This is an open-label, uncontrolled, multi-center, phase 1a MNPR-101-PCTA-177Lu dose-escalation study in patients with solid tumor cancers. Patients must have participated in the imaging study MNPR-101-D001 (actively recruiting, diagnostic study of MNPR-101-DFO*-89Zr).
* TITE-BOIN will be used to objectively determine dose increase, no dose change, or dose decrease for each group of two patients.
* The treatment period consists of two 12-week cycles. Patients will receive three equal fractions of MNPR-101-PCTA-177Lu with radioactivity ranging from 480-2240 MBq on each of Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (12 weeks after Cycle 1 Day 1).
* Patients will be followed for 12 weeks after their last dose of MNPR-101-PCTA-177Lu.
* Patients will be imaged at specific timepoints during the study.

Start Date01 Oct 2024

Sponsor / Collaborator

Monopar Therapeutics, Inc.

NCT06466135 / RecruitingPhase 2

Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of WAL0921 in Patients With Glomerular Kidney Diseases and Proteinuria

This is an adaptive prospective, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of WAL0921 in subjects with glomerular kidney disease and proteinuria, including diabetic nephropathy and rare glomerular kidney diseases (primary focal segmental glomerulosclerosis [FSGS], treatment-resistant minimal change disease [TR MCD], primary immunoglobulin A nephropathy [IgAN], and primary membranous nephropathy [PMN]). Subjects in this study will be randomized to receive the investigational drug WAL0921 or placebo as an intravenous infusion once every 2 weeks for 7 total infusions. All subjects will be followed for 24 weeks after their last infusion.

Start Date02 Jul 2024

Sponsor / Collaborator

Walden Biosciences, Inc.Startup

NCT06474806 / RecruitingPhase 2

An Open-label, Two-part, Phase 2 Clinical Trial to Investigate the Safety and Diagnostic Performance of uPAR PET Imaging for Non-invasive Classification of ISUP Grades Among Patients With Localised, Untreated Prostate Cancer.

The goal of this clinical trial is to test if the experimental agent accurately determines the aggressiveness of prostate cancer (biopsy-verified ISUP grade). The aim is that the diagnostic PET imaging agent may be used as an alternative or supplement to biopsies in the monitoring of patients with low-risk prostate cancer in active surveillance.
Patients diagnosed with untreated, low-grade, localized prostate cancer may participate in the trial. The experimental diagnostic agent 64Cu-DOTA-AE105 is a radiopharmaceutical which is injected into the veins and binds to uPAR expressing cells in the tumour which can then be visualized in a PET scanner.
The main question the trial aims to answer is: Can the test drug be used alone or as a supplement to repeated biopsies to accurately assess the aggressiveness of prostate cancer?
The trial is divided in 2 parts:
* Participants in the first part will receive 2 injections of test drug on 2 different days.
* The first day the participant will receive an injection of the test drug and then be asked to lie down in the PET/CT scanner so that images of the prostate can be taken. Before and after the injection/scanning procedure the participant will have tests done. These tests will include evaluation of health status, measurement of heart function by ECG plus blood and urine samples.
* After 8 days the procedures, including injection of test drug and scanning, will be repeated.
* Participants in the second part of the trial will only have 1 injection of the test drug and subsequent PET/CT scanning. Like in Part 1 of the trial, tests will be done before and after the injection/ scanning procedure.

Start Date01 Jun 2024

Sponsor / Collaborator

Curasight A/S

[+1]

100 Clinical Results associated with uPAR

100 Translational Medicine associated with uPAR

0 Patents (Medical) associated with uPAR

5,851

Literatures (Medical) associated with uPAR

31 Dec 2024·Renal failure

Clinical value of soluble urokinase-type plasminogen activator receptor in predicting sepsis-associated acute kidney injury

Article

Author: Zhou, Jing ; Li, Han ; Zhao, Xiaoru ; Yan, Lei ; Gu, Yue ; Wang, Juntao ; Deng, Xiaoyu ; Shao, Fengmin ; Zhang, Wenwen ; Jiao, Xiaojing

BACKGROUND:

Sepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients.

METHODS:

We prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves.

