• 
Copper T intrauterine device 
• 
Levonorgesterel-releasing intrauterine system 
(e.g., Mirena®)a 
• 
Implants: Etonogestrel-releasing implants: 
e.g., Implanon® or Norplan® 
• 
Intravaginal Devices: 
Ethinylestradiol/etonogestrel-releasing 
intravaginal devices: e.g., NuvaRing® 
• 
Injection: Medroxyprogesterone injection: 
e.g., Depo-Provera® 
• 
Combined Pill: Normal and low dose 
combined oral contraceptive pill 
• 
Patch: Norelgestromin/ethinylestradiol- 
releasing transdermal system: e.g., Ortho 
Evra® 
• 
Minipill: Progesterone based oral 
contraceptive pill using desogestrel: 
Cerazette® is currently the only highly 
effective progesterone-based pill 
a This is also considered a hormonal method 


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Collection of Pregnancy Information in female subjects who become pregnant, and female 
partners of male subjects 
• Please refer to the Study Manual for details on the pregnancy reporting procedure and 
associated report form 
• The Investigator will collect pregnancy information on any female subject or partner 
of a male subject who becomes pregnant while participating in this study. Information 
will be recorded on the appropriate form and submitted to the Sponsor within 24 
hours of learning of a subject's pregnancy. 
• The subject will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the subject and the neonate and the 
information will be forwarded to the Sponsor. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE. A spontaneous abortion is always considered to be an SAE and will be reported 
as such. Any post-study pregnancy related SAE considered reasonably related to the 
study intervention by the Investigator will be reported to the Sponsor as described in 
Section 8.3.4. While the Investigator is not obligated to actively seek this information 
in former study subjects, he or she may learn of an SAE through spontaneous 
reporting. 
• Any female subject who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 


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10.5. 
Appendix 5: Rating Scales 
10.5.1. 
Global cGVHD Activity Assessment – Physician Report 
 
 


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Source: (Lee, et al 2015) 


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10.5.2. 
cGVHD Lee Symptom Scale 
 
Source: (Lee, et al 2002) 


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10.6. 
Appendix 6: Abbreviations 
 
Abbreviation Term 
Description 
ADL 
Activity of Daily Living 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALP 
Elevation of Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
BAP 
Bone Alkaline Phosphatase 
BUN 
Blood Urea Nitrogen 
CCL3 
Chemokine (C-C Motif) Ligand 3 
cGVHD 
Graft Vs. Host Disease 
CIOMS 
International Organizations of Medical Sciences 
CK 
Creatine Kinase 
CNI 
Calcineurin Inhibitor 
CR 
Complete Response 
CrCl 
Creatinine Clearance 
CRF 
Case Report Form 
CSF-1 
Colony Stimulating Factor 1 
CSF-1R 
Colony Stimulating Factor 1 Receptor 
CSR 
Clinical Study Report 
CTX 
C-Terminal Telopeptide 
DLT 
Dose Limiting Toxicity 
DOR 
Duration of Response 
DREs 
Following Disease Related Events 
ECP 
Extracorporeal photopheresis 
EDC 
Electronic Data Capture 
FAS 
Full Analyses Set 
FDA 
Food and Drug Administration 


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Abbreviation Term 
Description 
FFS 
Failure Free Survival 
GCP 
Good Clinical Practice 
GGT 
Gamma Glutamyl Transferase 
GLDH 
Glutamate Dehydrogenase 
HBV 
Hepatitis B Virus 
hCG 
Human Chorionic Gonadotropin 
HCV 
Hepatitis C Virus 
HEENT 
Head, Ears, Eyes Nose and Throat 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRT 
Hormonal Replacement Therapy 
HSCT 
Hematopoietic Stem Cell Transplantation 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committees 
IHC 
Evaluated by Immunohistochemistry 
IL 
Interleukin 
INR 
International Normalized Ratio 
irAEs 
Immune-Related Adverse Events 
IRB 
Institutional Review Boards 
ITT 
Intent-to-Treat 
IV 
Intravenous 
kg 
Kilograms 
LFT 
Liver Function Test 
mAb 
Igg4 Monoclonal Antibody 
MABEL 
Minimum Anticipated Biological Effect Level 
MCP1 
Monocyte Chemoattractant Protein 1 
MTD 
Maximum Tolerated Dose 
NIH 
National Institute of Health 
NK 
Natural Killer 


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Abbreviation Term 
Description 
NOAEL 
No Observed Adverse Effect Level 
OBD 
Optimal Biologic Dose, defined as the lowest safe dose with the highest rate 
of biologic activity. Biologic activity is determined by 100% reduction of 
non-classical monocytes at the time of dose interval and plateaued increase of 
circulating CSF-1 levels that persist for an entire dosing level. 
ORR 
Objective Response Rate 
PD 
Pharmacodynamics 
PFT 
Pulmonary Function Test 
PK 
Plasma Pharmacokinetics 
PR 
Partial Response 
PRO 
Patient-Reported Outcome 
RBC 
Red Blood Cell 
SAE 
Serious Adverse Event 
SoA 
Schedule of Activities 
SRC 
Safety Review Committee 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TAMs 
Tumor-Associated Macrophages 
TEAE 
Treatment Emergent Adverse Event 
TGFb 
Transforming Growth Factor B 
ULN 
Upper Limit of Normal 
UVB 
Ultraviolet B 
WBC 
Blood Cell Count 
WOCBP 
Woman of Childbearing Potential 


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10.7. 
Appendix 7: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Prior Amendments 
Amendment 9, 27 December 2020 
Overall Rationale for the Amendment 
Section # and 
Name 
Description of Change 
Brief Rationale 
6.5 Dose Limiting 
Toxicity Criteria 
≥Grade 3 AST/ALT was removed from the 
Q4W bullet under non hematologic toxicity 
DLTsfrom the final bullet in the. 
To remove repetition. 
6.7.1 Guidelines 
for Toxicity 
Management 
≥ Grade 3 CK, amylase or lipase in the 
absence of any clinical symptoms 
management was adjusted to clarify that if 
there is end organ damage axatilimab 
should be discontinued permanently. 
To better clarify toxicity management 
procedures. 
Protocol Amendment 8, 12 June 2020 
Syndax has introduced the following modifications to protocol V8.0; these changes are presented 
in order of importance: 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
3. Objectives and 
Endpoints 
9.4.3 Efficacy 
analyses 
Revised language, reorganized 
objectives/endpoints, and deleted redundancy. 
Added secondary objective for Phase 2 dose 
expansion for joints and fascia response. 
For clarity 
To evaluate effects of SNDX-6352 on 
joints and fascia 
1.1 Synopsis 
4.1 Overall 
Design 
6.1 Study 
Intervention(s) 
Administered 
Updated language to allow evaluation of 
intermediate dose levels and/or alternative 
dosing schedules based on emerging data and 
the evaluation of the safety and tolerability data 
as a whole. 
This language was previously only 
described in Section 4.2 and 6.1. 
Language throughout the protocol was 
updated for consistency. 
1.1 Synopsis 
4.1 Overall 
Design 
5.1 Inclusion 
Criterion #3 
Modified the following sentence to indicate 
that the requirement for prior ibrutinib therapy 
applies to subjects ≥18 years of age: 
“Subjects ≥18 years of age with active cGVHD 
who have erythematous rash involving >25% 
body surface area or a NIH mouth score of >4 
must have received prior ibrutinib therapy.” 
The requirement for prior ibrutinib 
therapy applies to adult subjects 
consistent with the approved Prescribing 
Information for ibrutinib: 
https://www.accessdata.fda.gov/drugsatfd 
a_docs/label/2019/.pdf 


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Section # and 
Name 
Description of Change 
Brief Rationale 
1.2 Schedule of 
Activities (SOA) 
Revised the following rows to reflect the 
dosing schedule for the 3 mg/kg Q4W cohort: 
• Safety Laboratory: added footnote 9 for 
Cycle 1 Day 22 indicating samples are not 
required unless clinically indicated 
• Clarification of health care provider for cGVHD 
assessments (footnote 19) 
• Pharmacokinetics: added a PK sample to be 
drawn on C1D22 (footnote 23) 
• Pharmacodynamics (PD): added a PD 
sample for monocytes to be drawn on 
C1D22 (footnote 26) 
The addition of these footnotes resulted in re- 
numbering of previous footnotes 
Adjustments for the 3 mg/kg Q4W cohort 
due to the monthly dosing schedule 
1.2 SoA 
5.1 Inclusion 
Criteria #5 
8.1.5 Karnofsky/ 
Lansky 
Performance 
Status scale 
5.1 Inclusion 
Criterion #1, 
Diagnostic 
Assessments 
9.4.2 Safety 
Analyses: Phase 1 
and Phase 2 
Added Lansky performance status scale for 
patients under 16 years of age 
Lansky performance score is routinely 
used for patients under the age of 16 
5.1 Inclusion 
Criterion #1, Age 
Revised Inclusion Criterion #1 to allow 
subjects 6 years of age or older at the time of 
signing the informed consent to enter the study. 
The previous inclusion criterion allowed 
subjects 12 years of age or older at the time of 
signing the informed consent to enter the study. 
Expand treatment to younger population 
Lowered the age for eligibility to enter 
the study to 6 years or older. Investigators 
have requested this change based on their 
experience with SNDX-6352 and advice 
has been sought from the FDA. This 
change is supported by the safety and 
pharmacokinetic profile of SNDX-6352 
in this study, in patients with advanced 
cancer, and healthy volunteers. 
5.2 Exclusion 
Criterion #8, 
Prior/ 
Concomitant 
Therapy 
Added the following to Exclusion Criterion #8: 
“For approved or commonly used agents, a 
washout of 2 weeks or 5 half-lives, whichever 
is shorter, is required at study enrollment.” 
For clarity 


