Editing Scandion Oncology (section)

==== Data support FOLFIRI combination ====
First-line therapy for mCRC relies heavily on 5-fluorouracil (5FU)-based chemotherapy regimens, often supplemented with targeted therapies (should a molecular driver be present) and/or biologic agents (eg vascular-endothelial growth factor A, VEGF, targeting monoclonal antibody, bevacizumab). Later lines of therapy will also generally be formed around modification of 5FU-based regimens. A common treatment in this setting is FOLFIRI, a chemotherapy regimen consisting of leucovorin calcium, 5-fluorouracil and irinotecan. One of the active ingredients of this regimen, irinotecan, is a prodrug of the potent topoisomerase I inhibitor SN-38. Drugs of this class kill tumour cells by inhibiting DNA repair processes. The development of resistance to irinotecan chemotherapy through ABCG2 efflux pump overexpression and UTG1A1 activity is well documented, thus Scandion Oncology has identified FOLFIRI as a potentially attractive combination therapy for SCO-101. Indeed, analysis of CORIST patients treated with SCO-101 and irinotecan in Part I of CORIST has shown dramatically increased plasma levels of SN-38 at a 90mg/m2 dose when compared to SN-38 data from treatment with irinotecan at 180 mg/m2 (based on patients outside the CORIST study, Exhibit 6), although Edison Investment Research cautions that there are limitations to comparing data from different studies.

'''Exhibit 6: SN-38 plasma concentrations in CORIST patients<ref>Source: Scandion Oncology CMD update.</ref><br />'''

[[File:Image7-c31e427382287da7a43068acd0e06507.png|600px]]

While plasma concentrations in the CORIST patients were dramatically higher when compared to patients treated only with irinotecan (using data compiled from separate studies), Edison Investment Research notes that high plasma levels of SN-38 do not necessarily correlate with a clinical effect, especially in ABCG2 driven resistance. However, this data does provide support for the SCO-101/FOLFIRI combination with the lower 90mg/m2 CORIST dosing regimen for irinotecan (compared to 180mg/m2 commercial norm).