r&d Day Show Am v3

7/24/2019 r&d Day Show Am v3

1/102


2/102

GROWTH PHARMA


3/102

SAUNDERSBRENT

Chief Executive Officer and President


4/102

Customer Intimacy is Critical

CUSTOMER

Private

Companies VentureCapital

Regional

Players

PrivateEquity

Start-Ups

IDEAS

PATIENTS

DevelopmentPowerhouse

CommercialMachine

BusinessDevelopment

TherapeuticArea

Leader


5/102

SOURCE: Evaluate1 Excludes generics; Botox sales allocated by TA/Indication into Dermatology & Aesthetics, CNS, and Urology

2015 revenue1

Customer Intimacy & Therapeutic Area LeadershipDrive Commercial Success

Top Brands

global positionDermatology &

Aesthetics $2.1

global positionEye Care $3.0

in Alzheimers

#3 global positionCNS

$2.7

global position

#2 in anti-inflammatoriesGI $1.2

in US

Plan to double presence by 2020Womens Health $1.0

global positionUrology $0.4

Anti-infectiveUS leadership position

2 new breakthrough product launches$0.2

Sales ($B)

1

2

1

3

1

6

1

Ranking


6/102

SOURCE: Thomson Reuters, PitchBook database

A New Pharmaceutical Innovation EcosystemFueled by Significant Investments

500

1,000

1,500

2,000

2,500

3,000

3,500

0

0.51.1

1.6

2.2

2.7

3.3

3.8

4.34.9

5.4

6.0

6.5

Venturecapitalinvested,

$B

Numberofbiotech

startups

20102000 20051995 2014

Sustainability: Continued

VC funding

Scientificcreativity

Professionalmanagement


7/102

Revenues of all NME-grade compounds launched in a given year cumulated for 7-8 years. Includes all innovative compounds classified as NME or BLA, excludinggenerics, biosimilars and NDA products (new derivatives, new formulations etc.)SOURCE: Evaluate 2014

Pharma Innovation EcosystemSource of NMEs by originator type

14%Biotech & Start-upCompanies

24%Regional PharmaNon-profit AcademiaSpecialty

ACADEMIA

SPECIALTY

GLOBALPHARMA

BIOTECH &START-UPS

REGIONALPHARMA62%

Global Pharma

1998


8/102

22%Global Pharma

Evaluate Jul 20 Revenues of all NME-grade compounds launched in a given year cumulated for 7-8 years. Includes all innovative compounds classified as NME orBLA, excluding generics, biosimilars and NDA products (new derivatives, new formulations etc.)SOURCE: Evaluate 2014 14; McKinsey analysis

Pharma Innovation Ecosystem

50%Biotech & Start-upCompanies

ACADEMIA

SPECIALTY

GLOBALPHARMA

BIOTECH &

START-UPS

REGIONALPHARMA

28%Regional PharmaNon-profit AcademiaSpecialty

Source of NMEs by originator type

2013


9/102

New

ACADEMIA

GLOBALPHARMA

BIOTECH &START-UPS

REGIONALPHARMA

SPECIALTY

Pharma Innovation Ecosystem

TODAY


10/102

We discover, acquire, partner and collaborate on compounds at all stages of R&D with a strong preference for validated targets or compounds with proof of concept.

Allergan ModelDISCOVERY DEVELOPMENT COMMERCIALIZATION

CGRPs

Ozurdex

Latisse

Avycaz

Linzess

Kybella

XEN45

Bimatoprost SR

Restasis X

Abicipar

RelamoralinKYTH-105

JuvedermBotox

AGN-241660

Rapastinel

SER 120

Esmya

NebivololVraylarBystolic/Valsartan

Viberzi

Dalvance

OD-01

CUSTOMER

Teflaro

Combigan


11/102

SOURCE: Evaluate; Capital IQ1 Based on 2014 R&D spend/revenue and % of clinical non-generic NME, NDA, and biologic pipeline assets that are non-organic

Allergan is a Forerunner in

Low High

% pipeline externally sourced1

Low

High

R&D/

Sales1

Open science

Low-cost

Traditional


12/102

SOURCE: Evaluate; FDA; Press search1 Includes new fixed-dose combinations and co-developments2 NDA/NME approval time for assets with projected 2020 sales in Allergan-relevant TAs

Allergan Ranks Among the Top Development

PowerhousesNumber of NME/BLAapprovals 2009-2015 YTD

Average time between submissionof drug and approval (months)2

113

16


13/102

SOURCE: Evaluate1 Aesthetics & Derm, Eye Care, Urology, GI, Anti-infectives, CNS

is Sustainable:Approximately Half of All Phase 2 & Phase 3 Programs Are in Allergan TAs

