Diatos pre-clinical results published in Clinical Cancer Research DTS-108, a Breakthrough Second Generation Irinotecan, Shows Promising In Vivo Efficacy and Toxicology Results

Paris, France, 1 April 2008 – Diatos SA, an international biopharmaceutical company focusing on the research, development and commercialization of targeted anti-cancer drugs, announced that the peer-reviewed medical journal ‘Clinical Cancer Research’ has today published positive pre-clinical in vivo efficacy and toxicology results concerning DTS-108. The research demonstrated that DTS-108 has greater anti-tumoral efficacy and safety, compared to irinotecan, as a result of an efficient and non-hepatic mode of activation. This leads to significantly higher circulating levels of the active metabolite with reduced gastrointestinal toxicity. In addition, it is anticipated that DTS-108 will bypass the inter-patient variability which is a major limitation in the therapeutic use of irinotecan. This is due to enhanced delivery of the active metabolite by using Diatos’ linker peptide technology, Vectocell®, which safe guards the efficacy whilst reducing the toxic side effects of the anti-cancer product.

Irinotecan is an effective chemotherapeutic agent that is prescribed for advanced colorectal, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The principle side effect of irinotecan is severe (grade 3-4) diarrhoea observed in 30-40% of treated patients. A significant clinical advantage should therefore be gained from the direct administration of the active metabolite, SN38, using a drug delivery technology such as Vectocell®, which delivers higher concentrations of SN38, whilst bypassing the severe side effects.

Commenting on today’s announcement, Jonathan Kearsey, Ph.D, Director of Research at Diatos, said: “The search for cytotoxic molecules with enhanced efficacy and toxicity profiles is essential for improved cancer patient care. This peer-reviewed publication represents another step in the validation of the benefits of DTS-108 versus standard of care treatment.”

“Rapid completion of the preclinical toxicology program is expected to allow Diatos to further evaluate the benefit of DTS-108 and the Vectocell® technology platform in the clinical setting.” He added.

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Notes to Editors

The publication entitled “DTS-108, a novel peptidic prodrug of SN38: in vivo efficacy and toxicokinetic studies” appeared in 1st April edition of Clinical Cancer Research, Vol 14, Issue 7.

For a copy of the publication or further information on the release please contact:

Media

College Hill Life Sciences
Katja Stout / Justine Lamond / John McIntyre
Tel: +44(0)20 7866 7857
E-mail: diatos@collegehill.com 

Investors

Diatos SA
Dr John Tchélingérian
President & CEO
Tel: + 33 (0)1 53 80 93 81
Email:Jtchelingerian@diatos.com

About DTS-108

DTS-108 is an oncology drug product consisting of SN38 (the active metabolite of irinotecan, CPT-11, Campto®, Camptosar®) conjugated through a chemical linker to a Vectocell® peptide. DTS-108 aims to safeguard the efficacy of SN38 while reducing the toxic effects of irinotecan.

Irinotecan is a soluble prodrug of SN38 that is the standard of care for the treatment of metastatic colorectal cancer, however, only a small proportion (2 to 8%) of irinotecan is converted into SN38, mainly by liver carboxylesterase I and/or II. The complex hepatic metabolism of irinotecan results in the accumulation of high SN38 concentrations in the intestine, which leads to severe diarrhoeas, particularly late-onset grade 3 or 4 diarrhoeas that are observed in 30 to 40% of patients. Such patients require hospitalization, dose reductions and/or treatment interruptions in some cases leading to fatalities. This complex metabolism results in significant variability in terms of both safety and efficacy, which often results in these regimens being relegated to second-line therapy. Nevertheless, the overall survival benefit of irinotecan for patients with metastatic disease can be excellent and dose intensification (when possible) results in improved therapeutic responses. The development of a drug delivery system which could allow efficient and non-hepatic release of the active metabolite SN38 would resolve irinotecan’s main drawbacks, resulting in a safer and more effective drug.

To efficiently deliver SN38 with minimal variability and toxicity Diatos has conjugated a proprietary Vectocell® peptide to SN38. Vectocell® peptides (or DPVs for Diatos Peptide Vectors) are proprietary 15- to 23-residue peptide sequences whose physico-chemical properties make them convenient tools in enhancing the aqueous solubility, together with altering pharmacokinetic and tissue distribution characteristics of small therapeutic molecules. This has been found to result in an improved therapeutic index in a number of cases (Meyer-Losic et al., J. Med. Chem., 49 (23), 6908 -6916, 2006).

DTS-108 has very high water solubility and does not require any co-solvent for intravenous administration. The majority of the DTS-108 administered is converted into the active metabolite, SN38, in the blood and tissues. In appropriate animal models this non-hepatic mechanism of activation leads to much higher circulating levels of SN38 without the intestinal toxicity associated with irinotecan administration. This could be an important breakthrough because irinotecan dose intensification results in improved therapeutic responses (Van Cutsem et al., Br J Cancer 28 (92), 1055-62, 2005). Preclinical studies have shown that DTS-108 has a greater efficacy and better tolerance compared with irinotecan.

About Diatos – www.diatos.com 
Diatos is a biopharmaceutical company dedicated to the research, development and commercialization of innovative anti-cancer drugs with enhanced tumor targeting or improved biodistribution. Diatos is expanding its portfolio of drug candidates with new compounds that utilize its Vectocell® delivery technology or its Tumor-Selective Prodrug (TSP) technology as well as with in-licensed candidates and marketed cancer therapies. Diatos is headquartered in Paris, France and operates subsidiaries in Belgium and the United States of America.

About Diatos’ product portfolio

> DTS-201, a doxorubicin prodrug, increases the concentration of doxorubicin, a widely used cancer drug, at the tumor site by means of a reactivation mechanism specific to the tumor environment.

Exclusive European rights for DTS-201 were in-licensed from Medarex Inc. in 2003. DTS-201 has completed Phase I clinical studies in 2007. Phase II studies will be initiated in 2008.

> DTS-301, a paclitaxel depot formulation in the polymer gel ReGel®, releases paclitaxel, a widely used cancer drug, directly to the tumor site, avoiding systemic side effects. DTS-301 has completed Phase IIa clinical trials and phase IIb trials have been initiated. DTS-301 was in-licensed from Protherics PLC.

> DaunoXome®, a liposomal formulation of widely used cancer drug daunorubicin, improves the biodistribution of daunorubicin and fosters its sustained release in the blood, which potentially allows the administration of higher doses than with non-liposomal formulations. DaunoXome is marketed in Kaposi’s sarcoma and is being re-launched in acute leukaemia in Europe. DaunoXome was in-licensed from Gilead Sciences, Inc.

For further information please visit: www.diatos.com 

Diatos is a registered trademark of Diatos SA, Paris, France