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

• Degree in Medicine & MBA
• Director @several Health International

Projects in UN agencies (UNDP, WHO, UNICEF)

• Founder and CEO of several startups
• Dr. Pietro

tro Conti, ti, MD – Chief Financial Officer

• PhD in Pharmacology
• 20 yrs Research Director Schering

Plough

• 15 yrs VP Research Nicox SA
• Member of different evaluation

Commitees

• >200 peer reviewed papers, H-index 38
• Dr. Ennio Ongin

ini, , PhD – Chief Scientific Officer

• PhD in Pharmacology, Degree in

Biotech

• Founder of NeuroZone (President and

CSO)

• CEO of BrainDTech
• Director of Sanipedia Business Nursery
• >10 yr in Biotech/Pharma with

executive roles

• Dr. Fabio

io Bian ianco co, , PhD – Chief Executive Officier

• PhD in Pharmacology
• Degree in Medical Biotechnology
• Lab Manager in NeuroZone
• >10 yr expertise in cell culturing/ in vitro

drug discovery

• Dr. Noemi

i Tonna, , PhD – Lab Manager

• Degree in Economics @ Bocconi Univ.,

Milano

• >30 years expertise in Healthcare

Information Management Systems

• Founder & Board member of many

biotechs

• Dr. Elisa

sabetta ta Bore rell llo, MBA – Board Member

• Degree Medicine, Residency Neurology
• Master Epidemiology & Biostats @

Columbia University

• PhD in Neuroscience @ HSR
• Neurologist, Head of Laboratory of

Genetics @ HSR Institute

• > 120 peer-reviewed papers, PI of

National and EU funded grants

• Dr. Filipp

ippo Martin tinelli li Bonesch schi, i, MD – Scientific Advisor

• Currently, diagnosis of brain diseases is carried out ob
• bser

erving ing clinic linical al symptoms, which occur when most of the neurodegeneration has as alre ready ady occurr urred ed.

• For
• r exam

ample ple, Pa Park rkins nson

• n ‘s Disea

ease sympt ptom

• ms (trem

remor) r) mani anifest whe hen over er 70 70%

• f
• f dopa

paminer inergic gic neuro urons ns are dead ad (Park arkins inson

• n 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).

The issue (need)

Brain DEGENERA RATIO ION Brain INFLAMMATIO ION CLINICA CAL SYMPTOMS

10 – 15 years

BrainDTech proposal

Brain INFLAMMATIO ION  Neuroinflammation activates MICROGLIA LIA  Activated microglia produce MICROVESIC ICLES  Microvesicles contain microRNA  Microvesicles can be found in in LIQUID ID BIOPSY MICROVESICL ICLES FROM MICROGLIA IA

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

• ves

esic icle les released by microg roglia lia (the immune cells of the brain) years ears bef efor

• re

e any ny clinic inical al manif nifes estatio ion.

Bianco et al, EMBO J 2009

BrainDTech added value

MICROVES ESICLE LES S can be isolat ated ed from liquid biops psies es

Clinical data show that there are more re Microv rovesic icles les in the e Cereb rebros

• spin

pinal al Fluid id

• f

f Alzheimer’s Disea ease pat atien ients with respect to pre-Alzheimer,

• r Mild Cognitive Impaired patients

(Agosta et al ann Neurol 2014)

miRNAs can be analyzed ed in MICROV OVESIC ESICLES LES

We have observed that in different in vitro models, miRNA A from

• m micro

roglial glial micro rovesic icles les are e differe erent ntly ly up (gre reen) en) or down n (oran range ge) ) regu gulat lated ed, , creating pathology-specific patterns.

miRNA patter erns ns are SPEC ECIFI IFIC for each PATH THOLO LOGY

We have observed that in each pattern there are spec pecif ific ic miRNA whic ich are e exclus lusiv ively ly up or down n regu gulat lated ed in a pathological model, thus creating pathology specific patterns, which we have patented.

BrainDTech IP position

 2015/ 5/11 11 - Itali alian an paten ent submi bmissi ssion

• n (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

• n (PCT/

T/EP20 2016 16/06 06194 940) 0)

• 2016/

6/11 11 - Claim extension (Epilepsy, MS, Tourette Syndrome….+20 pathologies)

We have submitted the following patent: "Methods for diagn agnos

• sis

is, , prog

• gnos

nosis is and nd treat reatment nt monit itoring ring

• f neur

urolog

• logic

ical, neur urod

• deg

egene enera rativ ive e and d infla lammat ation ion – based disea eases via miRNA contained in micro roglia glial microv

• ves

esic icle les" Our strategy is to :

Develop pathology specific patterns to be patented and outlicenced for early diagnosis or companion diagnostics in drug development Since miRNA control several biochemical processes, we plan to study the miRNA patterns obtained and identifty novel therapeutical targets

Th The marke ket: t: Di Diagnos

• stics

ics in brain n diseas eases es

GLOBAL BIOMA OMARKERS MARKET $24 $24 Bill llion in 2015 $45,55 Bill llion by 2020 CURRENT T miR iRNA FOCUS AREAS CANCER CARDIO $1 $1 Bill llion by 2019 GLOBAL miRN RNA MARKET

2010 10

Acquisition of Avid Radiopharma: imaging agent t for Abeta ta plaque dete tectio ction

• $300 million cash
• Up to $500 million in milestones

2012 12

Acquisition of AD test from Memory Dx: Enable les diffe feren rentia tiatio tionAD vs vs dementia tia

• $18 million in equity shares
• Development milestone after phase 2
• 9% royalties on sales

2014 14

Lipid ipid test t for AD in bloo lood Nature Methods 2014

AFTER ER CLINICAL AL MANIFEST STAT ATION

CURRENT ENT STATE ATE OF ART

BEFOR ORE E CLINICAL AL MANIFEST STAT ATION MARKET APPLICATIONS 2016 16

BIOMAR MARKER KER MARKET KET FIGURES RES

The market for miRNA diagnostics is at a starting point, currently only focused

• n cancer and cardiovascular diseases,

but expected to grow exponentially in the upcoming years. 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 BRAIN

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

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

2016 2017 2018 2019

PoC AD vs PD PoC human CSF MV isolation MV identification plasma miRNA analysis AD vs PD clinical study

R&D Revenue stream

Services on MV isolation Support to R&D Pathology specific licencing

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. Then we will compare 2 indications (AD and PD), then we will proceed in stratifying patients. In parallel, we are testing the possibility of isolating microglial microvesicles from plasma. BrainDTech expects to obtain first revenue from pathology specific pattern licencing starting from 2019. In the meantime, drug discovery service activity to third parties with proprietary know how on microvesiclce isolation can be provided

BrainDTech info

BrainD nDTec ech h srl OpenZone Via Ariosto 21 20091 Bresso – MI Italy Tel: +39-02-84269000 info@braindtech.com www.braindtech.com Brain n DTech srl Registr trati ation

• n date:

e: 21/7/2016 VAT T number ber: : 09593150965 Shar are e capi pital al: 576 k€

• F. Bianco
• N. Tonna
• E. Ongini