Adalta Ltd. · ASX:1AD
Adalta — Investor Day (February 2017)
127 slides from Adalta's investor day presentation, Feb 21, 2017
Slide 1: Fibrosis symposium presentation material
ASX Announcement Fibrosis symposium presentation material MELBOURNE Australia 21st February 2017: AdAlta Limited (ASX: 1AD), the biotechnology company advancing AD-114, its lead i-body candidate for the treatment of idiopathic pulmonary fibrosis (IPF) and other human fibrotic diseases towards clinic
Slide 2: Notes to editors
Notes to editors AdAlta Limited (ASX:1AD) is an Australian based drug development company headquartered in Melbourne. The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic drugs to treat disease
Slide 3: Analyst and investor fibrosis briefing
Analyst and investor fibrosis briefing A new class of protein therapeutics to treat human disease February 2017
Slide 4: Analyst & investor fibrosis briefing
Analyst & investor fibrosis briefing AdAlta’s inaugural investor and analyst briefing aims to educate analysts and investors on our R&D technology platform as it relates to the science and the commercial opportunity to deliver value to shareholders AD-114 for idiopathic pulmonary fibrosis remains a
Slide 5: Analyst & investor fibrosis briefing
Analyst & investor fibrosis briefing Recent international partnerships and collaborations have independently assessed and validated our technology Expert presentation by non-executive Director Dr Robert Peach will outline what it takes to get an antibody to Phase III and an $8B acquisition AdAlta Ch
Slide 6: Agenda
Agenda Robert Peach From NZ to the US, a Phase III antibody and an $8B acquisition Robert will discuss the Receptos story and what it takes to get an $8B acquisition Mick Foley AD-114 a novel i-body for the treatment of fibrosis Mick will provide a summary of AD-114 data in therapeutic areas of lung
Slide 7: Agenda
Agenda Erica Fletcher Eye Fibrosis, causes, diseases and treatments Erica will discuss eye fibrosis and the various diseases including wet-AMD, what the current treatments and the drug development pipeline PANEL Getting a fibrosis drug to the clinic and a deal DISCUSSION: The panel includes a number
Slide 8: Receptos story – From NZ to the US, a Phase III antibody and an $8B acquisition
Receptos story – From NZ to the US, a Phase III antibody and an $8B acquisition Robert Peach 6
Slide 9: Dr Robert Peach
Dr Robert Peach Dr Peach has over 25 years of drug discovery and development experience in the pharmaceutical and biotechnology industry. In 2009 he co-founded Receptos, becoming Chief Scientific Officer and raising $59M in venture capital and $800M in an IPO and three subsequent follow-on offerings
Slide 10: Receptos Story – From NZ to the US, and an $8B Acquisition
Receptos Story – From NZ to the US, and an $8B Acquisi>on Robert Peach, Ph.D.
Slide 11: Presentation Outline
Presenta>on Outline Receptos experience Star>ng a biotechnology company in San Diego Licensing assets Raising venture capital Hiring staff and building a produc>ve culture Ozanimod: a small molecule drug for trea>ng relapsing mul>ple sclerosis and inflammatory bowel diseases Clinical data Market analy
Slide 12: The Path Towards Receptos – Key Roles
The Path Towards Receptos – Key Roles 1991-2000 Discovery and development of Orencia and Nulojix at Bristol-Myers Squibb; Sea\le and Princeton 2000-2003 Director An>body Discovery at IDEC. Rituxan (an>-CD20) for autoimmune diseases 2003-2007 Senior Director, Oncology Discovery at merged Biogen Idec.
Slide 13: Receptos Start-Up: 2009
Receptos Start-Up: 2009 Star>ng with a failure: Apoptos Receptos was founded in 2009 with technology licenses from The Scripps Research Ins>tute™ Focus primarily on autoimmune disease drug discovery and development, and a structure-based drug design technology plahorm 2009: A tough >me raising $25M
Slide 14: Receptos Location: Torrey Pines Mesa in San Diego
Receptos Loca>on: Torrey Pines Mesa in San Diego 12
Slide 15: What did we License from Scripps?
