Mitra Sehi, OD, PhD, MBA, FAAO

Director, Anterior Segment MSLs, Ophthalmology

ALLERGAN, PLC

BIMATOPROST SR: DISRUPTING THE GLAUCOMA TREATMENT PARADIGM

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GLAUCOMA PORTFOLIO will expand to provide more options to doctors and patients

2

Drops Portfolio

SustainedRelease

Surgical Devices

Disease Severity

Options to intervene at different stages

Ocular Hypertension

Early Moderate Severe

Bimatoprost Ocular RingBIMATOPROST SR

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Similar to those used in biodegradable sutures

Supplied preloaded in a single-use applicator

with a 28-gauge needle

Bimatoprost SR

Bimatoprost SR

Biodegradable Polymers

NOVADUR® platform

First-in-class sustained-release, biodegradable implant for the treatment of open-angle glaucoma or

ocular hypertension designed to lower IOP for at least 4 months, while freeing patients from daily

eyedrop regimens

Bimatoprost

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Bimatoprost SR Administration Procedure

Do not distribute, copy or publishCraven et al. AAO 2019

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• In vivo dog study

‒ Drug is detectable in the eye for up to 4 months after BimSR administration

‒ Targeted drug delivery to relevant sites of action of PGAs

Reprinted from Seal JR, et al, J Ocul Pharmacol Ther. 2019;35:50–57 and used under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0)

Seal et al. J Ocul Pharmacol Ther. 2019;35:50-57.

NondetectableNondetectable Nondetectable Nondetectable

Targeted Drug Delivery to the Relevant Site of Action of PGAs

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May Decrease Common Side Effects of Chronic Topical PGA Use

Walters, et al. ASCRS 2018.

Bim SR = Bimatoprost sustained-release implant*Patients counted only once within each preferred term and system organ class

Visible difference in common effects of chronic use of topical PGA

medication: Growth of eyelashes

Preferred Term* n (%)

Onset after 2 days of administration

Bim SR(N=75)

Bim 0.03%(n=75)

Conjunctival Hyperemia 13 (17.3) 21 (28.0)

Blepharitis 1 (1.3) 1 (1.3)

Erythema of eyelid 1 (1.3) 4 (5.3)

Eyelid edema 1 (1.3) 2 (2.7)

Growth of eyelashes 0 5 (6.7)

Iris hyperpigmentation 0 3 (4.0)

Conjunctival edema 0 1 (1.3)

Orbit atrophy 0 1 (1.3)

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Positive Phase 3 Studies Topline Data

June 13, 2018 and January 7, 2019Do not distribute, copy or publish

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ARTEMIS Phase 3 Study Design

*Phone call. †Two Bimatoprost SR treatment groups, administered either 10-µg or 15-µg implant. Only results for the proposed marketed dose strength, Bimatoprost SR 10 µg, will be presented.

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; BL, baseline; IOP, intraocular pressure.

Two Parallel-Group, Noninferiority Studies vs BID Timolol

Safety follow-up visits

SR treatment in study eye,

sham treatment and timolol BID

in fellow eye

No SR or sham treatment

Sham treatment in both eyes,

timolol BID in both eyes

• Primary efficacy endpoint: Noninferiority to timolol during primary efficacy period through

Week 12

Timolol BID

Week

BL 2 6 12 16 32 52

Month 20

Bimatoprost SR†

Primary efficacy period

Exit

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Baseline Characteristics of Patients and Study Eyes

Parameter

Bimatoprost SR 10 µg(N=374)

Timolol 0.5% BID(N=374)

Age, mean (SD), y 62.6 (12.1) 62.0 (11.7)

Range 23–88 19–90

Male, n (%) 198 (52.9) 180 (48.1)

Race/ethnicity, n (%)

White 238 (63.6) 234 (62.6)

Black or African-American 51 (13.6) 57 (15.2)

Hispanic 45 (12.0) 46 (12.3)

Other or not reported 40 (10.7) 37 (9.9)

Diagnosis

OHT 76 (20.3) 86 (23.0)

POAG 290 (77.5) 277 (74.1)

Pseudoexfoliation or pigmentary glaucoma 8 (2.1) 11 (4.0)

Hour 0 (8 AM) IOP, mean (SD), mm Hg 24.5 (2.6) 24.6 (2.6)

Hour 2 (10 AM) IOP, mean (SD), mm Hg 23.3 (2.9) 23.3 (3.0)

Phakic lens status, n (%) 287 (76.7) 279 (74.6)

CECD, mean (SD), cells/mm2 2455 (328) 2462 (329)

Range 1540-3396 1423-3643

Pooled study data, ARTEMIS 1 + ARTEMIS 2

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; CECD, central corneal endothelial cell density;

IOP, intraocular pressure; POAG, primary open-angle glaucoma; OHT, ocular hypertension. Do not distribute, copy or publish

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Bimatoprost SR Met the Primary Endpoint of Noninferiority to Timolol BID in IOP Lowering Through Week 12*

*Both 10 µg and 15 µg doses met the primary endpoint. Upper limit of 95% confidence interval of Bimatoprost SR − timolol difference was <1 mm Hg at Hours 0 and 2 at Weeks 2, 6, and 12 in each study, as well as in the pooled study dataset.

