Ardelyx, Inc. · NASDAQ:ARDX
Ardelyx — Investor Presentation (February 2015)
45 slides from Ardelyx's investor presentation, Feb 9, 2015
Slide 1: Investor Presentation February 2015
Exhibit 99.1 Investor Mike CEO FEBRU Raab Presentation A RY 2015
Slide 2: Forward-Looking Statements
Forward Special To made potential discovery differ reliance upon any 2Ardelyx_s the forward Sanofi pursuant significantly extent Note upon Looking for and business -looking for tenapanor Regarding that AstraZeneca design tothe the statements Statements from discovery insafe platform. statements. gen
Slide 3: The Power of Ardelyx's Discovery Platform
The1Power Clinical Oral, Fig History META- CARDIO IBS-C Figure CKD BOLIC Small 1of RENAL -Stage from Capital of Molecule, Ardelyx Sato Biopharmaceutical CKD-5D-Pi Efficiency T and Rapid, Clevers Balanced GI Efficient H., Company _Growing Drug Portfolio Discovery self-organizing of EarlyNon-Systemic,
Slide 4: The Result: A Robust Product Pipeline
The Result: PHASE PROGRAM Tenapanor Announced (NHE3 Validated Phase RDX002 2Q:2015 Research IBD, Bowel, RDX009 (K+ Hyper- RDX013 Wholly 4Undisclosed Channel Short 2bResearch 2aInhibitor) -Owned 2Data CKD-5D (NaP2b Programs CKD-5D Two Robust N/A INDICATION Research CKD IBS-C Partnered, (TGR5 Research
Slide 5: A History of Rapid, Efficient Drug Development
A History Idea TENAPANOR DEVELOPMENT NHE3 Company 2007 $26M FINANCINGS LICENSES 5Up toto2008 $870M $198M Series Lead P2aSodium of 2009 Data $35M IND Rapid, Afor $30M 2010 in Tenapanor NaP2b Filed Transport $15M 3Capital Years Series 2011 P1$25M Completed 2012 Efficient B Candidate $69M Upfront 2013D
Slide 6: Proven Management Team
ProvenRAAB MIKE ELIZABETH ANDY 6QA Management SPENCER, GRAMMER President PhD Team& VPChief VPand R&DExecutive Alliance General Management Counsel Officer JEREMY JEFF JACOBS, CALDWELL, PhD VPPhD Chemistry EVP &NARANI Chief Scientific ARASARATNAM Officer MARK VP KAUFMANN Corporate Controller Chief Fin
Slide 7: Investment Highlights
Investment Discovery PROPRIETARY Small 2Tenapanor: NaP2b Enhanced WHOLLY-OWNED Proprietary PROVEN VALIDATED Molecule Inhibition: Drug MANAGEMENT and AstraZeneca Highlights Screening Design Discovery PROGRAMS Therapeutics PLATFORM Sanofi PIPELINE Process ofCollaboration; Non-Systemic, Collaboration C
Slide 8: The Intestine Is Rich with Potential Drug Targets
Intestinal MANY 3,800 Brush Microvilli Translation 8Transporter Proteins Border POTENTIAL Epithelium Regulator Membrane IsTranscription THE RichINTESTINE with Potential Factor PROTEIN Enzyme Targets Regulator ANALYSIS Catalytic DRUG Enzyme TARGETS Receptor Antioxidant Structural Molecule Cellular Bi
Slide 9: Enhancing Drug Discovery: Powerful Translation Tool
Enhancing Ardelyx drug Standard Fig Harvest “THE Figure Translation Discovery: Powerful 1drug BENEFITS 1Stem Primary from orDrug Tool: Transwell Rapid to Cells Sato Humans: Discovery Mechanisms, Enterocyte TScreening Grow and Simulate Clevers inwith Monolayer and of Targets, APECCS Colonocyte Drugs
