Adalta Ltd. · ASX:1AD
Adalta — IPF Summit 2017
27 slides from Adalta's conference presentation, Aug 21, 2017
Slide 1: AdAlta CEO to present at the inaugural IPF Summit in Boston
ASX Announcement AdAlta CEO to present at the inaugural IPF Summit in Boston For personal use only MELBOURNE Australia, 21 August, 2017: AdAlta Limited (ASX:1AD), the biotechnology Company advancing its lead i-body candidate towards clinical development, announces CEO Sam Cobb has been invited to sp
Slide 2: Poster presentation details and About AdAlta
Details of the poster presentation Session date / time: Tuesday 22 August 2017 from 5:30 pm For personal use only Session title and details: i-body AD-114 targeting CXCR4 has anti-fibrotic activity A copy of the presentation and poster are attached with this cover note and will also be made availabl
Slide 3: i-bodies: a novel therapeutic approach for the treatment of IPF
For personal use only i-bodies: a novel therapeutic approach for the treatment of IPF August 2017 Sam Cobb, CEO and Managing Director [email protected]
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: i-body technology
i-body technology For personal use only AdAlta is developing a new technology platform that produces unique proteins known as i-bodies. An i-body is a human protein that combines the advantages of small molecules (stability) and antibodies (high affinity and specificity) in one powerful treatment. 3
Slide 6: i-bodies: human single domains
i-bodies: human single domains For personal use only Shark Human Human VNAR Ribbon Overlay NCAM Domain 1 i-body library 4
Slide 7: i-body technology advantages
i-body technology advantages For personal use only Challenging targets Because of the long binding loop of the i-body, that is lacking in traditional antibodies, i-bodies recognise and bind to a diverse range of therapeutically-relevant targets including those that are difficult/intractable to acces
Slide 8: 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 Mozobil (AMD3100) approved for single use. HIV-1 uses CXCR4 as a co-receptor for viral entry into host cells and CXCR4 has been associated with more than 23 t
Slide 9: Evidence supporting CXCR4 as a fibrosis target
Evidence supporting CXCR4 as a fibrosis target For personal use only Receptors & Clinical Investigation 2015; 2: e791. doi: 10.14800/rci.791; © 2015 by Leah Campeau, et al. http://www.smartscitech.com/index.php/rci Significant literature to support hypothesis of the involvement of CXCR4 in fibrosis
Slide 10: CXCR4 increased in disease
CXCR4 increased in disease For personal use only CXCR4 Normal human Diseased IPF lung tissue lung tissue IPF diseased lung tissue in upper right panel compared with normal lung tissue has increased CXCR4 expression CXCR4 present in hyperplastic epithelium (EP) of honeycomb cysts (HC), within a mucus
Slide 11: CXCR4 as a biomarker in IPF
590 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 179 2009 included. Diagnosis of IPF was based on guidelines of the American monary artery, carina, and 1 cm above the right diaphragm. Fibrotic changes Thoracic Society and European Respiratory Society (3). Surgical lung were quantif
Slide 12: CXCR4 increased in fast progressing IPF patients
CXCR4 increased in fast progressing IPF For personal use only patients Patients that rapidly progress express more CXCR4 compared to slow IPF progressors 10
Slide 13: CXCR4 as a biomarker in IPF
migration of CXCR4+ progenitor cells to the lung. 1.6-3 Objectives: area In this study, pulmonary CXCR4 expression was a sig evaluated using quantitative positron emission p=0. tomography (PET), in order to test its role as a p=0. Figure 2: CXCR4 PET/CT scan of a patient with IPF/UIP. CT p=0. potent
Slide 14: AD-114 binds to lung tissue from patients with fibrosis
AD-114 binds to lung tissue from patients with For personal use only fibrosis AD-114 was used for Immunohistochemical (IHC) staining of normal and diseased lung tissues to verify expression of CXCR4 in situ AD-114 does not bind lung tissue from AD-114 binds to lung tissue from lungs normal lungs wit
