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© 2025 CytomX Therapeutics, Inc. CX-2051: A Novel EpCAM-Directed ADC Phase 1 Interim Clinical Data in Advanced Colorectal Cancer May 12, 2025 1
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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 CX-2051. 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 CX-2051, 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 CX-2051, 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 CX-2051; 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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On Today’s Call 3 Sean McCarthy, D.Phil. Chairman and CEO Wayne Chu, MD Chief Medical OfficerSpeakers Addressing Major Unmet Need in Oncology Chris Ogden Chief Financial Officer
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© 2025 CytomX Therapeutics, Inc. 4 Introduction Sean McCarthy, D.Phil. Chairman and CEO, CytomX Therapeutics
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Colorectal Cancer Remains One of the Biggest Unmet Needs in Oncology 5 ~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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The Current Standard of Care in 3L+ Metastatic CRC Is Highly Inadequate Poor response rates and limited survival benefit 6 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 + Bevacizumab 3L 6% 77% 5.6 10.8 Abbreviations: DCR = disease control rate; ORR = overall response rate; OS = overall survival; PFS = progression free survival. Sources: Lonsurf® (trifluridine and tipiracil) Fruzaqla® (fruquintinib), Stivarga® (regorafenib) package inserts; Dasari et al. 2023; Grothey et al. 2013; Prager et al. 2023.
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Antibody Drug Conjugates are Transforming Cancer Care CX-2051 aims to bring 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 FRα / Ovarian Immunogen/AbbVie - $10B Acquisition EpCAM / CRC CytomX Therapeutics *CX-2051 PROBODY® ADC * CX-2051 is not an approved product and is in an ongoing Phase 1 clinical trial. ** Enhertu select indications only. Sources: Company announcements.
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No Patient Selection Needed Today’s Update: Positive Phase 1 Clinical Data Observed for CX-2051 8 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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© 2025 CytomX Therapeutics, Inc. 9 CX-2051 Molecular Design and Phase 1 Clinical Strategy
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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) • High and uniform expression across 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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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 CX-2051: A Novel EpCAM Targeting ADC The Right Target, The Right Payload 11 Masking domains designed to reduce EpCAM binding in normal tissues Abbreviations: DAR = drug antibody ratio. CX-2051 antibody and linker-payload licensed through collaboration with Immunogen.
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2.4, 4.8 mg/kg (n=2) 7.2 mg/kg (n = 5) 8.6 mg/kg (n = 6) DL6, DL7 Single patient cohorts at predicted sub-therapeutic doses 10 mg/kg (n = 7) CX-2051 Phase 1 Dose Escalation Study Current Status Focused in late-line mCRC. Dose expansions in progress. 12 Anticipated Maximum Assessed Dose CX-2051 Administered Q3W Expanding to n=20 Expanding to n=20 Expanding to n=20 RP2D(s) expected to be selected from these expansion doses Study Commenced April 2024 Patient Data Presented Today: • Unselected for EpCAM expression • 25 safety-evaluable patients treated 2.4‒10 mg/kg • 23 safety-evaluable patients treated 7.2‒10 mg/kg • 18 efficacy-evaluable at 7.2‒10 mg/kg* Primary Objectives: • Safety and tolerability of CX-2051 • Determine recommended Phase 2 dose (RP2D) Secondary Objectives include: • Objective response rate • Disease control rate • Progression free survival *5 patients not efficacy-evaluable: 4 pts on treatment that have not reached a post -treatment scan; 1 patient at 10 mg/kg dose discontinued for clinical progression prior to first post -treatment scan. Data cutoff 4/7/2025
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© 2025 CytomX Therapeutics, Inc. CX-2051 Phase 1 Interim Results Wayne Chu, MD Chief Medical Officer, CytomX Therapeutics 13
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CX-2051 Phase 1 Baseline Characteristics Heavily pre-treated advanced CRC population; median 5th line 14 Baseline Characteristics N=25 (Safety evaluable) 1 Number of prior lines of anti-cancer therapy, median (range) 4 (1-10) Prior irinotecan, n (%) 25 (100) Liver metastases, n (%) 16 (64) KRAS mutation, n (%) 16 (64) MSS, n (%) 24 (96) 1 Patients treated with at least one CX-2051 dose between 2.4 mg/kg and 10 mg/kg. MSS = microsatellite stable. Data cutoff 4/7/2025
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CX-2051 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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CX-2051 Anti-Tumor Activity 7.2-10 mg/kg 94% (17/18) disease control rate 16 0 10 20 30 40 50 60 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 0 1 2 3 4 5 6 7 8 9 10 Months Since Treatment Initiation 7.2 mg/kg 10 mg/kg 8.6 mg/kg CX-2051 Dose: SDPR PDRECIST Response: Patient remains on treatment Percent Change in Sum of Target Lesions From Baseline (%) Abbreviations: PD = progressive disease; PR = partial response; SD = stable disease. Data cutoff 4/7/2025
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Emerging Durability Results with CX-2051 Preliminary median progression free survival 5.8 months 17 7.2 mg/kg 8.6 mg/kg 10 mg/kg 0 1 2 3 4 Months Since Treatment Initiation 5 6 7 8 9 10 PD PD PD PD SW ID SW SW 5.8 mo. median PFS (95% CI 4.1‒NE) Patient remains on treatment • 10 of 18 patients continuing treatment • 3 of 5 patients with cPR continuing treatment • No discontinuations for TRAEs SDPR PDRECIST Response: Dose delayed Dose delayed and reduced Abbreviations: ID = investigator decision; PD = progressive disease; PR = partial response; SD = stable disease; SW = subject withdrawal. Data cutoff 4/7/2025.
