Oxurion Perspectives magazine 2020

2020

Progressing development of therapies for retinal vascular disorders and diabetic eye disease

"We focus on non-VEGF pathways"

Researching the dry AMD pathway

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p. 11

p. 32

2020

contents PROGRESSING DEVELOPMENT OF THERAPIES FOR RETINAL VASCULAR DISORDERS AND DIABETIC EYE DISEASE Patrik De Haes, M.D., CEO & Thomas Clay, Chairman of the Board of Directors

p. 7

"WE FOCUS ON NON-VEGF PATHWAYS"

THR-149, A HIGHLY POTENT PLASMA KALLIKREIN INHIBITOR TO TREAT DME

THR-687, A POTENT PAN-RGD INTEGRIN ANTAGONIST IN DEVELOPMENT FOR DME

Jean Feyen, PhD., CSO,

Preparing a phase 2 clinical trial

Preparing a phase 2 clinical trial

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p. 24

and Andy De Deene, M.D., Head of Development

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“OXURION IS WELL-POSITIONED TO DEVELOP PATHWAYS TO ADDRESS DRY AMD”

MAKING A DIFFERENCE IN THE GLOBAL RETINA COMMUNITY

Prof. Alan Stitt of Queen’s University

Oxurion joins forces with Prevent

in Belfast

Blindness and Retina Global

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p. 32

NEXT GENERATION I/O CANCER THERAPIES Ongoing clinical research

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contents Editorial

Perspectives 2020

contents Editorial Interview Patrik De Haes, M.D., CEO of Oxurion & Thomas Clay, Chairman of the Board

Progressing development of therapies for retinal vascular disorders and diabetic eye disease 2019 has been another transformational year for Oxurion. In this first year after the company's rebranding, we conducted three clinical trials. The results of two were encouraging and promising, those of the third rather mixed. Oxurion then made the strategic decision to focus its research on developing non-VEGF compounds to target an unmet medical need for people with diabetic retinal eye disease.

“2019 has been an important year for our clinical developments. We obtained excellent results from two phase 1 clinical trials evaluating two distinct and wholly-owned non-VEGF compounds: THR-149 and THR-687. These have given us a solid basis, a confirmation of our new focus, and a growth platform for the company's future development", says Patrik De Haes, M.D., CEO of Oxurion.

“The results from the clinical trials for our molecules THR-149 and THR-687 are indeed very promising. Both compounds not only proved to be very safe and well-tolerated, they also showed a substantial, clinically relevant early benefit and durability of effect.” This truly ticks all the boxes in developing the nextgeneration therapy for retinal disease.

Different course, ...

Thomas Clay, Chairman of the Board, confirms this. “Oxurion had two very successful phase 1 trials. The data from our study evaluating anti-PIGF (THR-317) for DME were clinically sound but did not show the outcome we were hoping for.

The choice to leave that pathway was obvious so we took that decision.”

“We also decided to stop actively promoting Jetrea® ourselves and seek a distribution licensee partner", Patrik De Haes adds. "With Inceptua Group we've found such a partner. In March 2020, Oxurion and Inceptua Group signed a global license agreement for further commercialization of Jetrea®. With that, we fulfilled our commitment to not only secure access to Jetrea® for those patients we believe can truly benefit from this first-in-class medicine, but to do it in a cost-neutral manner for the Company.”

“Our molecules are unique, and potentially first in class.”

Patrik De Haes, M.D., CEO of Oxurion

Finally, in 2019 Oxurion also decided to explore and research innovative new therapies for age-related macular degeneration (AMD). AMD is a leading cause of blindness in the world and comes in two varieties. There are treatments for wet AMD, but for dry AMD there are none. “The focus of the Oxurion preclinical research teams is currently almost exclusively on in-vivo and in-vitro validation of new pathways and compounds for the treatment of dry AMD. We hope to be able to present at least one preclinical proof of concept in 2020", Patrik continues. 

Perspectives 2020

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Editorial

... the same commitment While Oxurion's strategic course may have been fine-tuned in 2019, the commitment and focus have remained unchanged: developing therapies for people with diabetic eye disease or age-related macular degeneration.

"We bring experts and investors together, so the retina experts can explain directly the need for compounds we are developing."

Thomas Clay, Chairman of the Board

“Our therapeutic approach also means focusing resources, time, and energy on compounds we believe have the potential to make a life-changing improvement in a person’s vision. For many DME patients there is still a large unmet need. More than 40% of them have a suboptimal or zero response to treatment with an anti-VEGF, currently the standard of care for the bulk of DME patients. For them we need to find a solution, and we have two validated options in clinical development", Patrik explains.

Value creation “This strategy is also interesting for our shareholders and potential investors", Thomas Clay points out. "Our choice to develop non-VEGF compounds is a

Perspectives 2020

strategic one. When 40% of DME patients respond poorly to an anti-VEGF therapy, common sense says we should look at non-VEGF therapies for them. With THR-149 and THR-687, Oxurion has two unique and wholly owned compounds in clinical development that are very distinct from any of the anti-VEGF therapies now available or under development. Not only they represent a great opportunity for many DME patients out there, they also offer our shareholders and investors the best chance for future value creation. It is obvious that should we succeed in crafting a novel pathway towards a therapy for dry AMD, we expect this to also see this translated into additional value for our shareholders.”

THR-149 is a plasma kallikrein inhibitor to treat people with DME. This novel therapy yielded encouraging results in the phase 1 clinical trial, producing fast and durable improvement of vision.

"Oxurion does not hesitate to bring investors and experts together. We want our shareholders and investors to hear from key opinion leaders familiar with our programs why these are innovative and vital for patients”, Thomas continues.

"Meanwhile, we feel very encouraged to see key retina opinion leaders in Europe and the US also confirm the potential of THR-149 and THR-687 for treatment of DME.”

Read all about the study and clinical results of THR-687 on page 24.

Recruiting for two phase 2 trials Oxurion is preparing the start of two fully powered phase 2 clinical trials, next to the validation of new pathways towards a therapy for dry AMD. Final approvals for the phase 2 clinical trial evaluating THR-149 in DME are well underway, and Oxurion is making great headway with the prep work for its phase 2 with THR-687 as well.

Read all about the study and clinical results of THR-149 on page 16.

The results from the phase 1 evaluation of THR-687, a pan-RGD integrin antagonist, are promising. An almost immediate, significant and durable mean BCVA improvement of vision was reported

The two compounds target different patient groups. THR-149 will be evaluated in patients who do not or do not optimally react to anti-VEGF treatment (nonresponders/poor responders), while antiVEGF treatment naïve patients will be selected in the THR-687 phase 2 study.

Both studies will test whether multiple doses the compounds can increase and prolong the visual improvement observed in the phase 1 studies.

