developing next standard of care therapies for diabetic

Developing Next Standard of Care Therapies for Diabetic Eye Disease

Company Presentation Oxurion NV (Euronext : OXUR)

January 2021

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

• Team with proven Track Record : compound developed from the lab bench to the market

• Created new chapter in the treatment of Diabetic Eye Disease – Building DME franchise by providing a full range of therapeutic solutions holding potential for all DME patients

• THR-149 holding potential as optimal therapy for DME patients sub-optimally responding to anti-VEGF therapies (+ 40% of DME patients treated with anti-VEGF)

• THR-687 holding potential as SOC for all DME patients + broader potential DR, wet AMD and RVO

• Near-term value drivers : 2 Phase 2 clinical studies starting in 2020/21 :

• THR-149 in DME - Positive POC Phase 1 data – Phase 2 Study/ Part A RECRUITING – Data by mid 2021

• THR-687 in DME - Positive POC Phase 1 data – Phase 2 Study /Part A start planned by mid 2021 – Data H1 2022

• IP Protected : Composition of Matter protection THR-149 (2034-2039), THR-687 (2039-2044)

• €31.6 million in cash as of September 30, 2020

3Abbreviation(s): DME, diabetic macular edema; HQ; R&D, research & development; VEGF, vascular endothelial growth factor; US, United States

Oxurion Highlights

Oxurion Translating disease knowledge into much better medicines

Developing the next generation of disruptive and transformative diabetic retinal disease therapies

4Abbreviation(s): IP, intellectual property; KU, Katholieke Universiteit (Catholic University); R&D, research & development; VIB, Vlaams Instituut voorBiotechnologies (Flanders institute for biotechnology)

Unique retina disease platform - Understand disease (disease hallmarks), Identify (pathways & targets), Translate (molecules), Develop (medicines)

Two IP-protected lead programs THR-149 & THR-687 designed to deliver much improved treatment outcomes to patients with diabetic macular edema

Academic collaborations with recognized international ophthalmology research groups (Queen’s University Belfast, KU Leuven, VIB) Access disease models

Strategic partnerships with established biopharmaceutical innovators (Bicycle Therapeutics & Galapagos) Access to the “right” molecules

Led by strong specialist team with expertise across R&D

Chief Executive Officer

Oxurion management team

Seasoned leadership team with a solid drug development track record

Chief Medical Officer

Chief Development Officer

Chief Scientific Officer

Patrik De Haes,

M.D.

Grace Chang,

M.D., Ph.D.Andy De Deene,

M.D., M.B.A.

Jean Feyen,

Ph.D.

5

Chief Financial Officer

Tom Graney,

C.F.A., M.B.A.

Bringing new MoAs to DME and beyond

A unique wholly-owned R&D pipeline beyond VEGF pathway in the retina field

6

Completed stage Ongoing stage

Abbreviation(s): AMD, age-related macular degeneration; DME, diabetic macular edema; R&D, research & development; MoA, mechanism of action; RCT, randomized controlled trial; RVO, retinal vein occlusion; VEGF, vascular endothelial growth factor

R&D stage

Candidate TargetPotential indication Preclinical Phase I Phase II Phase III Filing

Status at a glance

THR-149Plasma

kallikreinDME

Ongoing Phase II RCT

THR-687Pan-RGD integrins

DMEPlanned Phase II RCT in 2021


Wet AMD - RVO

-

Early research programs

Undisclosed Dry AMD -

Diabetic Retinopathy is a serious chronic complication of diabetes

DR is a chronic, progressive, debilitating, sight-threatening, and life-altering disease and a major public health concern globally

Retina of the eye

Diabetic retinopathyNormal condition

Central retinal veinCentral retinal artery

Retinal venulesRetinal

arterioles

MaculaFovea

Optic discAneurysm

Hard exudates

“Cotton wool” spots

Hemorrhages

Abnormal growth of blood vessels

Patientvision

Blurring & scotomata

7Abbreviation(s): DR, diabetic retinopathy

DME can occur at any stage of DR

Diabetic macular edema is an accumulation of fluid in the macula* due to leaking blood vessels

Courtesy of Heidelberg Engineering Courtesy of Heidelberg Engineering

Diabetic macular edemaNormal eye

RetinaMacula

Macularedema

8* The macula is the part of the retina that controls detailed vision

Abbreviation(s): DR, diabetic retinopathy

DME is a significant AND growing opportunity

9

Abbreviation(s): 7WW, seven major worldwide markets (France, Germany, Italy, Japan, Spain, United Kingdom & United States); DME, diabetic macular edema; DR, diabetic retinopathy; VEGF, vascular endothelial growth factor

