EpiVax Company Overview

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 [email protected] (US/other) or [email protected] (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 [email protected] (US/other) or [email protected] (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 [email protected] (US/other) or [email protected] (EUR) for more info

Ovalbumin vs. Human Serum AlbuminEpiVax Services


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


http://bit.ly/ISPRI

http://bit.ly/ISPRI

http://bit.ly/PreDeFT

http://bit.ly/PreDeFT

http://bit.ly/PreDeFTht

http://bit.ly/PreDeFTht

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 sequences) 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


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 [email protected] (US/other) or [email protected] (EUR) for more info

http://bit.ly/EpiDeFT

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 [email protected] (US/other) or [email protected] (EUR) for more infohttp://bit.ly/Treg1

http://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.


http://bit.ly/Treg1

Tregitope Validation Checklist


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

http://bit.ly/Treg1

http://bit.ly/TregPub

http://bit.ly/TregPub

iVAX: Web-Based Vaccine Design

http://bit.ly/iVAX1

http://bit.ly/iVAX1

iVAX Toolkit – Online Access

Non-Confidential contact [email protected] (US/other) or [email protected] (EUR) for more infohttp://bit.ly/iVAX1

http://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 [email protected] (US/other) or [email protected] (EUR) for more infohttp://bit.ly/iVAX1

http://bit.ly/iVAX1

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Vaccine Design Tools and Techniques

http://bit.ly/iVAX1

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 [email protected] (US/other) or [email protected] (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)




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


EpiVax: Four Core Strengths

Confidential

EpiVax Company Overview

Technology

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