Advanced Solid Cancers 

MNPR-101, as a first-in-class anti-uPAR humanized monoclonal antibody, represents a potentially selective means for delivering cytotoxic agents to cancer cells. Conjugation of MNPR-101 to a radionuclide, for example Actinium-225, may produce a potent and selective cytotoxic agent with wide applicability for the imaging and treatment of advanced solid cancers. Monopar is pursuing development of a MNPR-101 RIT for these indications.  

Mechanism of Action

MNPR-101 Conjugated to Imaging Radioisotope

Maximizing the dose delivered to the tumor relative to normal tissue is of paramount importance in radiopharmaceutical therapy. Figure 1 below shows the before and after optimization of MNPR-101-Zr, Monopar’s radiopharmaceutical imaging agent for advanced solid tumors expressing uPAR. Monopar’s in-house radiopharmaceutical development team was able to significantly increase tumor uptake of MNPR-101-Zr while minimizing uptake in healthy tissue, as shown in this preclinical positron emission tomography (PET) sequential imaging time-series. The high specificity and durable tumor uptake are evident in the After Optimization panel below.

Figure 1

MNPR-101 Conjugated to Therapeutic Radioisotopes

Preclinical data to date demonstrate compelling and durable anti-tumor benefits with MNPR-101 conjugated to therapeutic radioisotopes. Figure 2 below shows preclinical efficacy data in a triple negative breast cancer as well as a pancreatic cancer human tumor xenograft mouse model utilizing two different therapeutic radioisotopes conjugated to MNPR-101; one of these radioisotopes has already been disclosed as being actinium-225 (Ac-225). The results in both show near complete elimination of the tumor after a single injection of the radiopharmaceutical agent. These studies demonstrate the potential of a MNPR-101 based radiopharmaceutical to provide a very meaningful clinical benefit to patients.

Figure 2