BioWorld International Correspondent

LONDON - Prolysis Ltd. raised $9.9 million in its second-round funding to advance its three lead antibiotic programs, focusing on bacteria that are becoming resistant to existing drugs, through to clinical development.

The fund raising was led by the existing investors, with Fujisawa Investments for Entrepreneurs LP and Fujisawa Investment for Entrepreneurs II LP, the investment arms of the Japanese pharmaceutical company Astellas Pharma Inc., investing for the first time.

Steve Ruston, CEO, said he set out to raise £8 million (US$14.6 million). "We are jolly grateful our investor base decided to support us," he told BioWorld International. "But there was a driver from Fujisawa to make the investment quickly because of internal corporate issues, and so we decided to draw a line [at $9.9 million]."

Oxford, UK-based Prolysis' most advanced program, CDI-538, is a small-molecule inhibitor of FtsZ, a protein essential for bacterial cell division. The inhibitor works by preventing the formation of the septum in dividing cells, blocking the separation of daughter cells and leading to cell death through lysis. It's a first-in-class compound against a novel target and Prolysis says there is the potential to produce multiple products.

The second program, CDI-936, also targets FtsZ, but is chemically distinct from CDI-538 and works through a different mechanism. However, the consequences are the same, in that bacteria fail to form a septum. CDI-538 is intended as a broad-spectrum antibiotic, while CDI-936 will be developed against methicillin-resistant Staphylococcus aureus.

The third program, GYR-767, is an inhibitor of DNA gyrase, an industry-validated target that is a topoisomerase enzyme involved in coiling and uncoiling DNA supercoils. Antibiotics of the quinilone family inhibit gyrase, but there is growing resistance to marketed products.

"Every antibacterial attracts resistance in time. If you go with a me-too' mode of action, you will see resistance at the outset: Our modes of action are novel and it will take longer for resistance to develop," Ruston said.

The funding will enable Prolysis to ready the lead programs for clinical development by the end of 2006. At the same time, further programs will be developed from hits identified using the founding technology.

Prolysis has collaborations with Evotec OAI for medicinal and computational chemistry, and with Proteom Ltd. for in silico molecular design. The company was set up in 1998 by Jeff Errington, an expert in bacterial cell cycle and cell morphogenesis at the Sir William Dunn School of Pathology at Oxford University, and has a collaboration agreement with the university. It raised £4.5 million (US$8.2 million) in its first round in November 2002.

The intention is to take compounds into Phase IIa and then out-license. "Being the size we are, we won't have a major clinical trials organization. But we do know there is a hunger for compounds with novel mechanisms of action among pharmaceutical and biotech [companies]," Ruston said.