Opthea Limited · ASX:OPT
Opthea — Circadian Technologies — Investor Presentation (May 2012)
42 slides from Opthea's investor presentation, May 2012
Slide 1: Circadian Technologies Limited
CIRCADIAN TECHNOLOGIES LIMITED (ASX.CIR, OTCQX.CKDXY) MAY 2012 Robert Klupacs, CEO & Managing Director
Slide 2: Disclaimer
DISCLAIMER Investment in Circadian Technologies Limited (‘Circadian’) is subject to investment risk, including possible loss of income and capital invested. Neither Circadian nor any other member company of the Circadian Group guarantees any particular rate of return or performance, nor do they guar
Slide 3: Who We Are
WHO WE ARE An emerging clinical stage company developing human therapeutic and diagnostic products from our extensive intellectual property assets in respect of VEGF-C, VEGF-D and VEGFR-3 and key relationships with leading cancer and eye research organisations.
Slide 4: Reasons to Invest
REASONS TO INVEST • Clinical Stage Assets • Increasing Diagnostics Portfolio generating revenues • A platform with major deal/partnering potential across a range of products over next 3-18 months • Investments coming up to major re-rating events • Capability to get to key value adding events • Exper
Slide 5: Our Products
OUR PRODUCTS • Developing antibody therapies to treat cancer and eye disease » Based on unique ability to starve blood vessel and lymphatic vessel growth » Targeting significant unmet clinical needs in oncology & ophthamology » Multi-billion dollar market opportunity • 2 molecules currently in USA P
Slide 6: Our Products Designed to Improve on Existing Anti-Angiogenic Therapies
OUR PRODUCTS ARE DESIGNED TO IMPROVE ON EXISTING ANTI-ANGIOGENIC THERAPIES WHICH TARGET VEGF-A Lucentis 2011 sales $US2.9B (wet AMD) Source Roche Avastin 2011 sales $US5.8B (cancer) Source Roche
Slide 7: Improving Anti-Angiogenesis: A Major Commercial Opportunity (Avastin)
IMPROVING ANTI-ANGIOGENESIS A MAJOR COMMERCIAL OPPORTUNITY • Avastin® (a humanised VEGF-A Antibody): • Effective but not in all patients – Not all patients respond to therapy (30-50% response rate) – 25-50% of responders become “resistant” within 12 to 18 months – Potential reasons: • Tumour growth
Slide 8: Improving Anti-Angiogenesis: A Major Commercial Opportunity (Lucentis)
IMPROVING ANTI-ANGIOGENESIS A MAJOR COMMERCIAL OPPORTUNITY • Lucentis® (a humanised VEGF-A Antibody): • Approved for use in “wet” AMD (new blood vessel growth in retina causing leakage) • Huge and Growing market due to aging • Effective but not in all patients – Not all patients respond to therapy (
Slide 9: Our Approach
OUR APPROACH Combine an VEGF-C antibody (VGX-100) with a VEGF-A antibody (Avastin or Lucentis) (or small molecule drugs which also target VEGF-A) to improve and maintain inhibition of new blood and/or lymphatic vessel growth
Slide 10: Combination Therapy Is the New Paradigm in Cancer Therapy
COMBINATION THERAPY OF TARGETED AGENTS IS BECOMING THE NEW PARADIGM IN CANCER THERAPY
Slide 11: Oncology
ONCOLOGY • Initially targeting “niche” tumours then expanding into larger tumour types / markets after securing clinical proof • Glioblastoma (“Brain cancer”) – First Indication • Ovarian cancers • Pancreatic cancers • Gastric cancers • Colorectal cancers (“Bowel”)