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Section # and 
Name 
Description of Change 
Brief Rationale 
6.4 Study 
Intervention 
Compliance 
Clarified observation period for potential 
infusion. 
For clarity 
6.5 Dose Limiting 
Toxicity Criteria, 
Non-hematologic 
toxicities 
Added the following statement: 
• “For Q4W dosing only, any asymptomatic 
≥Grade 3 AST, ALT, lipase, or amylase 
that lasts for ≥4 weeks.” 
Safety measure 
6.5 Dose Limiting 
Toxicity Criteria 
Removed the last sentence (shown below) 
because specific instructions for holding doses 
of SNDX-6352 are provided in Section 6.7, 
Dose Modification: 
“If the dose is held due to toxicity for more 
than 4 consecutive weeks, permanently 
discontinue study intervention.” 
To remove redundancy 
6.6.1 Prohibited 
Medications 
Clarified that only 1 systemic corticosteroid is 
allowed. 
For clarity 
6.7.1.1 AST, 
ALT, Bilirubin, 
CK and Amylase 
and Lipase 
2.3 Benefit/ Risk 
Assessment 
Added toxicity management guidelines for 
amylase and lipase. 
Safety measure 
6.7.1.5 Immune- 
related Adverse 
Events for 
SNDX-6352 
Added the following footnote to Table 7: 
“*A delay of SNDX-6352 for up to 6 weeks 
from the day they were scheduled to receive 
their next dose is acceptable for subjects who 
are actively receiving steroid treatment for the 
management of immune-related adverse 
events.” 
Extended the length of time a patient 
could be off SNDX-6352 to allow for 
administration and tapering of steroids to 
manage immune-related adverse events 
10.3.6 Reporting 
of SAEs 
Corrected the instructions for sending SAE 
reports. SAE reports are to be sent to Syndax, 
rather than to PPD. The email address for 
submitting SAE reports remains the same: 
 
Added instructions for reporting AESI. 
Corrections and clarifications 
General 
Ensured consistency and accuracy throughout 
the protocol, including correcting typographical 
errors, acronym definitions, formatting and 
style, as well as alignment across documents. 
Administrative 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Title Page 
Protocol 
Amendment 
Summary of 
Changes (SOC) 
Table 
10.7 Appendix 7: 
Protocol 
Amendment 
History 
Updated to identify the new Protocol Version 
number (8), Amendment number (8) and date 
(12 June 2020). 
Added a row for the Compound Name, 
axatilimab. 
Added the SOC for Protocol Amendment 8 and 
moved the SOC for Amendment 7 to Section 
10.7. 
Administrative 


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Amendment 7, 19 December 2019 
Syndax has introduced the following modifications to protocol V7.0, these changes are presented 
in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page 
1.1 Synopsis 
2.1 Study Rationale 
2.3 Benefit/Risk 
Assessment 
3.0 Objectives and 
Endpoints 
4.0 Study Design 
4.1 Study Design 
4.2 Rationale for Study 
Design 
4.3 Justification for Dose 
4.4 End of Study Definition 
5.0 Study Population 
5.1 Inclusion Criteria 
5.2 Exclusion Criteria 
8.0 Study Assessments and 
Procedures 
8.2 Efficacy Assessments 
8.6 Pharmacodynamics and 
Exploratory endpoints 
9.0 Statistical 
Considerations 
9.1 Statistical Hypotheses 
9.2 Sample Size 
Determination 
9.3 Populations for 
Analyses 
9.4 Statistical Analyses 
10.0 Supporting 
Documentation and 
Operational Considerations 
Updated language to include a Phase 2, Dose 
Expansion portion to the study. Up to 22 
subjects will be enrolled per cohort. 
PK, PD, clinical response and 
safety data from the Phase 1 
indicate that 1 mg/kg of SNDX- 
6352 is biologically active, 
induces organ specific responses 
and improves symptoms with no 
significant adverse events. Given 
this, the Phase 2 expansion 
portion of the study will be used 
to evaluate the preliminary 
efficacy of SNDX-6352 at 
1 mg/kg. 


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Section # and Name 
Description of Change 
Brief Rationale 
3.0 Objectives and 
Endpoints 
Updated language to include Phase 2 
Expansion primary and secondary objectives 
and endpoints 
PK, PD, clinical response and 
safety data indicate that 1 mg/kg 
of SNDX-6352 is biologically 
active, induces organ specific 
responses and improves 
symptoms with no significant 
adverse events. Given this, the 
Phase 2 expansion portion of 
the study will be used to 
evaluate the preliminary efficacy 
of SNDX-6352 at 1 mg/kg. 
4.0 Study Design 
Number of Subjects 
Update language to include up to 22 patients 
in Phase 2 dose expansion portion of the 
study. 
PK, PD, clinical response and 
safety data indicate that 1 mg/kg 
of SNDX-6352 is biologically 
active, induces organ specific 
responses and improves 
symptoms with no significant 
adverse events. Given this, the 
Phase 2 expansion portion of 
the study will be used to 
evaluate the preliminary efficacy 
of SNDX-6352 at 1 mg/kg. 
3.0 Objectives and 
Endpoints 
Phase 1 Dose Escalation: update language to 
include evaluation of reduction in calcineurin 
inhibitor use. 
Standard treatment for cGVHD 
includes both calcineurin 
inhibitors and corticosteroids 
1.2 Schedule of 
Assessments 
4.0 Study Design 
Update language to modify windows for 
response assessments from ±10 days for each 
response assessment to ±1 day for Cycle 1 
and ±3 days for each subsequent cycle. 
Shorten window for response 
assessment 
1.2 Schedule of 
Assessments 
8.2 Efficacy Assessments 
Updated language to specify that it is 
preferred that all cGVHD assessments be 
done by the same health care provider who 
completed the C1D1 assessment. At 
minimum, the C7D1 assessment should be 
performed by the same health care provider 
who performed the C1D1 assessment. In 
addition, any assessments leading to changes 
in cGVHD therapy must be confirmed by the 
PI or primary treating physician. 
To reduce inter-operator bias in 
cGVHD assessments 
1.2 Schedule of 
Assessments 
4.0 Study Design 
Clarified language to specify that after 6 
cycles of biweekly treatment, in subjects 
without cGVHD progression, the study 
intervention may be administered either 
Q2W or Q4W, at the Investigator’s 
discretion in discussion with the Sponsor 
Clarification to language 


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Section # and Name 
Description of Change 
Brief Rationale 
8.2.1 Response 
Determination according to 
2014 NIH Consensus 
definitions 
Updated language to specify dates for 
physician-assessed responses (C7D1). 
Clarification to language 
9.3 Populations for 
Analyses 
Added language to define evaluable 
populations as subjects who have received at 
least 1 cycle of treatment and have at least 
one evaluable response. 
Added additional population for 
analyses 
Title Page 
Protocol Amendment 
Summary of Changes 
(SOC) 
10.7 Protocol Amendment 
History 
Updated to identify the new Protocol Version 
number (7), Amendment number (7) and date 
(16 December 2019) 
Added the SOC for Protocol Amendment 7 
and moved the SOC for Amendment 6 to 
Section 10.7 
Administrative 
 
Amendment 6, 29 August 2019 
Syndax has introduced the following modifications to protocol V6.0, these changes are presented 
in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
5.1 Inclusion criteria 
Modified inclusion criterion #3 to indicate 
prior ibrutinib is required only for subjects 
with active cGVHD who have erythematous 
rash involving >25% body surface area or a 
NIH mouth score of >4. 
Investigators are reluctant to 
prescribe ibrutinib to subjects 
with cGVHD due to the organ 
system involvement of the 
patients that participated in the 
ibrutinib clinical development 
program. The ibrutinib pivotal 
trial required that patients have 
>25% body surface area 
erythematous rash or an NIH 
mouth score of >4 (Miklos, 
2017). The change in Inclusion 
criterion #3 matches the 
requirement in the ibrutinib 
pivotal study. 
Title Page 
1.1 Synopsis 
2.1 Study Rationale 
4.1 Overall Design 
Updated language to reflect the change in 
Inclusion criterion #3. Revised the Title to 
remove the requirement for prior ibrutinib 
therapy for all subjects. 
Revised wording to reflect the 
change in Inclusion criterion #3. 


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Section # and Name 
Description of Change 
Brief Rationale 
Title Page 
Protocol Amendment 
Summary of Changes 
(SOC) 
10.7 Protocol Amendment 
History 
Updated to identify the new Protocol Version 
number (6), Amendment number (6) and date 
(29 August 2019) 
Added the SOC for Protocol Amendment 6 
and moved the SOC for Amendment 5 to 
Section 10.7 
Corrected the year for Amendment 5 from 18 
Dec 2019 to 18 Dec 2018 
Administrative 
 
Amendment 5, 23 July 2019 
Syndax has introduced the following modifications to protocol V5.0, these changes are presented 
in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
5.1 Inclusion criteria 
Modify inclusion criteria 1 language 
Change eligibility age 
requirement from 18 years to 12 
years of age 
1.1 Synopsis 
4.1 Overall Design 
Update language for clarification 
Clarify that after 6 months of 
biweekly treatment, in subjects 
without cGVHD progression, the 
study intervention may be 
administered every 4 weeks until 
Month 12 at the Investigator’s 
discretion in discussion with the 
Sponsor. 
 
Amendment 4, 18 December2018 
Syndax has introduced the following modifications to protocol V4.0, these changes are presented 
in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global change impacting 
4.1 Overall Design 
8.6 Pharmacodynamics and 
Exploratory endpoints 
9.4.1 OBD Analyses 
10.6 Appendix 6: 
Abbreviations 
Update in definition of optimal biologic dose 
and biologic activity 
To clarify OBD definition 


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Section # and Name 
Description of Change 
Brief Rationale 
5.2 Exclusion criteria 
6.6.1 Prohibited 
Medications 
Modify inclusion criteria 8 regarding 
allowed/prohibited medication and updated 
relevant sections 
Per the request of the 
investigators, allowing prior use 
of a corticosteroid and calcineurin 
inhibitor for chronic GVHD to 
align with standard of care 
landscape. 
9.4 Statistical Analyses 
• 
Update tabular summaries to be 
provided for safety 
• 
Update exploratory analysis (reorder 
and clarify definition) 
• 
To include additional 
variables analyzed in tabular 
summaries (data output, 
TFLs) 
• 
To align with exploratory 
objectives/endpoints 
Section 3 
Objectives/Endpoints 
• 
Update safety objective/endpoints 
• 
Update and reorder exploratory 
objectives/endpoints 
To reflect changes in statistical 
section 
9.3 Populations for 
Analyses 
9.4 Statistical analysis 
Add Full analysis set (FAS) and define 
which analyses will be done on FAS. 
To include a subset of enrolled 
set who received at least 1 dose 
of SNDX-6352 and have required 
baseline data for certain analyses 
1.2 Schedule of Activities 
• 
Update 
• 
Add clarification footnote regarding 
pulmonary function test predose on 
Cycle 1 Day 1 
To reflect changes in the protocol 
and follow standard practice 
5.1 inclusion criteria 
Modify inclusion criteria 3 language 
Language clarification 
8.2 Efficacy assessment 
PRO corrected to exploratory 
To align with objective/endpoints 
and statistical section 
8.3.1 Time Period and 
Frequency for Collecting 
AE and SAE Information 
Update reporting period for AESI with study 
intervention 
To clarify when the reporting 
period for AESI ends 
8.3.5 Pregnancy 
Appendix 4 Contraceptive 
Guidance and Collection of 
Pregnancy Information 
• 
Specify for whom pregnancy data will 
be collected 
• 
Update reporting period 
• 
To include female partners 
of male subjects 
• 
To align with SAE and 
AESI reporting periods 
Appendix 3 AE Definitions 
and Reporting 
Change in CRO to PPD and update reporting 
of SAEs per revised processes 
Administrative change 
Global change 
Update glossary 
Minor editing, clarifications, typos, style 
To reflect changes in protocol 
To ensure consistency and 
alignment across document 


