OPT-302: A Novel Therapy for Eye Diseases

Transcription

1 OPT-302: A Novel Therapy for Eye Diseases Corporate & Investor Presentation ASX Small & Mid-Cap Conference Sydney, September Megan Baldwin PhD, CEO & Managing Director

2 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

3 Corporate Summary Novel technology and therapy for eye disease OPT-302, a new approach for the treatment of wet AMD and DME Market opportunity >USD$10 billion worldwide Two existing therapies (a-vegf-a) are sub-optimally clinically effective in the majority of patients Strategy is to develop OPT-302 for use in combination with existing treatments Reported Phase 1/2a data in wet AMD patients demonstrated: Safety of OPT-302 Evidence of improved vision and reductions in fluid Currently enrolling patients in two randomized, controlled clinical trials Phase 2b wet AMD and Phase 1b/2a DME studies Trials are recruiting patients in US, EU, Israel and Australia ASX: OPT Intra-vitreal injection 3

4 Financial Position (Unaudited) Key Financial Details Ticker Symbol Share Price (Aug ) ASX: OPT ASX:OPT ~A$0.62 Total Ordinary Shares on Issue 202,797,888 Options on Issue 46,913,324 Market Capitalisation (Aug ) ~A$126m (~USD91m) Trading Range (last 12 months) A$ Cash Balance (Jul ) Forecast Net Operating Cash Burn (CY 2018) ~A$30m ~$18m Top 20 Shareholders Own 69% Institutional Holders 84% Details Cash positive until end 20 Fully-funded through 351 pt Ph2B wamd trial (randomised, statistically powered) 117 pt Ph2A DME trial Accumm. tax and capital losses ~A$15m 4

5 AUD Shareholders & Analyst Coverage Share Price Performance (Sept Aug 2018) Shareholders by Region High Retail 16% US Funds 29% EU/Other Funds 20% Australian Funds 35% Analyst Coverage Shane Storey Tanushree Jain 5

6 Wet AMD (Age-Related Macular Degeneration) Normal Retina Wet AMD Fluid Vessels 6 Leading cause of blindness in people > 55 years Increasing in prevalence due to aging population Need for new therapies Est. >1.8m people in US

7 Diabetic Macular Edema (DME) 1/11 adults with diabetes worldwide > 2M worldwide with DME Diabetes: a global epidemic 415M adults worldwide 1/3 will develop diabetic eye disease Increasing prevalence due to growing diabetic population Large proportion undiagnosed Need for new therapies 7

8 8 Our Goal: To Improve Vision in Diabetic & Elderly Patients

9 Large Socio-Economic Impact of Vision Loss Fear of total blindness, feeling isolated, helpless, depression Psychological well-being Daily necessities: preparing meals, shopping, recognising faces Difficult to care for self, increased risk of injury Reliance on caregivers, guilt Costs to health-care system & support services Physical well-being IMPACT OF VISION LOSS Lost independence Work & Social Integration Work: going to work, continued employment 9 International Diabetes Foundation Fred Hollows Foundation.

10 New Therapies Aim to Improve Vision & Reduce Thickness (Fluid) at Back of Eye Visual Acuity SD-OCT Change in Visual Acuity (# Letters) from Baseline Change in Retinal Subfield Thickness (CST) from Baseline (Fluid) 10

11 Large and Growing Market Opportunity Existing therapies for wet AMD have same mechanism of action Target VEGF-A: one signal involved in vessel growth and leakage OPT-302 is different by targeting VEGF-C & VEGF-D VEGF-A Inhibitors Market Opportunity*: Novartis Genentech Regeneron Bayer Roche Genentech >$10BN Worldwide 2017: ~$9BN USD Off-Label Use 40% Market Share 60% Market Share 11 *Cowen Analyst Report: Ophthotech July

