Clinical trial NCT04210375
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: heart failure HFrEF neuregulin 1 NRG-1 heregulin HER3 HER4 ErbB3 ErbB4 reduced ejection fraction
Sponsor: Salubris Biotherapeutics Inc
Start date: 2020-09-21; Completion date: 2023-07-07
Enrollment: 14 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the safety, tolerability, immunogenicity, PK, and exploratory efficacy of JK07 in subjects 18 to 80 years of age with HFrEF ≤40%.

Initially 5 cohorts are planned with the option to expand the study to a total of 7 cohorts. The size of the cohorts will range from 5 to 9 subjects. Each cohort will include one single active unblinded sentinel subject receiving a single IV dose of JK07 prior to randomized single dose administration of JK07 or placebo \[3:1\] in the remainder of the cohort.

Detailed description:
This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the safety, tolerability, immunogenicity, PK, and exploratory efficacy of JK07 in HF subjects 18 to 80 years of age with LVEF ≤40%. Subjects must have been maintained on an optimal HF medical regimen for at least 2 months prior to enrollment and remain on the same treatment regimen throughout the course of the study, per the 2017 ACC/AHA/HFSA) treatment guidelines.

At screening, eligible subjects will undergo a physical examination, 2-dimensional transthoracic echocardiography (2D-TTE), ECG assessment, blood sampling for laboratory parameters, and urine testing. Safety assessments at screening will include hematology, biochemistry, coagulation, liver, and thyroid function.

Subjects will be observed in the hospital on continuous telemetry from the time of hospital admission until shortly before discharge approximately 48 hours later. During this time, they will additionally have safety labs, vital signs, PK and biomarker samples collected, and ECGs and 2D-TTEs performed.

Only a single dose of the investigational product will be administered and only a single hospital admission is planned per subject during the study. Subjects will complete follow-up visits through 180 days after administration of the investigational product.

Arms: arm 1: Single dose of JK07 administered by intravenous infusion over 60 minutes arm 2: Single dose of placebo administered by intravenous infusion over 60 minutes
Interventions: intervention 1: JK07 intervention 2: Matching Placebo
Intervention descriptions: intervention 1: Recombinant fusion protein consisting of a fully humanized immunoglobulin G1 monoclonal antibody and an active polypeptide fragment of the human growth factor NRG-1 intervention 2: Vehicle control

Protocol documents:
ICF_002.pdf: 
Salubris Biotherapeutics, Inc.  
 
Subject Number: ______________ 
Protocol Number: JK07.1.01 Amendment 3 
 
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paiConsent to Participate in a Research Study 
 
Full Title: 
A Randomized, Double-Blind, Placebo-controlled, Single-
ascending Dose Study to Assess the Safety, Tolerability, 
and Pharmacokinetics of JK07 in Subjects with Heart 
Failure with Reduced Ejection Fraction (HFrEF) 
 
Study Number: 
 
 
JK07.1.01 
Version: 
 
 
 
Amendment 3 
 
Sponsor: 
 
 
 
Salubris Biotherapeutics, Inc. 
 
Study Doctor Name: 
 
<INSERT SITE PI NAME>                        
Research Site Address(es):  
<INSERT SITE ADDRESS> 
Daytime Telephone Number(s): 
<INSERT SITE PHONE NUMBERS> 
24-Hour Contact Number(s) In Case of Emergency: <INSERT EMERGENCY PHONE #> 
Invitation: 
You are being asked to take part in this research study. Before you decide, we would like you to 
understand why the research is being done and what it would involve for you. The physician 
conducting the study or one of our team members will go through the consent form with you and 
answer any questions you have.  
 
• 
Part 1 of this document tells you the purpose of this study and what will happen to you if you take 
part. Part 1 allows you to gain a quick understanding of the study and decide if you want to read 
further details about participation. 
• 
Part 2 gives you more detailed information about the conduct of the study, providing further details 
for you to consider. 
 
Please read this consent form carefully and take as much time as you need to decide whether to take 
part in this study. You may want to discuss your participation with family, friends or your General 
Practitioner / Family Doctor (GP) / own Cardiologist. You have the right to have all your questions or 
concerns addressed prior to signing this Informed Consent Form. 
 
Things to know before deciding to take part in a research study:  
• 
The main goal of a research study is to learn things to help patients in the future. 
• 
The decision to join or not join the research study will not cause you to lose any medical 
benefits. If you decide not to take part in this study, your doctor will continue to treat you. 
• 
Standard care (or “routine care”) is the treatment normally given for a certain condition or 
illness. In this study, you will continue to receive the same standard care that you receive 
currently. 
• 
In addition to your standard care, in this study you may receive JK07, an experimental 
(investigational) study drug that is being tested for safety and potential beneficial effects on 
heart function in patients with heart failure due to decreased heart function. An 
investigational study drug is one that has not been approved by the U.S. Food & Drug 
Administration (FDA), an agency responsible for protecting and promoting public health in 
the USA. This drug has been tested in animals but not yet in people. This study tests 
different single doses of the drug to see what the effects are, if any, along with the usual 
approved standard therapy that you are already taking. 
• 
Your medical records may become part of the research record, but only after any 
information which would identify you is removed (de-identified). If that happens, your de-
identified medical records may be looked at and/or copied by the sponsor of this study and 


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government agencies or other groups associated with the study. However, your personal 
information will be kept private. 
• 
Your medical insurance may be billed for any standard medical care you receive during the 
research study.  
 
If you take part in this research study, you will be given a copy of this signed and dated consent form.  
 
PART 1 
1. 
What is the purpose of the study? 
The main purpose of the study is to evaluate the safety and activity of the investigational product in 
subjects with heart failure who have a lower than normal amount of blood pumped by the heart 
(weaker hearts). This study is a “first-in-human” study of the protein JK07 and will determine if, and 
at what dose, this product is safe and tolerable, how long it stays in your body, and whether it has 
any effect on your heart function. This study could lead to further and future studies of this product in 
larger patient populations. JK07 is a protein which was designed to stimulate your heart in a way that 
promotes regeneration and better functioning, including increasing the amount of blood that your 
heart pumps (stronger hearts). 
 
Different doses of the study drug will be given to groups of 5 to 9 study participants. Each participant 
will receive only one single dose. The first study participants will receive the lowest dose. If the drug 
does not cause significant side effects at these lower doses, it will be given to other study participants 
at progressively higher doses. The dose will continue to increase for every group of study participant 
until either side effects occur that require the dose to be lowered or stopped, or if significant 
improvement in heart function is observed.  
 
For each group receiving a dose of the study drug that hasn’t been tested previously, the first subject 
will receive the actual study drug. For the remaining participants in each group, 75% will receive the 
actual study drug and 25% will receive the placebo (inactive “look-alike”). The investigational product 
will be administered by intravenous injection or infusion, using the IV line. The investigational product 
will only be given once, on Day 1 after you are admitted to the hospital and a few tests are performed 
to compare with the same tests which will be performed after the infusion. You will not know at the 
time you start the screening process whether you will be the first person in the group who receives 
the study drug, or one of the other people in the group who could receive either JK07 or placebo. 
 
Sometimes we do not know what dose will be best for an investigational study drug. To find out, we 
need to compare different dose levels. We put people into groups and give each group a different 
dose. The results are then compared to see if one is better than the rest. To try to make sure the 
groups are the same to start with, patients are put into a group by chance (randomly).  
 
This study involves the use of a “placebo” and an investigational study drug. A “placebo” is an inactive 
product that has no therapeutic effect. The effects of JK07 will be compared to the effects of the 
placebo. Neither you nor your study physician will know if you’ve received JK07 or the placebo, unless 
you are the first subject in a new dose group. If you agree to participate in this study and are 
determined to be fully eligible based on other screening tests, you will be randomly assigned to 
receive either JK07 or the placebo. You will then be enrolled into the dose group which is actively 
enrolling at the time. If you are the first subject in a dose group, you will definitely receive JK07; you 
will not be randomly assigned, and you will not receive the placebo. If you are not the first subject in 
a dose group, you will have approximately a 75% chance of receiving JK07. If you do not receive 
JK07, you will receive a placebo. Note that you will only receive one dose of JK07 or placebo 
throughout your participation in the study.  
 
2. 
Why have I been invited? 
You are being invited to participate in this study because you have heart failure with reduced ejection 
fraction, in which your heart pumps a lower than normal amount of blood. This means that your heart 
does not pump blood out of the heart as well as it should. If you agree to participate in this study, your 
physician will conduct additional tests to ensure you are fully eligible for participation in this study.  Up 


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to 63 subjects will take part in this study at approximately 8 different medical facilities/hospitals in the 
United States. 
 
3. 
Do I have to take part? 
Your participation in this study is completely voluntary. You can leave the study at any time; you do 
not need to provide a reason. If you decide not to join the study or leave the study after you start the 
study, your access to medical care or the future benefits to which you are otherwise entitled will not 
be affected. 
 
4. 
How long will I be in this research? 
Your total involvement in this study would be approximately 7.5 months, with approximately 15 visits 
with the study team. The details of each visit are below. 
 
5. 
What will happen to me if I take part? 
If you agree to take part in the study, you will be asked to sign and date this consent form. If you do 
not sign this consent form, you will not be able to join the study. You will only receive a single dose 
of the of the investigational product in this study, during your first visit to the hospital, and all 
subsequent visits are only to monitor the effects of the product which was administered. 
 
• 
Smoking, e-cigarettes or the use of any nicotine-containing products (including patches) is not 
permitted from 2 weeks prior to receiving the study product until the final follow-up visit 6 months 
later. 
• 
Use of CBD (cannabidiol) products or use of any CBD-containing products (including foods and 
supplements) is not permitted from 2 weeks prior to receiving the study product until the final 
follow-up visit 6 months later. 
• 
Alcohol consumption will not be permitted from 3 days prior to receiving the study product (Day -3) 
through completion of study procedures on Day 3, and then within 24 hours prior to any 
subsequent visit. 
• 
Consumption of caffeine or xanthine-containing products (e.g., coffee, tea, cola drinks, chocolate) 
will not be permitted from 1 days prior to receiving the study product (Day -1) through completion 
of study procedures on Day 3, and then within 24 hours prior to any subsequent visit. 
 
Screening Visits 
Before you begin treatment in this study, you will need to have certain tests performed, called 
screening tests, to see if you meet the rules and requirements for taking part in the study. Your study 
doctor will ask you to sign this consent form before these tests or any other tests are performed, 
unless they would normally be performed as part of your standard care. 
 
The tests and procedures listed below will be done within 45 days prior to the day you receive the 
study product (either JK07 or placebo). These screening tests might not be done all in the same visit.  
 
A. Review of medical history (the study team will review your records for important medical 
history and a review of all medications you are taking; this may involve you answering some 
questions, so the study team fully understands your medical history); 
B. Physical exam (may include your height, weight and vital signs (for example, your heart rate, 
blood pressure, respiratory rate and temperature)); 
C. Urinalysis  
D. Blood draw: Approximately 5 teaspoons of blood will be drawn for a variety of tests (including 
a test for the function of your liver, kidneys, thyroid, heart, blood lipids like cholesterol and 
triglycerides, blood-clotting capability, and assessment of certain viral infections), to establish 
a “baseline” with which to compare your blood tests after receiving the study product; 
additionally, if you are a female of childbearing potential, you will also have a blood pregnancy 
test to ensure you are not pregnant; 


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E. Heart rhythm monitoring/recording for 14 days using a wearable patch; a small adhesive, 
water-resistant sensor will be placed on your chest to record the electrical activity of the heart 
for 14 days during the screening period; 
F. A standard electrocardiogram (“ECG”) where 12 electrodes will be affixed to your skin (chest, 
arms, legs) to record the electrical activity of your heart. 
G. Echocardiography, which uses high frequency soundwaves (ultrasound) to create a picture of 
your heart.  
 
Day of Receiving the Product (“Day 1”) 
You will be admitted to the hospital by 7:00 a.m. for at least a 2-day hospital stay. You must have 
abstained from food (called “fasting”) for 10 hours prior to arriving to the hospital. You will follow a 
prescribed meal plan during your hospital stay.  
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Urinalysis (additionally, if you are a female of child-bearing potential, you will have a urine 
pregnancy test to ensure you are not pregnant) 
C. Medical events and medications: Review of your medical records and a discussion with you 
to determine if you have had any medical events since your last office visit. The study team 
will also review all medications you are taking; this may involve you answering some questions 
for the study team to allow full understanding of your medical history; 
D. Blood collection from your IV tube 9 times over the course of the first day (approximately 6 
tablespoons of blood in total), and finger-pricks 8 times to also test levels of blood glucose 
(sugar) 
E. Echocardiography; 
F. ECG; 
G. Receive either JK07 or the placebo, administered intravenously (through a tube inserted in 
your vein); This will be the only dose of the investigational product that you will receive in this 
study. 
H. Checking for any adverse events and any new medications (an adverse event is a change in 
your health/condition, or injury, and should be reported to your investigator throughout the 
study); 
I. Checking your injection site for a reaction (if any). 
 
Day after Receiving the Product (“Day 2”) 
This will be the second day of your hospital stay. You will follow the prescribed meal plan, which 
includes fasting for 10 hours prior to your 24-hour procedures, which includes the following;  
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Checking for any adverse events and reviewing medications; 
C. Checking your injection site for any reaction; 
D. Blood collection from your IV tube (approximately 2 teaspoons of blood); including a finger-
prick to test levels of glucose (sugar) 
E. Echocardiography  
F. Urinalysis; 
G. ECG. 
 
Day 3 
You will likely be discharged on the third day of your hospital stay. Before discharge, the following 
procedures will be performed; 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Checking for any adverse events and reviewing medications; 
C. Checking your injection site for any reaction; 
D. Blood collection from your IV tube (approximately 6 teaspoons of blood); including a finger-
prick to test levels of glucose (sugar) 
E. Urinalysis; 
F. ECG. 
 


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Note for all visits – you must fast (abstain from food) for 10 hours prior to each visit, and you 
must also abstain from ingesting caffeine- or xanthine-containing products (such as coffee, 
tea, cola drinks and chocolate) or alcohol for 24 hours prior to each visit. 
 
Day 4 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 2 teaspoons of blood); including a finger-prick to test levels of 
glucose (sugar) 
D. Urinalysis; 
E. ECG. 
 
Day 7 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 6 teaspoons of blood); 
D. Urinalysis; 
E. ECG; 
F. Echocardiography. 
 
Day 11 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 1 teaspoon of blood); 
D. ECG. 
Note: Your physician may elect to have this Day 11 visit conducted remotely (by telehealth with the 
physician or the physician’s staff), due to coronavirus concerns and your safety versus the data to be 
collected. Should this visit be conducted remotely, the physical exam, blood draw and ECG may not 
be performed.  
 
Day 15 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 6 teaspoons of blood); 
D. Urinalysis; 
E. ECG; 
F. Echocardiography. 
 
Day 22 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 1 teaspoon of blood);  
Note: Your physician may elect to have this Day 22 visit conducted remotely (by telehealth with the 
physician or the physician’s staff), due to coronavirus concerns and your safety versus the data to be 
collected. Should this visit be conducted remotely, the physical exam and blood draw may not be 
performed.  
 
Day 30 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 7 teaspoons of blood); 
D. If you are a female of child-bearing potential, you will have a urine pregnancy test to ensure 
you are not pregnant; 
E. ECG; 


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F. Echocardiography. 
 
Day 60 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 6 teaspoons of blood); 
D. If you are a female of child-bearing potential, you will have a urine pregnancy test to ensure 
you are not pregnant; 
E. ECG; 
F. Echocardiography. 
 
Day 90 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 6 teaspoons of blood); 
D. If you are a female of child-bearing potential, you will have a urine pregnancy test to ensure 
you are not pregnant; 
E. ECG; 
F. Echocardiography. 
 
Day 135 
A. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
B. Adverse events and medications; 
C. Blood draw (approximately 5 teaspoons of blood); 
D. If you are a female of child-bearing potential, you have a urine pregnancy test to ensure you 
are not pregnant; 
E. ECG; 
F. Echocardiography. 
 
Day 180 (final visit) 
A. An End of Study or Day 180 Follow-up visit will be completed once you complete the study or 
in the event you need to leave the study early; 
B. Physical exam and vital signs (for example, your heart rate, blood pressure, respiratory rate 
and temperature); 
C. Adverse events and medications; 
D. Blood draw (approximately 6 teaspoons of blood); 
E. If you are a female of child-bearing potential, you will have a urine pregnancy test to ensure 
you are not pregnant; 
F. ECG; 
G. Echocardiography. 
 
6. 
Expenses and payments 
Study products and all study-related testing, including the 3-day in-hospital stay, will be provided to 
you by the sponsor at no charge. You will not need to pay for any tests and procedures which are 
performed just for this study. These study-related tests and study-related procedures include ECGs, 
echocardiograms, blood tests, urinalyses, pregnancy tests, blood draws to monitor the investigational 
product, or exams done by the physician. However, you and/or your health plan will need to pay for 
all other standard tests and procedures that you would normally have as part of your regular medical 
care. These standard tests and procedures are blood tests performed prior to receiving the 
investigational product, your prior and current medications, exams done by your regular physician, 
and various related costs.  
 
You will be paid for participating in this study, to cover reasonable expenses incurred for travel and 
accommodation for completing study visits. You will be paid $225 per day for your two full days in the 
hospital (“Day 1” and “Day 2”) and $75 for the day of discharge (“Day 3”) and each return visit (Days 


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4, 7, 11, 15, 22, 30, 60, 90, 135, 180). If you complete all study visits, you can expect to have received 
$1275 in total. Additionally, if you live more than 30 miles away from the study facility, you will be 
compensated $250 to cover a hotel stay the night prior to your hospital admission, since you must be 
admitted into the hospital study unit by 7:00 a.m. Ensure you inform your coordinator if you live more 
than 30 miles away and will stay at a hotel the night prior to your hospital admission for this study. 
 
If a commercial product is developed from this research, rights to the product will belong to the 
sponsor and their collaborators (persons or companies partnering with the sponsors). You and your 
family will not receive any financial benefits or compensation from or have any rights in any 
developments, inventions or other discoveries that might come out of this research. 
 
7. 
What do I have to do? 
If you take part in this research, you will be responsible to:  
• 
Follow the instructions you are given by the study doctor or other study staff; 
• 
Report to the study doctor or other study staff immediately any changes in your health; 
• 
Return to the study doctor’s office as scheduled for your visits; 
• 
Fast for 10 hours prior to every study visit; 
• 
If sexually active, employ adequate birth control/contraceptive measures for the duration of 
the study; 
• 
Abstain from smoking (or use of nicotine products) from 2 weeks prior to receiving the study 
product through the end of study participation (approximately 6 months after receiving the 
study product or the time of withdrawal from the study if earlier); 
• 
Abstain from use of CBD (cannabidiol) products or use of any CBD-containing products 
(including foods and supplements) is not permitted from 2 weeks prior to receiving the study 
product until the final follow-up visit 6 months later. 
• 
Abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, 
chocolate) from 1 day prior to receiving the study product (Day -1) through completion of study 
procedures on Day 3, and then within 24 hours prior to any subsequent visit; 
• 
Abstain from ingesting alcohol from 3 days prior to receiving the study product (Day -3) 
through completion of study procedures on Day 3, and then within 24 hours prior to any 
subsequent visit. 
• 
Tell the study doctor or study staff if you want to stop being in the research study. 
 
8. 
What are the alternatives for diagnosis or treatment? 
You may choose not to participate in this study. You do not have to be in this study to receive 
treatment for your heart failure. Other choices for treatment of your disease could be different drugs 
or drug combinations, or surgical procedures. There may be standard approaches or other 
investigational regimens available to you; you should discuss this with your doctor. Your study doctor 
will discuss the risks and benefits of these other options with you. 
 
9. 
What are the possible disadvantages and risks of taking part? 
There are risks associated with any treatment, whether investigational or standard care. The 
tests/procedures listed below are standard medical procedures but do come with their own risks or 
discomforts. 
 
Echocardiogram: 
An echocardiogram uses sound waves to produce images of your heart. This commonly used test 
allows your doctor to see how your heart is beating and pumping blood. A clear, easily wipe-able gel 
is placed on your chest and a blunt probe (transducer) is moved about on the skin to beam ultrasound 
waves to create a moving image of your heart structure and function. It is a safe, painless procedure 
and usually takes 30 minutes. There are no known complications associated with having it.  
 
Electrocardiogram (also called an ECG or EKG): 
An electrocardiogram records the electrical activity of the heart through small electrode patches 
attached to the skin on your chest, legs and arms. You will lie flat on a table for about 10 minutes 


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while the machine records the heart’s electrical activity. You may experience redness or itching where 
the pads were placed. There are no known complications associated with having it. 
 
ECG Patch: 
During the study screening period, an ECG patch with an attached sensor will also record the 
electrical activity of the heart, but only one device will be placed on the skin on your chest. You will 
wear this for 14 days, after which the device will be returned for reading. You may experience redness 
or itching where the patch was placed. There are no known complications associated with having it. 
 
Blood Sampling: 
Blood tests may cause pain, bruising, bleeding or swelling at the site where blood is taken or a needle 
is inserted. You may also experience dizziness or fainting while blood is being taken. There is also a 
very small risk that an infection may occur. 
 
10. 
What are the side effects of any treatment received when taking part? 
This is a “first-in-human” study, and, as such, JK07 has not been previously evaluated in human 
subjects.  
 
Since at this time, JK07 has not been administered to people, it is not known what side effects may 
be seen. The possible side effects that may be expected based on studies conducted with JK07 in 
animals given either similar or much higher doses, and in some cases multiple doses, were generally 
limited to occasional infusion reactions with flushing, increased salivation, transient weight loss, short-
term heart rate or rhythm changes, and transient elevations of liver function tests. 
 
The product consists of two different proteins which have been biologically fused together. One of 
them is a specific growth factor which is designed to help your heart to recover some of the function 
it has lost by generating more and stronger heart muscle cells. 
 
This is a highly specific protein for stimulating heart muscle development, and while there is no 
evidence that this particular growth factor is associated with stimulating abnormal tissue growth, or 
any indication it could stimulate early cancer growth anywhere in the body, the second protein has 
been included as part of the investigational study drug to block the interaction of the growth factor 
with proteins outside of the heart. This second protein is intended to protect you from any negative 
effects outside of the heart, but it will not block the effects in the heart.  
 
In many years of animal studies, as well as with prior experience over the past decade in humans 
using similar versions of the same growth factor, no apparent increased risk of cancer has been seen, 
even without this additional blocking protein designed to improve the safety of the treatment. 
 
Nevertheless, there is at least a theoretical possibility that this molecule could worsen an undetected 
pre-existing cancer. For additional safety monitoring, enrollment into this study will include a thorough 
cancer screening evaluation. 
 
Prior human studies using similar but different versions of the same growth factor, without the blocking 
protein, noted the occasional side effects of transient nausea, headache, fatigue, dizziness, minor 
skin rash, diarrhea, cough, abdominal cramping, temporary liver function test abnormalities, transient 
low blood sugar and low blood pressure, short-term chest pain, and transient ECG abnormalities of 
mild heart rhythm disturbances, including a temporary speeding up of the heart rate. The additional 
blocking protein may help to avoid some of these side effects. 
 
11. 
Harm to the unborn child 
Being a part of this study while pregnant may expose the unborn child to significant risks, some of 
which may be currently unforeseeable. Therefore, pregnant women will be excluded from the study. 
If you are a woman of childbearing potential, a blood pregnancy test will be done (using 1 teaspoon 
of blood drawn from a vein by needle-stick) during screening. On the day of study product 
administration (Day 1), you will have a urine pregnancy dipstick test to confirm absence of pregnancy. 
These must be negative before you can continue in this study.  


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Women cannot be pregnant or breast-feeding, nor should they attempt to become pregnant while 
participating in this study. If you are sexually active and able to have children, you must agree to use 
a highly effective method of contraception (e.g., condom, intrauterine device [IUD], oral contraceptive, 
or double-barrier method), for the duration of study participation.   
 
Men who are in this research study should not get a sexual partner pregnant while participating in the 
study. Men must be surgically sterile, abstinent, or if engaged in sexual relations with a woman who 
could become pregnant, must use an acceptable method of contraception (double-barrier methods 
such as condoms with spermicidal gel or foam) while taking part in this study. Male subjects with a 
pregnant or breastfeeding partner must remain abstinent or agree to use a double-barrier method of 
contraception (including the use of a male condom). 
 
If you or your partner become pregnant or think you or your partner may be pregnant while in the 
study, you must notify your study doctor immediately. 
 
12. 
What are the possible benefits of taking part? 
There is no guarantee or assurance that you will benefit from taking part in this research study. JK07 
is designed to promote cardiac function through repairing damaged heart muscle cells, and to protect 
your heart cells from dying. You may feel better if JK07 has its intended effect. Future patients with 
the same disease may also benefit from the results of this study. Risks and benefits of participating 
in this study should be discussed with the study physician.  
 
13. 
What happens when the research study stops? 
When the research study stops, your data, along with the data from other research subjects, will be 
analyzed and ultimately submitted to the FDA and other regulatory authorities. The results of this 
study may form the basis for further study of this product. 
 
Your study doctor may end your participation in the study early without your consent if he/she 
determines it is in your best interest.  
 
14. 
What if there is a problem? 
Any complaint about the way you have been dealt with during the study or any possible harm you 
might suffer will be addressed in Part 2. 
 
15. 
Will my taking part in the study be kept confidential? 
Yes. We will follow ethical and legal practice and all information about you will be handled in 
confidence. The details are included in Part 2.  
 
This completes part 1.  
 
If the information in Part 1 has interested you and you are considering participation, 
please read the additional information in Part 2 before making any decision. 
 


Salubris Biotherapeutics, Inc.  
 
Protocol Number: JK07.1.01 Amendment 3 
 
Page 10 of 12 
ICF Version: 5.0 02Aug2021 
Part 2 of the Information Sheet 
1. 
What if relevant new information becomes available? 
New information about JK07 may become available while this study is ongoing. If this happens, your 
research doctor will provide you with this information and discuss whether you should continue in the 
study. If you decide not to remain in the study, your research doctor will arrange for your care to 
continue. If you decide to continue in the study, he/she may ask you to sign an agreement outlining 
the discussion.  
 
If the study is stopped for any other reason, we will tell you and arrange your continuing care. 
 
2. 
What will happen if I don’t want to continue in the study? 
You can change your mind and refuse to participate in the study at any time before or after the study 
begins. You will not be penalized in any way if you decide to withdraw from this research study. You 
should inform your study doctor of your decision to withdraw in writing. You should consult your doctor 
who will advise you as to what treatment regimen you should follow after you end your participation 
in this study. Data collected up to the time of your withdrawal will be used and analyzed. 
 
If you decide not to continue, you will be asked to return for a final end-of-study visit to obtain final 
data. Please note that all visits after you receive the study product are intended to monitor your safety. 
See the section in Part 1 under Day 180 for the details of this end-of-study visit.  
 
3. 
Whom do I call if I have questions or problems? 
For questions about the study or a research-related injury, or if you have problems, concerns, 
questions or suggestions about the research, contact the study doctor listed on page 1 of this consent 
form. 
 
For questions about your rights as a research participant, or to discuss problems, concerns or 
suggestions related to the research, or to obtain information or offer input about the research, contact 
the [IRB name] Institutional Review Board (IRB) at (xxx)-xxx-xxxx. 
 
4. 
Injury 
You should notify the study doctor listed on page 1 as soon as you believe you have experienced any 
study-related illness or injury. However, there is no commitment by the study hospital or your study 
physicians to provide monetary compensation or free medical care to you in the event of a study-
related injury.  
 
In the event of an injury or illness that is determined to be directly related to the proper use of the 
study medication or properly performed study procedures, the sponsor, Salubris Biotherapeutics, Inc., 
will pay all reasonable and necessary medical expenses to treat such illness or injury (excluding the 
underlying disease or condition or any natural progression thereof) provided you have followed the 
directions of the study doctor and his/her staff [and are not otherwise eligible for reimbursement by 
your personal insurance, a government program or other third party coverage for such medical 
expenses]. No other compensation will be offered by the sponsor. Financial compensation for such 
items as lost wages, disability or discomfort due to research-related injury will not be made available.  
 
