Adalta Ltd. · ASX:1AD
Adalta — ILD Drug Development Summit 2021
26 slides from Adalta's conference presentation, Apr 28, 2021
Slide 1: AD-214 Results Presented at ILD Drug Development Summit
28 April 2021 ASX Announcement For personal use only AD-214 RESULTS PRESENTED AT ILD DRUG DEVELOPMENT SUMMIT MELBOURNE Australia, 28 April 2021: AdAlta Limited (ASX:1AD), the clinical stage biotechnology company developing novel therapeutic products from its i-body platform is pleased to announce th
Slide 2: Notes to Editors: About AdAlta
Notes to Editors About AdAlta AdAlta Limited is a clinical stage drug development company headquartered in Melbourne, Australia. The Company is using its proprietary i-body technology platform For personal use only to solve challenging drug targeting problems and generate a promising new class of si
Slide 3: CXCR4/CXCL12: A common molecular axis in multiple cell types with relevance in ILD
For personal use only CXCR4/CXCL12: A common molecular axis in multiple cell types with relevance in ILD ILD Drug Development Summit April 2021
Slide 4: 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 5: CXCR4: Role in IPF
CXCR4: Role in IPF CXCR4 plays a role in IPF CXCR4 CXCR4 is upregulated in Very limited expression in For personal use only CXCR4 is a critical player in many fibrotic IPF lung tissue normal or non-diseased tissues indications including: • Lung • Kidney • Heart • Eye Normal lung histology • Skin CXC
Slide 6: CXCR4 is expressed in both IPF and ILD patient lung tissue and in multiple cell types
CXCR4 is expressed in both IPF and ILD patient lung tissue and in multiple cell types For personal use only CXCR4 was abundantly expressed in both IPF and ILF donors compared with non-diseased controls CXCR4 is expressed on circulating immune cells and in patients with IPF and other fibrotic ILDs we
Slide 7: Why targeting CXCR4 could improve IPF/ILD outcomes
Why targeting CXCR4 could improve IPF/ILD outcomes For personal use only Observation Significance CXCR4 is up-regulated in ILD patients as well If AD-214 works in IPF it is more likely to work as IPF patients in ILD as well … and there are at least as many non-IPF ILD patients as IPF patients CXCR4
Slide 8: i-bodies: human single domains
i-bodies: human single domains For personal use only i-body inspired by the shark VNAR structure AD-114 is a CXCR4 binding i-body that binds in the ligand binding site and antagonizes the receptor 6
Slide 9: AD-214 retains specificity for CXCR4
AD-214 retains specificity for CXCR4 For personal use only AD-214 consists of the CXCR4 binding i-body (AD-114) fused to human Fc AD-214 had no binding to proteins other than CXCR4 7
Slide 10: AD-214 binds with high affinity to CXCR4
AD-214 binds with high affinity to CXCR4 For personal use only AD-214 binds to human A C CXCR4 lipoparticles with affinity of ~4pM (A) AD-214 binding to CXCR4 expressing CHO cells but not to parental cells (B) B Flow cytometry shows that AD-214 can bind to CXCR4 expressed on human CD3+ T cells (C).
Slide 11: AD-214 Phenotypic profile lung fibrosis panel
AD-214 Phenotypic profile lung fibrosis panel For personal use only SAEMyoF and MyoF consisting of a co-culture of lung Small Airway epithelial cells &f fibroblasts Fibroblasts fibroblasts and small airway epithelial cells. Key activities of AD-214: Col-III – AD-214 is not cytotoxic at the concentra
Slide 12: AD-214 attenuates fibrosis of the lung
AD-214 attenuates fibrosis of the lung For personal use only 6 Statistical significance# to 21d bleomycin Bleomycin induced lung fibrosis 5 ns ns ns ns – gold standard in vivo animal model of 4 Ashcroft Score pulmonary fibrosis * * ** ** ** Day 8 bleomycin 3 (start of treatment) AD-214 significantly
Slide 13: AD-114 is antifibrotic in a mouse model of kidney fibrosis
AD-114 is antifibrotic in a mouse model of kidney fibrosis For personal use only CXCR4 is upregulated in several models of kidney fibrosis AD-114 protects from liver damage in therapeutic mode of Folic acid kidney injury 11
Slide 14: NHP GLP toxicology: AD-214 well tolerated
