Phase 1 Study Using a Plasmid DNA Coding for Emm55 Streptococcal Antigen in Patients With Unresectable Stage III or Stage IV Cutaneous Melanoma
Phase: EARLY_PHASE1
Conditions: Cutaneous Melanoma, Stage III, Cutaneous Melanoma, Stage IV
Sponsor: TuHURA Biosciences, Inc.

IFX-HU2.0 
Clinical Study Protocol: CM 2017-01 
Morphogenesis, Inc. 
IND 17840, SN 0000 
Confidential 
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Clinical Study Protocol 
CM 2017-01 
 
Phase 1 Study Using a Plasmid DNA Coding for Emm55 Streptococcal Antigen in Patients with 
Unresectable Stage III or Stage IV Cutaneous Melanoma 
 
 
Protocol Identifying Number: 
CM 2017-01 
Principal Investigator: 
Joseph Markowitz, MD, PhD 
IND Sponsor: 
Morphogenesis, Inc. 
Funded By: 
Morphogenesis, Inc. 
Draft/Version Number: 
Version 7; September 1, 2020 
 NCT Number:                              03655756

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TABLE OF CONTENTS 
TABLE OF CONTENTS .......................................................................................................................... 2 
LIST OF ABBREVIATIONS ..................................................................................................................... 6 
STATEMENT OF COMPLIANCE ............................................................................................................. 8 
PROTOCOL SUMMARY ....................................................................................................................... 9 
SCHEMATIC OF STUDY DESIGN .............................................................................................................. 10 
1. KEY ROLES ................................................................................................................................ 11 
2. 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE .............................. 12 
2.1 
Background Information .................................................................................................... 12 
2.2 
Rationale .......................................................................................................................... 13 
2.3 
Potential Risks and Benefits ............................................................................................... 13 
2.3.1. 
Known Potential Risks ................................................................................................ 13 
2.3.2. 
Known Potential Benefits ........................................................................................... 14 
3 OBJECTIVES AND PURPOSE ....................................................................................................... 14 
4 STUDY DESIGN AND ENDPOINTS ............................................................................................... 14 
4.1 
Description of the Study Design ......................................................................................... 14 
4.2 
Study Endpoints ................................................................................................................ 15 
4.2.1 
Primary Endpoint ....................................................................................................... 15 
4.2.2 
Secondary Endpoints .................................................................................................. 15 
4.2.3 
Exploratory Endpoints ................................................................................................ 15 
5 STUDY ENROLLMENT AND WITHDRAWAL .................................................................................. 16 
5.1 
Participant Inclusion Criteria .............................................................................................. 16 
5.2 
Participant Exclusion Criteria ............................................................................................. 17 
5.3 
Strategies for Recruitment and Retention .......................................................................... 17 
5.4 
Participant Withdrawal or Termination .............................................................................. 17 
5.4.1 
Reasons for Withdrawal or Termination ..................................................................... 17 
5.4.2 
Handling of Participant Withdrawal or Termination ..................................................... 18 
5.5 
Premature Termination or Suspension of Study .................................................................. 18 
6 STUDY AGENT ........................................................................................................................... 18 
6.1 
Study Agent(s) Description ................................................................................................ 18 
6.1.1 
Acquisition ................................................................................................................ 18 
6.1.2 
Formulation, Appearance, Packaging, and Labeling ..................................................... 18 
6.1.3 
Product Storage and Stability ..................................................................................... 19 

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6.1.4 
Preparation ............................................................................................................... 19 
6.1.5 
Dosing and Administration ......................................................................................... 21 
6.1.6 
Route of Administration ............................................................................................. 21 
6.1.7 
Starting Dose and Dose Escalation Schedule ................................................................ 21 
6.1.8 
Dose Adjustments/Modifications/Delays ....................................................................... 21 
6.1.9 
Duration of Therapy ................................................................................................... 21 
6.1.10 
Tracking of Dose ........................................................................................................ 21 
6.2 
Study Agent Accountability Procedures .............................................................................. 21 
7 
STUDY PROCEDURES AND SCHEDULE ........................................................................................ 22 
7.1 
Study Procedures/Evaluations ........................................................................................... 22 
7.1.1 
Study-specific Procedures .......................................................................................... 22 
7.1.2 
Standard-of-care Study Procedures ............................................................................ 22 
7.2 
Laboratory Procedures/Evaluations ................................................................................... 22 
7.2.1 
Clinical Laboratory Evaluations .......................................................................................... 22 
7.3 
Study Schedule .................................................................................................................. 23 
7.3.1 
Screening ................................................................................................................... 23 
7.3.2 
Enrollment / Baseline ................................................................................................. 24 
7.3.3 
Optional Study Visits (for multiple dose cycle only) ..................................................... 24 
7.3.4 
Final Study Visit ......................................................................................................... 26 
7.3.5 
Early Termination Visit ............................................................................................... 26 
7.3.6 
Unscheduled Visit ...................................................................................................... 27 
7.3.7 
Schedule of Events Table ............................................................................................ 27 
7.4 
Concomitant Medications, Treatments, and Procedures ..................................................... 30 
8 
ASSESSMENT OF SAFETY................................................................................................................ 30 
8.1 
Specification of Safety Parameters ............................................................................................ 30 
8.1.1 
Definition of Adverse Events (AE) ................................................................................ 31 
8.1.2 
Definition of Serious Adverse Events (SAE) .................................................................. 31 
8.1.3 
Definition of Unexpected Adverse Drug Experience ..................................................... 31 
8.2 
Classification of an Adverse Event ...................................................................................... 32 
8.2.1 
Severity of Event ........................................................................................................ 32 
8.2.2 
Relationship to Study Event ........................................................................................... 32 
8.2.3 
Expectedness ............................................................................................................. 33 
8.3 
Time Period and Frequency of Event Assessment and Follow-up ......................................... 33 

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8.4 
Reporting Procedures ............................................................................................................ 33 
8.4.1 
Adverse Event Reporting ............................................................................................ 33 
8.4.2 
Serious Adverse Event Reporting ................................................................................ 34 
8.4.3 
Unexpected Adverse Drug Experience Problem Reporting ........................................... 34 
8.4.4 
Reporting of Pregnancy .............................................................................................. 34 
8.5 
Study Halting Rules ........................................................................................................... 34 
8.6 
Safety Oversight ................................................................................................................ 35 
9 
CLINICAL MONITORING ................................................................................................................. 35 
10 
STATISTICAL CONSIDERATIONS .................................................................................................. 35 
10.1 
Statistical and Analytical Plans ........................................................................................... 35 
10.2 
Statistical Hypotheses ............................................................................................................ 35 
10.3 
Analysis Dataset(s) ............................................................................................................ 36 
10.4 
Description of Statistical Methods ..................................................................................... 36 
10.4.1 
General Approach ...................................................................................................... 36 
10.4.2 
Safety Analyses .......................................................................................................... 36 
10.4.3 
Baseline Descriptive Statistics..................................................................................... 36 
10.4.4 
Planned Interim Analyses ........................................................................................... 36 
10.4.5 
Exploratory Analyses .................................................................................................. 37 
10.5 
Sample Size ....................................................................................................................... 38 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ...................................... 38 
12 
QUALITY ASSURANCE AND QUALITY CONTROL ...................................................................... 38 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................................... 39 
13.1 
Ethical Standard ................................................................................................................ 39 
13.2 
Institutional Review Board ................................................................................................. 39 
13.3 
Informed Consent Process ................................................................................................. 39 
13.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............. 39 
13.3.2 
Consent Procedures and Documentation .................................................................... 39 
13.4 
Participant and Data Confidentiality .................................................................................. 40 
14 
DATA HANDLING AND RECORD KEEPING ............................................................................... 40 
14.1 
Data Collection and Management Responsibilities ............................................................. 40 
14.2 
Study Records Retention ................................................................................................... 41 
14.3 
Protocol Deviations ........................................................................................................... 41 
14.4 
Publication and Data Sharing Policy ................................................................................... 41 

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15 
STUDY ADMINISTRATION ...................................................................................................... 42 
15.1 
Study Leadership ............................................................................................................... 42 
16 
CONFLICT OF INTEREST POLICY .............................................................................................. 42 
17 
LITERATURE REFERENCES ...................................................................................................... 43 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE(s) 
Adverse Event(s) 
AGE 
Agarose Gel Electrophoresis 
ANOVA 
Analysis of Variance 
APC 
Antigen Presenting Cells 
aPTT 
activated Partial Thromboplastin Time 
BOR 
Best Overall Response 
CBC 
Complete Blood Count 
CD 
Cluster of Differentiation 
CFR 
Code of Federal Regulations 
CMP 
Comprehensive Metabolic Panel 
CR 
Complete Response = complete regression of all lesions 
CRA 
Clinical Research Associate 
CRF(s) 
Case Report Form(s) 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
Cytotoxic T-Lymphocyte-Associated Protein 4 
DCR 
Disease Control Rate 
DLT 
Dose-limiting Toxicity 
DM 
Data Management 
DMF 
Drug Master File 
EBV 
Epstein-Barr Virus 
ECG 
Electrocardiography 
ECOG 
Eastern Cooperative Oncology Group 
eCRF(s) 
electronic Case Report Form(s) 
E. coli 
Escherichia coli 
EtBr 
Ethidium Bromide (DNA stain) 
FTA 
Fluorescent Treponemal Antibody 
GAPDH 
Glyceraldehyde 3-Phosphate Dehydrogenase 
GCP 
Good Clinical Practice 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HEK293T 
Human Embryonic Kidney cells 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
HTLV 
Human T Lymphotropic Virus 1 & 2 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IHC 
Immunohistochemistry 
IFx-Hu2.0 
pAc/emm55 DNA plasmid combined with in vivo-jetPEI® in the presence of glucose 
INFγ 
Interferon Gamma 

