Opthea Limited · ASX:OPT
Opthea — Circadian Technologies — Biomelbourne Network CEO Lunch Series (April 2009)
44 slides from Opthea's conference presentation, Apr 24, 2009
Slide 1: CEO Lunch Series: The New Circadian
CEO Lunch Series The New Circadian - Transforming from Biotech Incubator to Biologicals Drug Developer Mr Robert Klupacs CEO, Circadian Technologies Hosted by: Mr James Cherry Partner, Freehills Patent & Trade Mark Attorneys
Slide 2: Presentation to Biomelbourne Network
Presentation to Biomelbourne Network Friday, 24 April 2009 Robert Klupacs, CEO & Managing Director
Slide 3: 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 4: Circadian - Leader, Adapter, Survivor
CIRCADIAN-Leader, Adapter, Survivor CIRCADIAN-AN EVOLUTIONARY JOURNEY : FROM DEVELOPER, TO EARLY STAGE INVESTOR, TO INCUBATOR, TO FUND, TO BIOLOGICALS DEVELOPER
Slide 5: Mr Leon Serry
Mr Leon Serry
Slide 6: Circadian History - Melatonin phase
Circadian History –Melatonin phase • 1984: Leon Serry partners with Monash Uni to develop melatonin jet lag project • 1985: Circadian Listed on the ASX with $1M raising • 1985-1994: Additional investments in early stage projects • 1994: Eli Lilly granted exclusive licence to develop melatonin agonis
Slide 7: Circadian History - Melatonin phase
Circadian History –Melatonin phase • Eli Lilly sued for non performance in early 98 • Settled Xmas 1998 • $US3M settlement payment
Slide 8: Circadian Listings/Investments
Circadian Listings/Investments • Optiscan listed on ASX Aug 1997 • Metabolic listed on ASX Nov 1998 • Axon listed on ASX Mar 2000 • Initial investment in AMRAD May 2000 • ANP listed on ASX Nov 2001 • AVX obtained from AMRAD demerger 2003
Slide 9: Circadian Listings/Investments/Proceeds
Circadian Listings/Investments/Proceeds Stage • Proceeds realised on investments - Axon $31M (Gain $29.9M) acquired by Molecular Devices May 2004 - AMRAD $30M (Gain $7.5M) acquired by CSL Nov 2006 - Metabolic $16.2M (Gain $15.7m) - Avexa (from AMRAD demerger) $18.3M (Gain $4.8m) • 2 Significant plac
Slide 10: Circadian VEGF-C/D Biologicals Developer
Circadian VEGF-C/D Biologicals Developer • JV formed with Ludwig Institute and Licentia to commercialise VEGF-C, VEGF-D in Apr 2006 • Leon Serry announces retirement in Dec 2007 • New CIR leadership from Mar 2008 • New directions launched with 100% ownership of VEGF J/V company in Aug 2008
Slide 11: Circadian Today
CIRCADIAN TODAY A cashed up company developing novel anti- angiogenic therapeutics for cancer With a dominant IP platform And the potential for generating significant revenues in the near term.
Slide 12: Circadian Today
CIRCADIAN TODAY • Focused on the development of VEGF-C/D antibodies as biologics-based therapies for cancer through tumour starvation (“anti-angiogenesis”) • 12 person management and scientific team supported by international advisors, contracted testing agencies and relationships with leading acade
Slide 13: Why did we change strategy to become biologicals drug developer?
WHY DID WE CHANGE STRATEGY TO BECOME BIOLOGICALS DRUG DEVELOPER? Major focus of big pharma High Value early stage deals and M&A Exquisite targeting-improved probability of success Extremely large markets Avastin® Significant product opportunity in angiogenesis Unique, Deep and Dominant IP
Slide 14: Antibodies represent significant market opportunities
Antibodies represent significant market opportunities • Strong interest in antibodies from pharma in M&A and early stage licensing: • M&A over last 2 years: • Medimmune/AstraZeneca – US$15.5b • CAT/AstraZeneca – US$1.30b • Domantis/GSK – US$435m • Adnexus/BMS – US$425m • Morphotek/Eisai – US$325m •
Slide 15: Oncology Antibodies: Preclinical Deals continuing
Oncology Antibodies: Preclinical Deals continuing Parties Date Size Technology Micromet/Bayer-Schering Jan 09 $US396M Option to Ab against undisclosed oncology target Abbott/LICR Nov 08 $US150-200M Exclusive licence to 2nd generation EGFR Ab in oncology, which has completed 8 person Phase 1 study. B
Slide 16: Antibodies represent significant market opportunities
Antibodies represent significant market opportunities 19 antibody drugs on the market • Current sales of top ten antibodies > US$20bn p.a; • Total antibody sales growing by >30% annually • greater competitive barrier to entry • targeted profiles can provide cost v health economic advantage • probabi
Slide 17: 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
Slide 18: 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 19: α-VEGF Therapy (Avastin): Effective but not across the board
α-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 20: The Product Opportunity
The Product Opportunity Opportunity to develop a new class of antagonists to address resistance and/or non-responsiveness to anti-angiogenic therapies in cancer.
