GEMoaB - Next Generation Immunotherapies
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GEMoaB – Next Generation Immunotherapies
GEMoaB aspires to become a leading, fully integrated biopharmaceutical company
focused on the discovery, development, manufacturing and commercialization of
next generation immunotherapies for patients in underserved cancer indications
Not For Distribution 1
GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
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Building a Leading Next Generation Immunotherapy Company
Founded by
Prof. Gerhard Ehninger and
Prof. Michael Bachmann
Start of ATAC partnership
FIH ATAC FIH ATAC FIH FIH
GEM333 GEM3PSCA UniCAR-T-CD123 UniCAR-T-PSMA
2011 2012 2014 2016 2018 2019 2020
• Founded in 2011
• 3 platforms: UniCAR, RevCAR and ATAC
• 40+ publications in peer-reviewed journals
• 3 active clinical trials with ATAC & UniCAR lead assets
• GEM333, GEM3PSCA, UniCAR-T-CD123
• H2/2020 first patient in UniCAR in solid tumors:
• UniCAR-T-PSMA (IND submitted by 03/2020)
• Deep pipeline in solid tumors and hematological
malignancies
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GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
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ATAC, UniCAR & RevCAR: 3 Proprietary Highly Differentiated Therapeutic Platforms
ATAC UniCAR RevCAR
FIH Q2/2018 FIH H1/2020 (CD123/rrAML) FIH H2/2021
FIH H2/2020 (PSMA/rrCRPC)
ATAC: Affinity-Tailored Adaptors for T-cells UniCAR: Universal CAR RevCAR: Reversed universal CAR
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-
- -
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ATAC Platform: In-vitro and in-vivo Efficacy of GEM333 & GEM3PSCA
In vitro Efficacy of GEM333
• Fully humanized bispecific antibodies against CD3 and (AML target cell line)
CD33 or CD3 and PSCA
• High affinity against tumor antigen, lower affinity
against CD3 reduces auto-activation in the absence of
tumor antigen
• Short serum half-life (60 min) enables rapid clearance Arndt et al., Leukemia 2013
in case of overshooting on target/on tumor or on
In vivo Efficacy of GEM3PSCA
target/off tumor effects, and improves the safety (CDX CRPC mouse model)
profile
• Half-life extended versions are in preclinical
development
Feldmann et al., J Immunol 2012
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ATAC, UniCAR & RevCAR: 3 Proprietary Highly Differentiated Therapeutic Platforms
ATAC UniCAR RevCAR
FIH Q2/2018 FIH H1/2020 (CD123/rrAML) FIH H2/2021
FIH H2/2020 (PSMA/rrCRPC)
ATAC: Affinity-Tailored Adaptors for T-cells UniCAR: Universal CAR RevCAR: Reversed universal CAR
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-
- -
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UniCAR: Highly Differentiated & Flexible Next Generation CAR Technology
Efficacy similar to conventional CAR-T while Excellent in-vivo efficacy in AML and CRPC mouse models
allowing for excellent controllability
In vivo Efficacy of UC02-T-CD123 In vivo Efficacy of UC02-T-pPSMA
1 2 (CDX AML mouse model) (CDX CRPC mouse model)
ASH 2018 Oral/Poster 964; Loff et al. 2020 AACR 2020 Poster 2176/8
Antigen-specific targeting modules (TM)
3 can be based on a variety of binding
moiety types.
Post-PoC opportunity for broad portfolio
of assets against multiple antigens and
multi-targeting optionality (sequential,
combinations)
TM-scFv: single chain fragment variable, TM-nB: nanobody, TM-TCR: soluble T cell receptor,
Feldmann et al. 2017; Loff et al. 2020 TM-l: ligand, TM-p: (chemically synthesized) peptide
Cartellieri et al. 2016; Albert et al. 2017; Arndt et al. 2019; Bachmann et al. unpublished
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UniCAR Platform: Unique Molecular Design Enables Enhanced Therapeutic Window,
Maintenance of Efficacy & High Flexibility
The Narrow Therapeutic Window of CAR-T cells1 The broader Therapeutic Window of UniCAR
Existing CAR-T Platforms: Narrow therapeutic Window UniCAR Platform: Enhanced Therapeutic Window
Risk of acute toxicity (on target/on tumor) – CRS, NT Rapid switch on/off (within 4 h)2
Risk of long term toxicity esp. with less differentially Rapid switch on/off, stop TM infusion after 24 d2
expressed antigens compared to CD19 & BCMA
Current dose limitations may limit clinical efficacy Controllability and less cytokine release2
1 Adapted from Mathijssen et al. Nature Reviews Clinical Oncology 2014, PMID: 24663127
2 AACR 2020 Poster 2176/8, data on file
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UniCAR-T-pPSMA: Rapid Switch on/off Capability Due to Short Pharmacologic and
Pharmacodynamic Half-Life of TMpPSMA
t1/2 = 15.2 min
Pharmacologic plasma half- AUC = 42.1 µg/ml*min
life of TMpPSMA after i.v.