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IRB 
Institutional Review Board 
LDH 
Lactate Dehydrogenase 
LTF 
Lost to Follow Up 
MCB 
Master Cell Bank 
MHC 
Major Histocompatibility Complex 
MM 
Medical Monitor 
NED 
No Evidence of Disease 
OD 
Optical Density 
ORR 
Overall (Objective) Response Rate 
OS 
Overall Survival  
pAc/emm55 
DNA plasmid encoding the emm55 gene 
pAc/empty 
pAc/emm55 DNA plasmid without the emm55 gene 
PBRS 
Peachtree Bioresearch Solutions, Inc. 
PBS 
Phosphate Buffered Saline 
PCR 
Polymerase Chain Reaction 
PD 
Progressive Disease = ≥ 20% increase in tumor burden 
PD-1 
Programmed Cell Death Protein 1 
PE 
Phycoerythrin 
PET 
Positron Emission Tomography 
PFS 
Progression-Free Survival 
PI 
Principal Investigator 
PT 
Prothrombin Time 
PR 
Partial Response = ≥ 30% decrease in tumor burden 
QC 
Quality Control 
RAB-AP01 
Anti-Emm55 Rabbit Polyclonal Antibody 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RPR 
Rapid Plasmin Reagin 
RTPCR 
Reverse Transcriptase Polymerase Chain Reaction 
SAE(s) 
Serious Adverse Event(s) 
SC 
Subcutaneous 
SCB 
Starter Cell Bank 
SEM 
Standard Error of the Mean 
SD 
Stable Disease = % change in tumor burden is between -30% and +20% 
SOP 
Standard Operating Procedure 
S. pyogenes 
Streptococcus pyogenes 
SumL 
Sum of the Longest Diameters 
TCR 
T Cell Receptor 
TE 
10 mM Tris-Cl, pH 8.0, 1 mM Ethylenediaminetetraacetic acid 
TEAE(s) 
Treatment-emergent adverse event(s) 
UP(s) 
Unexpected Adverse Drug Experience 
VCOG 
Veterinary Cooperative Oncology Group 
WCB 
Working Cell Bank 

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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46). The Principal Investigator will assure that no deviation 
from, or changes to the protocol will take place without prior agreement from the sponsor and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection Training. 
I agree to ensure that all staff members involved in the conduct of this study are informed about their 
obligations in meeting the above commitments. 
 
 
 
 
 
Principal Investigator:   
 
 
 
Signature:  
 
Date:   
 

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PROTOCOL SUMMARY 
Title 
Phase 1 Study Using a Plasmid DNA Coding for Emm55 
Streptococcal Antigen in Patients with Unresectable Stage III or 
Stage IV Cutaneous Melanoma 
Short Title 
pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma 
Protocol Number 
Melanoma 2017-01 
Phase 
Phase 1 
Methodology 
Non-randomized, open-label, uncontrolled 
Study Duration 
Approximately 1 year 
Study Center(s) 
Single-center 
Objectives 
Primary: To assess safety and feasibility 
Secondary: To assess any antitumor response 
Number of Subjects 
Six 
Diagnosis and Main Inclusion 
Criteria 
Male or female, confirmed stage III or stage IV unresectable 
melanoma with lesions accessible for intralesional injection 
Study Product, Dose, Route, 
Regimen 
Plasmid DNA encoding a Streptococcal antigen in a cationic 
polymer-based solution in doses of 100 µg delivered 
intralesionally at a single time point “Week 0” with a maximum 
of three lesions injected. The primary endpoint (DLT) will be 
assessed at 4 weeks. 
Optional dosing 
After primary endpoint has been met (DLT), at the 
investigator’s discretion in consultation with the sponsor, 
patients may receive 
additional doses on a 3-week cycle. 
Follow-up - Primary 
Week 4; Day 28+/-7 business days. 
Follow-up – Optional. 
21 days +/- 7 business days from last dose administered. 
Follow-up – Long-term 
Obtain OS/subsequent treatments for melanoma after MCC 
19500 as of 11/16/2020 for all patients with clinical response if 
available. 
Study Procedures 
Six patients will receive IFx-Hu2.0 on an outpatient basis at a 
single time point in a single lesion, two lesions, or three lesions, 
as a monotherapy (a maximum of three lesions could be 
injected). These patients will be assessed for any immediate 
adverse reactions and at Week 4 (Day 28+/-7 business days) for 
any delayed adverse events. 
After the primary endpoint has been met (DLT), patients may 
receive additional doses on an optional 3-week cycle. 
Duration of Administration 
Single time point with option for additional doses 
Potential Risks 
Other cancer vaccine trial results have reported patients 
experiencing reactions such as mild fever, skin reactions, sweats 
and chills, which are often described as “flu-like” symptoms. 
Reference Therapy 
None 

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Statistical Methodology 
The data analysis is described to assess the safety of the 
injection of the study agent in six patients The intention-to-treat 
approach will be used for response to treatment data analysis of 
this trial (secondary objective). The exploratory testing will 
be mainly descriptive in this pilot set of patients 

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SCHEMATIC OF STUDY DESIGN 
 
 
 
 
Screening 
 
 
 
 
 
 
 
 
 
 
Visit 1 (Week 0) 
 
 
 
 
 
 
 
 
 
Visit 2 (Week 4) -Final- 
 
 
 
 
Note: If patient consents to additional treatment, this may be performed every three weeks with a 21- 
day follow-up visit. 
 
Informed consent eligibility, Physical exam w/vitals, 
Medical history, Concomitant meds, Clinical labs, ECG, 
Tumor sample/biopsy for immune response assays, CT 
and/or PET scan, Performance Status, Tumor Burden 
(lesion measurements) 
Physical exam w/vitals, Concomitant meds, AEs/SAEs, IFx-Hu2.0 
dosing, Blood for Immune Response Evaluation(baseline), Clinical 
labs, Performance Status, Tumor Burden 
Physical exam w/vitals, Concomitant meds, AEs/SAEs, 
Clinical labs, ECG, Blood for Immune Response Evaluation, 
Tumor sample/biopsy for histology and IHC, CT and/or PET 
scan, Performance Status, Tumor Burden 

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1. KEY ROLES 
Sponsor Contact 
Patricia Lawman, PhD 
Chief Executive Officer 
Morphogenesis, Inc 
10500 University Center Drive, Suite 110 
Tampa, FL 33612 
T: 813-875-6600 
E: PLawman@morphogenesis-inc.com 
 
Principle Investigator 
Joseph Markowitz, MD, PhD 
Medical Oncologist; Assistant Member-Department of Cutaneous Onc. 
H. Lee Moffitt Cancer Center 
12902 USF Magnolia Drive 
Tampa, FL 33612 
T: 813-745-4673 
E: Joseph.Markowitz@moffitt.org 
 
Clinical Laboratory 
Clinical Pathology Laboratory 
H. Lee Moffitt Cancer Center 
12902 USF Magnolia Drive 
Tampa, FL 33612 
T: 813-745-4673 
Data Collection 
Clinical Trials Office 
H. Lee Moffitt Cancer Center 
12902 USF Magnolia Drive 
Tampa, FL 33612 
T: 813-745-4673 
Data Management 
Peachtree BioResearch Solutions 
4985 Lower Roswell Rd, Bldg, 100 
Marietta, GA 30068 
T: 678-373-4660 
Study Statistician 
Dion Chen 
Peachtree Bioresearch Associates, Inc. 
4985 Lower Roswell Road 
Marietta, GA 30068 
 
 
 
 
     T: 678-373-4660 
 
Secondary Statistician for  
exploratory correlative data: 
     Youngchul Kim, PhD 
H. Lee Moffitt Cancer Center 
12902 USF Magnolia Drive 
Tampa, FL 33612 
T: 813-745-4673 
 

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2. INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 Background Information 
 
Chen and Mellman described what they termed the Cancer-Immunity Cycle, a series of stepwise events 
that must be carried out for an effective anticancer immune response to occur (Chen and Mellman 2013). 
These events must be initiated, allowed to proceed and then to expand. In the first step of this process 
neoantigens created by the accumulation of genetic alterations during oncogenesis must be released and 
captured by antigen presenting cells (APC), a process that must be accompanied by specific signals such 
as cytokines. We plan to optimize cancer immunity by intervening at the first step of the cycle. 
Emm55 is a serotyping protein normally expressed on the surface of the bacterium Streptococcus 
pyogenes (S. pyogenes) and is highly antigenic (Glikin and Finocchiaro 2014, Ramiya, Jerald et al. 2014). 
Intralesional injection of a novel plasmid DNA vaccine expressing the Emm55 protein derived from S. 
pyogenes showed clinical efficacy in an equine metastatic melanoma (Ramiya, Jerald et al. 2014). By 
utilizing a bacterial (foreign) antigen, it is possible to expose ‘self’ tumor antigens and overcome tolerance 
to them, regardless of their number or uniqueness. This can be done by transfecting the pAc/emm55 
plasmid into tumor cells ex vivo and administering the resultant ‘personalized’ whole-cell vaccine as an 
intradermal injection. It is also possible to create a ‘personalized’ vaccine by injecting the pAc/emm55 
plasmid DNA directly into a patient’s lesion. In this way, an immune response is initiated to the 
neoantigens relevant to each individual patient without the difficulties involved in developing 
individualized targeted therapies. 
The product being tested in this clinical study, IFx-Hu2.0, is a plasmid DNA, pAc/emm55, formulated with 
in vivo-jetPEI®, a cationic polymer that aids in cellular uptake of DNA, will be administered by intralesional 
injection. IFx-Hu2.0 is a cancer immunotherapy that stimulates the immune system to fight cancer. When 
introduced into a patient’s tumor cells, pAc/emm55 drives expression of the highly immunogenic Emm55 
protein in the cytoplasm and on the surface of the tumor cells. In this protocol, IFx-Hu2.0 will be utilized 
as a monotherapy in a feasibility study prior to combining it with checkpoint blockade. 
Cancer immune evasion transpires when two events occur: 1) immune surveillance fails to recognize the 
alterations and abnormalities of tumors and 2) tumors take advantage of inhibitory pathways which are 
hardwired into the immune system for avoiding autoimmunity (Chen and Mellman 2013). Surface 
expression of the Emm55 antigen through intralesional injection of pAc/emm55 engages the patient’s 
immune system and thwarts the tumor’s ability to evade surveillance by exposing multiple patient- 
specific tumor antigens and activating a wide array of naïve T cells. 
IFx-Hu2.0 primes the immune response to a broad array of patient-specific tumor antigens. Due to the 
antitumor response being directed specifically against abnormal tumor proteins, there have been no 
reported side effects associated with this therapy. However, when breaking tolerance to tumor- 
associated antigens, which are ‘self’ antigens, there is a possibility of inducing some form of 

