Disease Modifying Treatments for Diabetic Eye Disorders - Company presentation - September 2019 - Oxurion
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Disease Modifying Treatments for Diabetic Eye Disorders Company presentation – September 2019
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
person or published or reproduced, in whole or in part, by any medium or in any form for any purpose. All the numerical data provided in
this document are derived from Oxurion consolidated financial statements.
No representation or warranty expressed or implied is or will be made as to, and no reliance should be placed on, the fairness, accuracy,
completeness, or correctness of the information or opinions contained herein. The information set out herein may be subject to updating,
completion, revision, verification, and amendment, and such information may change materially. The Company is under no obligation to
update or keep current the information contained in this document or the presentation to which it relates, and any opinions expressed in it
are subject to change without notice. None of the Company or any of its affiliates, its advisors, or representatives shall have any liability
whatsoever (in negligence or otherwise) for any loss whatsoever arising from any use of this document or its contents or otherwise arising in
connection with this document.
The following information does not constitute investment advice, and shall not constitute an offer or invitation for the sale or purchase of
securities or assets of Oxurion in any jurisdiction. No securities of Oxurion may be offered or sold within the United States without
registration under the U.S. Securities Act of 1933, as amended, or in compliance with an exemption therefrom, and in accordance with any
applicable U.S. state securities laws.
2
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 clinical programs
• Strong momentum in 2019 – Recent positive top line data readout for THR-149
• Further important data read out – Phase 1 THR-687 in Q4
• End-to-end proven ability to discover and develop innovative ophthalmology therapies
• Solid financial position
• €67.6 million in cash on hand at June 30, 2019
• Listed on Euronext: OXUR
• 80 employees, HQ in Belgium, US office in New Jersey
• Partners and investors :
3
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 Sandoz (now Novartis)
o Former head of Roche’s Global Insulin Infusion division and CEO of Disetronic Medical Systems Inc (US).
o Transformed the Company from a cardiovascular startup to a global player in the retina space
Dominique Vanfleteren, CFO
o +25 years of experience in senior finance, operational, control and reporting roles in pharma
o Former CFO of UCB’s Asia Pacific Operations and Finance Director of GSK’s Diversified Healthcare Services
Jean Feyen, PhD, CSO
o +25 years of successful pharmaceutical research and development experience
o Former head of Galapagos ‘ biology and translational team.
o Held senior research positions at Bristol-Myers Squibb (US) and Sandoz (Switzerland)
Andy De Deene, MD, MBA, Global Head of Development
o +20 years of experience in drug development at small and large pharma companies
o Previously held senior R&D positions at Innogenetics & Jansen Pharmaceuticals (Johnson & Johnson)
o Led the development of Jetrea (ocriplasmin) from research to approval
4
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 eye expertise
research Best-in-Class clinical drug
✓ Drug targets / pathways
✓ Translational expertise candidates for complex retinal
“….omics” technologies ✓ Clinical Development diseases with large unmet needs
(e.g. single cell retina track-record
transcriptomics), ✓ Dedicated R&D team
biomarkers (30 FTEs)
Drug Formulation &
delivery technologies
5
Diabetic Retinopathy Market & Unmet Needs
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 Mio people with vision-threatening disease, including DME **
Normal vision Impact diabetic retinopathy
BLURRING & SCOTOMATA
* Any diabetic retinopathy is defined as the presence of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, diabetic macular edema, or any combination thereof
** Vision-threatening diabetic retinopathy is defined as the presence of proliferative diabetic retinopathy and/or diabetic macular edema
Abbreviation(s): DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; DME, diabetic macular edema 7
