Capo Therapeutics, Inc.Vaccine Therapies for Debilitating Diseases of the Brain

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San Diego, CA

■ M. Flint Beal, M.D. – Dr. Beal is an internationally recognized authority on neurodegenerative disorders. He is the Chairman of the Department of Neurology and Neuroscience at Weill Medical College of Cornell University and Director of the Neurology service at the New York Presbyterian Cornell Campus. He joined the neurology faculty at Harvard in 1983 and was Professor of Neurology at the Harvard Medical School. Dr. Beal's research has focused on the mechanism of neuronal degeneration in Alzheimer's Disease, Huntington's Disease, Parkinson's Disease and amyotrophic lateral sclerosis (ALS). Dr. Beal is the author or co-author of more than 300 scientific articles and more than 125 books, book chapters and reviews and a member of many professional organizations, including the Institute of Medicine of the National Academy of Sciences.

■ Lon Schneider, M.D. - Professor of psychiatry, neurology and gerontology at USC. He directs the USC State of California Alzheimer’s Disease Center and the clinical core and pharmacology program of the USC NIH/NIA Alzheimer’s Disease Research Center. He has enormous expertise in clinical trials methods, instruments and rating scales for dementia trials, meta-analyses, and drug development. He serves on the steering committees of the NIH ADCS, the NIH ADNI, and the Alzheimer Prevention Initiative. He is internationally recognized in clinical drug development for AD, neuropsychiatric, and behavioral disorders, has led numerous clinical trials for AD and MCI therapeutics, consults with numerous development programs, participated in the design and operations of several early and later phase proprietary development programs for AD, and directed multicenter trials in AD and major depression.

SCIENTIFIC ADVISORY BOARD

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Scientific Advisory Board David Cribbs, Ph.D. - Professor in Residence, Neurology, UCI School of Medicine and Associate Director of

the MIND Institute at University of California, Irvine is an expert on age-related factors responsible for theinitiation and the progression of AD, antibody-mediated clearance of Aß, identifying risk factors associated withimmunotherapy in elderly AD patients. He has been appointed to the Department of Veterans Affairs JointBiomedical Laboratory Research and Development and Clinical Science Research and Development Services.Dr. Cribbs is longtime collaborator of Dr. Agadjanyan and he is directly involved in their AD/PD vaccine projects.

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Key Statistics for Alzheimer’s Disease (AD) Epidemiology and Statistics

By mid-century, someone in the United States will develop the disease every 33 seconds.

5.3 million Americans have this disease, 44 million worldwide Cost of AD

$226 billion in the US (2015) and $604 billion worldwide $1.2 trillion projected in 2050

Current Market $6 billion for no effective treatments Should an effective treatment become available, the valuation is astronomical Therefore, Eli Lilly, Johnson & Johnson and Roche are actively buying

companies and developing their own programs. They are spending billions.

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Valuations in the AD Market

Year Developer Licensee/Buyer/Co-Developer Deal Type Deal size

(Millions)2016 Heptares Allergan Licensing $3,3002015 Avanir Otsuka America M&A $3,4702015 Trophos Roche M&A $5412015 Neurimmune Biogen Alliance $380

2014-2015 AC Immune Janssen Pharmaceutical Co-Development $5092014 Bionomics Merck Licensing $5062014 Astra Zeneca Lilly Licensing $5002014 iPierian Bristol- Myers M&A $7252013 Rinat Pfizer Licensing $5002012 AC Immune Roche/Genentech Licensing $418

2008 Affiris GlaxoSmithKline Licensing $5502008 Medivation Pfizer Licensing $225+$500

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Valuations as a Function of Maturity

Capo Now

Capo After Investment

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Business Strategy

Capitalize on tremendous need for AD treatment Capo Therapeutics IP has some of the most promising pre-clinical data

available and is based on extensive R&D supported by the NIH IND’s are ready to be written File IND’s and begin Phase 1 trials Build to sell Help patients

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Capo’s Scientific Strategy Many ongoing clinical trials using vaccines for AD

