A Phase II, Open-Label Safety and Tolerability Study of an Renal Autologous Cell Therapy (REACT) in Patients With Type 2 Diabetes and Chronic Kidney Disease (REGEN-003)
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus, Chronic Kidney Disease
Sponsor: Prokidney



ProKidney 
Renal Autologous Cell Therapy (REACT)  
REGEN-003 v1.7 
Confidential 
Page 3 
12 January 2021 
 
 
 
 
PROTOCOL SYNOPSIS 
Title: A PHASE II, OPEN-LABEL SAFETY AND TOLERABILITY STUDY OF A 
RENAL AUTOLOGOUS CELL THERAPY (REACT) IN PATIENTS WITH 
TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (REGEN-003) 
Therapeutic Product:  REACT is made from expanded autologous selected renal cells 
(SRC) obtained from each individual subject’s kidney biopsy. To manufacture REACT, 
kidney biopsy tissue from each enrolled subject will be sent to ProKidney, where renal cells 
will be expanded and SRC selected. SRC will be formulated in a gelatin-based hydrogel at a 
concentration of 100 x 106 cells/mL, packaged in a 10 mL syringe, and shipped to the 
clinical site for use. 
Study Objectives: 
Primary Objective: The primary objective of the study is to assess the safety of 
REACT injected in one recipient kidney. 
• Primary Outcome Measures:  procedure and/or product related adverse events 
(AEs) through 24 months post-injection. 
Secondary Objective: The secondary objective of the study is to assess the safety and 
tolerability of REACT administration by assessing renal-specific AEs over a 24-month 
period following injection. 
• Secondary Outcome Measures:  renal-specific laboratory assessments through 24 
months post-injection. 
Exploratory Objective: Exploratory objectives of the study are designed to assess the 
impact of REACT on renal function over a 24-month period following injection and on the 
Quality of Life. 
• Exploratory Outcome Measures: 1) clinical diagnostic and laboratory 
assessments of renal structure and function (including eGFR, serum creatinine, 
and proteinuria) to assess changes in the rate of progression of renal disease, 2) 
patient-reported outcomes from the Kidney Disease Quality of Life (KDQOL) 
and EQ-5D-5L surveys obtained at baseline (i.e., after randomization, but before 
REACT injection) through 24 months after the last REACT injection. 
Study Design: Multi-center, prospective, open-label, single-group study. All subjects will 
be treated with two REACT injections 6 months (+4 weeks) apart after biopsy. 
Randomization: Open-label, non-randomized. 
Control Group: Each subject will serve as his or her own control; the patient’s previous 
medical history, which must include a minimum 6-month period of observation of renal 
function, will serve as the control for rate of progression of renal insufficiency. 
Sample Size: Up to 10 patients will be treated with REACT. As this is a Phase II safety study, 
robust statistical analysis will not be performed. Therefore, the sample size proposed for this 
study is a size typical for in Phase 1 studies, allowing for identification of safety outcomes in 
a limited population. 
Study Population: Male or female patients 30 to 65 years of age with CKD and eGFR 
between 14 and 20 mL/min/1.73m2. Patients should have sufficient historical clinical data to 
determine their individual rate of CKD disease progression. 

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Inclusion Criteria: Unless otherwise noted, subjects must satisfy each inclusion criterion to 
participate in the study. Inclusion criteria will be assessed at the Screening Visit, prior to 
renal biopsy, and before each REACT injection unless otherwise specified. 
1. 
The subject is male or female, 30 to 65 years of age on the date of informed 
consent. 
2. 
The subject has an established diagnosis of T2DM. 
3. 
The subject has an established diagnosis of diabetic nephropathy as the underlying 
cause of renal disease. 
4. 
The subject has an established diagnosis of CKD not requiring renal dialysis, 
defined as having an eGFR between 14 and 20 mL/min/1.73m2 inclusive at the 
Screening Visit and prior to REACT injection. 
5. 
The subject has blood pressure less than 150/90 at the Screening Visit, prior to 
renal biopsy, and prior to REACT injection(s). At the time of the biopsy and 
injections, the subject’s BP should not be significantly below the previously 
recorded stable pressure. 
6. 
The subject has stable blood pressure and is maintained on a stable anti-
hypertensive medication regimen, if treatment for hypertension is necessary. If 
treatment includes an angiotensin-converting-enzyme inhibitor (ACEI) or an 
angiotensin receptor blocker (ARB), that treatment must have been initiated at 
least 8 weeks prior to renal biopsy. Treatment must be stable during the 6-week 
period immediately prior to REACT injection. Stable treatment is defined as dose 
adjustment to no less than one half of the current dosage or to no more than 2 times 
the current dosage. Dose interruptions up to 7 days due to medical necessity are 
allowed.  
7. 
A minimum of 3 measurements of eGFR or sCr should be obtained at least 3 
months apart prior to the Screening Visit or within the previous 24 months to 
define the rate of progression of CKD. The subject should have adequate, 
historical clinical data to provide a reasonable estimate of the rate of progression of 
CKD. The Medical Monitor may be consulted to ensure there is sufficient data. 
8. 
The subject is willing and able to refrain from NSAID consumption (including 
aspirin) as well as clopidogrel, prasugrel, or other platelet inhibitors during the 
period beginning 7 days before through 7 days after both the renal biopsy and 
REACT injection(s). 
9. 
The subject is willing and able to refrain from consumption of fish oil and platelet 
aggregation inhibitors, such as dipryridamole (i.e., Persantine®), during the period 
beginning 7 days before through 7 days after both the renal biopsy and REACT 
injection(s). 
10. The subject is willing and able to cooperate with all aspects of the protocol. 
11. The subject is willing and able to provide signed informed consent. 
 
Exclusion Criteria:  Subjects who satisfy any exclusion criterion listed below are not 
eligible to participate in the study. Exclusion criteria will be assessed at the Screening Visit, 
before renal biopsy, and before each REACT injection unless otherwise noted. 
1. 
The subject has a history of type 1 diabetes mellitus. 
2. 
The subject has a history of renal transplantation. 
3. 
The subject has a serum HbA1c level greater than 10% at the Screening Visit. 

ProKidney 
Renal Autologous Cell Therapy (REACT)  
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12 January 2021 
 
 
4. 
The subject has uncontrolled diabetes (defined as metabolically unstable by the 
Investigator). 
5. 
The subject has hemoglobin levels less than 9 g/dL prior to each REACT 
injection. 
6. 
The subject has abnormal coagulation status as measured by activated partial 
thromboplastin time (APTT), prothrombin time international normalized ratio (PT 
INR), and/or platelet count at the Screening Visit. 
7. 
The subject has a bleeding disorder(s) or is taking anticoagulants, such as 
Coumadin® (warfarin) or direct thrombin inhibitors that, in the judgment of the 
Investigator, would interfere with the performance of study procedures. 
8. 
The subject has small kidneys (average size less than 9 cm) or has only one 
kidney, as assessed by ultrasound and/or MRI prior to renal biopsy, unless earlier 
radiology reports (generated within 1 year of the Screening Visit) are made 
available to confirm kidney size and number. 
9. 
The subject has a known allergy or contraindication(s), or has experienced severe 
systemic reaction(s) to kanamycin or structurally similar aminoglycoside 
antibiotic(s) 
10. 
The subject has a history of anaphylactic or severe systemic reaction(s) or 
contraindication(s) to human blood products or materials of animal origin (e.g., 
bovine, porcine). 
11. 
The subject is not a good candidate to undergo percutaneous REACT injection, in 
the judgment of the surgeon or physician who will perform the procedure. This 
includes individuals who are morbidly obese (defined as BMI greater than 
45 kg/m2), have excessive fat surrounding the kidney, or who are otherwise at 
excessive risk for serious complications. 
12. 
The subject has a history of severe systemic reaction(s) or any contraindication to 
local anesthetics or sedatives. 
13. 
The subject has a clinically significant infection requiring parenteral antibiotics 
within 6 weeks of REACT injection. 
14. 
The subject has acute kidney injury or has experienced a rapid decline in renal 
function during the last 3 months prior to REACT injection. 
15. 
The subject has any of the following conditions prior to REACT injection:  renal 
tumors, polycystic kidney disease, anatomic abnormalities that would interfere 
with the REACT injection procedure or evidence of a urinary tract infection. 
Note: anatomic abnormalities are not exclusionary if the kidney remains 
accessible and meets the criteria to receive the REACT injection. 
16. 
The subject has incapacitating cardiac and/or pulmonary disorders. 
17. 
The subject has a history of cancer within the past 3 years (excluding non-
melanoma skin cancer and carcinoma in situ of the cervix). 
18. 
The subject has clinically significant hepatic disease (ALT or AST greater than 3 
times the upper limit of normal) as assessed at the Screening Visit. 
19. 
The subject is positive for active infection with Hepatitis B Virus (HBV), or 
Hepatitis C Virus (HCV), and/or Human Immunodeficiency Virus (HIV) as 
assessed at the Screening Visit. 
20. 
The subject has a history of active tuberculosis (TB) requiring treatment within 
the past 3 years. 

ProKidney 
Renal Autologous Cell Therapy (REACT)  
REGEN-003 v1.7 
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12 January 2021 
 
 
21. 
The subject is immunocompromised or is receiving immunosuppressive agents, 
including individuals treated for chronic glomerulonephritis within 3 months of 
REACT injection. 
Note: inhaled corticosteroids and chronic low-dose corticosteroids (less than or 
equal to 7.5 mg per day) are permitted as are brief pulsed corticosteroids for 
intermittent symptoms (e.g., asthma). 
22. 
The subject has a life expectancy less than 2 years. 
23. 
The female subject is pregnant, lactating (breast feeding), or planning a pregnancy 
during the course of the study. Or, the female subject is of child-bearing potential 
and is not using a highly effective method(s) of birth control, including sexual 
abstinence. Or, the female subject is unwilling to continue using a highly effective 
method of birth control throughout the duration of the study. 
Note: A highly effective method of birth control is defined as one that results in a 
low failure rate (i.e., less than one percent per year) when used consistently and 
correctly, such as implants, injectables, combined oral contraceptives, some 
intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner. 
24. 
The subject has a history of active alcohol and/or drug abuse that, in the judgment 
of the Investigator, would impair the subject’s ability to comply with the protocol. 
25. 
The subject’s health status would, in the judgment of the Investigator, be 
jeopardized by participating in the study. 
26. 
The subject has used an investigational product within 3 months prior to REACT 
injection without receiving written consent from the Medical Monitor. 
Number of Sites:  Up to 10 clinical centers will be included in the study. 
Study Duration: treatment to begin as soon as the REACT product is made available and 
assuming a one-month interval prior to receiving the first REACT injection, and assuming a 
6-month interval before receiving the second injection, plus a 24 month follow up period 
after the final injection, the duration of treatment would be: 
- 
31 months for a series of 2 REACT injections 
Study Enrollment: up to 10 subjects will be enrolled into the study. Patients who complete 
screening procedures satisfying all I/E criteria will be enrolled into the study immediately 
prior to the biopsy.  Patients who do not meet all criteria before the biopsy is taken will be 
considered screen failures.  Patients who have a biopsy but are not injected for whatever 
reason will be discontinued from the study and may be replaced. Once a patient has been 
injected, the patient will have completed treatment and every effort should be made to 
ensure the patient completes all follow-up visits. 
Investigational Plan: 
Screening: Subjects who satisfy eligibility criteria and provide written informed consent 
may be entered into the study. The subject should have adequate, historical clinical data to 
provide a reasonable estimate of the rate of progression of CKD (re: Inclusion 7). Screening 
procedures include a full physical exam, ECG, and laboratory assessments (hematology, 
clinical chemistry, and urinalysis). An ultrasound will be performed to confirm the presence 
of two kidneys with normal anatomic features. A MRI study will determine kidney size and 
volume. 
Renal Biopsy:  Three days or less before undergoing renal biopsy, enrolled subjects will 
report to the clinic and undergo an interim physical exam along with an ECG and renal MRI 
(if not completed during or after the Screening Visit). Laboratory tests, including renal 

ProKidney 
Renal Autologous Cell Therapy (REACT)  
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function, hemoglobin, and a pregnancy test for females will also be performed. Eligible 
subjects satisfying all inclusions and exclusion criteria will be admitted to the hospital / 
clinical research center to undergo a kidney biopsy. A minimum of 2 tissue cores measuring 
at 1.5cm a piece must be collected using a 16-gauge biopsy needle to provide sufficient 
material for the manufacture of REACT. Subjects who do not experience complications 
from the biopsy may be discharged the same day consistent with site standard practice. Each 
individual subject’s kidney biopsy tissue will be sent to ProKidney. 
REACT Injection:  Ten to 14 days before the scheduled injection date, subjects will 
undergo an interim physical exam for ongoing verification of inclusion and exclusion 
criteria. Subjects also will undergo renal scintigraphy (i.e., split kidney function scan) to 
find out what percentage each kidney contributes to total baseline kidney function. On the 
day of the scheduled REACT injection, eligible subjects will be admitted into the hospital / 
clinical research unit. After warming to liquefy the hydrogel, REACT will be injected into 
the same kidney that was previously biopsied using a percutaneous approach. This 
procedure will follow a standardized technique, such as that used in the ablation of renal 
masses by radiofrequency or cryogenic methods. Subjects without complications may be 
discharged the same day consistent with site standard practice. An ultrasound will be 
performed the day after injection to detect possible, subclinical AEs. It is anticipated that all 
subjects will receive 2 REACT injections given 6 months (+4 weeks) apart. The first and 
second injections will occur in the same kidney in which the biopsy was taken. Therefore, 
only one kidney will be used for the duration of this study. 
Follow-up: Subjects will complete follow-up evaluations on Days 1, 7, 14, 28 (± 3 days) 
and Months 2, 3, 4 and 5 (± 7 days) after the first REACT injection, and on Days 1, 7, 14, 
28 (± 3 days) and Months 2 and 3 (± 7 days) after the second REACT injection. Depending 
on when the second injection is administered (i.e., at 6 months [+4 weeks]), subjects may 
undergo evaluations at 6 months after the first REACT injection. Following the final 
REACT injection, subjects will complete long-term, follow-up assessments of safety and 
efficacy through 6, 9, 12, 15-, 18-, 21-, and 24-months post-treatment. 
Safety Monitoring:  Hemorrhage following REACT injection is a known and foreseeable 
risk to subjects participating in this study. Therefore, hemoglobin will be measured by the 
site’s local laboratory at the following times: a) before, b) after procedure per site standard 
practice. 
 Investigational Product, Dosage and Mode of Administration: 
Investigational Product:  REACT is made from expanded autologous selected renal cells 
obtained from each individual subject’s kidney biopsy. To manufacture REACT, biopsy 
tissue from each enrolled subject will be sent to ProKidney, in whose facilities renal cells 
will be expanded and SRC selected. SRC will be formulated in a gelatin-based hydrogel at 
a concentration of 100 x 106 cells/mL, packaged in a 10 mL syringe, and shipped to the 
clinical site. 
Dosage: The volume of REACT to be administered will be determined by pre-procedure 
MRI volumetric 3D evaluation or ellipsoid formula (Length x width AP plane x width 
Transverse plan x .62). Based on pre-clinical data, the dose of REACT will be 3 x 106 
cells/g estimated kidney weight (g KWest). Since the concentration of SRC per mL of 
REACT is 100 x 106 cells/mL, the dosing volume will be 3.0 mL for each 100 g of kidney 
weight. Using this dosing paradigm, the following table shows the dosing volume and 
number of SRC to be delivered relative to estimated kidney weight. The maximum volume 
of REACT injected into the biopsied kidney will be 8.0 mL. 
 

ProKidney 
Renal Autologous Cell Therapy (REACT)  
REGEN-003 v1.7 
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Estimated 
Kidney Weight (g KWest)* 
Dosing 
Volum
e (mL) 
SRC Delivered 
(Number of Cells x 
106) 
Median Weight 
(g) 
Weight Range (g) 
100 
95 – 108 
3.0 
300 
117 
109 – 125 
3.5 
350 
133 
126 – 141 
4.0 
400 
150 
142 – 158 
4.5 
450 
167 
159 – 175 
5.0 
500 
183 
176 – 191 
5.5 
550 
200 
192 – 208 
6.0 
600 
217 
209 – 225 
6.5 
650 
233 
226 – 241 
7.0 
700 
250 
242 – 258 
7.5 
750 
― ― ― 
>259 
8.0 
800 
*Kidney weight will be estimated from the results of an MRI study performed on or after the Screening Visit until Day 
0 (renal biopsy). 
Investigational Product, Dosage and Mode of Administration:  Dosage (continued) 
It is anticipated that all subjects will receive two planned REACT injections to allow dose- 
finding and evaluate the duration of effects. The first and second injections will occur in the 
same kidney in which the biopsy was taken. In some cases, a subject or the Investigator may 
decide to postpone or withhold the second REACT injection. For example, if there appears 
to be any untoward safety risk, or rapid deterioration of renal function, or the development 
of uncontrolled diabetes or uncontrolled hypertension, or the development of a malignancy 
or an intercurrent infection, then the second REACT injection should not be administered. 
Mode of Administration:  REACT will be injected into the biopsied kidney using a 
percutaneous approach. The percutaneous method will employ a standardized technique 
(such as that utilized in the ablation of renal masses by radiofrequency or cryogenic 
methods). 
Data Safety Monitoring Board:  A Data Safety Monitoring Board (DSMB) will be 
chartered to oversee subject safety, especially as it relates to unexpected investigational 
product-related events. The DSMB will minimally consist of 3 members who have expertise 
directly related to protocol-specified activities. It will function independently, and its 
members will have no other engagement with ProKidney. The DSMB will meet by 
teleconference at regular intervals, depending on the speed of subject enrollment and the 
amount of new data generated. The DSMB will advise ProKidney on aspects concerning the 
safety of subjects participating in the clinical trial. Apart from reviewing study data, the 
DSMB will consider feedback from the Sponsor and Investigators. The DSMB will share its 
recommendations with the study centers, Institutional Review Boards/Ethics Committees, 
and regulatory authorities, as appropriate. Other specific activities and responsibilities of the 
DSMB will be detailed in the DSMB charter. 

ProKidney 
Renal Autologous Cell Therapy (REACT)  
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Statistical Analysis Methods:  Statistical analyses will be primarily descriptive in nature 
and no statistical hypothesis testing is planned for the study. Unless otherwise specified, 
continuous variables will be summarized by presenting the number of non-missing 
observations (n), mean, standard deviation, median, minimum, and maximum. Categorical 
variables will be summarized by presenting frequency count and percentage for each 
category. 
 

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Table 1: 
Time and Events Table 
Clinical Assessment: 
Screening 
Visit 
Renal Biopsy 
Optional* 
Preparation and Shipment of REACT Product 
First 
REACT 
Injection 
Follow-up 
First 
REACT 
Injection 
Optionalb 
Last 
REACTc 
Injection 
Follow-up 
Last 
REACT 
Injection 
Follow-Up 
Long-Term 
Day 
- 60 to -3a 
Day 
-3 to -1 
Day 0 
Biopsy 
Day 1 
Follow-up 
Day 
–14 to – 10 
Day 0 
REACT 
j
i
Day 1 
Follow-up 
Day 7 
(±) 3 days 
Day 14 
(±) 3 days 
Day 28 
(±) 3 day 
Months 2, 3, 4, 
and 5 
(±) 7 days 
Month 6 
(±) 7 days 
Interval Between REACT Injections = 6 Months (+) 4 Weeks** 
Day** 
–14 to – 10 
Day 0 
REACT 
Injection
Day 1 
Follow-up 
Day 7 
(±) 3 days 
Day 14 
(±) 3 days 
Day 28 
(±) 3 days 
Month 2 
Month 3 
(±) 7 days 
Months 6, 9, 
12,15,18, 21 
(±) 7 days 
EOSd 
Month 24 
(±) 7 days 
Obtain Informed Consente 
X 
 
Verify I/E Criteria 
X 
X 
X 
X 
X 
X 
X 
 
Obtain Demographic Data 
X 
 
Obtain Medical History 
X 
X 
 
Record ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Perform Comprehensive PEf 
X 
 
Perform Interim PEf 
X 
X 
X 
X 
X 
X 
X 
Measure Vital Signsg 
X 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
X 
X 
X 
Conduct Laboratory Testsi 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Perform 12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
Perform Ultrasound 
Xj 
Xk 
Xk 
Xj 
Xk 
Xk 
Xj 
Xk 
Xk 
 
Xj 
Perform MRI Study 
 Xl 
 
 
X 
Perform Renal Scintigraphy 
Xm 
Xm 
Xm 
Xm 
Admit to Hospital 
Xp 
Xp 
Xp 
 
Perform Kidney Biopsy 
X 
 
Monitor /Record AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inject Autologous REACT 
Xn 
Xn 
 
CT Scano 
X 
X 
 
Discharge 
Xp 
Xp 
Xp 
 
Funduscopic Exam of Retinae 
X 
Xq 
X 
Administer KDQOL Survey 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Administer EQ-5D-5L Survey 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Abbreviations: AE (adverse event); ConMeds (concomitant medications); DSMB (Data Safety and Monitoring Board); ECG (electrocardiogram); EOS (End-of-Study Visit); I /E 
(inclusion /exclusion); KDQOL (Kidney Disease Quality of Life Survey); MRI (magnetic resonance imaging); REACT (Renal Autologous Cell Therapy); PE (physical 
examination). 
 