Phase 2

1,026

Gastro-Intestinal

827

Respiratory

Phase 3

Oncology &Immunomodulators

Phase 1

Blood/CV/Endocrine

Central Nervous System

Systemic Anti-infectives

Urology/Derm/Eye

571

Allergan relevant TAs

Other TAs33%

45%49%

TA pipeline assets in each clinical phase (%); total of ~2400 assets


14/102

SOURCE: McKinsey survey

We have the profile for partnering a key to open science

We Have the Profile for Partnering

A Key to

Expected

Execution

Speed

ExecutiveLeadership

Manufacturing

SharedVision

PriorRelationship

Legal

Research

DevelopmentPowerhouse

CommercialEngine

OpenMindset


15/102

21

Aesthetics &Dermatology

OxymetazolineRosacea

Aczone ReformAcne Vulgaris

Sarecycline

Acne

JuvedermGlobal NasalLabial Folds

VobellaLips Fine Lines

BotoxForeheadLines

VoliftNasolabial Folds

VolumaFiller for Temple

Voluma PlusFacial Volumes

Voluma GlobalMalar Augmentation

PhoenixBreast Augmentation

VoLiteFiller

VolumaFiller for Chin

OxybutyninHyperhidrosis

BimatoprostAndrogenic

Alopecia

MT10109LAesthetics

Facial Lines

HA ThreadsForehead & Neck

Skin Quattro DeviceDelivery for

Facial Fillers

Aczone ComboAcne Vulgaris

SetipiprantAndrogenic Alopecia

BimatoprostSubmental Fat Reduct 17

EyeCare

Tripligan(MMT) Ocular HTN & Glaucoma

FPR2Agonist Dry Eye Disease

MimetogenDry Eye

Bimatoprost SRGlaucoma

GanfortMDPF

RestasisMDPF

Omega 3 OTCDry Eye

Pilo/OxyPresbyopia

Cortisol AnalogDry Eye Disease

Brimo DDSAtrophic AMD

AndrogenEvaporative Dry Eye

Cyclosporine SRDry Eye

DARPinDME

Dual DARPinAMD

DARPinSRAMD

OCU Tearbud 1Dry Eye

Women s Health

4 EstradiolVaginal Cream VVA& Dyspareunia

UlipristalFibroids

EstradiolVag Caps VVA

& Dyspareunia

Etonogestral RingContraception

GI

LinzessOIC

LinzessColonic

Release CIC

LinzessLow Dose CIC

ViberziIBS-D

9CNS

RapastinelMDD

AGN-241689Migraine

Prophylaxis

UbrogepantAcuteMigraine

BotoxMDD

Vraylar Multiple

SempranaAcute Migraine

Vraylar Bipolar Depression

Botox X

Spasticity

AGN-241660MDD

9

Biosimilar XIndication X

AvycazcUTI, cIAI

5

Anti-Infective

DalbavancinOsteomyelitis

DalbavancinEndocarditis

Dalbavancin ABSSSISingle Dose

Nebivilol/ValsartanHypertension

BotoxMultiple

BevacizumabMultipleCancer

CetuximabMultiple

Cancer

TrastuzumabMultipleCancer

RituximabNon-Hodgkin

Lymphoma

TRV-027Acute Heart Failure

Armour ThyroidHypothyroidism

Other(Biosimilars, Cardiovascular

and other)

5

Urology

4BotoxPremature

Ejaculation

LiRISInterstitial

Cystitis

SER-120Adult Nocturia

BotoxIndication X

DARPinAMD

RelamorelinDiabetic

GastroparesisAztreonam /AvibactamGram Neg Infect


16/102

DAVIDNICHOLSON

Executive Vice President,Brand R&D


17/102

21




Sarecycline

Acne

JuvedermGlobal NasalLabial Folds

VobellaLips Fine Lines

BotoxForeheadLines

VoliftNasolabial Folds

VolumaFiller for Temple

Voluma PlusFacial Volumes

Voluma GlobalMalar Augmentation

PhoenixBreast Augmentation

VoLiteFiller

VolumaFiller for Chin

OxybutyninHyperhidrosis


Alopecia

MT10109LAesthetics

Facial Lines

HA ThreadsForehead & Neck

Skin Quattro DeviceDelivery for

Facial Fillers

Aczone ComboAcne Vulgaris


BimatoprostSubmental Fat Reduct 17

EyeCare

Tripligan(MMT) Ocular HTN & Glaucoma

FPR2Agonist Dry Eye Disease

MimetogenDry Eye

Bimatoprost SRGlaucoma

GanfortMDPF

RestasisMDPF

Omega 3 OTCDry Eye

Pilo/OxyPresbyopia

Cortisol Analog

Dry Eye Disease

Brimo DDSAtrophic AMD

AndrogenEvaporative Dry Eye

Cyclosporine SRDry Eye

DARPinDME

Dual DARPinAMD

DARPinSRAMD


Women s Health

4 EstradiolVaginal Cream VVA& Dyspareunia

UlipristalFibroids

EstradiolVag Caps VVA

& Dyspareunia

Etonogestral RingContraception

GI

LinzessOIC

LinzessColonic

Release CIC

LinzessLow Dose CIC

ViberziIBS-D

9CNS

RapastinelMDD

AGN-241689Migraine

Prophylaxis


BotoxMDD

Vraylar Multiple



Botox X

Spasticity

AGN-241660MDD

9


AvycazcUTI, cIAI

5

Anti-Infective

DalbavancinOsteomyelitis

DalbavancinEndocarditis



BotoxMultiple

BevacizumabMultipleCancer

CetuximabMultiple

Cancer

TrastuzumabMultipleCancer

RituximabNon-Hodgkin

Lymphoma

TRV-027Acute Heart Failure



and other)

5

Urology

4BotoxPremature

Ejaculation

LiRISInterstitial Cystitis


BotoxIndication X

DARPinAMD

RelamorelinDiabetic

GastroparesisAztreonam /AvibactamGram Neg Infect


18/102

21




Sarecycline

Acne


Alopecia


17

EyeCare

RestasisMDPF

Pilo/OxyPresbyopia

DARPinDME


Women s Health

4UlipristalFibroids

GIViberzi

IBS-D

9CNS

RapastinelMDD

AGN-241689Migraine

Prophylaxis


Vraylar Multiple


AGN-241660MDD

9

AvycazcUTI, cIAI

5

Anti-Infective


and other)

5

Urology

4


DARPinAMD

RelamorelinDiabetic

Gastroparesis


19/102

9



Botox

Multiple

Bevacizumab

Multiple Cancer

CetuximabMultiple Cancer

TrastuzumabMultiple Cancer

RituximabNon-Hodgkin Lymphoma

TRV-027 Acute Heart Failure


Other(Biosimilars, Cardiovascular and other)

