ProKidney Corp. Class A Ordinary Shares KOL event

Please go ahead, Ethan. Thank you, operator, and good morning everyone, and welcome to our webcast.

Before we begin, I'd like to remind everyone that we will be making forward-looking statements during the presentation today. I encourage you to refer to our most recent SEC filings regarding risk factors associated with these statements. On the webcast this morning are Dr. Bruce Culleton, ProKidney's CEO, Dr. Anthony Conway, ProKidney's Head of R&D, and Dr. Katherine Tuttle, Executive Director for Research at Providence Inland Northwest Health and Professor of Medicine at the University of Washington. I'd now like to turn the call over to Bruce.

Bruce? Thanks, Ethan. Good morning everyone, and thank you for joining us today.

At ProKidney, our mission is to transform the outlook for people with advanced chronic kidney disease by extending life without dialysis. Today's discussion will focus on the science supporting our work and the potential role of rilparencel within the evolving chronic kidney disease treatment landscape. I will start with a brief corporate update. Anthony Conway, our Head of Research, will then recap his team's presentation at the American Society of Nephrology's annual meeting, which just happened in Denver last week. These presentations provide an opportunity to examine the scientific rationale for rilparencel and how that research is advancing our understanding of its potential. You will hear how our MOA thesis is coming together.

We're also pleased to welcome Dr. Katherine Tuttle, who will discuss therapeutic options for patients with chronic kidney disease, the needs that remain despite advances in care, and where rilparencel, if successfully developed and approved, may play a role. For investors on the call today, we hope today's discussion provides a clearer understanding of both the science behind rilparencel and the clinical need we are working to address. Before I jump in any further, I do want to thank our presenters, Dr. Tuttle in particular, and Dr. Conway, our ProKidney team, and especially the patients and investigators participating in our studies. Here on this slide, for those of you who are unfamiliar with our story, rilparencel is an autologous cell therapy currently in late-stage clinical development. Our phase II data suggests that rilparencel may preserve kidney function in patients with diabetes and advanced chronic kidney disease.

In the U.S. alone, hundreds of thousands of people have Type 2 diabetes and advanced CKD. Each day, roughly 350 Americans begin chronic dialysis. A reminder of the urgent need for treatments that can preserve kidney function and extend life without dialysis. Next slide, please. 2027 will be a critical year for ProKidney. We are finishing 2026 with excitement and momentum. Patient recruitment into our phase III study exceeded our expectations. In August, we closed recruitment after a surge in screening across our 80-plus study sites. Previously, we guided to finish enrollment in 2026. Due to the surge in recruitment over the spring and summer, we will continue to enroll screened and eligible patients into the first quarter of next year. Our overall number of enrolled patients for the study has also changed from 470 to well over 500 participants.

I'm happy to state that we remain on track for the top-line readout of our phase III study in Q2 2027. As a reminder, this is an interim analysis for accelerated approval using eGFR slope as the surrogate endpoint. Importantly, all patients for inclusion in this readout have already been enrolled in the phase III study. Next slide. For those of you not familiar with our program, this is a depiction of our phase III PROACT 1 registrational study. This is a rigorous design in which eligible patients are randomized to either the treatment arm, you see here the rilparencel arm, or the sham controlled arm. Study participants, site investigators, and site personnel are blinded to the treatment allocation. For the surrogate endpoint analysis seen at the bottom of this slide, we are powered to detect a 1.5 ml per minute difference between the two groups in eGFR slope.

We are assuming an annual decline in eGFR slope of 3 mls per minute in the control arm of the study. We've heard from many nephrologists that if our readout is positive, this 1.5 ml per minute difference, which is a 50% difference in kidney function decline between groups, is very clinically meaningful, especially in these patients who are progressing to dialysis despite standard of care treatments. Now I'd like to hand it over to Dr. Anthony Conway to share recent scientific updates.

Anthony? Thanks so much, Bruce.

Today we will be sharing with you some recent data that we presented just a few days ago at ASN in Denver. Before I dig into that, for those of you who are not familiar, I wanted to go over how rilparencel is made and administered in patients with advanced CKD and type 2 diabetes. First, standard biopsies are taken from each individual patient's own kidney. Those cells are then sent to our manufacturing site in Winston-Salem, North Carolina, where the kidney cells are isolated and expanded to large amounts. Those cells are then cryopreserved and shipped back to the clinical site, where they are then injected back into the patient's kidneys via interventional radiologist with CT guidance, and then 3 months later into the contralateral kidney.

Since these cells come from each individual patient's own body, no immunosuppression is needed, and unlike CAR T, there is no preconditioning, no genetic modification, and these are outpatient procedures. The therapy has been well-tolerated in our phase II studies and has been associated with a 78% slower annual eGFR decline in patients with advanced CKD and diabetes in cohort 1 of our REGEN-007 study, which is the design which most closely mimics our phase III design. As Bruce mentioned, we have a top-line readout for our phase III study in Q2 of next year. One of the biggest missing pieces, though, is how rilparencel may be working. We have really promising clinical data, but how exactly is rilparencel mediating that effect? To be able to do that, we need to uncover what is happening in diseased kidney tissue after our product is administered.

A way that we have been addressing this is by developing and utilizing a variety of translational disease models to elucidate the mechanism of action of rilparencel. I will be talking through all of these different models today with data being presented at ASN just a few days ago on the in vitro, ex vivo, and in vivo rodent models. Each of these have various advantages and disadvantages. The in vitro model is relatively high throughput and can interrogate a wide variety of variables simultaneously to deconvolute specific aspects of the mechanism. The ex vivo model is from deceased donor, human donor kidneys, so replicates the disease pathology within the individual kidney biopsy obtained from those individuals, and then can assess molecular changes which are occurring after the introduction of rilparencel into culture.

Rodent models have whole body physiology that you can interrogate molecular and cellular changes after the administration of rilparencel directly injected into the kidney cortex as it is in the clinic. Taking an even further step back, because one of the questions that we always get is, "What is rilparencel?" This question, we started to ask where rilparencel, what cells within the individual kidney biopsies is rilparencel derived from. What we did is utilized 3 batches of process development made rilparencel, starting with kidney biopsies from patients with different stages of CKD. You can see stage 4, 2, and 3. Also, the end of the first passage after rilparencel is digested and plated into culture plastic, and then rilparencel itself, or a late-stage manufacturing product.