SAN DIEGO, April 09, 2007 /PRNewswire/ -- Nereus Pharmaceuticals, Inc., a pioneer in drug discovery and development from marine microbial sources, and its collaborators will present clinical and preclinical study results involving its cancer drug candidates at the American Association for Cancer Research Annual Meeting in Los Angeles April 14-18. Four posters and two minisymposia will highlight the novel mechanisms and anti-tumor activity in several tumor models for three Nereus compounds: the small molecule proteasome inhibitor NPI-0052, the tumor vascular disrupting agent (VDA) NPI-2358, and a new preclinical candidate NPI-1387, a highly selective, small molecule IKK modulator. Nereus will also present preliminary data from its Phase I dose escalation trial of NPI-2358 in patients with solid tumors and lymphoma.
In addition to the Company's single agent studies, Nereus collaborators from the University of Texas M.D. Anderson Cancer Center will describe research demonstrating markedly enhanced potency and apoptosis in human leukemia cells treated with NPI-0052 and various histone deacetylase (HDAC) inhibitors.
Nereus researchers and collaborators will make the following presentations at AACR:
Sunday, April 15, 2007
#1445: Sensitization of B-NHL resistant tumor cells overexpressing Bcl-xL to TRAIL-induced apoptosis by the novel proteasome inhibitor Salinosporamide A (NPI-0052)
Eriko Suzuki, Michael Palladino, Genhong Chen, Benjamin Bonavida. David Geffen School of Medicine at UCLA, Los Angeles, CA, Nereus Pharmaceuticals, San Diego, CA
#1453: Rituximab-mediated sensitization of resistant B-NHL cell lines to the proteasome inhibitor NPI-0052-induced apoptosis: pivotal role of PTEN induction and inhibition of Bcl-xL
Eriko Suzuki, Michael Palladino, Benjamin Bonavida. David Geffen School of Medicine at UCLA, Los Angeles, CA, Nereus Pharmaceuticals, San Diego, CA
#1454: A novel proteasome inhibitor, NPI-0052 is active in Hodgkin and Mantle cell lymphoma cell lines
Buglio Daniela, Georgios Georgakis, Victor Yazbeck, Ta-Hsiang Chao, Saskia Neuteboom, Michael Palladino, Annas Younes. University of Texas, M.D. Anderson Cancer Center, Houston, TX, Nereus Pharmaceuticals, San Diego, CA
#1455: Proteasome inhibitor NPI-0052 exhibits a distinct biological profile compared to non-leaving group analogs
Barbara Potts, Ta-Hsiang Chao, Janid Ali, Ajita Singh, Ramsharan Singh, Saskia Neuteboom, Vito Palombella, Aharminder Chauhan, Kenneth Anderson, Michael Palladino. Nereus Pharmaceuticals, San Diego, CA, Infinity Pharmaceuticals, Cambridge, MA, Dana-Farber Cancer Institute, Boston, MA
#1465: The proteasome inhibitor NPI-0052 reduces tumor growth and overcomes resistance of prostate cancer to rhTRAIL via inhibition of the NF-kB pathway
Ana Maria Barral, Ta-Hsiang Chao, Sanaz Kanabolooki, Gordafaried Deyanat- Yazdi, Benjamin Nicholson, David McConkey, Michael Palladino, Saskia Neuteboom. Nereus Pharmaceuticals, San Diego, CA, University of Texas, M.D. Anderson Cancer Center, Houston, TX
Monday, April 16, 2007 12:25 p.m. -- 12:40 p.m. Pacific Time -- Mini-symposium
#2486: The novel proteasome inhibitor, NPI-0052, synergizes with HDAC inhibitors to trigger apoptosis in leukemia cells
Claudia Miller, Joya Chandra. University of Texas, M.D. Anderson Cancer Center, Houston, TX
Tuesday, April 17, 2007
#3987: A Phase 1 accelerated titration dose escalation study of the vascular disrupting agent NPI-2358 utilizing DCE-MRI
Patricia LoRusso, Kyri Papadopoulos, Anthony Tolcher, Chia Chi Lin, Kenneth Lloyd, Elizabeth Morgan, Edward Ashton, Gillian Cropp, Matthew Spear. Wayne State University, Karmanos Cancer Center, Detroit, MI, Institute for Drug Development, San Antonio, TX, Nereus Pharmaceuticals, San Diego, CA
3:10 p.m. - 3:25 p.m. Pacific Time - Mini-symposium