RESULTS:

Of 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p < 0.05). The plasma suPAR had the highest area under the ROC curve of 0.700 (95% confidence interval (CI), 0.621-0.779) at 24-h post-sepsis diagnosis, at which the best discrimination ability for S-AKI was achieved with suPAR of ≥6.31 ng/mL (sensitivity 61.9% and specificity 71.6%). Logistic regression analysis showed that suPAR at 24-h post-sepsis diagnosis remained an independent S-AKI risk factor after adjusting for mechanical ventilation, blood urea nitrogen, and pH.

CONCLUSIONS:

The findings suggest that plasma suPAR may be a potential biomarker for early S-AKI diagnosis.

01 Oct 2024·BIOTECHNOLOGY AND BIOENGINEERING

An engineered ultrahigh affinity bi‐paratopic uPAR targeting agent confers enhanced tumor targeting

Article

Author: Lee, Robert B. ; Cherf, Gerald M. ; Mehta, Nishant ; Torres, Kathleen ; Clifford, Claire ; Cochran, Jennifer R. ; Kintzing, James R.

Abstract:

Urokinase‐type plasminogen activator receptor (uPAR) is overexpressed on tumor cells in multiple types of cancer and contributes to disease progression and metastasis. In this work, we engineered a novel bi‐paratopic uPAR targeting agent by fusing the binding domains of two native uPAR ligands: uPA and vitronectin, with a flexible peptide linker. The linker length was optimized to facilitate simultaneous engagement of both domains to their adjacent epitopes on uPAR, resulting in a high affinity and avid binding interaction. Furthermore, the individual domains were affinity‐matured using yeast surface display and directed evolution, resulting in a bi‐paratopic protein with affinity in the picomolar to femtomolar range. This engineered uPAR targeting agent demonstrated significantly enhanced tumor localization in mouse tumor models compared to the native uPAR ligand and warrants further investigation as a diagnostic and therapeutic agent for cancer.

01 Oct 2024·Reproductive Sciences

Novel Biomarkers: Soluble Urokinase-Type Plasminogen Activator Receptor and Procalcitonin- and Histological Chorioamnionitis after Preterm Premature Rupture of Membranes

Article

Author: Ampuja, Sinikka ; Aittoniemi, Janne ; Virtanen, Anita ; Huhtala, Heini ; Jalkanen, Kati ; Tihtonen, Kati ; Flinck, Heidi

Abstract:

Fetal inflammatory response syndrome or infection after preterm premature rupture of membranes (PPROM) increases neonatal morbidity in preterm deliveries. Biochemical markers from the amniotic fluid (AF) have been used to evaluate possible intra-amniotic infection during the asymptomatic phase after PPROM. This study aimed to describe whether soluble urokinase-type plasminogen activator receptor (suPAR) or procalcitonin (PCT) from AF or maternal sera could reveal fetal inflammatory response or infection after PPROM. AF and maternal serum samples were collected weekly after PPROM (23+ 0 − 34+ 6 gestational weeks) until delivery from twenty women and two women with possible chorioamnionitis with intact membranes. Levels of suPAR, PCT, interleukin-6 (IL-6), glucose, lactate dehydrogenase (LDH), and bacterial PCR were determined from AF and suPAR and PCT and IL-6 from maternal sera. Fetal infection or inflammation response were determined by the histology of the placenta after delivery. AF glucose was significantly lower and AF LDH higher in the fetal site histologic chorioamnionitis (HCA) group, while AF suPAR concentrations tended to be higher in this group. AF suPAR correlated significantly with AF glucose and LDH. Based on receiver operating characteristic (ROC) analysis, AF glucose had the best predictability for fetal site histological chorioamnionitis. The findings of AF PCT were insignificant considering HCA. AF glucose had the highest accuracy in predicting fetal site histologic chorioamnionitis. AF suPAR may be a promising marker; however, our findings were limited by a small study population.

