UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 9, 2015
ARDELYX, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-36485 | 26-1303944 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification Number) |
34175 Ardenwood Blvd.
Fremont, CA 94555
(Address of principal executive offices, including Zip Code)
Registrant’s telephone number, including area code: (510) 745-1700
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
| Item 7.01 | Regulation FD Disclosure. |
Attached hereto as Exhibit 99.1 is a corporate presentation of Ardelyx, Inc. (the “Company”) incorporated by reference herein.
The information furnished under this Item 7.01 shall not be considered “filed” under the Securities Exchange Act of 1934, as amended, nor shall it be incorporated into any future filing under the Securities Act of 1933, as amended, or under the Securities Exchange Act of 1934, as amended, unless the Company expressly sets forth in such future filing that such information is to be considered “filed” or incorporated by reference therein.
| Item 9.01 | Financial Statements and Exhibits. |
| (d) | Exhibits. |
| Exhibit No. |
Description | |
| 99.1 | Corporate presentation of Ardelyx, Inc. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: February 9, 2015 | ARDELYX, INC. | |||||
| By: | /s/ Mark Kaufmann | |||||
| Mark Kaufmann | ||||||
| Chief Financial Officer | ||||||
EXHIBIT INDEX
| Exhibit No. |
Description | |
| 99.1 | Corporate presentation of Ardelyx, Inc. | |
| Exhibit 99.1
|
Investor Presentation
Mike Raab
CEO FEBRU A RY 2015
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Forward Looking Statements and Further Information
Special Note Regarding 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 of tenapanor in treating the renal indications for which it is currently being evaluated, the potential for tenapanor in treating IBS-C patients, the availability and timing of data from ongoing tenapanor clinical trials, potential milestone payments from our collaboration partners, and the potential of our drug discovery and design platform. Such forward -looking statements involve substantial risks and uncertainties that could cause the development of tenapanor, 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 the clinical development process, Ardelyx_s reliance upon AstraZeneca for the development of tenapanor, and AstraZeneca_s right under the license agreement to choose which indication or indications for which tenapanor will be developed, Ardelyx_s reliance upon Sanofi for the discovery and development under the licensed NaP2b inhibitor program, and the uncertainties inherent in the research and discovery 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 third quarter report filed with the Securities and Exchange Commission on November 7, 2014.
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The Power of Ardelyx
Clinical -Stage Biopharmaceutical Company
Oral, Small Molecule, Rapid, Efficient Drug Discovery Non-Systemic, First-in-Class Drugs & Design Platform Provides Broad Drug Candidates
Fig 1
History of Capital Efficiency Balanced Portfolio of Early to Mid-Stage Candidates Across Partnered & Proprietary Programs
IBS-C
CARDIO
META- RENAL CKD-5D-Pi GI
BOLIC
CKD
Figure 1 from Sato T and Clevers H., _Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications._ Science. 2013 Jun 7;340(6137):1190 -4 3
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The Result: Robust Product Pipeline
PHASE 2
PROGRAM INDICATION RESEARCH PHASE 1 2a 2b STATUS
Phase 2b Data IBS-C Announced Oct1, 2014
Phase 2b Data
Tenapanor CKD-5D
Announced Two Partnered,
(NHE3 Inhibitor) HyperPi Feb2,2015
Validated Programs