5. 
Will my taking part in this study be kept confidential? 
This section gives more specific information about the privacy and confidentiality of your health 
information. It explains what health information about you will be collected during this research study 
and who may use, give out and receive your health information. It also describes your right to inspect 
your medical records and how you can revoke this authorization after you sign it. 
 


Salubris Biotherapeutics, Inc.  
 
Protocol Number: JK07.1.01 Amendment 3 
 
Page 11 of 12 
ICF Version: 5.0 02Aug2021 
Your health information includes your personal medical history, information from laboratory tests, 
blood tests, physical exams and other tests or procedures described in this consent form. Information 
learned during telephone calls and study visits done as part of this research study are also part of 
your health information. In addition, personal medical information located at other medical facilities 
where you received treatment will be used and given out to conduct the study and to evaluate the 
results. By signing this form, you agree that your health information may be used and disclosed during 
this research study. Again, neither your name, nor any personally identifiable information will be 
disclosed. Only information that is needed for the research study will be collected. Your health 
information will only be used and given out as explained in this consent form or as permitted by law. 
 
The data collected during this study will be the sole property of Salubris Biotherapeutics, Inc. The 
results may be presented in publication or presentation, but your identity will be kept confidential. 
 
Your study doctor, study staff, the institutional review board and their staff, legal counsel, research 
office and compliance staff, officers of the organization and other people who need to see the 
information in order to conduct the study or make sure it is being done properly will see your health 
information, and may give out your health information during the research study without identifying 
this health information as yours. 
 
Other persons and organizations including the sponsor of this study (Salubris Biotherapeutics, Inc.), 
or their representative will see and use your privacy-protected health information during this study. 
Government regulatory agencies such as the Office of Human Research Protections, the U.S. Food 
and Drug Administration, and Regulatory authorities in other countries may also review your health 
information. The study doctor may also notify your primary care physician and/or cardiologist of your 
participation in this research study. 
 
Please be aware that once your protected health information is disclosed to a person or organization 
that is not covered by the federal medical Privacy Rule, the information is no longer protected by the 
Privacy Rule and may be subject to redisclosure by the recipient.  
 
You do not have to give your authorization to use or give out your health information. However, if you 
do not give authorization, you cannot participate in this research study. 
 
You may cancel your authorization to use your personal health information at any time by giving a 
written notice to your study doctor. Once you cancel your authorization, no new health information 
about you will be gathered and you will no longer be able to participate in this study. However, 
information gathered before that date may be used or given out if it is needed for the research study 
or any follow-up.   
 
Your authorization to use and give out your health information will continue until you cancel your 
authorization. You have the right to look at your medical records at any time during this research 
study.  
 
6. 
Involvement of the General Practitioner/Family doctor (GP) 
Your personal doctor, in addition to your cardiologist, should be informed of your participation in this 
research study. By consenting to participate in this study, you also agree that the study doctor can 
inform your family doctor/general practitioner of your participation in this study. 
 
7. 
What will happen to any samples I give? 
You will have blood samples taken at nearly every study visit. These samples will be used in a variety 
of tests performed locally at the study hospital and also at a centralized laboratory. Some of your 
samples will be shipped to central laboratories for analysis. 
 


Salubris Biotherapeutics, Inc.  
 
Protocol Number: JK07.1.01 Amendment 3 
 
Page 12 of 12 
ICF Version: 5.0 02Aug2021 
8. 
What will happen to the results of the research study? 
The results of this study will be provided to the FDA and other regulatory authorities, which could lead 
to future studies and ultimately approval of JK07 for use in patients with heart failure. The results may 
also be included in publications, presentations and marketing/advertising. No personal information 
will be disclosed. 
 
A description of this clinical trial is available on http://www.ClinicalTrials.gov (NCT04210375), as 
required by U.S. Law. This Web site will not include information that can identify you. At most, the 
Web site will include a summary of the results. You can search this Web site at any time. 
 
9. 
Who is organizing and funding the research? 
This research is being organized and funded by Salubris Biotherapeutics, Inc. Salubris 
Biotherapeutics, Inc. is compensating the hospital for their staff’s time and effort to conduct this study. 
They are also paying for the costs of study-related procedures. 
 
10. 
Statement of Consent 
"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. 
I have been allowed to ask questions, and my questions have been answered to my satisfaction. I 
have been told whom to contact if I have questions, to discuss problems, concerns, or suggestions 
related to the research, or to obtain information or offer input about the research. I have read this 
consent form and agree to be in this study, with the understanding that I may withdraw at any time. 
By signing this consent form, I authorize for my personally identifiable data to be shared as described 
in this consent form. I have been told that I will be given a signed and dated copy of this consent 
form." 
 
 
 
__________________________________________ 
 
___________   ____________ 
Signature of Subject  
 
 
 
 
 
Date 
 
  Time 
 
 
 
__________________________________________ 
 
___________   ____________ 
Signature of Person Obtaining Consent 
 
 
 
Date 
 
  Time 
 
 
 

Prot_000.pdf: 
CONFIDENTIAL 
FINAL 
Protocol JK07.1.01- Amendment 3 
09 APR 2021 
Page 1 of 89 
 
 
 
 
 
TITLE PAGE 
Protocol Title: 
A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to Assess 
the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects with Heart Failure with 
Reduced Ejection Fraction (HFrEF) 
Protocol Number: JK07.1.01 Amendment 3 
Product: JK07 (recombinant fusion protein consisting of a fully human anti-human 
epidermal growth factor receptor 3 [HER3] immunoglobin G1 [IgG1] and an active 
polypeptide fragment from human neuregulin-1 [NRG-1]) 
Short Title: Phase 1 Study of JK07 in Subjects with Heart Failure with Reduced Ejection 
Fraction (HFrEF) 
Study Phase: Phase 1 
Sponsor Name: Salubris Biotherapeutics, Inc. 
Legal Registered Address: 45 West Watkins Mill Rd, Suite E, Gaithersburg, MD 20878 
Regulatory Agency Identifying Number(s): IND 142367 
 
 
Version 
Date 
Original 
21 November 2019 
Amendment 1 
19 February 2020 
Amendment 2 
03 March 2020 
Amendment 3 
09 April 2021 


CONFIDENTIAL 
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Protocol JK07.1.01- Amendment 3 
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Page 2 of 89 
 
 
SPONSOR SIGNATORY: 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
 
 
Sam Murphy, PhD 
Chief Executive Officer 
Salubris Biotherapeutics 
 
Date 
20-Apr-2021 | 13:42:27 PDT 
 
 
 
 
 
 
 
 
 
 
20-Apr-2021 | 13:58:05 PDT 
 
Date 
Consulting Chief Medical Officer and Medical Monitor 
Salubris Biotherapeutics 
Neal Salomon, MD 


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09 APR 2021 
Page 3 of 89 
 
 
TABLE OF CONTENTS 
SUMMARY OF CHANGES ................................................................................................... 7 
LIST OF ABBREVIATIONS ................................................................................................ 12 
1.0 
PROTOCOL SUMMARY ......................................................................................... 14 
1.1 
Synopsis ........................................................................................................... 14 
1.2 
Schema ............................................................................................................ 18 
1.3 
Schedule of Activities ..................................................................................... 19 
2.0 
INTRODUCTION ...................................................................................................... 24 
2.1 
Study Rationale .............................................................................................. 24 
2.2 
Background ..................................................................................................... 25 
2.3 
Benefit/Risk Assessment ................................................................................ 27 
3.0 
OBJECTIVES AND ENDPOINTS ........................................................................... 29 
4.0 
STUDY DESIGN ........................................................................................................ 30 
4.1 
Overall Design ................................................................................................ 30 
4.2 
Scientific Rationale for Study Design ........................................................... 30 
4.3 
Justification for Dose ..................................................................................... 32 
4.4 
End of Study Definition ................................................................................. 33 
4.5 
Dose Escalation Criteria ................................................................................ 33 
4.6 
Study Stopping Criteria ................................................................................. 33 
4.6.1 
Stopping Criteria for Individual Subjects .......................................... 34 
4.6.2 
Criteria for Stopping Dose Escalation ............................................... 34 
4.6.3 
Criteria for Stopping the Study .......................................................... 35 
5.0 
STUDY POPULATION ............................................................................................. 36 
5.1 
Inclusion Criteria ........................................................................................... 36 
5.2 
Exclusion Criteria .......................................................................................... 36 
5.3 
Lifestyle Considerations ................................................................................. 38 
5.3.1 
Meals and Dietary Restrictions .......................................................... 38 
5.3.2 
Caffeine, Alcohol, and Tobacco ........................................................ 38 
5.3.3 
Activity .............................................................................................. 39 
5.4 
Screen Failures ............................................................................................... 39 
6.0 
STUDY TREATMENT.............................................................................................. 40 
6.1 
Study Treatment(s) Administered ................................................................ 40 
6.2 
Preparation/Handling/Storage/Accountability ............................................. 41 
6.3 
Randomization and Blinding......................................................................... 41 
6.4 
Study Treatment Compliance ....................................................................... 42 
6.5 
Concomitant Therapy .................................................................................... 42 


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6.5.1 
Rescue Medicine ................................................................................42 
6.6 
Dose Modification ...........................................................................................42 
6.7 
Treatment after the End of the Study ..........................................................42 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL .................................................................43 
7.1 
Discontinuation of Study Treatment ............................................................43 
7.2 
Subject Discontinuation/Withdrawal from the Study ................................43 
7.3 
Lost to Follow-up ............................................................................................43 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .....................................................45 
8.1 
Efficacy Assessments ......................................................................................45 
8.2 
Safety Assessments .........................................................................................45 
8.2.1 
Physical Examinations .......................................................................46 
8.2.2 
Injection Site Assessment ..................................................................46 
8.2.3 
Pregnancy Test ...................................................................................47 
8.2.4 
Medical History .................................................................................47 
8.2.5 
Electrocardiograms ............................................................................47 
8.2.6 
Vital Signs .........................................................................................47 
8.2.7 
Clinical Safety Laboratory Assessments ............................................48 
8.2.8 
Immunogenicity Assessments ............................................................48 
8.2.9 
Two-dimensional Transthoracic Echocardiography ..........................49 
8.3 
Safety Monitoring and Reporting .................................................................49 
8.3.1 
Adverse Events ..................................................................................49 
8.3.2 
Serious Adverse Events .....................................................................49 
8.3.3 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................50 
8.3.4 
Method of Detecting AEs and SAEs .................................................51 
8.3.5 
Grading and Intensity of Adverse Events ..........................................51 
8.3.6 
Relationship to Study Drug ................................................................52 
8.3.7 
Recording AEs and SAEs ..................................................................53 
8.3.8 
Follow-up of AEs and SAEs ..............................................................55 
8.3.9 
Regulatory Reporting Requirements for SAEs ..................................55 
8.3.10 
Pregnancy...........................................................................................55 
8.3.11 
Protocol-Specified Serious Adverse Events ......................................56 
8.3.12 
Disease-related Events and/or Disease-related Outcomes Not 
Qualifying as AEs or SAEs................................................................56 
8.4 
Treatment of Overdose ..................................................................................56 
8.5 
Pharmacokinetics ...........................................................................................56 
8.5.1 
Collection of Samples ........................................................................56 
8.5.2 
Determination of Drug Concentration ...............................................57 
8.5.3 
Calculation of Derivation of Pharmacokinetic Variables ..................57 
8.6 
Pharmacodynamics ........................................................................................58 
8.7 
Genetics ...........................................................................................................58 
8.8 
Biomarkers ......................................................................................................58 
8.9 
Health Economics ...........................................................................................59 


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09 APR 2021 
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9.0 
STATISTICAL CONSIDERATIONS ...................................................................... 60 
9.1 
Statistical Hypotheses .................................................................................... 60 
9.2 
Sample Size Determination ............................................................................ 60 
9.3 
Populations for Analyses ............................................................................... 60 
9.4 
Statistical Analyses ......................................................................................... 60 
9.4.1 
Efficacy Analyses .............................................................................. 61 
9.4.2 
Pharmacokinetic/Pharmacodynamic Analyses .................................. 61 
9.4.3 
Safety Analyses .................................................................................. 61 
9.4.4 
Other Analyses ................................................................................... 62 
9.4.5 
Missing Data ...................................................................................... 62 
9.5 
Interim Analyses ............................................................................................. 62 
9.6 
Data Review Committee ................................................................................ 63 
10.0 
REFERENCES ........................................................................................................... 64 
11.0 
APPENDICES ............................................................................................................ 66 
Appendix 1 
Cancer Screening Guidelines .......................................................... 66 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations .......... 69 
Appendix 3 
Clinical Laboratory Tests ................................................................ 74 
Appendix 4 
Excluded Medications/Therapy ...................................................... 80 
Appendix 5 
2-D TTE Parameters ....................................................................... 81 
Appendix 6 
Contraceptive Guidance .................................................................. 82 
Appendix 7 
Summary of Changes ...................................................................... 85 
Appendix 8 
Signature of Investigator ................................................................. 89 


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TABLE OF TABLES 
Table 1 
Schedule of Assessments..................................................................................19 
Table 2 
Schedule of Digital ECG Assessments, Specimen Collection, and 
ECHO Assessments (Day 1 through 3) ............................................................22 
Table 3 
Study Objectives and Endpoints ......................................................................29 
Table 4 
Dose Escalation Per Cohort..............................................................................33 
Table 5 
Study Treatment Details ...................................................................................40 
Table 6 
Injection Site Reaction Grading Scheme .........................................................46 
Table 7 
Definitions of Serious Adverse Events ............................................................50 
Table 8 
Adverse Event Grade (Severity) Scale .............................................................52 
Table 9 
Relatedness of Adverse Events to Investigational Product ..............................53 
Table 10 
Plasma/Serum/Whole Blood Pharmacokinetic Parameters ..............................58 
Table 11 
Analysis Sets ....................................................................................................60 
Table 12 
Study Administrative Structure ........................................................................71 
Table 13 
Protocol-required Safety Laboratory Assessments ..........................................75 
Table 14 
Schedule of Protocol-required Safety Laboratory Assessments 
Performed by the Local Laboratory .................................................................77 
Table 15 
Schedule of Protocol-required Blood Collections to be Obtained by 
the Local Laboratory for Central Laboratory Analysis ....................................79 
Table 16 
Highly Effective Contraceptive Methods .........................................................83 
 
TABLE OF FIGURES 
Figure 1 
Study Schema ...................................................................................................18 
Figure 2 
Schematic Structure of JK07 ............................................................................24 


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09 APR 2021 
Page 7 of 89 
 
 
SUMMARY OF CHANGES 
Summary of changes for prior amendments may be found in Section 11.0 Appendix 7. 
Amendment 3: 09 APR 2021 
Rationale for the amendment: 
• Revision of descriptions of study procedures for clarification 
• Update to Sponsor signatory 
• Revision and updates to eligibility criteria to allow for improved documentation and 
investigator interpretation/discretion 
• Updates to the document for consistency including deletion of repetitive and unnecessary 
templated language 
• Minor editorial and grammatical corrections were made throughout the document. 
Where applicable added text is bolded and italicized. Deleted text has strikethrough. 
Section 
Change 
Reason 
Sponsor Signatory 
John Li CEO 
Sam Murphy, PhD, Chief Executive Officer 
Neal Salomon, MD, Chief Consulting Medical Officer and 
Medical Monitor 
Administrative 
Section 1.0: 
Protocol Summary, 
Section 3.0: 
Objectives and 
Endpoints and 
Section 11, 
Appendix 5: 2-D 
TTE Parameters 
Primary: Deletion of thyroid panel from list of laboratory 
parameters for assessment of change from baseline 
Exploratory: revision of 2D-TTE to be performed: 
• 
Microbubble contrast-enhanced 2-dimensional 
transthoracic echocardiography (2D-TTE) results: 
ejection fraction, including, but not limited to: LVEF, 
multiple 2 and 4-chamber left (LV) and right 
ventricular (RV) dimensions, including end systolic left 
ventricular volume (LVESV), end diastolic left 
ventricular volume (LVEDV), left atrial area and 
volume; right ventricular size and function, right 
ventricular global longitudinal strain, tricuspid valve 
regurgitation velocity, and mitral valve regurgitation 
grade (quantitative); as well as , valvular insufficiency 
and/or gradients, (IVC) size and collapsibility ratios; and 
multiple calculated monitoring parameters using velocity 
and flow measurements, including stroke volume (SV), 
cardiac output (CO), derived left ventricular filling 
pressure (E/e’). ) and systemic vascular resistance (SVR) 
calculations. 
Administrative 
Clarification of assessment 
parameters 
Section 1.0: 
Revision of language 
Clarification of directions 
Protocol Synopsis, 
regarding dose escalation 
Treatment Groups 
procedures by the DRC 
and Duration, 
Section 4.1: 
Overall Design 
Section 4.6.2: 
Criteria for 
Stopping Dose 
Escalation 


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Section 
Change 
Reason 
Section 1.3: Table 
1 - Schedule of 
Activities, Table 2 - 
Schedule of Digital 
ECG Assessments, 
Specimen 
Collection, and 
ECHO Assessments 
(Day 1 through 3); 
Section 5.3.1: 
Meals and Dietary 
Restrictions; 
Section 8.2.5: 
Electrocardiograms; 
Section 8.5.1: 
(Pharmacokinetics) 
Collection of 
Samples; 
Table 1 SoA revisions are listed below and are applicable to 
other tables and sections listed. 
Addition: Subjects must be fasted for 10 hours before each 
on-site visit 
Screening Visit; extension of screening period from Day -35 
to Day -45 
Footnotes: 
Vital signs; change in requirement for the need for to be 
performed at the same time as ECGs rather than immediately 
following. 
Footnote “a” In-patient stay addition: requirement for patients 
to receive a light breakfast/snack prior to IP administration. 
Footnote “c” Physical examination addition: requirement 
subjects must verify they have no prior history of malignancy 
and/or have undergone cancer screening. 
Footnote “g” Serum chemistry, liver, kidney, and coagulation 
assessments addition: coagulation panel will not be 
performed on Day 60, Day 90, or Day 135. Drugs of abuse to 
be performed as per local practices at Screening only. 
Footnote “i” Lipid Panel clarification: (fasting at screening 
and on Day 90) and should be performed as part of clinical 
chemistry at all timepoints indicated for clinical chemistry 
(see Table 14). 
Footnote “o” ECG clarification: following IP infusion, 0.5, 1, 
2, 4, and 8 hours from the end of the IP infusion, 24- and 48- 
hours after the start clock-time matched within ± 30 minutes 
of the IP infusion pre-dose Day 1 ECG assessment, prior to a 
light breakfast/snack. 
Footnote “q” clarification: PK Blood Samples: at 0.5, 1, 2, 4, 
8, 12, 24 hours (Day 2), and 48 hours (Day 3) from the end of 
the infusion timed to no more than 10 minutes following 
completion of ECG assessment. Addition of a +1 day 
window for sampling Day 7. 
Footnote “r” clarification: HbA1c to be performed at the 
Screening visit only. 
Footnote “u” Randomization update: Randomization will 
occur approximately one to two weeks prior to scheduled 
date of IP infusion, at the time of scheduling the inpatient 
admission, and will trigger shipment of IP and 
administration kit to site. See Section 6.3 for description of 
randomization procedures. 
Footnote “v”: Study Day 11 and 20 addition: Study visits on 
Day 11 and Day 22 may be conducted remotely at the 
discretion of the Principal Investigator based on their local 
risk assessment, in which case, the requirement for vital 
signs, ECGs, physical examination, and PK blood draws will 
be waived. The procedures will be performed as per the SoA 
if the visit take place at the clinical site. 
Update to and clarification 
of study procedures 
Section 4.6.1 Study 
Stopping Criteria 
• 
Any emergent symptomatic or asymptomatic cardiac 
arrhythmia requiring at least urgent medical intervention. 
• 
Any ≥ moderate (corresponding to Common Terminology 
Criteria for Adverse Events [CTCAE version 5 (v5)] 
Grade 2) hematologic, non-hematologic, hepato-cellular, 
renal toxicity ≥7 days. Any emergent Grade 3 or greater 
(>/=) toxicity except untreated nausea, diarrhea, 
Clarification of criteria. 


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Section 
Change 
Reason 
vomiting, constipation, abdominal pain. Any of these will 
be considered DLTs if persisting >72 hours despite 
appropriate  treatment.  Any  emergent  ≥  severe 
(corresponding to CTCAE v5 Grade 3) hematologic, non- 
hematologic, hepato-cellular, renal toxicity 
Section 5.1: 
Inclusion Criteria 
Criterion 2: Stable HF defined as no hospitalizations for 
cardiac-related issues within the previous 23 months prior to 
the screening visit or between screening and randomization, 
other than for routine percutaneous procedures such as 
device, battery, generator changes or pacemaker lead 
insertion/replacement. 
Criterion 4: Subjects must be taking clinician-directed 
appropriate pharmacological therapy for HF as per the 2017 
ACC/AHA/HFSA treatment guidelines (Yancy et al, 2017) 
and at investigator determined discretion at stable doses 
(except for diuretics) for at least 32 months prior to 
screeningsinformed consent. 
Criterion 5: Subjects without implantable cardioverter- 
defibrillators (ICDs) are eligible. Subjects with implantable 
ICDs if the devices are not “pacing are allowed at the 
discretion of the investigator, but only if both the following 
criteria are met: (a) paced beats cannot exceed 15% of beats 
as quantified by screening e-Patch, and (b) if a non-paced 
baseline ECG can be obtained on Day 1 prior to study drug 
administration. 
Criterion 6: Body mass index ≥18 kg/m2 and ≤4540 kg/m2 
Revision and clarification 
of criteria to allow for 
improved documentation 
and investigator 
interpretation/discretion. 
Section 5.2: 
Exclusion Criteria 
Criterion 4: Diagnosed with medically documented acute 
coronary syndrome within 3 months of screening or a 
medically documented acute myocardial infarction within 
6 months of screening. 
Criterion 8: Sustained systolic BP <90 <100 mm Hg and/or 
diastolic BP <50 mm Hg (confirmed by a duplicate seated 
reading) on at least 3 consecutive readings (self-monitored or 
office) ….. 
Criterion 9: Resting HR >100 beats per minute (bpm) at 
Screening (Visit 1) or prior to randomization which is 
sustained for >15 minutes in two episodes separated by one 
hour of observation except in sustained atrial fibrillation 
when HR of up to 110 bpm is acceptable. 
Criterion 10: Cerebrovascular accident or hospitalizations for 
CV (cardiovascular) causes other than routine percutaneous 
procedures such as device, battery, generator changes or 
pacemaker lead insertion/replacement or device generator 
changes, including HF, chest pain, stroke, transient ischemic 
attack, or arrhythmias within 32 months prior to screening. 
Criterion 11: Subjects at screening have an abnormal or 
clinically significant 12-lead ECG abnormality, (e.g. QRS 
>120 msec, PR >210 msec, heart rate (HR) <45 bpm, sustained 
HR >100 bpm) that, in the opinion of the Investigator, would 
affect efficacy or safety evaluation or place the subject at risk. 
Criterion 15: For subjects on warfarin or other anticoagulants, 
an INR (or PT/PTT) considered by the Principal Investigator 
as therapeutically appropriate will be allowed. 
Revision and clarification 
of criteria to allow for 
improved documentation 
and investigator 
interpretation/discretion. 


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Section 
Change 
Reason 
Criterion 18: Concurrent treatment with Class Ia or III 
antiarrhythmic drugs (unless the medication wasmust have 
been 
discontinued 
more 
than 
32 
months 
before 
enrollmentinformed consent). 
Criterion 20: Known history of or active alcohol abuse (no 
more than 14 units/week for males or 7 units/week for females) 
or use of illicit drugs within 1 year prior to randomization other 
than(excluding recreational use of marijuana or cannabis- 
cannabidiol [CBD]-based products). 
Criterion 22: history of pathologically confirmed malignancy 
of any type or any pathologically confirmed pre-malignant 
condition (e.g., ductal carcinoma in situ, colonic polyp with 
premalignant diagnosis, or cervical atypia). 
Section 6.0: Study 
Treatment 
New language added: This is a double-blind study. The 
investigational treatment and placebo infusions will be 
identical in physical appearance. Other than in the case of 
sentinel subjects, the treatment each subject will receive will 
not be disclosed to the Investigator, study center staff, 
subject, Sponsor, study vendors, or DRC. The treatment 
codes will be held by a third-party clinical research services 
vendor designated by the Sponsor. 
Where possible, and as applicable, hospital admission and IP 
administration should take place on Monday or Tuesday to 
allow for Day 7 follow-up visits to take place on the following 
Monday. 
With the exception of IP infusion administered to the sentinel 
subject in each cohort, all study staff will be blinded to IP 
identification. 
The total infusion time, inclusive of saline flush should be 60 
minutes and should not exceed 75 minutes. 
Addition of new language 
and revision of existing 
language to clarify study 
procedures. 
Section 6.2: 
Preparation, 
Handling, and 
Storage 
Revision to allow for pharmacy staff to document preparation 
of IP according to local standards of practice and to mandate 
that all records be available for inspection. 
Simplification of 
procedures 
Section 6.3: 
Randomization and 
Blinding 
Deletion of unnecessary templated language and insertion of 
language describing the IWRS procedures. 
Clarification of procedures 
Section 6.4.1: 
Treatment Strategy 
and Section 6.4.2: 
Warnings and 
Precautions 
Sections deleted. 
Deletion of unnecessary 
language. 
Section 6.5: 
Concomitant 
Medications 
Substitution of ‘time of informed consent” and deletion of 
“time of enrollment” as the starting timepoint for collection of 
data 
Clarification of study 
procedures. 
Section 6.6: Dose 
Modification 
Deletion of language. Addition of: As this is a single-dose 
study, dose modification within an individual subject is not 
applicable. 
Deletion of unnecessary 
template language and 
clarification of study 
procedure. 
Section 7.2: 
Subject 
Discontinuation 
Addition: Subjects withdrawing due to an AE should be 
followed up according to the follow-up visit at any time 
should be followed up until resolution, stabilization, the 
event is otherwise explained, the subject is lost to follow-up 
(Section 8.3.8) or until the end of their participation in the 
Clarification of study 
procedure 


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Section 
Change 
Reason 
study. Subjects should be encouraged to complete the End 
of Study visit activities. 
Section 8.2: Safety 
Assessments 
Addition: Subjects will be observed for injection site reactions 
until Day 4 following IP administration, for DLAEs until Day 
15 following IP administration, and for AEs and SAEs from 
the time of informed consent until 30 days after the IP 
administration. Following Day 30, only SAEs deemed at least 
possibly related to the study drug or study procedures will be 
collected until the End of Study visit (Day 180). 
Clarification of timelines 
for safety reporting. 
Section 8.2.5: 
Electrocardiograms 
Addition: During Screening and beginning no more than 45 
days before Day 1, all subjects will be supplied with, and 
instructed how to use a e-Patch for continuous 14-day heart 
rhythm monitoring as outlined in the Table 1 SoA. A 14- 
continuous day heart rhythm monitoring assessment will be 
collected using the e-Patch with monitoring completed no 
later than Day -10 unless confirmed with the sponsor. Where 
applicable, the screening ECG and Day 1 baseline ECG must 
be obtained without evidence of pacing. 
Addition of description of 
ePatch procedures 
Section 8.3.8: 
Follow-up of AEs 
and SAEs. 
Revision: All SAEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the subject 
is lost to follow-up (as defined in Section 7.3) or until the 
end of their participation in the study. Subjects should be 
encouraged to complete the End of Study visit activities. 
Clarification of duration of 
follow-up for SAEs. 
Section 8.4: 
Treatment of 
Overdose 
Revision: Obtain blood sample for PK analysis within 30 days 
from as specified in Table 1 SoA.the date of the last dose of 
study intervention if requested by the medical monitor 
(determined on a case-by-case basis). 
Revision of study procedure 
Section 8.8: 
Biomarkers 
Addition of lactate dehydrogenase 
Revision of study 
procedures 
Section 9.4.3: 
Safety Analyses 
For 12-lead ECG parameters: If relevant, analysis excluding 
ECGs capturing paced beats will be performed. 
Clarification of procedures 
Section 9.6: Data 
Review Committee 
Addition of description of procedures outlined in the synopsis. 
Clarification of procedures. 
Section 11: 
Regulatory, Ethical, 
and Study 
Oversight, 
Appendix 2: Study 
and Study 
Procedures 
Addition of language describing procedures for changes to the 
protocol. 
Update of study procedures 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
2D-TTE 
2-dimensional transthoracic echocardiography 
ACC/AHA/HFSA 
American College of Cardiology/American Heart Association Task Force on 
Clinical Practice Guidelines and the Heart Failure Society of America 
ACS 
American Cancer Society 
ADA 
anti-drug-antibody 
AE 
adverse event 
ANC 
absolute neutrophil count 
AUC(0-inf) 
area under the plasma concentration-time curve from time zero extrapolated 
to infinity 
AUC(0-last) 
area under the plasma concentration-time curve from time zero to the time of 
the last quantifiable concentration 
BP 
blood pressure 
bpm 
beats per minute 
BUN 
blood urea nitrogen 
BNP 
brain natriuretic peptide 
CBD 
cannabidiol 
CL 
systemic clearance 
Cmax 
maximum concentration 
CO 
cardiac output 
CPK 
creatine phosphokinase 
CPK-MB 
creatine phosphokinase – muscle/brain 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTnI 
cardiac troponin I 
CV 
cardiovascular 
DD2 
diastolic dysfunction Grade 2 
DLAE 
dose-limiting adverse events 
DRC 
Data Review Committee 
DRE 
disease-related events 
ECG 
electrocardiogram 
ECRF 
case report form 
eCRF 
electronic case report form 
E 
early diastole 
E/e’ 
derived left ventricular filling pressure 
EGF 
epidermal growth factor 
FIH 
first-in-human 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GI 
gastrointestinal 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HCSD 
highest confirmed safe dose 
HED 
human equivalent dose 
HER3 
human epidermal growth factor receptor 3 
HF 
heart failure 
HFpEF 
heart failure with preserved ejection fraction 
HFrEF 
heart failure with reduced ejection fraction 
HR 
heart rate 
hsCRP 
high-sensitivity C-reactive protein 
hs-troponin 
high-sensitivity troponin 


