Ironwood Pharmaceuticals, Inc. · NASDAQ:IRWD
Ironwood Pharmaceuticals — Digestive Disease Week 2024
26 slides from Ironwood Pharmaceuticals's conference presentation, May 21, 2024
Slide 1: Ironwood Late-Breaker Oral Presentation at Digestive Disease Week
Ironwood Late-Breaker Oral Presentation at Digestive Disease Week® Oral presentation on Ironwood’s pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in adult patients with short bowel syndrome with intestinal failure (SBS-IF). Pr
Slide 2: Efficacy and Safety of Apraglutide Once-Weekly in SBS-IF: The STARS Study
Abstract# 4094736 Efficacy and Safety of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): The STARS Study, A Global Phase 3, Randomized, Placebo- Controlled, Double-Blind Trial Francisca Joly’; Tim Vanuytsel2; Donald F. Kirby *; Simon Lal4; Kelly Tappend
Slide 3: Disclosures
Disclosures Francisca Joly declares ¢ Consultancy or advisory role for: Takeda, Ironwood; NorthSea Therapeutics, Hamni, Zealand, Mobile3esolutions, Carembouche ¢ Research funding from: Takeda Pharma, Ironwood, Zealand, Baxter, Mobile3esolutions, Carembouche e Lecturer role for: Baxter, BBraun, Frese
Slide 4: Introduction
Introduction * SBS-IF is a chronic malabsorptive condition requiring PS" Endogenous GLP-2 * SBS-IF is anatomically heterogeneous with a Enterocytes wide range of clinical response affected by the remnant bowel anatomy (stoma or CIC)! Wace ~~ Goblet cells * GLP-2 is an endogenous endocrine peptide th
Slide 5: STARS Study Design
STARS Study Design: Efficacy and safety of apraglutide in adult patients with SBS-IF A pivotal, Phase 3, double-blind, placebo-controlle PRIMARY ENDPOINT Global study 68 centers in 18 countries 21 KEY SECONDARY : KEY SECONDARY Two arms rancomzaugn ENDPOINTS : ENDPOINTS : apraglutide : Apraglutide vs
Slide 6: Inclusion & Exclusion Criteria
Inclusion & Exclusion Criteria Key Inclusion Criteria Major abdominal surgery within last 6 months + Receiving PS after surgical resection of the small intestine with <200 cm from duodeno-jejunal flexure, with either: + Acute cholecystitis, biliary obstruction, or IBD * Radiation enteritis, sclerode
Slide 7: Patient Disposition
Patient Disposition Apraglutide Placebo (n=110) (n=53) n n Stoma (n=80) 54 26 CIC (n=83) 56 27 Apraglutide Placebo (n=110) (n=53) n(%) n (%) 104 (94.5) 51 (96.2) CIC, colon-in-continuity Randomized N= 164 Completed Treatment n= 155 (95.1%) ued Prematurely from Treatment n=8 (4.9%) Apraglutide Placeb
Slide 8: Baseline Demographics
Baseline Demographics ameter Rerechtiee Age (years; mean [SD]) 51.1 (14.2) 52.3 (16.0) Sex (n, %) Male 44 (40.0) 27 (50.9) Race (n, %) White 94 (85.5) 43 (81.1) Asian 12 (10.9) 8 (15.1) Other 3 (2.7) 2 (3.8) Region (n, %) US 21 (19.1) 7 (13.2) EU + UK 75 (68.2) 75 (69.8) ROW 14 (12.7) 9 (17.0) Weigh
Slide 9: Baseline SBS-IF Characteristics
Baseline SBS-IF Characteristics Cause of SBS Overall Population (N=163) 26.4% WES 30.1% IBD Surgical 8-0% complications.» 35.5% *Other causes include injury from trauma, volvulus, ileus, adhesion, and intestinal malformation €ppw2024 IBD, Inflammatory bowel syndrome; SBS-IF, short bowel
Slide 10: Baseline SBS-IF Characteristics
Baseline SBS-IF Characteristics Cause of SBS Apraglutide | Placebo Overall Population SBS History & PS Dependence (n=110) (n=53) (N=163) Mean (SD) | Mean (SD) a Small intestine length (cm) 86.2(54.2) 91.3(53.5) 26.4% Mes qiterlc 30.1% Time fromlastintestinalresection 99 4 197 4) 99.2(95.7) IBD | (mo
Slide 11: Primary & Key Secondary Endpoints
10 Primary & Key Secondary Endpoints Overall population Primary Endpoint Key Secondary Endpoints + Additional 21 day/week off PS | - Relative change from - Additional 21 day/week off PS at Week 24 baseline in weekly PS volume | from baseline at Week 48 at Week 24 + Enteral autonomy at Week 48 ©ppw20
Slide 12: Primary Endpoint Met (overall population)
Primary Endpoint Met (overall population): Significantly greater relative reduction in weekly PS volume at Week 24 0% -5% -10% -15% -20% P=0.001 from Baseline -25% -30% =@ Apraglutide (n=110) "Ve Placebo (n=53) ee -35% Relative (%) Weekly PS Volume Reduction 4 8 12 16 20 24 Week Apraglutide treatmen
Slide 13: Key Secondary Endpoint Met (Stoma)
Key Secondary Endpoint Met (Stoma): Significantly greater relative reduction in weekly PS volume at Week 24 Key Secondary Endpoint Met Stoma 0% i+ Ko} °° Ss med oO e 10% oO — 2o oc > -20% o 2 ° Sa % 5 -30% = “ E -40% o 2 & “@- Apraglutide (n=54) @ -50% “ Placebo (n=26) 4 8 12 16 20 24 Week @§)ppw202
Slide 14: Both stoma and CIC contributed to meeting the primary endpoint
