VLPs A Vaccine Platform for the future!
Influenza Congress 2012Washington, DC, November 2012
Hector Munoz – Corp. Dev.
Innovative Technologies for Respiratory Vaccines
• TechnoVax is a biotechnology company based in Tarrytown - Westchester County (New York) that specializes in Viral Vaccine Development.
Welcome to TechnoVax
Creating a New Generation of Vaccines
• Company mission is to create and advance towards commercialization vaccines that are:– Safe– most effective – novel
• To achieve our mission, TechnoVax seeks:– strategic cooperations and partnerships to support vaccine
programs and advance candidates toward the market.
TechnoVax functions as a semi-virtual biotech company. The core team is composed of 9 full time employees with advanced degrees in their respective fields of specialty (virology, molecular biology, microbiology, immunology and vaccine R&D).
Dynamic Team, Big Ideas!
Dr. Jose Galarza is the Pioneer of the influenza Virus-Like Particle (VLP) Vaccine Technology.
The company is also supported by external collaborators from well known institutions such as Baylor College of Medicine, New York Medical College and CUNY (City University of New York).
• Our unique and innovative VLP technology is used to develop and produce vaccines for infectious diseases such as:
influenza,
respiratory syncytial virus (RSV),
para-influenza virus (PIV) and
other diseases including Dengue, HIV and cancer.
What We Do
TechnoVax’s VLP Technology
TechnoVax and its team of scientists have developed a new way to produce highly immunogenic, non-infectious monovalent and polyvalent virus-like particle (VLP) vaccines using a cell-based manufacturing system.
Influenza virus Influenza Virus Like Particle (VLP)
Resembles the virus but lacks nucleic acid and ability to replicate!
Production of Flu VLP Vaccines – 2 methods:
Advantages:
• Rapid and Flexible Cell Culture Manufacturing Systems.
• Platform technology suitable for multiple vaccine development.
• Highly immunogenic vaccines eliciting robust immune responses. Safe product without the need for inactivation
• High yield, larger production capabilities, shorter production time and lower cost.
• Creation of Master Cell Banks (Cont. Cell Line Sys.).
Advantages:
• Rapid and Flexible Cell Culture Manufacturing Systems.
• Platform technology suitable for multiple vaccine development.
• Highly immunogenic vaccines eliciting robust immune responses. Safe product without the need for inactivation
• High yield, larger production capabilities, shorter production time and lower cost.
• Creation of Master Cell Banks (Cont. Cell Line Sys.).
Baculovirus Vector Continuous Cell Line System
Rapid and Scalable Manufacturing System
Current “Egg” Process
Virus grown in embryonated chicken eggs
• Safety Concerns:• Killed vaccine requires chemical inactivation• Live attenuated vaccine requires extensive safety
evaluation• Toxic viruses (i.e. 1918, H5) kill the embryo and
prevent vaccine production
• Not adequate for pandemic response
Current “Egg” Process
Virus grown in embryonated chicken eggs
• Safety Concerns:• Killed vaccine requires chemical inactivation• Live attenuated vaccine requires extensive safety
evaluation• Toxic viruses (i.e. 1918, H5) kill the embryo and
prevent vaccine production
• Not adequate for pandemic response
VLP Technology
VLP are produced in a cell culture system
• VLPs are Non-Infectious:• No inactivation required• Reduced safety concerns during production.
• Rapid Response to emerging pandemic or epidemic influenza virus strains due to fast and flexible system.
VLP Technology
VLP are produced in a cell culture system
• VLPs are Non-Infectious:• No inactivation required• Reduced safety concerns during production.
• Rapid Response to emerging pandemic or epidemic influenza virus strains due to fast and flexible system.
0 1 2 3 4 5 6 7 8 9 10 Months
1st Wave - PandemicTVx 1st production
batch
TVX full production Egg-based 1st
pandemic batchEgg-based full production
Vaccine SupplyInfected CasesEgg-based
TVx
Reduced Manufacturing Costs & Capex
VLP PlantCell-Culture PlantEgg-Based Plant
Manufacturing cost (1 dose)
~ $1.25
Manufacturing cost (1 dose)
> $9.00
Manufacturing cost (1 dose)
> $1.50
< $10 million> $75 million$50 million
A fully functional manufacturing plant producing 20 million doses of VLP vaccine annually, will require an investment (CAPEX) of:
VLP PlantCell-Culture PlantEgg-Based Plant
Manufacturing cost (1 dose)
~ $1.25
Manufacturing cost (1 dose)
> $9.00
Manufacturing cost (1 dose)
> $1.50
< $10 million> $75 million$50 million
A fully functional manufacturing plant producing 20 million doses of VLP vaccine annually, will require an investment (CAPEX) of:
Working on a Strong Pipeline for the Future
Flu Vaccines:
TechnoVax is planning to file for an IND for its lead Seasonal Flu vaccine in 2013 and human clinical trials targeted for the end of 2013. However “Inhaled Powder” version might replace it
An “Universal” Flu vaccine is in development and currently in animal pre-clinical testing.
RSV Vaccine:
Is developing rapidly on an accelerated path for animal testing at Baylor College of med. sponsored by the NIH with a target goal to file for IND in H1-2013.
