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October 1st, 2016
IR THEMATIC CALL ON DUPILUMAB
1
Sanofi Forward-Looking Statements
2
This presentation contains forward-looking statements as defined in the Private Securi...
Regeneron Forward-Looking Statements
This presentation includes forward-looking statements that involve risks and uncertai...
4
Agenda
Unmet Needs in Atopic Dermatitis
● Bill Sibold – Senior Vice President, Global Franchise Head, Multiple Sclerosis...
UNMET NEEDS IN ATOPIC
DERMATITIS
5
Bill Sibold
Senior Vice President, Global Franchise Head,
Multiple Sclerosis, Oncology ...
6
Atopic Dermatitis is Characterized by Chronic or
Relapsing Inflamed Skin With Intractable Pruritus
Atopic Dermatitis (AD...
(1) Simpson EL et al, J Am Acad Dermatol. 2016;74(3):491-498
(2) Elman S et al. Br J Dermatol. 2010;162(3):587-593.
(3) Ch...
8
0
10
20
30
40
Prevalence
of fatigue
Regular
daytime
sleepiness
Insomnia
%ofpatients
Adults with AD Adults without AD
14....
There Remains an Unmet Need For Safe And Effective
Treatment Options For Patients With Moderate-to-Severe AD
9
(1) Akdis C...
32%
11%
21%
12%
17%
6%
13%
9%
5%
Manage pruritus
Reduce severity of flares
Achieve long term control
Reduce frequency of f...
A Broad Phase 3 Program in Adults
With Moderate-to-Severe AD
11
SOLO 1 Treatment period of 16
weeks
Patients inadequately
...
RESULTS FROM SOLO 1 & SOLO 2
PHASE 3 STUDIES
12
Professor Michael Cork
Head of the Academic Unit of Dermatology Research
D...
DUPILUMAB IN MODERATE-TO-SEVERE
ATOPIC DERMATITIS: RESULTS FROM TWO
RANDOMIZED PHASE 3 TRIALS (SOLO 1 & 2)
Eric L. Simpson...
Pre- And Post-Treatment: Patient Treated With
Dupilumab 300 mg Weekly
14
IGA, Investigator Global Assessment; BSA, Body Su...
Dupilumab: An Investigational IL-4/IL-13 Monoclonal
Antibody Targeting Type 2/Th2 Pathway
15
γc, common gamma chain; IL, i...
• Objective: Assess efficacy and safety of dupilumab monotherapy vs placebo in adults
with moderate-to-severe AD inadequat...
Baseline Disease Characteristics
17
SOLO 1 SOLO 2
Event
Placebo
qw
(n = 224)
Dupilumab
300 mg
q2w
(n = 224)
Dupilumab
300 ...
Co-Primary Endpoints: IGA 0 or 1 And EASI-75
Response
18
† Co-primary endpoint in EU and Japan; key secondary endpoint in ...
Pre- And Post-Treatment: Patient Treated With
Dupilumab 300 mg Weekly
19
IGA, Investigator Global Assessment; BSA, Body Su...
EASI: % Change From Baseline
20
LS, least squares; SE, standard error.
-80
-70
-60
-50
-40
-30
-20
-10
0
0 1 2 4 6 8 12 16...
Peak Pruritus NRS: % Change From Baseline
21
NRS, numerical rating scale.
-80
-70
-60
-50
-40
-30
-20
-10
0
0 2 4 6 8 10 1...
DLQI And POEM: Proportions of Patients Achieving
Improvement ≥ 4 (MCID) From Baseline at Week 16
22
DLQI, Dermatology Life...
HADS-A (Anxiety) And HADS-D (Depression):
Proportions of Patients Achieving Score < 8 at Week 16
23
1. Bjelland I, et al. ...
Adverse Events
24
SOLO 1 SOLO 2
Event
Placebo
qw
(n = 222)
Dupilumab
300 mg
q2w
(n = 229)
Dupilumab
300 mg
qw
(n = 218)
Pl...