Both stoma and CIC contributed to meeting the primary endpoint Key Secondary Endpoint Met Secondary Endpoint cic c 2 0% 0% o 3 3 xe -10% -10% o = 2a SE -20% 20% 28 Sa a § -30% -30% sf = 40% -40% $ 3s ~@ Apraglutide (n=54) ~@® Apraglutide (n=56) fe 790% -50% “> Placebo (n=26) "Y Placebo (n=27) 4 8 12
Slide 15: Key Secondary Endpoint Met (overall population)
Key Secondary Endpoint Met (overall population): Apraglutide significantly increased additional 21 day off PS per week at Week 24 Key Secondary Endpoint Met Overall population 50% P=0.040 40% 30% 27.5% 20% Percentage of Patients 10% 0% Additional21 day off per week €ppw2024 PS, parenteral support
Slide 16: More apraglutide patients gained additional 2 and 3 days off PS per week
Significantly more apraglutide-treated patients in the overall population gained additional 22 and 23 days off PS per week at Week 24 Key Secondary Endpoint Met Exploratory Endpoints Overall population Overall population 50% P=0.040 Hib praglutide (n=110) Placebo (n=53) 2 40% £ o P=0.021 ‘© 30% 27.5
Slide 17: Key Secondary Endpoint (CIC): Additional 1 day off PS at Week 48
Key Secondary Endpoint (CIC): Numerically more apraglutide-treated patients gained additional 21 day off PS per week at Week 48 60% P=0.348 51.8% 50% 44.4% 40% Percentage of Patients wo oO os 20% 10% 0% Additional21 day off per week €ppw2024
Slide 18: Numerically more apraglutide-treated CIC patients gained additional days off PS
Numerically more apraglutide-treated CIC patients gained additional 22 and 23 days off PS per week at Week 48 Key Secondary Endpoint Exploratory Endpoints cic cic 60% P=0.348 51.8% Hib Apragiutide (n=56) [§§ Placebo (n=27) 44.4% P=0.204 33.9% P=0.223 25% 22.2% Percentage of Patients 14.8% Additional
Slide 19: Enteral autonomy achieved in both stoma & CIC subgroups at Week 24
Enteral autonomy was achieved by apraglutide-treated patients in both stoma & CIC subgroups at Week 24 Secondary En int Met Overall Population at Week 24 15% P=0.006 CIC (n=4) Stoma (n=3) 7 (6.4%) Percentage of Patients with Enteral Autonomy 0 (0%) Apraglutide Placebo (n=110) (n=53) €ppw2024
Slide 20: Proportion of patients achieving enteral autonomy
Proportion of apraglutide-treated patients achieving enteral auto y Secondary Endpoint Met Key Secondary Endpoint Overall Population at Week 24 CIC at Week 48 15% P=0.006 P=0.387 7 (12.5%) 2e Fad 2 & ss Clic (n=4) 3 additional .=4 7 =. atients * az Stoma (n=3) (at Week 48) ; oD 2 (7.4%) £2 7 (6.4%)
Slide 21: Secondary Endpoint: More apraglutide patients were clinical responders
Secondary Endpoint: Significantly more apraglutide patients were clinical responders (220% PS volume reduction at both Weeks 20 and 24) Secondary Endpoint Overall population P=0.003 42.7% 20.8% Percentage of Clinical Responders Apraglutide Placebo (n=110) (n=53) €ppw2024 CIC, colon-in-continuity
Slide 22: Proportion of clinical responders in stoma & CIC patients
Proportion of clinical responders in stoma & CIC patients (220% PS volume reduction at both Weeks 20 and 24) Secondary Endpoint Secondary Endpoint Exploratory Endpoint Overall population Stoma cic P=0.003 P=0.020 P=0.079 44.6% 42.7% 40.7% Percentage of Clinical Responders 25.9% 20.8% 20% 15.4% 10% 0
Slide 23: Secondary Endpoint (Stoma): Clinical high responders
Secondary Endpoint (Stoma): Significantly more apraglutide-treated patients were clinical high responders (240% PS volume reduction at both Weeks 20 and 24) Exploratory Endpoint Secondary Endpoint Met Overall population Stoma P=0.018 P=0.009 30% n co) x Percentage of Clinical High Responders 10% 9.4
Slide 24: Safety & Tolerability
Safety & Tolerability: Apraglutide was well tolerated with few discontinuations due to adverse events I cre Caulaton was comparable between treatment arms ite INAS HalBE SS * One fatal SAE was reported (n=110) (n=53) : ‘ in apraglutide arm and assessed as unrelated AE 99 (90.0) 47 (88.7) No patients
Slide 25: Safety & Tolerability: Consistent with previous studies
Safety & Tolerability: Safety profile is consistent with previous apraglutide clinical studies Most Freq AEs throughWeek 48 Apraglutide * Relatively low incidence of AEs associated Preferred Terms Oo with Gl tolerability between treatment arms n(% * Incidence of injection site reaction* was reported
Slide 26: Apraglutide is the first once-weekly GLP-2 analog to show efficacy in Phase 3
Apraglutide is the first once-weekly GLP-2 analog to show efficacy in a Phase 3 trial for patients with SBS-IF * Efficacy was demonstrated by significantly greater relative PS volume reduction from Week 8 onward Efficacy of apraglutide in the overall population strongly supported by clinically meani
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