Cytomx Therapeutics, Inc. · NASDAQ:CTMX

Cytomx Therapeutics — Technical Presentation (November 2020)

20 slides from Cytomx Therapeutics's technical presentation, Nov 5, 2020

  1. Slide 1: CX-2029, a PROBODY Drug Conjugate Targeting CD71: First-in-Human Results

    CX-2029, a PROBODY Drug Conjugate Targeting CD71 (Transferrin Receptor): Results From a First- in-Human study (PROCLAIM-CX-2029) in Patients With Advanced Cancer Melissa Johnson,1 Anthony El-Khoueiry,2 Navid Hafez3,,Nehal Lakhani,4 Hirva Mamdani,5 Jordi Rodon,6 Rachel E. Sanborn,7 Thang Ho,8 Rachel

  2. Slide 2: PROBODY Therapeutics: Investigating Undruggable Targets

    PROBODY Therapeutics: Investigating Undruggable Targets • CD71 (transferrin receptor 1): attractive target for a PROBODY drug conjugate • CD71 is a transmembrane glycoprotein that efficiently internalizes iron-bound transferrin • Highly expressed on malignant cells • Expressed in healthy tissue with

  3. Slide 3: CX-2029: Probody Drug Conjugate Against CD71 With MMAE Warhead

    CX-2029: Probody Drug Conjugate Against CD71 With MMAE Warhead MONOMETHYL AURISTATIN E (MMAE): POTENT CYTOTOXIC MICROTUBULE INHIBITOR, BLOCKING CELL DIVISION Mask prevents/ significantly reduces binding in normal Linker-payload tissue Linker-payload Proteases cleave mc-vc-PAB-MMAE Linker-payload sub

  4. Slide 4: Expression of CD71 in Healthy Tissue and Multiple Cancers

    Expression of CD71 in Healthy Tissue and Multiple Cancers RNA and Protein Expression in Healthy Tissue Protein Protein RNA RNA Expression Expression Expression (NX) Expression (NX) (Score) (Score) Kidney & urinary Brain bladder Eye Male tissues Endocrine Female tissues tissues Lung Muscle tissues Pr

  5. Slide 5: Expression of CD71 in Healthy Tissue and Multiple Cancers

    Expression of CD71 in Healthy Tissue and Multiple Cancers RNA and Protein Expression in Healthy Tissue Expression by IHC using Commercial Antibody and Tissue Microarray Protein Protein Number of RNA RNA Expression Expression cases scored Expression (NX) Expression (NX) (Score) (Score) Kidney & urina

  6. Slide 6: Probody Platform: Enabling CD71 as a Drug Conjugate Target

    Probody Platform: Enabling CD71 as a Drug Conjugate Target PDC REGRESSES TUMORS AFTER PDC HAS EFFICACY ACROSS MULTIPLE IN NON-HUMAN PRIMATES, PDC A SINGLE DOSE IN MICE CELL LINE / PDX NON-CLINICAL MODELS CREATES THERAPEUTIC WINDOW Regression or Single-dose activity, OV-90 Models Type Stasis Neutroph

  7. Slide 7: Phase 1 Dose-Escalating Clinical Trial

    Phase 1 Dose-Escalating Clinical Trial Starting Dose Intravenous Dose TOTAL • Given nonclinical toxicity, broad expression of CD71, and (every 3 weeks) (n) novelty of target and platform, the starting dose was ~1/20 the HNSTD in the monkey 0.1 mg/kg 3 • Predicted toxicities (based on MMAE payload):

  8. Slide 8: Demographics and Exposure

    Demographics and Exposure All Cohorts (n=45) Age, median (min, max) 60 (31, 75) Sex, male / female (%) 62 / 38 Number of prior cancer treatments, median (min, max) 3 (1, 16) Baseline ECOG 0 / 1, % 29 / 71 CD71 staining,* n (%) High expression [2+/3+ by IHC] 15 (33) Low expression [0/1+ by IHC] 16 (3

  9. Slide 9: Adverse Event Overview

    Adverse Event Overview Patients, n (%) CX-2029 CX-2029 CX-2029 CX-2029 CX-2029 0.1–1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg 5.0 mg/kg (n=15) (n=8) (n=12) (n=6) (n=4) Any TEAE, n (%) 15 (100) 8 (100) 12 (100) 6 (100) 4 (100) Related to CX-2029 14 (93.3) 8 (100) 12 (100) 6 (100) 4 (100) TEAE grade 3+ 6

