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1© 2026 CytomX Therapeutics, Inc. Wells Fargo 21st Annual Healthcare Conference Dr. Sean McCarthy, CEO and Chairman September 8, 2026 Unmasking Advances in Oncology
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Legal Disclaimer 2 This presentation (including any oral commentary that accompanies this presentation) contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. 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. Terms such as “may,” “might,” “should,” “could,” “predict,” “potential,” “believe,” “expect,” “continue,” “will,” “anticipate,” “seek,” “estimate,” “intend,” “plan,” “projection,” “would,” “annualized” and “outlook,” or other words that convey uncertainty of future events or outcomes (including the negative of these terms) may identify these forward-looking statements. Such statements are based on current expectations and assumptions 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 (“Varseta-M”) and CX-801, and other development activities; uncertainties inherent in the initiation and enrollment of clinical trials; uncertainties regarding the availability and timing of data from clinical trials; the risk that initial clinical data, including data for Varseta-M 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 milestones, 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 Varseta-M 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 in our public filings with the U.S. Securities and Exchange Commission (“SEC”), including in Part II, Item 1A, “Risk Factors,” of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 7, 2026, and in our other filings we make with the SEC from time to time, which are available at www.sec.gov. 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. This presentation concerns products that have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to their safety or effectiveness for the purposes for which they are being investigated. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. This presentation contains trademarks, services marks, trade names and copyrights of the company and other companies, which are the property of their respective owners. The use or display of third parties’ trademarks, service marks, trade name or products in this presentation is not intended to, and does not imply, a relationship with the company, or an endorsement of sponsorship by the company.
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PROBODY® Therapeutic Design Right Target, Right Tumor, Right Effector Mechanism 33 PROBODY® Platform: Leading the field of masked therapeutics Clinical Programs: • Varsetatug masetecan (EpCAM PROBODY ® Topo-1 ADC)* for Colorectal Cancer and EpCAM-expressing tumors • CX-801 (PROBODY ® IFN-α2b) for Melanoma Financials: $330M cash as of Q2 2026; runway to 2nd half of 2028 – Additional $37M received from Regeneron in July 2026 Organization: Integrated R&D capabilities; multiple pharma alliances including research collaboration with Regeneron *Varsetatug masetecan (“Varseta-M”) - (formerly CX-2051) TARGET PRODOMAIN EFFECTOR Abbreviations: EpCAM=Epithelial Cell Adhesion Molecule; ADC=Antibody Drug Conjugate; IFN-α2b=Interferon alpha 2-b
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Varseta-M Efficacy in Late-Line CRC1 • Confirmed ORR of 20% at 8.6 mg/kg and 32% at 10 mg/kg • Preliminary PFS of 6.8 months at 8.6 mg/kg and 7.1 months at 10 mg/kg • High EpCAM expression confirmed in all patients with evaluable biopsies 4 Encouraging Safety Profile1,2 • AEs generally manageable and reversible with no pancreatitis, serious liver toxicity or ILD observed. • Hematologic profile may be attractive for future combinations. • Diarrhea was the most common Grade 3 TRAE (24%) across 7.2-10 mg/kg doses. Initial reported data from dose optimization suggests potential for improved rates of Grade 3 diarrhea with prophylaxis (10% Grade 3) 1) Based on Company data presentation on March 16, 2026 utilizing actual body weight (ABW) dosing; 2) Dose optimization safet y data based on March 2, 2026 data snapshot in 20 patients treated at 8.6 and 10 mg/kg adjusted ideal body weight (AIBW) dosing and updated prophylaxis regimen of anti-motility medication plus budesonide after 2 months of follow-up post treatment initiation; 3) World Health Organization, interactive data; Biller and Schrag, 2021, JAMA; American Cancer Society Abbreviations: R/R mCRC: Relapsed/Refractory metastatic colorectal cancer; ORR=Objective response rate; PFS=progression free survival; ILD= interstitial lung disease; TRAE=treatment related adverse event Varseta-M is the only EpCAM-Directed ADC in Development Granted FDA Fast Track Designation for R/R mCRC in August 2026 mCRC Development Strategy & Market Opportunity • 2nd leading cause of cancer death worldwide; 5-year survival rate of 13% in mCRC3 • Phase 1 monotherapy dose optimization ongoing with goal to start registrational study in 1H 2027 • Phase 1 combinations with bevacizumab and chemotherapy have potential to unlock earlier-line mCRC
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Product Candidate(s) Indication(s) Phase 1 / 2 Phase 3 / Registrational Varseta-M Monotherapy EpCAM Topo-1 ADC 3L+ metastatic CRC (mCRC) Varseta-M + bevacizumab 2L/3L mCRC Varseta-M + bevacizumab + chemotherapy1 1L/2L mCRC Varseta-M Gastric/GEJ, PDAC, BTC CX-801 (IFNα2b) Advanced Melanoma 5 Varseta-M Development Plan Continues to Broaden in CRC and Additional EpCAM-Expressing Gastrointestinal Indications 1. Chemotherapy combinations including Varseta-M with bevacizumab, 5-fluorouracil, and leucovorin • Phase 1 Update Expected by end of 2026 • Potential Registrational Study Start in 1H 2027 • FDA Fast Track Designation for R/R mCRC • Initiated Phase 1 in Q1 2026 • Evaluating Q2W and Q4W Doses Initiating Phase 1/2 in Q4 2026 Initiating Phase 1 in Q3 2026 Phase 1 Data CX-801 + KEYTRUDA ® Expected in 1H 2027 Varseta-M antibody and linker-payload licensed through collaboration with Immunogen.
