Adalta Ltd. · ASX:1AD
Adalta — IRD Invest 2021
62 slides from Adalta's conference presentation, Sep 21, 2021
Slide 1: Corporate Overview and IRD Invest 2021 Presentation
21 September 2021 ASX Announcement CORPORATE OVERVIEW AND IRD INVEST 2021 PRESENTATION MELBOURNE Australia, 21 September 2021: AdAlta Limited (ASX:1AD), the clinical stage drug discovery company developing novel therapeutic products from its i-body platform, is pleased to announce Dr Tim Oldham, CEO
Slide 2: About AdAlta and contacts
range of unique proteins capable of interacting with high selectivity, specificity and affinity with previously difficult to access targets such as G-protein coupled receptors (GPCRs) that are implicated in many serious diseases. i-bodies are the first fully human single domain antibody scaffold and
Slide 3: Corporate overview September 2021
Corporate overview September 2021
Slide 4: Disclaimer
INVESTOR PRESENTATION – SEPTEMBER 2021 2 Disclaimer Investment in AdAlta is subject to This presentation may contain forward- There is no guarantee that the investment risk, including possible loss looking statements regarding the Company’s research and development of income and capital invested. Ad
Slide 5: AdAlta's purpose
INVESTOR PRESENTATION – SEPTEMBER 2021 3 AdAlta’s purpose To use our unique i-body technology to create multiple novel therapeutics for debilitating diseases that have proven difficult to drug with traditional antibodies
Slide 6: AdAlta today
INVESTOR PRESENTATION – SEPTEMBER 2021 4 AdAlta today • i-body platform: can create therapeutics addressing targets underserved by traditional antibodies • Lead asset AD-214: preparing inhaled version for Phase II in IPF • US$3b IPF market today • Two co-development collaborations • GZMB PET imaging
Slide 7: What is the i-body advantage?
INVESTOR PRESENTATION – SEPTEMBER 2021 5 What is the i-body advantage? All the selectivity and specificity of antibodies with greater versatility and tunability Small size, flexible binding domain Confers unique binding capability for targets challenging traditional Accessing antibodies; enables mod
Slide 8: An immensely powerful drug discovery platform
INVESTOR PRESENTATION – SEPTEMBER 2021 6 An immensely powerful drug discovery platform i-body technology can enable a wide range of therapeutic and diagnostic products Wide range of target classes Wide range of product formats CAR-T Targeting agents Bi-specifics and multi-specifics That deliver To i
Slide 9: Idiopathic Pulmonary Fibrosis (IPF)
INVESTOR PRESENTATION – SEPTEMBER 2021 4 Idiopathic Pulmonary Fibrosis (IPF) AdAlta’s first target, already a $3b market, is a degenerative, fatal disease in dire need of improved treatment options: i-bodies have been designed to target a novel mode of action to address this medical need In IPF, sca
Slide 10: AD-214: first in class treatment for fibrosis
INVESTOR PRESENTATION – SEPTEMBER 2021 8 AD-214: first in class treatment for fibrosis AD-214’s initial focus is IPF CXCR4 First-in-class (novel mode Human of action) treatment for Lung Tissue fibrosis (can affect almost every organ) Brown stain shows increased amount of CXCR4 in fibrotic lung tissu
Slide 11: AD-214 Phase 1 clinical and pre-clinical imaging programs
INVESTOR PRESENTATION – SEPTEMBER 2021 9 AD-214 Phase 1 clinical and pre-clinical imaging programs The Phase 1 program has demonstrated the safety and target engagement of AD-214 in healthy volunteers Phase 1 protocol in healthy volunteers - COMPLETE Part A Part B Objectives of Phase 1 Part A and B:
Slide 12: AD-214 Phase I results
INVESTOR PRESENTATION – SEPTEMBER 2021 10 AD-214 Phase I results AD-214 is well tolerated in single doses to 20 mg/kg and multiple doses to 5 mg/kg* in healthy volunteers Results from single and multiple dose studies in health volunteers AD-214 is well tolerated • No dose limiting toxicities or adve
Slide 13: Phase II planned with inhaled formulation
