November 2014
THE in vivo ENGINE OF
CYTOTOXIC T CELLS TO FIGHT DISEASE
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.
2
Contents
•
•
•
•
Introduction
Discovery Platforms
Clinical Product Candidates
Financial Highlights & Upcoming Milestones
3
Immune Design: Bringing All the Pieces Together
Dual Discovery
Platforms
First-in-class
Clinical Product
Candidates
Strategic
Focus
Team
Two productive discovery platforms from
cutting-edge T cell immunology science
Clinical-stage product candidates in our two
approaches in both orphan and highincidence tumors
Immuno-Oncology -100% retained
•
with infectious, allergic and autoimmune diseases
optionality for partnering or additional growth
Experienced management, proven Board and
world-class advisors
4
Immune Design: A Premier Immuno-Oncology Company
Two Main Categories
Two T cell Therapies
Off-the-shelf,
In vivo
induction and
expansion of T
cells
Induce T
cells to kill
the tumor
Immuno-Oncology:
Two IMDZ Approaches
Specific Antigen
Endogenous
Antigen
the next pillar of
cancer treatment
Adoptive T cell
transfer
Remove the
blockade
(personalized, ex
vivo manipulation)
(checkpoint
inhibitors)
Tumor
CTLs
Tumor-induced
Immune Blockade
5
Experienced and Proven Leadership Team
Prior Experience
Carlos Paya, MD, PhD
Chief Executive Officer
President
Vice President
Stephen R. Brady, JD, LLM
VP Corporate Development
Chief Business Officer
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
Frank J. Hsu, MD
Vice President, Head of Oncology
Paul Rickey, CPA
Vice President, Finance & Administration
Executive Director
Chief Medical Officer
Senior Medical Director
Corporate Controller
Senior Auditor
6
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
William R. Ringo, Independent
Peter Svennilson, TCG
Brian Atwood, Versant
Scientific Advisors (SAB)
Larry Corey, MD,° Fred Hutch (Chair)
David Baltimore, PhD,* §° Caltech
Carl June, MD,° U of Penn
Phil Greenberg, MD, Fred Hutch.
Inder Verma, PhD,§° Salk Institute
Rafi Ahmed PhD,§ Emory University
Steven Reed, PhD, IDRI
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
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
7
DISCOVERY PLATFORMS
Specific Antigen
Approach
The Immune Design in vivo Difference
ZVex + Antigen RNA induces CTLs
CD8 T cells (CTLs)
In vivo expanded
CTLs attack tumors
DC
+
CD4 T cells
expand CTLs
GLA
TUMOR
GLAAS+ Antigen protein induces CD4 T cells
TUMOR
LYSIS
Endogenous Antigen
Approach
Separate & complementary MOAs induce/expand CTLs in vivo to kill tumors
GLAAS-activated DCs
uptake new released
antigens and expand CTLs
Expanded, diverse CTLs
attack the residual tumor
TUMOR LYSIS by:
DC
-
Radiation
Chemo
CTLs
Other
TUMOR
ADDITIONAL
TUMOR
LYSIS
Intra-tumoral GLAAS
9
The ZVex Advantage: First-in-class in vivo DC Targeting
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
Integration-deficient and
replication-incompetent
for safety
Capacity
for substantial
genetic payload
Lack of prior
immunity allows for
multiple dosing
10
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)
A
CTL responses in naïve mice,
immunized with 6.5E10 ZV ex-mTRP1 (A463M)
1 st
8
% CTL
% CTL
immunized with 8E9
6
6
4
ZVex-NY-ESO -1
2nd
3rd
4
2
2
0
0
11
14
17
20
23
26
29
0
32
0
5 7 9 12
5 7 9 12
16
Days Post 2
300
250
ZVex-mTRP1
150
100
21
nd
5 7 9 12
16
Days Post 3
21
rd
150
26
28 30
Days Post-Tumor Inoculation
33
35
ZVex-mTRP1 + αPD-L1
D
ZVex-mTRP1
100
0
23
ZVex-m TRP1
200
0
21
6E10
Anti-PD -L1
250
50
16
αPD-L1
300
50
14
Control Vector
350
Tumor Volume (mm3)
350
200
400
C
Buffer
5E9 ZVex-mTRP1
400
B16 melanoma
21
st
Normal mice
Normal mice
0
16
Days Post 1
Days Post-Immunization
Tumor Volume (mm3)
B
CTL responses in naïve mice,
0
B16 melanoma
3
7 10 14 17 21 24 28 31 35
Days Post-Tumor Inoculation
11
The GLAAS Advantage: GLA at the Core
Clinical-stage, synthetic TLR4 agonist potently activates DCs in vivo
Potential to also treat
Boosts pre-existing CTLs
multiple infectious and
allergic diseases
Induces CD4 T and B
cells. Enhances Natural
Demonstrated dose sparing
and antigen crossreactivity
Killer (NK) cells
Expanding favorable
safety database