PC

R

P3

P3

P2

PC

PC

PC

P2


20/102

BILLMEURY

Executive Vice President &President, Branded Pharma


21/102

GI


22/102

in Action

Use Open Science Modelto Sustain Leadership

Underlying Logic behindGI Strategy

Relamorelin


23/102

5

GI

LinzessLow Dose CIC

ViberziIBS-D

Linzess

OIC

LinzessColonic Release CIC P2

P2

P3

R

RelamorelinDiabetic Gastroparesis

P2


24/102

Delivering and Building a Leading GI PipelineViberzi(eluxadoline):

FDA approval 5/2015

- Recommended schedule IV

- Expected launch late 2015

EU submitted expected launch 2017

Delzicol(mesalamine):sNDA 4x100mg formulation approval 9/2015

Linzess(linaclotide): low dose (72mcg) Phase 3 Topline results 10/2015

Statistically signicant improvement on the 12-week Complete SpontaneousBowel Movements (CSBM)

Rates of diarrhea and discontinuation for the 72mcg dose lower than 145mcgfor CIC

Relamorelin:Phase 2b recruitment on schedule


25/102

Targets the core components of IBS-D, diarrhea and abdominal pain helpingprovide lasting relief

Treats IBS-D

VIBERZI Targets Opioid Receptors in the GI Tract

with low systemic bioavailability

First and only mu- and kappa-opioid receptoragonist, and delta-opioid receptor antagonist

= VIBERZISlows GImotility

Reduces

diarrhea

Reducesvisceral pain


26/102

*p=0.05; p


27/102

Rapid and Sustained Response

Rates Over Time

Dailycompositeresponderrate(%) 60

40

0

50

30

10

20

Placebo

Eluxadoline 75 mg

Eluxadoline 100 mg

Pooled IBS-3001 and IBS-3002 Data

7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112 119 126 133 140 147 154 161 168 175 182


28/102

Works in Loperamide Responders

and Non-RespondersSelf-report NOT AdequateControl with Loperamide

Placebo ELX 75mg BID ELX 100mg BID

Com

positeEndpointResponseRates(%)

Self-report AdequateControl with Loperamide

Placebo ELX 75mg BID ELX 100mg BID


29/102

Urgency and Sustained Symptom Relief

Most Important to GIs

GEs

Importance PerformanceOTC Medications

Attributes n = 41 n = 40

Provides sustained relief

of symptoms 76% 10%

Reduces urgency of diarrhea 76% 44%

Effective at relieving bothdiarrhea and pain 71% 22%

Provides effective relief

of abdominal pain 59% 15%

% of Respondent Rating Importance and Performance 6 or 7 on 1-7 scale (Top 2 Box)


30/102

Could Achieve $1B in Sales

Allergan will have fullPCP and GI coverage

Rxs

8MM

OTC Units62MM

Key to Successful Launch:

1. Viberzi is pharmacologically differentfrom OTCs and Xifaxan

2. Clinically high response rates& low relapse rates

Convert OTC marketthrough extensive consumeradvertising and education

Allergan will achieve shareof voice leadership inprofessional and consumeradvertising

IWD

Allergan GI

Allergan PCP

1,404 Reps

~450 Reps

Allergan Competitor

$15B Market (Rx & OTC)


31/102

PATIENT

EXPERIENCE


32/102

Linzess is hitting on all cylinders

Two near terms product improvements to accelerateconvert OTC market

Sprinkle formulations

Low dose 72 mcg

Indication for Opioid Induced Constipation

Next generation Linzess

Colonic delivery program

Better pain relief Low side effects

Linzess: Building a Blockbuster

Source: IMS NPA as of 1/30/15 , IMS Xponent of 1/2/15 and IMS Source of Business Report, Nov 2014

DTC fueling double digit growth

DTC LTC Launch

Linzess 10 Year Projection

2015-2024

$1B+Sprinkles Form

Low Dose

Colonic Delivery

OIC

Summary


33/102

RELAMORELIN


34/102

Diabetic Gastroparesis is a Chronic Disease

with

No Adequate TreatmentLimited Treatment Options Available

Current options (metoclopramide, domperidone) have a boxed warning or are notapproved worldwide. They are associated with side-effects and limit on Rx duration

Existing therapies lack durable long term efcacy

No newgastroparesis therapy approved in US in over 30 years

a

b

c

Relamorelin is a Potential Game-Changing Treatment


35/102

Relamorelin is a Potential Game-Changer Potential rst to market opportunity

Only Ghrelin agonist currently beingevaluated for Diabetic Gastroparesis (DG)

- Diabetic Gastroparesis is delayed

gastric emptying, slowing movementof food through the GI system

Twice daily subcutaneous injection

Alternative formulations underconsideration

Exploring additional indications


36/102

A. Lembo, et al. Lead Late-Breaker Presentation DDW June 2014.1. mITT=modied intention to treat population; 2. Subgroup of patients with vomiting symptoms at baseline. 3. Vomiting severity measured on a 0-10 scale.N=67-69/group in the mITT population.