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Abbreviation 
Definition 
ICD 
implantable cardioverter-defibrillators 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
INR 
international normalized ratio 
IP 
investigational product 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
IV 
intravenous 
IVC 
inferior vena cava 
IVRS/IWRS 
Interactive Voice/Web Response System 
LDH 
lactate dehydrogenase 
+LVdp/dtmax 
maximum rate of rise of left ventricular pressure 
LVEDV 
end diastolic left ventricular volume 
LVEF 
left ventricular ejection fraction 
LVESV 
end systolic left ventricular volume 
Max 
maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
minimum 
NHP 
non-human primates 
NOAEL 
no observed adverse effect level 
NRG-1 
neuregulin-1 
NT-proBNP 
N-terminal pro-brain natriuretic peptide 
NYHA 
New York Heart Association 
PBS 
phosphate buffered saline 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QTca 
heart-rate corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RCmax 
ratio of Cmax 
RAUC(0-inf) 
ratio of AUC(0-inf) 
RAUC(0-last) 
ratio of AUC(0-last) 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Assessments 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SVR 
systemic vascular resistance 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to maximal concentration 
ULN 
upper limit of normal 
WOCBP 
women of child-bearing potential 
λz 
terminal rate constant 


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1.0 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to Assess the Safety, 
Tolerability, and Pharmacokinetics of JK07 in Subjects with Heart Failure with Reduced Ejection Fraction (HFrEF) 
Rationale: JK07 is a recombinant fusion protein consisting of a human neuregulin-1 (NRG-1) active domain and an 
anti-human epidermal growth factor receptor 3 (HER3) monoclonal antibody, thus limiting HER3-mediated 
gastrointestinal (GI) toxicity and oncogenic potential while preserving/activating the HER4-mediated cardiovascular 
potential. The main purpose of the study is to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics 
(PK) of JK07, administered intravenously (IV) to subjects with heart failure with reduced ejection fraction 
(HFrEF ≤40%). Change in left ventricular ejection fraction (LVEF), potential predictive biomarkers of response to 
JK07, and changes in QT interval will be also explored. 
Objectives and Endpoints: 
 
Objectives 
Endpoints 
Primary 
• 
Assess the safety and tolerability profile, including 
immunogenicity, of JK07, administered intravenously 
according to protocol-defined dosing regimen. 
• 
Incidence and severity of treatment-emergent adverse 
events (TEAEs) and their relationship to the 
investigational product (IP). 
• 
12-lead electrocardiogram (ECG) parameters (heart rate, 
PR, QRS, QT, QTcF) change from baseline derived as 
mean from triplicate ECG recordings as well as QT and 
QTcF outlier analyses. 
• 
Change from baseline in the incidence of rhythm 
abnormalities (retrieved from telemetry readings for 
48 hours postdose). 
• 
Laboratory parameters – change from baseline each 
assessment time point per Table 1 Schedule of 
Assessments (SoA) postdose: hematology, chemistry, 
coagulation, and lipid panels. 
• 
Immunogenicity 
o 
Incidence of early and delayed-type 
hypersensitivity responses. 
o 
Presence of serum anti-JK07 antibodies 
(confirmed positive antibody response, titer, 
neutralizing antibodies). 
• 
Vital signs – change from baseline in vital signs and the 
relationship to JK07 compared with placebo, including: 
o 
Blood pressure (BP) 
o 
Temperature 
o 
Heart rate (HR) 
o 
Respiratory rate (RR). 


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Secondary 
• 
To determine the PK characteristics of JK07 
administered intravenously according to protocol- 
defined dosing regimen. 
• 
Pharmacokinetic parameters of intact JK07 including, 
but not limited to, maximum concentration (Cmax), time 
to Cmax (tmax), area under the concentration-time curve to 
the last quantifiable concentration and extrapolated to 
infinity [AUC(0-last) and AUC(0-inf)], half-life (t1/2), 
elimination rate constant (λz), systemic clearance (CL), 
and volume of distribution (Vz). Surrogate measurement 
of intact JK07 to be carried out through detection of 
both the JK07 antibody domain and the JK07 NRG-1 
peptide fragment in the evaluation of pharmacokinetic 
parameters. 
Exploratory 
• 
Explore left ventricular and systemic vascular resistance 
(SVR) performance indices measured by 2-dimensional 
transthoracic echocardiography (2D-TTE) of JK07, as 
change from baseline compared with placebo. 
• 
Explore potential predictive biomarkers of response to 
JK07 in this dosing regimen. 
• 
Explore relationship between JK07 plasma 
concentrations, if any, and changes in QT intervals 
during dosing. 
• 
Microbubble contrast-enhanced 2-dimensional 
transthoracic echocardiography (2D-TTE) results, 
including, but not limited to: LVEF, multiple 2 and 
4-chamber left (LV) and right ventricular (RV) 
dimensions, including end systolic left ventricular 
volume (LVESV), end diastolic left ventricular volume 
(LVEDV), left atrial area and volume, valvular 
insufficiency and/or gradients, and multiple calculated 
monitoring parameters using velocity and flow 
measurements, including stroke volume (SV), cardiac 
output (CO), derived left ventricular filling pressure 
(E/e’). 
• 
Observed biomarker concentrations and corresponding 
changes from baseline. 
• 
Concentration-QT correlation performed on baseline- 
corrected QTcF time matched with PK. 
 
Overall Design: 
This is a phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the safety, 
tolerability, immunogenicity, and PK of JK07 in subjects 18 to 80 years of age with HFrEF ≤40% (Figure 1). 
Initially 5 cohorts are planned with the option to expand the study to a total of 7 cohorts. The size of the cohorts will 
range from 5 to 9 subjects. Each cohort will include one single active unblinded sentinel subject receiving a single IV 
dose of JK07 prior to randomized JK07 or placebo administration in the remainder of the cohort. 
A Data Review Committee (DRC) will be established to review emerging data, to monitor safety aspects of the study, 
to select the JK07 dose during dose escalation, and to adapt the randomization scheme. The DRC will evaluate the 
emerging clinical, laboratory and cardiac safety data, inclusive from the first 48 hours after dosing of the sentinel 
subject, and prior to randomized blinded IP administration in the remainder of the cohort. 
Number of Investigators and Study Centers: 
Approximately 8 Investigators and study centers are expected to participate in this study. 
Number of Subjects: 
A maximum of 63 subjects will be randomized into dose escalation cohorts. Five dose escalation cohorts are planned. 
Two additional cohorts may be added as per the DRC recommendation (total up to 7 cohorts). 
Treatment Groups and Duration: 
In Cohort 1, if no clinical effect is observed in the sentinel subject, the DRC will decide whether to proceed with the 
randomization of 4 additional subjects (3:1, JK07: placebo) to receive blinded IP. Once the last subject in Cohort 1 
completes the evaluation period, the DRC will decide whether to proceed to Cohort 2. The evaluation period for dose 
escalation to the next cohort will be at a minimum, the available safety data through Day 15 following the 
administration of the IP on Day 1 for all subjects in the current dose cohort. Safety data will continue to be collected 


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up to 180 days following the administration of the IP and may additionally be taken into consideration for dose 
escalation when available. Cohort 2 and subsequent cohorts will proceed as Cohort 1 until either of the following 
occur: a sentinel subject exhibits, in the opinion of the DRC, a clinical effect (efficacy or safety observation), or a 
cohort exhibits, in the opinion of the DRC, a clinical effect. 
Once a clinical effect is observed, the DRC may, at its discretion, expand the size of that cohort in which a clinical 
effect is first observed, and subsequent cohorts, up to a maximum of 9 subjects (1 open-label JK07 sentinel subject, 
and 6:2 [JK07: placebo] randomized, double-blind subjects). 
Following observation of a clinical effect and a decision to expand the size of the cohort at which the clinical effect 
was observed, the DRC will decide whether to dose escalate after the last subject in the expansion cohort completes 
the evaluation period. If the DRC decides to escalate the dose, a single unblinded sentinel subject will receive JK07 
at the next dose level. If following the completion of the evaluation period of that sentinel subject the DRC decides to 
proceed, the remainder of the subjects in the expanded cohort size will receive JK07 or placebo according to the 
direction of the DRC, and this sequence will repeat until the highest planned dose level is reached or until the DRC 
determines not to dose escalate further. 
Cohort dose levels of JK07 are as follows: the starting dose has been selected at 1/30 of the human equivalent dose 
(HED) at the no-observed adverse effect level (NOAEL) in the cynomolgus monkey (3 mg/kg/week). A conservative 
approach of body surface area scaling was employed for this conversion (HED) at the monkey 
NOAEL = 0.97 mg/kg/week). The subsequent provisional doses have been set at a 3-fold increase from the prior dose 
for the first 2 dose escalations (Cohort 2 through Cohort 3). The subsequent dose escalations (Cohort 4 through 
Cohort 5) have been set at a 2-fold increase from the prior dose; based on emerging safety and/or PK results of the 
previous cohorts, the DRC can allow a 3-fold increase. Additionally, the DRC may also reduce the incremental dose 
escalations based on the results of the previous cohorts. 
 
Dose Level 
JK07 
Cohort 1 
0.03 mg/kg 
Cohort 2 
0.09 mg/kg 
Cohort 3 
0.27 mg/kg 
Cohort 4 
0.54 mg/kg 
Cohort 5 
1.08 mg/kg 
Note: Initially 5 cohorts are planned. Two additional higher cohorts may be added as per the DRC recommendation (total up to 
7 cohorts). The highest JK07 dose administered not to exceed 2.5 mg/kg without further amending the protocol. 
Subjects will be observed for injection site reactions until Day 4 following study treatment and will be monitored for 
signs of dose-limiting adverse events (DLAE) until Day 15 following study treatment. 
Beginning on Day 1 and prior to study drug administration, subjects will be observed on continuous telemetry for the 
duration of the hospital stay. During this period blood will be collected for PK, biomarkers and safety laboratory 
assessments, vital sign and ECG assessments will be performed, and 2D-TTE will be performed pre-dose, and at 6- 
and 30-hours post-dose, to observe for possible clinical activity. 
The DRC will evaluate each sentinel subject as well as active treatment subjects in each dose cohort for DLAEs. To 
support dose escalation decisions by the DRC, safety, and tolerability results for all subjects in each cohort through at 
least Day 15 will be included in this review. During the review of the safety and tolerability results the DRC may 
make the determination to escalate to the next dose level or expand the size of the current cohort further, if not already 
at the maximum size, following which further dose escalation could proceed. Alternatively, the DRC may determine 
to decrease to a lower dose level which may be an additional cohort at an intermediary dose or a pre-assigned cohort. 
In the case that an intermediary dose is selected, a single sentinel subject will receive JK07 prior to randomization of 
the remaining subjects in the cohort. Following a dose reduction, the DRC may subsequently decide to further reduce 
the dose level in a subsequent cohort or increase the dose in a subsequent cohort. A sentinel subject is required only 
if the selected de-escalated dose is above the previously Highest Confirmed Safe Dose (HCSD). 
At the time of the DRC safety review of the entire cohort, PK results if available for that cohort, will be evaluated 
(along with results of prior cohorts, as available). 
Statistical Methods: 
Sample size calculation: The sample size for this study is not based on statistical considerations but is typical for 
studies of this nature and is considered adequate to characterize the distribution of the planned endpoints. Any 
statistical testing will be considered exploratory and descriptive. 
Analysis sets: 


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• 
Safety Evaluation Population: All subjects randomly assigned to the IP and who take 1 dose of IP. Subjects 
will be analyzed according to the treatment they received. 
• 
DLAE Evaluation Population: All subjects who received 1 dose of IP and completed the 15-day DLAE 
follow-up period. 
• 
PK Evaluation Population: All subjects who received at least 1 dose of JK07 and have at least 1 quantifiable 
JK07 plasma concentration collected postdose without important protocol deviations/violations or events 
thought to significantly affect the PK results. 
• 
Exploratory PD/biomarker Evaluation Population: All subjects who take 1 dose of IP and have at least 
1 exploratory PD variable or biomarker endpoint collected postdose without important protocol 
deviations/violations or events thought to significantly affect the PD results. 
Safety Analyses: All data will be provided in data listings sorted by treatment group, subject number, and visit. 
Summary data will be presented in a tabular format by treatment group, by scheduled time point, visit, and overall (as 
appropriate). Categorical data will be summarized by the number and percentage of subjects in each category. 
Continuous data will be summarized by descriptive statistics including at a minimum sample size (n), mean, standard 
deviation, median, minimum, and maximum. Change from baseline will be calculated as value postdose subtracted 
by value at baseline. The baseline measure will be defined as the last non-missing measure prior to initiation of the 
IP. Outliers for QT and QTc defined under outcome measures will be summarized using cumulative counts and 
percentages by treatment and sampling time, if appropriate. Abnormal findings on 12-lead ECG will be summarized 
by treatment using descriptive statistics. 
PK Analyses: Intact JK07 concentrations, determined through detection of both the antibody domain and NRG-1 
peptide, and calculated parameters will be listed and descriptively summarized by active treatment for the PK 
Evaluation population. Dose proportionality will be explored graphically, and, if applicable, using a power model. 
Exploratory PD Analyses: Results of the exploratory endpoints (2D-TTE results and biomarkers) and their change 
from baseline values (as applicable) will be listed and descriptively summarized by treatment. Exploratory inferential 
comparisons with placebo may also be performed, if appropriate. An exploratory evaluation of a plasma concentration 
to QT (C-QT) relationship will be conducted using a linear mixed effects model, with the drug-free-corrected (i.e., 
predose-corrected) change from baseline in QTcF as the response variable. Independent variables will include the 
fixed effects time-matched JK07 plasma concentration obtained on Day 1, treatment indicator (treatment = 1 for 
subjects receiving JK07, and 0 otherwise), time point as a categorical variable, and random effects subject and time- 
matched JK07 plasma concentration obtained on Day 1. 
Data Monitoring Committee: Yes 


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1.2 
Schema 
Figure 1 
Study Schema 
 
Abbreviations: DLAE, dose-limiting adverse events; DRC, Data Review Committee. 


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1.3 
Schedule of Activities 
Table 1 
Schedule of Assessments 
(note that X denotes activity on a given day, but may denote a single or multiple instances of the indicated activity) 
 
Screening 
In Hospital 
Follow-up 
EOS/ 
180t 
Subjects must be fasted for 10 hours before each on-site visit 
Study Day 
-45 to 0 
1a 
2 
3 
4 
7 
11v 
15 
22v 
30 
60 
90 
135 
Window 
+1 
-1 
+/-2 
+/-2 
+/-2 
+/-5 
+/-5 
+/-7 
+/-10 
In-patient staya 
X 
X 
X 
Hospital dischargeb 
X 
Informed consent 
X 
Demographics 
X 
Past medical history 
X 
Height (at screening only) and 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (at same time point as 
ECGs) 
X 
X 
X 
X 
X 
X 
Xv 
X 
X 
X 
X 
X 
X 
Physical examinationc 
X 
X 
X 
X 
X 
X 
Xv 
X 
Xv 
X 
X 
X 
X 
X 
Blood-based pregnancy testd 
X 
Urine pregnancy testd 
X 
X 
X 
X 
X 
X 
IP administration 
X 
Check for injection site reactione 
X 
X 
X 
X 
Adverse eventsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry and liver, kidney, and 
coagulation panelsg 
X 
X 
X 
X 
X 
X 
Xg 
Xg 
Xg 
X 
Complete blood counth 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Screening 
In Hospital 
Follow-up 
EOS/ 
180t 
Subjects must be fasted for 10 hours before each on-site visit 
Study Day 
-45 to 0 
1a 
2 
3 
4 
7 
11v 
15 
22v 
30 
60 
90 
135 
Window 
+1 
-1 
+/-2 
+/-2 
+/-2 
+/-5 
+/-5 
+/-7 
+/-10 
Lipid paneli 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisj 
X 
X 
X 
X 
X 
Muscle and inflammatory 
biomarkersk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Additional biomarkers: Cardiac 
troponins, CPK-MB, CPK, and hsCRP 
assessmentl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity Assessmentm 
X 
X 
X 
X 
X 
X 
X 
Telemetryn 
X 
X 
X 
Digital 12-lead ECGo 
X 
X 
X 
X 
X 
X 
Xv 
X 
X 
X 
X 
X 
X 
2D-TTEp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample collectionq 
X 
X 
X 
X 
X 
Xv 
X 
Xv 
X 
X 
Fingerstick glucoser 
X 
X 
X 
X 
ECG patch recordings 
X 
Thyroid panel 
X 
Viral serology 
X 
Randomizationu 
X 
Abbreviations: 2D-TTE, 2-dimensional transthoracic echocardiography; β-hCG, beta-human chorionic gonadotrophin; CPK-MB, creatine kinase – muscle/brain; CPK, creatine 
phosphokinase; ECG, electrocardiogram; HbA1c, glycosylated hemoglobin; HDL, high density lipoprotein; hs-CRP, high-sensitivity C-reactive protein; ICD, implantable 
cardioverter-defibrillators; IP, investigational product; LDH, lactate dehydrogenase; LDL, low density lipoprotein; PK, pharmacokinetic. 
a Subjects should be admitted in the hospital study unit by 7:00 AM, or as early as practicable, on Day 1. The subject should arrive fasted (at least 10-hour fast). All baseline 
clinical and laboratory assessments should be conducted prior to light breakfast/snack being provided to the subject. Subjects will be scheduled for discharge on the morning of 
Day 3. 
b Subjects will be scheduled for hospital discharge on Day 3, after completion of all planned in-patient safety, PK, and exploratory PD/biomarker assessments. However, subjects 
may be asked to remain in the hospital study unit for more than 48 hours after the IP administration at the Investigator’s discretion. 
c A full physical examination will be performed at screening. An abbreviated physical examination will be conducted at all other visits. See Section 8.2.1. During screening all 
subjects must verify they have no prior history of malignancy and/or have undergone cancer screening or undergo cancer screening according to American Cancer Society 
Guidelines (Appendix 1 Cancer Screening Guidelines). 


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d Women of childbearing potential only. β-hCG blood test at screening, urine dipstick test upon admission on Day 1 prior to IP administration to confirm absence of pregnancy, and 
urine specimens at all time points thereafter. 
e See Section 8.2.2 for assessment times and parameters. 
fAll AEs, including SAEs will be collected from the time of study enrollment and until 30 days after the IP administration. Following the first 30 days, only SAEs deemed at least 
possibly related to the study drug or study procedures should be collected. Refer to Table 9 for additional details. 
g See Appendix 3  Clinical Laboratory Tests for a complete list of analytes and schedule of collections and analysis. Coagulation panel will not be performed on Day 60, Day 90, 
or Day 135. Drugs of abuse to be performed as per local practices at Screening only. 
h See Appendix 3  Clinical Laboratory Tests for parameters included in the complete blood count. 
i Lipid profile includes total cholesterol, HDL, LDL, and triglycerides, and should be performed as part of clinical chemistry at all timepoints indicated for clinical chemistry (see 
Table 14). 
j See Table 13 for a complete list of urinalysis parameters. 
k See Section 8.8 for a complete list of muscle and inflammatory biomarkers. 
l On Day 1 multiple blood samples for safety evaluation will be collected as follows: troponin I and/or hs troponin T, CPK, CPK-MB, and hsCRP prior to infusion and at 4, 8, and 
12 hours from end of infusion. 
m Refer to Section 8.2.8 for immunogenicity assessments. 
n Continuous telemetry monitoring will be started as soon as practicable after hospital admission on Day 1 and prior to IP infusion, and will be continued until 48 hours after the end 
of the IP infusion on Day 3. In the case of any abnormal finding, the Investigator will determine whether the finding constitutes an abnormal event and whether an unscheduled 
ECG should be conducted. 
o Triplicate 12-lead digital ECGs will be performed during screening and starting on Day 1 following admission to the hospital. ECG assessment will be performed at each specified time point 
after the subject has been supine for ≥5 minutes. At each time point at which triplicate ECGs are required, 3 individual ECG tracings should be performed as closely as possible 
in succession but no more than 2 minutes apart. The full set of triplicates should be completed in less than 5 minutes with no more than 2 min between them. Vital signs are 
scheduled at the same time points and will be collected prior to completion of the ECG assessment, and the ECG assessment will be prior to PK sample collections at simultaneously 
scheduled time points. 
• 
The post-screening times for the ECGs will be as follows: prior to the IP infusion, immediately following IP infusion, 0.5, 1, 2, 4, and 8 hours from the end of the IP 
infusion, 24- and 48-hours clock-time matched within ± 30 minutes of pre-dose Day 1 ECG assessment, prior to a light breakfast/snack (see Table 2 for additional 
details). 
• 
These ECGs will be read by the Investigator to ensure subject safety. These ECGs must be taken immediately before PK sampling. 
p On Day 1, 2D-TTE measurements will be performed pre-dose and at 6 ± 0.5 hours post-dose. On Day 2, the assessment is scheduled for 30 ± 0.5 hours post-dose. 
See Section 8.2.9 for a description of exploratory 2D-TTE assessments. 
q The PK blood samples will be collected as follows: Prior to the IP administration, at the end of the infusion, at 0.5, 1, 2, 4, 8, and 12 hours, at 24 hours (Day 2) and 48 hours (Day 
3) timed to no more than 10 minutes following completion of ECG assessment, at 72 hours (Day 4), 144 hours (Day 7), 240 hours (Day 11), 336 hours (Day 15), and 504 hours 
(Day 22) from the end of the infusion, and on Day 30 and Day 60 (see Table 2). Note that sample collection times may be modified based on emerging PK results and 
1 additional blood sample may be collected if deemed appropriate (up to 18 samples). Windows for the first 48 hours of PK collections are identified in Table 2; a ±8-hour 
window is permitted for PK collections on Day 4 and a +1 day is permitted on Day 7. Windows for subsequent PK sample collections are indicated in the SoA above. 
r Blood glucose samples will be collected by fingerprick test and read using standard glucometer at the same timepoint as the PK samples through 96h (Day 4) postdose. HbA1c to 
be performed at the Screening visit only. 
s During the screening period and no more than 45 days before Day 1, all subjects will be supplied with, and instructed how to use a e-Patch for continuous 14-day heart rhythm 
monitoring. Subjects must then perform 14 continuous days of heart rhythm monitoring using the e-Patch. Unless otherwise approved by the sponsor, monitoring should be 
completed no later than Day -10 to allow for processing of data by the manufacturer and evaluation of baseline ECG parameters and arrhythmia incidents by the site. 
t Subjects who do not complete all required visits or withdraw from the study early are required to complete End-of Study/Early-Termination assessments (Day 180) as described in 
Section 7.2. 
u Randomization will occur approximately one to two weeks prior to scheduled date of IP infusion, at the time of scheduling the inpatient admission, and will trigger shipment of IP 
and administration kit to site. See Section 6.3 for description of randomization procedures. 
v Study visits on Day 11 and Day 22 may be conducted remotely at the discretion of the Principal Investigator based on their local risk assessment, in which case, the requirement 
for vital signs, ECGs, physical examination, and PK blood draws will be waived. The procedures will be performed as per the SoA if the visit takes place at the clinical site. 


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NOTE: See Appendix 3 
Clinical Laboratory Tests, Table 13 for a complete list of protocol-required laboratory assessments that will be performed; see Table 14 for a list of 
safety laboratory assessments (and assessment timepoints) that will be performed by the local laboratory; see Table 15 for a list of safety and exploratory biomarker 
assessments that will be performed by a central laboratory. 
 
Table 2 
Schedule of Digital ECG Assessments, Specimen Collection, and ECHO Assessments (Day 1 through 3) 
 
Schedule of Assessments (Day 1 – Day 3) 
(Order of activities to be completed left to right, top to bottom) 
Day 1 
Time relative to dosea 
12-lead ECGb 
Specimen Collection (Labs) 
2D-TTE 
No food consumption for 10 hours before predose ECG assessment, specimen collection and ECHO 
Predose (prior to start of infusion) 
Xc 
Safety (local) 
Biomarkers (central) 
PK (central) 
Glucose (fingerstick) 
Urinalysis (local) 
Urine β-hCG (local) 
X 
Light Breakfast/ Snack 
XXXX 
Drug Infusion 
XXXX 
End of infusion (no later than 5 minutes 
from end-of-infusion) 
Xd 
PK (central) 
Glucose (fingerstick) 
0.5 hour from end-of-infusion 
X 
PK (central) 
Glucose (fingerstick) 
1 hour from end-of-infusion 
X 
PK (central) 
Glucose (fingerstick) 
2 hours from end-of-infusion 
X 
PK (central) 
Glucose (fingerstick) 
4 hours from end-of-infusion 
X 
Safety (local) 
PK (central) 
Glucose (fingerstick) 


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Schedule of Assessments (Day 1 – Day 3) 
(Order of activities to be completed left to right, top to bottom) 
Day 1 
Time relative to dosea 
12-lead ECGb 
Specimen Collection (Labs) 
2D-TTE 
6 hours from end-of-infusion 
X 
8 hours from end-of-infusion 
X 
Safety (local) 
PK (central) 
Glucose (fingerstick) 
12 hours from end-of-infusion 
Safety (local) 
PK (central) 
Glucose (fingerstick) 
Day 2 
12-lead ECGb 
Blood Collection (Labs) 
ECHO 
24 hourse from end-of-infusion 
X 
Safety (local) 
Biomarkers (central) 
PK (central) 
Glucose (fingerstick) 
Urinalysis (local) 
30 hours from end-of-infusion 
X 
Day 3 
12-lead ECGb 
Blood Collection (Labs) 
ECHO 
48 hoursf from end-of-infusion 
X 
Safety (local) 
PK (central) 
Glucose (fingerstick) 
Abbreviations: 2D-TTE, 2-dimensional transthoracic echocardiography; β-hCG, beta human chorionic gonadotrophin; ECHO, ECG, electrocardiogram; PK, pharmacokinetics 
a ±5-minute window will be allowed for PK samples taken up to 1-hour postdose; a ±15-minute window will be allowed for samples taken at 2 to 12 hours postdose, samples taken 
at 24- and 48-hours postdose must be taken within 10 minutes after the 24- and 48-hour ECG assessments. 
b At the time of ECGs, subject should have rested in a supine position for at least 5 minutes. 
c 12-lead digital ECG must be performed prior to the PK sample collection and should be collected as close to the scheduled times as possible. For 12-lead digital ECG 
assessments scheduled for up to and including 4 hours, the ECG assessments should be within 10 minutes prior to the PK sample collection; for subsequent ECG assessment, a 
window of 30 minutes prior to PK collection (or less) is desired. 
d All required ECG leads will be secured to the patient and attached to an ECG machine prior to administration of the IP to facilitate immediate post-infusion recording. 
e For the 24-hour time point on Day 2, the ECG assessment should be clock time-matched within ±30 minutes of the pre-dose Day 1 ECG assessment, prior to light 
breakfast/snack, and the PK sample should be clock time-matched to no more than 10 minutes following completion of the ECG assessment. 
f For the 48-hour time point on Day 3, the ECG assessment should be clock time matched within ±30 minutes of the pre-dose Day 1 ECG assessment, prior to light breakfast/ 
snack, and the PK sample should be clock time matched to no more than 10 minutes following completion of the ECG assessment. 