What did we License from Scripps? GPCR structural biology technology plahorm Established industry partnerships that raised $20M in non-dilu>ve capital Small molecule compound “hits” iden>fied in a high through-put screen targe>ng the ac>va>on of a protein called sphingosine 1-phosphate 1 receptor (S1
Slide 16: Drug Discovery Goals: Best in Class and Rapid Development
Drug Discovery Goals: Best in Class and Rapid Development Develop an oral daily pill that could be dosed chronically and had a superior safety profile to “same class” mul>ple compe>tor drugs, including Gilenya, that was close to comple>ng clinical development Cardiac toxicity including 1st dose heart
Slide 17: RPC1063 (Ozanimod)
RPC1063 (Ozanimod) O N O N NC *HCl NH HO Op>mal potency, selec>vity, oral bioavailability, absorp>on, distribu>on, metabolism, excre>on, toxicity, pharmacokine>c and pharmacodynamic proper>es 15
Slide 18: RADIANCE Phase 2/3 Trial Overview
RADIANCE Phase 2/3 Trial Overview Relapsing Multiple Sclerosis SPA Agreement with FDA Blinded Safety-Extension 1 mg RPC1063 Phase 2 0.5 mg RPC1063 1 mg RPC1063 0.5 mg RPC1063 Interim analysis of Phase 2 (Nov 2013) gated initiation of Phase 3 Phase 3 (Dec 2013) IFN β-1a 30 µg IM (N=400) 16
Slide 19: Cumulative Number of GdE Lesions
Phase 2 Primary Endpoint: Mean Cumula>ve Number of GdE Lesions From Wk 12 to Wk 24 14 CumulaCve Number of GdE 12 11.1 10 Lesions 8 6 86% decrease 86% decrease p < 0.0001 p < 0.0001 4 2 1.5 1.5 0 Treatment Group Placebo (N=88) RPC1063 0.5 mg (N=87) RPC1063 1 mg (N=83) 17
Slide 20: Change in Mean Heart Rate
First Dose Effect on Mean Heart Rate Hours 1 to 6: Comparison to Gilenya* 4 Change in Mean Heart Rate 2 RPC1063 0.25 mg Phase 2 0 0 1 2 3 4 5 6 (bpm) -2 -4 Gilenya 0.5 mg* -6 FREEDOMS Gilenya 0.5 mg* -8 TRANSFORMS Hours AOer First Dose *Data estimated from Novartis material at MSBoston2014; not a hea
Slide 21: Current Clinical Trial Status in Relapsing Multiple Sclerosis
Current Clinical Trial Status in Relapsing Mul>ple Sclerosis Two large phase 3 registra>onal trials ongoing Worldwide 1,300 pa>ents per trial 1 year of dosing 2 years of dosing Compared to Avonex, a currently approved drug $100,000/pa>ent; $130M/trial Clinical development completed in 2017 New Drug
Slide 22: RPC1063 Active in Mouse Model of Inflammatory Bowel Disease
RPC1063 is Ac>ve in a Therapeu>c SCID Mouse Model of Inflammatory Bowel Disease CD4+ CD45RBhigh T-Cell Adop4ve Transfer: Histopathology Chronic, transmural coli>s responsive to immunotherapy 20
Slide 23: Proportion of Patients in Remission
Phase 2 Ulcera>ve Coli>s: Propor>on of Pa>ents in Remission at Week 8 (April 2015) Primary Endpoint 20% p = 0.1422 p = 0.0482 16.4% ProporCon of PaCents in 15% 13.8% Remission 10% 6.2% 5% 0% Treatment Group Placebo (N=65) Ozanimod 0.5 mg (N=65) Ozanimod 1 mg (N=67) 21
Slide 24: The Relapsing Multiple Sclerosis Market is Valued at ~$16B
The Relapsing Mul>ple Sclerosis Market is Valued at ~$16B 2013 MS Market: ~$16B MARKET SIZE 11% CAGR (2009 – 2013) Tecfidera® Aubagio® 6% 1% Interferon-b ($6.8B) characterized by flu-like Gilenya® symptoms and injec>ons from weekly to 12% every-other day Copaxone® ($4.3 B) is similar in efficacy to INF
Slide 25: Oral Share of RMS IMS Scripts Rapidly Increasing
Oral Share of RMS IMS Scripts Rapidly Increasing Gilenya® and Tecfidera® drive rapid increases in oral market share gains 100.0% 90.0% 80.0% 70.0% 60.0% Tecfidera® Launch Q2 2013 50.0% Orals Gilenya® Launch Aubagio® Launch 40.0% Q3 2010 Q4 2012 ABCRs 30.0% 20.0% 10.0% 0.0% Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q
Slide 26: RPC1063 Poised to be Next S1P1,5R Modulator into RMS Market
RPC1063 Poised to be Next S1P1,5R Modulator into RMS Market RPC1063 Phase 3 (Receptos) MT-1303 (Mitsubishi Tanabe) Phase 2 in RMS and psoriasis Phase II Phase III Ceralifimod PosiCve Phase 2 outcome (ONO / Merck Serono) AV blocks; hepatotoxicity Merck Serono terminated license in June 2014 Siponimod
Slide 27: RMS Market Valued at $16B and Growing
RMS Market Valued at $16B and Growing Marke4ng Strategy for RMS Includes Compe4ng Head to Head with Tecfidera® in Front Line While “Bea4ng” Gilenya® in Later Lines PosiConing of MS Treatment OpCons Beta Interferons / Copaxone® ($11B) RPC1063 Tecfidera® ($0.9B) Gilenya® ($1.9B) Aubagio® ($0.2B), Dacliz
Slide 28: RPC1063 Profile Viewed More Favorably in Market Research
In Market Research, RPC1063 Profile Viewed More Favorably Than Tecfidera® on Efficacy and Tolerability and Gilenya® on Safety RPC1063 Viewed More Favorably Than RPC1063 Viewed More Favorably Than Tecfidera® on Efficacy and Tolerability Gilenya® on Safety GI effects 78% Cardiac profile 94% Overall safety 85%
Slide 29: The UC Market Opportunity for RPC1063 in the US
