vision medicines

Vision Medicines Inc. – Proprietary & Confidential

2015 Annual Ophthalmology Innovation Summit at AAO Vision Medicines, Inc.Science to See Tomorrow™

Chris Varma, PhDChairman & CEO

November 2015

Vision Medicines Inc. – Proprietary & ConfidentialVision Medicines Inc.

Focused on retina, the highest growth area in ophthalmology

Overview

• Treatments for severe retinal degenerative diseases; high unmet medical need

• Multi-billion dollar market opportunities; strong IP

• Proven management team and world-class scientific advisory board

Strategy

• Develop assets and drive consolidation in the ophthalmology marketplace

Programs

Phase 2/3 ready, VM100:

- Geographic atrophy (GA) and intermediate AMD (iAMD)

- Combined $20B market opportunity

IND-enabling studies ongoing, VM200 for Stargardt Disease (orphan disease):

- No current therapies; $6B market opportunity US/EU5/Japan

- $7.5M non-dilutive co-funding from Foundation Fighting Blindness

- Additional orphan indications: SLS, SSADH, and BEST Disease (~$1B)

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Sources: RBC Capital Markets Research Report, Back of the Eye Preview, 12-2-14 and Vision Medicines internal research


Pipeline addresses high unmet medical needs and multi-billion dollar market opportunities

Product MOA IndicationStage of Development

Market opportunityPreclin Ph 1 Ph2 Ph 3

VM100 (mAb)

Clearretinal Ab & comple-ment

Geographic Atrophy

Intermediate AMD

$20B WW for GA and iAMD- 2016 – Initiate P2/3 study- Dark adaptation data at 3 months- 6 mo interim data- 2017 – PoC in GA

VM200(small

molecule)

Alde-hydetrap

StargardtDisease (Orphan)

SLS* (Orphan)

SSADH*(Orphan)

Best Disease(Orphan)

Stargardt Disease $6B US/EU5/JPN- 2016 –Initiate P1/2 study- Autofluorescencebiomarker data at 3 months- 2018 – PoC in Stargardt

Additional indications: SLS, SSADH, Best Disease ~$1B WW

2018 PoC

3

Sources: RBC Capital Markets Research Report, Back of the Eye Preview, 12-2-14 and Vision Medicines internal research

2017 PoC

Phase 2/3 ready

*SLS=SjogrrenLarson Syndrome, SSADH=Succinincsemi-aldheydedehydrogenase deficiency


VM100: Key points of differentiation

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• Systemic treatment

• Treats both eyes simultaneously

• Less invasive than intravitreal (IVT) injections into each eye

• No safety signal; 61 patients treated in 2 Phase 1 trials

• Potential for less frequent dosing

• Potential for every other month or quarterly dosing

• Better convenience and compliance

• Effects multiple targets

• Beta amyloid (Aβ)

• Complement

• VEGF/PEDF


VM100: Why we believe

Target Validation

• Biogen has clinically validated Aβ as a driver of Alzheimer's disease

Mechanism

• Drusen are a biomarker for risk of progression to advanced AMD; drusencontain toxic Aβ and activated complement

• In post-mortem studies, ~100% of eyes with high drusen load also have retinal Aβ and Aβ oligomers are only present in eyes with drusen

• Aβ pathophysiology links to clinically-validated mechanistic pathways in advanced AMD (wet AMD and GA)

Data

• Anti-Aβ mAbs administered systemically decrease retinal Aβ and complement in two mouse models of dry AMD using several antibodies

• Improvement in retinal function was observed with VM100

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Luibl et al. Journal of Clinical Investigation. 116 (2006) 378-385

Anderson et al. Experimental Eye Research. 78 (2004) 243-256

Wang et al. Journal of Immunology. 181 (2008) 712-720

Wang et al. Journal Cell Physiol. 220 (2009) 119-128.

Yoshida et al. The Journal of Clinical Investigation. 115 (2005) 2793-2800

Moreth et al. Immunity & Ageing 2013, 10:18

Johnson PNAS 99:11830 (2002) – and replicated by 3 other groups


Goal: Treat GA and iAMD to prevent progression; $20B market opportunity

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Intermediate AMD

Advanced AMD (geographic atrophy)

Geographic atrophy (GA)Wet AMD

Advanced AMD(Blinding)

~10%/year

Intermediate AMD (dry)

Sources: EDPRG Arch Ophth 2004;122:564

AREDS Rep 18 Arch Ophth 2005;123:1570

Our focus

1 million in US No therapies

1.2 million in USMain treatment anti-VEGF

• 7.3 million in US• High risk of vision loss• No current treatments

Advanced AMD(Blinding)

~10%/year

Our focusIntermediate AMD (iAMD)