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 Heidelberg Engineering Courtesy of Heidelberg Engineering
8
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
DME – Anatomical Measurement
SD-OCT machine (f.e. Spectralis®)
Spectral Domain Optical Coherence Tomography
Central subfield thickness (CST) Macular Volume (MV)
2D
10Limited 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 non-
pharmacological treatment (e.g. laser)
• 80% of pharmacological treatments are based on anti-VEGF therapies, i.e. aflibercept (EYLEA®, Regeneron), ranibizumab
(LUCENTIS®, Roche), or off-label use of bevacizumab (AVASTIN®, Roche)
Intravitreal anti-VEGF therapy Laser photocoagulation Vitrectomy
Abbreviation(s): DR, diabetic retinopathy; DME, diabetic macular edema; VEGF, vascular endothelial growth factor
Source(s): adapted from Datamonitor Healthcare, 2018 11>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 change after 2
at 3 months years of anti-VEGFs treatment
Majority of patients maintain
33-49%
satisfactory vision response, but
≥10 letters
16-23% decline 10 letters
25-30%
5-9 letters 53-78% of patients remain
26-37% with unsatisfactory vision
5 letters
response 10 letters
Note: clinically satisfactory vision response is defined by a visual gain ≥ 10 letters
Abbreviation(s): DME, diabetic macular edema; VEGF, vascular endothelial growth factor
Source(s): Gonzalez VH et al. Am J Ophthalmol 2016;172:72-79; Bressler NM et al. Am J Ophthalmol 2018;195:93-100 12Major 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 complications
Durability | Longer
treatment
sustained treatment response
burden
Abbreviation(s): VEGF, vascular endothelial growth factor
Source(s): adapted from Datamonitor Healthcare 2018 13Our 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 Offering a solution for suboptimal responders to anti-VEGFs in DME
inhibitor
THR-317 Complementing anti-VEGF therapy for the treatment of DME
anti-PlGF mAb
THR-687
RGD Integrin Providing a broad therapeutic alternative for retinal vascular disorders
antagonist
Abbreviation(s): VEGF, vascular endothelial growth factor 14Clinical 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 Review THR-317 Phase 2b (DME)
THR-317 003 Phase 2 (MacTel 1) THR-317 Phase 2 (MacTel1)
THR-687 Phase 1 (DME) THR-687 Phase 2 (DME)
Plasma kallikrein PlacentalGrowth Factor Pan-RGD integrin
THR-149 THR-317 THR-687
Abbreviation(s): DME, diabetic macular edema; MacTel, macular telangiectasia
15THR-149 : Plasma Kallikrein Inhibitor
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
THR-317
PlGF inhibitor
THR-687
Integrin antagonist
Abbreviation(s): DR, diabetic retinopathy; PlGF, placenta growth factor 17THR-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
partnership with Bicycle
Therapeutics *
* Teufel et al. 2018 J.Med.Chem. 61: 2823-36
(Ki PKal = 0.4 nM)
18Pkal 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 13 14 15 16 17 18 19 20
DME patients ID # Adapted: Kita et al. 2015 Diabetes 64:3588–99
o Plasma kallikrein (PKal) is a key driver in diabetic macular edema
o PKal inhibitors have the potential as a stand-alone treatment in poor responders to
Standard of Care or in combination with anti-VEGF for all DME patients
19THR-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 generation
THR-149 in human vitreous and human plasma
in collaboration with
• Teufel et al. 2018 J. Med. Chem. 61: 2823-2836 20THR-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 letters 0.125 mg THR-149
Screening DAY 0 1 7 DAY 14 DAY 28 DAY 84
• Incidence of systemic and ocular adverse events on Day 0-84
• Occurrence of laboratory abnormalities up to the end of the study
21Positiive 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
• Mean BCVA gain occurred at every visit
• Mean change in BCVA from baseline was the highest at Day 14 and was maintained at Month 3
* Value before rescue carried forward
22THR-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 minimal and within the variability of measurement
BL, Baseline; D, Day; M, Month Overall mean CST at Baseline was 524µm
a Value before rescue carried forward
23THR-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
24THR-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 3: 6.4 letters
• Macular volume at BL seems to be indicative for BCVA response, and amongst the BCVA responders
macular volume was maintained over time
Overall gains noted in BCVA, and improvement in CST in some subjects are encouraging and