Oxurion believes that if these fully powered phase 2 trials replicate and maintain the observed benefit from the phase 1 studies, both compounds would become very compelling drug candidates with clear value to the market.

Editorial

“Of course, the data will speak for themselves, but we feel confident. After all, the Oxurion team has the important experience of successfully developing a medicine from the research bench all the way to the market. We know the way", says Patrik.

Part of a global retina family Whilst advancing its retina and vision research, Oxurion seeks to preserve close ties with those in the retina community and the patients they serve. Over the years it has developed close collaborative ventures with US and global organizations such as Prevent Blindness and Retina Global.

Oxurion proudly supports Retina Global’s efforts to educate people on eye disease and proper eye care and to send retina specialists to remote and less privileged corners of the world to provide specialized eye care to those in need.

In the past, we have joined forces with Prevent Blindness in order to boost their ‘Diabetic Eye Disease Awareness Month’-campaigns. Going forward, we are looking into how we can assist and support Prevent Blindness while staging their brand-new nationwide patient engagement and advocacy training program. At Oxurion, we also believe that patients are among the best placed to help create awareness about vision-threatening conditions, disease processes and the impact of these diseases on daily life.

Confidently looking to the future “Oxurion has completed its transformation to a full-fledged drug development company with a clear focus.

It now has two exciting phase 2 clinical trials under way evaluating two distinct and very innovative non-VEGF compounds for treatment of DME. We've also taken our first steps into the dry AMD arena with its large untapped potential and aim to make a substantial impact there", Patrik De Haes states.

“We view the future with confidence and ambition", Thomas Clay concludes.

In memoriam Claude Sander With profound sadness the Board, Management and Staff of Oxurion learned about the sudden passing of Dr Claude Sander on December 20th, 2019.

Claude Sander was Chief Legal Officer and Corporate Secretary to the board. He started his professional career as a Senior Researcher at the Center of European Integration Studies in Bonn. He joined Oxurion in 2011 and oversaw Legal, Corporate Compliance, Corporate Board and selected Market Access related activities at Oxurion.

Patrik De Haes, M.D., CEO of Oxurion: “It was a privilege and pleasure to have known Claude and to have worked with him for almost a decade. Claude always demonstrated exceptional leadership in his role as Chief Legal Officer and more recently as Corporate Secretary to the Board, even in challenging situations. He was both admired and respected for his relentless commitment, expertise and achievements. Claude will be deeply missed and will always have a very special place in our hearts.”

Perspectives 2020

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A strategic focus

A strategic focus Oxurion rises to the opportunity to address an unmet medical need.

Perspectives 2020

A strategic focus

Interview Jean Feyen, PhD., Chief Scientific Officer and Andy De Deene, M.D., Global Head of Development

"We focus on non-VEGF pathways" Oxurion has a mission: to prevent loss of vision loss and blindness by developing solutions for retinal diseases generally, and specifically for diabetic macular edema (DME) and age-related macular degeneration (AMD). To realize this ambition the company is focusing on non-VEGF pathways and compounds. Andy De Deene, M.D., Global Head of Development, and Jean Feyen, PhD., Chief Scientific Officer, explain this strategic direction.

The course may have been finetuned but the goal remains: to find treatments for retinal diseases such as DME and AMD. “The change means first and foremost leaving the VEGF pathway", Jean says.

"The decision to stop the development of our THR-317 compound was completely data-driven. THR-317 was a clinically sound compound, but compared to others it made much more sense to focus our time, energy and resources on developing non-VEGF pathways".

The importance of non-VEGF pathways cannot be overestimated. “At present the standard of care for DME is a monthly injection into the eye with an anti-VEGF medicine", Andy explains.

"An anti-VEGF is a good product but it only works for 60% of those with

DME, meaning there is no effective treatment for the other 40%. Exploring non-VEGF pathways might provide a chance to better address the current unmet medical need of those 40% DME patients."

In parallel with this, Oxurion is seeking to lower the burden for patients by developing a treatment requiring less frequent follow-up. “We're looking for a way to not just suppress symptoms but also modify the disease", Andy adds.

Two compounds, two target groups Th e co m p o un ds THR-149 an d THR-687 use a different pathway than anti-VEGF. “Each of these molecules has its own target group", Jean continues. “THR-149, our plasma kallikrein inhibitor, is a VEGF-independent compound specifically used to treat the accumulation of fluids in the retina.

As such it can improve vision. This compound only tackles some aspects of DME and is meant for people who have no or suboptimal response to anti-VEGF injections". 

"We're a data-driven biotech company. Every decision is supported by data. We believe this is the best way to select which pathways to develop."

Jean Feyen, PhD., Chief Scientific Officer

Perspectives 2020

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A strategic focus

THR- 687 is “a pan -RGD inte g rin antagonist and a non-VEGF compound. It has a broad mode of action and addresses different aspects of DME such as permeability, inflammation, angiogenesis, and fibrosis. Potentially it could treat diabetic retinopathy (with and without DME) and the wet variety of agerelated macular degeneration (AMD).

THR-687 does what an anti-VEGF does and more. This allows us to focus on treating naïve patients: those who have never received treatment for diabetic eye disease".

these clinical trials we hoped for an effect, but were surprised to see these impressive improvements this fast after the injection. One injection with THR-149 yielded an improvement in vision with 6.4 letters after three months. THR-687 performs even better. This kind of improvement is too significant to be the result of chance", Andy explains.

Fast & durable improvement

A chance to address dry AMD

In 2019, Oxurion conducted two phase 1 clinical trials to assess the safety of both THR-149 and THR-687.

We are currently preparing for two phase 2 trials.

“In testing treatment for eye diseases you want to see a fast and durable improvement of vision. Already in the phase 1 clinical trials we noticed signs of efficacy even with the limited group of test subjects. When we started

Read more about this phase 1 clinical study of THR-149 on page 16.

Oxurion is not staking its future on these two compounds alone. “We're always looking for ways to feed the pipeline and develop novel therapies for treating back of the eye diseases", Jean says. In 2019, Oxurion made the strategic choice to enter the pathway of dry AMD. “This past year our R&D teams have been working on dry AMD. This disease affects many people and

currently, there is no treatment available. We have the chance to address this problem and improve the lives of many people. For this we are collaborating with, among others, Professor Alan Stitt and Queen’s University in Belfast", Andy explains. Oxurion aspires to bring at least one dry AMD project to development.

Read more about this phase 1 clinical study of THR-149 on page 24.

Top team delivering high-quality work Collaborating with universities, both in Europe and the United States, is crucial for Oxurion. “To put us on the scientific map we must deliver high-quality work. Getting articles published in peer-reviewed scientific journals is one measure of quality. We are very lucky to work with a team of very talented people who have excellent success in publishing articles in scientific journals", Andy observes. “Exchanging knowledge is critical in scientific research.

