Creating a new wave of innovation in wet AMD treatment one drop at a time

Paul ChaneyPresident and CEO OIS@AAO Chicago

October 13, 2016

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Stepping forward with confidence PAN-90806: Topical eye drop for neovascular AMD

Clinical data and New Suspension Formulation development • Phase 1/2 study completed in treatment naïve patients with neovascular AMD (former

solution formulation)- Monotherapy up to 2 months (n=40)

- Maintenance therapy for 3 months following single IVT Lucentis injection (n=10)

• New suspension formulation shows significant risk reduction - Only consistent adverse event reported: Dose-dependent reversible keratopathy noted at higher

doses in animals and humans

• Regulatory requirements established for development as maintenance therapy

• Intellectual property recognized with US Patent issued Sept. 20

• Financing closed (Third Rock, SVLS, Novo Ventures) through amended IND/CTAs

• Clinic ready 2Q 2017 with potential for financing, partnership, risk share prior to study start

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Effects observed on vascular leakage, lesion morphology, and vision

PAN-90806: Encouraging Phase 1/2 results slated for late breaking developments at Retina Subspecialty Day

Week 8 VA: 71 CST: 213

Day 1 VA: 66 CST: 286Day 1 VA: 67 CPT: 381

Week 8 VA: 74 CPT: 242

Patient 1188 Patient 1174 Conclusions of Independent Retina Specialist Review:~50% of treated patients had anti-VEGF responses that provided patient benefit within the range of current approved anti-VEGF therapies and outside the expected course of natural disease history.

PAN-90806 – a novel topical treatment for neovascular AMDFriday Oct 14, 4:37 pm, North Hall B Scott W. Cousins, MD

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Physical chemistry is key:

• Aqueous solubility• Lipophilicity• Free drug fraction• Sustained target tissue concentration

• Highest initial drug concentration observed transiently in cornea• Partially inhibits signaling through a kinase receptor essential to

corneal epithelial homeostasis• Produces reversible dose-dependent corneal keratopathy

PAN-90806: Consistent exposure to the back of the eye regardless of formulation

Cornea >> Choroid > Retina > Aqueous > Vitreous

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PAN-90806: New suspension formulation significantly and favorably alters the cornea pK profile for safety

Total daily exposure of topical PAN-90806 (ug)0 50 100 150 200 250 300 350 400

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Prim

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Cor

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Former Phase 1 Solution Formulation

New Suspension Formulation

Cornea Concentration (C-max) as a Function of Total Daily Dose on day 21 in primate study

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While maintaining consistently low, constant cornea concentrations across dose range

240 360 720 6000

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0200400600800100012001400160018002000

Total Daily Exposure of Topical PAN-90806 (µg)

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Cen

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horo

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Central Choroid Conc (nM)New Suspension Formulation

Cornea Concentration (µM)New Suspension Formulation

IC50 at VEGFR2 = 1.27 nM

PAN-90806: New suspension formulation showed excellent dose-dependent bioavailability at the target tissues in the central choroid and retina

Tissue levels Cmax 1-hour post dose on day 21 as a function of total daily dose

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PAN-90806: Primate toxicity studies suggest new suspension formulation can favorably alter therapeutic index with expanded safe dose range

• No adverse findings have been observed to date with new suspension formulation in exploratory primate studies at up to 20 mg/ml for up to 28 days

• Safe PAN-90806 clinical dose range with new suspension formulation expected to be ≥ 6-10x human MTD with previous solution formulation

• Will enable amended IND and CTAs for New Suspension Formulation 1Q 2017

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Dose-ranging as monotherapy in treatment naïve nAMD (safety, efficacy, dose selection)• Up to 60 pts, 3-5 dose cohorts in Europe and US• Safety, anatomical & functional endpoints (SD-OCT, FA, VA); assess dose-

response

Select dose-range for chronic (6mo) GLP toxicity studies when approximately half of planned patients have completed 3 months treatment • Reduces risk for expensive / critical chronic GLP studies• Enables IND amendment for next, later phase trial by end of this trial (1H 2018)

Demonstrate improved tolerability, higher dose range, and more robust anti-VEGF activity and dose response to inform design of Ph2+ maintenance trial(s)

PAN-90806: Phase 1b/2a trial in 2017 will confirm benefit of suspension formulation as monotherapy and inform later stage trials with data 1H 2018

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Staged development program designed to minimize risk, achieve PoC, create value

2016JUL AUG SEP NOVOCT DECJUN APR MAY JUNJAN FEB MAR

2017

Mfg + Release GMP BFS supplies

3mo Rabbit GLP Tox: monoRx

• Dosing - Jul’16; Audited Draft Report – early Feb ’17

3mo Primate GLP Tox: monoRx + adjunct/maintenanc

• Dosing - Jul’16; Audited Draft Report – late Jan’17

Ph1b therapeutic window: GO

GMP Ph1b supply platform: GO

Submit IND Amend/CTAs

Ph1b PoCopen US

enrollment

EU Scientific Advice Mtgs for Ph1b

Phase 1/2 Results

Clin Results monotx + maint, Susp primate

tox/pK

Primate Tox & pK

EU Clin/Reg Prep

AAO ph1/2 pres, OIS pres, GLP tox in-life, Clin Supply

update

IND & CTAs Filed, Site

Prep, Clinic Ready Trial Initiation

US&EUClinical & Non-Clin DevGLP Tox initiation

EU Reg &InvestigatorMeetings

GLP Tox complete,GMP clin supply Campaign

Negotiations& Diligence

Financing/Partner Communication

Tox resultsIncl histopath

In-life tox complete

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Potential for:• Early partnership participation (option, cost-share, financing) 1Q 2017 • NDA filings on primary efficacy analysis in 2022-25 as maintenance tx

Setting the stage for significant commercial opportunity

2016 20182017 20242019 2020 2021 2022 2023

Phase 2/3 – 285-380 patients$25-31 Mil

Pivotal Phase 3 – 933 patients; $74 Mil

Phase 2/3 – 285-380 patients; $25-31 Mil

Phase 2/3 – 285-380 patients; $25-31 Mil

Accelerated Devt NDA filing

2022-3

Base CaseNDA Filing 2025

*Range based on trial design, potential initiation of chronic GLP tox for ph2+ trial

Phase 1/2 – 30-50 pts

$2-2.5 Mil

$8-15M to PoC*

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Accomplished ophthalmology-experienced management team, board of directors, and investor syndicate

Paul G. Chaney - President & CEO• 20 years of experience in ophthalmology• OSI Eyetech, Eyetech, Pharmacia (Pfizer)• Launches of Xalatan, Xalcom, Macugen

Martin B. Wax, MD - Chief Medical Officer & EVP, Product Development

• Former VP of R&D at Alcon

David P. Bingaman, DVM, PhD - Sr. Dir. & Head, Retina Development Kristine Curtiss - Executive Director, Clinical Operations Lori Forrest - Executive Director, Finance & Controller Angela Kothe, OD, PhD - Regulatory Affairs Consultant

David Guyer, MD - CEO, Ophthotech Corporation

Colin Goddard, PhD - CEO & Executive Chair, Coferon

Bruce Peacock - Venture Partner, SV Life Sciences

Mike Ross - Managing Partner, SV Life Sciences

Kevin Starr - Partner, Third Rock Ventures

Thomas Dyrberg, MD - Senior Partner, Novo Ventures

Paul Chaney - President & CEO, PanOptica Inc.

Management Team Board of Directors

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