Csl Limited · ASX:CSL
Csl — Technical Presentation (December 2002)
67 slides from Csl's technical presentation, December 2002
Slide 1: CSL R&D Investment
“CSL R&D INVESTMENT” December 2002 CSL Limited
Slide 2: Overview
OVERVIEW l R&D Investment Process l Future Value Drivers – HPV Merck Update – Haemostatic Dressing – rHDL and stroke – ISCOM® Adjuvant leverage • HCV • CerVax16 and AIN • ESO1 and cancer – Biotech therapy for blindness
Slide 3: Human Health R&D
HUMAN HEALTH R&D Parkville Broadmeadows Bern
Slide 4: Portfolio Management Structure
PORTFOLIO MANAGEMENT STRUCTURE PharmaPlan Strategy & Investment New Project Project Opportunities Commercial Management Review Identification Operations Performance Deal Making Evaluation Financial Testing Strategy
Slide 5: HPV Vaccine
HPV VACCINE l Merck worldwide Phase III Program under way – Australian site recruitment
Slide 6: Cervical Cancer: Human Papillomavirus Infection
CERVICAL CANCER: (Human Papillomavirus Infection) Significant Medical Need l HPV causes cervical cancer l 470,000 cases of cervical cancer annually worldwide – Second leading cause of cancer-related deaths particularly 35-55 year olds l In U.S. 50% of cervical cancers occur in patients screened l 50
Slide 7: Human Papilloma Vaccine: Phase III Program Underway
HUMAN PAPILLOMA VACCINE : Phase III Program Underway l Phase III quadrivalent vaccine program – Recombinant virus-like particles • (Types 6, 11, 16, 18) – HPV 16 and 18 associated with most cancer deaths l Phase II Proof-of-Concept Study with HPV 16 vaccine
Slide 8: HPV Intellectual Property
HPV INTELLECTUAL PROPERTY l CSL has licensed Merck exclusively a portfolio of intellectual property. l A patent has already been granted to CSL in Australia claiming a method of manufacturing a VLP/HPV vaccine and the vaccine itself. l The European Patent Office has published its intention to grant
Slide 9: A Controlled Trial of a Human Papillomavirus Type 16 Vaccine
The New England Journal of Medicine Copyright © 2002 by the Massachusetts Medical Society VOLUME 347 NOVEMBER 21, 2002 NUMBER 21 A CONTROLLED TRIAL OF A HUMAN PAPILLOMAVIRUS TYPE 16 VACCINE Laura A. Koutsky, PH.D., Kevin A. Autt, M.D., Cosette M. WHEELER, PH.D., DARRON R. Brown, M.D., ELIAV Barr, M.
Slide 10: Human Papilloma Vaccine: Proof-of-Concept Efficacy Study
HUMAN PAPILLOMA VACCINE: Proof-of-Concept Efficacy Study Incidence of Viral Infection and Cervical Intraepithelial Neoplasia (CINs) HPV 16 Placebo Vaccine Vaccine Endpoint Cases Cases Efficacy HPV 16 Infection and CIN 41 0 100% HPV infection 32 0 100% CIN Grade 1 5 0 100% CIN Grade 2/3 4 0 100%
Slide 11: Accompanying Editorial
ACCOMPANYING EDITORIAL “The Beginning of the End for Cervical Cancer?” by Christopher P. Crum, M.D. “Because the more pernicious cancers appear most often with HPV-16 and HPV-18, the level of protection from death due to cervical cancer could exceed 95 percent.” “Although it is premature to calculat
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Slide 13: New High Value Products from Plasma
NEW HIGH VALUE PRODUCTS FROM PLAMSA l Haemostatic Dressing (Fibrin Bandage) l Reconstituted High Density Lipoprotein (rHDL)
Slide 14: Haemostatic Dressing
HAEMOSTATIC DRESSING l Features: – Rapidly stops significant bleeding – Fully degradable in situ (natural proteins)
Slide 15: Haemostatic Dressing Structure
HAEMOSTATIC DRESSING Structure 2nd fibrinogen layer thrombin layer reabsorbable 1st fibrinogen grid layer
Slide 16: Haemostatic Dressing
HAEMOSTATIC DRESSING Mode of action: Solubilisation of the components after wetting by blood contact thrombin fibrinogen fibrin fibrin polymer (“blood clot“)
Slide 17: Haemostatic Dressing
HAEMOSTATIC DRESSING l Close collaboration with American Red Cross l IND successfully lodged with FDA l Commencement formal Phase I/II studies on track mid-2003
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Slide 19: Reconstituted High Density Lipoprotein (rHDL)
RECONSTITUTED HIGH DENSITY LIPOPROTEIN (rHDL) l HDL: “good cholesterol”. Mops up cholesterol, excreted through liver l Apolipoprotein A-I purified from unused plasma fractions l Reconstituted with lipid - rHDL l Additional value from plasma l IP on process and indications
Slide 20: Reconstituted HDL Development Indication
RECONSTITUTED HDL l Development 7 Cortex7 Striatum indication 6 6 STROKE 5 5 4 4 l New rat 3 3 preclinical data 2 2 l International 1 1 0 0 expert panel 1.20 -0.92 -4.80 1.20 -0.92 -2.80