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autoimmunity. Patients receiving other cancer vaccine therapies have experienced reactions including 
mild fever, skin reactions, sweats and chills, tachypnea and hypotension.  
2.2 Rationale 
The Emm55 Antigen 
 
M proteins, the cell surface antigens responsible for the M serospecificities of S. pyogenes, are encoded 
by emm genes. Emm55 is one of hundreds of M proteins. Anchored in the S. pyogenes cell wall, M proteins 
mediate adhesion to host cells and connective tissues as well as bacterial cell invasion. M proteins act as 
antiphagocytic factors which are crucial for defense against human innate immunity (Nitsche-Schmitz, 
Rohde et al. 2007). Due to high variability at the N-terminal region of M proteins, there have been more 
than 200 distinct types recorded in public databases. M proteins have been considered as vaccine 
candidates against group A Streptococcal-mediated strep throat and suppurative skin diseases (Dale, 
Smeesters et al. 2017). However, some M proteins bind collagen and may cause side effects such as acute 
rheumatic fever in humans through molecular mimicry of collagen (Dinkla, Nitsche- Schmitz et al. 2007). 
Emm55, though, has been shown not to bind collagen due to the conformational influences of flanking 
sequences (Reissmann, Gillen et al. 2012). In the IFx-Hu2.0 vaccine, the Emm55 protein acts as an 
immunologic priming antigen aimed at attracting the patient’s immune system to tumor cells. 
The product being tested in this clinical study, IFx-Hu2.0, is designed to exploit the inherent vulnerability 
of specific differences from patient to patient, lesion to lesion, and cell to cell. Regardless of the degree of 
complexity of an individual’s antigenic signature, this truly patient-specific approach capitalizes on the 
antigenic differences to create the broadest immune response possible. By introducing the emm55 gene 
from S. pyogenes into a patient’s tumors by intralesional injection, the highly immunogenic Emm55 
protein is expressed on tumor cells and initiates an immune cascade leading to the activation of multiple 
immune cells, including cytotoxic T cells. However, optimal T cell responses may be abrogated by tightly 
regulated inhibitory immune checkpoints whose job is to avoid collateral damage and autoimmunity.  The 
interplay between antigen presentation/T cell activation and T cell suppression is critically  important in 
determining the outcome of immunotherapeutic interventions. The goal of this study is to determine the 
feasibility of providing the IFx-Hu2.0 injections prior to combining this agent with checkpoint blockade in 
future clinical trials. The goal is to initiate a self-sustaining cycle of cancer immunity, enabling it to amplify 
and propagate. 
2.3 Potential Risks and Benefits 
 
2.3.1. Known Potential Risks 
 
IFx-Hu2.0 primes the immune response to a broad array of patient-specific tumor antigens. Due to the 
antitumor response being directed specifically against abnormal tumor proteins, there have been no 
reported side effects associated with this therapy. However, when breaking tolerance to tumor- 
associated antigens, which are ‘self’ antigens, there is a possibility of inducing some form of autoimmunity. 
Patients receiving other cancer vaccine therapies have experienced reactions including mild fever, skin 
reactions, sweats and chills, tachypnea and hypotension. However, the effectiveness and side effects of 
immunotherapies are bound by the same biological mechanisms and there may be an increased risk of 
autoimmunity with the IFx-Hu2.0. 

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2.3.2. Known Potential Benefits 
 
The therapeutic antitumor effect of intralesional injections of pAc/emm55 has been evaluated in horses 
with malignant melanoma, in C57BL/6 B16 tumor-bearing mice and companion animals with various types 
of cancers. Whether the plasmid DNA was formulated with water, TE buffer or in vivo-jetPEI® or injected 
with a tuberculin syringe and needle or a needleless injector, the study results support the hypothesis that 
pAc/emm55, when injected into tumor lesions in vivo, is expressed as an immunogenic Emm55 protein 
that stimulates a multi-pronged immune attack on tumor cells that is clinically beneficial. Further, no 
adverse events were reported in any of the 200+ animals receiving intralesional  or intranodal injections 
of pAc/emm55 plasmid DNA. Based on the results of these studies, Morphogenesis believes that 
pAc/emm55 may have significant antitumor activity and will be well tolerated in human patients with 
melanoma. 
 
3 OBJECTIVES AND PURPOSE 
3.1 Primary Objective 
Safety; i.e., to assess the safety, tolerability, and feasibility of vaccination with IFx-Hu2.0 as a monotherapy 
in patients with unresectable stage III or stage IV cutaneous melanoma. 
3.2 Secondary Objective(s) 
The secondary objectives include the evaluation of response rate and assessment of the antitumor 
immune responses induced by IFx-Hu2.0 in patients treated with this vaccine. 
 
4 STUDY DESIGN AND ENDPOINTS 
4.1 Description of the Study Design 
 
Six male and/or female adult patients (greater than or equal to 18 years old), of any ethnicity and race, 
with unresectable stage III or stage IV cutaneous melanoma with accessible lesions, will be eligible for 
enrollment and treatment with IFx-Hu2.0. Pediatric melanoma is quite rare and the National Cancer 
Institute estimates that approximately 500 children are diagnosed per year. The potential for 
development of this product for pediatric subjects with melanoma will be evaluated after the results of 
this study are available. 
To be eligible for this study, patients with unresectable metastatic disease must have failed, refused or 
been deemed not candidates for at least one form of systemic anti-PD-1-based immunotherapy as well as 
BRAF inhibition, if BRAF V600 mutated. 
Talimogene laherparepvec (IMLYGIC®) is indicated for local treatment of unresectable cutaneous, 
subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Therefore, 
patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after initial 
surgery must have failed, refused or been deemed not candidates for talimogene laherparepvec to be 
eligible for this study. 

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Enrollees will receive IFx-Hu2.0 at a single time point. Depending on the number of accessible lesions, a 
patient could receive up to three doses across three lesions (one dose per lesion). Forty millilters of 
peripheral blood will be collected from these patients prior to treatment administration and at the follow-
up visit four weeks later. The target dose will be 100 μg of plasmid DNA per lesion injected at a final dose 
volume of 200 μL per lesion. To allow for the observation of any acute toxicity in the first subject enrolled 
and prevent any occurrence of excessive toxicities in subsequent subjects, the first subject enrolled will 
receive a single dose of IFx-Hu2.0. Subsequent subjects will be administered the product after at least 
seven days. Beyond the first subject, the maximum number of lesions to be injected at any given time 
point in the study phase proposed is three lesions. These samples will be used to perform complete blood 
counts (CBC) and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and 
blood at the same frequency. Blood samples will be drawn for immune response evaluation as well. 
Peripheral blood collections, and where feasible, as determined by PI, tumor biopsies may be obtained on 
the first and subsequent treatment cycles. At the end of the study period a biopsy of the lesion injected 
and a non-injected lesion (if applicable) will be collected. At the discretion of the PI in consultation with 
the Sponsor, the patient will have the option of continuing the study at three-week intervals so long as 
the subject under study has not progressed. 
4.2 Study Endpoints 
 
4.2.1 Primary Endpoint 
 
The primary endpoints of this trial will be the safety and feasibility of the treatment regimen. Safety will 
be reported using Common Terminology Criteria for Adverse Events (CTCAE) version5.0. Feasibility will be 
defined as the ability to treat at least five of the six patients enrolled without dose-limiting toxicity (DLT). 
4.2.2 Secondary Endpoints 
 
The secondary endpoint consists of observing and monitoring objective response rates and, although not 
needed for the conclusion of this study, progression-free survival (PFS) will also be recorded when 
indicated. Patients who consent to additional injection cycles will be observed for toxicity over time. 
4.2.3 Exploratory Endpoints 
 
Exploratory endpoints include laboratory correlative studies including the laboratory based assessment of 
tumor-specific immunity. 
5 STUDY ENROLLMENT AND WITHDRAWAL 
5.1 Participant Inclusion Criteria 
 
1. Histologically confirmed unresectable stage III or stage IV malignant melanoma, with accessible 
cutaneous lesions 
2. Must have measurable disease greater than 3 mm 
3. At least one injectable lesion and one lesion for biopsy at study conclusion. Lymphocyte count ≥ 
500,000 cells/mL 
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
5. Willing and able to give written, informed consent 

