Product Update at PPL Therapeutics on AAT and Fibrin 1

May 18, 2002

 

Recombinant Alpha-1-Antiptrypsin (RecAAT)

On 5 December 2001, PPL Therapeutics plc (PPL) indicated that Bayer and PPL had delayed the start of their Phase III clinical trial evaluating PPL’s transgenically produced recombinant alpha-1-antitrypsin (recAAT) for the treatment of alpha-1-antitrypsin deficiency (hereditary emphysema). The delay provided time for PPL and its partner in the development of this product, Bayer Biological Products (Bayer BP), to conduct additional analyses of Phase II study data focussing on subjects who did not complete the trial.

Today the two companies announce a further delay to the start of the Phase III trials as follows:

PPL Therapeutics and Bayer Announce Delay of Phase III AAT Trial

PPL Therapeutics and Bayer Corporation, Biological Products Business Group, (Bayer Biological Products) today announced a further delay of the start of the Phase III clinical trials of PPL’s transgenically produced recombinant alpha-1 antitrypsin (recAAT) for the treatment of alpha-1 antitrypsin deficiency (hereditary emphysema).

In 2001, a Phase II study was conducted to confirm the safety and tolerability of an increased recAAT concentration administered via a new inhalation device. After reviewing the preliminary data from the Phase II study, the FDA suggested that further analysis be conducted in order to understand why a small number of Phase II subjects did not complete the study. Analyses conducted over the past few months were unfortunately inconclusive. As a result the companies have decided to investigate possible factors that might have caused these subjects not to complete the study. These include route of administration, dose, purity and formulation related issues.

Commencement of the Phase III trial will await the completion of this work. The companies expect this development to delay regulatory approval of recAAT until 2007. However, both companies are actively exploring approaches to shortening the clinical development plan that could expedite the launch of the product.

Dr. Gunnar Riemann, Global Head of Bayer Biological Products, said:
"Bayer remains committed to recAAT, and its potential to greatly increase product supply. Bayer’s long-standing commitment to this collaboration and to persons with alpha-1 antitrypsin deficiency remains unwavering; we will continue our efforts to provide safe and effective treatments to the alpha-1 community."

Geoff Cook, CEO of PPL, said:
"PPL is disappointed to have to delay the pivotal trial for this potentially break-through product that could improve the lives of patients with alpha-1 antitrypsin deficiency. We are fully committed to this project, and remain confident that we can meet these challenges."

RecAAT offers the potential to greatly increase AAT supply because it is not dependent on the availability of human plasma. In addition, an aerosol formulation of recAAT would allow delivery directly to the lungs via an inhalation system intended to improve patient convenience and, thus, compliance.

Forward-Looking Statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to substantial differences between the actual future results, financial situation, development or performance of the company and the estimates given here. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

 

Fibrin Sealant

PPL’s single component fibrin sealant, Fibrin I, which is used to arrest bleeding and seal wounds, offers a number of advantages over existing fibrin sealants including ease of use, its ability to reduce the severity and incidence of post-surgical adhesions and simplicity of manufacturing. PPL is developing this product from human plasma in the first instance as this offers the fastest route to market. A transgenically derived product will be developed as a second generation product. The plasma derived product has undergone a successful evaluation programme including process development, formulation and pre-clinical proof-of-concept testing. Currently, PPL is partnered with Smith & Nephew for certain indications and is in discussions with a number of other companies for further indications.

A recent EU directive, which comes into force in June 2002, will allow, PPL believes, Fibrin I to be developed as a device rather than as a medicine. This should significantly reduce the regulatory risk and simplify clinical trials. It is expected to gain product approval in 2005 and PPL is working with the appropriate bodies to get this underway as quickly as possible.

The current market for surgical sealants, which includes fibrin sealants as well as other tissue sealant technologies, is estimated to be close to $300 million and is expected to grow to greater than $600 million in the next 5 years. In addition, with its anti-adhesive properties, Fibrin I has the potential to capture a significant portion of the $600 million market for stand-alone anti-adhesives.

Contract Manufacturing Opportunities
The delay in the start of Phase III trials for recAAT provides PPL with a significant opportunity to maximise its revenues by using its existing manufacturing facility for the production of product for third parties. PPL is already in discussions with one company to exploit this opportunity.

Financial Implications to PPL of the above:
PPL is concentrating its resources on its core protein business and as a result expects to spin out its xenotransplantation and stem cells programmes. In addition, it is pursuing near term opportunities in contract manufacturing. With Fibrin Sealant now expected to reach the market ahead of recAAT, the Company believes that a combination of these strategies should enable it to fund the business up until its first product launch.

About Bayer
In August 2000, Bayer Biological Products and PPL signed an agreement to develop and market an aerosol formulation of recAAT. Under the agreement, Bayer is responsible for clinical development and marketing. PPL is responsible for exclusive product manufacturing.

Prolastin®, Alpha-1 Proteinase Inhibitor (Human), is currently the only product available for the treatment of alpha-1 antitrypsin deficiency and is manufactured by Bayer Biological Products. Company officials are eager to bring the next generation of safe and effective treatments for this deficiency to market. Complete prescribing information for Prolastin®, Alpha-1 Proteinase Inhibitor (Human) is available at www.bayerdirect.com .

Best known for its flagship product, Bayer Aspirin, Bayer Corporation produces a broad range of health care, life sciences, and chemical products that help diagnose and treat diseases, purify water, preserve local landmarks, protect crops, advance automobile safety and durability, and improve people’s lives.

Headquartered in Pittsburgh, Bayer Corporation had sales of $10.1 billion in 2000 and is one of Fortune magazine’s Most Admired Companies. The company employs 23,200 people. It is a member of the worldwide Bayer Group, a $29 billion international health care and chemicals group based in Leverkusen, Germany.

The Bayer Group (BAYG.DE) stock is a component of the DAX, and is listed on multiple foreign exchanges including the NYSE (BAY)

For more information contact:
PPL Therapeutics plc:
April D'Arcy
Tel +44 (0)131 440 4777

Financial PR Enquiries:
Alistair Mackinnon-Musson
Philip Dennis
Hudson Sandler
Tel +44 (0)20 7796 4133

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.

  2. PPL’s patented transgenic production of human proteins involves the introduction of copies of human DNA into the genetic material of another species. The resulting transgenic animals express the human gene product (protein) in the mammary gland allowing its collection and purification during lactation. The technique, which offers the opportunity to produce human proteins economically and in potentially unlimited quantities, is based on patented technology developed by the Roslin Institute in the 1980s for which PPL holds an exclusive licence.

  3. PPL’s three lead products are AAT, fibrin sealant, and bile salt stimulated lipase (BSSL).

  4. PPL is the only company to offer a wide range of animals for transgenic protein production, including sheep, cows, rabbits, and pigs.

  5. Further information on PPL, its products, and technologies can be found at: www.ppl-therapeutics.com .