Japanese Red Cedar Immunotherapy

Next Genera*on Immunotherapies Improving Health Allergy Immunotherapy Non-‐Confiden*al Presenta*on | Q2 2014 For addi(onal informa(on, visit www.immunomix.com

Headquarters: Hershey PA | Lab: Rockville, MD | 717-‐327-‐1919

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Immunomic Therapeu(cs (“ITI”) was founded in 2006 based on patented technology licensed exclusively from Johns Hopkins University and the laboratory of Dr. Thomas August. ITI is a privately held company incorporated in the State of Delaware. Since its incep(on, it has raised over $10 million in investment capital to support the development of novel therapeu(c vaccines. The Company is headquartered in Hershey, Pennsylvania where it also houses its manufacturing laboratory. The Company’s Research & Development laboratory is located in Rockville, Maryland. In addi(on to the development of allergy immunotherapeu(cs, Immunomic Therapeu(cs is also working with a major pharmaceu(cal partner to develop novel vaccines for animal health and with academic partners for important applica(ons in oncology

About Immunomic Therapeu*cs (ITI)

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!  Privately-‐held clinical stage biotechnology company

!  Developing next genera(on vaccines based on the patented LAMP Technology

!  Lead product is JRC-‐LAMP-‐vax, an allergy immunotherapy to treat pollen allergies caused by Japanese red cedar

ITI Has Achieved Significant Accomplishments

!  Phase I study of JRC-‐LAMP-‐vax demonstrated excellent safety and a posi(ve indica(on of immunogenicity – 100% of allergic Japanese-‐na(ve pa(ents converted from posi(ve to nega(ve skin test at the end of the Phase Ib

!  2012 IND filed for JRC-‐LAMP-‐vax Phase I; study ini(ated in Japanese pa(ents

!  2011 Animal health collabora(on with top 5 pharma company

!  2005 Sublicensed LAMP to major biopharma company for use in a cancer vaccine

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“LAMP” or Lysosomal Associated Membrane Protein refers to a class of proteins found in the lysosomal membrane of an(gen presen(ng cells. This class of protein has been iden(fied in all species with an immune system including humans, non-‐human primates, rodents, chickens and fish. The LAMP gene codes for a transmembrane protein that resides in the lysosomes of an(gen presen(ng cells. Our scien(fic founder, Dr. Tom August at Johns Hopkins University discovered that by inser(ng the coding sequence to an an(genic target into the LAMP gene one could effec(vely deliver the resul(ng protein sequence directly to the MHC-‐II complex in maturing lysosomes. This is the only mechanism known for delivering an(gens directly to the MHC-‐II complex. The unique design of the LAMP-‐an(gen chimeric protein “envelopes” the target within LAMP and within a cellular organelle providing a unique level of safety in allergy immunotherapy.

Patented LAMP Technology: A PlaMorm for Developing Potent Next Genera*on Vaccines

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Patented LAMP Technology: A PlaMorm for Developing Potent Next Genera*on Vaccines

Applied in Mul*ple Clinic Trials Allergy: Completed Phase I study of 24 subjects for pollen allergy Cancer: Prostate, melanoma, glioblastoma & AML studies have shown immune ac(va(on, safety, and trend towards posi(ve survival in over 100 pa(ents to date Literature: Over 70 publica(ons on therapeu(c LAMP vaccines and the mechanism of ac(on

ITI’s Allergen-‐LAMP Fusion Protein

YQTI-‐COOH Cytoplasmic domain Signal sequence YQTI directs fusion protein into the lysosome

Luminal domain Heavy glycosyla,on stabilizes an,gen-‐LAMP fusion protein trafficking to MHC-‐II compartment

O-‐glycan N-‐glycan

Allergen Sequence Cry j 2, op,mized for immunogenicity

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1.  Conven(onal Vaccines (far leg) u(lize a formula(on composed of either killed virus (e.g. influenza) or bacteria, ajenuated virus (e.g., yellow fever) or purified viral proteins (e.g., hepa((s B). In this case, the vaccine is delivered intramuscularly and is processed by the immune system through an(gen presen(ng cells.

2.  DNA Vaccines (center) without LAMP deliver a DNA or RNA sequence with or without electropora(on into (ssue (without specificity). The cells that take up the DNA synthesize the protein encoded in the vector into the cytoplasm of the cell where it is processed using the TAP pathway resul(ng in MHC-‐I presenta(on to the immune system. This method is dependent upon the inefficient cross-‐priming pathway to achieve MHC-‐II presenta(on.

