universal flu vaccine - who...bvx-003 2010 older adults (55-75) 60 bvx-004 2011 younger adults...

Universal Flu Vaccine - One • For All

Universal Flu Vaccine &

Pandemic Preparedness AHEAD of Outbreak

WHO meeting, May 2014


Forward Looking Statements

2

This presentation includes “forward-looking statements” within the meaning of applicable

securities laws. These forward-looking statements involve risks and uncertainties,

including those identified within the “Risk Factors” section of the Company's Shelf

Prospectus dated January 8, 2014.

Although management of the Company believes the expectations reflected in such

forward-looking statements are based on reasonable assumptions, the Company cannot

assure investors that these expectations will prove correct, and the actual results that the

Company achieves may differ materially from any forward-looking statements, due to

such risks and uncertainties.


Agenda

3

WHY? Today’s flu vaccines are strain-specific and do not

work against emerging strains

HOW? New generation flu vaccine active against seasonal

and pandemic, A and B Type strains

WHAT? Pre-clinical and clinical data support safety and

efficacy of BiondVax’s universal flu vaccine


Next What? How? Why?

Current Vaccines vs BiondVax’s New Approach

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CURRENT BiondVax’s M-001

Strain specific Universal

New vaccine every year Single formulation

Long production cycle Short year-round production &

vaccination

Limited effect Activates both arms of the immune

system, can serve as a primer

Hen egg allergy Non allergenic



BiondVax’s Partners

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Weizmann Institute of Science, Israel

Tel Aviv Sourasky Medical Center, Israel

Hadassah University Medical Center, Israel

MonoSol Rx, USA

State of Israel FP7 Consortium, EU

http://www.weizmann.ac.il/

http://www.weizmann.ac.il/

http://www.hadasit.co.il/?catid=993DDC65-4030-4FC9-BD94-39B5EAE5F0DF



A Game Changing Flu Vaccine

Both immune arms against all strains



BiondVax’s Universal Flu Vaccine (M-001)

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HemAgglutinin (HA)

Matrix protein (M1)

NucleoProtein (NP)

Design: Targets Common Regions Nine common regions are connected to make one recombinant protein called M-001

Production: Quick and Robust Produced easily and quickly all year-round within 6-8 weeks via fermentation in E.coli

The Influenza Virus



BiondVax’s Facility: GMP Production of M-001

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Up

stre

am

Do

wn

stre

am

Fermentation

Lysis

Ultrafiltration

Fill & Finish Chromatography

IB Solubilization

Fermentation (E. coli) 3 days

M-001 purification 5 days

Fill and finish 1 day

QC testing 6 weeks

Product Release 6-8 weeks

Stability (ongoing): 33 months



Universality

Pre-clinical and Clinical Data



High Homology with Seasonal & Pandemic Strains

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1 Homology to influenza strains was determined by Blast search in NCBI data base

Homology to Influenza Type & Strains (representative list) Epitope in M-001

H3N2, H5N1, H5N6, H5N8, H7N9, H10N8 A HA (T-helper)

H1N1, H3N2, H5N1, H5N6, H5N8, H7N7, H7N9, H10N8 A NP (T-helper)

H1N2, H2N2, H3N2, H5N1, H5N6, H5N8, H7N7, H7N9, H10N8 A NP (CTL)

H1N1, H1N2, H2N2, H3N8, H5N1, H5N2, H5N6, H5N8, H5N9, H6N1, H6N2, H6N9, H7N7, H7N9, H9N2, H10N8, H11N1, H11N8, H11N9, H14N5

A NP (CTL)

H1N1, H3N2, H4N6, H5N1, H5N2, H5N3, H5N6, H5N8, H6N1, H7N3, H7N7, H7N9, H9N2, H10N8

A M1 (B-cell & CTL)

H3N2 A HA (B-cell)

H1N1 A HA (B-cell)

H3N2 A HA (B-cell)

Both Victoria and Yamagata lineages: B/Hong Kong/330/2001; B/Beijing/1/87; B/Singapore/222/79; B/Oregon/5/80; B/Shangdong/7/97; B/Memphis/13/03; B/Los Angeles/1/02; B/Nebraska/1/01; B/Hong Kong/548/2000 B/Hong Kong/156/99; B/Vienna/1/99;strain B/Lee/40 And many more (over 100)