“Exchanging knowledge is critical in scientific research.

Once information can be released, it is crucial that it flows easily to the scientific community. We are lucky to work with a team of talented people who succeed in sharing results."

Andy De Deene, M.D., Global Head of Development

Perspectives 2020

A strategic focus

Once information can be released, it is crucial that it flows easily to the scientific community".

every opportunity. That is the only way to give our board well-informed advice about molecules and pathways".

“And the opposite is also true", Jean adds. “Our team members must know every development, every novelty, every breakthrough in this field. We expect them to be on top of their game, to test, experiment, and evaluate

“We're a data-driven biotech company.

Every one of our decisions is supported by data. We believe this is the best way to select which pathways to develop", Jean concludes.

Leading causes of blindness * 1.

Age-related macular degeneration (AMD)

2.

Cataract

3.

Glaucoma

4.

Diabetic retinopathy (DME)

5.

Trachoma

* Source: World Health Organisation: www.who.int

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THR-149

THR-149 In its drive to find solutions to treat diabetic eye disease and prevent loss of vision and blindness, Oxurion is developing and testing several compounds. One of these compounds for treating diabetic macular edema is THR-149.

What is THR-149?

Whom is THR-149 for?

THR-149 is a plasma kallikrein inhibitor. It’s a non-VEGF that inhibits DME independent of the VEGF pathway.

PKal inhibition could be an interesting proposition as a monotherapy in VEGF poor-responding patients or in combo therapy with VEGF as an effective target for treating DME.

Plasma kallikrein (PKal) is an enzyme crucial in the formation of bradykinins. Increased bradykinin levels result in the formation of edema and inflammation.

How does THR-149 work against DME? Literature data show that patients with DME have both elevated levels of plasma kallikrein and VEGF in the vitreous compartment. The elevated plasma kallikrein levels occur in a wide concentration range of VEGF varying from undetectable to high levels.

Inhibiting plasma kallikrein, as THR-149 does, can stop inflammation, permeability and the formation of microhemorrhages in DME patients. As such it improves eyesight.

Perspectives 2020

Over 40% of people with DME have little or no benefit from anti-VEGF treatment: their vision or the swelling of the retina does not improve. For them, non-VEGF therapies might make a big difference.

THR-149

What is retinal inflammation?

Inflammation is a biological response of the body. Retinal inflammation is an eye condition that causes vision impairment or, in the most severe cases, vision loss. Symptoms include blurred vision, sensitivity to light, and floaters in the eye, which may occur in one or both eyes.

What is vascular permeability?

Vascular permeability means the blood vessel wall is disrupted, causing fluids to penetrate the retina. Abnormal permeability causes edema in the retina, causing vision impairment or even vision loss. Symptoms include increasing number of floaters, floaters with flashes, shadows in peripheral vision, grey curtain over vision and sudden decrease in vision.

Collaboration with Bicycle Therapeutics THR-149 has been developed in partnership with Bicycle Therapeutics (Nasdaq: BCYC). Oxurion holds the exclusive license to the PKal inhibitor portfolio originating from this partnership.

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THR-149

Clinical update THR-149

THR-149, a highly potent plasma kallikrein inhibitor to treat DME In 2019, Oxurion announced positive topline data for the compound THR-149, a highly potent plasma kallikrein inhibitor to treat diabetic macular edema (DME). Not only was THR-149 safe and well-tolerated, the phase 1 clinical trial also showed fast onset of action in BCVA from day 1, following a single injection. “I am very encouraged to see signs of efficacy so early post-treatment, and to observe a clear durable benefit to the patient’s vision as measured by BCVA”, explains Dr. Pravin Dugel, M.D. Anti-VEGF is the standard of care for DME patients at the moment, but 40% has little or no benefit of these treatments. By targeting a VEGF independent pathway, an alternative treatment can be developed for poor or nonresponders to anti-VEGF treatment.

The macula is a very small, sensitive spot at the center of the retina. It is responsible for our central vision and color sight.

THR-149 is a plasma kallikrein (PKal) inhibitor, a preclinically well validated compound to prevent the induction of retinal vascular permeability (leading to edema), inflammation and the prevention of microhemorrhages.

Literature data show that patients with DME have elevated levels of plasma kallikrein and that the vitreous level of plasma kallikrein varies less compared to VEGF, making it a potentially more effective target for the treatment of DME.

Vitreous chamber is located behind the lens and before the optic nerve. It is filled with a thick, clear gel-like substance called the vitreous body.

Study set-up The phase 1 clinical trial for THR-149 evaluated the safety of a single intravitreal injection of THR-149 in 12

Perspectives 2020

patients with visual impairment due to center-involved DME. Three doses were tested: 3 patients were injected with 0.005 mg (‘low dose’), 3 with the middle dose (0.021 mg), and 6 with a high dose (0.125 mg). All 12 completed the study and attended all study visits from day 0 to day 90.

The retina is a thin layer of tissue on the inside of the back of the eye. It absorbs light and sends visual signals to the brain, which processes them into images.

Safety confirmed In the phase 1 clinical trial for THR-149 no dose-limiting toxicities and no serious adverse events were reported, indicating THR-149 is safe to use and well-tolerated. This means THR-149 is safe to use and well-tolerated.

THR-149

One adverse event was deemed related to study treatment (likely injection procedure). All ocular adverse events were likely due to the injection procedure, underlying disease progression or concomitant diseases.

Signs of efficacy Signs of efficacy were also observed in this clinical trial. Efficacy of treatments for diabetic macular edema (DME) is determined by measuring best corrected visual acuity (BCVA), mean central subfield of thickness (CST), and macular volume (MV). BCVA relates directly to vision, while CST and MV measure the edema level.

THR-149-001: Mean Change in BCVA From Baseline (Accounted for Rescue) All Treated Subjects, Overall

15 7.5 10

6.4

6.4 4.8

5.2

M1

M2

3.9 5

0

0 DL D1

D7

D14

M3

Impressively, a single injection with THR-149 improved BCVA from day 1 with 3.9 letters.

The mean improvement in BCVA was highest at day 14 (7.5), and improvement was maintained at 6.4 letters after 90 days.

THR-149-001: Mean Change in CST From Baseline (Accounted for Rescue) All Treated Subjects, Overall

100

0

Impact on swelling

26.4

50

-50 -100

10.5

30.4

30

M2

M3

20.4

0

-18

DL D1

D7

D14

M1

Changes in CST were marginal on day 1, followed by increase until study end.

Mean CST change was minimal and within the variability of measurement.

