Adalta Ltd. · ASX:1AD
Adalta — Investor Presentation (February 2018)
115 slides from Adalta's investor presentation, Feb 2, 2018
Slide 1: AdAlta investor and analyst briefing presentation material
ASX Release AdAlta investor and analyst briefing presentation material For personal use only MELBOURNE Australia 2 February 2018: AdAlta Limited (ASX: 1AD), the biotechnology company advancing AD-114 to the clinic is pleased to release the material that will be presented in Melbourne today at a spec
Slide 2: Notes to editors
Notes to editors AdAlta Limited (ASX:1AD) is an Australian based drug development company headquartered in Melbourne. For personal use only The Company is focused on using its proprietary technology platform to generate i-bodies, a new class of protein therapeutics, with applications as therapeutic
Slide 3: Analyst and investor briefing
For personal use only Analyst and investor briefing i-body: a new class of protein therapeutics to treat human disease ASX: 1AD February 2018
Slide 4: AdAlta analyst & investor briefing 2018
AdAlta analyst & investor briefing 2018 For personal use only AdAlta’s investor and analyst briefing aims to educate analysts and investors on our R&D technology platform, the i-body, as it relates to the science and the commercial opportunity to deliver value to shareholders AD-114 for idiopathic p
Slide 5: AdAlta analyst & investor briefing 2018
AdAlta analyst & investor briefing 2018 For personal use only The advancement of our understanding around drug targets, and how they influence disease pathology, requires new technologies. Investor Dr Bianca Ogden will discuss the drug discovery landscape, the problems and the solutions. A number of
Slide 6: Agenda
Agenda For personal use only Bianca Ogden Drug discovery, next generation antibodies: the landscape, the problems and the solutions Bianca will provide an overview of drug discovery and next generation antibodies, setting the scene in terms of the landscape, the problems and solutions. Carol Pollock
Slide 7: Agenda
Agenda For personal use only Anthony Brown Development of drugs that target GPCRs and ion channels: the commercial opportunity and therapeutic potential Anthony will discuss the commercial opportunity to selectively modulate intractable drug targets where standard antibody and small molecule approac
Slide 8: Dr Bianca Ogden
Dr Bianca Ogden For personal use only Molecular biology was Bianca’s first love before she discovered the joys and challenges of investing. After spending some time at Swiss pharmaceuticals company Novartis, researching new HIV drugs (one of which has been approved and in use today), Bianca went on
Slide 9: What comes after antibodies?
For personal use only What comes after antibodies?
Slide 10: Paul Ehrlich (1854-1915)
Paul Ehrlich (1854-1915) For personal use only 8
Slide 11: Seitenkettentheorie
Seitenkettentheorie For personal use only Cells have side-chains on their surface Upon attack they grow more side chains Side chains also break off and catch the toxins Side chains that target toxins are “magic bullets” 9
Slide 12: Healthcare ecosystem we live in
Healthcare ecosystem we live in For personal use only In-patient Hospitals Doctors Out-patient PBMs Diagnostic Life Science Insurers Distributors Pharmacies Clinical support Government Software Consumer Innovators Generic/other 10
Slide 13: Innovations
Innovations For personal use only Antibodies as therapeutic modality Targeted Therapy Sequencing of the genome HIV combination therapy HCV combination therapy Minimally invasive surgery 11
Slide 14: The Antibody
The Antibody For personal use only * On average 2-3 antibodies have been approved each year over the past 25 years *The most devoted therapeutic modality 12
Slide 15: For personal use only
Nature Reviews | lrmmunology 43 ~ Platinum ASSET MANAGEMENT
Slide 16: Anti-CD20
Anti-CD20 For personal use only CD20xCD 3 ??? 201 8 14
Slide 17: Past, current and future innovations
Past, current and future innovations For personal use only Chemicals Antibodies Gene Therapy Modified T cells RNAi CRISPR/Cas 15
Slide 18: Novel engineered structures
Novel engineered “structures” For personal use only Ig-related Non-Ig scaffolds A Smorgasbord of choice 16
Slide 19: Target, data, strategy
Target, data, strategy For personal use only 17
