PERSPECTIVES

A strategic focus for Oxurion: researching and developing non-VEGF pathways for diabetic eye disease

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”.

Jean Feyen, PhD, Chief Scientific Officer at Oxurion

Jean Feyen, PhD, Chief Scientific Officer at Oxurion

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

The compounds THR-149 and 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 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

 

THR-687 is “a pan-RGD integrin 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 age-related 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”.

Andy De Deene, MD, Global Head of Development at Oxurion

Andy De Deene, MD, Global Head of Development at Oxurion

Fast & durable improvement

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 eyesight. Already in the phase 1 clinical trials we noticed signs of efficacy even with the limited group of test subjects. When we started 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 eyesight 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.

A chance to address dry AMD

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.

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.

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

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

“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.

May 5th, 2020