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6. If male or female of childbearing potential must be willing to use a contraceptive during the study 
and for six months afterward. A woman is considered to be of child bearing potential unless she 
as had a surgical procedure that would accomplish sterility such a bilateral tubal ligation, 
hysterectomy or has not had menses for the past 12 months. 
7. Life expectancy greater than three months 
8. To be eligible for this study, patients with unresectable metastatic disease must have failed, 
refused or been deemed not candidates for at least one form of systemic anti-PD-1-based 
immunotherapy as well as BRAF inhibition, if BRAF V600 mutated. 
9. Patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after 
initial surgery must have failed, refused or been deemed not candidates for talimogene 
laherparepvec to be eligible for this study. 
10. The entry laboratory criteria for subject eligibility must be less than or equal to grade 1 adverse 
event levels for the parameters tested as defined by CTCAE v5.0: 
o Bone Marrow Function 
▪ 
HGB = <LLN - 10.0 g/dL; <LLN - 6.2 mmol/L; <LLN - 100 g/L 
▪ WBC = <LLN - 3000/mm3; <LLN - 3.0 x 109/L 
▪ PLT = <LLN - 75,000/mm3; <LLN - 75.0 x 109/L 
o Coagulation Parameters 
▪ 
INR = >1 - 1.5 x ULN 
▪ 
aPTT = >ULN - 1.5 x ULN 
o Renal Function 
▪ 
Creatinine = >ULN - 1.5 x ULN 
o Liver Function: 
▪ 
Bilirubin = >ULN - 1.5 x ULN 
▪ 
ALT = >ULN - 3.0 x ULN 
▪ 
AST = >ULN - 3.0 x ULN 
▪ 
ALP = >ULN - 2.5 x ULN 
▪ 
GGT = >ULN - 2.5 x ULN 
5.2 Participant Exclusion Criteria 
 
1. Known brain metastases greater than 1 cm at screening. 
2. Life expectancy of fewer than three months 
3. Prior systemic anti-cancer treatment within three weeks from start of treatment (Day 0) 
4. Current treatment with systemic immunosuppressive corticosteroid (greater than 10 mg of daily 
prednisone) doses or other immunosuppressants such as those needed for solid organ 
transplants. Medications needed to treat conditions such as reactive airway disease are not 
excluded. 
5. Pregnant or lactating women 
6. Presence of any uncontrolled and significant medical or psychiatric condition which would 
interfere with trial safety assessments 
7. Treatment with any investigational product within the three weeks preceding injection 
8. Immunizations for encapsulated bacteria were not given for patients who have undergone a 
splenectomy. 
9. Serious underlying medical or psychiatric conditions, active infections requiring the use of 
antimicrobial drugs, or active bleeding that would make the subject unsuitable or unable to 

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participate in the study 
10. Concurrent chemotherapy or biological therapy. Concurrent radiotherapy is allowed as long as it 
is not the same site as the injected lesion. 
11. Uncontrolled hepatitis B, hepatitis C, or HIV infection 
12. History of organ allograft transplantation 
5.3 Strategies for Recruitment and Retention 
 
This study will have a goal of six evaluable patients. It is the intent of the study team to recruit an additional 
two patients to be screened and enrolled if any of the existing patients are lost to follow-up, withdraw 
consent or exhibit disease progression. 
5.4 Participant Withdrawal or Termination 
 
5.4.1 Reasons for Withdrawal or Termination 
 
Participants are free to withdraw from participation in the study at any time upon request. An 
investigator may terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant. 
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
5.4.2 Handling of Participant Withdrawal or Termination 
 
Every effort will be made to undertake protocol-specified safety follow-up procedures to capture AEs, 
serious adverse events (SAEs), and unexpected adverse drug experience. Participant replacement will be 
permitted at the discretion of the Principal Investigator (PI). 
5.5 Premature Termination or Suspension of Study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to the PI, the IND sponsor, and regulatory authorities.  If the study 
is prematurely terminated or suspended, the PI will promptly inform the institutional review board (IRB) 
and will provide the reason(s) for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of AEs or SAEs that would warrant stopping 
• 
Insufficient compliance with protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed 
and satisfy the sponsor, IRB and/or the Food and Drug Administration (FDA). 

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6 STUDY AGENT 
6.1 Study Agent(s) Description 
 
6.1.1 Acquisition 
 
The manufacture of the drug substance (pAc/emm55) plasmid DNA will be conducted at Aldevron (Fargo, 
North Dakota). The mixing of the Investigational Product components (plasmid DNA, cationic polymer and 
glucose) for this Phase 1 study will be conducted at the clinical site pharmacy. 
6.1.2 Formulation, Appearance, Packaging, and Labeling 
 
The final Investigational Product is manufactured as a vaccine kit containing three vials; Vial 1- plasmid 
DNA, Vial 2- cationic polymer and Vial 3- glucose that are mixed at the clinical site in preparation for 
injection. This process is patient-specific and will occur at each clinical visit for each patient. The following 
table lists the final composition of Investigational Product, IFx-Hu2.0. 
 
 
Component 
Description 
Purpose 
Plasmid DNA 
Mammalian expression plasmid containing emm55 gene 
(pAc/emm55) in TE buffer (0.5 mg/mL) 
Drug substance 
Cationic Polymer 
Polyplus-transfection in vivo-jetPEI® cationic polymer 
(0.72 mg/mL) 
Excipient; cellular 
uptake of plasmid 
DNA 
Glucose 
5% Dextrose solution, USP 
Excipient; DNA- 
polymer complex 
stability 
 
6.1.3 Product Storage and Stability 
 
The final Investigational Product will be injected intralesionally within four hours of the final formulation 
at the pharmacy. A more comprehensive product stability assessment will be part of this Phase 1 study. 
6.1.4 Preparation 
 
Described below is the preparation of IFx-Hu2.0 Investigational Product intralesional injection using a 
vaccine kit that contains; (1) Vial 1-pDNA (drug substance), (2) Vial 2- cationic polymer (excipient), and 
(3) Vial 3-glucose (excipient). These components will be provided by Morphogenesis to the Pharmacy for 
mixing on site as per USP <797> guidelines for single-dose containers. When possible, the preparation 
should be performed in an ISO 5/Class 100 environment. The vaccine kits are stored at 2-8oC until 
preparation is performed. All components will have accompanying Certificates of Analysis. 
1. Incubate kit at room temperature (RT) for 30-60 minutes prior to mixing 
2. Place mixed final product label, provided in Bag 1 of kit, on Vial 1 
3. Remove flip cap from vials, wipe the exposed septum with alcohol as per standard clinical 
pharmacy procedures, and then draw up 0.1 mL of Vial 3 into a ½ mL tuberculin (TB) syringe 

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provided with kit 
4. Place Vial 1 upright on a flat surface, and using aseptic technique, insert needle and inject Vial 3 
solution into Vial 1, before removing the needle pull back on the syringe to release any pressure 
5. Using a new ½ mL TB syringe, provided with kit, draw up 0.2 mL of Vial 3 and inject solution into 
Vial 2 using the same technique described in Steps 3 & 4 
6. Vortex Vial 1 & Vial 2 individually at the “8” setting for five seconds, if this step is performed 
outside of the ISO 5 environment wipe vial septum with alcohol as performed in Step 3 
Note: This is a CRITICAL step to ensure complexes form properly 
7. Using a new ½ mL TB syringe, provided with kit, draw up 0.2 mL of Vial 2 and inject contents into 
Vial 1 using the same technique described in Steps 3 & 4 
8. Gently vortex Vial 1 using the same technique described in Step 6 
9. Allow to incubate at room temperature for 15 minutes; the mixed solution is stable for 4 hours 
at room temperature after components are combined 
10. The final drug product is now ready for intralesional administration using a TB syringe, supplied 
at the clinical pharmacy, at a dose of 0.2 mL/lesion 
11. The used vials should be placed in the designated biohazard bag, provided in the kit, and 
returned to Morphogenesis 

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6.1.5 Dosing and Administration 
 
The target dose will be 100 µg of plasmid DNA per lesion injected at a final dose volume of 0.2 mL per 
lesion. The maximum number of lesions to be injected at any given time point in the study phase proposed 
is three lesions. 
6.1.6 Route of Administration 
 
Intralesional injections using 1 mL tuberculin syringes. 
6.1.7 Starting Dose and Dose Escalation Schedule 
 
The dose/lesion treated will be constant through this study: 100 µg of plasmid DNA per lesion injected  at 
a final dose volume of 0.2 mL. However, depending on the subject, one, two, or three lesions would be 
injected at a time. 
The subjects will receive IFx-Hu2.0 at a single time point as a monotherapy. These patients will then be 
observed for any dose-limiting toxicity or adverse events for up to four weeks. The maximum number of 
lesions to be injected in this study is three lesions. 
6.1.8 Dose Adjustments/Modifications/Delays 
 
No dose adjustments or modifications will be part of this study phase. However, the protocol will allow 
for delays of up to 7 business days to accommodate participant clinic visit rescheduling due to any 
unforeseen circumstances. 
6.1.9 Duration of Therapy 
 
Participants enrolled in the study will receive IFx-Hu2.0 at a single time point. After primary endpoint 
has been met (DLT), at the investigator’s discretion in consultation with the sponsor, patients may 
receive additional doses on a 3-week cycle. 
6.1.10 Tracking of Dose 
 
Once the final Investigational Product is formulated, patient-specific labeling will be affixed showing two 
unique identifiers. 
6.2 Study Agent Accountability Procedures 
 
The final Investigational Product mixing involves the drug substance (pAc/emm55 plasmid DNA in TE 
buffer) with the remaining components; cationic polymer and glucose. This mixing of the final 
Investigational Product components will occur at the clinical site pharmacy. Once the final Investigational 
Product is prepared, patient-specific labeling will be affixed showing two unique identifiers. Any excess 
product will be de-identified and returned to Morphogenesis for laboratory studies. 

