Diatos announces positive Phase I results for DTS-201 Doxorubicin prodrug program

Paris, France -- June 4, 2007 -- Diatos SA, an international biopharmaceutical company focusing on the research, development and commercialization of targeted anti-cancer drugs, today announced data from a Phase I clinical trial of their anti-cancer compound, DTS-201, presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, USA.

DTS-201 is a doxorubicin prodrug developed for the targeted treatment of several solid cancers, including chemo-resistant tumours. The product is activated by enzymes specific to the tumour environment. During its Phase I clinical trial, DTS-201 was shown to be well tolerated and able to deliver high doses of free doxorubicin in humans.

The purpose of the DTS-201 Phase I clinical study was to assess the product’s Maximum Tolerated Dose (MTD), safety profile and pharmacokinetic profile in patients with advanced or metastatic solid tumours. In a poster presentation entitled “Results of a Phase I study of DTS-201, a peptidic prodrug of doxorubicin in patients with solid tumours (Abstract # 2547)”, 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. This corresponds to 3.75 times the standard dose of doxorubicin;
• DTS-201 was safe and well tolerated at cumulative doses of up to 2750 mg/m2;
• Evidence of clinical efficacy was observed: two patients showed partial responses and three patients with chemo-resistant tumours showed disease stabilisation;
• The recommended dose for Phase II clinical trials is 400 mg/m2.

The high levels of tolerance to the product and positive clinical responses observed during this Phase I trial strongly support an assessment of the efficacy of DTS-201 in a Phase II study.

“DTS-201 is a safe and active compound which allowed delivery of a high dose of doxorubicin without any unexpected side effects,” stated Jean-Pierre Delord, M.D., principal investigator from the anti-cancer center Claudius Régaud Institute in Toulouse, France.

“In particular, no severe toxicity has been observed even after the administration of six cycles of the agent in this Phase I trial. Furthermore, we have observed some encouraging activity in normally chemo-resistant cancers.”

DTS-201 was initially discovered by Pr André Trouet and his team at the Université Catholique de Louvain, Belgium, and exclusive European rights were in-licensed from Medarex Inc. in April 2003 as a preclinical compound.

President and CEO of Diatos John Tchelingerian, Ph.D, added: “I am satisfied that Diatos continues to make substantial progress in its clinical development programs based on novel, targeted anti-cancer chemotherapies. The positive results from our Phase I study with DTS-201, particularly the encouraging signs of improved efficacy versus standard doxorubicin treatment, represent a significant milestone in the development of our product. Diatos is poised to initiate a Phase II study for DTS-201 in Europe soon, advancing what we believe is a next generation anthracycline for the benefit of cancer patients.”

Notes to Editors:

About DTS-201

DTS-201 consists of doxorubicin, a marketed cytotoxic agent effective against a wide variety of solid tumors, conjugated to a proprietary peptide. The product was discovered in 1996 by Pr André Trouet and his team at the Université Catholique de Louvain, Belgium and in-licensed from Medarex Inc in April 2003. DTS-201 is also known as Super-Leu-Dox or CPI-0004Na in the USA.

DTS-201 is a prodrug designed to preferentially deliver doxorubicin to tumors as opposed to normal tissues. It consists of the tetrapeptide N-succinyl-ß-alanyl-L-leucyl-L-alanyl-L-leucine covalently linked to the aminoglycoside portion of doxorubicin.

Peptide-based targeting of tumors is an attractive approach for tumor selective drug delivery. The DTS-201 concept is based on the inactivation of doxorubicin by the coupling of a tetrapeptidic sequence that prevents cellular uptake. DTS-201 is stable in blood but cleavable by some specific peptidases present in the tumor environment. Preclinical studies have demonstrated that DTS-201 was less toxic in rodents and dogs than free doxorubicin and significantly more effective in a wide panel of human tumor xenograft models.

Reactivation of doxorubicin occurs extracellularly in the tumor through enzymatic cleavage of the peptide by at least two enzymes: CD10 (Neprilysin / CALLA) and Thimet Oligopeptidase (TOP). They produce two intermediate metabolites Ala-Leu-Dox and Leu-Dox which enter stromal and tumor cells and are converted into free doxorubicin.

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’ Portfolio
> 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 under review for the treatment of acute leukaemia in Europe. DaunoXome was in-licensed from Gilead Sciences, Inc. (NASDAQ: GILD).

> 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 is in Phase II clinical studies and was in-licensed from Protherics PLC (LSE: PTI / NASDAQ: PTIL).

> 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. DTS-201 has completed Phase I clinical studies in Belgium and France in Q2-07. Exclusive European rights for DTS-201 were in-licensed from Medarex Inc.

> DTS-108 is a prodrug of SN-38, 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 SN-38 while reducing the toxic effects of irinotecan. DTS-108 is in preclinical development.

Contacts

Press contacts
Northbank Communications
Katja Stout / Justine Lamond / Holly Griffiths
Tel.: +44 (0)20 7268 3242
Email: diatos@northbankcommunications.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 
&
c/o Guillaume Dussert, Associate BD & Marketing Manager
Tel.: +33-(0)1 53 80 93 83,
Email: gdussert@diatos.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 

For more information on Diatos, please visit www.diatos.com .

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