Relamorelin Improved Gastric Emptying

and Vomiting (Phase 2a Study)

Placebo RM-131 10mcg BID

-1.5

-1.1

-0.8

-0.4

0.0

p=0.005

p=0.006

Vomiting Severity3

-5

-4

-3

-1

0

p=0.041

p=0.033

Weekly Vomiting Episodes

mITT1 Subgroup2 mITT Subgroup

~60% Improvement vs Placebo in Vomiting Symptoms


37/102

Relamorelin: Rapid Recruitment in Phase 2b

Data Anticipated in Mid-2016 Randomized, double-blind, placebo-controlled, stratified, multiple-dose

and multi-national study

~ 395 patients with Type 1 Diabetes Melitus or Type 2 Diabetes Melitus who have both delayedgastric emptying at baseline and moderate to severe DG symptoms and 1 vomiting episodes perweek in Run-in Period

Study Endpoints:- Primary Endpoint:

Change-from-baseline to week 12 in number of vomiting episodes per week

- Secondary Endpoints: Change-from-baseline:

- DG symptoms (various combinations of up to 5 DG symptoms)- Gastric Emptying

Recruitment is on schedule


38/102

Relamorelin is a Novel Prokinetic

Actavis Market Research Study & Rhythm Patient Survey

Percent of Patients Reporting Unsatisfactory Relief

0%

20%

40%

60%

80%

Mild Moderate Severe

2.3MPatients

0.3

0.6

0.9

1.2

US Diabetic Gastroparesis Patients

Mild

Moderate

Severe

~ $6 billion in market potential Prokinetics are a multi-billion dollar market

Needed alternative given the limitations of metaclopramide(Reglan) and the withdrawal of cisapride (Propulsid)

Need for an effective/safe prokinetic

ro ne cs ea - ear x

TRx(M

M)

0

2

4

6

8

10

Propulsid (1998) Reglan (2008)

Prior prokinetics

>$1B>$1B


39/102

Scale and Leadership Gives Us Expansion Opportunities

into Multi-Billion Dollar Adjacencies by 2020

$9.4B

Ulcers

$1.3BDigestives$2.2B

IBS-D

$2.9B

ChronicConstipation& IBS-C

$5.9BUlcerative

Colitis

$5.1BGERD

$8.9B

CrohnsDisease

$2.1BObesity*

$1.4BEmesis

$0.6BDiarrhea

$2BUndevelopedMkt (NASH)*

Figures are illustrative; *Allergan estimateSource: EvaluatePharma, IMS Analytics Link

Allergan presence

No / Limited Allergan presence

Gastrointestinal

$1.5BGall Bladder

Disease


40/102

CNS


41/102

in Action


Underlying Logic behindCNS Strategy

Leading Therapies In:

MoodDisorders

Migraine

AlzheimersDisease CGRP

Psychosis


42/102

9

RapastinelMDD

AGN-241689Migraine Prophylaxis

Ubrogepant

Acute Migraine

BotoxMDD

VraylarMultiple


VraylarBipolar Depression

Botox X

Spasticity

AGN-241660MDD

CNSP1

P2

P2

P2

P3

P3

P2

P1

P1


43/102

Delivering and Building a Leading CNS PipelineIn-license 2 Merck oral CGRP antagonists

Naurex acquisition- Two rst-in-class differentiated therapies for MDD under development- Research Collaboration with Aptinyx on small molecules

Vraylar(cariprazine) FDA approval for schizophrenia and bipolar maniatype I 9/2015

Saphris(asenapine) FDA pediatric approval for schizophrenia andBipolar mania 3/2015

sNDA submitted memantine/donepezil FDC for Alzheimers on 9/20151

1Initiating patients on FDC for patients stabilized on Donepezil


44/102

MIGRAINEALLERGAN

CGRPs


45/102

Building a Migraine Powerhouse

Triptans

Semprana

Ubrogepant

AGN-241689 AGN-241689

Botox

CGRPsmAbs

Migraine Prophylaxis

Ubrogepant is for rst-line treatment of acute

Semprana alternative for triptan non-responders

AGN-241689 rst line option for migraine prophylaxis

Acute Migraine Frequent Episodic Chronic

Allergan Migraine Product Line Covers Continuum

CGRPsmAbs


46/102

Source: IMS data, Allergan market research

Migraine Prophylaxis is a Large MarketOverview

Large Addressable US Population

$10B US migraine prophylaxismarket, based on topiramateand off-label oral agents

Market could double based onprevalence of disease and newCGRP class

Multi-Billion Dollar Potential Market

US Migraine Patients Seeking Treatment

requent piso ic hronic

~10MM Rxs

~6MM Frequent Episodic andChronic Migraine patientsseeking care

urrent gra neProphylaxis Rx Market

Anticonvulsants

Antidepressants

Beta blockers

CCB

BotoxOther

4MM

2MM


47/102

Full Spectrum Migraine Portfolio

Type ofTreatments

AGN For

Migraine

Type ofMigraine

Episodic

Severe headache that comeson suddenly. Less than 15headache days per month

Chronic

More than 15 headache daysper month over a three monthperiod

Acute (abortive)

Reverse, or stop, theprogression of a headache

Preventive (prophylaxis)

Reduce the frequencyand severity of the migraineattack

Semprana: resolving CMCissues, anticipated launch2017

Ubrogepant (Oral CGRP)Initiate Phase 3 in 2016

Botox !only Rx in the market

AGN 241689 (Oral CGRPfor prevention) Ph2, expectedlaunch 2021


48/102

Potential First in Class Oral CGRP for Acute

and Prophylaxis Treatment of Migraine

Ubrogepant AGN-241689

Indication Acute Treatment of Migraine Prevention of Episodic and Chronic Migraine

Development status Phase 2 completed

Phase 3 program to start 2016

Phase 1 completed

Phase 2 dose-nding study to be conducted

Value Proposition

Ubrogepant efcacy to be comparableto triptans with better tolerability

Alternative for patients for whom triptansare not optimally effective and for those whodo not tolerate triptans

Alternative for triptan intolerant patients or

not well controlled patients

Efcacy comparable to CGRP mAb in development

Alternative to preventive medications (propranolol,topiramate, divalproex sodium) that are ineffectiveor not well tolerated in patients


49/102

Ubrogepant Achieves Acute Pain Relief

and Migraine Freedom at 2hrs in Phase 22-hr Pain Freedom

Proportion Responding (95% CI)

0

10

20

30

40

Placebo 1mg 10mg 25mg 50mg 100mg

PF 2

2-hr Total Migraine FreedomProportion Responding (95% CI)