Slide 12: Glioblastoma - A Major Unmet Clinical Need
GLIOBLASTOMA - A MAJOR UNMET CLINICAL NEED • In the US in 20101 – Estimated diagnosed: 22,020 – Estimated fatalities: 13,140 • The most aggressive malignant primary brain tumor in adults • Nearly always fatal • Possibility for fast track registration based on Phase 2b study. • Phase 2b study aim to
Slide 13: Glioblastoma - Major Commercial Potential
GLIOBLASTOMA - A MAJOR UNMET CLINICAL NEED WITH MAJOR COMMERCIAL POTENTIAL • Expected Treatment Cost $15-20,000 for 4 months therapy up to $30,000 for 6 months treatment • US patient pool initially up to 10,000 p.a, expanding to 50,000 ROW over subsequent years • Initial market size $300M p.a rising
Slide 14: U87MG Glioblastoma Xenografts: VGX-100 with Avastin
U87MG GLIOBLASTOMA TUMOR XENOGRAFTS: VGX-100 EFFECTIVE IN COMBINATION WITH AVASTIN 2600 Negative Isotype Control 2400 Avastin Mean Tumor Burden (mg) +/- SE 2200 2000 VGX-100 1800 1600 1400 1200 1000 VGX-100 + Avastin 800 600 400 200 0 0 10 20 30 40 Days Post-Tumor Implant At Day 49, VGX-100 + Avasti
Slide 15: VGX-100 Reduces Metastasis in Orthotopic Prostate Cancer Model
VGX-100 REDUCES METASTASIS IN AN ORTHOTOPIC PROSTATE CANCER MODEL 15
Slide 16: VEGF-C Is a Risk Factor for Colorectal Cancer
VEGF-C is a risk factor for colorectal cancer 69 CRC VEGF-C correlated with: • LN Metastases Low VEGF-C • Clinical Stage Elevated VEGF-C associated with: High VEGF-C • Decreased DFS • Decreased OS Hu et al., Eur Surg Res, 39: 229-238, 2007.
Slide 17: Eye Disease
EYE DISEASE • Age related macular edema (AMD) – a major unmet clinical need with significant commercial potential • Currently in the USA 1.75 million individuals are affected • 200,000 new cases are diagnosed each year. • Lucentis $3B sales in 2011 • Our market estimates based on “niche” non-respond
Slide 18: Dry Eye Disease
DRY EYE DISEASE • Multifactorial, immune-mediated disorder of the ocular surface affecting vision. • Affects ~5M people aged >50yrs in USA. • Adverse environmental conditions significant cause of DED. • Limited therapeutic options. Usually artificial tears. • Now known to be lymphatic mediated. Luce
Slide 19: VGX-100 Reduces Clinical Signs of DED
VGX-100 REDUCES THE CLINICAL SIGNS OF DED Corneal Fluorescein Score Goyal et al., Arch Ophthalmol., 130(1):84-9, 2012
Slide 20: Diagnostics - A Source of Near Term Revenue
CANCERS OF UNKNOWN PRIMARY DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE » Development partnered with Healthscope » CUP 7th largest cancer fatalities » Healthscope (Aus,NZ, Singapore & Malaysia) Circadian retains ROW rights » Market launch in Aust, NZ expected June/July 2012 » Market size in Healthsco
Slide 21: Key Financials (Consolidated)
KEY FINANCIALS (CONSOLIDATED) 30 June 11 31 Dec 2011 $000 $000 Cash 22,104 18,272 Listed investments (market value) 1,432 3,379 Net assets 21,824 Revenue 1,850 Operating expenses (incl. R&D, investment (12,893) related exp’s) Loss before tax (11,043) Net cash outflows (9,477) NTA per share $0.47 Cas
Slide 22: Financials - Cash Flows
