IMMUNE DESIGN

November 2015

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, 2015. 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.

3

Two types of CTL-

based Therapies

Two Main I-O

Categories

Adoptive T cell

transfer (CAR-T, TCR)

(personalized,

ex vivo)

Next-gen cancer

vaccination

(Off-the-shelf,

in vivo)

Remove the

Blockade

(checkpoint

inhibitors)

CD8 T cells

(CTLs)

tumor

killing

Immuno-Oncology The next pillar of

cancer treatment

Focused in Immuno-oncology to Induce T Cells in vivo

Two Product

Candidates

Clarifying the Landscape

Two Distinct

Approaches

Tumor

Blockade Killer T cells

CMB305

G100

4

CMB305: NY-ESO-1 first-in-class cancer vaccine

G100: intra-tumoral immune activation

Phase 2 and 1b

Initial PoC

readouts in 2016

Clinical validation

of MOAs in

Phase 1 trials

Validating

Partnerships

Onc: MRK, GNE

ID: Sanofi, Medi

Allergy: Sanofi

Finances enable

initial PoC

Tumor-induced

Immune

Blockade

Tumor

Killer T cells

Create the Army (IMDZ) + Remove the Defenses (CPIs)

Designed to make “cold tumors hot, and hot tumors hotter”

Re-arming Your Body with Next-gen Vaccination

Experienced Team

Platform beyond

current products

Innovative in vivo Product Candidates & Distinct MOAs

5

Four Partnered Non-oncology Programs

Two

Discovery

Platforms

Single or

Multi-MOA

Candidates

CMB305 LV305 “Prime” (vector+RNA Ag) & G305 “Boost” (TLR4+protein Ag)

G100 Potent TLR4 agonist

DC targeted to induce and expand Ag-

specific cytotoxic T cells

Activates DCs to present endogenous

Ags and expand pre-existing

cytotoxic T cells

Tumor Ag target = NYESO-1 Any antigen present in tumor

Intradermal and IM Injections Intratumoral Injection

ZVex

Platform (DC-tropic Lentivirus)

GLAAS

Platform (Synthetic TLR4 Ag)

CMB305 & G100 PRODUCT CANDIDATES

6

CMB305: Three Step Clinical Development Optimal Approach to Maximize Effectiveness of NY-ESO-1 Killer T cells

STEP 1

STEP 2

STEP 3

Combination

CPI

CMB305 Combined w/ CPI

LV305 G305

CMB305

LV305 G305

CMB305

+

Individual Building Blocks

G305 (GLAAS)

LV305 (ZVex)

Completed:

Data @ ASCO 2015

Ongoing:

Data H1’2016

Ongoing:

Initial Data H2’2016 Collaboration with Genentech

(atezolizumab)

✔

7

Tumor-induced

Immune

Blockade:

CPIs

Tumor

Killer T cells:

CMB305

G305 and LV305 Ph1 Data Support CMB305 Development

G305 LV305 CMB305 Im

munogenic

ity

Safe

ty

Clinic

al

Benefi

t

• Stable disease in 67% of

patients (med: 245d)

• CA125 response

• Stable disease in 67% of

patients (med: 208d)

• Progression cessation and

regression observed

• Favorable single agent

signal in sarcoma (PFR: 67%

(3mo)/42% (6mo))

G305: SD in 8/12pts at d70 (end TX); CA125 response (GCIG criteria) 600(D0)281(D70)207(D242)

LV305: SD in 8/12pts at d70 (end TX); 4/6 pts stopped tumor progression and tumor regression of 14% in one pt w/SD at

347+d; PFR=progression free rate (all LV305 patients had a form of sarcoma)

Ab: 9/12

CD4: 5/11

CD8: 2/10

n=12

CD4: 5/11 CD8: 6/11

n=12

3/11

CMB305

Phases 1

and 2

Underway

Predicted Immunogenicity with Both Agents

Safe (Grade 1-2 AEs only)

