EpiVax Introduction
Company Overview
2013

Annie De Groot M.D. CEO/CSO
Bill Martin, COO/CIO
1
EpiVax Corporate Summary
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Founded 1998 – in business/profitable for 15 years
Privately held (De Groot, Martin Prin...
EpiVax Management Team
www.epivax.com/about/management-team/

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•
•
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•

Dr. Anne De Groot, CEO/CSO
William Martin, CI...
EpiVax: Four Core Strengths
www.epivax.com
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Epitope Mapping
HLA Binding, Class I & II
T cell assays (naïve, memory...
EpiVax Services
Ovalbumin vs. Human Serum Albumin

Non-Confidential contact amarcello@epivax.com (US/other)
or pdegroot@ep...
In Silico Immunogenicity
Screening & Prediction
In Silico Immunogenicity
Screening Services
ISPRI Website: Cloud-based Interactive Protein Screening and
Reengineering Int...
ISPRI
Available Tools
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EpiMatrix
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Immunogenicity Protein Scale
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Rate the immunogenic potential of each T-cell ...
In Silico Tools
Protein Immunogenicity Scale
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Influenza-HA

Albumin
Immunogenic Antibodies*

†Average of Anti...
JanusMatrix
Algorithm that predicts cross-reactivity
of epitopes with human, human
microbiome and pathogen genomes

TCR

•...
Immunomodulation and
Deimmunization
DeFT – Deimmunization
of Functional Therapeutics

• Optimized amino acid substitution to eliminate T
cell epitopes without...
What is a Tregitope?
• Highly conserved peptide
sequences in Fc and Fab
regions of antibodies
• High affinity, promiscuous...
Tregitope Applications
Localized, specific suppression of immune response
• Auto-immune diseases (Type 1 diabetes,
multipl...
Tregitope Validation Checklist
 Tregitopes induce adaptive tolerance in C57Bl/6, D011.10, OTII
 Tregitopes suppress/trea...
iVAX: Web-Based
Vaccine Design

http://bit.ly/iVAX1
iVAX Toolkit – Online Access

http://bit.ly/iVAX1

Non-Confidential contact amarcello@epivax.com (US/other)
or pdegroot@ep...
iVAX – Quick Facts
• Comprehensive set of proprietary epitope mapping
algorithms for vaccine design and efficacy analysis
...
Vaccine Design Tools and Techniques

http://bit.ly/iVAX1

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Lab-Based Services

http://bit.ly/EpiLab
Lab Services Overview
• EpiVax regularly performs a number of in vitro, ex vivo
and in vivo analyses, internally and comme...
T Cell Immunogenicity Assays
•

Test Article
Whole, lysate, peptide

Assay
(Cell Culture)

Endpoints

Format
(Readout)

ht...
Summary
EpiVax Brings Value
• Expert team of thought-leaders and innovators in the
immunogenicity field
• USA based compan...
EpiVax: Four Core Strengths

Confidential
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EpiVax Company Overview

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A brief introduction to EpiVax. Learn about our history, immunogenicity screening services, vaccine design and development, novel immunomodulatory peptides and lab based assays.

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  • Slide 7 The Protein Immunogenicity Scale rates your protein against known immunogenic and non-immunogenic proteins. Scores range from approximately -80 to +80; any score above +20 indicates a significant potential for immunogenicity.
  • We have developed a preliminary version of a cross-reactivity prediction tool that we call Janus (for the two-faced god, looking at both MHC and TCR).  Given a query epitope, either experimentally determined or predicted from a provided sequence, Janus finds peptides in other genomes that are predicted to bind the same MHC allele(s) and present a similar interface to the T cell receptor.  The MHC-facing residues may differ, as long as EpiMatrix predicts that the same MHC will bind, but the TCR-facing residues must be the same, other than at most a specified number of conservative substitutions.  Janus enables interactive sorting and navigation of the predicted cross-reactive epitopes.Toenable efficient queries and interactive navigation, Janus employs a preprocessed and indexed database of predicted epitopes from genomes of interest for cross-reactivity analysis.  We have currently processed the human genome, a representative portion of the gut microbiome, and a set of different dengue strains.  
  • Not only do we need to think about the pathogen in selecting antigens. We also need to think about the host. We have always considered it to be important, if possible, to exclude vaccine components that are conserved with self. The rationale for avoiding cross-reactivity is self-evident.In addition, we’re now excluding sequences that are conserved with Human microbiota… can be seen as an extension of the self
  • The process is . . .ToolkitWe’ve applied this process to numerous pathogens
  • EpiVax Company Overview