FINANCIALS – CASH FLOWS • Current Cash - $15.5m (Unaudited) • Value of Listed Holdings - $2.5M (Unaudited) • Conservative Cash Burn 2011/12 and 2012/13 - $9-12M p.a • Well positioned to achieve key value adding milestones • Does not take into consideration: Increased R&D Tax Credit Royalties on
Slide 23: Financial Position & Shareholder Base
FINANCIAL POSITION & SHAREHOLDER BASE Top 10 shareholders: 52.8% Financial Summary @ 15 May 2012 Investor % of issued shares (unaudited) HSBC Custody Nominees 18.88 (Australia) Limited Stock code: CIR Licentia Ltd 6.79 Share price: 47.0c (AUD) Ludwig Institute for Cancer 6.73 Shares issued: 46,396,9
Slide 24: Key Development Milestones
KEY DEVELOPMENT MILESTONES Activity Timeline CUP Test Launch 6-7/2012 VGX-100 Phase 1 Clinical Trial update 8/2012 VGX-100 Phase 1 studies completed H2 2012 IMC-3C5 Phase 1 trials reported H2 2013 Phase II studies in cancer patients start (Multiple Indications) Q1 2013 VGX-100 IND Filing Eye Disease
Slide 25: An Investment with Significant Upside
AN INVESTMENT WITH SIGNIFICANT UPSIDE Research Report from Edison Research March 14 2012 “….On a DCF basis to March 2012, Edison estimates a revised indicative value of A$100m (A$2.16 per share). We expect value to develop strongly as the pipeline develops and as new VGX-100 indications become clear
Slide 26: Appendix
APPENDIX
Slide 27: VEGF-C: A Major Target for Improved Anti-Cancer Agents
VEGF-C A MAJOR TARGET FOR IMPROVED ANTI- CANCER AGENTS • Can stimulate VEGFR-2 and VEGFR-3 mediated angiogenesis (inhibition leads to “tumour starvation”) • Can stimulate VEGFR-3 mediated lymphangiogenesis, a major route of metatstatic spread (inhibition slows spread with survival benefits) • VEGF-C
Slide 28: VEGF-C Levels Correlate with Lymph Node Mets in Gastric Cancer
VEGF-C levels correlate with lymph node mets and decreased survival in gastric cancer 91 Gastric Adenocarcinomas VEGF-C VEGF-C correlated with: • LN metastases • Decreased survival VEGFR-3 is an independent prognosti markers Graph shows DFS Juttner et al., JCO, 24(2): 228-240, 2006.
Slide 29: Therapeutic Foci
THERAPEUTIC FOCI • Oncology – in combination with existing therapies • Front of Eye Disease (Cornea) – mono-therapy (separate presentation)
Slide 30: Therapeutic Focus Oncology
THERAPEUTIC FOCUS ONCOLOGY IMC-3C5 (fully human VEGFR-3 ab) Being developed by Imclone Phase 1 commenced April 2011 VGX-100 (fully human VEGF-C ab) In –house development Phase 1 commenced in USA January 2012 Lead indication -glioblastoma
Slide 31: H292 NSCLC Tumor Xenografts: VGX-100 with Avastin
H292 NSCLC Tumor Xenografts: VGX-100 effective in combination with Avastin Isotype Control Avastin 2000 VGX-100 VGX-100 + Avastin Mean Tumor Burden (mg) +/- SE Docetaxel Avastin + Docetaxel 1500 VGX-100 + Avastin + Docetaxel 1000 500 0 10 20 30 40 50 Days Post-Tumor Implant 32
Slide 32: VGX-100 Single-Agent & Combination Therapy in PC-3 Prostate Xenografts
VGX-100 SINGLE-AGENT & COMBINATION THERAPY IN PC-3 PROSTATE CANCER XENOGRAFTS 2200 Negative isotype Control 2000 Avastin Mean Tumor Burden (mg) +/- SE 1800 VGX-100 1600 Docetaxel Avastin + Docetaxel 1400 VGX-100 + Docetaxel 1200 VGX-100 + Avastin 1000 VGX-100 + Avastin + Doce 800 600 400 200 0 0 20