News (Medical) associated with uPAR

12 Sep 2024

·www.globenewswire.com

Monopar Announces Positive Early Human Clinical Data Validating the Tumor Targeting Ability of MNPR-101-Zr

WILMETTE, Ill., Sept. 12, 2024 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharma company focused on developing innovative treatments for cancer patients, today announced positive early data from its ongoing open-label MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial confirming MNPR-101-Zr’s tumor targeting ability in humans. MNPR-101 is Monopar’s proprietary first-in-class humanized monoclonal antibody that targets cancers expressing the urokinase plasminogen activator receptor (uPAR). These include a majority of all triple-negative breast, colorectal, bladder, ovarian, gastric, and pancreatic cancers. A total-body positron emission tomography (PET) image was taken at 168 hours (7 days) post administration of MNPR-101-Zr (a zirconium-89 imaging radioisotope conjugated to MNPR-101) of the first cancer patient in the trial with one of the known high uPAR-expressing cancer types. The results, seen in Figure 1, demonstrate the specificity, durability, and uptake of MNPR-101-Zr in the metastatic tumors relative to normal tissue. The regions of higher uptake also align with the locations of the previously observed metastatic tumors on conventional FDG PET imaging. “This is exactly what we had hoped to see – highly preferential uptake in the tumor,” said Andrew Cittadine, Monopar’s Chief Operating Officer. MNPR-101-Zr was evaluated against FDG, the gold standard for detecting metastatic tumors. Figure 2 shows FDG uptake in its highest-uptake tumor compared to MNPR-101-Zr uptake in the same tumor imaged on the same Siemens Biograph Vision Quadra™ PET/CT scanner. “At the Melbourne Theranostic Innovation Centre, we utilize one of the world's most sensitive PET/CT scanners. Using the same scanner for FDG and MNPR-101-Zr, the results show MNPR-101-Zr achieved uptake at sites of known disease with retention out to late points, which is promising for future therapeutic translation,” said Professor Rodney Hicks, MBBS(Hons), MD, FRACP, FICIS, FAAHMS, lead investigator on the MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial. Monopar recently received clearance in Australia to initiate an MNPR-101-Lu Phase 1 therapeutic clinical trial [link] which is currently scheduled to launch in the fourth quarter of this calendar year. “We are looking forward to sharing additional data at the upcoming European Association of Nuclear Medicine 2024 Annual Congress to be held in Hamburg, Germany on October 19-23, 2024, where our abstract has been accepted as a 'Top-Rated Oral Presentation' within the Scientific Program,” said Chandler Robinson, MD, Monopar’s Chief Executive Officer. Further information about the ongoing MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial is available at www.ClinicalTrials.gov under study identifier NCT06337084. About Monopar Therapeutics Inc. Monopar Therapeutics is a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, including Phase 1-stage MNPR-101-Zr for imaging advanced cancers, Phase 1-stage MNPR-101-Lu and late preclinical-stage MNPR-101-Ac225 for the treatment of advanced cancers, as well as early development stage programs against solid cancers. For more information, visit: www.monopartx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of these forward-looking statements include: the results show MNPR-101-Zr achieved uptake at sites of known disease with retention out to late points, which is promising for future therapeutic translation; and that an MNPR-101-Lu Phase 1 therapeutic clinical trial is currently scheduled to launch in the fourth quarter of this calendar year. The forward-looking statements involve risks and uncertainties including, but not limited to: that Monopar may not launch its MNPR-101-Lu therapeutic study in the fourth quarter of 2024, if at all; that the Phase 1 imaging and dosimetry clinical trial in advanced cancer patients with MNPR-101-Zr may not yield consistently satisfactory results; that future preclinical or clinical data may not be as promising as the data to date; that MNPR-101-Zr and/or MNPR-101-Lu may cause unexpected serious adverse effects or fail to be effective against the cancer tumors in humans; that Monopar may expend available funds sooner than anticipated or require additional funding due to change in circumstances or unanticipated events; and the significant general risks and uncertainties surrounding the research, development, regulatory approval, and commercialization of imaging agents and therapeutics. Actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Monopar's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Monopar undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Any forward-looking statements contained in this press release represent Monopar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. CONTACT: Monopar Therapeutics Inc.Investor Relations Karthik Radhakrishnan Chief Financial Officer karthik@monopartx.com Follow Monopar on social media for updates: Twitter: @MonoparTx LinkedIn: Monopar Therapeutics Photos accompanying this announcement are available at: https://www.globenewswire.com/NewsRoom/AttachmentNg/cda29080-7e74-46b0-8b93-5925a209f2abhttps://www.globenewswire.com/NewsRoom/AttachmentNg/cb0b4c63-91dc-46e1-a3c5-862ccc4251d8

