Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (March 2016)
27 slides from Actinogen Medical's investor presentation, Mar 10, 2016
Slide 1: Developing Xanamem for Alzheimer's disease
For personal use only Developing Xanamem™ for Alzheimer’s disease Cortisol, Stress & Alzheimer’s Cortisol Hypothesis Investor Presentation March, 2016
Slide 2: Forward Statements
Forward Statements This presentation has been prepared by Actinogen Medical Limited. (“Actinogen” or the “Company”) based on information available to it as at the date For personal use only of this presentation. The information in this presentation is provided in summary form and does not contain al
Slide 3: Actinogen Medical Management Board
Actinogen Medical Management Board A highly experienced team with a wealth of drug development, commercialisation, and clinical research expertise. For personal use only Martin Rogers • Biotechnology entrepreneur and executive, with financial market capital Executive raising experience, having raise
Slide 4: Xanamem Clinical Advisory Board
Xanamem™ Clinical Advisory Board Powerhouse advisory board of world experts to drive Xanamem™’s clinical development for early Alzheimer’s disease. For personal use only Prof. Craig Ritchie Prof. Colin Masters Prof. Jeffrey Cummings • Professor of Psychiatry of Aging, • Professor, University of Melb
Slide 5: Xanamem Overview
Xanamem™ Overview Cortisol, Stress and Alzheimer’s: A promising treatment for Alzheimer’s disease and cognitive impairment. For personal use only • A novel mechanism of action blocking the production of cortisol (the stress hormone) in the brain through selective inhibition of 11bHSD1. • Excess cort
Slide 6: Global Impact
Global Impact The increasing burden of dementia is a critical driver for innovation. For personal use only 6
Slide 7: Limitations of Current Treatments
Limitations of Current Treatments Creating a significant unmet need in the Alzheimer’s field. For personal use only Alzheimer’s disease is emerging as one of the most significant health challenges of our time. • Affects 11% of people aged 65 years and older, and 32% of people aged 75 years and older
Slide 8: Advances in Understanding Alzheimer's
Advances in Understanding Alzheimer’s Presenting opportunities for novel approaches CSF cortisol ug/dL AD dementia, • Brain pathological and structural changes precede the 0.555 For personal use only 0.55 onset of clinical symptoms. MCI-AD, 0.48 • Early detection and treatment before onset of struct
Slide 9: Cortisol Hypothesis
Cortisol Hypothesis Hypothalamic Pituitary Axis dysregulation is linked to neurodegeneration. For personal use only • The hypothalamic pituitary axis (HPA) is a stress-responsive neuroendocrine system that ties the CNS to the endocrine system. • Studies in humans show that HPA axis dysregulation, as
Slide 10: Peer Reviewed Medical & Scientific Literature
Peer Reviewed Medical & Scientific Literature Clear link between 11β-HSD1, elevated cortisol and cognition. For personal use only Extensive human and animal evidence impacting elevated cortisol in cognitive impairment: • 11β-HSD1 generates cortisol in brain regions important for cognition (Seckl et
Slide 11: Elevated Cortisol Associated with Cognitive decline, amyloid plaques and neural death
Elevated Cortisol Associated with: Cognitive decline, amyloid plaques and neural death. For personal use only • An increase of CSF cortisol levels in subjects with MCI of AD type is of similar magnitude as in participants with AD • Higher evening cortisol levels were associated with poorer dementia,
Slide 12: Cortisol: Amyloid plaques and loss of neuropsychological function
Cortisol: Amyloid plaques and loss of neuropsychological function. For personal use only • Higher HPA activity, as reflected by increased plasma cortisol levels, is associated with more rapid disease progression in subjects with Alzheimer type dementia. • 54 subjects (33 = very mild and mild Alzheim
Slide 13: Elevated Cortisol: Associated with hippocampal atrophy in Alzheimer's disease
Elevated Cortisol: Associated with hippocampal atrophy in Alzheimer’s disease. For personal use only • Aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. • The degree of
Slide 14: Xanamem: Suppressing cortisol production through inhibition of 11β-HSD1
