Prokidney Corp. · NASDAQ:PROK

Prokidney — Corporate Update (October 2026)

55 slides from Prokidney's corporate update, Oct 27, 2026

  1. Slide 1: ASN Kidney Week Recap & Corporate Update

    American Society of Nephrology (ASN) Kidney Week Recap & Corporate Update October 27, 2026 NASDAQ PROK Copyright © 2026 ProKidney Corp. All rights reserved.

  2. Slide 2: Forward-looking Statements

    Forward-looking Statements This presentation includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. ProKidney’s actual results may differ from its expectations, estimates and projections and consequently, you

  3. Slide 3: Today's Agenda and Speakers

    Today’s Agenda and Speakers Bruce Culleton, MD, CEO Anthony Conway, PhD, Head of R&D Katherine Tuttle, MD, KOL The Quest to Save Kidneys, Hearts, 1 Opening Remarks & Corporate Update 3 and Lives: Mechanisms Matter 2 Rilparencel MoA Findings 4 Q&A MoA = Mechanism of Action KOL = Key Opinion Leader 3

  4. Slide 4: Opening Remarks & Corporate Update

    BRUCE CULLETON, MD, CEO Opening Remarks & Corporate Update

  5. Slide 5: Redefining What's Possible in the Treatment of CKD Through Innovation and Execution

    Redefining What's Possible in the Treatment of CKD Through Innovation and Execution Rilparencel Potential first-in-class autologous cell therapy designed to preserve kidney function in patients with advanced CKD Phase 3 PROACT 1 trial in patients with Stage ONGOING (Q2 2027 readout) Pivotal Phase 3

  6. Slide 6: Anticipated Upcoming Milestones

    Anticipated Upcoming Milestones Timing Milestones Complete full enrollment for the Phase 3 PROACT 1 study. Anticipate enrolling over 500 patients (up from Q1 2027 470) driven by an acceleration in patient recruitment in mid-2026. Topline readout for the Phase 3 PROACT 1 surrogate endpoint (eGFR slop

  7. Slide 7: Rilparencel Phase 3 Registrational Study Design

    PHASE 3 REGEN-006 (PROACT 1) Rilparencel Phase 3 Registrational Study Design Topline results for the eGFR slope surrogate endpoint anticipated in Q2 2027 1st 2nd Rilparencel Rilparencel Rilparencel Cohort Biopsy Injection Injection n>500 End of Study (EOS) 3 3 3 months months months Screening R Sham

  8. Slide 8: Rilparencel Mechanism of Action (MoA) Findings

    A N T H O N Y C O N W A Y, P h D , H E A D O F R & D Rilparencel Mechanism of Action (MoA) Findings

  9. Slide 9: Rilparencel: A patient's own cells, from biopsy to kidney therapy

    Rilparencel: A patient's own cells, from biopsy to kidney therapy Process overview Rilparencel: Kidney cells x Then frozen for are isolated preservation & • Made from patient’s own kidney cells & expanded shipping to site 22 33 • No genetic modification • No preconditioning • No lifelong immunosuppr

  10. Slide 10: Utilizing translational disease models to elucidate rilparencel MoA

    Utilizing translational disease models to elucidate rilparencel MoA In vitro Ex vivo In vivo (rodent) In vivo (human decedent) Primary kidney cells Kidney biopsy explant culture Rodent models of CKD CKD donor Control Rilparencel Kidney-on-chip Advantages • Quick: Fast design-test-learn cycles • Nati

  11. Slide 11: Identifying the cellular origin of rilparencel from kidney biopsies

    Identifying the cellular origin of rilparencel from kidney biopsies Biopsy Early Passage Late Manufacturing / Rilparencel scRNA-seq 3 CKD donor kidneys LM Stage 4 CKD Stage 2 Biopsy CKD Early Late Stage 5 CKD For the purpose of this presentation, rilparencel may refer to selected renal cells (SRC),

