ProMIS Neurosciences: therapies for neurodegenerative diseasebased on a proprietary discovery platform

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Toronto Stock Exchange (TSX) Ccker: PMN.TO January 2019OTCQB Ccker: ARFXF

Forward looking statement: safe harbor

This slide deck may contain certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company’s current beliefs as well as assumptions made by and information currently available to it as well as other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this slide deck. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings available online at www.sedar.com. Actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

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ProMIS Neurosciences Overview• Growing portfolio of antibody therapies targeting the root cause of

neurodegenerative diseases like Alzheimer’s, Parkinson’s, ALS• Unique discovery platform enabling creation of highly selective antibodies at

the molecular species level, creating antibodies with a better selective binding profile than competitive antibodies – “best in class”

- traditional antibody creation strategies ineffective• Biomarker based development strategy, looking for a therapeutic impact on

disease pathology both clinically and preclinically, enabling rapid and cost effective development, and early value inflection points

• Highly experienced management team• TSX listed – PMN.TO • OTCQB listed - ARFXF

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ProMIS portfolio of antibodies targeting the root cause of neurodegenerative diseases:

Target identification Antibody generation

PMN310 - IND Enabling work underway

Preclinical validation IND enabling

Lead Antibody Selection

Lead Antibody Selection

Novel targets idenDfied

ProMISTechnology Platform:

Rational Design of highly

selective mAbsat the molecular

species level

Neurodegen(AD, other dementias, Parkinson’s,

ALS)

Other

Amyloid betaAlzheimer’s

Alpha -synuclein Parkinson’s &

Lewy Body Dementia

TDP43: ALS & Frontotemporal

Dementia

TauAlzheimer’s

��Phase 1★�

SOD1: ALS SelecDve AnDbodies Validated

★ Multiple dose phase 1 to include biomarkers for early evaluation of potential signs of neuronal protection

Parkinson’s Lewy Body Dementia

Alzheimer’s

ALSFTD

Neurodegenerative diseases: in need of disease modifying therapy attacking the root cause

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Disease Modifying TherapyNo Therapy “Marginal”

Symptomatic TherapyEffective Symptomatic

Therapy

Alzheimer’s

ALS

Parkinson’s

FTD

CTE

LBD

FTD = Frontotemporal dementiaLBD = Lewy Body dementiaCTE = Chronic traumatic encephalopathy

ProMIS is capitalizing on recent advances that are changing the game in neurodegenerative disease

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Advances in Scientific Understanding of Disease

Advances in Development Efficiency

ProMIS Unique Antibody Design

Platform

ProMIS starts with a biological understanding of disease at the protein species level based on tremendous recent advances in science

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Amyloid Beta

Alpha Synuclein

TDP43

tau

SOD1 These proteins/peptides are implicatedin neurodegenerative diseases…

AnAbody design requires understanding the different roles of different species of these proteins/pepAdes..

Monomer Toxic Oligomers

Inert Soluble

Aggregates

Toxic Soluble

Proto-Fibrils

Physiologic Soluble

Aggregates

Insoluble Plaque or

Fibrils

Neurodegenerative protein molecular species start as monomer and then aggregate…..into soluble forms with different biologic roles…..

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Insoluble Plaque, Fibrils

Monomer

Physiologic aggregates

Toxic oligomers

Inert aggregates

ProMIS is developing a portfolio of antibody therapies targeting the root cause of neurodegenerative diseases – protein misfolding

• Our platform goes beyond the “general” protein: we target at the molecular species level

• Different molecular species of alpha synuclein, amyloid, tau, TDP43, etc. have different biologic roles

- Some are toxic- Some are important in normal physiology- Some are inert

• Using our unique, proprietary design capabilities, we engineer and “tune” antibodies with the desired binding profile – “disease selective” antibodies

- Strong binding to toxic species (arrest disease process)- Avoid binding to physiologically important species (avoid harm)- Minimize binding to inert species (don’t waste therapeutic ammunition)

• ProMIS Discovery Strategy: DEGREE OF SELECTIVITY = DEGREE OF SUCCESS

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Model of Beta-amyloid

ProMIS unique antibody design platform allows us to “tune” antibodies with the desired binding profile, then assess functional performance and comparative binding to select a lead candidate

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Scientific Literature suggests an optimal “disease selective”

binding profile

Avoid physiologically important species

Minimize binding to inert species

Strong binding to toxic species

“ Tune” epitope to generate numerous an>body candidates

with disease selec>ve binding profile

Screen for evidence of functional benefit:

blocking neurotoxicity and

propagation

Compare binding selectivity and

strength to competitive antibodies

Phase 1 studies with biomarkers

If the scientific understanding of disease evolves further, ProMIS can uniquely “tune” epitopes and generate new

antibodies with the updated desired binding profile

Lead Candidate(s)