This means that changes in BCVA seem to be unrelated to changes in CST. ďƒ¨

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THR-149

This clinical trial also linked macular volume with BCVA improvement: lower macular volume is apparently indicative of better BCVA response. Macular volume was maintained over time in patients defined as BCVA responders among patients with 10 or more letters improvement in at least two consecutive visits. “Macular volume could potentially become a new anatomical predictor for BCVA improvement”, Pravin Dugel, M.D. notes.

treatment seems to be very good at stopping permeability but doesn’t work on inflammation. Preclinical models of diabetes show that PKal mediates vascular hyperpermeability, leukocytosis, inflammation, and microhemorrhages.

As a Pkal inhibitor, THR-149 is very promising because it allows us to possibly find a different mechanism of action”, Dr. Dugel explains.

Very promising

The results of the phase 1 study take THR-149 to a phase 2 clinical study with multiple injections. “These positive findings give us the information and confidence needed to plan

“Diabetic macular edema evolves from being driven by permeability to being driven by inflammation. Anti-VEGF

Potentially best-in-class

the next stage of THR-149’s clinical development. They also demonstrate that THR-149 has the clinical profile to potentially become the best-in-class PKal inhibitor and VEGF-independent therapy for treatment of DME”, says Patrik De Haes, M.D., CEO of Oxurion.

THR-149 could become a stand-alone therapy for suboptimal responders to the current standard of care (anti-VEGF injections). Or it could potentially be a therapy for all DME patients in combination with anti-VEGF treatment. As such, it could improve the vision (and lives) of millions of DME patients.

Measuring CST or BCVA?

BCVA

Diabetic macular edema is measured primarily by macular thickness (CST) or macular volume (MV).

It is thought that for BCVA to improve CST must come down. THR-149 indicates it is more complicated than this. In this trial, one injection with THR149 did not improve CST, but it did enhance vision with more than 6 letters for at least 90 days with a single injection.

Best corrected vision acuity (BCVA) is the measurement of the best vision correction achievable with tools like glasses or lenses. Vision acuity is measured on the standard Snellen eye chart. 20/20 vision is the aim: if you can pass that with your glasses, your BCVA is 20/20. There are many conditions that can cause bad vision, the most common being myopia (nearsightedness) or hyperopia (farsightedness). Retinal disorders like diabetic macular edema (DME) or age-related macular degeneration (AMD) are also a leading cause of bad visual acuity, so Oxurion is working to solve them.

Perspectives 2020

THR-149

Preparing a phase 2 study Oxurion is currently preparing a phase 2 trial for THR149 evaluating whether multiple doses of the compound can increase and prolong the visual improvement observed in the phase 1 study. THR-149 will be evaluated in patients who do not or do not optimally react to anti-VEGF treatment (non-responders/poor responders). Oxurion believes that if the phase 2 trial replicates and maintains the observed benefit from the phase 1 study, the compound can become a compelling drug candidate with clear value to the market.

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THR-149

Interview Pravin Dugel, M.D.

“Biological signal for efficacy of THR-149” “As an investigator of THR-149, I was encouraged to see the results from its clinical phase 1 trial.

The molecule was found to be safe, very safe even, and we got a biological signal that it worked," Pravin Dugel says.

The improvement in vision was measured only by BCVA, not in OCT. Why is that?

“That’s a question we get a lot. OCT, or optical coherence tomography, measures permeability, the amount of fluids the retina lets through. As of now it is the main biomarker to assess efficacy of DME treatment. For anti-VEGF drugs this is perfect. Anti-VEGF drugs stop permeability, so this marker can measure how well they work.

“VEGF-independent medicine possibly has a different method of action, for which there is no good biomarker at the moment. The next best thing is measuring vision improvement in the patients. And even in this small trial of only 12 patients, after 1 injection we found quick and maintained vision improvement from day 1 to day 90.

This improvement was bigger than could be expected through normal variability, so that is very promising.”

Why do we need a VEGF-independent pathway?

What is the future of THR-149?

“Because a significant part of DME patients cannot be treated successfully at the moment. We know that DME progresses from being driven by permeability to being driven by inflammation. Anti-VEGF drugs work for patients in the permeability phase but not for those in the inflammation phase. The problem is that we can’t tell which phase a patient is in because we have no biomarkers to test this.

Because of this, all patients with DME get anti-VEGF injections in the eye but about 40 percent respond poorly or not at all. A different approach is necessary to address these patients' need. For them a VEGF-independent pathway might be the solution.”

“THR-149 holds the potential to be the different method of action that poor- or non-responders to anti-VEGF treatment are waiting for. But first, a clinical phase 2 study will have to be designed to assess efficacy. Overall, the phase 1 study's data clearly warrant further clinical research with multiple injections of THR-149."

Pravin Dugel, M.D. is a clinical professor of ophthalmology and retinal specialist and works with Oxurion as an investigator and consultant.

Perspectives 2020

THR-149

Diabetic macular edema What is DME?

Current Treatment of DME

Diabetic macular edema (DME) is a diabetic eye disease caused by high glucose (blood sugar) levels. It damages and weakens the blood vessels in the eye, causing them to leak fluids. The result is swelling of the macula and eventually diabetic retinopathy.

DME can be treated with lasers, surgery, or medications injected into the eye to decrease or stop swelling of the macula.

The macula is responsible for sharp detailed vision, so these leaks can seriously degrade vision and in extreme cases even cause blindness.

Prevalence of DME Diabetes affects some 415 million people worldwide. Of these, 21 million (4.6%) were diagnosed with DME in the period 2015 to 2019. DME levels are highest in Africa (21.5%) and lowest in the USA. A third of people with diabetes do not know they have it, so these numbers may be underreported. *

Symptoms of DME DME can cause blurriness in the center of vision, appearance of dark spots or patches in the field of vision, dulling of colors, and difficulty in looking at bright light or glare. Objects might appear to change shape, size or color, or to disappear.

These symptoms can affect the ability to read, write, drive, and recognize faces.

Anti-VEGF injections block the protein that can make abnormal blood vessels grow and leak fluid. Injections of corticosteroid are also a possible treatment for DME. This medication reduces inflammation and swelling of the macula, but its side effects include pain and bruising around the injection site, face flushing, thin or pale skin, and insomnia.

At present, anti-VEGF medications are the first choice of treatment.

Why are new therapies needed?

The medications currently used to treat DME yield suboptimal results. Some 40% of patients do not respond to anti-VEGF injections or have a less than ideal response. The treatment burden is quite heavy: injections must be given every month, for at least a while, making the treatment time-consuming and costly.

New therapies are needed in order to successfully treat a larger number of patients.

20% of people with diabetes were diagnosed with DED (diabetic eye disease)* 7.6% have been diagnosed with DME*

* Source: https: www.diabetesresearchclinicalpractice.com/article/S0168-8227(19)31257-4/fulltext#secst035) https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(19)31257-4/fulltext#secst030

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THR-687

THR-687 The second target Oxurion has identified to treat diabetic macular edema and age-related macular degeneration, is integrin. To inhibit this target, Oxurion is currently clinically developing the molecule THR-687, a compound with a broad potential.

