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Item 1. Business

2026-03-18 compared with 2025-03-17 · 283 added, 265 removed, 655 unchanged (46% of the section changed)

Prior to July 11, 2022, we were a blank check company registered under the laws of the Cayman Islands and formed for the purpose of effecting a merger, capital stock exchange, asset acquisition, stock purchase, reorganization or similar business combination with one or more businesses.

On July 11, 2022, we completed the Business Combination pursuant to the Business Combination Agreement, that we entered into with PKLP.

Upon the completion of the Business Combination, we changed our name to “ProKidney Corp.” and the business of PKLP became our business.

We are a clinical-stage biotechnology company with a transformative proprietary cell therapy platform that has the potential to treat multiple chronic kidney diseases using cells isolated from the patient intended for treatment.

Our approach seeks to redefine the treatment of chronic kidney disease (“CKD”), shifting the emphasis away from management of kidney failure to the preservation of kidney function.

Our lead product candidate, rilparencel, is designed to preserve kidney function in a CKD patient’s diseased kidneys.

We are a late-clinical-stage biotechnology company pioneering the development of a first-in-class, autologous cell therapy that is intended to preserve kidney function in patients with advanced chronic kidney disease (“CKD”) and diabetes.

Our approach seeks to redefine the treatment of CKD, shifting the emphasis away from management of kidney failure to the preservation of kidney function.

Our lead product candidate, rilparencel, is the only cell therapy in Phase 3 clinical study for the treatment of advanced CKD and type 2 diabetes.

Rilparencel is a product that includes autologous Selected Renal Cells (“SRC”) prepared from a patient’s own (autologous) kidney cells.

The SRC are formulated rilparencel for reinjection into the patient’s kidneys using a minimally invasive outpatient procedure that is repeatable, if necessary.

The SRC are formulated as rilparencel for reinjection into the patient’s kidneys using a minimally invasive outpatient procedure.

Because rilparencel is a personalized product composed of cells prepared from a patient’s own kidney, there is no need for treatment with immunosuppressive therapies that are required during a patient’s lifetime when a patient receives a kidney transplant from another (allogeneic) donor.

We are currently conducting a Phase 3 clinical study and an ongoing Phase 2 clinical study for rilparencel in subjects with moderate to severe CKD and diabetes.

Rilparencel has received regenerative medicine advanced therapy (“RMAT”) designation from the United States Food and Drug Administration (the “FDA”).

We also completed a Phase 1 clinical trial for rilparencel in subjects with CKD due to congenital anomalies of the kidney and urinary tract (“CAKUT”) for which the last subject visit occurred in January 2023 and the clinical study report was submitted to the FDA in December 2023.

Our technology works by expanding and selecting kidney cells of a patient to preserve kidney function that is being lost due to chronic disease.

Our process begins when a small piece (biopsy) of a patient’s diseased kidney is sent to our manufacturing facility.

We process tissue taken from the biopsy and isolate SRC that are formulated into a personalized product for reinjection into the damaged kidney(s).

To date, clinical studies suggest that rilparencel has the capacity to positively impact kidney function by stabilizing the estimated glomerular filtration rate (“eGFR”) or attenuating the rate of eGFR decline in patients with CKD and diabetes.

Chronic kidney disease is segmented into five stages, from mild (CKD Stage 1) to severe (CKD Stage 5 or kidney failure), and it is estimated that over 37 million people in the United States currently suffer from CKD.

We are initially pursuing the development of rilparencel in the United States for use in patients with moderate to severe CKD and type 2 diabetes, a population that includes over one million people.

We are currently conducting a Phase 3 clinical study and recently completed a Phase 2 clinical study for rilparencel in subjects with advanced CKD and type 2 diabetes.

Rilparencel has received regenerative medicine advanced therapy (“RMAT”) designation from the United States Food and Drug Administration (the “FDA”), a status granted to accelerate the development and review of promising regenerative medicine therapies.

Rilparencel has, to date, been generally well tolerated by subjects with moderate to severe CKD in Phase 1 and 2 clinical testing.

Our patented technology includes multiple breakthroughs in the manufacturing and medical delivery of cellular therapy products.

Our technology works by expanding and selecting kidney cells of a patient in an attempt to preserve kidney function that is being lost due to chronic diseases.

Our process begins when a small piece or biopsy of a patient’s diseased kidney is sent to our manufacturing facility.

We are able to process cells taken from the biopsy and select specific cells with a reparative capacity.

These SRC are formulated into a personalized product for reinjection into the damaged kidney(s).

To date, clinical studies suggest that rilparencel has the capacity to, for a time, positively impact kidney function as reflected by stabilizing the estimated glomerular filtration rate (“eGFR”) or attenuating the rate of eGFR decline in patients with CKD and diabetes.

We are initially pursuing the development of rilparencel in the United States for use in patients with moderate to severe CKD and type 2 diabetes.

We estimate that approximately 36 million - 37 million adults, representing approximately 14% of the U.S.

adult population, currently suffer from CKD.

Chronic kidney disease is segmented into five CKD stages, from mild (CKD stage 1) to severe (CKD stage 5 or kidney failure).

With respect to those patients with stage 3b or 4 CKD and diabetes, we estimate that approximately 1.2 million to 1.8 million patients could be eligible for treatment with rilparencel in the United States.

The Phase 3 study includes other countries in North America, Latin America, and Asia Pacific.

