Adalta Ltd. · ASX:1AD
Adalta — Investor Presentation (March 2020)
70 slides from Adalta's investor presentation, Mar 3, 2020
Slide 1: Strategic plan Investor Briefing
For personal use only Strategic plan Investor Briefing 3 March 2020
Slide 2: 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 3: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 3
Slide 4: Presenters today
Presenters today For personal use only Dr Paul MacLeman Tim Oldham, PhD Chair CEO & Managing Director • >25 years broad life sciences sector experience • >20 years of international life sciences business in start-up and early stage commercialization development and commercialisation experience • Ext
Slide 5: International Board, Scientific Advisory Board
International Board, Scientific Advisory Board Extensive track record of drug, antibody development, capital raising and exits For personal use only Board Scientific Advisory Board Dr Paul MacLeman Dr Mick Foley Chair AdAlta CSO Expert in phage display Liddy McCall Director Brian Richardson In atten
Slide 6: Significant achievements in past months
Significant achievements in past 3 months A$1m BTB grant to Pre-clinical efficacy: mouse Pharmacokinetics and For personal use only radiolabel AD-214 for PET bleomycin model pharmacodynamics: non- imaging human primate 6 Receptor Occupancy - All animals Vehicle Statistical significance# to 21d bleom
Slide 7: AdAlta's purpose
AdAlta’s purpose For personal use only “Next generation protein therapeutics” “Drugging difficult targets” AdAlta Limited (ASX:1AD) is a late pre-clinical stage biotechnology company using its i-body platform to discover and develop next generation protein therapeutics acting on hard to drug targets
Slide 8: AdAlta's strategy, business model to create value
AdAlta’s strategy, business model to create value For personal use only Strategy Revenue model In-house pipeline Licence to pharma of drug candidates Major upfronts + milestones AD-214 i-body products in defined & royalties ”sweet spot” Outcome Invest to value inflection G (typically Phase I or II)
Slide 9: Near term strategic priorities
Near term strategic priorities For personal use only Create value inflections for AD-214 • Advance to clinic in IPF • Expand indications and licensing options Build internal pipeline of GPCR candidates Build external pipeline through partnerships Continuous i-body platform and AD-214 product improve
Slide 10: Growth trajectory to build value
Growth trajectory to build value C For personal use only Accelerate (from ~mid-2021) AD-214 • Phase I patient multi-dose B • Phase I licensing window opens Expand • Next indication pre-clinical A (~mid 2020 to late 2021) Internal pipeline Maximise catalysts from AD-214 • Discovery and proof of conce
Slide 11: Building a diversified, valuable pipeline
SUBJECT TO FINANCE Building a diversified, valuable pipeline Metric From AD-214 focus today … To multi-product by 2023 … For personal use only AD-214 development Pre-clinical in IPF Clinical in two indications Phase I partnering window Numerous milestones, inflection points Internal pipeline Substan
Slide 12: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 12
Slide 13: Strategic plan overview (1/2)
Strategic plan overview (1/2) For personal use only AdAlta’s i-body platform has potential to generate multiple therapeutic products against multiple difficult to drug targets in multiple therapeutic indications – i-body platform has been designed and demonstrated to be capable of generating single
Slide 14: Strategic plan overview (2/2)
Strategic plan overview (2/2) For personal use only Lead product candidate, AD-214, can drive substantial value – Compelling pre-clinical data in pulmonary fibrosis supportive of weekly or longer dosing – Proof of concept data in several $billion fibrotic indications creates many options; investing
Slide 15: i-bodies: targeting "difficult to drug" targets
i-bodies: targeting “difficult to drug” targets Small size, long loop of i-body can access unique, challenging binding sites For personal use only GPCRs Ligand binding Can we select i-bodies that bind to GPCRs? sites MCP-1 cytokine &&&&&&ApplicaDons:& Drug'discovery'tool' Assist'with'coLcrystalliza,
Slide 16: The journey to today
The journey to today For personal use only Coming of age • AD-214 to enter clinic • Validates platform, provides catalyst for acceleration Realising platform • Opportunity for rapid pipeline expansion potential • Multi-product, multi- partner platform 2020 2017-19 Next generation CXCR4 product candi
