On December 12, 2022 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported promising data with MNPR-202 from its ongoing collaboration with the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) (Press release, Monopar Therapeutics, DEC 12, 2022, View Source [SID1234625136]). The data are displayed in the poster that NUS and Monopar will be presenting this Sunday at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH 2022). Monopar has made the poster available on its website at the following link: View Source
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MNPR-202 is a promising DNA Damaging Response (DDR) 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, MD PhD, of CSI Singapore, which was highlighted by the Gates Cambridge in a recent article: View Source, 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.
Preclinical Results To-Date
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.