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VLP TherapeuticsGaithersburg, MD, USA
Tocombat21st centuryglobalpublichealthproblems,wedevelopnextgenerationvaccinesagainst
InfectiousdiseasesandCancer
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
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,[email protected]:1-240-801-4456Direct:1-301-704-2427
THANK YOU
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