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1© 2026 CytomX Therapeutics, Inc. 44th Annual JP Morgan Healthcare Conference Dr. Sean McCarthy, CEO and Chairman January 14, 2026 Unmasking Advances in Oncology
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Forward-Looking Statements 2 This presentation may contain projections and other forward-looking statements regarding future events, including those related to varsetatug masetecan and CX-801. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, technology platform, development strategy, prospective products, preclinical and clinical pipeline and milestones, regulatory objectives and likelihood of success, are forward-looking statements. Such statements are predictions only and involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, among others, the costs, timing and results of preclinical studies and clinical trials, including varsetatug masetecan and CX-801, and other development activities; uncertainties inherent in the initiation and enrollment of clinical trials; uncertainties on the availability and timing of data from clinical trials; the risk that initial clinical data, including data for varsetatug masetecan and CX-801, may not reflect later clinical trial results; the unpredictability of the duration and results of regulatory review; the uncertainty of market acceptance for approved products and innovative therapeutic treatments; competition; the potential not to receive partnership milestone, profit sharing or royalty payments; the possible impairment of or inability to obtain intellectual property rights; possible safety or efficacy concerns with our drug candidates, including varsetatug masetecan and CX-801; and general business, financial and accounting risks and litigation. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. More information concerning us and such risks and uncertainties is available on our website and in our press releases and in our public filings with the U.S. Securities and Exchange Commission. We are providing this information as of its date and do not undertake any obligation to update or revise it, whether as a result of new information, future events or circumstances or otherwise. Additional information may be available in press releases or other public announcements and public filings made after the date of this presentation. This presentation concerns products that have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). No representation is made as to their safety or effectiveness for the purposes for which they are being investigated.
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Company Snapshot Unmasking Advances in Oncology 33 PROBODY® Platform: Leading the field of masked therapeutics Clinical Programs: • Varsetatug masetecan (EpCAM PROBODY ® Topo-1 ADC)* for Colorectal Cancer • CX-801 (PROBODY ® IFN-b) for Melanoma Financials: Cash runway to Q2 2027, excluding any potential milestones or new business development Partners: Bristol Myers Squibb, Amgen, Astellas, Regeneron, Moderna Organization: ~70 employees; integrated R&D capabilities South San Francisco, CA *Varsetatug masetecan (“Varseta-M”) - (formerly CX-2051)
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PROBODY® Therapeutic Design Right Target, Right Tumor, Right Effector Mechanism 4 Targets with anti-tumor potential that need localization Matching effector to target to maximize anti- cancer activity Optimized tuning of masking to maximize potential therapeutic index TARGET PRODOMAIN EFFECTOR Optimized selection of target, pro-domain and effector function • Proprietary masking technologies • Applicable across multiple modalities • Drives novel pipeline programs Varsetatug masetecan EpCAM PROBODY® ADC ❖ Lead Indication: Colorectal Cancer CX-801 PROBODY ® INTERFERON ALPHA-2b ❖ Lead Indication: Melanoma Industry Leading platform:
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Economics Product Candidate(s) Indication(s) Preclinical Phase 1 Phase 1 Expansion Commercial Rights* Clinical Pipeline Varseta-M EpCAM Topo-1 ADC 3L+ metastatic CRC (mCRC) Varseta-M + bevacizumab 2L/3L mCRC Varseta-M Additional EpCAM+ indications CX-801 (IFNα2b) Advanced Melanoma Preclinical Programs CX-908 (P-Cadherin x CD3) Solid Tumors PROBODY® TCBs Solid Tumors PROBODY® mRNAs Oncology & Non- oncology 5 PROBODY® Platform Drives Highly Differentiated Pipeline Phase 1 expansion data expected in Q1 2026 Phase 1 data CX-801 + KEYTRUDA ® by 2026 Year-End Initiating in Q1 2026 Initiating in 2H 2026 *CytomX Commercial Rights include wholly-owned molecules or molecules in which CytomX has full development and commercial control
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© 2026 CytomX Therapeutics, Inc. Varsetatug masetecan (CX-2051) A Novel EpCAM-Directed ADC Focused in Colorectal Cancer (CRC) 6
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Antibody Drug Conjugates are Transforming Cancer Care Varseta-M brings the promise of ADCs to Colorectal Cancer 7 Nectin-4 / Bladder Seagen/Pfizer - $43B Acquisition TROP2 / Breast Immunomedics/Gilead - $21B Acquisition HER2 / Breast, Lung** Daiichi/Astra Zeneca - 2024 Sales ~$3.8B FR / Ovarian Immunogen/AbbVie - $10B Acquisition EpCAM / CRC CytomX Therapeutics *Varseta-M PROBODY® ADC *Varsetatug masetecan is not an approved product and is in an ongoing Phase 1 clinical trial. **Enhertu select indications only. Sources: Company a nnouncements.
