Novel T-cell Targets for Cancer Immunotherapies

Report
Novel T-cell Targets for
Cancer Immunotherapies
Immatics Biotechnologies, Germany
Texas FreshAir Conference
Houston, October 23, 2014
Dr. Harpreet Singh
Co-founder and Chief Scientific Officer
This presentatio is n intended solely for evaluation of investment opportunities..
© 2014 immatics biotechnologies GmbH. Not for further reproduction or distribution.
Immatics Biotechnologies (Germany)
An established company dedicated to off-the-shelf cancer immunotherapies
Founded in 2000 as a spin-out from the University of Tuebingen, Germany
by Harpreet Singh, Toni Weinschenk, Hans-Georg Rammensee et al.
Since 2004 Immatics Biotechnologies GmbH has:
Raised € 142m (~$180m) in four financing rounds plus ~€ 10m public funding
Established and continuously evolved its proprietary technology platform XPRESIDENT®
Built a robust pipeline with three off-the-shelf cancer vaccines in clinical development
With lead product IMA901 (Renal Cell Cancer) in phase 3 trial (in collaboration with Pfizer)
A number of preclinical candidates partnered with Roche
immatics key facts:
Proprietary antigen discovery
platform
Strong IP protection technology and
on all assets
Experienced management team
Strong investor base in Europe
(family offices, venture capital)
Based in Germany (HQ in
Tuebingen) employing 80 FTEs
2
HLA-presented tumor-associated peptides (TUMAPs)
The cancer immunopeptidome
Our mission:
Mapping the human immunopeptidome
as centrally relevant information for
all T-cell based immunotherapies.
T cell
Peptide
HLA
Immunopeptidome
Protein
Proteome
G
U
A
A
C
C
U
G
G
C
A
C
A
U
U
G
A
C
C
U
G
Tumor Cell
3
A
C
C
G
U
A
C
A
mRNA
DNA
A
C
A
Genome / Transcriptome
HLA-presented tumor associated-peptides (TUMAPs)
Novel targets for T cells and TCR-based/like drugs
Targets for vaccines and
adoptive cellular therapy
Targets for
mAbs/sTCRs
TCR-like
Antibody
T cell
Soluble
T-cell receptor
Anti-CD3
sTCR
G
U
G
U
A
A
A
C
C
U
G
A
C
C
G
G
U
A
C
C
A
U
G
U
G
A
U
C
A
C
A
C
U
G
A
C
C
A
C
A
G
C
U
G
A
C
A
U
A
C
C
G
U
A
C
A
4
U
G
A
C
A
A
C
C
XPRESIDENT® Discovery Platform
XPRESIDENT® Target Discovery Platform
Unique features
6

Access to naturally presented targets for immunotherapy
 the cancer immunopeptidome
 Discovered on primary tumor tissues = real cancer cells
 No artificial cell lines, no computer algorithm-based predictions

Immatics‘ immunopeptidome database – unique features
 Largest in size
 Quantitative data
 Human Immunopeptidome Program initiated in
2014  up to 3000 novel targets to be filed in
patent applications in 15 different tumor types
 Including cancer and normal tissues

Results in proprietary targets
 In contrast to others offering immunotherapies directed towards public targets
XPRESIDENT™ Discovery Platform:
Selection Process
Month 0
Screen
Month 12
–
Hit
–
Lead
–
Drug Candidate
99 %
1. Shotgun
Identification
2. Overexpression/
overpresentation analysis
Month 24
Pre-clinical Development
0.7 %
0.2 %
5. Pharmaceutical
characterization 50 %
7. GMP manufacturing
6. In vitro immunogenicity
testing 50%
8. Filing of IMPD/IND
3. Functional considerations
4. IP/FTO analysis
30-90 interesting
TUMAPs
10-20,000 non-redundnant
peptides found on selected
type of cancer (TUMAPs)
7
Phase 1
confidential
~10-30
validated
TUMAPs
Product
candidate
comprising
10-15
TUMAPs
immatics Clinical Vaccine Pipeline
Cancer Indication
Discovery/
Pre-clinical
Phase 1
Renal Cell Cancer A*02
(RCC)
IMA910
Glioma A*02
(GB)
IMA950
IMA942
Partnered with
Lung Cancer A*02/A*24
(NSCLC)
IMA932
Partnered with
Prostate Cancer A*02/A*24
(PC)
IMA962
Partnered with
Phase 3
MAA/BLA
In collaboration with
IMA901
Colorectal Cancer A*02
(CRC)
Gastric Cancer A*02/A*24
(GC)
Phase 2
Partnered with
IMA901 Renal Cell Cancer Vaccine
Single-dose CY associated with
improved survival (and reduced
regulatory T cells)
Breadth of immune response associated with
improved survival
XPRESIDENT® Discovery Platform
Melanoma
Renal Cell Cancer
Colorectal Cancer
Breast Cancer
Pancreatic Cancer
Glioma
Bladder Cancer
Gastric Cancer
Urethral TC Cancer
Non-small cell lung Cancer
Ovarian Cancer
Prostate Cancer
Testis Cancer
Liver Cancer
Clinical or near-clinical stage
CLL
Drug discovery stage
Feasibility stage
Rheumatoid
Arthritis
AML
adipose tissue
adrenal gland
artery
bone marrow
brain, whole
breast
colon
esophagus
gallbladder
heart
kidney
leukocytes
liver
lung
lymph node
ovary
pancreas
placenta
prostate
salivary gland
skeletal muscle
skin
small intestine
spleen
stomach
testis
thymus
thyroid
trachea
urinary bladder
uterine cervix
uterus
vein
GC2215T
GC2230T
GC2234T
GC2419T
GC2423T
GC2424T
GC2426T
GC2427T
GC2428T
GC2430T
GC2432T
GC2433T
GC2435T
GC2436T
GC2437T
GC2447T
GC2448T
GC2449T
GC2451T
GC2461T
GC2466T
GC305T
GC701T
GC702T
GC703T
GC704T
GC705T
GC766T
GC767T
GC772T
GC772T
GC775T
GC799T
healthy tissue
2.3
5.7
gastric cancer
6.1
7.5
8.0
5.7
10.6
13.9
13.9
13.9
13.0
19.7
18.4
16.0
13.9
21.1
26.0
Tumor-specific alternative splicing described in
literature results into inclusion of a particular exon
from which this peptide is derived
19.7
18.4
17.1
19.7
17.1
17.1
14.9
13.9
12.1
11.3
11.3
11.3
10.6
9.8
8.6
8.6
8.0
7.5
6.5
6.1
5.7
6.1
4.9
8.0
8.6
7.5
5.7
4.6
3.5
2.8
2.1
3.5
2.1
1.1
2.6
7.5
6.5
4.9
5.3
3.7
2.6
2.8
1.0
0.2
1.1
1.1
0.7
1.6
relative expression
29.9
P
P
P
A
A
P
P
P
P
P
P
A
M
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
P
Example 1: Cancer-specific splicing
Example 1: Cancer-specific splicing antigen
Type IV Collagen Alpha-3 Chain (COL6A3)-restricted peptide