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© 2026 CytomX Therapeutics, Inc. Varsetatug masetecan (Varseta-M)* A Novel EpCAM-Directed ADC Focused on Colorectal Cancer (CRC) and Gastrointestinal Tumors 6*Formerly known as CX-2051
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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 TROP2 / Breast Immunomedics/Gilead HER2 / Breast, Lung** Daiichi/Astra Zeneca FRα / Ovarian Immunogen/AbbVie EpCAM / CRC CytomX Therapeutics *Varseta-M PROBODY® ADC *Varsetatug masetecan is not an approved product and is in ongoing clinical development. **Enhertu select indications only. Sources: Company announcements. All trademarks & tradenames belong to their respective owners, as identified above.
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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 Sources: World Health Organization, interactive data; Biller and Schrag, 2021, JAMA; American Cancer Society
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By 2035 U.S. CRC Diagnosed Incidence Estimated to be 165K Patients Annually 1L mCRC ~90K U.S. Patients 3L+ mCRC ~40K U.S. Patients 2L mCRC ~50K U.S. Patients >$5 Billion TAM >$12 Billion TAM >$30 Billion TAM Varseta-M has the Potential to Address a Large Patient Population due to Broad and Consistent EpCAM Expression in CRC Sources and assumptions: 2035 DRG epidemiology and company estimates regarding pricing assumptions based on approved ADCs; es timated duration of treatment based on mCRC standard of care Abbreviations: TAM=Total Addressable Market 9 Metastatic CRC (mCRC)
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N O O O HO N NH F OON H OH N O N H OH N O N O O CAMP66 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 10Abbreviations: DAR = drug antibody ratio Varseta-M • EpCAM is abundant in CRC but previously undruggable due to normal tissue expression • CytomX protease cleavable masking platform reduces EpCAM binding in normal tissues • Masetecan Topo-1 payload selected to drive anti-tumor activity in CRC
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The Current Standard of Care in 3L+ Metastatic CRC Is Highly Inadequate Current therapies have limited survival benefit 11 Treatment Treatment Line ORR (%) DCR (%) Median PFS (months) Median OS (months) Fruquintinib1 3L/4L+ 2% 56% 3.7 7.4 Regorafenib2 3L/4L+ 1% 41% 2.0 6.4 Trifluridine/tipiracil3 3L/4L+ 2% 44% 2.0 7.1 Trifluridine/tipiracil + Bevacizumab4 3L 6% 77% 5.6* 10.8* Abbreviations: DCR = disease control rate; ORR = overall response rate; OS = overall survival; PFS = progression free survival. Sources: 1. Dasari et al. 2023, Fruzaqla® (fruquintinib) Prescribing information (PI); 2. Grothey et al. 2013; Stivarga® (regorafenib) PI; 3. Lonsurf® (trifluridine and tipiracil) 4. Prager et al. 2023. *SUNLIGHT study total patients; Patients previously treated with prior bevacizumab had median PFS of 4.5 months and OS of 9.0 months Data are not from head-to-head studies. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, sample size, inclusion and exclusion criteria, trial design and many other factors.
