Oxurion Nv · EURONEXT:OXUR

Oxurion Nv — Angiogenesis, Exudation, and Degeneration 2020

19 slides from Oxurion Nv's conference presentation, Feb 8, 2020

  1. Slide 1: A Phase 1 Study of THR-687: An Integrin Antagonist for DME

    A Phase 1 Study of THR-687: An Integrin Antagonist for the Treatment of Diabetic Macular Edema (DME) Angiogenesis, Exudation, and Degeneration 2020 February 8, 2020 Arshad M. Khanani, MD, MA Director of Clinical Research Sierra Eye Associates Clinical Associate Professor University of Nevada Reno, N

  2. Slide 2: Relevant Financial Disclosures

    Relevant Financial Disclosures - OXURION: Consultant and Research Support

  3. Slide 3: Integrin Receptors: Subclasses

    Integrin Receptors: Subclasses RGD integrin receptors implicated in multiple disease hallmarks of DR and wet AMD ANGIOGENESIS1 INFLAMMATION3 FIBROSIS4 RGD Integrin receptors - RGD: V3, V5, V , 51 51 - RGD: V3, V5, 51 - RGD: V3, V5, V6, 51 - Leukocyte: 41(-7), L2, M2 - Co

  4. Slide 4: THR-687: A Pan-RGD Integrin Antagonist

    THR-687: A Pan-RGD Integrin Antagonist Integrin antagonists work both upstream and downstream of VEGF; hence, they have a potential broader efficacy Diabetes Growth factors mellitus Cytokines VEGF Other mediators • THR-687 is a novel, potent RGD integrin antagonist1 Anti-VEGF Integrin • Inhibition o

  5. Slide 5: THR-687: Anti-angiogenic effect

    THR-687: Anti-angiogenic effect THR-687 potently inhibits angiogenesis-induced leakage in a cynomolgus monkey CNV model WEEK 2 Representative FA images WEEK 3 80 (after 2 IVT injections) 80 (after 3 IVT injections) 60 Control article 60 Grade 4 or 5 lesions Grade 4 or 5 lesions (%) (%) 40 40 ranibiz

  6. Slide 6: THR-687: Vascular leakage

    THR-687: Vascular leakage THR-687 potently inhibits vascular leakage in a diabetic rat STZ model Analysis: 4 weeks after diabetes onset: Vascular leakage FITC-BSA perfusion to assess retinal permeability 400 Fluorescence intensity ** Vitreous Vitreous *** (arbitrary units) 300 * * Retina 200 Mean +

  7. Slide 7: THR-687-001: Study Design

    THR-687-001: Study Design Open-label, Multicenter, 3+3 Dose-Escalation Study Total N = 12 subjects • Age ≥ 18 years • CI- DME; Study Treatment IVT CST ≥ 320 µm (SD-OCT*) • BCVA ≤ 62 (20/63) and ≥ 23 letters (20/320) 0.4 mg THR-687 (low dose) • History of response to prior 1.0 mg THR-687 (middle dose

  8. Slide 8: THR-687-001: Demographics

    THR-687-001: Demographics All Treated Subjects Low Dose Middle Dose High Dose Overall Characteristic N=3 N=3 N=6 N=12 Gender, n (%) Male 2 2 5 9 (75.0) Female 1 1 1 3 (25.0) Race, n (%) White 2 2 5 9 (75.0) Black or African American 1 1 1 3 (25.0) Age (years) Mean (SD) 58.0 (9.54) 59.7 (8.08) 56.8 (

  9. Slide 9: Baseline Ocular Characteristics in the Study Eye (1/2)

    THR-687-001: Baseline Ocular Characteristics in the Study Eye (1/2) All Treated Subjects Low Dose Middle Dose High Dose Overall Characteristic N=3 N=3 N=6 N=12 BCVA (ETDRS letters) Mean (SD) 59.3 (2.08) 54.7 (2.31) 55.7 (8.26) 56.3 (6.02) Median 60.0 56.0 58.0 58.0 Min, Max 57, 61 52, 56 39, 61 39,

  10. Slide 10: Baseline Ocular Characteristics in the Study Eye (2/2)

    THR-687-001: Baseline Ocular Characteristics in the Study Eye (2/2) All Treated Subjects Low Dose Middle Dose High Dose Overall Characteristic N=3 N=3 N=6 N=12 Type of DR, n (%) Moderate NPDR 1 2 6 9 (75.0) Severe NPDR 1 0 0 1 (8.3) PDR 1 1 0 2 (16.7) Prior Treatment for DME, n (%) Anti-VEGF 3 3 6 1