REGEN-006/PROACT 1 trial:

REGEN-006 (PROACT 1) is an ongoing Phase 3, randomized, blinded, bi-lateral kidney dosing, sham controlled arm, efficacy and safety study of rilparencel in subjects with advanced CKD and type 2 diabetes.

The related study protocol has been amended to focus on a subset of patients with Stage 4 CKD (eGFR between 20 and 30 mL/min/1.73m 2 ) and late Stage 3b CKD (eGFR between 30 and 35 mL/min/1.73m 2 with accompanying albuminuria UACR between 300 and 5000 mg/g).

This study is being conducted in clinical centers in the United States, Mexico, and Taiwan.

The primary objective of this study is to assess the efficacy of up to two rilparencel injections given three months apart and delivered into both kidneys using a minimally invasive percutaneous approach with a targeted enrollment of approximately 470 patients.

Subjects will be randomized (1:1) to the treatment group and the sham control group prior to kidney biopsy.

Subjects in the treatment group will receive two injections of rilparencel of 3x10 6 cells/g-KW est .

The surrogate endpoint to support a potential accelerated approval of rilparencel is annualized eGFR slope.

The efficacy analysis set is expected to contain approximately 360 patients and will include all patients with at least 6 months of follow-up after first injection.

We anticipate topline data readout of the surrogate endpoint (eGFR slope) in the second quarter of 2027 and anticipate topline data readout of the confirmatory endpoint (composite time-to-event) in the second half of 2029.

In May 2025, we completed our REGEN-007 trial, a multi-center Phase 2 open-label 1:1 randomized two-arm trial of rilparencel in patients with diabetes, CKD, and an eGFR of 20-50 mL/min/1.73m².

Full results were presented as a late-breaking clinical trial at the American Society of Nephrology Kidney Week 2025 and a more complete set of results were published in the Clinical Journal of the American Society of Nephrology in early 2026.

At randomization, patients were assigned to one of two treatment groups using different dosing regimens.

Group 1 replicated the dosing schedule of our ongoing Phase 3 PROACT 1 study in which patients receive two scheduled rilparencel injections (one in

each kidney), approximately three months apart.

Group 2 tested an exploratory dosing regimen to investigate whether disease progression triggers, rather than a time-based trigger, could optimize multiple administrations of rilparencel.

In Group 2, patients received a single rilparencel injection in one kidney and a second injection in the contralateral kidney only if triggered by a sustained eGFR decline from baseline of ≥ 20%, and/or an increase of >30% and >30mg/g in the urine albumin to creatinine ratio (“UACR”) from baseline.

The prespecified primary endpoint for REGEN-007 was the difference in annual eGFR slope (calculated using a linear mixed effects model) in the pre-injection period versus the period following the last rilparencel injection.

The pre-injection period included all historical eGFR values collected up to 24 months before the screening visit as well as the on-study central laboratory eGFR results prior to first rilparencel injection.

The period following the last injection included eGFR values from the last rilparencel injection to the end of study (“EOS”) visit.

Median follow-up after the last injection was approximately 18 months in both Group 1 and Group 2.

Fifty-three patients were randomized in the study, of whom 49 patients (mITT population) received at least one rilparencel injection.

Four patients did not receive any rilparencel injections.

The majority of patients were male (69%), and the mean age was 60 years.

At baseline, 38 of 49 patients (78%) had type 2 diabetes mellitus and 11 (22%) had type 1 diabetes.

Thirty-nine (80%) patients were receiving an ACEi or an ARB, and 18 (37%) were receiving a SGLT2 inhibitor.

At baseline, the mean (SD) eGFR was 33±10 mL/min/1.73m².

Notably, the median UACR was higher in Group 1 (792 mg/g) compared to Group 2 (229 mg/g).

In Group 1 (n=24), kidney function stabilized after receiving rilparencel.

The annual decline in eGFR slope improved by 78% from -5.8 mL/min/1.73m² in the pre-injection period to -1.3 mL/min/1.73m² in the period following the last rilparencel injection.

This 4.6 mL/min/1.73m² per year difference was statistically significant (p<0.001) and clinically meaningful.

Among Group 1 patients, 15 of 24 (63%) met key Phase 3 PROACT 1 inclusion criteria.

In this subgroup, treatment with rilparencel resulted in a 5.5 mL/min/1.73m² improvement in the annual decline in eGFR slope.

This 85% improvement was statistically significant and clinically meaningful.

In Group 2 (n=25), the annual change in kidney function as measured by eGFR slope was -3.4 mL/min/1.73m² in the pre-injection period versus -1.7 mL/min/1.73m² in the period following the last rilparencel injection, resulting in an improvement of 50%, or 1.7 mL/min/1.73m² per year.

This difference was not statistically significant (p=0.085) but suggests evidence of a dose response.

Out of the 25 patients in Group 2, 15 (60%) met the re-dosing trigger and received a second rilparencel injection.

The median time between the first and second injections in these 15 patients was approximately 11 months.

No rilparencel-related serious adverse events were observed across all patients in the study who received at least one rilparencel injection (n=49).

The overall study safety profile was consistent with previously reported study results and comparable to a kidney biopsy.

We currently operate a manufacturing facility that has been designed to comply with FDA and European Medicines Agency (“EMA”) quality standards and to produce rilparencel treatments from biopsied material.

Our manufacturing site, based in Winston-Salem, North Carolina, in the United States, has a potential capacity sufficient to supply our Phase 3 study as well as a potential commercial launch, should rilparencel receive regulatory approval.

