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OIS@AAO 2015 November 12, 2015 Abbie Celniker, PhD President and Chief Executive Officer

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Page 1: Eleven BioTherapeutics

OIS@AAO 2015

November 12, 2015

Abbie Celniker, PhDPresident and Chief Executive Officer

Page 2: Eleven BioTherapeutics

This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, clinical development of our protein therapies, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,”

“estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,”

“continue,” and similar expressions are intended to identify forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, although not all forward-looking statements contain these identifying words.

We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, our ability to successfully develop our product candidates and complete our planned clinical programs, our ability to obtain marketing approvals for our product candidates, expectations regarding our ongoing clinical trials, availability and timing of data from clinical trials, whetherinterim results from a clinical trial will be predictive of the final results of the trial or results of early clinical studies will be indicative of the results of future studies, the adequacy of any clinical models, expectations regarding regulatory approvals, our ability to obtain, maintain and protect our intellectual property for our technology and products, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements, other

matters that could affect the financial performance of the Company, other matters that could affect the availability or commercial potential of the Company’s product candidates and other factors discussed in the “Risk Factors” section of the

Company’s Report on Form 10-Q filed with the Securities and Exchange Commission on November 4, 2015, and other reports on file with the Securities and Exchange Commission. The forward-looking statements contained in this presentation reflect Eleven’s current views as of the date hereof with respect to future events, and Eleven assumes no

obligation to update any forward-looking statements except as required by applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.

Forward-Looking Statements

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Page 3: Eleven BioTherapeutics

• Developing differentiated protein therapeutics to treat ocular diseases of both front and back of the eye

• Isunakinra (EBI-005): Topically administered IL-1 receptor blocker in late stage development for ocular surface inflammatory diseases

‒ Phase 3 trial in moderate to severe allergic conjunctivitis topline data expected 1Q 16

• Phase 2 results reported in allergic conjunctivitis in October 2014

• Potential BLA filing 2H 17

‒ Composition-of-matter patent issued - coverage through 2031

• EBI-031: Long acting intravitreal IL-6 antibody for treatment of diabetic macular edema and uveitis

‒ IND planned for the 1H 16

• AMP-Rx platform for design and engineering of protein therapeutics with potential to leverage beyond current targets

• $46.4 million cash as of September 30, 2015

• Management team with extensive experience in biologics and ophthalmology

Company Highlights

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Page 4: Eleven BioTherapeutics

Development Pipeline

PROGRAM INDICATION

OUR COMMERCIAL

RIGHTS DISCOVERYPRE-

CLINICAL PHASE 1 PHASE 2 PHASE 3

Isunakinra(topical)

AllergicConjunctivitis

Worldwide

EBI-031 (long acting, intravitrealinjection)

DMEand Uveitis

Worldwide

VEGF pathway inhibitor(long acting, intravitreal injection)

Wet AMD and DME

Worldwide

DEVELOPMENT STAGE

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Page 5: Eleven BioTherapeutics

Allergic Conjunctivitis Patients Need Better Treatment Options

* Based on Eleven primary market research

Total Global Ophthalmic Market –Large and Growing

Glaucoma

Retinal Disease

Other

Dry Eye Disease

Allergy

4

1.8

5.2 U.S. Market:~5.8 Million*

Moderate

M

M

M

U.S. ~11 Million Diagnosed AC Patients*

Severe

Mild

Standard of Care:• Antihistamines• Mast cell stabilizers• Topical corticosteroids

Commercial Opportunity:

• We estimate that about half of the diagnosed patients with AC are not adequately treated with standard of care

• Reachable with a specialty sales force detailing to ophthalmologists and optometrists

Many allergic conjunctivitis patients inadequately treated

or require steroids

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Page 6: Eleven BioTherapeutics

U.S. Allergic Conjunctivitis Market Segmentation Provides Opportunity for Isunakinra

* Based on Eleven primary market research

MildMostly Seasonal

5.2 Million

ModerateSeasonal & Perennial

4.0 Million

Severe,Chronic, Seasonal, Perennial, VKC & AKC

1.8 Million

Mild Moderate Severe

The U.S. diagnosed population is estimated at ~11MM*

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Orange - Market Leader Blue - Newest Approval Green - Anti-inflammatory Purple - Isunakinra

Patanol (Olopatadine .1%)Pataday (Olopatadine .2%)Pazeo (Olopatadine .7%)Lastacaft (Alcaftadine .25%)Bepreve (Bepotastine)Elestat (Epinastine)Emadine (Emedastine .05%)Zaditor (Ketotifen, Alaway)- OTCAlamast (Pemirolast)Alcocril (Nedocromil)Livistin (Levocabastine) Alomide (Lodoxamide)

Acular (Ketorolac .5%)Alrex (Loteprednol .2%)

Isunakinra (Interleukin-1 Receptor Antagonist) 1

Off label steroids

Systemic immunosupression

Alrex (Loteprednol .2%)

Isunakinra (Intereukin-1 Receptor Antagonist)1

OTX-DP (Dexamethasonepunctal plug) 1

Inflammatory IL-1/Late Phase

1 In development

Histamine/Early Phase (Acute)

Page 7: Eleven BioTherapeutics

Isunakinra: Activity in Allergic Conjunctivitis Late Phase Response

Mean Change in Ocular Itching Following Multiple Days of Allergen

(Phase 2 Study Data)

*

*Study did not meet primary endpoint of reduction in EEC model.