(>1,000 subjects)
12
The GLAAS Advantage: GLA at the Core
A
C
B
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)
13
Specific Antigen Approach:
The Synergistic Prime-Boost of ZVex + GLAAS
Combination for CTL induction and expansion
PBS
+ GLAAS
PBS
+ ZVex
GLAAS
+ ZVex
CD4
CD8
(CTL)
TNF-α
0.75
0.05
0.05
3.16
2.82
15.7
Robust antigenspecific CTL
response
IFN-γ
Akin to:
G305
LV305
CMB305
GLAAS, in addition to enhancing number and quality of CTLs generated by ZVex ,
triggers a STRONG antigen-specific humoral response and innate immunity
14
Specific Antigen Approach:
The Synergistic Prime-Boost of ZVex + GLAAS
Methods
1. Day 0: Inoculation of B6
mice (n=10) with
B16F10 tumor cells in
the flank
2. Day 12: Start of
treatment
3. Weekly immunization
4. Prime/boost:
V.V.P.V.P.V.P*
5. CPI: weekly
*Mimics clinical LV305
regimen
* Zvex-mTRP1
** Recombinant mTRP1
15
Endogenous Antigen Approach
GLAAS Single Agent Efficacy
A GLA formulation from GLAAS demonstrates in vivo efficacy
without radiation or other lysing technology
Treated tumor
•
•
Untreated tumor
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
Data generated from collaboration with Dr. Ronald Levy, Stanford School of Medicine
16
CLINICAL PRODUCT
CANDIDATES
Specific Antigen Approach: ‘305 NY-ESO-1 Program
Assembling blocks towards maximum in vivo CTLS
STEP 3
Combination with
Checkpoint Inhibitors (CPI)
CMB305
CPI
STEP 2
Combine into
a Prime Boost Therapy
CMB305
STEP 1
Test Individual Building Blocks
G305
LV305
18
Specific Antigen Approach: ‘305 NY-ESO-1 Program
Assembling blocks towards maximum in vivo CTLS
Phase 1 trials
STEP #1 : Single Agent
LV305:
ZVex / NY-ESO-1
Phase 2 trials
STEP #3 : Combo Agents + a-PD1
STEP #2 : Combo Agents
LV305
Extend & Explore
CMB305 Randomized
(a-PD1) in NSCLC
CMB305
LV305 & G305
combo
CMB305 Single Arm
in Sarcoma (Orphan)
G305:
GLAAS+NY-ESO1
2Q14
4Q14
CMB305
Extend & Explore
1Q15
- Data from for LV305 & G305
- CMB305 P1 & LV305
expansion Studies Open
2H15
- Data from CMB305 and Exploratory Studies
- Phase 2 Studies Open
19
Specific Antigen Approach: ‘305 NY-ESO-1 Program
NY-ESO-1 expression
•
•
Diverse cancer types express this tumor-associated antigen
Known safety and immunogenicity from previous approaches
Cancer indications to be studied in:
Phase 1
NSCLC
Sarcoma
Breast
Melanoma
Ovarian


Phase 2
NSCLC (High incidence)
Sarcoma (Orphan indication)
Other cancers known positive for NY-ESO-1
Bladder (TCC)
Cholangiocarcinoma
Colorectal
Endometrial Cancer
Esophageal SCC
Gastric
H&N SCC
Hepatocellular
Multiple Myeloma
Neuroblastoma
NHL (DLCL)
Prostate
Renal (oncocytoma)
Thyroid (medullary)
Uterine
20
Endogenous Antigen Approach
Assembling blocks towards boosting CTLs
G100
TUMOR
G100
GLAAS activates DCs in
Existing CTLs are
tumor environment that expanded and new ones
are induced
uptake neo-antigens
•
•
•
TUMOR
LYSIS
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: MCC P1 - Orphan
G100: NHL + RoRx P1 - Orphan
2Q15
- Data from P1 Merkel cell carcinoma trial
- G100 in second tumor (NHL) study open
21
Endogenous Antigen Approach
Complete Response in Loco-Regional MCC
Pre-G100 Superficial node
Post-G100 Superficial node
2/7/2014
3/3/2014
MCC present
MCC absent
(brown dots using CK20)
(after 2 doses of G100)
H&E
CK20
•
•
•
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
22
First-in-class Immunotherapy Pipeline
Immuno-Oncology
Preclinical
Phase 1
Therapeutic Approach
LV305 (ZVex + NY-ESO-1)*
SPECIFIC ANTIGEN
G305 (GLAAS + NY-ESO-1)*
One Orphan (sarcoma) & One High
Incidence (NSCLC) Solid Tumor
CMB305 (LV305+G305 prime-boost)
ENDOGENOUS ANTIGEN
G100 (Intratumoral GLA**)
Infectious Disease & Allergy
One Orphan (Merkel Cell Carcinoma)
Preclinical
Phase 1
Phase 2
Partner
RSV Vaccine
Food Allergy Vaccine
G103 (HSV-2 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
23
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
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
Initiate Phase 2 studies of CMB305 in NSCLC and sarcoma
2H15
Phase 1 data on G100 in Merkel cell carcinoma
Establish additional non-oncology collaborations
2H14 - 2015
24