Opthea Limited · ASX:OPT
Opthea — Circadian Technologies — Investor Presentation (March 2009)
30 slides from Opthea's investor presentation, Mar 26, 2009
Slide 1: Corporate Presentation
Corporate Presentation 26 March 2009 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: Circadian Technologies Limited
Circadian Technologies Limited A cashed up company developing novel anti- angiogenic therapeutics for cancer and other serious diseases With a dominant IP platform And the potential for generating significant revenues in the near term.
Slide 4: Developing therapeutics for cancer and other serious diseases
Developing therapeutics for cancer and other serious diseases • Developing angiogenesis-based therapies for cancer and other serious diseases • World’s most comprehensive patent estate covering key angiogenesis targets VEGF-C, VEGF-D and VEGFR3 • Partnered programs with leading international biotech
Slide 5: What is angiogenesis?
What is angiogenesis? • Angiogenesis is the growth of new blood vessels • Tumour growth is caused by stimulation of new blood vessel growth by proteins (e.g. proteins VEGF-A, C, D) • Blocking these proteins blocks blood vessel growth, leading to tumour starvation
Slide 6: Avastin Story
Avastin® Story • First targeted anti-angiogenesis therapy to become drug (developed & sold by Genentech Inc and Roche) • Antibody that blocks angiogenic protein VEGF-A • First approved Feb 2004 • 2007 sales: in US $US2.3B, worldwide: $US6B ($10B+ 2009) • Fastest sales growth of any drug Avastin + ch
Slide 7: Anti-VEGF Therapy (Avastin): Effective but not across the board
-VEGF Therapy (Avastin®): Effective but not across the board….. Bergers et al., Nat.Reviews Cancer, 8: 592‐602, 2008. VEGF-C/D VEGF-C/D VEGF-C/D
Slide 8: Activity of Circadian's VEGF-C/D Inhibitors
Activity of Circadian’s VEGF-C/D Inhibitors
Slide 9: Circadian's approach and technology
Circadian’s approach and technology • Developing blockers of the two other angiogenic VEGF proteins (VEGF-C & D) - involved in tumour growth as well as in tumour spread (metastasis) • Blocking VEGF-C/D - not only starves tumours but additional major therapeutic potential for inhibiting tumour spread
Slide 10: Our strategy
Our strategy • Develop selected therapeutics to proof of efficacy in Phase II trials • Subsequent clinical development with partners – large pharmaceutical/biotechnology companies • Seize opportunity for earlier therapeutic partnerships if appropriate • Selectively exploit/commercialise parts of the
Slide 11: Circadian's Business Model
CIRCADIAN’s BUSINESS MODEL Existing Listed Cash Recurrent Revenues Investments $41.2M Royalties* Licence Fees $5M Interest* Future Partnerships Realised at R&D Projects Reagent/Diagnostics Sales appropriate VGX-100 VGX-200 Ark time VGX-300 ImClone Clinical Diagnostics Healthscope Research Reagents R
Slide 12: Deep Product Pipeline with mechanistically distinct mechanisms
Deep Product Pipeline with mechanistically distinct mechanisms
Slide 13: Other Potential Revenue generating assets
Other Potential Revenue generating assets • VEGF-C, VEGF-D ligands as research reagents, therapeutic development in wound healing, cardiovascular disease, lymphedema, neurodegenerative disease • Ownership and exclusive commercialisation rights to molecular diagnostic for Cancers of Unknown Primary (
Slide 14: Phase 3 Product Trinam - Ark Therapeutics
Phase 3 Product Trinam®- Ark Therapeutics • Commenced Phase 3 trials Jan 2009 under SPA. Expected recruitment 250 patients over 18 months. • VEGF-D gene therapy product. • Extends lifetime of dialysis access grafts. Phase 2 clinical trials 17 months v 4.5 months. • Major patient impact by reduced ne
Slide 15: IMC-3C5 (human anti-VEGFR-3 mAb) ImClone/Lilly
IMC-3C5 (human anti-VEGFR-3 mAb) ImClone/Lilly • Formal internal product development candidate • IND planned H1 2010 • Currently completing CHO cell line development and process • Wide range of peer reviewed literature • Confidential data in range of xenograft models • Likely first indication head &
Slide 16: Circadian has dominant IP rights in respect of VEGF-C/D antagonists
Circadian has dominant IP rights in respect of VEGF-C/D antagonists • Granted IP rights in major territories to VEGF-C/D proteins and VEGFR-3 and blockers • Applications in cancer and certain other diseases • IP rights over product candidates extend beyond 2020 • Further strategic IP filings being m
Slide 17: Deal-making drug development and operational track record
Deal-making drug development and operational track record • Robert Klupacs (CEO) Founder and former CEO, ES international and six other early stage companies. Entrepreneur and IP expert with extensive history of industry deals including Sanofi, Baxter, Aventis, Pharmacia, Novartis, Alexion, Pfizer.