#4948: NPI-1387 decreases IKKa kinase activity, inhibits NF-kB activation and induces apoptosis in hematological and solid tumor cell lines
Ta-Hsiang Chao, Ana Maria Barral, Gordafaried Deyanat-Yazdi, Venkat Macherla, Barbara Potts, Young-Ger Suh, Kenneth Lloyd, Michael Palladino, Saskia Neuteboom. Nereus Pharmaceuticals, San Diego, CA, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Nereus is conducting two Phase I clinical trials of NPI-0052, a novel, small molecule proteasome inhibitor. One study is in patients with solid tumors and lymphomas and the second study is in patients with relapsed/refractory multiple myeloma. NPI-0052 was discovered from the fermentation broth of Salinispora tropica, a new marine actinomycete identified in sediment from the ocean floor. The compound is a potent and broad inhibitor of human proteasome activity, a high-interest drug target for pharmaceutical companies after bortezomib was successfully developed to treat multiple myeloma and mantle cell lymphoma. Preclinical studies indicate NPI-0052 is active against myeloma cells from patients who are resistant to bortezomib, steroid therapy, thalidomide and lenalidomide. It also appears to have a preferable pre-clinical safety profile compared to bortezomib and has shown broad efficacy in a wide range of animal models for both hematological malignancies and solid tumors.
Nereus is conducting an open label, single-agent Phase I study of NPI-2358 in patients with solid tumors and lymphomas. NPI-2358 is one of over 200 analogues that were prepared following the discovery of Halimide from a marine fungus. In preclinical models of cancer, including breast, sarcoma, colon and prostate, NPI-2358 demonstrated potent and selective anti-tumor effects in combination as well as single-agent efficacy in a number of orthotopic models. NPI-2358 interacts with soluble beta-tubulin and prevents the polymerization of tubulin without a ltering dynamic microtubule function of formed microtubules. As demonstrated in pre-clinical testing, this target profile results in a highly specific nanomolar cytotoxicity while greatly reducing the traditional "class-related" side effects of cardiotoxicity, hemodynamic changes and neuropathies. Like other VDAs, NPI-2358 also combines effectively with standard of care chemotherapeutics in human tumor xenograft models.
Nereus has a family of over 400 synthetic small molecule diterpenes that modulate IKK and many downstream cytokines including TNF-alpha, IL-6, IL-8 and others. Three analogues, NPI-1387, NPI-1390 and NPI-1342 are being evaluated due to their increased cytotoxic activity on tumor but not normal cells and increased inhibition of cytokine synthesis. Constitutive activation of this pathway has been implicated in the development and resistance of cancers including pancreatic, colon, breast, and multiple myeloma to various therapies and has also been shown to promote the expression of VEGF and apoptosis protective proteins such as Bcl-xL and XIAPs. Studies of these analogs in models of inflammation and cancer models have shown exciting preclinical activity.
Nereus Pharmaceuticals pursues untapped sources of chemical diversity to discover and develop novel therapeutics. With unmatched expertise in marine microbiology and integrated technologies to identify novel biologically active compounds, the Company has two oncology drug candidates in Phase I clinical trials. The Company's discovery portfolio also 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.
CONTACT: Kobi M. Sethna, President & CEO of Nereus Pharmaceuticals, Inc.,+1-858-587-4093; or Pam Lord, Media & Investor Relations of Porter NovelliLife S ciences, +1-619-849-6003, , for NereusPharmaceuticals, Inc. firstname.lastname@example.org
Web site: http://www.nereuspharm.com/
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