INVESTOR PRESENTATION – SEPTEMBER 2021 11 Phase II planned with inhaled formulation Delivery of AD-214 by inhalation has potential to improve bioavailability, be more convenient for patients, be more cost effective, and improve partnering flexibility • AD-214 delivered direct to fibrotic areas • Fir
Slide 14: Key milestones to de-risk AD-214 development
INVESTOR PRESENTATION – SEPTEMBER 2021 12 Key milestones to de-risk AD-214 development Quarterly milestones to de-risk asset; extensive use of pre-clinical imaging; AD-214 partnering window from FY23 Key data readouts FY22 FY23 FY24 INHALATION PROGRAM MILESTONES Aerosol stability and formulation Pre
Slide 15: AD-214: multiple indication extension options
INVESTOR PRESENTATION – SEPTEMBER 2021 13 AD-214: multiple indication extension options Each additional indication could address multiple markets with U$ billion potential Data in tissue and animal models show that AD-214 may improve fibrosis across a range of fibrotic diseases and cancer: multiple
Slide 16: IPF late-stage clinical landscape: a narrow development field
INVESTOR PRESENTATION – SEPTEMBER 2021 14 IPF late-stage clinical landscape: a narrow development field AdAlta’s novel mode of action and Orphan Drug Designation expected to be attractive to partners as an alternative to, and in combination with other therapies Orphan Drug Company Drug Mode of actio
Slide 17: IPF partnering: valuable options as early as Phase I
INVESTOR PRESENTATION – SEPTEMBER 2021 15 IPF partnering: valuable options as early as Phase I IPF assets have recently yielded attractive deal terms at early stages of development – first partnering window for AD-214 in FY2023 Feb-21: License by Graviton Jul-19 license by Boehringer Ingelheim Phase
Slide 18: GZMB i-body asset: GE Healthcare co-development collaboration
INVESTOR PRESENTATION – SEPTEMBER 2021 16 GZMB i-body asset: GE Healthcare co-development collaboration Second asset in pre-clinical development; and could generate royalty revenue sooner than a therapeutic due to shorter diagnostic development timelines Pipeline asset at no financial cost to AdAlta
Slide 19: Immuno-oncology (I/O) PET imaging
INVESTOR PRESENTATION – SEPTEMBER 2021 17 Immuno-oncology (I/O) PET imaging US$6.4b PET imaging market: could help identify the 20-40% of patients who will respond to revolutionary I/O drugs faster Immuno-oncology (I/O) drugs PET imaging agents have substantially reactivate the patient’s own immune
Slide 20: i-body enabled CAR-T assets: Carina collaboration
INVESTOR PRESENTATION – SEPTEMBER 2021 18 i-body enabled CAR-T assets: Carina collaboration Third program entering discovery to generate precision engineered CAR-T products providing new hope for patients with cancer World-leading proprietary CAR-T technologies for superior access, potency and resil
Slide 21: CAR-T therapies are revolutionising cancer treatment
INVESTOR PRESENTATION – SEPTEMBER 2021 19 CAR-T therapies are revolutionising cancer treatment Reprogramming a patient’s own immune system to fight cancer is a fast growing market at the cutting edge of medicine earned by CAR-T therapy step 1 CAR engineered chemokine >US$1b products in 20203 step 2
Slide 22: Carina collaboration details
INVESTOR PRESENTATION – SEPTEMBER 2021 20 Carina collaboration details AdAlta and Carina will jointly develop up to 5 targets to create CAR-T, bi-specific CAR-T and dual CAR-T cell therapy products Up to 5 targets Significant new, shared IP – Proof of principle already achieved - Share costs, resear
Slide 23: AdAlta assets and business model
INVESTOR PRESENTATION – SEPTEMBER 2021 21 AdAlta assets and business model AdAlta’s value is the sum of multiple assets: the i-body platform itself + the internal pipeline of wholly owned assets developed for out-licensing + the external pipeline of assets co-developed with biopharmaceutical compani
Slide 24: An expanding pipeline of i-body enabled products