Source(s): Datamonitor Healthcare, 2017; Decision Resources Group, 2019; GlobalData, 2020

Urgent and growing need for novel therapies to better treat the underserved DME population

Epidemiology

7WW, 2019

Market

7WW, 2019

Over 37 million people with diabetes (diagnosed)

Over 13 million prevalent DR patients

Between 2.8-5.8 million prevalent DME patients

Growing population due to diabetes epidemic and ageing demographics

+$11.5 billion anti-VEGF therapy market

+$4.5 billion DME/DR market

0.3-0.5 million anti-VEGF-treated DME patients insufficiently responsive

0.7-1.2 million anti-VEGF-treated DME patients

Patients with DME have limited treatment options

Although anti-VEGF therapy is the mainstay of DME therapy, 40% of patients do not achieve clinically meaningful vision gains despite dosing regimens optimized under clinical trial conditions

10

* Based on Protocol T study (Wells et al. Ophthalmology 2016) and proportion of patients BCVA gain 2 lines at 2 years

Abbreviation(s): BCVA, best-corrected visual acuity; DME, diabetic macular edema; DR, diabetic retinopathy; IVT, intravitreal; VEGF, vascular endothelialgrowth factor

Source(s): Bressler at al. JAMA Ophthalmol 2016; Bressler et al. JAMA Ophthalmol 2018; Gonzalez et al. Am J Ophthalmol 2016

Non-drug options based on laser & surgical (vitrectomy) therapies

IVT sustained-release corticosteroids (usually second-line therapy)

IVT anti-VEGF therapy as mainstay treatment (first-line therapy)40% of DME patients treated with anti-VEGF therapies do not achieve clinically meaningful vision gain*

Treatmentmanagement

Anti-VEGFs have multiple unresolved challenges

Current therapy fails to meet the needs of a significant number of patients with DME

Abbreviation(s): BCVA, best-corrected visual acuity; DME, diabetic macular edema; VEGF, vascular endothelial growth factor

Patient needs

Improve treatment outcomes

Improve therapeutic effect in terms of visual function (BCVA) and response rate (proportion of patients)

Extent

of effect

Decrease treatment burden

Enhance convenience by simplifying the dosing regimen

Increase duration of response for longer treatment intervals

Duration

of response

Convenience

11

Speed

of onset

Reduce induction phase by reaching faster optimal therapeutic effect

Oxurion is targeting new biological pathways that could deliver a significant improvement in patient outcomes

* Currently, 2 other plasma kallikrein inhibitors and 2 other integrin antagonists in clinical development

Abbreviation(s): DME, diabetic macular edema; MoA, mechanism of action; VEGF, vascular endothelial growth factor 12

Anti-VEGFlimitations

Improvingextent of effect

Current and upcoming Anti-VEGF-based therapies seem to have reached a plateau in terms of efficacy that they can deliver

Durability is currently targeted by the upcoming anti-VEGF-based therapies, addressing only treatment convenience

Targeting new biological pathways is expected to deliver better patient outcome - overcoming the limitations observed with anti-VEGF-based therapies

THR-149 and THR-687 are both potentially best- or first-in-class drugs with limited competition in these new MoA fields*

13

Creating a new DME therapy paradigm

Durability (convenience)

Exte

nt o

f eff

ect

Effic

acy

(BC

VA im

pro

vem

ent)

Anti-VEGF-based

therapies

Plasma KallikreinInhibitor

THR-149

Pan-RGD integrinantagonist

THR-687

* Currently, 2 other plasma kallikrein inhibitors and 2 other integrin antagonists in clinical development

Abbreviation(s): BCVA, best-corrected visual acuity; DME, diabetic macular edema; MoA, mechanism of action; VEGF, vascular endothelial growth factor

By focusing on new MoAswe are confident we will deliver better treatment options for all DME patients

Limited competition in the field of these new MoAs*

Developing an industry leading DME franchise

Innovative DME franchise will provide a full range of therapeutic solutions to address patient’s individual needs through personalized treatment strategies

Abbreviation(s): DME, diabetic macular edema; MoA, mechanism of action; VEGF, vascular endothelial growth factor 14

DME franchise

THR-687 solutionTHR-149 solution

• Treatment-naïve (new) Treatment initiation

• Treatment-experienced (existing) Switch from anti-VEGFs

Initial target patient group

Market interest & solutions

• DME is an area of high unmet medical need - $ 4.5 billion market p.a.

