Phase 1 Trial of IFx-Hu2.0 to Evaluate Safety in Patients With Skin Cancer
Phase: PHASE1
Conditions: Cutaneous Squamous Cell Carcinoma, Basal Cell Carcinoma
Sponsor: TuHURA Biosciences, Inc.

Phase 1 Trial of IFx-Hu2.0 to Evaluate Safety in Patients with Skin Cancer 
Version 3.0
Protocol SC 2020-01 
02 Jun 2021
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Phase 1 Trial of IFx-Hu2.0 to Evaluate Safety  
in Patients with Skin Cancer 
Protocol Number SC 2020-01 
Protocol Version 3.0 
Date of Protocol Version 02 Jun 2021 
National Clinical Trial (NCT) Identifier TBD 
Investigational New Drug (IND) 
Application Number 017840 
Medical Monitor Georgia Latham, MD 
Data and Safety Monitoring Board 
(DSMB) None 
Sponsor Morphogenesis, Inc. 
Funding Entity Morphogenesis, Inc. 
Institutional Review Board (IRB) Advarra® 
Contract Research Organization (CRO) Peachtree BioResearch Solutions 
 
The terms “outcome measures” and “endpoints” are used interchangeably in this document. 
 
 

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Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Various pertinent 
sections 
• Removed cutaneous 
melanoma from the list of 
indications to be studied 
under this protocol 
• This was done in response 
to the FDA review team’s 
feedback from 25 May 2021 
• This was done to mitigate 
the risk of enrolling patients 
with brain metastases 
1.3 Schedule of Activities 
• Added testing for 
HIV/AIDS and hepatitis 
B/C 
• This was done in response 
to the FDA review team’s 
feedback from 25 May 2021 
5.2 Exclusion Criteria 
• An exclusion criterion was 
added to not inject lesions 
on scalp with bone 
erosions 
• This was done in response 
to the FDA review team’s 
feedback from 25 May 2021 
5.2 Exclusion Criteria 
• An exclusion criterion was 
added to not enroll 
patients with active 
HIV/AIDS or hepatitis B/C 
• This was done in response 
to the FDA review team’s 
feedback from 25 May 2021 
 
9.2 Sample Size 
Determination 
• The DLT definition was 
revised to include all AEs 
at least “possibly” related 
to the IP 
• This was done in response 
to the FDA review team’s 
feedback from 25 May 2021 
 
 

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Table of Contents 
TRIAL COMPLIANCE ....................................................................................................................................................... 5 
INVESTIGATOR AGREEMENT ......................................................................................................................................... 6 
SPONSOR AGREEMENT .................................................................................................................................................. 7 
1 Protocol Summary ...................................................................................................................................................... 8 
1.1 Synopsis ............................................................................................................................................................... 8 
1.2 Schema ................................................................................................................................................................ 9 
1.3 Schedule of Activities (SoA) ............................................................................................................................... 10 
2 Introduction .............................................................................................................................................................. 11 
2.1 Study Rationale .................................................................................................................................................. 11 
2.2 Background ........................................................................................................................................................ 11 
2.3 Risk/Benefit Assessment.................................................................................................................................... 19 
2.3.1 Known Potential Risks ................................................................................................................................. 19 
2.3.2 Known Potential Benefits ........................................................................................................................... 21 
3 Objectives and Endpoints ......................................................................................................................................... 22 
4 Study Design ............................................................................................................................................................. 23 
4.1 Overall Design .................................................................................................................................................... 23 
4.2 Justification for Dose ......................................................................................................................................... 23 
4.3 End of Study Definition ...................................................................................................................................... 23 
5 Study Population ...................................................................................................................................................... 24 
5.1 Inclusion Criteria ................................................................................................................................................ 24 
5.2 Exclusion Criteria ............................................................................................................................................... 24 
5.3 Lifestyle Considerations ..................................................................................................................................... 25 
5.4 Screen Failures ................................................................................................................................................... 25 
5.5 Strategies for Recruitment and Retention ......................................................................................................... 26 
6 Study Intervention .................................................................................................................................................... 27 
6.1 Study Intervention(s) Administration ................................................................................................................ 27 
6.1.1 Study Intervention Description ................................................................................................................... 27 
6.1.2 Dosing and Administration ......................................................................................................................... 27 
6.1.3 Study Procedures and Schedule ................................................................................................................. 27 
6.2 Preparation/Handling/Storage/Accountability .................................................................................................. 30 
6.2.1 Acquisition and accountability .................................................................................................................... 30 
6.2.2 Formulation, Appearance, Packaging, and Labeling ................................................................................... 30 
6.2.3 Product Storage and Stability ..................................................................................................................... 30 
6.2.4 Preparation ................................................................................................................................................. 31 
6.3 Study Intervention Compliance ......................................................................................................................... 31 
6.4 Concomitant Therapy ........................................................................................................................................ 31 
7 Study Intervention Discontinuation and Participant Discontinuation/Withdrawal ................................................. 32 
7.1 Discontinuation of Study Intervention .............................................................................................................. 32 
7.2 Participant Discontinuation/Withdrawal from the Study .................................................................................. 32 
7.3 Lost to Follow-Up ............................................................................................................................................... 33 
8 Study Assessments and Procedures ......................................................................................................................... 34 
8.1 Safety and Other Assessments .......................................................................................................................... 34 
8.2 Adverse Events and Serious Adverse Events ..................................................................................................... 34 
8.2.1 Definition of Adverse Events (AE) (21 CFR 312.32(a)) ................................................................................ 34 

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8.2.2 Definition of Serious Adverse Events (SAE) (21 CFR 312.32(a)) .................................................................. 34 
8.2.3 Classification of an Adverse Event .............................................................................................................. 35 
8.2.4 Time Period and Frequency for Event Assessment and Follow-Up ............................................................ 36 
8.2.5 Adverse Event Reporting ............................................................................................................................ 36 
8.2.6 Serious Adverse Event Reporting................................................................................................................ 37 
8.2.7 Reporting of Events to Participants ............................................................................................................ 37 
8.2.7 Reporting of Pregnancy .............................................................................................................................. 37 
9 Statistical Considerations ......................................................................................................................................... 38 
9.1 Statistical Hypotheses ........................................................................................................................................ 38 
9.2 Sample Size Determination................................................................................................................................ 38 
9.3 Populations for Analyses ................................................................................................................................... 38 
9.4 Statistical Analyses............................................................................................................................................. 38 
9.4.1 General Approach ....................................................................................................................................... 38 
9.4.2 Safety Analyses ........................................................................................................................................... 38 
9.4.3 Baseline Descriptive Statistics .................................................................................................................... 40 
9.4.4 Exploratory Analyses .................................................................................................................................. 40 
10 Supporting Documentation and Operational Considerations ................................................................................ 41 
10.1 Regulatory, Ethical, and Study Oversight Considerations ................................................................................ 41 
10.1.1 Informed Consent Process ........................................................................................................................ 41 
10.1.2 Study Discontinuation and Closure ........................................................................................................... 41 
10.1.3 Confidentiality and Privacy ....................................................................................................................... 42 
10.1.4 Future Use of Stored Specimens and Data ............................................................................................... 42 
10.1.5 Key Roles and Study Governance ............................................................................................................. 43 
10.1.6 Safety Oversight ........................................................................................................................................ 43 
10.1.7 Clinical Monitoring .................................................................................................................................... 43 
10.1.8 Compensation for Research-Related Injury .............................................................................................. 44 
10.1.9 Quality Assurance and Quality Control ..................................................................................................... 44 
10.1.10 Data Handling and Record Keeping ........................................................................................................ 44 
10.1.11 Protocol Deviations................................................................................................................................. 45 
10.1.12 Publication and Data Sharing Policy ....................................................................................................... 45 
10.1.13 Conflict of Interest Policy ........................................................................................................................ 46 
10.2 Abbreviations ................................................................................................................................................... 46 
10.3 Protocol Amendment History .......................................................................................................................... 47 
11 References .............................................................................................................................................................. 49 
Literature References .......................................................................................................................................... 49 
 
 
 

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TRIAL COMPLIANCE 
The trial will be carried out in accordance with the United States (US) Code of Federal Regulations (CFR) 
applicable to clinical trials (i.e. 45 C.F.R. § 46, 21 C.F.R. § 11, § 50, § 56, and § 312 (2020)) and applicable 
state and local research requirements. Investigators and clinical trial site staff who are responsible for the 
conduct, management, or oversight of the trial have completed Institutional Review Board (IRB)-approved 
Good Clinical Practice training (i.e. on US Food and Drug Administration (FDA) Regulations and ICH GCP 
E6(R2)). 
 
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 patient is enrolled. Any amendment to the protocol will require IRB review and 
approval before the changes are implemented to the study. In addition, all changes to the consent form 
will be IRB-approved; an IRB determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 

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INVESTIGATOR AGREEMENT 
I will conduct the trial in compliance with the protocol agreed to by the sponsor, and if required, by the 
regulatory authority(ies), and which was given IRB-approval/favorable opinion. 
 
I will not implement any deviation from, or changes to, the protocol without sponsor agreement and prior 
IRB review and approval/favorable opinion of an amendment, except where necessary to eliminate an 
immediate hazard(s) to patients, or when the change(s) involves only logistical or administrative aspects 
of the trial (e.g., change in monitor(s), change of contact information such as phone number(s)). 
 
I will document and explain any deviation from the IRB-approved protocol. 
 
I may implement a deviation from, or a change in, the protocol to eliminate an immediate hazard(s) to 
patients without prior IRB approval/favorable opinion. As soon as possible, I will submit the implemented 
deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s): 
 
a) To the IRB for review and approval/favorable opinion. 
b) To the sponsor for agreement and, if required. 
c) To the regulatory authority(ies). 
 
 
 
_______________________________________  
_________________ 
Investigator Name and Signature 
 
 
Date (DD Mon YYYY) 
 
 

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SPONSOR AGREEMENT 
I agree to the conduct of the trial in accordance with this protocol. 
 
