Plinabulin (NPI-2358) is a potent, selective tumor vascular disrupting agent (VDA) with best-in-class pre-clinical characteristics that is an analogue of a molecule with novel chemistry and activity derived from a marine fungus. The successful Phase 1 studies both as a single agent and in combination with docetaxel achieved:

• Proof of Mechanism milestone with decreases in tumor blood flow of up to 82% by DCE-MRI
• A recommended Phase 2 dose with a broad therapeutic window
• Excellent cardiac safety profile following extensive cardiac safety testing (ECG, echocardiography, BNP, and troponin)
• Excellent early response rate in combination with docetaxel; 75% of patients with tumor regressions in the Phase 1b portion of the study.

Plinabulin (NPI-2358) is now being evaluated in a randomized Phase 2 study in combination with docetaxel in patients with NSCLC having failed prior therapy. In pre-clinical studies, the compound: 1) shows an excellent safety profile, 2) is active against multi-drug resistant human tumor cell lines, 3) has a longer duration of action on tumor blood flow compared to other VDAs in clinical testing, 4) has high specificity for tumor vasculature, and 5) strongly enhances the efficacy of most chemo- or radio- therapeutic regimens in preclinical models while maintaining excellent tolerability.

NPI-0052 is a highly potent potentially best-in-class proteasome inhibitor derived from a novel marine actinomycete and is being evaluated for the treatment of multiple myeloma, solid tumors, lymphomas and leukemias in three Phase 1 clinical trials. NPI-0052 is also being evaluated in a Phase 1/2 clinical trial for the treatment of melanoma, pancreatic cancer, NSCLC, and NHL in combination chemotherapy with vorinostat (Zolinza). In preclinical studies, NPI-0052 was superior to bortezomib (Velcade) in demonstrating: 1) a longer duration of action; 2) a faster onset of action; 3) a proteasome inhibition profile that is more comprehensive (inhibits all three protease functions); 4) less cytotoxic for normal cells; 5) increased efficacy in a wider range of solid tumor models; 6) efficacy against Velcade, Revlimid, Thalomid and dexamethasone resistant tumor cells from multiple myeloma patients; 7) potential for administration by the oral, subcutaneous and intravenous routes; 8) marked enhancement of efficacy when used in combination with biologics and chemotherapeutics such as Avastin, Erbitux, irinotecan, FOLFOX, FOLFIRI, Revlimid, TRAIL and oxaliplatin, and; 9) dramatic synergy on a variety of tumor types in combination with HDAC inhibitors, including Zolinza and SNDX275.

Our IKK Series is a family of synthetic small molecule diterpene derived analogues that modulate NF-kB /IKK activity. Approximately 450 analogues were synthesized and screened and many are being evaluated that exhibit increased cytotoxic activity on tumors but not normal cells and increased inhibition of cytokine synthesis. Modulation of NF-kB /IKK activity impacts the disease related activation of NF-kB which has been implicated in the resistance of cancers to various therapies. Activation of NF-kB also promotes the expression of pro-inflammatory and pro-angiogenic activities such as TNF-α, IL-1, IL-6, IL-8 and VEGF. Animal POC has been demonstrated with three analogues and several analogues have shown strong preclinical activity when administered orally or systemically in models of cancer and/or inflammation.

Our anti-infectives are two novel pharmacophores with structures not previously described. They were identified in screens for broad spectrum antibacterial activity and activity against methicillin and vancomycin resistant strains. These interesting small molecule structures are still under evaluation by our research team.

Technology

Microbes from the ocean are proving to be an extraordinarily rich source of biologically active and diverse chemistry. Nereus has developed a highly efficient and scalable discovery process that integrates microbiology, screening and natural products chemistry in an iterative manner. This discovery platform provides one-of-a-kind access to novel pharmacophores, scaffolds and analogues that can be developed for therapeutic use. The unique requirements of marine microbiology make it inaccessible to pharmaceutical companies relying on conventional microbial production technology. This platform and approach also leads to strong composition of matter IP protection that can be expanded through proven pharmaceutical paradigms. All of Nereus’ pipeline compounds have strong, global IP coverage.

Investors/Funding History

In July 2007 the Company closed a Series D-2 preferred stock financing in which it raised ~$45M led by BankInvest of Copenhagen. Additional new investors included Roche Venture Fund, Astellas Venture Management, Boston Life Science Venture Corp, Taiwan Global Biofund, and Eminent Venture Capital Corporation. Continuing principal investors include HBM BioVentures, Forward Ventures, Alta Partners, Advent International, GIMV, InterWest Partners, Pacific Venture Group, Novartis BioVenture Fund. The Company previously raised ~$80M in Series A, B, C and D rounds.

Contact Information

 Number of employees - 25