ged-0301 webcast - final - 10.18 · 2019. 8. 22. · ged-0301-cd-001: trial design • 63 patients...

GED-0301 WebcastOctober 18, 2016

Forward Looking Statements and Adjusted Financial Information

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This presentation contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans,” “will,”“outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates,assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update anyforward-looking statement in light of new information or future events, except as otherwise required by law. Forward-lookingstatements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond ourcontrol. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result ofthe impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and ourother reports filed with the Securities and Exchange Commission.

In addition to unaudited financial information prepared in accordance with U.S. GAAP, this presentation also containsadjusted financial measures that we believe provide investors and management with supplemental information relating tooperating performance and trends that facilitate comparisons between periods and with respect to projectedinformation. These adjusted measures are non-GAAP and should be considered in addition to, but not as a substitute for, theinformation prepared in accordance with U.S. GAAP. We typically exclude certain GAAP items that management does notbelieve affect our basic operations and that do not meet the GAAP definition of unusual or non-recurring items. Othercompanies may define these measures in different ways. Further information relevant to the interpretation of adjustedfinancial measures, and reconciliations of these adjusted financial measures to the most comparable GAAP measures, maybe found on our website at www.Celgene.com in the “Investor Relations” section.

Agenda

Welcome / Introduction Scott Smith

CD-001 Interim Topline Results William Sandborn, MD

GED-0301 Data Overview & Development Program Updates Peter Callegari, MD

Next Steps Scott Smith

Q&A

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Advancing Development of GED-0301;Timelines on Track for Approval in 2019

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UC-002: Ulcerative Colitis POC (n=41)

UC-002: Ulcerative Colitis POC (n=41)

CD-002: 52 Week Pivotal Ph III (n=1,064)

CD-002: 52 Week Pivotal Ph III (n=1,064)

CD-003: 12 Week Pivotal Ph III (n=798)

CD-003: 12 Week Pivotal Ph III (n=798)

CD-001: Exploratory Ph Ib (n=63)

CD-001: Exploratory Ph Ib (n=63)

2015 2016 2017 2018 2019

Approval

CD-005: PD (n=20)CD-005:

PD (n=20)

CD-004: Long Term Extension (n~1,400)

CD-004: Long Term Extension (n~1,400)

CD-001 Conducted to Enhance Understanding of GED-0301 Activity and Potential Applications

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Objective: To explore signs of endoscopic improvement and clinical activity in a difficult-to-treat, moderate-to-severe Crohn’s patient population with confirmed endoscopic inflammation at baseline, including but not limited to:

• Both TNF-naïve and prior TNF-exposed patient population• Prior surgeries• Proximal and distal disease

All patients had significant clinical and endoscopic disease at entry and spanned a broader geography

CD-001 Study OverviewCD-001 Study Overview

CD-001 Interim Topline ResultsWilliam Sandborn, MDChief, Division of Gastroenterology Director, UCSD Inflammatory Bowel Disease CenterProfessor of Clinical Medicine, UC San Diego

A Randomized, Double-blind, Multicenter Study to Explore the Efficacy of Oral GED-0301 (Mongersen) on Endoscopic Activity and Clinical Effects in Both TNF-Naive and TNF-Experienced Subjects With Active Crohn’s DiseaseBrian G. Feagan1, Bruce E. Sands2, Guillermo Rossiter3, Xiaobin Li3, Keith Usiskin3, Xiaojiang Zhan3, Jean-Frédéric Colombel2

1Robarts Clinical Trials and University of Western Ontario, London, Ontario, Canada; 2Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Celgene Corporation, Summit, NJ, USA

ClinicalTrials.gov: NCT02367183. This study was sponsored by Celgene Corporation.7

GED-0301 (Mongersen) Overview

• GED-0301 (mongersen) is an antisense oligodeoxynucleotide that is complementary to the sequence of the messenger ribonucleic acid transcript of Smad7

• It is formulated as a delayed-release, pH-dependent tablet designed to deliver the active substance in the distal GI tract with negligible systemic exposure

