Developing OPT-302: A novel therapy for wet AMD

Developing OPT-302:
A novel therapy for wet AMD
February 2016
Opthea Limited
(ASX:OPT, OTCQX:CKDXY)
Megan Baldwin PhD, CEO & Managing Director
megan.baldwin@opthea.com
Disclaimer
Investment in Opthea Limited (‘Opthea’) is subject to investment risk, including possible loss of income and capital
invested. Neither Opthea nor any other member company of the Opthea Group guarantees any particular rate of
return or performance, nor do they guarantee the repayment of capital.
This presentation is not an offer or invitation for subscription or purchase of or a recommendation of securities. It
does not take into account the investment objectives, financial situation and particular needs of the investor.
Before making any investment in Opthea, the investor or prospective investor should consider whether such an
investment is appropriate to their particular investment needs, objectives and financial circumstances and consult
an investment advisor if necessary.
This presentation may contain forward-looking statements regarding the potential of the Company’s projects and
interests and the development and therapeutic potential of the company’s research and development. Any
statement describing a goal, expectation, intention or belief of the company is a forward-looking statement and
should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties,
particularly those inherent in the process of discovering, developing and commercialising drugs that are safe and
effective for use as human therapeutics and the financing of such activities. There is no guarantee that the
Company’s research and development projects and interests (where applicable) will receive regulatory approvals or
prove to be commercially successful in the future. Actual results of further research could differ from those
projected or detailed in this presentation. As a result, you are cautioned not to rely on forward-looking statements.
Consideration should be given to these and other risks concerning research and development programs referred to
in this presentation.
2
Opthea Limited

Clinical stage biotechnology company

Developing a novel therapy for wet AMD

Wet AMD is the leading cause of blindness in the Western
world in older adults

Technology is based on targeting signals that control blood
vessel growth and leakage

Lead compound OPT-302 blocks VEGF-C and VEGF-D

Ongoing Phase 1/2A clinical trial being conducted at US sites
in wet AMD patients

3

Potential to expand development program in a range
of eye diseases

Investigating OPT-302 as monotherapy and in
combination with existing treatments

Combination therapy more completely shuts down
pathways involved in disease progression
Near-term clinical milestones
OPT-302 Wet AMD Program:
Milestones
IND Approval for OPT-302
June 2015

Initiated Phase 1/2A clinical trial:
30 June 2015

Ph 1 Primary Data Analysis:
1Q16 (20 patients)
Ph 2A Primary Data Analysis:
2H16 (30 patients)
Financial Position (Unaudited)
Key Financial Details
ASX: OPT
Substantial Shareholders
% Holding
Ticker Symbol
ASX:OPT
18%
Share Price (as at Mar 1 2016)
~A$0.385
Biotechnology Value
Fund (BVF)*
Total Ordinary Shares on Issue
150,190,303
Baker Bros (NY, USA)
9%
Options on Issue
49,722,697
Packer & Co.
8.5%
Market Capitalisation
(as at Mar 1 2016)
~A$57.8m
Trading Range (last 12 months)
A$0.14 – 0.55
Share Price Performance (Feb ‘15 – Feb ‘16)
Biotechnology Value Fund (BVF)*
Baker Bros (NY, USA)
4
Cash Balance (at 31 Dec 2015)
~A$17.8m
Listed Investments
~A$0.9m
Top 10 Shareholders Own
69%
* Increased substantial holding 13% to 17.7% on June 25 2015
Packer & Co.
Board of Directors and Executive Management
Megan Baldwin, PhD, MAICD
CEO and Managing Director
Appointed CEO Feb ’14, joined company in 2008. Over 19 years experience in research and drug development of therapies
targeting angiogenesis. Previously held roles at Genentech (now Roche) in US, in R&D and commercial divisions. PhD in
Medicine from University of Melbourne & Ludwig Institute for Cancer research
Geoffrey Kempler, B.Sc Grad. Dip. App.Soc. Psych
Non-Executive Chairman
Appointed Chairman Dec ’15. Extensive experience in the global biopharmaceutical industry. Founded and currently CEO
Prana Biotechnology. Listed Prana on both ASX and NASDAQ. Strong investment markets experience and networks of
domestic and international sophisticated investors. Qualified psychologist, BSc (Monash University) and Grad. Dip.
App.Soc.Psych (Swinburne)
Michael Sistenich, MSc
Non-Executive Director
Appointed Dec ‘15. Over 18 years of experience as a healthcare specialist in international investment management and
investment banking. He is currently Head of Corporate Development at Nohla Therapeutics Inc and his previous roles
include Director of Corporate Finance at Bell Potter Securities and Director of International Equities and Head of Global
Healthcare Investments at DWS Investments, Deutsche Bank, Frankfurt
Mike Tonroe, ACA, MAICD
Chief Financial Officer and Company Secretary
Appointed May ‘14. Over 20 yrs experience in finance and company secretarial roles. Previously CFO of the Australian
Synchrotron Company Limited. Holds Graduate Degree in Business Studies from Buckingham University and is a Chartered
Accountant.
5
The disease process of ‘wet’ (neovascular) AMD
Normal Retina
Choroid
6
Figure: The Angiogenesis Foundation
‘Wet’ AMD
Monitoring Wet AMD & Treatment Efficacy




