Proact: A Study of REACT in Subjects With Type 2 Diabetes Mellitus and Chronic Kidney Disease

Inclusion Criteria:

1. The participant is male or female, 30 to 80 years of age on the date of informedconsent.

2. Documented diagnosis of type 2 diabetes mellitus (T2DM) and chronic kidney diseaseas the underlying cause of kidney disease (diagnosis does not have to be confirmedby kidney biopsy).

3. eGFR of at least 20 mL/min/1.73 m2 AND <30 mL/min/1.73 m2, not requiring kidneydialysis. UACR level cannot exceed 5000 mg/g (565 mg/mmol), OR

4. eGFR of 30 to ≤ 35 mL/min/1.73m2 AND UACR of 300 to ≤ 5000 mg/g (33.9 mg/mmolto ≤565 mg/mmol).

5. Serum glycosylated hemoglobin (HbA1c) of 9.5% or lower at Screening.

6. Systolic blood pressure of ≤ 140 mm Hg and diastolic blood pressure of ≤ 90 mm Hg atScreening, based on average of 3 consecutive measurements obtained seated or supine.Note: Retesting may be performed if initial screening blood pressure exceedseligibility criteria for systolic and/or diastolic blood pressure. Changes in bloodpressure Page 46 of 113 CONFIDENTIAL ProKidney Renal Autologous Cell TherapyClinical Protocol REGEN-006 USAN/INN: Rilparencel Version 6.0 medications will berecorded in the appropriate eCRF. (refer to BP procedures)

7. All participants should be strongly considered for treatment with sodium-glucosecotransporter 2 inhibitor (SGLT2i). For participants on SGLT2i medications, the dosemust be stable for at least 4 weeks prior to randomization. Note: The reason for aparticipant NOT receiving SGLT2i therapy at the time of randomization will bedocumented in the eCRF. (See Section 7.1 for additional guidance about ConcomitantTherapies).

8. On a clinically relevant, maximally tolerated dose of an angiotensinconverting-enzyme inhibitor (ACEI) OR an angiotensin receptor blocker (ARB), unlessnot tolerated or contraindicated. The dose must be stable for at least 4 weeks priorto randomization. Note: The reason for a participant NOT receiving an ACEI or ARB atthe time of randomization will be documented in the eCRF. (See Section 7.1 foradditional guidance about Concomitant Therapies).

9. Participant agrees, and in the judgement of the Investigator, is able to refrainfrom using therapies that may increase bleeding risk for the specified pre-procedureand postprocedure (biopsy/sham biopsy and rilparencel/sham injections) durations inthe discretion of the PI in consultation with the treating physician, in accordancewith the required minimum medication-specific guidelines for high-risk procedures59and patients with advanced CKD.

• Nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen and naproxen

• Aspirin

• Platelet aggregation inhibitors (PAIs) such as clopidogrel, prasugrel, anddipyridamole

• Factor Xa inhibitors

• Warfarin

• Heparin products

• Other anticoagulation.

8. Participant is willing and able to cooperate with all aspects of the protocol.

9. Participant is willing and able to provide signed informed consent.

Exclusion Criteria:

1. The participant has a history of type 1 diabetes mellitus.

2. The participant has a history of renal transplantation or other organtransplantation (corneal transplants are not an exclusion), solitary kidney,recurrent complicated urinary tract infections or complicated kidney stones. Urinarytract infections identified prior to renal biopsy or injection should be resolvedprior to procedures.

3. The participant has any other known underlying cause of kidney disease, includingbut not limited to: Autosomal dominant and recessive polycystic kidney disease,primary focal segmental glomerulosclerosis, vasculitis related CKD, IgA nephropathyand other immune modulated nephropathies, drug-induced CKD or other types of CKD oranatomic variants as determined by the Investigator or Sponsor that would interferewith biopsy and rilparencel injection procedure or confound study assessments. Note: The following are not considered exclusionary under the following conditions: (Unique situations should be discussed with the study Medical Monitor.)

• Concomitant hypertension-related CKD

• Anatomic abnormalities and benign conditions are not exclusionary if the kidneyhas accessible kidney cortex for biopsy and injection procedures and meets thecriteria to receive the rilparencel injection.

• Abnormalities on kidney biopsy (e.g., secondary focal segmentalglomerulosclerosis) which are considered secondary to diabetes with thefollowing conditions: lack of other identifiable etiology, full evaluation forother etiologies, no specific treatment administered other than diabetesmanagement.

4. History of acute kidney injury or major surgery (based on the judgement of theInvestigator and Medical Monitor) within 3 months prior to the Screening Visit.

5. Myocardial infarction, unstable angina, revascularization procedure (e.g. stent orbypass graft surgery), or cerebrovascular accident within 12 weeks beforerandomization, or a revascularization procedure is planned during the trial.

6. Current or history of heart failure of New York Heart Association (NYHA) Class IVcardiac disease.

7. History of malignancy within the past 3 years prior to Screening, except for basalcell and/or squamous cell carcinomas of the skin with apparent successful curativetherapy, carcinoma of the cervix in situ, or a malignancy that in the opinion of theInvestigator, along with agreement from the Medical Monitor, is considered treatedwith no evidence of disease and at minimal risk of recurrence.

8. Documented clinically significant liver disease, including acute or chronichepatitis B or hepatitis C. Note: At the discretion of the Investigator, aparticipant who gives a history of a treated and cured Hepatitis C infection may bescreened with a test for viral ribonucleic acid (RNA), and if a cure isdemonstrated, the participant may be enrolled.

9. Known infection with HIV, active syphilis, or other unresolved active genitourinaryinfection, or active tuberculosis requiring treatment at Screening.