Oxurion Nv · EURONEXT:OXUR
Oxurion Nv — ThromboGenics — Investor Presentation (May 2017)
46 slides from Oxurion Nv's investor presentation, May 2017
Slide 1: Developing Novel Disease Modifying Treatments for Diabetic Eye Disease
Developing Novel Disease Modifying Treatments for Diabetic Eye Disease Company & Investor Presentation – May, 2017
Slide 2: Disclaimer
Disclaimer By attending the meeting where this presentation is made, or by reading the presentation slides, you agree to be bound by the following limitations: o This document has been prepared by ThromboGenics NV (the "Company") and is being supplied to you solely for your information and use by yo
Slide 3: Today's Agenda
Today’s Agenda o ThromboGenics at a glance o Why diabetic eye disease? o Clinical candidates – THR-409 & THR-317 - in Phase II development o Pre-clinical candidates – THR-687 & THR-149 - progressing to Phase I/II studies o Oncurious – progress with TB-403 – Phase I/Iia recruiting patients o JETREA s
Slide 4: ThromboGenics - Pioneering treatments for retina and diabetic eye disease
ThromboGenics - Pioneering treatments for back of the eye (retina) disease, diabetic eye disease o Back of the eye disease (retina), focus on disease modifying treatments for diabetic eye disease o 4 novel treatments under development in Diabetic Macular Edema and/or Diabetic Retinopathy (DR) : 2 cl
Slide 5: 2016/2017: continue transition and execute clinical trial plans
2016/ 2017 : continue transition and execute clinical trial plans o Re-focused activities and resources on drug development for the treatment of diabetic eye disease o Unveiled innovative pipeline of drug candidates targeting diabetic retinopathy (DR) and diabetic macular edema (DME) o 4 novel disea
Slide 6: Why diabetic eye disease?
Why diabetic eye disease? TE, ThromboGenics’ ‘Advancing Science, Enhancing Vision.”
Slide 7: Diabetic retinopathy segment forecast to grow twice as fast as ophthalmic market
Diabetic retinopathy segment is forecast to grow twice as fast as the overall ophthalmic pharmaceuticals market $33.0 Bio 6,8% $19.6 Bio Ophthalmic pharmaceuticals market* $12.8 Bio 9,3% $7.2 Bio Retinal diseases market** 16,1% DR & DME segments market $4.2 Bio $1.6 Bio Worldwide sales estimates Wor
Slide 8: IDF Diabetes Atlas 2015 prevalence by region
North America and Caribbean 2015 44.3 million South and Central America 2015 29.6 million ‘Advancing Science. Enhancing Visio Europe 2015 59.8 million “SF 2040 72.1 million Africa 201514.2 million Western Pacific 2015 153.2 million * IDF Diabetes Atlas 2015
Slide 9: More than one in three people with diabetes will develop diabetic retinopathy
More than One in three (!) people with diabetes will develop diabetic retinopathy NPDR 35.4% Non-proliferative diabetic retinopathy PDR Proliferative diabetic retinopathy with or without DME Diabetic macular edema 9
Slide 10: ThromboGenics is developing novel therapies for all DR segments
ThromboGenics is developing novel therapies for all DR segments 35.4% NPDR without DME PDR without DME 23.6% 4.2% NPDR with DME PDR with DME 4.5% 3.0% ANY DR* * Any DR is defined as the presence of NPDR, PDR, DME or any combination thereof Abbreviation(s): DR, diabetic retinopathy; NPDR, non-prolife
Slide 11: Drug Development Targeting all DR segments: Multiple Shots on Goal
Drug Development Targeting all DR segments: ‘Multiple Shots on Goal!’ Therapeutic action PROGRAM HALLMARKS OF DIABETIC RETINOPATHY SEGMENT Inflammation Edema Angiogenesis Fibrosis Neurodegeneration THR-409 +++(1) (ocriplasmin) THR-317 ++ +++ ++(+) ++ ++ (anti-PIGF) THR-687 ++ ++ +++(2) (integrin ant
Slide 12: THR-409: ocriplasmin
THR-409 : ocriplasmin TE, ThromboGenics’ ‘Advancing Science, Enhancing Vision.”