Trial endpoints are well defined & accepted by FDA/EMA
Non-invasive & routine
Highly quantitative
Trial endpoints are relatively short (Ph 2 typically 6 months, Ph 3 typically 12 months)
Visual Acuity
Eye Chart
7
Anatomical Changes by Imaging (OCT,FA)
(Retinal fluid, thickness, area)
Lead Program: OPT-302 for Wet AMD

Lead molecule:
– OPT-302 (soluble VEGFR-3, VEGF-C/-D ‘Trap’)

Mechanism:
– Blocks VEGF-C and VEGF-D:
 Inhibits blood vessel growth
 Inhibits vessel leak

Strategy:
– To investigate activity as a monotherapy
– To develop OPT-302 for use in combination with existing VEGF-A inhibitors for the
treatment of wet AMD
– Achieve complete blockade of the VEGF pathway
– Blocks a mechanism of ‘escape’ from existing therapies
8
Resistance to anti-VEGF-A monotherapy







9
Long-term single-agent therapy with VEGF-A
inhibitors is associated with sub-optimal
response
 Sub-optimal improvements in VA (<15letter gain)
 Persistent fluid on OCT
Resistance to VEGF-A monotherapy may be
related to other VEGF family members
VEGF-C and VEGF-D bind and activate VEGFR-2
and VEGFR-3
Complete blockade of VEGFR-2 requires VEGF-A,
VEGF-C and VEGF-D inhibition
VEGFR-3 also stimulates angiogenesis via a
VEGF-A independent pathway
EyleaTM LucentisTM
OPT-302 combination therapy with an anti-VEGF-A inhibitor achieves more complete
suppression of the VEGF/VEGFR pathway
Targets functional redundancy and mechanisms of sub-response to VEGF-A inhibition
Large and growing market opportunity
Wet AMD is the leading cause of blindness in the western world
Increasing prevalence due to ageing population
Prevalence expected to double by 2020