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Amendment 3, 11 July 2018 
Syndax has introduced the following modifications to protocol V3.0, these changes are presented 
in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1 Overall 
Design 
Add a dose escalation decision tree figure 
To facilitate understanding of 
dose escalation 
process/decision tree 
Signature Page 
Update sponsor signatory details 
Due to personnel changes 
Global 
Minor style and alignment/consistency 
changes, correction of typos, update 
hyperlinks 
Minors therefore have not been 
summarized 
 
Amendment 2, 21 June 2018 
Syndax has introduced the following modifications to protocol V2 based on feedback received 
from the US FDA on June 20, 2018, these changes are presented in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global change 
impacting 
Title page 
1 Protocol Summary 
2 Introduction 
3. Objectives/Endpoints 
4 Study design 
6 Study Intervention 
8 Study Assessments 
9 Statistical 
consideration 
Removal of dose expansion part 
Per FDA, the dose expansion 
part will be submitted as an 
amendment to this protocol 
after the OBD is established. 
7.3 Stopping Rules 
Removed study stopping rules based on toxicity for 
dose expansion part 
There are built-in stopping 
rules in the 3+3 dose escalation 
design. 
3. Objectives/Endpoints 
Reorganize objectives and endpoints; moved 
efficacy objective/endpoints to be exploratory. Add 
pharmacodynamic and other exploratory endpoints 
for dose escalation. 
Organization of objectives and 
endpoints to match the revised 
study design 
1.1 Synopsis 
9 Statistical 
consideration 
Statistical hypothesis, sample size and analyses 
were updated to align with change in study design 
and objectives/endpoints 
Change in study design 
triggered changes to statistical 
consideration section 


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Section # and Name 
Description of Change 
Brief Rationale 
6.5 DLT Criteria 
Clarified DLT assessment window to be 28 days 
from initiation of treatment with SNDX-6352 or 
administration of third dose (C2D1), whichever is 
later and updated DLT section: 
• 
add ≥ Grade 3 ALT/AST elevation 
• 
removed exception for suspected liver 
cGVHD at baseline (anything less than a 
three-fold or greater increase in ALT or 
AST over baseline will not be considered 
a DLT unless assessed and reviewed 
between Investigator and Sponsor medical 
monitor) 
• 
Revised “toxicity resulting in.” 
• 
Added any adverse event requiring 
treatment discontinuation or delay ≥ 14 
days is a DLT (regardless of CTCAE 
grade 
• 
Per FDA, allowing 3-fold 
increases in AST/ALT for 
patients with baseline 
liver GVHD may result in 
a level that falls in the 
middle of Grade 3 
elevations (i.e. 9 x ULN). 
Patients with baseline 
liver GVHD are already at 
greater risk for liver 
toxicity, and higher levels 
of hepatotoxicity after 
treatment with study drug 
should not be tolerated 
• 
Added per FDA request 
as patients who require a 
delay in therapy of ≥ 2 
weeks for any grade 
toxicity should be 
considered to have had a 
dose-limiting toxicity 
4.1 Overall study design 
Revised dose escalation text 
To facilitate understanding of 
dose escalation 
process/decision tree 
5.2 Exclusion criteria 
Modified exclusion criterion 8 
To reflect change in study 
design 
8 Study Assessments 
Reorganize order of study assessment 
To reflect change in study 
design 
10.1.4 Safety Review 
Committee 
Clarify SRC role in the study 
To reflect change in study 
design 
Global 
Minor style and alignment/consistency changes, 
correction of typos, update hyperlinks 
Minors therefore have not been 
summarized 
 
Amendment 1, 18 June 2018 
Syndax has introduced the following modifications to protocol v2 based on feedback received 
from the US FDA on June 14, 2018, these changes are presented in order of importance: 
 
Section # and Name 
Description of Change 
Brief Rationale 
Title 
1.1 Synopsis 
4.1 Overall design 
4.2 Rationale for Study 
Design 
Modified study population to only include 
subjects with active GVHD who have failed at 
least 2 prior lines of therapy, including ibrutinib. 
Per FDA, ibrutinib is approved as 
standard of care for second line 
therapy. 


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Section # and Name 
Description of Change 
Brief Rationale 
5.1 Study Inclusion 
1.1 Synopsis 
3.1 Dose Finding Part 
Modified primary objective/endpoint to be based 
on optimal biologic dose (OBD). 
Per FDA, OBD is an appropriate 
objective/endpoint for this study. 
1.1 Synopsis 
4.1 Overall design 
9.5 Interim analysis 
Added gating rules before starting the Dose 
Expansion part, including definition of OBD, 
recommended dose, and data review by Safety 
Review Committee (SRC) 
Per FDA, precautionary steps 
were added prior to initiating the 
Dose Expansion part. 
7.3 Stopping Rules 
Added study stopping rules based on toxicity 
Per FDA, stopping rules based on 
toxicity were added as safety 
measures. 
1.2 Synopsis 
9.1 Statistical 
hypothesis 
9.2 Sample size 
determination 
Statistical hypothesis and sample size in Dose 
Expansion were updated to align with change in 
subject population 
Change in study population, 
triggered changes to statistical 
hypothesis and sample size 
determination 
6.5 DLT Criteria 
Updated DLT section to include: 
• 
all events meeting criteria (regardless of 
relationship to SNDX-6352), 
• 
revised exception for asymptomatic Grade 
≥2 AST to Grade 2 AST 
• 
revised exception for suspected liver 
cGVHD at baseline (anything less than a 
three-fold or greater increase in ALT or 
AST over baseline will not be considered a 
DLT unless assessed and reviewed between 
Investigator and Sponsor medical monitor) 
• 
removed exception for AST/ALT elevations 
attributed to concurrent drugs 
• 
a clarification of exception to Grade 3 
electrolyte abnormalities 
• 
Grade ≥ 3 periorbital edema and 
• 
a clarification that the 6-week time frame 
for subjects who received <70% of planned 
dose 
• 
Per FDA, all AEs should be 
considered relevant to 
determining dose 
• 
Clarified and revised per 
FDA request 
• 
Added per FDA request and 
previous clinical data; 
periorbital edema is a 
known class effect 
• 
Aim to have subjects 
receive 3 doses; 6-week 
time frame accounts for 
potential dose 
administration delays 
6.7.1 Guideline for 
toxicity management 
• 
Removed ‘at least possible due to SNDX- 
6352’ for all toxicities, 
• 
Removed investigator attribution of at least 
possibly related to SNDX-6352 
• 
Clarified that for Grade 3 toxicity, subjects 
who recover will resume study intervention 
at next lower dose level, 
• 
Clarified that prophylaxis measures for 
infusion related will be standardized 
Per FDA request, a conservative 
approach is adopted with clear 
instructions to investigators to 
ensure standardization 


Product: SNDX-6352 
Protocol Number: SNDX-6352-0503 
Date: 12 April 2022, Version 10.0 
Page 106 of 108 
CONFIDENTIAL 
SYNDAX PHARMACEUTICALS 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
4.1 Overall design 
Dose escalation rules for first 2 cohorts was 
updated to reflect 3+3 design if subject 
experience any Grade 2 AE 
Per FDA, toxicity rule was added 
2.3 Benefit/Risk 
assessment 
Added concluding remarks 
To further justify study conduct. 
1.2 SoA 
8.2.2 Neurological 
exam 
Added neurological examination at screening, day 
1 of each cycle and each follow-up visit and 
added cautionary statement about 
operation/driving heavy complex machinery. 
Per FDA, added as a safety 
measure because CSF-1R is 
expressed in the brain and healthy 
participants who received SNDX- 
6352 experienced higher rates of 
CNS disorders 
6.6.1 Prohibited 
Medication 
Revised text to allow only steroids at the time of 
enrollment; any other immune suppressive agents 
for treatment of chronic GVHD are not permitted. 
Revised to account for change 
patient population 
Global 
Minor style and consistency changes, correction 
of typos 


Product: SNDX-6352 
Protocol Number: SNDX-6352-0503 
Date: 12 April 2022, Version 10.0 
Page 107 of 108 
CONFIDENTIAL 
SYNDAX PHARMACEUTICALS 
 
 
 
11. 
REFERENCES 
Alexander KA, Flynn R, Lineburg KE, et al. CSF-1-dependant donor-derived macrophages 
mediate chronic graft-versus-host disease. J Clin Invest. 2014;124(10):4266-4280. 
 
Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D. Colony-stimulating factor 
1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):53. 
 
Crooks V, Waller S, Smith T, Hahn TJ. The use of the Karnofsky Performance Scale in 
determining outcomes and risk in geriatric outpatients. J Gerontol. 1991;46(4):M139-144. 
 
Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 
2015;125(4):606-615. 
 
Inamoto Y, Lee SJ, Onstad LE, et al. Refined National Institutes of Health response algorithm 
for chronic graft-versus-host disease in joints and fascia. Blood Adv. 2020;4(1):40-46. 
 
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development 
Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 
Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389- 
401 e381. 
 
Jaki T, Clive S, Weir CJ. Principles of dose finding studies in cancer: a comparison of trial 
designs. Cancer Chemother Pharmacol. 2013;71(5):1107-1114. 
 
Lansky SB, List MA, Lansky LL, Ritter-Sterr C, Miller DR. The measurement of performance in 
childhood cancer patients. Cancer. 1987;60(7):1651-1656. 
 
Lee S, Cook EF, Soiffer R, Antin JH. Development and validation of a scale to measure 
symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(8):444- 
452. 
 
Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host 
disease. National Institutes of Health consensus development project on criteria for clinical trials 
in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol 
Blood Marrow Transplant. 2015;21(6):984-999. 
 
MacDonald KP, Hill GR, Blazar BR. Chronic graft-versus-host disease: biological insights from 
preclinical and clinical studies. Blood. 2017;129(1):13-21. 
 
Merkel EC, Mitchell SA, Lee SJ. Content Validity of the Lee Chronic Graft-versus-Host Disease 
Symptom Scale as Assessed by Cognitive Interviews. Biol Blood Marrow Transplant. 
2016;22(4):752-758. 


Product: SNDX-6352 
Protocol Number: SNDX-6352-0503 
Date: 12 April 2022, Version 10.0 
Page 108 of 108 
CONFIDENTIAL 
SYNDAX PHARMACEUTICALS 
 
 
 
Miklos D, Cutler CS, Arora M, et al. Ibrutinib for chronic graft-versus-host disease after failure 
of prior therapy. Blood. 2017;130(21):2243-2250. 
 
O'Toole DM, Golden AM. Evaluating cancer patients for rehabilitation potential. West J Med. 
1991;155(4):384-387. 
 
Quail DF, Joyce JA. Molecular Pathways: Deciphering Mechanisms of Resistance to 
Macrophage-Targeted Therapies. Clin Cancer Res. 2017;23(4):876-884. 
 
Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, 
and guidelines. J Clin Oncol. 1984;2(3):187-193. 


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SAP_001.pdf: 
A Phase 1/2, Open-Label, Dose Escalation and Dose Expansion Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic 
Activity and Efficacy of SNDX- 6352 in Subjects with Active Chronic Graft 
Versus Host Disease who have Received at least 2 Lines of Prior Therapy 
SNDX-6352-0503 
Syndax Pharmaceuticals 
STATISTICAL ANALYSIS PLAN 
SAP Version: 
Date of Statistical Analysis Plan: 
Version 2.0 
04 January 2023 
NCT #: NCT03604692


Syndax Pharmaceuticals Inc. 
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Page 2 of 40 
 
 
 
 
 
SIGNATURE PAGE 
 
 
 
 
 
Electronically signed by: 
 
Reason: I am the author. 
Date: Jan 5, 2023 10:30 EST 
 
Date 
Prepared by: 
 
, Syndax 
 
 
 
 
Electronically signed by:
 
Reason: I am an approve
Date: Jan 5, 2023 08:44 EST 
Date 
Reviewed and Approved by: 
 
 Syndax 
 
 
 
 
 
Electronically signed by: 
 
Reason: I am an approve
Date: Jan 5, 2023 08:40 EST 
Date 
Reviewed and Approved by: 
 
, Syndax 


Syndax Pharmaceuticals Inc. 
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SAP Version 2.0: 04 January 2023 
Page 3 of 40 
REVISION HISTORY 
Version/Date 
Section 
Changes implemented 
Final 1.0/01Mar2022 
Not Applicable 
Not Applicable 
Final 2.0/04Jan2023 
Section 3.3.1 
Updated with additional summary on 
patients who started axatilimab taper 
Section 3.2.7 
Clarified the application of Analysis 
Sets on tables and figures 
Section 3.6 
Updated to reflect the taper dosing 
schedule 
Section 3.7 
Added definition for time to response 
Section 3.8.4 
Tabular summary of abnormal and 
normal findings of ECG was removed 
as listing will be sufficient 
Section 3.8.5 
Additional details on ADA analysis 
were added to be consistent with other 
studies in the program 
Section 3.9 
Additional details on PK analysis were 
added 
Appendix 6.2, 6.3 
Removed Appendix 6.2 and 6.3 as 
CTCAE v5.0 will be used as reference 


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Table of Contents 
REVISION HISTORY 
3 
1. 
INTRODUCTION 
10 
2. 
STUDY SUMMARY 
10 
2.1 
STUDY OBJECTIVES ................................................................................. 10 
Study objectives are summarized in protocol Section 3. ..................................... 10 
2.2 
STUDY ENDPOINTS .................................................................................. 10 
2.2.1 Primary Endpoint of Phase 1 ................................................................... 10 
2.2.2 Secondary Endpoints of Phase 1 .............................................................. 10 
2.2.3 Exploratory and Pharmacodynamic Endpoints of Phase 1 ...................... 11 
2.2.4 Primary Endpoint of Phase 2 Expansion ................................................. 12 
2.2.5 Secondary Endpoints of Phase 2 Expansion ............................................ 12 
2.2.6 Exploratory and Pharmacodynamic Endpoints of Phase 2 ...................... 13 
2.3 
STUDY DESIGN .......................................................................................... 13 
2.3.1 Number of Subjects and Sample Size Considerations ............................. 13 
2.3.2 Efficacy Assessments ............................................................................... 14 
2.3.3 Pharmacokinetic Assessments ................................................................. 16 
2.3.4 Pharmacodynamics and Exploratory Endpoints ...................................... 16 
2.3.5 Biomarkers ............................................................................................... 17 
2.3.6 Safety Assessments .................................................................................. 17 
2.3.7 Other Assessments ................................................................................... 17 
3. 
STATISTICAL METHODS 
18 


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3.1 
General Methods ........................................................................................... 18 
3.1.1 Computing Environment .......................................................................... 18 
3.1.2 Reporting of Numerical Values ............................................................... 18 
3.1.3 Baseline Value and Change from Baseline .............................................. 18 
3.1.4 Handling of Missing/Incomplete Values ................................................. 19 
3.2 
Analysis Sets ................................................................................................. 20 
3.2.1 Enrolled (Intent-to-treat) Set .................................................................... 20 
3.2.2 Full Analysis Set ...................................................................................... 20 
3.2.3 Evaluable Analysis Set ............................................................................ 20 
3.2.4 Safety Analysis Set .................................................................................. 20 
3.2.5 Pharmacokinetic Analysis Set .................................................................. 21 
3.2.6 Pharmacodynamic Analysis Set ............................................................... 21 
3.2.7 Applications of Analysis Sets .................................................................. 21 
3.3 
Disposition and Evaluability ......................................................................... 22 
3.3.1 Disposition ............................................................................................... 22 
3.3.2 Protocol Deviations .................................................................................. 22 
3.4 
Demographics and Baseline Characteristics ................................................. 22 
3.4.1 Demographics .......................................................................................... 22 
3.4.2 Baseline Disease Characteristics .............................................................. 22 
3.4.3 Medical History, Prior Medications, and Physical Exam ........................ 23 
3.5 
Concomitant Medications ............................................................................. 23 
3.6 
Treatment Exposure ...................................................................................... 23 


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3.7 
Efficacy Analysis .......................................................................................... 24 
3.8 
Safety Analysis .............................................................................................. 27 
3.8.1 Adverse Events ........................................................................................ 27 
3.8.2 Laboratory Evaluations ............................................................................ 29 
3.8.3 Vital Signs ............................................................................................... 29 
3.8.4 ECG ......................................................................................................... 29 
3.8.5 ADA ......................................................................................................... 29 
3.9 
Pharmacokinetic Analysis ............................................................................. 30 
3.10 Pharmacodynamic and Biomarker Analyses ................................................. 31 
4. 
CHANGES FROM PROTOCOL 
32 
5. 
REFERENCES 32 
6. 
Appendix 
33 
6.1 
Laboratory Test Groupings and Standard Normal Range ............................. 38 


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LIST OF ABBREVIATIONS 
 
Abbreviation Term 
Description 
AE 
Adverse Event 
ADA 
Antidrug Antibody 
ADaM 
Analysis Dataset Model 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Transaminase 
 
AUC0-inf 
Area under the Plasma Concentration-Time Curve 
from Time 0 Extrapolated to Infinity 
 
AUC0-t 
Area under the Plasma Concentration-Time Curve 
from Time zero to the Last Measurable Concentration 
BAP 
Bone Alkaline Phosphatase 
BMI 
Body Mass Index 
BQL 
Below the Quantifiable Limit 
BUN 
Blood Urea Nitrogen 
cGVHD 
Chronic Graft vs. Host Disease 
CI 
Confidence Interval 
CIOMS 
Internationals Organizations of Medical Sciences 
Cmax 
Maximum Plasma Concentration 
CR 
Complete Response 
DLT 
Dose-Limiting Toxicity 
DOR 
Duration of Response 
ECG 
Electrocardiogram 


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Abbreviation Term 
Description 
eCRF 
electronic case report form 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
FFS 
Failure Free Survival 
HCT 
Hematocrit 
HGB 
Hemoglobin 
HR 
Hazard Ratio 
irAEs 
Immune-Related Adverse Events 
ITT 
Intent-to-Treat 
IV 
Intravenous 
Kg 
Kilograms 
LDH 
Lactate Dehydrogenase 
LFT 
Liver Function Test 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Magnesium 
MTD 
Maximum-Tolerated Dose 
 
NCI-CTCAE 
National Cancer Institute Common Terminology 
Criteria for Adverse Events 
NK 
Natural Killer 
OBD 
Optimal Biologic Dose 
ORR 
Overall Response Rate 
PK 
Pharmacokinetic 
PR 
Partial Response 


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Abbreviation Term 
Description 
PT 
Preferred Term 
PT/INR 
Prothrombin Time or International Normalized Ratio 
RBC 
Red Blood Cell 
RP2D 
Recommended Phase 2 Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
t1/2 
Elimination Half-Life 
TEAE 
Treatment-Emergent Adverse Event 
 
Tmax 
Time at which Maximum Plasma Concentration was 
Observed 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
WHO 
World Health Organization 
λz 
Terminal Elimination Rate Constant 


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1. 
INTRODUCTION 
Clinical Trial SNDX-6352-0503 is an open-label Phase 1/2 dose escalation and dose 
expansion study to evaluate the safety, tolerability, pharmacokinetics (PK) and 
pharmacodynamics (PD), and efficacy of SNDX-6352 in subjects with active chronic 
Graft versus Host Disease (cGVHD) who have failed at least 2 prior lines of systemic 
therapy. The study will consist of a Screening period, a Treatment period, and a 
Safety Follow-up period. 
This SAP contains a detailed description of the data presentations and statistical 
analyses that will be included in the clinical study report for Protocol SNDX-6352- 
0503. The statistical methods and analyses described here are based on those presented 
in the study protocol (Version 10.0, 12 Apr 2022). 
 
