THE in vivo ENGINE OF

CYTOTOXIC T CELLS TO FIGHT DISEASE

November 2014

2

Forward-looking Statements

This presentation contains forward-looking statements with respect to, among other things,

our business, financial condition, strategy and prospects, and has been prepared solely for

informational purposes. All statements, other than statements of historical fact, regarding

our strategy, potential future products, prospects, plans, opportunities and objectives

constitute “forward-looking statements.” These statements are not guarantees of future

performance and involve a number of unknown risks, assumptions, uncertainties and

factors that are beyond our control. Given these risks, assumptions and uncertainties, you

should not place undue reliance on these forward-looking statements.

Important factors that could cause actual results to differ materially from those indicated

by such forward-looking statements include, among others, our history of net losses and

expected net losses for the foreseeable future, that we have no product candidates

approved for commercialization and may never achieve profitability, that we will require

additional capital to finance our operations, that we may not be able to successfully

develop, obtain regulatory approval and commercialize our product candidates, all of

which are novel and in early clinical development, and those other risks that will be set

forth under the header “Risk Factors,” “Note Regarding Forward-Looking Statements” and

“Management’s Discussion and Analysis of Financial Condition and Results of Operations” in

our periodic reports filed with the Securities and Exchange Commission, including our

Quarterly Report for the period ended September 30, 2014. All statements contained in this

presentation are made only as of the date of this presentation and are subject to

uncertainty and changes. Except as required by law, we expressly disclaim any

responsibility to update such forward-looking statements, whether as a result of new

information, future events or otherwise.

• Introduction

• Discovery Platforms

• Clinical Product Candidates

• Financial Highlights & Upcoming Milestones

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Contents

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Dual Discovery

Platforms

Two productive discovery platforms from

cutting-edge T cell immunology science

First-in-class

Clinical Product

Candidates

Clinical-stage product candidates in our two

approaches in both orphan and high-

incidence tumors

Team Experienced management, proven Board and

world-class advisors

Immune Design: Bringing All the Pieces Together

Strategic

Focus

Immuno-Oncology -100% retained• with infectious, allergic and autoimmune diseases

optionality for partnering or additional growth

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Two IMDZ ApproachesTwo T cell TherapiesTwo Main Categories

Adoptive T cell

transfer(personalized, ex

vivo manipulation)

Specific AntigenOff-the-shelf,

In vivo

induction and

expansion of T

cells

Remove the

blockade(checkpoint

inhibitors)

Induce T

cells to kill

the tumor

Immuno-Oncology: the next pillar of

cancer treatment

Endogenous

Antigen

Immune Design: A Premier Immuno-Oncology Company

Tumor

Tumor-induced

Immune BlockadeCTLs

Carlos Paya, MD, PhDChief Executive Officer

President

Vice President

Stephen R. Brady, JD, LLMChief Business Officer

VP Corporate Development

Wayne Gombotz, PhDChief Development Officer

Vice President

Senior Director

Richard T. Kenney, MD, FACPChief Medical Officer

Chief Medical Officer

Jan H. ter Meulen, MD, DTM&HChief Scientific Officer

Executive Director

Frank J. Hsu, MDVice President, Head of Oncology

Chief Medical Officer

Senior Medical Director

Paul Rickey, CPAVice President, Finance & Administration

Corporate Controller

Senior Auditor

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Experienced and Proven Leadership Team

Prior Experience

7

Exceptional Board and Advisors

Board of Directors

Ed Penhoet, PhD,° Alta (Chair)

David Baltimore, PhD,* §° Caltech

Franklin M. Berger, Independent

Carlos Paya, MD, PhD, IMDZ

Scientific Advisors (SAB)

Larry Corey, MD,° Fred Hutch (Chair)

David Baltimore, PhD,* §° Caltech

Carl June, MD,° U of Penn

Phil Greenberg, MD, Fred Hutch.

Clinical Advisors (CAB)

Mario Sznol, MD, Yale (Chair)

Jedd Wolchok, MD, PhD, MSKCC

Jeff Weber, MD, PhD, Moffitt

F. Stephen Hodi, MD, Dana Farber

Robert Maki, MD, PhD, Mt. Sinai

*Nobel Laureate, §National Academy of Sciences,

°Institute of Medicine of the National Academies

William R. Ringo, Independent

Peter Svennilson, TCG

Brian Atwood, Versant

Inder Verma, PhD,§° Salk Institute

Rafi Ahmed PhD,§ Emory University

Steven Reed, PhD, IDRI

Patrick Hwu, MD, MD Anderson

Nina Bhardwaj, MD, PhD,° Mt. Sinai

Kristen Hege, MD, Celgene

David Parkinson, MD,° NEA

Lawrence Baker, DO, U Michigan

DISCOVERY PLATFORMS

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Separate & complementary MOAs induce/expand CTLs in vivo to kill tumors

