4SC AG (Frankfurt, Prime Standard: VSC) a drug discovery and development company focused on autoimmune and cancer indications, announced the first treatment in a Phase I study evaluating 4SC-205, an oral Eg5 kinesin spindle protein inhibitor, in patients with solid tumours or malignant lymphomas.

This first-in-man Phase I, open label, dose escalation trial, the 'AEGIS' study, in patients to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally administered 4SC-205. Six dosage cohorts (3+3 design) will be enrolled and patients will be treated for two to three week treatment cycles with dosing on days one and eight of each cycle. After six weeks of treatment patients will undergo radiological disease assessments. Patients may remain on therapy beyond the initial two therapy cycles as long as they tolerate the treatment and do not demonstrate progressive disease. The study will be performed in two centres in Germany and is expected to report results in 2011.

4SC-205 is an oral inhibitor of the kinesin spindle protein Eg5 (also known as kinesin-5, KIF11), a motor protein that has been shown to be of crucial importance for proper cell division (mitosis) by mediating chromosome separation to the daughter cells. Inhibition of Eg5 leads to cell cycle arrest by interfering with microtubules, a component of the mitosis machinery, leading to apoptosis (programmed cell death). Other anti-mitotic agents which directly target microtubules, such as taxanes, are used extensively as chemotherapeutics, however, these also frequently lead to severe peripheral neurological side-effects. In contrast, targeting Eg5 is expected to provide an improved safety profile since its expression has been described to be confined to actively dividing (proliferating) cells. Therefore, 4SC-205 has the potential to generate a therapeutic effect analogous to other anti-mitotic drugs yet avoiding peripheral nerve damage commonly seen after taxane chemotherapy.

In preclinical studies 4SC-205 displayed encouraging anti-tumour activity in several in vitro and in vivo models.

Dr Bernd Hentsch, Chief Development Officer of 4SC commented, 'With the commencement of this trial, we have now extended our oncology pipeline to include a third compound. This anti-mitotic agent, based on earlier preclinical results, could be positioned in a variety of cancer indications. Over the last twelve months 4SC has now established a strong, clinical stage oncology franchise investigating multiple, innovative approaches for the treatment of both solid and haematological cancers.'

More information about this trial can be found on clinicaltrials.

About 4SC-205

4SC-205 is a small molecule inhibitor of the human kinesin spindle protein Eg5 which is of crucial importance for proper cell division (mitosis). Eg5 interacts with microtubules, a component of the cellular mitosis machinery, and mediates the segregation of the two spindle poles resulting in the correct distribution of the chromosomes to the daughter cells. Inhibition of Eg5 leads to cell cycle arrest in mitosis und subsequent programmed cell death (apoptosis). Mitosis is the fundamental process leading to cell division and tissue proliferation. The mitotic spindle apparatus has been for decades a primary target for the development of anti-mitotic agents such as the taxanes and vinca alkaloids which are broadly used in cancer therapies as single chemotherapeutic agents or in combination. In preclinical tests 4SC-205 has proven to be a particularly effective inhibitor of tumour cell proliferation of various cancer origins, both in vitro and in vivo.

Source
4SC AG