Slide 17: Shareholder, capital market and partner feedback
Shareholder, capital market and partner feedback For personal use only Like Want • Novel platform with capabilities to creating products • “Bold, creative” product selections with clear with pharmacology not achievable with conventional evidence of differentiation antibody or small molecule approach
Slide 18: Building a platform company: Ablynx case study
Building a platform company: Ablynx case study Strategy (2007) For personal use only A. Leverage platform to rapidly identify potential drug candidates • Core competence: discovery, in vitro/in vivo validation • No specific therapeutic area focus: >9 therapeutic areas (6 internal); multiple programs
Slide 19: Ablynx sets the activity benchmark; AdAlta ready to accelerate
Ablynx sets the activity benchmark to be on track for $billion exit, AdAlta ready to accelerate For personal use only Ablynx in 2007 (Euronext IPO) AdAlta in 2020 Products in clinic 1 1 (pending) Clinical stage pipeline 1-2 new products/year for next 4 years New AD-214 indications at proof of concep
Slide 20: AdAlta's purpose
AdAlta’s purpose For personal use only “Next generation protein therapeutics” “Drugging difficult targets” AdAlta Limited (ASX:1AD) is a late pre-clinical stage biotechnology company using its i-body platform to discover and develop next generation protein therapeutics acting on hard to drug targets
Slide 21: AdAlta's strategy, business model to create value
AdAlta’s strategy, business model to create value For personal use only Strategy Revenue model In-house pipeline Licence to pharma of drug candidates Major upfronts + milestones AD-214 i-body products in defined & royalties ”sweet spot” Outcome Invest to value inflection G (typically Phase I or II)
Slide 22: Building a diversified, valuable pipeline
SUBJECT TO FINANCE Building a diversified, valuable pipeline Metric From AD-214 focus today … To multi-product by 2023 … For personal use only AD-214 development Pre-clinical in IPF Clinical in two indications Phase I partnering window Numerous milestones, inflection points Internal pipeline Substan
Slide 23: Near term strategic priorities
Near term strategic priorities For personal use only Create value inflections for AD-214 • Advance to clinic in IPF • Expand indications and licensing options Build internal pipeline of GPCR candidates Build external pipeline through partnerships Continuous i-body platform and AD-214 product improve
Slide 24: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 24
Slide 25: AD-214 pre-clinical overview
AD-214 pre-clinical overview For personal use only Pre-clinical efficacy data from gold standard disease model now in hand to support commencement of human clinical studies of AD-214 and human therapeutic dose range beginning as low as 1mg/kg Pharmacokinetic (PK) and pharmacodynamic (PD) data suppor
Slide 26: AD-214 pre-clinical data package: lung fibrosis
AD-214 pre-clinical data package: lung fibrosis FOCUS TODAY For personal use only AD-214 study • High CXCR4 expression in fibrotic lung tissue (and other fibrotic organs) • High binding affinity to human CXCR4 • Very high specificity to CXCR4 in panels of GPCR and other membrane proteins In vitro •
Slide 27: AD-214 in vivo activity in bleomycin-induced mouse model
AD-214 in vivo activity in bleomycin-induced mouse model of lung fibrosis For personal use only AD214 10mpk group 11 Bleomycin group 2 AD-214 treatment aïve group 1 1000 µm 1000 µm 1000 µm Normal mouse IPF mouse lung tissue IPF mouse lung tissue + AD-214 lung tissue (21 days after bleomycin) (21 day
Slide 28: AD-214 induced reduction in progression of fibrosis in mouse model
AD-214 induced reduction in progression of fibrosis in mouse bleomycin model For personal use only 6 AD-214 reduced Ashcroft Score with Statistical significance# to 21d bleomycin statistical significance compared to 5 bleomycin treated mice at: ns ns ns ns – 1-30mg/kg every second day 4 Ashcroft Sco
Slide 29: Non-human primate GLP toxicology: Phase I dose justification
Non-human primate GLP toxicology: Phase I dose justification For personal use only Pharmacokinetics Pharmacodynamics • Elimination half-life 22-29h • >60% receptor occupancy* for 72h at >30mg/kg • Human equivalent: ~71h (estimate) • Human equivalent: ~10mg/kg (estimate) • AD-214 available for >3 day
