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OPT-302:
A novel therapy for
Wet AMD
Ophthalmology Innovation Summit, October 13 2016
Megan Baldwin, CEO & Managing Director
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
Disclaimer
3
Opthea: Developing OPT-302 for Wet AMD
• Opthea Limited is a public ASX listed
company (ASX: OPT)
• Exclusive worldwide rights to extensive
IP portfolio around members of the
Vascular Endothelial Growth Factor
family
• VEGF-C
• VEGF-D
• VEGFR-3
Key Financial Details ASX: OPT
Ticker Symbol ASX:OPT
Share Price (as at Aug 5 2016) ~A$0.73
Total Ordinary Shares on Issue 150,205,903
Options on Issue 49,707,097
Market Capitalisation
(as at Aug 5 2016)
~USD 84m
(AUD 110m)
• Lead compound OPT-302: a VEGF-C/-D ‘Trap’
• Neovascular effects (eg. inhibitor of angiogenesis & vascular permeability)
• Non-neovascular effects (eg. inflammation)
• Wet AMD program with potential in a range of eye diseases
• Combination therapy OPT-302 with an anti-VEGF-A inhibitor targets
mechanisms of incomplete response to VEGF-A inhibition
• Complementary to a-VEGF-A and other agents in development
• Phase 1/2a trial ongoing under IND at 14 clinical sites in US
4
• Long-term single-agent therapy with
VEGF-A inhibitors is associated with
sub-optimal response
 Sub-optimal improvements in visual
acuity (<15-letter gain)
 Persistent retinal fluid
• Resistance to VEGF-A inhibitors may be
related to other VEGF family members
Resistance to anti-VEGF-A Monotherapy
EyleaTM LucentisTM OPT-302
VEGF-B
PIGF VEGF-A
VEGF-C
VEGF-D
• OPT-302 combination therapy achieves
more complete suppression of the
VEGF/VEGFR pathway
• Targets incomplete response to VEGF-A
inhibition
OPT-302 (0.3 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
OPT-302 (1.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
OPT-302 (2.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
28DayDLTwindow
OPT-302 (2.0 mg)
Monotherapy*
IVT Q4W x 3
Cohort 4
Cohort 3
Cohort 2
Cohort 1
5
OPT-302 Phase 1/2a
• Comprises of 4 treatment cohorts of 5 subjects each
Phase 1: Dose-escalation
(Open-label)
PrimaryAnalysisafterall
subjectscomplete12weeks
Longtermfollow-upatWeek24
*Access to rescue anti-VEGF-A Tx
Follow-uptoweek12
OPT-302 (2.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3, ~n=15 pts
OPT-302 (2.0 mg)
Monotherapy*
IVT Q4W x 3, ~n=15 pts
Phase 2a: Dose-expansion
(Randomised)
Dose-escalation & dose-expansion of repeated IVT injections
ClinTrials.gov ID#: NCT02543229
6
OPT-302 Phase 1: Patient Demographics
• Run under FDA IND at 14 clinical sites in the US
• 20 pts (mean age 74.8)
• 14/20 females, 6/20 males
• 17/20 occult, 2/20 min classic, 1/20 predominantly classic
• Each patient received 3 intravitreal injections of OPT-302 either alone or in
combination with Lucentis ® every 4 weeks, with a week 12 follow-up one month
after the third dose.
• 70% difficult to treat patients sub-responsive to anti-VEGF-A therapy
• 30% treatment-naïve
Cohort Treatment # Naïve Pts # Prior
Treated Pts
1 OPT-302 (0.3 mg) + Lucentis® (0.5 mg) 2 3
2 OPT-302 (1.0 mg) + Lucentis® (0.5 mg) 0 5
3 OPT-302 (2.0 mg) + Lucentis® (0.5 mg) 2 3*
4 OPT-302 (2.0 mg) 2 3
*One pt with metastatic ovarian cancer died prior to the week 12 (day 78) visit due to
intercurrent illness unrelated to study drugs.
• OPT-302 successfully met primary safety objective in Phase 1 dose escalation study
• No dose limiting toxicities (and MTD not reached) through week 12 in:
• OPT-302 monotherapy (2.0 mg), and
• Cohorts of OPT-302 (0.3, 1, 2 mg) in combination with Lucentis® (0.5 mg)
• No signs of infection (endophthalmitis)
• No clinically significant changes in:
• Intraocular pressure
• ECGs
• Blood pressure
• Blood chemistry or other vital signs
• No evidence of drug-related immunogenicity
7
OPT-302 Safe & Well Tolerated in Phase 1 Study
8
Phase 1 Secondary Endpoints
• Overall, 16/19 evaluable pts maintained or gained vision from
baseline to week 12
• No patient lost more than 3 letters. All of the patients that
lost VA from baseline received combination OPT-302 +
Lucentis® therapy.
