Passionately Committed to Bettering the Lives of Patients with Kidney and Cardiovascular Diseases

Passionately committed to bettering the lives of patients with kidney and cardiovascular diseases

October 2020 Forward-Looking Statements

To the extent that statements contained in this presentation are not descriptions of historical facts regarding Ardelyx, they are forward- looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor of the Private Securities Reform Act of 1995, including statements regarding the potential for Ardelyx’s product candidates in treating the diseases and conditions for which they are being developed, the potential for the use of tenapanor as monotherapy and as part of a dual mechanism approach with tenapanor and binders for the control of serum phosphorus in chronic kidney disease (CKD) patients on dialysis, Ardelyx’s expected timing of the acceptance for substantive review by the FDA of the NDA for tenapanor for the control of serum phosphorus in CKD patients on dialysis, and Ardelyx’s expectation regarding the potential approval of such NDA and the expected timing thereof, the commercial potential for Ardelyx’s product candidates, Ardelyx’s expectations regarding the size of the patient populations for its product candidates, Ardelyx’s ability to establish collaborations in the future and Ardelyx’s expectations regarding the exhaustion of its current capital resources. Such forward-looking statements involve substantial risks and uncertainties that could cause the development of Ardelyx’s product candidates or Ardelyx's future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in research and the clinical development process; the uncertainties associated with the regulatory approval process; and the uncertainties in the drug commercialization process. Ardelyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ardelyx’s business in general, please refer to Ardelyx’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 6, 2020, and its future current and periodic reports to be filed with the Securities and Exchange Commission

2 Translating Scientific Breakthroughs into Promise for Patients

We are dedicated to improving the lives of patients by developing and commercializing first-in-class targeted therapies that advance patient care. Our research expertise on biological mechanisms and pathways has enabled us to develop a pipeline of drug candidates designed to address important clinical unmet needs, including better management of complications related to kidney and cardiovascular diseases with the goal of improving outcomes for this large population of underserved patients. Ardelyx Overview

• Tenapanor: First-in-class product candidate for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis • Three successful statistically significant Phase 3 studies • NDA Accepted September 2020; PDUFA Goal Date – April 29, 2021 • Large target market • ~2.7M phosphate binder prescriptions written per year in U.S.1 • Accessible with U.S. specialty-focused commercial organization; Ex-US commercialization through select collaborations • IBSRELA® (tenapanor) for IBS-C approved September 2019 • Discovery platform fuels additional pipeline programs • RDX013 is a novel approach for hyperkalemia • Cash of $204.8M2 supports operations into first half of 2022

1. IQVIA 2019 (Retail); Adding estimate for Rxs through dialysis organization specialty pharmacies 4 2. Cash, cash equivalents and short-term investments as of June 30, 2020 Tenapanor for Hyperphosphatemia

A first-in-class phosphate absorption inhibitor that provides an innovative and differentiated non-binder approach to phosphorus management - NDA accepted September 2020; PDUFA Goal Date – April 29, 2021 . HYPERPHOSPHATEMIA Phosphate Level is an Independent Predictor of Morbidity and Mortality in Patients on Dialysis1

Serious Potential Consequences From Elevated Phosphorus Increased serum phosphorus RelativeRelative Risk Risk of of Death Death Based on on Serum Serum Phosphorus Phosphorus Level Level levels of 0.5 to 1 mg/dL over

2.5 the reference range resulted Reference range 2.02 in a significant increase in Elevated serum phosphorus level 2 relative risk of death 1.67 1.43 1.5 1.25 1.07 Elevated serum phosphorus also 1 increases the relative risk of hospitalization by up to 38%

Relative Risk Deathof 0.5

0 4.0-5.0 5.0-6.0 6.0-7.0 7.0-8.0 8.0-9.0 ≥9.0 Serum Phosphorus Level, mg/dL

1. Block, GA, et al. Mortality, and Morbidity in Maintenance Hemodialysis. J Am Soc Nephrol 15: 2208–2218, 2004 6 2. Increased risk was not diminished by statistical adjustment for coexisting medical conditions, delivered dose of dialysis, nutritional parameters, or markers of noncompliance HYPERPHOSPHATEMIA There is a High Unmet Need for Novel Hyperphosphatemia Treatments

