Monopar Therapeutics announces MNPR-202 data from ongoing collaboration

Monopar Therapeutics released data with MNPR-202 from its ongoing collaboration with the Cancer Science Institute of Singapore at the National University of Singapore. The data are displayed in the poster that NUS and Monopar will be presenting this Sunday at the 64th American Society of Hematology Annual Meeting & Exposition. MNPR-202 is a DNA Damaging Response drug candidate, and analog of doxorubicin. It has the same potentially non-cardiotoxic backbone as camsirubicin, Monopar’s clinical stage drug candidate that has shown a favorable heart toxicity profile to-date across three trials, but MNPR-202 is modified at additional sites with the intention of evading certain tumors’ resistance mechanisms to doxorubicin. Prior exploratory preclinical studies in solid tumors have shown MNPR-202 to have a similar cytotoxic potency to doxorubicin while retaining that potency even in doxorubicin-resistant cancers. The present preclinical work by Dr. Anand Jeyasekharan corroborates MNPR-202’s similar cytotoxic potency to doxorubicin even in blood cancers, while expanding the research in several exciting new directions, including a comparison to doxorubicin on DNA damage response, immune activation, apoptosis, gene expression, and synergy with other cancer compounds for combination usage. Data from blood cancer preclinical studies to date show that MNPR-202: has a similar cytotoxic potency to doxorubicin; generates increased DNA damage compared to doxorubicin; has a unique immune activation profile versus doxorubicin; demonstrates increased apoptosis compared to doxorubicin; causes a distinct set of genes to be upregulated and downregulated versus doxorubicin; and may be superior to doxorubicin in certain combination treatment regimens. A combination drug screen with 183 compounds was performed, revealing distinct differences in the synergy profile between doxorubicin and MNPR-202 with other compounds. As example, MNPR-202 demonstrated a more favorable synergy profile with volasertib compared to doxorubicin. The results generated to date suggest doxorubicin and MNPR-202 have a similar cytotoxic potency, but likely work through distinct cellular pathways and cause a different ancillary innate immune activation. These intracellular differences also influence drug synergies observed with the two compounds, implying that in the context of certain combinatorial regimens, MNPR-202 may be superior to doxorubicin. MNPR-202 also shows the potential to work in cancers resistant to doxorubicin. Taken together, we believe MNPR-202 has potential to disrupt the current chemotherapy landscape and impact a broad range of cancers.