EpiVax IntroductionCompany Overview

2013

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Annie De Groot M.D. CEO/CSOBill Martin, COO/CIO

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EpiVax Corporate Summary

• Founded 1998 – in business/profitable for 15 years• Privately held (De Groot, Martin Principals)• Vaccine and protein design services• In silico epitope discovery, immunogenicity assessment,

and protein de-immunization• In vitro, ex vivo, and in vivo validation assays • Development of immunomodulatory products (vaccines,

therapeutics, Tregitope)• Successful mix of services and grant-funded research:

>14% growth, year over year, without venture funding.

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info 2

EpiVax Management Teamwww.epivax.com/about/management-team/

• Dr. Anne De Groot, CEO/CSO• William Martin, CIO/COO• Cliff Grimm, Managing Director• Dr. Leslie Cousens, Director of Protein Therapeutics• Dr. Lenny Moise, Director of Vaccine Research• Frances Terry, Bioinformatics Program Manager • Jason Centracchio, Laboratory Manager

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info 3

EpiVax: Four Core Strengthswww.epivax.com

Epitope Services • Epitope Mapping• HLA Binding, Class I & II• T cell assays (naïve, memory)• In vivo assays (HLA Tg mice)

Fee for Service

Vaccines • Grant funded R & D• Excellent proof of principle Grant Funded

2nd Generation Therapeutics

• Select targets• Funded research or joint developments• Develop molecule and license

Sponsored research / Joint Development

Immuno-modulation

• Tregitopes • In preclinical development - first in

class - allergy, autoimmunity, transplant

Grant fundedOptions available for selected “Field of Use”

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

Ovalbumin vs. Human Serum AlbuminEpiVax Services

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

In Silico Immunogenicity Screening & Prediction

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In Silico Immunogenicity Screening Services

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ISPRI Website: Cloud-based Interactive Protein Screening and Reengineering Interface, leased to large pharma world-wide. Your scientists use ISPRI to predict overall and regional immunogenicity. Available for annual lease for a set number of protein sequences (Limited) or Unlimited Sequences. Includes continued consultation and training with experts at EpiVax. http://bit.ly/ISPRI

PreDeFT: Highly detailed in silico immunogenicity analysis covering overall and regional immunogenic potential of a protein therapeutic. Delivered as a “FDA ready” report. EpiVax uses ISPRI for you. http://bit.ly/PreDeFT

HT Screening: High-throughput immunogenicity screening of large sets of antibody heavy-light chain combinations, for overall and comparative immunogenic potential. http://bit.ly/PreDeFTht

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

ISPRIAvailable Tools

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• EpiMatrix– Screen the protein sequences of product candidates for the presence of putative T cell epitopes.

• Immunogenicity Protein Scale– Rate the immunogenic potential of each submitted sequence on a normalized scale and compare

each protein to other immunogenic proteins and antibodies

• Tregitope Analysis– Identify within each submitted sequence putative regulatory T-cell epitopes (i.e. sub-regions

contained within the submitted sequences which may relate to natural regulatory T cells and which may help to dampen the immune potential of the submitted antibody sequence)

• ClustiMer– Identify T-cell epitope clusters contained within product candidates

• Immunogenic Cluster Scale– Rate the immunogenic potential of each T-cell epitope cluster on a normalized scale and compare

each T-cell epitope cluster to other well-known immunogenic epitope clusters

• BlastiMer– Blast T-cell epitope clusters against the non-redundant protein or patent database at GenBank

• OptiMatrix– The protein re-design algorithm that provides a list of critical amino acid residues and potential

amino acid substitutions that are conserved in existing databases (based on published seque- nces) and that do not introduce new epitopes.

In Silico ToolsProtein Immunogenicity Scale

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• EpiMatrix Predicted Excess/Shortfall in Aggregate Immunogenicity Relative to a Random Peptide Standard

• All scores are adjusted for the presence of Tregitopes.