Notes: 
* Day 1follow-up visit should only be conducted if there is a safety event identified during or after the kidney biopsy. 
**Every attempt should be made to ensure the second REACT injection is administered 6 months (+4 weeks) after the first injection. In the event that the subject cannot schedule 
his/her second REACT injection 6 months after receiving the first injection or cannot keep his/her scheduled 6-month visit, ProKidney and the Medical Monitor must be 
notified immediately. The expectation is that the subject and the clinical center will accommodate the Sponsor’s preference that the series of 2 REACT injections should be 
administered no more than 6 months apart. 
a. If the screening assessment falls outside of the 60-day window before renal biopsy, re-screening will be performed as described in Screening (Section 6.1). 
b. Because the second REACT injection will occur 6 months (+4 weeks) after the first injection, the 6-month visit may not be scheduled. 
c. In the event that a second REACT injection will not be administered, the subject will undergo all follow-up assessments after the last REACT injection at the 24-month EOS 
Visit. 
d. The EOS Visit will take place 24 months after the last REACT injection, or when the subject is terminated from the study by the Investigator (Section 8.6) or when the 
subject voluntarily discontinues from the study (Section 5.4). 
e. The Informed Consent Form must be signed and dated prior to conducting any study-specific procedures, including those at the Screening Visit. Signing the Informed Consent 
Form starts the 60-day timeline for screening. 
f. The PE and interim PE are described in Section 7.2.2. 
g. Vital signs include heart rate, resting blood pressure, respiration rate, and body temperature. (Section 7.2.1). At the Pre-Biopsy Visit (Day -3 to Day -1) and the Pre-Injection Visit 
(Day -14 to Day -10) three BP measurements will be taken and the average will be used to satisfy entry criteria. 
h. Vital signs (included are heart rate, blood pressure, and respiration rate) will be measured throughout the procedure. Temperature is not required to be recorded throughout the 
procedure. 
i. Refer to Table 2 for a schedule of laboratory assessments. 
j. Ultrasound will be performed at the Screening Visit to verify subject eligibility and to obtain baseline echogenicity reading. Subsequent Ultrasounds will monitor echogenicity. 
k. Ultrasound will be performed following the in-patient renal biopsy on Day 0 and Day 1, and following the in-patient REACT injection(s) on Day 0 and Day 1 with the 
aim of monitoring possible, subclinical AEs. 
l. A MRI study without contrast will be performed at the Screening Visit through Day -1 before renal biopsy to determine kidney size and volume.  
m. Renal scintigraphy will be performed before the first REACT injection, before the last REACT injection, at the 6-Month Visit after the last REACT injection, at the 12-Month 
Visit after the last REACT injection, and at the month 24/EOS Visit. 
n. The REACT preparation will be handled and injected according to procedures described in the Study Reference Manual. 
o. CT Scan must be used in conjunction with ultrasound for the REACT injection procedure. 
p. Subjects may be admitted to hospital per site standard practice. Subjects who do not experience complications may be discharged the same day consistent with site standard 
practice. 
q. Subjects will undergo a funduscopic exam with retinal photography of both retinae to monitor diabetic retinopathy at screening, month 12, and month 24/EOS visit. 

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Table 2: 
Laboratory Time and Events Table 
Laboratory Evaluation: 
Screening 
Visit 
Renal 
Biopsy 
Optional* 
Preparation and Shipment of REACT Product  
First 
REACT 
Injection 
Follow-up 
First 
REACT 
Injection 
Optionalb 
Interval Between REACT Injections  =  6 Months (+) 4 Weeks** 
Last 
REAC
Tc 
Injection 
Follow-up 
Last 
REACT 
Injection 
Follow-up 
Long-Term 
Day  
-60 to -3a 
Day  
-3 to -1 
Day 0 
Biopsy 
Day 1 
Follow-up 
Day 
-14 to - 10 
Day 0 
REACT Injection 
Day 1 
Follow-up 
Day 14 
 (±) 3 days 
Day 28 
(±) 3 days 
Months 2, 3, 4,  
and 5 
(±) 7 days 
Month 6 
(±) 7 days  
Day** 
- 14 to -10 
Day 0 
REACT Injection 
Day 1 
Follow-up 
Day 14 
(±) 3 days 
Day 28 
(±) 3 days 
Month 2 
Month 3 
(±) 7 days 
Months 6, 9, 12, 
15, 18, 21 
(±) 7 days 
EOSd 
Month 24 
(±) 7 days 
Clinical Chemistry 
Standard panel 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Renal analytes 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panel 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Pregnancy teste 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
FSH testf 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology 
HIV, HBV, HCV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
 
Standard cell counts/indices 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Hemoglobin, Hematocritg 
 
 
Xh 
 
 
Xh 
 
 
 
 
 
 
Xh 
 
 
 
 
 
 
Coagulation Status 
Platelet count 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
APTT 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
PT-INR 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Urine Collection 
Standard panel (Micro and 
Macro) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Chemistry 
 
X 
 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
24-hour 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
X 
X 
Test stick (Spot Urine) 
 
Xi 
Xi 
Xi 
Xi 
Xi 
Xi 
 
 
 
X 
Xi 
Xi 
Xi 
 
 
 
 
 
Additional Tests 
HbA1c 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Drugs of abuse 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
iPTH 
X 
X 
X 
 
 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
ß2-microglobulinj 
X 
X 
X 
 
 
 
X 
 
X 
X 
 
 
 
X 
 
X 
X 
NGAL 
X 
X 
X 
 
 
 
X 
X 
X 
X 
 
 
 
X 
 
X 
X 
Research (reserve) samplesk 
X 
X 
X 
 
 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 

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Abbreviations: APTT (Activated Partial Thromboplastin Time); FSH (Follicle Stimulating Hormone; HbA1c (glycosylated hemoglobin); HIV (Human Immunodeficiency Virus); 
HBV (Hepatitis B Virus); HCV (Hepatitis C Virus); NGAL (Neutrophil Gelatinase-Associated Lipocalin); REACT (Renal Autologous Cell Therapy); i PTH (Parathyroid 
Hormone, intact); PT-INR (Prothrombin Time-International Normalized Ratio) 
Notes: 
* Day 1 follow-up visit should only be conducted if there is a safety event identified during or after the kidney biopsy.
**Every attempt should be made to ensure the second REACT injection is administered 6 months (+ 4 weeks) after the first injection. In the event that the subject cannot schedule
his/her second REACT injection 6 months after receiving the first injection, or cannot keep his/her scheduled 6-month visit, ProKidney and the Medical Monitor must be 
notified immediately. The expectation is that the subject and the clinical center will accommodate the Sponsor’s preference that the series of 2 REACT injections should be 
administered no more than 6 months apart. 
a. If the screening assessment falls outside of the 60-day window before renal biopsy, re-screening will be performed as described in Screening (Section 6.1).
b. Because the second REACT injection will occur 6 months (+4 weeks) after the first injection, the 6-month visit may not be scheduled.
c. In the event that a second REACT injection will not be administered, the subject will undergo all follow-up assessments after the last REACT injection at the 24-month EOS 
Visit.
d. The EOS Visit will take place 24 months after the last REACT injection, or when the subject is terminated from the study by the Investigator (Section 8.6), or when the 
subject voluntarily discontinues from the study (Section 5.4).
e. The clinic will perform a urine dip-strip pregnancy test. If positive, then a confirmatory test will be performed by the central laboratory.
f. Post-menopausal women with a confirmatory FSH test do not have to undergo pregnancy testing throughout the study.
g. Within 48 hours before Days 0 for renal biopsy and REACT injection(s), hemoglobin levels will be verified as > 9 g/dL per site standard practices.
h. On Days 0 for renal biopsy and REACT treatment (s), hemoglobin and hematocrit will be measured before and after procedure per site standard practice at the local lab. These 
samples will be processed by the site’s local laboratory to accelerate notification of results and subsequent decisions affecting clinical care. Additionally, blood samples for 
hemoglobin and hematocrit after procedure will be sent to the central laboratory where results can be entered into the study database.
i. Prior to, day of, and day after biopsy and REACT injection(s), microscopic urinalysis will be performed using a dip (test) stick
j. β2-microglobulin will be assessed in both serum and urine samples.
k. Research samples (serum/plasma and urine) will be collected, frozen, and stored for the evaluation of novel biomarkers.

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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ................................................................................................................ 3 
TABLE OF CONTENTS ............................................................................................................ 14 
LIST OF TABLES ........................................................................................................................ 19 
LIST OF FIGURES ....................................................................................................................... 19 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................... 20 
1. 
INTRODUCTION AND BACKGROUND............................................................... 22 
1.1. 
Chronic Kidney Disease............................................................................................. 22 
1.1.1. 
Background ................................................................................................................ 22 
1.1.2. 
Progressive Staging of CKD ...................................................................................... 22 
1.1.3. 
Standard-of-Care in CKD .......................................................................................... 23 
1.2. 
Scientific Rationale .................................................................................................... 23 
1.3. 
Non-clinical Pharmacology Studies ........................................................................... 24 
1.3.1. 
Pharmacodynamics .................................................................................................... 24 
1.3.2. 
Safety Pharmacology ................................................................................................. 25 
1.3.2.1. 
Extra-Renal Activity .................................................................................................. 25 
1.3.2.2. 
Hemodynamic Effects ................................................................................................ 25 
1.3.2.3. 
Dose Volume.............................................................................................................. 26 
1.3.3. 
Kinetics, Migration, and Persistence.......................................................................... 26 
1.3.3.1. 
ZSF-1 Rat ................................................................................................................... 26 
1.3.3.2. 
Porcine Non-GLP Analysis of Non-Renal Tissue ..................................................... 26 
1.3.3.3. 
Canine Non-GLP Analysis of Non-Renal Tissue ...................................................... 27 
1.3.3.4. 
Conclusions ................................................................................................................ 27 
1.4. 
Toxicology Studies .................................................................................................... 27 
1.4.1. 
ZSF-1 Rat Single Dose Study .................................................................................... 27 
1.4.1.1. 
Renal-Related Findings .............................................................................................. 27 
1.4.1.2. 
Non-Renal Findings ................................................................................................... 28 
1.4.1.3. 
Clinical Pathology ...................................................................................................... 28 
1.4.1.4. 
Conclusions: ............................................................................................................... 28 
1.4.2. 
Initial Single Dose Canine Study ............................................................................... 28 
1.4.2.1. 
General Results .......................................................................................................... 28 
1.4.2.2. 
Renal-Related Results ................................................................................................ 28 
1.4.2.3. 
Non-Renal Findings ................................................................................................... 28 

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1.4.2.4. 
Procedure-Related Findings ....................................................................................... 29 
1.4.2.5. 
Conclusions ................................................................................................................ 29 
1.4.3. 
Repeat Dose Canine Study ......................................................................................... 29 
1.4.3.1. 
Study Results.............................................................................................................. 29 
1.4.3.2. 
Kidney-Related Findings ........................................................................................... 29 
1.4.3.3. 
Non-Kidney Related Findings ................................................................................... 30 
1.4.3.4. 
Conclusions ................................................................................................................ 30 
1.5. 
Non-clinical Conclusions ........................................................................................... 30 
1.6. 
Phase 1 Clinical Trial: Interim Results ...................................................................... 30 
1.6.1. 
Background ................................................................................................................ 30 
1.6.2. 
Adverse Events .......................................................................................................... 31 
1.6.3. 
Estimated Glomerular Filtration Rate (eGFR) ........................................................... 31 
1.6.4. 
Serum Creatinine........................................................................................................ 32 
1.6.5. 
Hemoglobin ................................................................................................................ 34 
1.6.6. 
Blood Pressure ........................................................................................................... 34 
1.7. 
Potential Risks............................................................................................................ 34 
1.7.1. 
Potential Risks Associated with Renal Biopsy .......................................................... 34 
1.7.2. 
Potential Risks Associated with REACT Product ..................................................... 35 
1.7.3. 
Potential Risks Associated with REACT Treatment ................................................. 35 
1.8. 
Potential Benefits ....................................................................................................... 36 
2. 
PHASE II TRIAL OBJECTIVES AND PURPOSE .................................................. 37 
2.1. 
Primary Objective ...................................................................................................... 37 
2.2. 
Secondary Objective .................................................................................................. 37 
2.3. 
Exploratory Objective ................................................................................................ 37 
3. 
INVESTIGATIONAL PRODUCT ............................................................................ 38 
3.1. 
Description of Study Drug ......................................................................................... 38 
3.2. 
Procurement and Manufacture of REACT ................................................................. 38 
3.2.1. 
Biopsy ........................................................................................................................ 38 
3.2.2. 
Selection of SRC ........................................................................................................ 38 
3.2.3. 
Formulation ................................................................................................................ 39 
3.2.4. 
REACT Product for Injection .................................................................................... 39 
3.2.5. 
REACT Dose ............................................................................................................. 39 
3.2.5.1. 
Rationale for Two REACT Injections ....................................................................... 40 
3.2.5.2. 
Safety of Two REACT Injections .............................................................................. 41 

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3.3. 
Study Drug Packaging ............................................................................................... 41 
3.4. 
Study Drug Label ....................................................................................................... 42 
3.5. 
Study Drug Transportation......................................................................................... 43 
3.5.1. 
Study Drug Accountability ........................................................................................ 43 
3.5.2. 
Study Drug Handling and Disposal ........................................................................... 44 
3.5.2.1. 
Disposition of Stored Specimens ............................................................................... 44 
3.5.2.2. 
Unused Specimens ..................................................................................................... 44 
4. 
INVESTIGATIONAL PLAN .................................................................................... 45 
4.1. 
Study Administrative Structure .................................................................................. 45 
4.2. 
Overall Study Design ................................................................................................. 45 
4.3. 
Number of Subjects .................................................................................................... 47 
4.4. 
Treatment Compliance ............................................................................................... 47 
4.5. 
Study Duration ........................................................................................................... 47 
5. 
STUDY POPULATION ............................................................................................ 48 
5.1. 
Subject Inclusion Criteria ........................................................................................... 48 
5.2. 
Subject Exclusion Criteria ......................................................................................... 49 
5.3. 
Prohibited and Concomitant Medications .................................................................. 50 
5.4. 
Subject Withdrawal Criteria ....................................................................................... 51 
6. 
STUDY VISITS ......................................................................................................... 52 
6.1. 
Screening .................................................................................................................... 52 
6.2. 
Biopsy ........................................................................................................................ 52 
6.3. 
REACT Injection ....................................................................................................... 53 
6.4. 
Discharge After REACT Injection ............................................................................. 54 
6.5. 
Follow-up Visits ......................................................................................................... 54 
6.6. 
End-of-Study Visit ..................................................................................................... 54 
6.7. 
Study Completion ...................................................................................................... 55 
7. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 56 
7.1. 
Demography and Medical History ............................................................................. 56 
7.2. 
Clinical Evaluations ................................................................................................... 56 
7.2.1. 
Vital Signs .................................................................................................................. 56 
7.2.2. 
Physical Examination ................................................................................................. 56 
7.2.3. 
ECG ............................................................................................................................ 56 
7.2.4. 
Concomitant Medications .......................................................................................... 56 
7.2.5. 
Funduscopic Exam of Retina ..................................................................................... 57 

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7.3. 
Laboratory Assessments ............................................................................................ 57 
7.3.1. 
eGFR .......................................................................................................................... 58 
7.3.2. 
Urine Collection ......................................................................................................... 58 
7.3.3. 
Hematology ................................................................................................................ 59 
7.3.4. 
Virus Serology ........................................................................................................... 59 
7.3.5. 
Drug Screen................................................................................................................ 59 
7.3.6. 
Pregnancy Screen ....................................................................................................... 59 
7.3.7. 
Research Samples ...................................................................................................... 59 
7.4. 
Renal Imaging ............................................................................................................ 59 
7.4.1. 
Ultrasound .................................................................................................................. 59 
7.4.2. 
Computerized Tomography ....................................................................................... 59 
7.4.3. 
Magnetic Resonance Imaging .................................................................................... 60 
7.4.4. 
Renal Scintigraphy ..................................................................................................... 60 
7.5. 
Surgical Procedures.................................................................................................... 60 
7.5.1. 
Biopsy ........................................................................................................................ 60 
7.5.2. 
REACT Injection ....................................................................................................... 61 
8. 
SAFETY ASSESSMENTS AND MANAGEMENT ................................................ 63 
8.1. 
Adverse and Serious Adverse Events ........................................................................ 63 
8.1.1. 
Definition of Adverse Events ..................................................................................... 63 
8.1.1.1. 
Definition of Serious Adverse Events ........................................................................ 63 
8.1.1.2. 
Other Significant Adverse Events .............................................................................. 64 
8.1.1.3. 
Procedure-Related Events .......................................................................................... 64 
8.1.1.4. 
Product-Related Events .............................................................................................. 64 
8.2. 
Adverse Event Intensity and Relationship Assessment ............................................. 65 
8.2.1. 
Intensity Scale ............................................................................................................ 65 
8.2.2. 
Relationship Assessment............................................................................................ 65 
8.3. 
Recording and Reporting Adverse Events ................................................................. 66 
8.3.1. 
Serious Unexpected Drug Reactions .......................................................................... 66 
8.3.2. 
Pregnancy ................................................................................................................... 67 
8.4. 
Data Safety Monitoring Board ................................................................................... 67 
8.5. 
Dose Adjustment Criteria ........................................................................................... 67 
8.6. 
Stopping Rules for an Individual Subject .................................................................. 67 
8.7. 
Study Suspension or Study Termination .................................................................... 68 
9. 
STATISTICAL METHODS AND PLANNED ANALYSES ................................... 69 

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9.1. 
Sample Size ................................................................................................................ 69 
9.2. 
Criteria for Evaluation ............................................................................................... 69 
9.2.1. 
Analysis Objectives and Endpoints............................................................................ 69 
9.2.1.1. 
Primary ....................................................................................................................... 69 
9.2.1.2. 
Secondary ................................................................................................................... 69 
9.2.1.3. 
Exploratory................................................................................................................. 69 
9.3. 
Demographic and Baseline Characteristics................................................................ 69 
9.4. 
Efficacy Analysis ....................................................................................................... 70 
9.5. 
Exploratory Analysis.................................................................................................. 70 
9.6. 
Statistical Methods ..................................................................................................... 70 
9.7. 
Safety Analysis .......................................................................................................... 70 
9.7.1. 
Laboratory Evaluations .............................................................................................. 70 
9.7.2. 
Adverse Events .......................................................................................................... 71 
9.7.3. 
Other Safety Evaluations ........................................................................................... 71 
9.8. 
Biopsy and REACT Injection(s) ................................................................................ 71 
10. 
ETHICAL AND REGULATORY CONSIDERATIONS ......................................... 72 
10.1. 
Good Clinical Practice ............................................................................................... 72 
10.2. 
Delegation of Principal Investigator Responsibilities ................................................ 72 
10.3. 
Institutional Review Board / Ethics Committee ........................................................ 72 
10.3.1. 
Subject Informed Consent .......................................................................................... 72 
10.4. 
Subject Confidentiality .............................................................................................. 73 
10.5. 
Substantial Amendment to the Protocol..................................................................... 73 
10.6. 
Protocol Deviations .................................................................................................... 73 
11. 
DATA HANDLING AND RECORDKEEPING ...................................................... 75 
11.1. 
Data Collection and Review ...................................................................................... 75 
11.1.1. 
Data Collection .......................................................................................................... 75 
11.1.2. 
Study Monitoring ....................................................................................................... 75 
11.2. 
Audits and Inspections ............................................................................................... 76 
11.3. 
Retention of Records .................................................................................................. 76 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................... 77 
13. 
PUBLICATION POLICY.......................................................................................... 77 
14. 
LIST OF REFERENCES ........................................................................................... 78 
 
 
 

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LIST OF TABLES 
Table 1: 
Time and Events Table .............................................................................................. 10 
Table 2: 
Laboratory Time and Events Table ............................................................................ 12 
Table 3: 
Abbreviations and Specialist Terms .......................................................................... 20 
Table 4: 
Summary of Classification and Prevalence Estimates for CKD ................................ 23 
Table 5: 
Summary of Non-clinical Pharmacology and Toxicology Studies ............................ 24 
Table 6: 
Serious Adverse Events Reported in Study RMTX-CL001 ...................................... 31 
Table 7: 
Estimated Glomerular Filtration Rate by Subject (RMTX-CL001) .......................... 32 
Table 8: 
Serum Creatinine by Subject (RMTX-CL001) .......................................................... 33 
Table 9: 
Investigational Product .............................................................................................. 38 
Table 10: REACT Dosing Relative to Estimated Kidney Weight ............................................. 40 
Table 11: Product Delivery System Components ...................................................................... 42 
Table 12: Clinical Laboratory Evaluations ................................................................................ 58 
 
 
LIST OF FIGURES 
Figure 1: 
Estimated Glomerular Filtration Rate Pre- and Post-REACT Treatment 
(RMTX-CL001) ......................................................................................................... 32 
Figure 2: 
Serum Creatinine Pre- and Post-REACT Treatment (RMTX-CL001) ...................... 33 
Figure 3: 
Product Delivery System ........................................................................................... 42 
Figure 4: 
REACT Shipping Container ...................................................................................... 43 
Figure 5: 
Study Administrative Structure .................................................................................. 45 
Figure 6: 
Study Design .............................................................................................................. 46 
 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 3: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
ACEI 
Angiotensin-Converting-Enzyme Inhibitor 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
APTT 
Activated Partial Thromboplastin Time 
ARB 
Angiotensin Receptor Blocker 
AST 
Aspartate Transaminase 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CKD 
Chronic Kidney Disease 
ConMed(s) 
Concomitant Medication(s) 
CRF 
Case Report Form 
CRP 
C-Reactive Protein
CTCAE 
Common Terminology Criteria for Adverse Events 
DMSA 
Dimercaptosuccinic acid 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
EC 
Ethics Committee 
eGFR 
Estimated Glomerular Filtration Rate 
EOS 
End-of-Study 
ESRD 
End Stage Renal Disease 
FDA 
Food And Drug Administration 
g 
Gram(s) 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
g KW
est
Gram(s) of Estimated Kidney Weight 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
Hb 
Hemoglobin 
HbA1c 
Glycosylated Hemoglobin 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HR-QoL 
Health-Related Quality of Life 
IB 
Investigator’s Brochure 
ICH 
International Conference On Harmonization 

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Abbreviation or Specialist Term 
Explanation 
I /E 
Inclusion /Exclusion 
IND 
Investigational New Drug 
INR 
International Normalization Ratio 
iPTH 
Intact Parathyroid Hormone 
KDQOL 
Kidney Disease Quality-of-Life Survey 
MedDRA 
Medical Dictionary for Regulatory Activities 
mo 
Month 
MRI 
Magnetic Resonance Imaging 
NCI 
National Cancer Institute 
NOAEL 
No-Observed-Adverse-Effect-Level 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
Nx 
Nephrectomy 
PE 
Physical Examination 
PI 
Principal Investigator 
PT 
Prothrombin Time 
PT-INR 
Prothrombin Time-International Normalization Ratio 
QA 
Quality Assurance 
RBC 
Red Blood Cell 
REACT 
Renal Autologous Cell Therapy 
SAE /SAR 
Serious Adverse Event /Serious Adverse Reaction 
sCr 
Serum Creatinine 
SPIO 
Superparamagnetic Iron Oxide 
SRC 
Selected Renal Cells 
SUSAR 
Suspect, Unexpected Serious Adverse Reaction 
T2DM 
Type 2 Diabetes Mellitus 
TB 
Tuberculosis 
UACR 
Urinary Albumin /Creatinine Ratio 
WBC 
White Blood Cell 

