Monopar Therapeutics

Oncology

Monopar Therapeutics develops small molecule and antibody therapies for the treatment of cancers and various chemotherapy and radiation associated side effects.

Approach

Validive (Clonidine MBT) for the treatment of severe oral mucositis -A common side effect of head and neck cancer radiation therapy is severe oral mucositis, which occurs as a result of radiation induced damage to the endothelium lining the upper GI tract. If left untreated, severe oral mucositis can lead to pain and malnutrition and can be fatal. Moreover, this side effect limits administration of higher doses of radiation therapy. It has previously been shown that the a2-adrenoceptor is expressed on the surface of invading inflammatory cells such as macrophages and that stimulating this receptor decreases the local concentration of proinflammatory cytokines. Validive combines an a2-adrenoceptor agonist with a mucoadhesive formulation (Lauriad,BioAlliance Pharma) to selectively deliver the agonist to the upper GI tract endothelium and thus limit mucositis causing inflammation.

MNPR-201 (Doxorubicin analogue)-Doxorubicin is a chemotherapeutic agent that functions by inhibiting DNA topoisomerase II activity. The cardiac toxicity of this drug is the main factor limiting therapeutic dose and duration. MNPR-201 is an engineered variant of doxorubicin that specifically targets DNA topoisomerase II-A and not the B variant. Since only the B variant is expressed in cardiomyocytes, the engineered variant of the drug should have lower cardiac-toxicity.

MNPR-101 (anti-uPAR mAB)-uPA is a serine protease that binds to its membrane-anchored receptor, uPAR. This binding interaction in-turn activates the promiscuous plasmin protease. Plasmin is implicated in a variety of proteolytic cascades that activate metastatic pathways. Antibodies that block the uPA/uPAR interaction have previously been shown to inhibit tumor metastasis. However, these antibodies do not have pro-apoptotic and anti-proliferative effects in tumors. MNPR-101 is different from these traditional antibody antagonists in that it does not block uPA/uPAR binding. Rather, MNPR-101 binds uPAR at an epitope that blocks CD11b and a5B1 integrin association. Inhibiting this integrin association has been shown to have anti-metastatic, anti-proliferative and apoptosis inducing effects in a variety of solid tumors. MNPR-101 has shown to be effective in broader range of cancers than traditional uPA/uPAR antagonists. The signaling pathways that this antibody modulates are still not fully understood.

Literature

Comparison of the Systemic and Local Pharmacokinetics of Clonidine Mucoadhesive Buccal Tablets with Reference Clonidine Oral Tablets in Healthy Volunteers: An Open-Labbel Randomised Cross-Over Trial
Basseur, B; Dufour, A; Houndas, L; Goodwin, H; Harries, K; Emul, NY; Hutchings, S. Advances in Therapy. 2017 Aug; 34(8): 2022-2032.

Comparative Effects of Doxorubicin and a Doxorubicin Analog, 13-deoxy, 5-iminodoxorubicin (GPX-150), on Human Topoisomerase IIβ Activity and Cardiac Function in a Chronic Rabbit Model.
Frank, NE; Cusack, BJ; Talley, TT; Walsh, GM; Olson, RD. Investigational New Drugs. 2016 Dec; 34(6): 693-700.

Phase I and Pharmacokinetic Study of the Novel Anthracycline Derivative 5-imino-13-deoxydoxorubicin (GPX-150) in Patients With Advanced Solid Tumors.
Holstein, SA; Bigelow, JC; Olson, RD; Vestal, RE; Walsh, GM; Hohl, RJ. Investigational New Drugs. 2015 Jun; 33(3)594-602.

Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b
Xu, X; et al. PLoS One. 2014; 9(1).

An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658) Blocks Prostate Cancer Invasion, Migration, Growth and Experimental Skeletal Metastasis in Vitro and In Vivo.
Rabbani, SA; Aeeq, B; Arakelian, A; Valentino, ML; Shaw, DE; Dauffenbach, LM; Kerfoot, CA; Mazar, AP. Neoplasia. 2010 Oct; 12(10): 778-88.

Select Patents

Full list of 9 patents assigned to Monopar Therapeutics, Inc

Treating Inflammation and Inflammatory Pain in Mucosa Using Mucosal Prolonged Release Bioadhesive Therapeutic Carriers

5-imino-13-deoxy Anthracycline Derivatives, Their Uses, and Processes for Preparing Them

Development Stage

ValidivePhase II clinical trial complete

MNPR-201-Phase II clinical trial complete

MNPR-101-Preclinical Development

Innovation Opportunity

  • Oncology
  • Small molecule
  • Antibody
  • Novel cancer mechanisms of action

Partnering

Monopar therapeutics is interested in acquiring or licensing cancer therapeutics at various stages of development that have demonstrated anti-cancer activity and safety in pre-clinical models. Current leads in development have come from a combination of academic and industry acquisitions and licenses.

Contact Information



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