9
Combination Therapy: All Patients (Full cohort) (Naïve & Prior-Tx)
0
1
2
3
4
5
6
7
8
9
10
OPT-302 + Lucentis
(n=14*)
Mean VA gain from
baseline at Week 12
MeangaininVA
fromBaseline(#letters)
8 Letters
MeanCST(µM)
250
275
300
325
350
375
400
425
450
Baseline Week 12
Mean decrease in CST from
baseline to Week 12
OPT-302 + Lucentis
(n=14*)
-91µM
* 1 pt not evaluable at W12
10
Combination Therapy: Treatment-Naïve Patients
16.5
9.5
0
2
4
6
8
10
12
14
16
18
Mean Gain VA from
Baseline
OPT-302 +
Lucentis®
(n=4)
MeangaininVisualAcuity
fromBaseline(#letters)
OPT-302 + Lucentis®
(n=4)
Week 12
0
100
200
300
400
500
600
Baseline
214 uM (42.7%)
Mean Central Subfield Thickness
MeanCST(uM)
11
Combination Therapy: Prior-Treated Patients
• Mean number prior treatment injections: 10.5 (range 3 – 55)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Mean Change VA
from Baseline
Week 12
OPT-302 + Lucentis®
(n=10)
4 letters
MeangaininVisualAcuity
fromBaseline(#letters)
330
340
350
360
370
380
390
400
Mean Central Subfield
Thickness
OPT-302 + Lucentis®
(n=10)
Week 12Baseline
42 uM (11%)
MeanCST(uM)
12
Prior-Treated Patient: OPT-302 (0.3 mg) + Lucentis® (0.5 mg)
VA: 77 letters
CST: 365 µM
VA: 83 letters
CST: 281 µM
VA: 79 letters
CST: 298 µM
Baseline Week 4 Week 12
• Male aged 64
• Occult lesion
• Prior treatment: Eylea®/REGN-910-3 x6
13
Prior-Treated Patient: OPT-302 (1.0 mg) + Lucentis® (0.5 mg)
• Female aged 71
• Occult lesion
• Prior treatment: Avastin® x10
VA: 74 letters
CST: 270 µM
VA: 74 letters
CST: 258 µM
VA: 84 letters
CST: 255 µM
Baseline Week 4 Week 12
OPT-302 Monotherapy
• 3/5 patients did not require ‘rescue’ therapy
• 2 patients were rescued (at d25 and d29). At week 12, both had lost vision compared
to baseline.
• At week 12, in patients that did not require rescue therapy, mean VA gain of 3.3
letters from baseline (range 2 to 6 letters) and mean increase in CST of 18 uM
Baseline Week 12
OPT-302 (2 mg)
Non Rescue pts (n=3)
250
275
300
325
350
375
400
MeanCST(uM)
Mean Central Subfield Thickness
+18µM
0
1
2
3
4
5
6
7
8
9
10
OPT-302 (2mg)
(n=5)
OPT-302 Non-
resue (2mg) (n=3)
Mean VA gain from
baseline at Week 12
0
1
2
3
4
5
6
7
8
9
10
OPT-302 (2 mg)
Non Rescue pts (n=3)
MeangaininVA
fromBaseline(#letters)
3 letters
• Large unmet medical need for wet AMD, current treatments only target VEGF-A
• OPT-302 targets VEGF-C and VEGF-D that are associated with incomplete response to
VEGF-A inhibition
• OPT-302 met primary objective of Phase 1 study: OPT-302 safe & well tolerated
• Evidence of clinical activity:
• Patients treated with combination OPT-302 + Lucentis® therapy showed mean
vision gains and retinal thickness improvements equal to or superior to historic, 12
week anti-VEGF-A (Lucentis®) alone, despite including heavily pre-treated, sub-
responsive patients with a high proportion of occult lesions
• Naïve pts: data suggests meaningful additional VA gain and reduction in CST with
OPT-302 + Lucentis® compared to historic data with Lucentis® alone
• Prior Tx pts: improved outcomes in difficult to treat, sub-responsive pts suggest
additional benefit of VEGF-A, VEGF-C and VEGF-D inhibition
• OPT-302 monotherapy maintained mean VA and CST
• Totality of data warrants advancing OPT-302 + Lucentis® to a Phase 2B randomised,
controlled trial
• Actively accruing into Phase 2A , planning for Phase 2B in 2017
15
OPT-302 Program Highlights
Suite 0403, Level 4,
650 Chapel Street,
South Yarra 3141 Victoria Australia
T +61 (0) 447 788 674
E megan.baldwin@opthea.com
www.opthea.com
17

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Posterior Segment Company Showcase - Opthea

  • 1. OPT-302: A novel therapy for Wet AMD Ophthalmology Innovation Summit, October 13 2016 Megan Baldwin, CEO & Managing Director
  • 2. 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 Disclaimer
