Oxurion Nv · EURONEXT:OXUR
Oxurion Nv — Investor Presentation (September 2019)
43 slides from Oxurion Nv's investor presentation, September 2019
Slide 1: Disease Modifying Treatments for Diabetic Eye Disorders
Disease Modifying Treatments for Diabetic Eye Disorders Company presentation – September 2019
Slide 2: Forward-looking statement
Forward-looking statement This document has been prepared by Oxurion NV (the "Company") and is being supplied to you solely for your information and use by you at the Company presentation. This document and its contents are confidential and may not be further distributed or passed on to any other pe
Slide 3: Oxurion Highlights
Oxurion Highlights • Forging new directions in diabetic eye disease therapies • Targeting multiple disease-modifying pathways • Enhancing & going beyond vascular endothelial growth factor (VEGF) inhibition • Near-term value drivers: robust pipeline and strong R&D engine • 3 distinct proprietary clin
Slide 4: Management team with extensive experience across all stages of drug development and commercialization
Management team with extensive experience across all stages of drug development and commercialization Patrik De Haes, MD, CEO o +25 years of successful international management experience in the Life Science industry o Led the global development and commercialization of the first biotech product at
Slide 5: Oxurion Business Model: A Unique Ophthalmology Engine
Oxurion Business Model: A Unique Ophthalmology Engine Leverage unique Back-of-the-eye expertise and capabilities to identify, acquire and develop best-in- class molecules addressing high unmet needs - mAb, scAb, nanobody generation Animal models, Unique Disease Platform translational ✓ Back of the e
Slide 6: Diabetic Retinopathy Market & Unmet Needs
Diabetic Retinopathy Market & Unmet Needs
Slide 7: Diabetic Retinopathy is a Serious Sight-Threatening Disease
Diabetic Retinopathy is a Serious Sight-Threatening Disease Diabetic retinopathy (DR) is a chronic, progressive, sight-threatening, and life-altering disease which has become a major public health concern globally 450 Mio people with diabetes 150 Mio people with any diabetic retinopathy * incl. 50 M
Slide 8: Diabetic Macular Edema is a Severe Complication of DR
Diabetic Macular Edema is a Severe Complication of DR Diabetic macular edema (DME) is an accumulation of fluid in the macula - part of the retina that controls our most detailed vision abilities - due to leaking blood vessels. DME can occur at any stage of DR. Normal eye Eye with DME Courtesy of Hei
Slide 9: DME – Functional Measurement
DME – Functional Measurement Best-corrected visual acuity (BCVA) Snellen test ETDRS test Ophthalmologist, Investigator optometrist Daily practice Clinical trials ≠ letters / line 5 letters / line 9
Slide 10: DME – Anatomical Measurement
DME – Anatomical Measurement SD-OCT machine (f.e. Spectralis®) Spectral Domain Optical Coherence Tomography Central subfield thickness (CST) Macular Volume (MV) 2D 10
Slide 11: Limited treatment options for DR & DME
Limited treatment options for DR & DME Diabetic eye disorder is expected to remain one of the fastest-growing segments of the retina disorder drugs market due to the diabetes epidemy • Patients with DME are treated with pharmacological treatment alone in 60% of cases, up to 80% when combined with no
Slide 12: >50% of DME patients are suboptimal responders to anti-VEGFs
>50% of DME patients are suboptimal responders to anti-VEGFs At least 50% of patients have an unsatisfactory early visual response with anti-VEGF therapies, without clinically meaningful visual improvement in the majority of cases over the time Early vision response to anti-VEGFs Long-term vision ch
Slide 13: Major Unresolved Challenges of anti-VEGFs in DME
Major Unresolved Challenges of anti-VEGFs in DME VEGF-independent therapies offer chance to improve treatment outcomes in DME Efficacy | Faster onset and Improve higher gain on visual acuity & visual function treatment Safety | Better long-term profile Decrease outcomes and/or less risk of complicat
Slide 14: Our Pipeline Addresses Limitations of Standard of Care
Our Pipeline Addresses Limitations of Standard of Care Oxurion is addressing unresolved SoC challenges by developing next-generation treatments for diabetic eye disorders Unresolved Challenges / Our Ambition OXUR program Improve treatment outcomes Decrease treatment burden THR-149 Plasma kallikrein