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7 STUDY PROCEDURES AND  SCHEDULE 
7.1 Study Procedures/Evaluations 
 
7.1.1 Study-specific Procedures 
 
• 
Medical history through interview and/or medical records review 
• 
Medication history to include current prescription and over-the-counter medications; a review 
of current medications will be part of the assessment of eligibility 
• 
Physical examination 
• 
Radiographic or other imaging assessments (photographs) 
• 
Biological specimen collection and laboratory evaluations; blood draws and urine collections will 
be made at each of the clinical visits in addition to tissue tumor tissue collection for research 
purposes. 
• 
A discussion of the results of any study-specific procedures will be provided to the participant 
• 
Assessment of adherence to study requirements and instructions 
• 
Collection of data on gender, race and ethnicity 
7.1.2 Standard-of-care Study Procedures 
 
Subjects will receive IFx-Hu2.0 as a monotherapy at a single time point and will be assessed for a period 
of four weeks. Once the four-week period expires and the toxicity/safety assessments have been 
completed, these patients will transition into standard-of-care or clinical trial protocols as determined by 
the PI and the clinical team. If the patient comes off study, PFS will need to be censored, but the time to 
first progression will be obtained during subsequent follow-up with the patient’s consent. If the patient 
has a response to therapy, the patient will have the option of continuing the study at three-week intervals 
at the discretion of the PI in consultation with the Sponsor. In this setting, PFS will be measured in the 
traditional way. Where feasible, as determined by PI, tumor biopsies and peripheral blood collections may 
be obtained on subsequent treatment cycles. 
7.2 Laboratory Procedures/Evaluations 
 
7.2.1 Clinical Laboratory Evaluations 
• 
Hematology: (Complete Blood Count - CBC) hemoglobin, hematocrit, white blood cells (WBC) 
with differential count, platelet count, blood clotting tests; prothrombin time (PT) and activated 
partial thromboplastin time (aPTT) 
• 
Biochemistry (Comprehensive Metabolic Profile - CMP): glucose, calcium, albumin, total protein, 
sodium, potassium, CO2, chloride, BUN, creatinine, total bilirubin, alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase 
(LDH), Thyroid tests (TSH and FT4) 
• 
Urinalysis: UA with microscopic evaluation 
• 
Serum pregnancy test, done within 24 hours prior to Investigational Product administration, and 
results must be available prior to administration of Investigational Product 
• 
Human leukocyte antigen (HLA) typing 

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• 
Serology screening for HBV, HCV, HIV, HTLV, EBV and T. pallidum (RPR); fluorescent treponemal 
antibody absorption (FTA-ABS), if necessary 
• 
Immunodeficiency Panel 
• 
Anti-double-stranded DNA (anti-dsDNA) antibody test 
• 
Anti-DNase B Titer, Serum 
7.3 Study Schedule 
 
7.3.1 Screening 
 
Screening Visit (Day -36 to -1) 
• 
Obtain informed consent of potential participant verified by signature on study informed 
consent form. 
• 
Verify inclusion/exclusion criteria. 
• 
Review medical history to determine eligibility based on inclusion/exclusion criteria. 
• 
Review medications history to determine eligibility based on inclusion/exclusion criteria. 
• 
Record Concomitant Medications. 
• 
Perform medical examinations needed to determine eligibility based on inclusion/exclusion 
criteria. 
• 
CT as clinically indicated and/or PET scan. Photographs may be utilized for melanoma confined 
to the skin. 
• 
Electrocardiogram (ECG) 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count; blood clotting tests: prothrombin time (PT) and activated partial 
thromboplastin time (aPTT) 
o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), 
Thyroid tests (TSH and FT4) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test: done within 24 hours prior to Investigational Product 
administration, and results must be available prior to Investigational Product 
administration 
o Human leukocyte antigen (HLA) typing 
o Serology screening for HBV, HCV, HIV, HTLV, EBV and T. pallidum (RPR); fluorescent 
treponemal antibody absorption (FTA-ABS), if necessary 
o Immunodeficiency Panel 
o Anti-double-stranded DNA (anti-dsDNA) antibody test 
o Anti-DNase B Titer, Serum 
• 
Where feasible, as determined by PI, research study biopsy for histology and/or immune 
response assays may be collected at the screening visit or the baseline visit. PI may also elect to 
use archival tumor at baseline. 

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o In the setting of known melanoma, archival tumor tissue may be utilized to confirm the 
diagnosis (Moffitt or from external source). 
o In this case, two 4-micron slices (positive charged slides, air dry overnight). are required 
for research IHC experiments under the direction of Dr. Markowitz. 
o The H&E stained slide from the biopsy may be digitally scanned. 
o For all portions of this protocol, fresh research biopsies will be obtained using a punch 
or shave biopsy technique. These samples will be placed in PBS or formalin and utilized 
for research purposes. The portion of the tissue divided for the PBS portion will be flash 
frozen and utilized for downstream assays. Dr. Markowitz will assess whether the tumor 
is of adequate size to split into two parts (PBS and formalin). 
• 
Assessment and recording of ECOG Performance Status. 
• 
Assessment and recording of Tumor Burden (lesion measurements). 
• 
Schedule study visits for participants who are eligible and available for the duration of the study. 
• 
Provide participants with general study procedures and instructions for clinical visits 
7.3.2 Enrollment / Baseline 
 
Enrollment/Baseline Visit (Visit 1, Day 0) 
• 
Obtain demographic information, medical history, medication history, alcohol and tobacco use 
history. 
• 
Record Concomitant Medications. 
• 
Record vital signs, results of physical examination, other assessments. 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count 
o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test: done within 24 hours prior to Investigational Product 
administration, and results must be available prior to Investigational Product 
administration 
o 40 mL of blood will be collected for research purposes in the laboratory of Dr. Joseph 
Markowitz, including immune response baseline evaluation. 
• 
Where feasible, as determined by PI, research study biopsy for histology and/or immune 
response assays may be collected at the screening visit or the baseline visit. 
• 
Administer the Investigational Product. 
• 
Assessment and recording of ECOG Performance Status 
• 
Assessment and recording of Tumor Burden (lesion measurements) 
• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
7.3.3 Optional Study Visits (for multiple dose cycle only) 
 
(Week 4 Day 28 +/-7 business days) 

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• 
Record vital signs, results of physical examination, other assessments 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count; blood clotting tests: prothrombin time (PT), activated partial 
thromboplastin time (aPTT) 
o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH); 
thyroid tests: (TSH and FT4) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test: done within 24 hours prior to Investigational Product 
administration, and results must be available prior to Investigational Product 
administration 
o 40 mL of blood will be collected for research purposes in the laboratory of Dr. Joseph 
Markowitz, including immune response evaluation. 
• 
Optional research study biopsy for histology and immune response assays may be collected. 
• 
Administer the Investigational Product. 
• 
Assessment and recording of ECOG Performance Status 
• 
Assessment and recording of Tumor Burden (lesion measurements) 
• 
Assessment and recording of Concomitant Medications 
• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
• 
CT as clinically indicated and/or PET scan (photographs may be utilized for melanoma confined 
to the skin) 
(Week 7 Day 49 +/-7 business days) 
• 
Record vital signs, results of physical examination, other assessments 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count 
o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test: done within 24 hours prior to Investigational Product 
administration, and results must be available prior to Investigational Product 
administration 
o 40 mL of blood will be collected for research purposes in the laboratory of Dr. Joseph 
Markowitz, including immune response evaluation. 
• 
Optional research study biopsy for histology and immune response assays may be collected. 
• 
Administer the Investigational Product. 
• 
Assessment and recording of ECOG Performance Status 
• 
Assessment and recording of Tumor Burden (lesion measurements) 
• 
Assessment and recording of Concomitant Medications 

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• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
7.3.4 Final Study Visit 
 
(Week 4 Day 28 +/-7 business days for Single Dose Cycle) 
 
OR 
(Week 21 +/- 7 business after the last dose for Multiple Dose Cycle) 
• 
Record vital signs, results of physical examination 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count; blood clotting tests: prothrombin time (PT), activated partial 
thromboplastin time (aPTT) 
o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH); 
thyroid tests: (TSH and FT4) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test 
o Anti-double-stranded DNA (anti-dsDNA) antibody test 
o Anti-DNase B Titer, Serum 
o 40 mL of blood will be collected for research purposes in the laboratory of Dr. Joseph 
Markowitz, including immune response evaluation. 
• 
Tumor sample biopsy of injected lesion for histology and immune response assays 
• 
Biopsy of non-target lesion (if applicable) 
• 
Assessment and recording of ECOG Performance Status 
• 
Assessment and recording of Tumor Burden (lesion measurements) 
• 
Assessment and recording of Concomitant Medications 
• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
• 
CT as clinically indicated and/or PET scan (photographs may be utilized for melanoma confined 
to the skin) 
 
Overall Survival Status:  Long Term Follow-up   
• 
On 11/16/2020 (± 4 weeks), the survival status and subsequent anti-cancer therapy since last being 
seen on trial will be obtained from the EMR. Subsequent therapies will be documented from the 
EMR for melanoma (immune-based therapy, chemotherapy, radiation, surgery) with clinical 
response if available.   
7.3.5 Early Termination Visit 
 
• 
Record vital signs, results of physical examination 
• 
Collect blood/urine for: 
o Hematology: CBC - hemoglobin, hematocrit, white blood cells (WBC) with differential 
count, platelet count; blood clotting tests: prothrombin time (PT), activated partial 
thromboplastin time (aPTT) 

