Pipeline

The NMS portfolio of projects includes numerous pharmacological approaches that aim at diversifying the mechanism of action proposed for the treatment of cancer and that, in line with prospects for future therapies, form the base for an anticancer action that may also be achieved by using a combination of two or more drugs.
Set forth below is a schematic summary of the various approaches.

In particular, studies are being made of the following:

• molecules capable of interacting with Signal Transduction.
  For example, inhibitors of B-RAF and PDK-1
  
  
• molecules capable of intervening in Cell Cycle Regulation.
  For example, inhibitors of Aurora, PLK-1 and CDKs
  
  
• molecules that interact with the DNA Processes.
  For example, DNA minor grove binders, CDC7 and PARP inhibitors, and Topoisomerase
  
  
• molecules that act on the cytoplasmatic proteins.
  For example, inhibitors of HSP-90.
  
  

The current pipeline of advanced projects includes a number of anticancer compounds in Phase I-II clinical trials:

Aurora inhibitors. Auroras are a family of serine/threonine kinases acting as key mitotic regulators required for genome stability. Auroras are involved in regulating multiple steps in mitosis, including centrosome duplication, formation of a bipolar mitotic spindle, and chromosome alignment on the mitotic spindle. These kinases are frequently overexpressed in various human tumour types, including colon, pancreas, ovary, breast, and bladder. NMS inhibitors are currently at various stages of  research and development.

Cyclin-dependent kinases (Cdks) inhibitors. Uncontrolled cell proliferation is a hallmark of cancer cells. Alterations of the expression and/or genetic mutations of  Cdks, and other components of the pRB pathway, controlling the correct entry and progression through the cell cycle, have been reported in more than 90% of human neoplasms, thus suggesting that Cdks inhibitors may be relevant in the treatment and prevention of cancer. Our Cdks inhibitors are currently undergoing clinical development.

Nemorubicin is a DNA-intercalator, topoisomerase I inhibitor, effective on a broad spectrum of tumour models and significantly different from other anthracyclines. The compound is active on selected tumours resistant to current treatment. Overall more than 300 patients have been treated in Europe, USA and China with nemorubicin given at different dose-schedules and by different routes of administration. Additional studies in Ph I/II are ongoing.

The exclusive world rights for brostallicin, a synthetic DNA minor grove binder, a drug developed in Nerviano and currently in clinical phase II, have been transferred to the research company Systems Medicine Inc. (SMI), that has now been taken over by the company Cell Therapeutics.

Within this system, the organisation of the various projects is carried out by the Project Teams, both preclinical and clinical. These count on the participation and contribution of representatives from the various specialist areas to achieve integration of expertise for the optimization of choices, procedures and timing.