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NASDAQ: OPHT January 2018
36th Annual J.P. Morgan Healthcare Conference
Glenn Sblendorio, Chief Executive Officer and President
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Forward‐looking statements
Any statements in this presentation about Ophthotech’s future expectations, plans and prospects constitute
forward‐looking statements for purposes of the safe harbor provisions under the Private Securities Litigation
Reform Act of 1995. Forward‐looking statements include any statements about Ophthotech’s strategy, future
operations and future expectations and plans and prospects for Ophthotech, and any other statements
containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend”, “goal,” “may”, “might,” “plan,”
“predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar
expressions. In this presentation, Ophthotech’s forward looking statements include statements about the
implementation of its strategic plan, Ophthotech's projected use of cash and cash balances, the timing,
progress and results of clinical trials and other development activities, and the potential for its business
development strategy, including any potential in‐license or acquisition opportunities. Such forward‐looking
statements involve substantial risks and uncertainties that could cause Ophthotech’s clinical development
programs, future results, performance or achievements to differ significantly from those expressed or implied
by the forward‐looking statements. Such risks and uncertainties include, among others, those related to the
initiation and conduct of clinical trials, availability of data from clinical trials, expectations for regulatory
matters and negotiation and consummation of in‐license and/or acquisition transactions, need for additional
financing and other factors discussed in the “Risk Factors” section contained in the quarterly and annual
reports that Ophthotech files with the Securities and Exchange Commission. Any forward‐looking statements
represent Ophthotech’s views only as of the date of this presentation. Ophthotech anticipates that subsequent
events and developments will cause its views to change. While Ophthotech may elect to update these
forward‐looking statements at some point in the future, Ophthotech specifically disclaims any obligation to do
so except as required by law.
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Science Driven and Retina Focused
• Deep Expertise in Ophthalmic Drug Development
- Multiple retina specialists
- Strong global KOL network to facilitate clinical execution
- Highly experienced clinical development team
• Current Clinical Programs
- Age‐related
Clinical trials in wet and dry AMD currently ongoing
Multi‐billion dollar market opportunities
- Orphan
Significant unmet medical need
Multiple programs ongoing or planned, led by a program in autosomal recessive Stargardt
disease
• Business Development Strategy
- Orphan ophthalmic and retinal diseases with therapeutic and gene therapy solutions
• Strong Cash Position
– ~$167 million in cash and cash equivalents as of 12/31/171
1 Unaudited estimate
Ophthalmology: Age‐related and Orphan Indications
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Value Creation: Multiple Track Strategy
Age‐related Diseases
Multiple opportunities
in large markets where medical
need remains for patients
Orphan Diseases
Focus on underserved
patients with the potential for
an accelerated path to market
Business Development
Disciplined approach to
evaluation of therapeutic and
gene therapy solutions to
ophthalmic diseases
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Diversified Pipeline in Age‐related and Orphan Diseases
Zimura® (Complement C5 inhibitor)
Autosomal Recessive
Stargardt Disease (Orphan)
• Phase 2b trial ongoing (monotherapy)
• ~ 120 Patients / Primary endpoint at Month 18
• Top‐line data expected in 2020
Wet AMD
• Phase 2a trial ongoing (in combination with anti‐VEGF)
• ~ 60 Patients / 6 month study
• Top‐line data expected in late 2018
Idiopathic Polypoidal Choroidal
Vasculopathy (IPCV)
• Phase 2a trial ongoing (in combination with anti‐VEGF)
• ~ 20 Patients / 9 month study
• Top‐line data expected in 2H/2019
Intermediate/Posterior Uveitis
(Orphan) • Phase 2a trial planning to initiate in 2018 (monotherapy)
Dry AMD (GA)
• Phase 2b trial ongoing (monotherapy)
• ~ 200 Patients / Primary endpoint at Month 12
• Top‐line data expected in 2H/2019
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Multiple Catalysts Near‐term and Beyond
Zimura (Complement C5 inhibitor)
Wet AMD
Complete Enrollment
2018 2019 2020
Wet AMD
Phase 2a data
Dry AMD (GA)
Phase 2b data
Stargardt Disease
Phase 2b data
Top‐line data based on current projections
Posterior Uveitis
Initiate Phase 2a
IPCV
Phase 2a data
Diagram is for visual purposes only and is not intended to
indicate specific timing of expected events
Clinical milestones based on current projections
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Zimura, C5 Complement Inhibitor
Geographic Atrophy Secondary to Dry AMD
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• Major unmet medical need
– Large market with no approved treatment options available
• Role of complement in dry AMD1
– Complement deposition increases with aging
– Complement activation leads to the formation and accumulation of
inflammasomes and Membrane Attack Complex (MAC)
– Inflammasomes and MAC lead to retinal pigment epithelial (RPE) cell death
– RPE degeneration leads to photoreceptor cell death and loss of vision
1 The Journal of Biological Chemistry Vol. 290, NO. 52, pp. 31189–31198, December 25, 2015. Invest Ophthalmol Vis Sci. 2013;54:110–120. J Immunol. 2015; 195:3382‐3389. Med
Sci Monit, 2010; 16(1): BR17‐23. Am J Ophthalmol 2002;134:411–431. Proc Natl Acad Sci USA. 2005, 102(20), 7053‐7054.
