A key strength of Oxurion is its collaborative mind-set. Its Science team displays this under the leadership of Susan Schneider, MD (Chief Medical Officer), Andy De Deene, MD (Global Head of Development) and Jean Feyen, PhD (Chief Scientific Officer). They guide development of the company’s innovative pipeline, driven by intensive research and based on solid scientific evidence.
“We work as a complimentary team, putting Oxurion in a unique position as a very agile biotech company,” says Susan Schneider, who joined the company’s leadership team in 2017. With nearly 15 years of experience in clinical drug development, she oversees the company’s global clinical and medical groups.
The exciting and innovative Oxurion’s pipeline persuaded Susan Schneider to join the team. “This is a small R&D company with big ambitions and various development opportunities for the future. We take a truly objective and scientific approach to understanding the retinal space and the underlying mechanisms of action in diabetic eye disease. That positions us well to address the pathophysiology at hand and to focus on developing important disease-modifying treatments. The close cross-functional interactions between our preclinical, clinical and medical teams clearly make that possible.”
“Development is cross-functional,” agrees Andy De Deene. “Our approach is unique because all teams stay involved throughout the process. In the clinical phase Development works hard on the regulatory, quality and safety aspects to get approvals in several countries. But our ultimate goal is to bring new therapies to clinics, so the medical side is involved from the beginning and critical at the end. And we continually consult the Preclinical Research people along the way. In bigger companies these fields are typically divided.”
Jean Feyen confirms: “Throughout the development, even in phase II and III trials, we remain accountable for the research targets we explored because every phase has preclinical aspects to address. This type of complimentary action lets us be fast and agile without sacrificing quality.”
Ophthalmology as science platform
In exploring innovative pathways to fight diabetic eye disease, Oxurion aims to understand key areas of unmet medical need. “We want to make a difference and to build on the insights and experience gained from developing ocriplasmin (JETREA®) for symptomatic VMA/VMT,” says Susan Schneider.
Jean Feyen confirms: “In the biotech field many companies have science platforms based on a certain technology, like antibodies. Ours is ophthalmology, and more specifically the retinal space. We have a wealth of knowledge and experience in understanding retinal diseases and patients’ unmet medical needs. Susan now brings additional extensive ophthalmology clinical development expertise, so together we can to map the Oxurion medical scientific strategy for the future.”
For the past two years the Science team has been working hard on drug development targeting diabetic retinopathy (DR). This yielded one program in clinical development and two more for which clinical trials are targeted to be initiated in 2018.
Combination study with THR-317
One of the compounds, THR-317, a placental growth factor antibody, is being evaluated to potentially treat diabetic macular edema (DME) in persons with diabetes mellitus. “In preclinical models this compound has some distinct pharmacology features compared to the current standard of care with anti-VEGF therapy,” explains Jean Feyen. “Like anti-VEGF, anti-PlGF also affects the edema aspect of diabetic retinopathy. But in addition, our research has shown a positive effect of anti-PlGF on inflammation, another key disease hallmark of DR. Moreover, our compound is neutral and perhaps even slightly beneficial for the neuronal compartment of the eye and inhibit collagen deposition in fibrotic eye lesions.”
Oxurion is running a phase II clinical study with THR-317 to investigate its efficacy and safety profile, in combination with anti-VEGF for the potential treatment of DME. “We want to see whether we can address additional components of diabetic eye disease, such as inflammation and/or neurodegeneration in this program”, says Susan Schneider. “That way we could potentially offer improved treatment outcomes for patients. Our focus on the patient helps to define our areas of concentration, that, in turn, drive our drug development goals.”
Jean Feyen continues: “Our ultimate goal is to research and develop innovative therapies with disease-modifying activity. DR is a chronic and degenerative disease for which there is currently no adequate treatment. Anti-VEGFs are saving patients’ vision, but they don’t cure the disease and require repeated injections in the eye. If we could modify the disease by combining current therapies and novel products with added benefits, this could potentially reduce the number of injections over time.”
Continued development of research targets
Oxurion has also initiated a phase I clinical study to evaluate THR-149, a plasma kallikrein inhibitor, for treatment of DME. “With plasma kallikrein as a validated target, this compound has a strong potential on the vascular leakage aspect of DR,” says Andy De Deene.
With THR-687, an integrin antagonist, Oxurion is aiming at a broader spectrum of DR hallmarks. A clinical trial with this compound will be initiated shortly. “This compound could have positive effects on inflammation and edema, but also on neovascularisation. It’s a powerful combination that could target both early- and later-stage DR,” says Jean Feyen.
Addressing a sub-optimal response to current therapies
“What’s important is that all our pathways are anti-VEGF independent,” adds Andy De Deene. “For example, we explore THR-317 also in combination with anti-VEGFs but they all can work independently. That is why we also focus on patient populations where anti-VEGFs don’t always work.”
Diabetes mellitus, as a systemic disease, is a pandemic globally and with that, an increase in the incidence of diabetic eye disease goes hand in hand. Diabetic retinopathy can result in vision loss and even blindness. “We believe that this is a growing area of unmet medical need in which new and innovative alternative and/or adjunctive treatments might be able to address its multifactorial nature and thus have the potential to improve outcomes,” says Susan Schneider.
Reaching out to the community
A vital success factor for the company’s clinical programs is its strong relationship with the ophthalmology community. “Interacting with scientists and clinical investigators is critical to us,” says Jean Feyen. “We’re not going to cure eye diseases by ourselves as a company. We depend on a broad community of retinal specialists, scientific experts and patient advocacy organizations. Our goal is to a have highly productive drug discovery engine by integrating the knowledge in the field and selected scientific collaborations.”
Oxurion therefore consults regularly with various experts during the research and development process for all compounds. “They bring complimentary knowledge from which we learn and can apply to our programs. It’s essential for us to stay scientifically sound and clinically relevant,” adds Susan Schneider.
“That is why we are excited and proud to see our preclinical work published in international peer-reviewed journals like Experimental Eye Research. It helps to illustrate the high quality of our science,” says Jean Feyen.
“Developing innovative medicines doesn’t happen in isolation. We look for as many interactions as possible that enable us to deliver innovative drugs. Regaining the global rights to JETREA® pushed us forward in that respect. We are now a true global player, giving us even more exposure to the medical community”, adds Andy De Deene.
“In the end, our primary focus is always on the patient,” says Susan Schneider. “Through insights gained from healthcare professionals, advocacy groups and the patients themselves, we hope to continue to gain a sound and relevant perspective on this very important aspect of drug development. That way we keep optimizing our potential to provide the best possible therapies to treat debilitating eye diseases.”
“The Science team is now highly focused on operationalizing aspects of its rich development pipeline in diabetic eye disease, which includes initiating these clinical programs and enrolling the first patients in these clinical trials,” says Susan Schneider. “We will also continue to look to optimize our programs in a data driven and patient-centric way.”
Meanwhile, the company is already looking to the future, exploring unmet medical needs in the broader area of retinal vascular diseases and in additional areas of interest in back of the eye disorders. “We’re at a crossroads: our rich DR portfolio is being developed but we also have some new targets being discovered. We intend to remain current with what’s happening in the ophthalmology space and in touch with the community to explore the best strategic paths moving forward to the future,” concludes Jean Feyen.