• Our new drugs with novel differentiated MoAs could deliver a step change in patient outcomes

THR-149Highly potent plasma kallikrein inhibitor targeting a VEGF-independent pathway

Potential to become the SOC for DME patients who respond sub-optimally to anti-VEGF therapy

New generation of DME treatments, beyond VEGF targeting, to answer substantial unmet medical needs

THR-149 Highly potent plasma kallikrein inhibitor for DME

Highly potent, selective and stable peptide targeting Plasma Kallikrein

(Ki PKal = 0.4 nM)

16* Teufel et al. J Med Chem 2018;61(7):2823-2836

Abbreviation(s): BK, bradykinin; DME, diabetic macular edema; FXII, factor XII; KKS, kinin kallikrein system; PK, PreKallikrein; PKal, plasma kallikrein

• Plasma Kallikrein is a clinically well validated target for edema, inflammation, and the prevention of microhemorrhages*

- PKal and bradykinins are elevated in diabetic eyes- Bradykinins cause retinal edema- PKal inhibition lowers bradykinins and reduce

edema in the retina

• THR-149 was developed in partnership with Bicycle Therapeutics

Rationale for targeting Plasma Kallikrein in DME patients

Two distinct, independent pathways linked to DME

0

500

1,000

1,500

2,000

2,500

3,000

3,500

0

5

15

10

20

PK

al (

fold

incr

ease

)

VEG

F (pg

/mL)

DME patients ID #

PKal levels

VEGF levels

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

17

• PKal is a key driver in DME

• PKal inhibitors have the potential as stand-alone therapy for sub-optimal responders to SOC, or for use in combination

Note: graph adapted from Kita et al. Diabetes 2015;64:3588-3599

Abbreviation(s): DME, diabetic macular edema; PKal, plasma kallikrein; SOC standard of care

THR-149 Preclinical evidence

THR-149 has demonstrated strong anti-inflammatory and anti-edema effects

18

Disease hallmarkin vitro assay/In vivo model

Biological activity

Lead indication

Vessel permeability• Rat paw edema model• Rat STZ model

DR, DME

Inflammation • Rat STZ model DR, DME

Abbreviation(s): DME, diabetic macular edema; DR, diabetic retinopathy; STZ, streptozotocin

THR-149 Diabetic retinal thickness : single vs. repeated injection

19

Repeat administration of THR-149 results in significant reduction (p<0.01) for the inner plexiform layer (IPL), inner nuclear layer (INL), outer nuclear layer (ONL) , and photoreceptor layer (PRL)

Multiple THR-149 IVT injections reduce the thickness of specific retinal layers in the STZ diabetic rat. Single THR-149 IVT injection had no significant impact.

Abbreviation(s): STZ, streptozotocin; IVT, intravitreal; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiformlayer; ONL, outer nuclear layer; PRL, photoreceptor layer

THR-149 Total retinal thickness: single vs. repeated injection

20

Multiple THR-149 IVT injections reduce retinal thickness in the STZ diabetic rat. Single THR-149 IVT injection had no impact.

Mean ± SEM; N=10-14; 1-way ANOVA, * p<0.05 (vs. vehicle)THR-149, 12.5 µg/eye IVT / week; VEGF-Trap, 2mg/kg IP / week

Abbrev.: STZ, streptozotocin; diabetic retinopathy, DR; IVT intravitreal; IV intravenous IP, intraperitoneal , 0

50150

200

250

Reti

na t

hic

kn

ess (

µm

)

* * *

Total retinal thickness @ Week 4

Ret

inal

th

ickn

ess

(

m)

Screening Primary Endpoint

Incidence of DLTs D0-14

THR-149 Clinical evidence Phase 1 study design in DME patients

Open-label, multicenter, 3+3 dose-escalation study to evaluate safety and preliminary efficacy (NCT03511898)

Study treatment

D84D28D0 D1 D14

0.005 mg THR-149

0.025 mg THR-149

0.125 mg THR-149

D7

Total N = 12 patients

Center-involved DME; CST ≥ 320 µm (OCT)

BCVA ≤ 62 and ≥ 23 letters

History of response to prior anti-VEGF / corticosteroid treatment

21Abbreviation(s): BCVA, best-corrected visual acuity; CST, central subfield thickness; D, day; DLT, dose-limiting toxicity; DME, diabetic macular edema; IVT, intravitreal; OCT, optical coherence tomography; VEGF, vascular endothelial growth factor