Phase 2a Data CKD
2Q:2015
RDX002 CKD-5D
Research (NaP2b Inhibitor) HyperPi
IBD, Short
RDX009
Bowel, Research (TGR5 Agonist) NASH
RDX013
Hyper-
(K+ Channel Research kalemia Modulator)
Wholly -Owned
Undisclosed N/A Research Pipeline Programs
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A History of Rapid, Capital Efficient Development
DEVELOPMENT
TENAPANOR
Idea to P2a Data in 3 Years
NHE3 Lead IND Filed P1 Completed
Company Sodium Transport Candidate 1st Subject P2a Results in P2b Results in P2b Results in Formed Inhibitor Proposed Identified Dosed IBS-C IBS-C CKD-5D HyperPi
2007 2008 2009 2010 2011 2012 2013 2014 2015
FINANCINGS
$26M Series A $30M Series B $69M IPO NEA & CMEA NEA & CMEA $61.2M net Amgen Ventures
LICENSES $35M $15M $25M Upfront Development Development Milestone Milestone
Up to $870M for Tenapanor
Up to $198M for NaP2b
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Proven Management Team
MIKE RAAB President & Chief Executive Officer JEREMY CALDWELL, PhD EVP & Chief Scientific Officer MARK KAUFMANN Chief Financial Officer DAVID ROSENBAUM, PhD SVP Drug Development ELIZABETH GRAMMER VPand General Counsel JEFF JACOBS, PhD VP Chemistry NARANI ARASARATNAM VP Corporate Controller GEORGE JUE VP Operations ROB BLANKS VP Regulatory Affairs and QA
ANDY SPENCER, PhD VP R&D Alliance Management
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Investment Highlights
Discovery and Design of Non-Systemic,
PROPRIETARY PLATFORM
Small Molecule Therapeutics
Tenapanor: AstraZeneca Collaboration;
2 VALIDATED PROGRAMS Phase 2 in Three Indications
NaP2b Inhibition: Sanofi Collaboration
Enhanced Drug Discovery Capabilities with Rapid,
WHOLLY-OWNED PIPELINE
Proprietary Screening Process
PROVEN MANAGEMENT TEAM Deep Domain Expertise
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Intestinal Epithelium Is Rich with Potential Targets
MANY POTENTIAL THE INTESTINE PROTEIN ANALYSIS DRUG TARGETS
3,800 Proteins
Microvilli
Brush Border Membrane
Transporter
Translation Regulator Transcription Factor Enzyme Regulator Catalytic Enzyme Receptor Antioxidant Structural Molecule Cellular Binding
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Enhancing Drug Discovery with APECCS
Ardelyx Primary Enterocyte and Colonocyte Culture System
drug drug
Standard or Transwell
Fig 1
Harvest Stem Cells Grow in Monolayer from Gut Format Measure Drug Response
THE BENEFITS
“ Discovery: Rapid Screening of Drugs
“ Translation to Humans: Simulate Relevant Gut Cell Physiology
“ Powerful Tool: Mechanisms, Targets, Phenotypic Screening
Figure 1 from Sato T and Clevers H., _Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. _ Science. 2013 Jun 7;340(6137):1190 -4 9
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Investment Highlights
Discovery and Design of Non-Systemic,
PROPRIETARY PLATFORM
Small Molecule Therapeutics
Tenapanor: AstraZeneca Collaboration;
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VALIDATED PROGRAMS Phase 2 in Three Indications NaP2b Inhibition: Sanofi Collaboration |
Enhanced Drug Discovery Capabilities with Rapid,
WHOLLY -OWNED PIPELINE
Proprietary Screening Process
PROVEN MANAGEMENT TEAM Deep Domain Expertise
10
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Tenapanor Reduces Sodium and Phosphorus Absorption
WITHOUT TENAPANOR WITH TENAPANOR
Dietary Sodium/Phosphorus Passes Diverts Sodium/Phosphorus Into Circulation from Circulation
Tenapanor
Sodium
Sodium
Phosphorus
Phosphorus
Local Activity in the Gut
11
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Significant Market Opportunity for Tenapanor
US . . EUROPE JAPAN # of Patients # of Patients #of Patients
IBS-C 4.4M 6.6M 3.4M 14M+