Adverse Events Reported in ≥ 5% of Patients
in Any Treatment Group
25
SOLO 1 SOLO 2
Event*
Placebo
qw
(n = 222)
Dupilumab
...
Conclusions
• In the pivotal phase 3 studies the primary endpoints were met
• Both dose regimens of dupilumab showed clini...
NEXT STEPS WITH DUPILUMAB
27
Robert Terifay
Executive Vice President, Commercial,
Regeneron
27
Uncontrolled Moderate-to-Severe Atopic Dermatitis
Represents a Significant Unmet Need in Adults
28
Those who have failed t...
Regulatory Milestones and Next Development Steps in AD
29
The European Medicines Agency (EMA) and FDA have conditionally a...
● Pivotal Study expected to start in 1Q 2017
● 16-week trial + 12-week follow up
Dupilumab Phase 3 Development in Pediatri...
31
Dupilumab: Clinical Studies in Multiple Indications
Nasal polyposis  Phase 3 to start in Q1 2017
Eosinophilic esophagi...
32
LIBERTY ASTHMA Program: Key Dupilumab Studies
Underway
QUEST (pivotal Phase 3) TRAVERSE VENTURE
Trial
Description
Adult...
Nasal Polyps and Eosinophilic Esophagitis Clinical
Studies Progressing
33
Nasal Polyps (NP) Eosinophilic Esophagitis (EoE)...
Preparing For Launch in Atopic Dermatitis
34
● Sustained efficacy confirmed in Phase 3 studies completed in
atopic dermati...
Q&A SESSION
3535
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2016/10 – IR call – Dupilumab

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2016/10 – IR call – Dupilumab

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2016/10 – IR call – Dupilumab

  1. 1. October 1st, 2016 IR THEMATIC CALL ON DUPILUMAB 1
  2. 2. Sanofi Forward-Looking Statements 2 This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Company’s ability to benefit from external growth opportunities and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic conditions, the impact of cost containment initiatives and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2015. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.
  3. 3. Regeneron Forward-Looking Statements This presentation includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned, including without limitation dupilumab; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates and new indications for marketed products, such as dupilumab for the treatment of adult patients with inadequately controlled moderate-to-severe atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis; unforeseen safety issues and possible liability resulting from the administration of products and product candidates in patients, including without limitation dupilumab; serious complications or side effects in connection with the use of Regeneron's products and product candidates in clinical trials; coverage and reimbursement determinations by third-party payers, including Medicare, Medicaid, and pharmacy benefit management companies; ongoing regulatory obligations and oversight impacting Regeneron's marketed products, research and clinical programs, and business, including those relating to the enrollment, completion, and meeting of the relevant endpoints of post- approval studies; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates, such as dupilumab; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance and commercial success of Regeneron's products and product candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary) on the commercial success of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare LLC (or their respective affiliated companies, as applicable), to be cancelled or terminated without any further product success; and risks associated with intellectual property of other parties and pending or future litigation relating thereto. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2015 and its Form 10-Q for the quarterly period ended June 30, 2016. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. 3