Slide 30: NHP GLP toxicology: AD-214 safe
NHP GLP toxicology: AD-214 safe 3 non-human primate studies completed For personal use only Good Laboratory Practice (GLP) study to evaluate safety and toxicology prior to initial human studies – 10mg/kg, 30mg/kg and 100mg/kg multiple doses over four weeks plus recovery (human equivalent dose 32mg/k
Slide 31: AD-214 radio-labelled PET tracer to enhance clinical development
AD-214 radio-labelled PET tracer to enhance clinical development For personal use only Situation Opportunity Benefits • No good biomarker for • Radio-label AD-214 with • Confirm binding of AD-214 CXCR4 expression and 89Zr and 64Cu so it can be to CXCR4 in patients blocking detected by PET imaging •
Slide 32: AD-214: first in-class anti-fibrotic with potential in multiple indications
AD-214: first in-class anti-fibrotic with potential in multiple indications For personal use only AD-214’s biological target, CXCR4: Only one approved drug targeting CXCR4: Mozobil Is important in maintaining stem cells in bone marrow (plerixafor or AMD3100)* Used by HIV-1 as a co-receptor for viral
Slide 33: Indication extension: establishing proof of concept
Indication extension: establishing proof of concept Number of ticks proportional For personal use only to strength of PoC signal AD-114 AD-214 Mouse bleomycin Mouse bleomycin Human IPF fibroblast Human IPF fibroblast - Lung Human airway basal cell planned IPF organoids Mouse laser induced CNV Mouse
Slide 34: Options for indication extension after phase I
Options for indication extension after phase I For personal use only Pre-clinical proof of concept next steps Phase Ib cancer • Mouse exploratory cancer model Indication extension options • Mouse UUO model Phase Ib/IIa kidney Value influenced by • Phase I patient results and target doses • Delivery
Slide 35: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 35
Slide 36: AD-214 phase I overview
AD-214 phase I overview For personal use only Proposed two part phase I clinical program features – Initial safety and pharmacokinetic assessment in single dose health volunteer cohort – Rapid transition to patient single and multiple dose cohorts, giving insights into effect of disease on pharmacok
Slide 37: Proposed two part phase I design
SUBJECT TO ETHICS APPROVAL Proposed two part phase I design For personal use only Phase I, dose-escalating study of the safety, tolerability, PK & PD of single and repeat doses of AD- 214 in healthy volunteers (HVs) and patients with interstitial lung disease (ILD) Part A Part B Primary Objective Si
Slide 38: Target patient population: ILD
Target patient population: ILD For personal use only Relative distribution of specific ILDs in US Eligible patients Other ILDs Idiopathic 10% pulmonary Clinical diagnosis of idiopathic fibrosis 20% Pneumoconioses pulmonary fibrosis (IPF) and 10% – Intolerant to, or have failed, standard of care trea
Slide 39: Dose rationale: Phase I doses within safety window
Dose rationale: Phase I doses within safety window, potential therapeutic range For personal use only Minimum Maximum 30mg/kg weekly in NHP gives >60% receptor occupancy for >3 days 20mg/kg is at top end of typical Therapeutic → Human equivalent 10mg/kg weekly or therapeutic protein doses effect for
Slide 40: AD-214 Phase I clinical development includes patients
AD-214 Phase I clinical development includes patients For personal use only Data read-outs Projected Range 2020 2021 2022 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Phase II Phase I patient MAD Phase I part B: patient SAD Trial protocol update/amendment to add PET tracer Phase I part A: healthy volunteer S
Slide 41: IPF Phase II trial designs
IPF Phase II trial designs FDA Fast FDA Orphan Phase II Phase III For personal use only Track Drug ISABELA 1 and 2 GLPG1690 12 weeks, 23 patients 52 weeks, 1500 patients total ✓ ZEPHYRUS Pamrevlumab 48 weeks, 103 patients 52 weeks, 565 patients ✓ ✓ Not defined, planning PBI-4050 12 weeks, 40 patient
Slide 42: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 42
Slide 43: Pipeline and partnerships summary
Pipeline and partnerships summary For personal use only Internal development projects to focus on a “sweet spot” encompassing G-protein Coupled Receptors (GPCRs) with well understood, complex pharmacology implicated in fibrosis, inflammation or oncology – A robust and comprehensive process will be u
Slide 44: Internal target and product selection process
