November 12, 2015
Breakthrough Opportunities in Retinal Disease and Cancer
William L. Greene, MDChief Executive Officer
Ophthalmology Innovation Summit
Snapshot
Tissue Factor: central to pathophysiology of retinal disease and cancer
– Targeting an “undrugged” pathway
– Leveraging advances in Tissue Factor biology, new scientific understandings
Addressing significant therapeutic needs in large markets
– Wet AMD: critical need for disease modifying agents
– Cancer: opportunity to treat tumor, vasculature, and microenvironment with a single targeted agent
Lead clinical candidate in Phase 2a for wet AMD
Expanding portfolio of development programs
– Ocular Melanoma, IND 1H 2016
Positioned for success
– World-class management team, advisors, Board
– Strong financial position and IP
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Product Pipeline
Indication Research Preclinical Phase 1 Phase 2 Phase 3 Near TermMilestones
Wet AMDTop line data
2H 2016
Additional Retinal Indications
Ocular Melanoma
IND 1H 2016
Solid Tumors
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Therapeutic Target: Tissue Factor (TF)
Human protein important in health and disease
– Key role in regulation of coagulation, inflammation
– Overexpression: drives pathologic angiogenesis and inflammation; increases metastatic potential, promotes escape from immune surveillance
– Historically difficult to target due to coagulation concerns
ICON-1: First-in-class human immunoconjugatefusion protein
– Engineered to safely bind TF by replacing its natural ligand without significant effect on coagulation function
– Acts similar to a therapeutic mAb
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Tissue Factor: Central Role in Wet AMD
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Macula with Wet AMD
CNV: TF overexpressed
on vessels and in vitreousAccessible to bind to anti-TF agent
Angiogenesis
Wet AMD
Hypoxia Inflammatory Cytokines
Increased Levels of TF
Macrophages (Inflammatory)
Inflammation
Increased VEGF
Release
Amplification of Angiogenic
Cytokines
Release of Proinflammatory
Cytokines (e.g., IL-6, IL-8)
ICON-1 for Wet AMD: Preclinical Data
A. Micrograph of control lesion: CNV growth prominent
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B. Micrograph of a lesion treated with mI-con1 (mouse version of ICON-1): little evidence of CNV
Bora et al. Proc Natl Acad Sci 2003.
• Murine models: prevention and regression of CNV after single dose
• Porcine model: dose response observed
• Excellent safety profile
Wet AMD Mouse Model
ICON-1 for Wet AMD: Phase 1 Study
First in human single dose trial: focused on safety
– Broad inclusion criteria; 9/18 subjects newly diagnosed
– 3 dose groups: 0.06 mg, 0.15 mg or 0.30 mg
Safety: no ocular or systemic safety issues; no immunogenicity seen
Signals of potential dose-related biologic activity
– Visual acuity increases, reduced retinal fluid, reduced leakage on angiograms
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58
+19
+4
+16
+11
+16 +21
467
-236
-57
-148-175
-215-238
Week 5 Week 8 Week 12 Week 16
-300
-250
-200
-150
-100
-50
0
50
100
150
200
250
300
30
35
40
45
50
55
60
65
70
75
80
Screen Wk 1 Wk 2 Wk 5 Wk 8 Wk 12 Wk 24
Micro
ns (μ
m)
Lett
ers
(ET
DR
S)
BCVA
OCT: CenterSubfield Change
Anti-VEGFTreatment
Treatment-naïve patient, 0.3mg dose group
ICON-1 Phase 1: Subject Case Study
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Treatment Naïve Patient Screening
Follow UpWeek 24
Single Dose ICON-1Week 5
Central Retinal Thickness (CRT) on Optical Coherence Tomography (OCT) and CNV leakage on Fundus Fluorescein Angiography (FFA)
VA (Letters) 58 (20/63)
VA (Letters)69 (20/40)
VA (Letters) 79 (20/25)
EMERGE Study: Data Expected 2H 2016Phase 2a, Double-Masked, Active-Controlled, Multicenter (U.S.), Initiated 2015
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“Rescue treatment” with Lucentis is available at any time during the study based on protocol-defined criteria.
ICON-1 300μg
1:1:1 Randomization
Lucentis 0.5mgICON-1 300μg
Lucentis 0.5mg
End of Study: Month 6
Primary Endpoint: Month 3
Treatment-NaïvePrimary, Active CNV
N=90
ClinicalTrials.gov Identifier: NCT02358889
ICON-1 for Ocular Melanoma
Broadly applicable cancer mechanism
– TF widely expressed on tumor cells, tumor vasculature, and in microenvironment
– Marker for aggressive tumor growth, poor prognosis; central to process of metastasis
TF overexpressed in cutaneous and ocular melanoma
Positive ICON-1 data in xenograft (cutaneous) melanoma model
Plan: initiate IND in OM 1H 2016
Ongoing research in other solid tumors
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Melanoma mouse xenograft treated with “murine version” of ICON-1
Hu Z, Sun Y & Garen A, Proc Natl Acad Sci (USA), 1999.
Leadership Team
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William Greene, MDChief Executive Officer
Gabriela Burian, MD MPHChief Medical Officer
Kirk DornbushCo-Founder and President
K. Peter Hirth, PhDSenior Scientific Advisor
Thi-Sau Migone, PhDHead of Research
George MontgomerySVP Financial Strategy
Board of Directors and Advisors
Board of Directors Scientific and Clinical Advisory Board
Kirk Dornbush, Iconic Founder
Todd Foley, MPM Capital
William Greene, MD, Iconic
K. Peter Hirth, PhD (Independent)
Johan Kördel, PhD, Lundbeckfond Ventures
Bruce Robertson, PhD, H.I.G. BioVentures
E. Jonathan Soderstrom, PhD, Yale
Evangelos S. Gragoudas, MD, Massachusetts
Eye & Ear Infirmary
Christine R. Gonzales, MD, Retina and
Vitreous Center
Darius M. Moshfeghi, MD, Stanford University
Elias Reichel, MD, Tufts University
Carl D. Regillo, MD, Wills Eye Hospital
Wolfram Ruf, MD, Scripps Research Institute
Steven D. Schwartz, MD, Jules Stein Eye
Institute, UCLA
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Investors
Summary
Breakthrough opportunities in retinal diseases and cancer
– Deep knowledge of TF biology
– Unique therapeutic applications based on known and emerging TF science
– Addressing critical therapeutic needs in large markets
Multiple product platform in development
– ICON-1: IND OM 1H 2016; Phase 2a Wet AMD data 2H 2016
– Additional targeted oncology molecules in development
Poised for execution, strong financial position
– World-class advisors and team members with proven track record
– $40 million raised to date; Series C financing in 2015
– Substantial near-term milestones
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