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1.
INTRODUCTION AND BACKGROUND
1.1. 
Chronic Kidney Disease 
1.1.1. 
Background 
Chronic Kidney Disease (CKD) is characterized by progressive nephropathy that without 
therapeutic intervention will worsen until the patient reaches end stage renal disease (ESRD). It is 
defined as reduced kidney function, demonstrated by decreased estimated glomerular filtration 
(eGFR) or evidence of kidney damage, such as increased excretion of urinary albumin. Global 
prevalence of CKD is estimated at 8-16%.1  CKD is associated with considerable morbidity, such as 
diabetes mellitus,2 and is often accompanied by adverse outcomes owing to underlying disease 
states or and/or risk factors such as hypertension and renovascular disease.3   Ninety-seven percent 
of patients with moderate to severe CKD have mostly asymptomatic Stage 3 disease, but even this 
stage of CKD bears a two- to four-fold rise in cardiovascular disease risk along with a significant 
increase in all-cause mortality.4, 5   Only a small proportion of patients progress to ESRD (i.e., Stage 
5 disease); even with costly treatments, however, patients with ESRD experience substantial 
morbidity and mortality.4   To survive, ESRD patients require renal replacement therapy (dialysis or 
kidney transplantation). Preventing or delaying adverse outcomes of CKD via early intervention is 
the primary strategy in CKD management.6 Nevertheless, early treatments have been less than 
optimal, resulting in a significant unmet medical need for improved interventional strategies to 
manage CKD and delay progression to ESRD. 
1.1.2. 
Progressive Staging of CKD 
The major causes of CKD are diabetes and hypertension. Nearly half of all CKD cases arise from 
diabetes with or without hypertension.2,5   The incidence of CKD continues to increase, primarily 
due to the increased incidence of Type 2 Diabetes Mellitus (T2DM).2
Staging and grading of kidney function is most often quantified by the estimated glomerular 
filtration rate (GFR), which is defined as “the volume of plasma from which a given substance is 
completely cleared by glomerular filtration per unit time”.7  Creatinine clearance is the principal 
endogenous marker that is used to measure GFR. In February 2002, with the aim of providing a 
uniform definition of CKD, the Kidney Disease Outcomes Quality Initiative of the US Kidney 
Foundation defined CKD and the various stages of CKD8 (Table 4). For example, the threshold for 
CKD is 60 mL/min/1.73m2, which is less than one-half of the GFR for a normal, young adult male 
(120-130 mL/min/1.73m2).9   Additionally, there is a heightened risk for CKD complications when 
the GFR is 60 mL/min/1.73m2 and lower. 
Table 4 defines CKD stages according to GFR measurements, and the relative prevalence and 
clinical action taken at each stage.13   The initial stage of diabetic nephropathy (Stage 1) occurs over 
a period of several years and is characterized by microalbuminuria (30-300 mg/24 hr.) followed by 
macroalbuminuria (> 300 mg/24 hr.). As the ability of the kidney to filter blood waste products 
declines, serum creatinine rises. With increasing kidney damage (Stages 2-4), rising blood pressure 
further exacerbates kidney disease. When the kidneys cease to function entirely (Stage 5 [ESRD]), 
renal replacement therapy (dialysis or transplantation) is required. 

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Table 4: 
Summary of Classification and Prevalence Estimates for CKD 
Stage* 
Description 
GFR (mL/min/1.73m2) 
1 
Kidney damage with normal or 
increased GFR 
≥90 
2 
Kidney damage with mild decrease in GFR 
60-89 
3 
Moderate decrease in GFR 
30-59 
4 
Severe decrease in GFR 
15-29 
5 
Kidney failure 
<15 (or dialysis) 
* Source: National Kidney Foundation, 2002. National Kidney Foundation. 2002. KDOQI clinical practice 
guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 39:S1-266. 
 
All-cause mortality rates were shown to increase as GFR declined; mortality rates were highest at 
Stages 4-5 of CKD.10,11,12  Populations defined as having an eGFR <60 mL/min/1.73m2 consistently 
exhibited a higher mortality rate than comparator groups where there was no evidence of CKD. 
1.1.3. 
Standard-of-Care in CKD 
Treatment of patients with CKD is focused on slowing progression and preparing for kidney failure 
/replacement. For many patients, CKD occurs as part of a complex comorbidity cluster, especially 
with cardiovascular disease and T2DM. 
Increased risk of cardiovascular disease can be a complication of CKD or an independent 
comorbidity associated with T2DM.14 Collectively, the aim is to lower cardiovascular risk and 
prevent or slow the progression of kidney failure via administration of: 1) angiotensin converting 
enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) to decrease proteinuria and 
control hypertension; 2) insulin and anti-diabetic agents for glycemic control (e.g., reduced serum 
hemoglobin A1c); and, 3) statin therapy to counter dyslipidemia. 
When a patient reaches ESRD, renal replacement therapy (i.e., dialysis or transplantation) is 
indicated. The vast majority of Stage 5 patients receive hemodialysis.15   Dialysis replaces about 5-
15% of kidney function, depending on the intensity and frequency of use; dialysis also helps to 
restore fluid and electrolyte balance when kidneys fail. However, the life-expectancy of an ESRD 
patient initiating hemodialysis is only 4-5 years.16   Additionally, hemodialysis has been associated 
with multiple, serious complications as well as interference with quality of life, such as the need to 
undergo dialysis up to three times per week. Although kidney transplantation remains the most 
effective form of therapy at this time; there is a chronic shortage of organs. If a patient is able to 
secure a kidney for transplantation, long-term immunosuppressive therapy is required to prevent 
rejection. Use of these regimens results in a higher incidence of infection and, over the long term, 
some types of cancer.17 Taken together, there is a critical medical need for improved therapies for 
CKD which could dramatically slow the progression of disease and significantly delay the need for 
renal transplantation. 
1.2. 
Scientific Rationale 
ProKidney is developing Renal Autologous Cell Therapy (REACT) based on extensive scientific 
evaluation of its biologically active component known as SRC (i.e., homologous, autologous 
selected renal cells). This cell population is naturally involved in renal repair and 
regeneration.18,19,20,21,22,23,24,25,26,27,28,29,30,31,32   Therapeutic intervention with REACT is intended to 

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improve renal function in subjects with CKD and T2DM and delay the need for renal dialysis or 
transplantation which, based on the current standard-of-care, is inevitable for ESRD. 
1.3. 
Non-clinical Pharmacology Studies 
In a series of pre-clinical studies, Tengion (a former regenerative medicine company) defined the 
pharmacological characteristics of SRC and delayed the progression of experimental models of 
CKD by augmenting renal structure and function.18,19,33,34,35,36   Tengion subsequently conducted 
safety pharmacology and GLP toxicology studies. An overview of these non-clinical studies is 
presented in Table 5 (Refer to the Investigator’s Brochure for more detailed information). 
Table 5: 
Summary of Non-clinical Pharmacology and Toxicology Studies 
Model 
Number 
Animals 
Study 
Length 
Dose per 
Kidney 
Weighta
106Cell/g 
Number 
Kidneys 
Injected 
Total Kidney 
Weight (g) 
Implanteda 
Totalb
Dose (mL) 
Total 
SRC x 
106 
SRC 
Conc. 
106/mL 
Study 
Pharmacology (efficacy, kinetics, migration, and persistence) 
5/6 Nephrectomy 
Lewis Ratd 
3 
6 mo 
5 - 10 
1 (1) 
1 
0.1 
5-10
50-100
1 
70% Nephrectomy 
Canined
4 
10 mo 
6 
1 (2) 
57.7 
5 
334 
66.8 
2 
ZSF-1e 
7 
12 mo 
3 
2 (2) 
3.2 
0.4 
10 
25 
3 
5/6 Nephrectomy 
Lewis Rate
77 
4 days 
5-15
1 (1) 
1 
0.1 
5-15
50-150
4 
Caninee 
1 
30 min 
12.5 
2 (2) 
120 
10 
1500 
150 
5 
Caninee 
4 
30 min 
1.5-9.2 
2 (1-2) 
120 
2.5-10 
92.7-553.5 37-55
6 
GLP Toxicology 
ZSF-1 ratd 
5M/5F 
3 mo 
3.13 
2 (2) 
2 
.25 
6.25 
25 
7 
5M/5F 
5M/5F 
6 mo 
3 mo 
3.13 
6.25 
2 (2) 
2 (2) 
2 
2 
.25 
.25 
6.25 
12.5 
25 
50 
5M/5F 
6 mo 
6.25 
2 (2) 
2 
.25 
12.5 
50 
Caninee 
2M/2F 
1 mo 
2.75 
1 (1) 
60 
3 
330 
110 
8 
2M/2F 
2M/2F 
3 mo 
1 mo 
2.75 
11.0 
1 (1) 
2 (1) 
60 
120 
3 
12 
330 
1320 
110 
110 
2M/2F 
3 mo 
11.0 
2 (1) 
120 
12 
1320 
110 
Canine,c,e 0 Months 2M/2F 
n/a 
5.5 
2 (2) 
120 
6 
660 
110 
9 
3 Months 
6 mo 
5.5 
2 (2) 
120 
6 
660 
110 
10 
Notes: 
a. Estimated kidney weight based on animal model. Actual weights are listed in the study reports where applicable.
b. Dose refers to SRC or REACT.
c. Two doses of REACT were administered, one at 0 months and the second at 3 months.
d. Delivered REACT to rodents using syringe affixed to sharp needle that pierced the capsule and deposited REACT.
e. Delivered REACT to dogs using cannula to pierce the capsule plus blunt-end delivery cannula to deposit REACT.
1.3.1. 
Pharmacodynamics 
Proof of principle for SRC as the biologically active component of REACT was established in 
multiple animal models of CKD. For example, the 5/6th nephrectomy (Nx) rodent mass reduction 
model of CKD allowed for an optimized selection of a therapeutically relevant SRC cell population. 
A 70% Nx canine model of CKD confirmed SRC activity in a large mammal, while the ZSF-1 rat 

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served as proof-of-principle for demonstrating the effects of SRC in a model relevant to T2DM.37 
SRC delivered directly into the kidney cortex in multiple experimental models of CKD induced a 
regenerative response through direct engraftment or tissue replacement, and also induced secretory 
factors via a putative paracrine mechanism.18,21,22,24, 26 
This intervention strategy significantly improved survival, stabilized disease progression, and 
extended the longevity in both the 5/6th Nx model and the ZSF-1 rodent models of CKD. 
Morphological normalization of multiple nephron structures was accompanied by functional 
improvements, including glomerular filtration, tubular protein handling, electrolyte balance, and the 
ability to concentrate urine. Lowered blood pressure and reduced levels of circulating renin were 
also observed in the ZSF-1 rat model. The observed functional improvements following SRC 
treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration 
and interstitial inflammation and fibrosis. No toxicologically significant in-life, clinical pathology, 
or histological changes were noted in the target organ or other tissues. Based on results from 
multiple pre-clinical studies conducted in different CKD animal models, SRC (i.e., active 
component of REACT) were effective in significantly delaying progression of CKD when 
implanted in the diseased organ prior to irreversible nephropathy. These results provide a rationale 
for investigating the effects of this cell-based intervention in patients prior to ESRD. 
1.3.2. 
Safety Pharmacology 
1.3.2.1. 
Extra-Renal Activity 
REACT (i.e., SRC formulated in a gelatin-based hydrogel) was administered in various rat and 
canine models to assess immediate cardiovascular and respiratory pharmacologic effects. The acute 
effects of lower and higher SRC concentrations formulated in varying percentages of gelatin (0.75-
1.0%) were evaluated in the rodent 5/6th Nx model. Potential changes in blood pressure were 
assessed immediately before, during, and shortly after REACT delivery in the normal canine model. 
No studies on the effects of REACT on the central nervous system were performed since: 1) 
animals exhibited normal behavior before, during, and after REACT injection; 2) no effects on the 
central nervous system were expected from an investigational product containing intact renal cells; 
and, 3) REACT was delivered into the kidney. 
1.3.2.2. 
Hemodynamic Effects 
Rats in the 5/6th Nx study (Study #4) received REACT or vehicle control, and potential 
hemodynamic effects were monitored over 4 days. Among the 77 animals treated in this REACT 
formulation study, 16 animals experienced apnea during or immediately after REACT delivery. A 
total of 9 animals died; the causes of death were classified as apnea (n=3), renal hemorrhage (n=2), 
and deaths associated with CKD (n=4). Six of the 16 animals that experienced apnea were not pre-
treated with atropine; of these animals that experienced apnea, two died under the influence of 
anesthesia prior to the use of atropine. Ten of the 16 animals that experienced apnea were treated 
with atropine, and all recovered from the surgical procedure and REACT injection. 
On the other hand, apnea, renal hemorrhage, and deaths that occurred in the 5/6th Nx rat study were 
not observed in the ZSF-1 rat study, or in the canine pharmacology study, or in two (intact) canine 
pilot studies that assessed the short-term effects of volume administration on blood pressure. Taken 
together, this model-specific hemodynamic response can be potentially attributed to:  1) altered 
hemodynamics of the severely mass-reduced rodent remnant kidney 38 2) transient changes in 
kidney interstitial pressure administration triggering a central autonomic response;39 40 and, 3) under 
perfusion of tissue or acute hypoxia from bleeding following delivery into the kidney. Pre-treatment 

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with atropine, a competitive antagonist of the parasympathetic nervous system, helped mitigate the 
model-specific hemodynamic changes. The effect of atropine suggests a possible autonomic 
response to REACT delivery that was specific to the severely mass-reduced, 5/6th Nx rodent model 
of CKD. 
1.3.2.3. 
Dose Volume 
Using a range of REACT doses, volumes, and concentrations, (Study #5), the normal canine was 
selected to evaluate blood pressure immediately before, during, and after REACT delivery into the 
kidney. In this study, each pole of each kidney received 2.5 mL of REACT; therefore, a total of 
10 mL/120 g, or 0.083 mL/g, was delivered at a dosage of 12.5 x 106 cells /gram of kidney mass. 
REACT treatment was well tolerated; there were no adverse systemic effects (physical or 
serological), nor were there any significant toxicological or histomorphological changes indicative 
of kidney injury or other tissue injury as a result of REACT delivery. In contrast to the severe mass 
reduction rodent model of CKD, no apnea, renal hemorrhage, or deaths were noted. 
1.3.3. 
Kinetics, Migration, and Persistence 
As with other cell-based therapies targeting soft organs, data on biodistribution of the 
investigational product has been limited. To that end, three additional studies provide evidence 
concerning the potential migration and persistence of REACT within the kidney at selected 
sampling times post-delivery.24,25,26   The results of these studies are summarized in this section; 
detailed information is provided in the Investigator’s Brochure. 
1.3.3.1. 
ZSF-1 Rat 
SRCs were labeled with the Rhodamine-B superparamagnetic iron oxide (SPIO) particle. This 
contrast agent is specifically formulated for cell labeling and is readily internalized by non- 
phagocytic cells. SPIO-labeled cells were administered to the ZSF-1 rat kidney. Twenty-four hours 
after delivery, SPIO-labeled cells were detected by MRI and whole organ optical imaging. In 
addition, ZSF-1 rats received SRCs labeled with CelSense-19F, which were quantified by Nuclear 
Magnetic Resonance at 3 hr., 24 hr., and 7 days after implantation.24,25 
Both acute ZSF-1 detection and long-term donor cell detection using the 5/6th Nx model of CKD 
showed significant retention of SPIO-labeled cells. Clinically relevant MRI detection at 24 hr. 
following cell delivery revealed a region at the anterior pole of the kidney where SPIO-labeled cells 
had been injected. Sectioning of the whole kidney and staining with Prussian blue demonstrated a 
bolus of iron labeled SPIO cells migrating and distributing from the cortical injection site, which 
confirmed their presence in tubular and peritubular spaces of the renal cortex and medulla. 
Likewise, whole organ fluorescent imaging highlighted cell detection at and around the site of 
injection located at the upper cortex of the anterior pole of the ZSF-1 rat kidney. Detection of 19F-
labeled SRC at 3 and 24 hr. after delivery confirmed nearly 100% retention in the kidney. After 7 
days, detection of 19F-labeled SRC was diminished by an order of magnitude, consistent with 
continuous urinary excretion. 
1.3.3.2. 
Porcine Non-GLP Analysis of Non-Renal Tissue 
In a pre-clinical, non-GLP study, SPIO-labeled SRC were delivered to the kidneys of living swine 
(n=11). Cellular distribution was monitored over the course of the 30-day study period using MRI. 
Labelled SRC were distributed in two major compartments:  urinary bladder and renal parenchyma. 

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The major route of excretion was urine. Notably, there was no evidence of ectopic SRC migration 
or site-specific engraftment at non-target organ sites.41 
1.3.3.3. 
Canine Non-GLP Analysis of Non-Renal Tissue 
In a pre-clinical, non-GLP study, SPIO-labeled SRC were delivered to the kidneys of living canine 
hosts. Cellular distribution was monitored at 30 minutes post-injection via MRI. Consistent with 
observations from the living porcine model demonstrating that injected SPIO-labeled SRC was 
retained in renal parenchyma or excreted in urine, SPIO-labeled SRC likewise were retained within 
the renal parenchyma at the injection site after 30 minutes. 
1.3.3.4. 
Conclusions 
•
SRC are distributed at the site of injection (renal parenchyma) and excreted via the
urine, based on SRC labeling studies with SPIO and CelSense-19F.
•
SRC delivered into rat, swine, and canine kidneys were not detected in non-target organs
(other than urinary tract during excretion), based on extensive histological evaluation.
•
Based on reports concerning allogenic mesenchymal stem cells as well as published data
concerning the safety of autologous mesenchymal stem cells in clinical trials, autologous
REACT-related materials should also not give rise to ectopic tissue growth, organ
dysfunction, or tumor development.42,43,44,45,46 
1.4. 
Toxicology Studies
To assess the safety of REACT, three GLP safety studies were conducted, i.e., one study was 
conducted in the rat ZSF-1 disease model of CKD and the other two studies were conducted in 
normal canines. A brief summary is presented below; detailed information is provided in the 
Investigator’s Brochure. 
1.4.1. 
ZSF-1 Rat Single Dose Study 
The purpose of this study was to assess the safety of a single administration of REACT in ZSF-1 
rats, a model of uncontrolled metabolic syndrome including T2DM, hypertension, and severe 
obesity. The rats received:  1) high dose REACT; 2) low dose REACT; 3) sham; or, 4) biomaterial 
only. Each animal received 4 injections of test article, one into each pole of each kidney. The results 
were assessed at 3- and 6-months post-treatment. 
1.4.1.1. 
Renal-Related Findings 
No treatment-related kidney findings were noted following evaluation of 8 areas of each kidney (3 
stains per area), including assessment and scoring of 150 glomeruli per kidney. Apart from changes 
related to implantation and/or injection site linear scars, all kidneys were considered normal within 
the context of the disease model. No test article-related kidney finding was observed at 3- or 6-
month post-treatment. All macroscopic and microscopic kidney changes were considered related to 
the natural progression of renal disease in the ZSF-1 obese rat, or to the injection procedure. 
Kidney changes in all groups were more severe in males, and consistent with differences in the 
disease stage between genders. Overall, there was an apparent trend of lower renal histological 
severity scores (i.e., lower glomerular injury score, tubule-interstitial injury score, and global 
nephron score) that was consistently noted in the low-concentration REACT treatment group when 
compared to the Sham control group 6 months post-procedure. 

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Based on the absence of differences across study groups, the No-Observed-Adverse-Effect-Level 
(NOAEL) was the high dose, 6.25 x 106 cells /g KWest. 
1.4.1.2. 
Non-Renal Findings 
No REACT safety-related findings were observed in non-target tissues. No ureteral or bladder 
(primary routes of REACT excretion) REACT-related changes were observed. There were no 
REACT- related effects, and no observable REACT cellular materials in any of the draining (lymph 
nodes) or filtering (liver, lung, spleen) tissues examined. 
1.4.1.3. 
Clinical Pathology 
The results of clinical laboratory tests (including hematology, clinical chemistry, and special 
urinalysis panels) were evaluated for differences between baseline and end of study (3- or 6-months 
post-treatment), and between treated and control groups. No REACT-related clinically significant 
laboratory abnormalities were identified. 
1.4.1.4. 
Conclusions: 
• All animals survived to the end of study (3- or 6-months post-treatment). 
• There were no significant safety-related clinical pathology findings or safety-related 
findings of toxicological significance attributable to treatment. 
• No REACT-related clinically significant laboratory abnormalities were identified. 
• The observed NOAEL was 6.25 x 106 cells /g KWest. 
1.4.2. 
Initial Single Dose Canine Study 
The initial canine toxicology study assessed the safety of a single administration of two different 
doses of REACT compared to sham treatment or treatment with the biomaterial. The test article was 
delivered into one pole of each kidney. A total of 32 mongrel dogs were entered into the study; 16 
were assessed at one month and 16 were assessed at 3 months. 
1.4.2.1. 
General Results 
All 32 animals survived to their designated termination time point at one or 3 months after 
treatment. The animals appeared to be in good health throughout the study. There were no 
significant clinical pathology findings. There were no signs of renal insufficiency (azotemia), and 
there were no indications of decreased GFR. 
1.4.2.2. 
Renal-Related Results 
No REACT delivery-related macroscopic or microscopic findings were observed at the one- or 3-
month endpoint. No treatment-related kidney findings were noted following enhanced evaluation of 
8 areas of each kidney (3 stains per area), including evaluation and scoring of 150 glomeruli per 
kidney. Apart from changes related to injection site scars all kidneys were normal. All macroscopic 
and microscopic kidney changes were considered background findings or related to the injection 
procedures. 
1.4.2.3. 
Non-Renal Findings 
No test article-related findings were identified in other (non-kidney) tissues. All macroscopic and 
microscopic changes were considered background changes and within normal limits. 