Specif

ic A

nti

gen

Appro

ach

Endogenous

Anti

gen

Appro

ach

TUMOR

LYSISTUMOR

GLAAS+ Antigen protein induces CD4 T cells

DC

In vivo expanded

CTLs attack tumorsCD8 T cells (CTLs)

ZVex + Antigen RNA induces CTLs

CD4 T cells

expand CTLs

DC

GLAAS-activated DCs

uptake new released

antigens and expand CTLs

ADDITIONAL

TUMOR

LYSISTUMOR

Expanded, diverse CTLs

attack the residual tumor

TUMOR LYSIS by:

- Radiation

- Chemo

- CTLs

- Other

Intra-tumoral GLAAS

+ GLA

The Immune Design in vivo Difference

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Dendritic Cells: the Key to inducing Tumor Killing CTLs

Selective in vivo DC

targeting for maximum

CTL generation

Each new

genetic payload =

potential new product

Capacity

for substantial

genetic payload

Integration-deficient and

replication-incompetent

for safety

Lack of prior

immunity allows for

multiple dosing

The ZVex Advantage: First-in-class in vivo DC Targeting

ZVex: breaks tolerance to self-antigen & induces CTL memory (A); can be dosed

repeatedly (B); controls B16 melanoma growth (C); and synergizes with CPIs (D)

C

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CTL responses in naïve mice,

immunized with 6.5E10 ZVex-mTRP1 (A463M)

Normal mice

A

0

2

4

6

8

0 1 1 1 4 1 7 2 0 2 3 2 6 2 9 3 2

Days Post-Immunization

%CTL

0

50

100

150

200

250

300

350

400

0 14 16 21 23 26 28 30 33 35

Tum

or

Vo

l um

e( m

m3)

Days Post-Tumor Inoculation

ZVex-mTRP1

Buffer 5E9 ZVex-mTRP1

B16 melanoma

0

50

100

150

200

250

300

350

400

0 3 7 10 14 17 21 24 28 31 35

T um

orV

olum

e(m

m3 )

Days Post-Tumor Inoculation

Anti-PD -L1

ZVex-mTRP1

ZVex-mTRP1 + αPD-L1

B16 melanoma

D Control Vector 6E10 ZVex-mTRP1

αPD-L1

B

0

2

4

0 5 7 9 12 16 21 5 7 9 12 16

2nd

Days Post 1st Days Post 2nd

21 5 7 9 12 16 21

Days Post 3rd

3rd

6

1st

CTL responses in naïve mice,

immunized with 8E9 ZVex-NY-ESO-1

%C

TL

Normal mice

The ZVex Advantage: First-in-class in vivo DC Targeting

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Clinical-stage, synthetic TLR4 agonist potently activates DCs in vivo

Boosts pre-existing CTLs

Induces CD4 T and B

cells. Enhances Natural

Killer (NK) cells

Expanding favorable

safety database

(>1,000 subjects)

Demonstrated dose sparing

and antigen cross-

reactivity

Potential to also treat

multiple infectious and

allergic diseases

The GLAAS Advantage: GLA at the Core

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GLA efficiently:

• activates two pathways for maximum DC

activation (A)

• is 100-1,000 more potent than MPL (B)

• induces both maturation of DCs in a

dose-dependent manner and cytokine

production by DCs in the absence of

antigen (C)

A B

C

The GLAAS Advantage: GLA at the Core

14

15.7

IFN-γ

TN

F-α

PBS

+ GLAAS

PBS

+ ZVex

CD4

CD8

(CTL)

0.05

3.16

0.75

0.05

2.82

Robust antigen-

specific CTL

response

GLAAS

+ ZVex

GLAAS, in addition to enhancing number and quality of CTLs generated by ZVex ,

triggers a STRONG antigen-specific humoral response and innate immunity

Combination for CTL induction and expansion

Akin to: G305 LV305 CMB305

Specific Antigen Approach:The Synergistic Prime-Boost of ZVex + GLAAS

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Methods1. Day 0: Inoculation of B6

mice (n=10) with B16F10 tumor cells in the flank

2. Day 12: Start of treatment

3. Weekly immunization4. Prime/boost:

V.V.P.V.P.V.P* 5. CPI: weekly

*Mimics clinical LV305 regimen

Specific Antigen Approach:The Synergistic Prime-Boost of ZVex + GLAAS

* Zvex-mTRP1

** Recombinant mTRP1

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A GLA formulation from GLAAS demonstrates in vivo efficacy

without radiation or other lysing technology

Endogenous Antigen ApproachGLAAS Single Agent Efficacy

Treated tumor Untreated tumor

Data generated from collaboration with Dr. Ronald Levy, Stanford School of Medicine

• A20 Tumor cells (5x106) SQ- R & L abdomen

• GLA ( 2 or 10 ug) or vehicle injected in R

abdomen on days 6, 8 and 11

CLINICAL PRODUCT

CANDIDATES

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Specific Antigen Approach: ‘305 NY-ESO-1 ProgramAssembling blocks towards maximum in vivo CTLS

