Akebia Therapeutics, Inc. · NASDAQ:AKBA
Akebia Therapeutics — Investor Day (April 2026)
55 slides from Akebia Therapeutics's investor day presentation, Apr 2, 2026
Slide 1: Bettering the Lives of People Impacted by Kidney Disease
Bettering the Lives of People Impacted by Kidney Disease R&D Day 2026 April 2, 2026 1 NASDAQ: AKBA
Slide 2: Cautionary note on forward-looking statements
Cautionary note on forward-looking statements Statements in this presentation regarding Akebia Therapeutics, Inc.’s (“Akebia’s”) strategy, plans, prospects, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform
Slide 3: Agenda
Agenda John P. Butler Opening Remarks President and CEO, Akebia Therapeutics Steven Burke, MD Praliciguat Head of R&D and Chief Medical Officer, Akebia Therapeutics Soluble Guanylate Cyclase (sGC) Stimulator James A. Tumlin, MD Chief Executive Officer, NephroNet Steven Burke, MD AKB-097 V. Michael H
Slide 4: Corporate strategy
Corporate strategy Our purpose is to better the lives of people impacted by kidney disease Drive Vafseo to be Build on our Create a future for standard of care commitment to those Akebia beyond kidney for the treatment of anemia impacted by kidney disease due to CKD for patients on disease dialysis
Slide 5: Drive Vafseo to be standard of care
Drive Vafseo to be standard of care 2025 Net Product Revenues Oral phosphate binder used to treat Oral treatment for anemia due to CKD in dialysis launched in January 2025 $227.3M hyperphosphatemia and anemia in patients with CKD Vafseo Set Up for Growth in a $1 billion market in 2026 and Beyond Acc
Slide 6: Leveraging our expertise to develop a robust kidney disease pipeline
Leveraging our expertise to develop a robust kidney disease pipeline ASSET MECHANISM INDICATION Preclinical Phase I Phase 2 Phase 3 Praliciguat sGC Stimulator FSGS IgAN Anti-C3d-Factor AKB-097 H Fusion Protein LN Kidney (ebribafusp alfa) Complement Inhibitor C3G Cardiac Surgery-Associated AKB-9090 H
Slide 7: Targeting severe kidney diseases with high unmet need
Targeting severe kidney diseases with high unmet need PRALICIGUAT AKB-097 AKB-9090 FSGS IgAN CS-associated AKI • Scarring (sclerosis) in parts • Characterized by the accumulation of IgA • Results from impact on (segmental) of some antibodies in the kidneys2 perfusion, hemolysis, (focal) glomeruli, t
Slide 8: Focus indications are multi-billion-dollar U.S. market opportunities
Focus indications are multi-billion-dollar U.S. market opportunities7 PRALICIGUAT AKB-097 AKB-9090 IgAN FSGS ~126,000 patients3 CS-associated AKI ~40,000 patients2 ~$120K-$390K/yr ~120,000 patients7 ~$120K/yr LN ~$20K/treatment 100,000 patients4,5 ~$65K-$155K/yr C3G 4,000 patients6 ~$505K/yr 1Market
Slide 9: Matching our technologies to diseases where MOA is best suited
Matching our technologies to diseases where MOA is best suited to potentially address the biological need Differentiated MOAs targeting specific biological activities PRALICIGUAT NO pathway is dysregulated in patients with kidney FSGS Soluble Guanylate Cyclase disease – less production, increased in
Slide 10: Introduction to presenters
Introduction to presenters Steven Burke, MD James A. Tumlin, MD V. Michael Holers, MD Jonathan Barratt, MD, Chief Medical Officer, Chief Executive Officer Professor, Medicine- PhD, FRCP Head of R&D NephroNet Rheumatology Mayer Professor of Akebia Therapeutics University of Colorado Renal Medicine Un
Slide 11: Praliciguat
Praliciguat 11
Slide 12: FSGS: Rare Disease with Limited Treatment Options-Significant Unmet Need
Focal Segmental Glomerulosclerosis (FSGS): Rare Disease with Limited Treatment Options-Significant Unmet Need FSGS is a descriptive phenotype of a glomerulopathy that is the product of multiple and varied pathologic mechanisms Prevalence of FSGS is growing; highest predilection among patients of Afr