Development of Zimura for Geographic Atrophy Secondary to
Dry AMD
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C3
C3b
C5
C4
C2
C3 C3
C3b
C3b
C4b
C4b C3b
C5b
C5b
C
8
C
9
C
9
C6
C7
Pathogen
C3bC3b
C2a
C6‐C9
Factor H
C1q
C1r C1s
CD46
CD46
Microbial Cell Surface
Alternative PathwayLectin Pathway Classical Pathway
Pathogen
Zimura ‐ Complement C5 Inhibitor
Inhibition of C5 prevents the formation of C5a and C5b‐9, regardless of complement pathway
Source: OPHT internal
Cell Death
Membrane Attack Complex
(MAC)
C5a
Cell Death
Inflammasome
Bb
Bb
Bb
Factor B
Factor D
Zimura®
X X
X
XX
X
X X
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Zimura Phase 1/2a Dry AMD (GA) – Completed*
Study Design
Intravitreal Zimura was administered for a maximum of 5 injections at one of
two dose levels (0.3 mg/eye or 1mg/eye)
47 Patients Enrolled
0.3 mg dose group (n=24)
1 mg dose group (n=23)
0 4 8 12 16 20 24 28 32 36 40 44 48Week
Zimura Dosed
*Uncontrolled safety trial; small sample size
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Zimura Phase 1/2a Dry AMD (GA) – Completed*
• Potential efficacy signal(s)
• Presence of a dose‐response
trend with “on‐off effect”
• Safety
• No Zimura related adverse
events
• Zero incidence of wet AMD in
eyes treated with Zimura
*Uncontrolled safety trial; small sample size
(n=24)
(n=23)
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Zimura Phase 2b Dry AMD (GA) Clinical Trial – Ongoing
• Phase 2b, randomized, double masked, sham controlled clinical
trial
• Study recently amended to accelerate anticipated timeline to
obtain data
• ~ 200 subjects will be treated with monthly study treatment
(Zimura or Sham) for 18 months
• Primary Efficacy Endpoint
– Mean rate of change in GA over 12 months measured by fundus
autofluorescence (FAF) at three time points
Top‐line data expected in 2H 2019
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Zimura, C5 Complement Inhibitor
Wet Age‐Related Macular Degeneration
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“The processes responsible for the
decrease in vision in CATT and
other studies are multiple, but seem
to be related to an increase in the
proportion patients with an
abnormally thin retina (< 120 µm),
an increase in prevalence of
geographic atrophy, . . . "
“These data highlight the need for
agents that can prevent or minimize
geographic atrophy . . . ”
Unmet Need
Current Standard of Care – Anti‐VEGF Monotherapy
Source: Ophthalmology 2016;123:1751‐1761
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• Unmet medical need remains– major market opportunity
• Anti‐VEGF monotherapy:
– Shown to reach a ceiling effect
– Majority of patients do not reach a visual acuity of 20/40 or better
– In the real world most patients lose vision over time
• Role of Complement in Wet AMD1
– VEGF Increases Complement Factor H (CFH) (regulator of complement activation)