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Non-target Liver Lesions Case Study: Confirmed Partial Response in mCRC CX-2051 7.2 mg/kg Q3W 18 • 46 y.o. male with metastatic CRC – KRAS wild-type – Microsatellite Stable (MSS) – Baseline tumor burden: liver, lung, lymph node • Prior therapies – Panitumumab + FOLFOX – Bevacizumab + FOLFIRI – Bevacizumab + trifluridine/tipiracil • Clinical Course on CX-2051 (7.2 mg/kg) – No dose modifications for adverse events – Partial response at 6-week tumor assessment with 47% reduction in liver target lesions – Clinical improvement - discontinuation of cancer- related pain medication – Partial response maintained through ~6 mos. Baseline Partial Response at 6-Week Scan (47% Reduction) Target Lesion #1: 21 mm Target Lesion #1: 11 mm Target Lesion #2: 18 mm Target Lesion #2: 10 mm
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Most Frequent Treatment Related Adverse Events (TRAE) Observed AEs generally manageable and reversible; no grade 4-5 TRAE 19 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)
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CX-2051 Preliminary Pharmacokinetics Observed Interim Analysis of Cycle 1 Pharmacokinetics • Rate of payload deconjugation was low and in line with other Topo I inhibitor ADCs (1 – 5%) • CX-2051 remained masked in circulation • Half life of approximately 5.9 days • CX-2051 showed dose linearity with respect to AUC and Cmax 20 0 100 200 300 400 500 0.1 1 10 100 1000 PK profile at 8.5 mg/kg Time Since Last Dose (h) Concentration (nM) Intact CX-2051 Total CX-2051 Free CAMP59 Total CX-2051 reflects masked + unmasked forms of ADC; Intact CX-2051 reflects only masked ADC 8.6 mg/kg Patient Data cutoff 4/7/2025
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Initial Phase 1 Data Supports Competitive Results for CX-2051 21 Treatment ORR (%) DCR (%) Median PFS (months) Median OS (months) CX-2051 (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 + Bevacizumab 6% 77% 5.6 10.8 3L+ CRC Landscape CX-2051 is an investigational early-phase therapy. Information in tables above is not intended to be a direct comparison to appr oved treatments. Additionally, information provided in the tables above is for illustrative purposes only and no head- to-head comparison of CX-2051 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. .Abbreviations: DCR = disease control rate; ORR = overall response rate; OS = overall survival; PFS = progression free survival. Sources: Lonsurf® (trifluridine and tipiracil) Fruzaqla® (fruquintinib), Stivarga® (regorafenib) package inserts; Dasari et al. 2023; Grothey et al. 2013; Prager et al. 2023.
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CX-2051 Monotherapy Dose Expansions Underway in Late-line CRC Plan to Initiate Phase 2 Study in 1H 2026 22 7.2 mg/kg 8.6 mg/kg 10 mg/kg Expanding to n=20 Expanding to n=20 Expanding to n=20 Phase 1 Expansions 2H 2025 70+ patient Phase 1 data update and Phase 2 design anticipated in Q1 2026
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© 2025 CytomX Therapeutics, Inc. 23 Concluding Remarks Sean McCarthy, D.Phil. Chairman and CEO, CytomX Therapeutics
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Broad Development Opportunity for CX-2051 in Metastatic CRC Pan-CRC design offers broad development potential across the treatment paradigm 24 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: CX-2051 is a “Pan-Tumor” Opportunity EpCAM is broadly expressed in many solid tumors in addition to CRC 25 High EpCAM expressing patients* NSCLC 135,000 pts 80% Ovarian 45,000 pts 83% Gastric 31,000 pts 79% TNBC 21,000 pts 83% Endometrial 36,000 pts 73% PDAC 32,000 pts 50% Select Non-CRC EpCAM Addressable Patients in U.S. Sources: *CytomX Internal prevalence study, ≥50% cells with 2+/3+ EpCAM Intensity or >10% 3+; 2029 Drug-treatable patient by tumor type from DRG.
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CX-2051 Phase 1 Interim Data Summary & Next Steps 26 Clinical PoC Demonstrated in CRC for EpCAM Topo-1 ADC Potential First-in-Class ADC Could Present a Multi-billion Annual Sales Opportunity Top Priority is Advancement Towards Potential 1st Approval in mCRC Potential Parallel Advancement into Combination Regimens in CRC in Earlier Lines and Exploration of Additional Tumor Opportunities
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© 2025 CytomX Therapeutics, Inc. CX-2051: A Novel EpCAM-Directed ADC Phase 1 Interim Clinical Data in Advanced Colorectal Cancer May 12, 2025 27