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Colorectal Cancer Remains One of the Biggest Unmet Needs in Oncology 8 ~1.9M patients per year, increasing to 3M by 2040 2nd leading cause of cancer death worldwide 5-year survival rate of 13% in mCRC Abbreviation: mCRC = metastatic colorectal cancer. Sources: World Health Organization, interactive data; Biller and Schrag, 2021, JAMA; American Cancer Society
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By 2040 U.S. CRC Incidence Estimated to be >170K Patients Annually 1L mCRC ~95K U.S. Patients 3L+ mCRC ~45K U.S. Patients 2L mCRC ~50K U.S. Patients Varseta-M has the Potential to Address a Large Patient Population due to Broad and Consistent EpCAM Expression in CRC Sources and assumptions: DRG epidemiology; Company estimates 9 Metastatic CRC (mCRC)
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EpCAM (Epithelial Cell Adhesion Molecule) An ideal CRC target enabled by the CytomX PROBODY platform 10 H&E Staining EpCAM IHC Maximum H-score of 300 (100% cells 3+ by IHC) • Uniformly high expression across CRC • EpCAM expression across all stages of CRC • Expression in normal tissues has limited drug development IHC Staining of CRC Patient Biopsy from Ongoing Phase 1 Study Abbreviations: IHC = immunohistochemistry; H&E = hematoxylin and eosin. Source: CytomX Internal Data, CTMX -2051-101 Study Patient Biopsy.
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EpCAM Has Been Clinically Validated But Not as a Systemic Therapy 11 Asset Company MOA Stage Status Solitomab Amgen EpCAM x CD3 BiTE Ph 1 GI tox; liver tox discontinued ING-1 XOMA EpCAM mAb Ph 1 Pancreatitis; discontinued 3622W94 GSK EpCAM mAb Ph 1 Pancreatitis; discontinued Systemic EpCAM approaches have been limited by toxicity EpCAM is clinically validated with a locally administered therapy KORJUNY® (catumaxomab): EpCAM x CD3 • Delivered by intraperitoneal infusion • Approved by EMA for treatment of malignant ascites • Launched in Germany in December 2025 Sources: Pharmanovia.com; de Bono et. All; de Bono et al. 2004; Gires et al. 2020
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L-ala-L-ala-L-ala (TAL) cleavable linker S DAR 8 Maleimidocaproyl CAMP59 TAL-CAMP59 Varsetatug masetecan: A Novel EpCAM Targeting PROBODY ® ADC The Right Target, The Right Payload 12 • Masking domains designed to reduce EpCAM binding in normal tissues • Unmasked antibody or ADC not expected to have a therapeutic window due to systemic toxicity Abbreviations: DAR = drug antibody ratio. CX-2051 antibody and linker-payload licensed through collaboration with Immunogen. Varseta-M
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The Current Standard of Care in 3L+ Metastatic CRC Is Highly Inadequate Poor response rates and limited survival benefit 13 Treatment Treatment Line ORR (%) DCR (%) Median PFS (months) Median OS (months) Fruquintinib 3L/4L+ 2% 56% 3.7 7.4 Regorafenib 3L/4L+ 1% 41% 2.0 6.4 Trifluridine/tipiracil 3L/4L+ 2% 44% 2.0 7.1 Trifluridine/tipiracil + Bevacizumab1 3L 6% 77% 5.6 10.8 Abbreviations: DCR = disease control rate; ORR = overall response rate; OS = overall survival; PFS = progression free surviva l. Sources: Lonsurf® (trifluridine and tipiracil) Fruzaqla® (fruquintinib), Stivarga® (regorafenib) package inserts; Dasari et a l. 2023; Grothey et al. 2013; Prager et al. 2023. 1. SUNLIGHT study total patients; Patients previously treated with prior bevacizumab had median PFS of 4.5 months and OS of 9 .0 months
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No Patient Selection Needed Varseta-M Interim Phase 1 Clinical Data in May 2025 Demonstrated an Encouraging Clinical Profile in Late-line Metastatic CRC 14 Pan-CRC Target • 28% confirmed ORR • 94% disease control • 5.8 mo. preliminary PFS High EpCAM expression in all tested tumors • No dose limiting toxicities • EpCAM target enabled by masking Robust Clinical Activity in mCRC* Favorable Safety Potential New Standard of Care in Late-line CRC Supports Development of Combinations in Earlier Lines of Therapy *Based on Interim Data cutoff 4/7/2025