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© 2026 CytomX Therapeutics, Inc. Varseta-M Development Strategy 12
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13 Goal for Varseta-M 1st FDA approval as monotherapy in late line mCRC 1L/2L mCRC potential through chemotherapy combinations Potential to Expand into additional EpCAM+ indications Varseta-M is a Differentiated, Potential First-in-Class ADC Positioned to Address a Broad EpCAM+ Patient Population 1 2 3 Unlocking Multiple Layers of Value Creation >40K U.S. Patients >90K U.S. Patients 350K+ U.S. Patients Sources and assumptions: DRG epidemiology projection (2040); Company estimates on CRC incidence growth, treatable patients in mCRC, other indications
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Broad Development Opportunity for Varseta-M in Metastatic CRC Potential across the treatment paradigm as monotherapy and in combinations 14 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; HER2= Human epidermal growth factor receptor 2. Adapted from Biller and Schrag, 2021 Varseta-M Combination Strategies to Replace Chemotherapy Varseta-M Late-Line Strategies
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© 2026 CytomX Therapeutics, Inc. 15 Varseta-M Monotherapy Development in mCRC
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2.4, 4.8 mg/kg (n=2) 7.2 mg/kg (n = 5) 8.6 mg/kg (n = 10) 10 mg/kg (n = 8) Varseta-M Phase 1 Monotherapy Focused in Late-Line Metastatic CRC Data to inform potential registrational study in 3rd or 4th line mCRC 11, 12 mg/kg (n = 11) 10 mg/kg (n = 14) 8.6 mg/kg (n = 10) 7.2 mg/kg (n = 13) 10 mg/kg (n = 20) 8.6 mg/kg (n = 20) Dose Escalation / Expansion Total enrollment (n=73) Dose Optimization Enrollment to-date (n=40)1,2 Phase 1 Study: 113 Monotherapy Patients Enrolled • Phase 1 Dose Escalation (began April 2024); Dose Expansions (began May 2025); Dose Optimization (began October 2025) Patient Enrollment: mCRC patients (pts) unselected for EpCAM expression; population enrolled had a median of 3 prior therapies; 49% of pts had ≥4 prior therapies; 76% of pts had liver metastases.3 40 patients enrolled as of April 2026 n=60 1. Adjusted ideal body weight (AIBW) dosing and optimized prophylaxis; 2. Enrollment Update as of May 7, 2026 CytomX Therapeutics Earnings Call; 3. As of January 16, 2026 data cutoff presented on March 16, 2026 16 Q3W Dosing
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© 2026 CytomX Therapeutics, Inc. 17 Varseta-M Combinations in Earlier-Line mCRC
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• Varseta-M + Bevacizumab has the potential to improve upon the standard of care in 3rd line mCRC Varseta-M Combination with Bevacizumab is Ongoing with Potential to Enable 3rd line CRC Development 18 Varseta-M Q2W + Bevacizumab Varseta-M Q4W + Bevacizumab Varseta-M + Bevacizumab vs. Lonsurf + Bevacizumab 4.5 months PFS, 9 months mOS2 Varseta-M + Bevacizumab Potential Later Phase Development* Varseta-M + Bevacizumab Phase 1 Dose Escalation in 3L+ mCRC1 3rd Line mCRC: Initiated in Q1 2026; Enrollment ongoing • Goal to determine a dose(s) and schedule for late phase development of the combination 1 Study CTMX-2051-101; 2Prager et al. 2023 *Illustrative only; actual future trial design to be determined based on emerging date, regulatory feedback, costs and other scientific and business factors .
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Planned Varseta-M Phase 1/2 Combination Study with Bevacizumab + 5-FU Enables Potential Irinotecan Replacement in 1st and 2nd line mCRC 19 Varseta-M Q2W + Bevacizumab, 5-FU/leucovorin (BFF) Varseta-M + Bevacizumab + 5-FU Phase 1 Dose Escalation Phase 2 Study • Goal to replace irinotecan in bevacizumab + FOLFIRI regimen in 2L mCRC Varseta-M + Bevacizumab, 5-FU/leucovorin (BFF) Phase 1 / 2 Study Enrollment in 2nd Line mCRC Varseta-M Q4W + Bevacizumab, 5-FU/leucovorin (BFF) • Beginning in Q4 2026
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© 2026 CytomX Therapeutics, Inc. 20 Varseta-M in EpCAM+ Gastrointestinal Cancers
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85% 77% 55% 55% GEJ Gastric PDAC BTC Varseta-M demonstrated clinical activity in heavily pretreated CRC, de-risking clinical profile in other GI indications: • Gastric/GEJ: proof of concept with Topo-1 ADCs, options limited for patients without targeted therapy options with poor outcomes in 2L+ • PDAC: EpCAM selected post Pan-RAS patients have high unmet need with limited treatment options • BTC: Potential for focused development path in EpCAM selected patients Broadening the Varseta-M Program to EpCAM+ GI Indications Patient enrollment to commence in Q3 2026 21 Gastric/GEJ* ~50K PDAC ~60K BTC ~20K US Incidence – Prioritized GI Cancers ~130K Patients Diagnosed Annually *Includes Esophogeal Adenocarcinoma EpCAM Highly Expressed in Prioritized GI Tumors1 Sources: 1. CytomX Prevalence Study EpCAM Expression based on IHC 3+ (>10%) Or 2+/3+ (>50%); 2.SEER Cancer Statistics, Company estimates