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o Biochemistry: CMP - glucose, calcium, albumin, total protein, sodium, potassium, CO2, 
chloride, BUN, creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH); 
thyroid tests: (TSH and FT4) 
o Urinalysis: UA with microscopic evaluation 
o Serum pregnancy test 
o Anti-double-stranded DNA (anti-dsDNA) antibody test 
o Anti DNAse B Titer, Serum 
o 40 mL of blood will be collected for research purposes in the laboratory of Dr. Joseph 
Markowitz, including immune response evaluation. 
• 
Tumor sample biopsy of injected lesion for histology and immune response assays 
• 
Biopsy of non-target lesion (if applicable) 
• 
Assessment and recording of ECOG Performance Status 
• 
Assessment and recording of Tumor Burden (lesion measurements) 
• 
Assessment and recording of Concomitant Medications 
• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
• 
CT as clinically indicated and/or PET scan (photographs may be utilized for melanoma confined 
to the skin) 
7.3.6 Unscheduled Visit 
 
• 
Record vital signs, results of targeted physical examination as indicated. 
• 
Collect blood/urine/research biopsies as indicated, at the discretion of the Investigator. 
• 
Assessment and recording of Concomitant Medications 
• 
Observation and recording of adverse or serious adverse events as defined by CTCAE v5.0 
• 
Assessment and recording of ECOG Performance Status 
 
 

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7.3.7 Schedule of Events Table 
 
Schedule of Events Table 
Schedule of Events: (Single dose cycle scenario) 
Procedure 
Screening 
(Day -36 to -1) 
Week 0 
(D=0) 
Week 4** 
(D=28)* 
Unscheduled 
visit 
Early 
Termination 
Visit 
Long-term 
Follow-up1 
Informed consent 
eligibility 
X 
 
 
 
 
X 
Physical exam w/vitals 
X 
X 
X 
X 
X 
 
Medical history 
X 
 
 
X 
X 
X 
Concomitant meds. 
X 
X 
X 
X 
X 
 
AEs/SAEs 
X 
X 
X 
X 
X 
 
IFx-Hu2.0 dosing 
 
X 
 
 
 
 
Blood for Immune 
Response 
Evaluation 
 
X 
X 
X 
X 
 
***Clinical labs 
 
 
 
 
 
 
CBC, CMP 
X 
X 
X 
X 
X 
 
LDH 
X 
X 
X 
X 
X 
 
Blood clotting tests 
(PT/PTT) 
X 
 
X 
 
X 
 
HLA typing 
(if not previously 
reported) 
X 
 
 
 
 
 
EBV ab 
X 
 
 
 
 
 
Hepatitis B and C, 
HTLV-1 & 2 
X 
 
 
 
 
 
HIV, RPR (FTA if 
necessary) 
X 
 
 
 
 
 
Thyroid Tests (Free T4, 
TSH) 
X 
 
X 
 
X 
 
Serum Pregnancy Test 
X 
X 
X 
 
X 
 
Immunodeficiency 
Panel 
X 
 
 
 
 
 
Urinalysis 
X 
X 
X 
X 
X 
 
Anti-double-stranded 
DNA 
(anti-dsDNA) 
X 
 
X 
 
X 
 
Anti-DNAse B Titer 
Serum 
X 
 
X 
 
X 
 

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ECG 
X 
 
 
 
 
 
Optional Tumor 
sample/biopsies for 
immune 
response assays 
X 
X 
X 
X 
X 
 
Optional Tumor 
sample/biopsies for 
histology 
X 
 
X 
X 
X 
 
CT and/or PET scan 
(Photographs may be 
utilized for melanoma 
confined to the 
skin) 
X 
 
X 
 
X 
 
Performance Status 
X 
X 
X 
X 
X 
 
Tumor Burden (lesion 
measurements) 
X 
X 
X 
X 
X 
 
Confirmation of 
histology by Moffitt 
(may use archival 
tissue) 
X 
 
 
 
 
 
Overall Survival 
 
 
 
 
 
X 
* +/-7 business days; **Final study visit; ***Screening labs may be performed within 7 days of treatment. 
 
1 A long-term follow-up on 11/16/2020 (± 4 weeks) that includes the survival status and subsequent anti-
cancer therapy since last being seen on trial will be obtained from the EMR. Subsequent therapies will be 
documented from the EMR for melanoma (immune-based therapy, chemotherapy, radiation, surgery) with 
clinical response if available. 
 
 

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Schedule of Events: (optional multiple dose cycle scenario, sample schedule for 3 cycles) 
Procedure 
Screening 
(Day -36 
to -1) 
Week 0 
(D=0) 
Week 4 
(D=28)* 
Week 7 
(D=49)* 
visit (21 
days 
after 
last dose 
Unscheduled 
Visit 
Early 
Term Visit 
Long-term 
Follow-up1 
Informed consent 
Eligibility 
X 
 
 
 
 
 
 
X 
Physical exam 
w/vitals 
X 
X 
X 
X 
X 
X 
X 
 
Medical history 
X 
 
 
 
 
X 
X 
X 
Concomitant 
meds. 
X 
X 
X 
X 
X 
X 
X 
 
AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
 
IFx-Hu2.0 dosing 
 
X 
X 
X 
 
 
 
 
Blood for Immune 
Response 
Evaluation 
 
X 
X 
X 
X 
X 
X 
 
***Clinical labs 
 
 
 
 
 
 
 
 
CBC, CMP 
X 
X 
X 
X 
X 
X 
X 
 
LDH 
X 
X 
X 
X 
X 
X 
X 
 
Blood clotting 
tests 
(PT/PTT) 
X 
 
X 
 
X 
 
X 
 
HLA typing 
(if not previously 
reported) 
X 
 
 
 
 
 
 
 
EBV ab 
X 
 
 
 
 
 
 
 
Hepatitis B and C, 
HTLV-1 & 2 
X 
 
 
 
 
 
 
 
HIV, RPR 
(FTA if necessary) 
X 
 
 
 
 
 
 
 
Thyroid Tests 
(Free T4, TSH) 
X 
 
X 
 
X 
 
X 
 
Serum Pregnancy 
Test 
X 
X 
X 
X 
X 
X 
X 
 
Immunodeficiency 
Panel 
X 
 
 
 
 
 
 
 

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Urinalysis 
X 
X 
X 
X 
X 
X 
X 
 
Anti-double-
stranded DNA 
(anti- dsDNA) 
X 
 
X 
 
X 
 
X 
 
Anti-DNAse B Titer 
Serum 
X 
 
X 
 
X 
 
X 
 
ECG 
X 
 
 
 
 
 
 
 
Optional Tumor 
sample/biopsies 
for immune 
response assays 
X 
X 
X 
X 
X 
X 
X 
 
Overall Survival 
 
 
 
 
 
 
 
X 
* +/-7 business days; **Final study visit; ***Screening labs may be performed within 7 days of treatment. 
 
1 A long-term follow-up on 11/16/2020 (± 4 weeks) that includes the survival status and subsequent anti-
cancer therapy since last being seen on trial will be obtained from the EMR. Subsequent therapies will be 
documented from the EMR for melanoma (immune-based therapy, chemotherapy, radiation, surgery) with 
clinical response if available. 

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7.4 Concomitant Medications, Treatments, and Procedures 
 
All concomitant prescription medications taken during study participation will be recorded on the case 
report forms (CRFs). For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be reported in the CRF are 
concomitant prescription medications, over-the-counter medications, and non-prescription 
medications.  
 
8 ASSESSMENT OF SAFETY 
8.1 Specification of Safety Parameters 
 
This study will comply with all applicable regulations on IND safety reporting requirements to the FDA in 
accordance with 21 CFR 312.32. This study will utilize CTCAE v5.0 for toxicity and AE reporting. All 
appropriate treatment areas at Moffitt Cancer Center have access to a copy of the CTCAE v5.0. Careful 
evaluation to determine the toxicity of IFx-Hu2.0 as a monotherapy will be performed. Adverse events will 
be documented beginning at initiation of treatment (Day 0) and continue at each visit detailed in the study 
treatment schema until progression, loss to follow-up, withdrawal of consent, or death. Subjects with 
treatment-related toxicity will be followed for the ongoing drug-related adverse events until resolved, 
return to baseline, deemed irreversible by the Moffitt treating physician, or until the subject is lost to 
follow up, withdrawal of study consent, removal of the subject from the trial by the Moffitt treating 
physician, or start of a subsequent anti-cancer therapy. 
8.1.1 Definition of Adverse Events (AE) 
An AE is defined as any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
An ongoing or intermittent adverse event should be recorded only once, with the highest/worst grade 
reported for the event. This study will utilize the Common Terminology Criteria for Adverse Events 
version 5 (CTCAE v5) for toxicity 
and adverse event reporting. A copy of the CTCAE v 5 can be downloaded from the CTEP home page 
http://ctep.cancer.gov/reporting/ctc.html. 
8.1.2 Definition of Serious Adverse Events (SAE) 
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: 
• 
death 
• 
life-threatening 
o An adverse event or suspected adverse reaction is considered “life-threatening” if, in 
the view of either the investigator or sponsor, its occurrence places the patient or 
subject at immediate risk of death. It does not include an adverse event or suspected 
adverse reaction that, had it occurred in a more severe form, might have caused death. 
• 
inpatient hospitalization or prolongation of existing hospitalization 
• 
results in a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 

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• 
a congenital anomaly/birth defect in the offspring of a subject 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
For reporting purposes, also consider the occurrences of pregnancy or overdose (regardless of adverse 
outcome) as events which must be reported as important medical events. All Grade 4 and 5 adverse 
events are by definition serious, and must be reported within 24 hours of the site becoming aware of 
the event, with follow-up reporting of outcome with the exception of grade 4 and 5 myelosuppression 
(including anemia, neutropenia, and thrombocytopenia that does not require hospitalization). 
 