Phase 1Clinical Result

21 Aug 2024

·www.globenewswire.com

Monopar Receives Clearance to Proceed with Phase 1 Therapeutic Trial of Novel Radiopharmaceutical in Advanced Cancers

WILMETTE, Ill., Aug. 21, 2024 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharma company focused on developing innovative treatments for cancer patients, today announced it has received Human Research Ethics Committee (HREC) clearance in Australia to commence a Phase 1 therapeutic trial of its novel radiopharmaceutical MNPR-101-Lu. MNPR-101-Lu combines the therapeutic radioisotope lutetium-177 (Lu-177) with Monopar’s proprietary first-in-class humanized monoclonal antibody MNPR-101, which is highly selective against the urokinase plasminogen activator receptor (uPAR). The MNPR-101-Lu Phase 1 clinical trial will enroll patients with advanced solid cancers and will be a therapeutic follow-on study to the currently ongoing MNPR-101-Zr imaging and dosimetry clinical trial. The results from preclinical studies of MNPR-101-Lu are promising. In a 90-day efficacy study in a human pancreatic cancer xenograft mouse model (Figure 1, below) as an example, MNPR-101-Lu demonstrated durable antitumor effects after a single injection, achieving complete elimination of tumors that lasted the duration of the study. The MNPR-101-Lu imaging data in a human pancreatic cancer xenograft mouse model presented in March (link, Figure 2 below) provides additional insight into the strong therapeutic effect observed after a single injection of MNPR-101-Lu. The imaging data demonstrates the high specificity and durable uptake of MNPR-101-Lu in the tumor relative to normal tissue. “We are excited about the HREC clearance and encouraged by the potential of MNPR-101-Lu to provide a meaningful clinical benefit to patients with uPAR-positive tumors. Several of the most aggressive, deadly cancers express uPAR, including triple negative breast cancer and pancreatic cancer,” said Chandler Robinson, MD, Monopar’s Chief Executive Officer. “We are looking forward to launching the trial as quickly as we can.” About Monopar Therapeutics Inc. Monopar Therapeutics is a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, including Phase 1-stage MNPR-101-Zr for imaging advanced cancers and late preclinical-stage MNPR-101-Lu and MNPR-101-Ac225 for the treatment of advanced cancers, as well as early development programs against solid cancers. For more information, visit: www.monopartx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of these forward-looking statements include: that the MNPR-101-Lu Phase 1 clinical trial will enroll patients with advanced solid cancers, and will be a therapeutic follow-on to the currently ongoing MNPR-101-Zr imaging and dosimetry clinical trial; the results from preclinical studies of MNPR-101-Lu are promising; that these data support the potential of MNPR-101-Lu to provide a meaningful clinical benefit to patients with uPAR-positive tumors; and that Monopar is looking forward to launching the trial as quickly as it can. The forward-looking statements involve risks and uncertainties including, but not limited to: that Monopar may not launch its MNPR-101-Lu therapeutic study even after receiving regulatory clearance; that the Phase 1 imaging and dosimetry clinical trial in advanced cancer patients with MNPR-101-Zr may not yield satisfactory results, if at all; that future preclinical or clinical data will not be as promising as the data to date; that MNPR-101-Zr and/or MNPR-101-Lu may cause unexpected serious adverse effects or fail to image or be effective against the cancer tumors in humans; and the significant general risks and uncertainties surrounding the research, development, regulatory approval, and commercialization of imaging agents and therapeutics. Actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Monopar's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Monopar undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Any forward-looking statements contained in this press release represent Monopar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. CONTACT: Monopar Therapeutics Inc.Investor RelationsKarthik RadhakrishnanChief Financial Officerkarthik@monopartx.com Follow Monopar on social media for updates: Twitter: @MonoparTx LinkedIn: Monopar Therapeutics Photos accompanying this announcement are available at https://www.globenewswire.com/NewsRoom/AttachmentNg/46065fd5-9a23-4688-9bbe-1bdb6e74954ehttps://www.globenewswire.com/NewsRoom/AttachmentNg/6fe00a55-f6db-4fba-a0b3-6d4f474b517c