Slide 15: AD-114 specifically reduced migration/invasion with IPF lung fibroblasts
AD-114 specifically reduced migration/invasion For personal use only with IPF lung fibroblasts No effect Inhibits Inhibits MIGRATION on normal slow IPF fast IPF AD-114 specifically inhibited migration of fibroblasts progressors progressors slow and rapid IPF fibroblast migration but did not have any
Slide 16: AD-114 reduced collagen secretion in IPF fibroblasts
AD-114 reduced collagen secretion in IPF For personal use only fibroblasts AD-114 reduced soluble collagen 1 expression in IPF patient fibroblasts The negative i-body had no effect on soluble collagen 1 production 14
Slide 17: AD-114 prevents fibrosis in Bleomycin mouse model
AD-114 prevents fibrosis in Bleomycin mouse For personal use only model Normal IPF lung tissue IPF lung tissue + AD-114 lung tissue (lung disease mouse model) dosed for 21 days (lung disease mouse model) AD-114 reduces collagen content and inflammatory cell infiltration in the Bleomycin mouse model
Slide 18: 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 signficiant effect on preventing fibrosis 16
Slide 19: AD-114 reduces fibrotic gene expression in Bleomycin mouse model
AD-114 reduces fibrotic gene expression in For personal use only Bleomycin mouse model RNA extracted and analyzed for collagen gene expression Both COL1A1 and COL3A1 reduced in mice treated with i-body AD-114 in the Bloemycin mouse model The negative control i-body had no effect on either COL1A1 or
Slide 20: AD-114 reduces pulmonary infiltration of fibrocytes in the Bleomycin mouse model
AD-114 reduces pulmonary infiltration of For personal use only fibrocytes in the Bleomycin mouse model Pulmonary infiltration of Cola1+, CD45+ and CXCR4+ cells were also evaluated in the bleomycin mouse model Mice treated with AD-114 had reduced levels of CXCR4+ cells in their lungs when compared to
Slide 21: AD-114 blocks infiltration of leukocytes
AD-114 blocks infiltration of leukocytes For personal use only AD-114 has also been evaluated for its anti-inflammatory activity In a mouse air-pouch model, the inflammatory stimulant CXCL12 is added to an air-pouch created on the back of a mouse, which results in a dramatic increase in the amount o
Slide 22: AD-114 does not mobilize stem cells in vivo
AD-114 does not mobilize stem cells in vivo For personal use only AD-114 does not mobilize stem cells in humanised mouse model unlike the small molecule AMD3100 (Mozobil) AD-114 does not mobilise stem cells in non-human primates with single dose IV and SC, nor via increasing doses This data demonstr
Slide 23: AD-114 efficacy and safety
AD-114 efficacy and safety For personal use only Efficacy Safety – Lung: IPF – NHP studies demonstrate AD- • Animal models 114 well tolerated and no adverse effect: • Human IPF tissue • PK: IV and SC • Biomarker assessments (Alfred Health & others) • Dose range finder • Multi dosing studies – Broad
Slide 24: AD-114 development: key milestones
AD-114 development: key milestones For personal use only FY2018 FY2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Manufacturing Toxicology studies Phase I 22
Slide 25: AdAlta summary
AdAlta summary For personal use only Powerful proprietary technology platform to develop a pipeline of i-bodies for the treatment of a wide range of human diseases – Extreme stability of i-body similar to single domain shark antibody – Long loop of i-body binds deep in GPCR pocket and has functional
Slide 26: Sam Cobb, CEO contact details
For personal use only Sam Cobb, CEO [email protected] www.adalta.com.au
Slide 27: I-body AD-114 targeting CXCR4 has anti-fibrotic activity (poster)
I-BODY AD-114 TARGETING CXCR4 HAS ANTI-FIBROTIC ACTIVITY K. Griffiths , D. M. Habiel , W. Darby , C. Hosking , C. M. Hogaboam and M. Foley 1 2 1 1 2 1 1 AdAlta Limited, 15/2 Park Drive Bundoora, Australia 3083 and Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La