Slide 20: Example Morphosys
Example Morphosys (E2.4b) For personal use only Celgene CD38 alliance Tremfya approval coming into focus E70.8Mio upfront MOR208 (CD19) in DLBCL emerging E46.2Mio equity investment Celgene CD38 alliance ends AD antibodies progressing Quiet 2 years with equity raising GSK GM-CSF licensing deal E22.5M
Slide 21: Example Pieris
Example Pieris ($342Mio) For personal use only AstraZeneca respiratory alliance (Il-4 Ra) E57.5Mio upfront 19
Slide 22: Ablynx
Ablynx (E3.9b) For personal use only Caplacizumab phase 3 data M&A 20
Slide 23: Partnerships are essential to the industry
Partnerships are essential to the industry For personal use only February 1990; Roche and Genentech alliance September 2003; Aventis (Sanofi) and Regeneron alliance (Sanofi holds 22.6%) December 2016; Incyte and Merus alliance (Incyte holds 16.5%) 21
Slide 24: Desire for innovation is immense
Desire for innovation is immense For personal use only ….particularly as everyone is aiming at the same targets 22
Slide 25: Professor Carol Pollock
Professor Carol Pollock For personal use only Carol Pollock is an academic nephrologist with over 300 publications in basic research and clinical medicine. She is an inaugural Fellow of the Australian Academy of Health and Medical Sciences (2015),was conferred a Vice Chancellors Award for Excellence
Slide 26: Ion Channels: drug discovery opportunity for fibrosis
For personal use only Ion Channels: what is an ion channel and the drug discovery opportunity for the treatment of fibrosis Professor Carol Pollock Royal North Shore Hospital, Kolling Institute and University of Sydney Australia
Slide 27: Ion Channels
Ion Channels For personal use only Ion channels are membrane proteins that allow ions to pass through the channel pore. Number of Ion Channel Drugs in various therapeutic areas The ion channel family is involved in almost all aspects of physiology and plays a critical role in diverse processes such
Slide 28: What is an Ion Channel?
What is an Ion Channel? For personal use only Ion Channels are transmembrane proteins that control the flow of ions between the intracellular and the extracellular environments. Ion Channels can be opened and shut in response to an electrical stimulus (voltage-gated) or binding of a drug compound (l
Slide 29: Ion channel drug opportunity
modulate ion channels will potentially deliver a large number of drugs, that address large unmet markets and is expected to be worth billions. Initial block buster success hasn’t been repeated in more than 20 years! Big pharma recognises the opportunity ion channel modulation presents. It has known
Slide 30: Why are Ion Channels difficult to drug?
sentation to elicit antibody generation (Chiarelli & Fazio, 2008; using constrained peptides suggests that this type Ebersbach et al., 2012). The aim of immunization methodologies is to extended to ion channels. It is worth noting that a p present an antigen to the host in a form which stimulates a
Slide 31: Kidney Fibrosis
Kidney Fibrosis For personal use only Kidney fibrosis is seen in virtually all progressive kidney diseases including diabetic nephropathy, allograft nephropathy or aging Normal Kidney CKD 29 #1ADiBody
Slide 32: Trends in End Stage Kidney Disease
Trends in End Stage Kidney Disease in Trends in ESKD in Australia and New Zealand Australia and New Zealand For personal use only 30 #1ADiBody
Slide 33: Estimated burden of diabetes in 2015
Estimated burden of diabetes in 2015 For personal use only 31 #1ADiBody
Slide 34: Requirement for novel therapies
Requirement for novel therapies For personal use only Residual risk of ESKD on conventional Rx Existing therapies only mildly reduce end stage renal disease. Risk reduction, 28% P=0.002 A number of novel drugs and End stage renal disease (%) targets are in the clinic, but many have failed. Current h
Slide 35: Potassium channels and kidney fibrosis
Potassium channels and kidney fibrosis For personal use only KCa3.1 ▪ KCa3.1 is voltage-independent potassium channel which is activated by intracellular calcium. ▪ KCa3.1 regulates membrane potential and calcium signalling in various types of cells. ▪ KCa3.1-mediated Ca2+ influx is associated with
Slide 36: KCa3.1 and kidney fibrosis
