Takara Bio Inc, (Otsu, Japan) announced that its partner, MolMed S.p.A. (Milan, Italy) confirmed successful achievement of primary endpoints for the TK007 Phase I/II clinical trial of the HSV-TK gene therapy, being developed jointly by Takara Bio in Asia and by MolMed in Europe and USA, and plans to move forward to Phase III in the European Union in the middle of this year. The scientific data were presented by MolMed at the 46th ASH (American Society of Hematology) annual meeting and exposition in San Diego, USA, December 4 -7, 2004.

Bone marrow transplantation in combination with chemo- and/or radiotherapy is the most effective treatment of choice for haematological malignancies such as leukaemia, lymphoma and myeloma. However, the majority of patients can not benefit from bone marrow transplantation due to the lack of suitable donors. The HSV-TK gene therapy is an adjunctive therapy to bone marrow transplantation that allows patients who have no suitable donors but have haplo-identical donors such as their parents or children to take bone marrow transplantation, since the therapy can quickly reconstitute the patient's immune system and also can control at the same time the major complication of bone marrow transplantation which is Graft versus Host Disease (GVHD), an immune attack of the donor's T cells against the patient's organs and tissues. If GVHD occurs, the patient receives a drug (ganciclovir) that leads to the selective elimination of the cause of GVHD, thus abrogating GVHD symptoms while preserving the underlying bone marrow and native immune system unaffected.

The TK007 Phase I/II multi-center trial is conducted in EU for haplo-identical Stem Cell Transplantation (Haplo-SCT) followed by HSV-TK suicide gene engineered donor lymphocytes infusion (TK-DLI) for patients with high risk hematological malignancies. The primary endpoints of the study are the evaluation of the timing of immune reconstitution after TK-DLI, the evaluation of the frequency of GVHD and the ability to abrogate it, and the evaluation of the Graft versus Leukaemia (GVL) effect.

The results of the interim analysis by MolMed S.p.A. confirm that TK-DLI is an effective and safe tool for promoting immune reconstitution and protecting patients from infectious mortality after Haplo-SCT while providing an effective and selective treatment for GVHD. Briefly, immune reconstitution was successfully achieved for so far 11 out of total 13 treated patients, at a median time of 24 days from TK-DLI. Such an early immune reconstitution resulted in complete control of viral infection and virtually eliminated late infections frequently reported after Haplo-SCT. Despite the high risk patient population, out of the 13 patients, 6 are alive and in CR (+553, +491, +232, +227, +175 and +126 days from Haplo-SCT). Out of the 11 patients who achieved immune reconstitution, 3 experienced severe acute GVHD and the symptoms were completely abrogated by ganciclovir at dosage used for treatment of CMV infection, even in the absence of any immunosuppressive drugs.

Based upon these promising results, both companies are confident to move forward to a Phase III study in EU, Phase I study in Japan and Phase I/II study in the US after completing the European Phase I/II study in 2005. MolMed received Orphan Drug designation for the HSV-TK gene therapy for the haplo-SCT setting from EMEA (the European Agency for the Evaluation of Medicinal Products) in 2003, and is currently discussing with EMEA the planned Phase III clinical trial.
Takara Bio Inc is in the regulatory process to initiate a Phase I clinical study with TK-DLI for leukemia relapsed patients in Japan in the middle of this year.

Takara Bio Inc. and MolMed S.p.A. have signed in 2003 an alliance agreement under which Takara Bio Inc. acquires exclusive rights to commercialise the HSV-TK gene therapy in Asia. Sharing clinical data as well as regulatory information obtained in each company's territory will forward development and commercialisation of the gene therapy product by Takara Bio Inc. or MolMed S.p.A. more quickly and effectively.

About Takara Bio Inc.
Takara Bio Inc. is an innovative biotechnology company based in Shiga, Japan. As a world leader in biotechnology research and development, Takara Bio was the first company to market PCR technology in Japan and is also the developer of the RetroNectin^® reagent, which is a world-standard in gene therapy protocols. In addition to providing research reagents and equipment to the life science research market, Takara Bio has active research and product development activities in the fields of gene and cell-based therapy, and agricultural biotechnology; and is committed preventing disease and improving the quality of life for all people through the use of biotechnology. Through strategic alliances with other industry leaders, the Company aims to extend its reach around the world. More information is available at http://www.takara-bio.com.

About MolMed
MolMed S.p.A. is a biotech company focused on the development of innovative therapies for the treatment of cancer and AIDS. The company is based in Milan (Italy) within the premier Italian biomedical research institute, the San Raffaele Biomedical Science Park.
MolMed has currently four promising products targeting cancer and AIDS in its development pipeline, three of which are in phase I/II clinical trials and one in phase I. MolMed's therapies encompass groundbreaking treatments such as gene therapy, therapeutic vaccination, and vascular targeting. These therapies are highly specific and improve therefore quality of life by considerably reducing toxicity. MolMed's products are protected by a strong intellectual property of 44 patent families which the company either owns or which it has licensed with exclusive or non-exclusive rights.

For more information:
Corporate Communications
Takara Bio Inc.
E-mail: bio-ir@takara-bio.co.jp

This article is translated from press release in Japanese for your convenience.

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