What is THR-687?

THR-687 is a small molecule pan RGD integrin antagonist.

Integrins play an important role in various biological processes including cell differentiation, adhesion, migration, invasion and proliferation.

Given their broad function, integrins are associated with various eye diseases such as diabetic macular edema (DME) and wet age-related macular degeneration (wet-AMD). Integrins are implicated in main pathologic hallmarks like neovascularization, inflammation, fibrosis and vascular leakage.

By targeting integrins, THR-687 could attenuate all these vision-threatening processes given its broad therapeutic potential.

How does THR-687 work?

THR-687 antagonizes RGD-binding integrin receptors in the low nanomolar range. The integrins are involved in the activation of multiple pathological pathways of DME and wet-AMD, by interacting with multiple growth factors or cytokine receptors in a direct or indirect manner.

Perspectives 2020

THR-687 has therefore the potential to attenuate different disease processes such as vascular leakage, inflammation, neovascularization and fibrosis induced by multiple stress factors (including but not limited to VEGF, cytokines,.‌.).

Therefore, THR-687 has a broader biological effect than antiVEGF therapy, the current golden standard of care for patients with DME or wet-AMD.

Whom is THR-687 for?

There is a large unmet medical need in the DME market, since a significant proportion of these patients do not respond well to current standard of care therapies.

Given the fact that THR-687 affects multiple signaling pathways simultaneously (including the VEGF pathway), it has the potential for treating all patients, including naĂŻve patients and patients sub-optimally responding to anti-VEGF therapy.

Besides DME, THR-687 has also the potential to be very promising in wet AMD and other ocular indications.

THR-687

What is angiogenesis?

Angiogenesis is a process by which new blood vessels are formed from pre-existing vessels. Pathological angiogenesis is associated with retinal diseases such as Diabetic Macular Edema, (Proliferative-) Diabetic Retinopathy and wet Age-related Macular Degeneration, leading to vision impairment or even blindness.

What is retinal fibrosis?

When retinal fibrosis occurs, abundant tissue (‘scar’) forms in the retina. It is a reparative process in response to retinal injury, which can be caused by inflammation. Excessive fibrotic scarring can lead to vision impairment or even blindness.

In-licensed from Galapagos THR-687 is derived from the small molecule integrin inhibitor library generated and owned by Galapagos, for which Oxurion has an exclusive worldwide license.

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THR-687

Clinical update THR-687

THR-687, a potent pan-RGD integrin antagonist in development for DME Oxurion kick-started 2020 with positive topline data from phase 1 clinical trial evaluating THR-687 for treatment of DME. This molecule showed a rapid onset of action across all doses after just one injection. Improvement was observed in vision, measured by best corrected visual acuity (BCVA), and macular swelling, measured by central subfield thickness (CST) on OCT (optical coherence tomography). “The positive phase 1 data indicates that THR-687 could potentially be an effective therapy for patients with DME”, notes Dr. Arshad Khanani, M.D., M.A. T H R- 6 87, a p a n - R GD i nte g r i n antagonist, has a broad therapeutic potential. This compound can target multiple disease hallmarks of diabetic retinopathy (DR), with and without DME, and also with wet age-related macular degeneration (AMD).

Preclinical models show that THR-687 is a potent inhibitor of angiogenesisinduce d vascular leakag e. The inhibition of integrins targets multiple processes involved in pathological angiogenesis and vascular leakage for common retina pathologies. An integrin antagonist drug has the potential to block several pathways, and as such reduces the expression of growth factors as well.

Set-up & safety The phase 1 study evaluated safety and tolerance of a single injection of THR-687 in 12 patients with DME with a history of response to prior antiVEGF, corticosteroid treatment or laser.

Perspectives 2020

Each patient received one of three doses: 0.4 mg (3 patients), 1 mg (3 patients) and 2.5 mg (6 patients). All 12 patients completed the study, with no dose limiting toxicities or serious adverse effects reported.

In each dose group, there was one subject with a non-serious adverse event that was deemed to be related probably to the injection procedure.

Otherwise, there were a few other side effects likely due to disease progression or concomitant diseases. In total, 9 adverse events were reported in 5 subjects. Three of them received rescue therapy.

with 9.2 letters gained. Most impressively, this improvement was mostly maintained post-single injection at month 3 with a mean overall gain of 8.3 letters.

Overall, a marginal impact on mean CST was noted up to month 1, followed by an increase until month 3.

“THR-687 could potentially be an effective therapy for patients with DME.” Arshad Khanani, M.D., M.A.

Immediate vision improvement At day 1 an immediate improvement in vision was found. The overall mean change in BCVA was rather modest at day 1 with 3.1 letters gained, but at day 7 it was already 7.2 letters. The highest mean change was reported at month 1

Dose response A pronounced dose response is observed for this single injection of THR-687.

Patients receiving the highest dose (2.5 mg) noted an improvement in BCVA of 12.3/12.5 letters at month 3.

THR-687

A mean CST decrease of 106 µm was reported at day 14 in the highest dose group.

This makes THR-687 a promising candidate for treatment of vision-threatening eye diseases such as DME and wet AMD. Potentially, it could become a standard of care for all DR patients, with or without DME, and wet AMD patients based on its broader biological effect than anti-VEGF therapy.

On track to start phase 2 clinical trial “I am very encouraged to see excellent signs of efficacy so quickly post-treatment. The study also demonstrated that THR-687 had a rapid positive effect on best corrected visual acuity (BCVA) that was durable for up to 3 months after just a single injection. This promising initial data indicate that THR-687 could potentially be an effective monotherapy for patients with DME”, says Dr. Arshad Khanani.

Patrik De Haes, M.D., CEO of Oxurion, said: “These encouraging findings from our phase 1 clinical trial with THR-687, along with the very positive feedback we have received from the retinal community, highlight the significant potential of this novel integrin antagonist. We are on track to start a phase 2 clinical study with THR-687 in treatment-naïve DME patients in H1 2021.”

THR-687-001: Mean Change in BCVA From Day 0 (Accounted for Rescue) All Treated Subjects, Overall

20 15 10

7.2

7.7

D7

D14

9.2

8.8

8.3

M1

M2

M3

3.1

5

0.0 0

D0 D1

THR-687-001: Mean Change in CST From Day 1 (Accounted for Rescue) All Treated Subjects, Overall 120 80 4.1

40 0 -40

-3.8

-80 -120

-43.9 D0 D1

-35.8

-38.9

D7

D14

M1

M2

M3

THR-687-001: Mean Change in BCVA From Day 0 (Accounted for Rescue) All Treated Subjects, By Dose

20

THR-687 0.4mg (N=3)

THR-687 1.0mg (N=3)

THR-687 2.5mg (N=6)

15 12.5 10 6.7

5 0

1.7 D0 D1

D7

D14

M1

M2

M3

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THR-687

Interview Arshad Khanani, M.D., M.A.