Our Clinical Trial Program

We are leveraging our cell therapy technology to develop product candidates designed to stop or delay kidney failure in CKD.

The following table summarizes our current clinical study pipeline:

Rilparencel is an investigational product that includes a mixture of kidney cells prepared from the participant’s own kidney tissue.

The initial kidney tissue is obtained by a standard kidney biopsy performed by a specially trained physician.

From this tissue, certain kidney cells, which are thought to heal the kidney, are grown and multiplied in a highly specialized manufacturing facility.

After several weeks, when sufficient cells are available, they are formulated in rilparencel and sent back to the clinical trial site for injection directly into the participant’s own kidneys.

It is believed that rilparencel may help a diseased kidney stabilize or improve function over time, thereby potentially delaying the need for dialysis or transplantation by preserving kidney function.

Clinical studies suggest that rilparencel can impact kidney function positively, as shown by by its stabilization of eGFR, or attenuation of the rate of eGFR decline, in patients with CKD and diabetes.

We have developed a cryopreserved version of rilparencel that allows for long-term product preservation to be used in our Phase 3 trial of rilparencel (called PROACT 1 or REGEN-006), as well as our Phase 2 trial of rilparencel (called REGEN-007).

In addition to the cryopreserved formulation of rilparencel, we used a gelatin-based hydrogel formulation in our Phase 2 trials (called RMCL-002 and REGEN-003) and Phase 1 trial in CAKUT (called REGEN-004).

The following table summarizes our current clinical study program:

Clinical studies suggest that rilparencel can impact kidney function positively, as shown by its stabilization of eGFR, or attenuation of the rate of eGFR decline, in patients with CKD and diabetes.

We have developed a cryopreserved version of rilparencel that allows for long-term product preservation and that is being used in our Phase 3 trial of rilparencel (called PROACT 1 or REGEN-006), and was used in our Phase 2 trial of rilparencel (called REGEN-007).

In addition to the cryopreserved formulation of rilparencel, we used a gelatin-based hydrogel formulation in other Phase 2 trials (called RMCL-002 and REGEN-003) and a Phase 1 trial in CAKUT (called REGEN-004).

Our Team and Corporate History

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We have assembled key management team members with expertise in kidney disease, cell therapy, development, regulatory affairs, operations, quality and manufacturing.

ProKidney LLC, formerly, a wholly owned subsidiary of PKLP (“ProKidney Bermuda”), was formed in December 2018 as a Bermuda limited liability company and was founded by a group of investors in the pharmaceutical industry.

ProKidney (formerly known as inRegen and, prior to that, RegenMed (Cayman) Ltd.

(d/b/a inRegen)) (“ProKidney-KY”) was duly incorporated under the Companies Act (as amended) of the Cayman Islands (the “Cayman Islands Companies Act”) on December 21, 2015, as an exempted company.

In 2020, ProKidney-KY’s name was changed from RegenMed (Cayman) Ltd.

to inRegen and subsequently changed to ProKidney.

ProKidney, LLC (formerly known as Twin City Bio LLC) (“ProKidney-US”) changed its name from Twin City Bio LLC to ProKidney, LLC.

ProKidney-US is a Delaware limited liability company formed on December 18, 2015.

In January 2019, ProKidney Bermuda acquired all of the equity interests in ProKidney-KY and ProKidney-US.

ProKidney Bermuda acquired the equity interests in ProKidney-KY to develop its renal autologous cell therapy.

ProKidney Bermuda acquired ProKidney-US to provide contractual development and manufacturing services to ProKidney-KY.

On August 5, 2021, PKLP was organized as a limited partnership under the Limited Partnerships Act, 1907 of Ireland (the “Irish LP Act”), and, as applicable, the Partnership Act 1890, of Ireland, with ProKidney Bermuda becoming a wholly owned subsidiary of PKLP.

In September 2021, ProKidney Bermuda distributed its equity interests in ProKidney-KY and ProKidney-US

to PKLP with the effect that ProKidney-KY and ProKidney-US became direct wholly-owned subsidiaries of PKLP.

Bermuda was dissolved in October of 2022.

References to “ProKidney” or the “Company” generally refer to PKLP after its reorganization and to ProKidney Corp.

following the Closing.

Effective July 1, 2025 (the “Domestication Date”), the Company completed a domestication process through which it changed its jurisdiction of incorporation from the Cayman Islands to the State of Delaware (the “Domestication”).

ProKidney Corp., the Cayman Islands exempted company (“ProKidney Cayman”) deregistered as an exempted company in the Cayman Islands pursuant to Sections 206 and 207 of the Companies Act (as amended) of the Cayman Islands (the “Companies Act”), and domesticated and continued its existence as a corporation incorporated in the State of Delaware pursuant to Section 388 of the General Corporation Law of the State of Delaware (the “DGCL”), effective as of the Domestication Date.

In connection with the Domestication, the Company also completed certain other restructuring transactions (such transactions, together with the Domestication, the “Restructuring”) on the Domestication Date.

Prior to the Restructuring, ProKidney Cayman.

conducted its business indirectly through ProKidney LP (“PKLP”), a limited partnership under the laws and regulations of Ireland and its subsidiaries.

