Developing new therapies is sometimes not enough: for retinal indications, accurate delivery is key to making a drug work. Lowering the patient burden by minimizing injections is also an important factor to consider. Oxular, an Oxford-based biotech and V-Bio Ventures portfolio company, has developed a technology platform to address the unmet need for less frequent dosing and better drug delivery in retinal diseases.
By Amy LeBlanc
Around the world, an increasing number of people are struggling with vision loss. With an aging world population, and diabetes sharply on the rise, millions of patients are struggling with retinal diseases that cause vision loss. As new products are being developed to try and help these people, the global retinal therapeutics market is set to surpass $14 billion by 2024.
However, several unmet needs remain, including improved formulation technology and drug delivery. Current treatments are still administered to the eye via an injection straight into the jelly-like interior of the eye, not directly to the structures that require intervention (like the macula at the back of the eye). Injections are also frequent, burdening patients with regular, costly and uncomfortable visits to the doctor’s office. Formulations need to be upgraded to enable long acting treatments and reduced dosing schedules.
Seeing this unmet need, an Oxford-based team decided to tackle the challenge. They founded Oxular: a company dedicated to safe and effective retinal drug delivery solutions and transformational treatments with a profound impact on patients’ quality of life.
Setting their sights on a painful problem
Oxular was founded in 2014 by CEO Tom Cavanagh and CSO Ronald Yamamoto and since 2016 supported by V-Bio Ventures. The company has created a technology platform for unparalleled drug delivery to back-of-the-eye structures like the macula, with a pipeline of treatments for several prevalent retinal diseases, including diabetic macular edema (DME), ocular cancers and other rare and orphan conditions. Tom Cavanagh explains the inspiration for Oxular’s genesis:
If we could design a product that could reduce the number of times someone has an injection in their eye, we could increase that patient’s quality of life dramatically. – Tom Cavanagh
“Both Ron and I were looking at unmet needs in ocular diseases, particularly for retinal diseases. At the time, the world was in the middle of a therapeutic revolution, where new types of drugs were transforming how retinal diseases are treated. Previously, options had been limited to laser eye surgery and other drug classes that weren’t as effective or had severe side effects. These new drugs, like anti-VEGFs, really changed the game.
However, the dosing regimen was very burdensome for patients. We felt that there was an opportunity to deliver retinal therapies prepared in longer lasting formulations in a more targeted way, to make it so that so patients would have to have fewer injections. For current anti-VEGF treatments, for example, treatments often start with around seven injections in the first year. And although the number of injections is typically lower in subsequent years, you’re still looking at about fifteen injections in a five-year period.
Nobody enjoys a needle to the eye, and the burden of the regular appointments, coupled with the cost of so many injections, has led to attrition rates as high as 40% where patients give up on their treatment altogether. We felt there was clearly an unmet medical need not being addressed. If we could design a product that could reduce the number of times someone has an injection in their eye, we could increase that patient’s quality of life dramatically.”
Eye-catching technology
Spurred on by this patient need, the Oxular team set out to develop a safer and longer lasting drug delivery system. Oxular’s technology platform is based on the combination of their slow-release drug product formulations, called Oxuspheres, combined with their unique drug delivery devices such as the OxuLumis.
The Oxuspheres are biodegradable drug-containing microspheres. They can be adjusted, depending on the drug, to release precise dosages per day over a long period of time. Because they are slow to degrade, they extend the duration of the drug release, with the aim of reducing treatment injections to only be required every twelve months.
Our long-acting drug formulation prolongs the effects of a single administration, so that there is less burden of frequent injections for the patients. This is particularly important for diabetic or elderly patients, who already have a large burden of care. – Tom Cavanagh
The medical device OxuLumis, about the size and shape of a pen, is a unique injection tool: it is semi-automated and is able to accurately access the back of the eye using the world’s smallest, illuminated microcatheter. The precision of the injection is unparalleled and allows for the pin-point delivery of drugs via the posterior suprachoroidal space in close proximity to macula itself, via the side of the eye rather than straight through it. Cavanagh confirms:
“The combination of long-acting drug product formulations with the accurate drug delivery is what makes Oxular’s technology platform unique in the ocular field. The devices allow us to deliver drugs to specific back-of-eye structures, increasing both the safety and efficacy of treatments. Other ocular injection devices simply inject drugs into the fluid space of the middle of the eye, letting the drug diffuse through the whole eye structure. This leads to less concentrated doses in the structures that actually require the drug, and potentially more side effects as the drug can affect off target structures.
Our long-acting drug formulation using the microspheres then prolongs the effects of a single administration, so that there is less burden of frequent injections for the patients. This is particularly important for diabetic or elderly patients, who already have a large burden of care. There are convergent technologies: together they help us address the unmet needs of patients with a wide variety of eye diseases.”
Easing the burden on children
The Oxular team are working on applications for their technology in a range of different applications. The lead program is for ocular steroids in Diabetic Macular Edema (DME) as well as Retinal Vein Occlusion (RVO) and Uveitis. They are also tackling several types of eye cancers using chemotherapy, including Retinoblastoma and Uveal Melanoma, as well as supporting the delivery of gene and cell therapies. Cavanagh elaborates:
“In addition to developing our own drug assets, we also work together with partners. Often these are companies that have a potent asset, but it has a short half-life. Even if you have a great drug, if it requires an injection once a month to work, that’s not going to be feasible for patients. By combining their drugs with our technology, we can extend the duration of the drug release, thereby making the assets practicable.”
When asked about his hopes for the future, Cavanagh spoke of one of the company’s secondary pipeline programs, chemotherapy delivery for retinoblastoma in children:
“We have a passion for the retinoblastoma program because it is an ocular cancer that affects very young children. The standard of care carries both significant procedural risks and/or drugs side effects. It may not be the company’s biggest program, but it is nevertheless our favorite. We want to help these kids, reduce the invasiveness of current procedures, and reduce the side effect profile of current treatments while preserving vision.”
