AdAlta Ltd. · ASX:1AD
AdAlta — Australia Biologics Festival 2024
27 slides from AdAlta's conference presentation, Feb 20, 2024
Slide 1: Australia Biologics Festival Presentation
ASX Announcement/Press Release | 20 February 2024 AdAlta Limited (ASX:1AD) Australia Biologics Festival Presentation AdAlta Limited (ASX:1AD) (“AdAlta” or “the Company”) is pleased to announce its participation in the Australia Biologics Festival to be held between 20 February and 21 February 2024 i
Slide 2: About AdAlta Limited
About AdAlta Limited AdAlta Limited is a clinical stage drug development company headquartered in Melbourne, Australia. The Company is using its proprietary i-body technology platform to solve challenging drug targeting problems and generate a promising new class of single domain antibody enabled pr
Slide 3: Dose estimation and optimization for a first-in-class anti-fibrotic therapeutic
For personal use only Dose estimation and optimization for a first-in-class anti-fibrotic therapeutic Tim Oldham PhD CEO and Managing Director AdAlta Limited (ASX:1AD) Australian Biologics Festival 1 20-21 February 2024
Slide 4: 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. For personal use only This presentation is not an offer or in
Slide 5: Summary
Summary § AdAlta’s i-body® platform: a powerful drug discovery tool for targets such as G-protein coupled receptors For personal use only (GPCRs) where traditional antibody drugs struggle § AdAlta’s AD-214 targets the GPCR CXCR4 and has been specifically designed for the high unmet need in fibrotic
Slide 6: AdAlta (ASX:1AD) at a glance
AdAlta (ASX:1AD) at a glance AdAlta’s i-body® platform is enabling a high-value product pipeline in two therapeutic areas of For personal use only significant unmet medical need i-body® discovery platform A co-developed immuno- A wholly owned fibrosis and enables development of oncology pipeline inf
Slide 7: Invention of i-bodies
Invention of i-bodies i-bodies mimic shark VNARs using a human NCAM domain 1 scaffold and randomized synthetic shark VNAR-like binding loops For personal use only CDR3 CDR3 CDR1 CDR1 Ribbon overlay* hNCAM Domain 1 i-body® library Shark VNAR Basic research on unique … led to discovery that the i-set
Slide 8: An immensely powerful drug discovery platform applicable to multiple therapeutic formats
An immensely powerful drug discovery platform applicable to multiple therapeutic formats Current For personal use only examples Direct therapeutics For challenging targets, such as GPCRs Future examples AD-214 Manufacturing and delivery • Delivery and expression ex vivo and in Targeting agents Bi-sp
Slide 9: AdAlta's pipeline so far: Five active assets plus growing i-body inventory
AdAlta’s pipeline so far: Five active assets plus growing i-body® inventory Discovery Non-clinical Clinical Target Product Indication Partner Lead Discovery Preclinical IND enabling Phase I Phase II optimisation For personal use only Lung, kidney IV Available fibrosis SC to license AD-214 Available
Slide 10: Bill van Nierop: IPF survivor on the challenge of living with IPF
Bill van Nierop: IPF survivor on the challenge of living with IPF For personal use only “… sadly I am one of a few who can actually “I talked with a 60 something grandmother, who really enjoyed days looking after relate to the lived experience with and without PF grandkids, but as disease progressed
Slide 11: The need: better outcomes for Idiopathic Pulmonary Fibrosis and other fibrotic diseases
The need: better outcomes for Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases 45% of developed world deaths have >490,000 a chronic fibrosis component For personal use only 72,000 worldwide 78,000 14,000 USA Europe Every organ vulnerable: 159,000 Japan of sufferers § Lung (US$4b) 6,0
Slide 12: The value: Pharma companies are actively licensing IPF assets for significant value
The value: Pharma companies are actively licensing IPF assets for significant value Upfront payment to Clinical Phase at Date Licensor/target Licensee/acquirer Transaction Contingent milestones licensor transaction For personal use only Feb 23 Acquisition# US$294m N/A 2 Jan 23 China only license US$
Slide 13: CXCR4 is an established GPCR target in fibrotic diseases
CXCR4 is an established GPCR target in fibrotic diseases CXCR4 is a critical player in many fibrotic indications including lung, kidney, heart, eye, skin CXCR4 imaging demonstrates strong CXCR4 expression correlated with areas of honeycombing in IPF For personal use only Changes in CXCR4 expression
Slide 14: AD-114 was selected as the lead candidate because of its optimal antifibrotic properties
AD-114 was selected as the lead candidate because of its optimal antifibrotic properties CXCR4 i-bodies demonstrate differential pharmacology, allowing optimization of target interaction For personal use only AD-114 AD-272 AD-523 Affinity to CXCR4 4.2 1.8 9.2 (KD/nM) Inhibition of β-arrestin 1.18 1.
