Iconic Therapeutics "Breakthrough Opportunities in Retinal Disease and Cancer" presented at OIS@AAO 2015

1. November 12, 2015
Breakthrough Opportunities
in Retinal Disease and Cancer
William L. Greene, MD
Chief Executive Officer
Ophthalmology Innovation Summit

2. 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
2

3. Product Pipeline
Indication Research Preclinical Phase 1 Phase 2 Phase 3
Near Term
Milestones
Wet AMD
Top line data
2H 2016
Additional
Retinal
Indications
Ocular
Melanoma
IND
1H 2016
Solid
Tumors
3

4. 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 immunoconjugate
fusion protein
– Engineered to safely bind TF by replacing its
natural ligand without significant effect on
coagulation function
– Acts similar to a therapeutic mAb
4

5. Tissue Factor: Central Role in Wet AMD
5
Macula with Wet AMD
CNV:
TF overexpressed
on vessels and in vitreous
Accessible 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)

6. ICON-1 for Wet AMD: Preclinical Data
A. Micrograph of control lesion: CNV
growth prominent
6
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

7. 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
7
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
Microns(μm)
Letters(ETDRS)
BCVA
OCT: Center
Subfield Change
Anti-VEGF
Treatment
Treatment-naïve patient, 0.3mg dose group

8. ICON-1 Phase 1: Subject Case Study
8
Treatment Naïve
Patient Screening
Follow Up
Week 24
Single Dose ICON-1
Week 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)

9. EMERGE Study: Data Expected 2H 2016
Phase 2a, Double-Masked, Active-Controlled, Multicenter (U.S.), Initiated 2015
9
“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 0.5mg
ICON-1 300μg
Lucentis 0.5mg
End of Study: Month 6
Primary Endpoint: Month 3
Treatment-Naïve
Primary, Active CNV
N=90
ClinicalTrials.gov Identifier: NCT02358889

10. 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
10
Melanoma mouse xenograft treated with
“murine version” of ICON-1
Hu Z, Sun Y & Garen A, Proc Natl Acad Sci (USA), 1999.

11. Leadership Team
11
William Greene, MD
Chief Executive Officer
Gabriela Burian, MD MPH
Chief Medical Officer
Kirk Dornbush
Co-Founder and President
K. Peter Hirth, PhD
Senior Scientific Advisor
Thi-Sau Migone, PhD
Head of Research
George Montgomery
SVP Financial Strategy

12. 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
12
Investors

13. 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
13

14. THANK YOU
www.IconicTherapeutics.com
14