  10. Slide 10: Treatment-Related AEs (>10% of Patients; N=45)

    Treatment-Related AEs (>10% of Patients; N=45) Patients, n (%) CX-2029 CX-2029 CX-2029 CX-2029 CX-2029 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg 5.0 mg/kg (n=3) (n=8) (n=12) (n=6) (n=4) Infusion-related reaction 3 (100) 8 (100) 9 (75) 6 (100) 3 (75) Anemia 2 (67) 6 (75) 9 (75) 5 (83) 4 (100) Neutropen

  11. Slide 11: Treatment-Related AEs (>10% of Patients; N=45)

    Treatment-Related AEs (>10% of Patients; N=45) Patients, n (%) CX-2029 CX-2029 CX-2029 CX-2029 CX-2029 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg 5.0 mg/kg (n=3) (n=8) (n=12) (n=6) (n=4) Infusion-related reaction 3 (100) 8 (100) 9 (75) 6 (100) 3 (75) Anemia 2 (67) 6 (75) 9 (75) 5 (83) 4 (100) Neutropen

  12. Slide 12: Treatment-Related Grade 3+ AEs; Transfusions

    Treatment-Related Grade 3+ AEs; Transfusions Patients, n (%) CX-2029 CX-2029 CX-2029 CX-2029 CX-2029 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg 5.0 mg/kg Treatment-Related Grade 3+ AEs (≥2 patients) (n=3) (n=8) (n=12) (n=6) (n=4) Anemia 1 (33) 5 (63) 7 (58) 5 (83) 4 (100) Neutropenia 0 0 4 (33) 3 (50)

  13. Slide 13: Pharmacokinetics

    Pharmacokinetics Dose level: 5 mg/kg (n=3) • Following 0.25–5.0 mg/kg, CX-2029 circulates 4 mg/kg (n=4) Intact Probody Concentration (nM) predominantly as intact CX-2029 (>90%) 100 3 mg/kg (n=5) 2 mg/kg (n=6) • For intact CX-2029: 1 mg/kg (n=3) 0.5 mg/kg (n=6) • No trends from dose-proportionality 0

  14. Slide 14: Waterfall Plot (Doses 2–5 mg/kg)

    Waterfall Plot (Doses 2–5 mg/kg) Change in Sum of Target Lesions from Baseline (%) Subject aNSC = non–small cell lung cancer (adenocarcinoma), CRC = colorectal cancer, HCC = hepatocellular carcinoma, HN = head and neck squamous cell carcinoma, MPM = malignant pleural mesothelioma, PAC = pancreatic c

  15. Slide 15: Waterfall Plot (Doses 2–5 mg/kg)

    Waterfall Plot (Doses 2–5 mg/kg) Change in Sum of Target Lesions From Baseline (%) Activity predominantly seen in patients with tumors of squamous histology Subject aNSC = non–small cell lung cancer (adenocarcinoma), CRC = colorectal cancer, HCC = hepatocellular carcinoma, HN = head and neck squamou

  16. Slide 16: Clinical Activity at CX-2029 Doses ≥2 mg/kg

    Spider Plot (Doses 0.1–1 and 2-5 mg/kg) Clinical Activity at CX-2029 Doses ≥2 mg/kg PD, progressive disease; PR, partial response; SD, stable disease. *Patient on treatment as of data cut-off. Data cut-off: April 20, 2020. MELISSA JOHNSON PROCLAIM-CX-2029 16

  17. Slide 17: 75-Year-Old Patient With Squamous NSCLC (3 mg/kg)

    75-Year-Old Patient With Squamous NSCLC (3 mg/kg) • Patient: diagnosed with stage III squamous NSCLC in August 2017 • Prior therapy: Carboplatin/paclitaxel with radiation (2 mo); durvalumab (10 mo); gemcitabine (2 mo); docetaxel/ramucirumab (8 mo; SD then PD) • Toxicity: Cycle 2 and cycle 3 grade 3

  18. Slide 18: Summary of Phase 1 Results

    Summary of Phase 1 Results • Safety: • CX-2029 produces dose-dependent hematologic toxicities consistent with MMAE payload • Anemia: most common hematologic toxicity, also seen in non-clinical species • CX-2029 at 3 mg/kg will be studied in the dose-expansion phase • No cycle 1 DLT; no discontinuati

  19. Slide 19: Conclusions

    Conclusions • The results of first-in-human trial validates CD71 (transferrin receptor 1) as a viable therapeutic target in cancer • Probody technology enables administration of a CD71 directed antibody drug conjugate at tolerable doses with clinical anti-tumor activity • CD71: a previously undrugga

  20. Slide 20: Acknowledgments

    Acknowledgments • We would like to extend our grateful thanks to our co-investigators, their research personnel, and our colleagues at CytomX Therapeutics, AbbVie and ICON • Our sincere thanks to all patients and their caregivers who took part in this clinical trial Investigator Clinical site Invest

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