TopoTarget A/S Symbion Science Park 3 Fruebjergvej DK-2100 Copenhagen, Denmark Phone: +45 39 17 83 90 www.TopoTarget.com Unique Oncological Biopharmaceutical Opportunity Snapshot January 26, 2005 TopoTarget A/S is a privately held biopharmaceutical company focused on developing novel pharmaceuticals for cancer† and cancer-related indications, as well as on the identification of new indications for existing compounds. The Company’s first internally developed product, Topotect, is in Phase III as an antidote for extravasation, a severe form of tissue damage resulting from an incorrect administration of cytotoxic anthracyclines or chemotherapy drugs. Pending approval, the Company could launch Topotect in winter 2005/2006. This product, based on the concept of deoxyribonucleic acid (DNA) damage control, would provide TopoTarget access to profitable, lower-risk markets. TopoTarget is also developing Topotect for the treatment of brain metastases, a life-threatening condition that affects approximately 60% of primary small cell lung cancer (SCLC) patients. Topotect recently entered Phase I/II clinical trials for this indication. Additionally, TopoTarget is heavily involved in the management of chromatins, the proteins responsible for the formation of DNA-containing chromosomes. The Company’s expertise in this area has led to the development of PXD101, a Phase I anti-cancer histone deacetylase (HDAC) inhibitor that interferes with cell cycle arrest and angiogenesis, and has demonstrated anti-tumor activity in vivo. TopoTarget expects to employ this drug to target a variety of cancer indications, including multiple myeloma, malignant lymphoma, and ovarian, colorectal, and prostate cancer. TopoTarget also has a library of diverse HDAC inhibitors that have demonstrated efficacy in a variety of cancer and non-cancer indications. Key Points TopoTarget has three products in clinical trials, as well as approximately a half-dozen preclinical stage compounds. The Company’s most advanced product, Topotect, was granted Orphan Drug designation as an antidote for anthracycline extravasation in Europe in 2001 and could receive approval within the next 12 months. Orphan Drug designation was also granted by the U.S. Food and Drug Administration (FDA) in 2004. Following approval, TopoTarget expects to sell the product in Europe and partner it outside of Europe with a large pharmaceutical company. In May 2004, the National Cancer Institute (NCI) and TopoTarget signed a letter of intent to enter into a Cooperative Research and Development Agreement (CRADA) to conduct the preclinical and clinical development of PXD101, TopoTarget’s proprietary HDAC inhibitor. The agreement involves the determination of the most appropriate anti-cancer agents for use in combination with PXD101. Also, the NCI and TopoTarget are collaborating on the identification of anti-cancer drug candidates from TopoTarget’s library of HDAC inhibitors. In June 2004, TopoTarget and U.S.-based CuraGen Corporation (CRGN-NASDAQ) announced a license, collaboration, and commercialization agreement on a small molecule inhibitor program targeting HDAC in oncology. TopoTarget was founded by clinical oncologists who have an understanding of the realities of clinical practice. This enables the Company to choose intelligently between an array of possibilities and targets. Additionally, the Company has proven in-house clinical trial capabilities. TopoTarget’s leadership team is experienced in medical products, biopharmaceuticals, and pharmaceuticals, and has a track record of success over many decades in research, drug EXECUTIVE INFORMATIONAL OVERVIEW development, clinical practice, and venture development. The Company has achieved all of its key business and scientific milestones since its last funding round in June 2002. Over the next 24 months, TopoTarget could achieve more than a half-dozen separate potential revenue-generating milestones. †BOLD WORDS ARE REFERENCED IN GLOSSARY ON PAGES 45-48. Table of Contents Snapshot ................................................................................................................................................1 Key Points .....................................................................................................................................................1 Executive Overview.......................................................................................................................................3 Growth Strategy.............................................................................................................................................7 Intellectual Property.......................................................................................................................................9 Management and Board of Directors ..........................................................................................................12 Core Story ...................................................................................................................................................15 Cancer ....................................................................................................................................................15 The Cancer Cell Cycle ......................................................................................................................15 Advanced Stage Development...............................................................................................................20 Chemotherapy...................................................................................................................................20 Extravasation................................................................................................................................21 Topotect for Extravasation ......................................................................................................26 Brain Metastases..........................................................................................................................30 Topotect for Brain Metastases ................................................................................................31 Histone Deacetylase (HDAC) Inhibitors for Multiple Indications ..................................................33 PXD101 ...................................................................................................................................34 Early Stage Development..................................................................................................................36 HDAC Inhibitor Library .................................................................................................................36 In-licensed .........................................................................................................................................37 Potential Milestones Within Next 12-24 Months..........................................................................................38 Historical Financial Results .........................................................................................................................39 Risks............................................................................................................................................................42 Recent Events .............................................................................................................................................44 Glossary of Lesser-Known Terms ...............................................................................................................45 Executive Informational Overview Page 2 Executive Overview TopoTarget A/S is a privately held biopharmaceutical company focused on developing novel compounds for cancer and cancer-related indications. The Company’s development efforts employ a broad understanding of the molecular mechanisms of cancer and the realities of clinical practice to develop new and potentially effective approaches to combat the various manifestations of the disease. Pipeline TopoTarget’s pipeline is based on two pillars: (1) early revenues from specialty products, and (2) value growth from more broad indication products. With regard to the first pillar, the Company could launch its first product, Topotect for extravasation, in winter 2005/2006. Topotect could provide the Company with a base for top-line growth and profitability by 2007. Additionally, TopoTarget is developing Topotect (currently in Phase I/II) for brain metastases and PXD101 (currently in Phase I) for multiple indications. The Company also possesses a range of preclinical compounds targeted at a variety of indications. Figure 1 provides a snapshot of the Company’s drug development pipeline, according to advanced stage and early stage development candidates. This is followed by an overview of its three leading and most advanced product candidates under development, as well as its earlier stage development candidates. Advanced Stage Development Figure 1 TopoTarget A/S DRUG DEVELOPMENT PIPELINE Product Indication Lead ID Lead OP Preclin Phase I Phase II Phase III Reg filing Sales Source: TopoTarget A/S. Executive Informational Overview Page 3 Topotect for extravasation. The Company’s first internally developed product, Topotect, is in Phase III as an antidote for extravasation, a severe form of tissue damage resulting from an adverse reaction to anthracyclines, a group of commonly used cytotoxic agents. Extravasation occurs when an anthracycline