 
 
_______________________________________  
_________________ 
Sponsor Representative Name and Signature 
 
Date (DD Mon YYYY) 
 

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1 PROTOCOL SUMMARY 
1.1 SYNOPSIS 
Title: 
Phase 1 Trial of IFx-Hu2.0 to Evaluate Safety in Patients with Skin Cancer 
Study Description: 
One hundred patients will receive IFx-Hu2.0 on an outpatient basis at a single time point in a single 
lesion. These patients will be assessed for any immediate adverse reactions and at Week 4 (Day 
28+/-5 days) for any delayed adverse events. 
Objectives: 
Primary Objective: 
To assess safety and feasibility 
Secondary Objective: 
To assess post-therapeutic pathological response 
Tertiary/Exploratory 
Objective: 
To assess anti-tumor immunity post-treatment. 
 
Endpoints: 
Primary Endpoint: 
The primary endpoints of this trial will be the safety and feasibility of the 
treatment regimen. Safety will be reported using the most current 
version of the Common Terminology Criteria for Adverse Events (CTCAE). 
Feasibility will be defined as the ability to treat at least 85 of the 
approximate 100 patients enrolled without investigational product (IP) 
related dose-limiting toxicity (DLT). 
 
Secondary Endpoints: 
The secondary endpoint is Pathological Response defined as a response 
assessment to IFx-Hu2.0 in tumor lesions excised by evaluating percent 
Residual Vial Tumor (%RVT), at four weeks as: 
• 
pathological complete response (pCR),  
• 
major pathological response (mPR),  
• 
partial pathological response (pPR), or  
• 
pathological non-response (pNR)  
 
Tertiary/Exploratory 
Endpoints: 
 
Patient samples (plasma and/or serum) will be assayed to detect tumor 
antigen specific antibody generation in addition to a protein biomarker 
discovery assay specific to immuno-oncology therapy assessments. 
IHC will be performed on pre- and post-treatment tissue samples to 
contrast the cell sub-types across time points. 
Study Population: 
Adult male or female subjects with confirmed cutaneous squamous cell carcinoma, or basal cell 
carcinoma with lesions accessible for intralesional injection. 
Phase: 
Phase 1 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
Approximately 5 NCI-designated cancer centers, academic medical centers, clinics, and doctor’s 
offices within the United States,  qualified to perform clinical studies under GCP. 
 
Description of Study 
Intervention: 
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”. 
Study Duration: 
12 Months 
Participant Duration: 
Up to six weeks 
 

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1.2 SCHEMA 
 
 

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1.3 SCHEDULE OF ACTIVITIES (SOA) 
 Procedure 
Screening Visit 
Day -14 to -1 
Baseline Visit 
Week 0/Day 0 
DLT Follow up 
Week 4/Day 28 
+/-5 days 
Unscheduled Visit 
Early Termination 
Visit 
Informed consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical exam w/vitals 
X 
X 
X 
X 
X 
Performance Status 
X 
X 
X 
X 
X 
Tumor Burden (lesion measurements) 
X 
X 
X 
X 
X 
Concomitant medications review 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
X 
 
X 
X 
X 
Pathology Report Confirming Diagnosis 
(specific to lesion marked for injection) 
X 
 
 
 
 
Clinical laboratory samples (safety)a 
X 
X 
X 
X 
X 
Pregnancy test 
Xb 
Xc 
Xb 
Xb 
Xb 
Blood for Immune Response Evaluation 
 
X 
X 
X 
X 
IFx-Hu2.0 dosing 
 
X 
 
 
 
Adverse event review and evaluation 
 
X 
X 
X 
X 
Tumor excision for pathological response 
(final) 
 
 
X 
 
X 
a Clinical laboratory samples (safety); samples will include blood and urine for the following tests: 
• 
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) 
• 
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) 
• 
Serology: Hepatitis B Core Antibody (IgM), Hepatitis C Antibody (Anti-HCV), HIV-1/2 Antigen and Antibodies 
• 
Urinalysis: UA with microscopic evaluation 
• 
Anti-double-stranded DNA (anti-dsDNA) antibody test 
• 
Anti-DNase B Titer, Serum 
b Serum pregnancy test – indicated only in women of childbearing potential 
c Urine pregnancy test done within 24 hours prior to IFx-Hu2.0 administration and results must be available prior to IFx-
Hu2.0 administration, – only in women of childbearing potential 
 
 

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2 INTRODUCTION 
2.1 STUDY RATIONALE 
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(1). 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(2). However, some M proteins bind 
collagen and may cause side effects such as acute rheumatic fever in humans through molecular mimicry 
of collagen(3). Emm55, though, has been shown not to bind collagen due to the conformational influences 
of flanking sequences(4). In the IFx-Hu2.0 immunotherapeutic, 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. The goal of this study is to determine the safety and feasibility 
of injecting IFx-Hu2.0 into cutaneous tumor lesions in patients with early-stage disease and to also 
evaluate each patient's pathological response at four weeks post-treatment. 
2.2 BACKGROUND 
IFx-Hu2.0, a plasmid DNA construct (pAc/emm55) formulated with in vivo-jetPEI®, a cationic polymer that 
aids in cellular uptake of DNA, and dextrose, will be administered by intralesional injection. IFx-Hu2.0 is a 
cancer immunotherapy that stimulates the immune system to fight cancer. When introduced into tumor 
cells, pAc/emm55 drives expression of the highly immunogenic Emm55 protein in the cytoplasm and on 
the surface of the tumor cells. IFx-Hu2.0 provides a stimulus for a targeted immune response against 
tumor cells in patients with skin cancer. In this protocol, IFx-Hu2.0 will be utilized as a monotherapy in a 
safety and feasibility study design that also evaluates each patient's specific pathological response post-
treatment. 
 
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(5) 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 Streptococcus pyogenes (S. pyogenes) into a patient’s tumors via 
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 immune checkpoints whose 
function is to avoid collateral damage and autoimmunity. The interplay between antigen presentation/T 

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cell activation and T cell suppression is critically important in determining the outcome of 
immunotherapeutic interventions. 
 
Epidemiology Data 
More than 5 million new cases of nonmelanoma skin cancer (NMSC) occur annually in the United States, 
including 80% basal cell carcinomas (BCCs), 20% squamous cell carcinomas (SCCs), and a few rarer types. 
Annual incidence is increasing by 4% for SCC and 1% for BCC in the United States. Of solid organ transplant 
recipients, 15% to 43% will develop NMSC within 10 years(6). 
Ultraviolet radiation from sun exposure is a major risk factor, causes mutations in key genes, and explains 
the predilection of NMSC for sun-exposed skin. Hedgehog signaling pathway mutations are involved in 
BCC pathogenesis. p53 Mutations are involved in both SCC and BCC pathogenesis, and in the development 
of actinic keratoses, which are the precursors of SCCs. There are several histopathologic subtypes of each 
NMSC. The more infiltrative or poorly differentiated variants are more clinically aggressive (e.g., 
morpheaform BCC and spindle cell SCC)(6). 
TNM staging classifications exist for most types of NMSC and depend on clinical characteristics, pathologic 
features, and radiologic evaluation of the primary tumor, adjacent structures, lymph nodes, and viscera. 
BCCs that are large, deep, or infiltrative may be locally aggressive and recurrent, but metastasize only 
rarely (0.003% to 0.55%). SCCs have a greater metastatic rate, especially those that are large, deep, or 
poorly differentiated; have perineural invasion; or are located on the lip, ear, temple, cheek, or sites of 
chronic infection, ulceration, or radiation(6). 
Primary treatment for both BCCs and SCCs is surgical. Mohs micrographic surgery is preferred for ill-
defined or aggressive lesions because it allows microscopic control of tumor margins. The 5-year local 
recurrence rate for primary BCC is 1% for Mohs surgery compared with 5% for other types of surgical 
excision. The 5-year local recurrence rate for primary cutaneous SCC is 3.1% for Mohs surgery compared 
with 7.9% for non-Mohs modalities. Alternative primary therapies include various forms of physical 
destruction and radiation therapy. Interferons and inducers of interferons (e.g., imiquimod) are useful in 
selected cases. Hedgehog pathway agents, retinoids, vitamin D3, and inhibitors of PD-1/PD-L1 and 
epidermal growth factor receptor (EGFR) are other promising adjunctive and chemopreventive 
modalities(6). 
Unmet Medical Need 
The application of IFx-Hu2.0 in a neoadjuvant setting may support an improvement in current recurrence 
rates for these cancers. This could materialize based on the mechanism of action of IFx-Hu2.0 and its 
ability to elicit therapeutically relevant cellular and humoral tumor-specific immune responses. Findings 
from prior human use of IFx-Hu2.0 in patients with stage III to IV cutaneous melanoma supports this 
biological outcome. 
Preclinical Pharmacology 
Study # 20151023 – Murine Melanoma Study 
In the preclinical murine melanoma model, no adverse events were reported for single or repeat dosing 
of the drug product. For monotherapy, a statistically significant reduction in tumor weight and tumor area 
as well as a statistically significant increase in percent survival were observed (treatment vs. control). For 
combination therapy, a statistically significant reduction in tumor area was observed (combination 
therapy vs. monotherapy). In conjunction with T cell infiltration and IFN-γ data for these mice, the immune 
responses observed were logically consistent with the hypothesized mechanism of action of IFx-Hu2.0. 