Slide 13: THR-409: Inducing a Total PVD with NPDR patients
THR-409: Inducing a Total PVD with NPDR patients (Ocriplasmin) o THR-409 is a disease modifying compound o A unique mode of action: Posterior vitreous detachment (PVD) o Potential step-change in the disease management in NPDR: o Study will explore progression rates to PDR o No other medical products
Slide 14: THR-409: Phase II Study Design Overview (CIRCLE)
THR-409 : Phase II Study Design Overview (TG-MV-015 - CIRCLE) Treatment population: o NPDR (stable DME allowed) randomised 2:2:1 THR-409 0,0625 mg THR-409 0,125 mg n=115 SAFETY FOLLOW-UP Sham D0 M1 M2 M3 M 15 M 24 EFFICACY EVALUATION : PVD SAFETY FOLLOW UP Explore progression to PDR 14
Slide 15: THR-317: anti-PlGF
THR-317 : anti-PlGF (Placental Growth Factor) 15
Slide 16: Biology background
Biology background Diabetic retinopathy (DR) - Current standard of care Anti-VEGF therapy - Improvement of visual acuity 1 THR-317 - Poor/non responders 2 - Adverse events: Vessel regression, fibrovascular membranes, neurodegeneration 3 X Clear need for alternative therapies with potential to reduce
Slide 17: THR-317: PlGF is an optimal target for advanced stages
THR-317: Placental growth factor (PlGF) is an optimal target to treat more advanced stages in diabetic eye disease PlGF levels in vitreous and aqueous humor* START DM NPDR PDR DME DME Increasing levels of PlGF correlate with increasing levels of retinal ischemia * Kovacs et al. (2015) Invest Ophthal
Slide 18: Preclinical evidence
Preclinical evidence Efficacy of PlGF inhibition on different DR hallmarks -> Akita/PlGF-/- Huang et al. 2015 Neurodegeneration -> Light-induced damage Izawa et al. 2015 -> Mouse CNV Van de Veire et al. 2010, Huang et al. 2011 Inflammation -> Mouse STZ PlGF or He et al. 2015 VEGFR-1 -> Mouse CNV and
Slide 19: Anti-PlGF and Inflammation
Anti-PlGF and Inflammation Mouse CNV – leukocyte infiltration % Inhibition of 25 IgG (3.1 µg/eye) CD45 positive cells % CD45 positive area/ anti-PlGF Ab (0.77 µg/eye) anti-PlGF Ab 49 total laser spot area 20 anti-PlGF Ab (1.5 µg/eye) anti-PlGF Ab (3.1 µg/eye) anti-VEGFR-2 Ab 0 15 * * anti-VEGFR-2 Ab
Slide 20: Anti-PlGF and Fibrosis
Anti-PlGF and Fibrosis Mouse CNV – collagen deposition % Inhibition of 25 IgG (3.1 µg/eye) collagen I positive area % Col1A positive area/ total laser spot area 20 anti-PlGF Ab (0.77µg/eye) anti-PlGF Ab 44 anti-PlGF Ab (1.5µg/eye) anti-PlGF Ab (3.1µg/eye) anti-VEGFR-2 Ab -1 15 * * anti-VEGFR-2 Ab (3
Slide 21: Anti-PlGF and neurodegeneration
Anti-PlGF and neurodegeneration Swiss mouse - Survival and apoptosis of ganglion cells A. B. Ganglion cell survival Ganglion cell apoptosis number of apoptotic ganglion cells/ *** Survival Apoptosis 5000 80 number of ganglion cells/ 4000 anti-PlGF Ab 60 retinal area +14% +10% retinal area * 3000 40
Slide 22: Anti-PlGF and neurodegeneration (mouse STZ)
Anti-PlGF and neurodegeneration Mouse STZ – neurodegeneration RGC number (Brn3a staining) % Inhibition of RGC count 18 Average number of RGC/ p=0.04 CAM anti-PlGF Ab - 250 µm cross section p=0.03 16 No injection NS PBS anti-VEGFR-2 Ab 20 14 Anti-PlGF Ab (5.4 µg/eye) * Anti-VEGFR-2 Ab (6.2 µg/eye) 12
Slide 23: Anti-PlGF and Pericyte coverage
