[December 06, 2012]

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

To be presented today at the 34th CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) in Texas, USA, the status of the clinical trial to evaluate Reparixin safety and pharmacokinetic profile, administered orally in combination with paclitaxel in women with metastatic breast cancer.

The second cohort has been completed in patients where limiting toxicity has not been 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 3 prominent Oncological Centers in the US.

Dr Anne Schott is the Coordinator and Investigator of the study as well as the author of the presentation. Dr Schott is Associate Professor in the Department of Internal Medicine at the University of Michigan Comprehensive Cancer Center. The discovery of the potential of Reparixin in the treatment of Cancer Stem Cells (CSCs) was contributed by the director of the UMCC, Prof Max Wicha.

"Reparixin is a promising molecule, with a good safety profile, as the positive conclusion of the second study cohort on women with metastatic cancer has shown - states Dr Anne Schott - Such results motivate us to continue the characterization of this molecule which could represent an innovative therapy for metastatic breast cancer, presently still hard to cure."

Based on the excellent safety profile demonstrated, it has been announced today, at SABCS, the setting up of a new, important, clinical study aimed at evaluating the effects of Reparixin in oral monotherapy on CSCs and on tumor microenvironment for the treatment of women with early stage breast cancer, before surgery.

The study will involve a total of 7 Clinical Centers in the US coordinated by Dr Lori Goldstein, Director of the Breast Evaluation Center and leader of the Breast Cancer Research Program at of the Department of Medical Oncology at the Fox Chase Cancer Center of Philadelphia (US).

The first center that has been activated is the Methodist Hospital Research Institute of Houston, Texas, which is expected to enroll the first patient in December.

"I have always believed that a therapy aimed at cancer stem cells could represent the future of research in the field of breast cancer and, more in general, in the fight against cancer. For such reasons, I have strongly supported the clinical development of Reparixin - asserts Dr Jenny Chang, Principal investigator and Director of the Methodist Hospital Research Institute of Houston - What we want to demonstrate with the new study is that Reparixin can represent a future opportunity for the treatment of both metastatic disease and early stage disease."

Reparixin is an inhibitor of the CXCR1 receptor activated by chemokine interleukin 8. The molecule, discovered and characterized in Dompé's 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 cue 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.

"Reparixin is one of the molecules fruit of our commitment in R&D and the results achieved so far, stimulate us to face a complex and innovative development program in the field of oncology, an area still characterized by a high therapeutical need - states Dr Eugenio Aringhieri, Chief Executive Officer of Dompé Group - We are proud to be able to contribute to the fight against this disease which affects millions of Patients globally, as well as establishing the fame of Italian research at the international level, by counting on the most important US centers of excellence, committed to preside over a hot area of research such as that of cancer stem cells."

About Reparixin

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.

About REP0111 - Study on Reparixin in HER-2 negative metastatic breast cancer

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.

About REP0111 - Study on Reparixin in early HER-2 negative metastatic breast cancer

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 (News - Alert)-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).

About Dompé

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 (News - Alert) Prize for Medicine) for serious eye diseases for which there are no effective treatments available.

For more information: www.dompe.com

Forward-looking statements

This press release refers to some information that may not correspond to future results. Dompé firmly believes in the soundness and reasonableness of the concepts expressed, but some of the information is subject to a margin of uncertainty, regarding research and development and appropriate inspections by the relevant regulatory bodies. Therefore, for the moment, Dompé cannot guarantee the consistency of expected results in relation to the above.

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