eleven biotherapeutics
TRANSCRIPT
OIS@AAO 2015
November 12, 2015
Abbie Celniker, PhDPresident and Chief Executive Officer
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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• 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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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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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
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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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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)
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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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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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
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CA
C 3
CA
C 2
CA
CD
ay-6
V1 V2 V3 V4 V5 V6
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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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
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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Glaucoma
Other
Allergy
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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
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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OIS@AAO 2015
November 12, 2015
Abbie Celniker, PhDPresident and Chief Executive Officer