Technologies being developed in Ireland are set to transform the treatment of hard-to-treat solid tumours, painful osteoarthritis and debilitating pelvic health conditions such as overactive bladder.

The projects are being funded under the Government’s Disruptive Technology Innovation Fund (DTIF) and by Enterprise Ireland.

Tumours

Since the 1960s, the rate of survival for cancer has vastly improved, thanks to medical advances. However, most of the gains have been made in blood cancers, with many solid tumours still untreatable.

In this context, the development of Irish technology that can deliver precision therapeutics, tailored to needs of an individual and capable of breaching the defences of solid tumours, is welcome.

Dublin-based Remedy Biologics with TCD, NUI Galway and aCGT Vector, Drogheda, received €6.8 million from the DTIF to do just that.

Remedy CEO Dan Crowley says the aim is to discover how the immune system, at the level of a cell, interacts with a disease.

“We are focused on disease biology and what the immune system is doing in response to the disease,” explains Crowley.

Professor Paul Leonard, the chief scientific officer with Remedy, is assistant professor in biomedical sciences at Dublin City University.

Leonard has been interested in developing new technology that can overcome the many inefficiencies in how drug discovery is done.

At the level of a cell, Leonard says, everyone’s disease is different and how that person’s immune system responds is also different.

“I’m interested in finding out what part of the immune system is right for tackling an individual’s disease,” says Leonard.

“We are looking at what cells are functioning when disease is present,” Leonard says. The goal is to tap into the disease-fighting capacity that exists inside all of us and let it loose on the disease.

“To use an analogy, we take really good athletes and we turn them into Olympic athletes,” says Leonard.

This involves looking at individual cells and how they are responding to disease – solid cancers in this case – in thousands of patients.

“We want to develop off-the-shelf therapies that will enhance a person’s treatment for their disease,” says Leonard.

Only about one in five people get a good response from drug therapy, he says, and he’d like to see that go up to four, or even five in five.

To do that, Leonard knows that he must better understanding the biology of how disease can disrupt an individual’s immune system.

Tumours are good at turning off immune cells that can kill them, he says, and Remedy wants to get these cancer killers working again.

Once an immune response can be triggered to a disease, even if it is initially low, it can trigger a further and stronger immune response.

“It’s like putting kindling on a fire, but the wood is a bit damp so it’s hard to get going,” says Leonard. “But once you get it gets going, the fire is strong and that is like a really strong immune response.”

Remedy is focused on using its new technology - called the nonreactive platform - to tackle lung and gastrointestinal cancer.

However, it expects that this approach will work for other cancers, including a wide range of hard-to-treat solid cancers.

In the process, it can help to change how cancer is perceived.

“Instead of thinking about it [cancer] as a location in the body, we think about it by virtue of its immune profile,” says Crowley, who is aiming to start clinical testing of the technology in 18 to 24 months.

Pelvis

It can take two and a half years for someone with pelvic health issues to see a specialist, and it’s the same the world over, says Brendan Staunton, co-founder and CEO of Amara Therapeutics.

“We identified a massive issue with the provision of front-line treatments for people with pelvic issues,” says Staunton.

People who attend a doctor with pelvic health complaints are quite often being prescribed medication on a speculative basis and in the absence of a diagnosis, he says, or sent for surgical procedures.

Amara received funding from the Enterprise Ireland commercialisation fund to develop a digital solution.

The common pelvic health conditions are stress-related urinary incontinence, organ prolapse and overactive bladder.

Staunton had noted software, in the form of apps, being developed in the USA for conditions where patients stood to benefit from behavioural, non-drug, interventions.

The FDA has, for example, approved several apps, or digital therapeutics, for people with diabetes, insomnia and IBS.

“Many people are not getting behavioural therapy, even though science shows it is equivalent, or superior, to medications,” says Staunton in relation to pelvic health conditions.

In the US, a patient with pre-diabetes might be prescribed an app to guide them through a 12-to-16-week intervention,” says Staunton.

There are now at least seven such apps approved by the FDA, he says, and it has become a real and effective way to treat patients.

Amara developed its own digital therapeutic, or app, called RiSolve for overactive bladder, which affects 52 million people in the USA and EU.

“People get an overwhelming urge to use the bathroom, don’t make it in time and have an episode of incontinence,” says Staunton.

The app is designed to reduce incontinence anxiety and guide patients through a cognitive behavioural therapy program.

“We built this eight-week intervention,” says Staunton. “It’s video and audio content, and the idea is that we teach them all about their condition: what the causes are and what the treatments are.”

“They get educational videos weekly and get tasks and challenges that they have to complete.”

Amara ran a trial of the app at Galway University Hospital, with 18 patients. Of these, 100% reported reduced symptoms after the eight weeks, while 83% said their quality of life had improved.

Algorithms developed by Amara act as questionnaires, which gather data from patients using the app that can be sent to the doctor.

The clinician can use this data to give an indicative diagnosis, and based on that, a behavioural intervention via the app is suggested.

Amara is aiming to be the leading global provider of behavioural, digital therapies for neurological and gynaecological conditions.

Osteoarthritis

As anyone who suffers from osteoarthritis of the knee will confirm, it is a painful, debilitating condition that impacts on quality of life.

Relevium, a Galway biopharmaceutical start-up, along with NUIG and HiTech Health, received €7million to develop a new treatment for knee osteoarthritis using a hydrogel-based pain-blocking product.

In Ireland, some 250,000 people suffer from this form of arthritis, with estimates of 14 million in the USA, and 18 million in the EU.

There are several steroid-based medicines that offer fast pain relief, but a price must be paid in terms of damaging cartilage.

There are also injectable hyaluronic acid products on the market, which produce variable results, with stem-cell solutions far off.

Relevium has conducted preclinical testing at NUIG of a new product called Hydrobloc, which is different to existing therapies.

“We started getting very good data,” says Dr Alison Liddy, co-founder of Relelvium and Principal Investigator on Hydrobloc.

Liddy and a research group at Professor Garry Duffy’s lab initially searched for a peptide molecule which had the potential to reduce the ability of nerve cells to signal pain.

They found a peptide that fit the bill, 315Y. The next job was to figure out how to deliver the molecule into the diseased knee.

Liddy decided to bind the peptide to gel-like hyaluronic acid, because it could hold the peptide in place within the joint and was already FDA-approved as a treatment for osteoarthritis of the knee.

“It ticked all the boxes,” says Liddy. “The molecule breaks down within the joint and the fragments block nerve fibres within the knee joint - we believe it is getting into subchondral bone as well.

“The biggest thing is pain relief and lubrication of the joints,” says Liddy. “It blocks all points of pain – inflammatory and nerve pain.”

The target is to provide pain relief and joint lubrication for six months, and two injections a year to fully manage the condition.

Liddy doesn’t expect that Hydrobloc will be available until 2029, as it is a medicine and will be put through all necessary clinical trials.

Liddy says that the product might also prove to be effective for osteoarthritic hips, and painful bladder syndrome in women.

Reporting: The Irish Times