This presentatio is n intended solely for evaluation of
investment opportunities.. 2014 immatics biotechnologies GmbH. Not
for further reproduction or distribution. 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
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Immatics Biotechnologies (Germany) An established company
dedicated to off-the-shelf cancer immunotherapies 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 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 2
Slide 3
HLA-presented tumor-associated peptides (TUMAPs) The cancer
immunopeptidome Immunopeptidome Proteome Genome / Transcriptome T
cell mRNA DNA Protein Peptide HLA Cell Tumor Our mission: Mapping
the human immunopeptidome as centrally relevant information for all
T-cell based immunotherapies. Our mission: Mapping the human
immunopeptidome as centrally relevant information for all T-cell
based immunotherapies. 3
Slide 4
HLA-presented tumor associated-peptides (TUMAPs) Novel targets
for T cells and TCR-based/like drugs T cell TCR-like Antibody
Anti-CD3 sTCR Soluble T-cell receptor Targets for vaccines and
adoptive cellular therapy Targets for mAbs/sTCRs 4
Slide 5
Slide 5 XPRESIDENT Discovery Platform TUMAPs as APIs for
Vaccines
Slide 6
XPRESIDENT Target Discovery Platform 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 6 Unique
features
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XPRESIDENT Discovery Platform: 7 Selection Process 1.Shotgun
IdentificationShotgun Identification 5.Pharmaceutical
characterization 50 % 10-20,000 non-redundnant peptides found on
selected type of cancer (TUMAPs) Product candidate comprising 10-15
TUMAPs 2. Overexpression/ overpresentation analysis 3. Functional
considerations 4. IP/FTO analysis 6. In vitro immunogenicity
testing 50% 7. GMP manufacturing 8. Filing of IMPD/IND ~10-30
validated TUMAPs 30-90 interesting TUMAPs 99 %0.7 %0.2 %
Pre-clinical DevelopmentPhase 1 Month 24Month 0Month 12 Screen Hit
Lead Drug Candidate confidential
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Slide 8 immatics Clinical Vaccine Pipeline Cancer Indication
Discovery/ Pre-clinical Phase 1 Phase 2 Phase 3 IMA901 IMA910
IMA950 Renal Cell Cancer A*02 (RCC) Colorectal Cancer A*02 (CRC)
Glioma A*02 (GB) Gastric Cancer A*02/A*24 (GC) IMA942 MAA/BLA
Partnered with Lung Cancer A*02/A*24 (NSCLC) Prostate Cancer
A*02/A*24 (PC) IMA932 IMA962 Partnered with In collaboration with
Pipeline & Partnerships
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Slide 9 IMA901 Renal Cell Cancer Vaccine Phase 2 results with
our Lead Therapeutic Cancer Vaccine Single-dose CY associated with
improved survival (and reduced regulatory T cells) Breadth of
immune response associated with improved survival
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Slide 10 XPRESIDENT Discovery Platform Tumor Entities Analyzed
to Date Drug discovery stage Non-small cell lung Cancer Gastric
Cancer Renal Cell Cancer Colorectal Cancer Glioma Clinical or
near-clinical stage Feasibility stage Urethral TC Cancer Bladder
Cancer Prostate Cancer Ovarian Cancer CLL AML Melanoma Rheumatoid
Arthritis Breast Cancer Testis Cancer Pancreatic Cancer Liver
Cancer
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Slide 11 Example 1: Cancer-specific splicing Parent protein not
overexpressed (mRNA) in cancer vs. normal tissues gastric
cancerhealthy tissue Tumor-specific alternative splicing described
in literature results into inclusion of a particular exon from
which this peptide is derived
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Example 1: Cancer-specific splicing antigen 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). 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). 12 Type IV
Collagen Alpha-3 Chain (COL6A3)-restricted peptide
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Example 2: Organ-specific genes vs. antigens 13 Differential
mRNA expression vs. peptide presentation Fibrinogen undisclosed
liver-specific target Peptide presentation in liver and HCC mRNA
expression Peptide presentation in HCC only mRNA expression
Slide 14
Example 3: Tumor-associated, low- abundance antigens 14
Slide 15
Example 4: Mutated peptides 15 Validation of NGS-identified
mutations with Mass Spec Predicting Immunogenicity of Tumor-
specific Mutations by Combining Mass Spectrometry & Exome
Sequencing Yadav et al., Nature 2014 (in press) Predicting
Immunogenicity of Tumor- specific Mutations by Combining Mass
Spectrometry & Exome Sequencing Yadav et al., Nature 2014 (in
press)
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 mutanome- derived APVACs
Approval by German Reg. Authority to start clinical phase I study
received started in October 2014 17
Slide 18
Slide 18 XPRESIDENT -derived Warehouse Approach A unique
toolbox for highly personalized cancer immunotherapy
Slide 19
Slide 19 XPRESIDENT-derived Warehouse Approach Development
Tracks in collaboration with MDACC scientists Peptide Warehouse
HLA/peptide multimer warehouse TCR Warehouse APVAC Actively
Personalized Vaccines ACTolog Adoptive Cellular Therapy with
endogenous T cells ACTolog Adoptive Cellular Therapy with
endogenous T cells ACTengine Adoptive Cellular Therapy with
engineered T cells ACTengine Adoptive Cellular Therapy with
engineered T cells Patrick Hwu Cassian Yee Laurence Cooper Willem
Overwijk
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Thank you 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] This is a
confidential presentation intended solely for internal use. 2014
immatics biotechnologies GmbH. Confidential. Not for further
reproduction or distribution.