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Table 1 Snapshot of Study # 20151023 
Animal Model – 
Cutaneous 
Melanoma 
Treatment Regimen 
Safety Profile 
Efficacy Signal 
Mus musculus 
(C57BL/6NCrl);  
B16-F10 syngeneic 
melanoma cell line 
(n=257) 
Monotherapy: 
0.02 mg of IFx-Hu2.0 
intralesional injection in 
three indexed cutaneous 
lesions once weekly for 
three doses 
(n=81) 
Combination Therapy: 
0.02 mg of IFx-Hu2.0 
intralesional injection in 
three indexed cutaneous 
lesions once weekly 
starting on day zero for 
three doses + 0.25 mg of 
PD-1 antagonist antibody 
(RMP1-14) 
intraperitoneal injection 
twice weekly starting on 
day eight for three doses 
(n=24) 
Other Therapies: 
IFx-Hu2.0 + immune 
response modifier 
(n=20) 
Controls: 
pAc/empty ± immune 
response modifier 
(n=132) 
Note: IFx-Hu2.0 
intralesional dose was 
limited by the physical 
size of palpable, 
cutaneous tumors in mice 
No Adverse Events: 
No secondary tumor 
growth, other injuries or 
signs of pain and no 
significant coat condition, 
disposition, and fecal or 
urine output findings 
(n=257) 
Monotherapy: 
Treatment vs. 
Control: 
Statistically 
significant increase in 
overall survival (OS) 
and decrease in 
tumor burden (tumor 
mass and area) 
 
Combination 
Therapy: 
Combination Therapy 
vs. Monotherapy: 
Statistically 
significant reduction 
in tumor burden 
(tumor area) 
In a series of experiments, mice transplanted with B16-F10 murine melanoma cells were treated with IFx-
Hu2.0 vaccine to measure the safety and antitumor effect of Emm55 protein-expressing tumor cells alone 
or in combination with immune response modifiers. The study encompassed a pilot proof-of-concept 

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experiment, nine exploratory experiments and a biodistribution experiment. In general, B16-F10 
melanoma cells (1x105 cells/100 mcL/mouse) were injected subcutaneously in syngeneic C57BL/6NCrl 
mice to establish tumors. The day of B16-F10 cell injection was designated Day 0. Approximately seven to 
ten days post injection, animals with palpable tumors (approximately 25 mm2) were randomly divided 
into experimental treatment cohorts. In some experiments, mice were subcutaneously injected with 
3x105 MO5 tumor cells, an OVA-expressing B16 cell line. Vaccination consisted of IFx-Hu2.0 or negative 
vector controls; pAc/empty or pAc/GFP-N1 plasmid DNA similarly complexed with in vivo-jetPEI® 
transfection reagent. A vaccine dose consisted of 20 mcg plasmid DNA in a total volume of 50 mcL. Three 
weekly vaccine doses were administered intralesionally. Studies were also carried out combining IFx-
Hu2.0 vaccine with antibodies targeting the immune response modifiers PD-1, CTLA-4 and 4-1BB. 
Throughout these studies, tumor growth was measured and monitored 2-3 times per week. 
All the experiments incorporated safety assessments of the mice as part of the continued safety 
monitoring and final safety evaluation. Mice were monitored twice per day by animal care technicians for 
adverse effects. This consisted of monitoring for presence of lesions other than at the site of B16-F10 
injection, adverse changes to the B16-F10 injection site, other injuries, coat condition, disposition, signs 
of pain, as well as fecal and urine output, according to the approved IACUC protocol for rodent husbandry 
(University of South Florida Division of Comparative Medicine SOP#400.14 issued 12/03 updated 7/16). 
No adverse findings were reported. 
The pilot experiment evaluated the feasibility of IFx-Hu2.0 administration and assessed potential 
bioactivity. Six of the exploratory experiments assessed bioactivity of IFx-Hu2.0 as a monotherapy and in 
combination with antibodies targeting immune response modifiers. Preliminary mechanism of action 
assays were also performed in multiple experiments. For the biodistribution study, mice received one 
dose of IFx-Hu2.0 or similarly complexed pAc/empty.  
Bioactivity experiments focused on the effect of IFx-Hu2.0 on animal survival, tumor mass and tumor area. 
In the pilot study, survival of animals vaccinated with IFx-Hu2.0 was compared to animals vaccinated with 
pAc/empty, or pAc/GFP-N1. There was a significant difference between treatment groups as assessed by 
Log rank Mantel-Cox survival test (p=0.017), with median survival times of 26 days for pAc/empty and 
pAc/GFP-N1 controls, and 40 days for IFx-Hu2.0 vaccine recipients. In a second survival test, there were 
significantly more IFx-Hu2.0 recipient mice alive than pAc/empty control mice (p=0.032) on Day 29, the 
median survival time for the pAc/empty group. For IFx-Hu2.0 recipients, median survival time had not yet 
been reached by Day 29, i.e. more than 50% of vaccinated mice were still alive. This difference in survival 
translated into a Hazard ratio (Mantel-Haenszel) of 5.7, which translates to a survival rate 5.7 times higher 
than that of pAc/empty recipients. 
Two experiments focused on the effect of IFx-Hu2.0 on tumor mass. In the first experiment, the mean ± 
standard deviation (SD) tumor mass of mice vaccinated with IFx-Hu2.0 was 315 mg ± 87 mg, while the 
mean ± SD tumor mass of mice treated with pAc/empty was 997 mg ± 335 mg. This approximately 3-fold 
decrease in tumor mass over 27 days was significant using a heteroscedastic Student’s T-test (p=0.0083). 
In the second experiment evaluating cotreatment with PD-1 antagonist, the mean tumor mass of mice 
receiving IFx-Hu2.0 was less than pAc/empty vaccinated animals after 25 days, irrespective of antibody 
cotreatment. 
The impact of IFx-Hu2.0 vaccination on tumor area over time was assessed in several experiments. In all 
experiments, mean tumor area from mice vaccinated with IFx-Hu2.0 was less than negative controls. 
Another experiment investigated the effects of IFx-Hu2.0 in combination with antibodies targeting the 
immune response modifiers PD-1, 4-1BB, and CTLA-4. The mean tumor area in mice given IFx-Hu2.0 was 
significantly less than the mean tumor area in mice receiving pAc/empty at Days 18, 21 and 25. Also, 

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pAc/empty combined with any of the three checkpoint Antagonists yielded significantly smaller mean 
tumor areas on Days 18, 21 and 25 than pAc/empty alone. The same or greater significance was observed 
at the same timepoints for IFx-Hu2.0 with checkpoint inhibition compared to pAc/empty, depending on 
the Antagonist. At Day 25, the mean tumor area in mice treated with IFx-Hu2.0 in combination with PD-1 
antagonist was smaller than IFx-Hu2.0 or PD-1 antagonist alone, significantly so for IFx-Hu2.0. 
Two experiments were designed to further investigate the effect of IFx-Hu2.0 in combination with PD-1 
antagonist on tumor area. In the first experiment, statistically significant differences in mean tumor area 
were detected at Day 22 between mice receiving pAc/empty compared to mice receiving IFx-Hu2.0 and 
IFx-Hu2.0 in combination with PD-1 antagonist. Furthermore, on Day 25, statistically significant 
differences in mean tumor area were again observed between mice receiving pAc/empty and mice 
receiving IFx-Hu2.0 in combination with PD-1 antagonist. On Day 27, statistically significant differences in 
mean tumor area were detected between mice receiving IFx-Hu2.0 versus mice receiving IFx-Hu2.0 in 
combination with PD-1 antagonist. These data suggest an additive effect of IFx-Hu2.0 in combination with 
PD-1 antagonist as suggested by previous data. 
Correlative pilot studies were performed to investigate IFx-Hu2.0 mechanism of action. Quantitative 
reverse transcriptase PCR showed expression of emm55 mRNA following injection of IFx-Hu2.0. 
Immune cell subsets in the spleen and tumors were characterized to determine if the antitumor effect of 
IFx-Hu2.0 was immune-mediated. TIL isolated from mice were analyzed for CD8 expression using flow 
cytometry. There was an approximately 5- to 6-fold increase in the number of infiltrating CD8+ T cells/mg 
tumor tissue in IFx-Hu2.0 injected mice compared to PBS and pAc/empty injected controls, suggesting the 
anti-tumor activity of IFx-Hu2.0 is T cell-mediated. This was further supported by immunohistochemical 
staining of tumors isolated from mice, which showed increased staining of CD3, CD4 and CD8 in the three 
treatment groups compared to the control group. 
Flow cytometric analyses of TIL isolated from mice resulted in a mean ± SD of 30.6% ± 5.8% CD8+ PD-1+ T 
cells in IFx-Hu2.0 injected mice. Expression of PD-1 suggests that the anti-tumor activity of IFx-Hu2.0 could 
be further enhanced using a combination therapy with PD-1 targeting antibodies. 
Cytotoxic T cell function was assessed using intracellular staining of TIL for IFN- and CD107a, a marker of 
CD8+ T cell degranulation, upon activation. The level of CD8+ IFN-+ CD107a+ T cells increased in IFx-Hu2.0 
treated mice compared to the control group.  
Splenocytes isolated from animals vaccinated with IFx-Hu2.0 as a monotherapy or in conjunction with PD-
1 antagonist, were evaluated for IFN- production using an ELISA. The level of IFN- was significantly higher 
(p=0.047) in the IFx-Hu2.0 + PD-1 antagonist treatment group compared to pAc/empty treated controls. 
To gain insight into tumor infiltration of immune cells following vaccination, an indirect analysis of antigen 
specific infiltration of tumors was carried out using the OT1-MO5 experimental model. The B16 subline, 
MO5, expresses an ovalbumin peptide in the context of H2Kb. OT-1 T cells express a T cell receptor (TCR) 
that recognizes the ovalbumin peptide. This results in MHC class I-restricted, ovalbumin-specific, CD8+ T 
cells (OT-1 cells), which primarily recognize the ovalbumin peptide when presented by MHC I. The level of 
OVA TCR-expressing cells in tumors of IFx-Hu2.0 recipient mice was significantly higher than that of control 
mice (p=0.0018), suggesting a vaccine-induced increase in antigen-specific T cell infiltration. Another 
experiment investigated infiltration of T cells by analyzing endogenous T cells in the spleen and tumor. In 
tumors, there was a significant reduction in CD8+ PD-1+ cells from IFx-Hu2.0 treated mice compared to 
pAc/empty control mice (p=0.035), which may be due to a vaccine-induced reduction in the number of 
exhausted T cells. 

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Taken together, these bioactivity and mechanistic studies highlight important points concerning the 
efficacy and mode of action of IFx-Hu2.0 in the selected melanoma model system. IFx-Hu2.0 significantly 
increased animal survival and decreased tumor burden. This effect was enhanced when used in 
combination with PD-1 antagonist.  
The B16-F10/C57BL/6NCrl murine melanoma study demonstrated that: 
a) pAc/emm55 (i.e. the drug substance) delays tumor growth and improves survival 
b) Intralesional injection of pAc/emm55 enhances T cell infiltration in tumors 
c) Systemic immune responses elicited by the pAc/emm55 are T cell-dependent 
d) Systemic immune responses elicited by pAc/emm55 are antigen specific 
Recently, Bunch et al. published the murine melanoma study (# 20151023) on 18 June 2020 in the Springer 
Cancer Immunology, Immunotherapy journal (7). The study was modeled after the murine melanoma 
study conducted by Liu et al (8, 9). Here, additional key efficacy insights will be summarized and presented 
from the Bunch et al. manuscript. 
Bunch et al. conclude that treatment with the pAc/emm55 vector drug substance increases T cell tumor 
infiltration and delays tumor growth, while the anti-tumor efficacy of the dug substance is T cell 
dependent and that this anti-tumor efficacy is improved with drug substance + PD-1 antagonist 
combination therapy. These conclusions are echoed in the study report and summary found in the IND. 
 