DLT criteria

Intraocular inflammation: 2+ inflammation on any of intraocular inflammation grading scales

BCVA: 10 ETDRS letter score decrease in BCVA from baseline

D56

22

THR-149 phase 1 Clinical evidence Safe and well-tolerated

All Treated Subjects

E, number of events; n, number of subjects in category; N, number of subjects with data available*Treatment-related

Confidential

Adverse event

Low DoseN=3

Middle DoseN=3

High DoseN=6

OverallN=12

n [E] n [E] n [E] n (%) 95% CI

1 subject, 2 events 3 subjects, 6 events 2 subjects, 2 events 6 subjects, 10 events

Anterior chamber inflammation 0 1 [1]* 0 1 (8.3) 0.21, 38.48

Conjunctival haemorrhage 0 1 [1] 0 1 (8.3) 0.21, 38.48

Corneal disorder 0 1 [1] 0 1 (8.3) 0.21, 38.48

Diabetic retinal oedema 1 [1] 1 [1] 1 [1] 3 (25.0) 5.49, 57.19

Eye pain 0 0 1 [1] 1 (8.3) 0.21, 38.48

Macular fibrosis 0 1 [2] 0 1 (8.3) 0.21, 38.48

Vitreous floaters 1 [1] 0 0 1 (8.3) 0.21, 38.48

Positive data

23

THR-149 phase 1 Clinical evidence Safe and well-tolerated

All Treated Subjects

• THR-149 is safe and well-tolerated

• No DLTs, no ocular SAEs

• There was one ocular AE related to study treatment (likely injection procedure) in the middle dose

cohort

• All other ocular AEs were unrelated to study treatment and were likely due to the injection procedure,

underlying disease progression or concomitant diseases

Confidential

Positive data

THR-149 phase 1 Clinical evidence Mean change BCVA from baseline*

BCVA increased rapidly and was maintained for 3 months after a single injection

0

3.9

6.4

7.5

4.8 5.2

6.4

0

5

10

15

Mea

n c

han

ge in

BC

VA

(SE

) fr

om

BLa

(ETD

RS

lett

ers)

Study visit

D14 M1BL D7D1 M2 M3

• A gain in mean BCVA was seen at every visit

• Mean change in BCVA from baseline was the highest at D14 and was maintained at M3

All treated subjects, overall

24

*Value before rescue carried forward

Abbreviation(s): BCVA, best-corrected visual acuity; BL, baseline; CST, central subfield thickness; D, day; DME, diabetic macular edema; ETDRS, early treatment diabetic retinopathy study; M, month

Positive data

0

-18

10.526.4 20.4

30.4 30

-100

-50

0

50

100

Mea

n c

han

ge in

CST

(SE

) fr

om

BLa

(µm

)

Study visit

D14 M1BL D7D1 M2 M3

THR-149 phase 1 Clinical evidence Mean change in CST from baseline*

Marginal impact on mean CST at D1 followed by increase until study end, but mean CST change was minimal and within the variability of measurement

25


Note: Overall mean CST at baseline was 524 µm

Abbreviation(s): BL, baseline; CST, central subfield thickness; D, day; M, month; SE, standard error


➢ A multicenter, randomized, 2-part study

➢ Target patient number: 122

➢ Target number of sites: 64 (US & EU)

➢ Goal:

➢ Part A: to select the dose of THR-149

➢ Part B: to compare THR-149 to aflibercept

➢ Part A: recruiting

➢ Dose selection: Mid 2021

➢ Part B Topline data: H1 2023

THR-149 Phase 2 in DME Recruiting Anti-VEGF poor responders

Positive data

26Abbreviation(s): BCVA, best-corrected visual acuity; CST, central subfield thickness; DME, diabetic macular edema

Speed of onset

• Rapid onset of action as of D1, with mean 3.9 letters gain

Extent of effect

• Highest BCVA gain at D14, with mean 7.5 letters gain

Duration of response

• BCVA gain maintained post-single injection at M3, with

mean 6.4 letters gain

Phase 1 single dose - results Phase 2 multiple-dose - recruiting

Safety

• Safe and well tolerated, no DLTs or ocular serious AEs

THR-149 Phase 2 study Design RecruitingPrimary Endpoint: BCVA – Secondary Endpoints: CST, AE’s

