Date: For immediate release, Wednesday 2 January 2002
Contact: Dr David Ayares, COO and VP of Research
Telephone: (540) 961-5559
PPL Therapeutics, Inc
Dr Ron James, Director
Dr Martyn Breeze, Product Development Director
Telephone: +44 20 7796 4133 (2/1/02)
                    +44 131 440 4777 (therafter)
PPL Therapeutics plc
Alistair Mackinnon-Musson
Philip Dennis
Telephone: 020 7796 4133
Email: ppl@hspr.co.uk
Hudson Sandler

 

PPL THERAPEUTICS PLC

WORLD’S FIRST ANNOUNCEMENT OF

CLONED ‘KNOCK-OUT’ PIGS

Christmas-born pigs are a major step towards successful production of animal organs and cells for human transplantation use

Blacksburg, Virginia: PPL Therapeutics Plc, one of the world’s leading biopharmaceutical companies in the application of transgenic technology to the production of human proteins for therapeutic and nutritional applications, is pleased to announce it has produced ‘knock-out’ piglets which were born as a result of using nuclear transfer (cloning) and PPL’s patented gene targeting technology. The five healthy births took place on Christmas Day, December 25, 2001. It has always been the objective of PPL’s xenotransplantation program to produce ‘knock-out’ pigs. In the future, this vital step should enable organs and/or cells from such animals to be transplanted into humans and not be rejected by the human recipient. A ‘knock-out’ pig has the specific gene that leads to the human immune system rejecting pig organs inactivated.

The announcement today achieves a key milestone that PPL has pursued in the area of xenotransplantation. In view of the fact that PPL’s financial resources are being focused primarily upon bringing its lead product recAAT, for the indication hereditary emphysema, to the market as quickly as possible, PPL proposes to find a ‘spin out’ partner to take the ‘xeno’ and stem cell areas forward. This development demonstrates PPL’s leading position in this area and it will be of significant interest to all companies involved in transplant technology.

Pigs are the preferred species for xenotransplantation on scientific and ethical grounds. It is anticipated the first application of this technology will be the testing of insulin-producing islet cells for the treatment of diabetes from the ‘knock-out’ pigs, first in primates, and soon thereafter in humans. Clinical trials could start in as little as four years and analysts believe the market could be worth over $5 billion for solid organs alone, and $6 billion for cellular therapies for Diabetes, Parkinson’s and Alzheimer’s Diseases.

The gene that has been ‘knocked-out’, the alpha 1,3 galactosyl transferase (GT) gene is responsible for making an enzyme that adds a sugar to the surface of pig cells which is recognised by the human immune system as foreign, and which therefore triggers an immune response leading to hyperacute rejection by the human patient, of the transplanted organ or cell, within minutes. The ability to delete or ‘knock-out’ this gene, therefore, provides a vital step in producing pigs with organs and cells useful in humans.

PPL’s comprehensive xenograft program relates to both its technology and its Intellectual Property portfolio. In addition to overcoming early hyperacute rejection, the Company has also shown proof-of-concept, and has patents for, solutions for all aspects of xenograft rejection including delayed xenograft refection, coagulopathy, and chronic T cell mediated rejection. Thus the ‘GT knock-out’ pig will serve as the platform for adding up to three more genes, and include a T cell tolerance regime, in order to address all stages of rejection.

The ‘knock-out’ work was carried out by PPL Therapeutics Inc, PPL’s US subsidiary located in Blacksburg, Virginia, and was partly supported by an ATP Grant from the US Government’s National Institute of Standards and Technology (NIST). The piglets, all females, were confirmed through DNA tests to have one of their two copies of the GT gene inactivated. They have been named: Noel, Angel, Star, Joy and Mary.

Dr. David Ayares, COO and VP of Research at PPL’s US Division stated:

"The birth of these pigs is a critical milestone in our xenograft program and should spark renewed vigor from both the scientific and investment communities. This advance provides a near term solution for overcoming the shortage of human organs for transplants as well as insulin-producing cells to cure diabetes."

Ron James, Director at PPL said:

"Today’s announcement is a natural breakpoint for PPL to spin out the valuable technology it has developed thus far. In light of this news, finding a third party at this particular time to take forward this very exciting area of science, which addresses major markets, will ensure that PPL’s shareholders gain maximum value, while protecting the Company’s limited cash resources needed to bring its lead product, recAAT, to market as quickly as possible."

Alan Colman, Research Director at PPL said:

"The successful cloning of these pigs is a major step in achieving PPL’s xenograft objective. Together with the Roslin Institute, we were the first to clone an adult mammal, Dolly. PPL was also the first to demonstrate gene targeting in livestock, the first to clone pigs, and now the first to report alpha 1,3 ‘GT knock-out’ in pigs for xenotransplantation. With one of the major technical hurdles and scientific risks overcome, the promise of xenotransplantation is now a reality, with the potential to revolutionize the transplant industry".

-Ends-

Notes to Editors:

  1. PPL Therapeutics is a biopharmaceutical company which is one of the world’s leaders in the application of transgenic animal technologies to the development and production of human proteins for therapeutic and nutritional applications. PPL’s three lead products are AAT, fibrinogen and bile salt stimulated lipase (BSSL). PPL is the only company to offer a wide range of animals for transgenic protein production, including sheep, cows, rabbits and pigs.

  2. Xenotransplantation is the transfer of cells, tissues, or organs from one species to another. The fundamental problem with transferring organs between species is rejection by the recipient’s immune system. PPL’s program has aimed to overcome the causes of rejection and allow the development of a stock of transgenic animals containing genetic modifications which can be used as organ donors for humans.

  3. For additional information on xenotransplantation please visit PPL’s web site:
    www.ppl-therapeutics.com

  4. In addition to its xenograft program, PPL has an advanced stem cell program which holds the promise of providing a human cell-based solution to diabetes, neurological and cardiovascular disease. The Company received a second ATP grant from NIST in January, 2001 for $2 million to fund its proprietary research on the generation of "ethical" stem cells. This method involves the de-differentiation of somatic cells to become ES-like cells, and has the advantage that no embryos are created or destroyed at any point in the process. This technology provides a solution to the shortage of stem cell lines for therapeutic applications.