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Proven Control
with ZEPOSIA1

Rapid and Sustained Clinical Remission at Weeks 10 and 521

Induction & Maintenance
Primary Endpoint

Clinical Remissiona at Weeks 10 and 521

Clinical Remissiona
at Weeks 10 and 521

Clinical Remission (Primary Endpoint) Graph at Weeks 10 and 52
Open-Label Extension
(Interim Analysis)2d

In the Subset Of Patients in
Clinical Remission at Week 52 and
Had Continuous ZEPOSIA
Exposure, 82% of Patients
Were
in Clinical Remission at Week 98 and 76% of Patients Were in Clinical Remission at Week 146 (Observed Cases)2,3d

Open-Label Extension (Interim-Analysis), Week 98 and week 146 Open-Label Extension (Interim-Analysis), Week 98 and week 146

OLE Study Design:
The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the Phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the Phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE as of the cutoff date (January 10, 2022). Mean ZEPOSIA exposure through the OLE was 2.7 years.2,4,5 For full study design, click here.

OLE endpoints were evaluated at Week 46 and Week 94 for a subset of patients who were in clinical remission or clinical response at Week 52 of the TRUE NORTH parent study and who had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study. The mean exposure to ZEPOSIA through the OLE was 2.7 years.2-4,6

Data were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.4

These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered OLE.3

In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 65% (54/83) were in clinical remission at Week 98 (Week 46 of OLE) and 49% (41/83) were in clinical remission at Week 146 (Week 94 of OLE).2,3

  • a

    Clinical remission is defined as: rectal bleeding subscore (RBS)=0, stool frequency subscore (SFS) 0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore 0 or 1 without friability.1

  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • dData cutoff of January 10, 2022.2

ITT=intent-to-treat; NRI=nonresponder imputation; OLE=open-label extension; SFS=stool frequency subscore; TNFI=tumor necrosis factor inhibitor.

Rapid and Sustained
Clinical Response at Weeks 10
and 521

Induction & Maintenance
Key Secondary Endpoint

Clinical Responsee
at Weeks 10 and 521

Clinical Response (Key Secondary Endpoint) Graph
Open-Label Extension
(Interim Analysis)2d

In the Subset Of Patients in Clinical Response at Week 52 and Had Continuous ZEPOSIA Exposure, 96% Were in Clinical Response at Week 98 and 91% Were in Clinical Response at Week 146 (Observed Cases)2d

Open-Label Extension (Interim-Analysis)2,3d Open-Label Extension (Interim-Analysis)2,3d

OLE Study Design: The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the Phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the Phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE as of the cutoff date (January 10, 2022). Mean ZEPOSIA exposure through the OLE was 2.7 years.2,4,5

OLE endpoints were evaluated at Week 46 and Week 94 for a subset of patients who were in clinical remission or clinical response at Week 52 of the TRUE NORTH parent study and who had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study.2-4,6

Data were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.4

In the NRI analysis of a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure, 71% (n=93/131) were in clinical response at Week 98 (Week 46 of OLE) and 56% (74/131) were in clinical response at Week 146 (Week 94 of OLE)2,3

These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.3

  • bTreatment difference (adjusted for
    stratification factors of prior TNFi exposure and
    corticosteroid use at baseline).1
  • cTreatment difference (adjusted for
    stratification factors of clinical remission and
    concomitant corticosteroid use at Week 10).1
  • dData cutoff of January 10, 2022.2
  • eClinical response is defined as a reduction from
    baseline in the 3-component Mayo score
    of ≥2 points and ≥35%, and a reduction from
    baseline in the rectal bleeding subscore of ≥1
    point or an absolute rectal bleeding subscore
    of 0 or 1.1

CS=corticosteroid; ITT=intent-to-treat; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor.

Post-Hoc Analysis:
Symptomatic Response and Remission Observed in Patients Treated With ZEPOSIA
Starting at Week 2 – 1 week
after completing the 7-day
dose titration7,8

Post-hoc Analysis of Symptomatic Responsegh
Patients in Symptomatic Response (%) Patients in Symptomatic Response (%)
Post-hoc Analysis of Symptomatic Remissionhi
Patients in Symptomatic Remission (%) Patients in Symptomatic Remission (%)

In a post-hoc analysis, patients treated
with ZEPOSIA observed a decrease
in RBS and SFS as early as Week 2,
1 week after completing the 7-day
dose titration.1,8

  • gSymptomatic response is defined as: a decrease from baseline of ≥1 point and ≥30% in the adapted partial Mayo score (sum of the RBS, SFS, and Physician Global Assessment subscore, ranging from 0-9 points) and a decrease of ≥1 point from baseline in RBS or an absolute RBS ≤1 point.5,7
  • hData are based on the nonresponder imputation.7
  • iSymptomatic remission is defined as: RBS=0 point and SFS ≤1 point (and a decrease of ≥1 from the baseline SFS).7

RBS=rectal bleeding subscore; SFS=stool frequency subscore.