1/7
~1.8m
Approved therapies for wet AMD target VEGF-A, but not VEGF-C or VEGF-D
Our approach is novel and differentiated from the existing therapies, yet targets a validated
pathway in wet AMD disease progression
Market Opportunity*:
2015: >$7BN
10
*Cowen Analyst Report: Ophthotech July 7 2015
60% Market Share
>$10BN
Worldwide
An unmet medical need despite availability of VEGF-A
inhibitors
Despite receiving a VEGF-A inhibitor (Lucentis®, Eylea® or Avastin®):
>50%
2/3
25%
11
do not achieve significant vision gain
will continue to have fluid at the back of the eye
will have further vision loss at 12 mos
Our goal:
To improve vision of wet AMD patients
 To increase the number of patients who experience a significant gain in vision
 To increase the magnitude of the vision gain
 To prolong response to therapy and prevent visual decline
 Potential to reduce dosing frequency
12
OPT-302 has comparable single-agent and additive
activity with Eylea® in mouse AMD
Combined inhibition of VEGF-A (Eylea®), VEGF-C and VEGF-D (OPT-302) is more
effective than inhibition of VEGF-A alone
EYLEA™
OPT-302
OPT-302 + EYLEA®
Wet AMD lesion area
Control
70%
78%
91%
*
* Pairwise comparison: OPT-302 vs Eylea + OPT-302 (p<0.02)
Eylea vs Eylea + OPT-302 (p<0.05)
13
Ophthotech and Opthea:
Distinct approaches for wet AMD combination therapy
Activity in in mouse wet AMD model
p<0.02
p<0.05
Control
14
Fovista®
Macugen® Fovista ® +
Macugen®
FOVISTA™
OPT-302
Preclinical: Activity as Monotherapy?
NO
YES
Preclinical: Activity in Combination?
YES
YES
Potential Use in DME?
Unlikely
YES
Drug Class
Aptamer
Protein
Mechanism
Strips pericytes (supportive cells for vessel wall)
which may enhance a-VEGF-A delivery/activity
Directly targets vessel wall (endothelium, through same and
independent pathway to Lucentis/Eylea). Blocks a
mechanism of resistance to existing a-VEGF therapies.
Valuation at NASDAQ listing
US$662 m (At end Phase 2)
N/A
Current Market Cap.
AUD$1.8 bn (Phase 3)
AUD$31 m (Phase 1)
“Macugen®” – targets VEGF-A165 isoform; “Fovista®” – aptamer targeting PDGF-b; Jo et al., Am.J.Pathol., 168(6), 2036-2053, 2006.
OPT-302 Phase 1/2A: Protocol: OPT-302-1001
Dose-escalation & dose-expansion of repeated IVT injections
Cohort 2
OPT-302 (0.3 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
subjects complete 12 weeks
OPT-302 (1.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
Primary Analysis after all
Cohort 3
OPT-302 (2.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3, ~n=15 pts
Long term follow-up at Week 24
OPT-302 (2.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
OPT-302 (2.0 mg)
Monotherapy*
IVT Q4W x 3, ~n=15 pts
28 Day DLT window
OPT-302 (2.0 mg)
Monotherapy*
IVT Q4W x 3
Cohort 4
Follow-up to week 12
Phase 2A: Dose-expansion
(Randomised)
Phase 1: Dose-escalation
(Open-label)
Cohort 1
*Access to rescue anti-VEGF-A Tx
• Comprises of 4 treatment cohorts of 5 subjects each
• Should a dose limiting toxicity (DLT) occur, 3
additional subjects will be enrolled in that cohort
15
IND #: 122162
Sterling IRB study #: 5123 (Approved)
ClinTrials.gov ID#: NCT02543229
Phase 1/2A Trial Endpoints
Primary Endpoint of Phase 1/2A trial:

Safety
Secondary Endpoints:

Preliminary measures of clinical activity

Vision (Eye-Chart)

Size of lesion

Fluid
Visual Acuity
Eye Chart
16
Anatomical Changes by Imaging (OCT,FA)
(Retinal fluid, thickness, area)
Clinical Advisory Board & Investigators
Near-term Clinical Milestones


17
Clinical Advisory Board of internationally recognised and
experienced key opinion leaders from Australia and US
Extensive experience in development of novel and FDA
approved therapeutics for wet AMD, including
Macugen™, Fovista ™, Eylea ™ and Lucentis™
-
Pravin Dugel MD (Retinal Consultants Arizona, Keck School
of Medicine USC)
-
Mark Gillies MD (Save Sight Institute, Sydney Uni.)
-
Peter Campochiaro MD (Johns Hopkins, Wilmer Eye
Institute)
-
Kameran Lashkari MD (Schepens Eye Research Inst.,
Mass.Eye & Ear)

Actively recruiting

ClinTrials.gov ID#: NCT02543229
OPT-302 Wet AMD Program:
Milestones
IND Approval for OPT-302
June 2015

Initiated Phase 1/2A clinical trial:
30 June 2015

Ph 1 Primary Data Analysis:
1Q16 (20 patients)
Ph 2A Primary Data Analysis:
2H16 (30 patients)
OPT-302: Intellectual Property
Summary covering sVEGFR-3 IP for Eye Disease
COMPOSITION OF MATTER
TERM
Covering sVEGFR-3 (inc. OPT-302)
• Granted Patents: Europe, Japan, Canada, Australia
• Granted Patent: USA
Covering OPT-302
• Recently filed new specific composition of matter PCT international patent
application
2022
2026
~2034
‘USE’ PATENT
• US Patent granted covering generic use of sVEGFR-3 capable of binding VEGF-C
to inhibit blood vessels in mammal having disease characterised by expression of
VEGFR-3 in blood vessels
PATENT TERM EXTENSION/EXCLUSIVITY
+5 years under patent term extension
OPT-302 entitled to data exclusivity (DE) and market exclusivity (ME) in many jurisdictions, eg.
• US (12 years DE for biologics
• Europe (10 years made up of 8 years DE + 2 years ME)
• Japan (up to 8 years de facto DE)
• South Korea (5 years DE)
• Canada (up to 8 years incl. up to 6 years DE + 2 years ME)
• Australia (5 years DE)
18
2023
Listed Ophthalmology Companies in Phase 1-3
$2.3BN
PDGF-B aptamer
Wet AMD
ROCK inhib., small mol.
Glaucoma
Gene therapy
Eye diseases
(Phase 3)
$593M
(Phase 3)
$357M
Opthea
(Phase 1/2)
Ohr
$226M
a-VEGF-A gene therapy
Wet AMD
Sustained delivery
Wet AMD
Market Cap (US $m) Listed Ophthalmology
Companies Ph1-3
(Phase 1/2)
Ocular Ther.
Avalanche
AGTC
$220M
(Phase 3)
Avg.
Aerie
Ophthotech
-
Squalamine
Wet AMD
OPT-302
Wet AMD
19
500
$177M
(Phase 2)
~$38M(b)
(Phase 1)
a At Jan 6 2016, in USD
b A$54M converted into USD
1,000
1,500
2,000
2,500
Opthea: Corporate Highlights
20