2011 2015 CKD-5D (ESRD) $1.5B $2.3B
270K 215K 220K Binder Market
Hyperphosphatemia
Sevelamer: $770M in 2014
Late Stage CKD (3b-4) 3.6M 8.5M 2.3M 64M (with Type 2 Diabetes) (1.8M) (1.7M) (0.6M) (Type 3-4)
Sources: Technavio Insights: Global Hyperphosphatemia Drugs Market 2011-2015, USRDS 2013 Atlas of CKD & ESRD, Dialysis Outcomes and Practice Patterns Study (DOPPS), Am J Kidney Dis. 2012 Jul, European ERA-EDTA Registry Annual report 2011, TherApherDial. 2010 Dec, JAMA. 2007 Nov, J Chin Med Assoc. 2010 Oct, BioTrends TreatmentTrends 2013, Patient Prefer Adherence 2008, Clin Gastroenterol Hepatol. 2012,
Aliment Pharmacol Ther. 2005, Aliment Pharmacol Ther. 2003; Sanofi press release 12
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Extensive Clinical Experience with Tenapanor in Multiple Indications
14 Clinical Trials
Constipation -Predominant CKD-5D CKD Irritable Bowel (IBS-C) Hyperphosphatemia Na & Fluid Overload n=417 n= 178 n=77
“ Phase 2b clinical trial met primary “ Phase 2b clinical trial met primary “ Data expected 2Q2015, earlier endpoint at 50 mg BID endpoint than previously reported (2H2015)
“ Most secondary endpoints met “ Decreased serum phosphate levels
“ Dose response observed “ Higher rates of diarrhea observed than in previous trials
13
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Tenapanor Generally Well-Tolerated
“ >1,000 individuals exposed to drug
“ Single Dose Up to 900 mg
“ 3 Months Up to 100 mg/Day
“ Non-Systemic: >99.3%ofAllTestedSerum Samples Had No Detectable Levels of Tenapanor (>3,000 samples)
“ Most AE_s Due to Exaggerated Pharmacology of Drug (e.g. Loose Stools/Diarrhea)
14
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Tenapanor for IBS-C
LIMITATIONS OF CURRENT TREATMENTS
“ OTC Drugs Inexpensive but Not Very Effective in Moderate to Severe Cases
“ Amitiza® and Linzess® Fall Short:
_ Achieve Endpoint in Only 7% to 20% of Patients
_ Side Effects (e.g., Diarrhea)
“ Medical Need for Improved Therapies with Better Efficacy, Excellent Safety and Tolerability
GI Disorder:
Constipation and Abdominal Pain
15
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Phase 2b Design for Tenapanor in IBS-C
IBS-C Phase 2b Protocol “ Design: Double-blind, placebo -controlled, randomized 1:1:1:1 into three treatment arms, 1 placebo arm (approximately 93 patients/group) for a total of 371 patients; 12 weeks treatment, 4 weeks follow-up
“ Primary Endpoint: Percent complete spontaneous bowel movement (CSBM)* responders (patient needs to have an increase of at least one CSBM from baseline for 6 of the 12 treatment weeks)
“ Secondary Endpoints :Overall Responder Rate, Abdominal Pain and Abdominal and IBS-C Symptoms
“ Treatment Arms: PlaceboBID
Tenapanor 5 mg BID
Randomization à Tenapanor 20 mg BID
Tenapanor 50 mg BID
*CSBM defined as a spontaneous bowel movement that feels complete and is not aided by the use of any other medication, like a laxative 16
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Phase 2b IBS-C Results: Responder Rates for 50 mg BID Dose (6 of 12 weeks)
Trial Met Primary Efficacy Endpoint At 50 Mg BID Dose Complete Spontaneous Bowel Movement (CSBM) Responder
70 P=0.026 P <0.001
60 65.5%
P <0.001 17.2% se 60.7%
50
27.0% 50.0%
40 48.3%
Respon 26.4% nt 30 Treatment
20 33.7% Placebo Perce 23.6% 10 0 Overall Responder CSBM Abdominal Pain Responder Responder
“ Overall Responder = dual composite endpoint of CSBM and abdominal pain responders, which is the primary regulatory endpoint in Europe and US (EMA draft guidance 2013, FDA guidance 2012)
17
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Phase 2b IBS-C Results: Responder Rates for 50 mg BID Dose (9 of 12 weeks)