Dengue Vaccine:
Is developing rapidly and on an accelerated path for preclinical testing to take place in 2013.
“Seasonal Tetravalent” Influenza VLP Vaccine
The tetravalent flu VLP vaccine incorporates an additional B antigen to those recommended by WHO, thus broadening vaccine protection.
Advantages:• Reduced manufacturing steps,
time and costs.
• Protects against multiple influenza virus strains.
• Increased efficiency by targeting multiple viruses.
The tetravalent flu VLP vaccine incorporates an additional B antigen to those recommended by WHO, thus broadening vaccine protection.
Advantages:• Reduced manufacturing steps,
time and costs.
• Protects against multiple influenza virus strains.
• Increased efficiency by targeting multiple viruses.
Flu VLP’s
HN
NH
O
O
NH
O
OH
O
HN
O
HO
OFPDK Excipient Particle
CricketTM Inhalation Device
“Self-Inhaled Powderized” Influenza VLP Vaccine
TechnoVax and MannKind Corp. have combined their respective technologies to create a Powder Formulation of VLP Influenza Vaccine for Intrapulmonary Self-Delivery by Inhalation.
TechnoVax and MannKind Corp. have combined their respective technologies to create a Powder Formulation of VLP Influenza Vaccine for Intrapulmonary Self-Delivery by Inhalation.
No Refrigeration
Self-Administered
Highly conserved subdominant epitopes are masked and poorly recognized by the immune systems
HA antigenic variation:
Drift and shift
“Universal” or “Broadly Neutralizing” VLP VaccineTechnoVax is developing a Concept of Universal Vaccine and Identification of Broadly Neutralizing Antibody in Humans.
HA2: 347-520
HA1: 241-346
Interior of VLP
Transmembrane and cytoplasmic domains: 521-568
A
B
C
Modified HA Molecules
Transmembrane and cytoplasmic domain: 521-568
HA2: 347-520
HA1: 281-346
HA1: 17 - 65
12 amino acid linker
Interior of VLP
B
C
A D
Transmembrane and cytoplasmic domain: 521-568
HA2: 347-520
Interior of VLP
Different structures of HA molecules without immuno-dominant antigenic sides
Evaluation of Induction of Neutralizing Antibodies
Elicitation of neutralizing antibodies by remodeled HA VLP vaccines is evaluated by an in-vitro micro-neutralization assay.
Mixtures of virus/antibodies are applied to MDCK cells and infection is assayed by detecting expression of influenza NP protein using an ELISA test.
TechnoVax’ VLP Approach For RSV Vaccine
Target antigens are incorporated on the surface of the VLP structure as a repetitive array of a single antigen or in combination with other molecules forming multiple antigenic VLP structures
Single antigenic VLP
Multiple antigenic VLP
VLP scaffold
Target antigens
Most important cause of lower respiratory tract infection (LRI) in infants, children and the elderly worldwide
Gradient purified respiratory syncytial virus-like particles (VLPs), produced in CHO, were negatively stained and examined by electron microscopy. The micrograph shows spherical particles (80-100nm) decorated with surface projections or “spikes” of the fusion protein F resembling the morphology of respiratory syncytial virus (RSV).
Respiratory Syncytial Virus-Like Particles (RSVLPs)
NIH sponsored animal studies in cotton rats planned for Dec.12/Jan.13 at Baylor Medical College.
Other VLP Vaccines under Preparation
Dengue vaccine:• Preparation of monovalent vaccines to evaluate efficacy in in-vitro
nutralization studies.• Tetravalent possibly at later stage.
Cancer and HIV vaccines:• Early concepts
VLP Delivery System:• Early concept: using VLP to carry small molecules and target desired cells.
Strategy: Flexible Win-Win Partnerships
TechnoVax is seeking Partnerships to create “Win-Win” Solutions
Focused on Moving PreclinicalCandidates to Clinical Proof-of-Concept
and towards Markets.
Target ID Discovery Preclinical Phase 1 Phase 2 Phase 3 NDA
Area of Partnership for TechnoVax and Pharma:
• TVx brings product expertize and initial R&D funding.
• Pharma Partner provides necessary resources to advance candidate through clinical POC.
Capital Efficient Milestone-Driven Partnerships
Defining optimal path to proof-of-concept with Partner: Managing key variables of time, capital, data Development risk management
Milesones:• Tox• IND• Phase 1• Phase 2
Formation
ExerciseOption:• Yes/No• Geography• FRF
Phase 3NDAMarketing
Reduced upfront cost
of entry.
Reduced risk of
clinical proof of concept financing.
Pre-defined Option Cost maximizing investment return and minimizing project risk.
Pharma to market
candidate as per chosen option for royalty.
Thank you
Acknowledgements:TechnoVaxMs. Hinna ZiaullahMr. Anil BhatesDr. Diana DalfoDr. Hui-Ting ChengDr. George MartinMr. Hector Munoz
TechnoVax, Inc.765 Old Saw Mill River RdTarrytown, NY 10591Tel. +1 (914) 345-52300Fax +1 (914) 345 6104
www.TechnoVax.com
Baylor College of MedicineDr. Innocent Mbawuike and Team
City College of New York (CUNY)Dr. Paul Gottlieb and Team