The UC Market Opportunity for RPC1063 in the US: Gastroenterologists Posi>on RPC1063 in Early Lines Against Immunosuppressants as well as Last Line Against An>-TNFs PosiConing of UC Treatment OpCons in Market Research Outcomes RPC1063 scored higher on key safety ajributes than anC-TNFs Most physicia
Slide 30: Market Research Results: US Gastroenterologist Estimated Patient Share in IBD
Market Research Results: US Gastroenterologist Es>mated RPC1063 Pa>ent Share in IBD UlceraCve ColiCs Treatment Algorithm Crohn’s Disease RPC1063 Current Treatment Current Treatment RPC1063 Pa>ent Share Choice by Line Choice by Line Pa>ent Share 7% * 5ASA 5ASA First Line 5ASA and 7.0% * Cor>costeroid
Slide 31: Receptos: 2015
Receptos: 2015 IPO (NASDAQ: RCPT) in May 2013. $83M raised. $14/share Addi>onal 3 capital raises in 2014, totaling ~$700M. Each raise over-subscribed 110 employees and growing Phase 3 clinical trials in relapsing mul>ple sclerosis and phase 2 in inflammatory bowel diseases (UC and Crohn’s disease) Ph
Slide 32: Key Strategies and Lessons Learnt
Key Strategies and Lessons Learnt Hire the “right” people and on an “as needed” basis. Wear lots of hats and preserve $$ Build a produc>ve, crea>ve, rewarding culture Focus, don’t waste >me or money. Understand the cri>cal path ac>vi>es Do rigorous science Don’t partner early Enact bold (but not rec
Slide 33: Kaikoura
Kaikoura 31 @ recepotos
Slide 34: AD-114 a novel i-body for the treatment of fibrosis
AD-114 a novel i-body for the treatment of fibrosis Mick Foley, CSO AdAlta Limited m.foley@adalta.com.au 32
Slide 35: A/Prof Mick Foley
A/Prof Mick Foley Mick is the founding scientist of AdAlta and a key inventor of AdAlta’s lead i-body candidate AD-114. Upon completion of his PhD he was awarded a Wellcome Training Fellowship and worked at the Walter and Elisa Hall Institute. In 1995 Mick was awarded an ARC QEII Fellowship where he
Slide 36: Disclaimer
Disclaimer Investment in AdAlta is subject to investment risk, including possible loss of income and capital invested. AdAlta does not guarantee any particular rate of return or performance, nor do they guarantee the repayment of capital. This presentation is not an offer or invitation for subscript
Slide 37: Fibrosis: unmet medical need with multiple indications
Fibrosis: unmet medical need with multiple indications Developing i-bodies as improved therapies for the treatment of fibrosis – a condition that is prevalent in 45-50% of all diseases Fibrosis can occur in many tissues of the body Lung Eye Liver as a result of inflammation or damage IPF Wet-AMD & P
Slide 38: i-body technology
i-body technology Long loop that enables access to AdAlta is developing a new technology platform that produces novel drug targets unique proteins known as i-bodies, that mimic the shape of shark antibody binding domain and engineers their key stability features into a human protein, for therapeutic
Slide 39: AD-114 lead program in Idiopathic Pulmonary Fibrosis (IPF)
AD-114 lead program in Idiopathic Pulmonary Fibrosis (IPF) AD-114 is lead i-body candidate in pre-clinical development – Demonstrates both anti-fibrotic and anti-inflammatory activity in the lung – Important for arresting and modifying the disease and tackling the treatment of idiopathic pulmonary f
Slide 40: CXCR4 and idiopathic pulmonary fibrosis (IPF)
CXCR4 and idiopathic pulmonary fibrosis (IPF) CXCR4 expression increased in fast progressing IPF patient tissue 590 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 179 2009 Patients that included. rapidly Diagnosis of IPF was progress based on guidelinesexpress of the Americanmore mon
Slide 41: AD-114 binds to lung tissue from patients with fibrosis
AD-114 binds to lung tissue from patients with fibrosis AD-114 was used for Immunohistochemical (IHC) staining of normal and diseased lung tissues to verify expression of CXCR4 in situ AD-114 does not bind lung tissue from AD-114 binds to lung tissue from lungs normal lungs with fibrosis 39
Slide 42: Migration/invasion specifically reduced with IPF lung fibroblasts
Migration/invasion specifically reduced with IPF lung fibroblasts No effect Inhibits Inhibits MIGRATION on normal slow IPF fast IPF AD-114 specifically inhibited migration of fibroblasts progressors progressors slow and rapid IPF fibroblast migration but did not have any effect on normal i-body AD-1
Slide 43: AD-114 prevents fibrosis in Bleomycin-induced mouse model of lung fibrosis
AD-114 prevents fibrosis in Bleomycin-induced mouse model of lung fibrosis Prophylactic or Preventative setting Normal IPF lung tissue IPF lung tissue + AD-114 lung tissue (lung disease mouse model) dosed for 21 days (lung disease mouse model) AD-114 reduces collagen content and inflammatory cell in
