Double Knock-Out Pigs Press Release

Date:	For immediate release, Thursday 22 August 2002
Contact:	Dr David Ayares, COO and VP of Research Telephone: (540) 961-5559 PPL Therapeutics, Inc
	Geoff Cook, Chief Executive Officer Telephone: +44 131 440 477 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 CLONED DOUBLE KNOCK-OUT PIGS

LACK BOTH COPIES OF GENE

INVOLVED IN HYPERACUTE REJECTION IN HUMANS

Blacksburg, Virginia: PPL Therapeutics Plc ("PPL"), one of the leading biopharmaceutical companies in the application of transgenic technologies is pleased to announce it has produced the World’s first double gene ‘knock-out’ piglets which were born as a result of using PPL’s proprietary gene targeting technology and nuclear transfer (cloning). Earlier this year PPL announced the birth of pigs in which a single copy of the alpha 1,3 galactosyl transferase (GT) gene had been knocked out - the single ‘knock-out’ pigs. This development is an extension of that work.

Four healthy piglets were born at PPL Therapeutics Inc, USA on 25 July, 2002 and continue to do well. A fifth piglet died shortly after birth of unknown causes. The gene that has been double ‘knocked-out’ in these pigs 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. This pig sugar (alpha 1,3 galactose) triggers an immune response in the human patient, leading to hyperacute rejection of the transplanted organ or cell within minutes. The ability to delete or ‘knock-out’ both copies of the gene, therefore, provides a vital step in producing pigs with organs and cells which can be used in humans. Because both copies of the gene have been inactivated, tissues from these pigs have been shown to be completely devoid of the pig sugar that cause the hyperacute rejection to take place.

As announced earlier in the year, PPL is in the process of ‘spinning out’ its regenerative medicine program (xenografts and stem cells), of which the knock-out pig program is part, in order to focus its resources on its lead protein products, recAAT for hereditary emphysema, Fibrin 1, and BSSL. It is also the Board’s belief that the resources required to bring a product to market in the area of regenerative medicine will be significant and beyond the current resources of PPL. The announcement today, however, recognises another key milestone for PPL in the area of xenotransplantation and demonstrates the company’s leading-edge position in this rapidly developing field. The company intends to have completed the spin-out by the end of the year.

As part of PPL’s ongoing collaboration with the University of Pittsburgh’s Thomas E. Starzl Transplant Institute, organs and cells from these double knock-out pigs will be used in pivotal transplantation studies aimed at testing for elimination of hyperacute rejection and long term survival of these xenografts.

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). In addition to these double knock-out pigs, the company has generated more than 60 male and female single gene GT knock-out pigs since the first litter was born in December 2001, demonstrating that this technology is now a reliable and reproducible tool for making very precise genetic changes in these animals.

David Ayares, COO and VP of Research at PPL Therapeutics Inc said:

"This advance brings us closer to the promise of a potential solution to the world-wide shortage of organs and cells for transplantation."

Geoff Cook, Chief Executive Officer said:

"This is an important step for PPL demonstrating our leading position in this exciting area. The news will support our efforts in spinning out PPL’s regenerative medicine business, that will then enable us to focus on our core protein work."

- Ends -

Notes to Editors:

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 Alpha-1-Antitrypsin (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.

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 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 filed patent applications relating to solutions for all aspects of xenograft rejection including delayed xenograft refection, coagulopathy, and chronic T cell mediated rejection. Thus the double ‘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.

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 has the potential to provide a solution to the shortage of stem cell lines for therapeutic applications.

The first application of this technology could be the testing of insulin-producing islet cells for the treatment of Type I Diabetes from the ‘double knock-out’ pigs, first in animals, and thereafter in humans. Testing of pig organs (heart and kidney) could follow after the first cell experiments. Human clinical trials could start in two to four years.

The US division of PPL also has a 3-year, $3.1 million contract with the US Dept. of Defence for biological warfare countermeasures. As part of this DARPA-funded program, the company is utilising its proprietary cloning and gene targeting technology to inactivate all the cow antibody-producing genes, and replacing them with human equivalents, in order to make large volumes of fully-human polyclonal antibodies, in cattle, as a means of immunising soldiers and civilians against biological warfare pathogens such as anthrax.

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