  4. 4. 4 Agenda Unmet Needs in Atopic Dermatitis ● Bill Sibold – Senior Vice President, Global Franchise Head, Multiple Sclerosis, Oncology and Immunology, Sanofi Genzyme Results from SOLO 1 & SOLO 2 Phase 3 Studies ● Professor Michael Cork – Head of the Academic Unit of Dermatology Research Department of Infection and Immunity, The University of Sheffield, UK Next Steps with Dupilumab ● Robert Terifay – Executive Vice President, Commercial, Regeneron Q&A Session Dupilumab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority. 4
  5. 5. UNMET NEEDS IN ATOPIC DERMATITIS 5 Bill Sibold Senior Vice President, Global Franchise Head, Multiple Sclerosis, Oncology and Immunology, Sanofi Genzyme 5
  6. 6. 6 Atopic Dermatitis is Characterized by Chronic or Relapsing Inflamed Skin With Intractable Pruritus Atopic Dermatitis (AD) ● Characterized by intense itching and recurrent eczematous lesions ● Multifactorial etiology involving immune-mediated inflammation, genetic factors, and environmental triggers ● High negative impact on quality of life ● Although it most often starts in infancy, it is also highly prevalent in adults Image of actual patients at entry in dupilumab studies
  7. 7. (1) Simpson EL et al, J Am Acad Dermatol. 2016;74(3):491-498 (2) Elman S et al. Br J Dermatol. 2010;162(3):587-593. (3) Charman CR et al. Arch Dermatol. 2004;140(12):1513-1519. (4) Yang Y et al. Eur J Health Econ. 2015;16:927-939. ‡Assessed using EuroQol (EQ-5D).(4) AD Sufferers Often Experience Severe, Persistent Itch Characteristics and Consequences of Itch in Moderate-to-Severe AD (N = 380 patients)(1) †Assessed using the Patient-oriented Eczema Measure (POEM).(3) *Assessed using the 5-D pruritus scale.(2) Severe Frequent Long-lasting Pain Disrupted sleep experienced severe or unbearable itching*61% 86% reported daily itch symptoms† 63% reported itching at least 12 hours a day* 77% reported moderate or extreme pain or discomfort‡ 4.4 per week, on average, were interrupted by itching†nights 7
  8. 8. 8 0 10 20 30 40 Prevalence of fatigue Regular daytime sleepiness Insomnia %ofpatients Adults with AD Adults without AD 14.3 12.2 8.8 10.3 9.9 Moderate-Severe AD Atopic Eczema Psoriasis Pruritis Chronic Urticaria U.S. 2012 National Health Interview Survey(1) AD has a large impact on patient quality of life Itch leads to disturbed sleep 0 5 10 15 20 Symptoms of depression Symptoms of anxiety %ofpatients Adults with AD Adults without AD Observational cross-sectional study conducted in 13 EU countries(2) Risk of depression and anxiety increases Mean DLQI score* Dermatology Life Quality Index: AD data observed from multinational clinical study (N=380) * DLQI score range of 0 to 30; higher scores indicate a greater impact (1) Silverberg JI et al, J Invest Dermatol. 2015;135(1):56-66 (2) Dalgard FJ et al, J Invest Dermatol. 2015 Apr;135(4):984-91 (3) Lewis V et al, J Investig Dermatol Symp Proc. 2004; 9:169-180 (4) Simpson EL et al, J Am Acad Dermatol. 2016;74(3):491-498 Atopic Dermatitis Impacts More Than Just The Skin Negative Impact of AD on Quality of Life and Mental Health Is Underestimated (3) (3) (3) (4) (3)
  9. 9. There Remains an Unmet Need For Safe And Effective Treatment Options For Patients With Moderate-to-Severe AD 9 (1) Akdis CA et al. Allergy. 2006;61:969-987 (2) Guidelines by the Practical Consensus Group EAACI+AAAAI. Japanese guidelines relatively similar (3) Grundmann SA et al, J Allergy (Cairo). 2012;2012:121797, (4) Akhavan A et al. Semin Cutan Med Surg. 2008;27:151-155 (5) Eichenfield LF at al. J Am Dermatol. 2014;71:116-132 Current AD Treatment Algorithm(2) Antibiotic therapy used on frequent basis with recurrent infections (most Staph. Aureus) TCS – Topical Corticosteroids TCI – Topical Calcineurin inhibitors Systemic therapy include oral corticosteroids and immunosuppressants (mostly used off-label, with the exception of cyclosporine, which is licensed for short-term treatment of severe refractory AD in European countries). Emollients, skin hydratation Low-mid potency TCS and/or TCI + Basic treatment Mid-high potency TCS/TCI + Basic treatment Systemic or UV therapy + Mid-high potency TCS/TCI + Basic treatment antihistamines mildmoderatesevere ● Phototherapy (UV): Inconvenient and not available for all patients(3) Limitations of Currently Available Therapies ● Immunosuppressants: Long-term use associated with significant toxicities, e.g. kidney & liver toxicity, potentially impacting use(4) ● Topical corticosteroids (TCS): Long-term use can cause irreversible skin atrophic changes, and may lead to adrenal suppression(5) Treatment guidelines recommend increasing intensity of therapy as disease severity advances(1)
