saving sight through transformative science

32
Saving Sight through Transformative Science February 2021

Upload: others

Post on 01-Dec-2021

3 views

Category:

Documents


0 download

TRANSCRIPT

Saving Sight throughTransformative Science

February 2021

Legal Disclaimer

Any reproduction or distribution of this presentation, in whole or in part, without the prior consent of Graybug Vision, Inc. is prohibited.

These slides and the accompanying oral presentation contain forward-looking statements within the meaning of the “safe harbor” provisions of the Private

Securities Litigation Reform Act of 1995, including, but not limited to statements regarding our clinical pipeline, our ability to advance GB-102, GB-103, GB-

401, or any future product candidate through clinical development, our ability to achieve our anticipated milestones within the timing outlined above or at all,

our ability to conduct planned operations within the evolving constraints arising from the COVID-19 pandemic, our operating results and cash positions, our

operations as a public company, our management and board of directors, and the timing and results of our clinical trials.

Any statements contained herein or provided orally that are not statements of historical fact may be deemed to be forward-looking statements. In some

cases, you can identify forward-looking statements by such terminology as ‘‘believe,’’ ‘‘may,’’ ‘‘will,’’ ‘‘potentially,’’ ‘‘estimate,’’ ‘‘continue,’’ ‘‘anticipate,’’ ‘‘intend,’’

‘‘could,’’ ‘‘would,’’ ‘‘project,’’ ‘‘plan,’’ ‘‘expect’’ and similar expressions that convey uncertainty of future events or outcomes, although not all forward-looking

statements contain these words.

You should not place undue reliance on forward-looking statements, as these statements are based upon our current expectations, forecasts, and

assumptions and are subject to significant risks and uncertainties that may cause our actual activities or results to differ significantly from those expressed in

any forward-looking statement, including risks and uncertainties described under the heading “Risk Factors” in our quarterly report on Form 10-Q for the

three months ended September 30, 2020, and the other reports we file from time to time with the Securities and Exchange Commission.

We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements

to actual results or to changes in our expectations or circumstances, except as required by law. Although we believe the expectations reflected in such

forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, you are cautioned not to

place undue reliance on these forward-looking statements.

2

Extensive experience in ophthalmology and healthcare

Novartis

Worldwide Head

Ophthalmology

Alcon

Global Franchise Head

Pharmaceuticals

Led extension of Novartis

ophthalmology pipeline:

Encore Vision, Lubricin®,

Luxturna®, Xiidra®

Novartis

VP and Global Head, Clinical

Development and

Therapeutic Area Head,

Ophthalmology

Ophthalmologist from

Moorfield’s Eye Hospital, UK

Ocular immunologist from

Schepens Eye Research

Institute, a Harvard affiliated

institute

Corium

CFO, IPO through PE sale

Codexis

CFO, Private to IPO

Aerogen

CFO, Public through Public

Sale

Ophthotech Corporation

Technical Operations

Aptalis Pharmaceuticals,

Global Supply Chain and

Manufacturing

Launched over 30 global

products including Zenpep®,

Lamictal®, Amrix®, Canasa®

and Metadate CD®

Fred Guerard

PharmD, CEORobert Breuil

CFO

Parisa Zamiri

MD, PhD, CMODan Salain

Chief Tech Ops OfficerBettina Maunz

Chief People Officer

Novartis

Global Head Enterprise

Communications

Alcon

VP and Global Head

Communications, President

Alcon Foundation

Led teams and culture

change as part of significant

business transformations

across Pharma, Biotech and

Medical Device industry

3

Dr. Rick Ferris

Ophthalmic Research

Consultants

National Eye Institute

(retired)