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2.0 
INTRODUCTION 
2.1 
Study Rationale 
Salubris Biotherapeutics, Inc. (hereafter referred to as SalubrisBio, or “the Sponsor”) is developing a 
therapeutic protein, JK07, for the treatment of chronic heart failure (HF) with reduced ejection fraction 
(HFrEF) (New York Heart Association [NYHA] Class II-III). JK07 is a recombinant fusion protein 
consisting of a fully human monoclonal antibody that antagonizes human epidermal growth factor (EGF) 
receptor 3 (HER3) and an active polypeptide fragment of human growth factor neuregulin-1 (NRG-1). The 
EGF-like domain of NRG-1β2α is fused to the C-terminus of the antibody heavy chain via a linker in a 
homodimeric configuration (Figure 2). 
Figure 2 
Schematic Structure of JK07 
 
 
Neuregulin-1 is a member of the EGF family. All isoforms of NRG-1 share a common EGF-like domain 
essential for its biological activity (Parodi and Kuhn, 2014). Neureglin-1 is known to be the ligand for 
HER3 and HER4 (Parodi and Kuhn, 2014). Binding of NRG-1 to either HER3 or HER4 enables 
heterodimerization of the bound receptor with HER2 and subsequent tyrosine protein kinase activation, 
which transduces intracellular signaling cascades. Human HER4, but not HER3, is expressed in adult 
myocardium (Sundaresan et al., 1998; Zhao et al., 1998; Rohrback et al., 1999). Upon engagement of HER4 
receptor, NRG-1 can induce cardiomyocyte differentiation, promote cardiac function, and protect 
cardiomyocytes from apoptosis (Sundaresan et al., 1998). 
Numerous animal studies have demonstrated that NRG-1 has an ameliorative effect in HF (Odiete et al., 
2012), including ischemic HF, dilated cardiomyopathy, chemotherapy-induced HF, and viral myocarditis. 
Several clinical studies in patients with HF have also shown that both full length NRG-1 (cimaglermin) and 
a recombinant NRG-1 protein fragment containing the EGF-like domain (recombinant human NRG-1 
[Neucardin®]) can have acute and sustained positive hemodynamic effects (Lenihan et al., 2016; Gao et al., 
2010; Jabbour et al., 2011). 
Three key factors, however, limit the clinical applications and utility of recombinant human NRG-1. Firstly, 
signaling of NRG-1 through HER3 may promote cancer development and/or progression, raising serious 
concerns for any application requiring chronic administration or without grave cardiovascular (CV) risk 
factors. Secondly, HER3 is normally expressed on the gastrointestinal (GI) tract and over-activation of 
HER3 by NRG-1 may disrupt GI epithelial integrity and homeostasis, leading to severe GI toxicity and 
thus, loss of a therapeutic window for NRG-1. In fact, several clinical studies testing recombinant NRG-1 
have reported that the most commonly observed treatment-related adverse events were GI in nature 
(Lenihan et al., 2016; Gao et al., 2010; Jabbour et al., 2011). Thirdly, both clinically tested recombinant 
human NRG-1 molecules (Neucardin and cimaglermin) have shown a short half-life, indicating that 
burdensome dosing and administration schedules may be required to achieve the desired therapeutic levels 
of exposure. Hence, there exists a need to provide an NRG-1-based therapeutic that retains clinically 
significant therapeutic potential across a variety of CV indications including HF but with a lower risk of 


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oncogenesis or promotion of cancer progression, better GI tolerability, and a more favorable 
pharmacokinetic (PK) profile. To that end, SalubrisBio has developed JK07, a recombinant protein in which 
a sequence corresponding to the EGF-like domain of NRG-1 is fused to the C-terminus of the HER3- 
specific antagonistic antibody heavy chain, to limit the HER3 activation in response to NRG-1 stimulation 
without compromising the activity of NRG-1 in inducing HER4 activation, and at the same time the 
antibody backbone format confers a molecular half-life of a typical monoclonal antibody, enabling more 
convenient dosing and administration, and a potentially favorable PK profile from the standpoint of efficacy 
and safety. 
This first-in-human (FIH), randomized, double-blind, placebo-controlled, single-ascending dose study for 
JK07 is intended to support development to reduce the risk of CV death and hospitalization for HF in 
patients with chronic HF (NYHA Class II-III) and reduced ejection fraction when administered in 
conjunction with other HF therapies. The nonclinical pharmacology program for JK07 exhibits its 
pharmacodynamic (PD) actions and efficacy in vitro and in non-human primate models of HFrEF and 
HFpEF, and a rodent model of HFrEF. The safety and toxicokinetic profile of JK07 for investigation in 
human clinical trials has been further established in single-dose and repeated-dose toxicology studies 
conducted in cynomolgus macaques and Sprague-Dawley rats. 
2.2 
Background 
Heart failure is a potentially fatal disease that affects more than 6.5 million people in the United States. 
Within 5 years of diagnosis, the mortality rate of diseased individuals is 50 % (Shah et al, 2017). Due to an 
aging population, the condition has continued to increase over the past several decades, and among 
Americans aged 40 and older, there is a 20 % lifetime risk of developing the disease (Chavey et al, 2017). 
JK07 consists of a fully human monoclonal antagonistic antibody specific for HER3 and an active 
polypeptide fragment of the cardioprotective growth factor NRG-1 (Figure 2). It is designed to stimulate 
cardioprotective signaling mediated by NRG-1 through HER4 while at the same time mitigating NRG-1 
stimulation of HER3 signaling, a pathway that is thought to cause side effects and toxicity without 
contributing to the therapeutic potential. 
In vitro studies have demonstrated that JK07 induced HER2:HER4 dimerization with potency similar to NRG-1; 
whereas its ability to induce HER2:HER3 dimerization was significantly reduced in comparison to NRG-1. In 
vivo, JK07 has demonstrated pharmacodynamic activity in rodent and non-human primate (NHP) models 
of heart failure. 
Briefly, in rodents, histopathological analysis of myocardial tissues performed at 4 weeks post-treatment 
showed that JK07 partially alleviated the pathological changes in the myocardial infarction zone, including 
significant reduction of necrotic cells, narrowed interstitial spaces between myocardial cells, and recovery 
of myocardial fiber arrangement towards normal structure. JK07 significantly improved cardiac 
contractility, increased ejection fraction and +LVdp/dtmax, partially reversed left ventricular enlargement, 
reduced left ventricular preload, reduced pulmonary edema and paw edema, lowered the plasma levels of 
N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptic (BNP), and alleviated 
myocardial pathological damage. 
Compared to other animal models, NHPs have a relatively longer life span and are more susceptible to 
diseases that are the high-risk factors for heart failure, such as hypertension, abnormal lipid metabolism, 
type 2 diabetes mellitus and other metabolic diseases (Gong et al., 2013), making them more prone to the 
development of spontaneous heart failure. NHPs with spontaneous heart failure are highly similar to 
humans in terms of etiology, pathogenesis, and progression of the disease. Therefore, NHP with 
spontaneous heart failure is a uniquely clinically relevant model for studying the pathogenesis of heart 
failure in humans, as well as for the pre-clinical evaluation of drugs treating heart failure. 


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Based on the systolic/diastolic functions of the left ventricle, heart failure is categorized into two 
types: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection 
fraction (HFpEF). JK07 was examined in a study of 26 middle/old-aged rhesus monkeys with spontaneous 
chronic heart failure with either HFpEF with diastolic dysfunctional characteristics of e’<8, E/e’>8 and 
grade II diastolic dysfunction (DD2) (13 monkeys), or HFrEF with systolic dysfunctional characteristics of 
left ventricular ejection fraction (LVEF) at 30-51 % and cardiac remodeling (13 monkeys). Enrolled 
animals were assigned into 3 groups and received weekly IV injection of JK07 1 mg/kg for a total of two 
injections (5 animals each with HFrEF and HFpEF), Entresto® (sacubitril/valsartan) at the human- 
equivalent dose (HED) (6.6 mg/kg/day) for a total of 49 days (7 weeks) (5 animals each with HFrEF and 
HFpEF), and placebo IV injection of phosphate buffered saline (PBS) (3 for each with HFrEF and HFpEF) 
for a total of two injections. 
JK07 significantly improved the systolic function in rhesus monkeys with HFrEF. Specifically, 3/5 animals 
in the JK07 group showed a statistically significant increase in LVEF from their corresponding baseline at 
3 weeks post-treatment, accompanied by significant improvement in cardiac remodeling. At 7 weeks post- 
treatment (6 weeks after the last dosing of JK07) LVEF remained significantly increased over baseline in 
2/5 animals. In contrast, none of the animals in the placebo group showed significant changes in LVEF 
throughout the study. In the sacubitril/valsartan group, 1/5 animal at 3 weeks post-treatment and 3/5 animals 
at 7 weeks post-treatment demonstrated statistically significant increases in LVEF from baseline. 
JK07 resulted in significant increases in peak velocity of mitral annulus at early diastole (e’) and significant 
decreases in ratio of peak velocity of mitral blood flow at early diastole to peak velocity of mitral annulus 
at early diastole (E/e’) from baselines in 3/5 animals with HFpEF at both 3- and 7- weeks post-treatment. 
The grade of diastolic dysfunction was improved by at least one grade in these 3/5 animals receiving JK07, 
according to the clinical criteria used for the diagnosis of diastolic dysfunction. In the sacubitril/valsartan 
group, only 1/5 animal demonstrated mild improvement in diastolic function after 7 weeks of continuous 
dosing. Animals receiving placebo showed no improvement from their baselines in diastolic function 
throughout the study. 
No incidences of AEs were observed during the study, except that mild elevations of some of the liver 
function indexes were detected in animals receiving JK07. Specifically, mild elevations in alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma glutamyl transferase (GGT) 
were detected from Day 10 to Day 11 in 2/10 animals receiving JK07 (1 mg/kg). Animals were each given 
0.3 g/day of glutathione through intramuscular injection for 3 days, and most liver function indexes were 
returned to baseline on Day 15. 
Overall, JK07 not only improved LVEF and alleviated cardiac remodeling in rhesus monkeys with 
spontaneous HFrEF, but also significantly improved the diastolic function in monkeys with HFpEF. 
Moreover, these improvements in systolic/diastolic function were sustained even after the treatment had 
been stopped for 6 weeks. No severe AEs were observed during the study, except for the abnormality in 
liver function which may arise in animals receiving repeat-dose of JK07. 
JK07 has also been tested in a comprehensive toxicology program. Single dose IV studies have been 
performed in monkey with a 2-week follow-up. Weekly Good Laboratory Practice (GLP) compliant repeat- 
dose IV studies for durations of up to 2 weeks in the rat, with a 2-week recovery period, and up to 4 weeks 
in the monkey with a 4- week recovery period, have also been completed. Tissue cross-reactivity of JK07 
with human tissues in vitro has been conducted. 
From the repeat-dose GLP toxicology study in the more relevant monkey species, the no-observed adverse 
effect level (NOAEL) was defined as 3 mg/kg which is equivalent to a dose of 0.96 mg/kg in humans. The 
lowest effective dose was 1 mg/kg in the monkey PD study, in which two doses were administered, and 
this dose level is equivalent to 0.32 mg/kg in humans (FDA 2005). Overall, single IV administration of 
JK07 support the proposed IV clinical route of administration. These studies demonstrate that an IV 
infusion of JK07 at an HED of 0.32 mg/kg has potential cardiac benefit in the absence of toxicity in 


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monkeys. The FIH starting dose is 0.03 mg/kg as a single 60-minute IV administration and is 32 x lower 
than the estimated NOAEL in humans derived from a repeat-dose toxicity study in monkeys and 10 x lower 
than the effective HED derived from the PD studies in monkeys with HFrEF. 
A detailed description of the chemistry, nonclinical pharmacology, pharmacological, and safety results of 
JK07 is provided in the Investigator’s Brochure. 
2.3 
Benefit/Risk Assessment 
JK07 is a FIH study and has, therefore, not been previously evaluated in human subjects with HFrEF; 
however, clinical safety reported with recombinant human NRG-1 therapies include most commonly GI 
disorders (e.g., nausea, diarrhea, vomiting, poor appetite) and reports of headache, dizziness, and fatigue 
(Lenihan et al., 2016; Gao et al., 2010; Jabbour et al., 2011). Gastrointestinal AEs were most often observed 
at the higher doses. Serious treatment-emergent AEs (TEAEs) were uncommon with both agents. 
While these initial studies showed that recombinant human NRG-1-based therapies were generally well 
tolerated in patients, the observance of long-term cardiac effects makes clinical evaluation in healthy 
volunteers unethical. It is the sponsor’s opinion that given the potential for an extended duration of CV 
effects, the FIH study should be conducted in subjects with HFrEF (LVEF ≤40 %). 
Additionally, consistent with findings in studies conducted and published with NRG-1 in humans 
(Lenihan et al., 2016; Jabbour et al. 2011), JK07 showed sustained ameliorative effects following an acute 
dosing period in rat and rhesus monkey models of HF, further reinforcing the rationale for a FIH study in 
patients. 
JK07 has been tested in a comprehensive toxicology program. A single dose IV study has been performed 
in monkeys with a 2-week follow-up. Repeat-dose IV studies for durations of up to 2 weeks in the rat, with 
twice-weekly administrations and a 2-week recovery period, and up to 4 weeks in the monkey, with weekly 
administrations and a 4-week recovery period, have also been completed. Tissue cross-reactivity of JK07 
with human tissues in vitro has been conducted. 
In the more relevant monkey species, two toxicology studies were conducted. In a single-dose non-GLP 
toxicology study, reflective of the single-dose study design proposed for the FIH clinical study, the NOAEL 
was 30 mg/kg, or 320 x the proposed starting HED of 0.03 mg/kg. Target organ effects were observed in 
heart and/or kidney in males and female animals given ≥10 mg/kg in this study, which is 107 x higher than 
the proposed starting HED. In a repeat-dose pivotal GLP toxicology study in monkeys, the NOAEL was 
3 mg/kg, or 32 x the proposed starting HED. 
Overall, IV administration in non-clinical studies of JK07 supports the proposed IV clinical route of 
administration.  These studies demonstrate that an IV bolus infusion of JK07 at HEDs of 0.16 to 
0.32 mg/kg/dose has potential cardiac benefit in the absence of toxicity in rats and NHP, respectively. 
In the GLP-compliant 4-week repeated-dose toxicity study in cynomolgus monkeys, minimal and transient 
JK07-related prolongation in heart rate corrected QT (QTca) intervals were observed. The maximum 
increase recorded was approximately 23 msec; a QTca dose response was not evident. The minimal and 
transient QTca prolongation observed in this study did not result in any cardiac electrical instability. No 
JK07-related abnormalities in rhythm or waveform morphology were found at any dose level based on 
comparison of predose and postdose electrocardiographic recordings. There were no JK07-related changes 
in ECG parameters and all ECGs evaluated in this study were qualitatively considered normal for 
cynomolgus monkeys. Nevertheless, an inpatient stay will be required in this FIH study in order to monitor 
subjects by ECG and telemetry during the first 48 hours after IP administration, with additional follow-up 
monitoring at later time points as detailed in Table 1 (SoA). 
The Sponsor will immediately notify the Principal Investigator if any additional safety or toxicology 
information becomes available during the study. This study will be performed in compliance with the 


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protocol, International Council for Harmonisation (ICH) Good Clinical Practice (GCP), and applicable 
regulatory requirements. Aspects of the study concerned with the investigational product(s) (IPs) will meet 
the requirements of Good Manufacturing Practice (GMP). 


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3.0 
OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints are described in Table 3. 
Table 3 
Study Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• Assess the safety and tolerability 
profile, including immunogenicity, of 
JK07, administered IV according to 
protocol-defined dosing regimen. 
• Incidence and severity of TEAEs and their relationship to the IP. 
• 12-lead ECG parameters (heart rate, PR, QRS, QT, QTcF) change from baseline 
derived as mean from triplicate ECG recordings as well as QT and QTcF outlier 
analyses. 
• Change from baseline in the incidence of rhythm abnormalities (retrieved from 
telemetry readings for 48 hours postdose). 
• Laboratory parameters – change from baseline each assessment time point per 
Table 1 SoA postdose: hematology, chemistry, coagulation, and lipid panels. 
• Immunogenicity 
o 
Incidence of early and delayed-type hypersensitivity responses. 
o 
Presence of serum anti-JK07 antibodies (confirmed positive antibody 
response, titer, neutralizing antibodies). 
• Vital signs – change from baseline in vital signs and the relationship to JK07 
compared with placebo, including: 
o 
Blood pressure (BP) 
o 
Temperature 
o 
Heart rate (HR) 
o 
Respiratory rate (HR) 
Secondary 
• To determine the PK characteristics of 
JK07 administered IV according to 
protocol-defined dosing regimen. 
• PK parameters of intact JK07 including, but not limited to, maximum 
concentration (Cmax), time to Cmax (tmax), area under the concentration-time curve 
to the last quantifiable concentration and extrapolated to infinity [AUC(0-last) and 
AUC(0-inf)], half-life (t1/2), elimination rate constant (λz), systemic clearance (CL), 
and volume of distribution (Vz). Surrogate measurement of intact JK07 to be 
carried out through detection of both the JK07 antibody domain and the JK07 
NRG-1 peptide fragment in the evaluation of PK parameters. 
Exploratory 
• Explore left ventricular and systemic 
vascular resistance (SVR) performance 
indices measured by 2-dimensional 
transthoracic echocardiography 
(2D-TTE) of JK07, as change from 
baseline compared with placebo. 
• Explore potential predictive 
biomarkers of response to JK07 in this 
dosing regimen. 
• Explore relationship between JK07 
plasma concentrations, if any, and 
changes in QT intervals during dosing. 
• Microbubble contrast-enhanced (2D-TTE) results, including, but not limited 
to: LVEF, multiple 2 and 4-chamber left (LV) and right ventricular (RV) 
dimensions, including end systolic left ventricular volume (LVESV), end 
diastolic left ventricular volume (LVEDV), left atrial area and volume, valvular 
insufficiency and/or gradients, and multiple calculated monitoring parameters 
using velocity and flow measurements, including stroke volume (SV), cardiac 
output (CO), derived left ventricular filling pressure (E/e’). 
• Observed biomarker concentrations and corresponding changes from baseline. 
• Concentration-QT correlation performed on the QTcF time matched with PK. 


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4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the 
safety, tolerability, immunogenicity, and PK of JK07 in HF subjects 18 to 80 years of age with 
LVEF ≤40 %. 
To be eligible for this trial, subjects must have been maintained on an optimal HF medical regimen for at 
least 2 months prior to informed consent and remain on the same treatment regimen throughout the course 
of the study, per the 2017 American College of Cardiology/American Heart Association Task Force on 
Clinical Practice Guidelines/Heart Failure Society of America (ACC/AHA/HFSA) treatment guidelines 
(Yancy et al, 2017). 
Subjects will give informed consent prior to initiation of screening procedures. During screening, all 
subjects will undergo 2D-TTE to measure the following parameters: left ventricular chamber dimensions, 
including LVESV and left ventricular end diastolic volume (LVEDV), LVEF, and multiple calculated 
monitoring parameters using velocity and flow measurements (i.e., stroke volume [SV], cardiac output 
[CO], derived left ventricular filling pressure (E/e’) according to the American Society of 
Echocardiography guidelines (full set of measurements provided in Section 11.0, Appendix 5). Subjects 
will also undergo a physical examination, 12-lead ECG assessment, blood sampling for laboratory 
parameters, and urine testing. Safety assessments at screening will include hematology, biochemistry, 
coagulation, liver, and thyroid function. There will be additional blood sample collection prior to 
IP administration for baseline myocardial biomarkers, PK, and immunogenicity assessment (Table 1). 
A Data Review Committee (DRC) will be established to review emerging data, to monitor safety aspects 
of the study, to select the JK07 dose during dose escalation, and to adapt the randomization scheme. The 
DRC will evaluate the emerging clinical, laboratory and cardiac safety data, from the first three days 
postdose for the sentinel subject, prior to randomized blinded IP administration in the remainder of the 
cohort. 
Initially 5 dose escalation cohorts are planned with the option at the discretion of the DRC to expand the 
study to a total of 7 dose escalation cohorts. The size of the cohorts will range from 5 to 9 subjects. A 
maximum of 63 subjects will be enrolled into dose escalation cohorts. Each dose escalation cohort will 
include one single active unblinded sentinel subject receiving a single IV dose of JK07 prior to randomized 
JK07 or placebo administration in the remainder of the cohort. 
Subjects will be observed in the hospital on continuous telemetry from as soon as practicable following 
admission and prior to IP administration, and until shortly before discharge on Day 3. During this time, 
they will additionally have safety labs, vital signs, PK, and biomarker samples collected, and ECGs and 
2D-TTEs performed. Hospital evaluation is performed for safety reasons. 12-lead ECG values will be 
extracted within 10 minutes prior to the time-matched PK sample collections. Subjects will be observed for 
injection site reactions until Day 4 following IP administration, for dose-limiting adverse events (DLAEs) 
until Day 15 following IP administration, and for SAEs from the time of enrollment until 30 days after the 
IP administration. Following the Day 30, only SAEs deemed at least possibly related to the study drug or 
study procedures should be collected. 
4.2 
Scientific Rationale for Study Design 
Compared with an open-label design, double-blind trials are an especially stringent way of conducting a 
trial that attempts to eliminate subjective, unrecognized biases carried out by experimental subjects (usually 
human bias) and conductors. In most cases, double-blind studies are regarded to achieve a higher standard 
of scientific rigor than single-blind or unblinded studies. 


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Evaluating JK07 using a rigorous double-blind trial in a patient population with HF provides more reliable 
data to assess the safety and exploratory efficacy of the product in patients affected by HF. Furthermore, 
since subjects enrolled in this trial must have been maintained on an optimal HF medical regimen (Yancy 
et al, 2017) for at least 2 months prior to informed consent and remain on the same treatment regimen 
throughout the course of the study, there is no detriment to the blinding, either to placebo group or the 
active treatment group. Specifically, subjects will remain on their standard clinician-directed appropriate 
pharmacological therapy, meaning there is no added risk related to medication changes for subjects enrolled 
in the trial. Moreover, initial confinement of subjects at the clinic and overall extensive safety assessments 
will permit careful monitoring of study effects under blinded conditions, and analysis by categorical and 
continuous descriptive statistics. 
Key inclusion criteria of this proposed phase 1 study are “subjects between ≥18 and ≤80 years of age with 
stable NYHA Class II or III HF diagnosis, LVEF ≤40 %, and on stable doses of HF therapy (except for 
diuretics) as per the 2017 ACC/AHA/HFSA treatment guidelines (Yancy et al, 2017) for at least 2 months 
prior to informed consent” (Section 5.1). This population is appropriate for the primary safety evaluation 
of JK07 in this FIH study and includes patients who may benefit from this treatment. In order not to 
confound the initial safety results with tenuous subjects, subjects with NYHA Class IV will not be included. 
Analogous recombinant human NRG-1 therapies were generally well-tolerated in NYHA Class II and III 
subjects (Lenihan et al., 2016; Gao et al., 2010; Jabbour et al., 2011). The cimaglermin phase 1 study 
enrolled adult patients with NYHA Class II and III HF with reduced ejection fraction (LVEF ≤40 %) 
(Lenihan et al., 2016). Similarly, patients with NYHA Class II and III HF with LVEF <40 % were enrolled 
in both published Neucardin phase 2 studies (Gao et al., 2010; Jabbour et al., 2011). All 3 studies enrolled 
patients on stable standard therapy. 
Generation of initial phase 1 data in this moderately affected HF population will provide support for the 
evaluation of safety and efficacy in future studies that may include more severe patients, including NYHA 
Class IV HF. While the sponsor expects more severe HF patients could benefit from treatment with JK07, 
inclusion of NYHA Class II patients showing mild symptoms and impairment due to HF is important, as 
these patients may have more of an opportunity to benefit from cardiac regeneration due to JK07 treatment 
earlier during disease, to slow, stabilize, or reverse disease progression. Moreover, although the primary 
objective of the study is to assess the safety of JK07, the recruitment of HFrEF patients rather than healthy 
volunteers may increase the ability of this study to detect signals of efficacy. 
The study will also include a sentinel subject (1 active treated subject) in each dosing cohort to protect the 
population involved in the study by potentially identifying any serious AE in a single subject prior to 
exposing an entire cohort to the treatment, thereby increasing the level of safety in this JK07 phase 1 trial. 
The low(er) dose cohorts are sized at 5 subjects (1 active lead-in followed by a randomized active: placebo 
[3:1] main cohort) to effectively escalate through dose levels not anticipated to exert any effects. Dose 
escalation will not occur until at least 14 days of safety data (i.e., through Day 15) have been evaluated by 
the DRC and the dose has been established as safe and well tolerated. Following observation of a clinical 
effect, the DRC has the option to expand the size of the cohort at which the clinical effect was observed 
and subsequent cohorts to a total of 9 subjects (1 active lead-in followed by a randomized active:placebo 
[6:2] main cohort). The expanded cohort size will allow a more robust evaluation of JK07 doses with 
clinical activity. All cohorts shall proceed per the treatment algorithm, with continuous monitoring of 
emerging safety data, including clinical signs, laboratory values, and cardiac safety monitoring. Although 
it is appreciated that some adverse effects could take longer to manifest, it is believed that the time frame 
between the dosing of the sentinel subject and the subsequent cohort of approximately 5x the anticipated 
half-life (t1/2) of the JK07 is enough to minimize this risk. 
A GLP-compliant 4-week repeated-dose toxicity study in cynomolgus monkeys showed minimal and 
transient JK07-related prolongation in QTca intervals (the maximum increase recorded was approximately 
23 msec; a QTca dose response was not evident). The current phase 1 study requires subjects to be confined 
in the hospital on continuous 12-lead Holter/telemetry combination prior to dose administration and for 


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48 hours following dose administration. Baseline-corrected (clock-time matched) QT and QT interval 
corrected for heart rate using Fridericia’s correction formula (QTcF) intervals will be evaluated for potential 
effects by JK07. If effects are evident, a concentration-response relationship between time-matched JK07 
concentrations and change in QTcF interval will be explored. 
In the same study dose-independent minimal to moderate myocardial degeneration was observed during 
autopsy. The current phase 1 study requires 2D-TTE monitoring at screening, during the hospital stay and 
at multiple follow-up visits to check for improvement or worsening of indexes of myocardium contractility. 
In the same study, there were also a dose-independent minimal JK07-related increases in cardiac troponin I 
(cTnI) at 10 and 30 mg/kg on Day 8 and at 30 mg/kg on Day 28, with recovery by Day 56. Although the 
highest cTnI values occurred in a control animal at multiple time points (Animal No. 1504, Days -7 through 
28), the increased frequency of values at 10 and 30 mg/kg suggested a possible JK07-related effect. Since 
the increases in cTnI could potentially be correlated with microscopic findings of myocardial degeneration, 
this phase 1 study will monitor a wide panel of safety and efficacy biomarkers which are useful to carefully 
detect any effect of JK07 on myocardium (NT-proBNP, total BNP, high-sensitivity C-reactive protein 
[hsCRP (], troponin-I, high-sensitivity [hs]-troponin T, creatine phosphokinase [CPK], creatine kinase- 
muscle/brain [CPK-MB]). It should be noted that NRG-1 directly activates NT-proBNP expression which 
complicates the normal relationship between the levels of that biomarker and cardiomyocyte damage. 
Changes in this biomarker, therefore, need to be interpreted with caution and in the context of the totality 
of the data. 
Systemic exposure of JK07 will be measured by utilizing an immunoassay targeting two different domains 
of JK07. The capture antibody will be specific for the NRG-1 sequence of JK07, and the detection antibody 
will be specific for the antibody domain, using a biotinylated anti-idiotype antibody binding to the variable 
sequence of JK07 antibody domain. Use of the two antibodies together will provide exposure data 
specifically for the intact JK07 molecule over time across JK07 dose levels. NRG-1 peptide cleaved from 
JK07, with or without the linker, is expected to have a very short half-life in circulation and to be below 
detectable levels in circulation. 
As JK07 is a monoclonal antibody, anti-drug antibody (ADA) response for JK07 will be evaluated 
periodically throughout the study with blood samples collected as early as 3 days after dose administration. 
4.3 
Justification for Dose 
Cohort dose levels of JK07 are as follows: the clinical starting dose of a single 0.03 mg/kg IV infusion has 
been selected at 1/32 of the HED at the NOAEL in the cynomolgus monkey (3 mg/kg/week). A conservative 
approach of body surface area scaling was employed for this conversion of HED at the monkey NOAEL 
(0.97 mg/kg/week). The subsequent provisional doses have been set at a 3-fold increase from the prior dose 
for the first 2 dose escalations (Cohort 2 through Cohort 3). The subsequent dose escalations (Cohort 4 
through Cohort 5) have been set at a 2-fold increase from the prior dose; based on emerging safety and/or 
PK results of the previous cohorts; the DRC can allow a 3-fold increase. Additionally, the DRC may also 
reduce the incremental dose escalations based on the results of the previous cohorts (Table 4). 
The sponsor and the FDA agreed that, as a conservative approach, a starting dose should be chosen which 
is unlikely to exhibit any clinical effect. On a molar equivalent basis, the starting dose is equivalent to the 
cimaglermin dose of 0.015 mg/kg, which is at the low end of the three pooled dose levels which did not 
show clinical efficacy with cimaglermin (0.007 mg/kg, 0.021 mg/kg, and 0.063 mg/kg), and 100 x below 
the dose level at which a DLAE was observed for cimaglermin. 


