Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® Technology
Akshaya Bio, Inc.
Re-educating Immune System
to Fight Diseases
Vaccines
Immunotherapy 1
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy © 2019 Akshaya Bio | www.akshayabio.com
2
Outline The Company
Management
Collaborators
Chimigen® Technology
Platform
Product Pipeline & Status
Akshaya’s Strengths
IP Portfolio
Highlights
Contact Information
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Akshaya Bio Inc. (Canada) / Chimigen Inc. (USA) – Privately held
• Founded in 2010
– Dendritic cell receptor-targeted vaccines
– Proprietary technology, strong IP Position
• 23 Issued Patents (13 Issued Patents on HBV)
• Combination patents filed, and additional product specific patents to be
initiated
– Acquired Chimigen® Technology from Paladin Labs Inc. (TSX) and
ViRexx Medical Corp. (TSX, AMEX)
• External Partners in Research and Development – NRC-IRAP, CHTD, AITF, Gates Foundation
• Unique technology platform • Improved antigen presentation
– “Mimics Body’s Own Natural Immune Response Process”
– No adjuvant, avoids adverse reactions
• Rich product pipeline – HBV, HCV, HIV, Cancer, Malaria, Shingles, Biodefense, Influenza, TB, Ebola
Akshaya Bio Inc. /Chimigen Inc.
© 2019 Akshaya Bio | www.akshayabio.com 3
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Satish Chandran, Ph.D
CEO & Board Member: Biotech/vaccine veteran with 25+ years
leadership experience; ex Pfizer, Nucleonics, Wyeth-Lederle
vaccines
Rajan George, M.Sc, Ph.D
President, CSO & Board Member: 25+ years R&D experience in
virology, immunology, molecular biology; Ex Paladin
Biosciences Exe.VP and CTO; ViRexx Medical Corp. Senior VP
史跃年(Eric) 博士, Board Chairman
1984: 北京医科大学,CUSBEA Program;1989:美国Dartmouth医学院 Ph.D
A biomedical scientist,the associate professor,and then full
Professor of Albert Einstein College of Medicine: 1994-2010
An entrepreneur: founder of several Bio-medical companies
Chimigen Inc. & Akshaya Bio Inc.
Executive Team
© 2019 Akshaya Bio | www.akshayabio.com
4
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy © 2019 Akshaya Bio | www.akshayabio.com
Collaborators
NIH
HBV Therapeutic Vaccine “PDP”
Transgenic HBV mouse experiments
HBV Product manufacturing assistance (Anticipated)
NRC-IRAP
Jeff Zidichouski, Ph.D
Charles Otieno, PhD, MBA
University of Alberta (HBV & HCV Clinical Research)
Klaus Gutfreund, M.D, Assoc. Professor, Medicine
Mang Ma, M.D, Assoc. Professor, Medicine
VIDO- Immunology in Animals
Qiang Li, Ph.D
Philip Griebel, Ph.D
5
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Problem & Solution
Safe & effective vaccines & therapeutics for infectious diseases and cancer.. Unmet need
• Reliance on old technologies: – Adjuvants- the cause of most of the severe side effects
• DNA vectored vaccines: – Ineffective, chance for recombination- SARS/MERS…
• Slow production speed: – Influenza
• 2014-15 vaccine wrong strain!
• 2016-2017 virus mutated, ineffective vaccine
• Solution: Chimigen® Technology
• “Mimics Body’s Own Natural Immune Response Process”
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Dendritic Cell Receptor-Targeted Vaccines
A Breakthrough Concept for
Vaccine & Immunotherapy Development
for Infectious Diseases and Cancer
“Mimics Body’s Own
Natural Immune Response Process”
7
Chimigen® Platform Technology
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® Vaccines - Features
© 2019 Akshaya Bio | www.akshayabio.com
8
• Characteristics of both Antigen (Ag) and Antibody (Ab)
– “Next generation” DC receptor- targeted technology without Ab
– Removes the off-target effect of full antibody
• Xenotypic (foreign) Ab fragment makes whole molecule
“foreign” & thus more immunogenic
• Adaptable platform
– Adaptable to disease-specific multiple molecular antigenic epitopes
– HBV, HCV, HIV, Cancer, Biodefence Applications (Alphaviruses),
Pandemic Preparedness (H5N1, H1N1), Malaria, Ebola, Zika etc.