VM100 clears harmful Aβ and complement to preserve retinal

structure and function in GA and iAMD

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VM100

VEGF, CFBPEDF, CFI


VM100 prevents Aβ and complement deposition in the aged/APOE/HFC diet mouse model of dry AMD, preserving retinal structure and function

VMI - Proprietary &

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Mouse model of dry AMD: Human ApoE KI mice, Aged > 1 year,fed high cholesterol diet

Source: Ding PNAS 108:E279 (2011)

Preservation of function (ERG) with VM100 (red line)

Normal diet (ND) (Red=Aβ)

High fat diet (HFC) (Red=Aβ)

HFC + VM100 (Red=Aβ)

Ret

ina

Imm

un

oh

isto

chem

istr

y

VM100 prevents deposition of Aβ

VM100 prevents deposition of activated complement

Preserves structure Preserves function

VM100


Phase 1a (Single ascending dose)

Phase 1b (Multiple ascending dose)

Design Single IV dose: 0.3, 1.0, 3.0, 10.0, 20.0, or 40 mg/kg, placebo

6 monthly IV doses: 5,10, or 15 mg/kg, or placebo

Size,Population

N=57 totalN=36 treatment groupdry AMD patients, including GA

N=24 totalN=18 treatment groupdry AMD patients, including GA

Safety • No clinically meaningful differences in AEs across treatment groups.

• 1 SAE (1 mg group, unrelated): carotid stenosis

• No deaths• Transient, low level ADAs in 8

with no clinical sequelae

• No clinically meaningful differences in AEs across treatment groups.

• 2 SAE (15 mg group, unrelated): syncope, anemia

• No deaths• No ADA

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VM100 safety data: 61 treated GA/iAMD patients in 2 trials with no drug-related safety signals; Ready for Phase 2/3


VM200: Key points of differentiation

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• Oral, systemic drug that treats both eyes

• Non-invasive application

• Treats the whole retina

• $7.5M non-dilutive co-funding from Foundation Fighting Blindness

• Prevalence estimated to be 100K in US, EU5 and Japan

• Enantiomer of an approved drug with established safety profile

• Suitable for all stages of disease

• Directly targets toxic all-trans retinal

• Strong pre-clinical animal PoC data in Stargardt disease

• Preserves retinal structure and function in mouse model

• General aldehyde trap mechanism provides option for multiple orphan indications including SLS and SSADH. Potential also in Best disease.


VM200 traps toxic all-trans retinal until it can be neutralized

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Normal state with intact transporter

Disease state without transporter

VM200 neutralizes all-trans retinal (toxic)

VM200 Treated

VM200

VM200


VM200 prevents retinal degeneration in the Abca4-/- Rdh8-/- mouse model of Stargardt disease

VM200 administered to Abca4-/-/Rdh8-/- mice 2 hours prior to light damage preserves retinal structure and function in a dose-dependent manner

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11-cis-retinal is a biochemical marker of intact photoreceptors

OCT is an in vivo retinal structure imaging technique

Source: Unpublished Data from PalcziewskiLab, Case Western Reserve University

Source: OCT data from Maeda et al. Nature Chem Biology. Feb 2012

0

20

40

60

80

100

0.05 0.2 0.5 211

-cis

ret

inal

(%)

VM200 Dose (mg)

0

1

2

3

4

0 0.5 2

OC

T S

core

VM200 Dose (mg)

No damage

Max damage

No dysfunction

HighDysfunction

VM200 preserves retinal structure VM200 preserves retinal function


Ophthalmology therapeutic area is ripe for consolidation

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< 2 Products / Company

35%

2-3 Products / Company

29%

3+ Products / Company

36%

Disease

Category

(All Companies)

# of

Companies

# of

Products

Products Per

Company

Mix of Total

Companies

Mix of

Total

Products

Oncology 1108 5046 4.55 22.5% 34.3%

Neurology 737 2179 2.96 15.0% 14.8%

Internal Medicine 974 2586 2.66 19.8% 17.6%

Cardiology 372 968 2.60 7.6% 6.6%

Endocrinology / Diabetes / Metabolism 489 1259 2.57 9.9% 8.6%

Allergy / Immunology 513 1232 2.40 10.4% 8.4%

Ophthalmology 245 561 2.29 5.0% 3.8%

Dermatology 248 487 1.96 5.0% 3.3%

Urology 236 403 1.71 4.8% 2.7%

Mean (All Companies) 547 1,636 2.63 N/A N/A

Median (All Companies) 489 1,232 2.57 N/A N/A

Products per company breakdown

Source: RW Baird investment banking data and Vision Medicines research. Note: Selection of AMA recognized specialty areas most relevant to pharmaceutical drugs. Neurology includes Psychiatric and Neurology for simplicity. Pediatric not included as manypediatric drugs are repurposed from other specialty areas. Per AMA classification, Internal Medicine includes specialty areas such as Hematology, Infectious Disease, Pulmonary, and Gastroenterology.

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