EARLY DI DIAGNOSIS IS OF BRAIN DI DISEASES via liquid id biopsy - PowerPoint PPT Presentation

EARLY DI DIAGNOSIS IS OF BRAIN DI DISEASES via liquid id biopsy psy, base sed d on miRNA NA patter erns ns in micr crogli glial al micr crovesic vesicles les

BrainDTech team Dr. Fabio io Bian ianco co, , PhD – Chief Executive Officier Dr. Pietro tro Conti, ti, MD – Chief Financial Officer PhD in Pharmacology, Degree in • Biotech Degree in Medicine & MBA • Founder of NeuroZone (President and • Director @several Health International • CSO) Projects in UN agencies (UNDP, WHO, CEO of BrainDTech • UNICEF) Director of Sanipedia Business Nursery • Founder and CEO of several startups • >10 yr in Biotech/Pharma with • executive roles Dr. Ennio Ongin ini, , PhD – Chief Scientific Officer Dr. Noemi i Tonna, , PhD – Lab Manager PhD in Pharmacology • 20 yrs Research Director Schering PhD in Pharmacology • • Plough Degree in Medical Biotechnology • 15 yrs VP Research Nicox SA Lab Manager in NeuroZone • • Member of different evaluation >10 yr expertise in cell culturing/ in vitro • • Commitees drug discovery >200 peer reviewed papers, H-index 38 • Dr. Elisa sabetta ta Bore rell llo, MBA – Board Member Dr. Filipp ippo Martin tinelli li Bonesch schi, i, MD – Scientific Advisor Degree Medicine, Residency Neurology • Degree in Economics @ Bocconi Univ., Master Epidemiology & Biostats @ • • Milano Columbia University >30 years expertise in Healthcare PhD in Neuroscience @ HSR • • Information Management Systems Neurologist, Head of Laboratory of • Founder & Board member of many Genetics @ HSR Institute • biotechs > 120 peer-reviewed papers, PI of • National and EU funded grants

The issue (need) 10 – 15 years Brain INFLAMMATIO ION Brain DEGENERA RATIO ION CLINICA CAL SYMPTOMS Currently, diagnosis of brain diseases is carried out ob obser erving ing clinic linical al symptoms, • which occur when most of the neurodegeneration has as alre ready ady occurr urred ed. For or exam ample ple, Pa Park rkins nson on ‘s Disea ease sympt ptom oms (trem remor) r) mani anifest whe hen over er 70 70% • of of dopa paminer inergic gic neuro urons ns are dead ad (Park arkins inson on Diseas ease Foun undat datio ion 2013 13). Before neuronal degeneration, there is a sustained inflammatory brain activity, • which results in exacerbated neuroinflammation leading to cell death. The onset of this inflammatory reaction can occur even 10-15 years before the • actual symptoms manifest (Lull et al Neurotherapeutics 2010).

BrainDTech proposal Brain INFLAMMATIO ION MICROVESICL ICLES FROM MICROGLIA IA Bianco et al, EMBO J 2009 Neuroinflammation activates MICROGLIA LIA  Activated microglia produce MICROVESIC ICLES  Microvesicles contain microRNA  Microvesicles can be found in in LIQUID ID BIOPSY  BrainD ainDTec ech represents a disru rupt ptiv ive e appro proac ach to brain disease diagnosis because it detects a signal (Micro roRNA) A) contained in microv oves esic icle les released by microg roglia lia (the immune cells of the brain) years ears bef efor ore e any ny clinic inical al manif nifes estatio ion.

BrainDTech added value Clinical data show that there are MICROVES ESICLE LES S more re Microv rovesic icles les in the e Cereb rebros ospin pinal al Fluid id can be isolat ated ed of f Alzheimer’s Disea ease pat atien ients from liquid biops psies es with respect to pre-Alzheimer, or Mild Cognitive Impaired patients (Agosta et al ann Neurol 2014) We have observed that in different in vitro models, miRNAs miRNA A from om micro roglial glial micro rovesic icles les can be analyzed ed are e differe erent ntly ly up (gre reen) en) or down n (oran range ge) ) regu gulat lated ed, , in MICROV OVESIC ESICLES LES creating pathology-specific patterns. We have observed that in each pattern there are miRNA patter erns ns spec pecif ific ic miRNA whic ich are e exclus lusiv ively ly up or down n are SPEC ECIFI IFIC regu gulat lated ed in a pathological model, thus creating for each PATH THOLO LOGY pathology specific patterns, which we have patented.