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1.4.2.4. 
Procedure-Related Findings 
The most common abnormalities included swelling at the incision sites (seroma formation) and 
weight loss at study termination. With regard to incision site swelling, ten of sixteen (10/16) 
animals had sterile seroma formation post-implantation, and nine of sixteen (9/16) post treatment. 
The animals had varying degrees of swelling at their retroperitoneal incisions and were treated as 
deemed necessary by a veterinarian. 
Numerous animals had mild inappetence following REACT administration (29 of 32) and treatment 
procedures (18 of 32). Most animals (28 of 32) experienced weight loss from baseline (prior to 
implantation) to termination. Of note, a greater amount of weight loss occurred between baseline (2 
weeks prior to treatment) and treatment (Day 0; renal injections) than between treatment and 
termination. Weight loss also occurred across all treatment groups and was judged to be related to 
the stressful nature of the study. 
1.4.2.5. 
Conclusions 
• All animals survived to their designated termination time point and were in good general 
health throughout the study based on clinical pathology, urinalysis, and veterinary 
assessment. 
• Neither the low or high dose of REACT produced macroscopic or microscopic adverse 
effects at one- or 3-months post-treatment, similar to observations following sham 
treatment or treatment with the biomaterial. 
• Pathological evaluation showed no REACT safety-related (macroscopic or microscopic) 
findings in the target (kidney) or non-target organs examined. 
• Based on anatomic pathology, the observed NOAEL was the higher concentration 
tested, i.e., 11.7 x 106 cells/g KWest. 
1.4.3. 
Repeat Dose Canine Study 
The second canine toxicology study assessed the safety of administering two repeat doses of 
REACT. Each dose was delivered into both kidneys at baseline (time zero) and 3 months. All 
animals were subjected to two renal biopsies per kidney 4 to 6 weeks prior to the baseline injection 
procedure. Control animals were injected with PBS. Animals were monitored for 6 months 
following the baseline injection. 
1.4.3.1. 
Study Results 
All 8 animals were in good clinical health throughout the study and survived to their designated 
termination time point at 6 months. There was mild or insignificant weight loss in 5 of 8 animals, 
with 2 animals losing >3% body weight for the duration of the study. Greater weight loss occurred 
between the renal implantation and initial treatment than between the initial treatment and 
termination. The clinical pathology and urinalysis data revealed no abnormal trends. There were no 
signs of renal insufficiency, and no indications of decreased GFR. 
1.4.3.2. 
Kidney-Related Findings 
No REACT implantation safety-related macroscopic or microscopic findings were observed at the 
6-month time point.  No treatment-related kidney findings were noted following enhanced 
evaluation of 8 areas of each kidney (3 stains per area), including evaluation and scoring of 150 
glomeruli per kidney. All kidneys appeared normal, apart from changes related to injection site 

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scars (fibrosis/chronic inflammation in the capsule; linear fibrosis/chronic inflammation and 
inflammatory cells in the cortex/medulla). 
1.4.3.3. 
Non-Kidney Related Findings 
No test article safety-related findings were identified in non-target tissues. All macroscopic and 
microscopic changes were considered background changes and thus, considered within normal 
limits. 
1.4.3.4. 
Conclusions 
• All animals survived to their designated termination time point, and appeared in good 
health based on clinical pathology, urinalysis, and veterinary assessment data. 
• Pathological assessment showed no REACT safety-related (macroscopic or microscopic) 
findings in either the target organ (kidney) or non-target organs examined. 
• At the 6-month time point, no detrimental effects of two repeat doses of REACT were 
observed in comparison to the control animals injected with PBS. 
1.5. 
Non-clinical Conclusions 
Evidence from multiple animal studies over a wide range of doses (3 to 15 million SRC/g of kidney 
tissue implanted), and extended periods of time post-REACT treatment (up to one year), including 
three GLP studies, indicates that the potential risk of complications from REACT delivery into the 
kidney is similar to the potential risk of complications associated with standard renal biopsy 
practice.47,48,49 
Apart from changes related to injection procedures and cardiovascular findings specific to 5/6th 
nephrectomy rodent mass reduction model of CKD, no unanticipated in-life, hematological, 
urological, serological, or histological changes were found in the target organ or non-target tissues 
following delivery of REACT. 
1.6. 
Phase 1 Clinical Trial: Interim Results 
1.6.1. 
Background 
In April 2013, a first-in-human clinical trial was initiated at the Karolinska University Hospital 
Huddinge in Stockholm, Sweden: A Phase 1, Open-Label Safety and Delivery Optimization Study 
of Renal Autologous Cell Therapy (REACT) in Patients with Chronic Kidney Disease 
(RMTX-CL001). This is a Phase 1, open-label, safety and delivery optimization study of REACT 
implanted into subjects with CKD. REACT will be manufactured from SRC obtained from a 
subject’s renal biopsy, formulated with gelatin biomaterial, and injected back into the subject’s left 
kidney. The primary objective is to assess the safety and optimal delivery of REACT implanted at 
one site in a recipient kidney as measured by procedure- and/or product-related adverse events 
(AEs) through 12 months post-treatment. The secondary objective is to assess renal function by 
comparing the results of laboratory tests from baseline through 12 months following REACT 
injection, followed by an additional observational period of 18 months. Each subject’s baseline rate 
of CKD disease progression serves as his/her own “control” to monitor for changes in renal 
insufficiency over time. Six subjects, recruited from the Karolinska University Hospital, were 
enrolled into the study. In addition, one subject was enrolled in the study at the University of North 
Carolina. 

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1.6.2. 
Adverse Events 
Among a cohort of 7 male subjects, 53 to 70 years of age, with pre-dialysis diabetic nephropathy 
(Stage 3b/4 of CKD), all subjects recovered from the laparoscopic REACT delivery procedure 
without immediate perioperative complications. Notably, no subject experienced hematuria, which 
was prospectively considered to be the most likely untoward event. One subject developed an 
intestinal volvulus on Day 2 after REACT injection, and required a partial colonic resection that 
was complicated by anastomotic hemorrhage. In the judgment of the Investigator, this event was not 
related to the investigational product or the procedure. One subject experienced a skin infection that 
was associated with the laparoscopic implantation procedure. Another subject recovered from the 
surgical procedure with inflammation of the respiratory tract. All serious adverse events (SAEs) 
associated with the clinical trial are presented in Table 6. 
Eight of the nine SAEs were considered possibly related to the implant surgery. There were no AEs 
or SAEs considered related to the biopsy procedure. To date, no delayed or late-onset adverse 
reactions related to REACT or other study procedures have been identified (e.g., negative immune 
mediated reactions). Based on the current data, the highest risk associated with REACT treatment 
appears to be from the implant surgery. Consequently, steps are being taken to decrease the duration 
of the surgical procedure and improve surgical outcomes. 
Table 6: 
Serious Adverse Events Reported in Study RMTX-CL001 
Subject 
Number 
MedDRA 
Preferred Term 
Intensity 
Time 
to 
Outcome of SAE 
Relationship to 
REACT 
001-002
Fatigue 
Mild 
4 days 
Recovered /Resolved Not Related 
001-001
Fatigue 
Mild 
5 days 
Recovered /Resolved Not Related 
001-001
Postoperative wound 
infection 
Mild 
0 days 
Recovered /Resolved Possibly Related 
001-002
Pneumonia 
Moderate 1 days 
Recovered /Resolved Possibly Related 
001-003
Urinary tract infection Mild 
7 days 
Recovered /Resolved Not Related 
001-004
Fatigue 
Mild 
4 days 
Recovered /Resolved Not Related 
001-005
Volvulus 
Moderate 2 days 
Recovered /Resolved Not Related 
001-003
Fluid retention 
Moderate 1 days 
Recovered /Resolved Not Related 
001-005
Anastomotic 
hemorrhage 
Moderate 0 days 
Recovered /Resolved Not Related 
Abbreviations: MedDRA (Medical Dictionary for Regulatory Activities); Renal Autologous Cell Therapy 
(REACT); SAE (Serious Adverse Event) 
1.6.3. 
Estimated Glomerular Filtration Rate (eGFR) 
Seven male patients with T2DM and Stage 3b/4 of CKD were implanted with REACT in the left 
kidney. Pre-implantation information from these subjects indicated that their average decline in 
eGFR was 6.1 ml/min/year. Following REACT treatment, eGFR decline for the combined group 
(all subjects) was -3.1 ml/min/year (green line in Figure 1). 

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scarring as the disease progresses. An increase in cortical thickness was associated with kidney 
regeneration in pre-clinical studies of REACT and was confirmed histologically in all 4 animal 
species studied (refer to the Investigator’s Brochure). In the clinical trials TNG-CL010 and TNG-
CL011, cortical thickness was evaluated using imaging technologies; no biopsies were taken to 
confirm the basis for the increased thickness. Cortical thickness was measured in both the right and 
left kidney to determine if the implanted left kidney exhibited any change in cortical thickness that 
could be attributed to REACT implantation. The right kidney served as a non-implanted control. 
On average, cortical thickness increased in the left kidney from 14 mm at baseline to approximately 
16 mm after one year of REACT treatment. This change in cortical thickness was not sufficient to 
cause an increase in the total volume of the left kidney (data not presented). No change in cortical 
thickness was observed in the right kidney cortex. 
1.6.5. 
Hemoglobin 
CKD can be associated with anemia due to an alteration in renal erythropoietin production as well 
as metabolic abnormalities resulting from chronic uremia.50   In the clinical trial RMTX- CL001, 3 
of 7 subjects exhibited improvement in hemoglobin levels after REACT treatment, while the 
remaining 4 subjects maintained normal levels during the study. 
1.6.6. 
Blood Pressure 
Blood pressure was monitored during the course of clinical trials TNG-CL010 and TNG-CL011. 
Subjects received medication to control their blood pressure. Notably, intake of antihypertensive 
medication was reduced in 3 of 6 subjects during the first six months following REACT treatment.51 
1.7. 
Potential Risks 
In general, potential risks associated with the clinical use of REACT can be broadly divided into 3 
categories:  kidney biopsy, REACT product, and delivery into the recipient kidney. An assessment 
of potential risks associated with each of these steps is presented in this Section. 
At this time, there are no specific warnings or precautions associated with the use of REACT. 
However, warnings and precautions for the renal biopsy and the percutaneous injection procedure 
must be considered with use of this product. The risks of renal biopsy have been well characterized 
in the 100 years that this procedure has been used and developed. Percutaneous needle 
instrumentation of the kidney has a shorter history. 
The risks of renal biopsy and percutaneous needle kidney injection include: 
1. Pain in flank / injection/biopsy site
2. Bleeding at injection/biopsy site which may occur around the kidney or anywhere along the
needle track and which may be sufficient to entail clinically significant anemia, acute kidney
injury (AKI), hematoma, and in the case of subcapsular bleeding, a “Page kidney” and acute
hypertension
3. Surgical damage to the kidney from needle injury, as well as injuries of other structures that
include connective tissues, bone, and intra-abdominal viscera
1.7.1. 
Potential Risks Associated with Renal Biopsy 
Autologous kidney cells will be obtained from individual subjects via a kidney biopsy performed 
according to standard medical practice 47,48,49 and consistent with standard operating procedures at 
participating hospitals /medical institutions. A minimum of 2 tissue cores from a single kidney 

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biopsy is needed to obtain sufficient renal cortical tissue for the production of REACT. A 16-gauge 
biopsy needle measuring approximately 10 mm in length will remove 0.01-0.02% of the average 
total volume of the diseased kidney. Since approximately 0.001% of the total number of renal 
glomeruli will be harvested,49   the biopsy is not expected to adversely affect kidney function. 
Kidney biopsies for diagnostic procedures are of low risk and often conducted under sedation on an 
outpatient basis in the US.52,53  When performed by qualified interventional physicians, a renal 
biopsy properly targeted towards the cortex produces limited renal damage.45   On the other hand, 
reports of kidney damage at the biopsy site describe vascular injury and varying degrees of 
ischemia and infarction. The severity of damage depends on the size and number of vessels injured 
during the biopsy procedure.54 
Hemorrhage is the most common AE associated with a routine kidney biopsy. Nearly all patients 
experience microscopic hematuria as a result of the biopsy, but this is not clinically significant.48,53
On the other hand, gross hematuria occurs in 3-9% of patients,52,53 and generally resolves by 24 hr. 
post-biopsy. The most serious complication is severe bleeding that requires transfusion and/or 
results in patient death. Transfusions are needed in less than 1% of renal biopsies, and death occurs 
in less than 0.01% of cases.55,56,57 
1.7.2. 
Potential Risks Associated with REACT Product 
The investigational product, REACT, is composed of autologous renal cells obtained from the same 
subject via kidney biopsy. Based on experience with autologous stem cell transplantation, the risk 
of an immune response (e.g., graft rejection) caused by REACT injection into the kidney seems 
unlikely. 
Since the kidney is a highly perfused organ, it is doubtful that the implanted SRC will remain 
localized at the injection site. The three locations considered to be the most likely destinations of 
migrated SRC are: 1) the sub-capsular space; 2) the systemic circulation; and, 3) the urinary tract. 
Leakage of SRC into the sub-capsular space is not expected to pose a risk to the subject. 
For example, the sub-capsular space is commonly used to implant endocrine tissue, such as islet 
cells.58 The renal capsule also serves as a niche for native stem cells capable of migrating into the 
renal parenchyma.59   Additionally, direct injection into the kidney mitigates the possible entry of 
SRC into the systemic circulation by providing a natural route of elimination via the urinary tract. 
Furthermore, intravenous administration of heterologous, allogeneic stem cells (i.e., mesenchymal 
stem cells) has been evaluated in clinical trials and yielded no significant risk to subjects.42,43,44,45,46 
Porcine Skin Type B gelatin used in the formulation of REACT meets Pharmaceutical and Edible 
Gelatin Monograph (European Pharmacopeia 7.0, US Pharmacopeia-National Formulary USP35 
NF30) requirements. Gelatin is widely used in pharmaceutical and medical applications, including 
cellular transplantation for regenerative products. Gelatin would not be expected to cause adverse 
effects in study subjects based on its biocompatible nature, widespread use, and results of GLP 
toxicology studies with REACT-containing porcine gelatin. Additional information on the porcine 
gelatin used to manufacture REACT is provided in the Investigator’s Brochure. 
1.7.3. 
Potential Risks Associated with REACT Treatment 
A percutaneous technique will be used to access the kidney for REACT delivery. The percutaneous 
approach has been used for over a decade in ablation of renal masses. A concise review of this 
method can be found in Salagierski and Salagierski (2010).60   Safety measures will be executed 

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during REACT treatment and post-surgical follow-up to reduce the potential for excessive bleeding 
and other AEs. Patients will be closely monitored as discussed in Section 6. 
Cain and coworkers (1976)61 reported that renal cell homogenates injected into rodent kidneys 
produced no significant AEs. Similarly, the observed morphological effects following REACT 
delivery into the kidney were consistent with those reported for repeated kidney biopsies taken from 
canines, i.e., the presence of a mature connective tissue track with no functional deficits linked to 
minimal structural changes.54  Increasing intracapsular kidney water volume in canines can elevate 
intra-kidney pressure as well as transient increases in kidney weight and systemic blood 
pressure.39,40  However, in the pilot canine studies that assessed the short-term effects of volume 
administration on blood pressure, there were no adverse effects on blood pressure following volume 
escalation up to 6 mL per kidney of REACT. 
1.8. 
Potential Benefits 
The potential to achieve clinically significant improvement in CKD is supported by studies that 
tested REACT in pre-clinical animal models of kidney insufficiency, i.e., surgical models for 
decreased kidney function in otherwise healthy rats and dogs plus the ZSF-1 rat model of T2DM. 
The main finding was that REACT significantly decreased the rate of structural and functional 
deterioration in already compromised kidneys to an extent that was clinically relevant in the animal 
model. Therefore, the potential exists for subjects participating in this clinical trial to realize 
therapeutic benefit from REACT treatment, such as a possible reduction in the rate of progression 
of CKD. 
 

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2. 
PHASE II TRIAL OBJECTIVES AND PURPOSE 
ProKidney is currently developing a regenerative cell-based product, Renal Autologous Cell 
Therapy (REACT), with the aim of improving renal function in subjects who have CKD and 
T2DM. Therapeutic intervention with REACT is intended to delay the need for renal replacement 
therapy (dialysis or transplant) which, based on the current standard-of-care, is inevitable for 
patients with end-stage CKD. The purpose of the present study is to compare the safety and efficacy 
of up to 2 injections of REACT given 6 months (+4 weeks) apart (maximum). Each subject’s 
annual rate of renal decline, based on adequate historical clinical data from 24 months prior to the 
Screening Visit, will serve as a comparator to monitor the rate of progression of renal insufficiency. 
We propose that REACT treatment will reduce the rate (slope) of eGFR decline and improve renal 
function over the 24-month period following the last REACT injection. 
2.1. 
Primary Objective 
To assess the safety of REACT injected in one recipient kidney. 
• Primary Endpoint: Procedure and/or product related AEs through 24 months post-
injection. 
2.2. 
Secondary Objective 
To assess the safety and tolerability of REACT administration by assessing renal-specific AEs over 
a 24-month period following injection. 
• Secondary Endpoints: Renal-specific laboratory assessments through 24 months post 
injection. 
2.3. 
Exploratory Objective 
To assess the impact of REACT on renal function over a 24-month period following injection. 
• Exploratory Endpoint: Clinical diagnostic and laboratory assessments of renal structure 
and function (including eGFR, serum creatinine, and proteinuria) to assess changes in 
the rate of progression of renal disease. 

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3. 
INVESTIGATIONAL PRODUCT
3.1. 
Description of Study Drug
REACT is an injectable product composed of SRC formulated in a biomaterial (gelatin-based 
hydrogel). Table 9 presents an overview of the investigational product. Refer to the Investigator’s 
Brochure for a detailed description of SRC and REACT as well as the manufacturing process. 
Table 9: 
Investigational Product 
Investigational Product 
Product Name: 
Renal Autologous Cell Therapy (REACT) 
Dosage Form: 
Renal cells obtained from autologous kidney biopsy tissue will be 
expanded and SRC selected. SRC will be formulated in a 
gelatin-based hydrogel at a concentration of 100 x 106 cells/mL. 
This sterile cell preparation (REACT) will be contained in a 
sterile 10 mL syringe and shipped to the clinical site for use. 
Unit Dose 
The dose of REACT will be adjusted to 3 x 106 cells/g 
estimated kidney weight determined from MRI study. 
Route of Administration 
Percutaneous injection into the cortex of the biopsied kidney 
Physical Description 
Sterile, labelled, 10 mL syringe containing up to 8 mL of REACT 
Manufacturer 
ProKidney, Winston-Salem, North Carolina, USA 
3.2. 
Procurement and Manufacture of REACT 
REACT will be manufactured in a GMP facility at ProKidney located in Winston-Salem, North 
Carolina, USA. 
3.2.1. 
Biopsy 
The biopsy material will be collected using standard surgical techniques to assess the left or right 
kidney. A minimum of 2 tissue cores each measuring in 1.5cm must be collected using a 16-gauge 
biopsy needle to provide sufficient material for the manufacture of autologous REACT. When the 
biopsy material is received at ProKidney, the samples will be labeled and strict documentation 
measures followed to insure that product traceability is maintained. ProKidney will notify the site 
concerning the adequacy and quality of the biopsy sample for the manufacture of REACT and 
confirm the scheduled date for REACT injection. If the biopsy material cannot be used, the subject 
should be discontinued from the study. 
3.2.2. 
Selection of SRC 
Approximately 4 weeks prior to the subject’s planned REACT treatment, autologous renal cells will 
be removed from the vapor phase of a liquid nitrogen freezer, thawed, and isolated from kidney 
tissue by enzymatic digestion. Cells will be cultured and expanded using standard techniques. 
The cell culture medium is designed to expand primary renal cells and does not contain any 
differentiation factors. Harvested renal cells will be subjected to density gradient separation to 
obtain SRC, which are composed primarily of renal epithelial cells known for their regenerative 

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potential.62   Other parenchymal (vascular) and stromal (collecting duct) cells may be sparsely 
present in the autologous SRC population. 
If sufficient cells are available, the same biopsy material will be used to make additional REACT 
preparations for research studies and stored, under GMP conditions, in the vapor phase of a liquid 
nitrogen freezer. 
It is anticipated that all subjects will receive a series of 2 REACT injections. The time and events 
table shows that the series of 2 REACT injections will be administered 6 months apart with a study 
visit window of 4 weeks. Regardless, every attempt should be made to ensure that the second 
REACT injection is administered 6 months after the first injection. ProKidney will notify the 
site to obtain information about the scheduled date for the second injection. 
3.2.3. 
Formulation 
SRC will be formulated in a gelatin-based hydrogel to improve stability during transport and 
delivery upon injection into the renal cortex. Porcine gelatin will be dissolved in buffer to form the 
thermally responsive hydrogel. Although fluid at room temperature, this biomaterial gels when 
cooled to refrigerated temperature (2 to 8ºC). Prior to injection, the REACT investigational product 
must be warmed to ≥20C up to 26°C to liquefy the hydrogel. 
3.2.4. 
REACT Product for Injection 
Ten to 14 days prior to the scheduled date for REACT injection, the subject will report to the clinic 
and undergo assessments to verify continued eligibility. If the subject does not qualify for REACT 
injection, the Investigator and the Sponsor will discuss possible options, for example, if there is 
sufficient stability to attempt an REACT injection at a future date. If the subject still qualifies, the 
REACT product will be manufactured and shipped to the clinical center. It is the responsibility of 
the site to ensure REACT shipments can be delivered directly to site personnel. REACT will be 
injected into the biopsied kidney of eligible subjects using a percutaneous approach. The 
percutaneous method will employ a standardized technique (such as that utilized in the ablation of 
renal masses by radiofrequency or cryogenic methods).60 
It is anticipated that all subjects will receive two planned REACT injections. However, if there 
appears to be any untoward safety risk, or rapid deterioration of renal function, or development of 
uncontrolled diabetes or uncontrolled hypertension, or development of a malignancy or an 
intercurrent infection, then the second REACT injection should not be administered. 
Renal cells that may have been frozen but not used to manufacture REACT will be remain in the 
vapor phase of a liquid nitrogen freezer at ProKidney until the EOS Visit. At that time, if these renal 
cells are no longer needed, they will be de-identified of all personal information and stored in the 
vapor phase of a liquid nitrogen freezer for a maximum of 5 years. The aim is to test these renal 
cells in laboratory research studies. During the informed consent process, each subject must provide 
written consent for the storage and future use of autologous cells not used for REACT injection. 
Subjects must have the option of having these cells destroyed upon study completion. 
3.2.5. 
REACT Dose 
The dose of REACT for subjects in the Phase 1 clinical trials (TNG-CL010 and TNG-CL011) was 
3 x 106 SRC /g estimated kidney weight (g KWest). Similarly, in the present study, each REACT 
injection will contain 3 x 106 cells/g KWest. Since the concentration of SRC is 100 x 106 cells/mL of 
REACT, the dosing volume will be 3.0 mL for each 100 g of kidney weight. The volume of 
REACT to be administered will be determined by pre-procedure MRI volumetric 3D evaluation or 