Slide 10: Investment Highlights
210 Investment Discovery PROPRIETARY Small Tenapanor: Molecule Enhanced WHOLLY VALIDATED Proprietary PROVEN and AstraZeneca Highlights Drug Design Therapeutics PLATFORM MANAGEMENT -OWNED Screening of PROGRAMS Discovery Collaboration; Non-Systemic, PIPELINE Process Phase Capabilities TEAM Deep with2R
Slide 11: Tenapanor Mechanism: Local Activity in the Gut
WITHOUT Dietary Local Phosphorus Sodium Tenapanor 11 Activity Sodium/Phosphorus Reduces TENAPANOR in theSodium Gut WITH and Passes Phosphorus TENAPANOR Diverts Sodium/Phosphorus Absorption Into Circulation from Circulation
Slide 12: Significant Market Opportunity for Tenapanor
Significant US IBS-C 2011 270K Sevelamer: Hyperphosphatemia Late Sources: European Hepatol. Aliment . Stage .2015 215K EUROPE 4.4M Pharmacol 2012, Technavio ERA-EDTA CKD-5D CKD Market $770M 220K 6.6M JAPAN (3b-4) Binder 3.4M Opportunity in Ther. Insights: (ESRD) 2014 Registry 3.6M #14M+ 2005, Market
Slide 13: Extensive Clinical Experience in Multiple Indications
Extensive 14 “Constipation 13 Phase Most Dose Clinical response secondary 2bClinical clinical Trials -Predominant observed endpoints Experience trial met“CKD-5D Higher primary met with “ Decreased rates Tenapanor “CKD Phase of Irritable diarrhea 2b serum inclinical Multiple Bowel phosphate observed
Slide 14: Tenapanor: Non-Systemic, Generally Well-Tolerated
“Tenapanor 14 >1,000 3Single Non-Systemic: Most Months AE_s Dose individuals Generally UpDue Up to>99.3%ofAllTestedSerum 100 to 900 Exaggerated exposed Well-Tolerated mg/Day mg to drug Pharmacology Samples of Drug Had (e.g. No Detectable Loose Stools/Diarrhea) Levels of Tenapanor (>3,000 samples)
Slide 15: Limitations of Current IBS-C Therapies
Tenapanor “_LIMITATIONS GI Constipation 15 Amitiza® OTC Medical Achieve Side Disorder: Effects Drugs Need Endpoint for and and Inexpensive (e.g., IBS-C OF Linzess® for Abdominal Improved CURRENT Diarrhea) in Only Fall but 7% Pain Therapies Not Short: TREATMENTS to Very 20% Effective of with Patients
Slide 16: IBS-C Phase 2b Trial Design
Phase IBS-C “weeks Randomization Tenapanor *CSBM Treatment Primary Secondary 2b follow-up Phase defined Design Endpoint: 5Arms: 50 Endpoints mg 2b mg àProtocol BID as for Tenapanor BID PlaceboBID aTenapanor Percent spontaneous :Overall “ Design: 20 complete mg in Responder bowel IBS-C BID Double-bli
Slide 17: IBS-C Phase 2b Trial Met Primary Endpoint
Phase Trial 70 60 P 27.0% 50 40 Respon “20 17 Overall <0.001 P=0.026 65.5% 48.3% 33.7% Met 2b 50.0% 26.4% 17.2% IBS-C Responder Primary Placebo P <0.001 ntResults: se30 Efficacy Perce 60.7% Treatment = dual 23.6% Responder Endpoint composite 10 0 Rates Overall Atendpoint 50for MgResponder 50BID ofmg
Slide 18: IBS-C Phase 2b Responder Results
Phase Responder +e1 40 17.3% 48.8% 50 P=0.022 60 R 20 Placebo 20.2% Percent 6.7% 0O 18verall P=0.01 esponse 23.8% mean 7.9% 2b 15.9% 10IBS-C CSBM 31.5% CSBM/week 13.5% Endpoint 30 P=0.004 Abdominal Results: Is More Treatment from Responder Pain baseline Stringent Responder Rates and e3 for Responder