2. 
STUDY SUMMARY 
 
2.1 
STUDY OBJECTIVES 
 
Study objectives are summarized in protocol Section 3. 
 
2.2 
STUDY ENDPOINTS 
 
2.2.1 
Primary Endpoint of Phase 1 
Optimal biologic dose (OBD) and recommended phase 2 dose (RP2D) of SNDX- 
6352 
 
2.2.2 
Secondary Endpoints of Phase 1 
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) 
Plasma PK of SNDX-6352 
Changes from baseline in CSF-1, IL-34 levels and their association with cGVHD 
response 
 
Changes from baseline in circulating monocyte number and phenotype (CD14/16) 


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Changes from baseline in inflammation biomarkers that may include MCP1, CCL3 
and CCL5 expression 
 
Presence of ADA 
 
2.2.3 
Exploratory and Pharmacodynamic Endpoints of Phase 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2.2.4 
Primary Endpoint of Phase 2 Expansion 
Proportion of subjects with CR or PR (ORR) at Cycle 7 Day 1 (Day 168) 
 
2.2.5 
Secondary Endpoints of Phase 2 Expansion 
 
Frequency and severity of AEs and SAEs 
Best Overall Response (BOR) 
FFS 
DOR 
SRR (CR or PR ≥ 20 weeks) 
 
Organ specific response based on 2014 NIH Consensus Development Project on 
Criteria for Clinical Trials in cGVHD 
 
Joints and fascia response based on refined NIH response algorithm for cGVHD 
Changes in subject-reported symptom activity using the Lee cGVHD symptom scale 
Proportion of subjects with a ≥ 7-point improvement in normalized score using the 
Lee cGVHD symptom scale. 
 
Percent reduction in average daily dose (or equivalent) of corticosteroid 
Proportion of subjects who discontinue corticosteroid use after study entry 
Percent reduction in average daily dose (or equivalent) of calcineurin inhibitor 
Proportion of subjects who discontinue calcineurin inhibitor after study entry 


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2.2.6 
Exploratory and Pharmacodynamic Endpoints of Phase 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.3 
STUDY DESIGN 
Phase 1 of Study SNDX-6352-0503 is the dose escalation phase and Phase 2 is the dose 
expansion phase. The dose escalation rules were defined in protocol Section 4. 
2.3.1 
Number of Subjects and Sample Size Considerations 
Phase 1 Dose Escalation: Up to 30 subjects will be enrolled in this study. 
Phase 2 Dose Expansion: A maximum of 22 subjects will be enrolled. A true ORR of 
60% is hypothesized. A response rate greater than 30% is considered the lower 
threshold. The number of responders needed to declare the study a success was based 
on single proportion binomial test with 91% power and 1-sided significance level of 
5%. Ninety percent 2-sided confidence interval of the observed one sample proportion 
will be calculated. The trial will be considered a success if the lower limit of 90% 
confidence interval is greater than 30%. Eleven responders out of 22 subjects will 
provide the lower limit of 90% confidence interval of 31.1% (90% CI [31.1%, 68.9%]). 


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2.3.2 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.2 
of the protocol). 
2.3.2.1 
Response Determination according to 2014 NIH Consensus 
definitions 
Overall physician- assessed responses will be evaluated as defined by the 2014 NIH 
Consensus Development Project on Clinical trials in cGVHD (Lee 2015). CR is defined 
as resolution of all manifestations in each organ or site, and PR is defined as 
improvement in at least 1 organ or site without progression in any other organ or site. 
Table 1 contains the Working Group proposed consensus definitions of CR, PR and 
progression for assessment of organ specific responses as well as a global response 
determination. 
Table 1: Response Determination for Chronic GVHD Clinical Studies based on 
Clinician Assessments 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin Score 
by 1 or more points 
Increase in NIH Skin Score 
by 1 or more points, except 0 
to 1 
Eyes 
NIH Eye Score 0 after 
previous involvement 
Decrease in NIH Eye Score 
by 1 or more points 
Increase in NIH Eye Score 
by 1 or more points, except 0 
to 1 
Mouth 
NIH Modified OMRS 0 
after previous involvement 
Decrease in NIH Modified 
OMRS of 2 or more points 
Increase in NIH Modified 
OMRS of 2 or more points 
Esophagus 
NIH Esophagus Score 0 
after previous involvement 
Decrease in NIH Esophagus 
Score by 1 or more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI 
Score by 1 or more points, 
except 0 to 1 
Lower GI 
NIH Lower GI Score 0 
after previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI 
Score by 1 or more points, 
except from 0 to 1 


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Liver 
Normal 
ALT, 
alkaline 
phosphatase, 
and 
Total 
bilirubin 
after 
previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2 ULN 
Lungs 
Normal 
%FEV1 
after 
previous involvement 
If PFTs not available, NIH 
Lung Symptom Score 0 
after previous involvement 
Increase by 10% predicted 
absolute value of %FEV1 
If 
PFTs 
not 
available, 
decrease 
in 
NIH 
Lung 
Symptom Score by 1 or more 
points 
Decrease by 10% predicted 
absolute value of %FEV1 
If 
PFTs 
not 
available, 
increase 
in 
NIH 
Lung 
Symptom Score by 1 or more 
points, except 0 to 1 
Joints and 
fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 
25 
after 
previous 
involvement by at least 1 
measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in P-ROM 
score by 1 point for any site 
Increase in NIH Joint and 
Fascia Score by 1 or more 
points or decrease in P-ROM 
score by 1 point for any site 
Global 
Clinician overall severity 
score 0 
Clinician overall severity 
score decreases by 2 or more 
points on a 0-10 scale 
Clinician overall severity 
score increases by 2 or more 
points on a 0-10 scale 
ULN = upper limit of normal. 
Source: (Lee 2015) 
 
2.3.2.2 
Physician-Reported Global and Organ Specific cGVHD Activity 
Assessment 
Changes in cGVHD severity as defined by the NIH 2014 Consensus Criteria will be 
evaluated using physician-reported global and organ-specific cGVHD activity 
assessment form (Appendix 1). The clinicians will provide a subjective assessment of 
current overall chronic GVHD severity on a 4-point scale (no chronic GVHD, mild, 
moderate, severe) independent of the recorded NIH global severity score (Table 1, last 
line) and their evaluations of cGVHD changes since the last assessment. Key organ 
assessments include skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and 
joint/fascia . 
2.3.2.3 
Patient-Reported cGVHD Activity Assessment 
Changes in patient-reported symptom activity will be evaluated using the cGVHD Lee 
symptom scale (Lee 2002), which has been recommended for use by the 2005 and 2104 
National Institutes of Health (NIH) Consensus Conferences to capture cGVHD 
symptoms. 


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The Lee cGVHD symptom questionnaire asks subjects to indicate the degree of 
“bother” that they experienced during the past 7 days due to symptoms in 7 domains 
potentially affected by chronic GVHD (Lee, 2002). Published evidence supports its 
validity, reliability, and sensitivity to cGVHD severity (Lee, 2015; Merkel, 2016). 
Seven-point improvement in normalized score using the Lee cGVHD symptom scale 
is considered clinically meaningful. 
For each subscale, if >=50% of the items are non-missing/complete, the total score is 
calculated as the sum of the non-missing item-level scores and use the following 
formula to transform the scores to 0-100: 
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 = (𝑠𝑠𝑠𝑠𝑠𝑠 𝑜𝑜𝑜𝑜 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠) ∗ 100/(4 ∗ 𝑚𝑚) ∗ ( 
𝑚𝑚 
) 
𝑁𝑁𝑁𝑁. 𝑜𝑜𝑜𝑜 𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 
𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 
 
where m= total number of items in the subscale (see Section 10.5.2 of the protocol). If 
<50% of the items in the subscale are non-missing/complete, then set the total score for 
this subscale to be missing. 
For the overall total score, if ≥4 subscale scores are non-missing/available, then the 
overall total score is calculated as the average of the non-missing/available subscale 
scores. If <4 subscale scores are non-missing/available, then the overall total score is 
set to be missing. 
2.3.3 
Pharmacokinetic Assessments 
Plasma samples will be collected to assess the PK of SNDX-6352. SNDX-6352 levels 
in plasma samples will be determined using a validated enzyme-linked immunosorbent 
assay (ELISA). One (1) blood sample will be collected at the time points specified in 
the SoA (Section 1.2 of the protocol). 
On each PK sample collection day, the time and date of SNDX-6352 administration, 
the start and stop time of SNDX-6352 administration, and the time and date of PK 
sample collection should be recorded in the eCRF. 
2.3.4 
Pharmacodynamics and Exploratory Endpoints 
The details on pharmacodynamics and exploratory endpoints are specified in Section 
8.6 of the protocol. 


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2.3.5 
Biomarkers 
The following blood samples will be collected from all subjects in this study and the 
immune correlate analyses biomarker research may be performed. 
Levels of blood immune parameters that may include CSF-1, IL-34, IFN-gamma, IL- 
1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha and 
sCD163, CD204/206 and change from baseline compared to PK, safety endpoints 
Levels of circulating classical and non-classical monocytes and change from baseline 
compared to PK, safety endpoints 
Analysis of numbers of circulating immune cell subsets including CD8+ T cells, CD4+ 
T cells, B cells, natural killer (NK) cells and change from baseline compared to PK and 
safety endpoints 
2.3.6 
Safety Assessments 
The following assessments will be performed to evaluate the safety profile of SNDX- 
6352 at the timepoints specified in SoA (Section 1.2 of the protocol). 
Vital signs: temperature, pulse rate, respiration rate, blood pressure (systolic and 
diastolic), and weight 
Body height (at Screening only) 
Karnofsky/Lansky Performance Scale 
Triplicate 12-lead ECGs 
Neurological examination 
AE and SAE recording 
Safety laboratory assessments 
2.3.7 
Other Assessments 
Other assessments include patient demographics, medical and disease history, prior 
medications, physical examinations, SNDX-6352 administration and accountability, 
concomitant medications and procedures, protocol deviations, post-treatment anti- 
cancer therapy, and clinical disease assessment, collected per Schedule of Activities 


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(Protocol Section 1.2). 
 