Screening Dose-level selection for Part B

D1 M1 M2 M3 M4 M5 M6

Part A : Dose level selection THR-149N=18, rando 1:1:1 Results by mid 2021

Part B: Topline data N=104, rando 1:1 Results by H1 2023

0.01 mg 0.04 mg 0.13 mg

Screening Primary EndpointSecondary endpoints

D1 M1 M2 M3 M4 M5 M6

Selected dose THR-149 Part A Aflibercept 2 mg

Anti-VEGF suboptimal responders:



≥ 5 anti-VEGF injections

6

6

6

52

52

Abbreviations: AE, adverse event; BCVA, best-corrected visual acuity; CST, central subfield thickness; D, day; DME, diabetic macular edema; M, month; N, number; OCT, optical coherence tomography; Rando, randomization; VEGF, vascular endothelial growth factor

N

N

USUK

ES

FRIT

DE CZSK Slovakia:

4 sites (1 activated)

Czech Republic:2 sites (1 activated)

Germany:6 sites

Italy:4 sites e.g., Dr. Bandello

UK:9 sites

France:5 sitese.g., Dr. Tadayoni

Spain:11 sites

US:23 sites (13 activated)e.g., Dr. Khanani

THR-149 Phase 2 : 64 Study Sites & Locations in US and EUPart A target: 35-40

THR-687Pan-RGD integrin antagonist with the potential to become the SOC for all DME patients, based on its broader biological effect than anti-VEGF therapy

New generation of DME treatments, beyond VEGF targeting, to answer substantial unmet medical needs

Abbreviation: DME, diabetic macular edema; SOC, standard of care; VEGF, vascular endothelial growth factor

THR-687 Pan-RGD integrin antagonist with a broad MoA

Potential to become the SOC for all DME patients based on its broad MoA, targeting receptors involved in multiple disease hallmarks

* Hu TT et al. Exp Eye Res 2019;180:43-52

Abbreviation(s): AMD, age-related macular degeneration; DME, diabetic macular edema; DR, diabetic retinopathy; MoA, mechanism of action; RGD, arginylglycylaspartic acid; VEGF, vascular endothelial growth factor

• THR-687 is a novel, potent RGD integrin antagonist*, licensed from Galapagos

• Inhibition of integrins targets multiple processes involved in pathological angiogenesis and vascular leakage

• Integrin antagonists work both upstream and downstream of VEGF, hence have broader potential efficacy

• THR-687 has a broad therapeutic potential:

- DR with and without DME

- Wet (neovascular) AMD

- RVO

Diabetic retinopathy

Inflammation

Leakage

Neo-vascularization

Fibrosis

Diabetes mellitus Growth factors

CytokinesOther mediatorsVEGF

Integrin antagonistAnti-VEGF

30

THR-687 Highly potent pan-RGD integrin antagonist

Characteristics & integrin receptor profiling

31

Integrin Integrin Receptor ClassTHR-687

IC50 ± SD (nM)

αvβ3

RGD binding

4.4 ± 2.7

αvβ5 1.3 ± 0.5

α5β1 6.8 ± 3.2

αvβ6 9.0 ± 5.3

αvβ8 1.5 ± 0.7

αvβ1 3.2 ± 1.3

αIIbβ3* 2,000 ± 1,500*

α4β1 Leukocyte-specific 3,800 ± 1,700

α2β1 Collagen binding 121,000 ± 25,000

α3β1 Laminin binding > 5,000,000

β1

β6

β8

β5

β3

IIb

5

V

8

RG

D In

tegr

in r

ece

pto

rs

* THR-687 did not affect platelet aggregation up to 100 µM (fibrinogen as ligand)

Note(s): full ovals represent integrin receptors involved in DR disease hallmarks

Abbreviation(s): DR, diabetic retinopathy; IC50, half maximal inhibitory concentration; RGD, arginylglycylaspartic acid; SD, standard deviation

Hu TT et al. Exp Eye Res 2019;180:43-52

THR-687 Preclinical evidence

THR-687 targets multiple disease hallmarks, supporting broad therapeutic potential

Disease hallmarkin vitro assay/In vivo model

Biological activity

Lead indication

Other indication(s)

Neovascularization

• Endothelial cell migration• Ex-vivo choroidal explant

• Monkey CNV model

DR Wet AMD

Vessel permeability

• Mouse VEGF-induced leakage model• Rat STZ model


DR, DME Wet AMD

Inflammation • Rat STZ model DR, DME Wet AMD

Fibrosis

• Alpha-smooth muscle actin expression• Collagen gel contraction


DR Wet AMD

32Abbreviation(s): AMD, age-related macular degeneration; CNV, choroidal neovascularization; DME, diabetic macular edema; DR, diabetic retinopathy; PDR, proliferative diabetic retinopathy; STZ, streptozotocin; VEGF, vascular endothelial growth factor