Different molecular species of alpha synuclein play different roles….some are the root cause of Parkinson’s…….others are physiologically important

• Recent evidence suggests that a-syn toxicity resides primarily with the oligomeric form vs monomers or insoluble fibrils1,2

• Aggregated a-syn shown to propagate from cell to cell in a prion-like manner in vitro3 and in vivo4

• Recent findings suggest that physiological a-syn tetramers inhibit aggregation and must be preserved for normal a-synhomeostasis5-7

• Maximal efficacy expected to require antibodies selective for the toxic forms of a-syn, oligomers and/or small soluble fibrils, while avoiding physiologic forms of a-syn

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1Fusco et al, 2017, Science; 2Westphal & Chandra, 2013, J Biol Chem; 3Choi et al, 2018, Cell Reports; 4Peelaerts et al, 2015, Nature; 5Nuber et al, Neuron, 2018; 6Dettmer et al, PNAS, 2015; 7Foulds et al, Scientific Reports, 2013

oligomers

Toxicity of a-syn oligomers1

Nuber et al 2018

Alpha synuclein biology presents a unique challenge for an antibody

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Optimum Binding Profile

Avoid Tetramer

Avoid Monomer

Bind Toxic Oligomers

Bind Soluble Fibrils

Minimize Binding Other Oligomers

Minimize Binding Lewy Bodies

PMN unique technology platform has created antibodies that achieve the targeted binding profile….better than other a-synuclein-directed antibodies

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Target Proper+es PMN Antibodies

Prothena/Roche

BioArctic/ABBVIE

Neurimmune/Biogen

No binding to monomers X +/- X

No binding to physiological tetramers

X +/- X

Binding to toxic oligomers/small soluble fibrils

Binding to native toxic a-synin LBD/PD brain extract

Little or no binding to insoluble fibrils (Lewy bodies)

X X X

Deal 2013$645MM + Profit

Share

Deal 2016$735MM + Royalties

ProMIS Alpha Synuclein Program

• Numerous ProMIS antibodies with target selective binding profile

• ProMIS antibodies differentiated – superior selectivity to competitive antibodies

• Goal: partnering deal in 2019 - encouraging progress to date

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Alzheimer’s Disease: Soluble toxic Ab oligomers, not plaque or monomers, are the most neuropathogenic Ab species

• Synapse abnormalities and memory impairment correlate poorly with plaque burden in human and mouse AD1,2

• Aβ monomers and Aβ insoluble fibrils (plaque) have little or no demonstrable toxicity in vitro or in vivo3-5

• Soluble Aβ oligomers show the highest degree of neurotoxicity6

• Toxicity in primary neuron cultures and brain slices3,5,7-9

• Induction of cognitive impairment in rodents3,4,10

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1Jacobsen et al, 22006, PNAS; 2Brier et al, 2016, Science Trans Med; 3Shankar et al, 2008, Nature Med; 4Cleary et al, 2005, Nature

Neuroscience; 5Hong et al, 2016, Science; 6Benilova et al, 2012, Nature Neuroscience - Review; 7Lacor et al, 2007, J Neuroscience; 8Jin et

al, 2011, PNAS; 9Lauren et al, 2009, Nature; 10Balducci et al, 2010, PNAS

Synaptotoxicity of human Ab oligomers on hippocampal neurons in vitro75min 6h 24h 24h control

Monomers Oligomers Fibrils

Normal Monomers Oligomers Fibrils

Ab species injected

In vivo impairment of recognition memory by Ab oligomers, not monomers and not fibrils10

Binding the right form of amyloid beta is critical: the toxic oligomer is the targetand PMN310 is the first oligomer selective antibody therapeutic

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Aducanumab• Phase 2 success• ARIA-E side effect

Solanezumab• Phase 2 failure• Phase 3 failure

Bapineuzumab• Phase 2 failure• Phase 3 failure• ARIA-E side effect

MONOMERS- binding wastestherapeutic ammunition

FIBRILS (Plaque)- binding wastestherapeutic ammunition- contributes to ARIA-Eside effect

OLIGOMERS*- the right target

PMN310• Selective binding to

oligomers-> Expected improvement in

efficacy & safety

* Synthetic oligomers

PMN310 shows superior binding to toxic oligomer-enriched fraction from human AD brains vs other antibodies directed against amyloid beta

