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Irish team develops therapy for deadly sepsis crisis

Inthelia Therapeutics, founded by two top Irish scientists, is switching focus to block infection getting a grip on patients in the first place

A breakthrough therapy for the treatment of life-threatening sepsis developed by two Irish scientists could save millions of lives a year worldwide.

Sepsis is a potentially fatal illness caused by a pathogen entering the bloodstream. Once it takes hold it begins attacking the lining of the blood vessels. If a patient’s immune system can’t muster a robust enough counterattack, the pathogen wins.

Successful treatment depends on early intervention. Otherwise, the risk of mortality increases by 8 per cent every hour a patient is left untreated.

Current figures for Ireland indicate that 60 per cent of all in-hospital deaths have a sepsis or infection diagnosis while 42 per cent of hospital beds are occupied by patients with an infection or sepsis. As things stand, sepsis treatment is not optimal due to delayed diagnosis, heavy reliance on antibiotics and growing antimicrobial resistance.


It is a crisis primarily of our making due to the over-prescription and overuse of antibiotics, says Steve Kerrigan, professor of precision therapeutics in the School of Pharmacy and Biomolecular Sciences at the Royal College of Surgeons in Ireland (RCSI).

“Sepsis affects approximately 49 million people every year and is responsible for around 11 million deaths. It currently ranks in the top three causes of adult hospitalisations and accounts for half of all hospital fatalities - in other words, deaths from a condition that we can’t successfully treat, and this is deeply concerning,” says Prof Kerrigan.

He has teamed up with pharma entrepreneur Ivan Coulter to found clinical-stage biopharmaceutical company Inthelia Therapeutics, which has taken a novel approach to tackling the infection.

“Currently the only treatment for sepsis is antimicrobials and ‘supportive care’ as in life support for organ failure. The problem with this approach is the rapid emergence of antimicrobial resistant strains of pathogens,” Prof Kerrigan says.

Having seen numerous attempts to tackle the escalating sepsis crisis fail, Prof Kerrigan believed the solution was not more antibiotics but a complete paradigm shift towards a new type of drug therapy that would work alongside existing treatments. However, this meant turning the traditional approach to treating infection – killing the bugs – on its head.

Kerrigan decided it was time to stop trying to beat the pathogens (which are very smart at evading attempts to zap them) and to focus on the host instead. The result is Cilengitide, a patented, first-of-its-kind host-targeted therapy that protects the host (iea the patient) and modulates their response to the infection rather than trying to kill the bugs.

The pathogens are still there but Cilengitide blocks a receptor called αvβ3 integrin, which is found on the cells lining the blood vessels, and it prevents the pathogens from binding to them. This stops and can even reverse sepsis progression and limit its capacity to trigger serious illness and organ damage while also addressing concerns about antimicrobial resistance.

“Many harmful pathogens (bacteria, virus, fungi) use this receptor to spread and cause the inflammation that leads to sepsis. Unlike conventional treatments that target emerging and evolving pathogens, Cilengitide targets a host receptor to which multiple pathogens can bind. Our solution is focused on a fixed target whereas current treatments focus on moving targets,” Prof Kerrigan says.

“Biomarker-guided precision medicine is the way of the future and we are currently investigating a new biomarker which, if successful, will serve as an early warning signal that a patient is at risk of developing sepsis or is in the early stages.”

The origins of the research underpinning Cilengitide (which will have applications for other serious infections, including Covid-19) go back to 2015, and bringing the drug to market came a step closer with the spin-out of Inthelia from the RCSI in 2021. Since then the company, which employs four people, has been progressing its clinical studies.

Prof Kerrigan’s area of expertise is the mechanisms of vascular dysfunction following infection and he is the lead inventor on 15 invention disclosures and patents. Dr Coulter is a pharmacologist with a PhD in cancer research who segued into the commercial world, where he has worked in senior management positions and has also been the driving force behind the formation of Sigmoid Pharma and Eden BioPharma.

To date, Inthelia has received funding by way of research grants of €2.8 million. The next step is a pre-seed round of €2 million followed by a further round of €10 million to build the team and conduct further trials.

Science Foundation Ireland, Enterprise Ireland and the Irish Research Council provided Inthelia with grant aid of €1.7 million but the remaining €1.1 million came from a more unexpected source – Barda or the Biomedical Advanced Research and Development Authority.

“Barda is part of the US department of health and, as such, has a responsibility to protect its citizens. Its ultimate goal is to identify potential therapies that can be stockpiled to protect the US against any future health threats,” Prof Kerrigan explains. “The US economy was so badly hit by Covid-19 that they do not want a situation where that could happen again.

“They have searched the world for companies or researchers working on areas to protect against future pandemics. Before they gave us the funding, we had simply engaged with them to let them know what we were doing. This is quite common in our field. But they encouraged us to apply for the funding as our work fitted nicely into their programme.”

Inthelia is expecting to get fast-track approval for Cilengitide from the FDA as it already has a significant amount of clinical data amassed and, with sepsis costing US healthcare providers an estimated €25 billion a year, the authorities there are keen for a solution that could reduce that burden. And the US is not alone. Sepsis is a massive cost to health services worldwide.

“Our innovation is positioned at the convergence of two lucrative markets: the sepsis therapeutic sector, which is expected to be worth $6.2 billion (€5.8 billion) by 2028, and the sepsis diagnostic market, which is expected to be worth $1.6 billion by 2030. The market for sepsis treatment is only going to grow as it’s a problem that’s getting worse not better,” Prof Kerrigan says.

All going smoothly, Cilengitide could be on the market within five years or less. That won’t be a moment too soon, says Prof Kerrigan.