Slide 44: AD-114 prevents fibrosis: Ashcroft Score, prophylactic
AD-114 prevents fibrosis in Bleomycin-induced mouse model of lung fibrosis Prophylactic or Preventative setting Ashcroft Score Prophylactic Mode 8 AD-114 significantly reduced the 6 Ashcroft score compared to the Ashcroft Score Bleomycin treated mice 4 2 The negative i-body at the same 0 dose as AD-
Slide 45: AD-114 prevents fibrosis in Bleomycin mouse model: therapeutic setting
AD-114 prevents fibrosis in Bleomycin-induced mouse model of lung fibrosis Therapeutic setting Normal IPF lung tissue IPF lung tissue + AD-114 lung tissue (lung disease mouse model) dosed for 13 days (dosing started at day 8 in lung disease model) AD-114 reduces collagen content and inflammatory cel
Slide 46: Ashcroft score, therapeutic setting
AD-114 prevents fibrosis in Bleomycin- induced mouse model of lung fibrosis Therapeutic setting Ashcroft Score Therapeutic Mode AD-114 significantly reduced the 8 Ashcroft score compared to the 6 Bleomycin treated mice Ashcroft score 4 AMD3100 (CXCR4 antagonist) also reduced the the Ashcroft score 2
Slide 47: AD-114 and non-alcoholic steatohepatitis (NASH)
AD-114 and non-alcoholic steatohepatitis (NASH) Non-alcoholic steatohepatitis (NASH) is a pandemic, metabolic disease which has both inflammatory and fibrotic components AD-114 is lead i-body candidate in pre-clinical development – Demonstrates both anti-fibrotic and anti-inflammatory activity in th
Slide 48: AD-114 prevents fibrosis in a mouse model of liver fibrosis
Normal Vehicle AD-114 prevents fibrosis in a mouse model of liver fibrosis ographs of HE-stained liver sections x50 x200 Therapeutic settingx50 x200 ID: 207 ID: 308 Vehicle i-body x200 x50 x200 x50 x200 Normal NASH liver tissue NASH liver tissue + AD-114 ID: 308 liver tissue (liver disease mouse mod
Slide 49: AD-114 prevents fibrosis in a mouse model of liver fibrosis
Figure 3. Biochemistry Figure 3.1. Serum ALT Figure 3.2. Liver AD-114 prevents fibrosis in a mouse model of liver fibrosis AD-114 decreased serum ALT levels and non-alcoholic fatty liver diseaseFigure 4.2. NAFLD Activity score (NAFLD) score compared with the vehicle or disease model group Figure 4.5
Slide 50: AD-114 and eye fibrosis
AD-114 and eye fibrosis Infections or inflammation in the eye result in impairment of visual function and can ultimately lead to fibrosis. Complications from common eye diseases that can result in fibrosis occur in age related macular degeneration (AMD) and diabetic retinopathy. AD-114 is lead i-bod
Slide 51: AD-114 prevents eye fibrosis
evaluated for collagen content using the Masson Trichrome Stain caused by laser induced retinal scarring (see Figure 3). In addition and at 21 AD-114 days post reduced geneadministration 150 expression of a number of fibrosis-related lesion size (u (which stains blue) and images are analysed as per
Slide 52: AD-114 reduces lesion size and number
AD-114 reduces lesion size and number AD-114 is able to reduce the number and size of the lesion in both preventative and therapeutic models of wet-AMD (CNV) AD-114 is able to significantly reduce fibrosis as measured by trichrome staining in both preventative and therapeutic models of wet-AMD (CNV)
Slide 53: AdAlta summary
AdAlta summary Powerful proprietary technology platform to develop a pipeline of i-bodies for the treatment of a wide range of human diseases – Extreme stability of i-body similar to single domain shark antibody – Long loop of i-body binds deep in GPCR pocket and has functional activity Advanced lea
Slide 54: Pulmonary fibrosis – current state of play in Idiopathic Pulmonary Fibrosis
Pulmonary fibrosis – current state of play in Idiopathic Pulmonary Fibrosis A/Prof Glen Westall Lung Fibrosis Service, Alfred Hospital NHMRC Centre of Research Excellence: Lung Fibrosis 52
Slide 55: A/Prof Glen Westall
A/Prof Glen Westall Dr Glen Westall received his undergraduate medical training at King’s College Medical School in London, UK, before training in general and respiratory medicine at the Royal Brompton Hospital in London and the Alfred Hospital in Melbourne. His clinical interests include advanced l
Slide 56: Lung fibrosis
• o Lungs • o Lungs become stiffbecome stiff • o Lungs Lung • o Lungs shrink Fibrosis shrink in size in size Scaring of the Lung Lungs become stiff Lungs shrink in size Normal CXR Normal CXR Lung Fibrosis Lu 54
Slide 57: Interstitial lung disease classification
Interstitial lung disease (ILD) classification Interstitial lung disease classification Interstitial lung disease Diseases of Idiopathic Granulomatous known cause interstitial lung diseases Other pneumonias Multiple subtypes – over 200 types of disorder in total! 55
Slide 58: Idiopathic Pulmonary Fibrosis (IPF)