Phase 1IND

14 Aug 2024

·www.globenewswire.com

Monopar Announces Initial Data for First Patient Dosed in Radiopharma Phase 1 Clinical Trial of MNPR-101-Zr

WILMETTE, Ill., Aug. 14, 2024 (GLOBE NEWSWIRE) -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharma company focused on developing innovative treatments for cancer patients, today announced the successful dosing of the first patient in its open-label Phase 1 imaging and dosimetry clinical trial of its uPAR-targeted imaging radiopharmaceutical MNPR-101-Zr. MNPR-101-Zr was well-tolerated with no serious adverse reactions reported through the last imaging timepoint and the corresponding initial safety review. Preliminary analysis of MNPR-101-Zr’s pharmacokinetics and biodistribution suggests the low radiation dose to healthy tissue aligns with what was anticipated based on the previously presented MNPR-101-Zr preclinical biodistribution data. Dosimetry analysis showed absorbed organ doses were well below accepted safety limits; for example, the radiation dose to red bone marrow was about 14 mGy, which is around 150 times less than the generally accepted limit of 2-to-3 Gy. No unanticipated or excessive uptake of MNPR-101-Zr was observed in any critical organs through the end of the subject’s imaging period. The patient has metastatic disease from a cancer type not known for high uPAR expression. The study aims to include several patients with cancers known to express high levels of uPAR to gain insight into MNPR-101-Zr’s tumor uptake profile, in addition to patients with cancers of unknown uPAR expression. “The safety profile observed thus far, along with the encouraging biodistribution data, gives us an increased confidence as we continue to advance our Phase 1 study and prepare to launch our therapeutic study,” said Andrew Cittadine, Monopar’s Chief Operating Officer. Further information about the ongoing MNPR-101-Zr trial is available at www.ClinicalTrials.gov under study identifier NCT06337084. About Monopar Therapeutics Inc. Monopar Therapeutics is a clinical-stage radiopharmaceutical company focused on developing innovative treatments for cancer patients, including Phase 1-stage MNPR-101-Zr for imaging advanced cancers and late preclinical-stage MNPR-101 radio-immuno-therapeutic (RIT) for the treatment of advanced cancers, as well as early development programs against solid cancers. For more information, visit: www.monopartx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of these forward-looking statements include statements concerning: that the study aims to enroll several patients with cancers known to express high levels of uPAR to gain insight into MNPR-101-Zr’s tumor uptake profile, in addition to patients with cancers of unknown uPAR expression; and that the safety profile observed thus far, along with the encouraging biodistribution data, gives Monopar an increased confidence as it continues to advance its Phase 1 study and launch its therapeutic study. The forward-looking statements involve risks and uncertainties including, but not limited to: the Phase 1 imaging and dosimetry clinical trial in advanced cancer patients with MNPR-101-Zr may not yield satisfactory results, if at all; that future preclinical or clinical data will not be as promising as the data to date; that MNPR-101-Zr and/or MNPR-101 conjugated to a therapeutic radioisotope may cause unexpected serious adverse effects or fail to image or be effective against the cancer tumors in humans; that Monopar may not advance its Phase 1 study and launch its therapeutic study; that Monopar may not regain compliance with Nasdaq listing standards within any extended Nasdaq deadline; that Monopar may expend available funds sooner than anticipated or require additional funding due to change in circumstances or unanticipated events; and the significant general risks and uncertainties surrounding the research, development, regulatory approval, and commercialization of imaging agents and therapeutics. Actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Monopar's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Monopar undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Any forward-looking statements contained in this press release represent Monopar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. CONTACT: Monopar Therapeutics Inc. Investor Relations Karthik RadhakrishnanChief Financial Officerkarthik@monopartx.com Follow Monopar on social media for updates:Twitter: @MonoparTx LinkedIn: Monopar Therapeutics

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