  10. 10. 32% 11% 21% 12% 17% 6% 13% 9% 5% Manage pruritus Reduce severity of flares Achieve long term control Reduce frequency of flares Reduce redness of lesions Reduce duration of flares Limit psychological impact Manage pain / soreness Reduce thickness of lesions Reduce sleep disruption due to AD Needs or Treatment Goals Rated by Order of Importance by Severe AD Patients (N=97)(1) (1) Source: Adelphi – Atopic Dermatitis Disease Specific Program, US 2014. ● Over 30% of patients with severe AD report managing pruritus (itch) as most important treatment goal ● Reduction of flare severity / lesion severity often comes second ● Greater emphasis on long-term control with favorable safety for severe patients Symptom Improvements and Long-term Disease Control Are Key in AD Patients’ Needs and Treatment Goals 10 Reduce frequency of flares Reduce redness of lesions Reduce duration of flares Limit psychological impact Manage pain / soreness Reduce thickness of lesions Reduce sleep disruption due to AD Most important 2nd most important 3rd most important 10
  11. 11. A Broad Phase 3 Program in Adults With Moderate-to-Severe AD 11 SOLO 1 Treatment period of 16 weeks Patients inadequately controlled with or inadvisable for topical medications 671 SOLO 2 708 SOLO- CONTINUE Treatment period of 36 weeks after completion of SOLO 1 or 2 Patients who achieved IGA 0-1 or EASI-75 at week 16 in SOLO 1 or 2 475 On-going CHRONOS Treatment period of up to 52 weeks (endpoints at 16 and 52 weeks) Patients inadequately controlled with topical medications 740 CAFÉ Treatment period of 16 weeks Severe patients only Uncontrolled or ineligible to oral CSA(2) 330 On-going OLE Open label extension for up to 3 years allowing use of topical therapy as needed Patients who participated to previous studies 2600 On-going Monotherapy 1 Concomitant administration with TCS 2 Study Design(1) Population N Status Open label extension 3 TCS – Topical Corticosteroids IGA – Investigator Global Assessment CSA – Cyclosporine A EASI – Eczema Area and Severity Index (1) All studies are randomized, double-blind, and placebo-controlled, except OLE (2) In patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable. Study conducted in EU countries and in the Russian Federation. 11
  12. 12. RESULTS FROM SOLO 1 & SOLO 2 PHASE 3 STUDIES 12 Professor Michael Cork Head of the Academic Unit of Dermatology Research Department of Infection and Immunity The University of Sheffield, UK 12
  13. 13. DUPILUMAB IN MODERATE-TO-SEVERE ATOPIC DERMATITIS: RESULTS FROM TWO RANDOMIZED PHASE 3 TRIALS (SOLO 1 & 2) Eric L. Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A. Beck, Andrew Blauvelt, Michael J. Cork, Jonathan I. Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M.H. Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D. Yancopoulos, Marius Ardeleanu 13 Slides presented at late-breaker session at EADV Congress, 2016.
  14. 14. Pre- And Post-Treatment: Patient Treated With Dupilumab 300 mg Weekly 14 IGA, Investigator Global Assessment; BSA, Body Surface Area; EASI, Eczema Area and Severity Index; NRS, Numerical Rating Scale. Baseline Week 16 Week 16: • IGA score: 1 • BSA affected: 2.5% • EASI score: 3.1 • Pruritus NRS: 1.6 Baseline: • IGA score: 4 • BSA affected: 86.5% • EASI score: 51.5 • Pruritus NRS: 7 • AD duration: 48 years Example of a patient who achieved IGA 1 in the clinical trial and is not representative of all patients. Individual results did vary. Photo used with permission.