diopathic Pulmonary Fibrosis (IPF) Idiopathic Pulmonary Fibrosis (IPF) Represents 50% of all Fibrotic Lung Conditions Male:Female 1.5:1 Age of Presentation 66 yrs Smoking history 70% Australian IPF Cases 5000-10,000 Diagnosed by MDT Meeting 56
Slide 59: IPF Diagnosis: Multi-Disciplinary Team (MDT) meeting
IPF Diagnosis: Multi-Disciplinary Team (MDT) meeting • Communication between clinician, radiologist and when appropriate pathologist • Clinical data • Presentation, Exposures, Smoking status, Associated disease, Lung function and Radiologic findings 57
Slide 60: Traditional Therapy for IPF: historical view
Traditional Therapy for IPF: historical view Historical View • Uncontrolled Chronic Inflammation • Corticosteroids • Cyclophosphamide • Azathioprine • N-acetylcysteine (NAC) 58
Slide 61: 2011 Evidence Based Guidelines: Treatment recommendations
2011 Evidence Based Guidelines: Treatment recommendations Agent For Against Corticosteroids Strong + Colchicine Strong + Cyclosporine A Strong + Corticosteroid and imm-mod Strong ++ Interferon gamma Strong ++++ Bosentan Strong +++ Etanercept Strong +++ NAC, predisolone, Weak ++ azathioprine NAC mono
Slide 62: 2011 Evidence Based Guidelines: Treatment recommendations
2011 Evidence Based Guidelines: Treatment recommendations Agent For Against Corticosteroids Strong + Colchicine Strong + Cyclosporine A Strong + Corticosteroid and imm-mod Strong ++ Interferon gamma Strong ++++ Bosentan Strong +++ Etanercept Strong +++ NAC, predisolone, Weak ++ azathioprine NAC mono
Slide 63: 2014: A big year for lung fibrosis! Pirfenidone
2014: A big year for lung fibrosis! Pirfenidone approved by FDA Reduction in mortality and decreased FVC Adverse Events Adverse Events NEJM 2014; 370: 2083 47% reduction in proportion of patients with a decline in FVC Pooled data: Ascend & Capacity studies All cause mortality Ð 48% NEJM 2014; 370: 2
Slide 64: 2014: A big year for lung fibrosis! Nintedanib
2014: A big year for lung fibrosis! Nintedanib approved by FDA Intracellular inhibitor of multiple tyrosine kinases Reduction in mortality and decreased FVC Adverse Events Adverse Events Intracellular inhibitor of multiple tyrosine NB: Not curative kinases Study drug 2° end-points NB: Not curative d
Slide 65: Unmet clinical need: drugs in development
Dysregulated repair following epithelial injury Unmet clinical need: drugs in development Current drugs have limited efficacy and substantial side effects Other anti-fibrotic and anti-angiogenic agents currently in development with multiple targets – Inhaled Pirfenidone – WNT signaling – FG-3019 – Z
Slide 66: Clinical trials.gov
ClinicalClinical trials.gov trials.gov Phase 1 Dasatinib (oral Bcr-Abl TK inhibitor, BMS) + Quercetin Vismodegib (hedgehog signalling pathway) + perfinidone (Genentech, Roche) CC-90001 (Celgene, JNK inhibitor) Mesenchymal stem cells Phase 2 Rituximab Tipelukast (medicnova) STX-100 (DvE6 integrin inh
Slide 67: Drug Discovery and translational research
Drug Discovery and translational research Translational Research In-vitro science Animal model Clinical Trials Human IPF Tissue Assessment of human IPF tissue provides additional evidence of efficacy prior to clinical trials 65
Slide 68: Alfred Tissue Bank
National Resource • Alfred Tissue Bank • Collaborations Alfred Lung(Academic & Commercial Tissue Bank entity) National resource • Creation of pilot Resource Collaborations • National data (Academic and Commercial entity) Creation of pilot data • Collaborations (Academic & Commercial entity) Conduit:
Slide 69: CXCR4 Role in IPF
CXCR4: CXCR4 Role in IPFRole in IPF Very limited expression in normal or non- diseased tissues Normal lung histology CXCR4 is upregulated in IPF tissue 67
Slide 70: Summary
Summary • Lung Fibrosis: • Increasing understanding of the pathophysiology • Treatments (albeit limited) • Many Lung Fibrosis services/clinics Need better therapies for a terminal disease!! 68
Slide 71: Renal fibrosis and chronic kidney disease
Renal fibrosis and chronic kidney disease Novel therapeutic targets for kidney fibrosis Professor Muh Geot Wong Royal North Shore Hospital, University of Sydney Australia George Institute for Global Health 69
Slide 72: Dr Muh Geot Wong
Dr Muh Geot Wong Dr Wong is Renal Physician at the Royal North Shore hospital, Sydney, Australia. He is also a senior research fellow at the George Institute of Global Health and a senior clinical lecturer at the University of Sydney. His PhD entitled “Novel therapeutic options in models of nephropa
Slide 73: Overview
Overview Residual risk of standard of care Mechanism of kidney fibrosis Novel therapies for kidney fibrosis Global market potential 71
Slide 74: Kidney Fibrosis
