Ardelyx (ARDX) 8-K IBS-C Phase 2b Results

IBS-C Phase 2b Results

October 2014

Exhibit 99.1

2

Tenapanor Reduces Sodium and

Phosphorus Absorption

Dietary Sodium/Phosphorus Passes

Into Circulation

Diverts Sodium/Phosphorus

from Circulation

WITHOUT TENAPANOR

WITH TENAPANOR

Tenapanor is a non-systemic small

molecule inhibitor of NHE3, a sodium

transporter present on the epithelia of

the GI tract

Tenapanor

Sodium

Phosphorus

Local Activity

in the Gut

Sodium

Phosphorus

3

Phase 2b Design for Tenapanor in IBS-C

•

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:

•

Treatment Arms:

IBS-C Phase 2b Protocol

RANDOMIZATION

*CSBM

defined

as

a

bowel

movement

that

feels

complete

and

is

not

aided

by

the

use

of

any

other

medication,

like

a

laxative

PLACEBO

BID

TENAPANOR 5 MG BID

TENAPANOR 20 MG BID

TENAPANOR 50 MG BID

Overall

Responder

Rate,

Abdominal

Pain and Abdominal and IBS-C Symptoms

4

Tenapanor in IBS-C Phase 2b Results: Efficacy

•

Trial met primary efficacy endpoint: complete spontaneous bowel movement

(CSBM) responder [60.7% in tenapanor 50 mg bid group vs. 33.7% placebo;

p<0.001]

•

The

overall

responder

rate

for

the

dual

composite

endpoint

(CSBM

responder

and

abdominal

pain

responder

in

6

of

12

weeks)

was

higher

in

the

tenapanor

50 mg bid group compared to the placebo group [50.0% vs. 23.6% placebo;

p<0.001]

•

This dual composite endpoint is the primary regulatory endpoint in Europe

and US (EMA draft guidance 2013, FDA guidance 2012)

5

Tenapanor in IBS-C Phase 2b Results: Efficacy (con’t)

•

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 doses; activity of tenapanor was maintained

throughout entire 12-week treatment period

•

Adequate relief of IBS symptoms was statistically significant (p=0.002) for

tenapanor 50 mg bid (63.1%) versus placebo (39.3%) at the endpoint week

(week 12 or last valid week)

•

Based

on

the

treatment

satisfaction

patient

scale

questionnaire,

more

subjects

receiving

50

mg

bid

responded

that

they

were

“quite

satisfied”

or

“very satisfied”

with tenapanor versus placebo [65% vs. 38% placebo;

p<0.001]

6

Tenapanor in IBS-C Phase 2b Results: Safety

•

Tenapanor well-tolerated across all treatment arms, and there were no

serious drug-related adverse events. 

•

The

most

common

adverse

events

at

50

mg

bid

(

5%)

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

•

Based on the analysis of plasma samples tested as part of the study, the

minimally systemic nature of tenapanor was confirmed

7

Tenapanor for IBS-C

GI Disorder:

Constipation and

Abdominal Pain

IBS-C MARKET

•

Medical Need for Improved Therapies with Better

Efficacy, Excellent Safety and Tolerability

–

Achieve Endpoint in Only 7% to 20% of Patients

–

Side Effects (e.g., Nausea and Diarrhea,

respectively)

•

Amitiza®

and Linzess®

Fall Short:

•

OTC Drugs Inexpensive but Not Very

Effective in Moderate to Severe Cases

LIMITATIONS OF CURRENT TREATMENTS

•

Approximately 1.4% of the US population,

or 4.4 million individuals, have IBS-C. 

•

About one million patients have been

diagnosed

8

Tenapanor Demonstrates Dose Level and Dose Frequency

Response; Stool and Urine Sodium Correlate

1

1

RDX5791-102

published

in

Spencer

et

al

Sci

Transl

Med

6,

227ra36

(2014)

*P

<

0.05

versus

placebo,

†P

<

0.05

versus

30

mg

once

daily.

Data

are

means

±

SEM.;

PHASE 1 IN HEALTHY ADULT VOLUNTEERS

-

10

20

30

40

50

Placebo

3 mg QD

10 mg QD

30 mg QD

100 mg

QD

-

10

20

30

40

50

Placebo

30mg QD

30mg BID

30mg TID

9

Phase 2a Had Demonstrated Activity with QD Dosing

DUAL ENDPOINT: >30% DECREASE IN WEEKLY ABDOMINAL PAIN SCORE AND >1

INCREASE IN CSBM FREQUENCY AS COMPARED TO BASELINE

*

p<0.05 versus placebo

*

severity

and

QOL

measurements

with

QD

dosing

although

the

primary

endpoint,

change

in

CSBM

from

Baseline to Week 4, was not

met in this Phase 2a study.

Percent

Responders

End of Treatment

0%

10%

20%

30%

40%

Week 1

Week 2

Week 3

Week 4

Follow-Up

Week 1

Follow-Up

Week 2

Placebo (n=47)

100mg QD (n=46)

Improvements

in

degree

of

bloating

and

abdominal

pain

were

noted,

as

well

as

relief

of

IBS

symptoms,

10

Tenapanor Program –

Renal Indications and IBS-C

PROGRAM

INDICATION

RESEARCH

PHASE 1

PHASE 2

STATUS

2a

2b

Tenapanor

(NHE3 Inhibitor)

ESRD-Pi (1)

Phase 2b Data

1H:2015

IBS-C (2)

Phase 2b Data

Announced

Oct 1, 2014

CKD (3)

Phase 2a Data

2H:2015

More information about clinical trials design can be found at the following links:

(1) ESRD-Pi: http://clinicaltrials.gov/ct2/show/NCT02081534

(2) IBS-C: http://clinicaltrials.gov/ct2/show/NCT01923428

(3) CKD: http://clinicaltrials.gov/ct2/show/NCT01847092