ProKidney Targets Q2 2027 Phase III Readout as Rilparencel Enrollment Surpasses 500

Key Points

• ProKidney expects a Q2 2027 interim Phase III readout for rilparencel after PROACT 1 enrollment surpassed 500 patients, above the original 470-patient target. Additional eligible patients may continue enrolling into early 2027.
• PROACT 1 is designed to test whether rilparencel slows kidney-function decline by 1.5 mL/min annually versus sham treatment, a target the company says could represent a 50% reduction in eGFR decline and support potential accelerated approval.
• Management reported consistent manufacturing, with product produced for more than 95% of patients, and no new safety signals beyond risks associated with kidney biopsy and injection procedures. If successful, rilparencel could complement existing CKD therapies for high-risk patients.

ProKidney NASDAQ: PROK said it remains on track to report top-line results from the interim analysis of its Phase III PROACT 1 study in the second quarter of 2027, following stronger-than-expected patient recruitment for its investigational autologous cell therapy, rilparencel.

Chief Executive Officer Bruce Culleton said the company closed recruitment in August after increased screening activity across more than 80 study sites. While ProKidney had previously guided to complete enrollment in 2026, it will continue enrolling screened and eligible patients into the first quarter of the following year. The planned study population has increased from 470 patients to more than 500 participants, he said.

Rilparencel is being developed for patients with advanced chronic kidney disease, or CKD, and type 2 diabetes. The therapy uses cells derived from each patient’s own kidney biopsy. Those cells are expanded at ProKidney’s manufacturing site, cryopreserved and returned to the clinical site for injection into the patient’s kidneys. Culleton said the autologous approach does not require immunosuppression, preconditioning or genetic modification.

Phase III Trial Focuses on Kidney Function Decline

PROACT 1 is a blinded, sham-controlled registrational trial in which eligible participants are randomized to receive rilparencel or a sham procedure. The interim analysis is intended to support potential accelerated approval using estimated glomerular filtration rate, or eGFR, slope as a surrogate endpoint.

According to Culleton, the study is powered to detect a 1.5 mL per minute difference in eGFR slope between treatment and control groups. The company assumes an annual eGFR decline of 3 mL per minute in the control arm, making the targeted difference equivalent to a 50% reduction in kidney-function decline.

Dr. Katherine Tuttle, executive director for research at Providence Inland Northwest Health and a professor of medicine at the University of Washington, said an eGFR-slope difference greater than 0.75 mL per minute per 1.73 square meters annually in studies lasting at least two years has been associated with a benefit on the clinical outcome of kidney failure. She said the 1.5 mL-per-minute target in PROACT 1 would be clinically meaningful if achieved.

ProKidney previously reported that rilparencel was associated with a 78% slower annual eGFR decline in a cohort from its Phase II REGEN-007 study. The company said that cohort’s design most closely resembled its Phase III program.

Mechanistic Findings Presented at Kidney Week

Anthony Conway, ProKidney’s head of research and development, reviewed preclinical and translational findings presented at the American Society of Nephrology’s Kidney Week meeting. The company’s work examined rilparencel in cell-culture systems, donated human kidney tissue and rodent models of CKD.

Conway said single-cell RNA sequencing of rilparencel batches found that the final product consists of cells originating from proximal and distal kidney tubules. Despite differences in starting biopsies from patients with varying CKD stages, he said the manufactured cell products demonstrated a consistent expression profile across the samples evaluated.

In a kidney-on-a-chip model designed to replicate CKD-related injury, ProKidney reported that rilparencel was associated with improved markers of endothelial-cell junctions and barrier integrity, lower inflammatory signaling and reduced permeability. The company also reported findings suggesting effects on oxidative stress, iron handling, mitochondrial function and lipid peroxidation in injured kidney epithelial cells.

In rodent studies, Conway said injected rilparencel cells were observed in kidney tissue after dosing, with some cells still present 28 days later. Spatial and molecular analyses in the models indicated signatures associated with extracellular-matrix remodeling, vascular development, endothelial cell junctions and tissue repair. He said the company plans additional work, including a human decedent study and analyses of clinical biomarkers, to further evaluate the therapy’s mechanism of action.

Positioning Alongside Existing CKD Treatments

Tuttle said CKD remains a major global health concern, driven in large part by diabetes and linked to elevated cardiovascular and kidney-failure risks. She described current treatment pillars for diabetic CKD as renin-angiotensin system inhibition, SGLT2 inhibitors, finerenone and GLP-1 receptor agonists.

While those therapies have improved care, Tuttle said some patients continue to face substantial residual risk despite guideline-directed medical treatment. She characterized rilparencel, if successful in development and approved, as a potential complementary “rescue” treatment for patients with advanced CKD who remain at high risk of dialysis or transplantation.

ProKidney said PROACT 1 participants are generally expected to receive standard therapies, including ACE inhibitors or ARBs and SGLT2 inhibitors, unless sites provide an explanation for their absence. Culleton said the company has observed high use of SGLT2 inhibitors and ACE inhibitors or ARBs in blinded baseline medication data, along with what he described as reasonable use of GLP-1 therapies.

Manufacturing and Safety Comments

Culleton said the current time from kidney biopsy to availability of product in the study is about 14 weeks, though manufacturing itself takes roughly three weeks. The company believes it may be able to reduce the overall interval to about eight weeks through greater efficiency.

On manufacturing reliability, Culleton said ProKidney has been able to manufacture product for more than 95% of patients, based on its clinical-program experience. He said insufficient biopsy samples have occurred only rarely.

Regarding safety, Culleton said the Phase III program has not shown findings that differ from the company’s prior Phase II experience. He said adverse events observed have been consistent with those expected from kidney biopsy and needle-based kidney procedures, rather than additional treatment-related events.

About ProKidney (NASDAQ:PROK)

ProKidney Corporation is a biotechnology company focused on developing cell-based therapies for chronic kidney disease (CKD). The company's lead investigational product is rilparencel, formerly known as REACT, an autologous cell therapy made from a patient's own kidney cells.

Rilparencel is designed to be injected into the patient's kidneys, where the cells are intended to support kidney function and potentially slow the progression of CKD. ProKidney is studying the therapy primarily in patients with diabetic kidney disease and advanced CKD, with the goal of delaying or reducing the need for dialysis or kidney transplantation.

ProKidney's operations are centered on the development and clinical testing of rilparencel, and the company does not currently have an approved commercial product.

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