bolus (elimination)
Pharmacodynamic half-life of t1/2 at 4°C = nd
t1/2 at 37°C = 23 min
TMpPSMA post target cell
binding (internalisation)
Confidential – not for distribution Report R-TMpPSMA-015, -016, AACR 2020 poster 2176/8 10Rapid Switch on/off Capability of UniCAR-T-PSMA
2nd cycle
TMpPSMA TMpPSMA
- +
66 h 1st 66 h
cycle
Wash
TMpPSMA TMpPSMA
-/+ or -/- +/+ or +/-
66 h 2nd 66 h cytotoxic response over time of Cytotoxic response at end-point
cycle
one representative donor (mean of 4 independent UniCAR-T donors)
Read-out
UC02: human primary T cell genetically modified to express UniCAR
version 02, clinical scale manufacturing process
Confidential – not for distribution AACR 2020, Poster 2176/8 11UniCAR Platform: Unique Molecular Design Enables Enhanced Therapeutic Window,
Maintenance of Efficacy & High Flexibility
NARROW Therapeutic Window & Loss BROAD Therapeutic Window & Maintenance of Efficacy
of Efficacy over Time2 due to pulsed activation of UniCAR
Existing CAR-T Platforms: Loss of Efficacy over time UniCAR Platform: Enhanced Therapeutic Window & Efficacy Over Time
Lack of engraftment, expansion and persistence, esp. in the solid Improved expansion, engraftment and tumor-reactivity by use of CD28
tumor setting co-stimulatory domain3
Downregulation of T-effector cells by tumor immunosuppressive Limited downregulation by Tregs through use of CD28 co-stimulatory
microenvironment domain4
T-cell exhaustion due to constant stimulation Time restricted application of TMs, switch on/off 3
Antigen escape leading to rapid relapse Optionality for dual targeting through sequential/combined use of TMs 5,6
Potential immunogenicity due to non-humanized CAR components Fully human, humanized or de-immunized scFvs, linkers and adapters3
1 Adapted from Mathijssen et al. Nature Reviews Clinical Oncology 2014, PMID: 24663127 2 Adapted from Watanabe et al. Frontiers in Immunology 2018, PMID: 30416506 3 Data on file, AACR 2020, Poster 2176/8 , Poster 2209/14, Poster 4232/6
4 Kegler et al. Oncoimmunology 2019, PMID: 31428518 5 Cartellieri et al. Blood Cancer Journal 2016, PMID: 27518241 6 Feldmann et al. Oncotarget 2017, PMID: 28404896
Not For Distribution 12UniCAR in Solid Tumors: UniCAR 28ζ Expand Faster and are not Suppressed by Tregs
Compared to UniCAR BBζ
1 UniCAR 28ζ expand faster as compared to UniCAR BBζ UniCAR 28ζ are not suppressed by Tregs as compared to UniCAR BBζ
3
s.c.injection
19d
PC3-PSCA
Dietrich et al., unpublished +/-
UniCAR 28ζ expand faster than conventional 28ζ CAR UniCAR-T
2
+ TM PSCA
+/-
UniCAR-Treg
Loff et al., unpublished
Not For Distribution Kegler et al., 2019, PMID: 31428518 13GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
Not For Distribution 14GEMoaB Leadership Team
Prof. Dr. Gerhard Ehninger Michael Pehl Dr. Armin Ehninger Dr. Marc Cartellieri
CMO CEO CSO CTO
• More than 700 publications in • 25+ years of leadership • Scientist at Auckland Cancer • Scientist at Massey University
peer reviewed journals experience in Biotech and Society Research Center, Swiss Palmerston North, and Technical
• Former Head of Hematology and Oncology Institute for Experimental Cancer University Dresden
Oncology, University of Dresden • CEO Immunomedics Research, German Cancer
• Former President of the German • President Oncology at Celgene Research Center and Technical • PhD from Technical University
Society of Hematology • SVP Global Marketing & Strategy University Dresden Dresden
• Former Head of German AML at Celgene • PhD from Ruprecht-Karls-
Study Group • Head of Hematology, Celgene University, Heidelberg
• Founder of German Bone Europe • Master Degree in Technical
Marrow Donor Database (DKMS) • Master Degree in Molecular Biology, University of Stuttgart
Biology, University of Munich
Not For Distribution 15GEMoaB Strategic & Scientific Advisory Board
Prof. Dr. Gerhard Ehninger Prof. Dr. Bob Löwenberg Dr. Thomas de Maizière Prof. Dr. Katy Rezvani