Signal of Individual Clinical Benefit

8

LV305 Ph1: NY-ESO-1 T-cell Responses Exceed Published Studies w/

Multiple Agents

9

0

10

20

30

40

50

60

70

80

LV305 2015 (n=12) Odunsi 2012(n=47)

Dhodapkar 2014(n=34)

Chen 2015(Arm A, n=18)

Percentage NY-ESO-1-specific T-cell responses in Patients*

All T cell responders CD4 CD8 CD4 & CD8

Odunsi, et al (2012) Efficacy of vaccination with vaccinia and fowlpox vectors expressing NY-ESO-1, PNAS 109:5797

Dhodapkar, et al (2014) Immunity with a Vaccine Targeting NY-ESO-1 to DEC-205, Sci Transl Med 6:232ra51

Chen, et al (2015) Immune responses with NY-ESO-1 in ISCOMATRIX and NY-ESO-1 fowlpox, Int J Cancer 136:E590 *CD4 and CD8, ELISPOT/ICS/Tetramer

ZVex Fowlpox DEC-205 mAb/NY-ESO-1/ NY-ESO-1 prot/IMX

+ Vaccinia Resiquimod/Poly-I:C + Fowlpox

49% 56%

44%

73%

0

10

20

30

40

50

60

70

80

2nd LineInactive

2nd LineActive

1st LineLow-High

range

IMDZ

PFR % at 3 months

10

0

10

20

30

40

50

60

2nd LineInactive

2nd LineActive

1st LineLow-High

range

IMDZ

PFR % at 6 months

* M. Van Glabbeke, et al. Progression-free rate as the principal end-point for phase II trials in soft-

tissue sarcomas. European Journal of Cancer 38 (2002) 543–549.

LV305 Ph 1:

Clinical Results Suggest Single Agent Activity in Sarcoma

21%

39%

67% 44-77%

8% 14%

>42%

30-56%

Active (low-high range)

Active (low-high range)

• Progression Free Rate (PFR) guides active vs. inactive therapies in Soft Tissue Sarcoma Trials*

• All LV305 patients had ≥ two prior treatments and <10cm in tumor size: 2nd line

• 4/6 patients had arrest of their sarcoma progression and tumor reduction (1/12) while on LV305

CMB305: Targeting NY-ESO-1 in Multiple Solid Tumors

CMB305 Dose Esc.

(LV305 & G305)

Q1’16 Q2’16 Q4’15

CMB305 Phase 1 dose escalation (DE) completed

CMB305 Phase 1 dose expansion in sarcoma, ovarian and lung at optimal

dose (n=32) – started Q3’15/ongoing

CMB305 randomized Phase 2 study with atezolizumab in soft tissue sarcoma

- initiated November ’15

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CMB305 rPh 2 in Soft Tissue Sarcoma - ONGOING

atezolizumab vs. atezolizumab & CMB305

CMB305 Ph1 Expansion – ONGOING Four tumors - signal seeking for additional indications

Potential: CMB305 Phase 2

Randomized in 2nd Indication

Q3’16

G100: Using a Tumor to Expand the Immune Response

STEP 2

Combination Opportunities with Check-point inhibitors (CPIs)

CPI

+

STEP 1

Single Agent + RadRx

G100

Initial Data

Presented at ASCO 2015

✔ + G100 +

CPI G100 +

Three Features of Intratumoral (i.t) Immune Activation:

1. Tumor lysis (e.g., tumor radiation) releases endogenous tumor antigens

2. i.t. G100 activates the pre-existing immune response and primes a new one to released

tumor antigens

3. i.t. G100 and tumor lysis may eliminate both the treated and distal (non-treated) tumors

(“abscopal effect”).

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Collaboration with Merck

(KEYTRUDA®)

13

• Cohort A: 2/2 pts with locoregional disease completed G100 followed by surgery plus RT

and are free of recurrence (336+ & 467+ days).

− Pt 002 had a pathologic CR following the G100 injections alone.