KCa3.1 and kidney fibrosis For personal use only 34 25 #1ADiBody
Slide 37: KCa3.1 blockade demonstrated effective in mouse model of fibrosis
KCa3.1 blockade demonstrated effective in For personal use only mouse model of fibrosis 26 35 #1ADiBody
Slide 38: KCa3.1 blockade demonstrated effective in mouse model of fibrosis
KCa3.1 blockade demonstrated effective in For personal use only mouse model of fibrosis KCa 3.1 inhibition by genetic deletion or pharmacologically reduced ▪ Extracellular matrix expression ▪ Inflammation (macrophage accumulation, adhesion molecule and MCP1 secretion) ▪ TGF B and down stream signall
Slide 39: Potassium channels and kidney fibrosis
Potassium channels and kidney fibrosis For personal use only Kv1.3 ▪ Kv1.3, a voltage-gated K+ channel is known to be involved in the regulation of energy homeostasis and body weight ▪ Kv1.3 inhibition has been shown to improve many adverse parameters associated with diabetes mellitus. o reduces wei
Slide 40: Multiple disease effects of Kv1.3
Multiple disease effects of Kv1.3 For personal use only The potassium channel Kv1.3 is involved in multiple diseases including cancer, Pleotropic effects diabetes, of Kv1.3 inflammation, anxiety and fibrosis Expert Opinion on Therapeutic Targets. 2018 30 38 #1ADiBody
Slide 41: Potassium channels and kidney fibrosis
Potassium channels and kidney fibrosis For personal use only Potassium § Kv1.3 channels expression is increased and in kidney kidney fibrosis lymphocytes § Inhibiting Kv1.3 may therefor limit fibrosis, improving end stage kidney Kv1.3 disease 33 39 #1ADiBody
Slide 42: GPCR CXCR4 increased in diabetic nephropathy and renal fibrosis
Results GPCR CXCR4 increased in diabetic For personal use only nephropathy and renal fibrosis Upregulation of CXCR4 in diabetic ren A. Normal Human Control Diabetic Kidney DN patients B. Control CXCR4 is significantly upregulated in fibrotic tissue from human diabetic nephropathy patients and not 20
Slide 43: AD-114 reduces fibrosis markers
For personal use only 41 Fibronetic Protein Level (% control) F ib r o n e c tin p r o te in le v e l #1ADiBody (% o f c o n tr o l) 0.0 0.5 1.0 1.5 2.0 2.5 Fibronectin F ib r o n e c tin p r o te in le v e l AD-114 reduces 0 .0 0 .5 1 .0 1 .5 2 .0 2 .5 Fibronectin C (% o f c o n tr o l) C o n on tr
Slide 44: AD-114 and kidney fibrosis
AD-114 and kidney fibrosis For personal use only Normal Diseased AdAlta’s lead i-body candidate, AD-114 has shown mouse Upregulation mouse of CXCR4 in UUO- andbroad FA-induced renal fibrosis anti-fibrotic and anti-inflammatory activity A. kidney Control kidney UUO B. – Increased Control CXCR4FA expr
Slide 45: GPCRs and Ion Channels involved in renal fibrosis and chronic kidney disease
GPCRs and Ion Channels involved in renal For personal use only fibrosis and chronic kidney disease A number of GPCRs Monocyte infiltration and Ion Channels are CCR2 and CXCR4 Mito Q, Blockade of Kv1.3, RAASi inhibition KCa3.1; SGLT2 inhibitors involved in kidney SSAO/VAP-1 inhibition SGLT2 NOX1/NOX4
Slide 46: Summary
Summary For personal use only There is a significant unmet need for new therapeutic options of kidney fibrosis There is also a global recognition, demand and commercial opportunity to develop new therapeutics for the treatment of chronic kidney disease CXCR4 and Potassium Channels are promising targ
Slide 47: Professor Carol Pollock
For personal use only Professor Carol Pollock Royal North Shore Hospital, Kolling Institute and University of Sydney Australia
Slide 48: A/Prof Mick Foley
A/Prof Mick Foley For personal use only 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 Mick was awarded a Wellcome Training Fellowship and worked at the Walter and Elisa Hall Institute. In 1995 Mick was awarded an ARC
Slide 49: GPCRs: unique pharmacology of the i-body and what this means therapeutically
For personal use only GPCRs: unique pharmacology of the i-body and what this means therapeutically Mick Foley, AdAlta Chief Scientific Officer
Slide 50: G Protein Coupled Receptors (GPCRs)
G Protein Coupled Receptors (GPCRs) For personal use only G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors GPCRs play a number of roles in the human body and increased understanding of these receptors has greatly affected modern medicine. GPCR Drug Sal
Slide 51: What is a GPCR?