Internal target and product selection process For personal use only 1 2 3 4 5 TPP and Idea Rapid Desk top Expert discovery gathering screening verification validation plan approval Broad and Qualitative Quantitative Detailed interviews Detailed continuous idea selection of analysis to assess with re
Slide 45: AdAlta's "sweet spot" facilitates rapid screening of product ideas
AdAlta’s “sweet spot” facilitates more rapid screening of internal product ideas For personal use only AdAlta’s internal development “sweet 1. Mechanism: Is there a GPCR clearly implicated in a disease spot” – i-bodies to ”difficult to drug” mechanism (validated target)? G-protein Coupled Receptors
Slide 46: GPCRs are very attractive drug targets
GPCRs are very attractive drug targets For personal use only Share of drug targets Share of approved drugs 56% G-protein Coupled Receptors (GPCRs) • Largest, most diverse group of membrane receptors • Act like an “inbox” for messages to cells about their environment or from other cells • Behave like
Slide 47: Many potential "difficult to drug" GPCR targets remain
Many potential “difficult to drug” GPCR targets remain For personal use only • 475 approved drugs target 108 GPCRs • 224 GPCRs with (34% of all FDA “broad, untapped approved drugs) therapeutic potential” 108 • >$150b annual sales • ~261 novel agents in clinical trials Total GPCRs with potential to b
Slide 48: Many GPCRs implicated in the fibrosis cascade
Many GPCRs (and other complex targets) implicated in the fibrosis cascade: examples For personal use only FFAR1 GPR84 CXCR4 MMP7 (matrix metalloproteinase) FFAR4 OXER1 CCR7 S1PR3 CCR2 CCR3 LPAR1 TRPV4 (ion channel) Realistic to build a pipeline around fibrosis (and similarly for inflammation or onco
Slide 49: Initial screening focused on existing targets to shorten discovery time
Initial screening is focused on existing targets to shorten discovery time* For personal use only >20 targets to which i-body* binders have Discovery process been found GPCRs ~5 months ~3 months ~6 months ~3-6 months ~6-12 months ~24 months Chemokine Idea Panning Molecular characterisation Affinity
Slide 50: Near term new targets into discovery
Near term aim: add 5 new targets into discovery For personal use only 20 existing targets* New ideas Not a GPCR (11) Mechanism Not target indication Need Not first/best in class potential (1) Competition ~9 potential Insufficient understanding of failures Opportunity targets under active No biased p
Slide 51: AdAlta target pipeline evolution
SUBJECT TO FINANCE, TECHNICAL SUCCESS AdAlta target pipeline evolution Today For personal use only 2022 target Preclinical, IND Class of Partner Product/ Indication Discovery product enabling Phase I Phase II Target Target dev studies AD-214: Idiopathic CXCR4 GPCR Pulmonary Fibrosis AD-214: Indicati
Slide 52: Differing strategies for partnering platform and products
Differing strategies for partnering platform and products For personal use only Platform partnering process Strategy: continuous lead generation and movement through the process Timeline: ~6-12 months process from confirmation to contract, high attrition Confirmed Prospect CDA MTA Term sheet Contrac
Slide 53: Market opportunity for IPF (lung fibrosis)
Market opportunity for IPF (lung fibrosis) For personal use only Idiopathic Pulmonary Fibrosis (IPF) is an irreversible, unpredictable and incurable disease THE STATISTICS People living with IPF 300,000 People die from IPF every year 40,000 Median length of survival after IPF diagnosis 3.8 years 53
Slide 54: Market benchmarks: fibrosis, antibodies and GPCR deals
Market benchmarks Breaking: Jan-20 Boehringer Ingelheim and Enleofen ink $1 Billion+ fibrosis deal For personal use only Fibrosis Nov-19 acquired by Roche Sep-15 acquired by Roche Jul-19 license by Boehringer $390m + $1b – Phase II lead AD-214 $105m + $475m milestones Ingelheim €45m + €1.1b Aug-15 B
Slide 55: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 55
Slide 56: Continuous i-body and AD-214 product improvement
Continuous i-body and AD-214 product improvement For personal use only Targeted investments in i-body platform and AD-214 product development secure the foundations for growth strategy and maintain AdAlta at the forefront of advanced antibody technologies Opportunities to enhance the i-body platform
Slide 57: Next generation i-body platform opportunity
