Context Therapeutics Inc. · NASDAQ:CNTX
Context Therapeutics — Investor Presentation (September 2024)
42 slides from Context Therapeutics's investor presentation, Sep 23, 2024
Slide 1: Corporate Presentation: Advancing T Cell Engagers for Solid Tumors
September 2024 Corporate Presentation Advancing T Cell Engagers for Solid Tumors
Slide 2: Important Notice and Disclaimers
Important Notice and Disclaimers Except for statements of historical fact, any information contained in this presentation may be a forward-looking statement that reflects the Company’s current views about future events and is subject to risks, uncertainties, assumptions and changes in circumstances
Slide 3: Building a T cell Engager Pipeline: Executive Summary
Building a T cell Engager Pipeline Executive Summary Context Therapeutics Inc. - September 20243 TCEs are Gaining Momentum Recent TCE clinical data demonstrates promising efficacy and safety in solid tumors • Clinical activity across a broad range of targets, including Claudin 18.2, DLL3, gp100, PSM
Slide 4: Pipeline
Executive Summary Pipeline Context Therapeutics Inc. - September 20244 PROGRAM TARGET ADDRESSABLE MARKET (U.S. ONLY) DISCOVERY DEVELOPMENT PHASE 1 PHASE 2 RECENT & ANTICIPATED MILESTONES CTIM-76 Claudin 6 (CLDN6) > 50,000 patients First patient dose expected Oct/Nov 2024 Initial data 1H 2026 CT-95 M
Slide 5: Pipeline Expansion with CT-95 and CT-202 Acquisitions
Pipeline Expansion with CT-95 and CT-202 Acquisitions Executive Summary Context Therapeutics Inc. - September 20245 Portfolio Alignment • Bispecific T cell engagers • Enriched in solid tumors • Target validation by antibody-drug conjugate (ADC) • High affinity CD3 to maximize efficacy High-quality A
Slide 6: T Cell Engager Strategy
T Cell Engager Strategy Contex t Therapeu t i cs Inc . - Sep tember 20246
Slide 7: T Cell Engaging (TCE) Bispecific Antibodies
T Cell Engaging (TCE) Bispecific Antibodies TCEs are engineered to activate an immune response against cancer cells T Cell Engager Strategy Context Therapeutics Inc. - September 20247 Mechanism of Action • T cell engagers (TCEs) are antibodies engineered to redirect the immune system’s T cells to re
Slide 8: Promising TCE Data in Solid Tumors
Promising TCE Data in Solid Tumors Tumor shrinkage with low rate of Grade ≥ 3 cytokine release syndrome (CRS) Asset Tarlatamab (AMG757) HPN328 IBI389 JANX007 Xaluritamig (AMG509) Target x Effector DLL3 x CD3 DLL3 x CD3 CLDN18.2 x CD3 PSMA x CD3 STEAP1 x CD3 Cancer Indication Small Cell Lung Small Ce
Slide 9: Realizing the Full Potential of T Cell Engagers
T Cell Engager Strategy Realizing the Full Potential of T Cell Engagers (TCE) Context Therapeutics Inc. - September 20249 $680M ACQUISITION Confirmed response rate of 35% (11/31) across all tumor types (SCLC and other neuroendocrine tumors), including three complete responses Generally well tolerate
Slide 10: Context's Approach to TCEs
Context’s ApproachHistorical TCE Challenges Context’s Approach to TCEs T Cell Engager Strategy Context Therapeutics Inc. - September 202410 Poor antigen selection Cytokine release syndrome Weak clinical activity Poor durability Targets validated by ADC Premedication + step-dosing High affinity CD3 b
Slide 11: CTIM-76: CLDN6 x CD3 bispecific antibody
CTIM-76 CLDN6 x CD3 bispecific antibody Contex t Therapeu t i cs Inc . - Sep tember 202411
Slide 12: CLDN6 Therapies Have the Potential to Reach a Large Patient Population
CLDN6 Therapies Have the Potential to Reach a Large Patient Population >50,000 patients per year in the United States in Relapse/Refractory (R/R) Setting CTIM-76 Program 12 Context Therapeutics Inc. - September 2024 Initial indications of interest based on: • CLDN6 prevalence • Patient population si
Slide 13: CLDN6 Target Validation via ADC and CAR-T
CLDN6 Target Validation via ADC and CAR-T CTIM-76 is designed to potentially address limitations of TORL-1-23 (ADC) and BNT211 (CAR-T) CTIM-76 Program Context Therapeutics Inc. - September 202413 CTIM-76 Addresses Limitations of ADC and CAR-THigh Response Rates with CLDN6 ADC and CAR-T CTIM-76 BNT21
Slide 14: CLDN6 is an Oncofetal Protein
CLDN6 is an Oncofetal Protein Oncofetal proteins are considered favorable candidates for immunotherapy • Normally present at higher levels during embryonic development • Turned off or have low levels of expression in adult tissues • Increased expression across many solid tumors CTIM-76 Program Conte
Slide 15: Developing a Highly Selective CLDN6 Antibody is Challenging