Approximately 95% of CKD patients on dialysis need phosphate control1

77% of patients treated with binders Sub-optimal and inconsistent were unable to consistently maintain phosphorus control with phosphorus levels <=5.5 mg/dL phosphate binders over a six-month period2

1. Savica, V Nephrol Dial Transplant 2006 21: 2065-2068 7 2. Spherix RealWorld Dynamix, Dialysis 2019 HYPERPHOSPHATEMIA Inherent Limitations with Phosphate Binder Mechanism of Action

BIND DIETARY LIMITED BINDING POOR PHOSPHATE IN THE GUT CAPACITY TOLERABILITY • MOA requires dosing • Number of pills • Constipation with every meal • Size of pills • Bloating • Dosing frequency • Formulation • Nausea • Diarrhea

Challenges with Efficacy and Patient Adherence

8 Tenapanor Clinical Development Program HYPERPHOSPHATEMIA Novel Mechanism of Action with Tenapanor Provides a Solution

Tenapanor TARGETS BLOCKS DOSED First-in-Class Approach primary pathway of paracellular uptake as one pill twice phosphate absorption of phosphorus* per day† Unlike phosphate binders, tenapanor is a phosphate absorption inhibitor that…

* King et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med 10, eaam6474. DOI: 10.1126/scitranslmed.aam6467. Accessed on August 29, 2018. 10 † In clinical trials, dosing is 1 pill BID HYPERPHOSPHATEMIA Comprehensive Development Program Supports Tenapanor Opportunity

NORMALIZE MONOTHERAPY DUAL MECHANISM MONOTHERAPY targeting normal short-term BENEFIT long-term serum phosphorus

Phase 3 BLOCK Phase 3 AMPLIFY Phase 3 PHREEDOM Extension Study NORMALIZE

Primary and Secondary Primary and Key Secondary Primary and Key Secondary Initial Analysis Demonstrates Endpoints met Endpoints met Endpoints met Increased % of Patients Achieving Goal

Expect FDA approval in Q2 2021

11 HYPERPHOSPHATEMIA BLOCK: Statistically Significant Pivotal Monotherapy Phase 3 Results

DESIGN EFFICACY SAFETY

12-week trial to evaluate different Primary endpoint statistically Well tolerated doses of tenapanor, as well as the significant (p<0.01) difference in 8-week open-label treatment period: efficacy, safety and tolerability of least squared mean serum tenapanor monotherapy in patients phosphorus change (0.82 mg/dL) • 39% diarrhea with CKD on dialysis • Only adverse event ≥5% between tenapanor and placebo n=219 • Mostly mild to moderate • Stool form and frequency changes, Secondary analyses: At the end of the 8- Primary Endpoint: Difference in change in on average, remained in normal week open label treatment period, range for healthy individuals serum phosphorus between pooled tenapanor-treated patients in the efficacy • 8% discontinuation due to diarrhea tenapanor-treated patients and placebo- analysis set (n=80) achieved a mean treated patients in the efficacy analysis decrease in serum phosphorus from set from the end of the 8-week treatment baseline of 2.56 mg/dL period to the end of the 4-week randomized withdrawal period

12 Block, GA, et al.. Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial. J Am Soc Nephrol 30: 641-652, 2019 HYPERPHOSPHATEMIA AMPLIFY: Statistically Significant Pivotal Phase 3 Results with Tenapanor and Binders

