The News

Diatos announces the successful completion of Phase I trial for DTS-201, a novel doxorubicin prodrug

22/10/2007

Paris, France – October 22, 2007 -- Diatos SA, an international biopharmaceutical company focusing on the research, development and commercialization of targeted anti-cancer drugs, today announced the successful completion of a clinical Phase I trial of its anti-cancer compound, DTS-201, at the American Association of Cancer Research (AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics) meeting in San Francisco, USA. DTS-201 was shown to be well tolerated and evidence of clinical efficacy was observed.

DTS-201 is a novel doxorubicin prodrug developed for the targeted treatment of several solid cancers, including chemo-resistant tumors. DTS-201 uses the Tumor Selective Prodrug (TSP) technology which causes the product to be activated by enzymes specifically expressed by the tumor whilst ignoring healthy cells.

The purpose of the DTS-201 clinical Phase I study was to assess the product’s Maximum Tolerated Dose (MTD), safety profile and pharmacokinetic profile in patients with advanced or metastatic solid tumors. Results from this trial will be presented at the AACR conference in a poster entitled “Results of a first in man phase I study assessing the safety and pharmacokinetics of a one hour intravenous infusion of DTS-201 every 3 weeks in patients with advanced or metastatic solid tumors. (abstract # 776)”.

From the trial, researchers concluded that:

 DTS-201 was well tolerated by twenty-five cancer patients treated with doses of up to 400 mg/m2 every three weeks

 Evidence of clinical efficacy was observed: More than 40% of patients had clinical benefit, nine patients with chemo-resistant tumors showed disease stabilisation for at least 4 treatment cycles and one patient showed partial response

 DTS-201 was safe and well tolerated at cumulative doses of up to 2400 mg/m2 (Doxorubicin equivalent dose is approximately 1300 mg/m2)

 The main dose limiting toxicity is reversable neutropenia (hematological) of short duration

 Non-hematological toxicity adverse events were mild to moderate and no drug related cardiac toxicity was observed

 Clinical data provide first proof of concept in man for the Tumor Selective Prodrug (TSP) technology

 The recommended dose for clinical Phase II trials is 400 mg/m2

The high level of safety and evidence of clinical efficacy observed during this clinical Phase I trial warrants further assessment of the product in multiple clinical Phase II studies.

President and CEO of Diatos John Tchelingerian, Ph.D, remarked: “This clinical Phase I study with DTS-201 provides us with initial human proof of concept of our Tumor Selective Prodrug technology. The expected initiation of multiple clinical Phase II studies for DTS-201 in the near future demonstrates the potential of our DTS-201 product and the Tumor Selective Prodrug platform technology.”

 

Notes to Editors:

About DTS-201
DTS-201 is a prodrug designed to preferentially deliver doxorubicin to tumors as opposed to normal tissues. Doxorubicin is a chemotherapy drug widely used to treat a variety of solid tumours and blood cancers. Systemic administration of doxorubicin causes serious, dose-limiting, adverse side effects.

DTS-201 is stable in blood due to the inactivation of doxorubicin by the coupling of a tetrapeptidic sequence which prevents cellular uptake. DTS-201 is cleavable by some specific peptidases present in the tumor environment such as CD10 and Thimet Oligopeptidase (TOP) which are specifically overproduced and released by tumor cells. They produce two intermediate metabolites Ala-Leu-Dox and Leu-Dox which enter stromal and tumor cells and convert DTS-201 into free doxorubicin.

Preclinical studies have demonstrated that DTS-201 was less toxic in animal models than free doxorubicin and significantly more effective in a wide panel of human tumor xenograft models.

DTS-201 was initially discovered by Pr André Trouet and his team at the Université Catholique de Louvain, Belgium, and exclusive European rights to the preclinical compound were in-licensed from Medarex Inc. in April 2003. DTS-201 is also known as Super-Leu-Dox or CPI-0004Na in the USA.

Diatos’ Tumor Selective Prodrug (TSP) technology
Diatos utilises its patented TSP technology platform to create prodrugs of a wide range of pharmacologically active drugs, including small molecules and proteins. The technology enables the conjugation of a specifically designed peptide with a cancer drug. The resulting new molecule is inactive while it is circulating in the body and activated in a tumor microenvironment. The molecule is cleaved by tumor-specific peptidases (enzymes) overproduced and released by tumor cells (CD-10 and TOP), thereby releasing the pharmacologically active form of the anti-cancer molecule to target cancer cells.

About Diatos
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 candidate and marketed cancer therapies. Diatos is headquartered in Paris, France and operates subsidiaries in Belgium and the United States of America.

About Diatos’ other products
> DTS-108 is a prodrug of SN38, the active metabolite of the widely-used cancer drug irinotecan, and is based on Diatos' Vectocell® technology. DTS-108 aims to increase the efficacy of SN38 while reducing the toxic effects of irinotecan. DTS-108 is in preclinical development.
> 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 will be 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. (NASDAQ: GILD).

Contact information

Press contacts
Northbank Communications
Katja Stout / Justine Lamond / Holly Griffiths
Tel.: +44 (0)20 7268 3242
Email: diatos@northbankcommunications.com

Medical enquiries
Dr Jamal Gasmi, MD, MSc, Chief Medical Officer / Head of Clinical Development & Regulatory Affairs
Tel.: +33 (0)1 53 80 93 53
Email: jgasmi@diatos.com

General enquiries
Dr John Tchelingerian, PhD, President & CEO                       
c/o Virginie Leplat, Director of Human Resources & Administration
Tel.: +33 (0)1 53 80 93 80
Email: vleplat@diatos.com

The Diatos logo and Vectocell® are registered trademarks of Diatos SA.