Figure 1 illustrates the anti-tumor efficacy of drug substance monotherapy and drug substance/PD-1 
antagonist combination therapy. 

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Figure 1.  IFNγ production increases upon the addition of pAc/emm55 and PD-1 antagonist therapy. 
Murine melanoma B16-F10 cells were injected subcutaneously on Day 0. 
pEmpty vector (control) or pEmm55 vector was injected on days 7, 14, and 21. Starting on day 8, mice received 
intraperitoneal injection of either isotype control antibody or PD-1 antagonist (250 μg/200μL/IP) twice weekly (A). 
(B) Splenocytes collected from mice treated with emm55 vector ± PD-1 antagonist therapy were co-cultured with 
B16-F10 melanoma cells and culture supernatants were collected after 24 hours. Levels of IFNγ were measured (p < 
0.01 utilizing unpaired T test with Bonferroni correction). (C) Tumor sizes for these B16-F10 tumors at day 25 were 
also measured and demonstrated an increased response with pEmm55/PD-1 antagonist compared to PD-1 
antagonist therapy alone (p < 0.01; unpaired T test). (D) Tumor growth curves from each treatment group (p<0.02; 
unpaired T test with Bonferroni correction). (N=12 for treatment groups, N=9 for control pEmpty group). 
 
 

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Study # 20170516 – Murine Melanoma Biodistribution Study 
A separate biodistribution murine melanoma study showed that IFx-Hu2.0 injections resulted in high 
levels of pAc/emm55 expression vector presence and emm55 mRNA expression in injected tumors. It also 
showed substantially lower levels thereof in all non-target (i.e. non-skin) organs tested. No adverse events 
were reported. 
The biodistribution and pharmacokinetic properties of IFx-Hu2.0 were evaluated in the B16-
F10/C57BL/6NCrl melanoma model. Mice initially received an injection of the syngeneic B16-F10 
melanoma cell line. After tumors were palpable, mice were randomly selected into treatment cohorts to 
receive a single vaccine injection of IFx-Hu2.0 or a similarly complexed negative control vector 
(pAc/empty), which lacks the emm55 coding region (20 mcg in 50 mcL). Animals were sacrificed and 
tissues were harvested one day post vaccination, which was the expected time of peak detection, and at 
seven and 14 days post-injection, to evaluate clearance of the emm55 transgene from tissues. Genomic 
DNA (gDNA), RNA and cDNA were prepared from the injected tumor and eight organs at each time point. 
A quantitative PCR assay meeting the sensitivity recommendation of ≤50 copies of vector/1 mcg DNA was 
used to measure the absolute level of pAc/emm55 transgene and relative levels of emm55 mRNA 
expression normalized to the endogenous control gene glyceraldehyde-3-phosphate dehydrogenase 
(GAPDH). 
To determine the biodistribution pAc/emm55, absolute levels of emm55 were measured in injected 
tumors and organs over time and are reported in copy numbers per µg gDNA. As expected, transgene 
levels were highest in tumor samples one day post vaccination, with a maximum level of 1.16x1010 copies. 
This represents ~7.3% of the copies injected. Although the transgene was detected in gDNA prepared 
from all organs, the absolute level was approximately 4 orders of magnitude higher in tumor gDNA than 
in the next highest tissue one day post injection, and was 4-7 orders of magnitude higher than in all other 
tissues at this timepoint. At seven days post injection, the transgene was detected at 3-6 orders of 
magnitude lower in other tissues than in tumor. At 14 days post injection, the transgene was detected at 
2-4 orders of magnitude lower than in tumor. 
To determine the kinetics of transgene expression, normalization was used to compare relative levels over 
time in each tissue. Normalized levels of emm55 mRNA in tumor (9.8910-01), kidney (9.01x10-05) and lung 
(5.82x10-04) peaked at one day post injection. In lymph node and spleen, peak levels were similar at days 
one and seven post injection relative to the SD of these samples. In liver, peak levels were detected at 
seven days post injection. In heart, peak levels were detected and 14 days post injection. Expression in 
brain and ovaries was uniform over time relative to SD. In addition to transgene biodistribution and 
expression kinetics, all animals involved in this study were monitored for vaccine-related adverse 
reactions. 
In conclusion, this study demonstrates that intralesional injection of IFx-Hu2.0 resulted in high levels of 
emm55 transgene uptake and mRNA expression in tumors with substantially lower levels in other organs 
in which it was detected. These residual levels did not result in any adverse events in the study animals.  
Previous Human Experience 
Phase 1 Study CM 2017-01 (NCT03655756) 
Morphogenesis has completed a Phase 1, non-randomized, open-label, uncontrolled, interventional, 
single-center trial of IFx-Hu2.0 monotherapy in six adult patients (≥ 18 years of age) with unresectable 
stage III or distant metastatic (stage IV) cutaneous melanoma refractory to prior therapy (chemotherapy 
and/or PD-1 antagonist +/- CTLA-4 antagonist therapies). Patients received a fixed dose of 0.1 mg of IFx-

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Hu2.0 per lesion in up to three lesions at a single time point. Subjects were observed for any acute adverse 
events post injection and for any delayed adverse events at Day 28 ± 7 days. 
The primary outcome was safety. The primary outcome measure was the number of Grade 3 to 5, 
treatment-related adverse events per CTCAE 5.0. This study accrued 6/6 evaluable patients. At the 
conclusion of the trial, no patient experienced any grade 3 to 5 treatment-related adverse events. One 
patient received injections at multiple time points. More than one patient had more than one lesion 
injected at a given timepoint. 
Clinical data available to date (i.e., tumor tissue biopsies and blood sample analysis) is presented below 
from 3 of the 6 evaluable patients (P1, P3, and P4). Tumor biopsies were analyzed via fluorescent multi-
color immunohistochemistry (mIHC) staining. 
This interim cellular analysis indicates that: 
1. all patients (3/3 patients) experienced a significant decrease in SOX10+ melanoma cells 
indicating melanoma cell death within the target lesion, and 
2. all patients (3/3 patients) experienced a decrease in FOXP3/CD8+ regulatory T cells mediating 
immunosuppression correlating with an improved overall prognosis (i.e., an increased likelihood 
of a clinical immune response), and 
3. P1 and P4 (2/3 patients) experienced hypocellularity indicating cell death within the target 
lesion. 
Clinically, P1 went on to receive nivolumab monotherapy (PFS of 19 months and SD), P3 went on to receive 
talimogene laherparepvec monotherapy (PFS of 12 months and SD), and P4 went on to receive 
nivolumab/ipilimumab combination therapy (PFS of 12 months and PR). The study intervention exhibited 
a strong safety profile with no Grade 3 to 5 treatment-related adverse events per CTCAE v5.0. 
 
2.3 RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS 
 
IFx-Hu2.0 primes the immune system to a broad array of patient-specific tumor antigens. When breaking 
tolerance to tumor-associated antigens, which are ‘self’ antigens, there is a possibility of inducing some 
form of autoimmunity. Since efficacy and adverse events of immunotherapies are in general mediated by 
the same underlying pathways and mechanisms, there may be an increased risk of autoimmunity with 
immunotherapies such as IFx-Hu2.0. Patients receiving immunotherapies have been reported to 
experience mild pyrexia, cutaneous reactions, diaphoresis, rigor, tachypnea and hypotension. 
In the IFx-Hu2.0 monotherapy phase I trial (NCT03655756), eight patients were screened, seven patients 
were enrolled and treated, and six patients were evaluable for the primary endpoint. There was one 
screen failure and one death unlikely related to the study drug as determined by the principal investigator. 
The primary outcome measure of this trial was the rate of DLTs defined as the rate of grade 3 to 5 
treatment-related adverse events (AEs) that were deemed unacceptable toxicities by the principal 
investigator. No grade 3 to 5 treatment-related adverse events (AE) per CTCAE v5.0 were reported (Grade 
1 – mild; Grade 2 – moderate). Table 2 and Table 3 reflect all AEs observed in this trial. 
 

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Table 2 Treatment-Related AEs based on preliminary data from the IFx-Hu2.0 monotherapy phase I 
trial (NCT03655756) 
All Treatment-Related Adverse Events (Attribution: 
possible to definite), n=6 
Number of Patients (%) Severity 
Injection site reaction 
4 (67%) 
Mild to Moderate 
Tumor hemorrhage            
2 (33%) 
Mild to Moderate 
Tumor pain 
1 (17%) 
Moderate 
Erythema 
1 (17%) 
Mild 
Paresthesia 
1 (17%) 
Mild 
Back pain 
1 (17%) 
Mild 
Lymphocyte count decreased 
1 (17%) 
Mild 
Muscle cramp 
1 (17%) 
Mild 
Pruritus 
1 (17%) 
Mild 
Total 
6 (100%) 
 
Table 3 All AEs based on preliminary data from the IFx-Hu2.0 monotherapy phase I trial (NCT03655756) 
All Adverse Events, n=7 
Number of Patients (%) 
Severity 
Injection site reaction 
4 (67%) 
Mild to Moderate 
Tumor hemorrhage            
2 (33%) 
Mild to Moderate 
Hypertension 
2 (33%) 
Mild to Severe 
Erythema 
1 (17%) 
Mild 
Paresthesia 
1 (17%) 
Mild 
Back pain 
1 (17%) 
Mild 
Lymphocyte count decreased 
1 (17%) 
Mild 
Muscle cramp 
1 (17%) 
Mild 
Pruritus 
1 (17%) 
Mild 
Anorexia 
1 (17%) 
Mild 
Dry mouth 
1 (17%) 
Mild 
Insomnia 
1 (17%) 
Mild 
Flatulence 
1 (17%) 
Mild 
Lymphedema 
1 (17%) 
Mild 
Constipation 
1 (17%) 
Moderate 
Tumor pain 
1 (17%) 
Moderate 
Gastric pneumatosis 
1 (17%) 
Severe 
Clostridial sepsis 
1 (17%) 
Death 
Multiple organ dysfunction syndrome 
1 (17%) 
Death 
Total 
7 (100%) 
Note:  Clostridial sepsis and multi organ failure was experienced by the same patient leading to death. 
These AEs were deemed unlikely related to the study drug based on the assessment of the principal 
investigator. 
 