Slide 15: Drug candidate AD-214 is a dual AD-114 i-body-Fc fusion protein
Drug candidate AD-214 is a dual AD-114 i-body-Fc fusion protein with optimized CXCR4 affinity and half-life For personal use only § AD-114 i-body® within AD-214 is highly Therapeutic candidate specific to the CXCR4 ligand binding AD-214 CXCR4 antagonist pocket i-body® Fc fusion protein § Selected fo
Slide 16: In vitro and ex vivo studies support proposed multiple modes of action
In vitro and ex vivo studies support proposed multiple modes of action A B For personal use only C B. Inhibiting epithelial cell proliferation, C. Inhibiting fibroblast migration, differentiation A. Inhibiting inflammatory cell and fibrocyte secretion of pro-fibrotic factors and EMT and ECM depositi
Slide 17: AD-214 efficacy validated in mouse model of IPF
AD-214 efficacy validated in mouse model of IPF; suggestive of minimum effective dose Normal mouse lung tissue For personal use only IPF mouse lung tissue 21 days after bleomycin IPF mouse lung tissue + AD-214 21 days after bleomycin and AD- 214 at 10mg/kg every 4 days from day 8 Results supportive
Slide 18: NHP toxicology studies support AD-214 CXCR4 engagement; Phase I dose selection
NHP toxicology studies support AD-214 CXCR4 engagement; Phase I dose selection Pharmacokinetics Pharmacodynamics For personal use only § Average elimination half-life 22-29 h § >60% occupancy of the CXCR4 receptor (RO) on T cells for 72 h at § AD-214 available for >3 days >30 mg/kg § High receptor b
Slide 19: Intravenous AD-214 Phase I healthy volunteer study confirms robust safety profile
Intravenous AD-214 Phase I healthy volunteer study confirms robust safety profile1 For personal use only AD-214 exposure (AUC), Cmax, Tmax increase in a dose proportional manner Elimination half-life (t1/2) 39 h at 20 mg/kg ✓ AD-214 well tolerated in both single and multiple dose arms ✓ No immune re
Slide 20: Transient increases in blood biomarkers demonstrate consistent target engagement
Transient increases in blood biomarkers demonstrate consistent engagement of the target receptor, CXCR4 For personal use only 5 mg/kg data shown; 10 mg/kg interim data comparable 1 Compiled from Tables and Listings of study NCT04415671 data collected and monitored by independent CRO 2Data from 5mg/k
Slide 21: Phase I clinical study supports sustained AD-214 CXCR4 engagement
Phase 1 clinical study supports sustained AD-214 CXCR4 engagement Understanding receptor occupancy is critical to inform dosing § White blood cells naturally express CXCR4, providing accessible surrogate for AD-214 target engagement § Sustained high levels of CXCR4 receptor occupancy (RO) by AD-214
Slide 22: Open question: what levels of receptor occupancy are needed for efficacy?
Open question: what levels of receptor occupancy are needed for efficacy? For personal use only A. AD-214 has demonstrated efficacy in multiple animal models of fibrotic disease B. In humans, AD-214 was able to maintain more than 60% receptor occupancy (blocking) for up to three weeks after IV infus
Slide 23: Clinically viable, two weekly IV and weekly SC dosing regimens can maintain target receptor occupancy
Clinically viable, two weekly IV and weekly SC dosing regimens can maintain target receptor occupancy for efficacy 1. Ex vivo cell migration is a model fibrotic process and inhibition of migration is a model of efficacy § Maximum efficacy at >80% inhibition of migration (green). Meaningful efficacy
Slide 24: PK models suggest two weekly IV and potentially weekly SC dosing regimens
PK models suggest two weekly IV and potentially weekly SC dosing regimens achieve target receptor occupancy For personal use only A. Dosing every two weeks B. Dosing every week 10 mg/kg 1 mg/kg 3 mg/kg Potential SC dose Target IV dose for to introduce at Phase II Phase III or lifecycle management Da
Slide 25: Phase I extension study validates model and safety of target Phase II dose
Phase I extension study validates model and safety of target IM ER Phase II dose INT LTS* RE SU For personal use only Receptor occupancy (RO) in line with model predictions for efficacy of 10 mg/kg infusion every two weeks Predicted RO Observed RO (mean) § >80% at one week after infusion ü >90% at o
Slide 26: AD-214 is a first in class CXCR4 antagonist, ready to move into Phase II
AD-214 is a first in class CXCR4 antagonist designed specifically for fibrotic disease, ready to move into Phase II Product Profile: AD-214 Product development strategy For personal use only Disease Area Fibrosis Target intravenous (IV) Potential subcutaneous (SC) Molecule class Protein therapeutic
Slide 27: A modern targeting system for next generation drugs
For personal use only A modern targeting system for next generation drugs For more information please contact: Tim Oldham CEO & Managing Director +61 403 446 665 [email protected] www.adalta.com.au 25