3. 
STATISTICAL METHODS 
 
3.1 
General Methods 
Phase 1 and Phase 2 will be summarized separately. For Phase 1, summary statistics 
will be provided at each dose level and all those dose levels combined. For Phase 2, 
summary statistics will be provided at 1 mg/kg Q2W. Summary of Phase 1 and Phase 
2 combined may also be performed. In general, subject listings will be provided to 
support summary tables. 
3.1.1 
Computing Environment 
All statistical analyses will be performed using SAS® Version 9.4 or higher. 
Programming specifications will be prepared, which describe the datasets and variables 
created for this study. The datasets will be prepared using the most recent version of 
CDISC’s Study Data Tabulation Model (SDTM) and Analysis Dataset Model (ADaM). 
3.1.2 
Reporting of Numerical Values 
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) 
will be calculated for continuous variables. Frequencies and percentages will be 
presented for categorical and ordinal variables. Percentages will be based on the 
number of subjects with non-missing assessments. If there are missing values, the 
number missing will be presented, but without a percentage. 
Means and medians will be reported to one decimal place more than the data reported 
in the clinical data management system. Standard deviations will be reported to two 
decimal places more than the data reported. Minimum and maximum will be reported 
to the same number of decimal places displayed in the clinical data management 
system. 
3.1.3 
Baseline Value and Change from Baseline 
Baseline will be defined as the most recent, non-missing value obtained prior to the 
first dose of any study drug (SNDX-6352). 


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Change from baseline will be calculated by subtracting the baseline value from the on- 
study assessment for each patient (i.e., post-dose – baseline). 
Percent change from baseline is calculated as (post-dose assessment – baseline 
value)/baseline value x 100. 
3.1.4 
Handling of Missing/Incomplete Values 
Adverse events 
Missing and incomplete adverse event start dates will be imputed based on the 
algorithm described below. The algorithm will be used only if the end date of the 
adverse event (if reported) indicates the event was not resolved before the first 
administration of study drug. The purpose of the imputation is to determine if an 
adverse event with a missing or incomplete start date is treatment emergent. Imputed 
adverse event dates will not be used to calculate the duration of adverse event episodes. 
Case 1: if year portion of AE start date is missing, then missing AE start date = first 
dose date; 
Case 2: if year portion of AE start date = year portion of first dose date, then, 
If month portion of AE start date is missing, then missing AE start date = first 
dose date. 
If month portion of AE start date = month portion of first dose date, then 
missing AE start date = first dose date. 
If month portion of AE start date is not equal to month portion of first dose date, 
then onset day of AE start date will be set to 1st day of the AE start month. 
Case 3: if year portion of AE start date > year portion of first dose date, then, 
If month portion of AE start date is missing, then onset day and month of AE 
start date is set to January 1. 
If month portion of AE start date is not missing, then onset day of AE start date 
is set to 1st day of the AE start month. 
Medications 
 
When determining prior or concomitant medications, partial start dates of prior and 
concomitant medications will be assumed to be the earliest possible date consistent 
with the partial date. Partial stop dates of prior and concomitant medications will be 


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assumed to be the latest possible date consistent with the partial date. In the case of 
completely missing stop date, medication will be assumed to be ongoing. In the case 
of complete missing start date, medication will be assumed to be prior medication. 
Lee cGVHD Symptom Score 
For handling of missing data in Lee cGVHD symptom questionnaire, please refer to 
Section 2.3.2.3. 
cGVHD diagnosis 
Missing date of cGVHD diagnosis will imputed based on the rule below: 
If month and day are missing, the date is set to June 30 
If day is missing, the date is set to the 15th of the month 
 
3.2 
Analysis Sets 
 
3.2.1 
Enrolled (Intent-to-treat) Set 
The Enrolled Set is defined as all subjects who sign the ICF and were enrolled into the 
study. 
3.2.2 
Full Analysis Set 
The Full Analysis Set (FAS) is a subset of all enrolled subjects, with subjects excluded 
for the following reasons: 
• 
Failure to receive at least one dose of SNDX-6352 
• 
Lack of baseline data for those analyses that require baseline data 
 
3.2.3 
Evaluable Analysis Set 
The Evaluable Analysis Set is defined as all subjects who have received at least 1 dose 
of treatment and have at least one post baseline response assessment unless the subject 
drops out early due to progression or treatment related AE. 
3.2.4 
Safety Analysis Set 
The Safety Analysis Set will include all subjects who received at least one dose of study 
drug. 


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3.2.5 
Pharmacokinetic Analysis Set 
The PK Analysis Set will include all treated subjects who have at least one plasma 
concentration measured. 
3.2.6 
Pharmacodynamic Analysis Set 
The PD Analysis Set will include all treated subjects who have evaluable PD samples 
at one or more scheduled collections. 
For skin biopsy and lung biopsy specimens, subjects with baseline and/or post dose 
samples will be evaluated. 
3.2.7 
Applications of Analysis Sets 
Unless otherwise noted, the analysis sets that will be used for table summaries of each 
type is provided in the following table. 
Table 2: Application of Analysis Sets on Tables and Figures 
 
Type 
Safety 
Enrolled 
Evaluable 
Summary of analysis sets 
 
X 
 
Disposition 
X 
 
 
Protocol deviations 
X 
 
 
Demographics 
X 
 
 
Baseline characteristics 
X 
 
 
Medical history 
X 
 
 
Treatment exposure 
X 
 
 
Safety evaluations 
X 
 
 
Efficacy evaluations 
 
 
 
Response-related 
analyses 
and 
Lee 
Symptom Scale analysis 
X 
 
X 
Failure  free  survival  and  reduction  in 
X 
 
 


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corticosteroid or calcineurin inhibitor use 
 
 
 
 
3.3 
Disposition and Evaluability 
 
3.3.1 
Disposition 
The numbers of subjects who were screened, enrolled, dosed, and the reasons for 
discontinuation of study intervention and reasons for discontinuation of study will be 
summarized. 
The number of patients who started axatilimab taper, and reasons for discontinuation 
of study intervention for those who started axatilimab taper, will also be summarized. 
3.3.2 
Protocol Deviations 
Protocol deviations will be presented in a subject listing. 
 
3.4 
Demographics and Baseline Characteristics 
 
3.4.1 
Demographics 
Summary statistics will be presented for age, sex, race, ethnicity, weight (kg), height 
(cm), and body surface area (m2) in Safety Analysis Set. 
Body surface area will be calculated using the Mosteller formula: 
 
 
Body surface area = √height (cm) × weight (kg) 
3600 
 
3.4.2 
Baseline Disease Characteristics 
The following baseline disease characteristics variables will be summarized in Safety 
Analysis Set: 
Number of transplants 
Type of transplant 
Type of donor 
HLA matching of cell graft between donor and recipient 


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Stem cell source 
Time from transplant 
Time from transplant to diagnosis of cGVHD 
Time from initial cGVHD diagnosis to first dose 
Number of involved organs 
Involved organ 
Karnofsky/Lansky Performance Status 
Number of prior lines of treatment of cGVHD 
Systemic prednisone (or equivalent) dose at C1D1 (mg/kg) 
Systemic calcineurin use at C1D1 
Prior ibrutinib therapy 
Prior ruxolitinib therapy 
Prior belumosudil therapy 
If the date of diagnosis is missing the day and/or month, the algorithm specified in 
Section 3.1.4 for incomplete dates will be used. 
3.4.3 
Medical History, Prior Medications, and Physical Exam 
Data regarding medical history, prior medications, and clinically significant findings 
from the physical and neurological exam will be presented in subject listings for the 
Safety Analysis Set. 
 
3.5 
Concomitant Medications 
Concomitant medications are defined as any medication that was taken on or after the 
first dose of study medication. If the start and stop dates of the concomitant medication 
do not clearly define the period during which a medication was taken, it will be assumed 
to be a concomitant medication. 
All medications will be coded using the World Health Organization (WHO) Drug 
Dictionary (September 2020 or later). The numbers and percentages of subjects taking 
concomitant medication will be presented for the Safety Analysis Set for both Phase 1 
and Phase 2. 
 
3.6 
Treatment Exposure 
The Safety Analysis Set will be used for summarizing treatment exposure. 


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The total number of cycles started, and the total number of cycles started by category 
(≥1, ≥2, ≥3, so on) will be tabulated. The treatment duration and cumulative dose of 
SNDX-6352 administered (in mg/kg) will be calculated. These data will be further 
summarized by calculating the mean, standard deviation, median, and range of these 
values. Treatment duration is defined as (minimum of [last dose date + x, death date] – 
first dose date)/7, where x=14, 28, or 56 if the last dose occurred in a cycle with Q2W, 
Q4W, or Q8W dosing, respectively. The actual dose intensity is calculated as [actual 
cumulative dose/(treatment duration)]*100. Relative dose intensity (RDI) is defined as 
actual dose intensity / planned dose intensity * 100, where planned dose intensity is 
defined as total planned dose (i.e. starting dose * number of cycles * 2 for Q2W, or 1 
for Q4W) divided by planned treatment duration (i.e. number of cycles started * 4). For 
patients who are on axatilimab taper, the taper dose during taper will be considered as 
planned dose. Relative dose intensity for the first 6 cycles will also be summarized. 
The number and proportion of subjects with one or more dosage modification (i.e., 
interruptions, reductions, or delay) will be tabulated along with the reasons for dosage 
modification. 
 