Anti-PlGF and Pericyte coverage Mouse CNV – pericyte coverage % Improvement of 500 IgG pericyte coverage SMA positive area 400 * Anti-PlGF Ab (25 mg/kg) anti-PlGF Ab 35 Anti-VEGFR-2 Ab (25 mg/kg) 300 anti-VEGFR-2 Ab 1 (µm2) 200 100 0 Mean+SEM Day 14 after laser N=10 * P<0.05 (vs IgG) • Anti-PlGF Ab
Slide 24: THR-317: Phase II Study Overview
THR-317: Phase II Study Overview Treatment population: o Anti-VEGF naïve patients o Anti-VEGF poor responders randomised 1:1 THR-317 low dose n=50 SAFETY FOLLOW-UP THR-317 high dose DAY 0 DAY 30 DAY 60 DAY 90 DAY 150 EFFICACY EVALUATION o BCVA o Retinal Thickness 24
Slide 25: THR-317: Key take aways
THR-317: Key take aways o THR-317 is disease-modifying o DME, with potential additional benefit in anti-inflammatory treatment and fibrosis prevention o THR-317 offers the potential for two treatment modalities o Stand-alone treatment in DME o Combination treatment with any anti-VEGF o Only drug in
Slide 26: THR-687: Integrin receptor antagonist
THR-687 : Integrin receptor antagonist 26
Slide 27: THR-687 Rationale: inhibiting VEGF versus integrin
THR-687 Rationale: differential effects of inhibiting VEGF and integrin Integrin antagonism provides multiple points of attack to treat diabetic retinopathy Angiogenesis cycle endothelial cell migration, proliferation, differentiation and maturation TARGETING VEGF TARGETING INTEGRIN New New Mature M
Slide 28: THR-687: potent inhibitor of multiple integrin receptors
THR-687: potent inhibitor of multiple integrin receptors THR-687 targets integrin receptors involved in angiogenesis and permeability THR-687 Integrin Integrin receptor class IC50 (nM) αvβ3 RGD binding 4.4 ± 2.7 αvβ5 RGD binding 1.3 ± 0.5 α5β1 RGD binding 6.8 ± 3.2 α2bβ3 RGD binding 105 ± 26 α2β1 Co
Slide 29: THR-687: potent anti-angiogenic effect
THR-687: integrin inhibition results in potent anti-angiogenic effect Inhibition of blood vessel sprouting in mouse choroidal explant cultures vehicle 40nM Adapted from: Shao et.al., 2013 PLoSONE 8(7): e69552 200nM 5000nM THR-687 inhibits spontaneous blood vessel formation at low µM concentrations i
Slide 30: THR-687: Key take aways
THR-687: Key take aways o THR-687 is a novel and potent integrin antagonist o THR-687 has a broad therapeutic potential o diabetic retinopathy with and without DME o NPDR / PDR indication o treatment of diabetic retinopathy o induction of total posterior vitreous detachment o Clinical Proof of Conce
Slide 31: THR-149: a Plasma kallikrein (PKal) inhibitor
THR-149 : a Plasma kallikrein (PKal) inhibitor 31
Slide 32: Plasma kallikrein & diabetic macular edema
Plasma kallikrein & diabetic macular edema Vascular injury & initial permeability Preclinical evidence o PKal mediates vascular hyper-permeability, leukostasis, cytokine PLASMA KALLIKREIN THR-149 production, and retinal thickness o PKal inhibition significantly inhibits retinal vascular leakage in a
Slide 33: Plasma kallikrein and DME patients
Plasma kallikrein and DME patients PKal levels 3500 VEGF levels 20 3000 PKal (fold increase) VEGF (pg/mL) 2500 15 2000 10 1500 1000 5 500 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 DME patients ID # • Plasma kallikrein is a key driver in diabetic macular edema • Potential as a stand-alon
Slide 34: THR-149: a novel, potent and selective PKal inhibitor