Slide 15: Clinical data read out in H2 2019 – Phase 2 studies starting in 2020
Clinical data read out in H2 2019 – Phase 2 studies starting in 2020 Clinical-stage programs are based on distinct mechanisms of action for better treatment outcomes 2019 2020/2021 H1 H2 THR-149 Phase 1 (DME) Planning Phase 2 THR-149 Phase 2 (DME sub-resp) THR-317 Phase 2a (DME) Analysis / Under Rev
Slide 16: THR-149: Plasma Kallikrein Inhibitor
THR-149 : Plasma Kallikrein Inhibitor
Slide 17: Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks
Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks Biological activity in preclinical animal models from differentiated mechanisms of action OXUR Hallmarks of Diabetic Retinopathy program Inflammation Edema Angiogenesis Fibrosis Neurodegeneration THR-149 Plasma kallikrein inhibitor TH
Slide 18: THR-149: Plasma Kallikrein Inhibitor for Diabetic Macular Edema
THR-149: Plasma Kallikrein Inhibitor for Diabetic Macular Edema Highly Potent Selective and Stable Peptide targeting Plasma Kallikrein • Plasma Kallikrein (PKal) is a clinically well validated target for edema, inflammation and the prevention of microhemorrhages • THR-149 was developed in partnershi
Slide 19: Pkal Pathway Seems to Be Independent of VEGF Pathway
Pkal Pathway Seems to Be Independent of VEGF Pathway Pkal Level elevated in All DME Patients - Two distinct, independent pathways PKal levels 3500 20 VEGF levels 3000 VEGF level in vitreous Pkal level in vitreous 2500 15 (fold increase) (pg/mL) 2000 10 1500 1000 5 500 0 0 1 2 3 4 5 6 7 8 9 10 11 12
Slide 20: THR-149 - A novel, potent and selective PKal inhibitor
THR-149 - A novel, potent and selective PKal inhibitor • Novel, potent reversible inhibitor of human PKal ➢ small constrained peptide, Ki = 0.40 nM • Specificity profile showed specificity over 20 human serine proteases ➢ no impact on coagulation pathway • Significant inhibition of bradykinin genera
Slide 21: THR-149-001: Phase 1 study design in DME patients
THR-149-001: Phase 1 study design in DME patients Open-label, Multicenter, Dose Escalation Study ClinicalTrials.gov Identifier: NCT03511898 Study Treatment n = 12-18 0.005 mg THR-149 • IVT administration • Age > 18 years 0.025 mg THR-149 • Central-involved DME CST >300 µm (OCT) • BCVA ≤ 62 and ≥ 23
Slide 22: THR-149-001: BCVA increased rapidly and was maintained for 3 months
Positiive Topline Data THR-149-001: BCVA increased rapidly and was maintained for 3 months after 1 injection Mean change in BCVA from baseline * All Treated Subjects, Overall Mean change in BCVA (SE) from baseline 15 7.5 (ETDRS letters) 10 6.4 6.4 4.8 5.2 3.9 5 0 BL D1 D7 D14 M1 M2 M3 Study Visit •
Slide 23: THR-149-001: Mean Change in CST From Baseline
THR-149-001: Mean Change in CST From Baselinea All Treated Subjects, Overall 100 Mean change in CST (SE) 30.4 30 from Baseline (µm) 26.4 20.4 50 10.5 0 0 -50 -18 -100 BL D1 D7 D14 M1 M2 M3 Study visit • Marginal impact on mean CST at Day 1 followed by increase until study end • Mean CST change was m
Slide 24: THR-149-001: Macular Volume over Time, by Subject, BCVA Response
THR-149-001: Macular Volume over Time, by Subject, BCVA Response Subjects defined as BCVA Responders * Subjects defined as Non-Responders In the BCVA responders, macular volume was maintained over time * 24 24
Slide 25: THR-149-001: Key Take Away Messages
THR-149-001: Key Take Away Messages • THR-149 is safe and well tolerated: o No DLTs o No ocular SAEs o 1 treatment-related ocular AE - considered related to the injection procedure • Mean BCVA gain was fast and maintained until end of study: o Day 1: 3.9 letters o Max at Day 14: 7.5 letters o Month
Slide 26: THR-317: anti-PlGF (Placental growth factor)
THR-317 : anti-PlGF (Placental growth factor)
Slide 27: Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks
Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks Biological activity in preclinical animal models from differentiated mechanisms of action OXUR Hallmarks of Diabetic Retinopathy program Inflammation Edema Angiogenesis Fibrosis Neurodegeneration THR-149 Plasma kallikrein inhibitor TH
Slide 28: THR-317: Humanized mAb Against Human PlGF
THR-317 : Humanized mAb Against Human PlGF PlGF (Placental growth factor)* PlGF signaling cascade • Member of the VEGF-family signaling via binding to VEGFR-1, NRP-1, NRP-2 but not to VEGFR-2 • Key molecule in pathological angiogenesis, edema and inflammation • DR is a progressive disease… Increasin