Slide 19: Results: Dose Response Relationship
Results: Dose was wee Randomization Week 19 maintained kresponse perDose s CSBM Response relationship End throughout Mofean treatment Relationship was entire observed 12-weekintreatment the primary period endpoint, as well as in most other secondary endpoints, although statistical significance was n
Slide 20: IBS-C Phase 2b Results: Efficacy
*“Tenapanor p<0.001) 20 Adequate Based _Quite_ onand in the relief IBS-C _very_ treatment of IBS Phase aresymptoms satisfaction 42b andResults: 5 respectively, was patient Efficacy statistically scale on aquestionnaire, 5-point significant scale (p=0.002) more subjects for tenapanor receiving50mgBID
Slide 21: Tenapanor Clean Safety Profile in IBS-C
Tenapanor “infections 21Tenapanor The Overall Basedmost onrates 5.6 in the common well-tolerated IBS-C percent of analysis discontinuation Phase adverse vs.of4.4 plasma 2b: across events percent Clean due all samples attreatment Safety to 50adverse mg tested Profile BID arms events as(e5%) part andw
Slide 22: Limitations of Phosphate Binders in CKD-5D
LIMITATIONS BREAKFAST Pill Sevelamer/Renagel/ Intolerable 0.8 Water Common in Ferric Safety 2-4g Calcification Tenapanor Based “NOR d10mg TENAPA Not CKD-5D Prescribed Non-Compliance Long-Term Gastrointestinal Reduced -2.4 Burden Actual of Dose Intake Citrate/Auryxia Binders and Twice ferric Grams Do
Slide 23: CKD-5D Hyperphosphatemia Phase 2b Design
CKD-5D Hyperphosphatemia Phase “toendof Consent Up Tenapanor Screening Placebo n=21 Endof 4-week 23Key Primary to to 32b Inclusion Treatment treatment weeks washout 26/group; BID Randomization Design Protocol “Endpoint: 3Design: 30mgBID mgcare; Criteria QD andaS for F/U 2-week 161 Randomized, washou
Slide 24: Tenapanor Produced Dose-Related Decrease in Serum Phosphate
CKD-5D Tenapanor 1Group -0.54 *LSMean 24mg BID (-1.21, n LSMean* Hyperphosphatemia = 23 Produced Least 0.13) -0.47square 95% ( -1.18, A Statistically CI mean. 0.24) Phase Change 3 mg Significant 2bBID Study: from21Baseline -1.18 Effects Dose-related (-1.93, on at End Serum -0.44) Decrease of Treatme
Slide 25: Gastrointestinal Adverse Events
31Adverse *Number 25mg 3 mg Diverticulum Events: of10mg patients 1Gastrointestinal Dyspepsia 30 mg who3 had mg1 at 30 Fecal least mg Disorders* Incontinence Preferred 1 AE in system Term 1 2BID organ 2 Feces BID class Soft BIDof1BID gastrointestinal GI Hypermotility QD QD Placebo disorders 1 GISound
Slide 26: Adverse Event Discontinuations
126 Adverse Discontinuation mg Events 3 3mg Discontinuations Diarrhea* Hyperphosphatemia Dizziness Atherosclerosis *The term 18Leading rate 610mg 12_diarrhea_ due 1due 1 3230 Nausea to also to3includes mg Discontinuations diarrhea 9 31 mg 13 Vomiting was 30 1mg higher 7 2similar Adverse AE/group** S
Slide 27: Approved Therapies for Hyperphosphatemia
