ADC Therapeutics SA · NYSE:ADCT

ADC Therapeutics SA — Technical Presentation (December 2018)

19 slides from ADC Therapeutics SA's technical presentation, December 2018

  1. Slide 1: Phase 1 Study of ADCT-301 (Camidanlumab Tesirine) in Relapsed/Refractory Classical Hodgkin Lymphoma

    Phase 1 Study of ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma M Hamadani1, GP Collins2, F Samaniego3, AI Spira4, A Davies5, J Radford6, P Caimi7, T Menne8, J Boni9, HG Cruz10, JM Feingold9, S He9, JU

  2. Slide 2: Structure and Components of ADCT-301 (camidanlumab tesirine)

    Structure and Components of ADCT-301 (camidanlumab tesirine) Val-Ala Self-immolative dPEG8 dipeptide group Drug-antibody ratio = 2.0 (± 0.3) Maleimide SG3199 (warhead) CD25-specific Tesirine/SG3249 (payload) HuMax-TAC 2

  3. Slide 3: Camidanlumab Tesirine Mechanism of Action

    Camidanlumab Tesirine Mechanism of Action Molecular mode of action Immunological rationale 1. Camidanlumab tesirine binds to the CD25 Targeting of CD25+ Tregs may increase the Teff:Treg ratio, antigen on the tumor cell surface thus promoting immunological tumor eradication3 2. ADC internalization, l

  4. Slide 4: Study Design

    Study Design Histologically confirmed relapsed/refractory NHL* or HL *Including Stage ≥Ib Cutaneous T-cell Lymphoma 2-part study: • Part 1: Dose escalation: continual reassessment method; • Part 2: Dose expansion(s) 1-hour intravenous infusion (3‒300 µg/kg); Day 1 every 3 weeks PRIMARY OBJECTIVE: Sa

  5. Slide 5: Inclusion and Exclusion Criteria

    Inclusion and Exclusion Criteria Key inclusion criteria Key exclusion criteria • Age 18 years or older • Active graft-versus-host disease • Pathologically confirmed relapsed or refractory • History of symptomatic autoimmune disease lymphoma • History of neuropathy considered of autoimmune • Failed,

  6. Slide 6: HL population: Baseline Characteristics

    HL population: Baseline Characteristics Patient characteristic Total (N=67) Sex, n (%) Male 40 (59.7) Female 27 (40.3) Race, n (%) White 55 (82.1) Black or African American 4 (6.0) Asian 3 (4.5) Other 5 (7.5) Age, years, median (min, max) 38.0 (19, 80) Number of previous systemic therapies, median (

  7. Slide 7: Pharmacokinetic Analysis Data

    Pharmacokinetic Analysis Data ➢ Exposure in serum increases with dose Camidanlumab tesirine mean (SE) AUC versus dose ➢ Half-life in patients with lymphoma is reasonably longa • PBD-conjugated antibody – 9.1 days (4.3, 25 days) 8 • Total antibody – 12.0 days (4.4, 62 days) Serum AUC PBD-Conjugated A

  8. Slide 8: Most Common All Grades TEAEs (≥20% Patients)

    HL population: Most Common All Grades TEAEs (≥20% Patients) (Safety Analysis Set) TEAEs, n (%) Dose (µg/kg) ≤20 (n=3) 30 (n=10) 45 (n=37) 60 (n=12) ≥80 (n=5) Total (N=67) Patients with any grade TEAE 3 (100) 10 (100) 37 (100) 12 (100) 5 (100) 67 (100) Fatigue 1 (33.3) 5 (50.0) 16 (43.2) 6 (50.0) 2 (

  9. Slide 9: HL population: Most Common TEAEs ≥Grade 3 (≥5% Patients)

    HL population: Most Common TEAEs ≥Grade 3 (≥5% Patients) (Safety Analysis Set) TEAEs ≥Grade 3, n (%) Dose (µg/kg) ≤20 (n=3) 30 (n=10) 45 (n=37) 60 (n=12) ≥80 (n=5) Total (N=67) Patients with grade ≥3 TEAE 2 (66.6) 6 (60.0) 24 (64.9) 7 (58.3) 5 (100) 44 (65.7) Maculopapular rash 1 (33.3) 2 (20.0) 7 (

