Opthea Limited · ASX:OPT
Opthea — Circadian Technologies — Biotech Showcase 2012
48 slides from Opthea's conference presentation, Jan 11, 2012
Slide 1: Biotech Showcase, San Francisco
BIOTECH SHOWCASE PARC 55, SAN FRANCISCO 11 JANUARY 2012 Robert Klupacs, CEO & Managing Director Circadian Technologies Ltd (ASX.CIR, OTCQX.CKDXY)
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 ASX listed 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 ocular research organisations.
Slide 4: Our IP Covers Major Components of VEGF Pathway
OUR IP COVERS MAJOR COMPONENTS OF VEGF PATHWAY VEGF-A
Slide 5: 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
Slide 6: Therapeutic Foci
THERAPEUTIC FOCI • Oncology – in combination with existing therapies • Front of Eye Disease (Cornea) – mono-therapy
Slide 7: Combination Therapy Is the New Paradigm in Cancer Therapy
COMBINATION THERAPY OF TARGETED AGENTS IS BECOMING THE NEW PARADIGM IN CANCER THERAPY
Slide 8: Our Approach in Oncology
OUR APPROACH IN ONCOLOGY Combine a VEGF-C antibody (VGX-100) with a VEGF-A antibody (Avastin) (or small molecule drugs which also target VEGF-A) to improve tumour starvation AND ongoing spread of tumours through the lymphatic system to improve patient overall survival
Slide 9: 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 10: VGX-100 Reduces Metastasis in Orthotopic Prostate Cancer Model
VGX-100 REDUCES METASTASIS IN AN ORTHOTOPIC PROSTATE CANCER MODEL 10
Slide 11: U87MG Glioblastoma Xenografts: VGX-100 Effective 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 12: H292 NSCLC Xenografts: VGX-100 Effective 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 12
Slide 13: VEGF-C May Be 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 14: 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 15: 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. • Very strong interest f
Slide 16: Oncology Clinical Development Timelines
ONCOLOGY CLINICAL DEVELOPMENT TIMELINES • Phase 1 studies (Arm A –monotherapy ) commenced Jan 12 • Phase 1 studies (Arm B, Combination) commences Q3 ’12 • Initial Safety data from Arm A and Arm B Sep ’12 • Phase 1 complete Dec ’12 • Phase 2 GBM studies commence Q1’13 • GBM patient enrolment complete
Slide 17: Therapeutic Focus: Front of Eye Disease
THERAPEUTIC FOCUS FRONT OF EYE DISEASE Inhibiting the growth of blood vessels and lymphatic vessels into the cornea (“front of eye”) resulting from disease or injury which cause the cornea to be clouded and result in blindness. VGX-100 (fully human VEGF-C ab) & VGX-300 (recombinant human soluble
Slide 18: Blood & Lymphatic Vessel Infiltration Causes Corneal Opacity
BLOOD & LYMPHATIC VESSEL INFILTRATION CAUSES CORNEAL OPACITY
Slide 19: Blood & Lymphatic Vessel Infiltration Causes Corneal Opacity
BLOOD & LYMPHATIC VESSEL INFILTRATION CAUSES CORNEAL OPACITY Huge ingrowth of blood vessels and lymphatics
Slide 20: Development Opportunity
DEVELOPMENT OPPORTUNITY • Significant development opportunity for VGX-100 as a treatment for ‘front of the eye’ disease. • Initial indications: • Corneal Neovascularisation (CNV) • Estimated that up to 4-5% of patients at eye clinics have CNV • Potential market >$1B p.a • Very limited competition •
Slide 21: Rejected Corneas Over-Express VEGF-C and VEGFR-3
REJECTED CORNEAS ARE INFILTRATED BY BLOOD AND LYMPHATIC VESSELS AND OVER-EXPRESS VEGF-C and VEGFR-3 Transplanted Corneas: 3 wks Post-Transplant ACCEPTED REJECTED Photomicrographs Flat-mount IHC stained corneas: VEGF-C expression LYVE-1 (lymphatics) increased 2-fold in CD31 (blood vessels) rejected v
Slide 22: VGX-100 Promotes Corneal Transplant Survival
VGX-100 PROMOTES CORNEAL TRANSPLANT SURVIVAL Our Goal is to commence clinical studies by Q1 ‘13 with fast track approval application lodged by H2’15 ARVO Annual Meeting 2010. Program#/Poster#1554/D995 22
Slide 23: Corporate & Financials
CORPORATE & FINA circadian”
Slide 24: Key Financials (Consolidated)
KEY FINANCIALS (CONSOLIDATED) 30 June 11 31 Dec 2011 (unaudited) $000 $000 Cash 22,104 18,500 Listed investments (market value) 1,432 3,474 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 sha
Slide 25: Financials – Cash Flows
FINANCIALS – CASH FLOWS • Current Cash - $18.5m (Unaudited) • Value of Listed Holdings - $3.5M (Unaudited) • Conservative Cash Burn 2011/12 and 2012/13 - $9.0M p.a • Well positioned to achieve key value adding milestones • Does not take into consideration: Increased R&D Tax Credit Royalties on S
