Antibody for prevention of Early graft dysfunction in high risk cadaveric kidneys

DGF incidence ranges from 40-60 % in high-risk kidneys, depending on organ donor state, and occurs when blood supply returns after lack of oxygen, ischaemia-reperfusion injury. Dialysis can be required for about seven days until the organ regains its function, increasing the chances of transplant failure.

In the case of the kidney, the immune system activation that damages the grafted organ is driven by toll-like receptor 2 (TLR2). The EU-funded MABSOT (Development of OPN-305 as an orphan drug for the treatment of delayed graft function post solid organ transplantation) project tested a novel antibody, OPN-305, for use in the prevention of DGF. OPN-305 has previously inhibited TLR2-mediated injury in a range of organ transplants. MABSOT researchers have manufactured and developed OPN-305 as an orphan drug.

In non-clinical trials, evaluation of the antibody formulation determined the maximum dose in non-human primates with no adverse side effects. Moreover, in Healthy humans, there was no concern about safety.

Molecular analysis of the damage-associated molecular patterns recognised by TLR2 identified serum amyloid A (SAA) as a TLR2 agonist. However, there was no positive link between SAA levels and DGF in renal transplant patients.

A Phase I trial was successfully completed and no serious adverse events occurred in healthy volunteers related to study medication. In renal transplant patients, part A of phase II trials indicated a positive effect in patients dosed with 0.5 mg/kg OPN-305 who received an extended criteria donor kidney.

Patents for OPN-305 have been granted in Australia, Europe, Mexico, New Zealand, South Africa, China, Japan, South Korea, Russia and the United States. MABSOT researchers expect that OPN-305 will be commercialised by another party following acquisition.

The advancement of OPN-305 into trials has significant clinical ramifications for alleviating DGF in organ-transplanted patients and enhancing longevity. The inhibition of TLR2-mediated injury has implications for the drug's use in the treatment of other solid organ transplantations where similar injury occurs.