ImmunoCellular Therapeutics
Industry-leading, next-generation, cancer
immunotherapy
November 2012
Disclaimer
This presentation contains certain “forward-looking statements” (statements as to
matters other than historical facts) as defined in the Private Securities Litigation Reform Act
of 1995. These statements involve risks and uncertainties that could cause actual events or
results to differ materially from the events and include statements about our plans,
objectives, expectations and intentions with respect to the potential for success of our
scientific approach to cancer immunotherapy, clinical development efforts, operations,
financial condition and other statements that are not historical in nature, particularly those
that use terms such as “will,” “potential”, “could,” “can,” “believe,” “intends,” “continue,”
“plans,” “expects,” “projects,” “estimates” or similar language.
Important factors known to us that could cause actual results to differ materially
from those expressed in such forward-looking statements include those set forth in our
most recent annual report on Form 10-K, quarterly reports on Form 10-Q and other reports
filed with the SEC.
You may obtain these documents for free by visiting EDGAR on the SEC website at
www.sec.gov. The information in this presentation speaks only as of the date hereof, and
except as required by law, we disclaim any obligation to update or revise any forwardlooking statement.
2
Disruptive Validated Technology
Cancer Stem Cell Targeting +
Potent Immunotherapy
= Effective Cancer Eradication
3
Why Cancer Vaccines Previously Failed?
Problem
Solution
• Late-stage disease
• Minimal residual disease
• Immune compromised patients
• Immune competent patients at
diagnosis
• Dendritic cells with persistent Tcell immune response
• Weak immune response
• Tumor mutation/escape
• Flawed trial endpoints
• Targeted tumor bulk
• Target multiple antigens
• Overall survival endpoint
• Target cancer stem cells
4
Without killing CSCs, it is like spraying for weeds without killing the roots.
The weeds (tumors) come back.
Immunotherapy Has Advantages in
Targeting Cancer Stem Cells
Immunotherapy can elicit T-cell mediated rejection of tumors
• T cells are the way the body kills cancer cells
• Improves specificity
• Targets intracellular & surface antigens
• Better safety profile
• Differentiates between CSCs and normal stem cells
Antibodies only target CSC antigens
on the surface of cancer cells
Cytotoxic T-cells target CSC
antigens cancer presented by MHCs
MHC
Antibody
Antigen
Antigen
Cancer cell
Cytotoxic T-cell
Cancer cell
6
Product Pipeline Overview
Multiple therapies in different cancer indications
Active immunotherapies
 ICT-107
̶ Dendritic cell vaccine targeting glioblastoma antigens and CSCs
̶ Phase I trial showed compelling clinical outcomes
̶ Phase II study results anticipated late 2013
 ICT-140
̶ Dendritic cell vaccine targeting ovarian cancer antigens and CSCs
̶ IND filing Q4/2012
 ICT-121
̶ Dendritic cell vaccine targeting CD133 (CSC marker)
̶ IND approved; plan enrollment Q4/2012
Antibody immunotherapies
 Licensed to Caerus Molecular Discovery, funded by BioWa
7
ICT-107 Preparation & Manufacturing
Multiple doses from only one apheresis procedure
GMP Manufacturing Facility
Ship
overnight
Apheresis
Apheresis
product
Patient

Culture with
cytokines
Peripheral blood
mononuclear cells
Activated
dendritic cells
Pulse w/ tumorassociated
antigens

Intradermal
injection
Ship back to
physician
ICT-107
Aliquot
& freeze
~30 doses
8
ICT-107
ICT-107 targets both tumor cells and CSCs
9
AIM2
TRP-2




CDX-110
(Celldex)
Tumor Lys
HER2/neu

HSP Ags
IL-13Rα2

EGFRvIII
MAGE-1
ICT-107
(IMUC)
gp100
ICT-107 Targets Antigens Overexpressed
on Glioblastoma Cancer Stem Cells

DC Vax
(Northwest Bio)

Prophage
(Agenus)