Slide 13: Physiologic Contributors to Podocyte Dysfunction & Apoptosis in FSGS
Physiologic Contributors to Podocyte Dysfunction & Apoptosis in FSGS Cytokines Permeability TGF-α & TGF-β Factors: Type I Interferons Cardiotrophin-Like Cytokine-1 Altered Genetics SuPAR Nephrin, Podocin, Soluble Urokinase α-actinin-4, TRPC6 Plasminogen Activator Receptor Endothelin-1 Reactive Oxyge
Slide 14: Podocyte Detachment Leads to Exposed Capillary Basement Membranes
Podocyte Detachment Leads to Exposed Capillary Basement Membranes: Contribute to Glomerular Sclerosis Exposed Basement Membrane due to detached Podocytes Normal Control 30-300 mg/24 hrs Exposed Basement Membranes Leads to Glomerular Sclerosis 300-3500 mg/24 hrs >3500 mg/24 hrs Conti et al Scientific
Slide 15: Podocyte Injury: Progression from Injury to Glomerulosclerosis
Podocyte Injury: Progression from Injury to Detachment to Tuft Adhesion to Glomerulosclerosis Normal Glomerular Capillary Post Injury Podocyte Detachment: Glomerular Tuft Adherence to Bowman's & Pre-Detached Adriamycin Foot Plate Effacement with Capsule. Initiation Glomerulosclerosis Injured Podocyt
Slide 16: FSGS-NOS Histology: Tuft Adhesions
FSGS-NOS Histology: Tuft Adhesions Pathologic Features Segmental occlusion glomerular capillaries by accumulation of extracellular matrix proteins Adherence of Glomerular Tuft to Bowman’s Capsule Hyalinosis: accumulation of eosinophilic, trichrome-red staining amorphous material beneath basement mem
Slide 17: Kidney Failure Attributed to FSGS: A USRDS Epidemiologic Analysis
Kidney Failure Attributed to Focal Segmental Glomerulosclerosis (FSGS): A USRDS Epidemiologic Analysis Count of period prevalent FSGS-attributed kidney failure patients FSGS-attributed kidney failure prevalence rate Prevalence Rate: 87.6 cases per 1,000, 000 population Bensink et al Kidney Med. 2024
Slide 18: Prescription Immunosuppressants Used for FSGS
Prescription Immunosuppressants Used for FSGS Glucocorticoids 50.6% CNI-Tacrolimus 13.9% Mycophenolate 12.0% Azathioprine 1.7% ACTHar Gel l 0.5% Rituximab 0.5% Cytoxan 0.2% 0 10 20 30 40 50 60 Percent (%) Treated FSGS Patients Redrawn from Kalantar-Zadeh et al Kidney Int Rep. 2021 Aug 9;6:2679–2688
Slide 19: The Structure of Podocytes and the Network of Podocyte Cytoskeletons
,, The Structure of Podocytes and the Network of Podocyte Cytoskeletons Ma et al Internal J Mol Sciences. 2024 Jan 4;25:647
Slide 20: Reduction in Urinary Protein Losses Is Universally Beneficial in FSGS
Reduction in Urinary Protein Losses Is Universally Beneficial in FSGS
Slide 21: Achieving Remission of Proteinuria Improves Kidney Outcomes
, Achieving Either Complete or Partial Remission of Proteinuria in FSGS Is Important For Improving Kidney Outcomes 1.0 0.9 0.8 0.7 Renal survival 0.6 Achieving complete or P<0.001 0.5 NR<PR<CR partial remission of 0.4 proteinuria in patients 0.3 with primary FSGS is a CR 0.2 PR valid therapeutic goa
Slide 22: Strong Association Between Proteinuria and Risk of Progression to ESKD
, There Is a Strong Association Between Proteinuria and Risk of Progression to ESKD Short-term changes and residual Proteinuria was the only baseline variable proteinuria predicted long-term disease that correlated with the rate of GFR decline progression regardless of BP control and and progression
Slide 23: Achieving UP/Cr Below 700 mg/gm Reduces Progression to ESKD
,, Achieving UP/Cr Below 700 mg/gm Reduces Progression to ESKD: Results of the Parasol Study PARASOL: Renal Survival with UP/Cr RaDaR: Renal Survival with UP/Cr < 700 mg/gm-Independent of Treatment < 700 mg/gm-Independent of Treatment 40% Progression 42% Progression by Year-8 by Year-8 Smith AR, et