Responder Endpoint Is More Stringent
+e1 mean CSBM/week from baseline and e3 CSBM/week for 9 of 12 weeks
60
P=0.022
50
48.8%
17.3%
40 esponse 30 P=0.004 Treatment
R P=0.01 31.5%
Placebo
20 23.8%
20.2% 15.9%
Percent 10 13.5%
6.7% 7.9%
0
Overall CSBM Abdominal Pain Responder Responder Responder
18
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Results: Dose Response Relationship
Dose response relationship was observed in the primary endpoint, as well as in most other secondary endpoints, although statistical significance was not achieved at the 5 mg or 20 mg BID doses; activity of tenapanor was maintained throughout entire 12-week treatment period
wee k per s CSBM M ean
Week
Randomization End of treatment
19
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Tenapanor in IBS-C Phase 2b Results: Efficacy
“ Adequate relief of IBS symptoms was statistically significant (p=0.002) for tenapanor 50mgBID (63.1%) versus placebo (39.3%) atthe endpoint week (week 12 or last valid week)
“ Based on the treatment satisfaction patient scale questionnaire, more subjects receiving 50mgBID responded thattheywere_quite satisfied_ or _very satisfied_ with tenapanor* versus placebo (65% vs. 38% placebo; p<0.001)
* _Quite_ and _very_ are 4 and 5 respectively, on a 5-point scale
20
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Tenapanor in IBS-C Phase 2b: Clean Safety Profile
“ Tenapanor well-tolerated across all treatment arms and there were no drug-related serious adverse events.
“ The most common adverse events at 50 mg BID (e5%) that occurred more frequently in tenapanor -treated patients compared to placebo -treated patients were diarrhea 11.2 percent vs. 0 percent and urinary tract infections 5.6 percent vs. 4.4 percent
“ Overall rates of discontinuation due to adverse events were 4.5 percent for the tenapanor -treated patients (50 mg BID) and 3.3 percent for the placebo -treated patients.
“ Based on the analysis of plasma samples tested as part of the study, the minimally systemic nature of tenapanor was confirmed
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Tenapanor for Hyperphosphatemia in CKD -5D
LIMITATIONS OF PILL BURDEN: PHOSPHATE BINDERS: TENAPANOR VS. BINDERS
BREAKFAST LUNCH DINNER
Pill Burden Calcium -Based Binders: Ca Acetate/PhosLo
“ CKD-5D Patients Take 10-14 Common Dose: Oral Medications Daily 1-2.5 Grams Each Meal
Sevelamer/Renagel/
“ Prescribed Binder Doses Renvela
Intolerable for Many Patients; Common Dose:
0.8 -2.4 Grams Each Meal
Water Intake Limited DERS Lanthanum/Fosrenol
Common Dose:
“ Non-Compliance Often Results BIN 0.5 -1.5 Grams of Elemental
in Reduced Efficacy Lanthanum Each Meal
Ferric Citrate/Auryxia
Safety and Tolerability Common Dose:
2-4g of ferric citrate each meal,
“ Long-Term Vascular Which is Equivalent to 1.3 to 2.5g of Elemental Iron per Day
Calcification with Calcium -
Tenapanor _ Targeted Daily
Based Binders
NOR Dose
“ Gastrointestinal Side Effects Targeted Dose:
d10mg Twice Daily
TENAPA (30mg Twice Daily Used for Illustration Purposes toRight)
Not Actual Size; However, Relative Sizes Are to Scale 22
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Phase 2b Design for Tenapanor in CKD-5D Hyperphosphatemia
CKD-5D “ Design: Randomized, double blind, placebo -controlled, multi-center, international study
Hyperphosphatemia
“ Key Inclusion Criteria : e 1.5 mg/dL increase in S-phosphate from screening
Phase 2b Protocol
toendof washout andaS -phosphate e 6.0mg/dat randomization
“ Primary Endpoint: Change from baseline of S-phosphate levels to end of treatment. Analysed using an ANCOVA with treatment group as a fixed factor, and baseline as a covariate.