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ellipsoid formula (Length x width AP plane x width Transverse plan x .62). Examples of 
dosing volumes based on estimated kidney weight are shown in Table 10. 
Table 10: 
REACT Dosing Relative to Estimated Kidney Weight 
Estimated Kidney Weight (g KWest)a,b
REACT Dosing 
 Volume (mL) 
SRC Delivered 
(Number of Cells x 
 Median Weight (g) 
Weight Range (g) 
100 
95 – 108 
3.0 
300 
117 
109 – 125 
3.5 
350 
133 
126 – 141 
4.0 
400 
150 
142 – 158 
4.5 
450 
167 
159 – 175 
5.0 
500 
183 
176 – 191 
5.5 
550 
200 
192 – 208 
6.0 
600 
217 
209 – 225 
6.5 
650 
233 
226 – 241 
7.0 
700 
250 
242 – 258 
7.5 
750 
― ― ― 
>259
8.0c
800 
Abbreviations: Estimated Kidney Weight (g KWest); SRC (Selected Renal Cells). 
Notes: 
a. The dose of REACT will be 3 x 106 cells/g estimated kidney weight.
b. Kidney weight will be estimated from an MRI study performed before renal biopsy.
c. 8 mL will be the maximum dosing volume (mL).
The dose of REACT will be based on kidney volume calculated via MRI. In contrast to other 
methods, measurements of renal volume using MRI are more accurate, and acquire true 
tomographic data along any orientation without the risk of ionizing radiation or nephrotoxic 
contrast agents. Renal volume measurements (mL) estimated from MRI are approximately 92 to 
97% of dry weight measurements in grams for isolated organs trimmed of perirenal fat. As a 
conservative approach, the REACT dose will be calculated using a conversion of one g equals one 
mL. The volume of REACT to be administered will be determined by pre-procedure MRI 
volumetric 3D evaluation or ellipsoid formula (Length x width AP plane x width Transverse plan x 
.62). This ensures that subjects will not receive REACT doses higher than those previously tested in 
animal studies. 
3.2.5.1. 
Rationale for Two REACT Injections 
It is anticipated that all subjects will receive two planned REACT injections to allow dose-finding 
and evaluate the duration of effects. The scientific rationale, based on non-clinical studies, is that 
the biologically active component of REACT (homologous, autologous, SRC) delays progression of 
experimental models of CKD by augmenting renal structure and function.18,19,33,34,35,36   As a result, 
the more cells that can be infused, the greater the potential improvement in renal function. 
The total number of cells that can be delivered into a kidney at one time is limited by the size of the 
kidney, however, as well as the inelasticity of the renal capsule. Consequently, it may be possible to 
improve therapeutic benefit by administering greater numbers of SRC via a second injection, given 
after cells from the first injection have become incorporated into the kidney. 
Apart from increasing SRC numbers by administering 2 REACT injections into the same kidney, 
the duration of effects can be evaluated. The processes by which functional nephrons become 
disabled in kidneys with CKD may, over time, adversely affect “new” cells delivered via REACT 

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injection. Consequently, REACT might not result in long-term, therapeutic benefit. Exploring the 
effects from a second REACT injection, given at an appropriate interval after the first injection, 
would address this question. 
In the present study, subjects will be administered a second REACT injection 6 months after the 
first injection, with a study visit window of 4 weeks. Regardless, every attempt should be made to 
ensure that the second REACT injection is administered 6 months after the first injection. In 
the event that the subject cannot schedule his/her second REACT injection 6 months after the first 
injection, ProKidney and the Medical Monitor must be notified immediately. 
However, if there appears to be any untoward safety risk, or rapid deterioration of renal function, or 
development of uncontrolled diabetes or uncontrolled hypertension, or development of a 
malignancy or an intercurrent infection, then the second REACT injection should not be 
administered. 
3.2.5.2. 
Safety of Two REACT Injections 
To assess the safety of administering two doses of REACT into the biopsied kidney, a canine GLP 
toxicology study was conducted (Refer to Section 1.4.2). Similar to the clinical study design, study 
animals (n=8) underwent renal biopsies at 4 to 6 weeks prior to baseline. Each dose was delivered 
into both kidneys at baseline and 3 months; animals were observed for 6 months following the 
baseline injection. While control animals received PBS, REACT-treated animals received a two-
fold greater dose than that used in the present clinical study. 
Briefly, no detrimental effects of two doses of REACT into the biopsied kidney were observed in 
comparison to control animals 6 months after baseline treatment. Pathological assessment showed 
no REACT safety-related (macroscopic or microscopic) findings in either the target organ (kidney) 
or non-target organs examined. No treatment-related kidney findings were noted following 
enhanced evaluation of 8 areas of each kidney (3 stains per area), including assessment and scoring 
of 150 glomeruli per kidney. All kidneys appeared normal, apart from changes related to injection 
site scars. There were no signs of renal insufficiency, and no indications of decreased GFR. 
Detailed information is provided in the Investigator’s Brochure. 
3.3. 
Study Drug Packaging 
The product delivery system consists of 3 components: 
1. 10 mL standard, Luer-Lok® syringe
2. Package for containment of the syringe
3. REACT shipping container for transportation of the package to the clinical site
The syringe containing REACT will be shipped to the clinical site encased in a package designed to 
maintain integrity of the product as well as sterility of the product and syringe. A representative 
image of the product delivery system is shown in Figure 3. 

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autologous subjects, the number of stored specimens remaining at ProKidney LLC, and disposal of 
unused materials. 
3.5.2. 
Study Drug Handling and Disposal 
Since transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products; appropriate blood and secretion precautions will 
be employed by all personnel in the shipping and handling of all specimens for this study, as 
currently recommended by the Centers for Disease Control and Prevention and the National 
Institutes of Health. 
All material containing investigational drug product will be treated and disposed of as hazardous 
waste in accordance with governing regulations and clinical site procedures. 
3.5.2.1. 
Disposition of Stored Specimens 
Specimens will be stored in the vapor phase of a liquid nitrogen freezer at ProKidney. Only 
Investigators or suitably qualified individuals who have received appropriate study-specific training 
and whose names are listed on the Delegation of Responsibility Log will have access to these 
specimens. 
3.5.2.2. 
Unused Specimens 
Renal cells that may have been frozen but not used to manufacture REACT will be remain in the 
vapor phase of a liquid nitrogen freezer at ProKidney until the EOS Visit. At that time, if these renal 
cells are no longer needed, they will be de-identified of all personal information and stored in the 
vapor phase of a liquid nitrogen freezer for a maximum of 5 years. The aim is to test these renal 
cells in laboratory research studies. 
During the informed consent process, each subject must be provided the option not to store or use 
their unused renal cells and research samples (as described in Table 2), and must provide written 
consent for the storage and future use of autologous cells not used for REACT injection if they 
consent to the long-term storage of unused specimens. Additionally, subjects may decide at any 
point during the study not to have their unused renal cells stored. In this case, the Investigator will 
destroy all known remaining samples attributed to that subject and report what was done to both the 
subject and to the IRB. Likewise, subjects must have the option of having their cells destroyed upon 
completion of the study. 

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4.3. 
Number of Subjects 
Up to 10 subjects who complete screening procedures and satisfy all inclusion and exclusion criteria 
will be enrolled. 
4.4. 
Treatment Compliance 
Eligible subjects will receive their autologous REACT preparations via a series of up to two 
injections.  The investigational product will be administered into the biopsied kidney using a 
percutaneous approach. REACT product preparation and dosing procedures are specified in this 
protocol as well as the Study Reference Manual. 
It is anticipated that all subjects will receive two REACT injections. In some cases, a subject or the 
Investigator may elect to delay or withhold the second REACT injection. For example, if there 
appears to be any untoward safety risk, or if the subject’s health status would, in the judgment of the 
Investigator, be jeopardized, then the second REACT injection should not be administered. 
4.5. 
Study Duration 
Subjects will begin their series of REACT injection(s) as soon as the autologous REACT 
preparation is made available. Assuming a one-month interval prior to the first REACT injection, 
and assuming a 6-month interval before the second injection, plus a 24-month follow-up period 
after the final injection, the study duration would be: 
• 31 months for a series of 2 REACT injections 

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5. 
STUDY POPULATION 
5.1. 
Subject Inclusion Criteria 
Unless otherwise noted, subjects must satisfy each inclusion criterion to participate in the study. 
Inclusion criteria will be assessed at the Screening Visit, prior to renal biopsy, and before each 
REACT injection unless otherwise specified. 
1. The subject is male or female, 30 to 65 years of age on the date of informed consent. 
2. The subject has an established diagnosis of T2DM. 
3. The subject has an established diagnosis of diabetic nephropathy as the underlying cause of 
renal disease. 
4. The subject has an established diagnosis of CKD not requiring renal dialysis, defined as 
having an eGFR between 14 and 20 mL/min/1.73m2 inclusive at the Screening Visit and 
prior to REACT injection. 
5. The subject has blood pressure less than 150/90 at the Screening Visit, prior to renal biopsy, 
and prior to REACT injection(s). At the time of the biopsy and injections, the subject’s BP 
should not be significantly below the previously recorded stable pressure. 
6. The subject has stable blood pressure and is maintained on a stable anti-hypertensive 
medication regimen, if treatment for hypertension is necessary. If treatment includes an 
angiotensin-converting-enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB), 
that treatment must have been initiated at least 8 weeks prior to renal biopsy. Treatment 
must be stable during the 6-week period immediately prior to REACT injection. Stable 
treatment is defined as dose adjustment to no less than one half of the current dosage or to 
no more than 2 times the current dosage. Dose interruptions up to 7 days due to medical 
necessity are allowed.  
7. A minimum of 3 measurements of eGFR or sCr should be obtained at least 3 months apart 
prior to the Screening Visit or within the previous 24 months to define the rate of 
progression of CKD. The subject should have adequate, historical clinical data to provide a 
reasonable estimate of the rate of progression of CKD. The Medical Monitor may be 
consulted to ensure there is sufficient data. 
8. The subject is willing and able to refrain from NSAID consumption (including aspirin) as 
well as clopidogrel, prasugrel, or other platelet inhibitors during the period beginning 7 days 
before through 7 days after both the renal biopsy and REACT injection(s). 
9. The subject is willing and able to refrain from consumption of fish oil and platelet 
aggregation inhibitors, such as dipryridamole (i.e., Persantine®), during the period beginning 
7 days before through 7 days after both the renal biopsy and REACT injection(s). 
10. The subject is willing and able to cooperate with all aspects of the protocol. 
11. The subject is willing and able to provide signed informed consent. 

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5.2. 
Subject Exclusion Criteria 
Subjects who satisfy any exclusion criterion listed below are not eligible to participate in the study. 
Exclusion criteria will be assessed at the Screening Visit, before renal biopsy, and before each 
REACT injection unless otherwise noted. 
1. The subject has a history of type 1 diabetes mellitus. 
2. The subject has a history of renal transplantation. 
3. The subject has a serum HbA1c level greater than 10% at the Screening Visit. 
4. The subject has uncontrolled diabetes (defined as metabolically unstable by the 
Investigator). 
5. The subject has hemoglobin levels less than 9 g/dL prior to each REACT injection. 
6. The subject has abnormal coagulation status as measured by activated partial thromboplastin 
time (APTT), prothrombin time international normalized ratio (PT INR), and/or platelet 
count at the Screening Visit. 
7. The subject has a bleeding disorder(s) or is taking anticoagulants, such as Coumadin® 
(warfarin) or direct thrombin inhibitors that, in the judgment of the Investigator, would 
interfere with the performance of study procedures. 
8. The subject has small kidneys (average size less than 9 cm) or has only one kidney, as 
assessed by ultrasound and/or MRI prior to renal biopsy, unless earlier radiology reports 
(generated within 1 year of the Screening Visit) are made available to confirm kidney size 
and number. 
9. The subject has a known allergy or contraindication(s), or has experienced severe systemic 
reaction(s) to kanamycin or structurally similar aminoglycoside antibiotic(s) 
10. The subject has a history of anaphylactic or severe systemic reaction(s) or 
contraindication(s) to human blood products or materials of animal origin (e.g., bovine, 
porcine). 
11. The subject is not a good candidate to undergo percutaneous REACT injection, in the 
judgment of the surgeon or physician who will perform the procedure. This includes 
individuals who are morbidly obese (defined as BMI greater than 45 kg/m2), have excessive 
fat surrounding the kidney, or who are otherwise at excessive risk for serious complications. 
12. The subject has a history of severe systemic reaction(s) or any contraindication to local 
anesthetics or sedatives. 
13. The subject has a clinically significant infection requiring parenteral antibiotics within 6 
weeks of REACT injection. 
14. The subject has acute kidney injury or has experienced a rapid decline in renal function 
during the last 3 months prior to REACT injection. 
15. The subject has any of the following conditions prior to REACT injection: renal tumors, 
polycystic kidney disease, anatomic abnormalities that would interfere with the REACT 
injection procedure or evidence of a urinary tract infection. 
Note: anatomic abnormalities are not exclusionary if the kidney remains accessible and 
meets the criteria to receive the REACT injection. 
16. The subject has incapacitating cardiac and/or pulmonary disorders. 

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17. The subject has a history of cancer within the past 3 years (excluding non-melanoma skin 
cancer and carcinoma in situ of the cervix). 
18. The subject has clinically significant hepatic disease (ALT or AST greater than 3 times the 
upper limit of normal) as assessed at the Screening Visit. 
19. The subject is positive for active infection with Hepatitis B Virus (HBV), or Hepatitis C 
Virus (HCV), and/or Human Immunodeficiency Virus (HIV) as assessed at the Screening 
Visit. 
20. The subject has a history of active tuberculosis (TB) requiring treatment within the past 3 
years. 
21. The subject is immunocompromised or is receiving immunosuppressive agents, including 
individuals treated for chronic glomerulonephritis within 3 months of REACT injection. 
Note: inhaled corticosteroids and chronic low-dose corticosteroids (less than or equal to 7.5 
mg per day) are permitted as are brief pulsed corticosteroids for intermittent symptoms (e.g., 
asthma). 
22. The subject has a life expectancy less than 2 years. 
23. The female subject is pregnant, lactating (breast feeding), or planning a pregnancy during 
the course of the study. Or, the female subject is of child-bearing potential and is not using a 
highly effective method(s) of birth control, including sexual abstinence. Or, the female 
subject is unwilling to continue using a highly effective method of birth control throughout 
the duration of the study.  
Note: A highly effective method of birth control is defined as one that results in a low 
failure rate (i.e., less than one percent per year) when used consistently and correctly, such 
as implants, injectables, combined oral contraceptives, some intrauterine devices IUDs, 
sexual abstinence, or a vasectomized partner. 
24. The subject has a history of active alcohol and/or drug abuse that, in the judgment of the 
Investigator, would impair the subject’s ability to comply with the protocol. 
25. The subject’s health status would, in the judgment of the Investigator, be jeopardized by 
participating in the study. 
26. The subject has used an investigational product within 3 months prior to REACT injection 
without receiving written consent from the Medical Monitor. 
5.3. 
Prohibited and Concomitant Medications 
• The consumption of NSAIDs (including aspirin) as well as clopidogrel, prasugrel, or other 
platelet inhibitors is prohibited during the study beginning 7 days before through 7 days 
after both the renal biopsy and REACT injection(s). 
• Aspirin, up to a dose of 100 mg/day, may be continued if doing so is the standard of care at 
the investigational site, for subjects with diabetes who are greater than 40 years of age or 
have additional risk factors for cardiovascular disease or stroke, and for whom the perceived 
benefits of aspirin therapy outweigh the risks associated with treatment. 
• Intake of fish oil and platelet aggregation inhibitors, such as dipryridamole (i.e., Persantine), 
is prohibited during the study beginning 7 days before through 7 days after both the renal 
biopsy and REACT injection(s). 

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• Subjects who are undergoing treatment with an ACEI or an ARB must have initiated therapy 
at least 8 weeks prior to renal biopsy. Treatment must be stable during the 6-week period 
immediately prior to REACT injection. Stable treatment is defined as dose adjustment no 
less than one-half of the current dosage and no more than 2 times the current dosage. In 
addition, except where medically necessary, no changes should be made to the ACEI or 
ARB dosing regimen from Screening through the 24-month EOS Visit. Dose interruptions 
up to 7 days due to medical necessity are allowed. 
• Medications that interfere with measurements of SCr should be avoided during the study, 
such as trimethoprim, dronedarone, and cimetidine. If such medications are required based 
on medical necessity, then the circumstance should be discussed with the Medical Monitor 
and documented within the CRF. 
• Use of investigational drugs is prohibited during the course of the study, unless preapproved 
by the Medical Monitor. Investigational drugs are defined as drugs that have not been 
approved for use by the FDA. 
5.4. 
Subject Withdrawal Criteria 
Subjects may withdraw from the study at any time and for any reason without penalty or prejudice, 
and without jeopardizing access to future medical care. If the Investigator determines that 
continuing in the study is no longer in the best interest of the subject, then the Investigator should 
withdraw the subject from the study. If a subject voluntarily withdraws from the study, the reason(s) 
should be documented. Subjects who withdraw from the study or are withdrawn by the Investigator 
should undergo procedures specified at the EOS Visit. 
If a subject withdraws from the study before having the renal biopsy, the subject will be considered 
a screen failure. If a subject withdraws from the study following the renal biopsy but before the first 
REACT injection, the subject will not be a screen failure, but will not be considered enrolled and 
may be replaced. If a subject withdraws from the study after REACT injection but before the end of 
the follow-up period, the subject cannot be replaced. 
Patients that do not meet I/E criteria on the RMCL-002 protocol but had a biopsy may be enrolled 
into REGEN-003.  Patients that have completed a biopsy in RMCL-002 will not undergo another 
biopsy if they enroll in REGEN-003. 

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6. 
STUDY VISITS 
The schedules of clinical assessments and procedures to be performed during the study are 
displayed in the time and events tables, i.e., Table 1. Similarly, the schedules of sample collection 
and clinical laboratory evaluations planned for the study are displayed in the laboratory time and 
events tables, i.e., Table 2. Before conducting any study specific assessments or procedures 
(including screening), the subject must provide written informed consent in accordance with ICH 
GCP guidelines and 21 CFR Part 50. 
Due to the COVID-19 pandemic that began in March 2020, subject follow-up visits may be 
conducted remotely or via home health services to ensure the safety of the subject. Any procedures 
listed in the schedule of events that are not completed due to COVID-19 pandemic restrictions will 
be documented as protocol deviations. Clinical laboratory evaluations are permitted to be completed 
by a local lab convenient for the subject. Results of all evaluations performed by local laboratories 
will be collected by ProKidney. 
6.1. 
Screening 
All screening assessments should take place in a timeframe that will allow for scheduling of the 
renal biopsy within 60 days of the Screening Visit.  
Renal ultrasound will be performed at the Screening Visit to verify subject eligibility (i.e., no 
evidence of renal tumors, polycystic kidney disease, renal cysts or other anatomic abnormalities that 
would interfere with the REACT injection procedure) along with obtaining a baseline echogenicity 
reading. Additionally, a MRI study without contrast will be performed from the time of Screening 
Visit through Day -1 before renal biopsy to determine kidney size and volume. 
To qualify for study enrollment, the subject’s eGFR must be between 14 and 20 mL/min/1.73m2 
inclusive at the Screening Visit. To define the eGFR for entry criteria, the site should use the eGFR 
assessed during screening and calculate using the CKD-EPI equation.63 
If a subject does not meet a specific eligibility criterion, but the Investigator believes that the 
subject would be an excellent candidate for the clinical trial, then that criterion may be reassessed 
one time. In general, a subject who does not qualify may be rescreened once as long as the 
Investigator has sufficient clinical justification. If the Investigator has any questions concerning the 
appropriateness of rescreening a subject, then the Investigator should contact the Medical Monitor. 
If, for whatever reason, the biopsy cannot be conducted within 60 days of the Screening Visit, then 
the Investigator and Medical Monitor should discuss and agree upon the need for repeating the 
screening assessments on a case-by-case basis. For example, laboratory assessments performed 
between 1 and 3 days before the renal biopsy might be used in place of the screening assessments to 
satisfy final eligibility criteria. In other cases, it may not be appropriate or necessary to repeat the 
clinical diagnostic procedures, including ECG or MRI studies. 
6.2. 
Biopsy 
The biopsy should be scheduled within 60 days of the Screening Visit. The biopsy should take place 
in a time frame that will allow for scheduling of the first REACT injection approximately one 
month later. Due to shipping and manufacturing schedules, the preferred day for collecting the renal 
biopsy cores is on a Wednesday or Thursday. Biopsies should not be collected on a Friday. 
Subjects will report to the hospital or clinical research center one to three days before the biopsy for 
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assessed to verify continued eligibility. After admission and final verification of inclusion and 
exclusion criteria, the biopsy should be performed as described in Section 7.5.1. 
A minimum of 2 biopsy cores measuring 1.5cm in length a piece and collected using a 16-gauge 
biopsy needle under sterile conditions from each enrolled subject should be sent to ProKidney using 
the refrigerated shipping container provided by ProKidney and according to procedures detailed in 
the Study Reference Manual. ProKidney will contact the site to confirm receipt of sufficient biopsy 
material to manufacture REACT. If the biopsy cannot be used to manufacture REACT, the subject 
should be discontinued from the study. 
Subjects who do not experience complications from the biopsy may be discharged the same day 
consistent with site standard practice. Otherwise, the subject should remain in the hospital overnight 
for observation. The subject may be discharged on the day after the biopsy so long as any biopsy-
related AEs have resolved, stabilized, or returned to baseline. 
6.3. 
REACT Injection 
Due to shipping and manufacturing schedules, REACT injection should be scheduled on a 
Wednesday, Thursday, or Friday. If it is necessary to schedule the REACT injection on a Tuesday, 
the site should contact ProKidney in advance to make certain that a Tuesday delivery can be 
accommodated. The REACT injection should not be scheduled on a Monday. 
Subjects will report to the clinic 10 to 14 days before the scheduled REACT injection for pre-
treatment assessments. If the subject remains eligible, based on verification of inclusion and 
exclusion criteria, the site will perform a renal scintigraphy study and contact ProKidney indicating 
that the REACT product should be produced for that particular subject. 
It is anticipated that all subjects will receive two planned REACT injections to allow dose-finding 
and to evaluate the duration of effects. As indicated on the time and events tables (i.e., Table 1), the 
series of 2 REACT injections will be administered 6 months apart with a study visit window of 4 
weeks. Regardless, every attempt should be made to ensure that the second REACT injection 
is administered 6 months after the first injection. In the event that the subject cannot schedule 
his/her second REACT injection 6 months after receiving the first injection or cannot keep his/her 
scheduled 6-month visit, ProKidney and the Medical Monitor must be notified immediately. The 
expectation is that the subject and the clinical center will accommodate the Sponsor’s preference 
that the series of 2 REACT injections should be administered no more than 6 months apart. 
In some cases, a subject or the Investigator may decide to postpone or withhold the second REACT 
injection. For example, if there appears to be any untoward safety risk, or rapid deterioration of 
renal function, or the development of uncontrolled diabetes or uncontrolled hypertension, or the 
development a malignancy or an intercurrent infection, then the second REACT injection should 
not be administered. 
If continued eligibility cannot be verified for a particular subject, the site should contact ProKidney 
who will alert the manufacturing staff not to prepare the REACT product. The Investigator and 
ProKidney will discuss the reason(s) that the subject did not qualify and determine the best course 
of action. For example, if the subject was excluded for a temporary condition (e.g., active infection) 
then it may be possible to manufacture REACT at a later date, assuming future eligibility can be 
established. If the results of pre-treatment assessments indicate that it is highly unlikely for that 
subject to become eligible for REACT injection(s), then the subject should be discontinued from the 
study. If REACT injection is delayed (e.g., due to an intercurrent illness), the renal scintigraphy 
study, if conducted, does not need to be repeated prior to injection. 