As part of the Restructuring, (i) PKLP contributed substantially all of its assets to a newly formed subsidiary, ProKidney Holdings, LLC, a Delaware limited liability company (“PK Holdings”) (other than its limited liability company interests in PK Holdings), (ii) PKLP commenced winding-up and made a liquidating distribution of its limited liability company interests in PK Holdings to its partners, including ProKidney Cayman., in redemption of their interests in PKLP, and (iii) ProKidney Corp.

GP Limited, the general partner of PKLP, sold its nominal economic interest in PK Holdings received in such liquidating distribution to ProKidney Cayman.

(collectively, the “Substitution”).

Immediately following the Domestication, ProKidney (“ProKidney-KY”), then a wholly owned subsidiary of PK Holdings and a Cayman Islands exempted company, re-registered as a Cayman Islands limited liability company and then deregistered as a limited liability company in the Cayman Islands and registered by way of continuation out for purposes of the Limited Liability Companies Act (as amended) of the Cayman Islands and domesticated and continued for purposes of the Delaware Limited Liability Company Act as a Delaware limited liability company named ProKidney IPCo, LLC (“ProKidney IPCo”).

As a result of the consummation of the Domestication and the other transactions involved in the Restructuring, the Company and the other former limited partners of

PKLP are now members of PK Holdings, and PK Holdings owns all of the subsidiaries that conduct the Company’s business, including ProKidney IPCo.

In connection with the Domestication and the other Restructuring transactions, the Company amended and restated certain of its material agreements, each originally dated July 11, 2022, on substantially similar terms in order to reflect updates to the Company’s corporate structure resulting from the Restructuring.

These amended and restated agreements included:

(i) an Amended and Restated Tax Receivable Agreement, (ii) an Amended and Restated Lock-Up Agreement, and (iii) an Amended and Restated Exchange Agreement.

In addition, on the Domestication Date, the Company, together with the other former limited partners of PKLP entered into the Second Amended and Restated Limited Liability Company Agreement of PK Holdings to provide for the governance of PK Holdings and reflect the changes to its capital structure resulting from the Restructuring.

After completing the Domestication and other Restructuring transactions, the Company also underwent a series of transactions to streamline its operating subsidiaries from a tax perspective (the “Post-Domestication Reorganization”).

The Post-Domestication Reorganization was finalized effective as of September 1, 2025.

References to PK Holdings herein refers to PKLP prior to the Domestication and PK Holdings subsequent to the Domestication.

References to ProKidney IPCo.

herein refer to ProKidney-KY prior to the Domestication and ProKidney IPCo.

subsequent to the Domestication.

Our goal is to become a fully integrated biopharmaceutical company pioneering treatments for CKD.

Key components of our business strategy include the following:

Obtain regulatory approval for, and successfully commercialize, rilparencel, initially as a treatment for patients with CKD and diabetes.

We intend to continue to pursue the clinical development of rilparencel through our Phase 3 REGEN-006 trial that has been reviewed by the FDA.

We activated the first site for our ongoing REGEN-006 (which we also call “PROACT 1”), in the fourth quarter of 2021 with the first Informed Consent Form signed and the first subject randomized into the trial in the first quarter of 2022.

We believe that PROACT 1 could be sufficient to support a potential Biologics License Application (“BLA”) submission.

Further, we believe that the accelerated approval pathway is available to rilparencel and that we could consider eGFR slope as a surrogate endpoint for accelerated approval.

We are continuing to engage with the FDA, under our RMAT designation, to further define the details supporting this accelerated pathway.

Obtain regulatory approval for, and successfully commercialize, rilparencel as a treatment for patients with CKD and diabetes.

We intend to continue to pursue the clinical development of rilparencel through our Phase 3 REGEN-006 trial.

We activated the first site for our ongoing REGEN-006 trial (which we also call “PROACT 1”), in the fourth quarter of 2021 with the first Informed Consent Form signed and the first subject randomized into the trial in the first quarter of 2022.

In the third quarter of 2025, the FDA confirmed in a Type B meeting that eGFR slope can serve as the surrogate endpoint and primary basis for a Biologics License Application (“BLA”) submission of rilparencel under the accelerated approval pathway.

The FDA also confirmed that PROACT 1 may serve as the confirmatory study to support full approval of rilparencel based on the primary time-to-event composite endpoint specified in the protocol.

In addition to PROACT 1, we are also sponsoring a long-term follow-up trial, REGEN-008, for subjects who received rilparencel as part of our trials.

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We have developed and built a manufacturing facility, intended to be operated in compliance with current good manufacturing practices (“cGMPs”), in which we manufacture rilparencel for clinical trials and plan to continue to develop for purposes of the eventual commercial manufacturing process, assuming receipt of necessary regulatory approvals.

Our current manufacturing facility is capable of manufacturing product for our ongoing clinical trials and could serve as our commercial launch facility.

We anticipate expanding our manufacturing footprint within our existing premises to meet demand for rilparencel upon commercialization.

Our current manufacturing facility has the capacity to manufacture enough product for PROACT 1 and is intended to serve as our commercial launch facility.

We initiated an expansion of our manufacturing footprint within our existing premises to prepare for the potential commercialization of rilparencel.

Discover and develop additional product candidates for the treatment of kidney diseases utilizing our cell therapy approach.

Our team has extensive experience in discovery research and deep expertise in kidney disease.

While executing its primary mission to develop and commercialize rilparencel, our team will investigate additional disease pathways associated with kidney disease, identify key targets for intervention and generate product candidates against these targets.