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; W, weeks.

Primary Efficacy Results:

Mean IOP

• Mean diurnal IOP consistently

maintained between 16–17

mm Hg

• During the primary efficacy

period, IOP lowering was

numerically greater with

Bimatoprost SR than timolol at

all 6 time points

Pooled study data, ARTEMIS 1 + ARTEMIS 2

Error bars indicate the standard deviation.

10

14

18

22

26M

ean

Diu

rna

l IO

P (

mm

Hg

)

Time

Bimatoprost SR 10 µg (N=374)

BL 2W 6W 12W

Administration #1

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Study Design and Primary Outcome

> 20-month Phase 3 study: OAG/OHT patients

(n=1122) were randomized to study eye

treatment with 3 administrations of Bimatoprost

SR 10 or 15 µg (Day 1; Weeks 16, 32) or topical

timolol 0.5% BID

> Primary endpoint: IOP lowering through

Week 12

Phase 3

> 2-year Phase 1/2 study: 75 OAG patients

received Bimatoprost SR 6, 10, 15 or 20 µg in

study eye, topical bimatoprost 0.03% QD in

fellow eye

> Interim analysis: Week 16

A P O L L

Phase 1/2

Week 2 through Week 16, 10 µg (n=21)

from a baseline of 24.5 mm Hg (Hour 0)

Week 2 through Week 12, 10 µg (n=374)

from a baseline of 24.5 mm Hg (Hour 0)

Up to

-7.7mm Hg

Up to

32%reduction from

baseline

Up to

-7.9 mm Hg

Up to

32%reduction from

baseline

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; OAG, open-angle glaucoma; OHT, ocular hypertension; QD, once daily. Do not distribute, copy or publish

Results

No. of patients

at risk

Days

IOP

Su

rviv

al

Pro

ba

bil

ity

(no

re

tre

atm

en

t o

r re

scu

e)

1.0

0.8

0.6

0.4

0.2

0.0

0280

42

232

42

186

29

141

19

121

14

0

13 11 7

90 180 270 360 480 600 720

12W 26W 39W 52W 16M 20M 24M

Time After Last Administration

Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; M, months; W, weeks.

Patients had Continued Duration of IOP Control With No Additional Treatment After Bimatoprost Release From Implant

Last Bimatoprost SR administration

80% IOP controlled with NO additional treatment at 1 year after 3 administrations of Bimatoprost SR 10 µg

Study #1 & #2

36%

1 Year

IOP controlled with NO additional treatment at 1 year after 1 administration of Bimatoprost SR 10 or 15 µg

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Topical Bimatoprost

Image on left used with permission of ARVO, from Morphological Changes in the Anterior Eye Segment after Long-Term Treatment with Different Receptor Selective Prostaglandin Agonists and a Prostamide, Richter et al,

Invest Ophthalmol Vis Sci. 44(10) 2003; permission conveyed through Copyright Clearance Center, Inc.

Monkey ciliary body after 1 year of topical

bimatoprost treatment

Remodeling enhances uveoscleral outflow

Bimatoprost SR: Proposed MOA*

Higher MMP expression, reduction in the ECM, may

lead to greater tissue remodeling, longer duration

of IOP reduction

*Artist’s rendition

Bimatoprost SR, bimatoprost sustained-release implant; ECM, extracellular matrix; IOP, intraocular pressure; MOA, mechanism of action; MMP, matrix metalloproteinase.

Rationale for Extended Duration of IOP Control

Pro

posed M

OA

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Significant Difference in Rate of Visual Field Progression Compared With Timolol in OAG Patients

Pooled study data, ARTEMIS 1 + ARTEMIS 2

• At planned primary database lock, 293 OAG patients in the Bimatoprost SR 10 µg and Timolol BID groups had available 1-year visual field data

*P = 0.049 vs timolol BID

MD values from Humphrey perimetry 24-2 full threshold or Swedish Interactive Threshold Algorithm (SITA) standard tests. Data after any use of rescue medication were excluded.

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; MD, mean deviation; OAG, open-angle glaucoma.