Slide 21: rHDL for Stroke
rHDL FOR STROKE
Slide 22: Stroke
STROKE l When blood cannot get to the brain – blockage (80%), bleeding (15%), other l Outcome – death - 3rd commonest cause in developed countries – long term disability - leading cause • ~50% people dependent afterwards • require assistance at home / nursing home
Slide 23: The Numbers
THE NUMBERS l USA – 750,000 strokes per year – 150,000 deaths per year l Australia – 25,000 strokes per year – 5,000 deaths per year
Slide 24: Current Treatment
CURRENT TREATMENT l Clot dissolving agent (tPA) – given to only 5% patients – must be given early, associated risk of bleeding l Blood thinning l “Stroke unit” l Rehabilitation l (Prevention)
Slide 25: Product Proposition
PRODUCT PROPOSITION l Reduce tissue damage in the brain after a stroke l Potential benefits – increase independence – reduction in need for rehabilitation, nursing home
Slide 26: Evidence in Support
EVIDENCE IN SUPPORT l Preclinical – multiple properties in vitro and in vivo consistent with tissue protection – reduction in stroke damage in rats (2 laboratories) l Clinical – trials in ~150 people (non-stroke) – very safe – biologically active
Slide 27: Treatment of Stroke in Rat Model
TREATMENT OF STROKE IN RAT MODEL control stroke stroke + rHDL With permission: D Howells et al, 2002
Slide 28: Progress
PROGRESS l Preclinical work ongoing l International expert panel meeting Nov 2002 – excited by data: eager to test clinically – clear clinical path outlined
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Slide 30: Leveraging ISCOM Technology
LEVERAGING ISCOM® TECHNOLOGY l Proprietary Adjuvant Technology l Integrated Immune Response l Importance of T-cells l Therapy for Infectious Diseases and Cancer l Process Optimisation l Registrable
Slide 31: ISCOM Adjuvant Products
ISCOM® ADJUVANT PRODUCTS HCV CerVax16 ESO-1
Slide 32: HCV - The Disease
HCV - THE DISEASE l Viral infection l 85% become chronic carriers l Causes chronic liver disease l Conditions – carrier – cirrhosis – liver cancer in about 5%
Slide 33: The Numbers
THE NUMBERS l 170 million people infected worldwide l USA – 3 million infected – ~10,000 deaths per year l Australia – ~200,000 infected – 10,000 new cases per year
Slide 34: Current Treatment
CURRENT TREATMENT l Interferon + ribovirin l Clears virus in ~40% – efficacy depends on type of HCV l Lots of side effects l Expensive
Slide 35: Product Proposition
PRODUCT PROPOSITION l Proprietary Chiron antigens plus CSL ISCOM® adjuvant l Induce immunity to HCV l Clear virus ® prevent further liver damage l Improve effectiveness of current treatment
Slide 36: Evidence
EVIDENCE l Preclinical – long lasting cellular immunity l Clinical – currently testing safety and immunity in volunteers
Slide 37: HCV Vaccine in Rhesus Macaque Monkeys - Duration of Cellular Immunity
HCV VACCINE in Rhesus Macaque Monkeys - DURATION OF CELLULAR IMMUNITY 100 80 % lysis 60 Core ISCOM RVV Core/E1 40 20 0 NT NT NT NT = not tested 4 14 18 45 51 Weeks post last dose Polakos, N. et al. (2001) J. Immunol 166: 3589-3598
Slide 38: Progress
PROGRESS l Safety & immunity study with test protein l Further safety test planned 2nd half 2003 – HCV infected patients
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Slide 40: CerVax16: HPV Therapy
HUMAN PAPILLOMA VIRUS (HPV) THERAPY CERVAX 16
Slide 41: AIN - The Disease
AIN - THE DISEASE l Persistent HPV infection causes; – cervical dysplasia ® cancer – anal dysplasia ® cancer – other genital diseases and cancer – (non-genital disease and cancer) l Sexually transmitted l Screening important in detection of dysplasia – ie Pap smears for cervical abnormalities
Slide 42: Anal Dysplasia - The Numbers
ANAL DYSPLASIA - THE NUMBERS l Only recently identified as major health problem l Especially gay males (& females) – high incidence dysplasia and cancer l USA ~180,000 new cases per yr
Slide 43: Current Treatment
CURRENT TREATMENT l Local destruction – surgery – freezing – burning l High recurrence l Side effects
Slide 44: CSL Product
CSL PRODUCT l ISCOM® / HPV fusion protein (E6E7) l Issued U.S. IP on all components
Slide 45: Product Proposition
PRODUCT PROPOSITION l Induce immunity to HPV – cellular and antibody l Clear virus ® healing of dysplasia – reduce the need for destructive treatment – reduce risk of developing cancer