Vehicle PBS THR-687

Vitreous Vitreous

GCL

IPL

INLOPL

ONL

PRL

THR-687 Vascular leakage

THR-687 potently inhibits vascular leakage in a diabetic rat STZ model

FITC-BSA

4 weeks after diabetes onset0

200

400

600Non-diabetic

Diabetic, vehicle aflibercept, 3x IP, 3x/week

Diabetic, aflibercept 2 mg/kg, 3x IP, 3x/week

Diabetic, vehicle THR-687, 3x IVT, weekly

Diabetic, THR-687 75 µg/eye, 3x IVT, weekly

Flu

ore

scen

ce in

ten

sit

y

(arb

itra

ry u

nit

s)

Mean + SEMN=10-141-way ANOVA** p<0.01; *** p<0.001

***

**

Vascular leakage

*****

Abbreviation(s): FITC-BSA, Fluorescein isothiocyanate labelled bovine serum albumin; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor layer; STZ, streptozotocin; IP: intraperitoneal; IVT: intravitreal


200

400

600Non-diabetic





Flu

ore

scen

ce in

ten

sit

y

(arb

itra

ry u

nit

s)


***

**

Vascular leakage

*****


200

400

600Non-diabetic





Flu

ore

scen

ce in

ten

sit

y

(arb

itra

ry u

nit

s)


***

**

Vascular leakage

*****

33

THR-687 Anti-angiogenic effect

THR-687 potently inhibits angiogenesis-induced leakage in a cynomolgus monkey CNV model

34

Control article

Ranibizumab

THR-687

0.45 mg

Con

trol

artic

le

ranib

izum

ab: 0

.5 m

g

THR-6

87: 0

.45

mg

THR-6

87: 2

.25

mg

THR-6

87: 4

.5 m

g

0

20

40

60

80

WEEK 2(after 2 IVT injections)

Gra

de 4

or

5 lesio

ns

(%)

Week 2(after 2 IVT of THR-687)

Con

trol

artic

le

ranib

izum

ab: 0

.5 m

g

THR-6

87: 0

.45

mg

THR-6

87: 2

.25

mg

THR-6

87: 4

.5 m

g

0

20

40

60

80WEEK 3

(after 3 IVT injections)

Gra

de 4

or

5 lesio

ns

(%)

Week 3(after 3 IVT of THR-687)

Representative FA images

Hu TT et al. Exp Eye Res 2019;180:43-52

Abbreviation(s): CNV, choroidal neovascularization; IVT, intravitreal

ScreeningPrimary Endpoint

Incidence of DLTs D0-14

THR-687 Clinical evidence Phase 1 study design in DME patientsOpen-label, multicenter, 3+3 dose-escalation study to evaluate safety and preliminary efficacy(NCT03666923)

Abbreviation(s): BCVA, best-corrected visual acuity; CST, central subfield thickness; D, day; DLT, dose-limiting toxicity; DME, diabetic macular edema; ETDRS, early treatment diabetic retinopathy study; OCT, optical coherence tomography

Study treatment

D84D28D0 D1 D14

0.4 mg THR-687

1.0 mg THR-687

2.5 mg THR-687

D7

Enrolment completed Topline data by end of 2019

35

Total N = 12 patients



History of response to prioranti-VEGF / corticosteroid treatment

DLT criteria

Intraocular inflammation: 2+ inflammation on any of intraocular inflammation grading scales

BCVA: 10 ETDRS letter score decrease in BCVA from baseline

Macular hole

D56

THR-687 Clinical evidence Summary of adverse events 1 | 2

Overall, 5 subjects developed 9 AEs in the study eye

Category

Low DoseN=3

Middle DoseN=3

High DoseN=6

OverallN=12

n [E] n [E] n [E] n (%) E

Overall

Any AE 1 [2] 1 [3] 4 [5] 6 (50.0) 10

Any AE in study eye 1 [2] 1 [3] 3 [4] 5 (41.7) 9

Any AE in non-study eye 0 0 0 0 0

Any non-ocular AE 0 0 1 [1] 1 (8.3) 1

Positive data

36Abbreviation(s): AE, adverse event; E, number of events; n, number of subjects in category; N, number of subjects with data available