3.7 
Efficacy Analysis 
For response related endpoints, the primary analysis set will be Safety Analysis Set and 
Evaluable Analyses set will be used as sensitivity analysis. Analysis for FFS and 
reduction in corticosteroid or calcineurin inhibitor use will be conducted in Safety 
Analysis Set. 
ORR at Cycle 7 Day 1 (Day 168) and BOR 
Responses by each organ (Skin, Eyes, Mouth, Esophagus, Upper GI, Lower GI, Liver, 
Lungs, Joints and Fascia and global) will be assessed using the NIH Consensus 
Development Project on Clinical trials (Table 1).The overall response at each visit will 
be derived using physician reported assessment for each organ based on the rule in 
Section 2.3.2.1. Best overall response will be derived based on response across all post- 
baseline visits. Best overall response will be categorized as complete response, partial 
response, no change, progression and other. ORR at Cycle 7 Day 1 is defined as CR 
and PR at Cycle 7 Day 1. Exact 95% confidence intervals (CIs) using binomial 
distribution will be calculated for ORR at Cycle 7 Day 1 at each dose and all those dose 


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levels combined for Phase 1 and at 1 mg/kg Q2W for Phase 2. Exact 90% CI for ORR 
at Cycle 7 Day 1 will also be calculated for Phase 2. 
ORR by Cycle 7 Day 1 and ORR will be conducted as supportive analyses. ORR by 
Cycle 7 Day 1 is defined as CR or PR by Cycle 7 Day 1, and ORR is defined as CR or 
PR at any post-baseline visit. Exact 95% confidence intervals (CIs) using binomial 
distribution will be calculated. 
Time to response is defined as the time from first dose of study intervention to the date 
of first CR or PR. 
Failure Free Survival (FFS) 
Failure Free Survival (FFS) is defined as the time from first dose of study intervention 
to unequivocal progression of cGVHD, or addition of another systemic immune 
suppressive therapy, or relapse of underlying malignancy, or discontinuation of study 
treatment due to toxicity, or death for any reason whichever date occurs first. 
Unequivocal progression of cGVHD is defined as treatment discontinuation due to 
clinical progression. 
Subjects who either didn’t start another treatment at the end of study or didn’t 
progress/relapse or are alive or didn’t discontinue study treatment due to toxicity (as of 
the data analysis cutoff date) will be censored at the last visit date. 
The duration of FFS as determined by the NIH 2014 Consensus Criteria will be 
evaluated using organ-specific cGVHD activity assessment form and will be 
summarized descriptively using the Kaplan-Meier method. FFS at 6 months and 12 
months will be estimated using Kaplan-Meier method. 
Duration of Response (DOR) 
 
Duration of response will be calculated for subjects who achieve CR or PR. For such 
subjects, DOR is defined as the time from the start date of the PR or CR (whichever 
response occurs first) to documented progression or start of another systemic treatment. 
The date of progression or censoring for DOR will be determined according to the 
conventions listed in Table 3. DOR will be summarized using the Kaplan-Meier 
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Table 3. Date of Progression or Censoring for Duration of Response 
 
Situation 
Date of Event or Censoring 
Outcome 
Documented progression 
Date of documented progression 
Event 
Started another systemic 
treatment without 
documented progression 
Date of first dose for another systemic 
treatment 
 
Event 
Without another systemic 
therapy and without 
documented progression 
Date of last evaluable disease 
assessment 
 
Censored 
Sensitivity analysis for DOR, defined as the time from the start date of initial response 
of CR or PR to documented progression from best response or start of another systemic 
treatment, whichever is earlier will also be performed. The date of progression or 
censoring for DOR will be determined according to the conventions listed Table 3. 
Sustained Response Rate 
The proportion of subjects with sustained response, defined as CR or PR ≥ 20 weeks 
(at least 20 weeks from the time of initial response), will be summarized. Exact 95% 
confidence intervals (CIs) will be calculated. 
Changes in Subject-Reported Symptom Activity 
 
Changes in subject-reported symptom activity will be assessed using the Lee cGVHD 
Symptom Scale summary score (Section 2.3.2.3). 
The proportion of subjects with a ≥ 7-point improvement in normalized score using 
the Lee cGVHD Symptom Scale in patients with baseline and at least one post-baseline 
assessment and exact 95% CIs using binomial distribution will be calculated. 
Responses by Organ System 
The proportion of subjects with a response (CR/PR) with skin, eyes, mouth, esophagus, 
upper GI, lower GI, liver, lungs, and joints and fascia will be summarized using the 
NIH Consensus Development Project on Clinical trials (See Table 1). Exact 95% 
confidence intervals (CIs) using binomial distribution will be calculated. Joints and 
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will be summarized. 
The proportion of subjects with a joint and fascia response based on refined NIH 
response algorithm for cGVHD and exact 95% CIs using binomial distribution will be 
calculated. 
Reduction in Corticosteroid or Calcineurin Inhibitor Use 
The best percent change in corticosteroid use (percent reductions in the average daily 
dose of prednisone (or equivalent) after study entry) will be summarized. 
The proportion of subjects who discontinue corticosteroids after study entry and along 
with exact 95% CIs will be calculated. The same analysis will be repeated for 
calcineurin inhibitor use. 
 
3.8 
Safety Analysis 
Safety analyses will be performed on the Safety Analysis Set. 
 
3.8.1 
Adverse Events 
AEs are classified as related, possibly related, probably related, unlikely related or 
unrelated to study treatment. Any AEs with missing or unknown relationship will be 
considered as related to study treatment. 
All AEs will be coded according to System Organ Class (SOC) and Preferred Term 
(PT) using the Medical Dictionary for Regulatory Activities (MedDRA) dictionary 
(Version 24.0 or later). 
TEAEs are defined as any AE occurring or worsening in severity after the 
administration of study drug and within 90 days of last administration of study drug. 
TEAEs will be summarized by system organ class (SOC) and preferred term (PT) by 
each dose level and all dose levels combined. All summaries will be ordered by 
decreasing frequency of total number of subjects in all dose levels combined category 
within SOC. In the case of equal frequency of number of patients, summaries of AEs 
will be sorted alphabetically. 
If AE start dates are completely missing or partially missing, the date imputation rules 
described previously in Section 3.1.4 will be applied for the determination of 
treatment-emergence. This algorithm will be used only if the end date of the AE (if 
reported) indicates the event was not resolved before the first administration of study 


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drug. Imputed AE dates will not be used to calculate the duration of AE episodes. 
 
For the phase 1, the observed DLT rate in each dose cohort will be calculated by the 
proportion of subjects who experienced DLT. 
 
The following AEs will be summarized: 
• TEAEs by SOC and PT 
• TEAEs by PT 
• Most common TEAEs (occurred in > 10% of patients) by PT 
• Drug-related TEAEs by PT 
• Most common drug-related TEAEs (occurred in > 10% of patients) by PT 
• Grade ≥ 3 TEAEs by PT 
• Drug-related grade ≥ 3 TEAEs by PT 
• TEAEs leading to study drug discontinuation by PT 
• Related TEAEs leading to study discontinuation by PT 
• Serious TEAEs by SOC and PT 
• Serious TEAEs by PT 
• Drug-related serious TEAEs by PT 
• AESI by PT 
• Drug-related AESI by PT 
• Fatal AE by PT 
• TEAE by PT and severity 
SOCs will be sorted alphabetically. Within an SOC, PTs will be presented by 
decreasing incidence overall. Incidences of SAEs, and incidence of related SAEs by 
PT only, will be presented by decreasing incidence overall. 
For subjects experiencing the same PT at multiple severities, the occurrence of the AEs 
with the greatest severity will be used in the analysis of incidence by severity. For 
subjects experiencing the same PT at multiple relationship levels, the occurrence of the 
AEs with the strongest relationship to study drug will be used in the analysis of 
incidence by relationship to study drug. 
All reported AEs, regardless of whether they were treatment-emergent, will be included 
in subject listings. Listings of all AEs leading to discontinuation of study drug will also 
be provided. 


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3.8.2 
Laboratory Evaluations 
The absolute values and change from baseline for each of these post-baseline values 
will be summarized. 
Whenever available, laboratory values will be assigned toxicity grades using the 
NCI-CTCAE, version 5.0. Analyses will be performed for shifts in NCI CTCAE 
toxicity grades relative to the baseline toxicity grade. Similar analyses may be 
performed for shifts above or below the normal range for selected laboratory tests. 
Percentages will be based on the total number of subjects with a baseline assessment 
and at least one post-baseline assessment for the given laboratory parameter. 
Laboratory test groupings and standard normal ranges are described in Appendix 6.1, 
and CTCAE toxicity grades for hematology and chemistry parameters are based on 
CTCAE v5.0, respectively. 
3.8.3 
Vital Signs 
Change from baseline for vital signs (temperature, pulse, systolic/diastolic blood 
pressure, respiration rate, and weight) will be summarized over time. 
3.8.4 
ECG 
 
Electrocardiogram results will be listed in terms of subjects with abnormal and normal 
findings, as reported by the Investigator, at the time points at which ECGs were 
assessed. 
 
Change in from baseline for ECG parameters (heart rate, PR interval, QRS duration, 
QT interval, and QTcF will be summarized. QTc will be calculated using Fridericia’s 
correction (QTcF). 
 
Subject listings of ECG overall interpretation as well as all ECG parameters will be 
provided. 
3.8.5 
ADA 
Negative ADA 
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considered negative. Samples that are determined to be positive in the ADA screening 
assay, but the result is not confirmed in the ADA confirmatory assay, will be considered 
negative. 
Positive ADA 
A sample that has been evaluated as positive in both the ADA screening and 
confirmatory assays will be considered positive. 
Positive Neutralizing ADA 
A sample that has been evaluated as positive in the neutralizing ADA assay will be 
considered positive. 
A patient is considered ADA positive if at least one post-baseline sample is ADA 
positive. 
Treatment-induced ADA positivity is defined as detection of post-baseline ADA in 
patients negative at baseline. 
Treatment-boosted ADA positivity is defined as detection of four-fold change in post- 
baseline ADA titers in patients who have detectable ADA at baseline. 
The overall percentage of subjects with at least one ADA positive sample will be 
provided. The overall percentage of subjects with at least one neutralizing ADA 
positive sample will be provided. The overall percentage of ADA positive patients, 
treatment-induced ADA positive patients, and treatment-boosted ADA positive 
patients will also be provided. 
 
3.9 
Pharmacokinetic Analysis 
 
PK analysis set will be used to describe the pharmacokinetic parameters of Cmax, Tmax, 
AUC0-t, AUC0-inf, t1/2, λz, as data permit. The PK parameters for the plasma 
concentrations of SNDX-6352 will be calculated via non-compartmental methodsusing 
the Phoenix WinNonlin™ software package. The PK parameters will be summarized 
using descriptive statistics to include mean, standard deviation, minimum, median, 
maximum, percent coefficient of variation (CV%), geometric mean, and geometric 
CV%. 


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The effects of patient factors (e.g., demographics, clinical chemistries, and disease) on 
SNDX-6352 PK may be evaluated. In addition, the relationship between SNDX-6352 
exposure parameters and indicators of safety may be assessed. Descriptive analyses 
may be performed to summarize the PK of SNDX-6352 and ADA for time points at 
which both are collected. 
 
All measurable plasma concentrations will be used for the analysis. For concentration 
values reported as no Results/not Reportable (NR), values will be treated as missing. 
Values below the quantifiable limit (BQL) that occur prior to the first measurable 
concentration will be treated as zero. All other BQL values will be treated as missing. 
The mean plasma concentration over time by treatment and the individual subject 
plasma concentration versus time data will be plotted. Nominal times will be used for 
plotting the mean plasma concentrations over time by treatment. 
The actual dose dates and times will be used to calculate the actual elapsed time from 
the start of the infusion for each PK plasma sample. Actual elapsed sampling times will 
be used for the individual figures and for the non-compartmental analysis. 
 