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Table 4 
Dose Escalation Per Cohort 
 
Dose Level 
JK07 
Cohort 1 
0.03 mg/kg 
Cohort 2 
0.09 mg/kg 
Cohort 3 
0.27 mg/kg 
Cohort 4 
0.54 mg/kg 
Cohort 5 
1.08 mg/kg 
Note: Initially 5 cohorts are planned. Two additional higher cohorts may be added as per the DRC recommendation (total up to 7 cohorts). 
The highest JK07 dose administered not to exceed 2.5 mg/kg without further amending the protocol. 
 
4.4 
End of Study Definition 
A subject is considered to have completed the study if he/she has completed all phases of the study including 
the last scheduled procedure shown in Table 1 SoA. 
4.5 
Dose Escalation Criteria 
The DRC will evaluate each sentinel, as well as active and placebo subjects in each dose cohort for DLAEs. 
To support dose escalation, safety, and tolerability results for all subjects within a cohort through at least 
Day 15 will be included in this review. At the time of the DRC safety review of the entire cohort, PK results, 
if available for that cohort, will be evaluated (along with results of prior cohorts, as applicable). 
At any time during the trial, the Sponsor has the right to discontinue the trial. Any consented subject who 
is withdrawn due to an AE or screen failure prior to the IP administration will be replaced. 
If recommended by the DRC, up to 2 additional higher dose cohorts, at incremental dose levels to be 
determined by the DRC, may be enrolled to further evaluate the safety and tolerability, PK parameters, and 
exploratory PD/biomarker endpoints of JK07 at doses greater than 1.08 mg/kg without a protocol 
amendment. The highest JK07 dose administered will not exceed 2.5 mg/kg without further amending the 
protocol. After due consideration, the DRC may recommend a modification to the Table 1 SoA based on 
emerging safety or PK results. Scheduled times of assessments may be modified without an amendment if 
the length of the study duration (end-of-study visit) is not extended, and the changes do not result in more 
than 1 additional visit. Furthermore, collection of blood for 1 additional set of laboratory evaluations, 1 PK 
sample, and/or 1 biomarker sample may also be added without a protocol amendment. Should the DRC 
make recommendations for more extensive changes to the study, the Sponsor may choose to amend the 
protocol to allow for these changes. 
Also see Section 4.1, Overall Design 
Note: Should a safety concern arise other than the DLAE, the DRC might recommend that the trial stop 
after discussion with the Sponsor. The dataset may be unblinded for each cohort but no less than 30 days 
after the DRC has made the decision to proceed to the next cohort. 
4.6 
Study Stopping Criteria 
Intravenous administration for any individual subject will be stopped if the subject experiences a serious 
adverse event (SAE) or a clinically significant, drug-related AE during the infusion, which in the opinion 
of the study physician, Principal Investigator, or Sponsor’s medical representative, warrants discontinuation 
of the study for that subject’s well-being. The definitions of an AE and an SAE can be found in Section 8.3. 


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The final determination of whether any AE observed following JK07 administration is considered dose- 
limiting will be at the discretion of the DRC. Guidance provided to the DRC will be to view as a possible 
DLAE any AE at least possibly related to IP that results in any new finding of the following if observed 
within the first 15 days of treatment (DLAE assessment period): 
• 
Any febrile neutropenia [absolute neutrophil count (ANC)] <1000/mm3, temperature >38.3 °C 
(101 °F)] for >1 hour. 
• 
Any signs and/or symptoms of myocardial ischemia/myocardial infarction (diagnosis to be based 
on Thygesen et al. 2018), and any asymptomatic/symptomatic significant (> 2 mm for > 2 minutes) 
new ST segment deviation (elevation or depression), as defined in Hicks et al. 2018. 
• 
Any emergent symptomatic or asymptomatic cardiac arrhythmia requiring at least urgent medical 
intervention. 
• 
Any ≥ QTc(F) prolongation of >500 msec or >60 msec above baseline (based on an average QTcF 
value of triplicate ECGs). 
• 
Any emergent ≥ severe (corresponding to CTCAE v5 Grade 3) hematologic, non-hematologic, 
hepato-cellular, or renal toxicity except for untreated nausea, diarrhea, vomiting, constipation, 
abdominal pain. Any of these will be considered DLTs if persisting >72 hours despite appropriate 
treatment. 
• 
Any at least moderate CD4 lymphocyte count ≤400 mm3. 
• 
Any at least moderate infusion-related reaction or inability to deliver a complete dose due 
to possible treatment-related toxicity. 
• 
An AE or SAE that, in the opinion of the DRC, is of potential clinical significance such that further 
dose escalation would expose subjects to unacceptable risk. In addition, the DRC may identify as 
a DLAE, any AE that impairs daily function, or abnormality occurring in subjects treated with JK07 
at any time during the trial. 
Each DLAE must be recorded in the eCRF. 
4.6.1 
Stopping Criteria for Individual Subjects 
The infusion for any individual subject will be stopped if the subject experiences a SAE or a clinically 
significant possibly drug-related related AE during the infusion, which in the opinion of the study physician, 
Principal Investigator, or Sponsor’s medical representative, warrants discontinuation of the infusion for that 
subject’s well-being. 
4.6.2 
Criteria for Stopping Dose Escalation 
The decision to stop dose escalation will be at the discretion of the DRC and all the criteria leading to this 
decision will be documented in the meeting minutes. 
If the DRC decides not to dose escalate, the current cohort may be expanded, if not already at the maximum 
size, following which further dose escalation could proceed. If the decision is to de-escalate to the prior 
cohort, up to 8 subjects randomized (6:2, JK07:placebo), without an additional unblinded sentinel subject 
may be added to the cohort, after which, safety and tolerability will be reassessed. If the decision is to de- 
escalate to an intermediate dose between the prior cohort and the cohort at which dose escalation was halted, 
the cohort will comprise a single sentinel subject receiving JK07 followed by randomization of a minimum 
of 4 subjects (3:1, JK07:placebo) in the cohort. See Section 9.6 for details regarding the number of subjects 
to be enrolled in de-escalated or intermediate de-escalated cohorts. 


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4.6.3 
Criteria for Stopping the Study 
Criteria for stopping the study will be at the discretion of the DRC and all decisions taken will be clearly 
documented in the meeting minutes. This decision will be based on the cumulative evaluation of the study 
results and include not only DLAE but also safety concerns other than DLAEs which may arise. 


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5.0 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol 
waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. 18 to 80 years of age, with stable NYHA Class II or III HF diagnosis, evident at least 6 months 
prior to enrollment as confirmed by medical history. 
2. Stable HF defined as no hospitalizations for cardiac-related issues within the previous 2 months 
prior to the screening visit or between screening and randomization, other than for routine 
percutaneous procedures such as device, battery, generator changes or pacemaker lead 
insertion/replacement. 
3. Subjects with clearly interpretable ECHO images and with a screening LVEF ≤40 % in the 
absence of ≥Grade 3 valvular disease on 2D-TTE. 
4. Subjects must be taking clinician-directed appropriate pharmacological therapy for HF as per the 
2017 ACC/AHA/HFSA treatment guidelines (Yancy et al, 2017) and at investigator determined 
discretion at stable doses (except for diuretics) for at least 2 months prior to informed consent. 
5. Subjects without implantable cardioverter-defibrillators (ICDs) are eligible. Subjects with ICDs 
are allowed at the discretion of the investigator, but only if both of the following criteria are met: 
(a) paced beats cannot exceed 15% of beats as quantified by screening e-Patch, and (b) if a non- 
paced baseline ECG can be obtained on Day 1 prior to study drug administration. 
6. Body mass index ≥18 kg/m2 and ≤45 kg/m2 
7. Screening hemoglobin ≥9.0 g/dL, platelets ≥100x109 /mL, ANC ≥1500/mL. 
8. Sexually mature male subjects must agree to use a medically accepted method of contraception 
throughout the study and be willing and able to continue contraception until the end of the study 
(6-month time point). 
9. Females of childbearing potential must present with a negative blood pregnancy test, must not be 
lactating, and must agree to employ adequate birth control measures for the duration of the study 
and be willing and able to continue contraception until the end of the study (6-month time point). 
10. Subject is capable of giving signed informed consent as described in Section 11.0 Appendix 2, 
which includes compliance with the requirements and restrictions listed in the informed consent 
form (ICF) and in this protocol. 
11. Subject is willing and able to comply with the requirements of the protocol. 
5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. Participating in any other study and have received any other investigational drug within 30 days 
prior to screening or 5-half-lives, whichever is longer, or any other investigational implanted device 
within 30 days prior to screening, or are taking part in a nonmedication study which, in the opinion 
of the Investigator, would interfere with study compliance or outcome assessments. 
2. Any past participation in a study that has investigated the NRG-1 pathway (e.g., Neucardin, 
cimaglermin). 


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3. Heart failure due to hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic 
right ventricular dysplasia (ARVD), stress-induced ("Takotsubo") cardiomyopathy, chemotherapy- 
induced 
cardiomyopathy, 
peripartum 
cardiomyopathy, 
infiltrative 
or 
inflammatory 
cardiomyopathies, and primary valvular disease. 
4. Diagnosed with medically documented acute coronary syndrome within 3 months of screening or 
a medically documented acute myocardial infarction within 6 months of screening. 
5. Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or 
valvuloplasty within 3 months prior to screening. 
6. Any subject who has received an indication for coronary revascularization within 3 months prior 
to screening. 
7. Any major surgical procedure within 1 month prior to screening or planned surgical procedure 
during the study period. 
8. Sustained systolic BP <90 mm Hg and/or diastolic BP <50 mm Hg (confirmed by a duplicate seated 
reading) on at least 3 consecutive readings (office) following informed consent and prior to 
randomization, or overt symptomatic hypotension defined as a decrease in systolic BP of 20 mm 
Hg or a decrease in diastolic BP of 10 mm Hg within three minutes of standing when compared 
with BP from the sitting or supine position or accompanied by dizziness, syncope, blurry vision. 
9. Resting HR >100 beats per minute (bpm) at Screening (Visit 1) or prior to randomization which is 
sustained for >15 minutes in two episodes separated by one hour of observation except in sustained 
atrial fibrillation when HR of up to 110 bpm is acceptable. 
10. Cerebrovascular accident or hospitalizations for CV (cardiovascular) causes other than routine 
percutaneous procedures such as device, battery, generator changes or pacemaker lead 
insertion/replacement, including HF, chest pain, stroke, transient ischemic attack, or arrhythmias 
within 2 months prior to screening. 
11. Subjects at screening have an abnormal or clinically significant 12-lead ECG abnormality, that, in 
the opinion of the Investigator, would affect efficacy or safety evaluation or place the subject at 
risk. 
12. History or evidence of clinically significant arrhythmias uncontrolled by drug therapy or use of an 
implantable defibrillator, long QT syndrome, or evidence of QT prolongation with QTcF >450 ms 
for males or QTcF >470 ms for females during screening and/or prior to randomization. 
13. Clinically significant renal dysfunction as measured by the estimated glomerular filtration rate of 
<45 mL/min/1.73m2 as calculated by local laboratory standards (Cockcroft-Gault equation for 
estimation of creatinine clearance [CrCl] [Cockcroft and Gault. 1976]) at screening, or a clinically 
significant change in renal function between screening and baseline. 
14. Clinically significant liver dysfunction as measured by: ALT >2.0 × the upper limit of normal 
(ULN), alkaline phosphatase > 2.0 × ULN, AST >2.0 × ULN, or GGT >2.0 × ULN or serum 
bilirubin ≥ 1.2 × ULN at screening, or a clinically significant change in liver function between 
screening and baseline. 
15. Subjects with alteration of the coagulation panel (international normalized ratio [INR]) and/or 
prothrombin time (PT) ≥1.5 × the ULN; activated partial thromboplastin time (aPTT) ≥1.5 × ULN, 
or serum albumin ≤3 gm/dL. For subjects on warfarin or other anticoagulants, an INR (or PT) 
considered by the Principal Investigator as therapeutically appropriate will be allowed. 
16. Subjects with values of total CPK and/or CK-MB >2.5x ULN per institutional standards at 
screening. 


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17. Any subject who by Investigator’s judgement, has a significant hematuria or proteinuria at 
screening. 
18. Concurrent treatment with Class Ia or III antiarrhythmic drugs (the medication must have been 
discontinued more than 2 months before informed consent). 
19. Positive screening for human immunodeficiency virus antibodies, hepatitis B surface antigen, or 
hepatitis C virus antibodies. 
20. Known history of or active alcohol abuse (no more than 14 units/week for males or 7 units/week 
for females) or use of illicit drugs within 1 year prior to randomization (excluding recreational use 
of marijuana or cannabidiol [CBD]-based products). 
21. Other medical or psychiatric condition that, in the opinion of the Investigator, would preclude 
obtaining voluntary consent/assent or would confound the secondary objectives of study. 
22. A history of pathologically confirmed malignancy of any type or any pathologically confirmed pre- 
malignant condition (e.g., ductal carcinoma in situ, colonic polyp with premalignant diagnosis, or 
cervical atypia). All subjects are to undergo cancer screening following study enrollment in 
accordance with American Cancer Society Guidelines (See Section 11.0 Appendix 1). 
23. Pregnant or lactating at screening. 
24. Subjects with clinically significant or poorly controlled disease including, but not limited to, 
endocrine (including diabetes and thyroid) disease, neurological or psychiatric (even mild), GI, 
hematological, urological, immunological, or ophthalmic diseases as determined by the 
Investigator. 
25. Subjects who are not non-smokers or light smokers (no more than 5 cigarettes per day) and who 
cannot abstain from smoking from 2 weeks prior to the administration of IP through the end of the 
study. 
5.3 
Lifestyle Considerations 
5.3.1 
Meals and Dietary Restrictions 
Subjects are required to fast for at least 10 hours prior to each visit, including the Day 1 hospital admission. 
On Day 1, pre-dose assessments will be performed after a minimum 10 hour fast. A light breakfast/snack 
will be provided after completion of all scheduled pre-dose assessments. Subjects will receive a typical 
institutional lunch and dinner for a HF patient. A snack may be allowed in the evening of Day 1. The snack 
must be consumed to allow for a minimum 10-hour fast so that the 24-hour Day 2 procedures are clock- 
time matched to the extent possible to predose of Day 1 (See Table 2). Subjects should receive the same 
lunch, the same dinner, and the same evening snack, at as close to the same times as possible, on Day 2. 
Subjects must again be fasted for at least 10 hours prior to the 48-hour Day 3 study procedures. 
5.3.2 
Caffeine, Alcohol, and Tobacco 
Subjects with a known history of alcohol abuse will be excluded from this study. From Day 1 until 
completion of the 12-lead ECG and related study procedures on Day 3, subjects will abstain from ingesting 
caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate). Subject will have 
to abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and 
chocolate) starting 24 hours before any subsequent visit. 
From Day -3 until completion of the 12-lead ECG and related study procedures on Day 3 subjects will 
abstain from alcohol intake and will have to abstain from alcohol intake starting 24 hours before all 
subsequent visits. 


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Subjects who use tobacco or e-cigarette products, or CBD products, will be instructed that use of 
nicotine-containing products (including nicotine patches) or CBD products will not be permitted from two 
weeks prior to IP administration until after the final follow-up visit. 
5.3.3 
Activity 
Subjects will remain in the hospital for Day 1 and the initial 48 hours of the postdose period for safety 
evaluations: vital sign assessments, physical exams, blood, and urine collections for PK (blood only), 
biomarkers, and safety laboratory assessments, and telemetry/ECG evaluation. During the full course of the 
study any contact or vigorous competitive sporting activity must be avoided. 
5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently assigned to study treatment. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting Trials 
publishing requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may not be rescreened 
without consent of medical monitor. 


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6.0 
STUDY TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or medical 
device(s) intended to be administered to a subject according to the study protocol (Table 5). 
This is a double-blind study. The investigational treatment and placebo infusions will be identical in 
physical appearance. Other than in the case of sentinel subjects, the treatment each subject will receive 
will not be disclosed to the Investigator, study center staff, subject, Sponsor, study vendors, or DRC. The 
treatment codes will be held by a third-party clinical research services vendor designated by the Sponsor. 
Where possible, and as applicable, hospital admission and IP administration should take place on Monday 
or Tuesday to allow for Day 7 follow-up visits to take place on the following Monday. 
6.1 
Study Treatment(s) Administered 
Table 5 
Study Treatment Details 
 
Study Treatmenta Name: 
JK07 (recombinant fusion protein 
consisting of a fully human 
immunoglobulin G1 monoclonal 
antibody and an active polypeptide 
fragment of the human growth factor 
NRG-1) 
JK07 matching placebo 
Dosage Formulation: 
Sterile solution 
Sterile solution 
Unit Dose Strength(s)/Dosage 
Level(s): 
20 mg/mL JK07 in 2 mL of formulation 
buffer containing 25 mM 
histidine/histidine-HCl, 205 mM sucrose, 
0.04 % (w/v) polysorbate 80, pH 6.0. 
Formulation buffer 
(25 mM histidine/histidine-HCl, 
205 mM sucrose, 0.04 % 
polysorbate-80, pH 6.0). 
Route of Administration: 
Intravenous (IV) infusion over 
60 minutes using a syringe pump or 
infusion pump 
IV infusion over 60 minutes using a 
syringe pump or infusion pump 
Dosing Instructions: 
Single dose per protocol treatment 
regimen 
Single dose per protocol treatment 
regimen 
Packaging and Labeling: 
Study treatment will be provided in a 
single-use vial or vials. Each vial will be 
labeled as required per country 
requirement. JK07 will be provided with 
the appropriate infusion kits as part of the 
Clinical Trial Supplies. 
JK07-matching placebo will be 
provided in the appropriate infusion 
kits as part of the Clinical Trial 
Supplies. 
Manufacturer: 
Emergent Camden 
Emergent Camden 
Prepared Solution Expiration: 
JK07 infusions will be prepared at the 
study center for administration within 4 
hours following the dose preparation. 
Placebo infusions will be prepared at 
the study center for administration 
within 4 hours after dose preparation. 
a With the exception of IP infusion administered to the sentinel subject in each cohort, all study staff will be blinded to IP 
identification 
The infusion will be managed through a syringe pump or infusion pump. A needle or catheter between 16G 
and 21G is required by this protocol (choice as per Site procedures); needles narrower than 21G are NOT 
allowed. The total infusion time, inclusive of saline flush should be 60 minutes and should not exceed 75 
minutes, and reasons to exceed this time must be reported. The infusion time should not be less than 
60 minutes under any circumstance. The date/time of start and time of stop of the infusion, infusion rate, 
volume infused, any interruption, and stop/restart will be documented in the eCRF. 


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A detailed description of the shipment, storage, and preparation of IP is provided in the Pharmacy Manual. 
In the event of a presumed acute infusion reaction, institutional standard of care treatment should be 
undertaken. If the infusion must be stopped in the opinion of the investigator due to an AE, the infusion 
may NOT be restarted (Section 4.6.1). The AE must be documented in the eCRF. 
6.2 
Preparation/Handling/Storage/Accountability 
1. All investigational drug supplies in the study will be stored at 2-8 °C in a secure place under the 
responsibility of the Investigator or other authorized individual. 
2. The Investigator or designee must confirm appropriate temperature conditions have been maintained 
during transit for all study treatment received and any discrepancies are reported and resolved before 
use of the study treatment. 
3. Only subjects enrolled in the study may receive study treatment and only authorized study center staff 
may supply or administer study treatment. Designated pharmacy staff will prepare the study drug. 
All study treatments must be stored in a secure, environmentally controlled, and monitored (manual 
or automated) area in accordance with the labeled storage conditions with access limited to the 
Investigator and authorized study center staff. Preparation of study drug will be documented in 
accordance with local site standard of practice. 
4. The Investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study treatment accountability, reconciliation, and record maintenance (i.e., receipt, 
reconciliation, and final disposition records). All records must be available for inspection. 
5. Further guidance and information for the final disposition of unused study treatment are provided in 
the Pharmacy Manual and Clinical Monitoring Plan. 
6.3 
Randomization and Blinding 
All subjects other than sentinel subjects will be centrally assigned to randomized study treatment using an 
Interactive Voice/Web Response System (IVRS/IWRS). Before the study is initiated, the telephone 
number and call-in directions for the IVRS and/or the log in information & directions for the IWRS will 
be provided to each study center. 
Subjects will be randomized to study treatment via stratified randomization. Separate randomization 
schedules will be used within each cohort (randomly permuted blocks within strata). 
 
Blind Break (IVRS/IWRS) 
The IVRS/IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the Investigator has the sole responsibility for determining if unblinding of a 
subject’s treatment assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the Investigator decides that unblinding is 
warranted, the Investigator should make every effort to contact the Trial Management 
Associate and Sponsor prior to unblinding a subject’s treatment assignment unless this could 
delay emergency treatment of the subject. Under no circumstances should there be any delay in 
emergency treatment of a subject. If a subject’s treatment assignment is unblinded, the Sponsor 
must be notified within 24 hours after breaking the blind. The date and reason that the blind 
was broken must be recorded in the source documentation and case report form (eCRF), as 
applicable. 
Blinded FIH which may 
require unblinding 
subject/cohort 
After each dose group, the DRC will determine the dosing regimen(s) for the next cohort. This 
decision will generally be made without breaking the randomization code. If judged necessary 
by the DRC, an individual or the complete cohort may be unblinded during evaluation of the 
study data. Before unblinding, a decision should be made about the action to be taken based on 
the revealed treatment allocation. The rationale for unblinding, etc., will be documented in 
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Sentinel Subject 
Each cohort at a new dose level higher than those previously tested shall have a single 
unblinded sentinel subject who will receive active treatment. 
Unblinding by cohort 
Thirty days following the decision by the DRC to dose escalate to a new dose level, unblinding 
of the previous cohort is permitted. 
6.4 
Study Treatment Compliance 
The prescribed dosage, timing, and mode of administration may not be changed. Any departures from the 
intended regimen must be recorded in the eCRFs. All dose administrations will be performed in the study 
center, in resting conditions under the supervision of appropriately trained staff. 
6.5 
Concomitant Therapy 
Any medication or vaccine (including over the counter or prescription medicines, vitamins, and/or [herbal] 
supplements) that the subject is receiving at the time of informed consent (within 30 days before informed 
consent) or receives during the study must be recorded in the eCRF along with: 
• 
Reason for use. 
• 
Dates of administration including start and end dates. 
• 
Dosage information including dose and frequency. 
All medications and concomitant treatment administered from screening through the final study visit (Early 
Termination or End of Treatment) will be recorded. Documentation will include the name of treatment, 
indication, dose (including units), and date(s) of administration. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or prior therapy. 
A list of excluded medications/therapy is provided in Section 11.0, Appendix 4. Initiation of any new 
medications after enrollment must be discussed with the CRO and Sponsor Medical Monitor prior to 
initiation. 
Other than in the event of an infusion reaction, acetaminophen use is prohibited for the period beginning 
7 days pre-dose and ending 15 days postdose, and outside of this time should be used only occasionally and 
at doses approved for the age of the subject. Occasional use of ibuprofen or naproxen sodium for pain relief, 
at doses approved for the age of the subject, is permitted. Other concomitant medication may be considered 
on a case-by-case basis by the Investigator in consultation with the Medical Monitor, if required. 
6.5.1 
Rescue Medicine 
Not applicable. 
6.6 
Dose Modification 
As this is a single-dose study, dose modification within an individual subject is not applicable. Dose 
escalation and de-escalation criteria within a cohort may be found in Section 4.5. 
6.7 
Treatment after the End of the Study 
The Sponsor will not provide any additional care to subjects after they leave the study because such care 
should not differ from what is normally expected for subjects with HFrEF, so these subjects will continue 
with the optimal therapy for HFrEF as established by the 2017 ACC/AHA/HFSA treatment guidelines 
(Yancy et al, 2017). 


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7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Treatment 
Subjects are free to withdraw consent and discontinue participation in the study at any time, without 
prejudice. A subject’s participation in the study may be discontinued at any time at the discretion of the 
Investigator, as further described in the protocol. 
The process for dose escalation and the stopping criteria for the study are described in Section 4.0. 
If a subject, who does not meet enrollment criteria, is inadvertently enrolled, and the failure to meet 
enrollment criteria is discovered prior to IP administration, the subject should be discontinued from the 
study and Sponsor or Sponsor designee must be contacted. If a subject, who does not meet enrollment 
criteria, is inadvertently enrolled in the study, and has already received IP administration, the subject should 
be allowed to continue with the study given that following the single IP administration there are no 
additional treatments or invasive tests other than standard blood draws. 
Any consented subject who is withdrawn prior to the IP administration will be replaced. 
7.2 
Subject Discontinuation/Withdrawal from the Study 
A subject may withdraw from the study at any time at his/her own request or may be withdrawn at any time 
at the discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. 
The following actions must be taken if a subject discontinues or withdraws from the study: 
• 
If the subject withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
• 
If a subject withdraws from the study, he/she may request destruction of any samples taken and not 
tested, and the Investigator must document this in the study center study records. 
• 
See Table 1 SoA, End of Study visit (Day 180) for data to be collected at the time of study 
discontinuation. Should a subject request or decide to withdraw from the study prior to the End of 
Study visit, all efforts must be made to complete and report the observations as thoroughly as 
possible up to the date of withdrawal. Subjects withdrawing due to an AE at any time should be 
followed up until resolution, stabilization, the event is otherwise explained, the subject is lost to 
follow-up (Section 8.3.8) or until the end of their participation in the study. Subjects should be 
encouraged to complete the End of Study visit activities. 
• 
Subjects who voluntarily withdraw will be termed dropouts. Dropouts and subjects withdrawn due 
to protocol violations may be replaced following discussion with the Principal Investigator and 
Sponsor. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits and 
is unable to be contacted by the study center. 
The following actions must be taken if a subject fails to return to the study center for a required study visit: 
• 
The study center must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether the subject wishes to and/or should continue in the study. 