• *Average of Antibodies Known to Induce Anti-Therapeutic Responses in More Than 5% of Patients

• †Average of Antibodies Known to Induce Anti-Therapeutic Responses in Less Than 5% of Patients

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Thrombopoietin

Human EPO

Immunogenic Antibodies*

Tetanus Toxin

Influenza-HA

Albumin

IgG FC Region

EBV-BKRF3

Non-immunogenic Antibodies†

Follitropin-Beta

Your Protein

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

JanusMatrix

TCR

MHC

Algorithm that predicts cross-reactivity

of epitopes with human, human microbiome and pathogen genomes

• Analysis of two “faces” of MHC ligand;The MHC-binding face (aggretope), and the TCR-interacting face (epitope)

• Compares TCR face of query epitope to genome database to find cross-reactive sequences

Source epitope

Human protein with cross-reactive epitopes

Cross-reactive human epitope

Source (pathogen) protein

Immunogenic pathogen sequences Cross-reactive Tregitopes

Immunomodulation and Deimmunization

DeFT – Deimmunization of Functional Therapeutics

• Optimized amino acid substitution to eliminate T cell epitopes without changing protein structure or sacrificing therapeutic function

• Introduction of Tregitopes- epitopes that promote immune tolerance

http://bit.ly/EpiDeFT Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

What is a Tregitope?

• Highly conserved peptide sequences in Fc and Fab regions of antibodies

• High affinity, promiscuous binders across HLA alleles

• Activate antigen-specific regulatory T cells

• Can be co-formulated or synthesized with therapeutic proteins or carriers

• Patented & discovered by EpiVax

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De Groot A.S., et al., Activation of Natural Regulatory T cells by IgG Fc-derived Peptide “Tregitopes”. Blood, 2008,112: 3303. http://tinyurl.com/ASDeGroot-Blood-2008

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more infohttp://bit.ly/Treg1

Tregitope Applications

Localized, specific suppression of immune response• Auto-immune diseases (Type 1 diabetes,

multiple sclerosis) • Auto-inflammatory conditions (Chrohn’s, IBS)• Promotion of lasting tolerance to allergens• Deimmunization of protein therapeutics:

co-expression or co-administration with immunogenic proteins.

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more infohttp://bit.ly/Treg1

Tregitope Validation Checklist

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more infohttp://bit.ly/Treg1

Tregitopes induce adaptive tolerance in C57Bl/6, D011.10, OTII

Tregitopes suppress/treat diabetes in NOD model (Scott/EpiVax)

Tregitopes suppress transplant rejection in CD28 KO mice (Scott)

Tregitopes suppression = IVIG in OVA/Allergy Model (Mazer)

Tregitopes suppress immune responses to AAV capsid (Mingozzi)

Tregitopes cause expansion of Tregs – iTreg or nTreg?

Continued publications – see here: http://bit.ly/TregPub

iVAX: Web-Based Vaccine Design

http://bit.ly/iVAX1

iVAX Toolkit – Online Access

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more infohttp://bit.ly/iVAX1

iVAX – Quick Facts

• Comprehensive set of proprietary epitope mapping algorithms for vaccine design and efficacy analysis

• Tools to build immunogenic and effective vaccines from whole genomes or sets of strain genomes.

• Applications to assay reagent development and diagnostics• Assess cross reactivity with variant strains, the human

genome, the human microbiome.• Interactive and user friendly• 24/7 access• On-site training program• Technical support service

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more infohttp://bit.ly/iVAX1

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Vaccine Design Tools and Techniques

http://bit.ly/iVAX1

Lab-Based Services

http://bit.ly/EpiLab

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Lab Services Overview

• EpiVax regularly performs a number of in vitro, ex vivo

and in vivo analyses, internally and commercially • Class I & II HLA Binding assays with purified HLA

molecules, licensed exclusively to EpiVax• T cell assays to determine activity, proliferation

and phenotype• IVIP long term culture for testing response to

novel antigens or therapeutics• HLA transgenic mice to measure human-like

antigen presentation in vivo

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info 21http://bit.ly/EpiLab

T Cell Immunogenicity Assays

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Test ArticleWhole, lysate, peptide

• Elispot• CBA• Elisa• Flow• CFSE

Format(Readout)

Assay(Cell Culture)

• Cytokine production (Elispot, Elisa)• Proliferation (CFSE)• Phenotype – Teff vs Treg (Flow

cytometry)Endpoints

• Exposed blood• Fresh (active cells)• Re-stimulation (memory)

• Naïve blood• Long term culture (IVIP)

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

http://bit.ly/EpiLab

Summary

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EpiVax Brings Value

• Expert team of thought-leaders and innovators in the immunogenicity field

• USA based company with a truly global presence, with major clients on almost all continents

• Highly published (170+) proven track record of successful projects and effective immunogenicity prediction and deimmunization

• Extremely flexible concierge-style service, with a focus on problem solving

• We will develop and/or optimize services to fit your companies' specific needs and goals

Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info

EpiVax: Four Core Strengths

Confidential