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