Slide 26: Financial Position & Shareholder Base
FINANCIAL POSITION & SHAREHOLDER BASE Top 10 shareholders: 52.8% Financial Summary @ 31 December 2011 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,
Slide 27: Expected Near Term Milestones
EXPECTED NEAR TERM MILESTONES
Slide 28: Key Value Adding Announcements Next 12-15 Months
KEY VALUE ADDING ANNOUNCEMENTS NEXT 12- 15 MONTHS • Ongoing VGX-100 Phase 1 clinical results – each 8-10 weeks from Jan 2012 • Key Non-Dilutive Financing Events –Q1 and Q3 ’12 • Launch of CUP Test by Healthscope – Q2 ‘12 • Results from Eli Lilly’s Clinical Trials with IMC-3C5 – Q2/Q3 ’12 • VGX-100 P
Slide 29: A Tremendous Investment Opportunity
A TREMENDOUS INVESTMENT OPPORTUNITY • We completely own 3 of the hottest targets in drug development for oncology & eye disease • We have Multiple clinical development opportunities with potential for further partnering over next 6-12 months • We have cash resources to achieve key value adding miles
Slide 30: Thank You! Q&A
THANK YOU! Q&A
Slide 31: Appendix
APPENDIX
Slide 32: Circadian Technologies Limited
Circadian Technologies Limited Cash Approx $19M at 22 November 2011 Staff 100% 100% 100% Cancer Polychip Vegenics Pty Ltd Therapeutics Limited Limited Oncology Ophthalmology Diagnostics Investments VGX-100 (PI Trials Dec ’11) VGX-100 VEGF-C ASX:ANP (Approx 11%) Front of eye EIA (Blood test) VGX-200
Slide 33: Our Business Model
OUR BUSINESS MODEL UTILISE CASH -strong cash reserves -increasing revenues from diagnostics and other therapeutic partnerships -controlled divestment of existing investments BRING OUR LEAD COMPOUNDS TO CLINICAL VALIDATION POINTS PARTNER, THROUGH CO-DEVELOPMENT DEALS WITH BIG PHARMA
Slide 34: 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 35: An Investment with Significant Upside
AN INVESTMENT WITH SIGNIFICANT UPSIDE Research Report from van Leeuwenhoeck Research 7 October 2011 “…Based on sum-of-the-parts valuation, we believe Circadian is gravely undervalued at the current share price of AUD 0.47. Using our valuation model, the Company’s total value is AUD 91 million, or AU
Slide 36: Mechanism of Circadian's Drugs in Solid Tumours
Mechanism of Circadian’s Drugs in solid tumours VGX-100 inhibits VEGF-C 36
Slide 37: Mechanism of Circadian's Drugs (2)
MECHANISM OF CIRCADIAN’S DRUGS (2)
Slide 38: VGX-100 Single-Agent & Combination Therapy in PC-3 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 39: 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 possible market size $300M p
Slide 40: 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 40
Slide 41: Partnering Antibodies for Cancer Therapy Can Be 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 42: 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 43: Our Diagnostics Portfolio
OUR DIAGNOSTICS PORTFOLIO 43
Slide 44: Diagnostics – A Source of Near Term Revenue
DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE • VEGF-D Diagnostics • VEGF-C Diagnostics • Cancers of Unknown Primaries 44
Slide 45: Diagnostics – VEGF-D
DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE VEGF-D Diagnostics – Marketed as biomarker test for LAM (degenerative lung disease in women) in USA by Cincinatti Children’s – Market expected to expand to 25-50,000 tests p.a within 2-3 years – $10-20M market (with 20-25% royalty) – Sales significantly in
Slide 46: Diagnostics – VEGF-C
DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE VEGF-C Diagnostics – Development accelerated – Based on MD Anderson study appears to be a major biomarker to monitor anti-angiogenic therapy “resistance” – Key product requirement for US re-imbursement agencies – Possible market 250,000 tests worldwide at
Slide 47: Diagnostics – Cancers of Unknown Primary Origin
DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE Cancers of Unknown Primary Origin » Market launch in Aust, NZ, Malaysia, Singapore expected Q1 2012 » Market size 10,000 tests p.a » Pricing at $1000-1500/test (Royalty > 15%) » Circadian retains rights to test to ROW » Partnership discussions ongoing » Ex
Slide 48: Preliminary Market Opportunity Assessment
PRELIMINARY MARKET OPPORTUNITY ASSESSMENT Corneal Allograft Rejection: # Corneal Transplants/Year (U.S.A): 40000 # High-Risk Corneal Transplants/Year (U.S.A): 10000 Annual Cost per Estimated Annual Revenue Patient/Year (U.S.A) (U.S.A.)* USD 15000 USD 150M Ex USA estimated to be equal in $$ value to