• Positive clinical results demonstrated in a phase 2 dose-ranging study in patients with active Crohn’s disease1

–Assessed 10mg, 40mg and 160mg doses relative to placebo

• GED-0301 is being evaluated for the treatment of patients with active Crohn’s disease and in patients with ulcerative colitis

1. Monteleone G, et al. N Engl J Med. 2015;372:1104-1113.8

GED-0301-CD-001: Trial Design

• 63 patients were enrolled from 23 sites in the United States, 4 sites in Canada, 4 sites in Australia, and 3 sites in Slovakia

Double-blind Induction Phase

Week 0 BL* Week 4 Week 8 Week 12

RA

ND

OM

IZE*

(1:1

:1)

Endoscopy Endoscopy

160 mg GED-0301 4 Weeks

160 mg GED-0301 12 Weeks

160 mg GED-0301 8 Weeks Placebo

Placebo

*Randomization stratified by distal colon involvement (yes/no) and prior biologic exposure (yes/no).

Observation phase (up to 52 weeks) followed

by extension phase (100

weeks) 160 mg(4 weeks GED/

4 weeks no GED)

9

Eligibility Criteria

• Key inclusion criteria–Active CD, defined as CDAI score ≥220 and ≤450 –Ileal, colonic, or ileocolonic CD–SES-CD score ≥7 at screening; SES-CD ≥4 (patients with ileitis only)–Therapeutic failure or intolerance to ≥1 of the following: aminosalicylates,

budesonide, systemic corticosteroids, immunosuppressants, or TNF-α antagonists

• Key exclusion criteria–Crohn’s colitis restricted to the left colon or complications of CD–Surgical resection within past 6 months/ intra-abdominal surgery within past 3

months–Prior treatment with >2 TNF-α antagonists or any prior treatment with integrin

antagonists

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Study Objectives

• Primary objective–Endoscopic outcomes with GED-0301 as measured by SES-CD

• Secondary objectives–Clinical activity of GED-0301 as measured by CDAI score–Safety and tolerability of GED-0301

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Baseline Demographics and Disease Characteristics

ITT PopulationTotalN=63

Age, mean (SD), y 41.5 (15)

Female, % 54

Duration of CD, mean (SD), y 11.6 (13)

Disease inclusive distal to mid transverse colon, % 46

TNF-α antagonist exposed, % 46

Corticosteroids,% 25

CDAI score, mean 294

SES-CD (central), mean 11.2

12

Patient Disposition

Note: 52 patients had an evaluable postbaseline endoscopy at Week 12.

Total Completed 54 (86%)

N=63

n=19

Discontinued 4Adverse event 2Lack of efficacy 1Withdrawal by patient 1

n=23


n=21


4 Weeks

Completed 15 (79%) Completed 20 (87%) Completed 19 (91%)

8 Weeks 12 Weeks

GED-0301 Treatment Group

13

-160

-140

-120

-100

-80

-60

-40

-20

0

Mea

n C

hang

e Fr

om B

asel

ine

in C

DA

I Sco

re†

CDAI Mean Change From Baseline Through Week 12Data From All Treatment Groups

Study Week8 122 40

-133

*

**

**P<0.0001

Note: sample size reflects number of patients on treatment at observation timepoint*CDAI mean change from baseline at Week 12 was determined in the intent-to-treat population using the last-observation-carried-forward methodology.

Bars indicate standard error.

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Clinical Response at Week 12

5344

67

0

10

20

30

40

50

60

70

80

90

100


4 Weeks 8 Weeks 12 Weeks(N=19) (N=23) (N=21)

Patie

nts

Ach

ievi

ng C

linic

al

Res

pons

e* (%

)

Bars indicate 95% CIs.*Response (CDAI decrease from baseline ≥100) at Week 12 was determined using the non-responder imputation methodology.15

Clinical Remission at Week 12

3235

48

0

10

20

30

40

50

60

70

80

90

100


4 Weeks 8 Weeks 12 Weeks(N=19) (N=23) (N=21)

Patie

nts

Ach

ievi

ng C

linic

al

Rem

issi

on* (

%)

Bars indicate 95% CIs.*Remission (CDAI <150 ) at Week 12 was determined using the non-responder imputation methodology.16

CDAI Remission by Subgroup at Week 12

Strong clinical improvement seen regardless of severity or location of diseaseBars indicate 95% CIs.*Remission (CDAI <150) at Week 12 was determined in all patients regardless of randomized group using the non-responder imputation methodology. †All patients had right sided disease (ileum and/or right colon). Patients with CD that included involvement distal to the midtransverse colon.