“Initial data points to clinical efficacy” “The study was phase 1 and designed to assess safety. From evaluating a small number of subjects, THR-687 showed a signal of clinical efficacy based on best corrected visual acuity," noted Arshad Khanani, M.D., M.A., an investigator in the study.

Dr. Khanani presented the topline re s u lt s at t h e Fe b r u a r y 2 02 0 Angiogenesis, Exudation and Degeneration meeting in Miami, Florida. “I was very pleased to present the data of the phase 1 clinical trial of THR-687. They were well received by my colleagues,” he reported.

Why were you pleased with the data?

“The primary endpoint of the study was safety, and THR-687 was found to be safe without any dose-limiting toxicities. The patients received prior treatment with either anti-VEGF or steroid injections and we still saw visual acuity improvements. These were relatively difficult patients to treat. The high-dose group showed clinically meaningful gains in vision and improvements in OCT, which is very encouraging.”

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What is the future of THR-687?

“Preclinical studies show that integrins work on several pathways linked to diabetic eye disease. As THR-687 is a pan-RGD integrin antagonist, it can block these pathways and improve vision. The result of the phase 1 clinical trial argues in favor of a phase 2 study in naive DME patients to establish the efficacy and safety of THR-687.

These initial data show that THR-687 can potentially be an effective monotherapy or adjunctive therapy for patients with DME."

Dr. Arshad Khanani, M.D., M.A. is an ophthalmologist and vitreo-retinal specialist and the managing partner and director of clinical research at Sierra Eye Associates, Reno, Nevada, USA. He is a consultant to the company and an investigator for both THR-149 and THR-687 clinical trials.

THR-687

Diabetic retinopathy What is DR?

Prevalence of DR

Diabetic retinopathy (DR) is a consequence of too much blood sugar, which damages and weakens blood vessels in the retina. The vessels can swell, leak or clog, or new vessels can start to grow. DR is a very common eye disease for people with diabetes and can cause vision impairment or, at worst, vision loss. DR is the most common cause of preventable blindness in the world.

At present, an estimated 146 million people are affected by DR and anyone with diabetes is at risk of developing it. Up to one third of diabetes sufferers will eventually develop DR.

Symptoms of DR Symptoms are blurriness, floating spots, dark areas of vision, and difficulty perceiving colors or contrast. These are typically absent in the disease's early stages.

There are two main stages in diabetic retinopathy: early (non-proliferative diabetic retinopathy, NPDR); and more advanced (proliferative diabetic retinopathy, PDR).

Treatment of DR

NDPR causes damaged blood vessels and blurred vision.

When these vessels start to leak fluids this is called diabetic macular edema (DME). The reverse is also a possibility: blood vessels in the retina close off so blood cannot reach the retina. This is called macular ischemia.

Why are new therapies needed?

PDR is the more advanced stage of DR and happens when new blood vessels start to grow in response to ischemia. This is called neovascularization.

In a survey, 79% of respondents said their vision impairment due to DR or DME made everyday activities - driving, working, cooking, cleaning their home - difficult and in some cases impossible.

Current treatment of DR consists of laser treatment, surgery or anti-VEGF injections. These reduce the swelling of the retina and slow vision loss.

About 40% of patients do not respond to anti-VEGF injections, or reaction is suboptimal. The treatment burden is also quite heavy: the injections must be given every month for at least a while. This makes treatment time-consuming and costly. Lastly, anti-VEGF only suppresses symptoms and does not get at the cause.

New therapies need to be developed to successfully treat a larger number of patients.

* Source: DR Barometer: https://drbarometer.com

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Researching the AMD pathway

Researching the AMD pathway The focus of the Oxurion research and preclinical development teams was in 2019 almost exclusively on in-vivo and in-vitro validation of new pathways and compounds for treatment of dry AMD. We hope to be able to present preclinical proof of concepts in 2020.

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Researching the AMD pathway

Interview Alan Stitt

“Oxurion is well-positioned to develop pathways to address dry AMD” In 2019, Oxurion made the strategic decision to also focus on research and development in dry age-related macular degeneration (AMD): a major cause of vision loss worldwide, but one with no effective treatment. This represents a huge challenge but Oxurion feels equal to the task. “The number of patients affected by dry AMD continues to increase and there is considerable research effort being channeled into better understanding the disease and, of course, developing an effective treatment”, explains Professor Alan Stitt, McCauley Chair of Experimental Ophthalmology at Queen’s University in Belfast.

Prof. Stitt: “Age-related macular degeneration occurs as two types, often referred to as wet or dry AMD. The vision loss associated with wet AMD (also called neovascular AMD) can be addressed using regular intravitreal delivery of drugs called antiVEGFs. There are efforts to improve such treatments, such as with Oxurion's THR-687 molecule. Dry AMD (also called geographic atrophy) affects a much greater proportion of patients, and unfortunately today their disease is largely untreatable.”

“Dr y AMD is a slow, progressive degeneration in the macular region of the retina causing central vision deficits. For sufferers this greatly diminishes their everyday life by reducing the ability to do normal activities like reading, driving or even recognizing faces. In the worst-case scenario it can become impossible to live an independent life.”

Challenging & complex disease An effective treatment for dry AMD could change many lives, but arriving there means navigating a long and challenging path.

“Dry AMD is a very complex disease to tackle”, Prof. Stitt points out. “Scientists are still trying to get a handle on what causes the onset of dry AMD and we still cannot reliably predict who will develop the condition and how rapidly it will progress. There can be distinct differences between patients diagnosed

with dry AMD although we know this is influenced by factors like genetics, gender, ethnicity and tobacco smoking.

There is much work under way to understand the drivers for this disease, especially in the early stages”.

“It would be ideal to intervene early when people still see reasonably well. Stopping dry AMD in its tracks will prevent progression to the late, sight-threatening stages of the disease.

Once cells in the retina have died it is hard to replace them”, he adds. 

“We want to develop a treatment that addresses the underlying causes of dry AMD so that progression of the disease is stopped or at least slowed down.”

Professor Alan Stitt

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Researching the AMD pathway

Tackling the cause of the disease Regarding treatment, Prof. Stitt is optimistic. “Our goal for both wet and dry AMD is to prevent the disease early when the retina's cells are not too badly damaged. Many researchers across the world are seeking to tackle the underlying causes of AMD so its progression can be stopped or at least slowed. While they have been extraordinarily successful, anti-VEGF treatment for diabetic macular edema (DME) or wet AMD can prevent vision loss but they only suppress symptoms and don’t resolve the underlying cause. Therefore, patients must return

regularly for an injection into the eye which, of course, is unpleasant and inconvenient. The recurring costs are also a burden for health service providers”.

