Diatos Announces Positive Clinical Results for its DTS-201 Doxorubicin Prodrug Program
PARIS--(BUSINESS WIRE)--Diatos SA, an international biopharmaceutical company focusing on the research, development and commercialization of targeted anti-cancer drugs, today announced that they presented data from a Phase I clinical trial of their anti-cancer compound, DTS-201, 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 tumors. The product is activated by enzymes specific to the tumor 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 is to assess the product’s Maximum Tolerated Dose (MTD), safety profile and pharmacokinetic profile in patients with advanced or metastatic solid tumors. In a poster presentation entitled “Results of a Phase I study of DTS-201, a peptidic prodrug of doxorubicin in patients with solid tumors (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 tumors 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. |