Slide 24: Praliciguat Augments Deficient NO-sGC-cGMP Signaling Pathways
Praliciguat Augments Deficient NO-sGC-cGMP Signaling Pathways in Glomerular Podocytes Praliciguat: Preclinical Studies Praliciguat NOS Mechanism of Action • Protamine sulfate-induced podocyte injury Arginine • TNFα-induced inflammation and TGF-β NO fibrosis in human proximal tubule cells NO • DSS ra
Slide 25: Multi-Faceted Functions of Praliciguat: Reduction in Glomerulosclerosis and Fibrosis
Multi-Faceted Functions of Praliciguat: Reduction in TGF-beta Dependent Glomerulosclerosis and Fibrosis in Hypertensive CKD Albuminuria Glomerulosclerosis Untreated Animals Interstitial Fibrosis TGF-beta Praliciguat 10 mg/kg/day Shea et.al. Am J Physiol Renal Physiol 318: F148–F159, 2020. TGF-beta =
Slide 26: Multi-Faceted Functions of Praliciguat: Blocks TGF-beta Induced Apoptosis
Multi-Faceted Functions of Praliciguat: Blocks TGF-beta Induced Apoptosis of Cultured Proximal Tubular Cells PTC Treated with TGF-beta TGF-beta + Praliciguat 1 µM (PRL1) and 10 µM (PRL10) Praliciguat was Superior to Anti-TGF-beta PTC Treated withTGF-beta + Praliciguat 1 µM Antibody Therapy Liu et.al
Slide 27: Praliciguat reduced proteinuria in Adriamycin mouse model of FSGS
Praliciguat treatment on a background of enalapril reduced proteinuria in Adriamycin mouse model of FSGS1 Urineprotein Urine protein//creatinine creatinineratio ratio 200 n i n e+/-r aSEM) tio *** *** a t imean 150 *** *** c r eratio *** n / (mg/mg # p r o/ creatinine 100 ** * * t e iratio n/ecreati
Slide 28: Praliciguat reduced glomerulosclerosis score in Adriamycin mouse model
Praliciguat treatment on a background of enalapril reduced the glomerulosclerosis score in Adriamycin mouse model of FSGS1 Glomerulosclerosis Glomerulosclerosis Score (0-4) Individual Significant differences from the Adriamycin group are denoted by †p<0.05, ††p<0.01. Significant differences from the
Slide 29: Praliciguat reduced tubulo-interstitial inflammation and tubular degeneration
Praliciguat treatment on a background of enalapril reduced tubulo-interstitial inflammation and tubular degeneration/regeneration scores in Adriamycin mouse model of FSGS1 Tubulo-interstitial Inflammation Significant differences from the Adriamycin group are denoted by †p<0.05, ††p<0.01. Significant
Slide 30: Praliciguat lowered albuminuria in the 5/6 nephrectomy rat model
Praliciguat treatment on a background of enalapril lowered albuminuria in the 5/6 nephrectomy rat model1 Urine Mean +/- SE Mean +_ SE (mg/mg) Albumin/Creatinine(mg/mg) UrineAlbumin/Creatinine Weeks after Nephrectomy *p < 0.05 vs Vehicle; # p < 0.05 vs Enalapril; ^ p < 0.05 vs respective monotherapy;
Slide 31: Praliciguat reduced serum creatinine in the 5/6 nephrectomy rat model
Praliciguat treatment on a background of enalapril reduced serum creatinine in the 5/6 nephrectomy rat model1 Serum Creatinine (mg/dL) Mean +/- SE 9 Weeks after Nephrectomy *p < 0.05 vs Vehicle; # p < 0.05 vs Enalapril; ^ p < 0.05 vs respective monotherapy; ** p < 0.05 vs all groups. AKB Cmpd is pra
Slide 32: Glomerulosclerosis reductions greatest with praliciguat plus enalapril
In the 5/6 nephrectomy model, glomerulosclerosis reductions were greatest when praliciguat was administered with enalapril compared to either agent alone1 * p < 0.05 vs Vehicle; # p < 0.05 vs Enalapril; ^ p < 0.05 vs respective monotherapy; ** p < 0.05 vs monotherapy @ 1.5, 3 mg/kg/day 32 AKB Cmpd i
Slide 33: Completed Phase 2 study in patients with DKD
Completed Phase 2 study* in patients with DKD receiving standard of care Objective: To assess safety and tolerability of praliciguat and its effect on renal function in patients with DKD on RAAS inhibitors Double-Blind Period [12 weeks] Patients [n=156] 1:1:1 Randomization Assessments • Type 2 diabe