INVESTOR PRESENTATION – SEPTEMBER 2021 22 An expanding pipeline of i-body enabled products IND PRODUCT/ PRECLINICAL, PROGRAM PARTNER DISCOVERY ENABLING PHASE I PHASE II INDICATION PRODUCT STUDIES DEV CXCR4 AD-214: Idiopathic Inhaled Pulmonary Fibrosis Intravenous AD-214: Indication 2 INTERNAL PIPELI
Slide 25: The potential of our strategy: Ablynx case study
INVESTOR PRESENTATION – SEPTEMBER 2021 23 The potential of our strategy: Ablynx case study Multiple internal and external assets drive value, attract partners GPCR platform exits Acquisition US$5B Feb-15 acquired by Sosei IPO Phase Ib + 7 preclinical leads US$182m US$400m +US$83m +US$112m +US$57m +U
Slide 26: Milestones for remainder of FY2022
INVESTOR PRESENTATION – SEPTEMBER 2021 24 Milestones for remainder of FY2022 Milestones extended through end of FY2022 AD-214 Other Assets ü Orphan Drug Designation for AD-214 in IPF ü Results of Phase I single dose studies in healthy volunteers ü Progressing the GE Healthcare collaboration from dis
Slide 27: Industry experienced leadership and advisors
INVESTOR PRESENTATION – SEPTEMBER 2021 25 Industry experienced leadership and advisors Team with experience from discovery through manufacturing, clinical and commercialisation Board Executive Scientific Advisory Board Dr Paul MacLeman Tim Oldham, PhD Brian Richardson Chair CEO & Managing Director D
Slide 28: Corporate snapshot
INVESTOR PRESENTATION – SEPTEMBER 2021 22 Corporate snapshot Key financial details (14 Sep 2021) Share price performance (last 12 months) 0.25 7.0 ASX code 1AD 6.0 Market capitalisation A$23.05m 0.20 Share price (12 month closing range) A$0.094 ($0.081 - 0.195) 5.0 Share price (A$) 12 month return (
Slide 29: Investment proposition
INVESTOR PRESENTATION – SEPTEMBER 2021 27 Investment proposition Lead asset advancing to Phase II 2 x co-development collaborations with i-body platform to create value biopharma to leverage platform Patented, validated i-body platform AD-214: first-in-class asset for multiple for asset creation: de
Slide 30: Contact
Contact: Tim Oldham, CEO and Managing Director enquiries@adalta.com.au www.adalta.com.au
Slide 31: Appendix: Strategy
Appendix: Strategy
Slide 32: Our strategy
INVESTOR PRESENTATION – SEPTEMBER 2021 39 Our strategy In-house pipeline of drug candidates Licence to Usually GPCRs in fibrosis, pharma inflammation, oncology Major upfronts + milestones A Invest to value inflection and royalties (typically Phase I or II) Multiple i-body drugs i-body technology Sel
Slide 33: Transition to the expansion phase of our growth plan
INVESTOR PRESENTATION – SEPTEMBER 2021 38 AdAlta has successfully transitioned to the expansion phase of our growth plan Accelerate (from ~mid-2021) Expand (~mid 2020 to late 2021) Maximise catalysts from current funded base (2020) From… Via… Towards 2023… • i-body platform in clinic for difficult •
Slide 34: Appendix: i-bodies
Appendix: i-bodies
Slide 35: i-bodies: next generation antibodies
INVESTOR PRESENTATION – SEPTEMBER 2021 41 i-bodies: next generation antibodies i-bodies are human proteins that belong to the class of next-generation antibodies Generation of the i-body 1 2 Two long loops are engineered onto the human protein. These enable 3 Each unique i-body has tight binding to
Slide 36: An immensely powerful drug development platform
INVESTOR PRESENTATION – SEPTEMBER 2021 42 An immensely powerful drug development platform Demonstrated i-body platform capability • G-protein coupled receptors (GPCRs) • Fibrosis, inflammation, oncology • Diagnostics (PET tracers; cancer imaging) • Chimeric antigen receptor (CAR) cell therapy GPCRs
Slide 37: Appendix: AD-214
Appendix: AD-214
Slide 38: AD-214: road to the clinic
INVESTOR PRESENTATION – SEPTEMBER 2021 36 AD-214: road to the clinic Validated target Novel mode of GMP NHP GLP NHP GLP action, IP manufacturing toxicology toxicology • CXCR4 • Patented CXCR4 • Fc-fusion format • Very clean tox • Bleomycin • Player in i-body antagonist • CDMO: KBI profile mouse mode
Slide 39: AD-214 inhibits key features of the fibrogenic pathway
