Nereus Pharmaceuticals, Inc., a
pioneer in drug discovery from marine microbial sources, announced
that enrollment has begun in a Phase 1b study evaluating the vascular
disrupting agent (VDA) NPI-2358 in combination with standard chemotherapy
in patients with non-small cell lung cancer (NSCLC). This study follows on
positive outcomes in a Phase 1 single-agent clinical trial assessing the
safety, pharmacokinetics, pharmacodynamics (PK/PD) and efficacy of NPI-2358
in various tumor types.
The open-label Phase 1b study will assess escalating doses of NPI-2358
in combination with docetaxel in patients with NSCLC who previously failed
at least one chemotherapy regimen. The existing preclinical and clinical
data suggests that VDAs may be complementary or synergistic with
chemotherapeutics and anti-angiogenesis agents due to the different targets
and mechanisms of action. NPI-2358 has a dual effect on tumors: It
selectively attacks existing tumor blood vessels leading to hemorrhagic
tumor necrosis without affecting normal vasculature, and it has a direct
apoptotic effect on tumors cells. NPI-2358 in combination with
chemotherapeutic agents in human xenograft models of NSCLC and other
cancers was markedly more effective than either treatment alone.
"We are excited to have a leading role in the clinical development of
Nereus' NPI-2358 for the treatment of non-small cell lung cancer. At The
Sir Charles Gairdner Hospital, we felt this combination study with NPI-2358
was a high priority given the favorable preclinical and clinical data we
have seen," said Michael Millward, M.D., Cancer Council Professor of
Clinical Cancer Research at The University of Western Australia based at
Sir Charles Gairdner Hospital, Perth.
"Our clinical program for NPI-2358 holds promise in non-small cell lung
cancer, a large market indication where novel compounds could make a
significant impact on patients. We're pleased to advance our clinical
program for NPI-2358 and involve first-rate cancer research centers with
unique expertise with this class of vascular disrupting agents," said Kobi
M. Sethna, President and CEO, 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
NPI-2358 into an international randomized Phase 2 study of approximately
150 patients at 30 centers late in 2008. Nereus is also evaluating NPI-2358
in other solid tumor indications.
About NPI-2358 -- A Novel Vascular Disrupting Agent
NPI-2358 is a vascular disrupting agent currently in clinical
development for the treatment of cancer by Nereus. Initial results from a
single-agent Phase 1 trial in various tumor types indicate NPI-2358 has a
favorable safety profile, including cardiac safety. It is also being
evaluated in a Phase 1b study in combination with docetaxel for the
treatment of non-small cell lung cancer. NPI-2358 is one of over 200
synthetic analogues that were prepared following the discovery of the
compound Halimide isolated from a marine fungus. In preclinical models of
cancer, including lung, breast, sarcoma, colon and prostate, NPI-2358
demonstrated potent and selective anti-tumor effects in combination with
docetaxel and other oncology therapies, 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 altering dynamic
microtubule function of formed microtubules. As demonstrated in preclinical
testing, this target profile results in a highly specific nanomolar
cytotoxicity while reducing the side effects seen in first-generation VDAs
due to cardiotoxicity, hemodynamic changes and neuropathies.
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 Phase I 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
nereuspharm.
Nereus Pharmaceuticals is a registered trademark of Nereus
Pharmaceuticals, Inc.
Nereus Pharmaceuticals, Inc.
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