Technology

Nereus has developed a highly efficient discovery process that integrates microbiology, screening and natural products chemistry in an iterative manner. This platform combines robust extraction and fractionation with streamlined upfront sample dereplication to rapidly discover new, unique pharmaceutical agents. The Company's marine microbial drug discovery program (licensed from the University of California, San Diego) has been industrialized to pharmaceutical standards to provide a predictable and continuous flow of new, high value medicinal entities. This new source is providing a prolific flow of biologically active and diverse chemistry. The unique requirements of marine microbiology make it inaccessible to pharmaceutical companies relying on conventional microbial production technology.

This pharmaceutical drug discovery approach, which is predictably scaleable, could exceed the productivity based on terrestrial microbes, a proven paradigm that has delivered over 120 commercially relevant pharmaceuticals (anti-infectives, anti-cancer agents, immunosuppressants, statins for cholesterol reduction, etc.). The Company's discovery platform provides access to one-of-a-kind novel chemical entities that can serve as starting points and scaffolds. The analogs derived from these novel chemical starting points significantly expand the pool of interesting candidates and provide additional opportunities for IP protection.

The breadth and depth of Nereus' pipeline permits the Company to leverage this asset through corporate partnerships without diminishing its own unique projects.

The Company is seeking to establish research collaborations with pharmaceutical companies. Nereus' library of marine microbes will undoubtedly deliver hundreds of new pharmaceutical leads in virtually all therapeutic areas. These research collaborations would be ideally structured to leverage Nereus and a partner's unique capabilities by marrying its vast library of marine microbes, and the diverse chemicals produced by them, with the assays and screening tests within the discovery research laboratories of pharmaceutical companies.

Development Programs



Plinabulin (NPI-2358) is a potent, selective vascular disrupting agent (VDA) with potentially best-in-class characteristics. Plinabulin (NPI-2358) was one of a couple hundred analogues that were produced after finding the initial activity and novel chemistry from a marine fungal extract. Plinabulin (NPI-2358) is made synthetically via a very straight-forward commercially viable process. In pre-clinical studies, the compound is active against multi-drug resistant human tumor cell lines, shows an improved side effect profile (cardio- and neuro- toxicity), high specificity for tumor vasculature, and strongly enhanced efficacy when used in combination with most chemo- or radio- therapy regimens.

NPI-0052 is a highly potent proteasome inhibitor derived from a novel marine-obligate actinomycete and is being evaluated for the treatment of multiple myeloma, lymphomas and solid tumors. Due to the success of Velcade™, the proteasome is a high interest drug target. In preclinical studies, NPI-0052 appears superior to Velcade and shows: 1) a broader and longer lasting proteasome inhibition profile; 2) efficacy against Velcade, Revlimid™, Thalomid™ and dexamethasone resistant tumor cells from multiple myeloma patients; 3) efficacy against a wider range of tumors, including many solid tumor models; 4) less cytotoxic to normal cells; 5) a 7 to 10 fold higher in vivo potency; 6) potential for administration both orally and by intravenous injection on a once-a-week schedule; 7) marked enhancement of efficacy when used in combination with chemotherapeutics and biologics such as Avastin™, Erbitux™, irinotecan, FOLFOX, FOLFIRI, and oxaliplatin.

Our NF-кB Series is a family of synthetic small molecule diterpenes that regulate NF-кB activation. Approximately 450 analogs were screened and three, NPI-1387, NPI-1390 and NPI-1342 were selected due to their increased cytotoxic activity on tumor but not normal cells and increased inhibition of cytokine synthesis. Constitutive activation of NF-кB has been implicated in the development and resistance of cancers including pancreatic, colon, breast, and multiple myeloma to various therapies. Activation of NF-кB also promotes the expression of pro-inflammatory and pro-angiogenic activities such as TNF-α, IL-1, IL-6, IL-8 and VEGF. Studies of these analogs in models of inflammation and pancreatic carcinoma characterized by the involvement of NF-кB have shown exciting preclinical activity.