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Varseta-M Monotherapy Cohort Expansions in GI Indications with High Unmet Need Initiating in Q3 2026 22 Varseta-M Ph1 GI Expansions Q3W Dose(s) N=~60 Gastric / GEJ, 3L+ Unselected PDAC, 2-3L+ EpCAM+ BTC, 2L+ EpCAM+ Phase 1 Study Overview • Key Endpoints: – Safety, tolerability, PK – Efficacy: ORR, PFS • Key Inclusion Criteria – Must have received at least 1 prior SOC regimen – Gastric/GEJ: no selection for EpCAM – PDAC/BTC selected for EpCAM Potential registrational strategies in late-line settings
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Q1 Q2 Q3 Q4 Q1 Q2 Multiple Varseta-M Milestones Anticipated Over Next 12 to 18 Months1 Program Varseta-M Monotherapy CRC Varseta-M Bevacizumab combination Varseta-M Additional EpCAM+ indications Phase 1 data update Align with FDA on registrational study and potential registrational study start Initial safety & efficacy data Initiating Phase 1 expansions in Gastric/GEJ, PDAC, BTC 2026 2027 Phase 1 Study initiation Phase 1 Expansion Data 23 Varseta-M Chemotherapy combination2 Phase 1/2 Study initiation 1. Reflects current expectations, subject to change 2. Chemotherapy combinations including Varseta-M with bevacizumab, 5-fluorouracil, and leucovorin
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© 2026 CytomX Therapeutics, Inc. CX-801 PROBODY® IFNα-2b A Novel Immunotherapy Focused in Melanoma 24
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IFNα-2b is a Powerful Cancer Immunotherapy With Ideal Properties to Combine with Checkpoint Inhibitor Therapy 25 Why IFNα-2b? IFNα-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 (peginterferon alfa-2b), renal (bevacizumab + IFN), and bladder cancer (nadofaragen firadenovec) • Potential to treat checkpoint resistant / refractory indications Adapted from Green et al., Mol. Ther. Onc. 2021 IFNα stimulates IFNα stimulates Dendritic cells IFNα induces MHC-1 IFNα direct killing IFNα stimulates NK cells Abbreviations: NK=natural killer cells; ISG=Interferon-stimulated gene; MHC=Major histocompatibility complex
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CX-801: Dually-Masked, Conditionally Activated PROBODY® IFNα2b IFNα2b • Dual-mechanism of action • Proven single agent activity • Increases APCs to enhance PD-1 blockade 26 Masking & Substrates Design Strategy • Dual-masking strategy with steric and affinity mask (peptide) • 1000X masking efficiency observed in 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 Abbreviations: APCs=Antigen Presenting Cells; Fc=Fragment crystallizable
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Metastatic Melanoma Landscape 27 Anti-PD-1 ± Anti-CTLA-4 or Anti-LAG3 1, 2, 3, 4, 5 BRAF WT (~50%) BRAF Mutations (~50%) BRAF inh. + MEK inh. Nivolumab and relatlimab- rmbw 8 Lifileucel (TIL) Salvage Chemotherapy (Decarbazine)9 Ipilimumab + Nivolumab.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 – Potential safe and tolerable alternative to TIL therapy Offers a novel opportunity for combination with immunotherapy 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 1L 2L+ Abbreviations: TIL=Tumor-infiltrating lymphocyte
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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 1. 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 28 • Combination dose escalation commenced in May 2025 • Plan to report initial Phase 1 clinical data in combination with KEYTRUDA ® in 1H 2027 Dose levels 2+ exceed approved doses of IFN Alpha in melanoma1 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 DL Cleared Initiated Combination enrollment in May 2025 SITC 2025 biomarker data
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© 2026 CytomX Therapeutics, Inc. 29 Milestones and Outlook
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Q1 Q2 Q3 Q4 Q1 Q2 Multiple Milestones Anticipated Over Next 12 to 18 Months1 Program Varseta-M Monotherapy CRC Varseta-M Bevacizumab combination Varseta-M Additional EpCAM+ indications Phase 1 data update Initial safety & efficacy data Initiated Phase 1 expansions in Gastric/GEJ, PDAC, BTC 2026 2027 Phase 1 Study initiation Phase 1 Expansion Data 30 Varseta-M Chemotherapy combination2 Phase 1/2 Study initiation 1. Reflects current expectations, subject to change 2. Chemotherapy combinations including Varseta-M with bevacizumab, 5-fluorouracil, and leucovorin CX-801 Advanced Melanoma Phase 1 initial clinical data in combination with KEYTRUDA® Align with FDA on registrational study and potential registrational study start
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31© 2026 CytomX Therapeutics, Inc. Unmasking Advances in Oncology September 2026