Slide 18: An investment with significant upside
An investment with significant upside • Dominant IP position over key mediators of angiogenesis. • Phase 3 product partnered and pipeline of product opportunities-multi-million royalty flow possible within 24-36 months. • Strong financial assets to support development/deal making • Extremely high va
Slide 19: Appendices
APPENDICES circadian technologies limited
Slide 20: VGX-100 Program Summary
VGX-100 Program Summary •VGX-100 is a fully human, high affinity, neutralising monoclonal antibody for VEGF-C •Development and clinical program designed to address resistance and non-responsiveness to anti-angiogenic therapies for cancer •Orphan drug designations likely •IND expected Q1 2011. •Precl
Slide 21: VGX-200 Program Summary
VGX-200 Program Summary •Humanisation and affinity maturation program complete •Lead hIgG1 mAbs identified based on fold-improvement in KD relative to murine parental VD1 antibody •Formal lead identified by Nov ’09 based on in vivo efficacy •IND anticipated H1/2011 •Orphan drug designation likely •P
Slide 22: VGX-300 Program Summary
VGX-300 Program Summary •Soluble receptor protein consisting of the first 3 Ig-like domains of hVEGFR-3 linked to the Fc region of hIgG1 •Neutralises both VEGF-C and VEGF-D •Stable CHO cell line expressing levels sufficient for research grade production •IND anticipated H2/2011 •Orphan drug designat
Slide 23: VEGF-C & VEGF-D levels correlate with LN mets in gastric cancer
VEGF-C & VEGF-D levels correlate with LN mets and decreased survival in gastric cancer 91 Gastric Adenocarcinomas VEGF-C VEGF-C and VEGF-D correlated with: • LN metastases VEGF-D • Decreased survival VEGF-D and VEGFR-3 are independent prognostic markers Graphs show DFS Juttner et al., JCO, 24(2): 22
Slide 24: Poor prognosis for NSCLC patients expressing VEGF-C and VEGFR-3
Poor prognosis for Non Small Cell Lung Cancer patients expressing VEGF-C and VEGFR-3 180 NSCLCs 5yr survival rates for patients: VEGF-C positive: 47% VEGF-C negative: 70% VEGF-C and VEGFR-3 correlated with: • Decreased survival • Pts with positive staining for both had poorest prognosis Arinaga et a
Slide 25: Poor survival of breast cancer patients with high VEGF and VEGF-C
Poor survival of breast cancer patients with high VEGF and VEGF-C levels 117 invasive breast cancer VEGF-C correlated with: • LVD • LN Metastases • Decreased OS Pts with high VEGF-C & VEGF levels have worst prognosis Mohammed et al., Brit. J. Cancer, 96: 1092‐1100, 2007.
Slide 26: VEGF-C and VEGF-D are risk factors for colorectal cancer
VEGF-C and VEGF-D are risk factors for colorectal cancer 78% 79% Overall Survival Rates: High VEGF-C/VEGF-D: 28% 40% Low VEGF-C/VEGF-D: 84% 32% 69 CRC VEGF-C correlated with: Elevated VEGF-C and VEGF-D • LN Metastases associated with: • Clinical Stage • Decreased DFS • Decreased OS VEGF-D correlated
Slide 27: Circulating VEGF-C & VEGF-D levels are elevated in cancer patients
Circulating VEGF-C & VEGF-D levels are elevated in cancer patients Indication VEGF-C Median or Mean Level Reference (pg/ml by ELISA) CRC HIGH vs Healthy Controls 35 U/ml vs 11.5 U/ml Duff, Int. J. Oncol., 2003. NSCLC HIGH vs Healthy Controls 1726 vs 941.2 Tamura, Cancer, 2003 NSCLC HIGH vs non-metas
Slide 28: LAM – Orphan Development Opportunity for VEGF-D Antagonists
LAM – Orphan Development Opportunity for VEGF-D Antagonists VEGF‐D is increased in Serum VEGF‐D levels distinguishable from other serum of patients with cystic and chylous lung diseases LAM Young et al. NEJM., 358(2), 199‐200, 2008 Seyama et al. Lymphatic Res & Biol., Vol 4, #3, 143‐152, 2006 VGX-20
Slide 29: LAM – Orphan Development Opportunity for VEGF-D Antagonists
LAM – Orphan Development Opportunity for VEGF-D Antagonists Lymphangioleiomyomatosis (LAM): cystic lung lesion, lymphatic abnormalities, abdominal tumors Proliferation of abnormal smooth muscle cells Often degenerative requiring lung transplant Frequently fatal Primarily affects women of r
Slide 30: Circadian Background
Circadian Background • Listed on the ASX in 1985 • In 2006, Circadian acquired 50% of Vegenics Limited. • In 2008 Circadian acquired 100% of Vegenics Limited put in place new leadership and transformed its business model to focus on the development of biologics-based therapies for cancer through inh
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