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, 73% of Patients
Were
in Clinical Remission at Week 98
(Observed Cases)2d

Open-Label Extension (Interim-Analysis), Week 98

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 cut-off date (September 30, 2020). Mean ZEPOSIA exposure in the OLE was 1.5 years.3,4 For full study design, click here.

Clinical remission, clinical response, endoscopic improvement, and CS-free remission were evaluated at Week 46 for all patients who entered the OLE from the TRUE NORTH parent study and in a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure.2,3

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.3

In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 53% (n=30/57) were in clinical remission at Week 98 (Week 46 of OLE).2

For all patients in OLE (N=823)3:

  • In the OC analysis, 45% of patients were in clinical remission at 46 weeks post-OLE entry
  • In the NRI analysis, 28% of patients were in clinical remission at 46 weeks post-OLE entry
  • aClinical 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 September 30, 2020.3

ITT=intent-to-treat; NRI=nonresponder imputation; OC=observed case; OLE=open-label extension; 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, 97% of Patients Were
in
Clinical Response at Week 98
(Observed Cases)2d

Open-Label Extension (Interim-Analysis)2d

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 cut-off date (September 30, 2020). Mean ZEPOSIA exposure in the OLE was 1.5 years.3,4

Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at Week 46 for all patients who entered the OLE from the TRUE NORTH parent study and in a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure.2,3

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.3

In the NRI analysis of a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure, 64% (n=61/95) were in clinical response at Week 98 (Week 46 of OLE).2

For all patients in OLE (N=823)3:

  • In the OC analysis, 80% of patients were in clinical response at 46 weeks post-OLE entry
  • In the NRI analysis, 48% of patients were in clinical response at 46 weeks post-OLE entry
  • 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 September 30, 2020.3
  • 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; RBS=rectal bleeding subscore; SFS=stool frequency subscore.

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 titration5

Patients in Symptomatic Responsef,g(%)
Patients in Symptomatic Response (%)
Patients in Symptomatic Remissiong,h(%)
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.1,7

  • fSymptomatic 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 from baseline.5
  • gData are based on the nonresponder imputation.5
  • hSymptomatic remission is defined as: RBS=0 point and SFS ≤1 point (and a decrease of ≥1 from the baseline SFS).5

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.6

Efficacy analyses of symptomatic response were not prespecified.6

  • gData are based on the nonresponder imputation.6
  • iSymptomatic 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 ≤1.6
  • jNonresponders 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.6

ZEPOSIA Demonstrated Mucosal Healing1

Defined by significant endoscopic-histologic
mucosal improvement1

Key Secondary Endpoints: Endoscopic Improvementk and Endoscopic-Histologic
Mucosal Improvement (EHMI)l 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
  • kEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.1
  • lEndoscopic-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
  • mThe 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.

Corticosteroid-Free Control Is Possible1

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, 71% of Patients Were in
CS-Free Remission at Week 98
(Observed Cases)2n,o

Open-Label Extension (Interim-Analysis), Observed Cases
  • Corticosteroid-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥12 weeks1
  • 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

In the NRI analysis of a subset of patients who were in clinical remission at Week 52 and who had continuous ZEPOSIA exposure, 51% (n=29/57) were in CS-free remission at Week 98 (Week 46 of OLE).2

  • cTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • dData cutoff of September 30, 2020.3
  • nData 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.3
  • oFor 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.3

Disease Control Across TNFi Subgroups1

Efficacy Observed at Weeks 10 and 521

Prespecified Subgroup Analysisp
(% 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-naïve patients at Week 10 vs TNFi-naïve 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
  • pEfficacy analysis by prior TNFi therapy was prespecified, but not powered to detect a difference in the treatment effect in these subgroups.7

Understand the Study Design

Review the
Demonstrated
Safety
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