Tenapanor 3 mg QD
Consent Randomization Tenapanor 30 mg QD Standard of
Up to 3 weeks care; washout Tenapanor 1mgBID phosphate (phosphate binders removed) Tenapanor 3 mg BID binders Tenapanor 10 mg BID
Screening
Tenapanor 30mgBID
Placebo BID
n=21 to 26/group; 161 total
Endof Treatment F/U visit
4-week treatment 2-week Washout period follow-up
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CKD-5D Hyperphosphatemia Phase 2b Study: Effects on Serum Phosphate
Tenapanor Produced A Statistically Significant Dose-related Decrease in Serum Phosphate Levels (P=0.012)
Group n LSMean* 95% CI
1 mg BID 23 -0.47 ( -1.18, 0.24) 3 mg BID 21 -1.18 (-1.93, -0.44) 10 mg BID 23 -1.70 (-2.41, -0.99) 30 mg BID 24 -1.98 (-2.67, -1.28) 3 mg QD 22 -0.56 (-1.28, 0.17) 30 mg QD 21 -1.11 (-1.85, -0.37) Placebo 26 -0.54 (-1.21, 0.13)
*LSMean = Least square mean. Change from Baseline at End of Treatment (mg/dL)
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Adverse Events: Gastrointestinal Disorders*
1 mg 3 mg 10mg 30 mg 3 mg 30 mg Preferred Term BID BID BID BID QD QD Placebo n/group 23 21 23 25 22 21 26 Abdominal Distension 1 Abdominal Pain 2 1 1 Abdominal Pain Upper 1 Diarrhea 6 6 11 17 4 11 3 Diverticulum 1 Dyspepsia 1 Fecal Incontinence 1 2 2 Feces Soft 1 GI Hypermotility 1 GISounds Abnormal 1 Hemorrhoids 1 Nausea 1 1 1 2 1 1 Rectal Prolapse 1 Steatorrhea 1 Vomiting 1 1 2
*Number of patients who had at least 1 AE in system organ class of gastrointestinal disorders
25
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Adverse Events Leading to Discontinuations
Discontinuation rate due to diarrhea was higher than expected in 30 mg groups
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mg 3 mg 10mg 30 mg 3 mg 30 mg Adverse Event Term BID BID BID BID QD QD Placebo n/group 23212325222126 |
Discontinuations due to 3 3 3 9 1 7 2 AE/group** Abdominal Pain 1
Diarrhea* 2 3 3 8 6 Nausea 1 Vomiting 1 Serum Calcium Decrease 1
Hyperphosphatemia 1 1 2
Dizziness 1
Atherosclerosis 1
*The term _diarrhea_ also includes similar changes in stool form or bowel habits **There may be multiple reasons for a single discontinuation
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Approved Therapies for Hyperphosphatemia in CKD-
5D Patients
AE_s Due To GI Disorders Are Common In Phosphate Binders
Adverse Events* Renvela®# Fosrenol®** Auryxia® Abdominal Pain 9% 5% Constipation 8% 8% Diarrhea 19% 21% Nausea 20% 11% 11% Vomiting 22% 9% 7%
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Data from package inserts |
# Label warning: Serious cases of dysphagia, bowel obstruction, and perforation have been associated with sevelamer use, some requiring hospitalization and surgery
**Label warning: Serious cases of GI obstruction, ileus and fecal impaction
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Tenapanor for Treating CKD
LIMITATIONS OF CURRENT TREATMENTS TO DELAY CKD PROGRESSION
“ Poor Compliance with Low Sodium Diets
“ Diuretics Lose Efficacy and Cause Electrolyte Disorders
“ ACE Inhibitors Reduce Blood Pressure but Hyperkalemia Limits Widespread Use in CKD Patients
Sodium and Fluid Overload