What is a GPCR? For personal use only GPCRs are receptors within the plasma membrane. When an external signaling molecule binds to a GPCR, it causes a conformational change in the GPCR. This change then triggers a number of pathways internal to the cell Agonist v antagonist Biased agonism v biased a
Slide 52: Why are GPCRs difficult to drug?
also been reported to have been raised using Pepscan Identification of functional antibodies directed to specific targets (chemical linkage of peptides to scaffolds) pep fundamentally relies on the selection of a suitable antigen and its pre- (Boshuizen et al., 2014). Generation of functional an senta
Slide 53: Therapeutic opportunity
Therapeutic opportunity For personal use only Current discovery approaches for GPCR and ion channel drugs are sub-optimal Current compound technologies are inadequately addressing this target space • Limited candidates identified (small molecule and toxin libraries are small) • Lack of selectivity (
Slide 54: Revolution in drug discovery
Revolution in drug discovery For personal use only Traditional drug development approach AdAlta’s approach Antibodies generated to fragments Small molecule libraries of ~1m AdAlta i-body library has 20 billion of the GPCR and not to the compounds screened to identify lead different i-bodies conforma
Slide 55: CXCR4 is involved in fibrosis and other disease states
CXCR4 is involved in fibrosis and other For personal use only disease states CXCR4 is important in maintaining stem cells in bone marrow with AMD3100 (Mozobil) approved for single use only. HIV-1 uses CXCR4 as a co-receptor for viral entry into host cells CXCR4 expression is low or absent in many he
Slide 56: AMD3100
AMD3100 For personal use only AMD3100: Plerixaflor (Mozibil) is a CXCR4 antagonist that is used to mobilise stem cells for transplantation. Side effects: – Toxic in animals – Increase in stem cells/white blood cells in peripheral circulation (Leukocytosis) – Can cross CNS and have off-target side ef
Slide 57: Screening the i-body library
Screening the i-body library Screening the i-body library For personal use only AdAlta can modify the i-body The library can be screened The i-body that binds to binding loops to create a against a drug target of the drug target has library of 20 billion different choice, to identify a unique potent
Slide 58: AdAlta approach: i-body to CXCR4
AdAlta approach: i-body to CXCR4 For personal use only In vitro Large diverse synthetic library of 20 billion i-body protein compounds that can bind to a broad range of Human cells therapeutically relevant targets i-body affinity matured i-body identified by to enhance target rapid screening on bind
Slide 59: AD-114: high affinity and specificity
AD-114: high affinity and specificity For personal use only High affinity: AD-114 binds to Highly specific: AD-114 tested against 167 CXCR4 at 4nM GPCRs and shown only to antagonise CXCR4 AD-114 CXCR4 57 #1ADiBody
Slide 60: GPCRs: exciting potential
GPCRs: exciting potential For personal use only GPCRs have ‘biased signaling’ Many traditional drugs to GPCRs have side effects because they activate several signaling pathways, some may be beneficial others may be detrimental Currently intense interest in finding ’biased drugs’ to selectively activ
Slide 61: Biased signaling: The opioid example
Biased signaling: The opioid example For personal use only When opioid drugs act on receptor they dull pain by activating the ‘painkilling’ pathway but they also activate respiratory suppression Biased drugs aim to trigger only the ‘painkilling’ pathway “There are many groups creating biased agonist
Slide 62: AD-114: exploiting biased signaling in GPCRs
AD-114: exploiting biased signaling in GPCRs For personal use only i-bodies have a long loop that can penetrate the binding pocket i-bodies AD-114, AD-272 and AD-523 each bind to CXCR4 with high affinity, however distinct footprints While binding to CXCR4 with high affinity, very few changes in each
Slide 63: Panel of i-bodies: differential/biased activity
Panel of i-bodies: differential/biased activity For personal use only b-arrestin BRET Assay cAMP Assay i-bodies with 1-2 amino acid changes all bind with high affinity to CXCR4. These single point Ca2+ Assay i-bodies block HIV infection mutations resulted in affects to signaling and in vitro activit