 

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2.3.2 KNOWN POTENTIAL BENEFITS 
 
Mechanism of Action 
IFx-Hu2.0 is an immunomodulator and belongs to the class of noncellular, therapeutic cancer vaccines. 
Injection of IFx-Hu2.0 into the target lesion facilitates the localized expression of the highly immunogenic 
Emm55 protein by the tumor cells on their surface. This expression is readily and prominently recognized 
by the immune system. This initial recognition primes an immune cascade that exposes tumor-specific 
and tumor-associated antigens to the effector mechanisms of the immune system. The immune response 
becomes systemic as epitope spreading activates subsequent neoantigen recognition which in turn 
induces reactive T cells. Hereby injected and non-injected lesions experience a treatment effect. 
 
Resensitizing the tumor immune microenvironment through immunomodulation with IFx-Hu2.0 could 
lead to an increase in tumor lymphocyte infiltration. This approach could overcome T cell exhaustion to 
achieve durable antitumor T cell responses for long-term tumor control (10-14). 
Equine Melanoma Model 
pAc/emm55 (drug substance) monotherapy showed 73% stable disease (SD) and 27% partial response 
(PR) per RECIST v1.1 (n=24).  Additional details regarding this study can be found in section 4.2.2.1 of the 
Investigator’s Brochure. 
B16-F10/C57BL/6NCrl Murine Melanoma Model 
IFx-Hu2.0 monotherapy showed a statistically significant increase in overall survival (OS) and a decrease 
in tumor burden (treatment vs. control). Combination therapy with a PD-1 Antagonist showed a 
statistically significant reduction in tumor burden (combination therapy vs. monotherapy).  Additional 
details regarding these studies can be found in section 4.2.1 of the Investigator’s Brochure. 
Phase 1 First-In-Human Trial of IFx-Hu2.0 in Stage III to IV Cutaneous Melanoma 
Correlative study findings for the first three evaluable patients indicate that all patients experienced a 
significant decrease in SOX10+ melanoma cells indicating cell death within the target lesion, all patients 
experienced a decrease in FOXP3/CD8+ regulatory T cells mediating immunosuppression correlating with 
an improved overall prognosis (i.e. an increased likelihood of a clinical immune response), and that 2 out 
of 3 patients experienced hypocellularity indicating cell death within the target lesion. This preliminary 
efficacy signal will be further evaluated in this trial. 
 

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3 OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
Primary 
Safety; i.e., to assess the safety, tolerability, and 
feasibility of treatment with IFx-Hu2.0 as a 
monotherapy in patients with skin cancer. 
The primary endpoints of this trial will be the safety and 
feasibility of the treatment regimen. Safety will be reported 
using the most current version of Common Terminology 
Criteria for Adverse Events (CTCAE). 
 
Feasibility will be defined as the ability to treat at least 80 of 
the approximately 100 patients enrolled without dose-
limiting toxicity (DLT). 
Secondary 
To assess post-therapeutic pathological response at 
four weeks post-treatment. 
The secondary endpoint is Pathological Response defined as a 
response assessment to IFx-Hu2.0 in tumor lesions excised by 
evaluating percent Residual Vial Tumor (%RVT), at four weeks as: 
• 
pathological complete response (pCR),  
• 
major pathological response (mPR),  
• 
partial pathological response (pPR), or  
• 
pathological non-response (pNR)  
Tertiary/Exploratory 
To assess anti-tumor immunity post-treatment. 
Patient samples (plasma and/or serum) will be assayed to 
detect tumor antigen specific antibody generation in 
addition to a protein biomarker discovery assay specific to 
immuno-oncology therapy assessments. 
 
IHC will be performed on pre- and post-treatment tissue 
samples to contrast the cell sub-types across time points. 

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4 STUDY DESIGN 
4.1 OVERALL DESIGN 
This is a multi-site, -open label, interventional, prospective, phase 1 trial to assess safety and tolerability 
of IFx-Hu2.0 in patients with basal cell carcinoma, or squamous cell carcinoma. 
 
A total of approximately one hundred (100) male and/or female adult patients (greater than or equal to 
18 years old), of any ethnicity and race, with at least one cutaneous squamous cell carcinoma, or basal 
cell carcinoma lesion accessible for direct injection, who meet all inclusion and no exclusion criteria, will 
be eligible for enrollment and treatment with IFx-Hu2.0. 
 
Enrollees will receive IFx-Hu2.0 as a single intralesional injection at a single time point. The target dose 
will be 100 μg of plasmid DNA per lesion injected at a final dose volume of 200 μL per lesion. The injected 
lesion will be completely excised at the follow-up visit four weeks later, and will be biopsied for 
confirmation of diagnosis and for the establishment of a pathological response baseline Peripheral blood 
will be collected from these patients prior to treatment administration and at the follow-up visit four 
weeks later. 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. 
4.2 JUSTIFICATION FOR DOSE 
IFx-Hu2.0 is composed of pAc/emm55 (plasmid DNA (pDNA)) complexed with in vivo-jetPEI® (linear 
polyethylenimine), a transfection reagent, and dextrose, a complex stabilizer. The ionic balance within the 
in vivo-jetPEI®/pDNA complexes is crucial. For effective cell entry, the complexes should be cationic. The 
N/P ratio is a measure of the ionic balance within the complexes and is defined as the number of Nitrogen 
residues of in vivo-jetPEI® per nucleic acid Phosphate. Approximately one in three nitrogen atoms within 
the in vivo-jetPEI® molecule is cationic. Therefore, electroneutrality of in vivo-jetPEI®/pDNA complexes is 
reached at an N/P ratio > 2 to 3. in vivo-jetPEI® is provided as a 150 mM solution (expressed as nitrogen 
residues). Given that 1 mcg of nucleic acid contains 3 nmoles of anionic phosphate, the amount of in vivo-
jetPEI® to be mixed with pDNA in order to obtain a specific N/P ratio is calculated using the following 
formula: 
 
 
 
The N/P ratio of 6 has been optimized for in vitro delivery of IFx-Hu2.0. This is the N/P ratio used for the 
preparation of clinical doses of IFx-Hu2.0. 
 
4.3 END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the study 
including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), Section 
1.3. The end of the study is defined as completion of the last visit or procedure shown in the SoA in the 
trial globally. 

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5 STUDY POPULATION 
5.1 INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the study 
3. Ability to receive intralesional injections 
4. Male or female, aged ≥ 18 years 
5. Histologically confirmed cutaneous squamous cell carcinoma, or basal cell carcinoma with accessible 
lesions (based on archival tissue or new tissue biopsy for histological confirmation) 
6. Life expectancy of at least 24 weeks at the time of screening 
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 
8. Must have measurable disease greater than 3 mm 
9. At least one injectable lesion 
10. Adequate organ function as defined below (Note: these screening laboratory tests must be obtained 
within two weeks prior to the baseline visit, Day 0): 
10.1. Hemoglobin (Hb) >10 g/dL 
10.2. Absolute Neutrophil Count (ANC) >1,500 cells/mcL 
10.3. Platelet Count (PLT) >75,000/mcL 
10.4. Prothrombin Time (PT) or International Normalized Ratio (INR) ≤1.5 times the institutional 
ULN unless patient is receiving anticoagulant therapy as long as PT or INR is within 
therapeutic range of the intended use of anticoagulants. 
10.5. Activated Partial Thromboplastin Time (aPTT) ≤1.5 times the institutional ULN unless patient 
is receiving anticoagulant therapy as long as aPTT is within therapeutic range of the intended 
use of anticoagulants. 
10.6. Serum Creatinine (SCr) ≤1.5 times the institutional ULN 
10.7. Total Bilirubin ≤1.5 times the institutional ULN 
10.8. Aspartate Aminotransferase (AST) ≤3 times the institutional ULN 
10.9. Alanine Aminotransferase (ALT) ≤3 times the institutional ULN 
10.10. Lactate Dehydrogenase (LDH) ≤2 times the institutional ULN 
10.11. Alkaline Phosphatase (ALP) ≤2.5 times the institutional ULN 
10.12. Gamma GT (GGT) ≤2.5 times the institutional ULN 
11. Lymphocyte count ≥500,000 cells/mL 
12. For females of reproductive potential: must have a negative urine or serum pregnancy test result 
within 24 hours prior to receiving IFx-Hu2.0; must use highly effective contraception (e.g.,licensed 
hormonal or barrier methods) for at least one month prior to screening and agreement to use such a 
method during study participation and for an additional 26 weeks after the end of study treatment 
13. For males of reproductive potential: use of barrier method or other methods to ensure effective 
contraception with partner 
5.2 EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Concurrent participation in any other clinical trial 
2. Inability to consent for self 
3. Lesions on scalp with bone erosions must not be selected as injection sites for IFx-Hu2.0 

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4. Life expectancy of fewer than 24 weeks at the time of screening 
5. Prior systemic anti-cancer treatment within three weeks from start of treatment (Day 0) 
6. Treatment with any investigational product within the three weeks preceding injection 
7. Concurrent chemotherapy or biological therapy. Concurrent radiotherapy is allowed as long as it is 
not the same site as the injected lesion. 
8. 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. 
9. Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration 
of the trial, starting with the pre-screening or screening visit through 26 weeks after the last dose of 
trial treatment 
10. Immunizations for encapsulated bacteria were not given for patients who have undergone a 
splenectomy 
11. 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 
participate in the study 
12. Active Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) or 
Hepatitis B/C. Patients with treated HIV/AIDS or Hepatitis B/C with no evidence of active infection 
may be enrolled 
13. History of organ allograft transplantation 
14. Presence of any uncontrolled and significant medical or psychiatric condition which would interfere 
with trial safety assessments 
5.3 LIFESTYLE CONSIDERATIONS 
During this study, participants are asked to: 
1. Refrain from altering (i.e., initiating, modifying, or discontinuing) dietary habits (incl. diets) other 
than those expressly mentioned below without consulting the treating physician. 
2. Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate 
for 6 hours before receiving IFx-Hu2.0 
3. Abstain from alcohol for 24 hours before receiving IFx-Hu2.0 
4. Participants who use tobacco products will be instructed that use of nicotine-containing products 
(including nicotine patches) will not be permitted while they are in the clinical unit.  
5. Abstain from strenuous exercise for 24 hours before each blood collection for clinical laboratory 
tests. Participants may participate in light recreational activities during participation in the study 
(e.g., watching television, reading). 
6. Minimize interactions with household contacts who may be immunocompromised. 
5.4 SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants, to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE). 
 