NHP GLP toxicology: AD-214 well tolerated 3 non-human primate studies completed For personal use only Good Laboratory Practice (GLP) study to evaluate safety and toxicology 10mg/kg, 30mg/kg and 100mg/kg multiple doses over four weeks plus recovery (human equivalent dose 32mg/kg) AD-214 well tolerate
Slide 15: NHP PK and PD results
NHP PK and PD results For personal use only Pharmaco-kinetics Pharmaco-dynamics • Elimination half-life 22-29h • >60% receptor occupancy* for 72h at >30mg/kg Receptor Occupancy - All 120 Vehicle Day 1 Male Day 25 Male 10 mg/kg 30 mg/kg 100 100 mg/kg 80 60 % RO 40 20 0 -20 Pre-Dose 2 hours post-SOI 4
Slide 16: AD-214 4-week toxicology study: Hematology
AD-214 4-week toxicology study: Hematology For personal use only White Blood Cells 60 10mg/kg 10, 30, 100mg/kg AD-214 Cell number (10^9/L) 30mg/kg administered twice weekly for 4 40 100mg/kg Vehicle weeks 20 Historical High Transient increase in total WBCs 2 0 Historical Low hours after administrati
Slide 17: AD-214 Phase I program in healthy volunteers
AD-214 Phase I program in healthy volunteers Part A: HV SAD Pooled Overall ✓ For personal use only Blinded/placebo controlled Variable Statistic Overall Placebo AD-214 0.01-20 mg/kg single dose 7 cohorts, 42 pts n 11 31 42 Age (years) at Screening Mean 36.2 36.5 36.4 Participants Cohort (active:plac
Slide 18: Single doses of AD-214 are well tolerated and achieve sustained, high receptor occupancy
Single doses of AD-214 are well tolerated and achieve sustained, high receptor occupancy For personal use only AD-214 has an excellent safety profile • No dose limiting toxicities or adverse events of clinical concern • No concerning clinical laboratory results • Consistent with Non-Human Primate (N
Slide 19: Single dose of AD-214 is well tolerated
Single dose of AD-214 is well tolerated For personal use only Adverse events (unblinded data) Immune response* • No dose limiting adverse events • No clinically significant cytokine release • No serious adverse events • Isolated incidences of minor cytokine elevation - Transient and primarily low le
Slide 20: AD-214 pharmacokinetics increase proportionally with dose
AD-214 pharmacokinetics increase proportionally with dose For personal use only Observed Elimination half-life t1/2 ~ 44±15 h Maximum & total exposure (Cmax & AUC0-inf) increase in ~ dose proportional manner AD-214 plasma concentrations (log and linear scale) Maximum and total plasma exposure 450 1,
Slide 21: Transient white blood cell and blood stem cell increases indicate CXCR4 engagement
Transient white blood cell and blood stem cell increases indicate CXCR4 engagement For personal use only 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 counts 30 Placebo 30 Mean white cell counts (x10^9/
Slide 22: Transient increase in SDF-1 suggests CXCR4 engagement
Transient increase in SDF-1 (natural ligand of CXCR4) suggests CXCR4 engagement For personal use only Transient increases in SDF-1 levels at 4 hours in some participants, returning to baseline at 24h consistent with CXCR4 blockade Statistically significant increase at 20 mg/kg only SDF-1 levels SDF-
Slide 23: Sustained high levels of CXCR4 receptor occupancy on T cells
Sustained high levels of CXCR4 receptor occupancy* on T cells For personal use only Mean occupancy of T cell CXCR4 receptors by CXCR4 is expressed on white blood cells in healthy individuals, providing an AD-214 0.01mg/kg 120 accessible proxy for AD-214 target 0.02mg/kg engagement 1 wk 0.1mg/kg 100
Slide 24: AD-214 Phase I program in healthy volunteers and patients
AD-214 Phase I program in healthy volunteers and patients For personal use only Phase 1 protocol in healthy volunteers Complete Q2-Q4 2021 i ve Part A: HV SAD Part B: HV MAD* Act ✓ • Dosing complete end 2021 Blinded/placebo controlled Blinded/ Placebo controlled • Supports Phase II/ FDA IND 0.01-20
Slide 25: Contacts for more information
For personal use only Contacts for more information: Mick Foley, CSO [email protected] www.adalta.com.au
Slide 26: Implications for AD-214: a clinician's perspective
Implications for AD-214: a clinician’s perspective For personal use only Un-met need in IPF/ILD remains: need to progress new therapies Research at The Alfred suggests that if targeting CXCR4 works in IPF it may also work in other ILD’s AD-214 is well tolerated and ready to move forward into multi-d