warrant further clinical research with multiple injections of THR-149
Phase 2 study THR 149 in DME expected to start in H1 2020
25THR-317 : anti-PlGF (Placental growth factor)
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
THR-317
PlGF inhibitor
THR-687
Integrin antagonist
Abbreviation(s): DR, diabetic retinopathy; PlGF, placenta growth factor 27THR-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… Increasing levels of PlGF
correlate with disease severity
THR-317
• Humanized monoclonal antibody against PlGF (IgG1 format)
• Affinity for PlGF in the low picomolar range
*Carmeliet et al. 2001 Nat Med 7: :575-83; Van de Veire et al. 2010 Cell. 141: 178-90; Van Bergen et al. 2017 28
Experimental Eye Res. 165 : 136-50Monotherapy
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 responders n=9 8 mg THR-317
• Randomized 1:1
• Centre-involved DME; CST ≥ 320 µm
• BCVA ≤ 20/40 and ≥ 20/320 DAY 0 DAY 30 DAY 60 DAY 90 DAY 150
Screening
• Incidence of systemic and ocular (S)AEs
• Proportion of subjects with a ≥ 15 ETDRS letters gain in BCVA from baseline
• Mean change from baseline in BCVA
• Mean change from baseline in CST-OCT
29Monotherapy – 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 mean BCVA shortly after first injection
• Increases in mean BCVA maintained to M5
• Trend for higher BCVA increases in the 8 mg arm
• Continued BCVA gain in the 8 mg arm, with highest increase at M3
BL, Baseline; PI, post-injection visit (7 days after each injection); LI, last injection 30
30Combination 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 (0.5 mg)
• Treatment naïve n= 48
Sham +
• Anti-VEGF poor responders n=24
ranibizumab
• Randomized 2:1
(0.5 mg)
• Centre-involved DME; CST ≥ 320 µm
• BCVA ≤ 20/40 and ≥ 20/320 DAY 0 DAY 28 DAY 56 DAY 84 DAY 140
DAY 7 DAY 35 DAY 63
Change from
baseline in
Screening
BCVA
Primary outcome measures
• Incidence of systemic and ocular adverse events
Secondary outcome measures
• Change from baseline in BCVA
• Change from baseline in CST
31Combination 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 observed with the combination
therapy in 2 pre-specified subgroups:
• poor (or non) responders to prior anti-VEGF
• patients with poor vision - baseline BCVA ≤65 letters
• Topline data confirm THR-317 in combination with ranibizumab is safe and well-
tolerated
32THR-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 DAY 28 DAY 56 DAY 84 DAY 140
DAY 7 DAY 35 DAY 63
Change from
Screening baseline in CST-OCT
Primary outcome measures
• Change from baseline CST-OCT by study visit
Secondary outcome measures • Change from baseline area of cystoid spaces by study visit
• Change from baseline in BCVA by study visit
• Incidence of systemic and ocular adverse events from day 0 to 140
33THR-687 : Pan-RGD Integrin Antagonist
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
THR-317
PlGF inhibitor
THR-687
Integrin antagonist
Abbreviation(s): DR, diabetic retinopathy; PlGF, placenta growth factor 35THR-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
• Inhibition of integrins targets multiple processes
Integrin
antagonist involved in pathological angiogenesis and vascular
leakage
INFLAMMATION
• THR-687 has a broad therapeutic potential:
LEAKAGE FIBROSIS
• Diabetic retinopathy (DR) with and without DME
• Wet (Neovascular) AMD
NEO-
VASCULARIZATION
* Hu et al. 2018 Experimental Eye Research 22: 43-52
Diabetic Retinopathy
36THR-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-out: mouse serum albumin (MSA)/mg retina samples
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37THR-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
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THR-687 potently inhibits angiogenesis-induced leakage in a monkey CNV model
38Enrolment 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
• Central-involved DME CST >300 µm
(OCT)
• BCVA ≤ 62 and ≥ 23 letters 2.5 mg THR-687
Screening DAY 0 1 7 DAY 14 DAY 28 DAY 84
• Incidence of systemic and ocular adverse events on Day 0-84
• Occurrence of laboratory abnormalities up to the end of the study
39THR-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 study completed enrolment patients V β1
8
β6
• Data read out by end of 2019
β8
40Financials
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 accepted unexercised warrants
➢ 675,000 warrants to be assigned
Oxurion NV Cash position (end of June 2019): €67,6 million
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