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Proteasome Inhibitor NPI-0052 in Solid Tumors Phase 1b trial


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Nereus Pharmaceuticals Initiates Combination Clinical Trial for Proteasome Inhibitor NPI-0052 in Solid Tumors

SAN DIEGO--(BUSINESS WIRE)--Nereus Pharmaceuticals, Inc., a pioneer in drug discovery from marine microbial sources, today announced that enrollment has begun in a Phase 1b study evaluating the proteasome inhibitor NPI-0052 in combination with vorinostat (Zolinza®, Merck & Co.) in patients with selected solid tumor malignancies. The open-label study will enroll approximately 40 patients with advanced non-small cell lung cancer, pancreatic cancer or melanoma for whom standard approved therapy is not available. The study follows on positive outcomes from preclinical studies of the combined agents and clinical trials with NPI-0052.

By inhibiting proteasomes, NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and induces apoptosis in cancer cells. The complementary anti-cancer agent vorinostat is a histone deacetylase inhibitor (HDACi) that is approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma. Investigational studies with vorinostat are ongoing in multiple solid tumor and hematologic malignancies. HDAC inhibitors stop tumor cell differentiation and growth, and when combined with NPI-0052 in preclinical in vitro and in vivo studies, show additive and synergistic anti-tumor activities. This ongoing research was presented by Nereus and its collaborators at this week’s American Association for Cancer Research Annual Meeting. The researchers also presented a new in vitro study highlighting the mechanisms by which NPI-0052 may prevent tumor metastasis and reverse resistance to apoptotic stimuli.

“Preclinical research with NPI-0052 and vorinostat demonstrated markedly enhanced potency in human cancer models, including those for melanoma, lung and pancreatic cancer, warranting evaluation of this combination in the clinic,” said Timothy J. Price, M.D., Medical Oncologist and Head of Clinical Oncology Research at The Queen Elizabeth Hospital in Adelaide, Australia, the trial’s principal investigator.

“Combining complementary anti-cancer agents to maximize their effects is proven strategy that we are excited to explore with our internally-discovered, second-generation proteasome inhibitor NPI-0052, and we have been particularly impressed with the preclinical results from this combination,” said Matthew A. Spear, M.D., Chief Medical Officer of Nereus Pharmaceuticals, Inc.

Upon successful completion of the Phase 1b trial and determination of the recommended doses for the combined agents, Nereus expects to advance the program into Phase 2 trials in 2009.

Nereus’ novel, small molecule NPI-0052 was discovered from a new marine-obligate gram-positive actinomycete (Salinispora tropica). The compound is a potent inhibitor of human proteasomes, a high-interest drug target for pharmaceutical companies after bortezomib (Velcade®, Millennium) was approved for the treatment of multiple myeloma and mantle cell lymphoma. Preclinical studies indicate that this next-generation compound may be superior to other proteasome inhibitors, with broader target inhibition, faster onset and longer duration of action, higher potency, and oral and intravenous availability. NPI-0052 has shown preclinical activity against many common cancers, including solid tumors, leukemias, lymphomas and myeloma, including cells from patients who are resistant to newer cancer therapies and steroid therapy. Multiple clinical trials evaluating NPI-0052 in patients with solid tumors, leukemias, lymphomas and multiple myeloma are ongoing.

About Nereus Pharmaceuticals, Inc.

Nereus Pharmaceuticals pursues novel sources of chemical diversity to discover and develop new therapeutics. Using its unmatched expertise in marine microbiology to identify unique biologically active compounds, Nereus has two oncology drug candidates in multiple Phase 1 single agent and Phase 1b combination clinical trials. NPI-2358, a novel vascular disrupting agent, is being evaluated in patients with solid tumors and lymphomas, and the second-generation proteasome inhibitor NPI-0052 is being developed in patients with solid tumors, lymphomas, leukemias and multiple myeloma. The Company’s discovery portfolio includes potential drug candidates for cancer, infectious diseases and inflammation. For more information, visit www.nereuspharm.com.

Nereus Pharmaceuticals is a registered trademark of Nereus Pharmaceuticals, Inc.

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