Slide 64: AD-114: novel ex vivo and in vivo activity
AD-114: novel ex vivo and in vivo activity For personal use only AD-114 does not mobilize stem cells in AD-114 specifically inhibited migration of humanised mouse model or in non- diseased IPF fibroblasts but did not have human primates unlike AMD3100 any effect on normal fibroblasts unlike (Mozobil
Slide 65: CXCR4 and fibrosis
CXCR4 and fibrosis For personal use only Broad fibrotic application with demonstration in other animal models and human tissues – Lung: IPF – Eye: wet-AMD Lung Eye Liver – Liver: NASH IPF Wet-AMD & PVR NASH & CIRRHOSIS – Kidney: CKD – Skin: HT Scarring AD-114 has demonstrated broad anti- fibrotic an
Slide 66: AD-114 best in class treatment for IPF
AD-114 best in class treatment for IPF For personal use only Mozobil BL8040 Nanobody Ulocuplumab AD-114 (Sanofi) (BiolineRx) (Ablynx) (BMS) Affinity for CXCR4 1-5nM 84nM 1-10nM 5nM 5nM Specificity for CXCR4 Yes No ? ? ? Extracellular and Transmembrane Extracellular Extracellular Extracellular CXCR4
Slide 67: AD-114: selective modulation
AD-114: selective modulation For personal use only As far as GPCRs are concerned, there is an opportunity to find i-bodies that modulate these targets in ways that small molecules cannot. AD-114 inhibits CXCR4 in a very selective way, blocking agonist induced cAMP generation, beta-arrestin recruitme
Slide 68: GPCRs and ion channels involved in respiratory disease and fibrosis
GPCRs and ion channels involved in For personal use only respiratory disease and fibrosis 118 J.A. Douthwaite et al. / Pharmacology & Therapeutics 169 (2017) 113–123 AdAlta has identified i- bodies that bind to a number of GPCR and ion channel targets and demonstrated unique in vitro and in vivo act
Slide 69: Summary
Summary For personal use only GPCRs are an important class of high value drug targets whose potential remains untapped or intractable i-bodies provide a novel drug discovery engine with unique pharmacology AdAlta has identified a number of i-bodies to both GPCRs and ion channels AD-114 binds to the
Slide 70: Mick Foley, CSO
For personal use only Mick Foley, CSO AdAlta Limited (ASX:1AD) m.foley@adalta.com.au www.adalta.com.au
Slide 71: Dr Anthony Brown
Dr Anthony Brown For personal use only Anthony entered the financial services sector on the buy-side at Royal Sun Alliance investment management after completing a Ph.D at the Institute of Cancer Research in London. RSAIM became part of F&C via two mergers and during this time Anthony won the Thomso
Slide 72: Development of drugs that target GPCRs and ion channels
For personal use only WG Partners Development of drugs that target GPCRs and ion channels: the commercial opportunity and therapeutic potential February 2018 partners WG
Slide 73: GPCR drugs have a strong pedigree
GPCR drugs have a strong pedigree For personal use only Drugs targeting G-protein coupled receptors are estimated to account for 25-35% of all drugs and include 6 of the top 20 highest selling drugs of all time Drug Generic name Indication Year of peak sales Plavix clopidogrel Anti platelet 2011 Abi
Slide 74: GPCR drugs continue to be important
GPCR drugs continue to be important For personal use only No. Of Deals Deal Value (US$m) 100 10,000 90 9,000 80 8,000 70 7,000 60 6,000 50 5,000 40 4,000 30 3,000 20 2,000 10 1,000 20082009201020112012201320142015201620172018 20082009201020112012201320142015201620172018 • The number of licensing dea
Slide 75: Ion channel drugs
Ion channel drugs ournal of Medicinal Chemistry Perspective try (e.g., Rb+ for potassium channels and Li+ for sodium Table 2. Some Common Ion Channel-Targeting Drugsa For personal use only • Low hanging fruit with hannels). Radiometric flux assays are hindered by safety and isposal challenges, while
Slide 76: Ion channel drugs continue to be important
Ion channel drugs continue to be important For personal use only No.Of Deals Deal Value (US$m) 80 9,000 70 8,000 60 7,000 6,000 50 5,000 40 4,000 30 3,000 20 2,000 10 1,000 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 • The number of licens
Slide 77: What are pharma companies looking for?
