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Diatos Announces Start of the Preclinical Toxicology Program of
DTS-108, a second generation irinotecan |
Paris, France, 17 October 2007 – Diatos SA, an international
biopharmaceutical company focusing on the research, development and
commercialization of targeted anti-cancer drugs, announced today the start of
its regulatory toxicology program of DTS-108, with a Phase I trial planned in
the first half of 2008. DTS-108 is a Vectocell® based prodrug of SN38, the
active metabolite of irinotecan that is currently used for the treatment of
colon and lung cancer.
Preclinical data suggest that DTS-108 could significantly improve on the
therapeutic benefit provided by irinotecan. DTS-108 improves the anti-tumoral
efficacy and safety compared to irinotecan as a result of an efficient and
non-hepatic mode of activation. This results in 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.
Commenting on today’s announcement, John Tchelingerian, Ph.D, President & CEO of
Diatos, said: “DTS-108 is the first drug utilising our Vectocell® technology
platform to reach the clinic. For Diatos, this is an important validation of our
technology platform and further demonstrates the ability of our in-house
Research and Development team to push new compounds into the clinic. If these
encouraging preclinical observations are reproduced in the clinic, then we will
have a second generation irinotecan that will provide a significantly improved
patient treatment option in the areas of colon and lung cancer. In addition,
clinical studies may indicate other potential novel indications where DTS-108
can be effective, and where irinotecan can not been used.”
– ends –
Notes to Editors
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 (fatal events during single-agent irinotecan
treatment have been reported with a prevalence of up to 5.3%). 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 (Van Cutsem et al., Br J
Cancer 28 (92), 1055-62, 2005). A drug delivery system that would allow
efficient and non-hepatic release of SN38 would resolve irinotecan’s main
drawbacks and result in a safer and more effective drug.
To efficiently deliver SN38 with minimal variability and toxicity Diatos has
conjugated a Vectocell® peptide to SN38. Vectocell® peptides (or DPVs for Diatos
Peptide Vectors) are proprietary 15- to 23-residue peptide sequences. Their
physico-chemical properties make them particularly convenient tools to greatly
enhance 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-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-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.
> 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.
Diatos is a registered trademark of Diatos SA, Paris, France.
Contacts:
Media
Northbank Communications Ltd.
Katja Stout / Justine Lamond / Holly Griffiths
Tel: +44 (0)20 7268 3242
E-mail:
diatos@northbankcommunications.com
Investors
Diatos SA
Dr John Tchélingérian
President & CEO
Tel: + 33 (0)1 53 80 93 81
Email:Jtchelingerian@diatos.com
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