VLP TherapeuticsGaithersburg, MD, USA

Tocombat21st centuryglobalpublichealthproblems,wedevelopnextgenerationvaccinesagainst

InfectiousdiseasesandCancer

Introduction

2016 GHIT GrantDevelopment of novel dengue virus-like particle (VLP) vaccines against all four serotypes

Professor Kouichi MoritaJapan

Director Tetsuro MatanoJapan

GHIT– A global partnership focused on translational development

Phase3Phase2 Approved

SanofiDengvaxia

NIAIDTV003/TV005

GSK/WRAIR/Fiocruz

TDENV-PIV

Phase1

MerckV180

NMRCTVDV

ButantanTV003

TakedaTDV

• VirusLikeParticles

• Virus-vectored

• NS1Protein

• DNA

• RecombinantFusion

Preclinical

Leading Dengue Vaccine Candidates

Subunit

WRAIRTDENV-LAVTDEN-PIV

Liveattenuated

Liveattenuated

Liveattenuated

DNA

Prime-boost

inactivated

Liveattenuated

Seronegative

Advantages of VLP Vaccines for Dengue

• VLP vaccine is appropriate for: Infants, children and adults

• Approved vaccine has only indicated for 9-45 year-old populations

0

100

200

300

400

500

600

700

DH

F C

ases

Age<12469111315

Dengue VLP

Native Dengue Virus

VLP Therapeutics Dengue Vaccine

VLP Therapeutics Dengue VLP Vaccine Concept

F108A

kDa75-

50-

E

Fusion LoopCellular

Membrane

VirusMembrane

Critical E Conformational ChangeDuring Viral Fusion

C E NS5NS3

prM

NS1

Nonstructural proteinStructural proteinNative Dengue

Dengue VLP

Results of GHIT – VLP Therapeutics Collaboration

: Preimmune: DNA_wild type: DNA_F108A: DENV VLP

DENV2 Against: DENV1

***

Nab

Tite

r (FR

NT 5

0)

10,000 ***

******

DENV4 DENV3

Detectionlimit

1,000

100

Nab

Tite

r (FR

NT 5

0)

10,000

1,000

100

Immunogenicity of VLP tetravalent Vaccine and DNA Vaccine in mice

12.5 µg each VLP +Alum

1.25 µg each VLP + Alum

0.125 µg each VLP +Alum

0 4 8 12 16 2010

100

1000

10000

0 4 8 1 2 1 6 2 01 0

1 0 0

1 0 0 0

1 0 0 0 0

Na

b T

ite

r (F

RN

T5

0)

0 4 8 1 2 1 6 2 0

1 0

1 0 0

1 0 0 0

1 0 0 0 0

w e e k s

Na

b T

ite

r (F

RN

T5

0)

0 4 8 12 16 20

10

100

1000

10000

w eeks

Results of GHIT – VLP Therapeutics CollaborationImmunogenicity of VLP tetravalent Vaccine in nonhuman primates (N=6)

DENV2 Against: DENV1

DENV3 DENV4

About VLP Therapeutics - Intellectual Property

Three Issued Patents Three Published Patent Applications

“DevelopmentofaNovelVirus-LikeParticleVaccinePlatformThatMimicstheImmatureFormofAlphavirus”ClinicalandVaccineImmunology,July2017,Volume24,Issue7

“Envelope-modifiedtetravalentdenguevirus-likeparticlevaccine:implicationforflavivirusvaccinedesign”JournalofVirology,December2017,Volume91,Issue23

About VLP Therapeutics – Publications“StructuralStudiesofChikungunyavirusmaturation”ProceedingsofNationalAcademyofSciencesoftheUnitedStatesofAmerica,December2017

“StructuralStudiesofChikungunyavirus-LikeParticlesComplexedwithHumanAntibodies:NeutralizationandCell-to-CellTransmission”JournalofVirology,February2016

“Cryo-EMstructureselucidateneutralizingmechanismsofanti-chikungunyahumanmonoclonalantibodieswiththerapeuticactivity”ProceedingsofNationalAcademyofSciencesoftheUnitedStatesofAmerica,November2015

Oncology

$300K SBIR Grant2017

MalariaDengue

$960K Grant2016

$2.4M Grant2016

$230K Grant2016

About VLP Therapeutics - Non-dilutive Funding

Life Science Grant 2015

Toxicology

Clinical TrialPhase I/IIa

Project Management

Manufacturing

Future GHIT CollaborationManufacturing and Clinical

JacobLichtChiefOperatingOfficerjlicht@vlptherapeutics.com240-421-9755

TherapeuticsVLPGaithersburg,MD,USA

WataruAkahata,PhDCo-Founder,CEO,CSOwakahata@vlptherapeutics.comTel:1-240-801-4456Direct:1-301-704-2427

THANK YOU

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