8.1.3 Definition of Unexpected Adverse Drug Experience 
An unexpected adverse drug experience (UP) is defined by the FDA as “any adverse drug experience, 
the specificity or severity of which is not consistent with the current investigator brochure. or, if an 

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investigator brochure is not required or available, the specificity or severity of which is not consistent 
with the risk information described in the general investigational plan or elsewhere in the current 
application, as amended”. 
This study will use the FDA definition of UP. 
8.2 Classification of an Adverse Event 
 
8.2.1 Severity of Event 
 
All AEs will be assessed by the clinician using NIH-NCI-DCTD-CTEP CTCAE v. 5.0, published: June 14, 2010. 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity: 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. 
8.2.2 Relationship to Study Event 
 
The clinician’s assessment of an AE’s relationship to IFx-Hu2.0 is part of the documentation process, but 
it is not a factor in determining what is or is not reported in the study. If there is any doubt as to whether 
a clinical observation is an AE, the event should be reported. All AEs must have their relationship to study 
agent assessed. To help assess, the following guidelines are used. 
• 
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 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. 
• 
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. 

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• 
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. 
8.2.3 Expectedness 
 
The PI will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information described in the current IB for IFx-Hu 2.0. 
8.3 Time Period and Frequency of Event Assessment and Follow-up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate 
CRF. Information to be collected includes an event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring during the study must be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time the participant is screened will be considered as baseline 
and not reported as an AE. However, if the study participant’s condition deteriorates at any time during 
the study, it will be recorded as an AE. UPs will be recorded in the data collection system throughout the 
study. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained. At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last 
visit. Events will be followed for outcome information until resolution or stabilization. 
8.4 Reporting Procedures 
 
8.4.1 Adverse Event Reporting 
 
All adverse events will be documented and reported to the FDA in the annual report. 

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8.4.2 Serious Adverse Event Reporting 
 
The study clinician will complete an SAE Form within the following timelines: 
• 
All SAEs, regardless of relationship, will be recorded on the SAE Form and submitted to the study 
sponsor within 24 hours of site awareness. 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested 
by the study sponsor and should be provided as soon as possible. The study sponsor will be responsible 
for notifying FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as 
possible but in no case later than 7 calendar days after the sponsor's initial receipt of the information. 
8.4.3 Unexpected Adverse Drug Experience Problem Reporting 
Incidents or events that meet the FDA criteria for UPs require the creation and completion of a UP report 
form. It is the site investigator’s responsibility to report UPs to their IRB and to the study sponsor. The UP 
report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome 
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents a UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
• 
UPs that are SAEs will be reported to the IRB and to the study sponsor within 24 hours of the 
investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB and to the study sponsor within 7 business days of the 
investigator becoming aware of the problem. 
 
8.4.4 Reporting of Pregnancy 
All women of childbearing potential should be instructed to contact the investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study 
participation.  
 
8.5 Study Halting Rules 
 
Administration of study agent will be halted when two grade-3 or greater AEs determined to be “possibly” 
or “probably” related are reported. The clinical team will notify the PI, the Peachtree Bioresearch 
Solutions, Inc. (PBRS) Medical Monitor (MM), and the Sponsor’s designated Drug  Safety Unit immediately 
when a second grade 3 event is reported, and the site will stop accepting new study participants. The PI 
will inform the PBRS MM and the Sponsor’s designated Drug Safety Unit within 24 hours of this occurrence 
and will provide both with AE listing reports. The PBRS MM will provide 

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recommendations for proceeding with the study to the clinical team and study sponsor. The study sponsor 
will inform the FDA of the temporary halt and the disposition of the study. 
8.6 Safety Oversight 
 
Safety oversight will be under the direction of the PBRS MM and the Sponsor’s designated Drug Safety 
Unit. The PBRS MM reviews and evaluates safety and/or efficacy data on an ongoing basis to ensure the 
safety of patients and the validity and integrity of data. The PBRS MM reviews SAEs, deviations, Interim 
analysis and final report forms, and can make the following determinations, Accepted, Acceptable with 
Corrective Action and Tabled. The PI shall provide a statistical report of the study’s progress and summary 
of adverse events and deviations based on the phase of the study and the associated risk of the study as 
often as is applicable. 
 
9 CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol/amendment(s), with good clinical practice 
(GCP), and with applicable regulatory requirements. 
The PI and the Clinical Research Coordinator assigned to the case will be responsible for collecting all study 
data and maintaining all study-related documents, including the Investigator’s Study File (ISF) and patient 
Case Report Forms (CRFs). All CRF entries will be made into paper CRFs provided by the study site and will 
be verified by the PBRS CRA against both paper source documentation and electronic medical records 
(EMR). The patient CRFs will be secured in a locked office in the Cutaneous Research Department. The 
review of medical records will be done in a manner to assure that patient confidentiality is maintained. 
Regulatory documents will be reviewed and CRFs will be monitored by the PBRS Clinical Research 
Associate (CRA) according to PBRS Standard Operating Procedures (SOPs). Monitoring will be performed 
regularly for accuracy, completeness, and 100% source data verification, validation of appropriate 
informed consent process, reporting of SAEs, and adherence to the protocol, Good Clinical Practice (GCP) 
guidelines, and all applicable regulatory requirements. 
To ensure adherence to the protocol, monitoring reports will be submitted to the sponsor according to 
the timelines specified in the PBRS Global Monitoring Plan. 
 
10 STATISTICAL CONSIDERATIONS 
10.1 Statistical and Analytical Plans 
 
The statistical and analytical plan was developed to assess safety in six patients. 
10.2 Statistical Hypotheses 
 
IFX-Hu2.0 may be given safely to patients with unresectable stage III/IV melanoma. 

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10.3 Analysis Dataset(s) 
 
Safety Analysis Dataset: the subset of participants for whom safety analyses will be conducted (e.g., 
participants who took at least one dose of Investigational Product). 
10.4 Description of Statistical Methods 
 
10.4.1 General Approach 
 
This is a feasibility study that is designed to evaluate the safety and the feasibility of IFx-Hu2.0 as a 
monotherapy in preparation for a combination trial with Keytruda® (pembrolizumab) for the treatment 
of unresectable stage III/IV metastatic melanoma. Safety will be assessed and reported based upon CTCAE 
v5.0 criteria. Feasibility will be defined as the ability to treat at least five of the six patients enrolled without 
dose-limiting toxicity. 
The secondary endpoints consist of the objective response rate and immune response assessments. 
Responses will be determined using standard criteria. Other secondary endpoints will be exploratory 
laboratory correlative endpoints of interest. This will include immunology assessments to include but not 
limited to: quantity of effector T cells in the circulation and expression of the Emm55 protein within the 
tumor tissue. The data analysis of exploratory laboratory correlative endpoints will be descriptive.  All 
study results will be preliminary and exploratory in nature due to the relatively small sample size of the 
trial. 
The data analysis will mainly be descriptive. The intention-to-treat approach will be used for response to 
treatment data analysis of this trial. Patients who are lost to follow-up or drop out of the study for any 
reason prior to their scheduled Final Study Visit will be censored for any time-to-event type of endpoints 
at the time of their last patient contact if no relevant event has occurred by then. The overall response 
(CR+PR) rate will also be summarized. 
10.4.2 Safety Analyses 
 
Safety endpoints will be analyzed as summary statistics during treatment and/or as change scores from 
baselines such as shift tables. AEs will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA), calculated (counted once only for a given participant), presented (severity, frequency, and the 
relationship of AEs to study agent will be presented by System Organ Class and preferred term groupings). 
The information reported about each AE will be the start date, stop date, severity, relationship, outcome, 
and duration). AEs leading to premature discontinuation from the study and serious treatment AEs will be 
presented either in an independent table or a listing. 
10.4.3 Baseline Descriptive Statistics 
 
Study cohorts and groups will be compared on baseline characteristics, including demographics and 
laboratory measurements, using descriptive statistics. 
10.4.4 Planned Interim Analyses 
 
10.4.4.1 
Safety Review 

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The safety analysis will be conducted on the Safety Population. The following safety parameters will be 
evaluated: adverse events, clinical laboratory tests, physical examinations, vital signs, ECOG  performance 
status, ECGs, radiographic or other imaging assessments , immune safety, and immunogenicity. All safety 
parameters will be summarized using descriptive statistics. 
• 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are defined as signs or symptoms that emerge during 
treatment or within 30 days of the last dose of Investigational Product, including those signs and 
symptoms that have been absent pre-treatment or that have worsened relative to the pre- treatment 
assessment. Any adverse event considered related to treatment will also be considered a TEAE, 
regardless of the elapsed time since the last dose of Investigational Product. 
An immune response AE, a subset of adverse events, is defined as a clinically significant AE of any 
organ that is associated with Investigational Product exposure of unknown etiology and is consistent 
with an immune-mediated mechanism. 
All AEs recorded during the study will be summarized by cohort using descriptive statistics. The 
incidence of TEAEs will be summarized by body system, preferred term, verbatim of adverse event, 
intensity (based on CTCAE Version 5.0 grade), and relationship to the Investigational Product 
• 
Vital Signs 
The observed vital signs at each visit and the change from baseline to each post-baseline visit will be 
summarized by cohort using descriptive statistics. 
• 
Physical Examination 
Abnormal findings in the physical examination will be summarized by dose cohort using descriptive 
statistics. 
• 
Clinical Laboratory Tests 
Clinical laboratory test values outside the normal range and clinically significant abnormal range will 
be flagged in the data listing. Laboratory data will be summarized by cohort using shift tables (baseline 
to notable post-baseline visit). The change from baseline will be summarized using descriptive 
statistics. 
• 
ECOG 
The data observed from ECOG performance status will be summarized appropriately. 
• 
Other Safety Evaluations 
The results of ECGs, radiographic or other imaging assessments, immune safety tests, and 
immunogenicity will be summarized appropriately. 
10.4.5 
Exploratory Analyses 
 