0

10

20

30

40

Placebo 1mg 10mg 25mg 50mg 100mg

TMF 2

For our phase 3 program, 2 hour pain freedom will be a co-primary endpointalong with absence of the most bothersome associated migraine symptom

(either photophobia, phonophobia, or nausea) at 2 hours post dose.Pooled data P006 & P007

(p=0.318)

(p=0.140)

(p=0.002)

(p=


50/102

Merck data on le

Ubrogepant sub-analyses showed historical triptans responsedid not appear to affect efcacy

Ubrogepant Demonstrates Equal Efficacy

in High and Low Triptan Responders

Triptan response was categorized as:

- High Responders (Those who typically respond to triptans greater than or equal to 75% of the time);- Low Responders (Those who typically respond to triptans less than 75% of the time OR those who

no longer take triptans due to a lack of efcacy);

- Triptan Naive (Those who have never taken a triptan);

Ubrogepant

Pain Free 2HR Placebo 25mg 50mg 100mg

N=113 N=104 N=106 N=102

Triptan HighResponders 11.4% 25.8% 20.7% 21.4%

Triptan LowResponders 11.8% 23.8% 25.9% 21.7%

Triptan Naive 5% 17.9% 23.7% 28.9%


51/102

Merck data on le

Ubrogepant has Favorable AE Profile

in Phase 2 (PN006) Overall AE rates similar to placebo, no signicant differences

No events occurred in more than 7 participants

Low rates or triptan-associated AEs

Ubrogepant

(%) Placebo 25mg 50mg 100mg

Dry Mouth 3.5% 2.9% 3.8% 4.9%

Nausea 3.5% 4.8% 6.6% 6.9%

Fatigue 2.7% 1.9% 0.9% 2.9%

Dizziness 0.9% 1.9% 1.9% 5.9%

Somnolence 5.3% 4.8% 2.8% 3.9%

Triptan-associatedAEs 2.7% 1.0% 1.9% 0%


52/102

Differentiated Structure and Metabolism ProfileUbrogepant/AGN-241689:

No anilide substructure, thus no anilinemetabolite

- Metabolism of anilines can form chemically reactivenitrosamine intermediates

Has a methyl substituted lactam instead ofa piperazinone moiety so chemically reactivediuorophenylglyoxal metabolites cannotbe formed

Diuorophenyl rings in MK-0974 and MK-3207

are replaced with a phenyl group in Ubrogepantand a triuorophenyl group in AGN-241689,respectively

MK-0974(telcagepant)

MK-3207

Ubrogepant AGN-241689


53/102

Ubrogepant and AGN-241689 Liver Profile Telcagepant and MK-3207 are thought to be metabolically activated to form

reactive intermediates that have the potential for producing liver toxicity*

Development of Ubrogepant and AGN-241689 will include robust safety monitoring to assess hepatic safety

Additional modeling planned to better understand telcagepants mechanism of hepatotoxicity and provideopportunity to distinguish Ubrogepant & AGN-241689 from the predecessor molecules

*The precise mechanisms responsible for the liver toxicity produced by telcagepant and MK-3207 remain unknown

Specific design modifications were made to both Ubrogepant and

AGN-241689 to prevent the formation of potentially reactive metabolitesand to increase the potency to decrease body burden


54/102

Source: Company press releases, Allergan and Merck market research, IMS data

POC established for anti-CGRP class Oral preferred over injectables

Impressive efcacy in both Frequent Episodic and ChronicMigraine prophylaxis

- 50-70% of patients experience>50% reduction in headachefrequency

- 10-20% of patients arehyper-responders (75-100%reduction in headachefrequency)

Safety/tolerability prole comparesfavorably to SOC

%o

fpatientspreferringRoA

at ent o re erence

0%

20%

40%

60%

80%

100%

Mode of Administration

Oral QD Oral BID

SC 1x3 mo SC 1xmoSC 1x2 wks IV 1x3 mo

Ubrogepant & AGN-241689 the Oral Anti-CGRPs


55/102

Source: Company press releases, Allergan and Merck market research, IMS data

13%

25%

Oct-09 Jul-10 Apr-11Jan-12Oct-12 Jul-13 Apr-14Jan-15

AUBAGIO AVONEX Total BETASERONCOPAXONE/generics GILENYA REBIF TotalTECFIDERA

U.S. MS Market TRx Share

0%

13%

25%

38%

50%

Mar-18 Jun-18 Sept-18 Dec-18 Mar-19 Jun-19 Sept-19

Humira Enbrel Cimzia OtezlaSimponi Stelara Remicade Cosentyx

U.S. Psoriasis Market TRx Share

Orals have Performed Well in Crowded Markets

with Established mAbs

Otezla

Tecfidera

Gilenya


56/102

DEPRESSION


57/102

Long History of Success in Depression Developed and commercialized 4 anti-depressants

2 anti-depressants reached $1-2B

Excellent understanding of MDD market and psychiatry community


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Rapastinel Could Transform Treatment of MDD

MaintenanceRecovery

Relapse

Rapastinel could be used as both acute and maintenance medication for MDD

SNRIs

Atypicals

SSRIs

Maintenance

Need for AcuteTreatment

Relapse Relapse


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Treatment effects evolve slowly,adverse events begin quickly1

30-50% of the treated patients

respond to their

rst antidepressant1

Getting the right medicine is a trial

and error process

Significant Medical Need Remains in DepressionAvailable anti-depressants

Typical time course ofimprovement with antidepressants

-18

-13.5

-9

-4.5

0

0 7 14 28 42 56

Placebo (n=191)ESC 10mg (n=580)ESC 20mg (n=506)

Day

M

eanchangeinHAM-D

21

1 STAR*D Study:Trivedi Mlt, et al. Am J Psychiatry 2006; 163 : 28-40


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Aiming for Rapid Acting Anti-depressantsUse of Ketamine

Initial studies showing rapidantidepressant effects with low doseketamine infusions in TRD

- Single IV dose of ketamine leadsto full effect in responders withinhours

- Efcacy of single IV dose lastsa few days in responders

Ketamine induces transient symptomsof dissociation/psychosis and is adrug with high abuse potential

Time course of improvementwith single IV dose of ketamine

-18

-13.5

-9

-4.5

0

0 7 14 28 42 56

Placebo (n=191)ESC 10mg (n=580)ESC 20mg (n=506)

Day

M

eanchangeinHAM-D

21


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Adapted from: Danysz W., Parsons C. G. (1998) Glycine and N-methyl- D-aspartate receptors: Physiological signicance and possible therapeutic applications.Pharmacological Reviews, 50, 597-664.

