ET-traps’ first seed investment round to deliver CKD clinical study
ET-traps has initiated its first seed investment round as it bids for £800,000 to put its patented novel therapeutic through the next stage of the clinical research paradigm.
The Cambridge start-up has developed a soluble form of a GPCR (G-protein coupled receptor) that binds to excess endothelin-1 to reduce its presence to non-disease levels.
Endothelin-1 is a potent vasoconstrictor which, when pathologically elevated in the body, leads to a number of problems such as inflammation, plus structural damage to tissues and organs such as fibrosis in the kidneys and sustained vasoconstriction.
So far the company, founded by Dr Arjun Jain – who was on the shortlist for the ‘Researcher of the Year’ title at the 2019 Cambridge Independent Science & Technology Awards – with his sister Ira Jain in 2015, has relied on “family funds and investment from friends”.
“That has funded pre-clinical work with mouse models,” says Ira. “We now plan to use larger animals, including rats, for toxicology studies.”
Arjun and his team are now looking to conduct advanced pre-clinical studies in chronic kidney disease (CKD) – an area with a huge gap in treatments, especially when it comes to managing the structural damage to the kidneys.
“My PhD work at the University of Cambridge showed pre-eclampsia has increased endothelin-1 levels and these are responsible for the different pathology in the disease,” Dr Jain told the Cambridge Independent. “However, we are currently focusing on CKD, as we have been advised by different members of the pharma industry that this is an area of unmet clinical need.”
Dr Jain completed his proof-of-concept studies in diabetes and found that ET-traps were efficacious in bringing endothelin-1 levels and different markers of heart and kidney function back to non-disease levels without any toxicity. This now-patented technology’s mechanism is such that it doesn’t disrupt the normal physiological action of the endothelin system and so does not cause any of the side effects that are seen in other therapies targeting endothelin-1.
Previous research has shown targeting the endothelin system provides significant benefit in reversing structural damage to kidneys even when added to maximum tolerated doses of current standard of care treatments – but the trick is to avoid eradicating endothelin-1 entirely when attempting to reduce its presence.
There are around 850 million people with chronic kidney disease globally, and a million deaths from untreated kidney disease. Diabetes is a leading cause of chronic kidney disease and 80 per cent of the costs and most of the fatalities in diabetes are from complications like heart and kidney disease. In the UK, only 20 per cent of those with kidney failure receive a transplant, with average wait of 2.5 years.
Chronic kidney disease places a financial burden on patients and carers through lost working days, morbidity and longer hospital stays. However, current therapeutics that target endothelin receptor antagonists (ERAs) have serious side effects as they block the normal physiological function of the endothelin system and so are not approved for chronic kidney disease.
“Endothelin-1 is implicated in a number of diseases,” says Ira. “It normally maintains vascular tone and cell growth but in diabetes and CKD it is elevated, which leads to inflammation in the body and structural damage to tissue and organs. ET-traps are designed like a receptor and sponge up the excess endothelin-1.
“Since we are targeting the elevated ET-1 levels directly instead of the receptors like ERAs do, we do not block the normal physiological function of the endothelin system and so we would not have any side effects.”
The treatment is administered by sub-cutaneous injection.
ET-traps received a US patent in August 2020 and a European patent in January 2021.
“We’ve already done the development of the molecule,” concludes Ira. “Now it’s testing work.
“We’re looking to raise £800,000 to help complete an advanced chronic disease study in a rat. The current studies will take eight months.”