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Individuals who do not meet the criteria for participation in this trial (screen failure) may be rescreened. 
Rescreened participants should be assigned the same participant number as for the initial screening. 
5.5 STRATEGIES FOR RECRUITMENT AND RETENTION 
This study will have a goal of 100 evaluable patients. It is the intent of the study team to recruit additional 
patients to be screened and enrolled if any of the existing patients are lost to follow-up or withdraw 
consent. 
 
Potential participants will be identified by sites through physician referrals, available recruitment 
databases, and other methods available to participating sites to identify potential participants. Specific 
recruitment materials  may be developed by the sponsor.   In addition, if any site decides to utilize 
participant-focused materials for recruitment, such materials and a usage plan will be submitted for IRB 
review and approval prior to implementation. A clinical enrollment manager (CEM) or sponsor designee(s) 
may locally support the research team and facilitate patient recruitment at the study site in addition to 
all other measures/efforts.  Under no circumstance will referral fees, incentives, or bonuses to physicians 
for recruitment be allowed. 
 
There is no specific plan to target participants based on race, gender, or age. All eligible potential 
participants will be approached for inclusion. 
 
It is anticipated that recruitment will take up to 12 months to complete at approximately five research 
sites.  Sites will be NCI-designated cancer centers, academic medical centers, clinics, and doctor’s offices 
within the United States. Sites can include community facilities as a primary site or a satellite site of a 
participating center as long as they meet the requirements regarding the proper handling and 
administration of the investigational agent.   
 
Due to the size and short duration of the study, there is no planned retention or compensation plan for 
participants.  Throughout the study, participants will be reminded about upcoming visits and the 
procedures to be performed at the visit.  New information that surfaces during the study will be 
communicated to participants through IRB-approved mechanisms. 
 
In alignment with the Internal Revenue Service (IRS) 2020 Standard Mileage Rate (Notice 2020-05), 
participants can be reimbursed at a rate of 17 cents per mile driven in an automobile for traveling for 
study-related medical purposes. This will be done approximately one month after travel receipts are 
submitted by study staff to the sponsor. 

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6 STUDY INTERVENTION 
6.1 STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
pAc/emm55, the drug substance (also known as the active pharmaceutical ingredient), is a recombinant 
plasmid expression vector containing the Streptococcus pyogenes serotype M55 (Isolate A928171) 
modified cell surface M virulence protein as an antigen. The plasmid backbone is derived from the Takara 
Bio stable, constitutive, nonviral, mammalian expression vector pAcGFP1-N1. pAc/emm55 is expressed in 
Escherichia coli (Thermo Fischer Scientific Invitrogen™ One Shot™ Stbl3™ (derived from HB101)). 
6.1.2 DOSING AND ADMINISTRATION 
 
The amount of drug administered to the participant is 0.1mg injected into a single lesion. IFx-Hu2.0 must 
be administered within 4 hours of constitution (see Investigator’s Brochure section 3.3). 
 
IFx-Hu2.0 is intended for intralesional (i.e. cutaneous, subcutaneous, or lymph nodal) injection. All 
participants will be monitored for 30 minutes after injection for any immediate adverse events. 
Participants must abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, 
and chocolate) for 6 hours and abstain from alcohol for 24 hours before the administration of IFx-Hu2.0. 
 
Administration 
1. Avoid placing fingers near the lesion being injected to prevent needlesticks. 
2. Use a single insertion point for each lesion. 
3. Inject evenly throughout the lesion on multiple tracks, pulling the needle back after injecting a 
portion of the drug without withdrawing it from the lesion, then rotating it radially on another track 
until the entire lesion is treated. If the lesion is resistant to drug injection, apply slow, steady 
pressure, moving the needle slightly as needed. Local anesthetic should not be injected into the 
lesion or the surrounding tissue, since it may alter pH and therefore drug stability. 
4. Withdraw the needle slowly to reduce the risk of drug leakage. 
5. Clean the injection site and surrounding area with an alcohol pad. 
 
A single dose (0.1mg) will be used in this trial and at a single timepoint, therefore no dose escalation or 
reduction is proposed. 
6.1.3 STUDY PROCEDURES AND SCHEDULE 
 
Participant engagement will involve a screening period, baseline visit, and follow-up/final study visit for a 
total of three visits.  The total duration of participation for each individual  participant is expected to be 
approximately six weeks.  A snapshot of the study schedule of events can be found in section 1.3. 
 
Screening (Day -14 to Day -1) 
1. Obtained signed, informed consent (if not obtained prior to this visit) 

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2. Demographic information 
3. Medical history 
4. Concomitant medications 
5. Physical exam, including vital signs, height, weight 
6. ECOG performance status 
7. Electrocardiogram (ECG) 
8. Tumor lesion measurement 
9. Tumor biopsy for histologic confirmation of carcinoma diagnosis 
9.1. If a diagnostic biopsy has previously  been performed, the report of the biopsy resultsof the 
tissue block would be acceptable to confirm diagnosis 
10. Electrocardiogram (ECG)  
11. Laboratory tests 
11.1. 
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) 
11.2. 
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) 
11.3. 
Urinalysis: UA with microscopic evaluation 
11.4. 
Anti-double-stranded DNA (anti-dsDNA) antibody test 
11.5. 
Anti-DNase B Titer, Serum 
12. Serum pregnancy tests for females of reproductive potential 
Baseline (Visit 1; Day 0) 
1. Concomitant medications 
2. ECOG performance status 
3. Physical exam, including vital signs, weight 
4. Laboratory tests 
4.1. 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) 
4.2. 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) 
4.3. Urinalysis: UA with microscopic evaluation 
4.4. Anti-double-stranded DNA (anti-dsDNA) antibody test 
4.5. Anti-DNase B Titer, Serum 
5. Adverse event recording per CTCAE v5.0 
6. Tumor lesion measurement (longest diameter) 
7. Urine pregnancy tests for females of reproductive potential; done within 24 hours prior to IFx-Hu2.0 
administration, and results must be available prior to IFx-Hu2.0 administration 

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8. 40 mL of blood for exploratory analysis 
9. IFx-Hu2.0 administration 
Final Visit (Day 28 ± 5 days) or Early Termination Visit 
1. Concomitant medications 
2. ECOG performance status 
3. Physical exam, including vital signs, weight 
4. Electrocardiogram (ECG) 
5. Laboratory tests 
5.1. 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) 
5.2. 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) 
5.3. Urinalysis: UA with microscopic evaluation 
5.4. Anti-double-stranded DNA (anti-dsDNA) antibody test 
5.5. Anti-DNase B Titer, Serum 
6. Adverse event recording per CTCAE v5.0 
7. Tumor lesion measurement (longest diameter) 
8. Serum pregnancy tests for females of reproductive potential 
9. 40 mL of blood for immune response evaluation 
10. Tumor excision (wide local excision) for pathological response (final) 
 
Unscheduled Visit  
If participants require a visit between the baseline and final study visits, then the following procedures 
may be performed, as indicated (per investigator discretion): 
1. Concomitant medications 
2. ECOG performance status 
3. Physical exam, including vital signs, weight 
4. Electrocardiogram (ECG) 
5. Laboratory tests 
5.1. 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) 
5.2. 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) 
5.3. Urinalysis: UA with microscopic evaluation 
5.4. Anti-double-stranded DNA (anti-dsDNA) antibody test 
5.5. Anti-DNase B Titer, Serum 
6. Adverse event recording per CTCAE v5.0 

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7. Tumor lesion measurement (longest diameter) 
8. Serum or urine pregnancy tests for females of reproductive potential 
6.2 PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
IFx-Hu2.0, the drug product, is composed of pAc/emm55, an immunomodulator, complexed with Polyplus 
in vivo-jetPEI® (linear polyethylenimine), a transfection reagent, and dextrose, a complex stabilizer. After 
compounding IFx-Hu2.0 per the Pharmacy Manual at the Investigational Drug Services (IDS) pharmacy, 
each vial contains 0.2 mg of pAc/emm55 in 0.4 mL of solution. 
 
The sponsor provides IFx-Hu2.0 as a vaccine kit with finished drug product preparation instructions and 
consumables (except for the final clinical site-supplied syringe for direct patient care). 
 
To request vaccine kits delivered to the site, the site personnel should complete the investigational 
product (IP) requisition form (Appendix A) and email it to IP-Requisition@Morphogenesis-Inc.com. 
Whenever the sponsor distributes IP to a site, a sponsor-initiated IP distribution form will accompany the 
order and require the dated signature of the receiving site personnel. 
 
Any unused IFx-Hu2.0 vaccine kits will be reverse-distributed by the site to the sponsor under the 
following conditions: 
a) A vaccine kit has met its retest date, 
b) The participation of the primary investigator at the clinical site has been discontinued, 
c) The participation of the clinical site has been discontinued, or 
d) The trial has been completed. 
To reverse distribute the unused vaccine kits from the site to the sponsor, site personnel should complete 
the IP reverse distribution form (Appendix B of the Pharmacy Manual), schedule delivery with the carrier 
noted on this form, copy the completed form for his or her own records and include the original, 
completed form in the delivery to the sponsor. 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
The sponsor provides the investigational product (IP) as a vaccine kit with drug product preparation 
instructions and consumables (except for the final clinical site-supplied syringe for direct patient care). 
 
Up-to-date information regarding the IP formulation, appearance, packaging, and labeling can be found 
in the Pharmacy Manual. 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
Store the IFx-Hu2.0 vaccine kits and their contents refrigerated at 2 – 8°C. 
 
