Slide 1: Advancing T Cell Engagers for Solid Tumors
Advancing T Cell Engagers for Solid Tumors Corporate Presentation June 2025
Slide 2: Forward Looking Statement Important Notice and Disclaimers
Executive Summary Forward Looking Statement Important Notice and Disclaimers Except for statements of historical fact, any information contained in this presentation Certain information contained in this presentation relates to or is based on studies, may be a forward-looking statement that reflects
Slide 3: Executive Summary: Building a T cell Engager Pipeline
Executive Summary Building a T cell Engager Pipeline TCEs are Recent TCE clinical data demonstrates promising efficacy and safety in solid tumors Gaining Momentum • Clinical activity across a broad range of targets, including Claudin 18.2, DLL3, gp100, PSMA, and STEAP1 • Responses in “cold” tumors,
Slide 4: Pipeline Overview
Executive Summary Pipeline Overview ADDRESSABLE MARKET PROGRAM TARGET DISCOVERY DEVELOPMENT PHASE 1 PHASE 2 RECENT & ANTICIPATED MILESTONES (U.S. ONLY) Phase 1 first patient dosed January 2025 CTIM-76 Claudin 6 (CLDN6) > 50,000 patients Initial data 1H 2026 Phase 1 first patient dosed April 2025 CT-
Slide 5: T Cell Engager Strategy
T Cell Engager Strategy 5 C o n t e xt T h e r a p e u t i c s I n c . - J u n e 2 0 2 5
Slide 6: T Cell Engaging (TCE) Bispecific Antibodies
T Cell Engager Strategy T Cell Engaging (TCE) Bispecific Antibodies TCEs are engineered to activate an immune response against cancer cells CD3 Mechanism of Action T Cell T cell engagers (TCEs) are antibodies engineered to redirect the immune system’s T cells to recognize and kill cancer cells TCE B
Slide 7: Realizing the Full Potential of T Cell Engagers (TCE)
T Cell Engager Strategy Realizing the Full Potential of T Cell Engagers (TCE) 2024 was a watershed year for TCEs HPN328 JANX007 / JANX008 Tarlatamab / DLL3 TCE + B7-H3 ADC4 (DLL3) (PSMA / EGFR) IMDELLTRATM (DLL3) Confirmed response rate of 83% (5/6) of JANX007 patients At 10mg, mPFS was 4.9 months 3
Slide 8: TCE Activity in “Cold” Tumors
T Cell Engager Strategy TCE Activity in “Cold” Tumors Tumor shrinkage with low rate of Grade ≥ 3 cytokine release syndrome (CRS) Tarlatamab Xaluritamig Ubamatamab Asset (AMG757) HPN328 IBI389 JANX007 VIR-5500 JNJ-78278343 (AMG509) (REGN4018) Target x Effector DLL3 x CD3 DLL3 x CD3 CLDN18.2 x CD3 PSM
Slide 9: Context’s Approach to TCEs
T Cell Engager Strategy Context’s Approach to TCEs Historical TCE Challenges Context’s TCE Approach ✘ Broadly expressed antigens Tumor restricted antigens ✘ Cytokine release syndrome Premedication + step-dosing ✘ Weak clinical activity High affinity CD3 binding ✘ Poor durability Combination with ADC
Slide 10: CTIM-76
CTIM-76 CLDN6 x CD3 bispecific antibody 10 C o n t e xt T h e r a p e u t i c s I n c . - J u n e 2 0 2 5
Slide 11: CLDN6 Therapies Have the Potential to Reach a Large Patient Population
CTIM-76 Program 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 Patient Selected Cancer Incidence CLDN6 Population R/R Incidence CLDN6 Positive indications (US Only) Med/High Based on R/R Incide
Slide 12: CLDN6 is an Oncofetal Protein
CTIM-76 Program CLDN6 is an Oncofetal Protein Oncofetal proteins are considered favorable candidates for immunotherapy Oncofetal Characteristics of CLDN6 • Normally present at higher levels during embryonic development • Turned off or have low levels of expression in adult tissues • Increased expres
Slide 13: Developing a Highly Selective CLDN6 Antibody is Challenging
CTIM-76 Program Developing a Highly Selective CLDN6 Antibody is Challenging Human CLDN Family Tree • CLDN6 antigen is conformationally dependent, which limits access to antibody-antigen binding • Antigen binding region is highly conserved with CLDN3, CLDN4, and CLDN9, making CLDN6- selective binding
