New approach to glioblastoma treatment addressing the critical unmet medical need.

WPD Pharmaceuticals conducts research related to the development of the WPD104 molecule - berubicin, as a novel drug in glioblastoma multiforme (GBM) therapy for children and adults patients, as a part of the project “New approach to glioblastoma treatment addressing the critical unmet medical need”.

Berubicin belongs to the anthracyclines, one of the most widespread and effective group of anticancer drugs. Anthracyclines currently used in the clinical practice (daunorubicin, doxorubicin, epirubicin) showed strong cytotoxic properties against many types of cancer, they are ineffective against brain tumors, including GBM, as they do not cross the blood-brain barrier (BBB). The advantage over the standard treatment is that berubicin overcomes the BBB and can affect cancer cells in the brain. Berubicin binds to DNA and inhibits topoisomerase II function, leading to the formation of double strand DNA breaks and apoptosis induction.

Standard GBM chemotherapy currently includes treatment with temozolomide (TMZ), a DNA alkylating agent. However, in about 60% of GBM patients, the lack of the methylation of the MGMT gene promoter region (O6-methylguanine-DNA methyltransferase), causes an increase in MGMT level and stimulation of DNA repair processes. Thus, MGMT limits or completely abolishes cytotoxic effects of TMZ.

In patients with high MGMT expression, berubicin could be an alternative therapy, replacing inefficient TMZ. In addition, during TMZ chemotherapy, many patients develop chemoresistance due to the induction of MDR proteins expression, which actively expel cytotoxic drugs from the cells. Previous preclinical studies on in vitro model have shown, that berubicin is highly effective apoptosis inducer even in the presence of MDR proteins.

Phase I clinical trail in patients with brain tumors, including GBM, showed significant therapeutic effect in 44% of the treated patients population. One of the patients achieved -an unexpected in this phase long-term therapeutic effect - an over 5-year survival without recurrence, which is recognized in oncology as a cure from the disease. Moreover, drug resistance was not observed and adverse effects were severely limited.

The main goal of the project is to implement the first in the world multicenter pediatric phase I clinical trial to determine maximum tolerated dose (MTD) and phase IB and II clinical trials in adults, thus confirming the efficacy of berubicin – an innovative drug to eliminate brain cancer cells that are resistant to temozolomide.

The projecy willalso include preclinical tests to determine the prospective use of berubicin with temozolomide and with other compounds developing by the WPDPharmaceuticals as a candidates for anticancer drugs.

This project is co-financed by the European Union from the European Regional Development Fund under the Smart Growth Operational Program 2014-2020, Sectoral Programme InnoNeuroPharm, Priority Axis I: Support R&D carried out by enterprises,Measure 1.2: Sectoral R&D Programmes, implemented under National Center for Research and Development.

Co-financing of the project from the EU: 22 033 066,00 PLN

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