Developing OPT-302: A novel therapy for wet AMD

Transcription

1 Opthea Limited (ASX:OPT, OTCQX:CKDXY) Developing OPT-302: A novel therapy for wet AMD March 2016 Megan Baldwin PhD, CEO & Managing Director; megan.baldwin@opthea.com

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 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 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) 3

4 Financial Position (Unaudited) Key Financial Details Ticker Symbol Share Price (as at Mar ) ASX: OPT ASX:OPT ~A$0.385 Total Ordinary Shares on Issue 150,190,303 Options on Issue 49,722,697 Market Capitalisation (as at Mar ) ~A$57.8m Trading Range (last 12 months) A$ Cash Balance (at 31 Dec 2015) Listed Investments Top 10 Shareholders Own 69% ~A$17.8m ~A$0.9m Substantial Shareholders Biotechnology Value Fund (BVF)* % Holding 18% Baker Bros (NY, USA) 9% Packer & Co. 8.5% Share Price Performance (Feb 15 Feb 16) Biotechnology Value Fund (BVF)* Baker Bros (NY, USA) Packer & Co. 4 * Increased substantial holding 13% to 17.7% on June

5 Board of Directors and Executive Management Megan Baldwin, PhD, MAICD CEO and Managing Director Appointed CEO Feb 14, joined company in 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

6 The disease process of wet (neovascular) AMD Normal Retina Wet AMD Choroid 6 Figure: The Angiogenesis Foundation

7 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 Anatomical Changes by Imaging (OCT,FA) (Retinal fluid, thickness, area) 7

8 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: Strategy: Inhibits blood vessel growth Inhibits vessel leak 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

9 Resistance to anti-vegf-a monotherapy Long-term single-agent therapy with VEGF-A inhibitors is associated with sub-optimal response Sub-optimal improvements in VA (<15- letter 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 Eylea TM Lucentis TM 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 9

10 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 /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*: >$10BN 2015: >$7BN 60% Market Share Worldwide 10 *Cowen Analyst Report: Ophthotech July

11 An unmet medical need despite availability of VEGF-A inhibitors Despite receiving a VEGF-A inhibitor (Lucentis, Eylea or Avastin ): >50% do not achieve significant vision gain 2/3 25% will continue to have fluid at the back of the eye will have further vision loss at 12 mos 11

12 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

13 Wet AMD lesion area 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 Control OPT % 78% 91% EYLEA OPT EYLEA * * Pairwise comparison: OPT-302 vs Eylea + OPT-302 (p<0.02) Eylea vs Eylea + OPT-302 (p<0.05) 13

14 Ophthotech and Opthea: Distinct approaches for wet AMD combination therapy Activity in in mouse wet AMD model p<0.02 p<0.05 Control 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) 14 Macugen targets VEGF-A 165 isoform; Fovista aptamer targeting PDGF-b; Jo et al., Am.J.Pathol., 168(6), , 2006.

15 28 Day DLT window Follow-up to week 12 Primary Analysis after all subjects complete 12 weeks Long term follow-up at Week 24 OPT-302 Phase 1/2A: Protocol: OPT Dose-escalation & dose-expansion of repeated IVT injections Phase 1: Dose-escalation (Open-label) Phase 2A: Dose-expansion (Randomised) OPT-302 (2.0 mg) Monotherapy* IVT Q4W x 3 Cohort 4 OPT-302 (2.0 mg) Monotherapy* IVT Q4W x 3, ~n=15 pts OPT-302 (2.0 mg) + Lucentis (0.5 mg) IVT Q4W x 3 Cohort 3 OPT-302 (2.0 mg) + Lucentis (0.5 mg) IVT Q4W x 3, ~n=15 pts OPT-302 (0.3 mg) + Lucentis (0.5 mg) IVT Q4W x 3 Cohort 1 OPT-302 (1.0 mg) + Lucentis (0.5 mg) IVT Q4W x 3 Cohort 2 *Access to rescue anti-vegf-a Tx 15 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 IND #: Sterling IRB study #: 5123 (Approved) ClinTrials.gov ID#: NCT

16 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 Anatomical Changes by Imaging (OCT,FA) (Retinal fluid, thickness, area) 16

17 Clinical Advisory Board & Investigators Near-term Clinical Milestones 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#: NCT 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) 17

18 OPT-302: Intellectual Property Summary covering svegfr-3 IP for Eye Disease COMPOSITION OF MATTER 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 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) TERM ~

19 Listed Ophthalmology Companies in Phase 1-3 PDGF-B aptamer Wet AMD ROCK inhib., small mol. Glaucoma $2.3BN (Phase 3) $593M (Phase 3) Market Cap (US $m) Listed Ophthalmology Companies Ph1-3 Gene therapy Eye diseases $357M (Phase 1/2) Opthea Ohr a-vegf-a gene therapy Wet AMD $226M (Phase 1/2) Ocular Ther. Avalanche AGTC Avg. Sustained delivery Wet AMD $220M (Phase 3) Aerie Ophthotech Squalamine Wet AMD $177M (Phase 2) ,000 1,500 2,000 2, OPT-302 Wet AMD ~$38M (b) (Phase 1) a At Jan , in USD b A$54M converted into USD

20 Opthea: Corporate Highlights 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 20

21 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

22 OPT-302 Investor Snapshot Asset Mechanism Rationale OPT-302: - Soluble form VEGFR-3 - A trap similar to Eylea with distinct MOA Inhibits VEGF-C & VEGF-D - Anti-angiogenic - Inhibits vascular leakage 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 Strategy Preclinical Data OPT a-vegf-a achieves more complete blockade of VEGF pathway - Targets a mechanism of resistance - Trial to investigate monotherapy and combination safety/activity As monotherapy, reduces wet AMD lesion size and leakage to comparable extent as Eylea Combination therapy significantly more effective than either agent alone Indication Market Opp. Unmet Medical Need Existing Therapies Landscape Intellectual Property 22 Wet AMD - Leading cause blindness in Western world in adults > 50 yrs - ~1.8M people in US have wet AMD* ~USD 10bn worldwide* ~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 OPT-302 potentially complementary to existing and emerging agents, incl. PDGFR inhibitors, based on MOA Granted Composition of Matter patients ( ) Composition of Matter patent pending ( ~2034) Granted Use Patent (2023, US) Clinical Trial Near Term Clinical Milestones Program Company Phase 1/2A trial ongoing in US under IND - Primary Objective: Safety - Routine, non-invasive endpts to monitor clinical activity - Clear regulatory path Phase 1 Primary Data Analysis 1Q 16 Phase 2A Primary Data Analysis 2H 16 Potential to develop OPT-302 for other eye diseases, incl. DME 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

23 Megan Baldwin, PhD CEO & Managing Director Opthea Limited (ASX:OPT, OTCQX:CKDXY) +61 (0)