• Designed to generate broad immune responses
– Cellular (Class I) – critical to clear virus infected & cancer cells
– Humoral (Class II) – Antibodies
• Potential Prophylactic & Therapeutic Applications
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® Vaccines - Features
© 2019 Akshaya Bio | www.akshayabio.com 9
Effective at low doses (µg)
– Targets multiple specific receptors on Antigen Presenting Cells
• Dendritic Cells (Fcγ, Lectin Receptors)
Minimal safety concerns
– Utilizes classical antigen presentation pathway
– Avoids off-target effects of antibody therapies
– No added adjuvant
• Eliminates many adverse events
• Eliminates T cell sequestration, dysfunction & deletion (Nat. Med. 2013,
Hailemichael et. al.)
Unique technology platform
– Excellent IP Portfolio (23 Issued patents, combination patents and formulations filed,
and additional product specific patents to be initiated)
Ease of production and scalability, Utilizes insect cell-based production
– Enhanced antigenicity through production in Insect Cells
– Imparts non-mammalian glycosylation; Highly immunogenic
– Used for Provenge® (Sipuleucel-T)- Prostate Cancer Immunotherapy
(First FDA-approved product produced in Sf9 Insect Cells)
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
10 © 2019 Akshaya Bio | www.akshayabio.com
Product Pipeline & Status Product Application Status
Chimigen® HBV Immunotherapy Chronic HBV-Immunotherapy IND/CTA Ready
Chimigen® HCV Vaccine HCV Prophylactic Vaccine IND/CTA Ready
Chimigen® PAP-Prostate Cancer Prostate Cancer Immunotherapy Preclinical
Chimigen® ShingVax Shingles- Prophylactic Preclinical
Chimigen® HIV Vaccine Prophylactic/Therapy Preclinical/Animal
study completed
Chimigen® Influenza H5&H1& Pan-Flu Prophylactic Vaccine Preclinical
Chimigen® Malaria Vaccine Prevention/Therapy Preclinical- Ready
for animal study
Chimigen® WEEV (Alphavirus) Prevention/Therapy (Biodefence) Preclinical Animal
efficacy trial done
Chimigen® Cancer Immunotherapy
Vaccines Breast, Ovarian, Colorectal Preclinical
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® HBV:
Immunotherapy for
Treating Chronic HBV Infection
Akshaya Bio Inc.
© 2019 Akshaya Bio | www.akshayabio.com 11
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
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257 million chronic carriers
HBV Infection: Shocking Epidemiology
Annually, close to 1 million people will die from HCC or
cirrhosis due to HBV without therapeutic intervention
© 2019 Akshaya Bio | www.akshayabio.com
Source: WHO Global Hepatitis Report 2017
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Considerations
• Over 257 million chronically infected (~2 million in US)
• One million deaths annually – Cirrhosis, Liver failure & HCC
• Current Antiviral Therapies
• Polymerase Inhibitors
• Effective in 30-40% of chronically infected patients
• Mutant (resistant) strains appear frequently
• Compliance issues with interferon treatment
• Market: >$2B
• Akshaya’s Chimigen® HBV Immunotherapy
• Contains T & B cell-relevant HBV antigens
• Able to elicit humoral and cellular response
• Potential prophylactic and therapeutic uses
• Ready to enter clinical studies
• NIH completed Product Development Plan
• Plan to initiate Phase I trial in 2019- 20-IND/CTA ready
Significant Unmet Need
S-S
S-S
S
S
HBV
S1/S2/Core
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
HBV
S1/S2/Core
S-S
S-S
S
S
HBV
S1/S2/Core
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
S-S
S-S
S
S
HBV
S1/S2/Core
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCHOCH2
IRD
TBD
6xHis
CH2
CHOCHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
HBV
S1/S2/Core
© 2018 Akshaya Bio | www.akshayabio.com 13
Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Efficacy, ex vivo
