Post on 02-Mar-2021
Universal Flu Vaccine - One • For All
Universal Flu Vaccine &
Pandemic Preparedness AHEAD of Outbreak
WHO meeting, May 2014
Universal Flu Vaccine - One • For All
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.
Universal Flu Vaccine - One • For All
Agenda
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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
Universal Flu Vaccine - One • For All
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
A Game Changing Flu Vaccine
Both immune arms against all strains
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
Universality
Pre-clinical and Clinical Data
Universal Flu Vaccine - One • For All
Next What? How? Why?
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)
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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)
*
*
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
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)
M-001 Efficacy Measured After Viral Ag Exposure
Enhanced HAI responses to strains NOT included in boost vaccine
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
M-001 as Pandemic Primer Immediate vaccination upon any pandemic declaration
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
Swine H1N1
M-001 Efficacy Measured After Viral Ag Exposure
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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)
*
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
Next What? How? Why?
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
Universal Flu Vaccine - One • For All
A Game Changer for Influenza
Thank You!
Contact Information
Email: gottlieb@biondvax.com
Website: www.biondvax.com
Phone: +972-8-9302529