EARLY DIAGNOSIS OF BRAIN DISEASES via liquid biopsy,

based on miRNA patterns

in microglial microvesicles

BrainDTech Team

Dr. Fabio Bianco, PhD – Chief Executive Officer

• Medical Biotech, Pharmacology• President/CSO @NeuroZone• +10yr in Biotech/Pharma• Board Member

Dr. Noemi Tonna, PhD – Lab Manager

• Medical Biotech, Pharmacology• Lab Manager@NeuroZone• +10yr in drug discovery

Dr. Pietro Conti, MD, MBA – President

• Medicine & MBA• Founder/CEO several startups• Director Health Int’l Projects @UN• Board Member

Dr. Elisabetta Borello, PhD – Board Member

• Economics-Bocconi Univ., Milano• +30 yrs in Healthcare Information

Management Systems • Founder /Board member many biotechs

Dr. Ennio Ongini, PhD – Chief Scientific Officer

• Pharmacology• 20yrs R&D Director Schering Plough• 15 yrs VP Research Nicox SA• +200 peer reviewed papers

Dr. Laura Ferro, MD, MBA – Board Member

• Medicine & Psychiatry• MBA @ Bocconi Univ., Milano• Top 10 innovative women managers in Italy • Founder /CEO several biotechs (including

Gentium, IPO at Nasdaq

Dr. Carlo Frati, MBA – Board Member

• Economics - Bocconi Univ; MBA, INSEAD• McKinsey & Co. (2000-2016): Partner• Capital Shuttle S.p.A. (2016): CEO• Banca Consulia (2017-present): CFO

Currently, diagnosis of brain diseases is carried out observing clinical symptoms,

which occur when most of the neurodegeneration has already occured

The issue (need)

Brain DEGENERATIONBrain INFLAMMATION CLINICAL SYMPTOMS

10 – 15 years

Brain INFLAMMATION

BrainDTech proposal

BrainDTech represents a disruptive approach to brain disease diagnosis

because it detecs a signal (MicroRNA in microvesicles)

released by microglia before clinical manifestation.

Neuroinflammation activates MICROGLIA

Activated microglia produce MICROVESICLES

Microvesicles contain microRNA

Microvesicles can be found in LIQUID BIOPSY

MICROVESICLES FROM MICROGLIA

Bianco et al EMBO J 2009

BrainDTech added value

MICROVESICLES

can be isolated

from liquid biopsies

Clinical data show that there are

more Microvesicles in the Cerebrospinal Fluid

of Alzheimer’s Disease patients

with respect to pre-Alzheimer,

or Mild Cognitive Impaired patients(Agosta et al ann Neurol 2014)

miRNAs

can be analyzed

in MICROVESICLES

We have observed that in different in vitro models,

miRNA from microglial microvesicles

are differently up (green) or down (orange) regulated,

creating pathology-specific patterns.

miRNA patterns

are SPECIFIC

for each PATHOLOGY

We have observed that in each pattern there are

specific miRNA which are exclusively up or down

regulated in a pathological model, thus creating

pathology specific patterns,

which we have patented.

BrainDTech IP position

Pathology specific patterns to be outlicenced

for early diagnosis or companion diagnostics

in drug development

Since miRNA control several biological processes,

we plan to study the miRNA patterns obtained

and identifty novel therapeutical targets

PATHOLOGY-SPECIFIC PATTERNS

DEVELOPMENT

NOVEL THERAPEUTIC TARGETS

IDENTIFICATION

EARLY DIAGNOSIS

COMPANION DIAGNOSTICS

PATENT STRATEGY

2015/11 - Italian patent submission (AD, PD, ischemia)

2016/07 - PCT patent extension

2016/11 - Claim extension (+20 pathologies)

PATENTS

The market: Diagnostics in brain diseases

GLOBAL BIOMARKERS MARKET

$24

Billion

in 2015

$45,55

Billion

by 2020

CURRENT miRNA

FOCUS AREAS

CANCER CARDIO

$1

Billion

by

2019

GLOBAL miRNA MARKET

2010

Acquisition of Avid Radiopharma:

imaging agent for Abeta plaque

detection• $300 million cash

• Up to $500 million in milestones

2012

Acquisition of AD test from Memory Dx:

Enables differentiationAD vs dementia• $18 million in equity shares

• Development milestone after phase 2

• 9% royalties on sales

2014

Lipid test for AD

in blood

Nature Methods 2014

AFTER CLINICAL MANIFESTATION

CURRENT STATE OF ART

BEFORE CLINICAL

MANIFESTATION

MA

RK

ET A

PP

LIC

ATI

ON

S

BIOMARKER MARKET FIGURES

The market for miRNA diagnostics is at

a starting point, currently only focused

on 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 fulfills an unmet need of pre-symptomatic diagnosis,

as well as specific companion diagnostic in drug development

2016

The market: competition

CANCER

BRAIN

Few innovative players in cancer diagnosis.

Brain solutions are currently focusing on

circulating miRNA in plasma for detection of AD

The main issue with circulating miRNA –based approachesis lack of specificity, given miRNA can be produced

by many different cell types

BrainDTech approach is revolutionarybecause 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 breakthroughbecause recent scientific evidence (Plog et al J.Neurosci 2015)

suggest that these vesicles could be present alsoin easily accessible biopsies such as plasma

(this hypothesis is currently being validated in our lab).

PoC AD vs MS Clinical PoC AD clinical study

2017 2018 2019

Cerebrospinal Fluid

Microvesicle isolationMicrovesicleidentification

miRNA analysis

Revenue stream

Blood

Pathology specificlicencing

2

Access to DATABASE

3

Outlicencing of non-core knowhow (microvesicle handling)

1

BrainDTech Development plan

BrainDTech info

BrainDTech srl

OpenZone

Via Ariosto 21

20091 Bresso – MI Italy

Tel: +39-02-84269000

info@braindtech.com

www.braindtech.comBrain DTech srl

Registration date: 21/7/2016

VAT number: 09593150965

Share capital: 576 k€

F. Bianco

N. Tonna

E. Ongini