NMDA Receptor Pharmacology

Rapastinel


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Acquisition of Naurex Offers Novel Game-Changing

Treatment Option for Depression

Rapastinel AGN - 241660

Fast Track by FDA

Antidepressant effect apparent within 2 hoursand lasting for 7 days after a single IV dose

Single dose IV administration also showedpromise of rapid acting antidepressant

IV formulation (1-2 minutes) in clinic/doctors ofce Oral formulation

Generally well tolerated, no indication of dissociation

Phase 3 ready Phase 2 oral formulation

Research collaboration Allergan and Aptinyx

- Preclinical small molecules

- Aim to identify additional molecules with similar moleculesfor oral administration


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Rapastinel Demonstrates Rapid Response

& Sustained Effect After Single Dose Separates from placebo in a matter of hours

Difference is sustained for 1 week after single IV dose

Days after dosing

HDRS-17,differenc

e

fromp

lacebo

-5

-3.75

-2.5

-1.25

0

1 3 7 14

Rapastinel 5 mg/kgRapastinel 10 mg/kgRapastinel 30 mg/kg

*

*

*

*

* p


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Rapastinel has No Psychotomimetic Effects

After Single Dose

0 2 4 6 8 10 120

2

4

6

8

10Placebo

1 mg/kg

5 mg/kg

10 mg/kg

30 mg/kg

GLYX-13

Time after dosing, hrs

BPRS+

No psychotomimetic effectsat any timepoint with Rapastinel:

Ketamine psychotomimetic effectsare evident within the rst two hours:

Berman et al. 2000

Brief Psychiatric Rating Scale (BPRS): scale used to measure psychiatric symptoms such as depression and anxiety, symptoms rated on scales from 1-7

Rapastinel


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Rapastinel Well Tolerated After Single Dose

Most Common Treatment Emergent Adverse Events (>10% of Subjects)

Adverse Event Rapastinel4 dose groups (n=83)

Placebo (n=33)

Any Event 71% 63%

Headache 17% 18%

Somnolence 12% 6%

Dizziness 10% 0%

Dysgeusia 7% 9%


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Rapastinel: Recent Studies Suggestive of Efficacy

and Tolerability and Patients Remain on Therapy

Phase 2b: Repeat Dose Study Open Label Study

# Rapastinel was administered adjunctivelyover 12 weeks with an SSRI or SNRI tosubjects who had partially responded(


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Rapastinel has Blockbuster Potential

24MM People for MDD

TreatmentResistant MDD

Suicidal Thoughts& Behaviors

ener c

Multi-billion Dollar Market

30-40%

TreatmentSettings

Office Setting Outpatient Clinic Hospital

Utility in multiple treatment settings


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VRAYLAR

(CARIPRAZINE)


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Most antipsychotics are D2 receptor antagonists

Abilify and Vraylar are partial D2 agonists Vraylar is a partial agonist with unique D3 activity

Low propensity for weight gain and metabolic changes

Good efcacy in multiple indications

VRAYLAR is Unique from Other Antipsychotic

Novel MOA


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Robust Efficacy Across Multiple IndicationsSchizophrenia

Type I DisorderFDA approval 9/15

FDA approval 9/15

Bipolar Mania

MDD Adjunct

NegativeSymptoms

Phase 3 Ongoing

Phase 2 CompletedBipolarDepression

Additional data supports efficacy and prevention of relapse

No drugs are approved for negative symptoms

Mania data demonstrates a large treatment effect

Additional data in Bipolar Depression also supports efficacy and safetyin treating bipolar patients with depressive symptoms

Only two other atypical antipsychotic agents have shown efficacy in thisdomain (quetiapine and lurasidone)

Positive Phase 2 data demonstrating cariprazines efficacy inadjunctive treatment of MDD

Gedeon RichterPhase 2 Completed

Indication Would Differentiate from Any Other Product on the Market

1

2

3

4

5


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VRAYLARSafe, Effective Treatment for Schizophrenia

PANSS: Positive and Negative Symptoms ScaleYMRS: Young Mania Rating Scale

1Schizophrenia


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Negative Symptoms Hinder Social Interactions

Lack of pleasure in everyday life

Lack of ability to begin and sustain activities

Face does not move with emotion

Talk in dull or monotonous voice

Negative Symptoms

Symptoms such as hallucinations,delusions, thought disorders

Positive Symptoms

No approved drugfor Negative Symptoms

Often addressed by currentlyavailable therapies


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VRAYLAR Demonstrates Convincing Efficacy

in the Treatment of Negative Symptoms Demonstrated signicant effect on treatment of negative symptoms versus

risperidone in a 26-week double-blind comparator controlled study in 461patients with predominant negative symptoms of schizophrenia

Demonstrated improvement on both efcacy (PANSS-NFS) and function (PSP)

PANSS-NFS: Positive and Negative Symptom Score of Schizophrenia- Negative Factor ScorePSP: Personal and Social Performance