17Human

ized PMN31

0

Aducanumab

Bapineu

zumab

huIgG10

10

20

30

40

50

Bin

ding

Res

pons

e (R

U) • Binding of antibodies to the toxic oligomer-

enriched LMW fraction of soluble human AD brain extract was evaluated by surface plasmon resonance (SPR)

• Results representative of over 10 SPR runs with extracts from 11 different AD brains

• huIgG1 = Background control

Source for comparative antibodies: Creative Biolabs

PMN310 has the molecular species selectivity to be best in class…

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Selectivity

Failed Studies Phase 2 Posi5ve Signal Poten5al “Best in Class”

Binds Monomer, or all species

Selective forAggregatedAmyloid

Selective forAmyloid toxicoligomer

All BACE inhibitorsBapineuzumabSolanezumabCrenezumab

AducanumabBAN2401

PMN310

A new development paradigm for Alzheimer’s could dramatically improve cost, risk….and success

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Old Model

Preclinical models- transgenic mouse- plaque reduction

Phase 2 studies - small

- no clear signal

Phase 3 studies- first POC?

New Model

Preclinical models based on toxic oligomer

- in vitro, in vivo

Phase 1 studies with biomarker initial POC

Phase 2 studies with biomarker and clinical POC

8 Years..

$1BB…

2-3 Years

$20MM

PMN310 blocks oligomer propagation and neurotoxicity in vitro

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Complete inhibition of oligomer* propagation in vitro

0 1 0 2 0

0

2 ´ 1 00 5

4 ´ 1 00 5

6 ´ 1 00 5

I n c u b a t i o n T i m e ( h r s )

Re

la

ti

ve

F

lu

or

es

ce

nc

e

Un

it

s

A ß 4 2 + 3 0 5 - 6 1A ß 4 2

Incubation time (hrs)

Rela

tive

fluor

esce

nce

units Ab42 Ab42 + PMN Mab

Inhibition of Ab oligomer* toxicity in vitro

CTL AβO 5:1 1:1 1:2 5:1 1:1 1:240

50

60

70

80

90

100

110

120

Cel

l Via

bilit

y (%

of c

ontr

ol)

AbO + PMN mAb PMN mAb alone

(Thioflavin-based assay) (Primary mouse cortical neurons)

Normal propagation

Inhibi0on by PMN an0body

*Synthetic oligomers

AbO +/- Mab Novel Object Recognition Assay• Control mice remember a familiar object when re-exposed

to it and spend more time exploring a new object

• Oligomer-injected mice lose the ability to discriminate

between known and novel objects and spend equivalent

amounts of time exploring both

7 days

-0.2

0.0

0.2

0.4

0.6

Vehicle AβOPMN310+ vehicle

PMN310+ AβO

Disc

rimin

atio

n In

dex

#

* *

Discrimination index = (Time exploring new object – time exploring familiar object) / total exploration timeResults press released January 9, 2017, www.promisneurosciences.com 21

N=12 per arm, *different from AβO (p < 0.05), #different from vehicle (p <0.05)

Administration of PMN310 to mice: prevents loss of short-term memory formation caused by toxic oligomers, by saving mouse neurons

THE RESULTSTHE EXPERIMENT• Mice are tested for discriminating objects after

brain injection of:

• Buffer (vehicle) - normal response

• Toxic Aβ oligomer

• PMN310 and buffer (vehicle)

• PMN310 and Aβ Oligomer

In vivo improvement of hippocampal synaptic and inflammation markers suggests cognitive benefit came from preventing neuronal damage

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Decrease in hippocampal marker of inflammation

Vehicl

eAβ

O

PMN Mab

+ AβO

PMN Mab

+ Vehicl

e0.0

0.5

1.0

1.5

TNF-α

(pg/

ug to

tal p

rote

in) TNF-a

#

*

#* #*

Vehicl

eAβ

O

PMN Mab

+ Aβ

O

PMN Mab

+ Veh

icle

2

3

4

5

6

7

8

9

PSD

-95

(pg/

ug to

tal p

rote

in)

Vehicl

eAβ

O

PMN Mab

+ Aβ

O

PMN Mab

+ Veh

icle

0

5

10

15

20

25

SNA

P25

(pg/

ug to

tal p

rote

in)PSD-95 SNAP25

#

*

#

*#

#

*

#

#*

Preservation of hippocampal synaptic proteins

*Different from Vehicle (p<0.05); # Different from AbO (p<0.05)

Draft phase 1 trial design: with patients in higher dose arms, biomarkers can give a signal suggesting therapeutic benefit early in clinical development