  12. Slide 12: Cellular trajectory from biopsy to rilparencel

    Cellular trajectory from biopsy to rilparencel Nephron (functional unit of kidney) CNT IC TAL PT INT EC & Immune Cortex Medulla Dimension 1 (UMAP1) Cell cycle phase Biopsy Early stage Late stage Rilparencel Actively Temporal inferred transition dividing Late-stage expression similarity cells Dimensi

  13. Slide 13: Distinct lineage-associated populations in rilparencel across 17 patient batches

    2 distinct lineage-associated populations in rilparencel present in 17 patient batches Population Markers scRNA-Seq Unbiased Clustering Proximal & Distal Population Clusters Dimension 1 (UMAP1) Dimension 1 (UMAP1) Dimension 2 (UMAP2) Dimension 2 (UMAP2) Proximal Distal Lineage-associated rilparencel

  14. Slide 14: Similar characterization marker expression across rilparencel batches

    Similar characterization marker expression across 17 rilparencel batches Rilparencel Characterization Panel (scRNA-Seq) Examples of Expression Trajectory from Biopsy to Rilparencel VEGFA MGST1 Rilparencel Biopsy Early Late Cells of proximal & distal tubule origin exhibiting a reparative, plasticity-

  15. Slide 15: Utilizing in vitro CKD models to assess resolution of disease state

    Utilizing in vitro CKD models to assess resolution of disease state by rilparencel Activation of Disease Rilparencel Resolution of Disease Kidney-on-chip State Phenotype Treatment State Phenotype Primary kidney cells v Workstream Goals • Develop advanced, human-relevant in vitro disease models for r

  16. Slide 16: In vitro functional assays measure common CKD pathway-relevant readouts

    In vitro functional assays measure common CKD pathway-relevant readouts CKD Inducers & Drivers Hyperglycemia Hyperlipidemia Hypoxia Common CKD Pathways Oxidative stress Metabolic dysregulation Cell death Inflammation Fibrosis Tuttle et al. Kidney International (2022) Functional Assay Testing Deconvo

  17. Slide 17: Rilparencel co-culture in injured kidney-on-chip experimental design

    Rilparencel co-culture in injured kidney-on-chip experimental design Kidney-on-chip Nephron (MIMETAS OrganoPlate) (functional unit of kidney) Key Considerations • Model captures endothelial : epithelial ECM Blood Vessels interface & crosstalk • Rilparencel is administered directly on ECM GMVEC RPTEC

  18. Slide 18: Rilparencel promotes endothelial junctional & barrier integrity

    Rilparencel promotes endothelial junctional & barrier integrity 3D Mechanistic Discovery 3D & 2D Functional Validation CD31 VE-Cadherin Barrier Permeability 10000 2000 a a b 8000 b 1.5×10 -5 1500 c 6000 c 1000 a 4000 Papp (cm/s) 2000 500 1×10 -5 0 0 b ol C ry ol C ry R R tr tr ju ju 5×10 -6 c +S +S

  19. Slide 19: Rilparencel promotes native endothelial metabolic state

    Rilparencel promotes native endothelial metabolic state Basal Respiration Spare Respiratory Capacity 30 40 Control (pmol/min/1x103 cells) (pmol/min/1x103 cells) 30 IM v2.0 20 IM v2.0 + PK014 Rilparencel-treated (2 donor batches) OCR OCR 20 IM v2.0 + PK025 10 10 0 0 1 4 1 4 Days Post-Treatment Days P

  20. Slide 20: Rilparencel attenuates pro-inflammatory signaling & recruitment cues

    Rilparencel attenuates pro-inflammatory signaling & recruitment cues Kidney-on-chip 3D in vitro testing platform (DAMP secretion assay) 2D In vitro testing platform (ELISA) Endothelial Compartment 60 IκBα NFκB Injury Rilparencel Fold Change over Control HMBG-1 : LDH Ratio ns ns Control 40 ✱ ✱ ✱ ✱ In

  21. Slide 21: Rilparencel lowers reactive iron species & activates lipid peroxidation repair

    Rilparencel lowers reactive iron species & activates a cytoprotective lipid peroxidation repair program in injured renal epithelial cells Total Iron Fe3+/Fe2+ Ratio Iron Fractions 50 15 60 Iron (μM/μg protein) Iron (μM/μg protein) a Ferric (Fe3+) 40 b b a Ferrous (Fe2+) Fe3+ : Fe2+ 10 40 30 20 b 5 2