Xanamem™: Supressing cortisol production through the inhibition of 11β-HSD1* For personal use only Xanamem™’s mechanism of action is a key differentiator *11β-HSD1 =11β-hydroxysteroid dehydrogenase type 1 14
Slide 15: Xanamem Candidate Series Profile
Xanamem™ Candidate Series Profile UE2343 selected as a development candidate for Alzheimer’s disease. Target Profile Achieved: For personal use only • Low nM potency vs. human 11β-HSD1. • High selectivity. • High cellular potency (IC50 = 24 nM). • High microsomal stability. • Low to medium plasma pr
Slide 16: Cognitive efficacy of UE2316
Cognitive efficacy of UE2316 Tg2576 model – precursor to Xanamem™ For personal use only Tg2576 mouse model of Alzheimer's: passive avoidance test: • Mice with normal learning and memory will avoid entering the chamber where they had previously been exposed to the shock. • Learning and memory is meas
Slide 17: Disease Modifying Potential of UE2316
Disease Modifying Potential of UE2316 Precursor to Xanamem™ For personal use only • Tg2576 mouse model of Alzheimer’s disease (Sooy et al., 2015) 17
Slide 18: Xanamem PK and PD profile in Humans
Xanemem™ PK and PD profile in Humans For personal use only Completed Phase I Studies: 1. single ascending dose (SAD) study 2. multiple ascending dose (MAD) studies 3. fed/fasted 35 mg BD 4. CNS PK 35 mg BD Conclusions of the MAD studies in healthy subjects: • Safe and well tolerated when given in mu
Slide 19: Goals for Xanamem Phase II
Goals for Xanamem™ Phase II “XanADu” Study For personal use only • Inputs in to the Alzheimer's Phase II trial design by the Scientific Advisory Board (Prof Brain Walker, Prof Alan Boyd, Dr Scott Webster, Prof Jonathan Seckl), the CEO Dr Bill Ketelbey and the Clinical Advisory Board (Prof. Craig Rit
Slide 20: Xanamem: Aspirational Positioning
Xanamem™: Aspirational Positioning Cognitive Impairment and mild Alzheimer’s disease. For personal use only “An oral agent that provides durable symptomatic and disease modifying benefits in mild Alzheimer’s disease by direct inhibition of cortisol production” Xanamem™ is a novel agent likely to be
Slide 21: Xanamem: The potential for a pipeline in a product
Xanamem™: The potential for a pipeline in a product. For personal use only Development opportunities: Xanamem™’s novel mechanism of action – blocking excess cortisol production – offers a number of additional potential indications with features of progressive cognitive impairment: • Diabetes cogniti
Slide 22: Direct Molecule Competition: 11β-HSD1 inhibitors in clinical development
Direct Molecule Competition: 11β-HSD1 inhibitors in clinical development. For personal use only *Clinical development of 11bHSD1 inhibitors for T2DM was unsuccessful: other candidates including MK-0736, RG4929, RG7234, AZD4017, LY2523199 were also discontinued for T2DM 22
Slide 23: ABT-384 Trial in mild-moderate Alzheimer's disease
ABT-382 Trial In mild-moderate Alzheimer’s disease Abbott’s ABT-384 did not show non-inferiority against donepezil for the primary end-point od ADAS-Cog score during a 12-week trial1. For personal use only Trial design raises doubt whether, at the doses tested in the phase II study, ABT-384 achieved
Slide 24: Xanamem: Predicted to have high brain penetration
Xanamem™: Predicted to have high brain penetration. For personal use only • CNS Multi-parameter Optimisation (MPO) Calculator shows Xanamem has characteristics that favour high CNS penetration. • In the phase I multiple ascending dose study, Xanamen demonstrated high pharmacologically active concent
Slide 25: Solid Patent Estate
Solid Patent Estate: Broad range of compounds, compositions and uses. For personal use only 25
Slide 26: Cortisol, Stress and Alzheimer's: Overview of Xanamem
Cortisol, Stress and Alzheimer’s Overview of Xanamem™ in Alzheimer's disease For personal use only Alzheimer's - a significant unmet need in a huge and growing global market. Xanamem’s™ novel mechanism of action targeting the stress hormone cortisol – a key differentiator. Cortisol inhibition hypoth
Slide 27: Thank You
For personal use only Thank You Email info@actinogen.com.au for further information, or to sign up for our newsletter.
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