  11. Slide 11: THR-687-001: Safety Overview

    THR-687-001: Safety Overview All Treated Subjects Low Dose Middle Dose High Dose Overall N=3 N=3 N=6 N=12 Category n [E] n [E] n [E] n (%) E Death 0 0 0 0 0 SAE 0 0 0 0 0 DLT 0 0 0 0 0 AE leading to withdrawal from study 0 0 0 0 0 Treatment-related (drug and / or procedure) AE – all in Study Eye, 1

  12. Slide 12: Adverse Events in the Study Eye

    THR-687-001: Adverse Events in the Study Eye All Treated Subjects Low Dose Middle Dose High Dose Overall N=3 N=3 N=6 N=12 Adverse event n [E] n [E] n [E] n (%) E 1 subjects, 2 events 1 subjects, 3 events 3 subjects, 4 events 5 subjects, 9 events Diabetic retinal edema 0 1 [1] 2 [2] 3 (25.0) 3 Conjun

  13. Slide 13: First Rescue Treatment

    THR-687-001: First Rescue Treatment All Treated Subjects Ranibizumab Aflibercept Bevacizumab 3 3 3 Low dose (N=3) Middle dose (N=3) High dose (N=6) Subjects (n) Subjects (n) Subjects (n) 2 2 2 1 1 1 1 1 1 0 0 0 Study visit Rescue criteria: Standard-of-care treatment for DME can be administered in th

  14. Slide 14: Mean Change in BCVA From Day 0, Overall

    THR-687-001: Mean Change in BCVA From Day 0 (Accounted for Rescue)a All Treated Subjects, Overall Mean change in BCVA (SE) from Day 0 20 15 (ETDRS letters) 10 9.2 8.8 7.7 8.3 7.2 5 3.1 0.0 0 D0 D1 D7 D14 M1 M2 M3 Study visit • A rapid onset of action in mean BCVA was observed as of Day 1 with 3.1 le

  15. Slide 15: Mean Change in BCVA From Day 0, By Dose

    THR-687-001: Mean Change in BCVA From Day 0 (Accounted for Rescue)a All Treated Subjects, By Dose Mean Change in BCVA from Day 0 20 THR-687 0.4mg (N=3) THR-687 1.0mg (N=3) THR-687 2.5mg (N=6) 15 (ETDRS Letters) 12.5 10 6,7 5 1.7 0 D0 D1 D7 D14 M1 M2 M3 Study visit • BCVA improvement was most pronoun

  16. Slide 16: Mean Change in CST From Day 1, Overall

    THR-687-001: Mean Change in CST From Day 1 (Accounted for Rescue)a All Treated Subjects, Overall Mean change in CST (SE) from Day 1 (µm) 120 80 40 4.1 0 -40 -3.8 -43.9 -38.9 -35.8 -80 -120 D0 D1 D7 D14 M1 M2 M3 Study visit • Overall, marginal impact on mean CST was noted up to Month 1, followed by a

  17. Slide 17: Mean Change in CST From Day 1, By Dose

    THR-687-001: Mean Change in CST From Day 1 (Accounted for Rescue)a All Treated Subjects, By Dose THR-687 0.4mg (N=3) THR-687 1.0mg (N=3) THR-687 2.5mg (N=6) 120 Mean Change in CST from Day 1 (µm) 80 85.0 40 0 4.3 -40 -36.5 -80 -120 D0 D1 D7 D14 M1 M2 M3 Study visit • A pronounced mean decrease in CS

  18. Slide 18: Change in BCVA and CST per Subject, High Dose

    THR-687-001: Change in BCVA From Day 0 & CST From Day 1 per Subject High Dose Change in BCVA from Day 0 (ETDRS letters) 25 250 2 Change in CST from Day 1 (µm) 200 20 4 150 1 R 100 15 5 3 50 R R 3 1 10 0 R -50 4 5 -100 6 6 -150 0 5 -200 2 -5 -250 D0 D1 D7 D14 M1 M2 M3 D0 D1 D7 D14 M1 M2 M3 Study visi

  19. Slide 19: Important Take-Home Messages

    THR-687-001: IMPORTANT TAKE-HOME MESSAGES • THR-687 is safe and well-tolerated: no DLTs , no SAEs occurred • Has a rapid onset of action resulting in significant BCVA gain and durability of mean BCVA • The high dose (2.5mg) had the most pronounced BCVA improvement and CST reduction 19

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