3.  LAMP-‐vax (right) u(lize the sequence iden(fy contained in the LAMP gene to direct the an(genic sequence directly into the MHC-‐II pathway. Helper T-‐cell ac(va(on is achieved while even enhancing CD8+ presenta(on.

The corresponding figure compares and contrasts the 3 major types of vaccines in use today:

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LAMP Uses a Novel An*gen Trafficking Mechanism to Induce a Robust & Effec*ve Immune Response

LAMP-Vax Vaccines Conventional Vaccines DNA Vaccines

Endogenous antigen presentation by MHC-I

Exogenous antigen presentation by MHC-II

Endogenous antigen presentation by MHC-I & MHC-II

Immune Response Humoral CD4 CD8

EP-‐ EP+ IM / ID

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Immunomic Therapeu(cs has exclusive rights to the LAMP Technology plaoorm which is protected by mul(ple patents issued worldwide. The Company has also secured access to suppor(ng technologies for delivery and manufacture of vaccine product.

ITI’s Intellectual Property: LAMP Technology

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ITI’s Intellectual Property: LAMP Technology

!  LAMP Technology is Secured By Issued Patents Worldwide –  Lysosomal Targe*ng of An*gens

•  US Patent number 5,633,234 •  Patented in Europe, Japan and North America

–  Chimeric Vaccines

•  US Patents 8,318,173 & 8,445,660 •  Issued in Japan, US, EU, Australia with protec(on un(l 2022

–  Addi*onal Patents Pending Worldwide •  ex. Nucleic Acids For Treatment Of Allergies (US App 61496866)

!  In-‐licensed IP –  State-‐of-‐the art processes for plasmid DNA fermenta(on

•  Manufacturing yields up to 5g/L in fermenta(on –  Plasmids with enhanced stability and gene expression in vivo –  An(bio(c resistance free immuniza(on vectors –  Needle free and dissolvable delivery of DNA vaccines

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The Company’s product development pipeline is focused on the allergy product area for internal development including products for global cedar / juniper / cypress allergy, peanut allergy and flea allergy in dogs. Additional opportunities working in collaboration with the laboratory of Dr. Tom August has led to a prototype therapeutic vaccine for HIV. In addition, a number of academic laboratories have been developing applications for LAMP-vax in oncology including a major study sponsored by our partner and licensee, the Geron Corporation (now Asterias), which showed a significant clinical response in leukemia patients (AML).

Human Health Pipeline: Internal & External Development

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Human Health Pipeline: Internal & External Development

An*gen(s) Design Valida*on Pre-‐clinical Ph. I Ph II Ph.III Partner /

Collaborator

Allergy JRC-‐LAMP-‐vax -‐ Japanese cedar Cry j1, j2, j3

ARA-‐LAMP-‐vax -‐ Peanut Allergy Ara h1, h2, h3 Mt. Sinai

Mul*-‐LAMP-‐vax -‐ Mul(valent Undisclosed

Infec*ous Disease

HIV-‐LAMP-‐vax Gag-‐pol-‐nef-‐tat-‐vif

HIV Clade B mRNA DC Therapy Tat, rev, nef U. Brussels

Oncology

GRNVAC1 -‐ AML hTERT BioTime / Asterias

GRNVAC1 -‐ Prostate Cancer hTERT BioTime / Asterias

TriMix DC Therapy -‐ Melanoma 4 major TAAs U. Brussels

pp65 DC Therapy -‐ Glioblastoma pp65 Duke University

VGRvIII DC Therapy -‐ GBM VGFRvIII Duke University

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JRC-‐LAMP-‐vax Vaccine for Treatment of Cedar Allergies

Immunotherapy for the treatment of vaccines has been in practice for over 100 years Standard immunotherapy involves subcutaneous delivery of small amounts of allergen over many months or years of continuous therapy

Therapy often involves 100 or more shots. More recently, allergen has been formulated as sublingual drops which can be delivered daily or weekly during allergy season.

Since conventional immunotherapy utilizes allergen or allergenic proteins, the patient is at risk for adverse events including anaphylaxis.

LAMP-vax Immunotherapy only requires a few shots (4 in the current study) to achieve an effect.

LAMP-vax does not expose the patient to free allergen greatly increasing the safety of the therapy.