12 Large Unmet Medical Need Despite Availability of VEGF-A Inhibitors Despite receiving a VEGF-A inhibitor (Lucentis, Eylea or Avastin) * : >50% Wet AMD 2/3 25% Do not achieve significant vision gains Will continue to have fluid at the back of the eye Will have further vision loss at 12 months DME 2/3 25% Do not achieve significant vision gains # Continue to have macula thickening/swelling^ Opportunity: New Products that Improve Efficacy and Durability 12 * Based on randomised, controlled clinical trial data; # Fail to achieve 2 lines improvement in BCVA; ^ SD-OCT CST 300 µm or Time-Domain OCT CST 250 µm

13 VEGF-C/D VEGF-C/D OPT-302: Opthea s Novel Therapy for wet AMD & DME Extra-Cellular Domains 1-3 hvegfr-3 higg1 Fc Existing therapies block VEGF-A OPT-302 blocks VEGF-C & VEGF-D Distinct members of the same family of signals that control blood vessel growth & leakage Not seeking to replace existing therapies, seeking to add-on, therefore: >$10bn market opportunity Used in combination, can more effectively block pathways involved in disease progression OPT-302 has the potential to improve vision & quality of life for patients with leading causes of blindness worldwide 13 Opthea is the Only Company Working on VEGF-C/D Unlike many disease areas eg. cancer, there are limited combination therapies in development

14 OPT-302 Product Development Wet AMD Combination Agent Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Status 1 o Data Analysis OPT-302 Target: VEGF-C/D Lucentis Target: VEGF-A Complete Ph 1/2a (n=51) April 2017 OPT-302 Target: VEGF-C/D Lucentis Target: VEGF-A Ongoing Ph 2b (n=351) 1H CY2020 Diabetic Macular Edema OPT-302 Target: VEGF-C/D Eylea Target: VEGF-A Ongoing Ph 1b/2a (n=117) 2019 Two Ongoing Randomised Controlled Clinical Trials in Two Different Eye Diseases 14

15 OPT-302: Phase 1/2a wet AMD Clinical Trial Results 15

16 OPT-302 Phase 1/2a Opthea s Phase 1/2a clinical trial in wet AMD enrolled 51 patients: OPT-302 Monotherapy n=13 patients Administered OPT-302 alone OPT Lucentis Naïve Patients n=18 patients Administered combination therapy to patients who had not previously received wamd therapy OPT Lucentis Prior-Treated Patients n=20 patients Administered combination therapy to patients who had previously received wamd therapy and shown a sub-response 16

17 V is u a l A c u ity (M e a n C h a n g e fr o m B a s e lin e ) Phase 1/2a Monotherapy Patients Mean Change in Visual Acuity in Non-Rescue Patients (10/13) 6.1 (9/13) (7/12) B a s e lin e W e e k 4 W e e k 8 W e e k 1 2 Gains in Visual Acuity in Patients Treated with OPT-302 Monotherapy Evidence of OPT-302 Biological Activity 17 One treatment-naïve patient in the monotherapy cohort with myocardial infarction died (on day 77) prior to the week 12 visit (unrelated to study drugs)

18 OPT Lucentis Phase 1/2a Treatment-Naïve Patients OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg) Mean Change in Visual Acuity from Baseline (letters) Mean Retinal Thickness (CST) (µm) MARINA* 5.9 Letters at Wk12 with Lucentis -119 mm Visual Acuity Gains and Reductions in Retinal Fluid Suggestive of Additive Benefit Compared to Historical Data with Lucentis Alone 18 Patients administered OPT Ranibizumab Q4Wx3. Number of Patients: 18; Mean Baseline VA = 56.5 Letters ; MARINA: Mean Baseline VA = 53.7 letters *Rosenfeld et al., NEJM, 355(14), pp , 2006; # Martin et al., NEJM, 364(20), pp

19 CNV Size (mm 2 ) % Patients with Absent CNV on FA Treatment-Naïve Patients: Reductions in CNV OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg) Reduction in CNV Size on FA % Patients with Absent CNV on FA % % % 0 Baseline Week 4 Week 12 0 Baseline Week 4 Week 12 OPT Ranibizumab OPT Ranibizumab 19 CNV: Choroidal Neovascularisation; Treatment Naïve Patients: n = 18; OPT-302 (0.3, 2.0 mg) + ranibizumab (0.5 mg)