DESIGN EFFICACY SAFETY

To evaluate tenapanor and Primary endpoint statistically Favorable tolerability phosphate binders (two distinct significant difference in reduction Well tolerated: 4% of patients in MOAs) when used in combination of serum phosphorus levels tenapanor arm discontinued vs. 2% n=235 (p=0.0004) compared to binders in the binder arm Primary Endpoint: Comparison of change alone at week 4 • 43% diarrhea; single adverse from baseline in serum phosphorus at event with a placebo-adjusted week 4 between tenapanor + phosphate ~2 times more patients achieved the rate >3% binder (tenapanor arm) and placebo + serum phosphorus treatment goal of • Mostly mild-to-moderate phosphate binder (binder arm) <5.5 mg/dL with tenapanor and • 3% severe diarrhea phosphate binders vs phosphate • Transient: median resolution binders alone (P≤0.0097) 4 days after onset • Resulted in treatment discontinuations in 3 out of 116 Secondary analyses: Statistically patients significant reduction (p-values≤0.0027) in FGF23 levels 13 HYPERPHOSPHATEMIA PHREEDOM: Statistically Significant Pivotal Long-term Monotherapy Phase 3 Results

DESIGN EFFICACY SAFETY

52-week trial to evaluate the long- Primary endpoint statistically Well tolerated term efficacy, safety and tolerability significant (p<0.0001) difference in 26-week open-label treatment period: of monotherapy tenapanor in CKD least squared mean serum patients on dialysis phosphorus change (1.4 mg/dL) • 17.2% of 419 tenapanor-treated n=564 patients vs. 22.6% of 137 sevelamer between tenapanor and placebo treated-patients (active safety control) Primary Endpoint: Difference in change in experienced an SAE serum phosphorus between pooled Secondary analyses: In the 26-week open tenapanor-treated patients and placebo- label treatment period, 77% of tenapanor • Diarrhea only adverse event >5% (52%) treated patients in the efficacy analysis patients in the intent-to-treat population • Vast majority mild to moderate; 5% severe diarrhea set from the end of the 26-week (n=408) achieved a decrease in serum treatment period to the end of the 12- phosphorus, with a mean decrease of 2.0 week randomized withdrawal period mg/dL

14 HYPERPHOSPHATEMIA Tenapanor Provided Phosphorus Control while Significantly Reducing Phosphate Binder Pill Burden Mean Change in Serum Phosphorus and Mean Change in Total Phosphate Binder Pills Over Time • 26-week trial in Japanese patients Tenapanor added 14.7 • 72% of patients achieved at least a 6.5 14 (line) Serum Phosphorus, mg/dL 30% decrease in total number of (bars) Number of Phosphate Binder pills/day phosphate binder and tenapanor pills 6.0 12 (P<0.001) 5.5 10 • 80% decrease in binder use (14.7 vs 3) 5.2 mg/dL 5.0 8 4.7 mg/dL • 27% of patients no longer required any phosphate binders at week 26 4.5 6

4.0 4

• Diarrhea was reported among 76% of 3.0 Serum Phosphorus, Serum Phosphorus, mg/dL patients and was mostly mild to 3.5 2

moderate Number of Phosphate pills/day Binder 3.3 mg/dL 3.0 0 0 2 Week 26

SAE, serious adverse event. 15 Akizawa T, et al. 57th ERA-EDTA Congress (virtual); Abstract P1404. Tenapanor Commercialization HYPERPHOSPHATEMIA Significant Opportunity for Tenapanor in Hyperphosphatemia Market

>550K 3-4% ~2.7M U.S. Dialysis Annualized Growth Rate of U.S. Phosphate Binder Patients1 U.S. Dialysis Population1 Prescriptions2

1. United States Renal Data System. 2019 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2019. 17 2. IQVIA 2019 (Retail); Adding estimate for Rxs through dialysis organization specialty pharmacies HYPERPHOSPHATEMIA The First-In-Class Mechanism of Tenapanor Addresses Limitations in the Management of Hyperphosphatemia

• Tenapanor’s first-in-class blocking mechanism targets primary pathway of phosphate absorption to deliver safe and effective phosphate control1 • Tenapanor’s first-in-class blocking mechanism effectively reduces phosphorus with one small 1 pill twice a day Current Binder Regimen Regimen on Tenapanor One-week dose of most One-week dose of prescribed phosphate binder Tenapanor1 ~3+ pills TID with meals 1 pill BID

18 1. As observed in clinical studies of 10-30 mg tenapanor, an investigational medicine, taken twice per day per study protocols. 10 mg shown here for illustrative purposes HYPERPHOSPHATEMIA Ardelyx is Well Prepared to Commercialize Tenapanor in the U.S.

