Slide 1: Efficacy and safety of tenapanor in patients with IBS-C: a 12-week phase 2b trial
Exhibit 99.2 Efficacy and Anthony Gastroenterology, Fremont, JCA, Lembo,2 safety USADepartment of James tenapanor A Phillips,3 of in Medicine, patients Davidwith Beth P Rosenbaum4 constipation-predominant Israel Deaconess 1Division Medical of Gastroenterology, irritable Center, Harvard bowel syndrom
Slide 2: Disclosures
Disclosures QOL Laboratories, Laboratories Medical, William James Synthetic SalixAPharmaceuticals, DPhillips Chey Biologics Consultancy: Consultancy: and Vibrant SK Biopharmaceuticals, Ardelyx, Ardelyx Pharma Asubio David Anthony PPharmaceuticals, Rosenbaum Sucampo J Lembo Consultancy: and Employmen
Slide 3: Tenapanor is a small-molecule NHE3 inhibitor acting locally in the gut
Tenapanor small-molecule antinociceptive daily 1992;267:9340–6 Eutamene (AZD1722) effects inhibitor H et al.on acts Gastroenterology ofstress-induced NHE3 locally Preclinical in themechanical gut 2011;140:S-57–8; toand reduce phase colorectal sodium 1 studies Schultheis absorption hypersensitivity s
Slide 4: Tenapanor phase 2a data in IBS-C
Tenapanor bowel with q.d. https://clinicaltrials.gov/ct2/show/NCT01340053 (n a habits ?=30% 47) is Tenapanor In adecrease potential IBS-C,instools 100 treatment abdominal mgareq.d. hard/lumpy forpain (nconstipation-predominant = 46) and IBS-C, an in ?increase (accessed 25% constipation-predominant o
Slide 5: 12-week dose-ranging study design and key criteria
12-week•?dose-ranging criteria exclusion structural https://clinicaltrials.gov/ct2/show/NCT01923428 abnormality Age criteria 18–75 •? IBS years of study with the•?evaluating gastrointestinal diarrhea IBS-C as(IBS-D), tenapanor defined tract by mixed (accessed in 5Rome mg, theIBS 620 III months (IBS-
Slide 6: Study design: endpoints and assessments
12-week an 12 assessments with baseline increase weeks a > for 30% dose-ranging Keyof >Adverse decrease 6/12 1secondary CSBM treatment event study in per endpoints abdominal reporting week evaluating weeks from Overall pain throughout baseline tenapanor and responder anfor the increase 5Placebo mg,
Slide 7: Statistical analysis methods (1/2)
Statistical are tenapanor based presented on 120 analysis degree mg as risk b.i.d. of methods differences freedom and tenapanor (1/2) for(slides CSBM the association 508,mg responder 10,b.i.d.) 11)between Aand rate screening responder (primary treatment testendpoint), rate, was (placebo performed st
Slide 8: Statistical analysis methods (2/2)
Statistical placebo differences ANCOVA areanalysis model, in presented meanwith methods changes astreatment differences (2/2) fromand Stool baseline inpooled LS consistency mean among investigator changes the (secondary placebo, from site asbaseline tenapanor endpoint), factors (slide and 20 abdomin
Slide 9: Patient demographics and baseline disease characteristics
Patient (76%) (0.4) (0.6) the bAssessed during weekly ITT SBMs 4.0 Baseline the demographics score population. (0.7) week for per was 4.0 each disease week cAssessed calculated (0.8) SBM Baseline 2.0 and IBS Placebo using (1.2) baseline weekly severityc from was 1.9 aTenapanor 5-point defined scores
Slide 10: Tenapanor resulted in a significantly higher CSBM responder rate than placebo
Tenapanor from baseline 50 mg for ?b.i.d. 6/12resulted treatment in weeks a significantly (ITT analysis) higher CSBM, CSBM responder complete spontaneous rate than placebo bowelPrimary movement endpoint (CSBM responder rate): proportion of patients with an increase of ? 1 CSBM per week
Slide 11: CSBM improvements were maintained over the 12 weeks
CSBMmovement bowel improvements *p <were 0.05,maintained tenapanor 50 over mgthe b.i.d. 12 weeks versus in placebo a dose-dependent †p < 0.05, tenapanor manner Placebo 20 mg b.i.d. Tenapanor and 505 mg b.i.d. versus Tenapanor placebo 20 mg b.i.d. Tenapanor 50 mg b.i.d. CSBM, complete spontaneous
Slide 12: Tenapanor 50 mg b.i.d. resulted in a higher overall responder rate
Tenapanor 1 CSBM per50week mg b.i.d. versusresulted baseline in afor significantly ? 6/12 treatment higherweeks overall CSBM, responder complete rate than spontaneous placebo Overall bowel movement responder rate: Tenapanor proportion b.i.d.of patients with a ? 30% decrease in abdominal pain and an
Slide 13: Improvements in other key secondary endpoints
Improvements 30% interval decrease in inabdominal other key secondary pain from endpoints baseline for with ? 6/12 tenapanor treatment Abdominal weeks; treatment pain responder comparisons ratea Stool versus consistencyb placebo represent BSFS, Bristol the riskStool difference Form bError Scale; LS,
Slide 14: Improvements in exploratory endpoints with tenapanor 50 mg b.i.d.
Improvements during weekly ausing weekabin 5-point Assessed exploratory scale: for endpoints 1each = none SBMtowith using 5 = tenapanor very a 5-point severe 50 scale: mg b.i.d. 1 = not a Assessed at all to 5daily = an using extreme a 10-point amount;scale: average 0 =weekly none tostraining 10 = ve
Slide 15: Tenapanor was generally well tolerated
Tenapanor 89) (3.3) meaningful systemic aMost specific (n9=common (10.2) AE 89) availability was changes led Any 6 generally (6.7) to AEs AE discontinuation from leading Tenapanor 438(4.5) (42.2) well baseline •? totolerated 43 Most discontinuation: concentrations (48.9) in were AEs > 2and reported
Slide 16: Adverse events occurring in ≥3% of patients
AEs occurring b.i.d. (1.1) (3.4) 250(2.2) Headache mg b.i.d. GERD in5 ?(5.6) (n3% 1=(1.1) 88) 6of(6.8) patients (n 3 (3.4) =189) (1.1) in 0(n(0.0) any 3=(3.4) 89) tenapanor 1 (1.1) Diarrhea GERD,Abdominal group gastroesophageal 0 (0.0) anddistension 7 more (8.0) frequently 11 reflux (12.4) 0 (0.0)di
Slide 17: Conclusions
Conclusions secondary endpoints for patientsaddressing endpoints with Tenapanor IBS-Ccompared a range 50 mgofb.i.d. with symptoms placebo, significantly in including patients improved with overall IBS-C CSBM responder Tenapanor responder rate,was rate abdominal generally (primary pain well endpoint)
Slide 18: Acknowledgments
Acknowledgments and Jocelyn TaboraThe frominvestigators Ardelyx Medical acknowledge writing support and thank was theprovided study participants, by Steven Inglis the study and centres Carolynand Brechin the clinical of Oxford teams PharmaGenesis, The clinical operations UK and was werefunded manage