  15. 15. Dupilumab: An Investigational IL-4/IL-13 Monoclonal Antibody Targeting Type 2/Th2 Pathway 15 γc, common gamma chain; IL, interleukin; IL-4Rα, IL-4 receptor alpha; IL-13Rα, IL-13 receptor alpha; JAK, Janus kinase; STAT, signal transducer and activator of transcription; TYK2, tyrosine kinase type 2. 15 • IL-4 and IL-13 are type 2/Th2 cytokines that are thought to mediate many features of AD • Dupilumab is a fully human monoclonal antibody directed against the IL-4Rα subunit of the IL-4 and IL-13 receptors IL-4Rα IL-4Rαγc IL-13Rα1 Type I receptor B cells, T cells, monocytes, eosinophils, fibroblasts Type II receptor Epithelial cells, smooth muscle cells, fibroblasts, monocytes, activated B cells IL-4 IL-13 • Dupilumab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority. Dupilumab
  16. 16. • Objective: Assess efficacy and safety of dupilumab monotherapy vs placebo in adults with moderate-to-severe AD inadequately controlled with or medically inadvisable for topical therapy • 671 patients in SOLO 1 and 708 patients in SOLO 2 16 SOLO 1 & SOLO 2: Pivotal Phase 3 Studies With Identical Study Design * Dupilumab, 600 mg; placebo, matching placebo. q2w, every other week; qw, weekly; R, randomization; SC, subcutaneously. Placebo SC qw Dupilumab 300 mg SC qw Post-treatment options: • Maintenance study • Open-label extension • Safety follow-up through Week 28 Screening Dupilumab 300 mg SC q2w Treatment period (16 weeks) Follow-up period (12 weeks) Loading dose on Day 1* Day –35 to –1 Baseline Week 28Week 16 R
  17. 17. Baseline Disease Characteristics 17 SOLO 1 SOLO 2 Event Placebo qw (n = 224) Dupilumab 300 mg q2w (n = 224) Dupilumab 300 mg qw (n = 223) Placebo qw (n = 236) Dupilumab 300 mg q2w (n = 233) Dupilumab 300 mg qw (n = 239) Duration of AD, median, years 28.0 26.0 26.0 26.0 24.5 24.0 BSA affected, median, % 57.0 53.4 54.5 53.3 50.0 50.0 EASI score, median 31.8 30.4 29.8 30.5 28.6 29.0 IGA score (range 0–4), % 3 (moderate) 50.4 51.8 52.5 51.3 50.6 53.1 4 (severe) 49.1 48.2 47.5 48.7 49.4 46.9 Peak pruritus NRS, median 7.7 7.6 7.7 7.7 7.8 7.8 Total SCORAD score, median 67.0 65.1 65.9 68.9 67.8 67.4 DLQI score, median 14.0 13.0 14.0 15.0 15.0 16.0 BSA, body surface area; DLQI, Dermatology Life Quality Index; NRS, numerical rating scale; SCORAD, SCORing Atopic Dermatitis.
  18. 18. Co-Primary Endpoints: IGA 0 or 1 And EASI-75 Response 18 † Co-primary endpoint in EU and Japan; key secondary endpoint in other regions. 14.7 11.9 51.3 44.2 52.5 48.1 0 10 20 30 40 50 60 70 80 SOLO 1 SOLO 2 10.3 8.5 37.9 36.137.2 36.4 0 10 20 30 40 50 60 70 80 SOLO 1 SOLO 2 * * * * * * * * * P < 0.0001 vs placebo * P < 0.0001 vs placebo EASI-75† at Week 16IGA = 0 or 1 and ≥ 2 points reduction from baseline at Week 16 Patients(%) Dupilumab 300 mg qwDupilumab 300 mg q2wPlacebo qw
  19. 19. Pre- And Post-Treatment: Patient Treated With Dupilumab 300 mg Weekly 19 IGA, Investigator Global Assessment; BSA, Body Surface Area; EASI, Eczema Area and Severity Index; NRS, Numerical Rating Scale. Baseline Week 16 Week 16: • IGA score: 1 • BSA affected: 2.5% • EASI score: 3.1 • Pruritus NRS: 1.6 Baseline: • IGA score: 4 • BSA affected: 86.5% • EASI score: 51.5 • Pruritus NRS: 7 • AD duration: 48 years Example of a patient who achieved IGA 1 in the clinical trial and is not representative of all patients. Individual results did vary. Photo used with permission.
