Out-licensing

Clinical Development of ARENEGYR: A Vascular Targeting Agent for the Treatment of Cancer

Introduction/Background

In the Western world, colorectal, liver, ovarian, prostate, small cell- and non small cell lung cancers, mesothelioma and soft tissue sarcoma account for over 1,5 million new cases each year, with a 5-year prevalence of 3,8 million patients. The overall market potential of ARENEGYR is considerable: it has use as a single agent therapy, as part of combination therapy with standard chemotherapy regimens, and in pre-surgery treatment as a neoadjuvant.

Aims/Hypothesis

MolMed plans to first develop ARENEGYR as a novel therapeutic option for relapsing disease in eight indications with high unmet medical need: colorectal, liver, ovarian, prostate, small cell- and non small cell lung cancers, mesothelioma and soft tissue sarcoma.

Results

ARENEGYR is a vascular targeting agent which selectively binds to and acts on tumour blood vessels. ARENEGYR is a recombinant fusion protein exploiting a tumour-homing peptide (NGR) that selectively binds to CD13 aminopeptidase N (CD13/APN), present only on endothelial cells of newly formed tumour blood vessels. The combination of this peptide with the human cytokine TNF-a generates a unique, complex interaction: ARENGYR-specific binding relies on dynamic interactions with receptors expressed by the tumour neovasculature endothelium, but not by normal vessels. This combination also provides ARENEGYR with unique biological properties. High doses of ARENEGYR induce tumour mass necrosis by vascular disruption, whereas low doses induce both a therapeutic effect due to a modulation of the immune response, and an increase in vascular permeability, thereby improving the effectiveness and therapeutic index of concomitantly administered cytotoxic drugs. ARENEGYR acts independently of tumour type, and has a low risk of inducing pharmacological resistance.

MolMed is completing the Phase I clinical development as a single agent, conducted in two dose-escalation trials for the treatment of solid tumours: a single centre study in Italy, limited to the low dose range and successfully completed, and a multicentre study in Germany and the Netherlands managed by the European Organisation for Research and Treatment of Cancer (EORTC) network. Overall, preliminary results of these trials are very promising, and primary endpoints in the low-dose range have already been successfully met, allowing to start Phase II trials in the low dose range and Phase I trials in combination with selected chemotherapeutic agents.

Phase II trials of single-agent, low-dose ARENEGYR are ongoing in colorectal cancer, hepatocarcinoma, small-cell lung carcinoma and mesothelioma.

A Phase I trial evaluating low-dose ARENEGYR in combination with doxorubicin has been successfully completed; Phase II trials of this combination in ovarian cancer and in sarcoma have received approval, and are planned to start in 2008.

A Phase I trial of low-dose ARENEGYR in combination with cisplatin is ongoing, and a Phase II trial in combination with Xelox in colorectal cancer is planned to start in 2008.

Conclusion

ARENEGYR is a unique vascular targeting agent for cancer treatment.

Relevance/Opportunity

MolMed is seeking a co-development or out-licensing partnership to take ARENEGYR through its full clinical programme to product commercialisation. MolMed is particularly interested in collaborations with major pharmaceutical or medical biotech companies seeking to strengthen their existing oncology portfolio.

Phase II