Slide 29: THR-317-001: DME Phase I/II
Monotherapy THR-317-001: DME Phase I/II Single-masked, multicenter study to evaluate the safety and efficacy ClinicalTrials.gov Identifier: NCT03071068 Study Treatment Follow-up Total n = 49 patients • IVT administration • Age > 18 years 4 mg THR-317 • Treatment naïve n= 40 • Anti-VEGF poor responde
Slide 30: THR-317-001: Mean Change in BCVA From Baseline – All Subjects
Monotherapy – Positive Topline Data THR-317-001: Mean Change in BCVA From Baseline – All Subjects 15 Mean change (95% CI) from 8 mg THR-317 Baseline (ETDRS letters) 6.8 10 5.1 4.8 4.8 5.1 4.1 3.7 5 0 -5 BL PI MI PI M2 PI M3 M5 1 month after LI 1 month after LI Study visits (months) • Increase in mea
Slide 31: THR-317-002: Phase 2 Study in THR-317 + ranibizumab for DME
Combination therapy THR-317-002: Phase 2 Study in THR-317 + ranibizumab for DME Randomized, single-masked, active-controlled, multicenter study ClinicalTrials.gov Identifier: NCT03499223 Study Treatment Follow-up Total n = 72 patients THR-317 (8 mg)+ • IVT administration ranibizumab • Age > 18 years
Slide 32: Topline data THR-317-002 THR-317 + ranibizumab for DME
Combination therapy – Mixed Topline Data Topline data THR-317-002 THR-317 + ranibizumab for DME Data Analysis ongoing – THR 317 for DME Program Under Review • Combination therapy did not show increase in BCVA in the overall population at Month 3. • Certain improvement in mean BCVA at Month 3 observe
Slide 33: THR-317-003: Phase 2 THR-317 for MacTel1 Study Design
THR-317-003: Phase 2 THR-317 for MacTel1 Study Design Investigator Initiated – Is MacTel1 PlGF drive disease? – Data Read out by end of 2019 Study Treatment Follow-up Total n = 10 patients • IVT administration • Age > 18 year • Macular edema due to MacTel1 with 8 mg THR-317 CST >300 µm (OCT) DAY 0 D
Slide 34: THR-687: Pan-RGD Integrin Antagonist
THR-687 : Pan-RGD Integrin Antagonist
Slide 35: Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks
Oxurion Programs Tackling Main Diabetic Retinopathy Hallmarks Biological activity in preclinical animal models from differentiated mechanisms of action OXUR Hallmarks of Diabetic Retinopathy program Inflammation Edema Angiogenesis Fibrosis Neurodegeneration THR-149 Plasma kallikrein inhibitor TH
Slide 36: 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 broad efficacy Diabetes Mellitus Growth factors Cytokines • THR-687 is a novel, potent RGD integrin antagonist VEGF Other mediators licensed from Galapagos * Anti-VEGF • Inhibitio
Slide 37: THR-687 Potently Inhibits VEGF-Induced Leakage
THR-687 Potently Inhibits VEGF-Induced Leakage Mouse VEGF-induced leakage model (C57BL/6J) 15000 M S A (n g /m g p r o te in ) 10000 ** * * * IVT injection of human VEGF (300 ng/1 µL per eye) Vehicle 5000 Aflibercept (25mg/kg IP, 24h prior VEGF) THR-687 (15mg/kg IP, 1h prior VEGF + 50µg IVT) Read-ou
Slide 38: THR-687: Potent Inhibition of Angiogenesis-Driven Leakage in Cynomolgus Monkey CNV Model
THR-687: Potent Inhibition of Angiogenesis-Driven Leakage in Cynomolgus Monkey CNV Model 80 80 WEEK 2 WEEK 3 CONTROL ARTICLE (after 3 IVT injections) (after 2 IVT injections) 60 Grade 4 or 5 lesions 60 Grade 4 or 5 lesions (%) (%) 40 40 RANIBIZUMAB 20 20 0 0 g g g le g g g g le g m m m m THR-687 tic
Slide 39: THR-687-001: Phase 1 study design in DME patients
Enrolment Complete – Topline Data by end of 2019 THR-687-001: Phase 1 study design in DME patients Open-label, Multicenter, Dose Escalation Study ClinicalTrials.gov Identifier: NCT03666923 Study Treatment Total n = 12-18 patients 0.4 mg THR-687 • IVT administration • Age > 18 years 1.0 mg THR-687 •
Slide 40: THR-687: Key Take-Aways and Next Steps
THR-687: Key Take-Aways and Next Steps • THR-687 is a novel and potent pan-RGD integrin antagonist in-licensed from Galapagos NV • THR-687 has a broad therapeutic potential • Diabetic retinopathy with and without DME • Wet AMD IIb RDG Integrins • Sizeable target populations β3 β5 5 • Phase 1 DME s
Slide 41: Financials
Financials OxURION:
Slide 42: Oxurion (OXUR) Shareholder Structure Overview
Oxurion (OXUR) Shareholder Structure Overview 8.78% 6.1 % 5.7% Mr. Thomas M. Clay and entities controlled by him Baron Philippe Vlerick and entities controlled by him Novartis Pharma AG Public – free float 79.4% Oxurion NV has (as of 31 March 2019) : ➢ 38,291,950 outstanding shares ➢ 1,139,750 accep
Slide 43: Oxurion: Advancing Science. Enhancing Vision.
OxXURION’ ADVANCING SCIENCE.® ENHANCING VISION.