– CFH decreases complement activation
– Anti‐VEGF Increases complement activation
– Patients receiving anti‐VEGF monotherapy may develop geographic atrophy2
• Adding Zimura to anti‐VEGF therapy may improve the efficacy and safety of
anti‐VEGF
1J Clin Invest. 2017;127(1):199‐214
2 Ophthalmology 2014; 121:150‐161.
Development of Zimura for Wet AMD
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Zimura Phase 1/2a Wet AMD – Completed*
46% 47%
60%
0%
15%
30%
45%
60%
0.3 mg 1.0 mg 2.0 mg
n=13 n=15 n=15
≥ 3‐ETDRS Lines Visual Gain at Week 24
%
P
a
t
i
e
n
t
s
• Included:
- Treatment‐naïve patients
- All CNV subtypes
- Patients receiving six monthly
doses of Zimura in combination
with Lucentis® 0.5mg
• Safety:
- All doses well tolerated; no safety
concerns were identified
*Uncontrolled safety trial; small sample size; subgroup analysis
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• Phase 2a open label clinical trial
• N = ~ 60 subjects
• Objectives:
– To assess the safety of intravitreal Zimura administered in combination
with Lucentis® 0.5 mg in treatment naïve subjects with wet AMD
– Dose ranging
– Validate results from previously completed Phase 1/2a
• Duration: 6 months
Top‐line data expected in late 2018
Zimura Wet AMD Clinical Trial – Ongoing
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Zimura, C5 Complement Inhibitor
Autosomal Recessive Stargardt Disease (STGD1)
(Orphan Indication)
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• High unmet medical need – Orphan disease
– No FDA or EMA approved treatment available
• Role of Complement in Stargardt Disease1
– Bisretinoids (visual cycle waste) activate complement
– Complement inhibition rescues photoreceptor cells in a Stargardt animal
model
– Anti‐C5 improved RPE cell viability in bisretinoid/complement cell culture
model
1 The Journal of Biological Chemistry. 2011; 286(21): 18593–18601. Proc Natl Acad Sci U S A. 2017; 114(15):3987‐3992. Invest Ophthalmol Vis Sci. 2013;54:2669‐2677
Development of Zimura in Autosomal Recessive Stargardt Disease
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ABCA4 Gene Mutation (Autosomal Recessive Stargardt, STGD1):
Waste Accumulation InflammationX
Complement inhibition may potentially lead to healthier RPE cells =
Better ability to process and recycle the waste and therefore slow down the
progression of Stargardt disease (1)
Waste Accumulation
Waste Accumulation
Energy Production
Waste Management Inflammation
Cell Damage
X
XX
X
X
(1) Sources: FASEB J. 2004 Mar;18(3):562‐4. Graefe’s Arch Clin Exp Ophthalmol (2002) 240:983‐988. The Journal of Biological Chemistry. 2011; 286(21): 18593–18601. Proc Natl Acad Sci U S A. 2017;
114(15):3987‐3992. Invest Ophthalmol Vis Sci. 2013;54:2669‐2677
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Stargardt Albino Abca4‐/‐Mice:
Complement Inhibition Rescues Photoreceptors
Expression of Complement Inhibitory Protein (CRRY)
~2 fold decrease in
bisretinoid accumulation
~30% increase in the number
of photoreceptor nuclei
Normalized Complement Activity
Source: Proc Natl Acad Sci U S A. 2017; 114(15):3987‐3992.
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• Phase 2b, randomized, double masked, sham controlled clinical
trial
• N = ~ 120 subjects
• Duration of treatment: 18 months
• Primary Endpoint: Mean rate of change in the area of ellipsoid
zone defect measured by en face SD‐OCT
Top‐line data expected in 2020
Zimura Stargardt Disease (STGD1) Clinical Trial ‐ Initiated
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• OPHT agreement with Foundation Fighting Blindness (FFB)
– Highly‐distinguished organization recognized for its scientific commitment
to orphan inherited retinal diseases
– Established network of scientists and a robust patient registry
• Access to FFB’s publicly available ProgStar study
– Largest Natural History Study of Stargardt Disease
– Data leveraged for Zimura Stargardt study design
OPHT / Foundation Fighting Blindness
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Become a leader in the development of novel therapeutics
for age‐related and orphan diseases of the eye
Orphan &
Retina
Indications
(opportunistic
in other ocular)
Seek Ophthalmology Assets in
Preclinical/Development
• Previously evaluated 125+
ophthalmology assets
• Seeking additional assets in target
diseases & novel science in other
ocular indications
Pursue Novel Technologies
Including:
• Gene therapy
• Gene editing
• Scalable platforms
Maintain Industry Leadership
• Build on relationships within the
retina and orphan ophthalmology
communities
In‐License Compelling MOAs
from Outside of
Ophthalmology
• Apply novel MOAs to the eye
(leverage prior development in
other indications)
Pipeline Expansion Strategy
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Financial Highlights
• ~$167 million in cash and cash equivalents as of 12/31/171
• External costs to bring Zimura programs to next phase of
development expected to range between $25 million and $35
million2
• Cash corporate overhead expenses expected to average less
than $2 million per month and continues to decline2, 3
1Unaudited estimate
2Guidance as of 11/8/17 and excludes any potential business development activities or any other changes to the Company’s current clinical
development programs
3Cash corporate overhead expenses consist of cash expenditures for employees and external G&A expenses
Strong Cash Position
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Zimura
Wet AMD Phase 2a ongoing
Dry AMD Phase 2b ongoing
Stargardt Disease Phase 2b ongoing
IPCV Phase 2a ongoing
Posterior Uveitis Phase 2a to initiate in 2018
Business Development
Orphan ophthalmic and retinal diseases with
therapeutic and/or gene therapy solutions
Executing on Strategic Plan:
Age‐related and Orphan Ophthalmic Indications
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Multiple Catalysts Near‐term and Beyond
Zimura (Complement C5 inhibitor)
Wet AMD
Complete Enrollment
2018 2019 2020
Wet AMD
Phase 2a data
Dry AMD (GA)
Phase 2b data
Stargardt Disease
Phase 2b data
Top‐line data based on current projections
Posterior Uveitis
Initiate Phase 2a
IPCV
Phase 2a data
Diagram is for visual purposes only and is not intended to
indicate specific timing of expected events
Clinical milestones based on current projections
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NASDAQ: OPHT January 2018
36th Annual J.P. Morgan Healthcare Conference
Glenn Sblendorio, Chief Executive Officer and President