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• 
Before a subject is deemed lost to follow-up, the Investigator or designee must make every effort 
to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a certified 
letter to the subject’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the subject’s medical record. 
• 
Should the subject continue to be unreachable, he/she will be considered to have withdrawn from 
the study. 
Discontinuation of specific study centers or of the study are handled as part of Section 11.0 Appendix 2. 


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8.0 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Table 1, Table 2, and Appendix 3, Table 13 and 
Table 14. 
• 
Protocol waivers or exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the Sponsor as soon as practicable upon 
occurrence or awareness to determine if the subject should continue or discontinue study treatment. 
• 
Adherence to the study design requirements, including those specified in the Table 1 SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential subjects meet 
all eligibility criteria. The Investigator will maintain a screening log to record details of all subjects 
screened and to confirm eligibility or record reasons for screening failure, as applicable. 
• 
Procedures conducted as part of the subject’s routine clinical management (e.g., blood count) and 
obtained before signing of the ICF may be utilized for screening or baseline purposes provided the 
procedures met the protocol-specified criteria and were performed within the time frame defined 
in the Table 1 SoA. 
• 
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, is expected not to exceed 420 mL. The 
planned blood collections over the first month of the study are not expected to exceed 270 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
• 
Demographic information, including date of birth, gender, ethnicity, race, height, and weight, will 
be recorded at the Screening Visit. 
8.1 
Efficacy Assessments 
Not applicable. 
8.2 
Safety Assessments 
Planned time points for all safety assessments are provided in Table 1, and Table 2, and Appendix 3, Table 
13 and Table 14. 
Subjects will be observed for injection site reactions until Day 4 following IP administration, for DLAEs 
until Day 15 following IP administration, and for AEs and SAEs from the time of informed consent until 
30 days after the IP administration. Following Day 30, only SAEs deemed at least possibly related to the 
study drug or study procedures will be collected until the End of Study visit (Day 180). 
The safety of JK07 in patients with heart failure with reduced ejection fraction will be evaluated based on 
criteria described by the CTCAE Version 5.0. 
The investigator will monitor the occurrence of all AEs during the first 30 days after administration of the 
study drug. All AEs must be recorded in the source documents and on the appropriate page(s) of the case 
report form. All SAEs including any deaths, which occur up to and including 30 days after administration 
of the study drug, must be reported to the Medical Monitor within one working day, whether or not 
considered causally related to the study drug. Following the first 30 days, only SAEs deemed at least 
possibly related to the study drug or study procedures should be collected and reported as such. All AEs 
and SAEs will be followed until resolution, stabilization, until the event is otherwise explained, until the 
end of their participation in the study, or until the subject is lost to follow-up. 


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8.2.1 
Physical Examinations 
A complete physical examination will be performed at screening and include, at a minimum, assessments 
of the CV, respiratory, GI, and neurological systems. Height (i.e., at screening only) and weight will also 
be measured and recorded. 
A brief physical examination will be conducted at all other visits and include, at a minimum, assessments 
of the skin, lungs, CV system, and abdomen (liver and spleen). 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.2.2 
Injection Site Assessment 
The site of infusion of the study drug will be assessed for local reactions at the times shown in the SoA 
(Table 1). Any findings (or lack thereof) will be documented in the subject’s eCRF. During Day 1 (1 early 
assessment and 1 late assessment/end of the day), the Investigator may choose to evaluate the infusion site 
as deemed appropriate. 
Infusion site evaluations will be made by clinical staff as described below; if an injection site reaction 
greater than that typically expected for the insertion of an IV line is observed, a physician will characterize 
and document the reaction as an AE. The infusion site will continue to be reviewed at the time points 
indicated in the SoA (Table 1), or until the AE is resolved. 
Infusion sites will be monitored for pain, tenderness, erythema and swelling. Each infusion site reaction 
will be categorized using the intensity grading scheme presented in Table 6; the intensity of each resulting 
AE will be categorized as described in (e.g., at least moderate intensity injection site reaction may be 
recorded as a mild AE if considered appropriate according to the Investigator’s judgement). 
Table 6 
Injection Site Reaction Grading Scheme 
 
Intensity Grading 
Reaction 
Absent 
(0) 
Mild a 
(1) 
Moderate a 
(2) 
Severe a 
(3) 
Potentially Life- 
threatening 
(4) 
Pain 
Absent 
Does not 
interfere with 
activity 
Repeated use of 
non-narcotic 
pain reliever or 
prevents daily 
activity 
Any use of 
narcotic pain 
reliver or 
prevents daily 
activity 
Hospital visit (A 
and E) or 
hospitalization 
Tenderness 
Absent 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at 
rest 
A and E visit or 
hospitalization 
Erythema/redness 
Absent 
2.5 to 5.0 cm 
5.1 to 10.0 cm 
>10.0 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/swelling 
Absent 
2.5 to 5.0 cm 
and does not 
interfere with 
activity 
5.1 to 10.0 cm or 
interferes with 
activity 
>10.0 cm or 
prevents daily 
activity 
Necrosis 
Otherb 
Absent 
Present 
Abbreviation: A and E; adverse event. 
a Measurements refer to the reaction at the greatest single diameter. 
b Any other reactions such as bruising, itching, or ulceration will be recorded as absent or graded as to severity. 


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8.2.3 
Pregnancy Test 
Subjects of childbearing potential will have a blood-based β-hCG pregnancy test performed at screening, a 
hospital-based qualitative immuno-assay for hCG in urine performed on Day 1 and confirmed negative 
prior to IP administration, and urine pregnancy tests performed at Days 30, 60, 90, 135, and 180. The 
screening and Day 1 results must be available and must be negative before the subject is administered the 
dose of the IP. A positive pregnancy test at screening or on Day 1 will disqualify the subject from the 
participation in the study. 
8.2.4 
Medical History 
A complete evaluation of past medical history will be performed at screening and will include details of 
subjects with a stable NYHA Class II or III HF diagnosis at least 6 months prior to screening and at the 
time of enrolment. 
8.2.5 
Electrocardiograms 
During Screening and beginning no more than 45 days before Day 1, all subjects will be supplied with, 
and instructed how to use a e-Patch for continuous 14-day heart rhythm monitoring as outlined in the 
Table 1 SoA. A 14-continuous day heart rhythm monitoring assessment will be collected using the e- 
Patch with monitoring completed no later than Day -10 unless confirmed with the sponsor. 
Triplicate 12-lead ECGs will be performed prior to PK sample collection as outlined in Table 1 and Table 
2. Local site will calculate heart rate and measure HR, PR, QRS, QT, and QTcF intervals for the first 48 
hours. Where applicable, the screening ECG and Day 1 baseline ECG must be obtained without evidence 
of pacing. 
All required ECG leads will be secured to the patient and attached to an ECG machine prior to 
administration of the IP to facilitate immediate post-infusion recording. 
Subject should be supine for ≥5 minutes prior to each ECG performed. 
At each time point at which triplicate ECGs are required, 3 individual ECG tracings should be performed 
as closely as possible in succession but no more than 2 minutes apart. The full set of triplicates should be 
completed in <5 minutes with no more than 2 min between them. 
All ECGs must be collected prior to simultaneously scheduled blood sample collections (PK, biomarker, 
and/or laboratory assessments). 
In the first 48-hours hours post-infusion, ECGs and PK samples must be performed in close proximity 
(within 10 minutes up to 4 hours postdose and after the 24- and 48-hour ECGs clock-time matched to the 
baseline ECG; within 30 minutes prior at other times greater than 4 hours postdose). 
For safety reasons triplicate 12-lead ECGs will be printed and evaluated onsite. 
8.2.6 
Vital Signs 
• 
Temperature, RR, HR, and BP measurements will be assessed. 
• 
BP and HR measurements will be assessed in resting position, with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
• 
BP should be measured using the arm not used for the IP administration. 
• 
BP and HR measurements should be preceded by at least 5 minutes of resting position for the 
subject in a quiet setting without distractions (e.g., television, cell phones). 


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• 
Vital signs (to be taken before blood collection for laboratory tests) will consist of 3 BP 
measurements (3 consecutive BP readings will be recorded at intervals of at least 1 minute). The 
average of the 3 BP readings will be recorded in the eCRF. 
• 
Vital signs will be collected at the same timepoint as scheduled ECG collections and prior to 
collection of blood for PK, biomarker and/or safety laboratory assessments. 
8.2.7 
Clinical Safety Laboratory Assessments 
• 
See Appendix 3 Table 13 for the list of clinical laboratory tests to be performed and to the Table 1 
SoA for the timing and frequency. See Appendix 3 Table 13 and Table 14, respectively for local 
and central laboratory assessments. 
• 
The Investigator must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports 
must be filed with the source documents. Clinically significant abnormal laboratory findings are 
those that are not related to HFrEF or any other pre-existing condition at the time of enrollment, 
unless judged by the Investigator to be more severe than expected for the subject’s condition. 
• 
All laboratory tests with values considered clinically significantly abnormal, relative to baseline 
values, within 30 days after the dose of study treatment should be repeated until the values return 
to normal or baseline or are no longer considered clinically significant by the Investigator or 
Medical Monitor. 
− 
If such values do not return to normal/baseline within a period judged reasonable by the 
Investigator, the etiology should be identified, and the Sponsor notified. 
− 
All protocol-required laboratory assessments, as defined in Appendix 3, must be conducted 
in accordance with the laboratory manual and the Table 1 SoA. 
− 
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the Investigator (e.g., SAE or AE or dose modification), then the 
results must be recorded in the eCRF. 
8.2.8 
Immunogenicity Assessments 
Antibodies to JK07 will be evaluated in serum samples collected from all subjects according to the Table 1 
SoA. Additionally, serum samples should also be collected at the final visit from subjects who discontinued 
study treatment or were withdrawn from the study. These samples will be tested by the Sponsor or Sponsor's 
designee. 
Serum samples will be screened for antibodies binding to JK07. Samples which show a positive response 
in the screening assay will be evaluated using a confirmatory ADA assay, and the confirmed positive 
samples will be reported and their potential for neutralizing activity will be explored. Other analyses will 
be performed to verify the stability of JK07 and to further characterize the immunogenicity of JK07. 
The detection and characterization of antibodies to JK07 will be performed using a validated assay method 
by or under the supervision of the Sponsor. Antibodies may be further characterized and/or evaluated for 
their ability to neutralize the activity of the study treatment(s). Samples may be stored for a maximum of 
10 years (or according to local regulations) following the last subject’s last visit for the study at a facility 
selected by the Sponsor to enable further analysis of immune responses to JK07. 


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8.2.9 
Two-dimensional Transthoracic Echocardiography 
Left ventricular and hemodynamic performance indices measured by 2D-TTE will be explored. Potential 
effects of JK07 will be evaluated as change from baseline and will be compared with changes from baseline 
in subjects receiving placebo. 
On Day 1, 2D-TTE will be performed locally following American Society of Echocardiography guidelines 
and recommendations, pre-dose and at 6 hours ± 30 minutes, and on Day 2 at 30 hours ± 30 minutes 
following completion of the dosing infusion, and at subsequent times described in the Table 1 SoA. 
The full examination will be evaluated locally for safety and will be digitally transferred to the Central 
Laboratory for centralized evaluation and centralized calculation of the measurements. Measurements taken 
by the Central Laboratory will include but are not limited to: ejection fraction, multiple LV chamber 
dimensions, including LVESV, LVEDV, as well as multiple calculated monitoring parameters using 
velocity and flow measurements including SV, CO, and E/e’ calculations (Please see Appendix 5 for 
detailed listing). 
8.3 
Safety Monitoring and Reporting 
8.3.1 
Adverse Events 
In accordance with the ICH E2A guideline, and 21 Code of Federal Regulations (CFR) §312.32, an AE is 
defined as any untoward medical occurrence in a clinical study subject administered a pharmaceutical 
product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new 
or exacerbated) temporally associated with the use of study treatment. 
This includes the following: 
• 
Any abnormal laboratory test results relative to baseline values (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical and 
scientific judgment of the Investigator (i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
8.3.2 
Serious Adverse Events 
An SAE is defined as an event that, at any dose, meets any of the criteria in Table 7. 


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Table 7 
Definitions of Serious Adverse Events 
 
Criteria 
Description 
Fatal: 
The AE resulted in death 
Life-threatening: 
The AE placed the subject at immediate risk of death. (This classification does not apply 
to an AE that hypothetically might have caused death if it had been more severe) 
Hospitalization/prolongation of 
hospitalization: 
The AE resulted in hospitalization or prolongation of hospitalization 
Disability/incapacity: 
The AE resulted in a disability, significant incapacity, or substantial disruption of the 
subjects’ ability to conduct normal life functions 
Congenital anomaly/birth defect: 
The AE was an adverse outcome in a child or fetus of a subject exposed to the study 
treatment regimen before conception or during pregnancy 
Medically important 
The AE was a medically important event that did not meet any of the above criteria, but 
may have jeopardized the subject and may have required medical or surgical intervention 
to prevent one of the outcomes listed above (examples include allergic bronchospasm that 
required treatment in an emergency room, seizures that do not result in hospitalization, or 
blood dyscrasias) 
This SAE classification does not apply for the following hospitalizations: 
• 
Admissions for social or situational reasons (e.g., no place to stay, live too far away to come for 
hospital visits) in the absence of any clinical AE 
• 
Admissions at the discretion of the Investigator 
• 
Admissions for elective or pre-planned treatment or procedure for a pre-existing condition that is 
unrelated to the condition under study and has not worsened since providing informed consent 
• 
Admissions for routine treatment (e.g., platelet transfusion, IV diuresis) or monitoring of the 
condition under study not associated with any deterioration in condition 
• 
Admissions for routine procedures (e.g., bone marrow aspiration, thoracentesis) associated with the 
disease under study 
• 
Emergency outpatient treatment or observation that does not result in admission, unless fulfilling 
other seriousness criteria above 
Note: Complications and/or prolonged admissions for routine treatment or procedure do require SAE 
reporting. 
8.3.3 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs, including SAEs will be collected from the time of enrollment and until 30 days after the IP 
administration. Following the first 30 days, only SAEs deemed at least possibly related to the study drug or 
study procedures should be collected. 
Medical occurrences that begin before the start of study treatment but after obtaining informed consent will 
be recorded on the Medical History/Current Medical Conditions section of the eCRF, not the AE section. 
Investigators are not obligated to actively seek AEs or SAEs for subjects after their study participation ends. 
However, if the Investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event to be reasonably related to the study treatment or 
study participation, the Investigator must promptly notify the Sponsor. 
All SAEs will be recorded on an SAE report form and reported to the Sponsor designee within 24 hours of 
the investigator’s awareness of the event. The Investigator will submit any updated SAE data to the Sponsor 


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designee within 24 hours of the investigator’s awareness of any follow-up information associated with the 
event. 
SAE reports will be submitted to IQVIA Biotech Safety Management Department via one of the following 
methods: 
Safety email in-box: Safety-Inbox.Biotech@IQVIA.com 
Safety Fax: +1 919.313.1412 (US Toll-free: 1-866-761-1274) 
For initial SAE reports, the following minimum criteria must be reported on the SAE form: 
• 
Subject Number 
• 
Date of event onset 
• 
Description of event 
• 
Study treatment 
• 
Relationship to study treatment 
8.3.4 
Method of Detecting AEs and SAEs 
Adverse events will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or the 
patient's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording events that 
meet the definition of an AE or SAE and remain responsible for following up AEs that are serious, 
considered related to JK07 or study procedures, or that caused the patient to discontinue JK07 or the study 
(see Section 7.0). 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and nonleading 
verbal questioning of the subject is the preferred method to inquire about AE occurrences. 
8.3.5 
Grading and Intensity of Adverse Events 
Adverse events will be graded using CTCAE v5 as shown in Table 8. The reported verbatim term should 
be the most descriptive medical diagnosis and does not have to be found in CTCAE v5. Regardless of 
severity, some events may also meet regulatory serious criteria (See Section 8.3.2). 
The terms “severe” and “serious” are not synonymous. Note the distinction between the severity and the 
seriousness of an AE. Severity refers to the intensity of an AE. A severe event is not necessarily an SAE. 
For example, headache may be severe (interferes significantly with the patient’s usual function) but would 
not be classified as serious unless it met one of the criteria for SAEs listed in Section 8.3.2. “Serious” is a 
regulatory definition and is based on subject or event outcome or action criteria usually associated with 
events that pose a threat to a subject’s life or vital functions. Seriousness (not severity) serves as the guide 
for defining regulatory reporting obligations. Severity and seriousness should be independently assessed 
when recording AEs and SAEs on the eCRF. 


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Table 8 
Adverse Event Grade (Severity) Scale 
 
Grade 
Severity 
Alternate Description a 
1 
Mild (apply event-specific NCI 
CTCAE v5 grading criteria) 
Transient or mild discomfort (<48 hours); no interference with the subject’s 
daily activities; no medical intervention/therapy required 
2 
Moderate (apply event-specific NCI 
CTCAE v5 grading criteria) 
Mild to moderate interference with the subject’s daily activities; no or minimal 
medical intervention/therapy required 
3 
Severe (apply event-specific NCI 
CTCAE v5 grading criteria) 
Considerable interference with the subject’s daily activities; medical 
intervention/therapy required; hospitalization possible 
4 
Very severe, life threatening, 
or disabling (apply event-specific NCI 
CTCAE v5 grading criteria) 
Extreme limitation in activity; significant medical intervention/therapy required, 
hospitalization probable 
5 
Death related to adverse event 
Source: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 
a. Use the alternative descriptions for Grade 1, 2, 3, and 4 events when the observed or reported AE does not appear in the NCI 
CTCAE v5 listing. 
8.3.6 
Relationship to Study Drug 
The investigators should use their knowledge of the subject, the circumstances surrounding the event, and 
an evaluation of any potential alternative causes to determine whether or not an AE is considered to be 
related to the study drug. Some considerations are presented in Table 9. 


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Table 9 
Relatedness of Adverse Events to Investigational Product 
 
NOT RELATED: 
This category is applicable to those AEs that are clearly due to extraneous causes (concurrent drugs, 
environment, etc.) and/or the clinically plausible temporal sequence is inconsistent with the onset of the 
event and the administration of the study drug and do not meet the criteria for drug relationship listed under 
UNLIKELY, POSSIBLY, or DEFINITELY RELATED. 
UNLIKELY 
RELATED: 
This category is applicable to those AEs that could easily be explained by the patient’s clinical status or 
other factors and/or there is a poor temporal relationship with the administration of the study drug. 
POSSIBLY 
RELATED: 
This category applies to those AEs that, are judged to be perhaps related to the study drug administration. 
An AE may be considered POSSIBLY RELATED when it meets at least one of the following criteria: 
1. 
It follows a reasonable temporal sequence from administration of the study drug. 
2. 
It could not readily have been produced by the patient’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the patient. 
3. 
It follows a known or expected response pattern to the study drug. 
DEFINITELY 
RELATED: 
This category applies to those AEs that are incontrovertibly related to study drug administration. An AE 
may be assigned to this category if it meets at least the first three of the following criteria: 
1. 
It follows a reasonable temporal sequence from administration of the study drug. 
2. 
It could not be reasonably explained by the known characteristics of the patient’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the patient. 
3. 
It disappears or decreases on cessation or reduction in study drug dose. There are exceptions when 
an AE does not disappear upon discontinuation of the drug, yet drug relatedness clearly exists 
(e.g., depression, fixed drug eruptions, tardive dyskinesia, etc.). 
4. 
It follows a known or expected response pattern to the study drug. 
5. 
It reappears or worsens when the study drug is re-administered. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study treatment administration will be considered 
and investigated. 
• 
The Investigator will also consult the IB in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that the 
Investigator always assess causality for every event before the initial transmission of the SAE data 
to the Sponsor. 
• 
The Investigator may change his/her opinion of causality considering follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
8.3.7 
Recording AEs and SAEs 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (e.g., 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The Investigator will then record all relevant AE/SAE information in the eCRF. Each event must be 
recorded separately. 


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It is not acceptable for the Investigator to send photocopies of the subject’s medical records in lieu of 
completion of the AE/SAE eCRF page. There may be instances when copies of medical records for certain 
cases are requested. In this case, all subject identifiers, except for the subject number, will be redacted on 
the copies of the medical records before provided. 
Each AE is to be evaluated for: 
• 
AE diagnosis or syndrome (if not known, signs or symptoms) 
• 
Dates of onset and resolution 
• 
Severity (including grade changes as per the CRF completion guidelines 
• 
Causal relationship with study drug or protocol-mandated procedures 
• 
Seriousness 
• 
Action taken 
• 
Outcome 
Whenever possible, a unifying diagnosis should be reported as opposed to a listing of individual symptoms. 
However, symptoms should be grouped into a diagnosis only if each sign or symptom is a medically 
confirmed component of that diagnosis as evidenced by current standard medical textbooks. If any aspect 
of a sign or symptom does not fit into a classic pattern of the diagnosis, the individual symptom should be 
reported as a separate AE. 
A preexisting medical condition is one that is present during the screening period for this study. Such 
conditions should be recorded as General Medical History and Baseline Conditions. A preexisting medical 
condition should be recorded as an AE only if the frequency, severity, or character of the condition worsens 
during the study. 
For hospitalizations or surgical or diagnostic procedures, the illness leading to the surgical or diagnostic 
procedure should be recorded as the SAE, not the procedure itself. The procedure should be captured in the 
narrative as part of the action taken in response to the illness. 
When reporting an SAE of progression of the disease under investigation, specific manifestations of the 
progression (e.g., acute coronary syndrome, acute pulmonary edema) should be reported, rather than the 
general term “disease progression.” 
Any emergent laboratory abnormality (e.g., clinical chemistry or hematology) or other abnormal assessment 
findings (e.g., ECG or vital signs) that meets any of the following criteria should be recorded as an AE or 
SAE: 
• 
Associated with clinical signs and/or symptoms 
• 
Requires medical or surgical intervention 
• 
May require a change in current therapy, and leads to study treatment discontinuation, delay, or 
interruption 
• 
Otherwise clinically significant as determined by the Investigator 
Whenever possible, the clinical diagnosis, rather than the laboratory result, should be reported by the 
Investigator (e.g., anemia versus low hematocrit). 
Emergent and clinically significant abnormal laboratory values occurring during the study will be followed 
until repeat tests return to normal, stabilize, or are no longer clinically significant. 
Laboratory abnormalities that are not deemed clinically significant by the Investigator should not be 
reported as AEs. 


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All deaths that occur during the protocol-specified AE reporting period, regardless of attribution, will be 
recorded on an eCRF and SAE report form, and expeditiously reported to the Sponsor. This includes death 
attributed to progression of disease. 
• 
When recording a death on an eCRF or SAE Report Form, the event or condition that caused or 
contributed to the fatal outcome should be recorded as the single medical concept. 
• 
Death is an outcome of an event. The event that resulted in death (e.g., sepsis, stroke, myocardial 
infarction, etc.) should be recorded in the eCRF and reported on the SAE report form. 
• 
If the death is attributed to progression of disease, record “disease progression” as the SAE term 
on the SAE Report Form. 
• 
The term “unexplained death” should be captured if the cause of death is not known. However, 
every effort should be made to capture the established cause of death, which may become available 
later on (e.g., after autopsy). 
8.3.8 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at subsequent 
visits/contacts. All SAEs will be followed until resolution, stabilization, the event is otherwise explained, 
or the subject is lost to follow-up (as defined in Section 7.3) or until the end of their participation in the 
study. Subjects should be encouraged to complete the End of Study visit activities. 
8.3.9 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a study 
treatment under clinical investigation are met. 
• 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. 
• 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
• 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and maintain 
it in the site’s regulatory binder along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
8.3.10 
Pregnancy 
Notify the sponsor or its designee regarding a pregnancy that occurs in either a study patient or occurs in 
the female partner of a male patient during his participation in this study within 24 hours. 
If a female subject becomes pregnant after consent and during the screening process but prior to IP 
administration, the subject should be withdrawn immediately, and should not receive IP. If a female subject 
becomes pregnant after treatment, the subject should be allowed to continue with the study given that 
following the single IP administration there are no additional treatments and no invasive tests or procedures. 
Counseling should be provided to the subject in order to inform their decisions on study continuation and 
on the pregnancy. 
While pregnancy itself is not considered an AE, any pregnancy complication should be reported to the 
sponsor or its designee. Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 


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congenital anomalies, ectopic pregnancy) are considered SAEs and should be reported to the sponsor or its 
designee as soon as the Investigator or his/her staff learns of the event. The outcome of all pregnancies 
(spontaneous miscarriage, elective termination, normal birth, or congenital abnormality) must be followed 
up and documented even if the patient was discontinued from the study. 
The Investigator will attempt to collect pregnancy information on any male subject’s female partner who 
becomes pregnant while the male subject is in this study. This applies only to male subjects who receive 
JK07. Details of all pregnancies in female partners of male patients will be collected after the start of JK07 
and until 28 days after IP administration. 
If a male subject has a female partner who becomes pregnant during the study, the subject must be unblinded 
in order to inform whether appropriate counseling of the female partner is necessary. In this circumstance, 
the unblinded male subject can remain on study and continue with follow-up visits as scheduled. 
After obtaining the necessary signed ICF from the pregnant partner directly, the Investigator will record 
pregnancy information on the appropriate form and submit it to the Sponsor designee within 24 hours of 
learning of the partner’s pregnancy, in the same fashion as an SAE, as noted in Section 8.3.3. 
The pregnant partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will be no longer 
than 6 to 8 weeks following the estimated delivery date. Any termination of the pregnancy will be reported 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
8.3.11 
Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study. 
8.3.12 
Disease-related Events and/or Disease-related Outcomes Not Qualifying as AEs or SAEs 
The DRC will carefully evaluate all AEs as to whether they are considered a TEAE or DLAE. 
 
8.4 
Treatment of Overdose 
The JK07 dose administered in this study should not exceed 2.5 mg/kg without further amending the 
protocol (See dose escalation in Table 4). An overdose is any dose above the assigned dose level for a given 
cohort that is administered over the pre-specified 60-minute period. 
In the event of an overdose, the Investigator/treating physician should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the subject for any AEs/SAEs and laboratory abnormalities until study treatment can 
no longer be detected systemically or through the EOS visit (180 days; whichever is longer). 
3. Obtain blood samples for PK analysis as specified in the Table 1 SoA. 
4. Document the quantity of the excess dose as well as the duration of the infusion in the eCRF. 
5. Overdose is reportable to Safety only when associated with an SAE. 
Decisions regarding dose interruptions or modifications will be made by the investigator in consultation 
with the medical monitor based on the clinical evaluation of the participant. 
8.5 
Pharmacokinetics 
8.5.1 
Collection of Samples 
Venous blood samples of approximately 5 mL will be collected for measurement of serum concentrations 
of JK07 at times as specified in the Table 1 SoA and Table 2. Instructions for the collection and handling 


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of biological samples will be provided by the Sponsor in a separate Laboratory Manual. Blood samples will 
be taken either by direct venipuncture or an indwelling cannula inserted in a forearm vein. The actual date 
and time (24-hour clock time) of each sample will be recorded. The start date/time and stop date/time of 
the infusion and other pertinent information (See Section 6.1) will also be recorded. Samples will be 
collected, labelled, stored, and shipped as detailed in the Laboratory Manual. 
Predose samples may be collected within 30 minutes prior to start of infusion. The end-of-infusion sample 
must be taken no later than 5 minutes from end-of-infusion. A 5-minute window will be allowed for samples 
taken up to 1-hour postdose; a 15-minute window will be allowed for samples taken at 2 to 12 hours 
postdose, a 10-minute window from the completion of ECG assessments at 24- and 48-hours postdose; a 
±8-hour window is permitted for PK collections on Day 4, and a +1 day window for Day 7. For all 
subsequent days, the PK sample should be collected within the Table 1 SoA specified windows. 
8.5.2 
Determination of Drug Concentration 
Samples for the determination of JK07 serum concentration will be analyzed on behalf of the Sponsor using 
appropriate validated bioanalytical methods. JK07 concentrations are to be determined from an 
immunoassay targeting both the antibody domain and the NRG-1 peptide fragment. Full details of the 
bioanalytical methods will be described in the separate Bioanalytical Report(s). 
All samples still within the known stability of the analyte of interest at the time of receipt by the 
bioanalytical laboratory will be analyzed. 
Remaining serum samples may be subjected to further analysis by the Sponsor or designee for the 
development of additional bioanalytical assays and/or for further investigation of JK07 
stability/degradation. Samples collected for analyses of JK07 concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
8.5.3 
Calculation of Derivation of Pharmacokinetic Variables 
Pharmacokinetic parameters will be derived using noncompartmental methods with Phoenix® WinNonlin® 
Version 8.0 or higher (Certara, L.P. Princeton, New Jersey, United States of America [USA]) and/or SAS® 
EG 7.23 or higher (SAS Institute, Inc., Cary, North Carolina, USA). Actual elapsed time from dosing will 
be used for the final serum PK parameter calculations. Nominal time from dosing will be used for any 
interim PK parameter calculations. 
The PK parameters in Table 10 will be determined for serum JK07 concentrations obtained from both 
assays, when possible. A minimum of 4 quantifiable postdose concentrations will be required for all 
calculations. 