The prepared drug product must be administered intralesionally within 4 hours from the time of 
complexing and final incubation. 

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6.2.4 PREPARATION 
 
Store all IFx-Hu2.0 vaccine kits and their contents refrigerated at 2 – 8°C. Remove vaccine kits from the 
refrigerator as needed when ready to prepare drug product. One vaccine kit makes a fixed dose for one 
intralesional injection. Perform each step aseptically in a primary engineering control (PEC) (i.e., a vertical 
laminar airflow workbench in an International Organization for Standardization [ISO] 5 environment) 
whenever feasible. Follow the current official United States Pharmacopeia (USP) <797> chapter as well as 
the instructions in the Pharmacy Manual to prepare one single-dose vial of IFx-Hu2.0. 
 
6.3 STUDY INTERVENTION COMPLIANCE 
To document study drug administration, vial identification information, time of administration, and any 
notes regarding the injection(s) will be documented by the administering investigator on the drug 
administration case report form. Study drug compliance will be reviewed by the study monitors and the 
principal investigator. 
6.4 CONCOMITANT THERAPY 
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 Case Report Form (CRF) are 
concomitant prescription medications, over-the-counter medications, and supplements taken during 
participation and over 90 days prior to enrollment. 

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7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 DISCONTINUATION OF STUDY INTERVENTION 
 
If a clinically significant finding is identified (including, but not limited to changes from baseline) after 
enrollment, the investigator or qualified designee will determine if any change in participant management 
is needed. Any new clinically relevant finding will be reported as an adverse event (AE). Subjects with 
treatment-related toxicity will be followed for the ongoing drug-related adverse events until resolved, 
return to baseline, deemed irreversible by the treating physician, the subject has been properly referred 
to an appropriately licensed practitioner for further evaluation and treatment, or until the subject is lost 
to follow up, withdrawal of study consent, removal of the subject from the trial by the treating physician, 
or start of a subsequent anti-cancer therapy. 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
1. Concomitant medications 
2. ECOG performance status 
3. Physical exam, including vital signs, height, weight 
4. Laboratory tests 
4.1. 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) 
4.2. 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) 
4.3. Urinalysis: UA with microscopic evaluation 
4.4.  
4.5. Anti-double-stranded DNA (anti-dsDNA) antibody test 
4.6. Anti-DNase B Titer, Serum 
5. Adverse event recording per CTCAE v5.0 
6. Tumor lesion measurement (longest diameter) 
7. Serum pregnancy tests for females of reproductive potential 
8. 40 mL of blood for immune response evaluation 
8.1. Tumor biopsy for pathological response (final) 
 
 
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
1. Pregnancy 

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2. Significant study intervention non-compliance 
3. 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 
4. Disease progression 
5. If the participant meets an exclusion criterion or fails to meet an inclusion criteria (either newly 
developed or not previously recognized) that precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded on the case 
report form (CRF). Subjects who sign the informed consent form but do not receive the study intervention 
may be replaced. Subjects who sign the informed consent form, and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study will be replaced. 
7.3 LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for scheduled visit(s) and is 
unable to be contacted by the study site staff. 
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
1. The site will attempt to contact the participant and reschedule the missed visit and counsel the 
participant on the importance of maintaining the assigned visit schedule and ascertain if the 
participant wishes to and/or should continue in the study. 
2. Before a participant is deemed lost to follow-up, the investigator or designee will make every effort 
to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a certified 
letter to the participant's last known mailing address or local equivalent methods). These contact 
attempts should be documented in the participant's medical record or study file. 
3. Should the participant continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 

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8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 SAFETY AND OTHER ASSESSMENTS 
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 the clinical sites will have access to a copy of the CTCAE v5.0. Careful 
evaluation to determine the toxicity IFx-Hu2.0 as a monotherapy will be performed. Adverse events will 
be documented beginning at initiation of treatment (Day 0) as well as at the follow-up visit whether that 
be end of study as planned or early termination. 
 
Subjects with treatment-related toxicity will be followed for the ongoing drug-related adverse events until 
resolved, return to baseline, deemed irreversible by the treating physician, the subject has been properly 
referred to an appropriately licensed practitioner for further evaluation and treatment, or until the subject 
is lost to follow up, withdrawal of study consent, removal of the subject from the trial by the treating 
physician, or start of a subsequent anti-cancer therapy. 
8.2 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) (21 CFR 312.32(A)) 
 
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. 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) (21 CFR 312.32(A)) 
 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect in the offspring of a participant. Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
 
 
 

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8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 SEVERITY OF EVENT 
 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity: 
1. Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
2. Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
3. 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. 
8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the investigator 
who examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect. 
 
1. Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (dechallenge) should be clinically plausible. The event must be pharmacologically 
or phenomenologically definitive., with use of a satisfactory rechallenge procedure if necessary. 
2. 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. 
3. Potentially 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. 
4. 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). 

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5. 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. 
8.2.3.3 EXPECTEDNESS 
 
The medical monitor 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 Investigator Brochure for IFx-Hu 2.0. 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or serious adverse event (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 case report form (CRF). Information to be collected includes 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 
while on study must be documented appropriately regardless of relationship.  
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the a pre-existing  condition deteriorates at any time 
during the study, it will be recorded as an AE, with use of descriptors in the AE term to designate that it is 
a pre-existing condition (e.g., worsening of or exacerbation of) 
 
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. 
 
The investigator will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. 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. 
8.2.5 ADVERSE EVENT REPORTING 
 
Adverse events will be documented.  The principal investigator at the site is responsible for notifying the 
sponsor of any adverse event as soon as possible.  The medical monitor will review all adverse event 
reports and ensure that participants are receiving appropriate clinical care and identify any potential 
safety concerns.  The medical monitor will assess the information provided to determine the relatedness 
of the event to the study intervention as well as propose any changes to the protocol and/or consent form 
based on the event.  All adverse events will be documented and reported to the FDA in the annual report.  
Adverse events that meet the requirements for reporting to the IRB will be reported within the guidelines 
required by the IRB of record, along with necessary supporting information and revised trial 
documentation, as necessary. 

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8.2.6 SERIOUS ADVERSE EVENT REPORTING 
 
Serious events will be documented on the current OMB approved FDA Form 3500A following the current 
instructions for reporting. The study clinician will immediately report to the sponsor any serious adverse 
event, whether or not considered study intervention related, including those listed in the protocol or 
investigator brochure.  The report  must include an assessment of whether there is a reasonable possibility 
that the study intervention caused the event. Study endpoints that are serious adverse events (e.g., all-
cause mortality) must be reported in accordance with the protocol unless there is evidence suggesting a 
causal relationship between the study intervention and the event (e.g., death from anaphylaxis).  
 
All serious adverse events (SAEs) will be followed until satisfactory resolution or until the site investigator 
deems the event to be chronic or the participant is stable. Other supporting documentation of the event 
may be requested by the study sponsor and should be provided as soon as possible. 
 
The medical monitor will review all adverse event reports and ensure that participants are receiving 
appropriate clinical care and identify any potential safety concerns.  The medical monitor will assess the 
information provided to determine the relatedness of the event to the study intervention as well as 
propose any changes to the protocol and/or consent form based on the event. The study sponsor will be 
responsible for notifying the Food and Drug Administration (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. In addition, the sponsor must notify FDA and all 
participating investigators in an Investigational New Drug (IND) safety report of potential serious risks, 
from clinical trials or any other source, as soon as possible, but in no case later than 15 calendar days after 
the sponsor determines that the information qualifies for reporting. 
8.2.7 REPORTING OF EVENTS TO PARTICIPANTS 
 
Changes in the risk profile and/or risk/benefit ratio from observed adverse and/or serious adverse events 
will be communicated to participants through an IRB-approved revised consent form or addendum, as 
deemed appropriate given the information to be provided. If re-consent of the participants is required for 
continued participation, it must be obtained prior to continuing study related procedures. 
8.2.7 REPORTING OF PREGNANCY 
 
All females of reproductive 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. 
All investigators are required to report any pregnancy that occurs during the study within 24 hours of 
learning of the pregnancy. The site shall complete the Pregnancy Report Form and forward to the 
Sponsor’s safety vendor Drug Safety Navigator (DSN). 
The investigator is not obligated to actively seek pregnancy information in former study participants, but 
if the investigator learns of a pregnancy through spontaneous reporting, a Pregnancy Report Form must 
be completed and faxed to DSN. 
 
 

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9 STATISTICAL CONSIDERATIONS 
9.1 STATISTICAL HYPOTHESES 
 
The null hypothesis is that IFx-Hu2.0 may not be given safely as a neoadjuvant to patients with cutaneous 
squamous cell carcinoma, or basal cell carcinoma. 
 
The alternative hypothesis is that IFx-Hu2.0 may be given safely as a neoadjuvant to patients with 
cutaneous squamous cell carcinoma, or basal cell carcinoma. 
9.2 SAMPLE SIZE DETERMINATION 
The intent of this study is to enroll approximately 100 evaluable patients to assess the safety of IFx-Hu2.0 
as a monotherapy. A sample size of 100 has the following precision for estimation of DLT rates ranging 
from 0.1 to 0.5. A DLT is defined as an adverse event equal to or greater than grade 3, at least possibly 
related to the investigational agent, occurring within a 4-week period following IP administration, and 
deemed as having unacceptable toxicity by the principal investigator and/or medical monitor. 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 0.099 with 95% confidence. 
9.3 POPULATIONS FOR ANALYSES 
Safety Analysis Dataset: the subset of participants who received  at least one dose of study intervention. 
9.4 STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
 
This is a safety and feasibility study that is designed to evaluate the safety and feasibility of IFx-Hu2.0 use 
as monotherapy. Safety will be assessed and reported based upon CTCAE v5.0 criteria. Feasibility will be 
defined as the ability to treat at least 80 of the 100 patients enrolled without dose-limiting toxicity. 
 
The secondary endpoint is Pathological Response defined as a response assessment to IFx-Hu2.0 in tumor 
lesions excised at four weeks as; pathological complete response (pCR), major pathological response 
(mPR), partial pathological response (pPR), or pathological non-response (pNR) by evaluating percent 
Residual Vial Tumor (%RVT)(15). 
9.4.2 SAFETY ANALYSES 
 
 
Maximum planned sample size 
100 
The event probability (θ) 
0.2 
Desired probability of early stopping 0.05 
 

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The trial will be stopped if the number of Dose Limiting Toxicities (DLTs) is equal to or exceeds bn out of n 
patients with completed follow-up. 
 