While executing its primary mission to develop and commercialize rilparencel, our team expects to investigate additional disease pathways associated with kidney disease, identify key targets for intervention and generate product candidates against these targets.

We may also in-license from, collaborate with, or acquire third parties to develop product candidates that we, based on our understanding of kidney diseases and pathways, believe are promising therapeutics.

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The most common causes of CKD among adults are diabetes, hypertension, and glomerular disease.

In the United States, it is believed that approximately 3.2 million patients per year suffer from stage 3b or 4 CKD and 1.2 to 1.8 million of those patients could be eligible for treatment with rilparencel.

In the United States, it is believed that approximately 3.2 million patients per year suffer from Stage 3b or 4 CKD and over one million of those patients could be eligible for treatment with rilparencel.

Our Approach:

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Due to one severe bleed that occurred during an early rilparencel injection procedure, we switched to the use of a noncutting needle design for the rilparencel procedure.

In non-clinical studies, SRCs injected into the cortex of a diseased kidney were found to

distribute from the injection site to throughout the kidney, with localization in the peritubular, juxta-tubular and intratubular regions.

To date, clinical studies suggest that treatment with rilparencel in patients with CKD and type 2 diabetes may positively impact kidney function, shown by a stabilization in eGFR or attenuations in the rate of eGFR decline.

Other improvements observed with non-clinical and clinical SRC treatment include metabolic, as well as filtration benefits, stabilization and/or reduction in urinary albumin-creatinine ratio (“UACR”), increased kidney cortical thickness, improved hemoglobin levels, and improvements in calcium phosphate and vitamin D3.

In non-clinical studies, SRCs injected into the cortex of a diseased kidney were found to distribute from the injection site to throughout the kidney, with localization in the peritubular, juxta-tubular and intratubular regions.

To date, clinical studies suggest that treatment with rilparencel in patients with CKD and diabetes may positively impact kidney function, shown by a stabilization in eGFR or attenuations in the rate of eGFR decline.

Other improvements observed with non-clinical and clinical SRC treatment include metabolic, as well as filtration benefits.

Rilparencel Tissue Acquisition-to-Injection Process Overview

Mechanism of Action of Rilparencel

SRC, injected into the kidney cortex, are believed to provide a molecular and mechanistic basis for activation of endogenous renal repair mechanisms that are still active in the chronically diseased kidney.

Non-clinical studies in multiple animal models of CKD have demonstrated that SRC injected directly into the kidney cortex could affect a reparative response in multiple locations of the nephron through direct cell-cell communication utilizing putative autocrine/paracrine mechanisms involving secreted factors.

SRC, injected into the kidney cortex, are believed to provide a molecular basis for activation of endogenous renal repair mechanisms that are still active in the chronically diseased kidney.

Non-clinical studies in multiple animal models of CKD have demonstrated that SRC injected directly into the kidney cortex could effect a reparative response in multiple locations of the nephron through putative juxtacrine and paracrine mechanisms involving direct cell-cell contact and secreted factors, respectively.

In animal models of CKD, treatment with SRC preserved kidney function, reduced proteinuria and provided a significant survival benefit.

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Our Product Candidate

Rilparencel is currently in Phase 3 development, as well as an ongoing Phase 2 clinical trial, for the treatment of moderate to severe CKD and diabetes.

We plan to conduct our Phase 3 study, PROACT 1, at approximately 75 clinical sites based in the United States, Asia and Latin America.

To date, clinical studies in participants with CKD and diabetes suggest that treatment with rilparencel may delay or prevent renal replacement therapy (“RRT”) by stabilizing eGFR.

Other potential improvements observed with rilparencel in earlier studies include stabilization in UACR, increased kidney cortical thickness, improvement in serum bicarbonate, and stabilization of hemoglobin levels.

The potential benefits of rilparencel will be evaluated in the Phase 3 study.

The ongoing clinical development program utilizes an image-guided percutaneous injection method into the kidney that is conducted using conscious sedation in an outpatient same-day procedure.

Rilparencel is currently in Phase 3 development for the treatment of advanced CKD and type 2 diabetes.

Our Phase 3 study, PROACT 1, is being conducted at approximately 80 clinical sites based in the United States, Mexico and Taiwan.

To date, clinical studies in participants with CKD and diabetes suggest that treatment with rilparencel may delay or prevent kidney failure by stabilizing eGFR.

The ongoing clinical development program utilizes an image-guided percutaneous injection into the kidney that is conducted using conscious sedation in an outpatient same-day procedure.

The procedure appears to be generally well tolerated with the most commonly observed procedure related events including nausea, vomiting, fever, and hematuria with kidney biopsy.

In the RMCL-002 trial, which used a different formulation of the rilparencel product and a different procedure method from that presently used in our Phase 3 trials, one participant experienced serious adverse events that included scarring or fibrosis and a decrease in

kidney function.

A second participant experienced decreased kidney blood flow observed on contrast-enhanced computerized tomography (“CT”) imaging and a decrease in kidney function.

Serious adverse events, including injection-related pain, kidney-related events such as hematoma, renal vascular events, eGFR decline and acute kidney injury, have also been reported.

Other serious adverse events, including acute myocardial infarction, acute respiratory failure, end stage renal disease, and coronary artery disease have been reported and are generally associated with the co-morbidities of patients with type 2 diabetes.

Other serious adverse events, including acute myocardial infarction, acute respiratory failure, end stage kidney disease, and coronary artery disease have been reported and are generally associated with the co-morbidities of patients with type 2 diabetes.

