Noxopharm Ltd. · ASX:NOX
Noxopharm — Shareholder Meeting (November 2017)
65 slides from Noxopharm's shareholder meeting presentation, Nov 6, 2017
Slide 1: EGM presentations
Date: 6 November 2017 Sydney, Australia For personal use only ASX Limited ASX: NOX 20 Bridge Street SYDNEY NSW 2000 Noxopharm Limited ABN 50 608 966 123 EGM presentations Registered Office: • NYX-104. Professor Gary Housley Suite 1 Level 6 • NYX-205. Dr Benny Evison 50 Queen St • NYX-330. Dr Ian Dix
Slide 2: Forward Looking Statements
Investor & Corporate Enquiries: Company Secretary: Prue Kelly David Franks M: 0459 022 445 T: +61 2 9299 9690 E: info@noxopharm.com E: dfranks@fa.com.au www.noxopharm.com For personal use only Forward Looking Statements This announcement may contain forward-looking statements. You can identify these
Slide 3: Targeting glutamate-mediated excitotoxicity in the brain using NYX-104
Targeting glutamate- For personal use only mediated excitotoxicity in the brain using NYX-104 Gary Housley, Ph.D. Translational Neuroscience Facility & Dept. Physiology, School of Medical Sciences, UNSW Sydney Industry Partner: Noxopharm Pty Ltd J. Parmar
Slide 4: Contributors
Contributors Translational Neuroscience Facility For personal use only UNSW Sydney Scientia Prof. Gary Housley Dr. Nagarajesh Gorlamandala Ms. Jasneet Parmar Dr. Chamini Perera Dr. Georg von Jonqueries Noxopharm Dr. Benny Evison Declaration: Gary Housley is a co-inventor on a patent filed by New Sou
Slide 5: For personal use only
http://www.asx.com.a u/asxpdf/20170316/p For personal use only df/43gv3ts2cl36bh.pdf https://www.finnewsnet work.com.au/CompanyR eports/Noxopharm/201 70316/Noxopharm- Announces-UNSW- Combine-on-Stroke- Project https://newsroom.unsw. edu.au/news/health/wor king-towards-drug-limit- brain-injury
Slide 6: Identification of NYX-104 as a neuroprotective drug
Translational Neuroscience – identification of NYX-104 as a neuroprotective drug to For personal use only reduce excitotoxic brain injury • Identification of a novel Ca2+ permeable ion channel (TRPC3) activated by mGluR as a new drug target for reducing the expansion of the penumbra following stroke
Slide 7: Epidemiology of Stroke
Epidemiology of Stroke For personal use only ▪ Annually, 15 million people worldwide suffer a stroke. ▪ Stroke is Australia’s second single greatest killer after coronary heart disease and a leading cause of disability. ▪ 65% of stroke survivors suffer a disability which impedes their ability to car
Slide 8: Brain ischemia and glutamate excitotoxicity
Brain ischemia from stroke and other brain injuries and Impairment of function (penumbra) pathologies causes excess For personal use only release of the excitatory neurotransmitter – Glutamate Structural lesion – which chronically activates neurons and drives spread of brain injury Oxygen-starved ne
Slide 9: Current treatments for Stroke are directed to re-perfusion
Current treatments for Stroke are directed to re-perfusion and are time-critical • For personal use only •
Slide 10: Glutamate released in excess with brain ischaemia
For personal use only Glutamate released in excess with brain ischaemia (Stroke) - Activates mGluR (G protein-coupled glutamate receptor) - Leads to activation of PLCB - Leads to production of DAG and IP3 - DAG activates TRPC3 ion channels - sole effector of mGluR-mediated sustained depolarizing pos
Slide 11: TRPC activation by mGluR
Transient Receptor Potential Canonical Channel (TRPC) - activation by mGluR For personal use only Glutamate mGluR 1 (GPCR) mGluR PiP2 Adapted from Fowler MA et.al ,2007
Slide 12: Localization of TRPC expression in cerebral cortex & cerebellum
Localization of TRPC expression in cerebral cortex & cerebellum For personal use only hybridisation Dong,2008
Slide 13: Activation of TRPC3 channels causes sustained Ca2+ entry
For personal use only Activation of TRPC3 channels by the mGluR1 agonist DHPG causes sustained Ca2+ entry. The figure shows Fluo 4 microfluorometry Ca2+ imaging data using HEK293 cells co-expressing mGluR1 and TRPC3c channels. DHPG is initially in Ca2+-free media to deplete IP3-mediated Ca2+ store r
