November 2012 ImmunoCellular Therapeutics Industry-leading, next-generation, cancer immunotherapy.
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Transcript of November 2012 ImmunoCellular Therapeutics Industry-leading, next-generation, cancer immunotherapy.
November 2012
ImmunoCellular TherapeuticsIndustry-leading, next-generation, cancer immunotherapy
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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 forward-looking statement.
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Disruptive Validated Technology
Cancer Stem Cell Targeting Potent Immunotherapy
= Effective Cancer Eradication
+
Why Cancer Vaccines Previously Failed?
Problem• Late-stage disease
• Immune compromised patients
• Weak immune response
Solution• Minimal residual disease
• Immune competent patients at diagnosis
• Dendritic cells with persistent T-cell immune response
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• Target multiple antigens• Overall survival endpoint• Target cancer stem cells
• Tumor mutation/escape• Flawed trial endpoints• Targeted tumor bulk
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
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Cancer cell Cytotoxic T-cell
Cytotoxic T-cells target CSC antigens cancer presented by MHCs
Antigen
MHC
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
Cancer cell
Antibody
Antigen
Product Pipeline OverviewMultiple therapies in different cancer indications
Active immunotherapies ICT-107
F̶ Dendritic cell vaccine targeting glioblastoma antigens and CSCsF̶ Phase I trial showed compelling clinical outcomesF̶ Phase II study results anticipated late 2013
ICT-140F̶ Dendritic cell vaccine targeting ovarian cancer antigens and CSCsF̶ IND filing Q4/2012
ICT-121F̶ Dendritic cell vaccine targeting CD133 (CSC marker)F̶ IND approved; plan enrollment Q4/2012
Antibody immunotherapies Licensed to Caerus Molecular Discovery, funded by BioWa
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ICT-107 Preparation & ManufacturingMultiple doses from only one apheresis procedure
GMP Manufacturing Facility
Apheresis
Patient
Apheresisproduct
Ship back to physician
ICT-107 ICT-107~30 doses
Peripheral blood mononuclear cells
Activated dendritic cells
Culture with cytokines
Intradermal injection
Pulse w/ tumor-associated
antigens
Aliquot & freeze
Ship overnight
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ICT-107 targets both tumor cells and CSCs
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ICT-107 Targets Antigens Overexpressed on Glioblastoma Cancer Stem Cells
gp100 MAGE-1
IL-13Rα2
HER2/neu AIM2 TRP-2 EGFRv
IIIHSP Ags
Tumor Lys
ICT-107(IMUC)
CDX-110(Celldex)
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)
Expression of Tumor Antigens in GBM by RT-PCRAll GBM patients express three or more antigens75% expressed all six
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Pt # Pt ID AIM gp100 MAGE TRP-2 Her-2 IL-13R1630 ++ ++ wk +++ ++++ ++++ wk <1E51636 +++ + wk +++ +++ ++++ + >1E51639 ++ + wk +++ +++ ++++ ++ >1E41640 +++ ++ wk +++ ++++ neg +++ >1E31597 ++++ ++ + +++ ++++ +++++ ++++ >1E21587 ++ wk wk ++ ++ ++++ +++++ >1E11544 ++ ++ wk ++ +++ ++1576 + wk neg ++ +++ ++1577 ++ + wk ++ ++ ++1551 +++ + + +++ +++ ++1552 ++ wk wk ++ +++ ++1562 ++++ + + +++ +++ ++1564 ++ wk wk ++ +++ +++1540 ++ + +++ +++ +++ ++++1542 +++ ++ wk ++ +++ ++++1519 ++++ wk ++ ++ +++ +1522 +++++ + + ++++ ++++ ++++1523 ++++ + + +++ +++ ++++1525 +++ wk wk ++ ++++ ++++1412 +++ + + ++++ ++++ +++++1466 ++ + wk +++ ++++ +++
2 1526 ++++ + + ++ +++ ++5 1351 +++ + wk +++ +++ ++++6 1431 ++++ + + +++ ++++ +++++7 1508 +++++ neg + ++ ++++ ++++8 1468 ++++ ++ neg ++++ neg +++++9 1498 + ++ wk ++ ++++ ++++
11 1539 +++ + wk ++ +++ +12 1561 ++ wk wk +++ +++ +++13 1550 ++ ++ neg +++ ++++ ++++14 1547 ++++ neg + ++ +++ ++++15 1594 ++ + wk ++ +++ +++16 1560 +++ neg wk neg +++ neg17 1578 +++ wk wk ++ ++ ++18 1585 ++ ++ wk +++ ++++ ++++19 1614 + + wk ++ +++ ++++
Patients from ICT-107 Phase I clinical trial
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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.