Chairman
• Former Head of Hematology • Professor of Hematology at • Member of the German • Director of Translational
and Oncology, University of Erasmus University, Parliament, member of the Research & Medical
Dresden Rotterdam, Netherlands Finance Committee of the Director, MD Anderson
• Former President of the • President of the German Parliament Cancer Center,
German Society of International Society of • Former Minister of State of
Hematology (DGHO) Finance of Saxony, Germany Houston/Texas
Experimental Hematology
• Founder of German Bone and the International • Former Minister of State of • Chief of the Section of
Marrow Donor Database Society of Hematology Justice of Saxony, Germany Cellular Therapy, MD
(DKMS) • Founder and first President • Former Federal Minister and Anderson Cancer Center,
• CEO of Cellex GmbH and of the Dutch-Belgian Head of Federal Chancellery Houston/Texas
founding shareholder of Cooperative Group on of Germany • Research program in
GEMoaB GmbH Hemato-Oncology in Adults • Former German Federal transplantation immunology
• Member of the Board of (HOVON) Minister of the Interior & with focus on natural killer
Directors at Rhön Klinikum • Former Editor-in-Chief of German Federal Minister of (NK) cells in leukemia &
AG “Blood” (2013-2020) Defense
lymphoma
Not For Distribution 16GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
Not For Distribution 17UniCAR Preferred Manufacturing Partnership with Sister Company Cellex:
Leveraging World Class CMC Capabilities in a Capital Efficient Manner
• Cellex is acting as CAR-T CMO of choice for several large companies
• Partnership is offering reduced manufacturing cost due to choice of vector, automated production process, reduced hands-on-time
• Key CMC efforts in place/ongoing
• Robust, automated production process over 10 – 14 d for phase I established
• Rapid QC tests in place for conditional release 48 – 72 h after product harvest for patients in need
• Full needle to needle autologous cell product supply chain in place
• Utilizing proprietary web-based scheduling tool accessible for all stakeholders (Oracle-based)
• Commercial readiness efforts on-going: optimizing production process to < 8 days, replacement of human serum, dual supply chain for cell
media and cytokine, optimization of needle-to-needle supply etc.
Not For Distribution 18GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred Partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
Not For Distribution 19CD123 Expression in Hematopoiesis and Hematologic Malignancies
CD123 expression in AML AML
• About 80% of AML patient are CD123 positive
• CD123 also expressed on unfavorable sub-types (e.g. FLT3-ITD, NPM1
mutations)
• CD123 surface expression higher on AML blasts compared to myeloid CD33+
progenitors
CD33+ CD123+
CD123 expression in ALL
• About 90% of B-ALL and 40% of T-ALL are CD123 positive Ehninger et al. 2014, PMID: 24927407
• T-cell effector cytokines induce up-regulation of CD123 on B-ALL
ALL
CD123 expression in HCL and BPDCN
• Close to 100% of leukemic cells express CD123 in these indications
While overexpressed in AML, ALL and certain lymphomas,
CD123 is also expressed on hematopoietic progenitors
and certain endothelial cells
• Need for effective immunotherapy with rapid switch on/off capability
Angelova et al. 2019
Not For Distribution 20PSMA Expression on Normal and Malignant Tissue
Normal tissue: Neovascular endothelial cells (NEC):
• Prostate: apical side of secretory-acinar epithelium % n
• Kidney: proximal tubules Prostate Cancer 13 32
Bladder Carcinoma 88 189
• Nervous system glia: astrocytes and Schwann cells Breast Carcinoma 87 115
• Small bowel: jejunal brush border Brain metastases from BrCa 90 19
• Salivary glands Colorectal Cancer 80 172
Gastric Cancer 33 127
Glioblastoma multiforme 93 43
Tumor tissue:
Liver, hepatocellular carcinoma 88 8
% n
