![]() 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0.001] • This dual composite endpoint is the primary regulatory endpoint in Europe and US (EMA draft guidance 2013, FDA guidance 2012) |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 |