ICT-107 targets six tumor antigens (nine amino acid epitopes
that elicit an immune response in HLA-A1/A2 patients)
10
Pt # Pt ID
1630
1636
1639
1640
1597
1587
1544
1576
1577
1551
1552
1562
1564
1540
1542
1519
1522
1523
1525
1412
1466
2 1526
5 1351
6 1431
7 1508
8 1468
9 1498
11 1539
12 1561
13 1550
14 1547
15 1594
16 1560
17 1578
18 1585
19 1614
AIM
++
+++
++
+++
++++
++
++
+
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++++
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++++
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++++
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++++
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++
++
++++
++
+++
+++
++
+
gp100
++
+
+
++
++
wk
++
wk
+
+
wk
+
wk
+
++
wk
+
+
wk
+
+
+
+
+
neg
++
++
+
wk
++
neg
+
neg
wk
++
+
MAGE
wk
wk
wk
wk
+
wk
wk
neg
wk
+
wk
+
wk
+++
wk
++
+
+
wk
+
wk
+
wk
+
+
neg
wk
wk
wk
neg
+
wk
wk
wk
wk
wk
TRP-2
+++
+++
+++
+++
+++
++
++
++
++
+++
++
+++
++
+++
++
++
++++
+++
++
++++
+++
++
+++
+++
++
++++
++
++
+++
+++
++
++
neg
++
+++
++
Her-2
++++
+++
+++
++++
++++
++
+++
+++
++
+++
+++
+++
+++
+++
+++
+++
++++
+++
++++
++++
++++
+++
+++
++++
++++
neg
++++
+++
+++
++++
+++
+++
+++
++
++++
+++
IL-13R
++++
++++
++++
neg
+++++
++++
++
++
++
++
++
++
+++
++++
++++
+
++++
++++
++++
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neg
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wk
+
++
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++++
+++++
<1E5
>1E5
>1E4
>1E3
>1E2
>1E1
Expression of
Tumor Antigens in
GBM by RT-PCR
All GBM patients express three
or more antigens
75% expressed all six
Patients from ICT-107
Phase I clinical trial
11
Phase I Trial with ICT-107
Nonrandomized, single-center study at Cedars-Sinai
 19 GBM patients
 16 newly diagnosed, 3 recurrent
 ~75% fully resected
Patients received
standard of care (surgery
and chemo-radiation)
followed by three
vaccinations of ICT-107
every two weeks.
12
Pre- and Post-Operative MRI Scans of
Four GBM Patients on ICT-107
13
ICT-107 Phase I Results
Newly diagnosed GBM patients (efficacy and safety)
RT/Chemo
Historical
Vaccine
Fully-resected
Progressive disease
= Death
ICT-107
B-06
B-04
B-07
B-10
B-14
B-15
B-19
B-20
B-13
B-18
Six patients without recurrence for over 4
years (3 of them over 5 years)
B-16
B-02
B-11
No Grade 3 or 4 toxicities.
Adverse events (Grade 1 or 2) include diarrhea,
fatigue, flushing, pruritis, rash, vomiting
B-12
B-09
B-17
0
10
20
30
40
50
Months from Surgery
Stupp et al. N Engl J Med. 2005 Mar 10;352(10):987-96 & Stupp et al. Lancet Oncol. 2009 May;10(5):459-66.
14
60
70
ICT-107 Improves Survival in GBM
Progression Free Survival (PFS)
Overall Survival (OS)
ICT-107
ICT-107
Historical standard of care
Historical standard of care
Significant increase in median PFS
 16.9 months for ICT-107
 6.9 months for historical SoC*
Significant increase in median OS
 38.4 months for ICT-107
 14.6 months for historical SoC*
*Surgery followed by radiation and temozolomide (TMZ). Stupp et al. N Engl J Med. 2005 Mar 10;352(10):987-96.
15
Correlation of PFS and OS with Antigen
Expression
16
CD133 Expression (CSC Biomarker)
Primary & recurrent tumor samples from the same patient
Chemotherapy
ICT-107
6.6
5.3
3.5
After2
12.3
7.6
2.1
2.5
0.6
A
After
12.3
19.1
CD133 Expression
Relative Increase in CD133 Expression
Before
B
C
D
E
F
Patient
0.2
1.4
0
0
0 0
G
H
I
Patient
Phuphanich et al. Cancer Immunol Immunother. 2012 Jul 31.
17
J
ICT-107 Phase II Trial Design
Randomized, placebo-controlled, double-blind trial
2:1 randomization
ICT-107 +
TMZ
Newly
Diagnosed
GBM Patients
(n=123)
Surgery
Placebo
Unloaded
DCs + TMZ
Apheresis
• 123 patients treated at 25 centers
 HLA-A1/A2 50-75% of US population
• 278 patients enrolled
• Primary endpoint: OS
• Secondary endpoints:
 PFS
 OS/PFS at various time intervals
 Immune response (T-cells)
 Safety
• Interim analysis (based on 50% events) in Q1/2013
• Final results in 2H2013
• Derisked by improving DC function, timing, frequency
Vaccinations
Radiation
TMZ
7 weeks
6 weeks
4 weeks
18
4 weeks
4 weeks
4 weeks
4 weeks
ICT-107 Phase II Trial Enrollment
25 clinical trial sites – 278 patients enrolled
300
250
200
150
100
50
Planned
19
Actual
AUG
JUL
JUN
MAY
APR
MAR
FEB
JAN
DEC
NOV
OCT
SEP
AUG
JUL
JUN
MAY
APR
MAR
FEB
0
JAN
Johns Hopkins University
New York University
University of Texas at Houston
Northwestern University
Arizona Cancer Center
New Jersey Neuroscience Institute
UC San Diego
Moffitt Cancer Center
Penn State
University of Pennsylvania
University of Virginia
Wake Forest
Cornell Presbyterian
Massachusetts General
Kentuckiana Cancer Institute
Cedars-Sinai Medical Center
University Hospital Case Medical Center
Rush University
Overlook Hospital
Baylor University
Cleveland Clinic
University of Alabama
Thomas Jefferson
Long Island Brain Center
FDA Approvals
Newly Diagnosed GBM
Gliadel
 Approval in 2003
 Double-blind, placebo-controlled, randomized Phase III trial showing
13.8 vs. 11.6 month survival
Temozolomide
 Approval in 2005
 Double-blind, placebo-controlled, randomized Phase III trial showing
14.6 vs. 12.1 month survival
20
Projected Costs: ICT-107 vs. Provenge
Lower cost of goods, better logistics
ICT-107
Provenge
60%-90%
15%-20%
Interleukin-12
Yes
No
Target antigens
Six
One
Doses/apheresis
~30
1
Liquid nitrogen
N/A
Administration
Intradermal injection
IV infusion
Cost of Goods
5%-10%
70%
% DCs/APC
Storage
Source: Quarterly earnings transcripts and public filings.
21
Other Immunotherapy Candidates
22
ICT-140: Ovarian Cancer Vaccine
Ovarian cancer is similar to GBM
 Minimal residual disease after surgery
 Immuno-responsive
Dendritic cell vaccine targeting CSCs
 Seven antigens over-expressed in ovarian cancer, including three
antigens used in ICT-107
̶ HER2/neu, IL-13Rα2, MAGE1, mesothelin, EphA2, & two more antigens
 File IND by Q4/2012
23
ICT-121: CSC-targeted Universal Vaccine
• Dendritic cell vaccine loaded with two CD133 peptides
• CD133 is highly expressed on CSCs
• CD133 is expressed on most solid tumors, including brain,
colon, non-small cell lung, melanoma, pancreatic, and breast
cancer
• Initial indication in recurrent GBM
• PI-sponsored Phase I trial at Cedars-Sinai Medical Center
 20 patients
 IND approved; plan
enrollment Q4/2012
24
Inverse Correlation between CD133
Expression with Survival on Gliomas
CD133 expression correlates inversely with
grade II to IV glioma patient survival time. The
survival time calculated from the day of
operation was plotted against the percentage
of CD133+ cells in the CD45-cell fraction from
the specimens of each patient. UD:
undetectable CD133 expression. Bold black
bars indicate the median survival time for
patients in groups with CD133+ cells either
lower or higher than 30% of total CD45-cells.
Source: Rebetz et al. PLoS ONE. 2008.
Strong IP Position
28+ patents and patent applications
 10 patents issued or allowed
 18+ patents pending
Vaccine patents and applications include





