BioWorld International Correspondent

LONDON - Lorantis Ltd. raised £11.5 million (US$16.51 million) in a second round of financing, enabling it to advance two lead immunotherapeutics into clinical trials, and fund development of a drug discovery platform around the company's Notch technology for controlling T-cell function.

Mark Bodmer, CEO, told BioWorld International, "This is more than we were looking for, so we are very pleased. The money will last two to two and a half years, allowing us to do all we can reasonably manage in that time."

The round was led by JP Morgan Partners, with existing shareholders Abingworth Management and Schroder Ventures Life Sciences, and new investor Quester Capital Management participating.

Notch is an immune-response modifier that occurs on the surface of T cells. In the absence of a signal from Notch, T cells are activated to attack any antigen presented by antigen-presenting cells. But if the antigen-presenting cells have a Notch ligand, the immune response is switched to allow the body to tolerate the antigen.

The advantage of using the Notch system to control the immune response is that it is antigen specific, making the body tolerant to specific antigens, rather than suppressing the immune system.

Lorantis, based in Cambridge, is taking two different approaches to developing therapeutics based on Notch: adding a soluble protein Notch ligand, or using Notch ligand genes. "Our initial candidates are in allergy, because this is the most straightforward way to prove the technology, and to find out if the protein or the gene is the best approach," said Bodmer. The company will first use Notch in conjunction with specific allergens, for example, house dust mites, but in the future will work on developing broad-spectrum anti-allergens.

The technology is also applicable to autoimmune diseases, and cell and organ transplant rejection. It will be a focused functional genomics platform. "We will not be using it to generate loads and loads of data, but to look at specific biological pathways in the immune system," said Bodmer.

The primary reason for developing the platform is to generate targets for internal consumption, but Lorantis would also like to partner it as a research platform, to license out targets and to carry out development work for partners.

"We won't partner our internal projects until we have proof of principle, but we may partner [Notch] in the area of tolerance to stem cell therapy, and will start talks later this year," Bodmer said.

Notch was discovered about 20 years ago as a developmental gene in drosophila. It also occurs in the worm, C. elegans.

"The fact that it turned up in the human immune system was a big surprise," Bodmer said. "But now [that] the mode of action is understood, it is not so surprising when you consider that in the immune system there is a continuing process of development." The role of Notch was elucidated by the scientific founders of the company, Maggie Dallman at Imperial College in London, and Jonathan Lamb and Gerald Hoyne, both of the University of Edinburgh.

Lorantis was established in 1998 with seed money from the venture capitalist Abingworth Ventures, and raised £3 million in its first round. There are currently 30 staff members, and Bodmer said the head count will be increased to 60.