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0.3mg/kg - HNV

Dose Escalation Design

1 mg/kg – HNV/AD pa=ents

3 mg/kg –AD Patients

10 mg/kg –AD Patients

20 mg/kg –AD Patients

80 mg/kg –AD Patients 3 Month placebo control, 9 month extension

Growing list of validated biomarkers (blood, CSF)

Possible to see biomarker trends suggesting dose dependent treatment effect (preserving neurons, synapses)

HNV = healthy normal volunteers

PMN310 preclinical data a direct proxy for clinical biomarker evidence in Phase 1 study

- In vivo mouse model - In vitro neurotoxicity

40 mg/kg –AD Pa=ents

Neurofilament light (NfL) is a measure of the rate of neuronal death…..Dose dependent reduction in NfL could be an early signal of treatment effect…

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Pg/ml

60

40

20Normal

Pathological MCI

FTD

AD

Sources: from AAIC 2018 ABBVIE, Wash U, U Sorbonnne; Rohrer et al, 2016 AAN; Mattson et al, JAMA Neurology 2017

Hypothetical example – Phase 1 biomarker readout for PMN310 could show a dose dependent reduction in neuronal death….addressing the root cause…

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NfL

100*

* 100 = patient baseline value

Months1260

Placebo/ Large natural history dataset

3 mg/kg dose of PMN310

10 mg/kg

20 mg/kg

40 mg/kg

80 mg/kg

Placebo dataset initiative in 2019 with consortia – create historical control as a ”common asset”

ProMIS PMN310 program in AD

• The toxic oligomer of amyloid beta is the root cause of AD, and the target for therapy

• PMN310 has superior selectivity for the human toxic oligomer in comparison to competitive antibodies – best in class

• Goal: Clinical data showing a treatment effect in 2020, using biomarkers

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The science tells us the key to “best in class” disease modifying therapies for neurodegenerative diseases…

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Degree of Selectivity = Degree of Success

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The three largest products in industry history were not first in class, but “best in class” …..ProMIS is following the “best in class” playbook in neurodegenerative disease

• Taking advantage of “proof of biology” developed by earlier products; of advances in science

• Using ProMIS proprietary science platform to design an improved product, which may yield superior clinical results

Lipitor Humira Sovaldi/Harvoni (Pharmasset)Cholesterol RA, Crohn’s Hepatitis C1996 2003 2014

PeakSales $BB’s

$12BB$16BB

$25BB

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ProMIS portfolio of selective, best in class antibodies in neurodegenerative diseases: significant near and medium term value creation opportunities in AD, ALS, PD

Target identification Antibody generation

PMN310 - IND Enabling work underway

Preclinical validation IND enabling

Lead Antibody Selection

Lead Antibody Selection

Novel targets identified

ProMISTechnology Platform:

Rational Design of highly

selective mAbsat the molecular

species level

Neurodegen(AD, other dementias, Parkinson’s,

ALS)

Other

Amyloid betaAlzheimer’s

Alpha -synuclein Parkinson’s &

Lewy Body DemenRa

TDP43: ALS & Frontotemporal

Dementia

TauAlzheimer’s

��Phase 1★�

SOD1: ALS Selective Antibodies Validated

★ Multiple dose phase 1 to include biomarkers for early evaluation of potential signs of neuronal protection

Partnering Discussions:

Potential deals in 2019

PotenRalClinical proof of concept, biomarkers, 2020, 2021

ProMIS Neurosciences: summary

• ProMIS has applied its unique antibody design capability to create differentiated antibodies with a selective binding profile capitalizing on the latest scientific understanding of neurodegenerative diseases

• ProMIS is in the vanguard of applying the “new model’ of development, using up to date preclinical models and seeking early clinical signals with biomarkers

• Numerous potential catalysts in 2019, including potential partnering deals

• Potential clinical data in 2020, 2021 with antibodies addressing the root cause of Alzheimer’s

• NASDAQ listing planned in 2019

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Thank You

Eugene Williams, Executive Chairmaneugene.williams@promisneurosciences.com+1 (617) 460-0978

Website: www.promisneurosciences.comTwitter: https://twitter.com/ProMISincLinkedIn:https://www.linkedin.com/company/promis-neurosciences

Please feel free to contact us with any additional questions.