PBMCs derived from individuals
un-infected and with chronic HBV infection
Chimigen® HBV Immunotherapy
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Binds to DCs - (CD32 & CD206)
• Appropriate antigen processing and presentation
• Efficacy in Normal and HBV carriers, ex vivo in DC/T cell APA
• Induces
– Proliferation of CD8+ and CD4+ T cells
– Production of IFN-γ and TNF-α in CD8+ and CD4+ T cells
– Production of granzyme B in CD8+ & CD4+T cells
– Production of HBV antigen-specific CD8+ T cells (Pentamer
Positive)
– HBV peptide-specific T cell responses (IFN- and TNF- )
– Targeted cell killing
• HBV antigen-loaded Un-infected & HBV Chronic carrier cells
– Production of T(resp) cells, removes T(reg) cells
(Indication of Breaking HBV Tolerance)
Chimigen® HBV Immunotherapy Results Summary, ex vivo
© 2019 Akshaya Bio | www.akshayabio.com 15
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Immunology, in vivo
Cellular and Humoral Responses in Sheep
© 2019 Akshaya Bio | www.akshayabio.com
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Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Results Summary, in vivo
• Chimigen® HBV Therapeutic Vaccine is immunogenic in sheep
• Chimigen® HBV Vaccine induced a dose-dependent antibody response
• Specificity for S1/S2 protein
• Significant response following the secondary immunization
• Kinetics of the antibody response similar to commercial HBV sAg vaccine
(Engerix-B, GSK), but with no added adjuvant
• Chimigen® HBV Vaccine induced a dose-dependent cell-mediated immune
response
• Specificity for S1/S2 protein
• Significant response following the secondary immunization
• Effective at low doses
• Systemic immune responses in blood was higher than the local immune
response in the lymph node draining the site of vaccination
• Induces immune activation in HBV-transgenic mice (NIH Study)
• HBV Vaccine is induces systemic cell-mediated immune response
© 2019 Akshaya Bio | www.akshayabio.com 17
Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Immunology, in vivo
HBV Transgenic Mice
© 2019 Akshaya Bio | www.akshayabio.com 18
Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® HBV Core Therapeutic Vaccine in HBV Transgenic Mice
Induced Immune Responses in the Liver Following Intradermal Injections
Study Carried out by NIH Expt. No. NHA-77
© 2019 Akshaya Bio | www.akshayabio.com
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Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Immune Responses are indicative of breaking
tolerance in HBV chronic carriers
• These novel responses are indicative of administering
a therapeutic effect
– Production of new epitope-specific CTLs
– The Killing of HBV-infected target cells
– Production of T responder cells
– Killing of T regulatory cells by T responder cells
– Cytokine induction in HBV transgenic mice
• “Product Development Plan” Completed; NIH (NIAID)
Therapeutic Value
© 2019 Akshaya Bio | www.akshayabio.com 20
Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Clinical Development Plan
© 2019 Akshaya Bio | www.akshayabio.com 21
Chimigen® HBV Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• IND-enabling preclinical efficacy studies completed
• PDP (NIH) – Completed
– Initiate GMP manufacture 2019
– Complete Toxicology
• Initiate Clinical studies 2019/2020
• Phase 1a (safety and immune response
– Naïve population (20-24 individuals)
• Phase 1b (POC, efficacy)
– Chronically infected individuals (+Antivirals)
© 2019 Akshaya Bio | www.akshayabio.com
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Chimigen® HBV Immunotherapy Development Plan
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® HCV Vaccine:
Prophylactic/Therapeutic Vaccine
Akshaya Bio Inc.