Slide 34: Phase 2 study showed rapid and sustained reduction in UACR
Phase 2 study* showed praliciguat treatment associated with rapid and sustained reduction in UACR in ITT and post-hoc mITT population ITT Population mITT (without site 36) (N=156) (N=133) DKD Study: LS Mean (90% CI) Change in Baseline in UARC (mg/g) ITT DKD Study: LS Mean (90% CI) Change in Baseline
Slide 35: Post hoc analysis of Phase 2 trial showed increased UACR responses
Post hoc analysis of Phase 2 trial* in patients with DN showed increased UACR responses Praliciguat n/N Placebo n/N Relative Risk UACR Cut-point Difference % 95% CI (%) (%) (RR) Any time in 12 weeks 0.3 g/g 24/84 (28.6) 8/46 (17.4) +11.2 1.64 0.804, 3.358 0.5 g/g 43/84 (51.2) 16/46 (34.8) +16.4 1.47
Slide 36: Praliciguat Phase 2 clinical trial in FSGS
Praliciguat Phase 2 clinical trial in FSGS Randomized, double-blind, placebo-controlled, dose-titration study to evaluate the efficacy and safety of praliciguat in adults with biopsy-confirmed FSGS. 24 WEEKS 24 WEEKS Praliciguat Praliciguat Phase 2 Study Randomization • Targeting up to 60 1:1 DOUBLE
Slide 37: AKB-097 Ebribafusp alfa
AKB-097 Ebribafusp alfa 37
Slide 38: The complement system and complement-mediated disease
The complement system and complement-mediated disease The body’s complement system is comprised of ~30 proteins Complement inhibitors work by binding to and produced by the liver and immune cells that work together as preventing the activation of specific complement part of the innate immune system.
Slide 39: Complement inhibitors approved for kidney diseases
Complement inhibitors approved for kidney diseases Eculizumab Classical Ravulizumab Pegcetacoplan Bkemv Lectin (C4) C3 C5 C5b-9 C3a C5a Alternative C3b Iptacopan Avacopan 39 Image adapted from: Thurman JM. . Targeting the complement cascade
Slide 40: AKB-097 aims to address limitations of current complement inhibitors
AKB-097 aims to address limitations of current complement inhibitors PROBLEM: POTENTIAL SOLUTION: • Limited activity: Reliant on systemic • Enhanced activity through tissue targeting: blockade to impact affected organ Differentiated approach to driving efficacy by inactivating convertases directly a
Slide 41: AKB-097 is a novel, tissue-targeted complement inhibitor
AKB-097 is a novel, tissue-targeted complement inhibitor Designed to target complement activity in tissues Targeting control of the amplification loop of all 3 to degrade alternative pathway convertases complement pathways (alternative, classical, and lectin) • AKB-097 binds with high affinity to C3
Slide 42: Presence of C3d in human glomeruli is a hallmark of numerous kidney diseases
Presence of C3d in human glomeruli is a hallmark of numerous kidney diseases C3dImmunostaining of C3dtissue staining in human in human glomeruli samples = complement activation Negative Controls DISEASE Acute Tubular Necrosis IgA Nephropathy Lupus Class IV Lupus Class V Minimal Change Disease Thin G
Slide 43: AKB-097 had durable kidney PK and PD in fH -/- mouse model of C3G
In the fH -/- mouse model of human C3G, AKB-097 had long term, durable kidney PK and PD CfH-/- + 5mg/kg IV C3d mAb fH1-5 (days after dosing) The fH-/- mouse model WT CfH-/- + 3 7 14 had uncontrolled PBS complement activation Tissue PD (anti-C3 AKB-097 showed robust fragment) inhibition of C3 activit
Slide 44: AKB-097 IV reduced complement activation and proteinuria in rat model
AKB-097 IV reduced glomerular complement activation and proteinuria in the rat model of membranous nephropathy **P<0.002 vs. PBS ***P<0.0001 anti-fx1A + PBS ***P<0.0001 vs. PBS AKB-097, dosed IV, inhibited proteinuria at AKB-097 dose-dependently decreased glomerular complement activation levels comp
