Medigene AG - EndoTAG TM-1

EndoTAG^TM-1

Cancer

Starving out cancer cells
EndoTAG^TM-1 directly attacks those blood vessels that are needed for the growth of a tumor. If these blood vessels (the endothelial cells) are destroyed, the cancer cell does not receive sufficient oxygen and nutrients. Hence, the tumor is "starved."

The drug candidate is based on the combination of lipids - i.e. fat molecules which also exist inside the cell membrane - and a therapeutic substance. In EndoTAG^TM, these components exist as "lipid complexes" or liposomes which can be pictured as minute, hollow globules. The therapeutic substance is embedded in these globules. In the case of EndoTAG^TM-1, this substance is Paclitaxel^®, one of the most effective substances in chemotherapy. The EndoTAG^TM liposomes are positively charged, enabling them to attach themselves selectively to the negatively charged, newly developing endothelial tumor cells (neovascular targeting) and to destroy them (vascular disrupting). This process is intended to suppress nutrient supply and inhibit further tumor growth.

With its novel mode of action, EndoTAG^TM adds an innovative variant to the successful anti-angiogenesis approach (inhibition of vascularization). Moreover, EndoTAG^TM offers a novel alternative to conventional chemotherapy. MediGene assumes that direct destruction of the endothelial cells does not lead to any resistance to the therapeutic substance applied. This would solve a common problem inherent to existing therapies. In addition, the EndoTAG^TM concept is expected to provide a wide range of applications. Principally, it could be suited for the treatment of all types of solid tumors which have their own vascularization.

EndoTAG^TM-1 is MediGene's first product candidate derived from the EndoTAG^TM platform technology and was undergoing an extensive phase II program. In a trial with over 200 patients participating, EndoTAG^TM-1 was combined with the drug Gemcitabine. In 2007, MediGene extended the development of EndoTAG^TM-1 and initiated a large-scale phase II trial for the treatment of hormone-resistant breast cancer. EndoTAG^TM-1 targets the treatment of severe types of cancer with high medical need.

Outlook
End of march 2008 MediGene could show excellent efficacy data as a result of the clinical phase II trial of EndoTAG^TM-1 in the indication pancreatic carcinoma. The trial showed substantially extended survival time of those patients treated with EndoTAG^TM-1 in combination with the standard drug gemcitabine, compared to those receiving only gemcitabine. The median survival time of the group treated with the highest dosage of EndoTAG^TM-1 increased by 30 % compared to the control group. The positive safety profile of EndoTAG^TM-1 shown in the interim analysis was maintained as well as its positive effect on the patients� quality of life. The detailed data evaluation will be published in the fourth quarter of 2008. . The results of the trial in the indication breast cancer are expected in 2009. Provided that the development of the product progresses successfully, EndoTAG^TM-1 has a potential of more than 1 billion €.

EndoTAG^TM attacking endothelial tumor cells

		Tumor cells
		Tumor releases signals inducing growth of blood vessels
		Endothelial cells divide, blood vessels grows towards tumor
		EndoTAG attacks activated endothelial cells and destroys blood vessel.Thereby the blood supply of the tumor is impaired
		EndoTAG^TM is a trademark of MediGene AG.

Webcast of the MediGene AG to Discuss the Results Obtained in a Clinical Phase II Trial of EndoTAG�-1 on April 7, 2008