  • 3. 3 Opthea: Developing OPT-302 for Wet AMD • Opthea Limited is a public ASX listed company (ASX: OPT) • Exclusive worldwide rights to extensive IP portfolio around members of the Vascular Endothelial Growth Factor family • VEGF-C • VEGF-D • VEGFR-3 Key Financial Details ASX: OPT Ticker Symbol ASX:OPT Share Price (as at Aug 5 2016) ~A$0.73 Total Ordinary Shares on Issue 150,205,903 Options on Issue 49,707,097 Market Capitalisation (as at Aug 5 2016) ~USD 84m (AUD 110m) • Lead compound OPT-302: a VEGF-C/-D ‘Trap’ • Neovascular effects (eg. inhibitor of angiogenesis & vascular permeability) • Non-neovascular effects (eg. inflammation) • Wet AMD program with potential in a range of eye diseases • Combination therapy OPT-302 with an anti-VEGF-A inhibitor targets mechanisms of incomplete response to VEGF-A inhibition • Complementary to a-VEGF-A and other agents in development • Phase 1/2a trial ongoing under IND at 14 clinical sites in US
  • 4. 4 • Long-term single-agent therapy with VEGF-A inhibitors is associated with sub-optimal response  Sub-optimal improvements in visual acuity (<15-letter gain)  Persistent retinal fluid • Resistance to VEGF-A inhibitors may be related to other VEGF family members Resistance to anti-VEGF-A Monotherapy EyleaTM LucentisTM OPT-302 VEGF-B PIGF VEGF-A VEGF-C VEGF-D • OPT-302 combination therapy achieves more complete suppression of the VEGF/VEGFR pathway • Targets incomplete response to VEGF-A inhibition
  • 5. OPT-302 (0.3 mg) + Lucentis® (0.5 mg) IVT Q4W x 3 OPT-302 (1.0 mg) + Lucentis® (0.5 mg) IVT Q4W x 3 OPT-302 (2.0 mg) + Lucentis® (0.5 mg) IVT Q4W x 3 28DayDLTwindow OPT-302 (2.0 mg) Monotherapy* IVT Q4W x 3 Cohort 4 Cohort 3 Cohort 2 Cohort 1 5 OPT-302 Phase 1/2a • Comprises of 4 treatment cohorts of 5 subjects each Phase 1: Dose-escalation (Open-label) PrimaryAnalysisafterall subjectscomplete12weeks Longtermfollow-upatWeek24 *Access to rescue anti-VEGF-A Tx Follow-uptoweek12 OPT-302 (2.0 mg) + Lucentis® (0.5 mg) IVT Q4W x 3, ~n=15 pts OPT-302 (2.0 mg) Monotherapy* IVT Q4W x 3, ~n=15 pts Phase 2a: Dose-expansion (Randomised) Dose-escalation & dose-expansion of repeated IVT injections ClinTrials.gov ID#: NCT02543229
  • 6. 6 OPT-302 Phase 1: Patient Demographics • Run under FDA IND at 14 clinical sites in the US • 20 pts (mean age 74.8) • 14/20 females, 6/20 males • 17/20 occult, 2/20 min classic, 1/20 predominantly classic • Each patient received 3 intravitreal injections of OPT-302 either alone or in combination with Lucentis ® every 4 weeks, with a week 12 follow-up one month after the third dose. • 70% difficult to treat patients sub-responsive to anti-VEGF-A therapy • 30% treatment-naïve Cohort Treatment # Naïve Pts # Prior Treated Pts 1 OPT-302 (0.3 mg) + Lucentis® (0.5 mg) 2 3 2 OPT-302 (1.0 mg) + Lucentis® (0.5 mg) 0 5 3 OPT-302 (2.0 mg) + Lucentis® (0.5 mg) 2 3* 4 OPT-302 (2.0 mg) 2 3 *One pt with metastatic ovarian cancer died prior to the week 12 (day 78) visit due to intercurrent illness unrelated to study drugs.
  • 7. • OPT-302 successfully met primary safety objective in Phase 1 dose escalation study • No dose limiting toxicities (and MTD not reached) through week 12 in: • OPT-302 monotherapy (2.0 mg), and • Cohorts of OPT-302 (0.3, 1, 2 mg) in combination with Lucentis® (0.5 mg) • No signs of infection (endophthalmitis) • No clinically significant changes in: • Intraocular pressure • ECGs • Blood pressure • Blood chemistry or other vital signs • No evidence of drug-related immunogenicity 7 OPT-302 Safe & Well Tolerated in Phase 1 Study
  • 8. 8 Phase 1 Secondary Endpoints • Overall, 16/19 evaluable pts maintained or gained vision from baseline to week 12 • No patient lost more than 3 letters. All of the patients that lost VA from baseline received combination OPT-302 + Lucentis® therapy.