BrainDTech IP position We have submitted the following patent: "Methods for diagn agnos osis is, , prog ognos nosis is and nd treat reatment nt monit itoring ring of neur urolog ologic ical, neur urod odeg egene enera rativ ive e and d infla lammat ation ion – based disea eases via miRNA contained in micro roglia glial microv oves esic icle les" 2015/ 5/11 11 - Itali alian an paten ent submi bmissi ssion on (n.10 n.1020 2015 1500 0000 00748 4820 20) (AD, PD, ischem emia) a)  2016/ 6/07 07 - PCT paten ent exten ensi sion on (PCT/ T/EP20 2016 16/06 06194 940) 0)  2016/ 6/11 11 - Claim extension (Epilepsy, MS, Tourette Syndrome….+20 pathologies)  Our strategy is to : Develop pathology specific patterns to be Since miRNA control several biochemical patented and outlicenced processes, we plan to study the miRNA for early diagnosis or patterns obtained and identifty novel companion diagnostics in drug development therapeutical targets

The marke Th ket: t: Di Diagnos ostics ics in brain n diseas eases es BIOMAR MARKER KER MARKET KET FIGURES RES CURRENT T miR iRNA FOCUS AREAS GLOBAL BIOMA OMARKERS MARKET The market for miRNA diagnostics is at GLOBAL miRN RNA MARKET a starting point, currently only focused $1 $1 on cancer and cardiovascular diseases, $45,55 $24 $24 Bill llion Bill llion Bill llion by but expected to grow exponentially in in 2015 by 2020 2019 the upcoming years. CANCER CARDIO CURRENT ENT STATE ATE OF ART BEFOR ORE E CLINICAL AL AFTER ER CLINICAL AL MANIFEST STAT ATION MARKET APPLICATIONS MANIFEST STAT ATION 2012 12 2010 10 2014 14 2016 16 Lipid ipid test t for AD Acquisition of Avid Radiopharma: Acquisition of AD test from Memory Dx: in bloo lood imaging agent t for Abeta ta plaque Enable les diffe feren rentia tiatio tionAD vs vs dementia tia Nature dete tectio ction $18 million in equity shares • Methods 2014 Development milestone after phase 2 • $300 million cash • 9% royalties on sales • Up to $500 million in milestones • Recent market highlights in the field (Alzheimer as an example), refer to diagnostics that help to characterize the patient once the symptoms appear. BrainDTech fulfil lfills ls an an unmet need of pre-symptomatic diagnosis, as well as specific companion diagnostic in drug development

The market: competition CANCER ER Few innovative players in cancer diagnosis. One player (Diamir) in brain diagnosis, still in R&D (reached a research agreement with Janssen) focused on circul culatin ting miRNA NA in plasma for detection of AD BRAIN The main issue with circulating miRNA – based approaches is lack of specificity, given miRNA can be produced by many different cell types BrainDTech approach is revolutionary because we isolate intact microvesicle from a specific cell type (microglia) and then analyze the content only of these organelles, thus significantly increasing specificity. BrainDTech approach is potentially breakthrough because recent scientific evidence (Plog et al J.Neurosci 2015) suggest that these vesicles could be present also in easily accessible biopsies such as plasma (this hypothesis is currently being validated in our lab).

BrainDTech Development plan R&D We are currently running the proof of concept in humans, testing AD patients in order to confirm data so far obtained in in vitro models. CSF PoC human PoC AD vs PD AD vs PD clinical study Then we will compare 2 indications (AD and PD), then we will proceed in stratifying patients. plasma MV identification MV isolation miRNA analysis In parallel, we are testing the possibility of isolating microglial microvesicles from plasma. Revenue stream Services on MV isolation BrainDTech expects to obtain first revenue from pathology specific pattern licencing starting from 2019. Support to R&D In the meantime, drug discovery service activity to third parties with proprietary know how on microvesiclce isolation can be provided Pathology specific licencing 2016 2017 2019 2018

BrainDTech info E. Ongini F. Bianco N. Tonna BrainD nDTec ech h srl OpenZone Via Ariosto 21 20091 Bresso – MI Italy Tel: +39-02-84269000 info@braindtech.com Brain n DTech srl www.braindtech.com Registr trati ation on date: e: 21/7/2016 VAT T number ber: : 09593150965 Shar are e capi pital al: 576 k €