Historically, novel mechanisms in renal Commercial Team with Experience in Kidney outperformed and built significant markets and Cardiovascular Diseases

Sensipar US Sales $M (from Launch)1 500

400

300

Millions 200

100

0 2004 2005 2006 2007 2008

Building Specialized U.S. • ~8,000 nephrology targets Commercial Organization • Clear unmet need • Innovative product with differentiated and novel MOA to meet unmet need

1. EvaluatePharma 2019 19 Sensipar was approved by the FDA in March 2004 HYPERPHOSPHATEMIA Nearly 3 out of 4 Nephrologists See a High Need for New Treatments and View Tenapanor as a Strong Improvement Over Phosphate Binders

How Much of a Need How Does Tenapanor Compare to Phosphate Binders? for New Treatments? Much Worse / Worse Same Better / Much Better

5% Dosing & administration 8% 91% 23% Patient adherence 10% 90%

72% Efficacy 27% 72%

Tolerability 8% 33% 59% Low need Moderate need High need

20 Ardelyx market research study conducted by Hawk Partners, December 2019 HYPERPHOSPHATEMIA There is a High and Growing Interest in Tenapanor – and Nephrologists Expect Tenapanor Uptake to be Quicker than that of the First Anticipated HIF

Interest in Tenapanor Timeline for Trial % indicating high interest % of respondents 74% 65% Tenapanor Roxadustat (AZ/FibroGen) 61% 40% 57% 50% 29% 30%

22% 23% 19%

13% 11% 10%

2% Q2 2017 Q2 2018 Q2 2019 Q4 2019 Q1 2020 (n=192) (n=201) (n=202) (n=200) (n=202) Right away Within three Within six Within a year More than a Never months months year

Spherix, RealTime Dynamix Bone and Mineral Metabolism, Q1 2020. Assuming tenapanor were FDA approved, how soon would you anticipate prescribing it to a dialysis patient? (n=202). Spherix, 21 RealTime Dynamix Anemia, Q1 2020. Based on what you currently know, how soon after approval would you estimate trial of roxadustat in the dialysis and non-dialysis settings? *Excerpt from RealTime Dynamix: Bone and Mineral Metabolism, Q1 2020 (n=202) HYPERPHOSPHATEMIA The Majority of Nephrologists in Two Distinct Studies Expect to Use Tenapanor as their First Line Hyperphosphatemia Therapy

Most Likely First Line Hyperphosphatemia Treatment Tenapanor Anticipated Line of Therapy % of respondents % of respondents

12% 12% Second line after 18% binder failure

33% 60% Tenapanor 39% Added to 41% binders

First line, Tenapanor + before binders 16% 55% Phosphate Binder 49% 41% 25% Phosphate Binder

Q2 2019 Q4 2019 Q1 2020

Ardelyx market research study conducted by Hawk Partners, December 2019. Assuming Product X [tenapanor] is established in the market, from a clinical perspective (removing cost and access considerations), what would you be most likely to prescribe as first line therapy in a dialysis patient who requires a phosphate lowering treatment and is naïve to any phosphate lowering therapy? (n=205) 22 Spherix, RealTime Dynamix Bone and Mineral Metabolism, Q1 2020. If tenapanor were approved by the FDA for the management of hyperphosphatemia, how would you be most likely to use it? (n=202) HYPERPHOSPHATEMIA Favorable Reimbursement Landscape for Novel Rx Therapies Like Tenapanor

Tenapanor expected payor Clinically-driven payor value proposition Tenapanor market opportunity mix is distributed between • Phosphorus management guidelines exist for Medicare patients persists Medicare and non-Medicare (KDOQI, KDIGO) in either a Part D or Dialysis • Significant proportion of patients unable to achieve Bundle environment clinical practice guideline target phosphorus levels • with phosphate binders, the only currently available Dialysis bundle provides access and 38% class of therapy affordability to the 33% of patients who face challenges in a Part D 62% • Tenapanor is a first-in-class therapy with a novel environment MOA that targets the primary pathway of phosphate absorption and is clinically demonstrated • Inclusion of oral-only medications was to provide effective phosphate control originally slated for 2014, then pushed to 2016, then pushed to 2025, with Dialysis Patient Payor Mix • Novel MOA enables dosing regimen of one small potential for further delay Medicare pill twice a day (47% of Medicare is Low Income • Tenapanor expected to earn a market Subsidy / Dual Eligible; 29% Standard • Patient access to this new class of therapy provides position that creates leverage in either Part D; 24% No Rx Coverage) opportunity for more patients to achieve target scenario Commercial / Medicaid / VA phosphorus levels per clinical practice guidelines