Method of use for six antigen vaccine (ICT-107)
Manufacturing process for production of ICT-107
Use of dendritic cells with chemotherapy for neural cancers
Immunotherapy targeting IL-13Rα2
Immunotherapy targeting CD133
Issued patents on monoclonal antibodies cover composition of
matter, therapeutic treatments and diagnostics
26
Experienced Management Team
John Yu, MD, Chairman & CSO, Interim CEO
 Neurosurgeon at Cedars-Sinai, Mass General Hospital, Harvard Medical School
Elma Hawkins, PhD, Head of Clinical Development
 Antigenics, Genzyme, Warner Lambert/Parke Davis
Jim Bender, PhD, MPH, VP of Manufacturing & Product Development
 IDM Pharma, Baxter Healthcare
David Fractor, CPA, CFO
 HemaCare, Andwin, Deloitte & Touche
Peter Ho, PhD, Director of Business Development
 Grey Healthcare Group, Prudential Equity Group, Allergan, D.E. Shaw
Experience in developing over 20 products in cell & gene therapy and vaccines
27
Product Pipeline
2011
Q1
Q2
2012
Q3
Q4
ICT-107
New GBM
Q1
Q2
2013
Q3
Q4
Q1
Q2
Q4
Q1
Preclinical
Final results
Phase I/II trial
IND
ICT-121
Recurrent GBM
Q2
Phase II trial
Interim analysis
ICT-140
Ovarian
Q3
2014
Preclinical
Phase I trial
IND
28
Q3
Q4
Recent & Upcoming Milestones
May 2012
NYSE MKT listing
July 2012
ICT-121 IND
October 2013
October 2012
SITC abstract
SITC abstract
December 2012
Q3 2013
ICT-121 Ph 1
ICT-140 Ph 1/2
Q1 2013
2H 2013
ICT-107 Ph 2 final
June 2013
November 2013
ASCO abstract
SNO abstract
ICT-107 Ph 2 interim
ICT-140 IND
November 2012
SNO abstract
August 2012
ICT-107 Ph 2 enrollment
29
Strong Financial Position & Capitalization
Cash (as of 9/30/2012) $10 million (A)
Burn rate $3 million per quarter
Outstanding debt None
Shares outstanding (as of
41.1 million (A)
9/30/12)
Market capitalization
$98 million
(as of 11/6/2012)
Warrants outstanding (as
8.9 million (A)
of 9/30/12)
10.4 million (average weighted
Options outstanding
exercise price of $1.15)
(A) In October 2012, we raised $19.3 million from the issuance of 10 million
shares of common stock and 4.5 million warrants.
30
ImmunoCellular Therapeutics
Industry-leading, next-generation, cancer
immunotherapy
November 2012