4 |

Dr. Jeff Heier

Ophthalmic Consultants

of Boston

Dr. Arshad Khanani

Sierra Eye Associates

University of Nevada,

Reno School of Medicine

Dr. Carl Regillo

Retina Service Wills

Eye Hospital

Thomas Jefferson

University School of

Medicine

Dr. David Boyer

Retina-Vitreous

Associates Medical

Group, California

USC/Keck School of

Medicine

Dr. Rishi Singh

Cole Eye Institute,

Cleveland Clinic

Lerner College of

Medicine

4

Our Scientific Advisory Board

Graybug investment highlights

5

Potentially transformative, long-acting treatments for vision-threatening diseases

Differentiated clinical-stage candidates targeting $15B+ markets

• GB-102 for wet age-related macular degeneration (wet AMD)

• GB-102 for diabetic macular edema (DME)

• GB-103 for diabetic retinopathy (DR)

• GB-401 for primary open-angle glaucoma (POAG)

Patent protection: GB-102/GB-103 through 2039, GB-401 through 2041

Numerous near-term milestones

5

2Q 2021: GB-102 Phase 2b results 2H 2021: Initiate 4 new trials

Proprietary ocular technologies promote controlled, sustained drug delivery

Extended durability & sustained drug deliveryDifferentiated mechanisms of action

Designed with safety in mindVersatile proprietary technologies

6

Particle aggregation and bioabsorption with GB-102 (1 mg) Observed over 6 months

Baseline 2 Weeks 1 Month 2 Months

4 Months3 Months 5 Months 6 Months

7

GB-102 depot images using wide field color fundus photography throughout the 6-month observation period in the ME study

Our pipeline of long-acting ocular drug candidates

8

GB-102(sunitinib)

6-month dosing

GB-103(sunitinib)

12-month dosing

GB-401(pro-drug)

6-month dosing

Wet Age-Related Macular

Degeneration (wAMD)

Diabetic Retinopathy (DR)

Primary Open-Angle Glaucoma

(POAG)

Ph2b ALTISSIMO Topline (wAMD)

2021 2022

1H 2H 1H

Initiate Ph3 Global Trials (wAMD)

Initiate Ph2b (DME)

Initiate Ph1/2a (DR)

IND Submission (POAG)

Program Indication Anticipated Milestone

Diabetic Macular Edema (DME)

Our Lead Retina Program: GB-102

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME)

Leading causes of acquired vision loss in young & middle-age adults

Age-related Macular Degeneration (AMD)

Leading cause of vision loss in the elderly worldwide

Retina: A growing $11B+ market with significant unmet need

|

10

Existing standard of care presents high burden of up to 12 intravitreal injections per year

US and Global AMD reference: Pennington and DeAngelis Eye and Vision (2016)

10-15% patients

with wAMD

~11M AMD patients in U.S.

(~170M WW)

8% annual growth

$7.9B WW

~30M diabetic patients in U.S.

(~460M WW)

700M diabetic

patients WW in 2035

$3.7B WW

~1.5M DME

patients in U.S.

(~20M WW)

~10M DR patients in U.S.

(~90M WW)

Hariprasad SM et al. Journal of Ophthalmology, Volume 2012, Article ID 690641

SAILOR PRN

PIER Q12 w

ANCHOR Q4 w

MARINA Q4 w

Stability and maintenance of vision requires frequent injectionsLonger-acting therapies are #1 unmet need for retina specialists

Low visual outcomes due to high burden of up to 12 intravitreal injections per year

Begin dosing quarterly (PIER) and as-needed (SAILOR)

ANCHOR (dosed every 4 weeks, n=279)

Me

an

VA

* c

ha

ng

e

fro

m b

as

eli

ne (

lett

ers

)MARINA (dosed every 4 weeks, n=478)

SAILOR (dosed as needed, n=946)

0 3 6 9 12 15 18 21 24

15

10

5

0

-5

Months*Visual Acuity

All studies were conducted with ranibizumab (Lucentis®)

Each square, rhombus, or triangle represents an anti-VEGF injection; each circle represents a measurement visit

Vision declines without regular injections

PIER (dosed every 12 weeks; n=121)