23 Ardelyx is Well-Positioned to Commercialize Tenapanor Outside of the U.S. with Established Partners

Ex-U.S. Cardiorenal Partnerships

CANADA CHINA JAPAN Knight Therapeutics, Inc. Fosun Pharma Kyowa Kirin Co., Ltd. Up to CAD $25M in upfront $12M upfront payment, $30M upfront payment, payment and milestones, tiered up to $113M in milestones, up to $55M and 8.5B Yen royalties ranging from mid-single mid-teen to 20% royalties in milestones, high-teen digits to low twenties royalties

24 RDX013 for Hyperkalemia

Investigational, first-in-class secretagogue non-binder approach

Leverages the GI tract’s natural ability to secrete potassium into the lumen of the gut to reduce serum potassium levels RDX013 FOR HYPERKALEMIA Expanding our Renal Footprint In Vivo Fecal Potassium Excretion

5 0

) * * * *

h * * * *

4 0 4 • RDX013 produces dose-

2 * * *

/ dependent increases in g • Novel, oral small molecule potassium 3 0

m fecal potassium

(

secretagogue program + excretion in rodents

K 2 0

l a

c 1 0 • Preclinical studies e

• Small pill dosing F indicate once-daily 0 dosing is effective • Increases fecal potassium excretion; V e h i c l e 3 1 0 2 0 reduces serum potassium

R D X 0 1 3 ( m g / k g , p o , b i d )

)

/ q

• May allow for optimal dosing of E 1000

(

anti-hypertensives t

i 100

c a

p ~1,000x a

C 10 • ~1000x improved in vivo

n Improved In Vivo

i t

potency vs binders e 1 Potency vs Binders*

+ 0.1 K SPS Patiromer RDX7675 RDX013

26 *K+ binding capacity determined in mouse RDX013 FOR HYPERKALEMIA Significant Hyperkalemia Market Exists DRIVERS TO CREATING A HYPERKALEMIA MARKET 200k THE POTENTIAL FOR RDX013 patients with ESRD on dialysis1 Target Product Profile • Preferred dose formulation • Potent • Safer alternative 2M 900k 900k patients in US with patients • Potential to enable administration of lifesaving patients with hyperkalemia that 3 with Stage drugs that can cause hyperkalemia (RAASi’s, heart failure require treatment 3/4 CKD2 Entresto, etc.)

Build upon the market being created by recent new branded entrants

1. Independent Market Research, Spherix Global Insights 2. Einhorn LM, et al. Arch Intern Med. 2009 Jun 22;169(12):1156-62 27 3. Mozaffarian D, et al. Circulation. 2015 Jan 27;131(4):e29-322 Financials & Milestones Key Financial Items

$204.8 MM Cash runway into first half of 2022 Cash and Investments ~ $50 MM of debt of as of June 30, 2020 ~ 89.1 MM shares outstanding

29 24-Month View of Potential Milestones and Catalysts

• AMPLIFY Phase 3 results to be presented at scientific meetings throughout 2020+ • PHREEDOM Phase 3 results to be presented at scientific meetings throughout 2020+ • NORMALIZE Extension study results to be presented at scientific meetings throughout 2020+ • Ongoing market development and pre-commercial activities • NDA acceptance September 2020 • PDUFA goal date for tenapanor approval for hyperphosphatemia April 29, 2021 • Expect guidance from EMA for European Development • Advancing our kidney and cardiovascular franchise with RDX013 • Ongoing progress with our partners in Japan, China and Canada

30 Thank You