  22. Slide 22: Rilparencel rescues oxidative damage & mitochondrial dysfunction

    Rilparencel rescues oxidative damage & mitochondrial dysfunction in continuously injured renal epithelial cells Control Injury Injury + SRC Coupling Efficiency Spare Capacity Bioenergetic Health 6 15 #^ #^ # 120 BHI (% of control) Cellular RCRbasal Cellular RCRmax #^ #^ #^ #^ #^ # 100 4 10 80 60 2 *

  23. Slide 23: GPX4 activity is required for rilparencel-mediated rescue

    GPX4 activity is required for rilparencel-mediated rescue of oxidative damage & mitochondrial dysfunction in epithelial cells Total Glutathione Glutathione Redox Balance 5×10 4 2.5 a (normalized to cell count) ab a 4×10 4 ab 2.0 ab a a (total/oxidized) b GSH/GSSG 3×10 4 1.5 b RLU c c c 2×10 4 1.0 1×

  24. Slide 24: Factors expressed by rilparencel with potential mechanistic relevance

    Rilparencel Factors expressed by rilparencel with potential mechanistic relevance Upregulation of Increased expression of chemotactic, protective paracrine & cytoprotective, & stress- microenvironmental adaptation factors regulators Downregulation of baseline prostaglandin catabolism, amino acid met

  25. Slide 25: Designing a multiomic approach to probe MoA in rodent CKD models

    Designing a multiomic approach to probe MoA in rodent CKD models • Preclinical proof-of-concept: Intracortically administered syngeneic selected renal cells (SRC) extended survival & stabilized renal function (sCR, BUN) in rodent (Kelley et al., 2010) & dog CKD models, improved survival & stabilized

  26. Slide 26: Rilparencel distributes to subcapsular & intraparenchymal renal compartments

    Rilparencel distributes to subcapsular & intraparenchymal renal compartments, partially persists through Day 28 Humanized NSG-IL15 mice fed adenine 1-day post-dose 28 days post-dose hKu80+ hmCD45- = Rilparencel hKu80+ hmCD45+ = Human immune cells hKu80- hmCD45+ = Mouse immune cells Vascular smooth m

  27. Slide 27: Aligning multiomic analytical modalities after rilparencel injection

    Aligning multiomic analytical modalities after rilparencel injection IHC Spatial transcriptomics Human nuclei (rilparencel) Rilparencel-associated gene All nuclei 27

  28. Slide 28: Graft-associated cells have a distinct transcriptional signature in injected rats

    Graft-associated cells have a distinct transcriptional signature in injected rats • Significantly upregulated genes in graft area cells 3 days post-rilparencel are associated with ECM remodeling & vascular development, including matrix organization & turnover, collagen biosynthesis, & blood vessel m

  29. Slide 29: Transcriptional signature of graft-associated cells evolves over time

    Transcriptional signature of graft-associated cells evolves over time Days post-rilparencel injection • The injured kidney’s response to rilparencel is dynamic & evolves over time • An initial higher upregulation in ECM remodeling gene expression drops over the first week after treatment but is main

  30. Slide 30: Aligning multiomic analytical modalities after rilparencel injection

    Aligning multiomic analytical modalities after rilparencel injection Single nuclei RNA-seq Rilparencel-treated Vehicle-treated Healthy Control IHC Spatial transcriptomics Human nuclei (rilparencel) Rilparencel-associated gene All Nuclei 30

  31. Slide 31: Cell junction & ECM adhesion signaling upregulated in rat kidney endothelial cells

    Cell junction & ECM adhesion signaling is upregulated in rat kidney endothelial cells Endothelial junction & Endothelial adhesion & • Kidney snRNA-seq at 28 days post-dose in RNU rats with ECM programs stability programs adenine-induced CKD; endothelial nuclei identified using rodent kidney cell atl