G305 LV305

Test Individual Building Blocks

STEP 1

STEP 2

STEP 3

CMB305

Combine intoa Prime Boost Therapy

CPI

Combination withCheckpoint Inhibitors (CPI)

CMB305

CMB305LV305 & G305

combo

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G305: GLAAS+NY-ESO-

1

CMB305 Randomized

(a-PD1) in NSCLC

- Data from for LV305 & G305

- CMB305 P1 & LV305

expansion Studies Open

- Data from CMB305 and Exploratory Studies

- Phase 2 Studies Open

1Q15 2H15

LV305

Extend & Explore

CMB305 Single Arm

in Sarcoma (Orphan)

LV305: ZVex / NY-ESO-1

2Q14 4Q14

STEP #1 : Single Agent STEP #2 : Combo Agents STEP #3 : Combo Agents + a-PD1

Phase 1 trials Phase 2 trials

Specific Antigen Approach: ‘305 NY-ESO-1 ProgramAssembling blocks towards maximum in vivo CTLS

CMB305

Extend & Explore

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• Diverse cancer types express this tumor-associated antigen

• Known safety and immunogenicity from previous approaches

Cancer indications to be studied in:

Phase 1 Phase 2

NSCLC NSCLC (High incidence)

Sarcoma Sarcoma (Orphan indication)

Breast

Melanoma

Ovarian

Other cancers known positive for NY-ESO-1Bladder (TCC) Multiple Myeloma

Cholangiocarcinoma Neuroblastoma

Colorectal NHL (DLCL)

Endometrial Cancer Prostate

Esophageal SCC Renal (oncocytoma)

Gastric Thyroid (medullary)

H&N SCC Uterine

Hepatocellular

Specific Antigen Approach: ‘305 NY-ESO-1 ProgramNY-ESO-1 expression

• G100 product potential as a stand-alone therapy

or in combination with tumor lysis agents

(radiation, chemotherapy, other)

• P1 in Merkel Cell Carcinoma (MCC) study ongoing:

first CR recorded

• Second P1 in NHL planned for 2Q15 2015

G100

- Data from P1 Merkel cell carcinoma trial

- G100 in second tumor (NHL) study open

2Q15

G100: MCC P1 - Orphan

G100: NHL + RoRx P1 - Orphan

Existing CTLs are

expanded and new ones

are induced

G100

TUMOR

LYSIS

TUMOR

GLAAS activates DCs in

tumor environment that

uptake neo-antigens

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Endogenous Antigen ApproachAssembling blocks towards boosting CTLs

MCC present(brown dots using CK20)

H&E

CK20

Pre-G100 Superficial node2/7/2014

Post-G100 Superficial node3/3/2014

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MCC absent (after 2 doses of G100)

• Patient presents with groin induration that is biopsied showing MCC

• Patient receives 2 doses of G100 (5 ug/dose) one week apart

• Patient staging is negative for metastasis and undergoes eradicative surgery

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Endogenous Antigen ApproachComplete Response in Loco-Regional MCC

Immuno-Oncology

G100 (Intratumoral GLA**)

SPECIFIC ANTIGEN

One Orphan (sarcoma) & One High

Incidence (NSCLC) Solid Tumor

CMB305 (LV305+G305 prime-boost)

LV305 (ZVex + NY-ESO-1)*

G305 (GLAAS + NY-ESO-1)*

ENDOGENOUS ANTIGENOne Orphan (Merkel Cell Carcinoma)

Infectious Disease & Allergy Phase 1 Phase 2 PartnerPreclinical

G103 (HSV-2 Vaccine)

Food Allergy Vaccine

RSV Vaccine

*Although G305 could have potential therapeutic benefit as a single therapy, we plan to evaluate G305 with LV305 as CMB305. In addition,

although we believe CMB305 should be more effective than LV305 alone, we are preserving the ability to further develop LV305, as well

**Proprietary formulation of GLA from GLAAS

Phase 1 Therapeutic ApproachPreclinical

First-in-class Immunotherapy Pipeline

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Financial Highlights and Upcoming Milestones

• Cash as of September 30, 2014: $83.4 million

• Net proceeds from July IPO: $57.8 million

• Proceeds from July exercise of warrants: $8.1 million

• Total shares outstanding (Nov 2014): 16.9 million

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Event Timing

Phase 1 data on LV305 and G305 in solid tumors

1Q15

Initiate Phase 1 study of CMB305 in solid tumors

Initiate Phase 1 study of G100 in second tumor type 2Q15

Phase 1 data on CMB305 in solid tumors and LV305 expansion

2H15Initiate Phase 2 studies of CMB305 in NSCLC and sarcoma

Phase 1 data on G100 in Merkel cell carcinoma

Establish additional non-oncology collaborations 2H14 - 2015