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Eligible subjects will arrive at the hospital or clinical research center on the morning of REACT 
treatment. The subject will be injected with autologous REACT using a percutaneous approach as 
discussed in Section 7.5.2. 
6.4. 
Discharge After REACT Injection 
On the day after REACT injection and prior to discharge, an ultrasound will be performed to detect 
possible, subclinical adverse effects (e.g., swelling, fluid accumulation). If product- or procedure- 
related AE’s occurred following REACT injection, the subject should not be discharged until the 
AE’s have resolved, stabilized, or returned to baseline. If consistent with the site’s standard 
practice, the subject may be discharged the same day as the REACT injection after no less than 2 
hours of observation and monitoring. 
6.5. 
Follow-up Visits 
The subject will return to the clinic for follow-up visits on Days 1 (if discharged day of REACT 
injection), 7, 14, and 28 (± 3 days) and Months 2, 3, 4 and 5 (± 7 days) after the first REACT 
injection, and on Days 1 (if discharged day of REACT injection), 7, 14, and 28 (± 3 days) and 
Months 2 and 3 (± 7 days) after the second REACT injection (Table 1 and Table 2).The subject will 
also report to the clinical center 10 to 14 days before the planned, final REACT injection to undergo 
pre-treatment assessments. Every attempt should be made to ensure that the second REACT 
injection is administered 6 months after the first injection. 
Following the final REACT injection, subjects will complete long-term, follow-up assessments of 
safety and efficacy through Months 6, 9, 12, 15, 18, 21, and 24 (± 7 days) post-treatment. 
6.6. 
End-of-Study Visit 
This section describes situations in which a subject will undergo the EOS visit; for example, due to 
premature discontinuation from the study or completion of all protocol-specified follow-up visits. 
• If a subject discontinues from the study after undergoing the renal biopsy but before 
REACT injection, then that subject should complete all EOS assessments except for the 
MRI and/or renal scintigraphy studies. These imaging studies should only be completed 
if, in the judgment of the Investigator, one and/or the other would provide critical safety 
information needed for patient care. If the subject is experiencing an investigational 
product- or study procedure-related SAE, then the subject will not be discontinued until 
the SAE has resolved, stabilized, or returned to baseline. 
• If a subject discontinues from the study after undergoing one or two REACT injections 
but before completing all of the protocol-specified follow-up visits, then he/she should 
have the EOS Visit at the time of discontinuation. For these subjects, the Investigator 
will determine whether or not it is clinically prudent to perform one or both of the 
imaging studies (i.e., MRI and renal scintigraphy). If the subject is experiencing an 
investigational product- or study procedure-related SAE, then the subject will not be 
discontinued until the SAE has resolved, stabilized, or returned to baseline. 
• If a subject completes all of the protocol-specified follow-up visits, he/she will undergo 
all EOS assessments 24 months after the final REACT injection at the EOS Visit. If the 
subject is experiencing an investigational product- or study procedure-related SAE, then 
the subject will not be discontinued until the SAE has resolved, stabilized, or returned to 
baseline. 

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6.7. 
Study Completion 
Completion of the study is defined as the time when the last subject completes the EOS Visit, or 
when the last subject is considered lost to follow-up, withdraws consent, or dies. 

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7. 
STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Demography and Medical History 
Demographics characteristics will be obtained for each subject at the Screening Visit. 
All CKD-related medical history and all other significant medical history will be recorded in the 
CRF beginning at the Screening Visit. Throughout the study, medical conditions that are still 
ongoing will be regularly updated in the CRF. 
7.2. 
Clinical Evaluations 
7.2.1. 
Vital Signs 
Vital signs to be measured include systolic/diastolic blood pressure, heart rate, respiration rate, and 
temperature. Blood pressure will be measured after the subject has rested in a sitting position for a 
minimum of 5 minutes. At the Pre-Biopsy Visit (Day -3 to Day-1) and Pre-Injection Visit (Day -14 
to Day -10 Visit), three BP measurements will be taken and the average of the 3 measurements (for 
systolic and diastolic pressure) used to satisfy entry criteria and entered into the CRF. 
7.2.2. 
Physical Examination 
The Investigator or designee will perform the PE. The comprehensive examination will assess all 
pertinent body systems while the interim examination will include specific assessments of those 
body systems deemed appropriate for that subject by the Investigator. As a general rule for the 
interim examination, the Investigator will review the subject’s AEs prior to, or in conjunction with, 
the examination and include assessment of related body systems as appropriate. Only clinically 
significant abnormalities will be recorded in the CRF. 
The subject’s weight will be measured at every visit that includes a complete or interim physical 
examination. The subject’s height will be taken at the Screening Visit. Body Mass Index (BMI) will 
be calculated as kg/m2. 
7.2.3. 
ECG 
A 12-lead ECG will be obtained after the subject has been resting on their back for 5 minutes. 
7.2.4. 
Concomitant Medications 
Concomitant medications will be recorded in the CRF as follows: 
• Screening Visit until first REACT injection:  Record any CKD-specific medications 
as well as medications that may affect renal hemodynamics and/or serum creatinine 
measurements. In addition, record any medications used to treat an AE that is 
documented in the CRF. Surgical medications used during the biopsy procedure do not 
need to be captured in the CRF unless their use falls outside of expected dosages and/or 
frequencies of administration. 
• First REACT injection until 6 to 7 months of follow-up: Record any medications 
taken until 6 to 7 months after treatment, depending on when the second REACT 
injection will be administered. Surgical medications used during the REACT injection 
procedure do not need to be captured in the CRF unless their use falls outside of 
expected dosages and/or frequencies of administration. 

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• Second (Final) REACT injection until 6 months of follow-up: Record any 
medications taken until 6 months after the last REACT treatment. Surgical medications 
used during the REACT injection procedure do not need to be captured in the CRF 
unless their use falls outside of expected dosages and/or frequencies of administration. 
• 6 months of follow-up through the EOS Visit:  Record CKD-specific medications, 
that may affect renal hemodynamics and medications that may affect serum creatinine 
measurements. Record medications used to treat any AE documented in the CRF. 
7.2.5. 
Funduscopic Exam of Retina 
This exam should be completed at screening, month 12, and month 24/EOS to monitor for diabetic 
retinopathy of both eyes. Retinal photography should be collected and kept within the patient 
records and any worsening from baseline should be reported as an AE if not already documented in 
medical history. 
7.3. 
Laboratory Assessments 
Planned clinical laboratory evaluations are listed in Table 12. Analyses will be conducted by a 
central laboratory, except as noted. The schedule for collecting biological samples during the study 
are shown in Table 2.  
 
 

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Table 12: 
Clinical Laboratory Evaluations 
Clinical Chemistry 
Hematology 
Urinalysis (24hr and Urine 
Chemistry) 
Alkaline phosphatase 
ALT 
AST 
ß2-Microglobulin 
Bilirubin 
Creatinine kinase 
FSH (females only) 
GGT 
HbA1c
LDH 
PTH (intact) 
Hematocrit 
Hemoglobin 
RBC count & indices 
WBC count & differential 
Albumin 
ß2-Microglobulin 
Creatinine Protein 
Protein & Albumin:Creatinine Ratio 
NGAL 
Pregnancy 
hCG (serum) – 
confirmatory 
Serology 
Standard Panel 
HBV 
HCV 
HIV 
pH Ketones 
Protein 
 Blood 
Glucose  
Microscopic analysis 
 Renal Analytes 
Coagulation Status 
Albumin 
BUN 
Calcium 
CO2, total 
Creatinine 
Cystatin-C 
CRP 
eGFR (calculated) 
Glucose 
Phosphorus 
Potassium 
Sodium 
APTT 
PT-INR 
Platelet count 
Lipid Panel 
Drug Screen 
Cholesterol 
LDL 
HDL 
LDL:HDL 
ratio 
Triglycerides 
Amphetamine 
Barbiturates 
Benzodiazepines 
Cocaine  
Opiates 
Tetrahydrocannabinol 
Phencyclidine 
Abbreviations: ALT (Alanine Aminotransferase); APTT (Activated Partial Thromboplastin Time);AST (Aspartate 
Aminotransferase); BUN (Blood Urea Nitrogen); CRP (C-Reactive Protein); FSH (Follicle-Stimulating Hormone); 
GGT (gamma-glutamyl transferase); HbA1c (glycosylated hemoglobin); HBV (Hepatitis B Virus); hCG (Human 
Chorionic Gonadotropin); HCV (Hepatitis C Virus ); HDL (High Density Lipoprotein); HIV (Human Immuno- 
deficiency Virus); LDL (Low Density Lipoprotein); NGAL (Neutrophil Gelatinase-Associated Lipocalin); iPTH 
(Parathyroid Hormone, intact); PT-INR (Prothrombin Time- International Normalized Ratio). 
7.3.1. 
eGFR 
GFR will be estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 
equation that incorporates both serum creatinine and Cystatin C.63 The specific assay for measuring 
creatinine will be defined by ProKidney, and the samples will be analyzed by the central laboratory. 
For comparison to each subject’s historical values, it may be necessary to perform a second analysis 
at the site laboratory used to generate the historical data. The need for any additional assays 
conducted locally by the site laboratory will be defined at the Site Initiation Visit. 
7.3.2. 
Urine Collection 
Urine will be collected and analyzed via standard panel and urine chemistry. The schedules for 
collecting each type of urine sample are shown in Table 2. 
Urine will be collected over two different time periods: 24-hour collection and “spot” urine. Spot 
urine collections will be used for dipstick urinalysis (test stick) assessments. The schedules for 
collecting each type of urine sample are shown in Table 2. To provide a comprehensive picture of 
protein and albumin excretion, both total protein and albumin will be assessed in all samples. 

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7.3.3. 
Hematology 
Hemorrhage following biopsy and REACT injection is a known and foreseeable risk to subjects 
participating in this study. Therefore, hemoglobin and hematocrit will be measured by the site’s 
local laboratory before and after each procedure and compared to baseline levels. Other bleeding 
parameters (e.g., APTT, PTT-INR, platelets) also will be measured throughout the study. 
7.3.4. 
Virus Serology 
The biopsy cores obtained from each subject will be used for the expansion and selection of SRC. 
Contamination with HIV, HBV, and/or HCV would prevent ProKidney from manufacturing 
REACT product for that subject. Therefore, each subject will undergo testing for viral blood-borne 
pathogens, including HIV, HBV, and HCV. 
7.3.5. 
Drug Screen 
Consistent with Exclusion Criterion #24 (See Section 5.2), subjects are not eligible to participate in 
the study if they have an “…active history of … drug abuse that, in the judgment of the 
Investigator, would impair the subject’s ability to comply with the protocol.” Therefore, subjects 
will undergo testing for drugs of abuse. 
7.3.6. 
Pregnancy Screen 
A qualitative urine pregnancy test will be performed at the site using a test-strip. If the test is 
positive, then a confirmatory test will be performed by the clinical laboratory. If site practices do 
not accept the results of a test-strip, then a urine sample should be sent to the central laboratory for 
analysis. Post-menopausal women with a confirmatory FSH test do not have to undergo pregnancy 
testing throughout the study. 
7.3.7. 
Research Samples 
Research samples (serum/plasma and urine) will be collected, frozen, and stored for the evaluation 
of novel biomarkers. Participating subjects can opt out of long-term storage of their unused 
specimens during the informed consent process or at any time during the study (Section 3.5.2.2).  
7.4. 
Renal Imaging 
7.4.1. 
Ultrasound 
Renal ultrasound will be performed at the Screening Visit to verify subject eligibility (i.e., no 
evidence of renal tumors, polycystic kidney disease, renal cysts or other anatomic abnormalities that 
would interfere with the REACT injection procedure) along with obtaining a baseline echogenicity 
reading. Ultrasound will also be performed following the in-patient renal biopsy on Day 0 and Day 
1 and following the in-patient REACT injection(s) on Day 0 and Day 1 with the aim of monitoring 
possible, subclinical AEs. Findings from the ultrasound (e.g., resistance index, length, etc.) will be 
recorded on the CRF. An ultrasound may be conducted at other times, in the judgment of the 
Investigator, if needed for additional safety evaluation(s). 
7.4.2. 
Computerized Tomography 
Computerized tomography (CT) must be used in conjunction with ultrasound during the REACT 
injection procedure, according to the usual standards of care at the investigative site. Use of 
fluoroscopic CT may be used in conjunction with ultrasound. 

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7.4.3. 
Magnetic Resonance Imaging 
An MRI study without contrast will be performed from the Screening Visit through Day -1 before 
renal biopsy to determine kidney size and volume. During the site initiation visit, the MRI process 
will be defined for each site, depending on the MRI equipment available. Generally, a 1.5-T unit 
should be used. MRI imaging studies will help determine kidney volume (for dosing calculations). 
MRI will be performed using standard sequences without injection of contrast agents. Renal volume 
measurements may be calculated, for example, using a fast 3D gradient- echo sequence, VIBE, with 
an acquisition time of 22 seconds and spatial resolution of 2 x 1.4 x 1.2 mm. Imaging parameters 
will be recorded in the source documents and CRF. A total of two MRIs will be performed on 
patients. 
7.4.4. 
Renal Scintigraphy 
Renal scintigraphy will be used to assess left and right kidney function using the radioactive tracer 
99mTc- dimercaptosuccinic acid (DMSA) or Tc99m MAG3 (Mercaptoacetyl triglycine). This 
method is considered as the most reliable for measuring renal cortical function and is the preferred 
agent for this clinical trial. If the site standard practice is to use a radiopharmaceutical other than 
99mTc-DMSA or Tc99m MAG3 then the site must discuss their procedure with ProKidney or the 
Medical Monitor prior to site initiation. If the site’s standard practice is considered sufficiently 
equivalent to the procedure using 99mTc-DMSA or Tc99m MAG3, then the site will be allowed to 
follow their procedure. In this case, a copy of the site’s procedure will be signed/dated by the 
Project Leader from ProKidney and maintained in the site’s regulatory binder. All patients in this 
study will receive five renal scintigraphy studies. Renal scintigraphy will be performed before the 
first REACT injection, before the last REACT injection, at the 6-Month Visit after the last REACT 
injection, at the 12-Month Visit after the last REACT injection, and at the EOS Visit for all patients. 
7.5. 
Surgical Procedures 
7.5.1. 
Biopsy 
Renal biopsy will be performed under sterile conditions using an ultrasound- or CT-guided 
approach consistent with site practices. Two biopsy cores will be needed to provide sufficient 
material for the selection of SRC and manufacture of REACT. Likewise, a 16-gauge needle should 
be used to insure adequate cortical material is obtained. If required, a 15-gauge needle may be used 
following consultation with the Medical Monitor and Manufacturing Facility. Bedside examination 
of the biopsy cores may be performed, if available, to ensure sufficient cortical material has been 
obtained. 
Since the biopsy tissue will be used to manufacture REACT, the site must ensure that the tissue 
cores are harvested using sterile conditions so that the risk of contamination during subsequent cell 
expansion and selection is minimized. Contamination of the tissue cores could significantly 
jeopardize the ability of ProKidney to manufacture REACT product for that subject. 
Guidance on wound care and pain management following the biopsy procedure will be provided in 
the Interventional Radiologist Manual. Briefly, the subject will remain supine for 4 hours with 
monitoring of hemoglobin, blood pressure, gross hematuria, abdominal/flank pain, and flank 
ecchymosis. As long as any biopsy-related AEs have resolved, stabilized, or returned to baseline, 
the subject can be discharged from the hospital on the day after the biopsy consistent with site 
standard practice. Importantly, any pain medication administered after the renal biopsy should be 
selected carefully, avoiding medications with nephrotoxic potential. 

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If a subject experiences significant AEs following the biopsy that, in the opinion of the Investigator, 
would put the subject at increased risk for significant adverse effects following REACT injection, 
then he/she will not be treated with REACT but will be followed until resolution of the event(s) and 
then discontinued from the study. 
7.5.2. 
REACT Injection 
Before performing the REACT injection, the operating physician will evaluate the subject as 
follows: 
• Perform a physical examination to determine the feasibility of the procedure. 
• Evaluate bleeding parameters, including coagulation panel, PTT-INR, platelets, 
hemoglobin, hematocrit, and other pertinent laboratory studies. 
− Note: Hemorrhage following REACT injection is a known and foreseeable risk to 
subjects participating in this study. Therefore, hemoglobin and hematocrit will be 
measured before and after each REACT injection per the site’s standard practice 
and compared to baseline levels. 
• Review imaging studies, including ultrasound, MRI, and CT or fluoroscopic CT, to 
determine route of access, depth of kidney, and appearance of cortical-medullary 
junction. 
• Map potential REACT cell deposition sites. 
• Determine classification and associated perioperative /post-operative risk according to 
the American Society of Anesthesiologists (ASA) with respect to airway assessment, 
medical history, allergies, and medications. 
• Interview the subject and the subject’s family/supporters to discuss the procedure, its 
risks and possible complications. Answer questions and obtain written informed consent. 
Prophylactic antibiotics will be given intravenously according to site standard practice. An initial 
CT scan may be ordered, if necessary, to evaluate adjacent viscera, renal location, and the presence 
of renal cysts. A CT scan must be used in conjunction with ultrasound to locate the cortical-
medullary junction. 
REACT is targeted for injection into the kidney cortex via a needle/cannula and syringe compatible 
with cell delivery. The intent is to introduce REACT via penetration of the kidney capsule and 
deposit REACT into multiple sites of the kidney cortex. Initially, the kidney capsule will be pierced 
using a 15- to 20-gauge trocar /access cannula inserted approximately 1 cm into the kidney cortex. 
In the Phase 1 clinical study, REACT was administered via an 18-gauge needle. The proposed 
Phase 2 study will utilize an 18-gauge or smaller needle for REACT delivery. The needle will be 
threaded inside the access cannula and advanced into the kidney, from which the REACT will be 
administered. Injection of the REACT will be at a rate of 1 to 2 mL/min. After each 1-to-2-minute 
injection, the inner needle will be retracted along the needle course within the cortex to the second 
site of injection, and so forth, until the needle tip reaches the end of the access cannula or until the 
entire REACT product has been injected. Using a percutaneous delivery approach, placement of the 
access cannula /trocar and delivery needle will be performed using direct, real-time imaging. A CT 
scan must be used in conjunction with ultrasound for the REACT injection procedure. 
During the procedure, moderate conscious sedation will be employed; vital signs will be measured 
continuously. REACT injection will cease if there is imaging evidence of cell extravasation into 

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central or peripheral renal blood vessels, the medullary portion of the kidney, or through the renal 
cortex and into the retroperitoneal soft tissues, or evidence of active bleeding. 
Following completion of the REACT injection, the inner needle will be withdrawn, and the outer 
cannula will remain in place for track embolization. During removal of the outer cannula (trocar), 
the site of the renal cortex puncture and needle track through the retroperitoneum will be embolized 
with absorbable gelatin particle/pledgets (e.g., Gelfoam® [Pfizer]) or fibrin sealant (e.g., TISSEEL 
[Baxter]) or other suitable agent to prevent excessive renal bleeding. 
Upon completion of the procedure, non-contrast CT scan or ultrasound with color Doppler 
evaluation will be performed to image puncture site cell injection and any hematoma or bleeding 
events. The subject will be monitored for 2 to 3 hours post-procedure in a recovery-room 
environment with nursing assessment and measurement of vital signs. Subjects who do not 
experience complications may be discharged the same day as REACT injection, consistent with site 
standard practice. 