  32. Slide 32: Aligning multiomic analytical modalities after rilparencel injection

    Aligning multiomic analytical modalities after rilparencel injection Single nuclei RNA-seq Rilparencel-treated Vehicle-treated Healthy Control IHC Spatial Transcriptomics Human nuclei (rilparencel) Rilparencel-associated gene Mass spec imaging (MSI) All Nuclei PI O-32:0 PE 40:3 32

  33. Slide 33: MSI reveals a distinct tissue remodeling signature at the injection site

    MSI reveals a distinct tissue remodeling signature at the rilparencel injection site Signature domains hKu80 (rilparencel) • MSI spatially resolved protein & lipid biomarkers within an injection-defined ROI encompassing the hKu80-associated rilparencel injection site at day 3 post-injection • ROI sh

  34. Slide 34: Translational studies suggest multifactorial MoA for rilparencel

    Translational studies suggest multifactorial MoA for rilparencel How rilparencel may Human proximal tubule epithelial cell & glomerular vascular be able to preserve Primary kidney cells endothelial cell models of metabolic & inflammatory stress cultured with rilparencel showed (ASN poster TH-PO1128)

  35. Slide 35: The Quest to Save Kidneys, Hearts, and Lives: Mechanisms Matter

    The Quest to Save Kidneys, Hearts, and Lives Mechanisms Matter Katherine R. Tuttle, MD, FASN, FACP, FNKF Executive Director for Research Providence Inland Northwest Health Professor of Medicine Nephrology Division and Kidney Research Institute University of Washington School of Medicine In the spiri

  36. Slide 36: CKD Is A Global Public Health Crisis

    CKD Is A Global Public Health Crisis Western Europe USA 44 MILLION Worldwide Extremely common Increasing 850 death rate 40 MILLION MILLION 2017- 41.5% from 1990 to 2017 and in 2023 2023 caused 5th 144,000 1 in10 9th 13th 147,000 in 2023 19th deaths 2040 people in the general 2013 2016 2019-2025 (pre

  37. Slide 37: What Problem are We Trying to Solve?

    What Problem are We Trying to Solve? 589 million 2024 and 850 million 2050 Tuttle KR et al. CJASN 2022;17:1092-1103 International Diabetes Federation Atlas 11th edition, 2025

  38. Slide 38: Cardiovascular-Kidney-Metabolic Syndrome: Kidney in the Middle

    Cardiovascular-Kidney-Metabolic Syndrome Kidney in the Middle Tuttle KR et al. Clin J Am Soc Nephrol 2026; online ahead of print Ndumele CE et al. Circulation 2023; 148:1636-1664

  39. Slide 39: Goal: Mitigate High Kidney & Cardiovascular Risk

    GOAL: MITIGATE HIGH KIDNEY & CARDIOVASCULAR RISK Grams ME et al. JAMA 2023;330:1266-1277.

  40. Slide 40: Combination Therapy and the 4-Pillars

    Combination Therapy and the 4-Pillars Diabetic and Non-Diabetic CKD Neuen B et al. Nephrol Dial Transplant 2025:40 (S1):i59-i69

  41. Slide 41: Complementary Mechanisms for CKM Therapies

    Complementary Mechanisms for CKM Therapies Alicic RZ, Neumiller JJ, Tuttle KR. Nephrol Dial Transplant 2025; 40 (S1):i3–i17

  42. Slide 42: Combination Therapy and Kidney Outcomes

    Combination Therapy and Kidney Outcomes Added to RAS Blockade Neuen BL et al. Circulation 2024;149:450–462

  43. Slide 43: Combination Therapy and Cardiovascular Outcomes

    Combination Therapy and Cardiovascular Outcomes Added to RAS Blockade Neuen BL et al. Circulation 2024;149:450–462

  44. Slide 44: Time to Events for Survival and Kidney Function in CKD

    Time to Events for Survival and Kidney Function in CKD Population Level and Person Level Tuttle KR et al. Clin J Am Soc Nephrol 2026; online ahead of print

  45. Slide 45: Residual Risks with Current CKD Therapies

    Residual Risks with Current CKD Therapies Questions and Potential Roles for Rilparencel • Who are treatment responders and non-responders? • TBD • What therapy or combination will work best? • TBD • When is the right time to deploy therapy? • Rilparencel as a reparative tool • Why does a therapy wor

  46. Slide 46: What Can We Learn from Mechanistic Studies?

    What Can We Learn from Mechanistic Studies?