Developing a Highly Selective CLDN6 Antibody is Challenging CTIM-76 Program Context Therapeutics Inc. - September 202415 • CLDN6 antigen is conformationally dependent, which limits access to antibody-antigen binding • Antigen binding region is highly conserved with CLDN3, CLDN4, and CLDN9, making CL
Slide 16: CTIM-76: Claudin x CD3 T cell Engaging Bispecific Antibody
CTIM-76: Claudin 6 x CD3 T cell Engaging (TCE) Bispecific Antibody Optimized structure for CLDN6 selectivity, potency, and manufacturability • Highly selective CLDN6 binding fragment antibody-binding (Fab) arm • Immunostimulatory CD3 binding single-chain fragment variable (scFv) domain is functional
Slide 17: CTIM-76 is a Highly Selective and Potent CLDN6 x CD3 Bispecific Antibody
CTIM-76 Program CTIM-76 is a Highly Selective and Potent CLDN6 x CD3 Bispecific Antibody Context Therapeutics Inc. - September 202417 Selectivity Potency In Vivo Efficacy • CTIM-76 CLDN6 EC50 of 3.41 nM (binding) • CTIM-76 preferentially binds to CLDN6 over CLDN3/4/9 • CLDN3/4/6/9 were transiently t
Slide 18: CTIM-76 Phase 1a/b Study
CTIM-76 Phase 1a/b Study An open-label, multi-center, dose escalation / expansion, safety, and PK study (NCT06515613) • Target population ̶ Platinum resistant ovarian cancer ̶ Endometrial and testicular cancer relapsed to standard of care • Biomarker stratification ̶ CLDN6+ positive (10% ≥ 1+) ovari
Slide 19: CTIM-76 Competitive Landscape
CTIM-76 Competitive Landscape CLDN6 x CD3 T Cell Engaging Bispecifics Active Discontinued CTIM-76 XmAb541 SAIL66 NBL-028 AMG794 Company Context Xencor Chugai NovaRock Amgen Stage Ph 1 Ph 1 Ph 1 Ph 1 (China) Ph 1 (Discontinued July 2024)1 Bispecific Format 1 + 1 2 + 1 Dual Specific Fab 1 + 1 HLE Bite
Slide 20: CT-95: MSLN x CD3 bispecific antibody
CT-95 MSLN x CD3 bispecific antibody Contex t Therapeu t i cs Inc . - Sep tember 202420
Slide 21: MSLN Therapies Have the Potential to Reach a Large Patient Population
MSLN Therapies Have the Potential to Reach a Large Patient Population >100,000 patients per year in the United States in Relapse/Refractory (R/R) Setting CT-95 Program 21 Context Therapeutics Inc. - September 2024 Selected Cancer indications Incidence (US Only) R/R Incidence MSLN Positive MSLN Med/H
Slide 22: Mesothelin (MSLN) Target Validation via ADC and CAR-T
Mesothelin (MSLN) Target Validation via ADC and CAR-T CT-95 has the potential to be used after RC88 and HBM-9033, or in combination CT-95 Program 22 Context Therapeutics Inc. - September 2024 CT-95 Use CaseRecent Investor and Strategic Interest in MSLN December 2023 Pfizer licensed ex-Asia rights to
Slide 23: MSLN Target Biology
MSLN Target Biology Fragmented (shed) MSLN in tumor microenvironment requires a creative solution to overcome CT-95 Program Context Therapeutics Inc. - September 202423 • MSLN is bound to tumor cells via a GPI-anchor • Like many GPI-anchored proteins, MSLN can be cut into smaller fragments1,2 • The
Slide 24: CT-95: MSLN x CD3 T cell Engaging Bispecific Antibody
CT-95: MSLN x CD3 T cell Engaging (TCE) Bispecific Antibody Novel design to overcome mesothelin (MSLN) sink • Binds to membrane-proximal MSLN epitope • Cooperative binding results in high affinity binding of CT-95 to tumor Potentially wide therapeutic window • No crosslinking by shed MSLN, mitigatin
Slide 25: Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge
Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge CT-95 Program 25 Binds MSLN Epitope Close to Cell Surface Activates T cells Through Cooperative Binding + CD3 Potent T cell activationNo T cell activation No crosslinking with shed MSLN MSLN on tumor crosslinks CD3Far From cell surface C
Slide 26: CT-95 Intended to Overcome MSLN Sink
Medium MSLN Expression 4k copies per cell High MSLN Expression 27k copies per cell CT-95 Intended to Overcome MSLN Sink HPN-536 (Harpoon Therapeutics) binds to MSLN fragments in a dose proportional manner, limiting therapeutic exposure CT-95 Program Context Therapeutics Inc. - September 202426 CT-95
Slide 27: CT-95 is Highly Active and Well Tolerated Across In Vivo Models
CT-95 is Highly Active and Well Tolerated Across In Vivo Models Complete tumor regressions in mice at doses ≤ 0.05 mg/kg CT-95 Program Context Therapeutics Inc. - September 202427 Primary Lesion Model Metastatic Lesion Model OVCAR3 pre-passaged in mice to generate aggressive, metastatic tumor model
Slide 28: CT-95 Phase 1 Study