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Varseta-M Anti-Tumor Activity at Doses Selected for Expansion Confirmed ORR: 28% (5/18) overall, 43% (3/7) at 10 mg/kg 15 Percent Change in Sum of Target Lesions From Baseline (%) 0 10 20 30 40 50 60 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 SD SD PD SD SD SD SD SD SD SD SD cPR cPR cPR cPR cPRSD SD 7.2 mg/kg 10 mg/kg 8.6 mg/kg CX-2051 Dose: cPR = Confirmed partial response; PD = Progressive disease; SD = Stable disease Patient remains on treatment 3 4 9 3 3 4 4 3 6 4 6 3 8 4 5 3 5 10 N Y N Y Y Y Y Y Y Y Y Y N Y Y N N Y Y Y Y Y Y N Y Y Y N N N N Y N Y Y Y Prior lines of systemic therapy KRAS mutation (Y/N) Liver metastases (Y/N) Baseline EpCAM H-Score1 Not evaluable H-Score > 280 1 Maximum immunohistochemistry (IHC) H-Score is 300; H-score captures the proportion of EpCAM+ cells in the biopsy and intensity of EpCAM expression. Data cutoff 4/7/2025 ORR: Overall Response Rate
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Initial Phase 1 Data Supports Competitive Profile for Varseta-M 16 Treatment ORR (%) DCR (%) Median PFS (months) Median OS (months) Varseta-M (7.2‒10 mg/kg) 28% 94% 5.8 1 N/A Fruquintinib 2% 56% 3.7 7.4 Regorafenib 1% 41% 2.0 6.4 Trifluridine/tipiracil 2% 44% 2.0 7.1 Trifluridine/tipiracil + Bevacizumab2 6% 77% 5.6 10.8 3L+ CRC Landscape Varseta-M is an investigational early-phase therapy. Information in tables above is not intended to be a direct comparison to approved tr eatments. Additionally, information provided in the tables above is for illustrative purposes only and no head -to-head comparison of Varseta-M has been conducted against any product or investigational therapy. Differences exist between study or trial designs and subject characteristics, and caution should be exercised when comparing data across unrelated studies. 1 Preliminary PFS as of 4/7/2025 data cutoff. .2SUNLIGHT study total patients; Patients previously treated with prior bevacizumab had median PFS of 4.5 months and OS of 9.0 months
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17 Sources: CytomX Therapuetics May 12, 2025 Varseta-M Data Presentation *As of the clinical data reported on May 12, 2025. Varseta-M GR3+ AEs were GR3 only as of April 7 th data cutoff. As reported subsequently in August 2025, a single Grade 5 treatment-related acute kidney injury occurred in a patient with a complex medical history including having a so litary kidney. Varseta-M Initial Safety Profile* Presented in May 2025 is Encouraging and Enabled by Masked PROBODY® ADC Design • Adverse events (AEs) generally manageable and reversible with most events Grade 1/2 • No signs of pancreatitis or serious liver toxicity which have limited prior EpCAM antibodies • No evidence of interstitial lung disease (ILD) observed • Hematologic profile may be attractive for future combinations • Diarrhea was the most common treatment-related adverse event (22% Grade 3) Prophylaxis implemented in Phase 1 expansions. Varseta-M Phase 1 Safety Profile*
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Varseta-M Monotherapy Dose Expansions Underway in Late-line CRC Phase 1 expansion data update on track for Q1 2026 18 7.2 mg/kg 8.6 mg/kg 10 mg/kg Expanding Expanding Expanding Phase 1 Expansions Ongoing • 73 patients enrolled as of August 2025, projected to enroll ~100 patients by Q1 data update • Goals for Phase 1 Expansion Data Update: ‒ Evaluate efficacy profile in larger sample size ‒ Characterize AE profile in larger number of patients, including GI AE management strategies utilized to-date • 2026 Goal: ‒ Select a dose or doses for a potential registrational study in late-line CRC Q1 2026 Phase 1 Expansion Update:
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Broad Development Opportunity for Varseta-M in Metastatic CRC Combo study with bevacizumab starting in Q1 2026 to enable earlier lines of therapy 19 1st Line 2nd Line 3rd Line+ KRAS/NRAS/BRAF WT (50% of mCRC) KRAS/NRAS mutant (35-45% of mCRC) BRAF mutant (5-10% of mCRC) MSI-H/MMR-D (5% of mCRC) HER2 amplified (2-5% of mCRC) FOLFOX / FOLFIRI ± biologics FOLFOX / FOLFIRI ± biologics Immune checkpoint inhibition EGFR mAb + G12C KRAS inhibitor FOLFOX / FOLFIRI ± biologics 1 Regorafenib Fruquintinib Lonsurf Bevacizumab + Lonsurf HER2-directed therapy FOLFOX / FOLFIRI ± biologics 1 EGFR mAb + BRAF inhibitor 2 FOLFOX + EGFR mAb + BRAF inhibitor 1 Whichever regimen that was not previously given in 1L. 2 If BRAF inhibitor not previously given in 1L. Abbreviations: FOLFIRI = fluorouracil, folinic acid, irinotecan; FOLFOX = fluorouracil, folinic acid, oxaliplatin. mAb = monoclonal antibody. Adapted from Biller and Schrag, 2021 CX-2051 Combination Strategies to Replace Chemotherapy CX-2051 Late-Line Strategies
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Beyond CRC: Varseta-M is a “Pan-Tumor” Opportunity EpCAM is broadly expressed in many solid tumors in addition to CRC 20 U.S. High EpCAM expressing patients* NSCLC 135,000 pts 69% Ovarian 45,000 pts 83% Gastric 31,000 pts 71% TNBC 21,000 pts 83% Endometrial 36,000 pts 73% PDAC 32,000 pts 50% Sources: *CytomX Internal prevalence study, ≥50% cells with 2+/3+ EpCAM Intensity or >10% 3+; 2029 Drug -treatable patient by tumor type from DRG. 98% CRC 149,000 pts Lead Indication
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21 1st FDA Approval as monotherapy in late line mCRC CRC combinations to replace chemotherapy in 1L/2L mCRC Expand into additional EpCAM+ Indications Varseta-M is a Differentiated, First-in-Class ADC Positioned to Address a Broad EpCAM+ Patient Population 1 2 3 Varseta-M: Unlocking Multiple Layers of Value Creation >35K U.S. Patients >95K U.S. Patients 350K+ U.S. Patients Sources and assumptions: DRG epidemiology forecast, internal estimates
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© 2026 CytomX Therapeutics, Inc. CX-801 PROBODY® IFNα-2b A Novel Immunotherapy Focused in Melanoma 22
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IFNα-2b is a Powerful Cancer Immunotherapy With Ideal Properties to Combine with Checkpoint Inhibitor Therapy 23 Why IFN-2b? IFN-2b Mechanism of Action • Kills cancer cells directly leading to immunogenic cell death • Stimulates antigen presenting cells to activate tumor-reactive T cells • Modulates NK, stromal and vascular cells • Approved for treating melanoma (Sylatron ), renal (Avastin® + IFN), and bladder cancer (Adstiladrin®) • Potential to treat checkpoint resistant / refractory indications Adapted from Green et al., Mol. Ther. Onc. 2021 IFN stimulates IFN stimulates Dendritic cells IFN induces MHC-1 IFN direct killing IFN stimulates NK cells
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CX-801: Dually-Masked, Conditionally Activated PROBODY® IFN2b IFNα2b • Dual-mechanism of action • Proven single agent activity • Increases APCs to enhance PD-1 blockade 24 Masking & Substrates Design Strategy • Dual-masking strategy with steric and affinity mask (peptide) • 1000X masking efficiency based on preclinical models Validated, High Potential Target • Approved immunotherapy in multiple tumors • Enhanced anti-cancer activity in combination with PD-1 • Limited clinical use due to poor tolerability CX-801 Affinity Masking Steric Masking (Fc Portion) EFFECTOR PRODOMAIN TARGET
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Metastatic Melanoma Landscape 25 1L Anti-PD-1 mAB ± Anti-CTLA-4 or Anti-LAG3 1, 2, 3, 4, 5 BRAF WT (~50%) BRAF Mutations (~50%) BRAF inh. + MEK inh. Opdualag8 Lifileucel (TIL) Salvage Chemotherapy (Decarbazine)9 2L+ Ipi. + Nivo.6 or Pembrolizumab7 High Unmet Need in PD-1 Refractory Melanoma Patients CX-801 has potential to enhance responsiveness to checkpoint inhibitors CX-801 Development Opportunities in Melanoma ❖ Combine with anti-PD-1 inhibitors in post-PD-1 setting – Improve on activity of PD-1 inhibitors (7% ORR)9 – Safe and tolerable alternative to TIL therapy ❖ Novel IO combinations to enhance activity in earlier-line settings 1 Robert et al. 2015; 2 Robert et al. 2023; 3 Tawbi et al. 2022; 4 Wolchock et al. 2017; 5Wolchock et al.2022; 6 VanderWalde et al.; 7 Olson et al. 2021 2023; 8 Ascierto et al. 2023; 9 Robert et al. 2011
