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Safety and efficacy of dupilumab for

moderate-to-severe atopic dermatitis in

patients using topical corticosteroids

(TCS): Greater efficacy observed with

combination therapy compared to TCS

alone

Diamant

Thaçi,

Margitta

Worm,

Haobo

Ren,

Steven

Weinstein,

Neil

Graham,

Gianluca

Pirozzi,

Franck

Skobieranda,

Marius

Ardeleanu

Universität

Lübeck,

Germany;

Charite-Universitätsmedzin

Berlin,

Germany;

Regeneron

Pharmaceuticals,

Inc.,

Tarrytown,

USA;

Sanofi,

Bridgewater,

USA

Exhibit 99.1

Disclosures

D Thaçi is a consultant for Astellas, Novartis,

Regeneron, Celgene, Abbott, Pfizer, Janssen-Cilag,

MSD, Leo-Pharma

M Worm has nothing to disclose

H Ren, S Weinstein, N Graham, and M Ardeleanu are

employees and shareholders of Regeneron

G Pirozzi is an employee and shareholder of Sanofi

F Skobieranda was an employee of Sanofi when the

study was conducted

Study (NCT01639040) funded by Regeneron

Pharmaceuticals, Inc. and Sanofi

Introduction

Moderate-to-severe atopic dermatitis (AD) is characterized by

eczematous dermatitis with intractable pruritus associated with sleep

disturbance and lower quality-of-life

For many patients, current therapies are inadequate and can be

associated with unwanted side effects

IL-4 and IL-13 are thought to be central to T-helper 2 (Th2)

inflammation, which mediates many features of AD

Dupilumab is a fully human monoclonal antibody targeting the IL-4

receptor alpha subunit (IL-4R ), thus blocking the intracellular signaling

of both IL-4 and IL-13

Earlier clinical trials indicated that dupilumab monotherapy had

acceptable safety profile and was efficacious in patients with moderate

to severe AD who cannot be adequately controlled with topical

medications

Since topical corticosteroids (TCS) are commonly used in AD, we

assessed the safety and efficacy of dupilumab co-administered with

TCS

TGF-

IL-10

T cells in immune mediated diseases

IFN-

IL-2

(IL-10)

TNF-

LT-a

IL-4

IL-5

IL-10

IL-13

(TNF-

)

IL-17A

IL-17F

IL-21

IL-22

(IL-10)

(TNF-

)

RORc2

Foxp3

GATA-3

IL-22

IL-13

(IL-10)

FGF´s

(TNF-

)

ALLERGY

INFLAMMATION,

INFECTION

EPITHELIAL

INTEGRITY

LIMITATION

INFLAMMATION

Th1

Th2

Th17

Th22

iTreg

T naive

Atopic dermatitis: a disease of altered

skin barrier and immune dysregulation

Boguniewicz M, Leung DM. Immunol Rev. 2011 Jul;242(1):233-46.

Dupilumab blocks the

IL-4/IL-13 receptor/ligand system

Type I Receptor

B cells, T cells, Monocytes,

Eosinophils, Fibroblasts

Type II Receptor

Epithelial cells, Smooth muscle

cells, Fibroblasts, Monocytes,

Activated B cells

Study treatment

(weekly SC injection for 4 wks)

Dupilumab 300 mg + TCS (n=21)

Screening

Safety follow-up

(7 wks)

n=31

Randomized, double-blind, parallel-

group, placebo-controlled study

(NCT01639040) conducted in EU

Placebo + TCS (n=10)

Adult

moderate-to-

severe AD

patients

All patients received concomitant treatment

with a potent TCS product on a standardized

regimen: daily applications to active lesions,

followed by applications two days per week

once lesions were under control

Topical treatment of any

residual active AD lesions

continues at the discretion of

the investigator

Study endpoints:

•

Primary endpoint was incidence and severity of adverse events (AEs)

•

Exploratory efficacy endpoints included EASI-50, IGA

1, SCORAD score

Key inclusion/exclusion criteria

Inclusion

•

Male or female

18 yrs

•

Chronic AD > 2 yrs

•

IGA

•

SCORAD > 20

•

10% BSA of AD involvement

•

Active AD lesion(s) for which

treatment with potent TCS is

indicated

Exclusion

•

Hypersensitivity to TCS

•

50% of the cumulative lesional

surface located on face, flexural, or

genital areas (generally unsuitable

for treatment with potent TCS)

•

Acute or chronic infections

•

Recent treatment with immuno-

suppressive/immunomodulating

drugs

•

Significant co-morbidities or lab

abnormalities

Baseline demographics

Placebo + TCS

(n=10)

Dupilumab SC

300 mg +TCS

(n=21)

Mean age, yrs (SD)

37.8 (16.7)

36.0 (11.3)

Race, n (%)

Caucasian

10 (100%)

20 (95.2%)

Non-Caucasian

1 (4.8%)

Gender, n (%)

Male

5 (50.0%)

8 (38.1%)

Female

5 (50.0%)

13 (61.9%)

Mean BMI, kg/m

(SD)

23.92 (3.47)

25.26 (3.26)

Baseline disease characteristics

[mean (SD)]

Placebo + TCS

(n=10)

Dupilumab SC

300 mg +TCS

(n=21)

AD duration, yrs

32.4 (16.8)