*27 Approved 5D AE_s Adverse Patients Due # Label **Label Data Events* Therapies To from GI Disorders warning: warning: Renvela®# package for Hyperphosphatemia Serious Serious Are inserts Fosrenol®** cases cases Common of InAuryxia® ofdysphagia, Phosphate in CKD- GI obstruction, bowel Abdominal ileu
Slide 28: Limitations of Current Treatments to Delay CKD Progression
Tenapanor “LIMITATIONS Sodium 28 ACE Poor Compliance Diuretics Inhibitors andfor Lose Fluid Treating OFEfficacy Reduce Overload with CURRENT CKD Low Blood and Sodium Cause TREATMENTS Pressure Electrolyte Diets but Hyperkalemia Disorders TO DELAYLimits CKD Widespread PROGRESSION Use in CKD Patients
Slide 29: CKD Phase 2a Trial Design
“CKD 29 Objective: Primary Other Doses: Status: “Phase Design: Endpoints 5, Enrollment Endpoint: 15, 2a Safety, Clinical 30, Double-Blind, :orPharmacodynamic Tolerability, Changes Completed, 60Trial mg Capsules. Design in12Urine and Data Weeks Pharmacodynamics Expected Albumin Starting Effects of Tr
Slide 30: AstraZeneca/Tenapanor Collaboration Terms
The Upfront Additional PAYMENTS Up Milestones $50M2H2015 “Royalties OTHER Responsibilities: AstraZeneca Ardelyx *Exercisable **Subject Co-Funding to AstraZeneca/Tenapanor Development Rights: TERMS “to$35M Incremental, cap Within Option $20M “on “$237.5M Right All obligation 60 1H atLaunch R&D Days 1
Slide 31: RDX002: NaP2b Inhibition
RDX002: Discovery PROPRIETARY Small 2Tenapanor: WHOLLY PROVEN 31 VALIDATED Molecule NaP2b MANAGEMENT and -OWNED AstraZeneca Design PROGRAMS Therapeutics PLATFORM and PIPELINE Our ofCollaboration; Non-Systemic, Collaboration TEAM Phase Enhanced Deep 2 inwith Three Domain Drug Sanofi Indications Disco
Slide 32: Phosphate Binder vs. Phosphate Transport Inhibitor
Binder Phosphate with Capillary Enterocyte 32 Metal Phosphate Binder Based Binders Transport vs. Phosphate Phosphate Inhibitor Phosphate Transport Transport Inhibitor Inhibitor NaP2b Transporter
Slide 33: RDX002 Reduces Urine Phosphorus in Rats
RDX002: 0R ** -20 Vehicle 500 Combination NTX1942 Data eduction *** mg/kg Shown *** Sevelamer NTX1942 Response -10 50 -30 isofmg/kg (%) the Sevelamer Mean NTX1942 Is Reduces Superior ±SEM; andCombo Urine NTX1942 to **Sevelamer =Phosphorus p<0.01; Is Additive at ***H Levels =p<0.001, 1/10 in of Norma
Slide 34: Sanofi/NaP2b Collaboration Terms
The Upfront PAYMENTS Up Milestones Royalties “Commercialize 34 Ardelyx NaP2b Sanofi toSanofi/NaP2b Potential Responsible Patent “Has $198M Incremental, the NaP2b Portfolio Additional Right Collaboration Total for Inhibitors to Tiered $1.25M Completing and Co-Promote Devt./Reg Related (Mid-Single Pre
Slide 35: Investment Highlights
Investment Discovery PROPRIETARY Small 2Tenapanor: Enhanced WHOLLY Proprietary PROVEN 35VALIDATED Molecule Drug MANAGEMENT and -OWNED AstraZeneca Highlights Screening Design Discovery PROGRAMS Therapeutics PLATFORM PIPELINE Process ofCollaboration; Non-Systemic, Capabilities TEAM Phase Deep 2 inwith
Slide 36: RDX009: TGR5 Agonist