Kidney Fibrosis Kidney or renal fibrosis is seen in virtually all progressive kidney diseases including diabetic nephropathy, allograft nephropathy or aging Normal Kidney CKD 72
Slide 75: Causes of end stage kidney disease over time
Causes of end stage kidney disease over time AUSTRALIA USA No diabetes Type 2 diabetes Type 1 diabetes Villar et al., Diabetes Care 2007; 30: 3070-6 73
Slide 76: Renin Angiotensin Aldosterone system
Renin Angiotensin Aldosterone system 74
Slide 77: Residual risk of end stage renal disease on conventional therapy
Residual risk of end stage renal disease on conventional therapy Risk reduc>on, 28% P=0.002 End stage renal disease (%) Brenner B, et al. N Engl J Med 2001 Vilayur et al.Nat Rev Nephrol (2009) 75
Slide 78: Kidney fibrosis
INSULTS Genetic susceptibility Imbalance between injury and repair Inflammation Kidney fibrosis Hypoxia Fibroblast activation Dysregulated autophagy Mononuclear & EMT ER stress T-cell infiltration Epigenetic modification EndoMT Kinases, proteases, Inflammatory cytokines RAAS & ROS, enzymes, Transcri
Slide 79: Chronic kidney disease associated pathways are shared between renal diseases
Chronic kidney disease associated pathways are shared between renal diseases 77 Martini S et al. JASN 2013
Slide 80: Therapeutic targets in kidney fibrosis
Monocyte infiltration CCR2 inhibition SSAO/VAP-1 inhibition RASi Tie2 receptors NOX1/NOX4 TGFb/ CTGF Stat 4 antagonists LOXL2i PDE4 inhibitors MCR inhibition 78 Drug Discovery Today. March 2015
Slide 81: Novel therapies and status
Novel therapies and status Anti TGFB antibody (LY2382770): Negative Study Pirfenidone: Study withdrawn Nox1/4 inhibitor: negative trial Tranilast and analogues FT011: In Phase 1b Clinical Trial Anti-CTGF Antibodies FG3019: Studies terminated CCR2/MCP1 inhibition: Larger clinical trial with hard rena
Slide 82: CXCR4 promising therapeutic strategy for treatment of kidney fibrosis
CXCR4 promising therapeutic strategy for treatment of kidney fibrosis CXCR4 expression was increased in disease state compared with normal tissue Collaboration between Kolling Renal Research and AdAlta i- body technology in exploring CXCR4 as therapeutic strategy to prevent the development of fibros
Slide 83: Challenges for clinical trial in CKD/Fibrosis
Challenges for clinical trial in CKD/Fibrosis Patients with CKD usually excluded from major trial Lack of intermediate endpoints/ biomarkers that regulatory agencies will accept for approval High trial failure rate Lack of coordination between scientists, investors, clinical trialists, pharma compan
Slide 84: EMPA-REG
EMPA-REG Zinman et al. N Eng J Med Sept 17 2015 ê14% ê38% ê35% ê32% 82
Slide 85: Effects of empagliflozin on renal outcomes
Effects of empagliflozin on renal outcomes Hazard ratio 95% Ci p value Incident/worsening of nephropathy 0.61 0.53 – 0.70 <0.001 New onset macroalbuminuria 0.62 0.54 - 0.72 <0.0001 Doubling creatinine or ESKD 0.54 0.40 - 0.75 0.0002 Doubling of serum creatinine 0.56 0.39 - 0.79 0.0009 ESKD 0.45 0.21
Slide 86: SGLT2 inhibition: glycosuria and natriuresis
SGLT2 inhibition: glycosuria and natriuresis 84
Slide 87: LEADER study: Liraglutide in type 2 diabetes
LEADER study: Liraglutide in type 2 diabetes Number needed to treat (NNT) in 3 years to prevent primary outcome=66, and to prevent death from any cause=98 Marso et al NEJM July 2016 85
Slide 88: Projecting the estimated number of patients receiving RRT from 2010 to 2030
Projecting the estimated number of patients receiving RRT from 2010 to 2030 8.0 World 3.0 Region Number of RRT (x million) Number of RRT (x million) 7.0 6.0 Asia 2.0 (0.97→2.16) 5.0 5.44 4.53 4.0 North America 3.78 3.0 (0.64→1.26) 3.13 2.62 1.0 La>n America 2.0 (0.37→0.90) Europe (0.53→0.83) 1.0 Afr
Slide 89: Global “push”
Global “push” International Society of Nephrology (ISN) established working groups to establish and validate novel therapeutic targets to retard progression of CKD. Four goals – Improve the identification of “druggable’”targets that are amenable to therapeutics – Enhance the capacity for pre-clinica
Slide 90: Global Market Opportunity
Global Market Opportunity According to Decision Resources Group, the CKD market will achieve total sales of $11.7 billion in 2022. Erythropoietin-stimulating agents (ESAs), phosphate binders, calcium mimetics, active vitamin D analogues, antihypertensive agents, IV iron and emerging CKD therapies fo
Slide 91: Summary
Summary An unmet need for new therapeutic options of kidney fibrosis Global recognition, demand and commercial opportunity to develop new therapeutics in CKD Promising novel targets needs clinical translation and hard renal outcomes Collaborative effort among scientists, clinicians, investors, trial
Slide 92: Eye Fibrosis, causes, diseases and treatments
