posterior segment company showcase - panoptica
TRANSCRIPT
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
2
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
3
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
4
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
5
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
0
10
20
30
40
50
60
Prim
ate
Cor
nea
conc
entra
tion
(uM
)1
hr fo
llow
ing
last
dos
e on
day
21
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
6
While maintaining consistently low, constant cornea concentrations across dose range
240 360 720 6000
10
20
30
40
50
60
0200400600800100012001400160018002000
Total Daily Exposure of Topical PAN-90806 (µg)
Cor
nea
conc
entra
tion
(µM
)
Cen
tral C
horo
id C
onc
(nM
)
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
7
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
8
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
9
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
10
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*
11
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
12