11

Higher fluctuations in retinal thickness correlate with poor visual outcomes

Decreasing Vision

12

Increasing Fibrosis

12

High

Low

High

Low

Fluctuation:

Fluctuation:

Association between variation in retinal thickness and visual function, Evans R, Chakravathy U, Reeves, BC, ARVO 2019 poster #3456

High Retinal Thickness

Normal Retinal Thickness

Pan-VEGF Inhibitor Neuroprotectant

Sunitinib is a potent pan-VEGF inhibitor and neuroprotectant

13

DLK: Dual Leucine Zipper Kinase

Oral sunitinib inhibits

CNV in murine model

(Takahashi 2006)

Oral sunitinib inhibits

CNV in cancer patients

(Hulpus et al 2014)

No ocular toxicity in long-term

safety surveillance studies

(Motzer et al 2013 Porta et al 2016)

Potent anti-angiogenic

in laser-CNV model

(Campochiaro et al 2019)

CNV: Choroidal Neovascularisation

10

10.5

11

11.5

12

12.5

13

13.5

14

Control 40 80 150CN

V V

olu

me (

log c

onvert

ed)

Dose (mg/kg)

Sunitinib has well documented safety and efficacy in choroidal

neovascularization

14

Baselin

e

Month 8

0.00

0

0.01

0.02

0.015

0.03

0.025

Mouse Laser CNV Model Aflibercept vs. GB-102

*

Day 0:• Aflibercept x 1 dose

Intravitreal• GB-102 x 1 dose Intravitreal

**

Mean

CN

V A

rea

(mm

2)

0.5M 2M 3.5M 5M 6M

Months

* p<0.05 (GB-102 or aflibercept vs. fellow eye control)

*GB-102

No Effect Range

(Placebo)

aflibercept

*

Baseline

8 months

Competitive advantages of GB-102Microparticle depot formulation of sunitinib

Extended durability demonstrated

in Phase 1/2a

Twice a year versus up to 12 times

Reduction of fluctuation in retinal thickness

Differentiated mechanisms of action

Blocks all VEGF receptor types allowing for

broader MOA

Dual Leucine Zipper Kinase (DLK) inhibitor

may have neuro-protective effect

15 |

Versatile proprietary technologies

Tailored durability

Tunable drug elution profile

Designed with safety in mind

Biodegradable/bioabsorbable

Approx. 100 patients exposed

15

≤ 3 months duration

≥ 8 months duration 4-5 months duration

≥ 6 months durationAnti-VEGF injection prior to study entry GB-102 injection Patient leaving study unrelated to treatment

16

Time to first use of

supportive therapy

Percentage of

patients (n)

≤ 3M 12% (1/8)

≥ 4M 88% (7/8)

≥ 6M 88% (7/8)

≥ 8M 50% (4/8)

GB-102 1 mg

Open label, dose ranging, safety, durability and pharmacodynamics study

Phase 1/2a ADAGIO: single injection of GB-102 in patients with wet AMD previously treated with short-acting anti-VEGFs

GB-102 1 mg single injection maintained visual acuity for 6+ months

17

Anti-VEGF injections GB-102 injection

GB-102 1 mg (n=8)• Mean Pre anti-VEGF/year = 8.8 ± 1.9• Mean Pre BCVA = 61 ± 12 (6/8)• Mean Final BCVA = 65 ± 11

30

40

50

60

70

80

90

30

40

50

60

70

80

90

Pre Baseline 1M 2M 3M 4M 5M 6M 7M 8M

30

40

50

60

70

80

90

30

40

50

60

70

80

90

Mean

BC

VA

(E

TD

RS±

SD

)O

bserv

ed d

ata

GB-102 0.25 mg (n=8)• Mean Pre anti-VEGF/year = 8.8 ± 1.9 • Mean Pre BCVA = 57 ± 16 (7/8)• Mean Final BCVA = 47 ± 17

