Nereus Pharmaceuticals Inc. secured funding to move its lead oncology candidates into Phase II programs with a $45 million Series D-2 financing round.

Funds will be drawn down in two tranches, based on milestone achievements. That arrangement is similar to the company's first Series D round, which brought in $24.3 million in December 2004, with an additional $18.3 million added upon the completion of company goals, including the filing of investigational new drug applications for lead programs NPI-0052 and NPI-2358.

The recent round will be used to complete ongoing safety studies for those compounds and, "hopefully, allow us to begin our Phase II programs sometime next year," said Kobi Sethna, president and CEO of San Diego-based Nereus. (See BioWorld Today, March 7, 2006.)

Both products emerged from the company's marine microbial drug discovery platform, licensed from the University of California in San Diego. NPI-0052 was derived from Salinispora tropica, a marine-obligate Gram-positive actinomycete. A proteosome inhibitor, the drug closely resembles Velcade (bortezomib), an approved multiple myeloma drug from Cambridge, Mass.-based Millennium Pharmaceuticals Inc., though NPI-0052 is a second-generation compound that showed in preclinical studies a broader inhibitor effect, faster action, longer duration and greater potency at less-frequent dosing, Sethna said, adding that the compound also "demonstrated activity in Velcade-resistant cells."

If all runs smoothly, Nereus could complete Phase I studies of NPI-0052 in the next six months to nine months.

Its second clinical compound, NPI-2358, an analogue of a marine fungal extract, is a vascular-disrupting agent (VDA), a relatively new class of cancer drugs aimed at disrupting tumor blood flow. Other firms have shown promising clinical results with VDA agents, such as Waltham, Mass.-based OxiGene Inc., which recently reached agreement with the FDA on a special protocol assessment for Zybrestat (Combretastatin A4 phosphate) in anaplastic thyroid cancer, and partners, EpiCept Corp., of Tarrytown, N.Y., and Myriad Genetics Inc., of Salt Lake City, which is in Phase II testing with VDA candidate Azixa for brain cancer. Last month, London-based Antisoma plc reported that ASA404 missed its endpoint in a Phase II ovarian cancer trial, though the company's partner, Novartis AG, is planning to move into pivotal studies with the drug in non-small-cell lung cancer in 2008.

San Diego-based MediciNova Inc. and Australian company Bionomics Ltd. are in earlier-stage development with their respective VDA candidates. MediciNova's MN-029 has completed Phase I trials in solid tumors, and Bionomic's BNC105 is expected to enter the clinic shortly in cancer.

While Nereus' drug also is in early stage development - NPI-2358 currently is in a Phase I dose-escalating study - the company's preclinical data suggested that it might demonstrate a preferable safety profile to other candidates in development, Sethna said.

"One of the biggest issues with this class [of drugs] is CNS toxicity and cardiotoxicity," he told BioWorld Today, "and we do not see that in animal studies" of NPI-2358. Another advantage might be the drug's apparently dual mechanism, which not only disrupts blood flow but also promotes apoptotic activity.

So far, Nereus has retained sole rights to both NPI-0052 and NPI-2358. With the recent Series D-2 round, and pending successful results from Phase I trials and upcoming Phase II studies, the company is in a good position, Sethna said. "We could elect to take one or both lead products" into late-stage development and commercialization, or the firm could opt to partner one compound, while holding co-promotion rights.

"We've given ourselves options going forward," he said. "We have a rich pipeline and a discovery engine" and by adding that latest financing to the company's balance sheet, "we'll be positioned in the next six to 12 months to make those kinds of decisions."

Nereus' preclinical pipeline includes a program targeting NF-kB activation for cancer and inflammatory diseases and a class of broad-spectrum antibiotics for infectious diseases.

The company previously had raised about $80 million. The Series D-2 round was led by new investor BankInvest Biomedical Venture, of Copenhagen, Denmark, and included five other new investors: Roche Venture Fund, of Basel, Switzerland; Astellas Venture Management, of Los Altos, Calif., Boston Life Science Venture Corp., of Taipei, Taiwan; and Taiwan Global Biofund and Eminent Venture Capital Corp., both also of Taipei. They were joined by existing investors Baar, Switzerland-based HBM BioVentures; San Francisco-based Alta Partners; San Diego-based Forward Ventures; Boston-based Advent International; Antwerp, Belgium-based GIMV, Menlo Park, Calif.-based InterWest Partners; and Encino, Calif.-based Pacific Venture Group.

Jesper Zeuthen, of BankInvest, and Erich Platzer, of HBM Partners, joined the board.