Slide 46: Evidence
EVIDENCE l Preclinical - in mice – prevents HPV-related cancer from growing – shrinks established HPV-related cancer l Clinical - phase 1 study – safe, well tolerated – induces desired immunity
Slide 47: Treatment of HPV Cancer in Mice
TREATMENT OF HPV CANCER IN MICE 100 90 80 70 60 % alive at 50 2 months 40 30 20 10 0 buffer IMX E6E7 CerVax alone alone CSL data on file, 2002
Slide 48: Randomised Placebo Controlled Trial of CerVax16
A randomised placebo controlled trial of CERVAXTM 16, an immunotherapy for CIN, demonstrating vaccine-induced immunogenicity and possible reduction in tissue HPV viral load Frazer I.H.1, Quinn M.2, Nicklin J.3, Tan J.2, Perrin L.3, Ng P.4, O’Connor V.5, White O.1, Wendt N.1, Martin J.1, Mitchell S.V
Slide 49: Progress
PROGRESS l Currently - further testing for optimal dose & schedule l Discussing anal dysplasia study with National Centre in HIV Epidemiology and Clinical Research
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Slide 51: ESO1 Cancer Antigen for Melanoma: Ludwig Institute Collaboration
ESO1 CANCER ANTIGEN FOR MELANOMA: Ludwig Institute collaboration
Slide 52: The Diseases
THE DISEASES l NY-ESO1 is a cancer-related protein – only rarely on normal tissues l Found on many cancers – melanoma ~35% of cases – lesser extent: bladder, lung, breast, prostate, others
Slide 53: Melanoma - The Numbers
MELANOMA - THE NUMBERS l USA – 51,000 new cases per year – 7,800 deaths l Australia – 8,500 new cases per year – 1,000 deaths
Slide 54: Current Treatment for Melanoma
CURRENT TREATMENT FOR MELANOMA l surgery l radiotherapy l interferon l chemotherapy l (prevention)
Slide 55: CSL Product
CSL PRODUCT l NY-ESO1 protein / ISCOM® Adjuvant
Slide 56: Product Proposition
PRODUCT PROPOSITION l Induce immunity to NY-ESO1 – cellular and antibody l Stimulate immune system to destroy cancer cells l Clinical goals – shrink established metastatic melanoma ® prolong life – mop up invisible remaining cancer cells after surgery in localised melanoma ® increase cure rate
Slide 57: Progress
PROGRESS l Preclinical – cellular and humoral immunity l Clinical – phase 1 study completed with Ludwig Institute for Cancer Research, Melbourne – safe – clear induction of cellular immunity l Proof-of-concept trial in melanoma with Ludwig Institute in discussion for 2003
Slide 58: Phase I Study of NY-ESO-1 ISCOMS
A phase I study of NY-ESO-1 ISCOMS in patients with NY-ESO-1 positive cancers and minimal residual disease Jonathan S. Cebon, Ian D Davis, Phillip Parente, Mark Shackleton, Wendie Hopkins, Heather Goldie, Eugene Maraskovsky, Weisan Chen, Qiyuan Chen, Heather Jackson, Ludwig Institute for Cancer Rese
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Slide 60: Topical Biotech Treatment Blindness
TOPICAL BIOTECH TREATMENT BLINDNESS l Big unmet need l Flinders University IP l AMD l Glaucoma l Uveitis, corneal graft rejection
Slide 61: Flinders Medical Centre Publication
FLINDERS MEDICAL CENTRE PUBLICATION “Penetration of engineered antibody fragments into the eye” M. A. THIEL*, D. J. COSTER*, S. D. STANDFIELD*, H. M. BRERETON*, C. MAVRANGELOS†, H. ZOLA†, S. TAYLOR‡, A. YUSIM‡ & K. A. WILLIAMS* *Department of Ophthalmology, Flinders University of South Australia, Ad
Slide 62: Product Proposition
PRODUCT PROPOSITION l Topically delivered recombinant antibody therapy for treating serious eye diseases
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Slide 64: Expanding Current Business
EXPANDING CURRENT BUSINESS – Influenza Vaccine • Thiomersal-free • Premium products – IVIGs - nano, liquid, CSL/ZLB – Rhophylac
Slide 65: Intravenous Immunoglobulins
INTRAVENOUS IMMUNOGLOBULINS Continuous improvement of key product l Worldwide first nanofiltered IVIG (Early 2003) l 12 g format available in USA l Liquid formulation (12%) with improved purity (2004) l Liquid state of the art product using combined ZLB/CSL technology (2006) -- quality-yield-capacit
Slide 66: Rhophylac (Plasma Derived Anti-D)
RHOPHYLAC (Plasma Derived Anti-D) l Features – Purity, yield l Indications – HDN l Anticipated Indications – ITP in adults and children l US Registration – Submission accepted 2002 – Launch 2004
Slide 67: CSL R&D Leverage
CSL R&D LEVERAGE l Access and add value to IP l Novel immunotherapeutics based on ISCOM® adjuvant technology l World class plasma products