Patie

nts

Ach

ievi

ng

Clin

ical

Rem

issi

on* (

%)

Patie

nts

Ach

ievi

ng

Clin

ical

Rem

issi

on* (

%)

4630

0

20

40

60

80

Baseline CDAI ≤300 Baseline CDAI >300

43 30

0

20

40

60

80

Baseline SES-CD ≤12 Baseline SES-CD >12

50

24

0

20

40

60

80

TNF-α antagonist naive TNF-α antagonist exposed

4431

0

20

40

60

80

Proximal disease only Proximal and distal disease

18/42 6/20 7/2917/34

15/33 9/30 15/34 9/29

Endoscopic Severity TNF-α Antagonist Exposure

Clinical Severity Extent of Disease

†

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Endoscopic Response at Week 12:SES-CD Reduction by ≥25% and ≥50%

• Two patients had endoscopic remission (SES-CD ≤2) at Week 12– Both patients had SES-CD score of 0 at Week 12

*Data as observed.

SES-CD Reduction by ≥25%

All Evaluable Patients

Baseline SES-CD >12

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63

0

20

40

60

80

100

Patie

nts

Ach

ievi

ng E

ndos

copi

c R

espo

nse*

(%)

19/52 10/16n/N=

15

31

0

20

40

60

80

100

8/52 5/16n/N=

SES-CD Reduction by ≥50%

All Evaluable Patients

Baseline SES-CD >12

Patie

nts

Ach

ievi

ng E

ndos

copi

c R

espo

nse*

(%)

Bars indicate 95% CIs.18

43

29

0

20

40

60

80

TNF-α antagonist naive TNF-α antagonist exposed

12/28 7/24

TNF-α Antagonist Exposure

Endoscopic Response: SES-CD Reduction by ≥25% by Subgroup

†Patients with CD that included involvement distal to the mid transverse colon. All patients had right-sided disease (ileum and/or right colon).

Patie

nts

Ach

ievi

ng E

ndos

copi

c R

espo

nse*

(%)

Patie

nts

Ach

ievi

ng E

ndos

copi

c R

espo

nse*

(%)

*Data as observed.

3242

0

20

40

60

80

Proximal disease only Proximal and distal disease

10/249/28

Extent of Disease

†

Bars indicate 95% CIs.

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Change in Overall FCP and hsCRP in Patients With Elevated Baseline Levels

Baseline value: 19.85Baseline value: 1401.00

-16.6-21.95

-10.2

-50

-40

-30

-20

-10

0

10

20

30

40

50

Week 4Week 8Week 12

Med

ian

Perc

ent C

hang

e Fr

om B

asel

ine*

hsCRP ≥10 mg/L at BL

-24.85

-39.85

-31.4

-50

-40

-30

-20

-10

0

10

20

30

40

50

Week 4Week 8Week 12

Med

ian

Perc

ent C

hang

e Fr

om B

asel

ine†

FCP >250 mg/kg at BL

*95% CI excludes 0

Data From All Treatment Groups

†Median percent change from baseline determined using the last-observation-carried-forward methodology.