THR-149 - A novel, potent and selective PKal inhibitor o Novel, potent reversible inhibitor of human PKal o small constrained peptide, Ki = 0.36 nM o Specificity profile showed specificity over 20 human serine proteases o no impact on coagulation pathway o Significant inhibition of bradykinin genera
Slide 35: Inhibition of plasma kallikrein results in strong anti-edema effect
Inhibition of plasma kallikrein results in strong anti-edema effect BRADYKININ FORMATION HUMAN PLASMA PAW EDEMA IN RAT 120 1.0 Bradykinin level (%, normalized) 100 IC50 = 115 ± 60 nM 0.8 Edema 0-2 h severity 80 0.6 60 0.4 40 0.2 20 0 0 0.1 1 10 100 1000 10000 100000 Ctrl INDO 3.0 10 30 THR-149 (nM)
Slide 36: THR-149: Key take aways
THR- 149 : Key take aways o THR-149 is a potent and selective plasma kallikrein inhibitor o THR-149 is targeting the treatment of diabetic macular edema (DME) o impact on disease on-set and progression o THR-149 offers the potential for two treatment modalities o stand-alone therapy in diabetic reti
Slide 37: Diabetic Eye Disease – pipeline / newsflow
Diabetic Eye Disease – pipeline / newsflow 37
Slide 38: Drug Development Targeting all DR segments: different mechanisms of action
Drug Development Targeting all DR segments: ‘Multiple Shots on Goal´ – different mechanisms of action 2017 2018 2019 THR-409 PHASE II ! ! (ocriplasmin) Endpoint : Total PVD M24 PDR progress - Exploring THR-317 PHASE I/ II ! PREP CLINICAL PHASE II b (anti-PIGF) BCVA at M3 THR-687 (integrin antagonist
Slide 39: JETREA
JETREA (ocriplasmin) Intravitreal Injection, 2.6 mg/mL TE, ThromboGenics’ ‘Advancing Science. Enhancing Vision.”
Slide 40: JETREA Commercial Update
JETREA® Commercial Update o Achieved break even in the US o JETREA® in the US is available with smaller team and a well-oiled specialized distribution channel o Online resources for patient, physician information, including enrollment and reimbursement o OASIS 2 year follow up data reporting better
Slide 41: Developing TB-403 for pediatric cancers
Developing TB-403 for pediatric cancers 41
Slide 42: Oncurious update
Oncurious update o Evaluating TB-403 for medulloblastoma o TB-403’s safety has previously been studied in 70 adult cancer patients (Lassen 2012, Martinsson-Niskanen 2011) o Compelling data on therapeutic action of TB-403 in medulloblastoma (Harvard) o Phase I/ II a has been initiated – development o
Slide 43: Summary & key take aways
Summary & key take aways TE, ThromboGenics’ ‘Advancing Science, Enhancing Vision.”
Slide 44: ThromboGenics today: disease modifying treatments for diabetic eye disease
ThromboGenics today : disease modifying treatments for diabetic eye disease + upside potential ONCURIOUS Diabetic Eye Disease TB-403 for medulloblastoma Disease Modifying Treatments Tackling Unmet Medical Needs in Phase I/IIa Diabetic Retinopathy THR-409 – ocriplasmin – Phase II THR-317 – anti-PlGF
Slide 45: 2016/2017 – Continue transition and execute clinical trial plans
2016/ 2017 – Continue transition and execute clinical trial plans o Re-focused activities and resources on drug development for the treatment of diabetic eye disease o Unveiled innovative pipeline of drug candidates targeting diabetic retinopathy (DR) and diabetic macular edema (DME) o 4 novel disea
Slide 46: Thank you for your interest
Thank you for your interest For questions and information : Please send us a message via [email protected]