    1. 1. EpiVax Introduction Company Overview 2013 Annie De Groot M.D. CEO/CSO Bill Martin, COO/CIO 1
    2. 2. 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
    3. 3. EpiVax Management Team www.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
    4. 4. EpiVax: Four Core Strengths www.epivax.com • • • • 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 Immunomodulation • • Tregitopes In preclinical development - first in class - allergy, autoimmunity, transplant Grant funded Options available for selected “Field of Use” Epitope Services Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    5. 5. EpiVax Services Ovalbumin vs. Human Serum Albumin Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    6. 6. In Silico Immunogenicity Screening & Prediction
    7. 7. In Silico Immunogenicity Screening Services 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 7
    8. 8. ISPRI Available Tools • EpiMatrix – • Immunogenicity Protein 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 – • Identify T-cell epitope clusters contained within product candidates Immunogenic Cluster Scale – • 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 – • Rate the immunogenic potential of each submitted sequence on a normalized scale and compare each protein to other immunogenic proteins and antibodies Tregitope Analysis – • Screen the protein sequences of product candidates for the presence of putative T cell epitopes. 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. 8
    9. 9. In Silico Tools Protein Immunogenicity Scale - • • • • Influenza-HA Albumin Immunogenic Antibodies* †Average of Antibodies Known to Induce Anti-Therapeutic IgG FC Region Responses in Less Than 5% of Patients Non-immunogenic Antibodies† Follitropin-Beta - 60 - - 50 - 40 - - 30 - - 20 - - Tetanus Toxin - 10 - - 00 - - -10 - - -20 - - -30 - - -40 - -50 - -60 - - -70 - - *Average of Antibodies Known to Induce Anti-Therapeutic Responses in More Than 5% of Patients EBV-BKRF3 70 - Human EPO - - All scores are adjusted for the presence of Tregitopes. Thrombopoietin - - EpiMatrix Predicted Excess/Shortfall in Aggregate Immunogenicity Relative to a Random Peptide Standard 80 -80 - Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info Your Protein 9
    10. 10. JanusMatrix Algorithm that predicts cross-reactivity of epitopes with human, human microbiome and pathogen genomes TCR • 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 HTREG_IGGC-167 MHC Source (pathogen) protein Source epitope HTREG_IGGC-289 Cross-reactive human epitope Human protein with cross-reactive epitopes Immunogenic pathogen sequences Cross-reactive Tregitopes
    11. 11. Immunomodulation and Deimmunization
    12. 12. 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
    13. 13. 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 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) http://bit.ly/Treg1 or pdegroot@epivax.com (EUR) for more info 13
    14. 14. 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 Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    15. 15. 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 Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    16. 16. iVAX: Web-Based Vaccine Design http://bit.ly/iVAX1
    17. 17. iVAX Toolkit – Online Access http://bit.ly/iVAX1 Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    18. 18. 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 http://bit.ly/iVAX1 Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info
    19. 19. Vaccine Design Tools and Techniques http://bit.ly/iVAX1 19
    20. 20. Lab-Based Services http://bit.ly/EpiLab
    21. 21. 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 http://bit.ly/EpiLab Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info 21 21
    22. 22. T Cell Immunogenicity Assays • Test Article Whole, lysate, peptide Assay (Cell Culture) Endpoints Format (Readout) http://bit.ly/EpiLab • • • • Exposed blood • Fresh (active cells) • Re-stimulation (memory) Naïve blood • Long term culture (IVIP) Cytokine production (Elispot, Elisa) Proliferation (CFSE) Phenotype – Teff vs Treg (Flow cytometry) • • • • • Elispot CBA Elisa Flow CFSE Non-Confidential contact amarcello@epivax.com (US/other) or pdegroot@epivax.com (EUR) for more info 22
    23. 23. Summary 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 23
    24. 24. EpiVax: Four Core Strengths Confidential

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