Next generation i-body platform opportunity For personal use only i-body platform today i-body 2.0: improved i-body platform goals Core patent expires 2025 Extend patent protection over AdAlta’s platform technology Structural data and sequence – More cost effective and comprehensive than an “IP land
Slide 58: AD-214 continuous product improvement
AD-214 continuous product improvement AD-214 product development status: clinically Why invest in continuous improvement For personal use only viable process and formulation, acceptable for now? stage of development, opportunities to add Process changes for biologics take time, value more difficult
Slide 59: Continuous improvement initiatives
Continuous improvement initiatives For personal use only i-body2.0 Integrate high Evaluate throughput alternate scaffold Synthesise and enhancements, QC new library File new IP sequences pharmaceutic selection steps 4-6 months AD-214 product development Wave 1: Upstream process yield Wave 2: Formula
Slide 60: Agenda today
Agenda today For personal use only Welcome and overview Vision and strategic goals AD-214: pre-clinical update and PET tracer AD-214: Phase I clinical strategy Pipeline and partnership expansion Continuous i-body platform and AD-214 product improvement Staging growth 60
Slide 61: Staging growth: summary
Staging growth: summary For personal use only Bringing AD-214 to the clinic provides catalyst for accelerating growth, creates many growth options – Currently funded to end of healthy volunteer component of Phase I Expand access to growth opportunities while healthy volunteer safety data is delivere
Slide 62: Using AD-214 Phase I as catalyst for growth
Using AD-214 Phase I as catalyst for growth For personal use only What getting AD-214 to clinic means Benefits of gaining pipeline scale Validates platform and AdAlta capability to Multiple potential revenue sources produce clinical candidates Portfolio effect: overall company risk reduced Removes c
Slide 63: Financial results: funded into Phase I
Financial results: funded into Phase I AUD million For personal use only Financial year cash flows Quarterly cash flows FY20 H1 Net inflows* Cash FY18 FY19 Net outflows** (AUD (AUD (AUD 10 Cash at end of quarter million) million) million) 8 Operating inflows 1.86 2.11 3.88 6 4 Operating/investing (5
Slide 64: Growth trajectory to build value
Growth trajectory to build value C For personal use only Accelerate (from ~mid-2021) AD-214 • Phase I patient multi-dose B • Phase I licensing window opens Expand • Next indication pre-clinical A (~mid 2020 to late 2021) Internal pipeline Maximise catalysts from AD-214 • Discovery and proof of conce
Slide 65: Target growth milestones
Accelerate Target growth milestones Expand Funded base For personal use only 2020 2021 2022 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Partnering Ongoing partnering 2 programs Pipeline pre-clinical Internal discovery 5 discovery programs to Platform i-body2.0 animal model PoC Ph II: x2 Phase I licensing wi
Slide 66: Financing strategies and options
Financing strategies and options Today: GE For personal use only Equity capital likely to New platform partnerships: define the rate at which typically be low margin – target pipeline can accelerate in low double digit cost recovery near term building over several years Size, timing and form of equi
Slide 67: 2020 news flow
2020 news flow Early 2020 For personal use only ü Patent granted covering AD-214 granted in the US ü Publication of role of CXCR4 in fibrosis ü Pre-clinical efficacy and PK/PD of AD-214 ü AdAlta strategy update (AD-214 clinical development and i-body platform growth) Mid-2020 – PET tracer pre-clinic
Slide 68: Financial position
Financial position For personal use only Key financial details Share price performance (last 12 months) ASX code 1AD Share price (28 February 2020) AUD$0.08 Market capitalisation AUD$13.12m Ordinary Shares 163,945,613 Listed Options 23,348,803 Unlisted Options 7,514,067 Current cash (31 December 201
Slide 69: AdAlta strategy summary
AdAlta strategy summary For personal use only i-body platform for generating multiple products against “difficult” targets – Internal pipeline focused on GPCRs implicated in fibrotic and inflammatory disease and cancer – External pipeline leveraging partner expertise to pursue wider range of targets
Slide 70: Contact us
For personal use only Contact us: Tim Oldham, CEO and Managing Director t.oldham@adalta.com.au www.adalta.com.au