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CKD Phase 2a Clinical Trial Design
CKD “ Design: Double-Blind, 12 Weeks of Treatment, Targeted Phase 2a Protocol n=140 (70 Active/70 Placebo); 154 enrolled
“ Objective: Safety, Tolerability, and Pharmacodynamics of Tenapanor in CKD Patients with Type 2 Diabetes Mellitus and Albuminuria
“ Primary Endpoint: Changes in Urine Albumin to Creatinine Ratio (UACR), Baseline to Week 12
“ Other Endpoints : Pharmacodynamic Effects of Tenapanor on Urinary Na Excretion; Mean Weekly Stool Consistency and Stool Frequency
“ Doses: 5, 15, 30, or 60 mg Capsules. Starting Dose is 15 mg BID Orally for 12 Weeks
“ Status: Enrollment Completed, Data Expected Q2 2015
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The AstraZeneca/Tenapanor Collaboration
PAYMENTS
Additional
Upfront Development Launch and Sales
Up to
Milestones $35M $237.5M $597.5M $870M Total
$50M2H2015 $20M 1H 2015 ($10M if IBS-C only) $25M Received May 2014 $15M Received December 2013
Royalties “ Incremental, Tiered (High Single Digit _High Teen Percentages)
“ Co-Funding Option at 1st P3 Trial: Buy Up to 1%, 2% or 3% of Royalties with $20M, $30M or $40M* Respectively
OTHER TERMS
AstraZeneca
Responsibilities: “ All R&D and Commercialization Expenses**
Ardelyx Rights: “ Right to Co-Promote in the US
*Exercisable Within 60 Days After Decision to Proceed to P3 Clinical for the First Indication for Tenapanor
**Subject to cap on obligation for IBS-C reimbursement 30
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RDX002: NaP2b and Our Collaboration with Sanofi
Discovery and Design of Non-Systemic,
PROPRIETARY PLATFORM
Small Molecule Therapeutics
Tenapanor: AstraZeneca Collaboration;
2 VALIDATED PROGRAMS Phase 2 in Three Indications RDX002 NaP2b Inhibition: Sanofi Collaboration
WHOLLY -OWNED PIPELINE Enhanced Drug Discovery Capabilities with Rapid, Proprietary Screening Process
PROVEN MANAGEMENT TEAM Deep Domain Expertise
31
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Phosphate Binder vs. Phosphate Transport Inhibitor
Binder Phosphate Transport Inhibitor
Phosphate Binder Phosphate Phosphate Transport Inhibitor NaP2b Transporter
Enterocyte
Capillary
with Metal Based Binders
32
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RDX002: NTX1942 Reduces Urine Phosphorus Levels in Normal Rats and Is Additive to Sevelamer
0
Reduction -10 (%)
-20
** *** *** -30
Vehicle Sevelamer NTX1942 Combo
500 mg/kg 50 mg/kg
Combination of Sevelamer and NTX1942 Is Additive
NTX1942 Response Is Superior to Sevelamer at H 1/10 of the Dose
Data Shown is the Mean ±SEM; ** = p<0.01; *** =p<0.001, by one-way ANOVA, n= 12 33
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The Sanofi/NaP2b Collaboration
PAYMENTS
Upfront Potential Additional Devt./Reg Milestones
Up to
Milestones $198M Total $1.25M
Royalties “ Incremental, Tiered (Mid-Single Digit _Low Teen Percentages)
“ NaP2b Patent Portfolio and Related Know-how for Research to Licensed Complete Activities under Preclinical Development Plan Technology “ Option to Obtain Exclusive License to Develop, Manufacture and Commercialize NaP2b Inhibitors