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Page 8: Eleven BioTherapeutics

Isunakinra: Late Phase Response Measured by Multiple Endpoints at Multiple Time-Points in Phase 2 Study

• Response to drug with multiple allergen challenges

• Statistically significant separation from vehicle for itching, tearing and nasal symptoms

p=0.033

p=0.046

p = 0.027

p = 0.044 p = 0.004p = 0.011

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Page 9: Eleven BioTherapeutics

Isunakinra Phase 3 Study in Allergic Conjunctivitis Fully Enrolled

• Natural environmental study• Double masked, vehicle controlled• U.S. study, 250 patients enrolled• Inclusion criteria: Late Phase AC

‒ Failure or incomplete response to antihistamines/mast cell stabilizers

‒ Required topical steroids‒ Atopic Keratoconjunctivitis

Objectives• Primary: Ocular itching• Secondary: Ocular tearing, Total nasal

Symptoms, Conjunctival redness• Safety, tolerability, and immunogenicity

• Patient diaries• Monitor pollen counts

Days -35 to -7 Day 1 Week 2 CA

C 1

Week 4

EVALUATION VISITS FOLLOW UP

Week 6

Up to 35

Days

2Week

Follow UpVehicle Control — 3 times daily

(125 patients)

EBI-005 5 mg/ml — 3 times daily(125 patients)

Screening Randomization Off Treatment

9

CA

C 3

CA

C 2

CA

CD

ay-6

V1 V2 V3 V4 V5 V6

Page 10: Eleven BioTherapeutics

U.S. Market:~746,0002

Many Diabetic Macular Edema Patients Not Adequately TreatedTotal Global Ophthalmic Market –

Large and Growing

Glaucoma Retinal Disease*

Other Dry Eye Disease

Allergy

Diabetic Macular Edema Global Population: ~922K and expected to

grow to 1.2MM in 20231

* Retinal disease includes macular edema, age related macular degeneration and uveitis

1 Globaldata 2014 epiCast report on Macular Edema, Global represents UK, France, Germany, Spain and Italy, Japan, U.S.

2 JAMA Ophthalmol. 2014 Nov;132(11):1334-40.

Standard of Care:• Anti-VEGF• Steroids

Diabetic Macular Edema (DME), a retinal disease, is one of the leading

causes of vision loss occurring in nearly 10% of diabetic patients

Commercial Opportunity:• IL-6 blockade may provide increased efficacy

by simultaneously targeting angiogenic and inflammatory components of disease with less frequent intravitreal injections

U.S.

EU +Japan

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Page 11: Eleven BioTherapeutics

Targeting needs in DME

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1 Nguyen QD, Ophthalmology. 2012;119:789-801

Unmet Needs Today

Nearly 25% of DME patients do not benefit from anti-VEGF Tx1

DME patients are known to have elevated levels of IL-6 in the circulation and vitreous, therefore, potent complete blockade is needed

Multiple intravitreal injections are inconvenient and uncomfortable for patients

Dual action of blocking both VEGF dependent and VEGF independent mechanism can be achieved by blocking IL-6

Binding to Site 2 epitope may offer complete IL-6 blockade for higher affinity and potency than tocilizumab and EBI-031 could provide more complete target blockade

Increased vitreal half life could result in lower frequency of injections for patients

EBI-031 Has the Potential to Address the Needs

Page 12: Eleven BioTherapeutics

EBI-031: Anti-IL-6 in Diabetic Macular Edema

• Inflammation drives onset of DME and IL-6 Production

• IL-6 drives VEGF production, leukocyte infiltration and Tie2 antagonism

• In animal model, blocking IL-6 can reduce CNV comparably to blocking VEGF

• Published clinical studies show blocking IL-6 can reduce uveitis associated CME

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Page 13: Eleven BioTherapeutics

Glaucoma

Other

Allergy

13

IVT PK in animals predicts a half life in animals >2X of VEGF inhibitors

1 Gaudreault et al. 2 Eylea EMA guidance 3 Steward et al. 2011 (review) 4 Struble et al. 2011 5 Krohne et al., 2012 6 Zu et al. 2013 7 Miyake et al. 2010

8 Xu et al, 2013

EBI-031 could result in target blockade for up to 3 months or more

EBI-031 Potency and Extended Half-Life Could Lead to Less Frequent Injections

Binding Constants

Drug Target Kd

EBI-031 0.5 pM

Tocilizumab 750* pM

*FDA pharmacology review

Page 14: Eleven BioTherapeutics

Key Upcoming Milestones

Isunakinra Begin Phase 3 in allergic conjunctivitis 3Q 15

Isunakinra Topline Phase 3 allergic conjunctivitis results 1Q 16

EBI-031 File IND 1H 16

Isunakinra Begin 2nd Phase 3 in allergic conjunctivitis 2H 16

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Page 15: Eleven BioTherapeutics

OIS@AAO 2015

November 12, 2015

Abbie Celniker, PhDPresident and Chief Executive Officer