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Table 10 
Plasma/Serum/Whole Blood Pharmacokinetic Parameters 
 
Pharmacokinetic Parameter 
Definition 
Cmax 
Maximum concentration obtained directly from the observed concentration versus time 
data. 
tmax 
Time to Cmax. 
AUC(0-inf) 
Area under the serum concentration-time curve from time zero extrapolated to infinity, 
calculated by linear up/log down trapezoidal summation. If the percentage of AUC 
obtained by extrapolation is greater than 30%, AUC(0-inf) and related parameters (CL 
and Vz) will be listed but not included in any summaries or inferential analyses. 
AUC(0-last) 
Area under the serum concentration-time curve from time zero to the time of the last 
quantifiable concentration, calculated by linear up/log down trapezoidal summation. 
CL 
Systemic clearance. 
Vz 
Volume of distribution. 
t½ 
Terminal half-life: a minimum of 3 points will be used for estimation. 
λz 
Terminal rate constant: if Rsq(adj) is <0.800, then λz, t½, and related parameters will be 
listed but not included in any summaries or inferential analyses 
Dose normalized exposure parameters will also be calculated. 
Additional serum parameters may be calculated if deemed appropriate. Further details with respect to the 
PK analysis will be provided in the Statistical Analysis Plan (SAP). 
Drug concentration information that may unblind a given cohort will not be reported to study centers or 
blinded personnel until that cohort has been unblinded. 
Any changes in the timing or addition of time points for any planned study assessments must be documented 
and approved by the relevant study team member and then archived in the Sponsor and study center study 
files but will not constitute a protocol amendment. 
8.6 
Pharmacodynamics 
Pharmacodynamics will not be evaluated in this study. The exploratory 2D-TTE assessments are described 
in Section 8.2.9. Exploratory biomarker assessment details are outlined in Section 8.8. 
8.7 
Genetics 
Genetics will not be evaluated in this study. 
8.8 
Biomarkers 
• 
Collection of samples for biomarker research is a component of the safety monitoring for this study 
and also an exploratory part of this study. Samples will be tested for predictive muscle and 
inflammatory biomarkers to evaluate their association with the observed clinical responses to JK07. 
The following samples for the safety and exploratory muscle and inflammatory biomarkers will be 
collected from all subjects in this study as specified in the SoA: 
− Additional biomarkers: hsCRP, troponin-I and/or hs-troponin T, CPK, CPK-MB, and 
lactate dehydrogenase. 
− 
Exploratory biomarkers: NT-proBNP, total BNP 
• 
Venous blood samples of approximately 10 mL will be collected at several time points as per the 
SoA (Table 1) and Appendix 3, Table 15, for measurement of exploratory biomarkers. Instructions 


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for the collection and handling of biological samples will be provided by the Sponsor in a separate 
Laboratory Manual. 
• 
Serum biomarker samples will be analyzed by the Sponsor designated clinical laboratory 
(Q2 Solutions). 
8.9 
Health Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters are not evaluated in 
this study. 


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9.0 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
Formal statistical hypothesis testing is not planned for this study. All analyses will be considered 
exploratory and descriptive. 
9.2 
Sample Size Determination 
The study will enroll up to a maximum of 63 subjects who will be randomized into dose escalation cohorts. 
The sample size is not based on statistical considerations but is typical for studies of this nature and is 
considered adequate to characterize the distribution of the planned endpoints. Any statistical testing will be 
considered exploratory and descriptive. 
9.3 
Populations for Analyses 
For purposes of analysis, the analysis sets are defined in Table 11. 
Table 11 
Analysis Sets 
 
Analysis Set 
Description 
Safety Evaluation Population 
All subjects randomly assigned to the IP and who take at least 1 dose of IP. Subjects 
will be analyzed according to the treatment they received. 
Dose-limiting Adverse Event (DLAE) 
Evaluation Population 
All subjects who received at least 1 dose of IP and completed the 15-day DLAE 
follow-up period. 
Pharmacokinetic (PK) Evaluation 
Population 
All subjects who received at least 1 dose of IP and have at least 1 quantifiable IP 
plasma concentration collected postdose without important protocol 
deviations/violations or events thought to significantly affect the PK results. 
Exploratory Pharmacodynamic 
(PD)/Biomarker Evaluation 
Population 
All subjects who take at least 1 dose of IP and have at least 1 exploratory PD variable 
or biomarker endpoint collected postdose without important protocol 
deviations/violations or events thought to significantly affect the PD results. 
9.4 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the subject analysis sets to 
be included in the analyses, and procedures for accounting for missing, unused, and spurious data. This 
section focusses on the summary of the planned statistical analyses of the primary and secondary endpoints. 
All analyses, summaries, and listings will be performed using SAS® software (EG 7.23 or higher). Results 
will be summarized by treatment and overall, where appropriate. Subjects who received placebo will be 
combined into 1 treatment group for purposes of analysis. Change from baseline will be calculated as value 
postdose subtracted by value at baseline. The baseline measure will be defined as the last non-missing 
measure prior to initiation of IP. 
The following descriptive statistics will be used as applicable to summarize the study data unless otherwise 
specified: 
• 
Continuous variables: sample size (n), mean, standard deviation (SD), median, minimum (min), 
and maximum (max). 
• 
Summaries for JK07 concentrations will include the coefficient of variation and PK parameter 
summaries will also include the geometric mean (except for tmax which will only be presented as 
min, median, max). 
• 
Categorical variables: frequencies and percentages. 


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Individual subject data will be presented in listings. 
9.4.1 
Efficacy Analyses 
See Section 9.4.4 for assessment of exploratory efficacy analyses. 
9.4.2 
Pharmacokinetic/Pharmacodynamic Analyses 
PK Analysis: 
JK07 concentrations derived from the validated assay, concentration ratios, and calculated parameters will 
be listed and descriptively summarized by active treatment for the PK population (subjects who have 
received JK07 and do not have any protocol deviations/events which may affect the PK results). JK07 
serum concentration-time profiles will be graphically displayed by treatment on linear and semilogarithmic 
scale for each assay, as appropriate. Scatter plots of individual values and geometric means of PK 
parameters, area under the plasma concentration-time curve from time zero extrapolated to infinity 
(AUC(0-inf) [or area under the plasma concentration-time curve from time zero to the time of the last 
quantifiable concentration (AUC(0-last)) if AUC(0-inf) is not calculable in most subjects]), Cmax as well as dose- 
normalized exposure parameters versus dose will be presented. 
Dose proportionality of PK parameters such as Cmax and AUC(0-inf) [or AUC(0-last) if AUC(0-inf) is not 
calculable in most subjects] over the administered dose range may also be explored using a power model. 
Further details will be presented in the SAP. 
Exploratory Exposure-Response Analysis: 
An exploratory evaluation of a plasma concentration to QT (C-QT) relationship will be conducted using a 
linear mixed effects model, with the drug-free-corrected (Day -1-corrected) change from baseline in QTcF 
as the response variable, denoted as ∆QTcF. Independent variables will include the fixed effects time- 
matched JK07 plasma concentration obtained on Day 1, treatment indicator (treatment = 1 for subjects 
receiving JK07, and 0 otherwise), time point as a categorical variable, and random effects subject and time- 
matched JK07 plasma concentration obtained on Day 1. The analysis will be performed for the exploratory 
PD/biomarker population. Figures for mean time-matched change from baseline QTcF values versus JK07 
mean concentrations (time-matched with QTcF) on Days 1 will also be generated. Hysteresis will be 
examined via by-subject hysteresis plots. Departures from a linear relationship will be examined 
graphically, and additional C-QT relationships other than the linear relationship may be explored if 
supported by data. A detailed plan of this analysis will be presented as part of the statistical analysis 
plan. The results for the C-QT analysis will be included in the CSR for this study. Further details will be 
presented in the SAP. 
Exposure-response relationships may also be explored for safety and/or biomarker endpoint. Details 
regarding these analyses will be provided in the SAP. 
Pharmacokinetic data from this study may be pooled with data from other future study(ies) and analyzed 
using population modeling approaches or used to explore exposure-response relationships. If performed, 
separate analysis plan(s) will be prepared; results from these analyses will not be part of the clinical study 
report. 
9.4.3 
Safety Analyses 
All safety analyses will be performed on the Safety Population. 
All safety data will be listed according to treatment group, subject number, and visit. 
The AEs are defined in Section 8.3.1. The DLAE are defined in Section 4.6. 


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AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 22. The 
number of AEs and incidence rates will be tabulated by preferred term and system organ class. 
The AEs will be coded by maximum severity, relationship to study treatment, as SAEs or DLTs as needed, 
and will be categorized and tabulated for each treatment group (cohort). 
DLAEs will be presented in the same manner as the AEs. 
Incidence of injection site reactions will be summarized by treatment group, and if appropriate by 
assessment time. 
All laboratory test results, vital signs measurements, ECG results, weight, and body mass index will be 
summarized for each treatment group using descriptive statistics at each visit for raw numbers and change 
from baseline. The incidence of treatment-emergent abnormal laboratory, vital sign, and ECG values will 
also be summarized using descriptive statistics. 
For 12-lead ECG parameters (HR, PR, QRS, QT, QTcF), the 90 % confidence interval will also be 
presented for each parameter mean and change from baseline values. Outliers for QT and QTcF defined 
under outcome measures will be summarized using counts and percentages by treatment and sampling time, 
if appropriate and using subject-level maximum over time by treatment. The following categories will be 
presented by treatment and overall, for JK07: 
• 
outlier QT and QTcF intervals (450-480 ms, 480-500 ms and >500 ms) 
• 
change from baseline in QT and QTcF intervals (30-60 ms and >60 ms) 
Additional corrections to QT may also be similarly analyzed. If relevant, analysis excluding ECGs 
capturing paced beats will be performed. 
Abnormal findings on 12-lead ECG will be summarized by treatment using descriptive statistics. 
All recorded ECGs will be interpreted on site and subsequently collected, digitized, and sent for central 
laboratory standardized measurements. The incidence (number of subjects and percent) of a confirmed 
positive ADA response will be summarized by treatment. The incidence of neutralizing anti-drug antibody 
response will also be summarized, if appropriate. 
All data will be provided in data listings sorted by treatment group, subject number, and visit. 
9.4.4 
Other Analyses 
Results of the exploratory endpoints (2D-TTE and biomarkers) and the change from baseline values (as 
applicable) will be listed and descriptively summarized by treatment and scheduled time point. Exploratory 
inferential comparisons to placebo may also be performed, if appropriate. 
9.4.5 
Missing Data 
Data from subjects who withdraw from the study, including AEs and any follow-up, will be included in the 
analyses of all outcomes. 
Missing data will be excluded from the analyses. No imputation will be performed, unless specified. 
9.5 
Interim Analyses 
No formal interim analyses are planned. Pharmacokinetic parameters will be calculated using available 
JK07 concentrations and scheduled sampling times to support JK07 dose escalation decisions, as applicable. 
Handling of the safety results obtained up to Day 15 after dose administrations will be described in the 
DRC Charter which will be prepared separately from the protocol. 


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9.6 
Data Review Committee 
A DRC consisting of members who are independent from the Sponsor will be established. The DRC will 
be composed of a minimum of 3 qualified cardiologists (independent voting members), and 3 non-voting 
members (including a biostatistician and Sponsor’s medical monitor). When needed, ad hoc members or 
subject matter experts can be invited to participate as nonvoting participants. The DRC will have a separate 
charter from the protocol. 
The DRC is responsible for reviewing and evaluating unblinded safety data for sentinel subjects, and 
blinded safety data (and safety data unblinded only on an as-needed basis) collected for at least 14 days and 
subsequently cumulatively at regularly scheduled meetings as defined in a separate DRC charter (minimum 
prior to each planned dose escalation). The DRC may also meet in ad hoc meetings at its discretion as 
needed in response to events occurring in the study. The DRC will be responsible for making 
recommendations as to whether it is scientifically and ethically appropriate to continue enrollment, 
discontinue treatment groups, or stop the study. Additional responsibilities for the DRC include initiation 
of enrollment at the next dose level. The DRC meetings will be documented in written meeting minutes. 
In the first cohort, if no clinical effect is observed in the sentinel subject, the DRC will decide whether to 
proceed with the randomization of four additional subjects (3:1, JK07: placebo) to receive blinded IP. Once 
the last subject in the first cohort completes the evaluation period, which includes assessments through Day 
15, the DRC will decide whether to proceed to the second cohort. The second cohort and subsequent cohorts 
will proceed as the first cohort until either of the following occur: a sentinel subject exhibits in the opinion 
of the DRC, a clinical effect (efficacy or safety observation), or a cohort exhibits, in the opinion of the 
DRC, a clinical effect. 
Once a clinical effect is observed, the DRC may, at its discretion, expand the size of that cohort in which a 
clinical effect is first observed, and subsequent cohorts, up to a maximum of nine subjects (1 open-label 
JK07 sentinel subject, and 6:2 [JK07:placebo] randomized, double-blind subjects). 
Following observation of a clinical effect and a decision to expand the size of the first cohort at which the 
clinical effect was observed, the DRC will decide whether to dose escalate after the last subject in the 
expansion cohort completes the evaluation period. If the DRC establishes to escalate the dose, a single 
unblinded sentinel subject will receive JK07 at the next dose level. If following the completion of the 
evaluation period of that sentinel subject the DRC decides to proceed, the remainder of the subjects in the 
expanded cohort size will receive JK07 or placebo according to the direction of the DRC, and this sequence 
will repeat until the highest planned dose level is reached or until the DRC determines not to dose escalate 
further. 
During the review of the safety/tolerability results the DRC may make the determination to expand the size 
of the current cohort further, if not already at the maximum size, following which further dose escalation 
could proceed. Alternatively, the DRC may determine to decrease to a lower dose level with an additional 
cohort, which may be an intermediary dose or a pre-assigned cohort, which would include up to eight 
subjects randomized 6:2 [JK07: placebo], with or without an additional unblinded active sentinel subject. 
If the decision is to de-escalate to an intermediate dose between the prior cohort and the cohort at which 
dose escalation was halted, the cohort will comprise a single sentinel subject receiving JK07 followed by 
randomization of a minimum of 4 subjects (3:1, JK07: placebo) in the cohort. For any dose reduction to a 
dose below the highest established safe dose (i.e., below a dose for which the DRC approved expansion 
from a sentinel subject to enrollment of a full cohort), no sentinel subject will be required. Following a dose 
reduction, the DRC may subsequently decide to further reduce the dose level in a subsequent cohort of 
similar size or increase the dose in a subsequent cohort with or without the inclusion of a sentinel subject 
at the discretion of the DRC. 


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10.0 REFERENCES 
 
Chavey WE, Hogikyan RV, Van Harrison R, et al. Heart Failure Due to Reduced Ejection Fraction: Medical 
Management. Amer Fam Phys. 2017;95(1):13-20. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance form serum creatinine. Nephron. 
1976;1691):31-41. 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Published: November 27, 2017. 
Available at: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_ 
5x7.pdf Accessed October 28, 2020. 
FDA: US Department of Health and Human Services. Food and Drug Administration, Center for Drug 
Evaluation and Research (CDER). Guidance for Industry Estimating the Maximum Safe Starting Dose in 
Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. July 2005. Available at: 
https://www.fda.gov/media/72309/download. Accessed October 23, 2020. 
Gao R, Zhang J, Cheng L, et al. A phase 2, randomized, double-blind, multicenter, based on standard 
therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients 
with chronic heart failure. J Am Coll Cardiol. 2010; 55:1907-1914. 
Gong L, Zeng W, Yang Z, et al., Comparison of the Clinical Manifestations of Type 2 Diabetes Mellitus 
Between Rhesus Monkey (Macaca mulatta lasiotis) and Human Being. Pancreas. 2013; 42:537-542. 
Hicks KA, Mahaffey KW, Mehran R, et al. 2017 Cardiovascular and Stroke Endpoint Definitions for 
Clinical Trials. J Am Coll Cardiol. 2018;71(9):102134 
Jabbour A, Hayward CS, Keogh AM, et al. Parenteral administration of recombinant human neuregulin-1 
to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic 
responses. Eur J Heart Fail. 2011; 13:83-92. 
Lenihan DJ, Anderson SA, Lenneman CG. A phase 1, Single Ascending Dose Study of Cimaglermin Alfa 
(Neuregulin 1β3) in Patients with Systolic Dysfunction and Heart Failure. JACC Basic Transl Sci. 
2016; 1:576-586. 
Odiete O, Hill MF, Sawyer DB. Neuregulin in cardiovascular development and disease. Circulation Res. 
2012;111(10):1376-1385. 
Parodi EM, Kuhn B. Signaling between microvascular endothelium and cardiomyocytes through 
neuregulin. Cardiovascular Research. 2014;102(2):194-204. 
Rohrbach S, Yan X, Weinberg EO, Hasan F, Bartunek J, Marchionni MA, Lorell BH. Neuregulin in cardiac 
hypertrophy in rats with aortic stenosis. Differential expression of erbB2 and erbB4 receptors. Circulation. 
1999;100(4):407-12. 
Shah A, Gandhi D, Srivastava S, et al. Heart Failure: A Class Review of Pharmacotherapy. P&T: A Peer- 
reviewed Journal for Formulary Management. 2017;42(7):464- 472. 
Sundaresan S, Roberts PE, King KL, Sliwkowski MX, Mather JP. Biological response to ErbB ligands in 
nontransformed cell lines correlates with a specific pattern of receptor expression. Endocrinology. 1998; 
139(12):4756-4764., Volume 139, Issue 12, 1 December 1998, Pages 4756–4764. 
The Joint European Society of Cardiology/ American College of Cardiology Committee JACC Vol. 36, 
No. 3, 2000; September 2000:959–69 
Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. Circulation. 
2018;138: e618-e651 [Universal Definition of Myocardial Infarction (UDMI] 


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Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA 
Guideline for the Management of Heart Failure: A Report of the American College of 
Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure 
Society of America. Circulation. 2017;136(6):e137-e161. 
Zhao YY, Sawyer DR, Baliga RR, Opel DJ, Han X, Marchionni MA, Kelly RA. Neuregulins promote 
survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult 
ventricular myocytes. J Biol Chem. 1998;273(17):10261-10269. 


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11.0 APPENDICES 
Appendix 1 
Cancer Screening Guidelines 
AMERICAN CANCER SOCIETY GUIDELINES FOR THE 
EARLY DETECTION OF CANCER 
Screening tests are used to find cancer before a person has any symptoms. Here are the American Cancer 
Society's recommendations to help guide you when you talk to your doctor about screening for certain 
cancers. 
Breast cancer 
• 
Women ages 40 to 44 should have the choice to start annual breast cancer screening with 
mammograms (x-rays of the breast) if they wish to do so. 
• 
Women age 45 to 54 should get mammograms every year. 
• 
Women 55 and older should switch to mammograms every 2 years or can continue yearly 
screening. 
• 
Screening should continue as long as a woman is in good health and is expected to live 10 more 
years or longer. 
• 
All women should be familiar with the known benefits, limitations, and potential harms linked to 
breast cancer screening. 
Women should also know how their breasts normally look and feel and report any breast changes to a 
health care provider right away. 
Some women – because of their family history, a genetic tendency, or certain other factors – should be 
screened with magnetic resonance imaging (MRIs) along with mammograms (the number of women who 
fall into this category is very small.) Talk with a health care provider about your risk for breast cancer and 
the best screening plan for you. 
Colon and rectal cancer and polyps 
For people at average risk for colorectal cancer, the American Cancer Society recommends starting 
regular screening at age 45. This can be done either with a sensitive test that looks for signs of cancer in a 
person’s stool (a stool-based test), or with an exam that looks at the colon and rectum (a visual exam). 
Talk to your health care provider about which tests might be good options for you, and to your insurance 
provider about your coverage. No matter which test you choose, the most important thing is to get 
screened. 
If you’re in good health, you should continue regular screening through age 75. 
For people ages 76 through 85, talk with your health care provider about whether continuing to get 
screened is right for you. When deciding, take into account your own preferences, overall health, and past 
screening history. 
People over 85 should no longer get colorectal cancer screening. 
If you choose to be screened with a test other than colonoscopy, any abnormal test result needs to be 
followed up with a colonoscopy. 
Cervical cancer 
• 
Cervical cancer testing should start at age 21. Women under age 21 should not be tested. 


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• 
Women between the ages of 21 and 29 should have a Pap test done every 3 years. HPV testing 
should not be used in this age group unless it’s needed after an abnormal Pap test result. 
• 
Women between the ages of 30 and 65 should have a Pap test plus an HPV test (called “co- 
testing”) done every 5 years. This is the preferred approach, but it’s OK to have a Pap test alone 
every 3 years. 
• 
Women over age 65 who have had regular cervical cancer testing in the past 10 years with 
normal results should not be tested for cervical cancer. Once testing is stopped, it should not be 
started again. Women with a history of a serious cervical pre-cancer should continue to be tested 
for at least 20 years after that diagnosis, even if testing goes past age 65. 
• 
A woman who has had her uterus and cervix removed (a total hysterectomy) for reasons not 
related to cervical cancer and who has no history of cervical cancer or serious pre-cancer should 
not be tested. 
• 
All women who have been vaccinated against HPV should still follow the screening 
recommendations for their age groups. 
Some women – because of their health history (HIV infection, organ transplant, DES exposure, etc.) – 
may need a different screening schedule for cervical cancer. Talk to a health care provider about your 
history. 
Endometrial cancer 
The American Cancer Society recommends that at the time of menopause, all women should be told 
about the risks and symptoms of endometrial cancer. Women should report any unexpected vaginal 
bleeding or spotting to their doctors. 
Some women – because of their history – may need to consider having a yearly endometrial biopsy. 
Please talk with a health care provider about your history. 
Lung cancer 
The American Cancer Society recommends yearly lung cancer screening with a low-dose CT scan 
(LDCT) for certain people at higher risk for lung cancer who meet the following conditions: 
 
Are aged 55 to 74 years and in fairly good health 
and 
 
Currently smoke or have quit smoking in the past 15 years 
and 
 
Have at least a 30 pack-year smoking history. (A pack-year is 1 pack of cigarettes per day per 
year. One pack per day for 30 years or 2 packs per day for 15 years would both be 30 pack-years.) 
Before getting screened, you should talk to your health care provider about: 
• 
Your risk for lung cancer 
• 
How you can quit smoking, if you still smoke 
• 
The possible benefits, limits, and harms of lung cancer screening 
• 
Where you can get screened 
You should also talk with your insurance provider about your coverage. 
Prostate cancer 


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The American Cancer Society recommends that men make an informed decision with a health care 
provider about whether to be tested for prostate cancer. Research has not yet proven that the potential 
benefits of testing outweigh the harms of testing and treatment. We believe that men should not be tested 
without first learning about what we know and don’t know about the risks and possible benefits of testing 
and treatment. 
Starting at age 50, men should talk to a health care provider about the pros and cons of testing so they can 
decide if testing is the right choice for them. 
If you are African American or have a father or brother who had prostate cancer before age 65, you 
should have this talk with a health care provider starting at age 45. 
If you decide to be tested, you should get a PSA blood test with or without a rectal exam. How often 
you’re tested will depend on your PSA level. 
Source: https://www.cancer.org/healthy/find-cancer-early/american-cancer-society-guidelines-for-the- 
early-detection-of-cancer.html Accessed March 30, 2021 


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Appendix 2    Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki of World Medical Association and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. 
− Applicable ICH Good Clinical Practice (GCP) Guidelines. 
− Applicable laws and regulations. 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, Administrative Letters, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by the Investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC and regulatory authority approval, when 
applicable, before implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to subjects. 
• 
The Investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC. 
− 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures. 
− 
Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC and 
all other applicable local regulations. 
• 
After reading the protocol, each Investigator will sign the protocol signature page and send a copy 
of the signed page to the Sponsor or representative (Appendix 8 Signature of Investigator). The 
study will not start at any study center at which the Investigator has not signed the protocol. 
Adequate Resources 
The Investigator is responsible for supervising any individual or party to whom the Investigator delegates 
study-related duties and functions conducted at the study center. 
If the Investigator/institution retains the services of any individual or party to perform study related duties 
and functions, the Investigator/institution should ensure this individual, or party is qualified to perform 
those study-related duties and functions and should implement procedures to ensure the integrity of the 
study-related duties and functions performed and any data generated. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial information 
as requested to allow the Sponsor to submit complete and accurate financial certification or disclosure 
statements to the appropriate regulatory authorities. Investigators are responsible for providing information 
on financial interests during the study and for 1 year after completion of the study. 
Insurance 
Sponsor will provide insurance in accordance with local guidelines and requirements as a minimum for the 
subjects in this study. The terms of the insurance will be kept in the study files. 


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Informed Consent Process 
• 
The Investigator or his/her representative will explain the nature of the study to the subject and 
answer all questions regarding the study. 
• 
Subjects must be informed that their participation is voluntary. Subjects will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
• 
The medical record must include a statement that written informed consent was obtained before the 
subject was entered in the study and the date the written consent was obtained. The authorized 
person obtaining the informed consent must also sign the ICF. 
• 
Subjects must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
• 
A copy of the ICF(s) must be provided to the subject. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples for optional 
exploratory research. The Investigator or authorized designee will explain to each subject the objectives of 
the exploratory research. Subjects will be told that they are free to refuse to participate and may withdraw 
their consent at any time and for any reason during the storage period. A separate signature will be required 
to document a subject’s agreement to allow any remaining specimens to be used for exploratory research. 
Subjects who decline to participate in this optional research will not provide this separate signature. 
Data Protection 
• 
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets that 
are transferred to the Sponsor will contain the identifier only; subject names or any information 
which would make the subject identifiable will not be transferred. 
• 
The subject must be informed that his/her personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to the 
subject. 
• 
The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
Administrative Structure 
In addition to safety monitoring by the investigators, safety will be monitored by the DRC as described in 
Section 9.6. The Principal Investigator and the Sponsor, when appropriate, will invite other specialist 
individuals to participate in the review, e.g., PK scientists, statisticians, clinical specialists etc. The 
administrative structure of the study is described in Table 12. 