Slide 33: VGX-100 Enhances Avastin + Docetaxel in OVCAR-8 Ovarian Tumours
VGX-100 enhances Avastin + Docetaxel therapy in OVCAR-8 ovarian cancer tumours 2000 Isotype Control Docetaxel Mean Tumor Burden (mg) +/- SE Avastin + Docetaxel 1500 VGX-100 + Avastin + Docetaxel 1000 500 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Day Post-Implant CONFIDENTIAL 34
Slide 34: VGX-100 Active as Monotherapy in KP4 Pancreatic Xenografts
VGX-100 is active as a monotherapy in KP4 human pancreatic tumour xenografts mean tumor burden (mm3) ± SE 2000 Negative isotype Control VGX100 (20mg/kg) 1500 VGX100 (40mg/kg) VGX100 (60mg/kg) 1000 Avastin (10mg/kg) VGX100 (40mg/kg) + Avastin 500 0 0 10 20 30 Days post tumor implant CONFIDENTIAL 35
Slide 35: VEGF-C May Be a Predictive Biomarker for Avastin Resistance
HAVE NOW SHOWN THAT VEGF-C MAY BE A PREDICTIVE BIOMARKER FOR AVASTIN RESISTANCE * * VEGF-C levels begin to rise BEFORE tumours Stop responding to Avastin. Highlights major potential for improving therapy by combining VEGF-A and VEGF-C blockade C.Lieu et al., "The Association of Alternate VEGF Ligand
Slide 36: VGX-100 Target Product Profile in Oncology
VGX-100 TARGET PRODUCT PROFILE IN ONCOLOGY • Indication: – Co-administered with anti-angiogenic agent eg (Sutent®, Nexavar®, Avastin® ) and standard of care – Targeting glioblastoma and colorectal cancer as first indications – To develop through collaborations at least one of breast, lung, renal and
Slide 37: VGX-100 Phase I First-in-Human Study
VGX-100 PHASE I FIRST-IN-HUMAN STUDY Legend: A - Avastin® 100 – VGX-100 100 L1 L – dose level Solid tumour 100 L2 (advanced or metastatic) 100 L3 No further 100 L4 treatment options 100 L5 Multicentre 100 L6 “3+3” design (N = approx 27 A+100 L2 to 33) A+100 L3 A+100 L4 38
Slide 38: Experienced Management & Advisors
TREMENDOUS & EXPERIENCED MANAGEMENT & ADVISORS - Prof George Morstyn ex Amgen - Dr Errol Malta ex Amgen - Dr Ralph Smalling ex Amgen - Dr Russell Howard ex Maxygen/NIH - Dr Jonathan Skipper Ludwig Institute - Mr Carlo Montagner ex Abraxis/Sanofi-Aventis - Prof Kari Alitalo University of Helsinki - D
Slide 39: Partnering Antibodies for Cancer Therapy Can Be Very Lucrative
PARTNERING ANTIBODIES FOR CANCER THERAPY AT EARLY STAGE CAN BE VERY LUCRATIVE Parties Date Size Technology BioInvent/Thrombogenics Jun 08 $US800M Exclusive licence to PlGF (anti- /Roche angiogenic) Abs in oncology. $US75M upfront. $US700M milestones. Double digit royalties Pierre Fabre/Abbott Feb 10
Slide 40: Competitive Landscape: Biological Anti-Angiogenic Agents
COMPETITIVE LANDSCAPE BIOLOGICAL ANTI-ANGIOGENIC AGENTS Company Molecule Target Partner & Clinical Indication Relevance To CIR Partnering Stage Stage Regeneron Aflibercept VEGF-A Sanofi P3 1st and 2nd line CRC Positioned as direct competitor (VEGF Trap) PlGF Phase 1 2nd line NSCLC to Avastin, NOT as
Slide 41: Our IP Covers Major Components of VEGF Pathway
OUR IP COVERS MAJOR COMPONENTS OF VEGF PATHWAY VEGF-A
Slide 42: Our IP Covers Major Components of VEGF Pathway
OUR IP COVERS MAJOR COMPONENTS OF VEGF PATHWAY Avastin VEGF-A VGX-100/VGX-300 IMC-3C5
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