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Phase 1 Dose Escalation is Designed to Assess CX-801 Clinical Profile as Monotherapy and in Combination with KEYTRUDA® Monotherapy Dose Escalation Combination Dose Escalation Source: Package Insert - SYLATRONTM Focused in Advanced Melanoma CX-801 + Keytruda® DL 3 CX-801 + Keytruda® DL 4 CX-801 ≤ Monotherapy MTD/MAD + Keytruda® DL 1 (n=1) CX-801 + Keytruda® DL 2 CX-801 DL 1 (n=1) CX-801 DL 2 (n=1) CX-801 DL 3 (n=3) CX-801 DL 5+ CX-801 DL 4 26 • Combination dose escalation commenced in May 2025 • Initial biomarker data presented at SITC 2025 • Phase 1 CX-801 + Keytruda® combination data in 2026 Dose levels 2+ exceed approved doses of IFN Alpha in melanoma Currently enrolling KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA KEYTRUDA® to be administered on approved dose and schedule Currently enrolling Initiated Combination enrollment in May 2025 SITC 2025 biomarker data
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CX-801 Monotherapy Shows Intended MOA in Tumor Biopsies Strong induction of interferon stimulated genes in multiple cell types 27 Baseline On-Treatment Cell Type Melanoma Cells Stromal Cells Immune Cells LAG3PD-1PD-L1 Baseline On-Tx 0 200 400 600 800 Baseline On-Tx 0 200 400 600 800 1000 Baseline On-Tx 0 2000 4000 6000 Normalized Expression NanoString Induction of Checkpoint Gene Expression Checkpoint gene expression represented by PD-L1, PD-1, and LAG3 induced by CX-801 measured by NanoString platform (RNA).
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CX-801 Promotes Chemokine Induction in the Tumor Microenvironment Driving Lymphocyte Infiltration into Tumor Tissue 28 Immune/Stomal CellsCell Type Melanoma Cells CD8+ T-cells Vasculature CX-801 Activates Cytotoxic T-cells
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© 2026 CytomX Therapeutics, Inc. 29 2026 Milestones and Outlook
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Q1 Q2 Q3 Q4 Q1 Q2 CytomX Has Significant Pipeline Momentum Entering 2026 Multiple milestones expected while advancing toward later phase development Program Varseta-M Monotherapy CRC Varseta-M Bevacizumab combination Varseta-M Additional EpCAM+ indications CX-801 Advanced Melanoma Additional data at major medical meeting(s) in 2026 Align with FDA on registrational study Initial safety & efficacy data Initiate Phase 1 expansions Phase 1 combo data with KEYTRUDA® 2026 2027 Phase 1 Study initiation Phase 1 Expansion Data 30
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31© 2026 CytomX Therapeutics, Inc. Appendix
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Most Frequent Treatment Related Adverse Events (TRAE) Observed in Varseta-M Phase 1 Interim Dose Escalation Data Presented on May 12, 2025 32 Data cutoff 4/7/2025 Preferred Term, n (%) 2.4‒4.8 mg/kg (n = 2) 7.2‒10 mg/kg (n = 23) All grade Grade 3 All grade Grade 3 Hematologic Adverse Events (in > 1 patient) Anemia 0 0 5 (21.7) 3 (13.0) Neutrophil count decreased 0 0 2 (8.7) 2 (8.7) Neutropenia 0 0 2 (8.7) 1 (4.3) Non-hematologic Adverse Events (in > 1 patient) Diarrhea 0 0 18 (78.3) 5 (21.7) Nausea 0 0 11 (47.8) 1 (4.3) Vomiting 0 0 8 (34.8) 0 Fatigue 0 0 8 (34.8) 1 (4.3) Hypokalemia 0 0 3 (13.0) 1 (4.3) Abdominal pain 0 0 3 (13.0) 0 Alanine aminotransferase increased 0 0 2 (8.7) 0 Aspartate aminotransferase increased 0 0 2 (8.7) 0 Decreased appetite 0 0 2 (8.7) 0 Weight decreased 0 0 2 (8.7) 0 Serious Adverse Events* (all patients) 0 0 5 (21.7) 4 (17.4) *Serious adverse events occurred in 5 patients: Grade 3 Diarrhea (n=1); Grade 3 Anemia (n=1); Grade 3 colitis (n=1); Grade 3 Diarrhea and Acute kidney injury (n=1); Grade 2 Asthenia (n=1)