Background and Unmet Need

Chronic Kidney Disease

CKD is characterized by progressive disease that, without therapeutic intervention, will worsen until the afflicted person dies or reaches end-stage renal disease (“ESRD”).

CKD patients have progressive damage and loss of function in their kidneys, evidenced by decreased eGFR and / or increased excretion of urinary albumin, as observed through laboratory testing.

CKD is characterized by progressive disease that, without therapeutic intervention, can worsen until the afflicted person reaches end-stage kidney disease (“ESKD”) or dies.

CKD patients have progressive damage and loss of kidney function as evidenced by decreased eGFR and / or increased excretion of urinary albumin and as observed through laboratory testing.

The global adult prevalence of CKD is estimated to be 10% with ranges of 8-16% in various populations.

CKD is often associated with considerable comorbidities, such as diabetes, and is often accompanied by adverse outcomes due to underlying disease states and/or risk factors such as cardiovascular disease, hypertension and diabetes, causing an increased risk of mortality.

CKD is often associated with considerable comorbidities, such as diabetes, and is often accompanied by adverse outcomes due to underlying disease states and/or risk factors for cardiovascular disease, such as hypertension and diabetes, causing an increased risk of mortality.

Ninety-seven percent of patients with moderate to severe CKD have asymptomatic disease, and this stage of CKD is associated with a two-to four-fold rise in cardiovascular disease risk, along with a significant increase in all-cause mortality.

Only a small proportion of CKD patients progress to ESRD (i.e., Stage 5 disease), but the increasing life expectancy of humans has led to growing numbers of patients with chronic diseases and end-stage organ failure.

Even with costly treatments, patients with ESRD experience substantial morbidity and mortality.

To survive, ESRD patients require renal replacement therapy (RRT) with peritoneal dialysis, hemodialysis or kidney transplantation.

Only a small proportion of CKD patients progress to ESKD (i.e., Stage 5 disease), but the increasing life expectancy of humans has led to growing numbers of patients with chronic diseases and end-stage organ failure.

Even with costly treatments, patients with ESKD experience substantial morbidity and mortality.

To survive, ESKD patients require renal replacement therapy (“RRT”) with peritoneal dialysis, hemodialysis or kidney transplantation.

Preventing or delaying progression of CKD, delaying the onset of medical complications and treating comorbidities are key strategies for CKD management.

Approved therapies for patients with CKD have been shown to delay CKD progression in some patients.

However, many patients continue to lose kidney function and progress to ESRD.

However, many patients continue to lose kidney function and progress to ESKD.

The major causes of CKD in adults are diabetes and hypertension.

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Staging and grading of kidney function relies upon eGFR and urine measurement of albumin excretion (“albuminuria”).

KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease provided guidelines intended to aid general practitioners and nephrologists in the evaluation, classification, and management of CKD in both adults and children.

As set forth below, Figure 1 categorizes the risk of ESRD from “low” to “very high” based on both eGFR measurements, ranging from >90 mL/min/1.73m 2 to <30 mL/min/1.73m 2 , and albuminuria classifications ranging from <30 mg/g to >300 mg/g.

KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease provides guidelines intended to aid general practitioners and nephrologists in the evaluation, classification, and management of CKD in both adults and children.

As set forth below, Figure 1 categorizes the risk of ESKD from “low” to “very high” based on both eGFR measurements, ranging from >90 mL/min/1.73m 2 to <30 mL/min/1.73m 2 , and albuminuria classifications ranging from <30 mg/g to >300 mg/g.

Chronic kidney failure occurs when eGFR is < 15 mL/min/1.73m 2 for 3 or more months, and is often treated by dialysis or kidney transplantation.

Summary of Classification Estimates for CKD

Treatment of patients with CKD focuses on treating comorbidities (such as diabetes and hypertension) and medical complications, reducing cardiovascular risk, slowing decline of kidney function and preparing for kidney failure or kidney replacement therapy.

replacement therapy.

For many patients, CKD occurs as part of a complex comorbidity cluster including cardiovascular disease and type 2 diabetes.

Pharmacological therapy may include the administration of any or all of the following:

angiotensin converting enzyme (“ACE”) inhibitors or angiotensin receptor blockers (“ARB”), sodium-glucose cotransporter-2 (SGLT-2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (“nsMRAs”), insulin and/or other anti-diabetic agents for glycemic control and lipid lowering therapy.

When a patient reaches ESRD, RRT in the form of kidney dialysis or transplantation is generally required to prolong life.

angiotensin converting enzyme (“ACE”) inhibitors or angiotensin receptor blockers (“ARB”), sodium-glucose cotransporter-2 (“SGLT-2”) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (“nsMRAs”), glucagon-like peptide-1 receptor agonist (“GLP-1 RA”), insulin and/or other anti-diabetic agents for glycemic control and lipid lowering therapy.

When a patient reaches ESKD, RRT in the form of kidney dialysis or transplantation is generally required to prolong life.

The vast majority of dialysis patients in the United States and certain other developed countries receive dialysis primarily in the form of center hemodialysis, peritoneal dialysis or home hemodialysis.

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Hemodialysis has been associated with multiple, serious complications as well as interference with quality of life.

Although kidney transplantation currently remains the most effective form of RRT for ESRD, there is a chronic shortage of organs.

Although kidney transplantation currently remains the most effective form of RRT for ESKD, there is a chronic shortage of organs.