Slide 14: CLDN6 Target Validation via ADC and CAR-T
CTIM-76 Program 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) High Response Rates with CLDN6 ADC and CAR-T CTIM-76 Addresses Limitations of ADC and CAR-T CTIM-76 BNT2111 TORL-1-232,3 Basket1 Basket2 51% ORR (n=1
Slide 15: CTIM-76: Claudin 6 x CD3 T cell Engaging (TCE) Bispecific Antibody
CTIM-76 Program 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) doma
Slide 16: 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 Selectivity Potency In Vivo Efficacy 600 Tumor Volume (mm3) 450 >500x 300 >10,000x 150 Tumor Regression 0 0 7 14 21 Day Vehicle 0.01mg/kg 0.1mg/kg 1.0mg/kg • CTIM-76 CLDN6 EC50 of 3.41 nM (binding) • Potency ass
Slide 17: CTIM-76 Phase 1a/b Study
CTIM-76 Program CTIM-76 Phase 1a/b Study An open-label, multi-center, dose escalation / expansion, safety, and PK study (NCT06515613) Part 1 – Dose Escalation (~40 patients) • Target population Single patient (Cohorts 1 and 2) ̶ Platinum resistant ovarian cancer ̶ Endometrial and testicular cancer r
Slide 18: CTIM-76 Competitive Landscape
CTIM-76 Program CTIM-76 Competitive Landscape CLDN6 T Cell Engaging Bispecifics Clinical Programs Discontinued CTIM-76 XmAb541 ARC101 SAIL66 AMG794 Company Context Xencor Third Arc Chugai Amgen Ph 1 Stage Ph 1 Ph 1 Ph 1 Ph 1 (Discontinued July 2024)1 Bispecific Format 1+1 2+1 1+1 Dual Specific Fab H
Slide 19: CT-95
CT-95 MSLN x CD3 bispecific antibody 19 C o n t e xt T h e r a p e u t i c s I n c . - J u n e 2 0 2 5
Slide 20: MSLN Therapies Have the Potential to Reach a Large Patient Population
CT-95 Program 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 Patient Selected Cancer Incidence MSLN MSLN Population R/R Incidence indications (US Only) Positive Med/High Based on R/R Incidence
Slide 21: Mesothelin (MSLN) Target Validation via ADC and CAR-T
CT-95 Program 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 Recent Investor and Strategic Interest in MSLN CT-95 Use Case Potential to be used as a monotherapy or in combination December 2023 with MSLN ADC or FRα A
Slide 22: MSLN Target Biology
CT-95 Program MSLN Target Biology Shed mesothelin (sMSLN) in tumor microenvironment requires a creative solution to overcome Overcoming Fragmented MSLN in the Tumor Microenvironment Tumor Cell MSLN is bound to tumor cells via a GPI-anchor Precursor MSLN Protein GPI Like many GPI-anchored proteins, M
Slide 23: CT-95: MSLN x CD3 T cell Engaging (TCE) Bispecific Antibody
CT-95 Program CT-95: MSLN x CD3 T cell Engaging (TCE) Bispecific Antibody Novel design to overcome mesothelin (MSLN) sink • Binds to membrane-proximal MSLN epitope α-MSLN Fab • Cooperative binding results in high affinity binding of CT-95 to tumor Potentially wide therapeutic window • No crosslinkin
Slide 24: Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge
CT-95 Program Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge Binds MSLN Epitope Close to Cell Surface Activates T cells Through Cooperative Binding Far No crosslinking with shed MSLN MSLN on tumor crosslinks CD3 From cell surface Tumor Amatuximab MORAb-009 mAb Anetumab + BAY 94-9343
Slide 25: CT-95 Intended to Overcome MSLN Sink
CT-95 Program CT-95 Intended to Overcome MSLN Sink HPN-536 (Harpoon Therapeutics) binds to MSLN fragments in a dose proportional manner, limiting therapeutic exposure Low MSLN Expression CT-95 HPN-536 +10nM MSLN 4k copies per cell +10nM MSLN +30nM MSLN +30nM MSLN Medium MSLN Expression CT-95 HPN-536
Slide 26: CT-95 is Highly Active and Well Tolerated Across In Vivo Models
CT-95 Program CT-95 is Highly Active and Well Tolerated Across In Vivo Models Complete tumor regressions in mice at doses ≤ 0.05 mg/kg Primary Lesion Model Metastatic Lesion Model Ovarian cancer line OVCAR3 OVCAR3 pre-passaged in mice flank implantation tumor model to generate aggressive, metastatic