-16.60

-10.20

-31.40

20


Safety Population, n (%)4 Wksn=19

8 Wksn=23

12 Wksn=21

TotalN=63

≥1 AE 13 (68) 16 (70) 12 (57) 41 (65)

Drug-related AEs 3 (16) 4 (17) 2 (10) 9 (14)

AEs leading to discontinuation 2 (11) 1 (4) 1 (5) 4 (6)

Serious AEs 1 (5) 1 (4) 1 (5) 3 (5)

Deaths 0 0 0 0

Overview of Adverse Events

• Most treatment-emergent AEs were in the gastrointestinal system organ class, likely related to CD• There were few serious AEs; they were balanced across treatment groups*• Negligible systemic exposure verified at Weeks 4, 8, and 12

*One drug-related SAE; intestinal obstruction/perforation at Day 15 in a patient with a history of terminal ileum stricture by CT who had significant baseline ileal stenosis. 21

Conclusion

• The patient population in the current study had significant disease by both clinical and endoscopic criteria

–Both TNF-α antagonist naive and exposed patients –All patients had right-sided disease with 46% also having distal disease

• Increasing clinical improvement (response and remission) was seen over time, with the GED-0301 12-week treatment group demonstrating greater efficacy

• Oral GED-0301 (mongersen) resulted in meaningful endoscopic improvement at an early time point

• No specific safety signals were identified

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Peter Callegari, MDCVP, Global Medical Affairs, Celgene I&I

GED-0301 Data Overview & Development Program Updates

CD-001 Interim Results Provide Compelling Early Signal of GED-0301 Efficacy

Key Findings

Signs of remission and response seen across a broader geography, in a more heterogeneous and difficult-to-treat patient population

Signs of endoscopic improvement with greater reduction seen in patients with more extensive baseline disease

Activity seen using established clinical efficacy measures and biomarkers important in IBD

Safety and tolerability consistent with previous trials

Negligible systemic exposure observed to date

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Disease Control Important to Achieve Earlier in Treatment, Enabling Endoscopic Improvement to Occur in Longer Term

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0-3 months: 6 months: 12 months +

• Clinical remission• Symptom control• No worsening of disease• Early endoscopic

improvement

Objectives

Endpoints• CDAI remission (< 150) • CDAI reduction ≥ 100 • Stool Frequency ≤ 3 AND

Abdominal Pain ≤ 1 • SES-CD reduction ≥ 25%*

• Ongoing clinical remission• Continued endoscopic

improvement

• CDAI < 150 • SES-CD reduction ≥ 50%

• Endoscopic remission• Durability of response• Steroid free remission

• SES-CD ≤ 2• CDAI < 150 • SES-CD reduction ≥ 50%

*If endoscopy not available, biomarkers (fecal calprotectin, CRP) may provide surrogate for endoscopic efficacy

Treatment Goals in Crohn’s Disease

Significant Evolution in Approach to Assessing Efficacy in Crohn’s Disease Trials

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Earlier CD StudiesBaseline Characteristics:• Disease magnitude

Active disease as defined by CDAI• BIO naïve • Shorter disease duration

Treatment Goal:• CDAI remission/response• Steroid-free remission

Newer CD StudiesBaseline Characteristics:• Disease magnitude

– Active disease defined by CDAI or other PROs AND– Endoscopically confirmed disease of defined magnitude

• BIO naïve and refractory• Longer disease duration

Treatment Goal:• CDAI remission* (or patient Reported Outcomes,

i.e., AP and SF)• Endoscopic remission*• Sustained remission• Steroid-free remission

Evolution of Crohn’s Disease Clinical Trials

Different populations studied (disease severity, previous therapies, surgical history, etc), inclusion criteria (even endoscopic inclusion criteria or the lack of endoscopic assessment), endpoints (clinical and endoscopic) all point to the challenge of any cross trial comparisons

2005(SONIC)

Present(CD-001)

1998(Remicade® Approval)

*Endpoints critical for registration; AP and SF=abdominal pain and stool frequency

Study CD-002: 52 Week Pivotal Treat-Through

Phase III Registration Trial Design

27

Week 12 Week 52

Randomization 1:1:1:1

GED 160mg – 4 weeks on/ 4 weeks off

GED 40mg – daily

GED 40 mg – 4 weeks on/ 4 weeks off

Placebo

Primary endpoint

Stratified by concomitant use of corticosteroids,

immunosuppressants and by prior biologic use Secondary endpoint

GED 160mg (n=266)