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8.
SAFETY ASSESSMENTS AND MANAGEMENT
8.1. 
Adverse and Serious Adverse Events 
8.1.1. 
Definition of Adverse Events 
An AE is the development of an undesirable medical condition (including abnormal laboratory 
findings) or the deterioration of a pre-existing medical condition following or during exposure to a 
study treatment, whether or not considered to have a causal relationship with study procedures or 
the investigational product. A pre-existing condition is a clinical condition (including a condition 
being treated) that is diagnosed before the subject signs the Informed Consent Form and is 
documented as part of the subject’s medical history. Pre-existing conditions that are stable or 
unchanged should not be considered AEs. 
The Investigator is responsible for ensuring that all AEs observed by the Investigator or reported by 
the subject that occur from the day of the biopsy procedure through 24 months after the final 
injection of REACT are monitored and recorded in the subject’s medical record as well as the CRF 
provided by the Sponsor or its designee. 
Treatment-emergent adverse events (TEAEs) are defined as any AE that started after the first 
injection of REACT or started prior to the first injection but increased in severity or frequency after 
the first injection of REACT. 
Unscheduled visits may be performed at any time during the study as judged necessary by the 
Investigator to assess and conduct follow-up on AEs. Evaluations and procedures to be performed 
at unscheduled visits will be at the Investigator’s discretion in consultation with the Sponsor and 
may be based on those listed in the Schedule of Events. 
The Investigator’s clinical judgment is used to determine whether a subject is to be removed from 
treatment due to an AE. 
An AE is considered unexpected if it is not consistent in nature or severity with information 
contained in the current version of the Investigator’s Brochure provided by the Sponsor. 
8.1.1.1. 
Definition of Serious Adverse Events 
An SAE is an AE that occurs during any phase of the study (i.e., baseline, treatment, washout, or 
follow-up) at any dose of the investigational product, comparator, or placebo, and fulfils one or 
more of the following: 
•
Results in death
•
It is immediately life-threatening
•
It requires in-patient hospitalization or prolongation of existing hospitalization
•
It results in persistent or significant disability or incapacity
•
Results in a congenital abnormality or birth defect
•
It is an important medical event that may jeopardize the subject or may require medical
intervention to prevent one of the outcomes listed above.
All SAEs that occur from the day of the biopsy procedure, during treatment, or within 24 months 
following the final REACT injection, whether or not they are related to study procedures or the 

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investigational product, must be recorded in the subject’s medical record as well as the CRF 
provided by the Sponsor or its designee. 
8.1.1.2. 
Other Significant Adverse Events 
Significant events of particular clinical importance include SAEs and AEs leading to premature 
discontinuation of subjects from the study. These events will be recorded in the subjects’ medical 
records as well as the CRF provided by the Sponsor or its designee. Narratives of these events may 
be prepared for inclusion in the Clinical Study Report. 
The following sections describe “adverse events of special interest” concerning procedure- and 
product-related events. Subjects should be carefully monitored for the occurrence of these potential 
AEs. 
8.1.1.3. 
Procedure-Related Events 
Post-procedure pain:  If the subject experiences pain following the biopsy or REACT injection, 
administration of paracetamol or paracetamol-codeine combinations is recommended. More severe 
pain in the loin or abdomen requires ultrasonography to exclude significant perirenal hemorrhage. If 
severe pain occurs, administration of opiates may be necessary. If analgesic doses higher than the 
maximum authorized doses are required to alleviate pain, then the Investigator must perform 
additional clinical evaluations to ascertain the probable cause(s) of excessive pain. 
Hemorrhage: Following renal biopsy and REACT injection procedures, subjects undergo regular 
hemoglobin and blood pressure monitoring. Subjects will be confined to bed and monitored for 
maintenance of normal coagulation indices. If bleeding occurs and the subject is hypotensive 
despite bed rest, a blood transfusion may be considered. If the bleeding is still not controlled, 
surgery may be considered. In rare cases, renal angiography may be performed to identify the 
source of bleeding. Coil embolization can be performed during the same procedure. 
Other complications:  In very rare cases, other organs (such as liver, gallbladder and lungs) may 
be penetrated during the biopsy procedure. In these cases, appropriate treatment and follow- up may 
be discussed with consulting surgeons. 
Death: Deaths resulting from renal biopsies occur in <0.01% of patients.55,56,57  Adherence to strict 
inclusion /exclusion criteria will ensure that subjects who may be predisposed to uncontrolled or 
excessive bleeding will not be enrolled in this trial. 
8.1.1.4. 
Product-Related Events 
No REACT product-related events are expected to occur. This assumption is based on the 
autologous nature of REACT (i.e., REACT is manufactured from renal cells isolated from the same 
kidney to which they are being returned), the lack of product-related events observed in pre- clinical 
animal studies, and the lack of specific REACT- related events seen during and following implant 
of the first 5 subjects in the Phase 1 clinical trial. However, subjects will be extensively monitored 
throughout the course of the study for any unexpected events. 
If an event occurs which is assessed as related to the investigational product, REACT, then the 
event will be immediately reviewed by the Investigator and Medical Monitor. 

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8.2. 
Adverse Event Intensity and Relationship Assessment 
8.2.1. 
Intensity Scale 
Intensity will be assessed by the Investigator using the “Common Terminology Criteria for Adverse 
Events” (CTCAE) version 4.03, from the US National Cancer Institute (refer to  
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf). 
If the AE is not included in the CTCAE, then the Investigator will determine the intensity of the AE 
according to the following criteria: 
• Mild (Grade 1): The AE is noticeable to the subject but does not interfere with routine 
activity. 
• Moderate (Grade 2):  The AE interferes with routine activity but responds to 
symptomatic therapy or rest. 
• Severe (Grade 3):  The AE significantly limits the subject’s ability to perform routine 
activities despite symptomatic therapy. Severe events are usually incapacitating. 
• Life-Threatening (Grade 4): The subject is at immediate risk of death. 
• Death (Grade 5) 
If the intensity (grade) changes within a day, the maximum intensity (grade) should be recorded. If 
the intensity (grade) changes over a longer period of time, the changes should be recorded as 
separate events (having separate onset and stop dates for each grade). 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Definition of Serious Adverse Events (See 
Section 8.1.1.1). Therefore, an AE of severe intensity may not necessarily meet the criteria for 
seriousness. 
8.2.2. 
Relationship Assessment 
An Investigator listed on Form FDA 1572 may make the determination of relationship to the study 
procedure or investigational product for each AE. The Investigator should judge whether there is a 
reasonable possibility that the AE may have been caused by the study procedure or investigational 
product. If no valid reason exists for suggesting a relationship, then the AE should be classified as 
“not related.” If there is any valid reason, even if undetermined, for suspecting a possible cause-
and-effect relationship, then the AE should be considered “possibly related” or “related” to the 
study procedure or investigational product. 
Definitions of relatedness categories are: 
• Not Related: Exposure to the study treatment did not occur, or the occurrence of the AE 
is not reasonably related in time, or the AE is considered unlikely to be related to the 
study treatment. 
• Unlikely Related:  The study treatment and the AE were not closely related in time, 
and/or the AE could be explained more consistently by causes other than exposure to the 
study treatment product. 
• Possibly Related:  The study treatment and the AE were reasonably related in time, and 
the AE could be explained equally well by causes other than exposure to the study 
treatment product. 

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• Related:  The study treatment and the AE were reasonably related in time, and the AE 
was more likely explained by exposure to the study product than by other causes, or the 
study treatment was the most likely cause of the AE. 
For the purpose of safety analyses, all AEs judged by the Investigator to be “possibly related” or 
“related” will be considered treatment-related adverse events. 
8.3. 
Recording and Reporting Adverse Events 
Adverse events spontaneously reported by the subject and/or in response to an open question from 
study personnel, or revealed by observation, or documented via laboratory reports, imaging reports, 
consult notes, survey instruments and other data collection tools, will be recorded in the subject’s 
medical records and CRF provided by the Sponsor or its designee. 
Adverse events will be reported using standard medical terminology, whenever possible. A 
clinically significant change in laboratory values or vital signs need not be reported as an AE unless 
the abnormal change constitutes an SAE and/or leads to discontinuation of treatment or withdrawal 
from the study. 
For each AE, the Investigator will record the start date, the stop date, the intensity of each 
reportable event, the Investigator’s judgment of the relationship to the study procedure or 
investigational product, the action taken, severity (if applicable), and whether the event resulted in 
discontinuation of treatment or withdrawal from the study. Follow-up information on any SAE may 
be requested by ProKidney or its designee. 
All SAEs must be promptly reported by the Investigator to ProKidney or its designee within 24 
hours from the time when the Investigator first becomes aware of the event. All SAEs must be 
reported whether or not they are considered causally related to the study procedure or 
investigational product. SAE forms will be provided to each clinical site. 
The information collected will include subject number, a narrative description of the event, and an 
assessment by the Investigator as to the intensity of the event and relatedness to the investigational 
product. The Investigator must complete, sign and date the SAE pages, and verify the accuracy of 
the information recorded against the corresponding source documents. Follow-up information on 
the SAE may be requested by ProKidney or its designee. 
Contact information for reporting SAEs appears below: 
Email: CTISafety@ctifacts.com 
SAE Hotline: 1877-755-0742 
eFax: 1-800-541-1501 
 
ProKidney or its designee is responsible for notifying the relevant regulatory authorities of certain 
AEs. It is the Principal Investigator’s responsibility to notify the IRB /EC of all SAEs that occur at 
the site. 
8.3.1. 
Serious Unexpected Drug Reactions 
If there are serious, unexpected adverse drug reactions (SUSARs) associated with the use of the 
investigational product, ProKidney or its designee will notify the FDA and all participating 
Investigators on an expedited basis and in accordance with applicable regulations. It is the 
responsibility of the Investigator to promptly notify the IRB /EC and other appropriate institutional 
regulatory bodies of all unexpected serious adverse drug reactions involving risk to human subjects. 

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8.3.2. 
Pregnancy 
Pregnancy is neither an AE nor an SAE, unless a complication relating to the pregnancy occurs. All 
reports of congenital abnormalities /birth defects are SAEs. Spontaneous miscarriages should be 
reported and handled as SAEs. However, elective abortions without complications should not be 
handled as AEs. 
All pregnancies experienced by female subjects enrolled in this study are to be reported in the same 
time frame as SAEs using the Pregnancy Form of the CRF. The course of all pregnancies, including 
perinatal and neonatal outcome, regardless of whether the subject has discontinued participation in 
the study, will be followed until resolution, including follow-up of the health status of the newborn 
to 6 weeks of age. 
The effects of administration of the investigational product on the pregnant female or the 
developing fetus are unknown. Therefore, female subjects of child-bearing potential who are 
planning a pregnancy during the course of the study, or who are not using a highly effective 
method(s) of birth control, or who are unwilling to continue using a highly effective method of birth 
control throughout the duration of the study are not eligible to participate in the study. (Refer to 
Exclusion Criterion # 23; Section 5.2). 
8.4. 
Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB) will be chartered to oversee subject safety, especially as 
it relates to unexpected investigational product-related events. The DSMB will minimally consist of 
3 members who have expertise directly related to protocol-specified activities. It will function 
independently, and its members will have no other engagement with ProKidney. The DSMB will 
meet by teleconference at regular intervals, depending on the speed of subject enrollment and the 
amount of new data generated. The DSMB will advise ProKidney on aspects concerning the safety 
of subjects participating in the clinical trial. Apart from reviewing study data, the DSMB will 
consider feedback from the Sponsor and Investigators. The DSMB will share its recommendations 
with the study centers, Institutional Review Boards /Ethics Committees, and regulatory authorities, 
as appropriate. Other specific activities and responsibilities of the DSMB will be detailed in the 
DSMB charter. 
8.5. 
Dose Adjustment Criteria 
The dates for the first 3 subjects who are scheduled to receive a second REACT injection under 
IND 16482 will be staggered at a minimum of 3-week intervals. The DSMB will sequentially 
review the status of each of these subjects prior to the next subject undergoing his/her second 
REACT injection. After the third subject has received his/her second REACT injection, the DSMB 
will meet to assess AEs and other safety parameters obtained to date for these 3 subjects described 
in the protocol. The DSMB may recommend changes concerning the second REACT injection as 
well as protocol-specified study evaluations, and/or follow-up procedures. 
Apart from reviewing study data, the DSMB will evaluate relevant feedback from the Sponsor and 
Investigators. 
8.6. 
Stopping Rules for an Individual Subject 
The Investigator, Medical Monitor, DSMB, and Sponsor may remove any subject from the study 
for: 

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• Any clinical AE, laboratory abnormality, intercurrent illness, other medical condition or 
situation whereby continued participation in the study would not be in the best interest of 
the subject. 
• Development of any exclusion criterion. 
If a subject is terminated from the study, EOS assessments should be conducted at the last visit. 
If any of the following events occur, no additional subjects can receive REACT injections until 
review by the DSMB has been completed: 
• An SAE that is rated as severe or life-threatening and, in the judgment of the 
Investigator, is related to REACT or study procedures 
• Death of an enrolled subject 
• Similar SAE’s in more than one subject that are related to REACT, in the judgment of 
the Investigator 
• Inability to deliver a minimum of 50% of the dose of REACT in more than one subject 
due to surgical or other issues 
8.7. 
Study Suspension or Study Termination 
As long as subjects are enrolled and participating in the study, including follow-up, the Medical 
Monitor, DSMB, IRB /EC, Sponsor, FDA and other regulatory agencies will review serious, 
unexpected, procedure- and product-related AEs. 
Enrollment in the study will be suspended if any patient develops an apparent tumor, whether in the 
kidney or at a remote anatomic site. A DSMB review will then determine whether or not study 
amendment or termination is needed. The study will also be suspended in the event that two or more 
patients develop a similar unexpected SAE or AEs that are more severe than expected with the 
study drug or study procedures.  A DSMB review will then determine whether or not study 
amendment or termination is needed. If a decision is made to suspend or terminate the study, the 
ProKidney will notify the Investigators /sites and ProKidney as well as the IRB /EC and regulatory 
authorities, as required. 
The DSMB, IRB /EC, Sponsor, Investigator(s), FDA and other regulatory authorities, as part of 
their duties to ensure human subject protection, may suspend the study at any time due to concerns 
for the safety of study subjects. Once the clinical trial is halted (i.e., no new enrollments and no 
further REACT injections), a report will be submitted to the IRB /EC. 

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9. 
STATISTICAL METHODS AND PLANNED ANALYSES 
9.1. 
Sample Size 
Up to 10 subjects who complete screening procedures and satisfy all inclusion and exclusion criteria 
will be enrolled. 
Statistical analyses will be primarily descriptive in nature and no statistical hypothesis testing is 
planned for the study. Unless otherwise specified, continuous variables will be summarized by 
presenting the number of non-missing observations (n), mean, standard deviation, median, 
minimum, and maximum. Categorical variables will be summarized by presenting frequency count 
and percentage for each category. 
9.2. 
Criteria for Evaluation 
9.2.1. 
Analysis Objectives and Endpoints 
9.2.1.1. 
Primary 
To assess the safety of REACT injected in one recipient kidney. 
• Primary Endpoint: Procedure and/or product related AEs through 24 months post-
injection. 
9.2.1.2. 
Secondary 
To assess the safety and tolerability of REACT administration by assessing renal-specific AEs over 
a 24-month period following injection. 
• Secondary Endpoints: Renal-specific laboratory assessments through 24 months post 
injection. 
9.2.1.3. 
Exploratory 
To assess the impact of REACT on renal function over a 24-month period following injection and 
on the Quality of Life. 
• Exploratory Endpoints: 1) Clinical diagnostic and laboratory assessments of renal 
structure and function (including eGFR, serum creatinine, and proteinuria) to assess 
changes in the rate of progression of renal disease, 2) patient-reported outcomes from the 
Kidney Disease Quality of Life (KDQOL) and EQ-5D-5L surveys obtained at baseline 
(i.e., after randomization, but before REACT injection) through 24 months after the last 
REACT injection. 
9.3. 
Demographic and Baseline Characteristics 
Demographic data and baseline characteristics will be summarized via sample size, mean, standard 
deviation, median, minimum, and maximum for the continuous variables as well as the frequency 
and proportion for categorical variables. These summaries will be produced for both the full 
analysis set and the injection analysis set. Demographic and baseline characteristic information will 
be presented as descriptive statistics; generating inferential statistics is not planned. These data will 
be provided in a tabular listing. 

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9.4. 
Efficacy Analysis 
The primary efficacy endpoint is serial measurements of eGFR obtained at 1, 3, 6, 12, 15, 18, 21, 
and 24 months after the last REACT injection.  GFR will be estimated using the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation that incorporates both serum creatinine 
and Cystatin C. [1] 
Estimated GFR measured at each time point will be summarized by presenting descriptive statistics 
of raw data and change from baseline values for each treatment group. 
9.5. 
Exploratory Analysis 
An exploratory analysis will be conducted to examine potential changes in health-related Quality of 
Life (HR-QoL). 
9.6. 
Statistical Methods 
Subjects will complete the KDQOL-SF™ survey (i.e., Kidney Disease and Quality of Life Short 
Form). The KDQOL-SF is a 36-item, validated, HR-QoL instrument relevant to patients with 
kidney disease.64   This disease-specific, HR-QoL instrument consists of the following subscales: 
• The “SF-12 measure of physical (PCS) and mental (MCS) functioning” contains items 
about general health, activity limits, ability to accomplish desired tasks, depression and 
anxiety, energy level, and social activities. 
• The “Burden of Kidney Disease subscale” contains items about how kidney disease 
interferes with daily life, takes up time, causes frustration, or makes the respondent feel 
like a burden. 
• The “Symptoms and Problems subscale” contains items about how bothered a 
respondent feels by sore muscles, chest pain, cramps, itchy or dry skin, shortness of 
breath, faintness/dizziness, lack of appetite, feeling washed out or drained, numbness in 
the hands or feet, nausea, or problems with dialysis access. 
• The “Effects of Kidney Disease on Daily Life subscale” contains items about how 
bothered the respondent feels by fluid limits, diet restrictions, ability to work around the 
house or travel, feeling dependent on doctors and other medical staff, stress or worries, 
sex life, and personal appearance. 
9.7. 
Safety Analysis 
9.7.1. 
Laboratory Evaluations 
Baseline values will be collected immediately prior to REACT injection. Observed and change from 
baseline laboratory data will be summarized via sample size, mean, standard deviation, median, 
minimum, and maximum for the continuous variables as well as frequency and proportion for the 
categorical variables. Laboratory abnormalities will be defined using the NCI CTCAE grading 
scheme. Abnormal laboratory values will be flagged as above or below the normal range. The 
results of laboratory testing for renal function, specifically sCr, BUN, and urinary albumin, are of 
particular interest for this study. 
The incidence of treatment-emergent laboratory abnormalities, defined as values that increase at 
least one toxicity grade between baseline and any time post-baseline up to six months following 
REACT injection, will be summarized. If baseline data are missing, then the latest value between 

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biopsy and injection will be used as the baseline value. If baseline and pre-injection data are 
missing, then any graded abnormality (i.e., at least a Grade 1) will be considered as treatment- 
emergent. These values will be summarized for both the full analysis set and the injection analysis 
set. Observed and change from baseline values will be presented as descriptive statistics; generating 
inferential statistics is not planned. These data will be provided in a tabular listing. 
9.7.2. 
Adverse Events 
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 18.1 by System Organ Class (SOC) and Preferred Term (PT). Adverse events 
will be graded using the CTCAE version 4.03 from the US National Cancer Institute. 
A treatment-emergent AE will be defined as any AE that started after the first injection of REACT 
or started prior to the first injection but increased in severity or frequency after the first injection of 
REACT. Summaries (frequency and proportion) of treatment-emergent AE’s will be presented by 
SOC and PT. Additional summaries will include, but are not limited to, treatment- emergent AE 
judged to be related to the procedure and/or investigational product, intensity, reason for subject 
withdrawal, SAEs, and deaths. The numbers of events (occurrence) and the number of subjects 
(incidence) who experienced treatment-emergent AEs will be reported by treatment group. Adverse 
event data will be provided in a data listing. 
9.7.3. 
Other Safety Evaluations 
Change from baseline for vital signs will be calculated for each subject and provided in a data 
listing. The number and percent of subjects who exhibit change(s) in their physical examinations 
(such as from normal to abnormal) will be summarized via a data listing. The number and percent 
of subjects who develop abnormal heart rhythms or QT-interval prolongation during the study will 
be provided in a data listing. Data from medical history, concomitant medications, ultrasound, renal 
scintigraphy, and MRI assessments will be provided in a data listing. 
Descriptive statistics for these evaluations will be generated as warranted. 
9.8. 
Biopsy and REACT Injection(s) 
Biopsy and REACT injection data will be provided in a data listing. 

