BioWorld International Correspondent

LONDON PPL Therapeutics plc announced a further delay to the start of Phase III trials of its lead product, transgenically produced alpha-1-antitripsin, pushing the expected launch date back from 2005 to 2007, and putting the company in a tight cash position.

As a result of the delay, Edinburgh, Scotland-based PPL expects its fibrin sealant, Fibrin 1, used to stop bleeding and seal wounds, in 2005 to be its first marketed product. To eke out its cash, the company plans to use its alpha-1-antitripsin (AAT) production facility to manufacture product for third parties, and said it is in discussions with one potential client.

Shares of the company fell by 7 pence, closing at 44 pence on the news.

Geoff Cook, newly appointed CEO of PPL, said he was disappointed with the delay of the AAT pivotal trial, but said the company is “fully committed to this project, and remain confident we can meet these challenges.”

On Dec. 5, PPL said it was delaying the start of Phase III trials of AAT in the treatment of hereditary emphysema because the FDA asked for additional information on why a small number of patients did not complete a Phase II study.

That study was carried out using a new inhalation device belonging to Bayer Biological Products, PPL’s partner and the manufacturer of prolastin, the only product available for the treatment of hereditary emphysema.

On Monday, PPL announced that further analyses of the Phase II data were inconclusive. The companies now will investigate possible factors that might have caused the subjects not to complete the study, including route of administration, dose, purity and formulation-related issues.

Bayer emphasized that it remains committed to recombinant AAT. Gunnar Riemann, global head of Bayer Biological Products, said, “[Our] long-standing commitment to this collaboration and to persons with AAT deficiency remains unwavering.”

The latest setback is bad news for PPL, which in September succeeded in a last-ditch attempt to raise money, securing £30 million from existing investors in a discounted rights issue. In April 2001, the company was forced to pull out of a £45 million rights issue due to lack of interest.

A successful rights issue was one of the conditions specified by Bayer when it agreed in July to provide security for a £15 million loan to build the AAT manufacturing facility.

In September, PPL said that the £30 million was enough to get it through to 2005 the then-expected launch of AAT. Now it’s pinning its hopes on Fibrin 1. It says a European directive coming into effect in June will allow the product to be developed as a device rather than a medicine. This will reduce the regulatory risk and simplify clinical trials. The company is developing fibrin from human plasma as the fastest route to market, but plans to develop a transgenic version as the second-generation product.

PPL previously announced it was to spin off other applications of the cloning technology that produced Dolly the sheep, to concentrate on its core business of producing human proteins in the milk of transgenic animals. It believes the change in the status of fibrin, plus the revenues it hopes to get from contract manufacturing, will enable it to fund its business up until its first product launch in 2005.