• Cohort B: 2/6 patients with metastatic disease have an ongoing PR after 2 cycles of therapy

and are in follow-up.

- Pt 006 had 28% regression in the injected tumor following G100 alone; this regressed

completely after the second cycle consisted of RT plus G100.

0 50 100 150 200 250 300 350 400

001-002

001-004

001-001

001-003

001-005

001-006

001-007

001-008

001-110

DAYS SINCE 1ST DOSE

G100 CLINICAL RESPONSE

Rx: d0,7 (LR) & d21 (Met, each cycle)

Radiation + 6 weekly doses cycles 2-4

NED (incl. surgery and/or XRT)

PR (incl. surgery and/or XRT)

Progressive Disease

Radiation Therapy

Surgery

Locoregional

Metastatic

G100: MCC Phase 1 Combined Treatment ORR of 50%

G100 +/- RadRx: MCC Ph1 –

Orphan; n=10

G100+RadRx +/- KEYTRUDA: f-NHL Ph1/2 Randomized

Orphan; n=30

✔

14

G100: Potential in Wide Range of Accessible Tumors

Q1’16 Q2’16 Q4’15 Q3’16

G100 Ph1 in Merkel cell carcinoma

data presented at ASCO 2015 (n-8/10) – 50% ORR per protocol

Full enrolled – data expected H2’16

Safe (Grade 1/2)

• Ph1/2 G100 + Rad Rx in NHL with/without KEYTRUDA planned for H2’15

Immuno-Oncology (ZVex & GLAAS)

Infection & Allergy (GLAAS)

Phase 2 Phase 1

First-in-class Immunotherapy Pipeline

G103 HSV Vaccine

Food Allergy Vaccine

RSV Vaccine

Exclusive License

Exclusive License

Joint Program

G100 (Merkel cell carcinoma)

G100 + KEYTRUDA® Randomized (f-NHL)

G305

LV305 DE & Expansion (sarcoma, ovarian, lung)

LV305 + KEYTRUDA® Expansion (melanoma)

CMB305 DE & Expansion (sarcoma, ovarian, lung)

CMB305 + atezolizumab vs. atezolizumab Randomized (Soft Tissue Sarcoma)

15

TEAM, FINANCE AND STRATEGIC OUTLOOK

16

Carlos Paya, MD, PhD Chief Executive Officer

President

Vice President

Stephen R. Brady, JD, LLM Executive Vice President, Strategy & Finance

VP, Corporate

Development

Wayne Gombotz, PhD Chief Development Officer

Vice President

Senior Director

Richard T. Kenney, MD, FACP Chief Medical Officer

Chief Medical Officer

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

Executive Director

Frank J. Hsu, MD Vice President, Head of Oncology

Chief Medical Officer

Senior Medical Director

Christopher Whitmore, CPA Vice President, Finance & Administration

Sr. Director Finance

Corporate Controller

17

Team: Experienced and Proven Executive Leadership

Prior Experience

18

Board of Directors

Ed Penhoet, PhD,° Alta (Chair)

David Baltimore, PhD,* §°Independent

Franklin M. Berger, Independent

Carlos Paya, MD, PhD, IMDZ

Scientific Advisors (SAB)

Rafi Ahmed PhD,§ Emory (Chair)

David Baltimore, PhD,* §° Caltech

Larry Corey, MD,° FHCRC

Phil Greenberg, MD, FHCRC

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

William R. Ringo, Independent

Peter Svennilson, TCG

Brian Atwood, Versant

Lewis W. Coleman, Independent

Carl June, MD,° U of Penn

Ron Levy, MD,§° Stanford

Steven Reed, PhD, IDRI

Inder Verma, PhD,§° Salk Institute

Patrick Hwu, MD, MD Anderson

Nina Bhardwaj, MD, PhD,° Mt. Sinai

Kristen Hege, MD, Celgene

David Parkinson, MD,° NEA

Lawrence Baker, DO, U Michigan

*Nobel Laureate, §National Academy of Sciences, °Institute of Medicine of the National Academies