Slide 45: AKB-097 protects podocytes from foot process effacement
AKB-097 protects podocytes from foot process effacement in the membranous nephritis model1 Healthy Control Vehicle AKB-097 Treatment with AKB-097 shows In the rat model, there is extensive foot Transmission electron microscopy substantial preservation of podocyte process effacement (yellow arrows) S
Slide 46: Phase 1 weekly SC dosing met desired exposures
In a Phase 1 study*, weekly SC dosing met desired exposures for predicted complement tissue inhibition without systemic AP pathway inhibition SAD Cohort 1(0.1 mgkg IV) Mean (SD) Plasma AKB-097 Weislab AP Activity Mean % of Baseline Concentration (μg/ml) SAD Cohort 2 (0.2 mgkg IV) 450 mg SC weekly wi
Slide 47: Phase 2 dose identified from Phase 1 study
Phase 2 dose identified: 450 mg SC met desired exposure goals in Phase 1 study1 Mean (SD) AKB-097 Plasma Concentration (μg/ml) Drug levels predicted to provide maximal tissue complement inhibition and activity based on mouse, rat and NHP preclinical data No serious or severe adverse events (AEs), no
Slide 48: AKB-097 could become the SOC in multiple rare kidney diseases
AKB-097 could become the SOC in multiple rare kidney diseases alone or in combination with other therapies IgAN LN C3G Role of Lack of complement inhibitors in Overactivation of the complement Drives inflammation and kidney SLE, accelerates the complement cascade leads to injury1 system in disease d
Slide 49: Ebribafusp alfa Phase 2 open-label rare kidney disease basket trial
Ebribafusp alfa Phase 2 open-label rare kidney disease basket trial The trial is designed to evaluate the safety, PK/PD, and clinical activity of ebribafusp alfa in patients with IgAN, LN, and C3G. 26 WEEKS 4 WEEKS Ebribafusp alfa Follow up Phase 2 study Subcutaneous injections weekly Targeting ~30
Slide 50: AKB-9090
AKB-9090 50
Slide 51: CS-AKI affects a significant number of patients and there is unmet need
CS-AKI affects a significant number of patients and there is unmet need for treatment 3 AKI is a sudden decrease in kidney function measured within a week and often associated with another serious illness or condition.1 Can arise from cardiac surgery-related procedures that cause hypoperfusion, hemo
Slide 52: AKB-9090 is a novel HIF-PH inhibitor being evaluated in CS-AKI
AKB-9090 is a novel HIF-PH inhibitor being evaluated in CS-AKI The case for HIF- stabilization in AKI Injury to the tubular epithelium and microvascular endothelium underlie the pathophysiology of AKI1 Stabilization of HIF, a transcription factor, by prolyl hydroxylase inhibition leads to coordinate
Slide 53: AKB-9090 mechanism of kidney protection
AKB-9090 mechanism of kidney protection1 Investigational agents for AKI targeting a single pathway have not worked, including Cell Survival recombinant alkaline phosphatase, p53 inhibitor, HGF mimetic, BMP peptide or α-MSH inhibitor. Metabolic Anti- Reprogramming Inflammatory Decrease ROS Response U
Slide 54: AKB-9090 reduced kidney injury in a kidney ischemia-reperfusion animal model
AKB-9090 reduced kidney injury in a kidney ischemia-reperfusion animal model / 54 From Study Report IU-AKB-0017, 1520-2302890 and Addendum to 1520-2302890
Slide 55: Multiple value enhancing milestones expected over the next 12+ months
Multiple value enhancing milestones expected over the next 12+ months AKB-097 Phase 2 basket trial initial data VOICE top-line data 2027 Q1 2027 AKB-9090 Phase 1 top-line data Q1 2027 VOCAL top-line data Q4 2026 Initiate AKB-097 Phase 2 basket trial 2H 2026 Initiate AKB-9090 Phase 1 trial Q2 2026 Do