GB-102 0.5 mg (n=8)• Mean Pre anti-VEGF/year = 7.2 ± 2.8 • Mean Pre BCVA = 61 ± 12 (4/8)• Mean Final BCVA = 70 ± 13

GB-102 2 mg (n=8)• Mean Pre anti-VEGF/year = 9.9 ± 2.0 • Mean Pre BCVA = 59 ± 8 (5/8)• Mean Final BCVA = 58 ± 13

BCVA = Best corrected visual acuity

M = month

GB-102 1 mg single injection maintained retinal thickness for 6+ months

18 |18

GB-102 1 mg (n=8)• Mean Pre anti-VEGF/year = 8.8 ± 1.9• Mean Pre CST = 376 ± 133• Mean Final CST = 287 ± 85

100

200

300

400

500

Pre Baseline 1M 2M 3M 4M 5M 6M 7M 8M

100

200

300

400

500

100

200

300

400

500

100

200

300

400

500

C O N F I D E N T I A L A N D P R O P R I E T A R Y

GB-102 0.25 mg (n=8)• Mean Pre anti-VEGF/year = 8.8 ± 1.9 • Mean Pre CST = 394 ± 141• Mean Final CST = 312 ± 208

GB-102 0.5 mg (n=8)• Mean Pre anti-VEGF/year = 7.2 ± 2.8 • Mean Pre CST = 401 ± 89• Mean Final CST = 266 ± 76

GB-102 2 mg (n=8)• Mean Pre anti-VEGF/year = 9.9 ± 2.0 • Mean Pre CST = 410 ± 144 • Mean Final CST = 293 ± 78

Mean

CS

T (μ

SD

)O

bserv

ed

data

CST = Central sub-field thickness

M = month

Anti-VEGF injections GB-102 injection

20 |19

GB-102 1 mg controlled ~80% of wAMD patients for 6 months or moreWhile being well tolerated

• GB-102 1 mg single injection in patients previously on ~8 injections of anti-VEGF annually (ADAGIO)

Reduced mean frequency of anti-VEGF injections by 80%

Controlled 7/8 patients for 6 months or more and 4/8 patients for more than 8 months

Maintained retinal thickness and visual acuity for 6 months or more

• GB-102 1 mg met primary endpoint of safety and tolerability (ME trial)

No ocular SAE or dose-limiting toxicity

Majority of patients had no drug-related AEs, including no inflammation

All AEs were mild to moderate without long-term consequences

• Phase 2b 12-month treatment phase completed in December 2020 (ALTISSIMO)

Top-line read-out expected in Q2 2021

58% of patients have entered 6-month extension period to observe further durability of GB-102 1 mg

GB-102 Phase 2b trial in wet AMD (ALTISSIMO) will read-out in Q2 2021

20

Extension study to provide information on GB-102 1mg beyond month 12

Primary endpoint: time to first use of additional supportive therapy

Monitoring Visit

50 out of 56 patients completed 12-

month treatment phase*

(LPV Dec 2020)

58% of patients who completed

Month 12 visit were eligible and

agreed to continue clinical monitoring

in six-month trial extension

*6 patients withdrew for reasons unrelated to their treatment

Lucentis($3,386M WW2)

BevacizumabOff-label

Commercialized

Products

FaricimabPhase 3 Completed

GB-102Phase 2b Treatment Completed +

Extension Study Ongoing

Ranibizumab(Surgical Implant of Port Delivery System)

Phase 3 Completed

In Development

GB-102 most clinically-advanced IVT drug targeting ≥6-month duration1

Longest lasting therapy currently approved is Beovu with 55% patients reaching 3 months

1 Products and product candidates shown are in different stages of development and have been studied in different numbers and types of patients, so direct comparisons of efficacy, duration, or commercial success may not be possible2 2020 global sales from GlobalData as of February 2021