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Negative Symptom Claim Would

be Key Advantage for VRAYLAR

53MM

13MM

5MM

Market Prescriptionsfor Atypicals

~25% Schizophrenia

~40% NegativeSymptoms

Atypical Anti-Psychotics

Negative SymptomMarket Segment Value $3B


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VRAYLARSafe, Effective Treatment for Bipolar Mania

2 Manic or Mixed Episodes Associatedwith Bipolar I Disorder

PANSS: Positive and Negative Symptoms ScaleYMRS: Young Mania Rating Scale


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VRAYLAR as an Adjunct to Antidepressants

in the Treatment of MDDAdjunct MDD3


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VRAYLAR was Effective in the Treatment

of Bipolar DepressionBipolar Depression4


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Pharmacologically different: D2/D3partial agonist

Clinically, Vraylar has tolerabilityadvantages over other atypical

anti-psychotics Bipolar Depression and MDD

are fastest growing segments

Vraylar will be launched in two stages

- Stage 1: Schizophrenia & Mania

- Stage 2: MDD, NegativeSymptoms, and BipolarDepression

1. Other (Autism, ADHD, OCD, Anxiety, other personality disorders total $6 billion and not included in estimate above GfK Schizophrenia Physician Study 2013

VRAYLAR has Potential in Multiple Indications

$5.1B$7B $3.3B$2.1B

Schizophrenia Mania BP Dep MDD

$15$20B in Sales

Treatment Failure Rates are High

28%Switch dueto efficacy

32%

Switch dueto sideeffects

Over 50%of patientsfail 2ndline

therapy

Weight Gain EPS Somnolence

Anti-Psychotic Market Potential1


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1. Schizophrenia Placebo Adjusted data based on package inserts.2. Akathisia:97% reported as mild/moderate. Discontinuation rate 0.5%Vraylar weight reects recommended doses. For somnolence and akathisia, data reects average of recommended doses.For Risperdal, data reects 1-8mg/day which is the most commonly used dose range in schizophrenia as two dose ranges are included in PIMost package inserts, somnolence is reported as a group term including somnolence and sedation. Rexulti PI only reports sedation.

Vraylar has a Competitive Risk Profile

20%

18%

16%

14%

12%

10%

8%

6%

4%

2%

0%

Zyprexa 19%

Seroquel 17%

Vraylar 3%

Risperdal 6% Seroquel XR 5% Abilify 5%

Rexulti 6-7%

Latuda 2%

Saphris 3%

Weight >7%1

Risperdal 7%

Abilify 6%

20%

18%

16%

14%

12%

10%

8%

6%

4%

2%

0%

Zyprexa 4%

Seroquel 0%

Vraylar 7%

Seroquel XR 1% Rexulti 1%

Latuda 10%

Saphris 3%

Akathisia1,2

Risperdal 8%

Abilify 5%

20%

18%

16%

14%

12%

10%

8%

6%

4%

2%

0%

Zyprexa 16%

Seroquel 10%

Vraylar 2%

Seroquel XR 15%

Rexulti 1%

Latuda 10%

Saphris 6%

Somnolence1


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VRAYLAR has Blockbuster Potential

Vraylar will be launched in two stages

- Stage 1: Schizophrenia & Mania

- Stage 2: MDD, Negative Symptoms,and Bipolar Depression

Superior tolerability prole in termsof weight gain and metabolic effect

2015 2018 2019 2020

SchizophreniaBipolar Mania

BipolarDepression

Negative Symptomin schizophrenia

5 Potential Indications withCombined Potential >$1B

MDD

$1B+


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Parkinsons

$4BParkinsons

$7BDepression

$7BAlzheimers

$3BMigraine

$9BSchizophrenia

$8BEpilepsy

$25BMultipleSclerosis

$0.3BHuntingtons

$4B

SleepDisorders

$5BADHD

Figures are illustrativeSource: EvaluatePharma, IMS Analytics Link

Allergan presence


Central Nervous System


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HERBERT Y.

Professor of Psychiatry and Behavioral Sciences,Pharmacology, and Physiology

Northwestern University

MELTZER M.D.

STEVEN G.

POTKIN M.D.Professor Department of Psychologyand Human Behavior

University of California, Irvine


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WOMENS HEALTH& UROLOGY


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in Action


Underlying Logic behind Our WH & URO Strategy

Building and Delivering

Contraception Gynecology

Urology


86/102

Womens Health

EstradiolVaginal Cream VVA & Dyspareunia

UlipristalFibroids

EstradiolVag Caps VVA & Dyspareunia

Etonogestral RingContraception P3

P3

P1

P14


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Developing and Building

the WH and Urology PipelineLiletta(levonorgestrel-releasing intrauterine system) FDA approvalFebruary 2015, (2-handed inserter) launched 3/2015 sNDA Single Handed Inserter February 2016 approval targeted

Diafert EU approval for diagnostic for infertility March 2015

Esmya Phase 3 trials; patient screening completed

SER-120 Phase 3 Topline results met endpoints


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ESMYA (ulipristal) is a First in Class Selective

Progesterone Receptor Modulator (SPRM) Laproscopic power morcellators for broids recalled; concerns regarding spread

of malignant cells

2 ongoing Phase 3 studies in US target indication for treatment of abnormal uterinebleeding in women with leiomyomas:

UL-1208 UL-1309

Target of 400 planned patients Target of 150 planned patients

5mg and 10mg Ulipristal, 2 treatment cycles 5mg and 10mg Ulipristal, 1 treatment cycle

Topline data expected 2017Topline data expected 2016.Randomization completed

Co-primary endpoints% of patients who achieve absence of bleeding dueto uterine broids during 1sttreatment cycle, time to

absence of bleeding

Secondary endpoints Absence of bleeding at day 11 Symptom severity on a broid symptom scale Quality of life

Expected NDA submission 2017 with expected approval 2018


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Ulipristal Has Proven Efficacy and Safety With