Slide 27: CT-95 Phase 1 Study
CT-95 Program CT-95 Phase 1 Study An open-label, multi-center, dose escalation / expansion, safety, and PK study (NCT06756035) Part 1 – Dose Escalation (~30 patients) • Target population Single patient (Cohorts 1 and 2) ̶ Platinum resistant ovarian cancer ̶ Mesothelioma, Pancreatic, Colorectal, NSCL
Slide 28: CT-95 Competitive Landscape
CT-95 Program CT-95 Competitive Landscape • 1st generation MSLN T cell engagers (TCE) were discontinued due to a lack of efficacy • Lack of efficacy may have been attributed to lower drug exposure due to binding to shed mesothelin (sMSLN)1,2 Clinical Programs – 2nd Generation 1st Generation CT-95 ZW
Slide 29: CT-202
CT-202 Nectin-4 x CD3 bispecific antibody 29 C o n t e xt T h e r a p e u t i c s I n c . - J u n e 2 0 2 5
Slide 30: Nectin-4 Therapies Have the Potential to Reach a Large Patient Population
CT-202 Program 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 Patient Selected Cancer Incidence Nectin-4 Nectin-4 Population R/R Incidence indications (US Only) Positive Med/High Based on R
Slide 31: CT-202: Nectin-4 x CD3 T cell Engaging (TCE) Bispecific Antibody
CT-202 Program CT-202: Nectin-4 x CD3 T cell Engaging (TCE) Bispecific Antibody Novel design incorporating logic gating to spare Nectin-4 in normal tissue • Because of its expression in healthy epidermal keratinocytes, sweat glands, and α-Nectin-4 hair follicles, Nectin-4 targeted treatments are ass
Slide 32: Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin
CT-202 Program Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin Logic Gating Through pH Dependency Increased Target Selectivity Through Avidity 30x gain of activity in acidic tumor microenvironment versus healthy cells1 High on-/off-rate when bound Avidity-enhanced to Nectin-4 monomer
Slide 33: CT-202 is Highly Active and Well Tolerated Across In Vivo Models
CT-202 Program CT-202 is Highly Active and Well Tolerated Across In Vivo Models Complete Tumor Regressions Reduced Cytokine Release CT-202 demonstrated similar efficacy in BT474 breast cancer xenograft CT-202 treatment resulted in significantly lower IL-6 induction compared to enfortumab TCE control
Slide 34: CT-202 Competitive Landscape
CT-202 Program CT-202 Competitive Landscape Competitor TCE programs lack conditional activation, avidity enhancement, and high potency immune activator – BT7480: 2 partial responses out of 33 patients treated in a Phase 1 dose escalation trial, pursuing combination studies going forward1 – RNDO-564:
Slide 35: Corporate
Corporate 35 C o n t e xt T h e r a p e u t i c s I n c . - J u n e 2 0 2 5
Slide 36: Focus on Execution
Corporate Experienced Leadership Team Martin Lehr Karen Chagin, MD1 Chief Medical Officer CEO and Director Focus on Execution • Experienced management team Jennifer Minai Alex Levit, Esq • Clinical team has developed T cell Chief Financial Officer Chief Legal Officer therapies • Our management team
Slide 37: Investment Highlights (Nasdaq: CNTX)
Corporate Investment Highlights (Nasdaq: CNTX) Large High-Value Anticipated Strong Cash Unmet Need Targets Milestones Team Runway Solid Tumors Claudin 6 CTIM-76 Deep oncology Expected initial data experience cash runway + + 1H 2026 into 2027 Mesothelin + ADC Resistance + CT-95 Focus on Nectin-4 init
Slide 38: Advancing T Cell Engagers for Solid Tumors
Advancing T Cell Engagers for Solid Tumors © Context Therapeutics 2025
Slide 39: Glossary
Glossary ADC Antibody drug conjugate ORR Overall response rate AE Adverse event PFS Progression free survival CAR-T Chimeric antigen receptor T cell therapy RP2D Recommended Phase 2 dose CD3 Cluster of differentiation 3 TCE T cell engager CLDN Claudin TRAE Treatment-related adverse event CRS Cytokin