Symptomatic Clinical Responsej Observed Among Week 10 Nonrespondersk Treated With ZEPOSIA8

49% of Nonresponders Who
Entered OLE at Week 10 After the
Induction Period
Observed
Symptomatic Clinical Response by
Week 20 (OLE Week 10)
% of Observed Symptomatic Clinical Response by Week 20 % of Observed Symptomatic Clinical Response by Week 20

This analysis examined ZEPOSIA efficacy in patients from TRUE NORTH who were treated with double-blind ZEPOSIA but did not achieve clinical response at Week 10 and subsequently continued ZEPOSIA in the OLE (N=150) and observed extended treatment with ZEPOSIA for an additional 10 weeks.9

Efficacy analyses of symptomatic response were not prespecified.8,9

  • hData are based on the nonresponder imputation.9
  • jSymptomatic clinical response is defined as a reduction from baseline in the partial Mayo score of ≥1 point and ≥30% and a ≥1-point decrease in RBS or absolute RBS ≤1.9
  • kNonresponders were patients who did not achieve clinical response (defined as a reduction from baseline in the 3-component Mayo Score of ≥2 points and ≥35%, and a reduction from the baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1) on ZEPOSIA at Week 10 of induction and entered the OLE.1,9

OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore.

ZEPOSIA Demonstrated Mucosal Healing1

Defined by significant endoscopic-histologic
mucosal improvement1

Key Secondary Endpoints: Endoscopic Improvementl and Endoscopic-Histologic
Mucosal Improvement (EHMI)m at Weeks 10 and 52 (% of Patients)1
Key Secondary Endpoints: Endoscopic Improvement and Endoscopic-Histologic Mucosal Improvement (EHMI) at Weeks 10 and 52 (% of Patients) Key Secondary Endpoints: Endoscopic Improvement and Endoscopic-Histologic Mucosal Improvement (EHMI) at Weeks 10 and 52 (% of Patients)

The relationship of endoscopic-histologic mucosal improvement, as defined in UC Study 1 and UC Study 2 at Weeks 10 and 52, to disease progression and long-term outcomes, was not evaluated.1

  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • lEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.1
  • mEndoscopic-histologic mucosal improvement is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0).1
  • nThe relationship of EHMI, as defined in UC Study 1 and UC Study 2 at Weeks 10 and 52, to disease progression and long-term outcomes, was not evaluated.1

EHMI=endoscopic-histologic mucosal improvement; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

Corticosteroid-Free Control Is Possible1,2

CS-Free Remission -
Key Secondary Endpoint1

Remission at Week 52

CS-Free Remission - Key Secondary Endpoint CS-Free Remission - Key Secondary Endpoint
Open-Label Extension
(Interim Analysis)2d

In The Subset Of Patients in Clinical Remission at Week 52 and Had Continuous ZEPOSIA Exposure, 80% Were in CS-free remission at Week 98 and 74% Were in CS-free remission at Week 146 (Observed Cases)2,3op

Open-Label Extension (Interim-Analysis), Observed Cases week 98, week 146 Open-Label Extension (Interim-Analysis), Observed Cases week 98, week 146
  • Corticosteroid-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥12 weeks1,2
  • Clinical remission is defined as: rectal bleeding subscore (RBS)=0, stool frequency subscore (SFS) 0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore 0 or 1 without friability1,2

In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 64% (n=53/83) were in CS-free remission at Week 98 (Week 46 of OLE) and 48% (n=40/83) were in CS-free remission at Week 146 (Week 94 of OLE).2

These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered OLE.3

  • cTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • dData cutoff of January 10, 2022.2
  • oData were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.4
  • pFor all patients in OLE (N=823): In the OC analysis, 42% were in CS-free remission at 46 weeks post-OLE entry. In the NRI analysis, 26% were in CS-free remission at 46 weeks post-OLE entry.4

CS=corticosteroid; ITT=intent-to-treat; NRI=non-responder imputation; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore.

Disease Control Across TNFi Subgroups1

Efficacy Observed at Weeks 10 and 52q

Prespecified Subgroup Analysisq
(% of Patients)

TNFi-naїve patients at Week 10

TNFi-naïve patients at Week 10

TNFi-exposed patients at Week 10

TNFi-exposed patients at Week 10

TNFi-naїve patients at Week 52

TNFi-naїve patients at Week 52

TNFi-exposed patients at Week 52

TNFi-exposed patients at Week 52
  • Clinical remission is defined as: rectal bleeding subscore (RBS)=0, stool frequency subscore (SFS) 0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore 0 or 1 without friability1
  • Clinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 11
  • Endoscopic improvement is defined as a Mayo endoscopy score=0 or 1 without friability1
  • Endoscopic-histologic mucosal improvement is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0)1
  • The relationship of endoscopic-histologic mucosal improvement, as defined in UC Study 1 and UC Study 2 at Weeks 10 and 52 to disease progression and long-term outcomes was not evaluated1
  • qEfficacy analysis by prior TNFi therapy was prespecified, but not powered to detect a difference in the treatment effect in these subgroups.8

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Demonstrated
Safety
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