CuraGen Corporation And TopoTarget A/S Announce Presentation Of PXD101 Phase I Results At American Society of Hematology

BRANFORD, Conn., Dec. 12 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S announced today that Phase I data on PXD101, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of advanced hematologic and solid cancers, were presented at the American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia, December 10 to 13, 2005. Preliminary results on 16 patients show that PXD101 is well-tolerated following intravenous administration and has demonstrated potential anti-tumor activity against multiple myeloma, non-Hodgkin's lymphoma (NHL) and transformed chronic lymphocytic leukemia (CLL).

The Phase I clinical findings, plus results from preclinical studies evaluating PXD101 activity on a number of hematologic and multi-drug resistant cancer cell lines, were presented in a poster entitled, "Activity of the Histone Deacetylase (HDAC) Inhibitor PXD101 in Preclinical Studies and in a Phase I Study in Patients with Advanced Hematological Tumors."

The Phase I open-label study was designed to determine the safety, maximum-tolerated dose (MTD) and potential clinical activity of intravenously administered PXD101. PXD101 was administered as a single agent to patients with advanced hematologic tumors, including multiple myeloma, NHL and CLL. The drug was generally well-tolerated with the most common adverse events being fatigue, nausea and vomiting, consistent with what has been seen in a larger parallel Phase I study for patients with solid tumors. Two patients with multiple myeloma developed an acute decrease in renal function concomitant with decrease in tumor burden, consistent with possible tumor lysis syndrome, an indication of potential clinical activity. In addition, it was reported that one patient with NHL had stable disease for five cycles and one patient with transformed CLL had stable disease for nine cycles.

Preclinical studies conducted with PXD101 were also reported in the presentation. PXD101 monotherapy inhibited the growth of various hematological cancer cell lines at sub-micromolar potency and was highly effective even on cell lines that are resistant to other chemotherapeutics. Moreover, the combination of PXD101 with Velcade(R) (bortezomib) showed greater growth-inhibitory activity, as compared to either drug used alone, on a multiple myeloma cell line.

In a second presentation, additional preclinical data on PXD101 in multiple myeloma was reported yesterday by the University of Pittsburgh Cancer Institute in a poster entitled, "Combination of the Proteasome Inhibitor PS- 341 (Velcade(R)) with the Histone Deacetylase Inhibitor (HDAC) PXD101 Shows Superior Anti-Myeloma Activity and Inhibits Osteoclastogenesis." The results showed that PXD101 monotherapy had antiproliferative activity on myeloma cells and inhibited osteoclast formation. Furthermore, synergistic activity was observed when PXD101 was combined with Velcade in antiproliferative and osteoclast formation in vitro assays, and this drug combination strongly inhibited myeloma tumor growth in an animal model. These preclinical data support the evaluation of PXD101 as monotherapy and in combination with Velcade(R) in clinical trials of patients with multiple myeloma. This work was supported under the Clinical Trials Agreement between CuraGen and the Division of Cancer Treatment and Diagnosis for the development of PXD101.

"We are very pleased with the preliminary data from this Phase I trial of PXD101 for patients with hematologic tumors," stated Timothy M. Shannon, M.D., Executive Vice President of Research and Development and Chief Medical Officer at CuraGen. "These results formed the basis for our ongoing Phase II clinical trial, which is currently evaluating PXD101 for the treatment of advanced multiple myeloma. We anticipate that preliminary results from this Phase II study will be available by mid-2006."

Reprints of the poster presentation and published abstracts, as well as information about ongoing clinical trials are available on CuraGen's website, http://www.curagen.com, or by emailing info@curagen.com.

About HDAC inhibitors and PXD101

A growing body of research highlights the role of histone deacetylases (HDAC) in regulating gene expression, particularly the expression of cancer- related genes. HDAC inhibitors represent a new mechanistic class of anti- cancer therapeutics that target HDAC enzymes, and have been shown to: arrest growth of cancer cells (including drug resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance phenotype when used in combination with other anti-cancer agents. HDAC inhibitors are believed to play a role in a wide range of solid tumors, such as breast, colon, lung and ovarian cancers, and hematological malignancies, such as lymphoma, leukemia and myeloma.

CuraGen and TopoTarget currently have five ongoing clinical trials evaluating PXD101. In addition to two Phase I trials evaluating PXD101 for solid and hematologic cancers, PXD101 is being evaluated in Phase II for the treatment of advanced multiple myeloma, in a Phase Ib trial exploring the safety and potential activity of PXD101 in combination with 5-fluorouracil for solid tumors, including colorectal cancer, and a Phase Ib trial exploring the safety and potential activity of PXD101 in combination with paclitaxel and/or carboplatin for solid tumors, including ovarian cancer. Additional proof-of- concept studies studying other solid and hematologic cancers will be initiated throughout 2005 and 2006 in order to evaluate both the safety and activity of PXD101 alone and in combination with other active anti-cancer treatments.

About CuraGen

CuraGen Corporation is a biopharmaceutical company dedicated to improving the lives of patients by developing a pipeline of novel protein, antibody, and small molecule therapeutics in the areas of oncology, inflammatory diseases, and diabetes. CuraGen has established broad development alliances with Abgenix, TopoTarget, and Bayer, and its experienced preclinical and clinical teams are advancing its pipeline of products for unmet medical needs. CuraGen is headquartered in Branford, CT. For additional information please visit http://www.curagen.com.

About TopoTarget

TopoTarget (CSE: TOPO) is a publicly listed biopharmaceutical company based in Denmark, UK and Germany, dedicated to finding answers to cancer and developing improved therapies with a strong focus on cancer patient needs. TopoTarget both develops novel pharmaceutical compounds and identifies new indications for existing drugs, combining its broad and in-depth understanding of the molecular mechanisms of cancer with a wide experience in clinical oncology practice. Having grown both organically and through acquisitions/in- licensing, TopoTarget has built substantial platforms in HDAC and topoisomerase II inhibitors as well as a clinical pipeline comprising eight programmes with the most advanced drug candidate in regulatory review. TopoTarget is also establishing its own specialist sales force in Europe. For more information, please refer to http://www.topotarget.com.

Safe Harbor

This press release contains forward-looking statements including statements about the potential anti-tumor activity of PXD101, CuraGen's anticipation that preliminary results from the Phase II study will be available in mid-2006, and CuraGen's anticipation that additional proof-of- concept studies studying other solid and hematologic cancers will be initiated throughout 2005 and 2006 in order to evaluate both the safety and activity of PXD101 alone and in combination with other active anti-cancer treatments. We caution investors that there can be no assurance that actual results or business conditions will not differ materially from those projected or suggested in such forward-looking statements as a result of various factors, including, but not limited to, the following: the risk that any one or more of the drug development programs of CuraGen and/or TopoTarget will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources; the success of competing products and technologies; technological uncertainty and product development risks; uncertainty of additional funding; CuraGen's history of incurring losses and the uncertainty of achieving profitability; CuraGen's stage of development as a genomics-based pharmaceutical company; government regulation; patent infringement claims against CuraGen's products, processes and technologies; the ability to protect CuraGen's patents and proprietary rights; uncertainties relating to commercialization rights; and product liability exposure. Please refer to CuraGen's Quarterly Report on Form 10-Q for the period ended September 30, 2005 for a complete description of these risks. CuraGen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, unless required by law.

Contacts: CuraGen Corporation Glenn Schulman, PharmD, MPH gschulman@curagen.com (888) 436-6642

CuraGen Corporation

CONTACT: Glenn Schulman, PharmD, MPH of CuraGen Corporation,+1-888-436-6642, gschulman@curagen.com

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