Efficacy of Mirococept (APT070) for Preventing Ischaemia-Reperfusion Injury associated with Kidney Transplantation-2 (EMPIRIKAL-2)

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About half of all kidney transplant patients experience a delay in the recovery of the new organ, and this puts them at greater risk of losing the kidney prematurely through inflammation, rejection and scarring. We have invented an anti-inflammatory treatment that targets a key component of the inflammatory system produced in the kidney. The particular component is called 'complement' due to its natural ability to complement the immune response against infection. In the absence of infection, however, complement proteins can turn against the organ being transplanted. Our solution is to inhibit the complement system, borrowing from natural protection against self-injury. The finished product is called Mirococept. It has a unique design where the natural complement inhibitor CR1 (meaning complement receptor type 1) has been cloned and engineered to have a tail. The tail allows us to plant the therapeutic in the donor kidney, where it is retained and protects the organ following its implantation into the recipient. Work in laboratory animals has shown that treated kidneys undergo better recovery, raising the prospect of using less-damaged kidneys for clinical transplantation and giving the donor organ a longer life. The treatment has already undergone safety evaluation in humans and no safety concerns have arisen. A randomised controlled trial would determine whether it fulfils the promise to reduce the rate of delayed graft function and identify the most effective dose. The proposed trial will be a springboard for wider development to determine whether Mirococept improves the lifespan of the kidney and the recipient and is cost-effective for the NHS. This is crucial since donor organs are in short supply and the number of transplants with delayed function has increased and is likely to rise further with the recent change in legislation allowing presumed consent for organ donation. The potential indications for complement inhibitors go wider than organ transplantation and include conditions such as coronary artery surgery, age-related blindness and current clinical trials for COVID-19 lung inflammation. The proposal would add proof to the idea that 'organ painting' with anti-inflammatory drugs will improve the effectiveness of treatment without causing general side effects.