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Considerations
• HCV is a global health care problem (WHO)
• 3-4 million new infections each year
• 170 million chronically infected
• 2.7 million in US
• Cirrhosis and loss of liver function, HCC
• Current Therapies
• Antivirals (Harvoni and Sovaldi)
• No prophylactic vaccine available
• Akshaya’s HCV vaccine is designed for prophylactic and therapeutic applications
• Design and process development completed
• Preclinical studies completed
• Ready for clinical development
• IND/CTA ready
Hepatitis C Virus (HCV) Infection
S-S
S-S
S
S
HCV
E1-E2-NS5A
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
HCV
E1-E2-NS5A
CHO CHO
S-S
S-S
S
S
HCV
E1-E2-NS5A
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
HCV
E1-E2-NS5A
CHO CHO
Contains two B cell and one T-cell relevant HCV antigens
© 2019 Akshaya Bio | www.akshayabio.com 24
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Considerations
• Considered pandemic by WHO
• From 1981 to 2006, more than 25 million deaths
• Estimated 33.3 million people living with HIV/AIDS (2009 estimate)
• 2.6 million new infections per year, 1.8 million deaths
• Sexual contact, IV drug use and perinatal transmission are most common routes of
infections
• No vaccines are currently available
• Current therapies include antivirals (protease, polymerase and integrase inhibitors)
• Akshaya’s HIV Vaccine : Ready for out-license/clinical trial
– Contains multiple antigens (Six)
– Potential for prophylactic and therapeutic use
– Preclinical studies show excellent potential
– Cellular & humoral immune responses
– In PBMC immune response assays, ex vivo
– In rats, in vivo
Chimigen® HIV Vaccine
S
S
S-S
S-S
S
S
HIV antigensGag/env/tat/rev/vpr/vpu
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHOCH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
Peptide
CHO
CHO CHO
TBD
HIV antigensGag/env/tat/rev/vpr/vpu
S-S
S-S
S
S
HIV antigensGag/env/tat/rev/vpr/vpu
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHOCH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
Peptide
CHO
CHO CHO
TBD
HIV antigensGag/env/tat/rev/vpr/vpu
S-S
S-S
S
S
HIV antigensGag/env/tat/rev/vpr/vpu
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHOCH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
CHO CHO
TBD
HIV antigensGag/env/tat/rev/vpr/vpu
Targets the virus at
various stages of the infection
Supported by CHTD NRC-IRAP/ Gates Foundation
© 2019 Akshaya Bio | www.akshayabio.com 25
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Multiple HIV Antigen Targets
S-S
S-S
S
S
HIV antigens Gag/Env/Tat/Rev/Vpr/Vpu
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHO CH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
CHO
CHO CHO
TBD
HIV antigens Gag/Env/Tat/Rev/Vpr/Vpu
Chimigen® HIV Vaccine
© 2019 Akshaya Bio | www.akshayabio.com 26
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
M2 (Universal): HA (1-9) can be produced, stored as Baculovirus stock
S-S
S-S
S
S
Influenza
H5(H1)-M2
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
Influenza
H5(H1)-M2)
Chimigen® Influenza/Pandemic Vaccines
New Vaccines Needed for Emergent Resistant Strains
Chimigen® Pan-Influenza Vaccine
Generates B Cell and T cell Immunity
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Cancer Vaccine Program: Early Discovery
Antigen Cancers MUC1 Overexpressed in multiple cancers;
Breast, ovarian, colon, pancreas, rectal
Carbonic anhydrase IX (CA9) 75% of Cervical and colon cancers and 95% of renal cancers
Carcinoembryonic antigen (CEA)
65% of breast cancers, 70% of lung cancers and almost 100% of colon cancers
HER 2/neu Breast, ovarian and colorectal solid tumors
Prostatic acid phosphatase Prostate Cancer
Rationale Chimigen® Vaccine designs have demonstrated ability to,
• Target dendritic cells
• Produce functional CTLs
• Overcome immune tolerance
• Overcome immune anergy
• Overcome antigenemia
Novel immunotherapy without the individualized (Autologous) vaccine concept
Cancer Targets
In early stage
research/development/
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCH2
IRD
TBDCH2
CHO
CH3
CH2
CH3
S
S
S
S
S
S
Peptide
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCHOCH2
IRD
TBDCH2
CHOCHO
CH3
CH2
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
MUC1
5xTandem
Repeat
MUC1
5xTandem
Repeat
CHOCHO
MUC1
5xTandem
Repeat
MUC1
5xTandem
Repeat
MUC1 is over-expressed in a large number of carcinomas