B HA (B-cell)



No treatment-related Severe Adverse Events

Most adverse events were mild1

All adverse events observed were transient

M-001: Clinical trials

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Total N Population (age) Year Trial

63 Younger Adults (18-49) 2009 BVX-002

60 Older Adults (55-75) 2010 BVX-003

200 Younger Adults (18-49) 2011 BVX-004

120 Elderly (65+) 2012 BVX-005

443

1Mild Side Effects: • Local reactions: injection site pain, erythema (skin redness), swelling • Systemic reactions: myalgia (muscle ache), malaise (general discomfort) fever

No significant differences between treatment and control groups



M-001: Good Safety Profile & Well-Tolerated

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BVX-005: 120 elderly (65+ Y) M-001 x2

+TIV M-001 x1 +TIV

Alum/M-

001x1 +TIV

Placebo x1

+TIV

Rhinitis 3 (10%) 1 (3.3%) 6 (20%) 4 (13.3%)

Malaise/asthenia 2 (6.7%) 2 (6.7%) 4 (13.3%)

Sore throat 1 (3.3%) 1 (3.3%) 3 (10%) 2 (6.7%)

Injection site pain 3 (10%) 1 (3.3%)

Cough 1 (3.3%) 3 (10%)

Headache 1 (3.3%) 2 (6.7%)

Diarrhea 2 (6.7%) 1 (3.3%)

Neck pain 1 (3.3%) 2 (6.7%)

Fever 1 (3.3%) 1 (3.3%)

Back pain 1 (3.3%) 1 (3.3%)

Injection site erythema 1 (3.3%)

Arthralgia 1 (3.3%)

Rash 1 (3.3%)

Flushing 1 (3.3%)

Dizziness 1 (3.3%)

Decreased blood pressure 1 (3.3%)

TOTAL 13 8 23 12



M-001 Activates CD4+ IFNg+ in Elderly 65+

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Mechanism of action & potential cellular biomarker

0

0.05

0.1

0.15

0.2

0.25

0.3

% p

osi

tive

ce

lls

(Me

an +

SE)

M-001 twice Day 0

M-001 twice Day 42*

*

* *

*

Peripheral blood mononuclear cells (PBMCs) from whole blood were exposed ex vivo to the indicated antigens. Intracellular staining for IFN-gamma and CD4 frequencies were analysed by FACS.

* P<0.05



M-001 Activates CD8+ IFNg+ in Elderly 65+

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Mechanism of action for pandemic primer & universal products

BVX 005: Peripheral blood mononuclear cells (PBMCs) from whole blood were exposed ex vivo to the indicated antigens. Intracellular staining for IFN-gamma and CD8 frequencies were analysed by FACS.

* P<0.05

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

A/Brisbane/10/07 H3N2 A/California/7/09 H1N1 A/Perth/16/09 H3N2 B/Brisbane/60/08 Flumist 2011

% p

osi

tive

ce

lls (M

ean

+ S

E)

Baseline

Day 42 (after M-001 x2)

*

*



0

10

20

30

40

50

60

70

A/California/7/09 A/Perth/16/09 B/Brisbane/60/08

% S

ero

con

vers

ion

TIV Twice M-001 + TIV*

0

10

20

30

40

50

60

70

80

A/Brisbane/59/07 A/Brisbane/10/07 B/Brisbane/60/08%

ser

oco

nve

rsio

n

TIV Twice M-001 + TIV

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More people seroconverted (HAI) to all tested seasonal strains

BVX-003: 500 mcg M-001, TIV (Vaxigrip 2009) and Placebo (either PBS or adjuvanted PBS)

BVX-005: 500 mcg M-001, TIV (Vaxigrip 2011) and Placebo (PBS).