All treated subjects

Positive data

THR-687 Clinical evidence Summary of adverse events 2 | 2

There were no serious AEs, and all AEs deemed treatment-related by the investigator were in the study eye, with one subject at each dose

Positive data

37

Category

Low DoseN=3

Middle DoseN=3

High DoseN=6

OverallN=12

n [E] n [E] n [E] n (%)

Treatment-related (drug and/or procedure) AE

Any AE 1 [2] 1 [1] 1 [1] 3 (25.0)

Any AE in study eye 1 [2] 1 [1] 1 [1] 3 (25.0)

SAE

Any SAE 0 0 0 0

All treated subjects

Abbreviation(s): AE, adverse event; E, number of events; n, number of subjects in category; N, number of subjects with data available

Positive data

THR-687 phase 1 Clinical evidence Safe and well tolerated

• THR-687 is safe and well-tolerated

• No DLTs, no SAEs occurred in the study

• All treatment-related AEs were likely injection-procedure related

• Other AEs were likely due to the underlying disease progression or concomitant diseases

• 3 subjects received rescue medication with an anti-VEGF; one in the middle dose group at M2 and two in the high dose group (one at M1 and one at M2)

Positive data

38Abbreviation(s): DLT, dose-limiting toxicity; SAE, serious adverse event; AE, adverse event; M, month; VEGF, vascular endothelial growth factor

Positive data

THR-687 phase 1 Clinical evidence Mean change BCVA from Day 0*

Rapid onset of action - mean BCVA improvement was observed at D1 (3.1 letters gain), with the highest mean BCVA improvement at M1 (9.2 letters), and maintained post-injection at M3 (8.3 letters)

Positive data

39*Value before rescue carried forward

Abbreviation(s): BCVA, best-corrected visual acuity; D, day; ETDRS, early treatment diabetic retinopathy study; M, month; SE, standard error

0.0

3.1

7.2 7.7

9.28.8 8.3

0

5

10

15 All treated subjects, overall

D14 M1D0 D7D1 M2 M3

Study visit

Mea

n c

han

ge in

BC

VA

(SE

) fr

om

D0

a(E

TDR

S le

tter

s)

Positive data

0

5

10

15 THR-687 0.4mg (N=3) THR-687 1.0mg (N=3) THR-687 2.5mg (N=6)

6.7

1.7

THR-687 phase 1 Clinical evidence Mean change BCVA from Day 0*

Largest BCVA improvement in the high dose group, with a mean BCVA gain of 12.5 letters at M3

12.5

Positive data

40*Value before rescue carried forward

Abbreviation(s): BCVA, best-corrected visual acuity; D, day; ETDRS, early treatment diabetic retinopathy study; M, month; SE, standard error

All treated subjects, by dose

D14 M1D0 D7D1 M2 M3

Study visit

Mea

n c

han

ge in

BC

VA

fro

m D

0(E

TDR

S le

tter

s)

Positive data

THR-687 phase 1 Mean Change in BCVA from Baseline*

*Value before rescue carried forwardBaseline defined as the day of the injection. SE is only presented for overall data (across dose levels)Abbreviation(s): BCVA, best-corrected visual acuity; D, day; ETDRS, early treatment diabetic retinopathy study; M, month; SE, standard error

41


High dose had the most pronounced BCVA improvement, with mean 12.5 letters gain at Month 3

Positive data

Study visit

3.1

7.2 7.79.2 8.8

8.34.3

9.811.2 10.8 11.2

12.5

0

5

10

15Overall (N=12) THR-687 2.5mg (N=6)

D14 M1D0 D7D1 M2 M3

Mea

n c

han

ge in

BC

VA

(SE

) fr

om

Bas

elin

e (E

TDR

S le

tter

s)

THR-687 phase 1 Clinical evidence Mean change in CST from D1*

Overall, marginal impact on mean CST was noted up to M1, followed by increase until M3

-43.9 -38.9 -35.8

-3.8

4.1

-120

-80

-40

0

40

80

120

Positive data

42


Note: SD-OCT not assessed at D0

Abbreviation(s): CST, central subfield thickness; D, day; ETDRS, early treatment diabetic retinopathy study; M, month; SD-OCT, spectral domain-optical coherence tomography; SE, standard error

Mea

n c

han

ge in

CST

(SE

) fr

om

D1

(µ

m)

Study visit

D14 M1D0 D7D1 M2 M3


Positive data

-24-5.7

18.7

-6.74.3

0

-42.7

62

-62.7

71.385

-54.5

-106

-49.7-39.8

-36.5

-120

-80

-40

0

40

80

120THR-687 0.4mg (N=3) THR-687 1.0mg (N=3) THR-687 2.5mg (N=6)

