MIAMI--(BUSINESS WIRE)--Makana™ Therapeutics, a global leader in the field of xenotransplantation, announced today that the company’s scientists have discovered that pigs contain a fourth gene that when inactivated will greatly reduce the risk of organ rejection in a human recipient.
Makana’s Triple Knockout Pig (“TKO”) is the current foundational genetics used across the field, and is deficient in three genes which drive hyperacute rejection of pig tissue transplanted into humans. In 2012, Makana scientists discovered the first two of the TKO’s genetic pig modifications and, in 2014, discovered the third. Now in 2024, Makana has found a fourth genetic knockout required to address the early rejection seen in clinical application of pig organs transplanted into human recipients.
In recently publicized pig-to-human xenotransplantations, the transplanted organs were rejected by their human recipients within a two-month period. Each of those transplants were approved under “compassionate use” protocols and were not part of a U.S. Food and Drug Administration (FDA) clinical trial. These consistent early losses led Makana to direct its discovery efforts to identify the mechanism responsible for the failures. Every human sample Makana analyzed contained antibodies to the antigen eliminated by Makana’s fourth genetic target.
Joe Tector, MD, PhD, FACS, Makana’s founder and a practicing transplant surgeon at the Miami Transplant Institute, said, “Our research continues to focus on better understanding the mechanisms of organ rejection in xenotransplantation. As a result, we have discovered an additional human immune system response responsible for early xenograft organ failure. We have already created healthy pigs that inactivate the fourth gene to evade this immune response. This is a major breakthrough that will pave the way for clinical success in xenotransplantation.”
Mark Platt, Makana’s Chief Executive Officer, said pigs incorporating this knockout were produced last year as part of its research collaboration with the University of Miami. He added that Makana is preparing to launch its Definitive Preclinical Study in 2025 with plans to conduct a First-in-Human Clinical Trial in kidney xenotransplantation in early 2026 (upon FDA approval).
Specifics of Makana’s research will be detailed in a scientific paper to be published in the coming weeks.
Platt said Makana’s first focus will be in the kidney space. According to the National Kidney Foundation, there were 786,000 patients in the U.S. living with kidney failure in 2021. In 2022, there were approximately 25,000 kidney transplants performed in the U.S. However there are still an estimated twelve people dying each day in the U.S. while waiting to receive a life-saving kidney transplant. Currently there are more than 93,000 people on the U.S. kidney transplant waitlist. “This has been an enduring challenge for organ transplantation, with the waiting list substantially larger than the supply of donor organs,” Platt said. “Our sole focus is to restore an entirely normal life to every patient with organ failure.”
About Makana Therapeutics
Founded in 2009, Makana Therapeutics is focused on developing swine with reduced xenoantigen expression, making human transplantation of cells, tissues and organs from these animals possible. Makana's focus on scientifically validated genetics, optimized pig cloning techniques and careful patient selection is expected to streamline product development and result in safer more efficacious products. For more information on Makana, please visit www.makanatherapeutics.com.