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Pre- and Post-Operative MRI Scans of Four GBM Patients on ICT-107
B-17
B-09
B-12
B-11
B-02
B-16
B-18
B-13
B-20
B-19
B-15
B-14
B-10
B-07
B-04
B-06
0 10 20 30 40 50 60 70
Months from Surgery
ICT-107 Phase I ResultsNewly diagnosed GBM patients (efficacy and safety)
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= Death
Historical Fully-resected
RT/Chemo Vaccine Progressive disease
ICT-107
Six patients without recurrence for over 4 years (3 of them over 5 years)
No Grade 3 or 4 toxicities.Adverse events (Grade 1 or 2) include diarrhea, fatigue, flushing, pruritis, rash, vomiting
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.
ICT-107 Improves Survival in GBM
*Surgery followed by radiation and temozolomide (TMZ). Stupp et al. N Engl J Med. 2005 Mar 10;352(10):987-96.
Historical standard of care
ICT-107
Significant increase in median PFS 16.9 months for ICT-107 6.9 months for historical SoC*
Progression Free Survival (PFS)
Significant increase in median OS 38.4 months for ICT-107 14.6 months for historical SoC*
Historical standard of care
ICT-107
Overall Survival (OS)
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Correlation of PFS and OS with Antigen Expression
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CD133 Expression (CSC Biomarker)Primary & recurrent tumor samples from the same patient
A B C D E
19.1
6.65.3
3.52.5
Chemotherapy
Patient
Rela
tive
Incr
ease
in C
D13
3 Ex
pres
sion
F G H I J
12.3
2.1
7.6
0
12.3
0.60 0 0
1.4
0.2
ICT-107Before After After2
Patient
CD13
3 Ex
pres
sion
Phuphanich et al. Cancer Immunol Immunother. 2012 Jul 31.
ICT-107 Phase II Trial DesignRandomized, placebo-controlled, double-blind trial
Newly Diagnosed
GBM Patients (n=123)
ICT-107 +TMZ
PlaceboUnloaded DCs + TMZ
2:1
rand
omiza
tion
• 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
7 weeks 6 weeks 4 weeks 4 weeks 4 weeks 4 weeks
TMZRadiation
4 weeks
Surgery Apheresis Vaccinations
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ICT-107 Phase II Trial Enrollment25 clinical trial sites – 278 patients enrolled
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Johns Hopkins UniversityNew York UniversityUniversity of Texas at Houston Northwestern University Arizona Cancer Center New Jersey Neuroscience InstituteUC San DiegoMoffitt Cancer CenterPenn StateUniversity of PennsylvaniaUniversity of VirginiaWake ForestCornell PresbyterianMassachusetts GeneralKentuckiana Cancer Institute Cedars-Sinai Medical CenterUniversity Hospital Case Medical Center Rush UniversityOverlook Hospital Baylor University Cleveland ClinicUniversity of AlabamaThomas JeffersonLong Island Brain Center
JAN
FEB
MAR
APRM
AYJU
N JUL
AUG SEP
OCTNOV
DECJA
NFE
BM
ARAPR
MAY
JUN JU
LAUG
0
50
100
150
200
250
300
Planned Actual
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FDA ApprovalsNewly 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
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Projected Costs: ICT-107 vs. ProvengeLower cost of goods, better logistics
ICT-107 Provenge% DCs/APC 60%-90% 15%-20%
Interleukin-12 Yes No
Target antigens Six One
Doses/apheresis ~30 1
Storage Liquid nitrogen N/A
Administration Intradermal injection IV infusion
Cost of Goods 5%-10% 70%
Source: Quarterly earnings transcripts and public filings.
Other Immunotherapy Candidates
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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-107̶F HER2/neu, IL-13Rα2, MAGE1, mesothelin, EphA2, & two more antigens
File IND by Q4/2012
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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
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Inverse Correlation between CD133 Expression with Survival on Gliomas
Source: Rebetz et al. PLoS ONE. 2008.
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.
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
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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
Product Pipeline
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2011
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
2012
Q1 Q2 Q3 Q4
2013
Q1 Q2 Q3 Q4
2014
ICT-107New GBM Phase II trial
Phase I/II trial
Phase I trial
Preclinical
Preclinical
ICT-140Ovarian
ICT-121Recurrent GBM
Interim analysis Final results
IND
IND
Recent & Upcoming Milestones
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July 2012ICT-121 IND
October 2012SITC abstract
November 2012SNO abstract
August 2012ICT-107 Ph 2 enrollment
Q1 2013ICT-107 Ph 2 interimICT-140 IND
2H 2013ICT-107 Ph 2 final
Q3 2013ICT-140 Ph 1/2
October 2013SITC abstract
November 2013SNO abstract
May 2012NYSE MKT listing
June 2013ASCO abstract
December 2012ICT-121 Ph 1
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Strong Financial Position & Capitalization
Cash (as of 9/30/2012) $10 million (A)Burn rate $3 million per quarter
Outstanding debt NoneShares outstanding (as of
9/30/12) 41.1 million (A)
Market capitalization (as of 11/6/2012) $98 million
Warrants outstanding (as of 9/30/12) 8.9 million (A)
Options outstanding 10.4 million (average weighted 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.
November 2012
ImmunoCellular TherapeuticsIndustry-leading, next-generation, cancer immunotherapy