What are pharma companies looking for? For personal use only In licensing Acquisitions • Good strategic fit • Unencumbered pipeline (multiple assets) • Validated target • Platform technology • Clinical proof of concept • Confidence in the lead • Strong IP program (avoid paying • Strong pre-clinical
Slide 78: Ablynx 0-US$4.8bn: a case study
Ablynx 0-US$4.8bn: a case study For personal use only 76
Slide 79: Ablynx: a case study
Ablynx: a case study For personal use only 77
Slide 80: Ablynx: GPCR deals
Ablynx: GPCR deals For personal use only • Boehringer Ingleheim • €8m payment for Ph1 GPCR nanobody to CX3CR1 + €125m milestones & royalties • This novel Nanobody blocks the function of the G-protein coupled receptor (GPCR), CX3CR1, a protein that has proven to be difficult to address with conventio
Slide 81: Ablynx: Ion Channel deal
Ablynx: Ion Channel deal For personal use only • Merck • In October 2012, Ablynx and a subsidiary of Merck & Co, Inc. entered into a collaboration to develop and commercialise Nanobody candidates directed towards a voltage gated ion channel, with the option to develop and commercialise a Nanobody to
Slide 82: Heptares: a case study
Heptares: a case study For personal use only • Acquired by Sosei in Feb-2015 for US$400m: at the time had 1 product phase 1b and 7 pre-clinical leads • Heptares use Structure Based Drug Design (SBDD) ie have to know structure of GPCR before can design drug Allergan upfront milestone in FY16 drives v
Slide 83: Heptares: case study
Heptares: case study For personal use only • Allergan M4: US$3.3b deal (US$125m upfront and US$665m in milestone payments for three targets) • Teva CGRP: US$10m upfront and US$400m in milestone payments + royalties • US$5m payment for selection of candidate • AstraZeneca A2A: US$10m upfront and US$5
Slide 84: Conclusions
Conclusions For personal use only • Pharma is hungrier than ever for innovative approaches to difficult to drug targets. • GPCR (and ion channel) drugs will continue to be important but may need new approaches as low hanging fruit has gone. • Pharma acquires companies with: • Validated platforms (cl
Slide 85: Panel: Clinical development of a drug and the need for novel drug discovery tools
For personal use only PANEL Clinical development of a drug and the need for novel drug discovery tools partners WG
Slide 86: The panel
For personal use only The panel 84
Slide 87: Sam Cobb
Sam Cobb For personal use only 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
Slide 88: i-bodies – a new class of protein therapeutics to treat human disease
For personal use only i-bodies – a new class of protein therapeutics to treat human disease Analyst Briefing, February 2018 Sam Cobb, CEO and Managing Director AdAlta Limited (ASX:1AD) s.cobb@adalta.com.au
Slide 89: Disclaimer
Disclaimer For personal use only 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 in
Slide 90: Corporate and investment summary
Corporate and investment summary For personal use only AdAlta Limited (ASX:1AD) is a drug discovery and development company using its powerful technology platform to generate a promising new class of protein therapeutics, known as i-bodies, for treating a wide range of human diseases. Investment hig
Slide 91: Financial position
Financial position 29/1/18, 3)36 pm Charts For personal use only Code: 1AD Display Key Financial Details Adalta Ltd [1AD] ASX code 1AD View Saved Chart: Standard Default Compare Upper Indicators Lower Charts (up to 2) Chart Style Save Refresh Share price (31st January 2017) AU$0.295 Date Range: 1d |
Slide 92: i-body platform
