Unibioscreen Announces Progress Of Phase I Clinical Trial For UNBS1450 In Europe In Cancer Patients With Advanced Solid Tumors

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 08 Jan 2009 - 4:00 PDT

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Unibioscreen S.A., the Brussels-based specialist oncology company, is pleased to announce that the clinical testing of its second experimental anti-cancer drug, UNBS1450, which is being administered in cancer patients since October 2008, is progressing well.

The trial is being conducted under the supervision of Dr Patrick Schöffski and Dr Hans Gelderblom at the Gasthuisberg University Hospital in Belgium and at the Leiden University Medical Center in the Netherlands. The objectives of the clinical phase I trial are to assess safety and to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) by applying a dose-escalation schedule with a limited number of patients and to define the recommended Phase II dose. The study will allow Unibioscreen to assess tolerability and to obtain pharmacokinetics' and pharmacodynamics' data. During the trial tumor samples will be analyzed. In addition, once the maximum dose is reached, a maximum of 10 patients will be treated at that dose level to further evaluate the safety profile, pharmacokinetics, any preliminary evidence of antitumor activity and to perform non-mandatory sequential tumor-sampling for assessment of surrogate markers of drug activity.

The drug candidate is being administered IV to patients with advanced solid tumors or lymphoma.

"We are very pleased with the interim results from the clinical study of our novel cancer compound. So far, no drug-related serious side effects have been reported. We are hopeful that the development will continue positively and are looking forward to offering this novel compound to oncology patients in the future", said Christiane Verhaegen, CEO of Unibioscreen.

Dr Patrick Schöffski and Dr Hans Gelderblom, Principal Investigators who are leading the clinical trials commented: "We are confident that promising compounds with unique mechanism of action such as UNBS1450 may offer novel treatments to patients with advanced cancer."

About Unibioscreen

Unibioscreen is a specialist oncology drug discovery and development company, working on novel, first-in-class compounds, with two blockbuster-potential drugs candidates in clinical development.

Unibioscreen's core business is the identification and development of new chemical entities for the targeted treatment of cancer and its metastases. The company's focus is on cytotoxic/cytostatic chemotherapeutics that kill apoptosis-resistant and multidrug resistant cancer cells, and anti-migratory drug candidates that fight metastases. Most of Unibioscreen's drug candidates are derived from molecules observed in nature. Unibioscreen will continue to develop novel compounds in the clinic.

More information is available on: http://www.unibioscreen.com

About UNBS1450

UNBS1450 is a hemi-synthetic derivative of the novel cardenolide 2''-oxovoruscharin, identified by Unibioscreen in the root bark of Calotropis procera.

UNBS1450 has a unique mechanism of action: it is a sodium pump antagonist; it binds to the alpha subunit of the sodium pump. The general mechanism of action associated with UNBS1450-mediated anti-cancer effects relates to its disorganization of the actin cytoskeleton, which seems in turn to be mediated by compound-induced cellular ATP depletion. The sodium pump family of trans-membrane transporter, are, alongside protein kinases, regarded as the most promising targets available to the drug industry.

UNBS1450 targets all solid cancers over-expressing the alpha 1 and/or alpha 3 subunit of the sodium pump (40% of all solid cancers), esp. glioblastoma, Non Small Cell Lung Cancer (NSCLC), melanomas and prostate cancer.

The available nonclinical data show that UNBS1450 overcomes major pathways responsible for the failure of existing cancer chemotherapy.

UNBS1450 kills cancer cells through the activation of several non-apoptotic cell death pathways (like autophagy).

It has shown in vitro & in vivo anti-proliferative and anti-metastatic activity and has shown in vitro that it kills apoptosis-resistant cancer cells, including multidrug-resistant cancer cells.

UNBS1450 differs markedly in structure from classic cardenolides (i.e. ouabain, digitoxin and digoxin) and displays notably higher binding affinity for sodium pump α subunits, resulting in increased anti-cancer activity; UNBS1450 has demonstrated in vitro i) activity against multi-drug resistant cancer lines, ii) 10 fold greater toxicity to cancer cells compared to normal cell lines (IC50 values in the 10-50nM range against cancer cells but in the ~μM range in normal cells), iii) irreversible growth arrest in cancer cells even after limited exposure (1-2h), iv) autophagy-like rather than apoptotic cell death (which may indicate the potential to circumvent major apoptosis resistance pathways responsible for the failure of chemotherapy in certain cancers) and v) effects on downstream signaling pathways, provoking nucleolar targeting and irreversible c-Myc down-regulation.

UNBS1450 displays potent in vivo anti-tumor activity in biologically aggressive human orthotopic and subcutaneous xenografts of NSCLC, prostate cancers and gliomas, and to a lower extent in orthotopic xenografts of human colon cancers, and subcutaneous xenografts of human breast cancers and melanomas.

Cancer patients are being recruited for the Phase I trial that started in Western Europe in October 2008 at the Gasthuisberg University Hospital in Belgium and at the Leiden University Medical Center in the Netherlands.

Unibioscreen