*

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All Ocular Treatment-Emergent Adverse Events Reported in ≥3% of Study Eyes in Either Treatment Group

Onset at Any Time Onset or Worsening >2 Days After Implant/Sham Administration

Adverse Event, n (%)BimSR 10 µg

(N=372)Timolol BID

(N=370)BimSR 10 µg

(N=372)Timolol BID

(N=370)

Any adverse event 233 (62.6) 166 (44.9) 140 (37.6) 96 (25.9)

Conjunctival hyperemia 101 (27.2) 62 (16.8) 36 (9.7) 19 (5.1)

Foreign body sensation 38 (10.2) 13 (3.5) 11 (3.0) 0

Eye pain 36 (9.7) 16 (4.3) 4 (1.1) 4 (1.1)

Photophobia 32 (8.6) 4 (1.1) 7 (1.9) 1 (0.3)

Conjunctival hemorrhage 28 (7.5) 22 (5.9) 2 (0.5) 3 (0.8)

Eye irritation 26 (7.0) 27 (7.3) 6 (1.6) 4 (1.1)

Dry eye 25 (6.7) 15 (4.1) 12 (3.2) 7 (1.9)

IOP increased 22 (5.9) 8 (2.2) 19 (5.1) 8 (2.2)

Vision blurred 19 (5.1) 9 (2.4) 5 (1.3) 2 (0.5)

Corneal endothelial cell loss 18 (4.8) 1 (0.3) 11 (3.0) 1 (0.3)

Iritis 18 (4.8) 1 (0.3) 10 (2.7) 1 (0.3)

Punctate keratitis 16 (4.3) 18 (4.9) 1 (0.3) 7 (1.9)

Anterior chamber cell 14 (3.8) 1 (0.3) 7 (1.9) 0

Lacrimation increased 13 (3.5) 11 (3.0) 1 (0.3) 1 (0.3)

BID, twice daily; BimSR, bimatoprost sustained-release implant; IOP, intraocular pressure. Do not distribute, copy or publish

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Corneal Endothelial Cell Density

Pooled study data, ARTEMIS 1 + ARTEMIS 2

Error bars show the standard deviation.

BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; BL, baseline; CECD, corneal endothelial cell density; M, months; W, weeks.

44W 52W 20M0

500

1000

1500

2000

2500

3000

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88

Mean

CE

CD

(cell

s/m

m2)

Time

Bimatoprost SR 10 ug (n=372)

Timolol BID (n=370)

Fellow eyes, all patients (n=1111) (treated with timolol BID)

BL 12W 28W 44W 52W 20M

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Central Corneal Thickness and Visual Acuity StabilityWith Bimatoprost SR 10 µg

Pooled study data, ARTEMIS 1 + ARTEMIS 2

• No change in CCT and visual acuity in patients with corneal AEs

AE, adverse event; BCVA, best-corrected visual acuity; Bimatoprost SR, bimatoprost sustained-release implant; CCT, central corneal thickness..

All Patients(n=153)

Patients With Corneal AE (n=16)

Safety Parameter Baseline 20 Months Baseline 20 Months

Mean CCT (µm) 555.4 555.6 567.9 566.0

Mean BCVA (ETDRS letters) 82.7 83.5 83.1 83.4

Bimatoprost SR 10 µg Patients in the Dataset Who Had Completed 20 Months

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Clin

ical

Pro

gram Bimatoprost SR Clinical Trial Program

18

One Phase 1/2 Study Two Ph3 Studies (US) Two Ph3 Studies (EU)

OAG/OHT OAG OAG/OHT OAG/OHT

Comparator Topical Bimatoprost Timolol SLT

Duration 24 months 20 months 12 months

No. of Administrations 1 or 2 3 2-3

A P O L L

Ahmed, et al. AGS 2019 Do not distribute, copy or publish

Sum

mar

y• First-in-class sustained-release, biodegradable implant for the treatment of open-angle

glaucoma or ocular hypertension designed to lower IOP for at least 4 months while freeing patients from daily eye drop regimens

• In P3 and P1/2 studies, BimSR demonstrated an extended duration of effect of 1 year (83%) or 2 years (36%) in many patients

• Sustained IOP lowering may involve durable MMP-mediated remodeling of aqueous outflow

• The value of extended duration of effect is reduced treatment burden, improved adherence with more sustained pressure lowering, less hyperemia, less orbitopathy

• Empowers physicians by putting IOP control in their hands

Bimatoprost SR Risk/Benefit was favorable in both Phase 3 studies

NDA submitted

Bimatoprost SR

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Thank You to Patients and Investigators!

Over 1000 patients have been enrolled in Bimatoprost SR studies

to date at > 300 investigative sites in over 30 countries

Patients of Thomas Walters, MD, Austin, TX

Bimatoprost SR Investigator

Ahmed, et al. AGS 2019 Do not distribute, copy or publish