30.9 (13.0)

EASI score (0-72)

24.10 (12.70)

23.12 (12.35)

IGA score (0-5)

3.35 (0.47)

3.43 (0.60)

SCORAD score (0-103)

58.20 (13.83)

66.31 (13.01)

% BSA of AD

38.85 (24.05)

40.43 (20.91)

Pruritus Numeric Rating

Scale (NRS) score (0-10)

5.00 (1.40)

6.43 (2.00)

EASI=Eczema Area Severity Index; IGA=Investigator’s Global Assessment; SCORAD=scoring of atopic dermatitis;

BSA = baseline body surface area; NRS=numeric rating scale

Treatment emergent adverse events

Placebo + TCS

(n = 10)

Dupilumab + TCS

(n = 21)

Total number of AEs

Total number of serious AEs

Deaths

Number (%) of patients discontinued from study

due to AE

1 (10.0%)

Number (%) of patients with:

Any AE

7 (70.0)

12 (57.1)

Any serious AE

1 (10.0)

Most

common

AEs

(

dupilumab

groups)

•

Nasopharyngitis

2 (20.0)

5 (23.8)

•

Headache

1 (10.0)

3 (14.3)

•

Oropharyngeal pain

1 (10.0)

3 (14.3)

•

Rhinitis

2 (9.5)

•

Cough

2 (9.5)

•

Influenza

2 (9.5)

•

Somnolence

2 (9.5)

Dupilumab+TCS significantly improved

measures of efficacy vs TCS alone

Placebo+TCS

300 mg DPL+TCS

Placebo+TCS

300 mg DPL+TCS

EASI-50 Responders

(Patients achieving 50%

Reduction in EASI)

Pruritus Numeric Rating Scale

100

Study Day

-80

-70

-60

-50

-40

-30

-20

-10

Study Day

*p=0.0015

**p=0.0051

DPL=dupilumab

TCS=topical corticosteroids

Placebo+TCS

300 mg DPL+TCS

Placebo+TCS

300 mg DPL+TCS

SCORAD

EASI

-50

-40

-30

-20

-10

Study Day

-20

-10

Study Day

Dupilumab+TCS significantly improved

measures of efficacy vs TCS alone

*p=0.0191

**p=0.0042

DPL=dupilumab

TCS=topical corticosteroids

Dupilumab+TCS achieved superior

clinical outcomes vs TCS alone

DPL=dupilumab

TCS=topical corticosteroids

Placebo+TCS

300 mg DPL+TCS

TCS Used Weekly (g)

Wk 1

Wk 2

Wk 3

Wk 4

*p=0.1413

Placebo+TCS

300 mg DPL+TCS

IGA Score

-3.0

-2.0

-1.0

Study Day

**p=0.0281

Summary

In this study of adults with moderate-to-severe AD, concomitant

treatment with SC dupilumab+TCS exhibited an acceptable safety

profile (primary endpoint)

–

Most common treatment-emergent AEs were nasopharyngitis (23.8% vs

20% for placebo), headache and oropharyngeal pain (both14.3% vs 10%

for placebo)

At 4 weeks, dupilumab+TCS group achieved superior clinical

outcomes compared to TCS alone (exploratory efficacy endpoints)

–

EASI-50: 100% responder rate for dupilumab +TCS, compared to 50% for

placebo+TCS

–

Significantly better improvement from baseline in EASI, SCORAD, IGA,

and pruritus NRS for dupilumab + TCS vs. Placebo + TCS

Patients on dupilumab + TCS used approximately 50% less TCS

during the treatment period compared with patients on placebo + TCS

(48.7g vs 99.4g), associated with faster clearing of active AD lesions

Acknowledgements

Marius Ardeleanu

Elisa Babilonia

Nancee Basinger

Warren Brooks

Josh Cantor

Linda Williams

Diamant Thaci

Margitta Worm

Martin Kaatz

Rolf Dominicus

Beatrice Gerlach

All participating patients

Investigators

Beate Schwarz

Noemi Bakos

Lajos Kemeny

Marcin Ambroziak

Maria Czubek

Sanofi

Tara Coughlan

Judy Cusick

Evelyn Dorsey

Kristen Dougherty

Chad Fish

Usman Chaudhry

Melissa Hager

Jennifer Hamilton

Rebecca Indibi

Richard Kao

Dan Kropas

Jacquie Kuritzky

Vicky Lai

Haobo Ren

Dawn Rich

Tara Seeliger

Regeneron

Jennifer Cairns

Jeffrey Ming

Susan

Slaytylak-Cheeks

Maris Juszkiewicz-Borowiec

Andrzej Kaszuba

Dorota Bystrzanowska

Athanasios Tsianakas

BACK UP

The march of atopic eczema

T naive

Th2

Th1

Th17

APC

Eosinophil

(Aero)allergen

acute eczema: allergen-specific

immune response

(Th2, IgE, eosinophils)

microbial products/

auto-antigens

Th2

B cell

IFN-

IL-13

IL-4

local lymph node

dermal vessel

chronic eczema: microorganisms,

auto-allergy, remodelling

(Th1, Th2,

Th17/Th22)

IL-22

IL-17

IDEC

TSLP

IgE

filaggrin

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REGENERON PHARMACEUTICALS, INC. Reports

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