  20. 20. EASI: % Change From Baseline 20 LS, least squares; SE, standard error. -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 6 8 12 16 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 6 8 12 16 −37.6 −30.9 −72.3* −67.1* −72.0* −69.1* * P < 0.0001 vs placebo* P < 0.0001 vs placebo SOLO 1 SOLO 2 LSmeanpercentchange inEASIfrombaseline(±SE) WeekWeek Dupilumab 300 mg qw (censored)Dupilumab 300 mg q2w (censored)Placebo qw (censored) Censored analysis categorized patients who received rescue treatment as missing data from the time of rescue, missing data were imputed by multiple imputation.
  21. 21. Peak Pruritus NRS: % Change From Baseline 21 NRS, numerical rating scale. -80 -70 -60 -50 -40 -30 -20 -10 0 0 2 4 6 8 10 12 14 16 -80 -70 -60 -50 -40 -30 -20 -10 0 0 2 4 6 8 10 12 14 16 * −15.4 −44.3* −48.3* * * P < 0.0001 vs placebo * P < 0.0001 vs placebo SOLO 1 SOLO 2 LSmeanpercentchangein peakpruritusNRSfrombaseline(±SE) WeekWeek Dupilumab 300 mg qw (censored)Dupilumab 300 mg q2w (censored)Placebo qw (censored) −26.1 −51.0* −48.9* * * Censored analysis categorized patients who received rescue treatment as missing data from the time of rescue, missing data were imputed by multiple imputation.
  22. 22. DLQI And POEM: Proportions of Patients Achieving Improvement ≥ 4 (MCID) From Baseline at Week 16 22 DLQI, Dermatology Life Quality Index; MCID, minimal clinically important difference; POEM, Patient-Oriented Eczema Measure. 30.5 27.6 64.1 73.1 58.4 62.0 0 10 20 30 40 50 60 70 80 SOLO 1 SOLO 2 26.9 24.4 67.6 71.7 63.1 64.0 0 10 20 30 40 50 60 70 80 SOLO 1 SOLO 2 * * * * * Nominal P < 0.0001 vs placebo * Nominal P < 0.0001 vs placebo * * ** DLQI POEM Patients(%) Dupilumab 300 mg qwDupilumab 300 mg q2wPlacebo qw
  23. 23. HADS-A (Anxiety) And HADS-D (Depression): Proportions of Patients Achieving Score < 8 at Week 16 23 1. Bjelland I, et al. J Psychosom Res. 2002;52:69-77. HADS, Hospital Anxiety and Depression Scale; HADS-A, HADS Anxiety subscale; HADS-D, HADS Depression subscale. Dupilumab 300 mg qwDupilumab 300 mg q2wPlacebo qw 12.4 6.1 41.0 39.5 36.3 41.2 0 10 20 30 40 50 60 70 80 SOLO 1 SOLO 2 * Nominal P < 0.0001 vs placebo † Nominal P = 0.0001 vs placebo * † * * Patients(%) • Analysis conducted in patients with clinical symptoms of anxiety or depression at baseline (i.e., HADS-A or HADS-D ≥ 8)1
  24. 24. Adverse Events 24 SOLO 1 SOLO 2 Event Placebo qw (n = 222) Dupilumab 300 mg q2w (n = 229) Dupilumab 300 mg qw (n = 218) Placebo qw (n = 234) Dupilumab 300 mg q2w (n = 236) Dupilumab 300 mg qw (n = 237) Patients, n (%) ≥ 1 AE 145 (65) 167 (73) 150 (69) 168 (72) 154 (65) 157 (66) ≥ 1 SAE 11 (5) 7 (3) 2 (1) 13 (6) 4 (2) 8 (3) Death 0 0 0 0 1 (< 1) 1 (< 1) AEs leading to treatment discontinuation 2 (1) 4 (2) 4 (2) 5 (2) 2 (1) 3 (1) Infections and infestations* 63 (28) 80 (35) 74 (34) 76 (33) 65 (28) 68 (29) Skin infections (adjudicated) 18 (8) 13 (6) 14 (6) 26 (11) 14 (6) 15 (6) Non-skin infections 49 (22) 69 (30) 67 (31) 57 (24) 58 (25) 61 (26) Herpes viral infections† 9 (4) 15 (7) 9 (4) 8 (3) 10 (4) 12 (5) * MedDRA System Organ Class. † MedDRA High Level Term. AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious AE.