KSI-301Phase 3 Initiated

Eylea($8,285M WW2)

Beovu($190M WW2)

21

Duration(Primary endpoint)

Safety

Control

Patients treatment-free for 6 months

>50% of patients treatment-free for 4 months

No irreversible vision-threatening inflammation

<15% of 1mg patients have medication present in the anterior chamber

BCVA and CST trending in parallel to control arm

ALTISSIMO outcomes required to be competitive with market leaders

22

Our Glaucoma Program: GB-401

Glaucoma: Significant unmet need due to lack of patient compliance

wAMD

~ 76M glaucoma patients worldwide

~$3.8B in 2026

~2.7M patients in U.S.

~$2.9B in 2026

50% of patients

stop treatment

within

6 months

>50% non-compliance

https://www.nei.nih.gov/learn-about-eye-health/resources-for-health-educators/eye-health-data-and-statistics/glaucoma-data-and-statistics

24

GB-401 could provide at least 6 months of sustained intraocular pressure

(IOP) control

32 | C O N F I D E N T I A L A N D P R O P R I E T A R Y

• Preclinical pharmacological effect similar to timolol eye drops

• At least six-month therapeutic drug level demonstrated in animal models

Phase 1/2a clinical trial in POAG planned to be initiated in 2H 2021

*

*Ki = Inhibition Constant

25

IP, Operations & Financial Highlights

Large number of patent families protected through 2041

• Sole owner of ten patent families with 83 granted or pending patent applications

• Licensed five patent families from Johns Hopkins with 50 granted or pending patent applications

GB-102/GB-103

6 issued orange bookable patents

GB-401

3 issued orange bookable patents

Expiration window of issued patents and patent applications

2039

2041

27

Manufacturing process amenable to scale-up

28

• Currently relying on third-party manufacturing at Lubrizol Life Science Health for clinical trial supply

• Intention to build own manufacturing capabilities:

Gain more control and protect know-how

Reduce cycle times

Increase robustness and consistency of process

Reduce cost of goods for commercial production

Optimize commercial scale process

Recent IPO funds current operations

• Priced IPO at $16 on September 25, 2020

• Net proceeds totaled $92.1M, including full over-allotment option exercised in October 2020

• Cash and cash investments of $95.0M at September 30, 2020

• Sufficient to begin patient enrollment in both Phase 3 trials of GB-102 in wAMD in Q4 2021

• 21.0M shares outstanding as of November 6, 2020

• All common, no preferred, no debt

• >10% shareholders: Deerfield, Orbimed, Fidelity1

29

1 As reported on Form 13-G/A filed Feb 8, 2021

Looking Ahead

Our pipeline of long-acting ocular drug candidates

31

GB-102(sunitinib)

6-month dosing

GB-103(sunitinib)

12-month dosing

GB-401(pro-drug)

6-month dosing

Wet Age-Related Macular

Degeneration (wAMD)

Diabetic Retinopathy (DR)

Primary Open-Angle Glaucoma

(POAG)

Ph2b ALTISSIMO Topline (wAMD)

2021 2022

1H 2H 1H

Initiate Ph3 Global Trials (wAMD)

Initiate Ph2b (DME)

Initiate Ph1/2a (DR)

IND Submission (POAG)

Program Indication Anticipated Milestone

Diabetic Macular Edema (DME)

Graybug investment highlights

3

2

Potentially transformative, long-acting treatments for vision-threatening diseases

Differentiated clinical-stage candidates targeting $15B+ markets

• GB-102 for wet age-related macular degeneration (wet AMD)

• GB-102 for diabetic macular edema (DME)

• GB-103 for diabetic retinopathy (DR)

• GB-401 for primary open-angle glaucoma (POAG)

Patent protection: GB-102/GB-103 through 2039, GB-401 through 2041

Numerous near-term milestones

2Q 2021: GB-102 Phase 2b results 2H 2021: Initiate 4 new trials

32