RDX009: Inflammatory _TGR5 “ARDELYX 36 Anti-Inflammation Enhances Gattex® Intercept No Long Significantly Daily Gallbladder ShortLastingIncretin Gallbladder STIMULATION Lasting Injections TGR5 =and GLP1andGLP2 TGR5 GLP2 Emptying Bowel Improves Exelixis/BMS Incretin Agonists Issues AGONISTS approved
Slide 37: RDX013: Potassium Secretagogue
RDX013: THE “ARDELYX 37 All Augment Therapeutic The To Used Maintain Move Potassium CHALLENGE Limiting as aHyperkalemia Potassium Normal Patient Stand POTASSIUM Dose Factorin Binders Alone Compliance Serum forinto Kayexelate, Efficacy (e.g. or (Elevated Colon Potassium SECRETAGOGUE in Patiromer) Com
Slide 38: Financial Overview
$Financial Cash Annualized Debt Capital Series Nasdaq: 2008 *Ventures September MILLIONS From$0 2011 and AArdelyx_s Raised ARDX $26M Cash Overview 2014 30, Operating 2014) Equivalents Series third =BExpenses* $12,171 quarter $30M $112.0M IPO 10Q: * .12$69M month/9 $22,915 (as of 9/30/14) total month
Slide 39: Investment Highlights
Investment Discovery PROPRIETARY Small 2Tenapanor: Enhanced WHOLLY Proprietary PROVEN 39VALIDATED Molecule Drug MANAGEMENT and -OWNED AstraZeneca Highlights Screening Design Discovery PROGRAMS Therapeutics PLATFORM PIPELINE Process ofCollaboration; Non-Systemic, Capabilities TEAM Phase Deep 2 inwith
Slide 40: Appendix
APPENDIX
Slide 41: Tenapanor Phase 1 in Healthy Adult Volunteers
12 -Dose Tenapanor PHASE 50 (m — Placebo (m (m31RDX5791 Level 40 mg IN Demonstrates Sodium HEALTHY QD Response 10 -101 mg 30 Sodium -102; (1) 30 Dose ADULT somemg 50Level Dose 100 30 VOLUNTEERS data Sodium mg and Frequency Placebo Dose 30inFrequency published Fecal Response 30mg Fecal QDetResponse S
Slide 42: Tenapanor Phase 2a Fluid Subset in CKD-5D Patients
2 Study D5611C00001 42 Tenapanor PHASEDiverts 2a FLUID DietaryIN Sodium SUBSET Mean Placebo to the 24hr OFFeces CKD-5D BID FecalCKD-5D Dosing Sodium PATIENTS 50N=8 40 Patients (mmol) 30 N=8 10 202-
Slide 43: Comparative Sevelamer vs. Tenapanor Fecal Phosphorus
Comparative Sevelamer SEVELAMER Fecal 40 30 20 010 Baseline Dose 1Similar 010 40 15,000 30 20 Phosphorus Results, Burke 1gvs. TID mg/Day Human Tenapanor et 1But 2.5g TENAPANOR al. Fecal 1/500 1997; Response: 30 TID Phosphorus mg/Day in5g th 2Healthy Study the TID2Dose Baseline D5611C00002 (mmol/Day
Slide 44: Sodium and Phosphorus Studies in CKD
**P<0.05 Studies SODIUM Proteinuria ACE 2.5 012.40 DaVita Systolic 140 1.60 115 Regular 1. 2.00 Inhibition Support Fresenius Slagman, <3 1.40 0.5 1ACE (Kalantar Relative PHOSPHORUS Regular 3-4 Sodium Blood 2.20 v135 4-5 Impact et1.20 al., 5-6 (Block, SodiumRisk -Zadeh, Pressure inhibiŸon Diet BMJ of
Slide 45: Beneficial Effects of Tenapanor in CKD Models
2** Beneficial SODIUM Urinary 5/6th Albumin/ *** 150 SBP 100 0N *ACE Nephrectomized 5Systolic ormal Albumin/Creatinine th p<0.01;PHOSPHORUS Vehicle 200 *** *** Effects Blood 5/6th 05/6 =Vehicle Enalapril; *** ofOne Tenapanor Tenapanor p<0.001 ACE* Rats vs. Aortic Nephrectomized Nephrectomized Pressu