If a patient can secure a kidney for transplantation, long-term immunosuppressive therapy is required to prevent rejection.

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And while xenotransplantation might be a promising alternative approach in the future to bridge the gap between the supply and demand of human organs, tissues, and cells, immunological barriers are limiting factors in clinical xenotransplantation at the current time.

While patients continue to lose kidney function while on existing therapies, the cost of CKD treatment is high and the rates of CKD and ESRD, along with the associated expenditures, are expected to continue to rise.

A major source of healthcare expenditure in the United States, the annual Medicare fee-for-service (“FFS”) spending for all beneficiaries with CKD was $86.1 billion in 2021, or 22.6% of total spend, and patients with ESRD accounted for $52.3 billion of spend.

ESRD only affects 1% of Medicare beneficiaries but historically has accounted for approximately 7% of Medicare spending, and dialysis treatments account for a large part of the economic burden.

Per-person per-year (“PPPY”) expenditures in 2021 for all dialysis ESRD patients on Medicare averaged $82,167.

On the private insurance side, dialysis is significantly more expensive than Medicare.

Mean spending in the first 12 months after a patient started dialysis based on an analysis from 2015-2017 was $238,126 for private insurance compared to $80,509 for FFS Medicare.

Clinical Development

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the name of the product candidate tested in the trials was changed after completion of some of the trials from Neo-Kidney Augment (“NKA”) to REACT or rilparencel.

The summary below also includes interim results which are based on a preliminary analysis of then available data, the results, related findings and conclusions of which are subject to change following a more comprehensive review of the data related to the specific trial.

In particular, we announced interim results from our ongoing REGEN-007 Phase 2 clinical trial in June 2024.

Interim results from clinical trials that we may complete are not necessarily indicative of results from future data and are subject to the risk that one or more of the clinical outcomes may materially change as more patient data become available.

Preliminary or topline results also remain subject to audit and verification procedures that may result in the final data being materially different from any preliminary data that we may previously publish.

As a result, interim and preliminary data should be viewed with caution until the final data are available.

CKD and Diabetes or CAKUT

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The data from TNG-CL011 was accepted by FDA as part of a clinical data package submitted to progress to Phase 2.

Phase 2 Clinical Development (RMCL-001, RMCL-002, REGEN-003, and REGEN-007)

Phase 2 Clinical Development

RMCL-001 was a Phase 2, open-label safety and efficacy study of rilparencel in subjects with CKD and type 2 diabetes.

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The first subject was enrolled in this study in February 2017, and all subjects have completed follow-up.

delivered into the biopsied kidney using an outpatient, minimally invasive, percutaneous approach under conscious sedation completed in less than 90 minutes.

The aggregate number of subjects enrolled in the Phase 2 clinical trial was 83.

Upon withdrawal and/or replacement of two subjects, 81 subjects were enrolled as of December 2020, of which 41 subjects were enrolled into the active treatment group and 42 subjects were enrolled into the deferred treatment group.

The primary objective of this study was to assess the safety and efficacy of up to two rilparencel injections given six months (+ 4 weeks) apart in patients with CKD and type 2 diabetes with eGFRs between 20 and 50 ml/min/1.73m 2 , with both doses delivered into the biopsied kidney using an outpatient, minimally invasive, percutaneous approach under conscious sedation completed in less than 90 minutes.

Patients received two doses of rilparencel of 3x10 6 cells/g-KW est each.

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Consequently, the study design included a randomized control group receiving standard-of-care treatment for the first 12 months and a randomized, active treatment group receiving up to two rilparencel injections and follow-up evaluations during the same period of time.

The aggregate number of subjects enrolled in the Phase 2 clinical trial was 83.

The final results for safety and efficacy were presented at the 61 st ERA Congress in May 2024.

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An open label extension portion of the study (part 2) was added in February 2021 to follow all subjects for an additional 3 years.

Visits will be conducted at 3-month intervals to give a total of 5 years (part 1 + part 2) of follow-up after the last rilparencel injection.

The final results indicated a safety profile in line with previously reported data from earlier Phase 1 and Phase 2 trials, with tolerability similar to that of a routine kidney biopsy.

Overall, the trial data demonstrated rilparencel’s potential for kidney function preservation in patients with advanced CKD and type 2 diabetes, with the most notable potential benefit shown in patients who had the highest risk of kidney failure (CKD Stage 4 with moderate to severe albuminuria).

Visits are being conducted at 3-month intervals to provide a total of 5 years (part 1 + part 2) of follow-up after the last rilparencel injection.

Overall, the trial data final results demonstrated rilparencel’s potential for kidney function preservation in patients with advanced CKD and type 2 diabetes, with the most notable potential benefit shown in patients who had the highest risk of kidney failure (CKD Stage 4 with moderate to severe albuminuria).

The results also indicated a safety profile in line with previously reported data from earlier Phase 1 and Phase 2 trials, with tolerability similar to that of a routine kidney biopsy.

REGEN-003 is a completed Phase 2, prospective, open-label, single-arm, safety and tolerability study of rilparencel in subjects with CKD and type 2 diabetes, specifically those with high-risk late Stage 4 CKD.

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Two patients (20%) completed the study (24 months after the second injection) without advancing to RRT.

One patient died due to complications related to COVID, and an additional subject died due to a myocardial infarction approximately 18 months after enrollment.

One patient died due to complications related to COVID, and an additional

subject died due to a myocardial infarction approximately 18 months after enrollment.