* = P<0.05

BVX-003 55-75 Y

BVX-005 65-91 Y

M-001 Efficacy Measured After Viral Ag Exposure

H1N1 pandemic swine flu strain


Next What? How? Why? 16

Strains not included in the boost

H1N1 A/New Caledonia/20/99, A/Wuhan/371/95, A/Brisbane/59/07

H3N2 A/New York/55/04, A/California/07/07, A/Wisconsin/67/05, A/Perth/16/09, A/Brisbane/10/07

Influenza B Victoria and Yamagata

B/Malaysia/2506/04, B/Johannesburg/5/99, B/Shanghai/361/02

H5N1 Clade 2.1 (A/Duck/Hunan/795/02) Clade 2.2 (A/Bar headed goose/Qinghai/1A/05) Clade 2.3 (A/Duck/Laos/3295/06)


Enhanced HAI responses to strains NOT included in boost vaccine



One Protein, Multiple Pathways/Products

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• Trial: M-001 + pandemic vaccine vs pandemic vaccine

• Endpoint: current antibody immune marker (HAI)

Pandemic Primer

Enhancer of pandemic strain specific vaccines

• Trial: M-001 vs placebo

• Endpoints: clinical efficacy

Universal Flu Vaccine

Standalone multi-strain, multi-season



M-001 as Pandemic Primer Immediate vaccination upon any pandemic declaration



BARDA’s Model of Pandemic Preparedness

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Source:

HHS Pandemic Influenza Vaccine Program VRBPAC Meeting November 14, 2012

Robin Robinson, PhD Director of BARDA1, HHS, USA

1http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM330392.pptx

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM330392.pptx







BiondVax’s Pandemic Preparedness Plan (PPP)

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1 2 3 4 5 6 7 8 9 mos Inter pandemic Phase

Pandemic Declaration

Today's situation:

BiondVax's PPP:

Saving time = Saving lives

Key benefits: Vaccination schedule starts IMMEDIATELY upon ANY pandemic

declaration (instead of 6 months later)

More subjects reach level of protection to pandemic and evolving strains after ONE boost



Swine H1N1


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Enhanced HAI responses to pandemic strains

In human: 500mcg M-001 twice, TIV (Vaxigrip 2011) and Placebo (PBS). In mice: 150mcg M-001 thrice, 0.67mcg H5N1 once (A/Vietnam/1203/04 Clade 1, Aventis Pasteur, non adjuvanted) Seroconversion: % of mice with mean fold increase in HAI GMT ≥4x and HAI GMT≥ 1:40 post-immunization

* P<0.05

Human clinical trial: Age 65+

0

10

20

30

40

50

60

70

TIV M-001 + TIV

% S

ero

con

vers

ion

(HA

I) *

Avian H5N1

Mouse Model

0

10

20

30

40

50

60

70

80

90

100

H5N1 vaccine M-001 + H5N1 vaccine%

Ser

oco

nve

rsio

n (H

AI)

*



In mice: 250mcg M-001 twice, partial dose of H5N1 vaccine (A/Vietnam/1194/04)

Seroconversion: % of mice with mean fold increase in HAI GMT ≥4x and HAI GMT≥ 1:40 post-immunization

Strains: Clade 2.1 (A/Duck/Hunan/795/02); Clade 2.2 (A/Bar headed goose/Qinghai/1A/05); Clade 2.3 (A/Duck/Laos/3295/06)

Priming Broadens Immunity to Drift Strains

22 22

0

10

20

30

40

50

60

70

80

90

100

clade 2.1 clade 2.2 clade 2.3

% S

ero

con

vers

ion

(HA

I)

PBS+H5N1

M-001 +H5N1

*

Response to non H5N1 vaccine strains

* P<0.05



Clinical Trials for a Universal Pandemic Primer

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Prime Boost

1 M-001 Pandemic Vaccine

2 Saline Pandemic Vaccine

Population: Adults eligible to receive the pandemic vaccine (H5N1 or H7N9)

Endpoints: Safety Elevated Hemagglutination inhibition (HAI) CMI 2 seasons follow up

Sample size: 400 Experimental and 200 Control per age group

Planned as part of UNISEC consortium for 2015



Take Home

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One • For All: against A & B-Type, seasonal & pandemic strains

Safe: no adjuvant required

Active: induces cellular responses and enhances HAI responses

Pandemic Primer: preparedness AHEAD of any outbreak & sparing

NEXT: Clinical trials for each indication


A Game Changer for Influenza

Thank You!

Contact Information

Email: [email protected]

Website: www.biondvax.com

Phone: +972-8-9302529

mailto:[email protected]

http://www.biondvax.com/

universal flu vaccine - who...bvx-003 2010 older adults (55-75) 60 bvx-004 2011 younger adults...

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