GED 160mg (n=266)

GED 160mg (n=266)

Placebo (n=266)

Screening

Patient Population: moderate to severe active CD– Adults with CD for at least 3 months prior to screening– Active CD, defined as CDAI ≥ 220 and ≤ 450– SES-CD ≥ 6 (SES-CD ≥ 4 if ileitis only)– Failed or intolerant to a previous therapy for CD: budesonide, systemic corticosteroids, immunosuppressants or biologics

Primary Endpoint : Proportion of subjects achieving clinical remission (AP and SF improvement – US; CDAI score < 150 – EU) at Week 12

Key Secondary Endpoints: Endoscopic remission at Week 52; clinical remission at Week 52

CD-003 (confirmatory pivotal): 12 weeks of active treatment; includes adult and adolescent patients

Week 0

Footnote: AP and SF=abdominal pain and stool frequency

GED-0301 – A Potentially Transformational Profile

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Clinical Response and Remission


Once-dailyOral DosingOnce-daily

Oral Dosing

Negligible Systemic Exposure


Endoscopic ImprovementEndoscopic

Improvement

Evidence demonstrated in IGON program

Efficacy in TNF-exposed PatientsEfficacy in TNF-

exposed Patients

Rapid Onset of Clinical EfficacyRapid Onset of

Clinical Efficacy

Efficacy in Left-sided Disease


Long-term Endoscopic Remission


To be assessed in future trialsLegend:

GED-0301

AEs and SAEs Similar to Placebo


GED-0301 – A Potentially Transformational Profile

29



Once-dailyOral DosingOnce-daily

Oral Dosing



Endoscopic ImprovementEndoscopic

Improvement

Evidence demonstrated to-date

Efficacy in TNF-exposed PatientsEfficacy in TNF-

exposed Patients

Rapid Onset of Clinical EfficacyRapid Onset of

Clinical Efficacy





To be assessed in future trialsLegend:

GED-0301



Scott SmithPresident, Global I&I

Next Steps

Potential for GED-0301 to Change IBD Treatment Paradigm

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GED-0301• Clinical improvement seen in difficult-to-

treat patients with endoscopic proven disease across variety of patient types

• Negligible systemic exposure

• Convenient regimen with oral dosing

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New data enhance emerging differentiated

benefit/risk profile

GED-0301 has the potential to transform the treatment

of Crohn’s disease

Extracellular Pathways Intracellular Pathways

Advancing Development of Industry-Leading IBD Product Portfolio

Celgene is currently investigating three agents with distinct mechanisms of action for the treatment of Crohn’s disease and ulcerative colitis

S1P1,5R ModulationRegulation of Lymphocyte Trafficking

SMAD7 Antisense Restoration of TGF-β Mediated Anti-

inflammatory Response

PDE4 Inhibition Modulation of Pro-and Anti-Inflammatory Cytokines

OzanimodOzanimodGED-0301GED-0301 OTEZLA®OTEZLA®

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CD-00312-Week Crohn’s Confirmatory

Pivotal

Multiple Data Readouts from Celgene’s IBD Program

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2016 2017 2018

Crohn’s Phase II

UC-002Ulcerative Colitis Proof of Concept

CD-001 Crohn’s Phase Ib -Treatment Phase

GED-0301

ozanimod

GED-0301

CD-001Crohn’s Phase Ib - Observation

Phase

GED-0301CD-002

52-Week Crohn’s Treat Through Pivotal

GED-0301

GED-0301

Ulcerative Colitis Phase IIIPivotal

ozanimod

UC-001Ulcerative Colitis Proof of Concept

Preparing for Upcoming Cascade of Global Launches for Celgene I&I

Significant Growth through 2020 and beyond

OTEZLA®

PsA / Psor2014

OzanimodRMS

2018E

OzanimodUC

2019E

GED-0301CD

2019E

Multiple Blockbuster Products Expected in I&I

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GED-0301 WebcastOctober 18, 2016

ged-0301 webcast - final - 10.18 · 2019. 8. 22. · ged-0301-cd-001: trial design • 63 patients...

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