i-body platform For personal use only 11 212 Two2longTwo 3i-body loops called long loops Two 2 “CDR” long loops called called Each “CDR” unique Each Each unique i-body 3 i-body unique 1 Two“CDR” CDR3loops 3areonto Each i-body has regions regions are engineered are regions are engineered onto onto en
Slide 93: i-bodies combine benefits of small molecules and conventional antibodies
i-bodies combine benefits of small molecules and For personal use only conventional antibodies Long loop that enables access to Small Conventional AdAlta novel drug targets Molecule Antibody i-body High selectivity-specificity Low toxicity: no off target effects Cavity binding and new epitopes Stabi
Slide 94: Fibrosis: unmet medical need with multiple indications
Fibrosis: unmet medical need with For personal use only 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 Lung Eye Liver body as a result of inflammation or
Slide 95: CXCR4 increased in disease
CXCR4 increased in disease CXCR4 For personal use only Normal human Diseased IPF lung tissue lung tissue IPF diseased lung tissue has increased CXCR4 expression compared with normal lung tissues Significant CXCR4 expression is present in fibrotic regions of the lung including hyperplastic epithelium
Slide 96: AD-114 prevents lung fibrosis in Bleomycin mouse model
AD-114 prevents lung fibrosis in Bleomycin For personal use only mouse model Extensive pre-clinical AD-114 studies have demonstrated positive in vitro (in the lab) and in vivo (in animals) data Normal IPF lung tissue IPF lung tissue + AD-114 lung tissue (lung disease mouse model) dosed for 21 days (
Slide 97: AD-114 prevents fibrosis in Bleomycin mouse model
AD-114 prevents fibrosis in Bleomycin mouse For personal use only model AD-114 significantly reduced the Ashcroft score compared to the Bleomycin treated mice The negative i-body at the same dose as AD-114 had no significant effect on preventing fibrosis 95 #1ADiBody
Slide 98: AD-114: novel in vitro and in vivo activity
AD-114: novel in vitro and in vivo activity For personal use only AD-114 does not mobilize stem cells in AD-114 specifically inhibits migration of humanised mouse model or in non- diseased IPF fibroblasts but does not human primates unlike AMD3100 have any effect on normal fibroblasts (Mozobil), whi
Slide 99: CXCR4 as a biomarker in IPF
Objectives: In this study, pulmonary CXCR4 expression was evaluated using quantitative positron emission tomography (PET), in order to test its role as a Figure 2: CXCR4 PET/CT scan of a patient with IPF/UIP. CT potential biomarker for IPF. CXCR4 as a biomarker in IPF scan shows the definite UIP pat
Slide 100: Global market interest in fibrosis treatments
Global market interest in fibrosis treatments For personal use only Fibrosis assets acquired 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-51 at end of Phase I for IPF Therap
Slide 101: IPF Phase II readouts generate $1.4billion market value
IPF Phase II readouts generate $1.4billion market For personal use only value (NASDAQ:FGEN) $869 million added to its market cap on announcement (7 August 2017) of meeting primary endpoint in Phase IIb study Pamrevlumab (FG-3019) 103 patients 48 weeks (Euronext:GLPG; NASDAQ:GLPG) $555 million added
Slide 102: AD-114 has broad application in treating fibrosis
AD-114 has broad application in treating fibrosis For personal use only AdAlta data shows that AD-114 can improve fibrosis across a range of fibrotic diseases LUNG: Idiopathic Pulmonary Fibrosis EYE: Wet Age Related Macular Degeneration Lung Eye Liver LIVER: NASH IPF Wet-AMD & PVR NASH & CIRRHOSIS S
Slide 103: AD-114 reduces fibrosis in mouse wet-AMD
For personal use only 101 Lesion leakage size (µm2) 0 2 4 6 8 N eg at Sa iv lin e e i-b od y (5 02 #1ADiBody µM * A ) D -1 14 *** eye model 20 1µ M Ey Lesion Size le a (5 2 2µ M ) Fibrosis vs Choroid Thickness Ratio 0 2 4 6 N eg Ve at hi iv e cl e i-b od y (5 02 µM A ) D *** **** -1 Fibrosis 14 (2 0