“ Sanofi Responsible for Completing Pre-Clinical Development Plan, and if It Exercises the Option, for All Development and OtherTerms Commercialization at Its Expense
“ Ardelyx Has the Right to Co-Promote in the US
34
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Investment Highlights
Discovery and Design of Non-Systemic,
PROPRIETARY PLATFORM
Small Molecule Therapeutics
Tenapanor: AstraZeneca Collaboration;
2 VALIDATED PROGRAMS Phase 2 in Three Indications NaP2b Inhibition: Sanofi Collaboration
Enhanced Drug Discovery Capabilities with Rapid,
WHOLLY -OWNED PIPELINE
Proprietary Screening Process
PROVEN MANAGEMENT TEAM Deep Domain Expertise
35
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RDX009: TGR5 Agonists for
Inflammatory Bowel Disease (IBD), Short Bowel or NASH
TGR5 STIMULATION
“ Enhances GLP1andGLP2 (Incretins) Secretion Directly totheGI Mucosa
“ Anti-Inflammation and Mucosal Healing Effects
“ Gattex® = GLP2 approved for Short Bowel Syndrome _ Studied in Crohn_s
_ Daily Injections
“ Intercept and Exelixis/BMS Both Have Systemic TGR5 Agonists
_ Gallbladder Emptying Issues
_ ShortLastingIncretin Secretion
ARDELYX TGR5 AGONISTS + DPP4 INHIBITOR
“ No Gallbladder Issues
“ Long Lasting Incretin Secretion
“ Significantly Improves Mucosal Damage In Mouse Model of IBD
36
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RDX013: Hyperkalemia (Elevated Serum Potassium)
THE CHALLENGE
“ All Potassium Binders (e.g. Patiromer) Have Limited Efficacy onperGramBasis
“ Therapeutic Dose for Kayexelate, Patiromer or ZS-9 Substantially the Same (15-30 g/day)
“ The Limiting Factorin Efficacy isNotBinder Capacity but Availability of Potassium in the Colon
ARDELYX POTASSIUM SECRETAGOGUE
“ To Move Potassium into Colon and Increase Fecal Excretion
“ Used as a Stand Alone or in Combination with Potassium Binder
“ Augment Patient Compliance
“ Maintain Normal Serum Potassium with Optimal Dosing of Antihypertensives (RAAS Blockade Drugs)
37
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Financial Overview
$ MILLIONS
Cash and Cash Equivalents $112.0M (as of 9/30/14)
Annualized Operating Expenses* .
Debt $0
Capital Raised
Series A $26M Series B $30M IPO $69M
Nasdaq: ARDX
Ventures
2008 2011 2014
* From Ardelyx_s third quarter 10Q: $22,915 total operating expenses for the 9 months ended September 30, 2014 (p3), less $10,744 (p15 _AstraZeneca collaboration development expense_ for the 9 months ended September 30, 2014) = $12,171 * 12 month/9 months = $16.2M 38
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Investment Highlights
Discovery and Design of Non-Systemic,
PROPRIETARY PLATFORM
Small Molecule Therapeutics
Tenapanor: AstraZeneca Collaboration;
2 VALIDATED PROGRAMS Phase 2 in Three Indications NaP2b Inhibition: Sanofi Collaboration
Enhanced Drug Discovery Capabilities with Rapid,
WHOLLY -OWNED PIPELINE
Proprietary Screening Process
PROVEN MANAGEMENT TEAM Deep Domain Expertise
39
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APPENDIX
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Tenapanor Demonstrates Dose Level and Dose Frequency Response 1