  10. Slide 10: HL population: Selected Toxicities Summary

    HL population: Selected Toxicities Summary All Grades (Safety Analysis Set), Dose (µg/kg) Potentially PBD-related toxicities (SMQ) ≤20 30 45 60 ≥80 Total (n=3) (n=10) (n=37) (n=12) (n=5) (N=67) Edema or effusion 1 (33.3) 3 (30.0) 10 (27.0) 2 (16.7) 1 (20.0) 17 (25.4) Skin related 1 (33.3) 9 (90) 25

  11. Slide 11: Drug Exposure

    HL population: Drug Exposure Camidanlumab tesirine exposure Time to first AE leading to dose modification 1.0 Censored Median (min, max) no. of cycles received Probability of dose modification 0.9 30 µg/kg 4.5 (1, 9) 0.8 45 µg/kg 4.0 (1, 10) 0.7 60 µg/kg 2.5 (2, 8) 0.6 At 45 µg/kg: 0.5 80 µg/kg 4.0

  12. Slide 12: HL population: Response Rates

    HL population: Response Rates (Efficacy Analysis Set) Dose (µg/kg) Response*, n (%) ≤20 30 45 60 ≥80 Total (n=3) (n=10) (n=37) (n=12) (n=5) (N=67) Overall response rate (CR+PR) 1 (33.3) 5 (50.0) 32 (86.5) 7 (58.3) 4 (80.0) 49 (73.1) Complete response (CR) 0 (0) 4 (40.0) 16 (43.2) 5 (41.7) 2 (40.0) 2

  13. Slide 13: Waterfall Plot Showing Responses for Individual Patients

    HL population: Waterfall Plot Showing Responses for Individual Patients (Efficacy Analysis Set) 100 80 60 Best Percent Change from 40 Baseline (%) 20 0 -20 -40 -60 -80 -100 Patients Total Subjects 5 µg/kg (N=1) 13 µg/kg (N=1) 20 µg/kg (N=1) 30 µg/kg (N=10) 45 µg/kg (N=27) 60 µg/kg (N=11) 80 µg/kg (N

  14. Slide 14: Swimmer Plot Showing Responses for Individual Patients

    HL population: Swimmer Plot Showing Responses for Individual Patients (Efficacy Analysis Set) Treatment T 5 µg/kg 13 µg/kg T Complete response start T T Partial response start 20 µg/kg Stable disease start Progressive disease or death Patients T 30 µg/kg Censor* 40.3% (27/67) CR 32.8% (22/67) PR Las

  15. Slide 15: Overall Response Rate by Prior Treatment

    Overall Response Rate by Prior Treatment (Efficacy Analysis Set), 45 µg/kg and All Doses Groups 45 µg/kg dose All doses Prior Treatments (n=37) (n=67) ORR 86.5% ORR 73.8% Brentuximab vedotin (32/37 patients) (48/65 patients) Brentuximab vedotin ORR 88.5% ORR 72.3% Checkpoint Inhibitor (23/26 patient

  16. Slide 16: Duration of Response and Progression-free Survival

    HL population, 45 µg/kg dose group: Duration of Response and Progression-free Survival Median duration of response: 7.69 months Median progression-free survival: 8.25 months 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 Probability Probability 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 At risk: 32 24

  17. Slide 17: Duration of Response by PR/CR

    Duration of Response by PR/CR – 45 µg/kg HL patients 1.0 censored Median: 0.9 All responders: 7.69 months CR: 7.69 months 0.8 PR: 7.03 months 0.7 Probability 0.6 0.5 0.4 0.3 0.2 0.1 0.0 At risk: CR 16 14 10 9 9 7 6 5 3 3 2 1 1 0 PR 16 10 6 6 3 3 2 2 1 0 0 0 0 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time (

  18. Slide 18: Conclusions

    Conclusions ➢ In patients with R/R HL, therapy with camidanlumab tesirine provided impressive OR and CR rates in a heavily pre-treated patient population ▪ This includes ORR 88.5% in patients in the 45 µg/kg dose group who had received prior BV and CHPi ➢ Camidanlumab tesirine has shown encouraging

  19. Slide 19: Acknowledgments

    Acknowledgments ➢ Investigators and affiliations ➢ ADC Therapeutics: ▪ M Hamadani, Division of Hematology and Oncology, ▪ J Boni, ADC Therapeutics America, Inc, Murray Hill, NJ, USA Medical College of Wisconsin, Milwaukee, WI, USA ▪ HG Cruz, ADC Therapeutics SA, Epalinges, Switzerland ▪ GP Collins,

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