Context Therapeutics Inc. · NASDAQ:CNTX

Context Therapeutics — Investor Presentation (June 2025)

39 slides from Context Therapeutics's investor presentation, Jun 2, 2025

  1. Slide 1: June 2025 Corporate Presentation: Advancing T Cell Engagers for Solid Tumors

    June 2025 Corporate Presentation Advancing T Cell Engagers for Solid Tumors

  2. 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

  3. Slide 3: Building a T cell Engager Pipeline: Executive Summary

    Building a T cell Engager Pipeline Executive Summary Context Therapeutics Inc. - June 20253 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, PSMA, an

  4. Slide 4: Pipeline Overview

    Executive Summary Pipeline Overview Context Therapeutics Inc. - June 20254 PROGRAM TARGET ADDRESSABLE MARKET (U.S. ONLY) DISCOVERY DEVELOPMENT PHASE 1 PHASE 2 RECENT & ANTICIPATED MILESTONES CTIM-76 Claudin 6 (CLDN6) > 50,000 patients Phase 1 first patient dosed January 2025 Initial data 1H 2026 CT-

  5. Slide 5: T Cell Engager Strategy

    T Cell Engager Strategy Context Therapeut ics Inc . - June 20255

  6. Slide 6: 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. - June 20256 Mechanism of Action T cell engagers (TCEs) are antibodies engineered to redirect the immune system’s T cells to recognize

  7. Slide 7: Realizing the Full Potential of T Cell Engagers

    Realizing the Full Potential of T Cell Engagers (TCE) 2024 was a watershed year for TCEs T Cell Engager Strategy Context Therapeutics Inc. - June 20257 $680M ACQUISITION Confirmed response rate of 35% (11/31) across all tumor types (SCLC and other neuroendocrine tumors), including three complete res

  8. Slide 8: TCE Activity in "Cold" Tumors

    TCE Activity in “Cold” Tumors Tumor shrinkage with low rate of Grade ≥ 3 cytokine release syndrome (CRS) Asset Tarlatamab (AMG757) HPN328 IBI389 JANX007 VIR-5500 JNJ-78278343 Xaluritamig (AMG509) Ubamatamab (REGN4018) Target x Effector DLL3 x CD3 DLL3 x CD3 CLDN18.2 x CD3 PSMA x CD3 PSMA x CD3 KLK2

  9. Slide 9: Context's TCE Approach

    Context’s TCE ApproachHistorical TCE Challenges Context’s Approach to TCEs T Cell Engager Strategy Context Therapeutics Inc. - June 20259 Cytokine release syndrome Weak clinical activity Poor durability Premedication + step-dosing High affinity CD3 binding Combination with ADC or Checkpoint ✘ ✘ ✘ Br

  10. Slide 10: CTIM-76 CLDN6 x CD3 bispecific antibody

    CTIM-76 CLDN6 x CD3 bispecific antibody Context Therapeut ics Inc . - June 202510

  11. Slide 11: 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 11 Context Therapeutics Inc. - June 2025 Initial indications of interest based on: • CLDN6 prevalence • Patient population size •

  12. Slide 12: 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

  13. Slide 13: Developing a Highly Selective CLDN6 Antibody is Challenging

    Developing a Highly Selective CLDN6 Antibody is Challenging CTIM-76 Program Context Therapeutics Inc. - June 202513 • 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-

  14. Slide 14: 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. - June 202514 CTIM-76 Addresses Limitations of ADC and CAR-THigh Response Rates with CLDN6 ADC and CAR-T CTIM-76 BNT2111 TO

  15. Slide 15: 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

  16. 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 Context Therapeutics Inc. - June 202516 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 transf

  17. Slide 17: 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 ̶ CLDN6+ positive (10% ≥ 1+) • Trial objectives ̶ Assess safe

  18. Slide 18: CTIM-76 Competitive Landscape

    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 Stage Ph 1 Ph 1 Ph 1 Ph 1 Ph 1 (Discontinued July 2024)1 Bispecific Format 1 + 1 2 + 1 1 + 1 Dual Specific Fab HLE Bite CL

  19. Slide 19: CT-95 MSLN x CD3 bispecific antibody

    CT-95 MSLN x CD3 bispecific antibody Context Therapeut ics Inc . - June 202519

  20. Slide 20: 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 20 Context Therapeutics Inc. - June 2025 Selected Cancer indications Incidence (US Only) R/R Incidence MSLN Positive MSLN Med/High P

