BioWorld International Correspondent

AM-Pharma BV raised 9 million (US$10.8 million) in a Series B round to progress three clinical programs involving two drug candidates.

The company, based in Bunnik, the Netherlands, needed just two investors to raise the cash. Inventages Venture Capital Investments Inc. led the transaction, with a 6 million investment, while ABN Amro Capital Life Sciences, an existing backer, contributed the remainder. Bart Bierman, chief operating officer and chief medical officer at AM-Pharma, told BioWorld International that the company is seeking an additional 3 million to close out the round. The 9 million it has raised at first closing will be payable in four separate tranches that are tied to clinical development milestones.

The company is pursuing two separate indications with a bovine form of the enzyme alkaline phosphatase. In sepsis, it is recruiting participants onto a Phase IIa trial, which commenced in August of last year. The recruitment target is 32 patients, although the current total stands at 18. The company has revised the inclusion criteria and added extra clinical centers in order to accelerate the process. "So now the study is up to speed again, and we are expecting to complete it by April of next year," Bierman said.

So far, Xigris (drotrecogin alfa), marketed by Eli Lilly and Co., of Indianapolis, is the only compound approved for the notoriously difficult indication, but the product has not been a commercial success since gaining FDA approval in 2001. That drug, a recombinant form of human activated protein C, combats the thrombotic effects of sepsis by inhibiting Factor Va and Factor VIIIa, but it has so far failed to match pre-launch expectations.

Lilly last month reported an 8 percent sales drop for the third quarter of 2005, with global sales of $45.4 million. "We would say to clinicians that alkaline phosphatase gets more to the root of the sepsis, when the bacterial toxins are being released," Bierman said. It acts by dephosphorylating the toxic lipopolysaccharides released from the cell wall of Gram-negative bacteria.

AM-Pharma also is developing the product for irritable bowel disease (IBD). It will deliver the enzyme to the duodenum via a nasal drip. It completed a Phase I trial in this program this week, and aims to commence a small-scale Phase IIa study involving eight patients before the year end. The same presumed mechanism of action is being investigated in that indication.

"We have proved this concept in animals," Bierman said. In parallel, the company is pursuing the development of a human recombinant form of alkaline phosphatase, although it will take up to two years for that program to enter the clinic.

The sepsis program is long term, Bierman said. Its third clinical program is more likely to generate clinical data that will lead to near-term licensing or additional financing opportunities. It is based on an antimicrobial peptide, hLF1-11, derived from human lactoferrin, an iron-chelating protein with antimicrobial activity found in human secretions such as milk, tears and saliva. AM-Pharma purchased the program from fellow Dutch company Pharming Group NV, of Leiden, during the latter company's bankruptcy period.

The product also has completed a Phase I trial and will move into a Phase IIa trial in January as a prophylactic treatment for prevention of opportunistic infection in patients undergoing allogeneic bone marrow stem cell transplantation.

Between one-third and one-half of patients develop bacterial infections following the procedure, Bierman said, while another 5 percent to 10 percent develop fungal infections. Half of all infected patients subsequently die. The company is planning four Phase II studies in total, the first three of which it will complete by the end of next year. At that point, Bierman said, the company should have data from an open-label study and will then opt either to partner or seek additional financing for a blinded, placebo-controlled Phase IIb study.

But its potential as an anti-infective therapy goes beyond the targeted indication. Moreover, the company and its academic partners have developed variants of hLF1-11 that exhibit greater efficacy in preclinical studies.

"There's a lot to develop and obviously far, far more than AM-Pharma can handle," Bierman said. The company would need either to out-license the program or raise further financing to pursue additional indications. "This is really something we have to develop a strategy on in the months to come," he said.

The company, which was formed in July 2002 via the merger of AM-Pharma BV and PharmAAware Sepsis BV, had previously raised about 11 million. Following the latest transaction, and assuming the company hits its milestones, ABN Amro would hold 44 percent of its equity and Inventages would hold 25 percent.