Elliot Goldstein, MD, CEOelliot.goldstein@promisneurosciences.com+1 (415) 341-5783

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Name

Experienced leadership team

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Prior ExperienceTitle Years of Experience

Executive Chairman

CEO

Chief Science Officer

Chief Physics Officer

CFO

Chief Development Officer

25+

25+

25+

20

25+

25+

§ Former SVP at Genzyme, with senior roles integrating commercialization, drug development, and deal making

§ Recently the CEO of Dart Therapeutics, an Orphan Disease drug development company

§ Founder and director of Adheris, which became the largest company in the patient adherence/compliance area

§ Held positions as SVP of Strategic Product Development at SmithKline Beecham (now GSK)

§ Chief Operating Officer and Chief Medical Officer of Maxygen§ Chief Operating Officer at DART Therapeutics

§ Holds the Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases,

§ Serves as the Director of the University of British Columbia ALS Centre,

§ Awarded the Jonas Salk Prize for biomedical research in 2000

§ Professor at UBC in the Department of Physics and Astronomy since 2001§ Appointed as the Canada Research Chair in Theoretical Molecular Biophysics§ Associate member of the Genome Sciences and Technology Program, the

Bioinformatics Program, and the Institute for Applied Mathematics at the University of British Columbia

§ Founding Managing Director of Danforth Advisors§ Served as the Chief financial officer of Homology, Inc, GenePeeks,

Inc., Transkaryotic Therapies, Inc., Cidara, Inc., Apellis, Inc. and Stealth BioTherapeutics, Inc.

§ Former VP of Research at Genzyme§ Associate Immunopathologist at SmithKline Beecham where she

established an Immunotoxicology program§ Her work has resulted in over 60 scientific publications and multiple patents

Gene Williams

Elliot Goldstein

Neil Cashman

Steven Plotkin

Dan Geffken

Johanne Kaplan

James Kupiec Chief Medical Officer 25+

§ Former VP, Global Clinical Leader for Parkinson’s disease, and Clinical Head of the Neuroscience Research Unit for Pfizer, Inc

§ Clinical focus on development of therapies for neurodegenerative disorders§ Held positions at Sanofi-Synthelabo and Ciba-Geigy Pharmaceuticals

Name

Anthony Giovinazzo

Richard Gregory

Bill Wyman

Johannes Roth

Pat Kirwin

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Independent board of directors

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Prior ExperienceYears of Experience25+

25+

15+

§ President and CEO of Sunovion CNS Development Canada ULC

§ President, CEO and a Director of Cynapsus Therapeutics from 2009 to 2016 and one of the three original inventors and patent holders of the company’s Parkinson’s focused technology

40+

§ Chief Scientific Officer & Executive VP for Research at ImmunoGen

§ Held a variety of roles at Genzyme and Sanofi-Genzyme, including Vice President for Gene Therapy, Head of Corporate Research and Head of R&D

§ Co-founded the management consulting firm, Oliver Wyman & Co

§ Former President of the Management Consulting Group called Booz Allen and Hamilton

§ Founding director and partner at FiveT Capital Holding AG§ A board member of Insilico Biotechnology AG

§ Senior partner at Kirwin LLP§ Advises and represents businesses in a range of industries and

sizes from local to multinational30+

Name

34 6

Prior ExperienceYears of Experience

Scientific Advisory Board (SAB)

Business Advisory Board

Todd Golde, MD, PhD.

Lary Walker, PhD.

Bill Mobley, MD, PhD.

§ Director of the Center for Translational Research in Neurodegenerative Disease at the University of Florida

§ Associate Professor of Neurology and Research Professor at Emory University Yerkes National Primate Research Center

§ Dean for Neurosciences Initiatives, Distinguished Professor of Neurosciences, and Florence Riford Chair for Alzheimer Disease at the University of California, San Diego

Mara Aspinall, MBA § Executive Chairman of GenePeeks§ Former President and CEO of Ventana Medical Systems, a division

of Roche Group, a worldwide leader in the development and commercialization of tissue-based cancer diagnostics

Nigel Burns, PhD. § CEO and Founder of SweetSpot Therapeutics Ltd§ Served as Senior Vice President of Cambridge Antibody Technology

Michael Higgins, MBA § Currently an Entrepreneur-in-residence at Polaris Partners§ Previously at Genzyme, served as VP Corporate Finance & VP

Business Development. Was involved with multiple business units, including Cell Therapy, Gene Therapy and Orphan Diseases

25+

20+

25+

25+

25+

20+

Sharon Cohen, MD 20+ § Medical Director & Principal Investigator of Toronto Memory Program§ FRCPC in neurology from Royal College of Physicians of Canada and

a fellowship in Behavioural Neurology from the University of Toronto

Rudy Tanzi, PhD. 20+ § Professor of Neurology at Harvard University, Vice Chair of Neurology, Director of Genetics & Aging Research Unit, Co-Director McCance Center for Brain Health at Mass General Hospital