Hitting Cancer at Its Core: At San Antonio Breast Cancer Symposium Eyes Focused on Reparixin, a Drug Fruit of Dompé’s Research, with Action Aimed at Breast Cancer Stem Cells

Hitting Cancer at Its Core: At San Antonio Breast Cancer Symposium Eyes Focused on Reparixin, a Drug Fruit of Dompé’s Research, with Action Aimed at Breast Cancer Stem Cells

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To be presented today at the 34th (SABCS) in Texas, USA, the status of the to evaluatesafety and pharmacokinetic profile, administered orally in combination with paclitaxel in women with metastatic breast cancer.

The second cohort has been completed in patients where observed, supporting the safety profile for the candidate drug. The evaluation of the third cohort is being carried out and will be completed in the first quarter 2013. A further 9 patients are expected to be enrolled at prominent Oncological Centers in the US.

Dr is the Coordinator and Investigator of the study as well as the author of the presentation. Dr is Associate Professor in the Department of Internal Medicine at the. The discovery of the potential of Reparixin in the treatment of (CSCs) was contributed by the director of the UMCC, .

“states –

Based on the excellent safety profile demonstrated, it has been announced today, at SABCS, the aimed at evaluating the effects of Reparixin in oral monotherapy on CSCs and on tumor microenvironment for the treatment of women with , before surgery.

The study will involve a total of coordinated by , Director of the and leader of the Breast Cancer Research Program at of the (US).

The first center that has been activated is the , Texas, which is expected to enroll the in .

asserts , Principal investigator and Director of the Methodist Hospital Research Institute of Houston –

Reparixin is an inhibitor of the CXCR1 receptor activated by chemokine interleukin 8. The molecule, discovered and characterized in research laboratories – a biopharmaceutical company – has demonstrated to be able to selectively attack cancer stem cells of breast cancer.

Therapies aimed at CSCs represent a great promise for the cure of cancer but the uniqueness of the mechanism requires innovative approaches and the development of specific biomarkers able to address the selection of the patient and to follow the drug action. Obtaining a proof of concept in planned studies can have important implications even in therapies of other tumoral forms still lacking therapies.

In fact, the particular action mechanism of Reparixin, which modifies the microenvironment in which cancer stem cells are produced and developed, could be applied not only for breast cancer but also as a therapy for other tumors.

“states , Chief Executive Officer of Dompé Group –

Reparixin is an inhibitor of the CXCR1 receptor which in the body is activated by chemokine interleukin-8 that plays a key role in anti-inflammatory response.

It is the first in a novel class of low-molecular weight inhibitors that can selectively modulate the receptor activity via an allosteric mechanism of action. An allosteric inhibitor can freeze the receptor in an inactive position binding it to a different site than the site taken by the natural ligand (IL-8). Made in collaboration with the research team led by Prof. Alberto Mantovani, world leading expert in chemokine research, the characterization of the action mechanism of Reparixin is a mainstay in the research of drugs capable of modulating the activity of this important receptor family.

Phase 1b of the study gave the “go ahead” to REP0210, Reparixin has demonstrated in preclinical studies, to be efficacious both as a monotherapy as well as combined with (synergic effect) classical chemotherapies used for breast cancer (docetaxel in particular) to reduce cancer stem cells.

The primary objective of the study is the evaluation, in women over 18 with HER-2 metastatic breast cancer, of the pharmacokinetic and safety profile for the combined treatment with Reparixin on CSCs, on the tumoral microenvironment and on plasmatic levels of inflammatory cytokines, and the analysis of the tumor response to the treatment as an indicator of efficacy.

Patients receive a cycle of 3 days of treatment with Reparixin oral tablets 3 times a day followed by a cycle of combined treatment with paclitaxel 80mg/m2/week + oral Reparixin 3 times per day for 21 days, in three different dosages (400 mg, 800 mg, 1200 mg). Safety is evaluated after the first cycle, and the treatment will continue until the observation of clinical benefits.

Currently, the second cohort of 3 patients where no toxicity has been observed has been completed to confirm the safety profile of the candidate drug. The third cohort is currently enrolling and will be concluded in the first trimester 2013. Another 10 patients are expected to be enrolled at three clinical sites in the US.

REP0210 is a pilot clinical study in 40 patients with operable breast cancer, subdivided in 2 different subgroups based on the receptor characteristics of the tumor, and treated in monotherapy with Reparixin orally before surgical treatment. The study aims at evaluating, in the two subgroups, the effects of Reparixin on cancer stem cells (CSCs) in early stage tumors and in the tumoral microenvironment, namely to verify whether Reparixin is effectively able to reduce CSCs and related markers, and to evaluate possible differences between the two subgroups with the aim to precisely identify the “ideal” target population for this innovative treatment. The two subgroups of patients will be Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+)/HER2– respectively, and ER– and/or PR–/HER2–.

CSCs will be measured through cytofluorimetry in samples of bioptic tissue, which will be subjected to PCR-RT and/or immunohistochemistry and to the dosage of: epithelial-mesenchymal markers, of the serine/threonine protein-kinase AKT, of the focal-adhesion-kinase(FAK) and of receptor CXR1 levels. Analogously, the study will also measure antinflammatory and angiogenesis marker levels, infiltrating leucocytes and markers of autophagy (P62 and LC3).

A leading pharmaceutical company in Italy Dompé develops innovative treatment solutions for diseases that have a high social impact, which are often orphan diseases. Based in Italy with HQ in Milan Dompé focuses on Research in areas where there are still unmet treatment needs such as juvenile diabetes, ophthalmology and oncology. Its industrial site in L’Aquila (Abruzzi) has biotechnology facilities for the production of monoclonal antibodies and the development of Primary Care drugs that are sold internationally in over 60 countries. In 2012, Dompé acquired Anabasis, an Italian biotech company that develops innovative drugs based on rhNGF (whose discovery earned Professor Rita Levi Montalcini the Nobel Prize for Medicine) for serious eye diseases for which there are no effective treatments available.

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