All of these vaccines have failed and those still ongoing will fail DUE TO DIFFICULTY TO GET HIGH TITERS OF THERAPEUTIC ANTIBODIES IN HUMANS (AS OPPOSED TO MICE)

Capo IP has overcome this obstacle (competitive advantage) We have combined three key elements: Strong Multi-TEP platform, Novel

proprietary adjuvant (Advax) and Aβ immunogen Using this, we can generate titers of therapeutic antibodies 1000x higher than

competitors – including in monkeys We can use this cocktail for AD and also for Parkinson’s Disease Pre-clinical and experimental animal data rock solid. Pre-IND with FDA

suggested that FDA will not question our clinical application

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Aβ tau and/or tau/Aβ

α-synAβ &/or tau

“Targeting the Right Pathology at the Right Time” Vaccination strategy is to target appropriate pathological molecules, such as Aβ, tau, α-syn & their combinations at specific disease stages

CAPO’S TREATMENT STRATEGY

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Vaccine Sponsor B cell epitope

Carrier/vaccine platform/

adjuvant

Anti-Aβ B cells immune responses

Mice Monkeys Humans

Status**

ACC001 Pfizer/Elan/Janssen

Aβ1-7 Dithteria toxin/QS21

NR* +/- Discontinued

V950 Merck Aβ1-15 Carrier unknown+ISCOMATRIX

NR Discontinued

AD02 Affiris &GlaxoSmithKline

Aβ1-6 KLH/Alum + NR +/- Discontinued

AD03 Affiris &GlaxoSmithKline

Aβpyroglutamate

KLH/Alum NR NR NR Discontinued

CAD106 Cytos/Novartis Aβ1-6 Bacteriophage QβAlum

+++ +/- -/+ Phase 2completed

ACI-24 ACImmune/Roche/Genentech

Aβ1-16 Liposome/MPLA +++ NR NR Phase 1/2

UB311 United Biomedical Inc Aβ1-14 2 Th epitopes (UBITh Aum/CpG)

NR +++ NR Phase 2 initiated in 2015

LU AF20515

Lundbeck/OtsucaTested IMM/UCI

Aβ1-12 P30/P2 TT Thepitopes (developed

by IMM group)

+ ++ NR Phase 1

AV1959 Capo Therapeutics 3 copiesAβ1-11

MultiTEP platformAdvax/CpG for mice

DNA for monkeys

+++++ +++ not started IND Pending

MultiTEP Immunogenicity Comparison Table

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1 0 0

1 0 0 0

1 0 0 0 0

Antibody responses in Tg2576 vaccinated with AV-1959R formulated in AdvaxCpG vs LU AF20515+ Alum

(600 times stronger)

Ant

i-Aβ

antib

ody

conc

. (µg

/ml)

Tg2576 mice T5x mice

LU AF20515 AV-1959R

3µg/ml 1800µg/ml

Antibody titers in Tg2576 mice

(Davtyan et al., 2014) 11

ACI-35 AV-1980R

1:100 1:160000

Antibody titers in Tau PS19 Tg mice

Ant

i-tau

ant

ibod

y le

vel

(OD

450)

Tg4510 mice PS19 mice T5x mice

Vaccinated with AV-1980R+AdvaxCpG.

Sera was diluted 1:160000

Antibody responses in PS19 vaccinated with AV-1980R formulated in AdvaxCpG vs ACI-35+ Alum

(1600 times stronger)

0.0

0.5

1.0

1.5

2.0

12

0

1 0

2 0

3 0

4 0

5 0

AV-1959R MultiTEP-Based Epitope Vaccine Prevents Cognitive Dysfunction and Aβ-plaques in APP/Tg Mice

************

******

Esca

pe L

aten

cy, s

ec

Days of Training

The escape latency to reach the platform

Non-vaccinatedIrrelevant antigen

AV-1959R vaccinated

Wild-type

1 2 3 4 5 6 7 8 9 1 0 1 1 1 20

2 0

4 0

6 0

8 0

0

5

1 0

1 5

2 0

2 5

6E10

-pos

itive

Aβ-

load

Control AV-1959R

Num

ber o

f ThS

-pos

itive

pl

aque

s

Control AV-1959R

********

13

0

1 0 0

2 0 0

3 0 0

AV-1980R MultiTEP-Based Epitope Vaccine Prevents the Development of Motor, Learning and Memory