© 2019 Akshaya Bio | www.akshayabio.com
Project initiated with
AITF Assistance
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
S - S
S - S
S
S
Peptide Linker
Portion of C H 1
Hinge Region
Xenotypic Murine Fc
CHO C H 2
IRD
TBD CH2
CHO
C H 3
C H 2
C H 3
S
S
S
S
S
S
S - S
S - S
S
S
Peptide Linker
Portion of C H 1
Hinge Region
Xenotypic Murine Fc
CHO CHO C H 2
IRD
TBD CH2
CHO CHO
C H 3
C H 2
C H 3
S
S
S
S
S
S
S
S
CHO CHO
MUC1
10xTandem Repeat
MUC1
10xTandem Repeat
CHO CHO
MUC1 MUC1
Tandem repeat sequence:
ACC TCG GCC CCG GAC ACC AGG CCG GCC CCG GGC TCC ACC GCC CCC CCA GCC CAC GGT GTC
T S A P D T R P A P G S T A P P A H G V
Chimigen® MUC 1 Cancer Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
S - S
S - S
S
S
PAP
Peptide Linker
Portion of C H 1
Hinge Region
Xenotypic
( Murine ) Fc
CHO C H 2
IRD
TBD CH2
CHO
C H 3
C H 2
PAP
C H 3
S
S
S
S
S
S
S
S
CHO CHO
Chimigen® Prostate Cancer Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
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Can eliminate the need for “autologous treatment” regimen
used for Provenge® (Sipuleucel-T)- Prostate Cancer Immunotherapy
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
S - S
S - S
S
S
CEA
Peptide Linker
Portion of C H 1
Hinge Region
Xenotypic
( Murine ) Fc
CHO
C H 2
IRD
TBD CH2
CHO
C H 3
C H 2
CEA
C H 3
S
S
S
S
S
S
S
S
CHO CHO
Chimigen® CEA Cancer Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• 5th leading cause of death worldwide
• Endemic in 108 countries
• 40% (3 billion) of world population
exposed to parasite
• Estimated 247 million cases worldwide
• Over 1 million deaths annually
• 80% deaths occur in children under 5
(weak acquired immunity)
• Pregnant women more susceptible
(pregnancy associated malaria)
• Vertical transmission is a major cause
of miscarriage and stillbirth
• No approved vaccine to prevent malaria
• Ready for animal studies
S-S
S-S
S
S
Malaria
antigens(CSP/AMA-1/LSA-
120 repeats/MSP-142)
HBV Core
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHOCH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHO
CHO CHO
Malaria
antigens(CSP/AMA-1/LSA-
120 repeats/MSP-142)
HBV Core
TBD
S-S
S-S
S
S
Malaria
antigens(CSP/AMA-1/LSA-
120 repeats/MSP-142)
HBV Core
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHOCH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
CHO CHO
Malaria
antigens(CSP/AMA-1/LSA-
120 repeats/MSP-142)
HBV Core
TBD
Chimigen® Malaria Vaccine
Targets the parasite
at multiple stages of the infection
Initial Development
Funded by
Gates Foundation Award
GCE 3
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Alphaviruses – Viral Encephalitis
• Single stranded RNA viruses: Venezuelan Equine
Encephalitis (VEEV), Western Equine Encephalitis
(WEEV), Eastern Equine Encephalitis (EEEV)
• Viruses can be aerosolized and are highly infectious
• No definitive anti-viral treatment
• VEEV and WEEV have been successfully weaponized
• Current Vaccine development focused on live, attenuated viruses
• Significant side effects
• Potential to mutate into virulent strains
• Conventional Adjuvant Vaccines not showing promise
• Applied for NIH (BARDA) grant, 2007- 2008
• US $14.8 mil. (3+1 Years)
• Received high technical merit ranking (109)
• possible to reapply
• Missed funding due to Anthrax priority (92 & 121)
No Approved Vaccine Currently Available
Chimigen® WEEV Vaccine
S-S
S-S
S
S
WEEV
E1-E2
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
WEEV
E1-E2
S-S
S-S
S
S
WEEV
E1-E2
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
WEEV
E1-E2
Showed efficacy
in challenge model at DRDC-Suffield
© 2019 Akshaya Bio | www.akshayabio.com
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Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Multiple Ebola Virus Antigen Targets
S-S
S-S
S
S
Ebola antigens
GP-NP-VP40
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
(Murine)Fc
CHO CH2
IRD
6xHis
CH2
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
CHO
CHO CHO
TBD
Ebola antigens
GP-NP-VP40
Chimigen® Ebola Virus Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
Predicted to Induce Humoral and Cellular Immune Responses 34
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
• Caused by Mycobacterium tuberculosis
• 8.7 million new cases in 2011
• 1.4 million deaths in 2011
– 430,000 people with HIV
– 70,000 children
– Leading killer of people with HIV
• 630,000 people with MDR-TB in 2011