Slide 21: Activity of Circadian's VEGF-C/D Inhibitors
Activity of Circadian’s VEGF-C/D Inhibitors
Slide 22: Deep Product Pipeline with mechanistically distinct mechanisms
Deep Product Pipeline with mechanistically distinct mechanisms
Slide 23: 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 24: 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 25: 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 26: Circadian's Business Model - Maintaining Cash for R&D
CIRCADIAN’s BUSINESS MODEL – MAINTAINING CASH FOR R&D Existing Listed Cash Recurrent Revenues Investments $41M Royalties* Licence Fees $4.4M Interest* Future Partnerships Realised at R&D Projects Reagent/Diagnostics Sales appropriate VGX-100 VGX-200 Ark time VGX-300 ImClone Clinical Diagnostics Heal
Slide 27: 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 28: 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 29: VGX-100 slows growth of orthotopic prostate tumors
VGX-100 slows growth of orthotopic prostate tumors PC-3 Growth rate 10000 Untreated IgG1 Control 7500 VGX-100 5000 2500 0 0 10 20 30 40 50 Day Dosing: 20 mg/kg every 7d.
Slide 30: VGX-100 inhibits PC-3 metastasis
VGX-100 inhibits PC-3 metastasis Lymph Node Metastatic Frequency N 6 8 7 7 50 25 0 Untreated VGX-100 VEGF-C mAb1 VEGF-C mAb4 VEGF-C mAb3
Slide 31: Dose-dependent inhibition of breast cancer xenografts
Dose-dependent inhibition of breast cancer xenografts MDA-MB-231 Growth 4000 Control IgG CAT002 (20 mg/kg) (20mg/kg) VEGF-C mAb V069D09 VGX-100 1 (20 mg/kg) (20mg/kg) (20mg/kg) VEGF-C V069D09 VGX-100 mAb 1 (10 mg/kg) (10mg/kg) (10mg/kg) 3000 V069D09 VGX-100 VEGF-C mAb(5mg/kg) (5mg/kg) 1 (5 mg/kg) No
Slide 32: VGX-100 Development Program
VGX-100 Development Program Dec 2009 2010 2011 ‘08 cGMP Program 1H’11 Pre- IND IND Phase I Dec Apr Oct Dec Mar Sept Res.Gde Prodn. Stable clonal CHO Res.Gde GLP Tox Production/ Drug cell line dev. Prodn. Material Formulation/Fill Product (CHO) Prodn. -Finish Drug Available Product Animal studies-onc
Slide 33: 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 34: 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 35: VEGFR3 Ab +/- chemotherapy in head and neck cancer xenograft model
VEGFR3 Ab +/- chemotherapy in head and neck cancer carcinoma xenograft model AACR 2009 Abstract #4089 O’Mahoney et al
Slide 36: VEGFR3 Ab +/- chemotherapy in NSCLC xenograft model
VEGFR3 Ab +/- chemotherapy in NSCLC xenograft model (NCI-H292) AACR 2009 Abstract #4089 O’Mahoney et al
Slide 37: Circadian has dominant IP rights in respect of VEGF-C/D antagonists
Circadian has dominant IP rights in respect of VEGF-C/D antagonists • Over 500 granted and pending patents worldwide • 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 b
Slide 38: Experienced and talented management team
Experienced and talented management team • Robert Klupacs (CEO) • Dr Alex Szabo (Head, Business Development) • Natalie Korchev (CFO & Head of Operations) • Dr Megan Baldwin (Head Pre-clinical Development) • Dr Mike Gerometta (Head, CMC Development) • Dr Richard Chadwick (Head, Intellectual property)
Slide 39: Product Development Advisory Committee
Product Development Advisory Committee • Team with experience in over 150 drug developments - Errol Malta (Chair): ex-Amgen - George Morstyn: ex-CMO Amgen - Russell Howard: CEO Maxygen - Ralph Smalling: ex-Amgen Reg Affairs - Richard Morgan: ex Glaxo-Wellcome - Carlo Montagner: ex Aventis, Schering,
Slide 40: Scientific Advisory Board
Scientific Advisory Board • World leaders in angiogenesis research - Prof Kari Alitalo (Chair): Finnish Academy of Sciences - Assoc Prof Marc Achen: Ludwig Institute - Assoc Prof Steve Stacker: Ludwig Institute
Slide 41: Last 6 months
Last 6 months CIR.AX as of 22-Apr-2009 +302 T T T T T T +202 4CIR.AX +102 oz -102 1“aorp -202 -302 i i i i i i Novos Decos Janog Feboo Marog Aprog 100 200 T T T T T T 3 BY¥olume 8 50.00 F | 4 ‘= - 0,00 | u 1 ul | im A |, i | l LL | ul a la 1 Aan 1 li | Copyright 2009 Yahoo! Inc. http://finance .yaho
Slide 42: Next 12 Months
NEXT 12 Months • Expand management and scientific team • Complete cell line development and manufacturing of VGX-100, VGX-200 and VGX- 300 • Complete initial rounds of xenograft experiments • Develop serum based assays for VEGF-C/D • IMC-3C5 commences clinical studies • Partner(s) identified
Slide 43: 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 44: Biobreakfast
BIOBREAKFAST Tuesday, 12th May ‘How can Biotech Companies Navigate the Current USA Patent Climate?’
Circadian Technologies — Biomelbourne Network CEO Lunch Series (April 2009) on 6ix