Slide 14: Drug Discovery program based on Ca2+ reporter cell line
Drug Discovery program based on rHEK293-GCaMP5G Ca2+ reporter cell line Gq activation using carbachol Ca2+ free perfusion For personal use only FlexStation 3 multi-modal microplate Block of Ca2+ re-entry using PyR3 (10 µM) – reader - Molecular Devices a TRPC3 channel blocker
Slide 15: NYX-104 blocked Ca2+ dynamics of Gq signalling
NYX-104 blocked Ca2+ dynamics of Gq signalling in HEK293 cells For personal use only NYX-104 (4 µM) NYX-104 Noxopharm unpubl. data
Slide 16: NYX-104 provided optimal block of Ca2+ dynamics
NYX-104 provided optimal block of Ca2+ dynamics of Gq signalling For personal use only in HEK293 cells NYX-104 NYX-104 Noxopharm unpubl. data
Slide 17: Photo-thrombotic stroke model
Photo-thrombotic stroke model For personal use only 5 min illumination @ 561 nm Rose bengal
Slide 18: For personal use only
4DPI WT mouse Photothrombotic lesion Add 3d recon rotating image For personal use only Gorlamandala - Housley et al. unpubl
Slide 19: NYX-104
For personal use only NYX-104 NYX-104 Noxopharm unpubl. data
Slide 20: NYX-104
For personal use only NYX-104 NYX-104 Noxopharm unpubl. data
Slide 21: Conclusions
CONCLUSIONS For personal use only • NYX-104 is very effective at blocking neuronal Ca2+ dynamics mediated by a dominant cell signalling pathway in neurons that is over-driven during brain injury associated with excessive release glutamate neurotransmitter. This arises in conditions such as stroke, e
Slide 22: References
References For personal use only Kim Y, Wong ACY, Power JM, Tadros SF, Klugmann M, Moorhouse AJ, Bertrand PP, Housley GD (2012) Alternative splicing of the TRPC3 ion channel calmodulin / IP3 receptor-binding domain in the hindbrain enhances cation flux. Journal of Neuroscience 32(33):11414-23. doi:
Slide 23: For personal use only
For personal use only
Slide 24: NYX-205 program and peripheral neuropathy
For personal use only NYX-205 program and peripheral neuropathy Dr Benny J. Evison Noxopharm Non-Oncology Program Director
Slide 25: Peripheral and central nervous system
For personal use only Peripheral nervous system = nerves outside Central nervous system CNS (CNS) = brain and spinal cord From: www.study.com
Slide 26: Peripheral neuropathy
For personal use only Peripheral neuropathy • Damage to these nerves = peripheral neuropathy Peripheral nervous system = nerves outside • Sensory symptoms: CNS • tingling, • numbness, • burning sensations, • considerable pain From: www.study.com
Slide 27: Peripheral neuropathy
For personal use only Peripheral neuropathy • Associated with: • diabetes, • inflammatory bowel disease (IBD), • traumatic injury, • treatment with certain cancer medications
Slide 28: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) • Acute or chronic • Affects 30 – 70% of people receiving chemotherapy • Can result in chemotherapy cessation • No effective prophylactic or therapeutic treatment • Nyrada Inc’s initial goal is to deliver an effective treatment
Slide 29: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) Nerve cell = “neuron” From: www.pixabay.com From: www.study.com
Slide 30: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) • Neurons are susceptible to cancer chemotherapies, e.g. paclitaxel From: www.pixabay.com
Slide 31: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) • Neurons are susceptible to cancer chemotherapies, e.g. paclitaxel From: www.pixabay.com
Slide 32: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) • Neurons are susceptible to cancer chemotherapies, e.g. paclitaxel From: www.pixabay.com
Slide 33: Chemotherapy induced peripheral neuropathy (CIPN)
Chemotherapy induced peripheral For personal use only neuropathy (CIPN) • Neuroinflammation From: www.pixabay.com
Slide 34: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • NYX-205 has shown promise as a therapy for inflammatory diseases • But not neuroinflammatory diseases From: www.pixabay.com
Slide 35: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • Why? • Blood-nerve barrier NYX-205 NYX-205