– 150,000 deaths annually from MDR-TB
– 10% of MDR-TB are EDR-TB
• Current vaccine (M. bovis BCG) low
efficacy
– Not recommended in HIV+ children
(WHO Global Advisory Committee)
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Targets tuberculosis at
various stages of the
infection
Tuberculosis (TB)
Chimigen® TB Multi-antigen Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
35
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
Peptide
CHOCHO
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
S-S
S-S
S
S
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
S
S
Peptide
CHOCHO
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Mtb Antigens
(Ag85b/ESAT6/
Rv2660c/HspX/
RpfA/RpfD)
Targets tuberculosis at various stages of the infection
Chimigen® Mtb Multi-antigen Vaccine
© 2019 Akshaya Bio | www.akshayabio.com
36
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Zika Virus • Insect borne viral infection transmitted mainly by Aedes genus
mosquitos such as Aedes aegypti
• Most common symptoms are fever, rash, joint pain and conjunctivitis
• Trans-placental infection of the fetus leads to microcephaly
• Single positive-stranded RNA virus of the family Flaviviridae
• 10794 bp genome codes for polyprotein with:
• Three structural proteins
• capsid (105 aa), premembrane/membrane (187 aa), envelope
(505 aa)
• Seven nonstructural proteins
• NS1 (352 aa), NS2A (217 aa), NS2B (139 aa), NS3 (619 aa), NS4A
(127 aa), NS4B (255 aa), NS5 (904 aa)
© 2019 Akshaya Bio | www.akshayabio.com
37
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® Zika Virus Vaccine
S - S
S - S
S
S
Zika Virus antigens (E-NS1-NS4A )
Peptide Linker
Portion of C H 1
Hinge Region
Xenotypic (Murine)Fc
CHO C H 2
IRD
6xHis
CH2
C H 3
C H 2
6xHis
C H 3
S
S
S
S
S
S
CHO
CHO CHO
TBD
Zika Virus antigens
Induces multi-antigen, multi-epitopic
cellular and humoral immune responses
Multiple Zika Virus Antigen Targets
© 2019 Akshaya Bio | www.akshayabio.com
(E-NS1-NS4A )
38
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
39
Primary Varicella Zoster Virus (VZV) infection results in varicella (chickenpox)
• VZV becomes latent, Shingles (Herpes Zoster.HZ) results from reactivation
• Common shingles-related complications Postherpetic neuralgia (PHN) and HZ
ophthalmicus (HZO)
Current approved vaccines:
• SHINGRIX Herpes Zoster vaccine (GSK) (non-live recombinant, AS01B
adjuvanted)
• ZOSTAVAX® Zoster Vaccine Live (Merck)
• Common side effects include nausea, fever, chills and body aches and pain,
swelling and redness at the site of injection
• In some cases, pulmonary and angioedema, cardiovascular events
Chimigen® ShingVax
• Recombinant fusion protein of mouse Fc and VZV Glycoprotein gE
• Produces the required cell-mediated immunity for prevention of HZ
• No side effects resulting from added adjuvants
• Currently in discovery
© 2019 Akshaya Bio | www.akshayabio.com
Shingles
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Chimigen® ShingVax
Re-activates memory T cells for effective cellular and
humoral immune responses
© 2019 Akshaya Bio | www.akshayabio.com
40
S-S
S-S
S
S
VZV-gE
Peptide Linker
Portion of CH1
Hinge Region
Xenotypic
Murine Fc
CHOCH2
IRD
TBD
6xHis
CH2
CHO
CH3
CH2
6xHis
CH3
S
S
S
S
S
S
CHOCHO
VZV-gE
Avoids side effects observed with current vaccines
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Akshaya Advantage Product candidates meet major unmet needs
No vaccine/therapy available
Eliminates off-target effects of antibody-based treatments
Strong IP Protection
23 issued patents, several pending applications
Mimics body’s natural immune process: Re-educates the immune system
Targets Dendritic Cell Receptors
Most efficient and natural process of antigen delivery to DCs
Induces cascade of natural, precise and potent immune responses
Efficacy Demonstrated
Proof of Concept established
Using immune cells from HBV Chronic Carriers
Breaks the immunological tolerance to HBV antigens
Quicker path to develop vaccines
No Adjuvant
Eliminates majority of the adverse reactions
© 2019 Akshaya Bio | www.akshayabio.com
41
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Intellectual Property Portfolio:
Issued Patents
Akshaya Bio Inc.
© 2019 Akshaya Bio | www.akshayabio.com
42
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Akshaya Bio Inc. CHIMERIC ANTIGENS FOR ELICITING AN IMMUNE RESPONSE
Country Status Application No. Filing Date Patent No.