Team: Exceptional Board and Advisors

Financial Highlights & Upcoming 2015-16 Newsflow

• Cash as of September 30, 2015 $120.5 million

• Expected 2015 net operating cash burn $36-40 million

• Expected YE-2015 cash balance ~$110 million

• Total shares outstanding ~20 million

19

Data** Timing*

• Phase 1 data on CMB305 dose escalation

• Initial Phase 1 data on CMB305 signal-seeking expansion arm (sarcoma)

• Phase 1 data for all patients in G100 in Merkel Cell Carcinoma

• Initial Phase 1 data on LV305 expansion study

Q1’16

• Phase 2 randomized study – initial data on CMB305 + atezolizumab in sarcoma

• Phase 1b randomized study – initial data on G100+KEYTRUDA® in NHL H2’16

Trial starts Timing*

• Initiate Phase 1 study of G100 + KEYTRUDA® in NHL

• Initiate Phase 1 LV305 expansion + KEYTRUDA® in melanoma NRs to α-PD1

Initiate Phase 2 randomized study of CMB305 + atezolizumab in sarcoma

Q4’15

Q4’15

Q4’15

*Timing is estimated. Although data may be available, we may elect to submit it for presentation at an appropriate medical meeting.

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IMMUNE DESIGN

ZVex

Platform

GLAAS

Platform

Single

Agent

CPIs

Radiation

CAR-T/TCR

Oncolytic Virus

Other

✓

✓

✓

Poised for a Central Role in the I-O Landscape

BACKGROUND INFORMATION

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An Immune Response is Key for Checkpoint Inhibitors

22

1. and Image. Tumeh, Paul C., et. al. “PD-1 blockade induces responses by inhibiting adaptive immune resistance.” Nature, 515: 568-571 (27 November 2014).

2. Taube, JM, et al. “Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune

escape,” Science of Translational Medicine 2012 March 28; 4(127). Available at: http://www.ncbi.nlm.nih.gov/pubmed/22461641. Accessed August 2015 and Sznol, M. and L.

Chen “Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer,” Clinical Cancer Research 2013 March 1; 19(5): 1021-1034. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/23460533. Accessed August 2015

3. J Clin Oncol 33, 2015 (suppl; abstr 9005)

Large Potential Opportunity:

• IMDZ’s agents are designed to create T anti-tumor T cells that should synergize with CPIs for tumor killing

• 34% ORR in metastatic melanoma patients treated with pembro + ipi (KEYNOTE-001) 3 –

• Potential market entry in remaining ~66% of patients exhibiting an inadequate response to treatment w/ CPIs

Tumor regression after treatment

with αPD-1 requires T Cells1

TIL (-) PD-L1 (-)

TIL (-) PD-L1 (+)

TIL (+) PD-L1 (+)

TIL (+) PD-L1 (-)

41% 1% 38% 20%

Significant % of melanoma

patients do not have pre-existing

T Cells2 N=110

G305 Ph1: Broad Antibody and CD4 T cell Response

Antibody (9/12) CD4 (5/11) CD8 (2/10) Clinical

Patient Pre Response Pre Response Pre Response Follow Up

1 + = + = - - 162

2 + ++ + = - - 305

3 + ++ N/E N/E N/E N/E 365+

4 + ++ + ++ - ++ 161

5 - ++ - - - - 335+

6 - ++ - ++ - - 70

7 - - - - - - 62

8 - ++ - ++ - - 70

9 + ++ + = - N/E 70

10 + ++ - ++ - ++ 191

11 + ++ - ++ - - 247+

12 + = + = + = 252+

Cohort 1 2 µg x 3

Cohort 2 5 µg x 3

Cohort 3 10 µg x 3

"+" in the "Pre" column indicates a pre-existing measureable immune response.

"++" in the "Response" indicates for Ab: 4-fold rise or newly positive response; T cell: ELISPOT >50 spots & >2-fold rise and/or

ICS >2- fold over baseline.