Eye Fibrosis, causes, diseases and treatments Professor Erica L Fletcher Department of Anatomy and Neuroscience The University of Melbourne Email: elf@unimelb.edu.au 90
Slide 93: Prof Erica Fletcher
Prof Erica Fletcher Erica Fletcher is Professor in the Department of Anatomy and Neuroscience, at The University of Melbourne where she heads the Visual Neuroscience Laboratory. She is a clinically trained optometrist who holds both MSc and PhD degrees. She completed her PhD at The University of Mel
Slide 94: The eye
pote? THE UNIVERSITY OF = MELBOURNE Department of Anatomy & Neuroscience 92
Slide 95: Fibrosis and the eye
Fibrosis and the eye Definition: – Scarring of the retina leading to vision loss Diseases of the retina associated with fibrosis: – Retinal vascular disease: • Diabetic retinopathy and Age related macular degeneration. – Retinal detachment: • Fibrosis (PVR): 8-10% of all patients undergoing primary
Slide 96: The retina and its vasculature
The retina and its vasculature retina choroid {Image: Prof Erica Fletcher Univ Melb} {Image: Friedlander, 2007 J Clin Invest} 94
Slide 97: Blindness: 50-100,000 Australians
Blindness: 50-100,000 Australians Others Refractive Error Neuro-ophthalmic 4% 8% Retinitis Pigmentosa 3% 1.5% Diabetes and Age related other Retinal 10% 48% Macular Degeneration Cataract 12% 14% Glaucoma {Image: Prof Robyn Guymer, CERA} 95
Slide 98: Age related macular degeneration
Age related macular degeneration {Image: Prof Robyn Guymer, CERA} 96
Slide 99: {Image: Prof Robyn Guymer, CERA}
97 {Image: Prof Robyn Guymer, CERA}
Slide 100: {Image: Prof Robyn Guymer, CERA}
98 {Image: Prof Robyn Guymer, CERA}
Slide 101: First medical treatment for wet AMD
First medical treatment for wet AMD 2002 Italic Sub • Bullet points 18 pt text • Bullet points 18 pt text • Bullet points 18 pt text 99 {Image: Prof Robyn Guymer, CERA}
Slide 102: Anti-VEGF treatments
Anti-VEGF treatments Vision (letters) 10 Lucentis treatment 5 0 2 4 6 8 10 12 14 16 18 20 22 24 Month -5 -10 -15 Untreated Adapted from: Rosenfeld et al, N Engl J Med 2006; 355(14): 1419. Brown et al, N Engl J Med 2006; 355(14); 1432 100
Slide 103: Incidence rates of legal blindness from AMD
Incidence rates of legal blindness from AMD Denmark population based observational registry study Incidence rate of blindness 80 Introduction of antiVEGF treatment (cases/year/100,000) 60 AMD 40 47% Reduction 20 Other causes 0 1998 2000 2002 2004 2006 2008 2010 2012 Year 101 {Adapted from: Bloch SB
Slide 104: Long term effects: A sting in the tail!
Long term effects: A sting in the tail! Initial study HORIZON SEVEN-UP 15 * Vision (Letters) 10 5 * 0 -5 -10 -15 -20 1 2 3 4 7.3 Years ~50% of patients are legally blind 102
Slide 105: There is a problem: fibrosis
There is a problem: fibrosis 103
Slide 106: Reducing vision in wet AMD
Reducing vision in wet AMD Abnormal growth New of blood vessels targets Leakage of blood vessels CXCR4 New Influx of Inflammatory cells targets Tissue remodelling New targets Scarring/vision loss 104
Slide 107: Drugs in Development
Drugs in Development Current drugs have limited efficacy with ~45% of patients being legally blind after 7 years. Other anti-fibrotic and anti-angiogenic agents currently in development with multiple targets – Platelet-Derived Growth Factor Receptor – Anti-αvβ1 integrin – Anti-αvβ3 integrin – Androg
Slide 108: Fibrosis of the retina
Fibrosis of the retina Fibrosis is a major factor leading to vision loss in a number of conditions including: – Treatment-resistant age related macular degeneration; – End stage diabetic retinopathy; and – Surgical repair of retinal detachment and trauma. Few if any current treatments Common causes
Slide 109: Getting a fibrosis drug to the clinic and a deal
Getting a fibrosis drug to the clinic and a deal Stewart Roberts (chair) Dr Brian Richardson Dr John Westwick Dr Robert Peach 107
Slide 110: Stuart Roberts, Chair
Stuart Roberts, Chair Stuart Roberts has been involved in the healthcare and biotechnology sector since the early 2002, initially as a sell- side analyst doing equities research in the sector in Australia, then, from the start of 2015, as an executive inside biotech companies, before he returned to
Slide 111: Brian Richardson, John Westwick, Robert Peach
Brian Richardson John Westwick Robert Peach Brian was most recently a member John has extensive experience in Dr Peach has over 25 years of drug of The Leadership Team and The drug discovery in the Pharmaceutical discovery and development Global Head of The Musculoskeletal Industry and as a Professo
Slide 112: Drug development pathway
Drug development pathway What does it take to get a fibrosis drug to the clinic? What does orphan drug designation mean? Which fibrosis indication? 110
Slide 113: Fibrosis deals: IPF, NASH, Renal