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Table 12 
Study Administrative Structure 
 
Function 
Responsible Organization 
Study Operations Management 
Medical Monitoring 
CRO (IQVIA Biotech) 
Neal Salomon, MD - Consulting Chief Medical Officer and Medical 
Monitor 
Study Master File 
CRO (IQVIA Biotech) 
Randomization Code 
CRO (IQVIA Biotech) 
Data Management 
CRO (IQVIA Biotech) 
Clinical Supply Management 
3rd Party 
Biostatistics Medical Writing 
CRO (IQVIA Biotech)/ IQVIA 
Laboratory Assessments 
3rd Party 
Electrocardiogram Collection, Review, and Analysis 
3rd Party 
Pharmacokinetic Sample Testing 
3rd Party 
Management of Event Adjudication 
CRO (IQVIA Biotech) 
Adjudication Committee 
CRO (IQVIA Biotech) 
Steering Committee 
N/A 
Safety Monitoring Committee (see Section 9.6) 
CRO (IQVIA Biotech) 
Medical Monitor 
Neal Salomon, MD 
Consulting Chief Medical Officer and Medical Monitor, SalubrisBio 
Phone: 410-419-8501 (cell) 
Fax: 
410-560-1562 
Email: neal.salomon@salubrisbio.com 
Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. It shall be 
accompanied by a summary written in a manner that is understandable to laypersons. 
Data Quality Assurance 
• 
All subject data relating to the study will be recorded either as printed source documents from the 
subject’s medical record, or will be recorded on printed eCRF’s, it will then be entered into the 
study’s electronic data capture system (EDC), unless it is data that is being transmitted to the 
Sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the eCRF. 
• 
The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the eCRF. 
• 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
• 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 


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• 
Study monitor will perform ongoing source data verification to confirm that data entered into the 
eCRF by authorized study center personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, ICH 
GCP, and all applicable regulatory requirements. 
• 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 2 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
Source Documents 
The Investigator/institution should maintain adequate and accurate source documents and study records 
that include all pertinent observations on each of the study center’s subjects. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be 
traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an audit 
trail). 
• 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s study center. 
• 
Data reported on the eCRF or entered in the eCRF that are transcribed from source documents must 
be consistent with the source documents or the discrepancies must be explained. The Investigator 
may need to request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
• 
Definition of what constitutes source data can be found in the Clinical Monitoring Plan. 
Changes to the Protocol 
This protocol is to be followed exactly. Amendments must receive IRB/IEC approval prior to 
implementation. As appropriate, protocol amendments will be submitted to regulatory authorities on a 
timely basis. 
Administrative changes (not affecting the subject benefit/risk ratio) may be made without the need for a 
formal amendment. All amendments and administrative change directives will be distributed to all protocol 
recipients with appropriate instructions. 
The IRB/IEC will be informed of any safety issues that require alteration of the safety monitoring scheme 
or amendment of the ICF. 
Study and Study Center Closure 
The Sponsor designee reserves the right to close the study center or terminate the study at any time for any 
reason at the sole discretion of the Sponsor. Study centers will be closed upon study completion. A study 
center is considered closed when all required documents and study supplies have been collected and a study 
center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor or Investigator may include but are not 
limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or local 
health authorities, the Sponsor’s procedures, or GCP guidelines. 


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• 
Inadequate recruitment of subjects by the Investigator. 
• 
Discontinuation of further study treatment development. 
Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor may make the 
results of the study publicly available. The publication policy with respect to the Investigator and study 
center will be set forth in the Clinical Trial Agreement. 
• 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor at least 30 days before 
submission. This allows the Sponsor to protect proprietary information and to provide comments. 
• 
The Sponsor will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of multicenter 
studies only in their entirety and not as individual study center data. In this case, a Coordinating 
Investigator will be designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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Appendix 3 
Clinical Laboratory Tests 
• 
Blood will be collected for local laboratory assessments at times when the central laboratory results 
are not expected to be available in time for either study treatment administration and/or response 
evaluation. The local laboratory results must be entered into the eCRF. Table 14 identifies local 
laboratory assessments scheduled for this study (and the specific timepoints for assessment) but 
may not be fully comprehensive in cases where additional safety follow-up deemed appropriate by 
the Investigator. Table 15 identifies blood draw requirements for central lab assessment. 
• 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in Section 5.0 of 
the protocol. 
• 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations. 
• 
All results must be recorded in the eCRF. 


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Table 13 
Protocol-required Safety Laboratory Assessments 
 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
WBC Count with Differential: 
RBC Count 
Neutrophils 
Hb 
Lymphocytes 
Hct 
Monocytes 
RBC Indices: 
Eosinophils 
MCV 
Basophils 
MCH 
MCHC 
%Reticulocytes 
Clinical Chemistry 
ALT/ SGPT 
Albumin 
Phosphate 
ALP 
Potassium 
AST/ SGOT 
Total bilirubin (conjugated and unconjugated 
if clinically indicated) 
BUN 
Direct bilirubin 
Calcium 
Total Cholesterol 
Carbon dioxide (bicarbonate) 
Total Protein 
Chloride 
Triglycerides 
Creatinine 
Uric acid 
Fasting Glucose 
GGT 
HDL Cholesterol 
LDL Cholesterol 
Coagulation 
INR 
aPTT 
Prothrombin time (PT) 
Fibrinogen 
Additional biomarkers 
CPKa 
hs CRP 
CPK-MBa 
Troponin I b 
hs Troponin T b 
LDH 
Urinalysis 
Leucocytes 
RBCs 
Protein 
pH 
Bilirubin 
Nitrite 
Urobilinogen 
Specific gravity 
Ketones 
Glucose 
Microscopy (if clinically indicated) 
Myoglobin 
Viral serology 
HIV I and II 
HCV 
HBsAg 
HBV PCR 
Drugs of abuse and 
alcoholc 
Thyroid profile 
TSH 
Total T4 
T3 
T4 
Total T3 
Glycosylated 
hemoglobin 
HbA1c 
Other screening tests 
Urine β-hCG pregnancy test (as needed for subjects of childbearing potential) 
Study-required laboratory assessments will be performed by local and central laboratories. Table 
14 shows the Safety Laboratory Assessments Performed by Local Laboratories. Table 15 lists the 
protocol required local laboratory collections for Central Laboratory Analysis. 


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Laboratory 
Assessments 
Parameters 
The results of each test must be entered in the eCRF. 
Abbreviations: ALP, alkaline phosphatase; aPTT, activated partial thromboplastin time; AST, aspartate aminotransferase; ALT, 
alanine aminotransferase; β-hCG, beta human chorionic gonadotrophin; BUN, blood urea nitrogen; CPK, creatine 
phosphokinase; CPK-MB, creatinine phosphokinase – muscle brain fraction; GGT, gamma glutamyl transferase; Hb, 
hemoglobin; HBV, Hepatitis B Virus; HCT, hematocrit; HCV, Hepatitis C Virus; HDL, high-density lipoprotein; HIV, Human 
Immunodeficiency Virus; hs-CRP, high sensitivity C-reactive protein; INR, International Normalized Ratio; LDH, lactate 
dehydrogenase; LDL, low-density lipoprotein; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin 
concentration; MCV, mean corpuscular volume; PCR, polymerase chain reaction; PT, prothrombin time; RBC, red blood cell; 
SGOT, serum glutamic-oxaloacetic transferase; SGPT, serum glutamic-pyruvic transaminase; T3, free triiodothyronine; T4, free 
thyroxine; TSH, thyroid stimulating hormone; WBC, white blood cell 
a For safety laboratory assessments performed by the local laboratory, if CPK and CPK-MB are not included together on a single 
panel, then CPK-MB alone can be measured. If CPK and CPK-MB are not included together on a single panel and there is no 
local test available for CPK-MB, then CPK alone may be measured. 
b For local laboratory safety assessments, only one of either Troponin I or hs Troponin T must be included, and the second 
biomarker may be optionally included. 
c Performed as per local standard of practice/guidelines at Screening visit only 


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Table 14 
Schedule of Protocol-required Safety Laboratory Assessments Performed by the 
Local Laboratory 
 
Day 
Time (hours) 
Panel 
Comment 
Screening 
No more than 
45 days prior to 
IP administration 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRP, LDH 
HIV/HBV/HCV 
β-hCG (blood sample) 
Urinalysis 
Thyroid profile 
Day 1 prior to 
IP 
administration 
Upon admission 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Glucose 
Fingerstick 
Urinalysis 
Including urine-based pregnancy dipstick for pre- 
menopausal women 
Day 1 postdose 
End of infusion 
Glucose 
Fingerstick 
4 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Glucose 
Fingerstick 
8 hours postdose 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Glucose 
Fingerstick 
12 hours postdose 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Glucose 
Fingerstick 
2 
24 hours postdose 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Glucose 
Fingerstick 
Urinalysis 
3 
48 hours postdose 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Hematology 
Glucose 
Fingerstick 
4 
72 hours postdose 
Glucose 
Fingerstick 
7 
Chemistrya 
Hematology 
Coagulation 


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Day 
Time (hours) 
Panel 
Comment 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Urinalysis 
15 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I and/or hs Troponin T, 
hsCRPc, LDH 
Urinalysis 
30 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRPc, LDH 
60 
Chemistrya 
Hematology 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRPc, LDH 
90 
Chemistrya 
Hematology 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRP, LDH 
135 
Chemistrya 
Hematology 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRPc, LDH 
180 
Chemistrya 
Hematology 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRPc, LDH 
End-of-study 
(prior to Day 
180 due to 
patient or 
investigator- 
initiated 
withdrawal) 
Chemistrya 
Hematology 
Coagulation 
Additional biomarkers 
CPK b, CPK-MB b, Troponin I c and/or hs Troponin T c, 
hsCRP 
Abbreviations: β-hCG, beta human chorionic gonadotrophin; CPK, creatine phosphokinase; CPK-MB, creatinine phosphokinase 
– muscle brain fraction; hs-CRP, high sensitivity C-reactive protein; LDH, lactate dehydrogenase 
a All clinical chemistries are to be drawn FASTING >10hours. 
b For safety laboratory assessments performed by the local laboratory, if CPK and CPK-MB are not included together on a single 
panel, then CPK-MB alone can be measured. If CPK and CPK-MB are not included together on a single panel and there is no 
local test available for CPK-MB, then the test may be omitted. 
c For local laboratory safety assessments, only one of either Troponin I or hs Troponin T must be included, and the second 
biomarker may be optionally included. 
Investigators must document their review of each laboratory safety report. 
Laboratory results that could unblind any blinded cohort will not be reported to study centers or other 
blinded personnel until the cohort has been unblinded. 


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Table 15 
Schedule of Protocol-required Blood Collections to be Obtained by the Local 
Laboratory for Central Laboratory Analysis 
 
Day 
Sample to be Collected for Central Lab Analysis by the Local 
Laboratory 
Day 1 (Pre-infusion) 
Exploratory biomarkersa / PK / Immunogenicity 
Day 1 (End of infusion [EoI]) 
PK 
Day 1 (0.5 hour from EoI) 
PK 
Day 1 (1 hour from EoI) 
PK 
Day 1 (2 hours from EoI) 
PK 
Day 1 (4 hours from EoI) 
PK 
Day 1 (8 hours from EoI) 
PK 
Day 1 (12 hours from EoI) 
PK 
Day 2 (24 hours from EoI) 
Exploratory biomarkersa / PK 
Day 3 (48 hours from EoI) 
PK 
Day 4 (72 hours from EoI) 
PK / Immunogenicity 
Day 7 
Exploratory biomarkersa / PK / Immunogenicity 
Day 11 
PK 
Day 15 
Exploratory biomarkersa / PK / Immunogenicity 
Day 22 
PK 
Day 30 
Exploratory biomarkersa / PK / Immunogenicity 
Day 60 
Exploratory biomarkersa / PK 
Day 90 
Exploratory biomarkersa / Immunogenicity 
Day 135 
Exploratory biomarkersa 
Day 180 / End of Study Visit 
Exploratory biomarkersa / Immunogenicity 
Abbreviations: EOI, end of infusion; PK, pharmacokinetics 
a BNP, hsCRP, NT-proBNP, Troponin I, hs Troponin T 


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Appendix 4 
Excluded Medications/Therapy 
Excluded medications/therapy is listed below. The use of an excluded medication/therapy is a protocol 
violation and must be recorded in the eCRF. 
• 
Any recombinant neuregulin apart from JK07 
− 
Neucardin and cimaglermin 
• 
Class 1a (including procainamide, quinidine, disopyramide) and Class 3 (including amiodarone, 
sotalol, dofetilide, ibutilide) antiarrhythmics 
• 
Acetaminophen for the period beginning 7 days pre-dose and ending 15 days postdose 
• 
Drugs that are known to prolong QT: 
− 
Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin 
− 
Macrolides: erythromycin, azithromycin, clarithromycin 
− 
Antifungal agents: ketoconazole, itraconazole, pentamidine 
− 
Antipsychotics: thioridazine, haloperidol, droperidol, atypical antipsychotic, 
(e.g., ziprasidone) 
− 
Antidepressants: citalopram, escitalopram 
− 
Antiemetics: dolasetron, droperidol, ondansetron, granisetron 
− 
Others: propofol, chloroquine 
For a complete listing of all prohibited medications, please consider the listed drugs in the following website 
as “known” to prolong QT: 
https://crediblemeds.org/pdftemp/pdf/CombinedList.pdf 


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Appendix 5    2-D TTE Parameters 
• 
LVIDs (mm) 
• 
LVIDd (mm) 
• 
LVIDd diameter/BSA (mm/m2) 
• 
LVIDd diameter/height (mm/m2) 
• 
Septal thickness (cm) 
• 
Posterior Wall thickness (cm) 
• 
Biplane MOD 
• 
LVEDV (mls/m2) 
• 
LVESV (mls/m2) 
• 
LVSV (mls/m2) 
• 
LVEF (%) 
• 
Circumferential Shortening (CS) + EDC-ESC/EDC 
• 
Cardiac Output/Cardiac Index & Stroke Volume (LVOT VTI pulsed wave Doppler method) 
• 
Diastolic Function Grade (E/A ratio, E/E′  ratio) 
• 
Mitral Valve Regurgitation Grade (Quantitative) 
• 
Left Atrial Area and Volume 
• 
Right Ventricular Size and Function 
• 
Tricuspid Valve Regurgitation Velocity 
• 
Peak Mitral Valve Regurgitant Velocity 
• 
Left Ventricular Outflow Tract Doppler Time Velocity Integral 
Abbreviations: BSA, body surface area; CS, circumferential shortening; E/A ratio, ratio of early (E) to late (A) ventricular filling 
velocity; EDC, end diastolic circumference; ESV, end systolic circumference; LV, left ventricular; LVEDV, left ventricular end- 
diastolic volume; LVESV, left ventricular end-systolic volume; LVEF, left ventricular ejection fraction; LVIDd, left ventricular 
internal end-diastolic diameter; LVIDs, left ventricular internal end-systolic diameter; LVOT left ventricular outflow tract; MOD, 
method of disks; SVR, systemic vascular resistance; VTI, ventricular time integral 


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Appendix 6 
Contraceptive Guidance 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless permanently 
sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
Note: Documentation can come from the study center personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or hormonal therapy. 
However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 
b) Females on hormone therapy and whose menopausal status is in doubt will be required to use 1 of 
the non-estrogen hormonal highly effective contraception methods if they wish to continue their 
hormone therapy during the study. Otherwise, they must discontinue hormone therapy to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
Male subjects 
• 
Male subjects with female partners of childbearing potential are eligible to participate if they agree 
to ONE of the following [during the protocol-defined time frame in Section 5.1]: 
− 
Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent for duration 
of study and for no less than 90 days after the administration of study treatment. 
− 
Agree to use a male condom and have their partner use of a contraceptive method with a 
failure rate of <1 % per year as described in Table 16 when having penile- vaginal 
intercourse with a woman of childbearing potential who is not currently pregnant. 
• 
In addition, subjects must refrain from donating sperm for the duration of the study and for no less 
than 90 days after the administration of study treatment. 
• 
Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration during 
the protocol-defined time frame. 


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Female subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly effective 
method of contraception consistently and correctly as described in the table below. 
Table 16 
Highly Effective Contraceptive Methods 
 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1 % per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulationb 
Oral. 
Intravaginal. 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
Oral. 
Injectable. 
Highly Effective Methods That Are User Independent a 
Implantable progestogen only hormonal contraception associated with inhibition of ovulationb 
Intrauterine device (IUD). 
Intrauterine hormone-releasing system (IUS). 
Bilateral tubal occlusion. 
Vasectomized partner 
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male sexual partner of the 
WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be 
used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the study and the preferred and usual lifestyle of the subject. 
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with local 
regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the efficacy of the 
contraceptive method. In this case, 2 highly effective methods of contraception should be utilized during the treatment period 
and for at least 90 days, corresponding to time needed to eliminate study treatment plus 30 days for study treatments with 
genotoxic potential after the last dose of study treatment. 
 
Pregnancy Testing: 
• 
WOCBP should only be included after a confirmed menstrual period and a negative highly sensitive 
urine pregnancy test. 
• 
Additional pregnancy testing should be performed at times specified in the schedule of assessments 
during the treatment period and at timepoints corresponding to protocol-defined time frame in 
Section 5.1 after the dose of study treatment and as required locally. 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is otherwise 
suspected. 


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• 
Pregnancy testing, with a sensitivity of 10 mIU/mL will be performed in a certified laboratory 
and in accordance with instructions provided in its package insert. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is 
always considered to be an SAE and will be reported as such. 
• 
Any post-study pregnancy related SAE considered reasonably related to the study treatment by the 
Investigator will be reported to the Sponsor as described in Section 8.3.10. While the Investigator 
is not obligated to actively seek this information in former subjects, he or she may learn of an SAE 
through spontaneous reporting. 
• 
Any female subject who becomes pregnant while participating in the study will discontinue study 
treatment or be withdrawn from the study. 


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Appendix 7 
Summary of Changes 
Amendment 1: 19February2020 
Rationale for the amendment: 
The main purpose of this amendment is to: 
• Update the Schedule of Activities 
• Revision and update of the Background and Benefit/Risk sections 
• Clarification of blood sampling and volumes for biomarkers, PK, and immunogenicity 
• Update of PK assessment methods and variables 
• Correction of justification for dose 
• Clarification of eligibility criteria and study procedures including discontinuation criteria and 
adverse event relatedness to study drug 
• Update the medical monitor 
• Updates to the document for consistency 
• Minor editorial and grammatical changes 
Where applicable added text is bolded and italicized. Deleted text has strikethrough. 
Section 
Change 
Reason 
Title Page 
JK07 (recombinant fusion protein consisting of a fully human 
anti-human epidermal growth factor receptor 3 [HER3] 
immunoglobin G1 [IgG1] monoclonal antibody and an active 
polypeptide fragment from human neuregulin-1 [NRG-1]) 
Administrative update 
Synopsis and 
Pharmacokinetic parameters of intact JK07 including, but not 
Clarification of PK 
Section 3.0: 
limited to, maximum concentration (Cmax), time to Cmax (tmax), 
assessment 
Objectives and 
area under the concentration-time curve to the last quantifiable 
Endpoints 
concentration and extrapolated to infinity [AUC(0-last) and 
AUC(0-inf)], half-life (t1/2), elimination rate constant (λz), 
systemic clearance (CL), and volume of distribution (Vz). 
Surrogate assessment measurement of intact JK07 stability to 
be evaluated carried out through parallel assays to detect both 
the JK07 antibody domain and the JK07 NRG-1 peptide 
fragment in the evaluation of pharmacokinetic parameters. 
Table 1: SoA, 
new footnote “e” 
All AEs, including SAEs will be collected from the time of study 
enrollment and until 30 days after the IP administration. Following 
the first 30 days, only SAEs deemed at least possibly related to the 
study drug or study procedures should be collected. Refer to Table 9 
for additional details. 
Clarification of AE 
assessment timing 
Section 2.2: 
Background 
Revision of text and 
reference format 
Section 2.3: 
Benefit/Risk 
Assessment 
Revision of text and 
reference format 
Table 1: SoA 
and Section 4.1: 
Study Design 
Day 1: Addition of blood sample collection prior to IP 
administration of baseline myocardial biomarkers, PK and 
immunogenicity assessment. 
Clarification of blood 
sampling 
Section 4.2: 
Deletion of monitoring of MCP-1 (monocyte chemoattractant 
Clarification of biomarkers 
Scientific 
protein), IL-6 (interleukin-6), aldosterone, pro-collagen 5, 
Rationale and 
aldolase, and myoglobin. 
Section 8.8: 
Clarification of the immunoassays to be used for assessment of 
Biomarkers 
JK07 exposure. 


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Section 
Change 
Reason 
Section 4.3: 
Justification of 
Dose 
Cohort dose levels of JK07 are as follows: the clinical starting 
dose of a single 0.03 mg/kg IV infusion has been selected at 
1/3032 of the human equivalent dose at the NOAEL in the 
cynomolgus monkey (3 mg/kg/week). 
Correction 
Section 5.2: 
Exclusion 
Criterion 8 
Sustained systolic blood pressure <100 mm Hg and/or diastolic 
blood pressure <50 mm Hg (confirmed by a duplicate seated 
reading) on at least 3 consecutive readings (self-monitored or 
office) following informed consent and prior to randomization, 
or overt symptomatic hypotension defined as a decrease in 
systolic blood pressure of 20 mm Hg or a decrease in diastolic 
blood pressure of 10 mm Hg within three minutes of standing 
when compared with blood pressure from the sitting or supine 
position or accompanied by dizziness, syncope, blurry vision. 
Clarification 
Section 5.2: 
Exclusion 
Criterion 9 
Sustained Resting heart rate >100 beats per minute (bpm) at 
Screening (Visit 1) or prior to randomization which is sustained 
for >15 minutes in two episodes separated by one hour of 
observation. 
Clarification 
Section 5.3: 
Lifestyle 
Considerations 
Subjects should be in a fasted state (at least 10 hours) at assigned 
or designated times as per the study team for all other visits. 
Addition of fasting prior to 
all visits 
Section 5.3.2: 
Caffeine, 
Alcohol, and 
Tobacco 
CBD products will not be permitted from two weeks prior to IP 
administration until after the final follow-up visit. 
Addition of restriction on 
use of CBD products. 
Section 7.1: 
Discontinuation 
of Study 
Treatment 
If a subject, who does not meet enrollment criteria, is 
inadvertently enrolled, that subject must and the failure to meet 
enrollment criteria is discovered prior to IP administration, the 
subject should be discontinued from the study treatment and the 
Sponsor or Sponsor designee must be contacted. An exception 
mayIf a subject, who does not meet enrollment criteria, is 
inadvertently enrolled in the study and has already received IP 
administration, the subject should be granted in rare 
circumstances for which there is a compelling safety reason to 
allow the subject allowed to continue. In these rare cases, the 
Investigator must obtain documented approval from the Sponsor 
or Sponsor designee to allow the subject to continue in the study 
with the study given that following the single IP administration 
there are no additional treatments and no invasive tests. 
Clarification of 
discontinuation criteria 
Section 8.3.6: 
Relationship to 
Study Drug; 
Table 9 
Relatedness 
Revision of table and definitions 
Clarification of definition of 
degrees of relatedness 
Section 8.5.3: 
Calculation of 
Derivation of 
Pharmacokinetic 
Variables; 
Table 10 
Deletion of RCmax, RAUC(0-inf), and RAUC(0-last) 
Update to PK assessment 
Section 8.8: 
Biomarkers 
Venous blood samples of approximately 1410 mL will be 
collected at several time points 
Clarification of blood 
volume 
Section 11: 
Appendix 1 
Insertion of complete American Cancer Society Guidelines for 
Screening 
Addition 


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Section 
Change 
Reason 
Section 11: 
Appendix 2 
Deletion of Mark Tulchinskiy, MD as medical monitor 
Addition of Neal Salomon, MD as medical monitor 
Administrative update 
 
Amendment 2: 03March2020 
Rationale for the amendment: 
The main purpose of this amendment is to: 
• Update the Schedule of Activities to reflect Day 3 activities and Holter/telemetry monitoring 
• Compliance with regulatory requests regarding inclusion/exclusion criteria and 
Investigational Product expiration 
• Updates to the document for consistency 
• Minor editorial and grammatical changes 
Where applicable added text is bolded and italicized. Deleted text has strikethrough. 
Section 
Change 
Reason 
Section1.3: SoA, 
footnote “a” 
Day 3 marked for in-patient hospital stay and telemetry in 
the Schedule of Activities. Subjects will be scheduled for 
discharge on the morning of Day 3. 
Telemetry monitoring will 
continue until 48 hours after 
completion of IP which 
extends into Day 3. 
Section 1.3: SoA, 
footnote “m” 
Continuous telemetry monitoring will be started as soon as 
practicable after hospital admission on Day1 and prior to IP 
infusion, and will be continued until 48 hours after the end 
of the IP infusion on Day 3. 
Administrative update 
Section 4.2: 
Scientific Rationale 
for Study Design 
Holter/telemetry combination prior to dose administration 
and for 48 hours following dose administration. 
Consistency 
Section 5.1: 
Inclusion Criterion 1 
Male or female adult subjects between 18 and 80 years of 
age, with stable NYHA Class II or III HF diagnosis 
(ischemic or nonischemic confirmed by medical history) at 
least 6 months prior to enrollment. 
Compliance with FDA 
request to make inclusion/ 
exclusion criteria mutually 
exclusive with respect to 
non-ischemic 
cardiomyopathy. 
Section 5.2: 
Exclusion Criterion 3 
Heart failure due to hypertrophic cardiomyopathy, 
restrictive cardiomyopathy, arrhythmogenic right 
ventricular dysplasia (ARVD), stress-induced 
("Takotsubo") cardiomyopathy, chemotherapy-induced 
cardiomyopathy, peripartum cardiomyopathy, infiltrative 
or inflammatory cardiomyopathies, and primary valvular 
disease, in the opinion of their treating cardiologist, to 
etiologies other than ischemic or nonischemic. Examples of 
exclusionary HF etiologies include primary valvular 
disease, infiltrative or inflammatory cardiomyopathies 
Compliance with FDA 
request to make inclusion/ 
exclusion criteria mutually 
exclusive with respect to 
non-ischemic 
cardiomyopathy 
Section 6.1: Table 5 
JK07 infusions will be prepared at the study center for 
administration within 4 6 hours following the dose 
preparation. 
Placebo infusions will be prepared at the study center for 
administration within 4 6 hours following the dose 
preparation. 
Intravenous (IV) infusion over 60 minutes using a syringe 
pump or infusion pump. 
Compliance with FDA 
request to reduce IP hold 
time from six hours to four 
hours. 
Administrative change: To 
provide greater flexibility to 


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Section 
Change 
Reason 
sites in delivering the 
specified infusion volume in 
the allotted time. 
Section 6.2: 
Preparation/ 
Handling/ Storage 
All investigational drug supplies in the study will be stored 
at 2-8 °C -4ºC in a secure place under the responsibility of 
the Investigator or other authorized individual. 
Administrative change: The 
storage temperature was 
incorrectly listed as -4°C, 
which does not allow for 
standard temperature 
variance under refrigeration. 
Table 13: Safety 
Laboratory 
Assessments 
Myoglobin added to the list of analytes for urinalysis 
Administrative update 
Table 14: Schedule 
of Protocol-required 
Safety Laboratory 
Assessments 
Performed by the 
Local Laboratory 
LDH added to the list of additional biomarkers at 
Screening, Day 1 prior to IP administration, Day 1 at 4, 8, 
& 12 hours post dose, Day 2 at 24 hours post dose, Day 3 at 
48 hours post dose, and on Days 7, 15, 30, 60, 90, 135, and 
180. 
Administrative update 


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Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the study center in 
which the study will be conducted. Return the signed copy to Salubris Biotherapeutics, Inc. 
Appendix 8    Signature of Investigator 
PROTOCOL TITLE: A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to 
Assess the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects With Heart Failure With 
Reduced Ejection Fraction (HFrEF) 
PROTOCOL NO:    JK07.1.01 
VERSION: 
Amendment 3 
This protocol is a confidential communication of Salubris Biotherapeutics, Inc. I confirm that I have read 
this protocol, I understand it, and I will work according to this protocol. I will also work consistently with 
the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good 
Clinical Practices and the applicable laws and regulations. Acceptance of this document constitutes my 
agreement that no unpublished information contained herein will be published or disclosed without prior 
written approval from the Sponsor. 
 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
Signature of Investigator: 
  
 
Date:  
 
Printed Name: 
  
 
Investigator Title: 
  
 
 
 
Name/Address of Center: 
 
 
 
 
 
 

SAP_001.pdf: 
 
 
CONFIDENTIAL 
Page 1 of 37 
Salubris Biotherapeutics, Inc. 
Protocol #: JK07.1.01 Amendment 3 
 
A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to 
Assess the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects with Heart 
Failure with Reduced Ejection Fraction (HFrEF) 
 
Statistical Analysis Plan 
 
Version 4.0 
Document last saved: 12-May-2025 11:03 AM 
 
Prepared for: 
Sam Murphy 
Chief Executive Officer 
 
 Salubris Biotherapeutics, Inc 
45 West Watkins Mill Road, Suite E 
Gaithersburg, MD 20878 
 
Prepared by: 
 
Ninon Francois 
            Associate Biostatistician 
 
 
IQVIA Biotech 
 
2400 Ellis Road, Pod A, Level 4 
Durham, NC 27703