20 OPT Lucentis Phase 1/2a Prior-Treated Patients OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg) Mean Change in Visual Acuity from Baseline (letters) Mean Retinal Thickness (CST) (µm) mm Visual Acuity Gains and Reductions in Retinal Fluid in Patients Sub-responsive to anti-vegf-a Therapy 20 Patients administered OPT Ranibizumab Q4Wx3. Number of Patients: 18; Mean Baseline VA = 56.5 Letters ; MARINA: Mean Baseline VA = 53.7 letters *Rosenfeld et al., NEJM, 355(14), pp , 2006; # Martin et al., NEJM, 364(20), pp

21 OPT-302 Phase 1/2a Key Take-Aways OPT-302 met the primary safety objective of its Phase 1/2A study (well tolerated) Evidence of clinical activity of OPT-302 When administered alone as a monotherapy As a combination, including in treatment naïve (49%) and heavily pre-treated patients (51%), and in a study with a high proportion of patients with occult (73%) wet AMD lesions. A consistency of responses in patients: With different treatment histories Across various secondary outcome measures (visual acuity, retinal thickness) 21

22 OPT-302 Product Development Wet AMD Combination Agent Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Status 1 o Data Analysis OPT-302 Target: VEGF-C/D Lucentis Target: VEGF-A Complete Ph 1/2a (n=51) April 2017 OPT-302 Target: VEGF-C/D Lucentis Target: VEGF-A Ongoing Ph 2b (n=351) 1H CY2020 Diabetic Macular Edema OPT-302 Target: VEGF-C/D Eylea Target: VEGF-A Ongoing Ph 1b/2a (n=117) 2019 Two Ongoing Randomised Controlled Clinical Trials in Two Different Eye Diseases 22

23 Opthea: Large Potential for Upside Approved Approved Approved Phase 3 Phase 3 Phase 3 Phase 3 Phase 3 Phase 3 Phase 2/3 Phase 2 Phase 2 Phase 2 PreClinical 2.8BN 2.4BN 2.3BN 1.1BN 621M 427M 332M 260M 218M 177M 476M 213M 91M 51M Glaucoma Glaucoma Retinitis Pigmentosa (RP) Gene Therapy wamd, GA Choroideremia, RP Gene Therapy wamd Dry Eye, Ocular Pain Sealant, Delivery Uveitis, DME, RVO Suprachoroidal delivery Dry Eye, Uveitis A1AT Deficiency, wamd Gene Therapy DME wamd, DME Retinitis Pigmentosa Gene Therapy 23 All figures in USD. Valuations shown = Mkt Cap ( ) Cash/Eq

24 OPT-302: fully funded through a diversified clinical development program H 17 1H 18 2H 18 1H 19 2H 19 1H 20 2H 20 Initiate 351 patient Phase 2B wet AMD trial Phase 2b wet AMD Topline Data: Phase 2b wet AMD Initiate ~117 patient Phase 2A DME Phase 1b/2a DME Topline Data: Phase 1b/2a DME 24 Note: Dates provided in timelines are estimates, and indicative only, and subject to change as a result of a number of factors outside of Opthea s control.

25 Opthea Developing OPT-302 for Eye Diseases 25 OPT-302 program is diversified in two ocular indications Investigates activity in combination with two standard of care therapies Targets a validated pathway May address large proportion of patients that do not optimally respond to existing therapies Very large marked opportunity >$10BN p.a. Wet AMD & DME landscape includes only a limited number of novel combination therapies OPT-302 met primary safety objective of Phase 1/2a study (well tolerated) Clinical activity in a 51 patient Phase 1/2a clinical trial Opthea is fully funded through 2020 & its clinical development program: Wet AMD: 351 patients DME: 117 patients

26 Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia T +61 (3) E megan.baldwin@opthea.com