While still committed to finding better treatments for DME and wet AMD, Oxurion recently announced that it is exploring new pathways for dry AMD. Since he shares Oxurion’s interest in these important diseases and its commitment to improve patients' lives, Prof. Stitt was happy to accept an official partial consultancy role in the company.

The company's research teams are working on preclinical models in dry AMD. “I believe the basic knowledge Oxurion has already developed with THR-149 and THR-687 in DME and wet AMD is very transferable to dry AMD. Its combination of established expertise in both retinal disease and therapeutic target development, plus translation into clinical results, positions Oxurion very well to do this”, Prof.

Stitt concludes .

Alan Stitt is an academic researcher at Queen’s University in Belfast (Northern Ireland). He researches diabetic retinopathy, age-related macular degeneration and regenerative medicine, and is internationally recognized for his research in ophthalmology. In September 2019 he took a partial consultant position at Oxurion.

His role is to advise on target preclinical development related to macular degeneration, diabetic edema and retinal disease.

Ambitious plan for dry AMD in 2020 “Oxurion aims at delivering at least one dry AMD preclinical proof of concept. In collaboration with top retina experts such as Prof. Stitt, we are identifying the most promising pathways for treating dry AMD. Our goal is to make a difference in the life of these patients”,

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Patrik De Haes, M.D., CEO of Oxurion, says. “It must be clear that as soon as we can craft a value path for those patients, we expect this will automatically translate into value creation for our shareholders as well”, Thomas Clay, Chairman of the Board, adds. .

Researching the AMD pathway

Age-related macular degeneration What is AMD? Age-related macular degeneration (AMD) is a progressive eye disease associated with aging. It is caused by degeneration or deterioration of cells in the macula, the region at the back of the eye responsible for central vision and critical for activities like reading, writing and driving. AMD is the leading cause of blindness is the United States.

It is not known what causes AMD, although hereditary and environmental factors are thought to play a role. Smoking is a known risk factor: it doubles the chance of developing AMD. With wet AMD being female, over 60 and Caucasian also increase the risk.

There are two types of AMD: wet and dry.

• • • •

About 85 to 90 percent of people with AMD have dry AMD. This back of the eye disease occurs when the retina thins as part of the aging process. Dry AMD worsens over time, although much slower than the wet variety. Dry AMD usually affects both eyes.

Wet AMD is a more advanced stage of AMD and develops when abnormal blood vessels grow into the macula and start to leak fluids or blood, leading to formation of scar tissue in the macula. The main consequence is rapid loss of central vision.

The disease has three stages: early, intermediate, and late. It is only in late-stage AMD that vision loss becomes noticeable.

Prevalence of AMD Worldwide, 170 million people suffer from AMD. Wet AMD only affects 10 percent of AMD patients but is responsible for 90 percent of all AMD-related vision loss.

Symptoms of AMD Reduced central vision in one or both eyes Blurry or blind spots in the field of vision Decreased intensity or brightness of colors (‘grayness’) Distortions of center frame of vision (straight lines seem bent)

A common early sign of dry AMD is large and numerous drusen: tiny yellow or white deposits under the retina.

Treatment of AMD For dry AMD there is currently no treatment. Wet AMD is treated the same way as diabetic retinopathy and diabetic macular edema. A complicating factor is that most people only know they have AMD when they experience vision loss, by which time it is usually too late to effectively treat it. It is also very hard to predict the disease's progression.

Going on a diet, exercising, wearing sunglasses, and quitting smoking might help in halting the development or progression of AMD.

* Source: https://yoursightmatters.com/what-is-amd-and-what-are-the-symptoms/

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Part of the global eye community

Part of the global eye community Oxurion joins forces with NGOs and patient advocacy organizations like Prevent Blindness and Retina Global to prevent vision loss and fight blindness worldwide.

Perspectives 2020

Part of the global eye community

Prevent blindness

“By partnering with Oxurion we reach more people” For the second year in a row, the American non-profit organization Prevent Blindness has partnered with Oxurion to encourage people to make their eye health a priority. “Partnerships with companies like Oxurion help us spread the important message to take care of yourself and your eyes. And it’s working: each year we notice much more traffic to our website and more requests for information on eye diseases related to diabetes,” notes Jeff Todd, president & CEO of Prevent Blindness.

Prevent Blindness has been a patient advocate for healthy vision for over a century. “Through awareness and education, our goal is to minimize the damaging effects that diabetes can have on vision,” Jeff says.

“Through awareness and education, our goal is to minimize the damaging effects that diabetes can have on vision.”

Jeff Todd, President and CEO of Prevent Blindness

Diabetic retinopathy (DR), diabetic macular edema (DME), and agerelated macular degeneration (AMD) are among the eye diseases Prevent Blindness is working to prevent.

Oxurion is seeking solutions for these eye diseases, so the collaboration is only natural.

“Our partnership with Oxurion during Diabetes-Related Eye Disease Awareness Month in November allows us to spread the message, to promote on social media and lead more people to our website for education,” Jeff concludes.

Empowering patients To reach more people and educate them about serious eye diseases that can cause significant vision loss and even blindness, Prevent Blindness will continue to work to empower patients in 2020.

Jeff Todd: “We want to get patients involved; we want to hear their voices.

Prevent Blindness has always been about representing patients with eye disease. Now we want to also empower them and their caregivers to advocate for themselves. By sharing real life stories we're certain we can reach more people and educate them on eye diseases, how to prevent and treat them.” 

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Diabetes-related eye disease For people with diabetes, preventing damage to their eyes starts with controlling blood sugar levels. That means taking diabetes medication, eating healthy, exercising, and getting eye exams at least yearly. “We cannot stress enough how important it is for those living with diabetes to see their eye doctor at least once a year. The earlier we can detect these eye diseases, the more successful treatment can be,” Jeff emphasizes.

But of course, before they can see an eye doctor to check for diabetesrelated eye disease people must know they have diabetes. This isn’t always the case. They may not recognize the symptoms or realize that their problems are serious. Making people aware of diabetes symptoms is also an important goal.

Frequent urination

Abnormally hungry Abnormally thirsty

Experiencing blurred vision Tingling feet or hearing loss and itchy skin

Part of the global eye community

Retina global

“Our goal is to train the people on the ground to obtain a sustainable outcome” Retina Global sends retina specialists to parts of the world having a great need for expert eye care. “These specialists volunteer their time, effort and expertise to areas that lack retina specialists. They perform eye checks, provide treatment, or do surgery. On top of that they also train medical staff on the ground so they can work independently”, explains Rajat Agrawal, M.D., CEO of Retina Global. “It is always our goal to have a sustainable outcome.”