Completed $17.4M fundraising (Nov ‘14) to advance wet AMD program

Supported by institutional healthcare investors from US, EU and Australia

Fully funded through 2017 and Phase 1/2A and Phase 2B clinical studies in wet AMD patients

Changed company name (Circadian to Opthea) to reflect focus on ophthalmology

Advanced OPT-302 through IND and ongoing Ph 1/2A clinical trial through US FDA regulatory
system
OPT-302: Program Highlights

OPT-302 is a fully owned asset with broad development potential in a range of eye diseases

Structurally similar to multi-billion dollar marketed product (Eylea), but with differentiated
mechanism of action

Targets validated pathway involved in wet AMD progression

Large unmet medical need and market for wet AMD

Assembled world class CAB, advisors and trial investigators

Near-term clinical milestones
 Primary analysis Phase 1 data 1Q’16
 Phase 2A data 2HQ’16
21
OPT-302 Investor Snapshot
Asset
Mechanism
OPT-302:
- Soluble form VEGFR-3
- A ‘trap’ similar to Eylea™ with distinct MOA
Inhibits VEGF-C & VEGF-D
- Anti-angiogenic
- Inhibits vascular leakage
Rationale
Targets over-lapping & distinct pathways to VEGF-A inhibitors
- Validated VEGFR-2 pathway via VEGF-C/-D inhibition
- VEGFR-3 pathway is VEGF-A independent
Indication
Wet AMD
- Leading cause blindness in Western world in adults > 50 yrs
- ~1.8M people in US have wet AMD*
Market Opp. ~USD 10bn worldwide*
Unmet
Medical
Need
Existing
Therapies
~50% of people receiving Lucentis™/Eylea™ do not experience a significant
gain in vision
Majority (50-70%) continue to have retinal fluid
Target VEGF-A, but not VEGF-C/-D
- Include blockbusters Lucentis™, Eylea™, off-label Avastin™
Landscape
OPT-302 potentially complementary to existing and emerging
agents, incl. PDGFR inhibitors, based on MOA
Intellectual
Property
Granted Composition of Matter patients (2022-2026)
Composition of Matter patent pending (… ~2034)
Granted ‘Use’ Patent (2023, US)
22
Strategy
OPT-302 + a-VEGF-A achieves more
complete blockade of VEGF pathway
- Targets a mechanism of resistance
- Trial to investigate monotherapy and
combination safety/activity
Preclinical
Data
As monotherapy, reduces wet AMD lesion
size and leakage to comparable extent as
Eylea
Combination therapy significantly more
effective than either agent alone
Clinical
Trial
Phase 1/2A trial ongoing in US under IND
- Primary Objective: Safety
- Routine, non-invasive endpts to
monitor clinical activity
- Clear regulatory path
Near Term
Clinical
Milestones
Phase 1 Primary Data Analysis 1Q’16
Phase 2A Primary Data Analysis 2H’16
Program
Potential to develop OPT-302 for other
eye diseases, incl. DME
Company
Opthea raised funds for wet AMD
program from US/EU/Aus healthcare
investors (Nov’14)
Funded through Ph1/2A and Ph2B trials in
wet AMD, mkt cap ~USD 50m
Megan Baldwin , PhD
CEO & Managing Director
Opthea Limited (ASX:OPT, OTCQX:CKDXY)
Megan.baldwin@opthea.com
+61 (0) 447 788 674