CT-95 Phase 1 Study An open-label, multi-center, dose escalation / expansion, safety, and PK study • Target population ̶ Platinum resistant ovarian cancer ̶ Mesothelioma, pancreatic, and lung cancer • Biomarker stratification ̶ Due to high MSLN prevalence, ovarian cancer does not require prospective
Slide 29: CT-95 Competitive Landscape
CT-95 Program CT-95 Competitive Landscape 29 Active Discontinued CT-95 ZW171 NAV-003 HPN-536 ABBV-428 NM28-2746 Company Context Zymeworks3 Navrogen4 Harpoon AbbVie Numab5 Format 2 + 2 2 + 1 2 + 2 TriTAC 2 + 2 Trispecific PK Enhancement Fc Fc Fc Albumin Fc Albumin Avoids MSLN sink n.d. ✘ ✘ High poten
Slide 30: CT-202: Nectin-4 x CD3 bispecific antibody
CT-202 Nectin-4 x CD3 bispecific antibody Contex t Therapeu t i cs Inc . - Sep tember 202430
Slide 31: Nectin-4 Therapies Have the Potential to Reach a Large Patient Population
Nectin-4 Therapies Have the Potential to Reach a Large Patient Population >125,000 patients per year in the United States in Relapse/Refractory (R/R) Setting CT-202 Program 31 Context Therapeutics Inc. - September 2024 Selected Cancer indications Incidence (US Only) R/R Incidence Nectin-4 Positive N
Slide 32: Nectin-4 Target Validation via ADCs
Nectin-4 Target Validation via ADCs TCE have an opportunity to improve upon best-in-class ADCs CT-202 Program 32 Many Nectin-4 ADCs in Development Rationale for Combining ADC with TCETCE May Address ADC Resistance Context Therapeutics Inc. - September 2024 Padcev Approved in 2021 BT8009 Phase 2/3 CR
Slide 33: CT-202: Nectin-4 x CD3 T cell Engaging Bispecific Antibody
CT-202: Nectin-4 x CD3 T cell Engaging (TCE) Bispecific Antibody CT-202 Program Context Therapeutics Inc. - September 202433 α-Nectin-4 Fab α-CD3 scFv IgG1 backbone Silenced Fc Novel design incorporating logic gating to spare Nectin-4 in normal tissue • Because of its expression in healthy epidermal
Slide 34: Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin
Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin CT-202 Program 34 Logic Gating Through pH Dependency + Increased Target Selectivity Through Avidity 1 Chang, PNAS, 2021 CD3 Potent T cell activationNo T cell activation High on-/off-rate when bound to Nectin-4 monomer Avidity-enhanced Ne
Slide 35: CT-202 is Highly Active and Well Tolerated Across In Vivo Models
CT-202 is Highly Active and Well Tolerated Across In Vivo Models CT-202 Program Context Therapeutics Inc. - September 202435 Complete Tumor Regressions CT-202 demonstrated similar efficacy in BT474 breast cancer xenograft compared to enfortumab TCE control antibodies in mice Reduced Cytokine Release
Slide 36: CT-202 Competitive Landscape
CT-202 Program CT-202 Competitive Landscape Company Context Therapeutics Bicycle Therapeutics Rondo Therapeutics Asset CT-202 BT74802 RNDO-5643 Format 2 + 2 (pH dependent) 1 + 2 (Bicycle) 1 + 1 (Fixed light chain) Conditionally active ✘ ✘ Avidity enhanced ✘ ✘ Immune Activator CD3 CD137 / 4-1BB CD28
Slide 37: Corporate
Corporate 37 Contex t Therapeu t i cs Inc . - Sep tember 2024
Slide 38: Experienced Leadership Team
Corporate Experienced Leadership Team • Experienced management team • Clinical team has developed T cell therapies • Our management team is supported by a Board with deep oncology experience, including Harpoon, Mariana Oncology, and Convergent Focus on Execution Martin Lehr CEO and Director Alex Lev
Slide 39: Key Anticipated Milestones
Key Anticipated Milestones 2024 2025 2026 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 CTIM-76: 1st Patient CTIM-76: Initial data CT-95: 1st Patient CT-95: Initial data CT-202: IND filing 39 Context Therapeutics Inc. - September 2024 Corporate
Slide 40: Investment Highlights
Corporate Investment Highlights (Nasdaq: CNTX) Solid Tumors + ADC Resistance Large Unmet Need Claudin 6 + Mesothelin + Nectin-4 High-Value Targets CTIM-76 first patient Oct/Nov 2024 CT-95 first patient Q1 2025 CT-202 IND filing Mid 2026 Anticipated Milestones Deep oncology experience + Focus on clin
Slide 41: Advancing T Cell Engagers for Solid Tumors
Advancing T Cell Engagers for Solid Tumors © Context Therapeutics 2024
Slide 42: Glossary
Glossary ADC Antibody drug conjugate AE Adverse event CAR-T Chimeric antigen receptor T cell therapy CD3 Cluster of differentiation 3 CLDN Claudin CRS Cytokine release syndrome Fab Fragment antigen-binding region GPI Glycosylphosphatidylinositol IHC Immunohistochemistry IND Investigational new drug
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