Slide 36: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • LIPROSE technology as a solution • Lipid protective shield • Used by Noxopharm to deliver idronoxil into the brain
Slide 37: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • LIPROSE technology as a solution NYX-205
Slide 38: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • LIPROSE technology as a solution • Lipid = NYX-205
Slide 39: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • Lipid-NYX-205 traverses blood nerve barrier NYX-205
Slide 40: NYX-205 as a treatment for CIPN
For personal use only NYX-205 as a treatment for CIPN • Neuroinflammation subsides NYX-205 NYX-205
Slide 41: Summary
For personal use only Summary • CIPN associated with neuroinflammation, • No therapy exists, • NYX-205 has established anti- inflammatory properties, • LIPROSE will be applied to help NYX-205 traverse blood nerve barrier: • To enable a therapeutic effect
Slide 42: An eye on the future
For personal use only An eye on the future • Other diseases are neuroinflammatory, • Alzheimer’s disease, • motor neuron disease, • multiple sclerosis, etc. • Nyrada Inc is evaluating these indications as targets of NYX-205/LIPROSE From: www.wiktionary,org
Slide 43: Disclaimer
For personal use only Disclaimer • This presentation has been prepared by Noxopharm Limited a company listed as [ASX:NOX] (NOX or the Company). It should not be considered as an offer or invitation to subscribe for or purchase any shares in NOX or as an inducement to make an offer or invitation to s
Slide 44: Cardio Therapeutics Pty Ltd and the PCSK9 inhibitor drug program
For personal use only Cardio Therapeutics Pty Ltd and the PCSK9 inhibitor drug program Cardio Therapeutics is part of the Altnia Group and subject to acquisition by Nyrada Inc. All rights reserved 1 Version v1.1
Slide 45: Forward Looking Statements
Forward Looking Statements For personal use only This document may contain forward-looking statements. You can identify these statements by the fact they use words such as “aim”, “anticipate”, “assume”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “may”, “plan”, “predict”, “projec
Slide 46: The PCSK9 story outline
The PCSK9 story outline For personal use only What Why Who How An important & valuable new treatment for atherosclerosis and cardiovascular disease
Slide 47: Our goal
Our goal is to : Have a tablet (oral) drug to target and inhibit PCSK9- For personal use only LDL Receptor interaction to treat hypercholesterolemia (high LDL-cholesterol levels) and cardiovascular diseases by daily use PCSK9 inhibitor Injectable PCSK9 oral tablet to treat Monoclonals to high LDL- t
Slide 48: Why is this important: hypercholesterolemia
Why is this important The medical need is large For personal use only Hypercholesterolemia - also called high cholesterol :- cholesterol (a sterol) is essential for our body cholesterol is carried in our blood in lipoproteins (fat protein) lipoproteins are named after their density - very lo
Slide 49: Why is this important: atherosclerosis
Why is this important The medical need is large For personal use only Atherosclerosis (arteriosclerotic vascular disease) * :- atherosclerosis is a disease in which plaque builds up inside your arteries arteries are blood vessels that carry oxygen-rich blood to your heart and other parts of yo
Slide 50: Why is this important: atherosclerosis
Why is this important The medical need is large For personal use only Atherosclerosis (arteriosclerotic vascular disease) https://library.med.utah.edu/WebPath/ATHHTML/ATH006.html www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis 7
Slide 51: Why is this important: coronary heart disease
Why is this important The medical need is large For personal use only Coronary heart disease – the most common cause of heart attacks stable plaques cause angina and pain, anxiety and discomfort – and in more severe cases a loss of mobility and independence unstable plaques can lead to a blood
Slide 52: Why is this important: cardiovascular disease
Why is this important The medical need is large For personal use only Cardiovascular disease * kills one Australian every 12 minutes. affects one in six Australians or 4.2 million people was the main cause for 490,000 hospitalisations in 2014/15. claimed the lives of 45,392 Australians (ne