INVESTOR PRESENTATION – SEPTEMBER 2021 37 AD-214 inhibits key features of the fibrogenic pathway with novel MOA Block fibrocyte recruitment Inhibit epithelial cell secretion of into the damaged tissue pro-fibrotic factors and epithelial to mesenchymal transition Injury Entry Entry Inflammatory media
Slide 40: Ashcroft Score
INVESTOR PRESENTATION – SEPTEMBER 2021 38 AD-214 induced reduction in progression of fibrosis in mouse bleomycin model AD-214 reduced Ashcroft Score with statistical significance compared to bleomycin treated mice at: • 1-30mg/kg every second day Ashcroft Score • 10-30mg/kg every fourth day Day 8 bl
Slide 41: NHP GLP toxicology: AD-214 safe
INVESTOR PRESENTATION – SEPTEMBER 2021 29 NHP GLP toxicology: AD-214 safe 3 non-human primate studies completed Good Laboratory Practice (GLP) study to evaluate safety and toxicology 10mg/kg, 30mg/kg AD-214 well tolerated with no deaths, no AD-214-related Minor, transient, Small, transient, and 100m
Slide 42: Non-human primate GLP toxicology: Phase I dose justification
INVESTOR PRESENTATION – SEPTEMBER 2021 30 Non-human primate GLP toxicology: Phase I dose justification 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-214v
Slide 43: AD-214 Phase I healthy volunteer results
INVESTOR PRESENTATION – SEPTEMBER 2021 41 AD-214 Phase I healthy volunteer results AD-214 is well tolerated in single doses to 20 mg/kg and multiple doses to 5 mg/kg* AD-214 molecule is well tolerated in single and multiple doses (see Appendix for more detail)* • No dose limiting toxicities or adver
Slide 44: Phase I healthy volunteer study: safety findings
INVESTOR PRESENTATION – SEPTEMBER 2021 42 AD-214 Phase I healthy volunteer study: safety findings Single doses to 20 mg/kg (42 participants) Multiple doses 5 mg/kg (8 participants) • No dose limiting adverse events • No dose limiting adverse events • No serious adverse events • Safety Management Com
Slide 45: Phase I healthy volunteer study: immune response findings
INVESTOR PRESENTATION – SEPTEMBER 2021 43 AD-214 Phase I healthy volunteer study: immune response findings Single doses to 20 mg/kg (42 participants) Multiple doses 5 mg/kg (8 participants) • Isolated instances of minor cytokine elevation • Sporadic and primarily low level elevation of cytokines • T
Slide 46: AD-214 pharmacokinetics increase proportionally with dose
INVESTOR PRESENTATION – SEPTEMBER 2021 32 AD-214 pharmacokinetics increase proportionally with dose (single doses) • Maximum exposure, Cmax, increases in a dose proportional manner • Total exposure, AUC0-inf, increases in a more than dose proportional manner • Elimination half-life t1/2 ~40h AD-214
Slide 47: AD-214 pharmacokinetics
INVESTOR PRESENTATION – SEPTEMBER 2021 32 AD-214 pharmacokinetics Maximum exposure, Cmax, and total exposure, AUC0-inf, increase in a dose proportionate manner and are consistent across multiple doses of AD-214 at 5 mg/kg, supporting absence of drug induced tolerance or clearance Maximum and total p
Slide 48: Transient white blood cell and blood stem cell increases indicate CXCR4 engagement
INVESTOR PRESENTATION – SEPTEMBER 2021 33 Transient white blood cell and blood stem cell increases indicate CXCR4 engagement Observed in Phase I HV SAD* Transient, dose dependent, increase in WCC and CD34+ counts at 4-12 hours consistent with CXCR4 blockade WCC counts WCC counts at 4h CD34+ cell cou
Slide 49: Transient increase in SDF-1 consistent with CXCR4 engagement
INVESTOR PRESENTATION – SEPTEMBER 2021 34 Transient increase in SDF-1 (natural ligand of CXCR4) consistent with CXCR4 engagement Transient increases in SDF-1 levels at 4 hours in some participants, returning to baseline at 24h consistent with CXCR4 blockade * Single ascending dose data presented as
Slide 50: Biomarkers of CXCR4 receptor engagement at 5 mg/kg
INVESTOR PRESENTATION – SEPTEMBER 2021 33 Biomarkers of CXCR4 receptor engagement at 5 mg/kg Transient increases in blood biomarkers demonstrate consistent engagement of the target receptor, CXCR4 across multiple AD-214 doses 16 CD34+ cells Biomarker data confirm single dose findings, consistent acr