Liver metastases, from CRC 95 22
Prostate Cancer (PC) 94 1154 Lymph node metastases from CRC 80 5
Non-small cell lung cancer 78 366
mPC (non-specified) 100 20
Lymphoma 60 10
mPC (bone) 88 8 Melanoma 85 14
mPC (lymph node) 44 18 Ovarian Carcinoma 100 31
Pancreatic Carcinoma 83 161
Bladder Carcinoma 6 130
Renal: Clear Cell Carcinoma 84 91
Non-small cell lung cancer 20 367 Squamous Cell Carcinoma 75 96
Thyroid Cancer 51 330
Report R-TMpPSMA-001
Sarcoma 57 57
Not For Distribution 21UniCAR-T-CD123 Phase IA Study – UniCAR & TM Dosing and Scheduling
Adaptive Study Design
21d prior LEU max. -26 -12 -5 -3 0 1 d25 (EOT) EOT +7d EOT +28d 3M 6M
Screening period Salvage therapy LD TM123 application (continuous, IV) Safety Follow-up
LEU period UniCAR02-T production/release Logistic UC02-T IV Inactive UC02-T
Active drug Post-treatment DLT evaluation period
DLT evaluation period (32 resp. 53 days)
Response evaluation period
UniCAR-T-CD123
Therapeutic Target • CD123+ relapsed/refractory AML, ALL
Primary Objective • Determine safety, MTD dose and incidence of dose- ALL: Acute Lymphoblastic Leukemia
limiting toxicities (DLT) during the DLT period. AML: Acute Myeloid Leukemia
CR: Complete Remission
Secondary • Determine RP2D efficacy DLT: Dose Limiting Toxicity
LEU: Leukapheresis
Objectives • Reduction in bone marrow blasts LD: Lymphodepletion
• CR/PR rate OS: Overall Survival
• Remission duration PFS: Progression Free Survival
PR: Partial Response
• PFS and OS RP2D: Recommended Phase II Dose
Not For Distribution 22Clinical and Pre-Clinical Pipeline Overview
Asset Indication Target Pre-Clinical Phase I Planned IND Planned FPI
GEM333* rrAML CD33
met. NSCLC, CRPC, Bladder Ca, Renal Ca, Pancreatic
GEM3PSCA* PSCA
Ca, Breast Ca
UniCAR-T-CD123 rrAML, rrALL CD123
met. CRPC, NSCLC, Breast Ca (incl. TNBC), CRC, other
UniCAR-T-PSMA PSMA H1/2020** H2/2020
PSMA expressing solid tumors
met. CRPC, NSCLC, Breast Ca (incl. TNBC), CRC,
UniCAR 3 undisclosed H1/2022
Pancreatic Ca, Stomach Ca
UniCAR 4 Multiple Solid Tumors undisclosed H1/2022
RevCAR 1 AML, Multiple Myeloma undisclosed H1/2022
RevCAR 2*** undisclosed undisclosed undisclosed
*Programs partnered with BMS **IND submitted 03/2020 *** Program partnered with Intellia Therapeutics
Not For Distribution 23GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
Not For Distribution 24Value Inflection Points
• Lead assets*
– UniCAR-T-CD123 PoC: H2/2020 rrAML Phase IA data readout, H2/2021 rrAML Phase IB data readout
– UniCAR-T-PSMA PoC: H2/2021 rrCRPC Phase IA data readout, H2/2022 rrCRPC Phase IB data readout
• Pipeline
– IND submissions for two UniCAR programs and one RevCAR program; continue allogeneic workstreams
• Team
– Further buildout of clinical development & operations (incl. safety and regulatory)
* Estimates – actual timing is depending on actual study enrollment
Not For Distribution 25GEMoaB Key Success Factors
• Differentiated next generation immunotherapy platforms
Technology
– Specifically designed to target high unmet need hematological and solid tumor indications
• Seasoned Management Team & Scientific Founders
People
– Science driven with a proven track record in oncology
• Deep cellular manufacturing expertise
Manufacturing
– Preferred Partnership with sister company Cellex leveraging existing GMP manufacturing site
Clinical • Clinical excellence through established network of centers
Execution – Strong roots in German study group networks
• Clear path to value inflection
Value
– Multiple near-term readouts for lead assets UniCAR-T-CD123 & UniCAR-T-PSMA
Not For Distribution 26Company Contact
• General Inquiries
– Jana Fiebiger, Executive Assistant
– Email: jfiebiger@gemoab.com
– Phone: +49 351 4466-45012
• Investor Contact
– Michael Pehl, CEO
– Email: mpehl@gemoab.com
– Phone: +49 351 4466-45030
Not For Distribution 27Thank You Not For Distribution 28
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