Positive data

THR-687 phase 1 Clinical evidence Mean change in CST from D1*

Largest mean decrease in CST was noted in the high dose group, with a decrease of 106 µm at D14

43


Note: SD-OCT not assessed at D0

Abbreviation(s): CST, central subfield thickness; D, day; ETDRS, early treatment diabetic retinopathy study; M, month; SD-OCT, spectral domain-optical coherence tomography; SE, standard error

Mea

n c

han

ge in

CST

(SE

) fr

om

D1

(µ

m)

All treated subjects, by dose

D14 M1D0 D7D1 M2 M3

Study visit

Positive data

THR-687 phase 1 Mean Change in CST from Baseline*

High dose had more pronounced CST decrease of 106 µm at Day 14

*Value before rescue carried forwardBaseline defined as the day after the injection. SE is only presented for overall data (across dose levels)Abbreviation(s): CST, central subfield thickness; D, day; M, month; SE, standard error

44


Positive data

-43.9

-38.9-35.8

-3.84.1

-54.5

-106

-49.7

-39.8 -36.5

-120

-80

-40

0

40Overall (N=12) High dose (N=6)

Mea

n c

han

ge in

CST

(SE

) fr

om

Bas

elin

e (µ

m)

Study visit

D14 M1D0 D7D1 M2 M3

➢ A multicenter, randomized, 2-part study

➢ Target patient number: 200-300

➢ Target number of sites: 70 (US & EU)

➢ Goal:

➢ Part A: to select the dose of THR-687

➢ Part B: to compare THR-687 to aflibercept

➢ Start Part A : mid 2021

➢ Dose selection: H1 2022

➢ Topline Part B data: H2 2023

THR-687 Preliminary Phase 2 Plans in Treatment Naïve DME

Positive data

45Abbreviation(s): BCVA, best-corrected visual acuity; CST, central subfield thickness; DME, diabetic macular edema

Phase 1 single dose Phase 2 multiple-dose

Extent of effect

• 9.2 letters gain at Month 1

Long Duration of action

• BCVA gain maintained at Month 3 >> +12.5 letters in high dose

• Safe and well tolerated, no DLTs or ocular serious AEs

Safety

Speed of onset

• 3.1 letters BCVA gain as of the day after the injection

Broader biological effect than anti-VEGF

therapy

Bringing new MoAs to DME and beyond

A unique wholly-owned R&D pipeline beyond VEGF pathway in the retina field

46

Completed stage Ongoing stage

Abbreviation(s): AMD, age-related macular degeneration; DME, diabetic macular edema; R&D, research & development; MoA, mechanism of action; RCT, randomized controlled trial; RVO, retinal vein occlusion; VEGF, vascular endothelial growth factor

R&D stage

Candidate TargetPotential indication Preclinical Phase I Phase II Phase III Filing

Status at a glance

THR-149Plasma

kallikreinDME

Ongoing Phase II RCT


DMEPlanned Phase II RCT in 2021


Wet AMD - RVO

-

Early research programs

Undisclosed Dry AMD -

Oxurion aims to be a GAME CHANGER in the treatment of DME

47Abbreviation(s): DME, diabetic macular edema; IVT, intravitreal; SOC, standard of care; VEGF, vascular endothelial growth factor

• Potential to become SOC for DME patients, sub-optimally responders to anti-VEGF therapy

• Targeting a VEGF-independent pathway

• Positive Phase 1 study after a single IVT injection

• THR-149 Phase 2 study Multiple injections - Part A recruiting, data mid 2021

• THR-687 Phase 2 study Multiple injections - Part A expected to start recruiting by mid 2021

• Targeting a market opportunity worth $4.5 billion p.a.

• Potential to become SOC for all DME patients

• Broader biological effect Potential to replace anti-VEGF therapy

• Positive Phase 1 study after a single IVT injection

Pan-RGD integrinantagonist

THR-687

Plasma KallikreinInhibitor

THR-149

Oxurion shareholder structure overview

79.4%

5.7%6.1 %

8.8%

Mr. Thomas M. Clay and entities controlled by him

Baron Philippe Vlerick and entities controlled by him

Novartis Pharma AG

Public - free float

Oxurion NV (Euronext Brussels: OXUR) - as of September 30, 2020):

- 38,291,950 shares outstanding

- €31.6 million in cash

48

developing next standard of care therapies for diabetic

Documents