"=" indicates a pre-existing response that did not boost,

N/E: not evaluable

Follow-up: A ‘+’ indicates stable disease as of 13 May 2015 23

G305 Ph1: Stable Disease Across Different Tumors

Efficacy:

• Stable disease: 8/12 patients (67%) achieved a best response of SD

— Median duration of SD of 245+ days (range: 161 to 365+ days).

• One patient (#3) had a CA125 response on d70 (based on GCIG Criteria)

24

LV305 Ph1: CD8 and Broad T-cell Responses

25

Cohort 1

108 vg x 3

Cohort 2

109 vg x 4

Cohort 3

1010 vg x 4

Cohort 1A

108 vg x 4

Antibody: 0/12 CD4: 5/11 CD8: 6/11

Pre Response Pre Response Pre Response

1 + = + ++ + ++

2 + = - ++ - ++

3 - - - - - -

4 + = - ++ - -

5 + = + ++ - -

6 - - - - - -

7 - - - - - ++

8 + = - - - ++

9 + = N/E N/E N/E N/E

10 - - - ++ - ++

11 + = - - - -

12 - - - - - ++

"+" in the "Pre" column indicates a pre-existing measureable immune response.

"++" in the "Response" indicates for Ab: 4-fold rise or newly positive response; T cell: ELISPOT >50 spots & >2-fold rise and/or ICS >2-

fold over baseline.

"=" indicates a pre-existing response that did not boost,

N/E: not evaluable

Follow-up: A ‘+’ indicates stable disease as of 13 May 2015

LV305 Ph1: Stable Disease & Progression Arrest in STS

26 26

• Stable Disease (SD):

— 8/12 (67%) at the end of treatment; median duration 208 d (139-347 +)

— PFR (Progression free rate): 67% (3 months) and >42% (6 months)

• 4/6 pts with evidence of prior tumor growth stabilized and stopped progression

— Tumor regression of up to 14% observed in one pt w/ SD at 347+ days

Rx: d0,21,42 (Cohort 1) & d63 (Cohorts 1A-3); Staging CT: d0, d63 (Cohort 1) or d84 (Cohorts 1A-

3), then every 8 wks; 1 pt did not complete all planned doses due to PD; "+" indicates pts with

documented pre-LV305 tumor growth: "+" indicates those pts who stabilized following LV305

0 50 100 150 200 250 300

151006

150014

151016

151020

150035

150051

151039

150050

151026

151119

151057

151070

DAYS SINCE 1ST DOSE

PA

TIEN

T N

UM

BER

L

347+

326+ Cohort 1

108 vg x 3

Cohort 2

109 vg x 4

Cohort 3

1010 vg x 4

Cohort 1a

108 vg x 4

Stable Disease

Progressive Disease

Staging CT

Eval. Tumor growth per irRC

Tumor growth

before LV305

+

-

+

+

-

+/-

+

-

+

-

-

+

# Prior Tx

5

1

3

2

3

4

Surg/rad

Surg/rad

2

3

Rad

3

Sindbis envelope

provides selective in

vivo DC targeting

Integration-deficient

and replication-

incompetent for safety

Lack of prior immunity

allows for multiple

dosing

ZVex: First in vivo DC Targeting Gene Delivery Vector

Designed to generate CD8s in vivo

Sindbis

Lenti

27

*Immune Design data.

Capacity for substantial genetic payload = new potential products

Activates innate

immunity (G100)

(TH1 cytokines,

chemokines and NK cells)

Activates adaptive

immunity (GLAAS + Ag)

(De novo induction of Ag-

specific CD4 T and B cells)

Expanding favorable

safety and efficacy

database

(>1,200 subjects)

Potential in oncology,

and infectious and

allergic diseases

GLAAS: Potent TLR4 Agonist - Broad Clinical Exposure

28

*Immune Design and IDRI data; Lambert et al., PLoS One, 2012

Designed to induce CD4s, ABs & NK cells in vivo