The exploratory laboratory correlative endpoints of interest will be reported descriptively. A fresh tumor 
biopsy will be utilized to quantitatively measure the level of immune response to Emm55 expression. 
Subsequent 

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assays will be to measure immune cell subsets within peripheral blood and biopsy samples. If additional 
material is available after these preliminary assays, further immunological assessment of available 
material will be performed as suggested by our pre-clinical work. 
10.5 Sample Size 
 
The intent of this study is to enroll six evaluable patients to assess the safety of IFx-Hu2.0 as a 
monotherapy. The sample size has the following precision for estimation of DLT rates for estimating 
ranging from 0.1 to 0.5. A DLT is defined as an adverse event equal to or greater than grade 3, definitely 
related to the investigational agent within a 4 week period. Precision is measured by 1-sided 95% upper 
confidence limit on the estimated DLT rate via exact binomial distribution. For example, if no DLT is 
observed in patients on IFX-Hu 2.0, then the true underlying DLT rate is lower than 0.393 with 95% 
confidence. 
 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Moffitt Cancer Center will maintain appropriate medical and research records for this trial in compliance 
with ICH E6 and regulatory and institutional requirements for the protection of confidentiality of 
participants. 
Source data are all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Examples of these original 
documents and data records include, but are not limited to, hospital records, clinical and office charts, 
laboratory notes, memoranda, participant’s memory aids or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after verification 
as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x- 
rays, and participant files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical trial. 
To ensure that anyone who would access the patient medical record has adequate knowledge that the 
patient is participating in a clinical trial, it is not acceptable for the CRF to be the only record of a patient’s 
participation in the study. CRF entries must contain information which is also recorded elsewhere in the 
patient’s medical record. 
 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
Quality Control (QC) procedures will be implemented beginning with the Data Management (DM) provider 
data entry system and data QC checks that will be run on the database will be generated. Any missing data 
or data anomalies will be communicated to the site for clarification/resolution. 
Following written standard operating procedures, the monitor will verify that the clinical trial is 
conducted, and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable regulatory requirements. 

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Moffitt Cancer Center will provide direct access to all trial-related sites, source data/documents, and 
reports, for the purpose of monitoring and auditing by the sponsor and the sponsor’s designee and for 
inspection by local and regulatory authorities. 
 
13 ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 Ethical Standard 
 
The PI will ensure that this study is conducted in full conformity with Regulations for the Protection of 
Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the ICH E6. 
13.2 Institutional Review Board 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
13.3 Informed Consent Process 
 
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants 
 
Consent forms describing in detail the study agent, study procedures, and risks will be given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study product. 
13.3.2 Consent Procedures and Documentation 
 
Informed consent is a process that is initiated prior to the individual’s agreement to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be IRB-
approved, and the participant will be asked to read and review the document. The investigator will explain 
the research study to the participant and answer any questions that may arise. All participants will receive 
a verbal explanation in terms suited to their comprehension of the purposes, procedures, and potential risks 
of the study and of their rights as research participants. Participants will have the opportunity to carefully 
review the written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with their surrogates or think about it prior to agreeing to participate. The 
participant will sign the informed consent document prior to any procedures being done specifically for the 
study.  
When, in the judgment of the chairman of the local IRB, the Investigator, and/or the Sponsor, an amendment 
to the protocol substantially alters the study design and/or increases the potential risk to the subject, the 
currently approved written ICF will require similar modification and IRB approval.  In such cases, repeat 
informed consent will be obtained from subjects enrolled in the study before continued participation under 
the new amendment. 

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The FDA has recently issued guidance to address the Coronavirus Disease 2019 (COVID-19) public health 
emergency. If the trial participant cannot return to the study site, the consent form may be sent to the 
trial participant (or representative who can provide the document to the trial participant) by facsimile,  
email or mail, and the consent interview may then be conducted by telephone when the trial participant 
can read the consent form during the discussion. After the consent discussion, the trial participant can 
sign and date the consent form. Options for returning the document to the clinical investigator may 
include facsimile, a photographic image sent through electronic means, scanning the consent form and 
returning it through a secure email account, or posting it to a secure internet address. Alternatively, the 
trial participant may bring the signed and dated consent form to his/her next visit to the clinical site or 
mail it to the clinical investigator. The medical records for each trial participant must document the 
method used for obtaining consent and that informed consent was obtained prior to their continued 
participation in the trial. The person signing the consent form must receive a copy of the consent form. 
Although FDA regulations do not require the trial participant’s copy to be a signed copy, FDA recommends 
that a copy of the signed consent form be provided. The participants may withdraw consent at any time 
throughout the course of the trial. The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. 
13.3.3 
Participant and Data Confidentiality 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor and their agents. This confidentiality is extended to cover testing of biological samples and genetic 
tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without the prior written 
approval of the sponsor. 
The study monitor, other authorized representatives of the sponsor, or representatives of the IRB may 
inspect all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at the clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by local IRB and institutional regulations. 
Data will be captured in paper CRFs provided by PBRS. The CRFs will be reviewed periodically by sponsor-
designated monitors throughout the conduct of the trial per the clinical  trial agreement and the PBRS 
Global Monitoring Plan. This review will include source data verification utilizing research subjects’ 
medical records. 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be stored at PBRS. The study systems used by clinical site research staff will be secured and password 
protected. The DM provider’s system will store subject data in a 21 CFR Part 11 compliant electronic data 
management system. 
 
14 DATA HANDLING AND RECORD KEEPING 

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14.1 Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, 
OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
Paper CRFs will be provided for use as data collection documents and maintained for recording data for 
each participant enrolled in the study. Data derived from source documents and reported in the CRF 
should be consistent with the source documents, or the discrepancies should be explained and captured 
in a query and maintained with the paper CRF. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be captured on paper CRFs provided by PBRS. 
14.2 Study Records Retention 
 
No records will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
14.3 Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or current clinical practice 
requirements at Moffitt Cancer Center. The noncompliance may be either on the part of the participant, 
the investigator, or the study site staff. As a result of deviations, corrective actions are to be developed by 
the site and implemented promptly. 
These practices are consistent with ICH E6: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2 
It is the responsibility of the site to use continuous vigilance to identify and report deviations within seven 
working days of identification of the protocol deviation or within seven working days of the scheduled 
protocol-required activity. All deviations must be addressed in study source documents. Protocol 
deviations must be sent to the local IRB per their guidelines. The site PI/study staff is responsible for 
knowing and adhering to their IRB requirements. 
14.4 Publication and Data Sharing Policy 
 
This study will adhere with the details set forth in the clinical trial agreement between Morphogenesis, 
Inc. (sponsor) and Moffitt Cancer Center (clinical site) as it pertains to the sharing and publication of clinical 
research data. 

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The International Committee of Medical Journal Editors (ICMJE) member journals has adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy and 
the Section 801 of the Food and Drug Administration (FDA) Amendments Act of 2007 requires that all 
clinical trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine. 
15 STUDY ADMINISTRATION 
15.1 Study Leadership 
 
Study leadership will be the responsibility of the PI and the clinical coordinator in collaboration with the 
study sponsor and/or its representative. Study leadership will meet periodically as needed. 
This trial will be monitored continuously by the PI, who will be assisted by the assigned clinical trial 
coordinator. 
 
16 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the trial. 
17 LITERATURE REFERENCES 
Chen, D. S. and I. Mellman (2013). "Oncology meets immunology: the cancer-immunity cycle." Immunity 
39(1): 1-10. 
 
Dale, J. B., P. R. Smeesters, H. S. Courtney, T. A. Penfound, C. M. Hohn, J. C. Smith and J. Y. Baudry 
(2017). "Structure-based design of broadly protective group a streptococcal M protein-based vaccines." 
Vaccine 35(1): 19-26. 
 
Dinkla, K., D. P. Nitsche-Schmitz, V. Barroso, S. Reissmann, H. M. Johansson, I. M. Frick, M. Rohde and G. 
S. Chhatwal (2007). "Identification of a streptococcal octapeptide motif involved in acute rheumatic 
fever." J Biol Chem 282(26): 18686-18693. 
 
Glikin, G. C. and L. M. Finocchiaro (2014). "Clinical trials of immunogene therapy for spontaneous tumors 
in companion animals." ScientificWorldJournal 2014: 718520. 
 
Nitsche-Schmitz, D. P., M. Rohde and G. S. Chhatwal (2007). "Invasion mechanisms of Gram-positive 
pathogenic cocci." Thromb Haemost 98(3): 488-496. 
 

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Ramiya, V. K., M. M. Jerald, P. D. Lawman and M. J. Lawman (2014). "Autologous tumor cells engineered 
to express bacterial antigens." Methods Mol Biol 1139: 243-257. 
 
Reissmann, S., C. M. Gillen, M. Fulde, R. Bergmann, A. Nerlich, R. Rajkumari, K. N. Brahmadathan, G. S. 
Chhatwal and D. P. Nitsche-Schmitz (2012). "Region-specific and worldwide distribution of collagen- 
binding M proteins with PARF motifs among human pathogenic streptococcal isolates." PLoS One 7(1): 
e30122.