Slide 51: Sustained high levels of CXCR4 receptor occupancy on T cells
INVESTOR PRESENTATION – SEPTEMBER 2021 35 Sustained high levels of CXCR4 receptor occupancy on T cells White blood cells naturally express CXCR4 in healthy individuals, providing an accessible surrogate for AD-214 target engagement or receptor occupancy (RO) Understanding duration of RO is critical
Slide 52: PET imaging studies inform dosing and route of administration
INVESTOR PRESENTATION – SEPTEMBER 2021 50 PET imaging studies inform dosing and route of administration PET imaging with radiolabelled AD-214 supports early transition to inhaled route of administration Rapid liver distribution and clearance reduces bioavailability Consistent with pharmacokinetic pr
Slide 53: Inhalation in IPF
INVESTOR PRESENTATION – SEPTEMBER 2021 51 Inhalation in IPF Numerous drugs have been formulated for inhalation in IPF and respiratory disease, a substantial number of biologics are in development for inhalation and off-the-shelf devices are available for rapid translation from intravenous route Inha
Slide 54: A clinician's perspective on AD-214 results so far
INVESTOR PRESENTATION – SEPTEMBER 2021 36 A clinician’s perspective on AD-214 results so far • Un-met need in IPF/ILD remains – need to progress new therapies • Research at The Alfred suggests if targeting CXCR4 works in IPF it may work in other ILD’s • AD-214 is well tolerated and ready to move for
Slide 55: IPF Landscape: narrow and narrowing development field
INVESTOR PRESENTATION – SEPTEMBER 2021 43 IPF Landscape: narrow and narrowing development field AdAlta’s novel mode of action expected to be attractive to partners ORPHAN DRUG COMPANY DRUG MODE OF ACTION PHASE DESIGNATION Reduction in pulmonary artery pressure through direct vasodilation of the pulm
Slide 56: Appendix: CAR-T
Appendix: CAR-T
Slide 57: Advantages of CAR-T therapy
INVESTOR PRESENTATION – SEPTEMBER 2021 55 Advantages of CAR-T therapy For patients, CAR-T therapies offer a potentially curative, single shot therapy that is precision engineered to find and kill cancer Can be curative Long lasting Highly targeted Even in patients whose Living therapy: a single Prec
Slide 58: CAR-T market opportunity
INVESTOR PRESENTATION – SEPTEMBER 2021 56 CAR-T market opportunity The CAR-T market formed in 2017, has already reached US$1b and is forecast to reach US$20b by 2028 Sales and market share growth for CAR-T products3 ü >$US1 billion earned by CAR-T therapy products in 2020 ü Revenue of $US20.3 billio
Slide 59: Current approved CAR-T products
INVESTOR PRESENTATION – SEPTEMBER 2021 57 Current approved CAR-T products Five FDA approved CAR-T products for blood cancers generate strong revenues and are in high demand Manufacturer Product Notable CAR-T UPenn and Novartis Gilead acquired Kite Gilead acquired Kite Celgene acquired Juno Celgene a
Slide 60: Collaboration synergies
INVESTOR PRESENTATION – SEPTEMBER 2021 58 Collaboration synergies By joining forces, AdAlta and Carina access complimentary expertise to create a toolbox to address three main challenges facing solid tumour CAR-T therapies. AdAlta expands its pipeline and further validates the i-body platform Precis
Slide 61: i-bodies in CAR-T format
INVESTOR PRESENTATION – SEPTEMBER 2021 59 i-bodies in CAR-T format • i-bodies are approximately half the size of the traditional CAR binding domain • Enables greater flexibility in CAR design • Ideally suited to bispecific CARs • i-bodies are specifically designed to target antigens considered diffi
Slide 62: Advantages of i-body enabled CAR-T
INVESTOR PRESENTATION – SEPTEMBER 2021 60 Advantages of i-body enabled CAR-T i-body enabled CAR-T cells may demonstrate improved precision, performance and persistence, particularly in bi-specific and dual CAR-T cells i-body enabled mono / dual CAR i-body enabled Delivering precision to difficult bi