3.10 
Pharmacodynamic and Biomarker Analyses 
Immune correlate values may be summarized in a descriptive manner. For immune 
correlates measured on a continuous scale, the number of subjects with non-missing 
data, mean, standard error or standard deviation, median, minimum, and maximum 
values will be presented. For discrete data, the frequency and percent distribution will 
be presented. 
• Reduction of non-classical monocytes at the time of dose interval and plateaued 
increase of circulating CSF-1 levels that persist for an entire dose level 
• Changes in CSF-1, IL-34, MCP-1, CCL3 and CCL5 from baseline to day 8, day 
15, C2D1, C4D1 and end of treatment 
• Changes in monocyte number and phenotype (CD14/16) from baseline to day 
8, day 15, C2D1, C4D1 and end of treatment 
• Changes from baseline in skin macrophages, Langerhans cells and dendritic 
cells in skin or pulmonary biopsy prior to SNDX-6352 and after 2 cycles of 
SNDX-6352 treatment 


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• Frequency of immune cells in peripheral circulation, including natural killer 
(NK) cells, T-cells, and B-cells 
• Bone metabolism will be assessed by measuring changes in concentration of 
BAP and CTX in serum 
 
4. 
CHANGES FROM PROTOCOL 
ITT and FAS are removed as efficacy analysis population since evaluable population 
is more appropriate for an early phase study. Evaluable population definition is updated 
to include patients who discontinued treatment early due to progression or treatment 
related AE without any post-baseline response assessment. 
PK analysis set definition is updated to be consistent with other studies in the program. 
2-sided CI for DLT rate is removed. 
5. 
REFERENCES 
 
Alexander, K. A., Flynn, R., Lineburg, K. E., Kuns, R. D., Teal, B. E., Olver, S. D., 
Lor, M., Raffelt, N. C., Koyama, M., Leveque, L., Le Texier, L., Melino, M., Markey, 
K. A., Varelias, A., Engwerda, C., Serody, J. S., Janela, B., Ginhoux, F., Clouston, A. 
D., Blazar, B. R., Hill, G. R. and MacDonald, K. P. (2014). "Csf-1-dependant donor- 
derived macrophages mediate chronic graft-versus-host disease." The Journal of 
clinical investigation 124(10): 4266-4280. 
 
Inamoto, Y., Lee, S. J., Onstad, L.E., Flowers, M. E. D., Hamilton, B.K., Jagasia, 
M.H., et al. (2020). "Refined National Institutes of Health response algorithm for 
chronic graft-versus-host disease in joints and fascia." Blood Adv 4(1): 40-46. 
 
Jagasia, M. H., Greinix, H. T., Arora, M., Williams, K. M., Wolff, D., Cowen, E. W., 
Palmer, J., Weisdorf, D., Treister, N. S., Cheng, G. S., Kerr, H., Stratton, P., Duarte, 
R. F., McDonald, G. B., Inamoto, Y., Vigorito, A., Arai, S., Datiles, M. B., 
Jacobsohn, D., Heller, T., Kitko, C. L., Mitchell, S. A., Martin, P. J., Shulman, H., 
Wu, R. S., Cutler, C. S., Vogelsang, G. B., Lee, S. J., Pavletic, S. Z. and Flowers, M. 
E. (2015). "National institutes of health consensus development project on criteria for 
clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging 
working group report." Biology of blood and marrow transplantation : journal of the 
American Society for Blood and Marrow Transplantation 21(3): 389-401 e381. 


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Jaki, T., Clive, S. and Weir, C. J. (2013). "Principles of dose finding studies in 
cancer: A comparison of trial designs." Cancer chemotherapy and pharmacology 
71(5): 1107-1114. 
 
Lee, S., Cook, E. F., Soiffer, R. and Antin, J. H. (2002). "Development and validation 
of a scale to measure symptoms of chronic graft-versus-host disease." Biology of 
blood and marrow transplantation : journal of the American Society for Blood and 
Marrow Transplantation 8(8): 444-452. 
 
Lee, S. J., Wolff, D., Kitko, C., Koreth, J., Inamoto, Y., Jagasia, M., Pidala, J., 
Olivieri, A., Martin, P. J., Przepiorka, D., Pusic, I., Dignan, F., Mitchell, S. A., 
Lawitschka, A., Jacobsohn, D., Hall, A. M., Flowers, M. E., Schultz, K. R., 
Vogelsang, G. and Pavletic, S. (2015). "Measuring therapeutic response in chronic 
graft-versus-host disease. National institutes of health consensus development project 
on criteria for clinical trials in chronic graft-versus-host disease: Iv. The 2014 
response criteria working group report." Biology of blood and marrow transplantation 
: journal of the American Society for Blood and Marrow Transplantation 21(6): 984- 
999. 
 
Merkel, E. C., Mitchell, S. A. and Lee, S. J. (2016). "Content Validity of the Lee 
Chronic Graftversus-Host Disease Symptom Scale as Assessed by Cognitive 
Interviews." Biology of blood and marrow transplantation : journal of the American 
Society for Blood and Marrow Transplantation 22(4): 752-758. 
 
 
6. 
Appendix 
Appendix 1: Global cGVHD Activity Assessment -Physician Report 


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Source: 


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cGVHD Lee Symptom Scale 
 


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Appendix 2: 
 
6.1 
Laboratory Test Groupings and Standard Normal Range 
 
 
 
Analyte 
 
Standard 
Unit 
 
Significant 
Digits 
Directional 
Change of 
Interest 
 
Standard 
Normal Range† 
Lab group = Hematology, WBC with Differential 
WBC count‡ 
109 cells/L 
XX.X 
Decrease 
3.2 – 9.8 
Basophil count 
106 cells/L 
XX 
Decrease 
15 – 50 
Eosinophil count 
106 cells/L 
XXX 
Decrease 
50 – 250 
Lymphocyte count‡ 
106 cells/L 
XXXX 
Decrease 
1500 – 3000 
Monocyte count 
106 cells/L 
XXX 
Decrease 
285 – 500 
Neutrophil count‡ 
106 cells/L 
XXXX 
Decrease 
3000 – 5800 
Lab group = Hematology, Erythrocytes and Platelets 
 
Hematocrit 
 
Fraction of 1.00 
 
0.XX 
 
Decrease 
0.33 – 0.43 (female) 
0.39 – 0.49 (male) 
 
Hemoglobin‡ 
 
g/L 
 
XXX 
 
Decrease 
115 – 155 (female) 
140 – 180 (male) 
RBC count 
1012/L 
X.X 
Decrease 
3.5 – 5.0 
Platelet count‡ 
109/L 
XXX 
Decrease 
130 – 400 
Lab group = Hematology, Coagulation 
PT 
seconds 
XX 
Increase 
9 – 12 
PTT‡ 
seconds 
XX 
Increase 
22 – 37 
† Standard normal ranges are provided for reference and not will be used in analysis unless laboratory 
normal ranges are missing. Source: Laposta, M: SI Unit Conversion Guide, The New England Journal of 
Medicine Books, Boston, 1992. 
‡ If present, indicates CTCAE toxicity grade is defined for the analyte. 


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Laboratory Test Groupings and Standard Normal Range (continued) 
 
 
 
 
Analyte 
 
Standard 
Unit 
 
Significant 
Digits 
Directional 
Change of 
Interest 
 
Standard 
Normal Range† 
Lab group = Chemistry, Hepatic 
Albumin‡ 
g/L 
XX 
Decrease 
40 – 60 
Alk Phos‡ 
U/L 
XXX 
Increase 
30 – 120 
ALT‡ 
U/L 
XXX 
Increase 
0 – 35 
AST‡ 
U/L 
XXX 
Increase 
0 – 35 
Lactic dehydrogenase 
U/L 
XXX 
Increase 
50 – 150 
Total Bilirubin‡ 
micromol/L 
XX 
Increase 
2 – 18 
Total Protein 
g/L 
X.XX 
Decrease 
60 – 80 
Lab group = Chemistry, Renal 
BUN 
mmol/L of urea 
X.X 
Increase 
3.0 – 6.5 
Creatinine‡ 
micromol/L 
XXX 
Increase 
50 – 110 
Creatinine clearance 
mL/min 
XXX 
Decrease 
75 – 125 
Creatinine kinase‡ 
U/L 
XXX 
Increase 
50-200 
Pancreatic 
Amylase 
U/L 
XXX 
Increase 
27-130 
Lipase 
U/L 
XXX 
Increase 
0-160 
† Standard normal ranges are provided for reference and not will be used in analysis unless laboratory 
normal ranges are missing. 
Source: Laposta, M: SI Unit Conversion Guide, The New England Journal of Medicine 
Books, Boston, 1992. 
‡ If present, indicates CTCAE toxicity grade is defined for the analyte. 


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Laboratory Test Groupings and Standard Normal Range (continued) 
 
 
 
 
Analyte 
 
Standard 
Unit 
 
Significant 
Digits 
Directional 
Change of 
Interest 
 
Standard 
Normal Range† 
Lab group = Chemistry, Electrolytes 
Bicarbonate‡ 
mmol/L 
XX 
Both 
22 – 28 
Calcium‡ 
mmol/L 
X.XX 
Both 
2.20 – 2.56 
Chloride 
mmol/L 
XXX 
Both 
95 – 105 
Magnesium‡ 
mmol/L 
X.XX 
Both 
0.80 – 1.20 
Phosphorus 
mmol/L 
X.XX 
Both 
0.80 – 1.60 
Potassium‡ 
mmol/L 
X.X 
Both 
3.5 – 5.0 
Sodium‡ 
mmol/L 
XXX 
Both 
135 – 147 
Lab group = Chemistry, Metabolic 
Glucose‡ 
mmol/L 
XX.X 
Both 
3.9 – 6.1 
Uric Acid 
micromol/L 
XXX 
Increase 
120 – 420 
† Standard normal ranges are provided for reference and not will be used in analysis unless laboratory 
normal ranges are missing. 
Source: Laposta, M: SI Unit Conversion Guide, The New England Journal of Medicine 
Books, Boston, 1992. 
‡ If present, indicates CTCAE toxicity grade is defined for the analyte.