Slide 104: AD-114 prevents fibrosis in a mouse model of liver fibrosis
ID: 101 ID: 207 Normal Vehicle AD-114 prevents fibrosis in a mouse model of liver For personal use only fibrosis rographs of HE-stained liver sections x50 x50 x200 x200 Therapeutic setting ID: 207 ID: 308 Vehicle i-body x200 x50 x200 x50 x200 Normal NASH liver tissue NASH liver tissue + AD-114 ID: 3
Slide 105: AD-114 prevents fibrosis in a mouse model of liver fibrosis
Figure 4.3. Steatosis score Figure 3. Biochemistry Figure 3.1. Serum ALT Figure 3.2. Liver tr AD-114 prevents fibrosis in a mouse model of For personal use only liver fibrosis AD-114 decreased serum ALT levels and non-alcoholic fatty liver diseaseFigure 4.2. NAFLD Activity score (NAFLD) score compar
Slide 106: AdAlta business model – strategy to create value
AdAlta business model – strategy to For personal use only 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 R
Slide 107: Market benchmarks
Market benchmarks For personal use only Fibrosis Sep-15 acquired by Roche Aug-15 acquired by BMS Nov-14 acquired by BMS lead AD-114 $105m + $475m milestones $150m + $1.25b milestones $444m phase I asset phase IIa asset phase I asset Next gen April-16 with Abbvie May -17 with AZ July-17 with Sanofi a
Slide 108: 2017 Highlights
2017 Highlights For personal use only Manufacturing agreement of AD-114 kicked off with Fuji Innovation Connection Grant with Alfred Health; a collaboration with local IPF clinicians to evaluate AD-114 as a biomarker Presented at a number of international conferences including Discovery on Target, B
Slide 109: Increasing global recognition and engagement
Increasing global recognition and engagement For personal use only • Interest in AD-114 led to AdAlta’s CEO Sam Cobb being invited to present at the inaugural IPF Summit in the US, alongside big pharma in August 2017 • This activity was followed by CSO, A/Prof Mick Foley speaking at the Anti-Fibroti
Slide 110: AD-114 development: key milestones
AD-114 development: key milestones For personal use only 2017 2018 2019 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Manufacturing Partnering of lead candidate Toxicology based on other studies benchmark deals Phase I Publication of data BD and partnerships 108 #1ADiBody
Slide 111: Expected news flow next months
Expected news flow next 12 months For personal use only H1 2017 ü Orphan Drug Designation (US FDA) ü Data available from AD-114 NASH animal studies ü Manufactured material for toxicology testing available H2 2017 ü Additional grants to support pre-clinical development of AD-114 including NHMRC Devel
Slide 112: Management and Board in place to deliver strategy
Management and Board in place to For personal use only 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 compa
Slide 113: Scientific Advisory Board
Scientific Advisory Board For personal use only Internationally recognised with proven track record of drug development Dr Mick Foley, AdAlta CSO John Westwick: pulmonary drug Expert in phage display discovery and development NIH, NHMRC, ARC, Gates funding and over 70 Over 14 years experience at Nov
Slide 114: AdAlta summary
AdAlta summary For personal use only 2018 major milestones: phase I clinical trials of AD-114 in lung fibrosis and development of i-body pipeline Initial focus on treating Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases - high unmet clinical need AD-114 has significant pre-clinical v
Slide 115: Sam Cobb, CEO
For personal use only Sam Cobb, CEO AdAlta Limited (ASX:1AD) Email: s.cobb@adalta.com.au Web: www.adalta.com.au Twitter: @AdAltaCEO Linkedin: AdAlta Ltd