The next stage of clinical development of MNPR-201 is planned to include Phase 2 trials that will evaluate MNPR-201 in cancer indications where doxorubicin has shown efficacy but its use is restricted due to cardiotoxicity. The objective of these trials would be to demonstrate signals of efficacy where MNPR-201 dosing does not have to be restricted due to cardiotoxicity. For example, several clinical studies completed in the 1990s demonstrated that concurrent doxorubicin (60 mg/m2, 8 cycles) and paclitaxel gave a 94% overall response rate in patients with metastatic breast cancer but led to 18% of these patients developing congestive heart failure (Gianni et al., 1995). Reduction of doxorubicin to 4-6 cycles of treatment decreased occurrence of congestive heart failure, but also reduced response rate to 45-55% (Sparano et al., 1999; Valero et al., 2001). A potential Phase 2 screening trial in patients with metastatic breast cancer would evaluate concurrent MNPR-201 plus paclitaxel to see if a higher response rate than 45-55% could be observed in the absence of irreversible cardiotoxicity. Concomitant administration of paclitaxel and MNPR-201 in the absence of cardiotoxicity would also provide rationale for this same combination in other clinical settings. Similar studies are also under consideration for the combination of MNPR-201 + trastuzumab in metastatic HER2+ breast cancer patients. Additional studies will evaluate cross-over to MNPR-201 in patients benefiting from doxorubicin that have reached their lifetime limit of doxorubicin exposure in soft tissue sarcoma and other cancer indications including several pediatric cancer indications. The results of these Phase 2 studies would be used to inform an initial registration strategy for MNPR-201.