Slide 53: Why is this important: ischemic stroke
Why is this important The medical need is large For personal use only Ischemic stroke occurs when the blood supply to part of the brain is suddenly blocked “In the U.S. it is estimated that 6.4 million adults have suffered a stroke and another 13 million may have experienced a “silent stroke,” los
Slide 54: Present treatments to reduce LDL-cholesterol
Why is this important For personal use only The present treatments to reduce LDL-cholesterol Diet, smoking & lifestyle (exercise) Some people have a genetic predisposition that diet etc. cannot resolve, others are unable to achieve control Statins – Atorvastatin (LipitorTM), Fluvastatin, Lov
Slide 55: It is a huge commercial opportunity
Why is this important For personal use only It is a huge commercial opportunity Statins were originally discovered from fungi are now off patent (generics) and cheap reached a peak of US$19 billion sales p.a. (2005) have safety and toxicity problems * “a sizable proportion of statin-treate
Slide 56: How new drugs are brought forward
What we are doing For personal use only How new drugs are brought forward The old approach many old drugs came from medicines derived from natural sources (hit-n-miss medicine over many years) e.g. penicillin from mould (antibiotic) and quinine from bark of the cinchona tree (anti malaria) the
Slide 57: Genomics and hypercholesterolemia
Genomics and hypercholesterolemia For personal use only 2003 – enter PCSK9 (Proprotein convertase subtilisin/kexin type 9) the PCSK9 gene is associated with increased risk of coronary artery disease * the PCSK9 gene produces a protein (PCSK9) that is produced by liver cells and enters the bloo
Slide 58: LDL receptor, LDL cholesterol and PCSK9
LDL receptor, LDL cholesterol and PCSK9 1. With PCSK9 bound to the LDL For personal use only Receptor, there are less LDL 3. Without PCSK9, more of the LDL Receptors to traffic LDL cholesterol Receptors traffic back to the cell out of the blood and into the cell – membrane 4. ready to shuttle becaus
Slide 59: Next-generation inhibition of PCSK9
What we are doing Next-generation inhibition of For personal use only PCSK9 genomics and the success of the existing biologic PCSK9 inhibitors tells us that PCSK9 is a good “target” i.e. something to inhibit to treat atherosclerosis and vascular disease oral drugs are much more acceptable to p
Slide 60: Next-generation inhibition of PCSK9
What we are doing Next-generation inhibition of PCSK9 For personal use only Cardio Therapeutics has shown that a small molecule from structure based design (e.g. ALT-30) can indeed effectively inhibit the PCSK9- LDL-Receptor interaction in in vitro assays and in-silico screening Model of PCSK9 (so
Slide 61: Who we are
Who we are For personal use only Dr Ian Dixon Director and Founder of Altnia Group • Co-inventor of Cardio Therapeutics Pty Ltd PCSK9 technology • PhD in Biomedical engineering from Monash University • MBA and Engineering experience • Director of Noxopharm (ASX-NOX) a listed clinical-stage anticance
Slide 62: Other members of the team
Other members of the team Person Key roles Relationship or affiliation For personal use only Dr Jim Palmer Medicinal chemistry Consultant Dr Herbert Treutlein * Structure-based and fragment- Sanoosa based drug design tools based www.sanoosa.com on their MFMD technology Dr Jun Zeng * Structure-based
Slide 63: The pathway to our PCSK9i as a drug
How - The pathway to our PCSK9i as a drug For personal use only Further Preclinical Clinical trials Registration Sales optimisation testing Further rounds Manufacture Phase I of synthesis GMP-grade and testing drug Phase IIa Animal testing Extensive Phase IIb of compounds preclinical for efficacy an
Slide 64: The PCSK9 story outline
The PCSK9 story outline For personal use only What Why Who How An important & valuable new treatment for atherosclerosis and cardiovascular disease
Slide 65: Thank you for your attention
For personal use only Thank you for your attention