Deficits in Tau/Tg Mice

**

Late

ncy

to fa

ll (s

econ

d)

Rota-Rod Performance Test

ACCELERATION

Non-vaccinated AdvaxCpG AV-1980R/ AdvaxCpG

Normal Tau/Tg Tau/Tg

***

0

1 0

2 0

3 0

4 0

Y-maze activity: PERCENT of TIME SPENT in the NOVEL ARM

% o

f tim

e sp

ent i

n N

ovel

Arm

Treatment Non-vaccinated AdvaxCpG AV-1980R/ AdvaxCpG

Mice Normal Tau/Tg Tau/Tg

****

Learning and Memory Motor

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MultiTEP Platform: Universal Th cell epitopes: synthetic (PADRE) or TT (P epitopes), HBV (nc and sAg) and Flu (MT)

P23 P21 P30PADRE HBsAgHBV nc MTP32 P2 P7 P17 P28

Active Component3 copies of Tau2-18

B cell epitopeAV-1980R

MultiTEP Platform

MultiTEP-based AD Epitope VaccineTargeting Tau

Targeting AβActive Component3 copies of Aβ1-11

B cell epitope

P23 P21 P30PADRE HBsAgHBV nc MTP32 P2 P7 P17 P28

AV-1959RMultiTEP Platform

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Capo’s Therapeutics Pipeline

Disease Vaccine Target epitope

Type of Vaccine(DNA or Protein)

Pre-clinical Immunogenicity &

Efficacy

Pre-clinical Safety IND

Phase I Trial

AD AV-1959D N terminus of Aβ1-11 DNA

DONE

Funded by NINDS

R01 and U44

Ongoing

Funded NIA U01

Funded

by NIA

U01

AD AV-1959R N terminus of Aβ1-11

Protein + Advax CpG

adjuvantDONE

Funded by NINDS

R01

*

ADAV-1980R

AV-1980DN terminus of Tau2-18

Protein + Advax CpG

adjuvant

DNA

DONE

Funded by NINDS

R01

*

Lead Vaccine Products

Use of funds16

Capo Therapeutics Pipeline (cont’d)Next Generation of Vaccine Products for AD/PD/DLB/FTD

Disease Vaccine Target B cell epitopeType of Vaccine

(DNA or Protein)

Pre-clinical Immunogenicity &

EfficacyPre- clinical

Safety IND

AD AV-1960CP Pyroglutamated Aβ3p-11Chemically

modified proteinIn progress

Funded by IMM * *

AD AV-1991CP Phosphorylated Tau396/404Chemically

modified proteinIn progress

Funded by IMM * *

AD AV-1992CP Acetylated TauK174Chemically

modified proteinIn progress

Funded by IMM * *

PD♯ AV-1947D a-Syn (Epitope 85-88) DNAIn progress

Funded by NIA R01

* *

PD♯ AV-1948D a-Syn (Epitope 109-126 ) DNAIn progress

Funded by NIA R01

* *

PD♯ AV-1949D a-Syn (Epitope 126-140) DNAIn progress

Funded by NIA R01

* *

PD♯AV-1950R

AV-1950Da-Syn (85-88/109-126/126-140)

Protein +Advax CpG

DNA

In progress Funded by R01 * *

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Milestones and Timing

Prepare and submit IND for AV-1959D (Q1 2017): Funding in place, toxicology studies ongoing, pre-IND meeting with FDA completed and another pre-IND FDA meeting will be scheduled after receiving safety/toxicology data (funds from NINDS U01)

Prepare and submit IND for AV-1959R (Q1-Q3 2017): Dependent on fundraising Prepare and submit IND for AV-1980R (Q3 2017): Dependent on fundraising Design Phase I clinical trial for AV-1959D, work with CRO’s to identify best partner,

begin Phase I (Q3 2017 – Q2 2018): Dependent on fundraising

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