Pioneering research may help kidney patients – and that may be just the start

IT STARTED with a cup of coffee. Australian pharmacologist Mark Heffernan was on the lookout for a business opportunity in Irish biotech; a team of Trinity immunologists was wondering whether to take the plunge in commercialising interesting research.

That “cold call” led to the creation, in 2004, of Opsona Therapeutics. Seven years on, the company is on the verge of entering clinical trials with what it believes is a “game changing” drug for inflammatory diseases that works by blocking an element in the body’s immune system.

Toll-like receptors 2 (TLR2) are a protein that triggers an immune system response when it detects a foreign presence.

“Aberrations or dysfunctions of this target [TLR2] seem to be associated with an increasing number of very important human diseases, not only renal transplantation but also cancer . . . cardiovascular disease, myocardial infarction, stroke, auto-immune disease, even atherosclerosis,” says Dr Bernd Seizinger, executive chairman of Opsona.

Luke O’Neill, a Trinity professor and Boyle medal winner for his work in immunology, is one of the three academics behind the company. “What’s become clear from my side, as a scientist, is that this thing in the middle, TLR2, turns out to be a key driver of all these diseases . . . and at Opsona, we are the lead company going after that target. That’s what distinguishes us from the competition. We are the first one with an antibody to bring into clinical development, so it is a first-in-class drug candidate.”

The company has just been awarded funding of €5.9 million under the European Commission’s Seventh Framework Programme as part of a consortium of nine companies put together across Europe especially to progress clinical trials of its lead new drug candidate – OPN-305 – as a treatment to prevent delayed graft function in renal transplantation.

Delayed graft function is a serious complication in the immediate post-operative period of kidney transplants and increases the risk of organ rejection.

OPN-305’s has been deemed an “orphan drug” by the European Union, indicting that it is targeting an unmet medical need in a small patient population. Should it progress through the clinical trial stage, the status would grant it market exclusivity for a decade after its eventual approval for use.

“If you actually see the situation in kidney transplantation, about 50 to 75 per cent of patients waiting for kidney transplant in the end don’t get one, and by the time they would get one it is too late because they will have died,” says Bernd Seizinger. “There are not enough kidneys available.

“Here we believe we have the opportunity to work with an innovative drug that goes for the primary disease mechanisms and that could, if successful in phase II, be a game changer for this disease.”

And Opsona’s management team believes renal transplantation may be “only one relatively small slice of the cake for us”.

The Phase I study being initiated this summer will ascertain the safety of the drug in healthy humans. Success there will see OPN-305 enter Phase II trials to test its efficacy in the renal transplant indication. But the same safety trial will also prepare the ground for further studies.

“We see this as a new basis from which we can go into a variety of other clinical development enterprises as well, and one we are exploring right now and hopefully you will hear more over the next six to 12 months is oncology,” says Seizinger.

As recently as eight months ago, there was no real good evidence for a link between TLR2 and cancer but new research carried out by other labs has pointed strongly in that direction.

“They’re both inflammatory diseases in a way,” says O’Neill, “and what’s happening here is that the drug is able to block metastasis, which is the spread of tumours. And it turns out, cancers use the immune system to spread, they hijack it. And blocking TLR2 shuts that down. We are getting closer to the source of all these diseases, basically, and we’ve got a drug. We’re the only company to have a drug that blocks TLR2 very effectively. We’ve got all our data together preclinically . . . and now we are the first to go into humans with a TLR2 blocker.”

By 2013, if all goes to plan, Opsona Therapeutics expects to have completed the phase II trial for OPN-305 in renal transplantation and, ideally, have a second indication, most likely oncology, in phase II.

Funding is not a problem after a spectacularly successful fundraising in 2009. Led by Irish VC group Fountain Healthcare and Novartis’s VC arm, the funding round raised €21.3 million – at the time, the second largest series B investment in Europe, according to Fountain Healthcare’s managing partner Dr Manus Rogan

“Since then, there has been considerable progress in the company around key targets on TLR2 and Nalp3 [the company’s other drug candidate targeting rheumatoid arthritis, gout, diabetes and asthma],” says Rogan. “The company is at an exciting juncture as it is moving into the clinical phase and phase II trials next year.”

Rogan said Opsona was now a world-class Irish biotech company at the cutting edge of new drug development in the area of inflammation.

To push that forward, the Dublin business has recruited a new chief medical officer and appointed O’Neill as chief scientific officer. Dr Leon Hooftman, whose background includes clinical trial experience in transplantation and oncology, will lead Opsona’s clinical development initiatives as chief medical officer. He was most recently in the same role at Chroma Therapeutics in the UK and, before that, director of clinical science for oncology and immunology at Celltech.

Following the departure for personal family reasons of Heffernan, the company is also hunting for a new CEO, which, Seizinger says, has attracted “high international interest”.

Much about the company’s future will be determined by the outcome of the trials over the next 30 months but Seizinger acknowledges further development in areas such as Alzheimer’s disease and diabetes, if pursued, would require the “muscle and financial support of additional pharma partners”. In the meantime, he hopes to grow the company value strongly by delivering “proof of concept in one or two most practical target areas”.