herphu-mab - effective therapeutic antibody … 2 titel s s s s s s | prof. dr. michael roggendorf...

HerpHu-mAb - Effective

therapeutic antibody against

Herpes Simplex Virus Infections

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Prof. Dr. Michael Roggendorf

Institute of Virology

University Duisburg-Essen

Germany

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2 | Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes Simplex Virus Infections

Stranska R, J Clin Virol. 2005

Morfin F, J Clin Virol. 2004

Doerr, 2010 Medizinische Virologie

HSV-1 / HSV-2: associated diseases

Herpes labialis (HSV-1)

Herpes genitalis (HSV-2)

Keratitis, Retinitis (Eye)

Herpes simplex encephalitis (Brain)

Disseminated Herpes (Lung, Liver)

Eczema Herpes (Skin)

Epidemiology:

Worldwide, ∼90% of

people are seropositive

for one or both virus types.

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Antivirals:

HSV-1 / HSV-2: therapy and resistance

Aciclovir Foscarnet Cidofovir Nucleoside analogue Pyrophosphate analogue Nucleoside analogue

Drug resistance:

Alternatives:?

0.1 – 0.6% normal population

4 – 7% AIDS/HIV-patients, chemotherapy recipients, eye infections

14 – 27% patients after stem cell transplantation

Multiresistant strains (ACV, PFA, CDV)

Stranska R, J Clin Virol. 2005; Morfin F, J Clin Virol. 2004

Monoclonal antibody HerpHu-mAb Humanized HSV-1/2 gB-targeting antibody

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HerpHu-mAb

HerpHu-mAb: Inhibition of the cell-to-cell spread

No comparable antibody generated in humans (or not isolated so far)!

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man

An

ti-H

SV

-Ab

H

erp

Hu

-mA

b

Phase contrast HSV-1 Anti-human-Fc

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1 Malkin JE, Herpes 2004

2James SH, Antiviral Res. 2009 3 Farooq, AV; Shukla, D , Survey of ophthalmology 2012

Herpes Simplex Genitalis1:

Epidemiology: estimated incidences in US and Europe range from 5 to

24 per 100 people per year

Herpes Simplex Encephalitis2:

• Epidemiology: approx. 1 per 250,000 to 500,000 individuals per year

• Mortality: untreated about 70%, with Acyclovir about 28%

• Morbidity: 62% of survivors having some form of neurologic debility

only 2.5% return to normal neurologic function

Ocular HSV diseases: Keratitis3 and Retinitis:

Epidemiology: estimated number of 40.000 new cases of severe monocular

visual impairment or blindness each year, global incidence of HSV-induced

ocular disease is roughly 1.5 million

HSV: Disseminated and severe diseases

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Immunsuppression: Disseminated disease

Herpes genitalis (HSV-1/2)

Disseminated Herpes (Lung, Liver)

Herpes simplex encephalitis (Brain)

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Immunosuppression: Generalized HSV (lethal)

1Krawczyk et. al., PNAS. 2013

Model: NOD/SCID mice

Infection: vaginal, 1 x 106 TCID50

Virus: HSV-1 R10.2 (resistance: ACV, PFA, CDV)

ACV: 50 mg/kg body weight; each 12h

HerpHu-mAb: 24h, 40h und 56h post infection (300 µg/kg bw i.v.)

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Ocular HSV diseases: Keratitis

Keratitis (Eye)

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Ocular HSV diseases: Retinitis

Retinitis (Eye)

Mic

e w

ith

acu

te r

etin

al necro

sis

[%

]

0

20

40

60

80

100

PBS ACV P PEP P PEPT Topical

Controls mAb 2c mAb hu2c

p=0.47

p=0.09

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Summary

Market volume (estimated): > 500 mio US-$/year

Antiviral efficacy of HerpHu-mAb towards HSV-1/2 ( including drug

resistant clinical isolates) was demonstrated in cell culture and animal

models

Protection of highly immunodeficient NOD/SCID mice from generalized,

lethal infections

Highly effective prevention of HSV-mediated Keratitis and Retinitis

Promising compound to fight severe and/or drug resistant HSV infections

Patent applications filed in US, Europe, Canada, China, Japan, India and

Brasilia

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1.PhaseI clinical trials

2.Charaterization of the B Cell epitope of this HerpHu-mAb

3.Development of a HSV1/2 Vaccine containing the relevant

B Cell epitopes

Perspectives und future projects

Universitätsklinikum Bonn

Institut für Virologie

Anna-Maria Eis-Hübinger

Eduard Schneweis +

Nationales Centrum für

Tumorerkrankungen Heidelberg

Michaela Arndt

Jürgen Krauss

Universität Tübingen

Abteilung für Immunologie

Ludger Große-Hovest

Universitätsklinikum Essen

Institut für Virologie

Adalbert Krawczyk

Michael Roggendorf

University of Pennsylvania

Department of Microbiology

Florent Bender, Ph. D

University College London

Department of Biochemistry

and Molecular Biology

Andrew C.R. Martin

herphu-mab - effective therapeutic antibody … 2 titel s s s s s s | prof. dr. michael roggendorf...

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