  21. Slide 21: 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 21 Context Therapeutics Inc. - June 2025 CT-95 Use CaseRecent Investor and Strategic Interest in MSLN December 2023 Pfizer licensed ex-Asia rights to HBM-

  22. Slide 22: MSLN Target Biology

    MSLN Target Biology Shed mesothelin (sMSLN) in tumor microenvironment requires a creative solution to overcome CT-95 Program Context Therapeutics Inc. - June 202522 MSLN is bound to tumor cells via a GPI-anchor Like many GPI-anchored proteins, MSLN can be cut into smaller fragments1,2 The MSLN gene

  23. Slide 23: 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

  24. Slide 24: Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge

    Two-Pronged Approach to Overcoming Soluble MSLN Sink Challenge CT-95 Program 24 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

  25. Slide 25: CT-95 Intended to Overcome MSLN Sink

    Low MSLN Expression 4k copies per cell Medium 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. - June 202525 CT-95 +10nM

  26. Slide 26: 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. - June 202526 Primary Lesion Model Metastatic Lesion Model OVCAR3 pre-passaged in mice to generate aggressive, metastatic tumor model Ovari

  27. Slide 27: CT-95 Phase 1 Study

    CT-95 Phase 1 Study An open-label, multi-center, dose escalation / expansion, safety, and PK study (NCT06756035) • Target population ̶ Platinum resistant ovarian cancer ̶ Mesothelioma, Pancreatic, Colorectal, NSCLC adenocarcinoma, Cholangiocarcinoma, others • Biomarker stratification ̶ Due to high M

  28. Slide 28: CT-95 Competitive Landscape

    CT-95 Program CT-95 Competitive Landscape 28 Clinical Programs – 2nd Generation 1st Generation CT-95 ZW171 AMG-305 HPN-5361 ABBV-4282 Company Context Zymeworks3,4 Amgen5 Harpoon AbbVie Format 2 + 2 2 + 1 1 + 1 + 2 CDH3 + MSLN dBiTE TriTAC 2 + 2 PK Enhancement Fc Fc Truncated Fc Albumin Fc Avoids MSL

  29. Slide 29: CT-202 Nectin-4 x CD3 bispecific antibody

    CT-202 Nectin-4 x CD3 bispecific antibody Context Therapeut ics Inc . - June 202529

  30. Slide 30: 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 30 Context Therapeutics Inc. - June 2025 Selected Cancer indications Incidence (US Only) R/R Incidence Nectin-4 Positive Nectin

  31. Slide 31: 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. - June 202531 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 kera

  32. Slide 32: Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin

    Two-Pronged Approach to Overcoming Nectin-4 Expression in Skin CT-202 Program 32 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

  33. Slide 33: 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. - June 202533 Complete Tumor Regressions CT-202 demonstrated similar efficacy in BT474 breast cancer xenograft compared to enfortumab TCE control antibodies in mice Reduced Cytokine Release CT-2

  34. Slide 34: CT-202 Competitive Landscape

    CT-202 Program CT-202 Competitive Landscape Company Context Therapeutics Bicycle Therapeutics Rondo Therapeutics Henlius Asset CT-202 BT74802 RNDO-5643 HLX-309 Format 2 + 2 (pH dependent) 1 + 2 (Bicycle) 1 + 1 (Fixed light chain) n.d. Conditionally active ✘ ✘ n.d. Avidity enhanced ✘ ✘ n.d. Immune Ef

  35. Slide 35: Corporate

    Corporate 35 Context Therapeut ics Inc . - June 2025

  36. Slide 36: 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 Focus on Execution Martin Lehr CEO and Director Alex Levit, Esq Chief Legal Officer Karen Chagin, MD1 Chief M

  37. Slide 37: Investment Highlights

    Corporate Investment Highlights (Nasdaq: CNTX) Solid Tumors + ADC Resistance Large Unmet Need Claudin 6 + Mesothelin + Nectin-4 High-Value Targets CTIM-76 initial data 1H 2026 CT-95 initial data Mid 2026 CT-202 IND filing Mid 2026 Anticipated Milestones Deep oncology experience + Focus on clinical e

  38. Slide 38: Advancing T Cell Engagers for Solid Tumors

    Advancing T Cell Engagers for Solid Tumors © Context Therapeutics 2025

  39. Slide 39: 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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