  25. 25. Adverse Events Reported in ≥ 5% of Patients in Any Treatment Group 25 SOLO 1 SOLO 2 Event* Placebo qw (n = 222) Dupilumab 300 mg q2w (n = 229) Dupilumab 300 mg qw (n = 218) Placebo qw (n = 234) Dupilumab 300 mg q2w (n = 236) Dupilumab 300 mg qw (n = 237) Patients, n (%) Nasopharyngitis 17 (8) 22 (10) 25 (12) 22 (9) 20 (9) 20 (8) Conjunctivitis 2 (1) 11 (5) 7 (3) 1 (< 1) 9 (4) 9 (4) Upper respiratory tract infection 5 (2) 6 (3) 11 (5) 5 (2) 7 (3) 9 (4) Injection-site reaction 13 (6) 19 (8) 41 (19) 15 (6) 32 (14) 31 (13) Atopic dermatitis 67 (30) 30 (13) 21 (10) 81 (35) 32 (14) 38 (16) Headache 13 (6) 21 (9) 11 (5) 11 (5) 19 (8) 22 (9) Allergic conjunctivitis 2 (1) 12 (5) 7 (3) 2 (1) 2 (1) 3 (1) * MedDRA Preferred Term.
  26. 26. Conclusions • In the pivotal phase 3 studies the primary endpoints were met • Both dose regimens of dupilumab showed clinically meaningful improvement and statistical significance versus placebo in: – AD signs and symptoms (including itch/pruritus and sleep) – Health-related quality of life – Symptoms of anxiety/depression • Significant improvement in itch was observed as early as Week 2 • Most AEs were mild or moderate – Injection site reactions and conjunctivitis were more frequent with dupilumab – Overall, there were no observed increases in infections with dupilumab • Dual targeting of IL-4 and IL-13 represents a potential therapeutic option in adults with moderate-to-severe AD 26 Dupilumab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
  27. 27. NEXT STEPS WITH DUPILUMAB 27 Robert Terifay Executive Vice President, Commercial, Regeneron 27
  28. 28. Uncontrolled Moderate-to-Severe Atopic Dermatitis Represents a Significant Unmet Need in Adults 28 Those who have failed topical and eligible for systemic therapy 1 Those who have failed oral/systemic steroids 2 3 These patients face substantial burden of disease and may need new treatment options At Launch, Focus on Patient Groups with Greatest Need 28 Those who have failed and/or are intolerant to immunosuppressant therapy
  29. 29. Regulatory Milestones and Next Development Steps in AD 29 The European Medicines Agency (EMA) and FDA have conditionally accepted Dupixent® as the trade name for dupilumab. TCS – Topical corticosteroids BLA – Biological license application ● Positive Phase 3 data when administered in monotherapy (SOLO 1, SOLO 2) and concomitantly with TCS (CHRONOS) ● Clinically meaningful and significant improvements in skin clearing (IGA scores) disease severity (EASI scores) and symptoms (pruritus NRS) ● Favorable safety profile ● Most common adverse events in the dupilumab groups, compared to placebo, were injection site reactions and conjunctivitis ● Designation as Breakthrough Therapy in adult AD indication in the U.S. and as Promising Innovative Medicine in the UK ● BLA accepted for priority review by the FDA with an action date of March 29, 2017 ● EU and Japan submission expected in Q4 2016 ● CONTINUE and CAFÉ studies ongoing ● Phase 3 pediatric studies in AD and in asthma to begin in 2017 DUPIXENT®