Retina Global currently operates in Belize, the Bahamas, Burundi and Bolivia.

Projects in Haiti, Mexico and Ethiopia will start soon. “In these underserved areas there is a great need to treat diabetic retinopathy (DR). Everywhere we go we see people with DR, and often treatment is unaffordable or there simply isn’t a retina specialist available. Doctors in these countries don’t always have the knowledge or the tools to diagnose these eye diseases.”

The BOLDR project Retina Global plans to change that. With the support of Oxurion it started the BOLDR (Bolivian Diabetic Retinopathy) project. BOLDR is committed to reducing the number of people going blind due to the increasing prevalence of diabetic retinopathy in Bolivia, and to combating the rising incidence of age-related macular degeneration (AMD) in this South American country.

“Everywhere we go we see people with DR. Treatment is often not available for them.”

Rajat Agrawal, M.D., CEO of Retina Global

“We are currently focusing our efforts in Bolivia on the city of Cochabamba, the country's fourth largest city with some 650,000 inhabitants. There were no trained retina specialists in public health care. Most patients with diabetes go to a primary care physician, but these don't always know they need to also screen for eye diseases as. Courses and lectures for medical staff supported by Oxurion will change that”, Rajat Agrawal explains.

Public Awareness Not only doctors and nurses need information on these diseases: patients and patient groups do as well. “Raising public awareness of diabetic eye disease is another of our goals. People need to know they need regular eye screening and how to recognize the symptoms. By providing information to patient groups and running campaigns, we are confident we can make people aware of DR and get them to turn to their doctors and seek treatment. Of course, we also need to train doctors and medical staff so they can do the necessary eye checks and give treatments.”

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Oncurious

Oncurious

Perspectives 2020

Oncurious

Next-generation I/O cancer treatments Oncurious is preparing a preclinical proof of concept from its portfolio of immuno-oncology assets acquired from VIB, the Flemish Institute of Biotechnology. The ambition is to develop nextgeneration immunotherapies targeting a very broad spectrum of cancers.

Im m u n o - o n co lo g y i s a ra p i d ly evolving branch of science. It’s a specific type of immunotherapy that stimulates the immune system to fight cancer cells and tumors. It could offer an alternative or complementary treatment to chemotherapy, radiation, and surgical removal of tumors.

Unfortunately, the first generation of immunotherapies brought to market only helps a minority of patients.

Many do not respond to them, and for multiple types of cancer they are not effective at all. Research on new ones is thus urgently needed.

Oncurious joined forces with VIB two years ago to take immuno-oncology research to the next level. Their

combined expertise pursues a single goal: to develop innovative therapies targeting a very broad spectrum of cancers, thus benefiting a large group of patients.

Research groups are working on a preclinical proof of concept for a portfolio of innovative immunooncology assets that the company plans to present in I/O in 2020.

Clinical trial researching treatment of medulloblastoma

tumor that is the most common malignant brain tumor in children.

TB-403, an anti-PIGF, blocks the PIGF signals and stops the tumor cell s f ro m g row in g . Pre clinic al studies suggest this anti-PIGF leads to tumor regression, decreased metastasis, and higher survival rates.

At the same time, anti-PIGF therapy will probably be much less toxic than chemotherapy.

Oncurious is still recruiting patients with relapsed or refractory medulloblastoma to conduct a phase 1/ phase 2a clinical trial to evaluate the safety of different doses of TB-403.

One project Oncurious is to develop an alternative treatment for medulloblastoma, a rare life-threatening

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About Oxurion

About us Oxurion at a glance Oxurion is a biopharmaceutical company developing treatments to preserve vision for patients with diseases affecting the back of the eye.

The Company has engineered a diverse portfolio of clinical stage drug candidates for treatment of diabetic eye disease, including DR and DME, a leading cause of blindness in people of working age worldwide.

Oxurion is headquartered in Leuven, Belgium, and is listed on Euronext Brussels under the symbol OXUR.

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About Oxurion

Our team People at Oxurion Oxurion employs 77 people worldwide, all are united by a shared goal: to make Oxurion a global leader in developing and commercializing innovative treatments for back of the eye disorders.

Most members of the Oxurion international team hold a master’s or PhD degree. The majority work at our headquarters in Leuven (Belgium) or from our office in New Jersey (U.S.).

Each member of the Oxurion team provides a distinct viewpoint and set of experiences in the biopharmaceutical industry. The diversity and experience of the team stimulates creativity and problem-solving while enabling the company to successfully develop and commercialize therapeutics to preserve the vision of patients worldwide.

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About Oxurion

Shareholders information Listing

Paying agent services

Oxurion is listed on Euronext Brussels under the symbol OXUR.

KBC Bank acts as the paying agent. The paying agent will not charge shareholders with respect to payments of dividends, the exercise of subscription rights and other events concerning Oxurion shares. Shareholders should inform themselves about the amounts that other financial intermediaries may charge in connection with paying agency services.

Investor relations Our investor relations policy includes: • Providing reliable, accurate and valuable information in a timely manner to help shareholders make informed decisions.

• Full transparency • Operating within the company’s policies and adhering to relevant security laws and regulations • Strengthening our dialogue with the investment community • Providing access to the senior management team

Shareholding structure As of 31 December 2019, Oxurion has a total number of 38,291,950 outstanding shares and a total number of 1,301,000 warrants, of which 697,800 are accepted unexercised, 417,000 are offered, but not yet accepted and 186,200 are to be assigned.

Shareholder

Mr Thomas M. Clay and entities controlled by him Baron Philippe Vlerick and entities controlled by him Novartis Pharma AG Public

Perspectives 2020

% of voting rights

8.8% 6.1% 5.7% 79.4%

Financial calendar Date

Event

05 May 2020 07 May 2020 17 Sep 2020 15 Oct 2020

Annual Shareholder’s Meeting Business Update Q1 2020 Half Year Results FY 2020 Business Update Q3 FY 2020

About Oxurion

Contact information Corporate HQ

Contact Information

Oxurion nv Gaston Geenslaan 1 B-3001 Leuven Belgium T +32 16 75 13 10 F +32 16 75 13 11 info@oxurion.com

Responsible editor: Wouter Piepers Global Head of Investor Relations and Corporate Communications T: +32 (0) 16 75 13 10 M: +32 478 33 56 32 F: +32 16 75 14 66 wouter.piepers@oxurion.com www.oxurion.com

USA ThromboGenics, Inc. - subsidiary of Oxurion nv 101 Wood Avenue South Suite 610 Iselin, NJ 08830 USA T +1 732 590 2900 T +1 855 301 1600 info@oxurion.com

Ireland Oxurion nv Irish Branch Office 109A 12 Camden Row Dublin 8, Ireland T +353 1 479 0596 info@oxurion.com

Creation & Copywriting Cantilis www.cantilis.be

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