Long-Term Intermittent Therapy Approved in EU Long term treatment - STET treatment courses of 12 weeks each approved in EU (May 2015 )

for treatment of moderate to severe symptoms of uterine broids

Pearl IV data demonstrated efcacy was maintained and safety prole was unchangedwith the repeated courses of therapy !support intermittent and long term use

aAmenorrhea dened as no more than one day of spotting within a 35-day intervalbPatients with missing values were excluded from the analysiscN and % include withdrawn patientsdData from EU SPC: May 27, 2015

atents

After treatment course 2 After treatment course 4

5 mg10 mg

PEARL IVN= 205 N= 197

PEARL IVN= 227 N= 220

Percent of Patients in Amenorrheaa,b,c,d


90/102

Reduces tumor size, relieves pain and bleeding, and time to surgery

Esmya (ulipristal acetate)

Breakthrough Treatment for Uterine Fibroids

Large market with over 10 million women

Women 25-49 in US52MM

Women at Risk forUterine Fibroids

36MM

Diagnosed withUterine Fibroids11MM

r sta rescr pt ons

0

2,500

5,000

7,500

10,000

Q3 13 Q1 14 Q3 14 Q1 15 Q3 15

Successful launch in Canada

Canadaperformance in US

terms points to$1B opportunity


91/102

UrologyBotoxPremature Ejaculation

LiRISInterstitial Cystitis


BotoxIndication X

P2

P3

P2

PC

4


92/102

SER-120 for the Treatment of Nocturia

Developed in collaboration withSerenity Pharmaceuticals

Novel low dose desmopressin(synthetic analog of vasopressin)nasal spray for the treatment ofnocturia in adults

Leads to reduction in urineproduction and postpones theneed for voiding

Unique pharmacokinetic prolewith short overnight action whendosed in evening

Nocturia becomes more prevalentafter the age of 50 years

Affects about 25-34% of thepopulation aged 50 years andolder

Often associated with other lowerurinary tract symptoms as OAB/overactive bladder and BPH/benign prostatic hyperplasia

Nocturia: UnmetClinical Need

SER-120(desmopressin nasal spray)


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4 placebo-controlled phase 3 studies completed(DB1, DB2, DB3, DB4)

DB3 study: 0.75mcg, 1.0mcg, 1.5mcg (doubleblind placebo phase completed Nov. 2012),including Open label long term extension

(completed in June 2015)

DB4 study: 0.75mcg, 1.5mcg, placebo; nalphase 3 study (completed May 2015)

DB3 and DB4 pivotal studies with a 12 weekrandomized double-blind period: bothdemonstrated statistical signicance overplacebo in reduction of nocturic episodes

SER-120 Phase 3 Studies CompletedDevelopment status in US

Ongoing FDA interactions to prepare

for submission Submit US NDA in 2016

Start European development in 2016

Next Steps


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Allergan presence


$2.8B

IBS-C

$5.8BHormone Therapy /

MenopauseManagement

$1.3BEndometriosis

$5.8BHormonal

Contraception

$1BUterineFibroids

$1.5BFertility

$0.5BFemale SexualDysfunction*

$0.3BNon-Hormonal

IUDs

$0.3BGU Anti-Infectives

Figures are illustrative; *Allergan estimateSource: EvaluatePharma, IMS Analytics Link

Womens Health


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ANTI-INFECTIVE


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in Action


Underlying Logic behind Our Anti-lnfective Strategy

Building and DeliveringGRAM-POSITIVE

ABSSSICABP

Osteomyelitis

GRAM-NEGATIVEcUTI

cIAI


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5

Anti-Infective

AvycazcUTI, cIAI

Dalbavancin Osteomyelitis

Dalbavancin Endocarditis


P3

R

P3

P3

Aztreonam/AvibactamGram Neg InfectP2


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Delivering and Building the AI PipelineAVYCAZ(ceftazidime-avibactam)

Approved February 2015 for cIAI, cUTI

sNDA ling with Phase 3 cIAI 4Q2015

sNDA ling with Phase 3 cUTI 2016

DALVANCE(dalbavancin) EU approval (ABSSSI) March 2015

sNDA ling for single dose for ABSSSI on July 2015

TEFLARO(ceftaroline fosamil) sNDA for bacteremia and short infusion approved in August 2015

AZTREONAM/AVIBACTAM

Gram-negative pathogens

Different microbiological prole than Avycaz

Initiating development


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In Gram-negative pathogens resistant to ceftazidime, ceftazidime-avibactam plus metronidazole resulted in:

Similar clinical cure rate to meropenem

Similar clinical cure rate to ceftazidime-susceptible pathogens

CAZ-AVI + MTZ(n=413)

MER(n=410)

ComparisonBetween Groups

Pathogen n Clinical Curen (%) nClinical Cure

n (%)Difference, %

(95% CI)

All ceftazidime-resistant

47 39(83.0)

64 55(85.9)

3.0(17.89, 10.60)

All ceftazidime-susceptible

289 237(82.0)

292 256(87.7)

5.7(11.57, 0.17)

with Ceftazidime-Resistant Bacteria (RECLAIM data)is Effective in Treating cIAI Patients Infected


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is Effective in Treating cUTI (RECAPTURE data)Avycaz demonstrated non-inferiority compared with doripenemsymptomatic resolution and favorable microbiological response at test-of-cure in the mMITT population

Numerical response trend in favor of Avycaz for microbiological response

and combined symptomatic/microbiological response at test-of-cure

Avycaz was effective in treating cUTI patients infected withceftazidime-resistant bacteria

sNDA to be filed 2016 with aim of removing limitation statement for cUTI


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Key New Product Launch Performance

Zerbaxais a registered trademark of MerckOrbactivis a registered trademark of Medicines Company

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Dalvance


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