  30. 30. ● Pivotal Study expected to start in 1Q 2017 ● 16-week trial + 12-week follow up Dupilumab Phase 3 Development in Pediatric AD Will be by Successive Age Groups 30 ● Pivotal Study expected to start in H1 2017 ● 16-week trial + 12-week follow up ● Pivotal Study expected to start in 2018 ● 16-week trial + 12-week follow up Adolescents 12-17 years 6-11 years 6 months to 5 years
  31. 31. 31 Dupilumab: Clinical Studies in Multiple Indications Nasal polyposis  Phase 3 to start in Q1 2017 Eosinophilic esophagitis  Phase 2 ongoing Asthma  Phase 3 fully enrolled Atopic dermatitis  Phase 3, March 29 FDA Action Date Additional Indications Type 2, including Th2-mediated diseases DUPILUMAB
  32. 32. 32 LIBERTY ASTHMA Program: Key Dupilumab Studies Underway QUEST (pivotal Phase 3) TRAVERSE VENTURE Trial Description Adult and adolescent (>12 years) patients with persistent asthma inadequately controlled by ICS + second controller Long-term safety/tolerability in severe uncontrolled asthmatic patients who participated to previous dupilumab studies Evaluating reduction in use of OCS in adult and adolescent patients (>12 years) with severe steroid-dependent asthma Target N 1638 2082 150 Length of Trial 69 wks (5-wk screening + 52-wk treatment + 12-wk follow-up) 112 wks (96-wk treatment + 12- wk follow-up) 46 wks (10-wk screening + 24-wk treatment + 12-wk follow-up) Active Treatment Arms • Loading Dose (400 mg) + 200 mg Q2W • Loading Dose (600 mg) + 300 mg Q2W • Loading Dose (400 mg) + 200 mg Q2W • Loading Dose (600 mg) + 300 mg Q2W • Loading Dose (600 mg) + 300 mg Q2W Primary Endpoint Severe exacerbation events over 52 weeks and FEV1 change at week 12 Number of AEs at week 112 Change in OCS dose at week 24 Fully enrolled OCS – oral corticosteroids FEV1 – Forced expiratory volume in one second AEs – Adverse events sBLA – supplemental BLA sBLA in asthma indication will include results from Phase 2b study and LIBERTY ASTHMA QUEST 2nd sBLA Filing in AsthmaInitial sBLA Filing
  33. 33. Nasal Polyps and Eosinophilic Esophagitis Clinical Studies Progressing 33 Nasal Polyps (NP) Eosinophilic Esophagitis (EoE) (1) Bachert C et al, JAMA 2016;315(5):469-79 (The study included 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids) NP is a disease characterized by symptoms related to inflammation of the upper airways with obstruction of the sinus and nasal passages ● Positive Phase 2 trial reported(1) ● Phase 3 study expected to begin in early 2017 EoE is a chronic disease characterized by symptoms related to esophageal dysfunction and eosinophilic-predominant inflammation ● Proof-of-concept, Phase 2 trial underway
  34. 34. Preparing For Launch in Atopic Dermatitis 34 ● Sustained efficacy confirmed in Phase 3 studies completed in atopic dermatitis ● Unique mechanism of action; potentially the first monoclonal antibody to launch in atopic dermatitis ● Sanofi’s Specialty Care Business Unit (Sanofi Genzyme) and Regeneron preparing for launch ● Sanofi and Regeneron to co-promote in the U.S. ● Major presence at congresses, including EADV ● Comprehensive patient support program
  35. 35. Q&A SESSION 3535

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