A new drug which could significantly reduce the chances of rejection by kidney transplant patients has been developed by Irish biotech company Opsona Therapeutics and is about to enter phase-two clinical trials. The trial could result in the drug being approved for use in patients within the next two years and follows a successful fundraising round of €33 million from a consortium of 10 investors.
Opsona was founded by three Trinity College Dublin immunologists, Professors Luke O'Neill, Kingston Mills and Dermot Kelleher, from Science Foundation Ireland-funded research programmes.
“It took about a year to secure this latest investment,” says Luke O’Neill. “It was very much a triple-act between me and the other two founders. I must have made more than 50 presentations before we finally got the whole thing together. It was a very complicated deal involving 10 different venture capital funds.”
O’Neill and Opsona have been engaged in research into proteins known as toll-like receptors (TLRs) for many years. These play a significant role in inflammatory conditions like rheumatoid arthritis and are also involved in the process that leads to the kidney transplant rejection.
“What we are doing addresses a very real need”, O’Neill explains. “Where you have a living donor who is a relative and a good match there is a very good chance of the transplant taking and not being rejected. However, in other cases where the kidney does not come from a live donor there is a 40 per cent chance of rejection.
"Dialysis is a horrible treatment for a patient and is a great burden on the health system. We believe there is a good possibility that our treatment could reduce the rejection rate by half and with more than 2,000 patients awaiting transplants in Europe at any one time this would be very significant."
Global market
This latest trial is being carried out in 52 hospitals in the US and Europe and is a two-part multi-centred, double-blinded and placebo-controlled clinical study to evaluate the safety, tolerability and efficacy of the new product in renal transplant patients at high risk of rejection.
A phase-one clinical trial in healthy human volunteers has already proved successful while what is known as a “phase zero” study in a small number of patients who have had transplants has demonstrated the safety of the drug. “The trial will cost around €19 million and will take around a year and a half to complete,” O’Neill adds. “We’ll know then if it has been a success or not. This is what I call the ‘man-from-Del-Monte moment’ when we get the news if it will be approved.”
The science behind the drug is no less interesting than its potential as a treatment. There are 10 types of toll-like receptor and Opsona is targeting one of them: TLR2.
TLR2 is very important not only because of its role in certain inflammatory kidney conditions but also for the part it plays in rheumatoid arthritis as well as for problems following heart attacks.
“If you take a kidney from a dead donor it becomes irritated and inflamed and the TLR2 proteins become overactive as if they were reacting to an acute infection,” O’Neill explains. “What happens is a classic reperfusion injury. The blood supply is cut off from the kidney until it is transplanted into the recipient and reperfusion takes place. The absence of oxygen during the ischemic period actually results in a condition where injury takes place when oxygen is restored. TLR2 activity plays a role in this injury. We believe that if you administer our drug to the patient about an hour before reperfusion takes place you can reduce or eliminate that reaction and help lower rejection rates.”
This also has implication for heart attack patients. The damage done to the heart tissue after a myocardial infarction, or heart attack, is actually as a result of the reperfusion of blood into the heart after the doctor releases the flow by removing the clot. Once again, administering the Opsona drug during or prior to reperfusion could help reduce the inflammation and therefore limit the damage done.
Looking ahead, O’Neill sees the end of the current trial as marking a natural conclusion for Opsona as well. “The phase-two clinical trial is underway and, while we are confident in the outcome, it has been a big gamble for our backers and investors over the years. Overall, including the latest round, about €60 million has been invested in the company since we established it in 2004 and this is the key moment for that. If the trial proves successful the next stage will see the company being sold to a major pharmaceutical company which will be able to take the drug and market it globally.”
Return for investors
That could be what O’Neill describes as a “mega-deal” with estimates of valuations of €300 million and more being discussed. “Our investors need to get their money back and see a return on their investment and this will be the moment for them.”
He pays tribute to the backing both he and Opsona have received from Science Foundation Ireland (SFI) over the years.
"This is an example of payback both for SFI and for the country. This investment round was the biggest in the world for a company our size this year and this was against a backdrop of venture capital companies being very risk-averse at the moment. The investment in world-class research in Ireland by SFI is really paying dividends."