  47. Slide 47: Reduced Albuminuria and Stabilized eGFR

    Reduced Albuminuria and Stabilized eGFR Semaglutide treatment compared to placebo UACR Change in eGFR after 52 weeks: Creatinine-cystatin C-based Change from baseline (mL/min/1.73 m ) 2.0 2 • UACR reduced 40% 4 (ETR 0.60, 95% CI 0.41;0.88, p=0.008) 1.5 Ratio to baseline 2 • eGFR differences • Creati

  48. Slide 48: Reduced Kidney Fat and Renal Arterial Resistance with Stabilized Cortical Fibrosis

    Reduced Kidney Fat and Renal Arterial Resistance with Stabilized Cortical Fibrosis Kidney fat Renal arterial resistive index Cortical ADC Semaglutide treatment compared to placebo 1.75 1.06 1.10 Perirenal Sinus ETR 0.96 [95% CI 0.93;0.99] after 52 weeks: ETR 0.75 ETR 0.87 p = 0.008 [95% CI 0.58;0.97

  49. Slide 49: Indicators of Improved Glomerular Filtration and Barrier Function

    Indicators of Improved Glomerular Filtration and Barrier Function Creatinine clearance Filtration fraction 16 1.50 ETD 12.0 (95% CI 0.7;23.3) p = 0.038 Change from baseline (m L/min) 12 Semaglutide treatment compared ETR 1.19 [95% CI 0.98;1.45] to placebo after 52 weeks: 8 3.0 p = 0.086 Ratio to bas

  50. Slide 50: Transcriptomic Reprogramming in Glomerular Endothelial Cells

    Transcriptomic Reprogramming in Glomerular Endothelial Cells Glom erular endothelial cells 1 Glom erular endothelial cells 2 Regulation Natural killer T cell Down Proxim al tubule cells 2 Up Connecting nephron Connecting nephron - im m une UMAP dimension 2 -75 75 -50 50 -25 25 0 25 50 75 Num ber of

  51. Slide 51: Ligand-Receptor Interactions between Glomerular Endothelial Cells and Immune Cells

    Ligand-Receptor Interactions between Glomerular Endothelial Cells and Immune Cells – snRNAseq Semaglutide promotes glomerular endothelial repair and remodeling programs: Type 4 collagen, integrins, PECAM1 (CD31), CDH5 (VE cadherin) Tuttle KR, Bjornstad P… Kretzler M et al. Nat Med 2026 Oct 1. Online

  52. Slide 52: Spatial Transcriptomics Glomerular Endothelial and Natural Killer T Cells

    Spatial Transcriptomics Glomerular Endothelial and Natural Killer T Cells, Monocytes/Macrophages Tuttle KR, Bjornstad P… Kretzler M et al. Nat Med 2026 Oct 1. Online ahead of print. PMID: 42823485

  53. Slide 53: Reduced Fractional Intimal Area of Most Diseased Arterioles

    Reduced Fractional Intimal Area of Most Diseased Arterioles and Periglomerular Immune Cells Semaglutide Pre Post Tuttle KR, Bjornstad P… Kretzler M et al. Nat Med 2026 Oct 1. Online ahead of print. PMID: 42823485

  54. Slide 54: Pathophysiological Interpretation of Semaglutide's Mechanisms-of-Action in CKD and T2D

    Pathophysiological Interpretation of Semaglutide’s Mechanisms-of-Action in CKD and T2D Semaglutide Functional MRI Clinical/biochemical Endothelial measures Reduced intrarenal and Improved glomerular Attenuated metabolic and transcriptional perirenal fat hemodynamics fibro-inflammatory signaling Hist

  55. Slide 55: ProKidney

    PROKIDNEY.:::

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