The results from this study suggest that rilparencel has the potential to delay dialysis in high-risk Stage 4 and Stage 5 CKD patients.

REGEN-007 is an ongoing Phase 2, prospective, randomized, open-label, repeat dose, two group, safety and efficacy study of rilparencel in subjects with type 1 or 2 diabetes and CKD.

The primary objective of Group 1 is to assess the safety and efficacy of up to two rilparencel injections given three months apart (up to 60 days after target date) in patients with CKD and type 1 and 2 diabetes with eGFRs between 20 and 50 ml/min/1.73m 2 and delivered into biopsied and non-biopsied contralateral kidneys using a minimally invasive percutaneous approach.

Additionally, the primary objective of Group 2 is to administer a single rilparencel injection followed by monitoring and a potential administration of a second rilparencel injection delivered into the non-biopsied contralateral kidney triggered by a 20% decrease in eGFR and/or a 30% increase in urinary albumin-creatinine ratio (UACR) delivered within approximately 60 days of the trigger being met.

In previous Phase 2 studies we injected rilparencel into the same kidney twice.

Based on a generally favorable safety profile observed in previous studies, in REGEN-007 we are now proceeding with the injection of rilparencel into both kidneys.

We expect the data generated by REGEN-007 will enable us to better understand the impact of rilparencel on kidney function from injections in both kidneys, which is the dosing regimen for our Phase 3 study.

By injecting both kidneys, patients have maximal exposure to rilparencel cells, with the potential to impact a greater proportion of kidney mass.

Further, the number of glomeruli (the filtering units of the kidney) that are amenable to regenerative therapy is effectively doubled when injecting both kidneys.

Subjects will receive up to two injections of rilparencel of 3x10 6 cells/g-KW est per dose.

The study will enroll subjects between the ages of 30 and 80 with an eGFR >20 and ≤50 mL/min/1.73m 2 .

Subjects will be randomized (1:1) before kidney biopsy into two groups.

Group 1 will receive the two rilparencel injections three months apart.

Group 2 will receive the first rilparencel injection, and a trigger, as described below, must be met to qualify for the second rilparencel injection more than three months after the first dose.

Each of the subjects in Group 1 will receive the first rilparencel injection as soon as the rilparencel product is manufactured and shipped to the clinical site.

After three months, subjects will receive a second injection, as appropriate.

Subjects in Group 2 will also receive one rilparencel injection as soon as the rilparencel product is manufactured and shipped to the clinical site.

For Group 2, a second rilparencel injection will only be administered if a subject meets one or more clinical surrogate marker criteria.

The second rilparencel injection will be administered to subjects in Group 2 no less than three months after the first injection, within 30 days (up to four weeks after target date) of meeting the re-dose trigger.

The re-dose triggers include (1) a 30-day sustained decline in eGFR by at least 20% from baseline and (2) an increase in the baseline UACR of at least 30% greater than 30mg/gram, measured 30 days after the baseline measurement is taken.

For all subjects who receive a second injection, the second injection will be administered in the non-biopsied contralateral kidney.

During this time, subjects in Group 2 will receive contemporaneous, standard-of-care therapy for CKD while undergoing follow-up evaluations at one, 14 (up to 7 days after target date) and 28 days (up to 7 days after target date) following the first injection, and then at three months (up to 10 days after target date) following the first injection, similar to subjects in Group 1.

All subjects will continue with long-term follow-up visits at three month intervals for a period of 18 months following the last injection.

In addition, each subject’s baseline rate of kidney decline, based on adequate historical, clinical data obtained 24 months prior to the first rilparencel injection, will serve as a comparator for monitoring the rate of progression of renal insufficiency over time.

The primary efficacy endpoint of REGEN-007 is attenuation of the rate of kidney function decline as indicated by the change from pre-injection baseline value in total (acute + chronic) slope of eGFR over 18 months.

The primary safety endpoint is treatment-emergent adverse events through 18 months following the last rilparencel injection.

REGEN-007 is an unblinded study in which Group 1 patients will receive the same treatment regimen as the patients in our Phase 3 program that are randomized to the active arms.

We believe that REGEN-007 may provide insight regarding the clinical benefit that could be observed in our Phase 3 program.

We completed enrollment in REGEN-007 with a total of 53 subjects.

In Group 1, as of May 7, 2024, patients with at least 12 months follow-up after the second injection of rilparencel (n=13) show stabilized kidney function for 18 months (average eGFR change from baseline to 18 months was -1.3 mL/min/1.73m 2 ).

Importantly, similar results were observed in a subset of these patients (n=10) who met key inclusion criteria currently used in our Phase 3 clinical study program (average eGFR change from baseline to 18 months was -0.6 mL/min/1.73m 2 ).

Additional analyses will be performed as Group 1 data matures.

Twenty-five patients received at least one rilparencel injection in Group 2;

12 patients received a second rilparencel injection based on eGFR criteria (n=3) or UACR criteria (n=9).

In May 2025, we completed our REGEN-007 trial, a multi-center Phase 2 open-label 1:1 randomized two-arm trial of rilparencel in patients with diabetes, CKD, and an eGFR of 20-50 mL/min/1.73m².

At randomization, patients were assigned to one of two treatment groups using different dosing regimens.

Group 1 replicated the dosing schedule of our ongoing Phase 3 PROACT 1 study in which patients receive two scheduled rilparencel injections (one in each kidney), approximately three months apart.