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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Screen Wk 1 Wk 2 Wk 5 Wk 8 Wk 12 Wk 24

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Lett

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(ET

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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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THANK YOU

www.IconicTherapeutics.com

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