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ETHICAL AND REGULATORY CONSIDERATIONS
10.1. 
Good Clinical Practice
This study will be conducted in compliance with the protocol, in accordance with ICH E6 
Harmonized Tripartite Guideline (ICH-GCP), in general agreement with the most recent version of 
the Declaration of Helsinki, and in accordance with all applicable United States and European 
regulations. 
10.2. 
Delegation of Principal Investigator Responsibilities 
The Investigator will ensure that all persons assisting with the trial are adequately informed about 
GCP requirements, the protocol, any amendments to the protocol, the study treatments as well as 
their trial-related duties and functions. The Investigator will maintain a list providing the names, 
positions, signatures, and initials of sub-investigators as well as other appropriately qualified 
personnel, including those authorized to make entries and corrections on the CRF. 
10.3. 
Institutional Review Board / Ethics Committee 
The final study protocol, Investigator’s Brochure, subject informed consent, subject recruitment 
materials (if applicable), and patient-reported questionnaires/surveys (if applicable), including 
respective version dates, must be approved or given a favorable opinion in writing by an IRB /EC as 
appropriate. A copy of the written approval must be provided to the Sponsor. This documentation 
should clearly mention the approval/favorable opinion of the protocol, the subject Informed 
Consent Form, and subject recruitment materials (if applicable), and patient-reported 
questionnaires/surveys (if applicable) along with the respective version dates. The written approval 
and a list of current membership, or Department of Health and Human Services (DHHS) Assurance 
Number, or letter from the IRB /EC stating that the membership list is on file, must be provided to 
the Sponsor prior to the release of clinical study supplies to the investigational site and 
commencement of the study. If any member of the IRB /EC has direct participation in this clinical 
trial, written notification regarding his or her abstinence from voting must also be obtained. 
The Investigator must inform the IRB /EC of any amendment to the protocol, provide updates about 
the ongoing trial at intervals (at least annually) specified by the respective IRB /EC, and submit 
final study reports to the IRB /EC. In addition, the IRB /IEC must approve all advertising used to 
recruit subjects for the study along with any written information to be provided to subjects (e.g., 
diaries, calendars, patient-reported surveys) and updates to the Informed Consent Form. 
It is the Investigator’s responsibility to notify the IRB /EC of all SAEs that occur at his or her site. 
The Sponsor is responsible for notifying the relevant regulatory authorities of certain safety events, 
including unexpected, serious, drug-related adverse reactions that occur during the clinical study. 
The Investigator is responsible for notifying its IRB /EC of these unanticipated SAEs. 
Initial IRB approval, and all materials approved by the IRB for this study including the subject 
consent form and recruitment materials must be maintained by the Investigator and made available 
for inspection. 
10.3.1. 
Subject Informed Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continuing throughout the individual’s study participation. The Investigator will ensure 
that potential participants (and their families) are given full and adequate oral and written 

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information about the nature, purpose, possible risk(s) and benefit(s) of the study. IRB-approved 
consent forms explaining study procedures and the investigational product /intervention(s) will be 
provided. The Investigator will explain the research study and answer any questions that may arise. 
Potential participants should have sufficient time to discuss the study, ask questions, and process the 
information during the consent process before deciding whether or not to participate. 
The rights and welfare of potential subjects will be protected by emphasizing that the quality of 
their medical care will not be adversely affected should they decide not to participate in the research 
study. Those individuals who agree to enroll must sign and date the current version of the Informed 
Consent Form prior to starting any study-related procedures, including screening. Subjects may 
withdraw consent at any time throughout the course of the clinical trial without penalty or prejudice 
toward future medical care. 
The acquisition of informed consent will be documented in the participant’s medical records, as 
required by 21 CFR 312.62. The Informed Consent Form will be signed and personally dated by the 
participant and the person who conducted the informed consent discussion. A copy of the signed 
Informed Consent Form must be given to the subject while the original, signed Informed Consent 
Form must be retained by the Investigator. 
10.4. 
Subject Confidentiality 
Individual subject medical information obtained as a result of this study is considered confidential 
and disclosure to third parties is prohibited. Such medical information may be given only after 
approval of the subject to his/her physician or to other appropriate medical personnel responsible 
for the subject’s well-being. The Sponsor affirms the subject’s right to protection against invasion 
of privacy. Only a subject identification number and/or initials (where allowed by local or national 
regulations) will identify subject data retrieved by the Sponsor. However, ProKidney requires the 
Investigator to permit the Sponsor, its designated representative(s), the IRB /EC, and when 
necessary, representatives of the regulatory health authorities to review and/or to copy any medical 
records relevant to the study. 
10.5. 
Substantial Amendment to the Protocol 
A substantial amendment to the protocol must be agreed upon in writing by the Sponsor, then 
submitted to and approved by the respective regulatory authority before the amendment can be 
implemented. It is the responsibility of ProKidney or its designee to ensure compliance with the 
appropriate regulatory requirements. 
Written approval of a protocol amendment is not required prior to implementation of changes that 
eliminate an immediate hazard to the study subject; however, approval must be obtained as soon as 
possible thereafter. Any protocol amendment also must be signed by the Investigator, who will 
provide a copy to the IRB /EC. 
10.6. 
Protocol Deviations 
A protocol deviation is any noncompliance with the protocol or GCP requirements. The 
noncompliance may be attributed to the subject, the Investigator, or the site staff. All protocol 
deviations will be documented and reported by the monitor during the course of the study as 
described in the Study Monitoring Plan. ProKidney will work with the site to develop and 
implement any corrective actions to address protocol deviations, as appropriate. 

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Serious breaches of the protocol that are likely to significantly affect the safety of a subject or the 
integrity of the data generated must be reported to the Sponsor, IRB /EC, and regulatory 
authorities. 
Although, in principle, no deviations from or changes to the protocol are permitted, under 
emergency circumstances protocol deviations may proceed without prior approval from ProKidney, 
IRB /EC and regulatory authorities to protect the rights, safety, and well-being of study subjects. 

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11. 
DATA HANDLING AND RECORDKEEPING 
11.1. 
Data Collection and Review 
11.1.1. 
Data Collection 
ProKidney or its designee will provide the clinical sites with access to CRFs for each subject. A 
CRF must be completed for every subject who provides written, informed consent and has 
undergone at least one protocol-specified, study-specific assessment. CRF completion instructions 
will be provided to the site in the Study Reference Manual. The Investigator or designated 
representative should complete the CRFs as soon as possible after the information has been 
collected. The Investigator is responsible for ensuring the accuracy, completeness, and timeliness of 
the data reported in a subject’s CRF. Source documentation supporting the CRF data should 
indicate the subject’s participation in the study and document the dates and details of study 
procedures, AEs, and subject status. 
When a subject completes the study, the Investigator must review and sign the CRF indicating that 
he/she has reviewed the completed CRF and pertinent clinical data for that subject and that, to the 
best of his/her knowledge, all data recorded in the CRF accurately reflect the subject’s clinical 
performance in the study. 
11.1.2. 
Study Monitoring 
Before an investigational site can enter a subject into the study, a representative of ProKidney or its 
designee will visit the investigational study site to: 
• Determine the adequacy of the facilities. 
• Discuss with the Investigator(s) and other personnel their responsibilities under the 
protocol as well as the responsibilities of ProKidney. This will be documented in a 
Clinical Study Agreement between ProKidney and the Investigator. 
During the study, a study monitor appointed by ProKidney or its designee will have regular contacts 
with the site and conduct on-site monitoring visits as described in the Study Monitoring Plan. 
Monitoring and auditing procedures, approved by the Sponsor, will ensure that the study is 
conducted in accordance with the protocol and regulatory requirements while ensuring the safety of 
all study subjects. Apart from on-site visits, the monitor will maintain frequent communication with 
the Investigator and site personnel via letters, e-mails, telephone, and FAX. 
Duties of the monitor include, but are not limited to: 
• on-site review of the CRFs for completeness and clarity 
• confirmation that the facilities remain acceptable 
• confirmation that investigational product accountability checks are being performed 
• confirmation that AEs and SAEs are properly documented in the CRFs, and that any 
SAEs have been forwarded to ProKidney or its designee and the IRB /EC 
• recording and reporting of any protocol deviations not previously sent to ProKidney, the 
IRB /EC, and regulatory authorities, as required 
• clarification of administrative matters 

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The monitor will perform source data verification, including a comparison of the data in the CRF 
with the subject’s medical records at the hospital or clinic, and other records relevant to the study. 
Source data verification requires direct access to all original records for each subject. The review of 
medical records will be performed in a manner that ensures subject confidentiality. 
Regulatory authorities and the IRB /EC may request access to all source documents for on-site 
inspection or an audit. Likewise, the Sponsor or its designee may conduct a quality assurance to 
ensure compliance with GCP and all applicable regulatory requirements. Direct access to source 
documents must be guaranteed by the Investigator, who will provide support at all times for these 
activities. 
11.2. 
Audits and Inspections 
The purpose of an audit or inspection by the Sponsor, regulatory authorities, the IRB /EC, or other 
appropriate institutional bodies is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and the data were 
recorded, analyzed, and accurately reported, in accordance with the protocol, ICH-GCP, and any 
applicable regulatory requirements. The Investigator and the site /institution must provide support at 
all times for on-site audits or inspections by providing direct access to all source documents, CRFs, 
and other study documentation. The Investigator must notify ProKidney or its designee immediately 
if contacted by a regulatory agency about an inspection. 
Additionally, the Sponsor or its designee will be allowed to conduct site visits to the investigational 
facilities for the purpose of monitoring any aspect of the study. The Investigator agrees to allow the 
monitor to inspect the drug storage area, study drug stocks, drug accountability records, subject 
charts, study source documents, and other records relative to study conduct. 
11.3. 
Retention of Records 
The Investigator agrees to keep records and those documents that include (but are not limited to): 
the identification of all participating subjects; medical records; study-specific source documents; 
source worksheets; all original signed and dated Informed Consent Forms; records of any body 
fluids or tissue samples retained; query responses; and, detailed records of investigational product 
accountability to enable evaluations or audits from regulatory authorities, the Sponsor, or its 
designees. 
These documents are to be retained until at least two years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region, or at least two years have elapsed since the formal discontinuation of clinical 
development of the investigational therapy. If the Investigator cannot meet this obligation, he/she 
must ask the Sponsor for permission to make alternative arrangements; details of these 
arrangements should be documented. If the Investigator withdraws from the responsibility of 
retaining the study records, custody must be transferred to a person willing to accept the 
responsibility. ProKidney must be notified in writing if a custodial change occurs. 

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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Independent quality assurance (QA) and clinical quality control (QC) systems are implemented and 
maintained using written standard operating procedures (SOPs) to ensure that the trial is conducted, 
and data are generated, documented (recorded), and reported in compliance with the protocol, ICH-
GCP, and the applicable regulatory requirements. 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
ProKidney may conduct a quality assurance audit. Refer to Audits and Inspections (Section 11.2) 
for more details regarding the audit process. 
13. 
PUBLICATION POLICY 
All information regarding the investigational therapy is the confidential property of ProKidney. The 
Investigator agrees to use this information to conduct the study and will not use it for other purposes 
without written approval from the Sponsor. It is understood that there is an obligation to provide 
ProKidney with complete data obtained during the study. ProKidney retains full rights over any 
invention, discovery, or innovation, patentable or not, that may occur during the conduct of the 
clinical trial. 
It is anticipated that the results of this study will be presented at scientific meeting(s) and/or 
published in a peer-reviewed journal(s). A Publications Committee, composed of Investigators 
participating in the study and representatives from the Sponsor, will oversee the publication and 
presentation of study results, which will reflect the experience of all participating clinical sites. 
The International Committee of Medical Journal Editors has adopted a trials-registration policy 
requiring that all clinical trials be registered in a public database (such as ClinicalTrials.gov and 
clinicaltrialsregister.eu) as a condition for publication in member journals. It is the responsibility of 
ProKidney to register the present study in an acceptable clinical trial registry on or before the onset 
of subject enrollment. 

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14. 
LIST OF REFERENCES 
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3. Khan SS, Kazmi WH, Abichandani R, Tighiouart H, Pereira BJ, Kausz AT. Health 
care utilization among patients with chronic kidney disease. Kidney Int. 2002;62:229-
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4. Keith DS, Nichols GA, Gullion CM, Brown J, Smith DH. Longitudinal follow-up and 
outcomes among a population with chronic kidney disease in a large managed care 
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6. National Institute for Health and Clinical Excellence (NICE). Chronic kidney disease: 
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9. Levey AS, Eckardt K-U, Tsukamoto Y, et al. Definition and classification of chronic 
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16. US Renal Data System. 2012 Annual data report:  Atlas of chronic kidney disease 
and end-stage renal disease in the US. National Institutes of Health, National Institute 
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used as maintenance therapy in kidney transplantation: a systematic review and meta- 
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18. Bruce AT, Ilagan RM, Guthrie KI, et al. Selected renal cells modulate disease 
progression in rodent models of chronic kidney disease via NF-κB and TGF-β1 
pathways. Regen Med. 2015;10:815-39. 
19. Bruce AT, Cox BR, Watts B, et al. Exposure of cultured human renal cells induces 
mediators of cell migration and attachment and facilitates the repair of tubular cell 
monolayers in vitro. Experimental Biology Meeting, Washington, DC, 2011. 
20. Genheimer CW, Ilagan RM, Spencer T, et al. Molecular characterization of the 
regenerative response induced by intrarenal transplantation of selected renal cells in a 
rodent model of chronic kidney disease. Cells Tissues Organs. 2012;196:374-84. 
21. Ilagan R, Choudhury S, Bruce AT, et al. Exosomes derived from primary renal 
cells contain microRNAs that can potentially drive therapeutically-relevant 
outcomes in models of chronic kidney disease. TERMIS Conference, Orlando, FL, 
2010. 
22. Ilagan R, Guthrie KI, Cox BR, et al. Secreted factors from bioactive kidney 
cells attenuate NF-kappa-B. TERMIS Conference, Orlando, FL, 2010. 
23. Ilagan R, Guthrie KI, Sangha N, et al. Characterization of primary adult canine renal 
cells (CRC) in a three-dimensional (3D) culture system permissive for ex vivo 
nephrogenesis. KIDSTEM Conference, Liverpool, UK, 2009. 
24. Kelley R, Bruce A, Spencer T, et al. A population of selected renal cells augments renal 
function and extends survival in the ZSF-1 model of progressive diabetic nephropathy. 
Cell Transplant. 2013;22:1023-39. 
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preserves renal functions and extends survival in the ZSF-I model of progressive diabetic 
nephropathy. ADA Conference, San Diego, CA, 2011. 
26. Kelley R, Werdin ES, Bruce AT, et al. Bioactive renal cells augment kidney function in 
a rodent model of chronic kidney disease. ISCT Conference, Philadelphia, PA, 2010. 
27. Kelley RW, Bruce AT, Wallace SM, et al. Enhanced renal cell function in dynamic 
3D culture system. KIDSTEM Conference, Liverpool, UK, 2008. 
28. Kelley RW, Werdin ES, Bruce AT, et al. Bioactive renal cells augment renal function in 
the ZSF-1 model of diabetic nephropathy. TERMIS Conference, Orlando, FL, 2010. 
29. Presnell SC, Bruce AT, Wallace SM, et al. Isolation, characterization, and expansion 
(ice) methods for defined primary renal cell populations from rodent, canine, and 
human normal and diseased kidneys. Tissue Engineering Part C Methods. 2010;17:261-
73. 
30. Presnell SC, Bruce AT, Wallace SM, et al. Isolation and characterization of 
bioresponsive renal cells from human and large mammal with chronic renal 
failure. Experimental Biology Meeting, New Orleans, LA, 2009. 

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31. Wallace SM, Bruce AT, Choudhury S, et al. Quantitative ex vivo characterization 
of human renal cell population dynamics via high-content image-based analysis 
(hca). ISCT Conference, Philadelphia, PA, 2010. 
32. Yamaleyeva LM, Guimaraes-Souza NK, Krane LS, Atala A, Aboushwareb T, Yoo JJ. 
Primary human kidney cell cultures containing erythropoietin-producing cells improve 
renal injury. TERMIS Conference, Orlando, FL, 2010. 
33. Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders 
for patients needing cystoplasty. Lancet. 2006;367:1241-46. 
34. Jayo MJ, Jain D, Ludlow JW, et al. Long-term durability, tissue regeneration and neo- 
organ growth during skeletal maturation with a neo-bladder augmentation construct. 
Regen Med. 2008;3:671-82. 
35. Jayo MJ, Jain D, Wagner BJ, Bertram TA. Early cellular and stromal responses in 
regeneration versus repair of a mammalian bladder using autologous cell and 
biodegradable scaffold technologies. J Urol. 2008;180:392-7. 
36. Jayo MJ, Watson DD, Wagner BJ, Bertram TA. Tissue engineering and regenerative 
medicine:  role of toxicologic pathologists for an emerging medical technology. 
Toxicol Pathol. 2008;36:92-6. 
37. Bilan VP, Salah EM, Bastacky S, et al. Diabetic nephropathy and long-term treatment 
effects of rosiglitazone and enalapril in obese ZSF-1 rats. J Endocrinol. 2011;210:293-08. 
38. Brenner BM. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985;249: 
F324-37. 
39. Montgomery AV, Davis JC Jr, Prine JM, Swann HG. The intrarenal pressure; its 
relation to age, weight, blood pressure, and sex. J Exp Med. 1950;92:637-42. 
40. Swann HG, Prine JM, Moore V, Rice RD. The intrarenal pressure during experimental 
renal hypertension. J Exp Med. 1952;96:281-291. 
41. Basu J, Sangha N, Rivera E, Guthrie K, Bertram T, Jain D. Dynamic distribution of 
therapeutically bioactive selected renal cells in large animal pre-clinical model. 
International Society for Stem Cell Research, Annual Conference, Vancouver, BC, 
2014. 
42. Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs autologous 
bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in 
patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 
2012;308:2369-79. 
43. Hare JM, Traverse JH, Henry TD, et al. A randomized, double-blind, placebo-controlled, 
dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) 
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44. Heldman AW, DiFede DL, Fishman JE et al. Transendocardial mesenchymal stem 
cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT 
randomized trial. JAMA. 2014;311:62-73. 
45. Lee JS, Hong JM, Moon GJ, et al. A long-term follow-up study of intravenous 
autologous mesenchymal stem cell transplantation in patients with ischemic stroke. 
Stem Cells. 2010;28:1099-106. 
46. Malliaras K, Makkar RR, Smith RR, et al. Intracoronary cardiosphere-derived cells after 

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myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of 
the CADUCEUS trial (Cardiosphere-derived autologous stem cells to reverse 
ventricular dysfunction). J Am Coll Cardiol. 2014;63:110-22. 
47. Lees GE, Cianciolo RE, Clubb FJ Jr. Renal biopsy and pathologic evaluation 
of glomerular disease. Top Companion Animal Med. 2011;26:143-53. 
48. Nass K, O'Neill WC. Bedside renal biopsy: ultrasound guidance by the nephrologist. 
Am J Kidney Dis. 1999;34:955-9. 
49. Oberholzer M, Torhorst J, Perret E, Mihatsch MJ. Minimum sample size of kidney 
biopsies for semiquantitative and quantitative evaluation. Nephron. 1983;34:192-
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51. Stenvinkel P, Bloomberg P, Brismar T, et al. et al, A "first-in-human study" of 
implantation of Neo-Kidney Augment, an autologous selected renal cell population, in 
Type-2 diabetic CKD stage 3-4 patients. World Congress of Nephrology, Cape Town 
South Africa, 2015. 
52. Khajehdehi P, Junaid SM, Salinas-Madrigal L, Schmitz PG, Bastani B. Percutaneous 
renal biopsy in the 1990s: safety, value, and implications for early hospital discharge. 
Am J Kidney Dis. 1999;34:92-7. 
53. Manno C, Bonifati C, Torres DD, Campobasso N, Schena FP. Desmopressin acetate in 
percutaneous ultrasound-guided kidney biopsy: a randomized controlled trial. 
Am J Kidney Dis. 2011;57:850-5. 
54. Groman RP, Bahr A, Berridge BR, Lees GE. Effects of serial ultrasound-guided renal 
biopsies on kidneys of healthy adolescent dogs. Vet Radiol Ultrasound. 2004;45:62-
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55. Hergesell O, Felten H, Andrassy K, Kuhn K, Ritz E. Safety of ultrasound-guided 
percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol 
Dial Transplant. 1998;13:975-7. 
56. Lin WC, Yang Y, Wen YK, Chang CC. Outpatient versus inpatient renal biopsy: 
a retrospective study. Clin Nephrol. 2006;66:17-24. 
57. Walker PD. The renal biopsy. Arch Pathol Lab Med. 2009;133:181-8. 
58. Medarova Z, Vallabhajosyula P, Tena A, et al. In vivo imaging of autologous islet grafts 
in the liver and under the kidney capsule in non-human primates. Transplantation. 
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approach in kidney tumor management. Cancers (Basel). 2010;2:1895-900. 
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following intrarenal doses of various kidney homogenates and hemogenate fractions in 
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62. Humphreys BD, Valerius MT, Kobayashi A, et al. Intrinsic epithelial cells repair 

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the kidney after injury. Cell Stem Cell. 2008;2:284-91. 
63. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate 
from serum creatinine and cystatin C. N Engl J Med. 2012;367:20–9. 
64. Hays RD, Kallich JD, Mapes DL. Kidney Disease Quality of Life Short Form 
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Calif.: 1995. www.rand.org/health/surveys_tools/kdqol.html. Accessed 28 April 2016. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol Summary of Changes 
 
REGEN-003 Version 1.6 to 1.7 
 
 
Page 1 
 
 
 
 
A PHASE II, OPEN-LABEL, SAFETY AND TOLERABILITY STUDY OF A RENAL AUTOLOGOUS 
CELL THERAPY (REACT) IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY 
DISEASE (REGEN-003) 
Summary of Changes from Protocol Version 1.6 (05MAR2019) to Version 1.7 (12JAN2021) 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol Summary of Changes 
 
REGEN-003 Version 1.6 to 1.7 
 
 
Page 2 
 
Administrative and formatting changes are not highlighted below but can be found in the “track-changes” version of the protocol. 
 
 
Protocol Section 
Original Text 
Updated Text 
Reason for Change 
Throughout 
V 1.6 05MAR2019 
V 1.7 12JAN2021 
Updated protocol version 
and date as needed. 
Throughout 
10 Market Street, #688 Camana Bay 
Grand Cayman, Cayman Islands KY1-
9006 
8020 Arco Corporate Drive, Suite 118 
Raleigh, NC 27617 
Updated Sponsor address 
as needed. 
Throughout 
inRegen 
ProKidney 
Updated Sponsor Name as 
needed.  
Throughout 
Twin City Bio LLC or Twin City Bio 
ProKidney, LLC or ProKidney 
Updated Manufacturer 
Name as needed.  
Throughout 
NKA  
REACT 
Updated product name as 
needed 
Throughout 
Autologous Neo-Kidney Augment 
Renal Autologous Cell Therapy 
Updated product name as 
needed 
Section 6 Study Visits 
 
Due to the COVID-19 pandemic that began 
in March 2020, subject follow-up visits may 
be conducted remotely or via home health 
services to ensure the safety of the subject. 
Any procedures listed in the schedule of 
events that are not completed due to 
COVID-19 pandemic restrictions will be 
documented as protocol deviations. Clinical 
laboratory evaluations are permitted to be 
completed by a local lab convenient for the 
subject. Results of all evaluations performed
by local laboratories will be collected by 
ProKidney. 
Updated collection of 
laboratory assessments to 
allow for more flexibility 
due to the pandemic.