  • 9. 9 Combination Therapy: All Patients (Full cohort) (Naïve & Prior-Tx) 0 1 2 3 4 5 6 7 8 9 10 OPT-302 + Lucentis (n=14*) Mean VA gain from baseline at Week 12 MeangaininVA fromBaseline(#letters) 8 Letters MeanCST(µM) 250 275 300 325 350 375 400 425 450 Baseline Week 12 Mean decrease in CST from baseline to Week 12 OPT-302 + Lucentis (n=14*) -91µM * 1 pt not evaluable at W12
  • 10. 10 Combination Therapy: Treatment-Naïve Patients 16.5 9.5 0 2 4 6 8 10 12 14 16 18 Mean Gain VA from Baseline OPT-302 + Lucentis® (n=4) MeangaininVisualAcuity fromBaseline(#letters) OPT-302 + Lucentis® (n=4) Week 12 0 100 200 300 400 500 600 Baseline 214 uM (42.7%) Mean Central Subfield Thickness MeanCST(uM)
  • 11. 11 Combination Therapy: Prior-Treated Patients • Mean number prior treatment injections: 10.5 (range 3 – 55) 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 Mean Change VA from Baseline Week 12 OPT-302 + Lucentis® (n=10) 4 letters MeangaininVisualAcuity fromBaseline(#letters) 330 340 350 360 370 380 390 400 Mean Central Subfield Thickness OPT-302 + Lucentis® (n=10) Week 12Baseline 42 uM (11%) MeanCST(uM)
  • 12. 12 Prior-Treated Patient: OPT-302 (0.3 mg) + Lucentis® (0.5 mg) VA: 77 letters CST: 365 µM VA: 83 letters CST: 281 µM VA: 79 letters CST: 298 µM Baseline Week 4 Week 12 • Male aged 64 • Occult lesion • Prior treatment: Eylea®/REGN-910-3 x6
  • 13. 13 Prior-Treated Patient: OPT-302 (1.0 mg) + Lucentis® (0.5 mg) • Female aged 71 • Occult lesion • Prior treatment: Avastin® x10 VA: 74 letters CST: 270 µM VA: 74 letters CST: 258 µM VA: 84 letters CST: 255 µM Baseline Week 4 Week 12
  • 14. OPT-302 Monotherapy • 3/5 patients did not require ‘rescue’ therapy • 2 patients were rescued (at d25 and d29). At week 12, both had lost vision compared to baseline. • At week 12, in patients that did not require rescue therapy, mean VA gain of 3.3 letters from baseline (range 2 to 6 letters) and mean increase in CST of 18 uM Baseline Week 12 OPT-302 (2 mg) Non Rescue pts (n=3) 250 275 300 325 350 375 400 MeanCST(uM) Mean Central Subfield Thickness +18µM 0 1 2 3 4 5 6 7 8 9 10 OPT-302 (2mg) (n=5) OPT-302 Non- resue (2mg) (n=3) Mean VA gain from baseline at Week 12 0 1 2 3 4 5 6 7 8 9 10 OPT-302 (2 mg) Non Rescue pts (n=3) MeangaininVA fromBaseline(#letters) 3 letters
  • 15. • Large unmet medical need for wet AMD, current treatments only target VEGF-A • OPT-302 targets VEGF-C and VEGF-D that are associated with incomplete response to VEGF-A inhibition • OPT-302 met primary objective of Phase 1 study: OPT-302 safe & well tolerated • Evidence of clinical activity: • Patients treated with combination OPT-302 + Lucentis® therapy showed mean vision gains and retinal thickness improvements equal to or superior to historic, 12 week anti-VEGF-A (Lucentis®) alone, despite including heavily pre-treated, sub- responsive patients with a high proportion of occult lesions • Naïve pts: data suggests meaningful additional VA gain and reduction in CST with OPT-302 + Lucentis® compared to historic data with Lucentis® alone • Prior Tx pts: improved outcomes in difficult to treat, sub-responsive pts suggest additional benefit of VEGF-A, VEGF-C and VEGF-D inhibition • OPT-302 monotherapy maintained mean VA and CST • Totality of data warrants advancing OPT-302 + Lucentis® to a Phase 2B randomised, controlled trial • Actively accruing into Phase 2A , planning for Phase 2B in 2017 15 OPT-302 Program Highlights
  • 16. Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia T +61 (0) 447 788 674 E megan.baldwin@opthea.com www.opthea.com
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