Issue
Date
Expiry
Date
United
States Issued
10/365,620 13-Feb-03
8,029,803 04-Oct-11
05-Feb-24
Country Status
Application
No. Filing Date Patent No. Issue Date Expiry Date
United States Issued 10/912,969 5-Aug-04 8,025,873 27-Sept-11 05-Feb-24
United States Issued 13/209,979 15-Aug-11 8,465,745 18-Jun-13 13-Feb-23
HEPATITIS B FAMILY
CHIMERIC ANTIGENS FOR BREAKING HOST TOLERANCE TO
FOREIGN ANTIGENS
Country Status
Application
No. Filing Date Patent No. Issue Date Expiry Date
Germany
(Europe) Issued
602004045
169.9
6-Aug-04
166270 21-May-14
06-Aug-24
France
(Europe) Issued
04761663.9 06-Aug-04
166270 21-May-14
06-Aug-24
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Akshaya Bio Inc. HEPATITIS B FAMILY
CHIMERIC ANTIGENS FOR BREAKING HOST TOLERANCE TO
FOREIGN ANTIGENS
Country Status Application No. Filing Date Patent No. Issue Date
Expiry
Date
United
States Issued
10/913,171 5-Aug-04
8,007,805 30-Aug-11
05-Feb-24
China Issued 200480022
747.1
6-Aug-04 ZL
200480022
747.1
27-Apr-11 6-Aug-24
Eurasia
(validated in
RU)
Issued 200600390.
0
6-Aug-04 13070 26-Feb-10 6-Aug-24
India Issued 00256/MU
MNP/20
6-Aug-04 225281 5-Nov-08 6-Aug-24
UK (Europe) Issued 04761663.9 6-Aug-04 1664270 21-May-14 6-Aug-24
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Akshaya Bio Inc.
Japan Issued 2006-522192 6-Aug-04 5200201 22-Feb-13 6-Aug-24
New Zealand Issued 545048 6-Aug-04 545048 8-Oct-09 6-Aug-24
Singapore Issued 200600745-4 6-Aug-04 119567 29-Aug-08 6-Aug-24
HEPATITIS B FAMILY
CHIMERIC ANTIGENS FOR BREAKING HOST TOLERANCE TO
FOREIGN ANTIGENS
Taiwan Issued 93123603.0 6-Aug-04 I364294 21-May-12 6-Aug-24
South Africa Issued 2006/00804 6-Aug-04 2006-0804 25-Apr-07 6-Aug-24
Korea Issued 10-2006-
7002648
6-Aug-04 10-1327719 4-Nov.13 6-Aug-24
Australia Issued 2012200998 6-Aug-04 2012200998 27 Feb.14 6-Aug-24
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Akshaya Bio Inc. HEPATITIS C FAMILY
CHIMERIC HEPATITIS C VIRUS ANTIGEN FOR ELICITING AN IMMUNE
RESPONSE Singapore Issued 200802303-8 13-Oct-06 141061 29-Oct-10 13-Oct-26
South
Africa
Issued 2008/04078 13-Oct-06 2008/040
78
30-Sep-09 13-Oct-26
Si RNA FAMILY
ANTIGENIC COMPOSITIONS AND USE OF SAME IN THE TARGETED
DELIVERY OF NUCLEIC ACIDS
New
Zealand Issued 584306 29-Aug-08
584306 29-Jan-
13
29-Aug-
28
China Issued
20088011360
1.6 29-Aug-08
ZL20088011
36016
10-Dec-
14
29-Aug-
28
USA Issued USA Issued
12/67556
0
26-Feb-
10
8637477 28-
Jan-14
4-Mar-
29
Australia Issued 2008291604 29-Aug-08 20082916
04
20-Mar-14 29-Aug-28
© 2019 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Contact Information
Rajan George, MSc, PhD
President & Chief Scientific Officer 8223 Roper Road Edmonton Alberta, T6E 6S4 Canada
Telephone 780 431 9503
Mobile 780 493 1706
email [email protected]
Web www.akshayabio.com
Akshaya Bio Inc./ Chimigen Inc.
© 2019 Akshaya Bio | www.akshayabio.com
47
Akshaya Bio Inc./Chimigen Inc. …..Vaccines/Immunotherapy
Thank You…….
© 2018 Akshaya Bio | www.akshayabio.com
Akshaya Bio Inc.