Number of 
Patients, n 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Boundary, bn 
- 
- 
3 
4 
4 
5 
5 
6 
6 
6 
7 
7 
7 
8 
8 
8 
9 
9 
9 
10 
Number of 
Patients, n 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 
Boundary, bn 
10 
10 
11 
11 
11 
11 
12 
12 
12 
13 
13 
13 
13 
14 
14 
14 
15 
15 
15 
15 
Number of 
Patients, n 
41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 
Boundary, bn 
16 
16 
16 
17 
17 
17 
17 
18 
18 
18 
18 
19 
19 
19 
20 
20 
20 
20 
21 
21 
Number of 
Patients, n 
61 
62 
63 
64 
65 
66 
67 
68 
69 
70 
71 
72 
73 
74 
75 
76 
77 
78 
79 
80 
Boundary, bn 
21 
21 
22 
22 
22 
22 
23 
23 
23 
23 
24 
24 
24 
24 
25 
25 
25 
25 
26 
26 
Number of 
Patients, n 
81 
82 
83 
84 
85 
86 
87 
88 
89 
90 
91 
92 
93 
94 
95 
96 
97 
98 
99 
100 
Boundary, bn 
26 
26 
27 
27 
27 
27 
28 
28 
28 
28 
29 
29 
29 
29 
30 
30 
30 
30 
31 
31 
 
This boundary is equivalent to testing the null hypothesis, after each patient, that the event rate is equal 
to 0.2, using a one-sided level 0.008340 test. 
 
Sequential boundaries will be used to monitor dose-limiting toxicity rate. The accrual will be halted if 
excessive numbers of DLTs are seen, that is, if the number of DLTs is equal to or exceeds bn out of n 
patients with full follow-up. This is a Pocock-type stopping boundary that yields the probability of crossing 
the boundary at most [probability of early stopping] when the rate of DLTs is equal to the acceptable rate 
[event probability θ] (16). 
 
θ 
φ* 
E[Y] 
SD[Y] 
E[N] 
SD[N] 
E[Y/N] 
SD[Y/N] 
0.20 
0.0497 
19.31 
4.40 
96.58 
16.21 
0.21 
0.10 
0.30 
0.6116 
20.12 
7.86 
67.08 
34.29 
0.37 
0.16 
0.40 
0.9883 
11.85 
6.31 
29.65 
22.10 
0.50 
0.18 
0.50 
1.0000 
7.61 
3.56 
15.22 
10.91 
0.61 
0.19 
0.60 
1.0000 
5.71 
2.31 
9.52 
6.29 
0.71 
0.19 
0.70 
1.0000 
4.62 
1.63 
6.60 
3.96 
0.79 
0.17 
0.80 
1.0000 
3.89 
1.14 
4.86 
2.51 
0.87 
0.14 
0.90 
1.0000 
3.37 
0.69 
3.74 
1.41 
0.94 
0.11 
1.00 
1.0000 
3.00 
0.00 
3.00 
0.00 
1.00 
0.00 
 
Definitions: 
Y = the number of events, random, between 0 and N 
N = the number of patients, random, between 1 and K 
φ* = the actual probability of early stopping (hitting the boundary) 
E[ ] denotes the expected value (mean) 
SD[ ] denotes the standard deviation 
 
Resource: http://cancer.unc.edu/biostatistics/program/ivanova/ContinuosMonitoringForToxicity.aspx  
 
The medical monitor will provide 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. 
 

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9.4.3 BASELINE DESCRIPTIVE STATISTICS 
 
Study cohorts and groups will be compared on baseline characteristics, including demographics and 
laboratory measurements, using descriptive statistics. 
9.4.4 EXPLORATORY ANALYSES 
 
The tumor-specific immune response elicited by the investigational therapy will be assessed based on 
laboratory correlative studies performed on liquid biopsies and tumor biopsies pre- and post-treatment. 

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
Written documentation of informed consent, including detailed description of the study agent, study 
procedures, and risks, is required prior to performing any study related procedures. 
10.1.1.2 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. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of the signed 
informed consent document will be given to the participants for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the form 
signed, before the participant undergoes any study-specific procedures.  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. If additional new information surfaces 
throughout the study that may affect the participant’s willingness or ability to continue, it will be provided 
to them. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
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 investigator, the Investigational New Drug (IND) sponsor 
and regulatory authorities. If the study is prematurely terminated or suspended, the Principal Investigator 
(PI) will promptly inform study participants, the Institutional Review Board (IRB), and sponsor, and will 
provide the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 

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• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of the utility pathologic response assessment 
• 
Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, and 
satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
10.1.3 CONFIDENTIALITY AND PRIVACY 
 
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 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, representatives of the Institutional 
Review Board (IRB), regulatory agencies (including the Food and Drug Administration [FDA]) or 
pharmaceutical company supplying study product 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 each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for 2 
years after the completion of an BLA filing or determination not to pursue, or as long a period as dictated 
by the reviewing IRB, Institutional policies, if longer. 
 
Data will be captured in a 21 C.F.R. § 11-compliant electronic data capture (EDC) system. The EDC system 
will be reviewed periodically by sponsor-designated monitors throughout the conduct of the trial per the 
clinical trial agreement and the monitoring plan. This review will include source data verification utilizing 
patients’ medical records. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA 
 
Data collected for this study will be analyzed and stored by the sponsor. After the study is completed, the 
de-identified, archived data will be stored by the sponsor. 
 
With the participant's approval and as approved by local Institutional Review Boards (IRBs), de-identified 
biological samples will be stored by the sponsor. These samples would be used to research the response 
to IFx-Hu2.0 by evaluating tumor-specific immune responses post-treatment. 
 
During the conduct of the study, an individual participant can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent regarding biosample 
storage may not be possible after the study is completed. 

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10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
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. 
Study Sponsor 
Patricia D. Lawman, PhD 
Chief Executive Officer 
Morphogenesis, Inc. 
10500 University Center Dr, Ste 110 
Tampa, FL 33612-6419 
813-875-6600 ext. 102 
plawman@morphogenesis-inc.com 
Medical Monitor 
Georgia Latham, MD 
Peachtree Bioresearch Solutions, Inc. 
4985 Lower Roswell Rd, #100 
Marietta GA 30068-4337 
336-707-2170 
georgia.latham@peachtreebrs.com 
Institutional Review Board 
Advarra 
6940 Columbia Gateway Dr, Ste 110 
Columbia, MD 21046-2878 
410-884-2900 
Contract Research Organization 
Peachtree Bioresearch Solutions, Inc. 
4985 Lower Roswell Rd, #100 
Marietta GA 30068-4337 
678-373-4660 
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of the medical monitor and the Sponsor’s designated Drug 
Safety Unit. The medical monitor 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 medical monitor reviews SAEs, 
deviations, Interim analysis and final report forms, and can make the following determinations, Accepted, 
Acceptable with Corrective Action, or Tabled. The PI shall provide a 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. 
 
10.1.7 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. 

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The site PIs 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 by the study site into the sponsor-
provided EDC. eCRFs will be verified by the sponsor-contracted monitor against both paper source 
documentation and electronic medical records (EMR). 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 CRA according to 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 Clinical Monitoring Plan (CMP). 
10.1.8 COMPENSATION FOR RESEARCH-RELATED INJURY 
Participants will be asked to notify study staff immediately if they become ill or are injured during study 
participation. The sponsor will pay for those medical expenses necessary to treat a participant’s research-
related injury that is not covered by medical insurance or any other third-party coverage. Participants are 
notified in the informed consent form that they will not lose any legal rights or release any research 
personnel of liability by signing the informed consent form. Participants will also be notified that insurance 
and Medicare information (if applicable) will be collected for treatment and reporting purposes. 
10.1.9 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Each clinical site will perform internal quality management of study conduct, data and biological specimen 
collection, documentation and completion. An individualized quality management plan will be developed 
to describe a site's quality management. 
 
Quality Control (QC) procedures will be implemented beginning with the Data Management 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 (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated, and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)). 
The clinical site(s) 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. 
10.1.10 DATA HANDLING AND RECORD KEEPING 
10.1.10.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 

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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. 
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report form 
(eCRF) derived from source documents should be consistent with the data recorded on the source 
documents. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into a 21 CFR Part 11-compliant data capture system provided by the 
sponsor. The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be 
entered directly from the source documents. 
10.1.10.2 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. 
10.1.11 PROTOCOL DEVIATIONS 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or current clinical practice 
requirements at the clinical site. 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 GCP: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
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 are responsible for 
knowing and adhering to IRB requirements. 
10.1.12 PUBLICATION AND DATA SHARING POLICY 
 
This study will adhere with the details set forth in the clinical trial agreements between Morphogenesis, 
Inc. (sponsor) and the clinical site(s) 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 have 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 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. 
10.1.13 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. 
10.2 ABBREVIATIONS 
AE 
Adverse Event 
ANCOVA Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 

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ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS Least-squares Means 
MedDRA Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
10.3 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
1.1 
27 Oct 2020 Original version 
n/a 
2.0 
11 May 2021 Updates and revisions prior to 
patient enrollment: 
• Eliminated the pre-treatment 
tissue requirement 
• Week 0 pregnancy test 
requirement changed from 
serum to urine 
Clarification, feasibility, 
current investigational 
product safety information, 
and relevance to patient 
population 

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• Updated required laboratory 
tests 
• Amended post-injection 
observation time from four 
hours to 30 minutes 
• Revised the consenting policy 
3.0 
02 Jun 2021 • Removed cutaneous 
melanoma from the list of 
indications to be studied 
under this protocol 
• An exclusion criterion was 
added to not inject lesions on 
scalp with bone erosions 
• An exclusion criterion was 
added to not enroll patients 
with active HIV/AIDS or 
hepatitis B/C 
• The DLT definition was revised 
to include all AEs at least 
“possibly” related to the IP 
• Added testing for HIV/AIDS 
and hepatitis B/C 
This was done in response to 
the FDA review team’s 
feedback from 25 May 2021 
 

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