PHASE 1 IN HEALTHY ADULT VOLUNTEERS
50 Dose Level Response (1) 50 Dose Frequency Response (2) 50 Same Total Daily Dose (2) mol) 40 mol) 40 mol)
(m (m (m 40 Sodium 30 Sodium 30 Sodium 30 Fecal Fecal Fecal 24hr 20 24hr 20 24hr 20 Mean 10 Mean 10 Mean 10
— -
Placebo 3 mg QD 10 mg 30 mg 100 mg Placebo 30mg QD 30mg 30mg Placebo 30mg QD15mg BID QD QD QD BID TID
| 1 |
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RDX5791 -101 |
| 2 |
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RDX5791 -102; some data published in Spencer et al Sci Transl Med 6, 227ra36 (2014) 41 |
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Tenapanor Diverts Dietary Sodium to the Feces CKD-5D Patients
PHASE 2a FLUID IN SUBSET OF CKD-5D PATIENTS 2
Mean 24hr Fecal Sodium (mmol)
50 40 30 20
10
-
Placebo BID Dosing N=8 N=8
| 2 |
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Study D5611C00001 42 |
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Comparative Human Response:
Sevelamer vs. Tenapanor in Healthy Adult Volunteers
SEVELAMER 1 TENAPANOR 2
Fecal Phosphorus Fecal Phosphorus (mmol/Day (mmol/Day Mean ± SE) Mean ± SE)
40 40
30 30
20 20
10 10
0 0
Baseline 1g TID 2.5g TID 5g TID Baseline 15mg BID (5g Group)
Dose 15,000 mg/Day 30 mg/Day
Similar Results, But 1/500 th the Dose
| 1 |
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Burke et al. 1997; 2 Study D5611C00002 43 |
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Studies Support Impact of Treating Elevated Sodium and Phosphorus
SODIUM 1 PHOSPHORUS 2
Proteinuria Relative Risk of Death *
ACE Inhibition
2.5 DaVita (Kalantar -Zadeh, et al.) ACE Inhibition -ARB
| * |
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Fresenius (Block, et al.) 2 N = 40,538 1.5 Proteinuria * 2.60 (g/Day) * ! |
| 1 |
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2.40 0.5 2.20
0 2.00 Regular Sodium Diet Low Sodium Diet 1.80
Systolic Blood Pressure
1.60
140 1.40 135 1.20 Systolic * 130 * Blood 1.00 Pressure 125 (mmHg) 120 0.80
115 <3 3-4 4-5 5-6 6-7 7-8 8-9 >9 110 Serum Phosphorus (mg/dL)
Regular Sodium Diet Low Sodium Diet *Not adjusted for active vitamin D intake; serum phosphorus 4-5 mg/dL was normalized to 1.0
1. Slagman, et al., BMJ (2011) 343:d4366: 2. Block, et al. JASN (2004) 15:2208 -2218: 3. Kalantar -Zadeh, et al. KI (2 006) 70:771-780
*P<0.05 v ACE inhibiŸon on regular sodium diet. P<0.05 v ACE inhibiŸon plus ARB on regular sodium diet. !P<0.05 v ACE inhibition on low sodium diet 44
|
|
Beneficial Effects of Tenapanor on Sodium and Phosphorus in CKD Models
SODIUM PHOSPHORUS
Urinary Albumin/Creatinine Aortic Mineral Content
5/6th Nephrectomized Rats Aortic P 2.5 (mg/g tissue)
| 2 |
|
th |
Albumin/ 5/6 Nephrectomized Rats 1.5 15 Creatinine 1 (mg/mg) ** 0.5 ** 0 10 Normal Vehicle ACE* Tenapanor Tenapanor + ACE*
Systolic Blood Pressure
| 5 |
|
5/6th Nephrectomized Rats |
*** 200
150 ***
SBP *** 0
100 Vehicle Tenapanor (mmHG) 50
0
Normal Vehicle ACE* Tenapanor Tenapanor + ACE*
*ACE = Enalapril; One way Anova, followed by Dunnett_stest;
** p<0.01; *** p<0.001 vs. vehicle; p<0.05; ; p<0.01; p<0.001 vs. sham; N=12/group 45