Fibrosis deals: IPF, NASH, Renal IPF Sep-15 acquired by Roche Aug-15 acquired by BMS Nov-14 acquired by BMS $105m + $475m milestones $150m + $1.25b milestones $444m phase I asset phase IIa asset phase I asset NASH May-15 acquired by BI April-16 acquired by Gilead Sep-16 acquired by Allergan $40m + $
Slide 114: i-bodies – a new class of protein therapeutics to treat human disease
i-bodies – a new class of protein therapeutics to treat human disease February 2017 Sam Cobb, CEO and Managing Director AdAlta Limited (ASX:1AD) s.cobb@adalta.com.au
Slide 115: Sam Cobb
Sam Cobb Sam is the founding CEO of AdAlta and has over fifteen years’ experience in business development and commercialisation of early stage scientific technologies. Prior to AdAlta, Sam was the Business Development Director at the Co-operative Research Centre for Diagnostics. Sam has also worked
Slide 116: Disclaimer
Disclaimer Investment in AdAlta is subject to investment risk, including possible loss of income and capital invested. AdAlta does not guarantee any particular rate of return or performance, nor do they guarantee the repayment of capital. This presentation is not an offer or invitation for subscript
Slide 117: Corporate and investment summary
Corporate and investment summary A drug discovery and development company Capital structure focused on using its proprietary technology ASX code 1AD platform to generate a new class of protein Shares on issue* 101,037,617 therapeutics, known as i-bodies, for treating a Share price (31 January) AU$0.
Slide 118: Fibrosis: unmet medical need with multiple indications
Fibrosis: unmet medical need with multiple indications Developing i-bodies as improved therapies for the treatment of fibrosis – a condition that is prevalent in 45-50% of all diseases Fibrosis can occur in many tissues of the body Lung Eye Liver as a result of inflammation or damage IPF Wet-AMD & P
Slide 119: Global market interest in fibrosis treatments
Global market interest in fibrosis treatments Recent transactions confirm that big pharma are actively acquiring fibrosis assets at an early stage – typically based on Phase I results Date Company Target Acquired by Deal value (US$) Deal commentary Sep-15 Adheron SDP051 Roche $105M upfront, plus SDP
Slide 120: AD-114 development: key milestones
AD-114 development: key milestones CY2017 CY2018 Q1 Q2 Q3 Q4 Q1 Q2 Manufacturing Partnering of lead candidate Toxicology studies based on other benchmark deals Orphan designation Phase I Publication of data Other fibrosis indications BD and partnerships 118
Slide 121: Expected news flow next 12 months
Expected news flow next 12 months Q3 & Q4 2016 ü Commence manufacturing of material for toxicology testing with FujiFilm Diosynth Biotechnologies ü Additional AD-114 IPF fibrosis data ü Completion of evaluation of AD-114 with IPF clinicians Alfred Hospital ü Completion of AD-114 NASH animal study H1
Slide 122: AdAlta business model – strategy to create value
AdAlta business model – strategy to create value Pharma & biotech partnerships Revenues: Upfronts, i-body FTEs, milestones & royalties i-bodies new technology drug class platform and Potential in multiple library In-house disease indications Licence to pipeline of pharma drug Revenues: major candida
Slide 123: Market benchmarks
Market benchmarks Fibrosis lead AD-114 Sep-15 acquired by Roche Aug-15 acquired by BMS Nov-14 acquired by BMS $105m + $475m milestones $150m + $1.25b milestones $444m phase I asset phase IIa asset phase I asset Next gen antibodies April-16 with Abbvie Dec -15 with Roche Nov-15 with Novo-Nordisk $40m
Slide 124: Management and Board in place to deliver strategy
Management and Board in place to deliver strategy Sam Cobb: Founding CEO and Director Dr John Chiplin: Independent Director Extensive experience in raising equity, contract and CEO of investment Company NewStar Ventures grant funding Managing Director of acquired antibody company 15 years of commerc
Slide 125: Scientific Advisory Board
Scientific Advisory Board Internationally recognised with proven track record of drug development David McGibney: pre-clinical and John Westwick: pulmonary drug clinical advisor discovery and development 20 years with Pfizer, including Head of Over 14 years experience at Novartis, head of European R
Slide 126: AdAlta investment summary
AdAlta investment summary Powerful proprietary technology platform to develop a pipeline of i-bodies for the treatment of a wide range of human diseases Initial focus on treating Idiopathic Pulmonary Fibrosis and other fibrotic diseases - high unmet clinical need Advanced lead candidate with signifi
Slide 127: Thank-you
Thank-you Sam Cobb, CEO and Managing Director s.cobb@adalta.com.au www.adalta.com.au 125