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JRC-‐LAMP-‐vax Vaccine for Treatment of Cedar Allergies

Japanese Red Cedar & Japanese Cypress Allergy Market

!  Leading causes of allergy and asthma in Japan

!  Approximately 35 million are allergic to cedars & cypress pollen

!  Es(mated $1.7 – 2.0B spent trea(ng allergic symptoms

!  Alternate immunotherapies and drugs have low efficacy

!  JRC-‐LAMP-‐vax excep(onally safe due to unique mechanism of ac(on

!  Treatment will require 4 or less shots and surpass tradi(onal immunotherapy in efficacy

JRC-‐LAMP-‐vax has the poten*al to revolu*onize the treatment of allergies in Japan

a cloud of “sugi” pollen

Mature Japanese red cedar trees can produce 2kg of highly allergenic pollen

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Phase I Study Design of JRC LAMP-‐Vax

Summary of trial parameters Objec*ve: Evaluate safety and immunological ac(vity in first-‐in-‐humans trial Study Size: 24 Japanese subjects Study dura*on: 48 day delivery of vaccine immunotherapy followed by 180 day follow up Pre-‐treatment lab tes*ng: safety, blood, chemistry, electrolyte, PFT tes(ng Immunological tes*ng to monitor safety through an( LAMP, JRC Immunocap, Mountain Cedar Immunocap and an(gen-‐specific IgE, IgG and IgG isotypes

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Phase I Protocol

Dosing at 14 day intervals (2 or 4 mg)

Monitoring at Days 132 & 220 Day 14 of Study

Safety Screening Subjects monitored for adverse events, immunological profies

Long Term Monitoring of Response

Subjects monitored for skin test & immunologiical profiles

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Summary of Phase I Clinical Studies of JRC-‐LAMP-‐vax

Subjects that received the vaccine were all skin test negative by 220 days after their initial dose None of the control group (negative skin test at day zero) developed any indication of an allergic response to the vaccine (no IgE & no skin test reactivity) All of the subjects who were skin test positive for JRC converted to skin test negative by the end of the study period. No subjects who converted to skin test negative reverted back to positive. Up to 50% of the unrelated allergens monitored in the study also converted to skin test negative suggesting a broad treatment for allergy as a result of the JRC-LAMP-vax therapy.

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Summary of Phase I Clinical Studies of JRC-‐LAMP-‐vax

Efficacy & Safety Goals for JRC-‐LAMP-‐vax Phase 1a Results Phase 1B

EFFICACY:

Elimina(on of JRC/Mtn C/CryJ2 skin test reac(vity 14 of 16 subjects 100% conversion

Conversion skin test from posi(ve to nega(ve 15 of 16 subjects 100% conversion

SAFETY:

No anaphylac(c / allergic responses (CryJ2 sequestered intracellular no leakage)

Achieved Maintained

No an( LAMP an(body genera(on Achieved Maintained

No severe adverse reac(ons Achieved Maintained

Skin test nega(ve pa(ents remain nega(ve 8 of 8 subjects Maintained

IgE levels stable or decreasing Achieved TBD

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ITI’s Vision for Allergy Immunotherapy

Immunotherapy has the potential to drastically reduce the dependence on drugs such as Benadryl, Claritin and other drugs that treat symptoms only. This can be accomplished by using a therapeutic approach that reverses the “net allergic charge” in the immune system, moving from an IgE / Th2 allergenic response to an IgG / Th1 response. In model animal systems for flea allergen, red cedar allergens and peanut allergens, we have observed a strong Th1 response to these potent allergens. In our first human study, we observed that the LAMP-vax therapy reversed the skin test profile of all the subjects. We also observed that the specific therapy induced conversion of non-related allergens suggesting a systemic response. Our vision is to exploit the response to strong allergens to create a universal allergy vaccine that will treat most allergens with just a few doses and then annual maintenance.

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ITI’s Vision for Allergy Immunotherapy

Number of extracts manufactured by ALK to be reduced by 2016… while ITI aims to revolu,onize allergy: with mul(valent immunotherapies for the major classes of allergy

Conceptual design of environmental allergy vaccine

Cedar Pollens

Weed Pollens

Other Tree

Pollens

Grass Pollens

Cat, Dog, Other

2016

378 Extracts

In 2010, ALK manufactured

983 Extracts

2020 Mul(valent Formula(on

2012

698 Extracts

ALK ITI

LAMP PlaMorm Pollens: Trees & Grasses Food: Legumes, Tree Nuts,

Milk & Eggs Insect / Mite Animal Dander Fungi / Mold

Dust Mite

Immunomic Therapeutics, Inc. [email protected] www.immunomix.com 240-401-7496 follow us on Twitter at www.twitter.com/immunomix

Japanese Red Cedar Immunotherapy

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