12
COL6A3 encodes the alpha-3 chain of type VI collagen, a component of the extracellular matrix
Cancer-specific splicing of COL6A3 has been described for colon, bladder, prostate, and pancreatic cancer
COL6A3 levels are increased in response to cisplatin in tumors. Endotrophin, a cleavage product of COL6A3,
causes cisplatin resistance through induction of epithelial-mesenchymal transition
Peptide COL6A3-002 (HLA-A*02-restricted) derived from cancer-specific exon 6 identified by XPRESIDENT® on
60 cancer samples from several entities (including pancreatic, NSCLC, colorectal, gastric cancer), but not on any
normal tissue (N>120 covering different organ classes)
Figure below: COL6A3 presentation on three PC tumor tissues compared to various healthy tissues (left panel) and
grouped analyses of healthy tissues and different tumor types (right panel). Insert in left panel showing exemplary
data of in vitro-primed COL6A3-002 specific T cells from HLA-A*02-positive and -negative healthy donors, the first
step required to generate TCRs to this target and Boxplot of RPKM values for tumor (T) and autologous normal (N)
tissues (N=29, TCGH research network) showing tumor-specific expression of the exon 6 (middle).
Example 2: Organ-specific genes vs. antigens
Differential mRNA expression vs. peptide presentation
Peptide presentation in liver and HCC
undisclosed
liver-specific target
Fibrinogen
mRNA expression
13
mRNA expression
Peptide presentation in HCC only
Example 3: Tumor-associated, lowabundance antigens
14
Example 4: Mutated peptides
Validation of NGS-identified mutations with Mass Spec
15
Actively Personalized Vaccines (APVACs)
17
Glioma Actively Personalized
Vaccine Consortium
GAPVAC
• Establish an actively personalized vaccination (APVAC) approach for
treatment of glioblastoma patients
• Consortium with 14 partners funded
by EU FP7 with € 6 mn
• Coordinator: Immatics
• Chief Investigator: Wolfgang
Wick (Heidelberg)
• Up to 30 glioblastoma
patients treated with
warehouse and mutanomederived APVACs
• Approval by German Reg.
Authority to start clinical phase I
study received  started in October 2014
XPRESIDENT®-derived Warehouse Approach
XPRESIDENT®-derived Warehouse Approach
Peptide Warehouse
HLA/peptide
multimer warehouse
TCR Warehouse
APVAC
ACTolog
ACTengine
Actively Personalized
Vaccines
Adoptive Cellular Therapy
with endogenous T cells
Adoptive Cellular Therapy
with engineered T cells
Cassian
Yee
Patrick
Hwu
Willem
Overwijk
Laurence
Cooper
CONTACT
immatics biotechnologies GmbH
Paul-Ehrlich-Str. 15
72076 Tuebingen, Germany
Phone +49-7071-5397-0
Fax +49-7071-5397-900
www.immatics.com
[email protected]
Thank you
This is a confidential presentation intended solely for internal use.
© 2014 immatics biotechnologies GmbH. Confidential. Not for further reproduction or distribution.
Intellectual Property
Processes & technologies
•
•
•
•
XPRESIDENT®
Formulation
Methods of treatment
TKIs + Vaccines
Specific pharmaceutical
compositions (e.g. multipeptide vaccine products)
IMA901
(RCC)
IMA910
(CRC)
Substance-of-matter
• TUMAPs (peptides)
• mAbs and sTCRs
• Corresponding nucleic
acids
• Biological products
IMA942
(GC)
IMA950
(GBM)

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