Highlights of these abstracts are presented below:

Transcription

1 PharmaMar announces the presentation of 15 abstracts on Yondelis and Aplidin at the 46 th annual meeting of the American Society of Clinical Oncology (ASCO) Madrid, 9 June 2010: PharmaMar SA (Grupo Zeltia, ZEL.MC) announces the presentation of 13 abstracts of Yondelis and another 2 with Aplidin at the annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago, June 4-8. Highlights of these abstracts are presented below: Four papers provide new results with Yondelis (trabectedin) in ovarian cancer patients based on data from OVA-301, a phase III study comparing Yondelis with pegylated liposomal doxorubicin (PLD) versus PLD alone in 672 relapsed ovarian cancer patients progressing after one prior platinum-based regimen: A new analysis confirms that this novel non-platinum, non-taxane combination is an efficacious regimen in patients with relapsed ovarian cancer with reasonable long-term tolerability in patients who received at least 6 cycles of the Yondelis combination. Results of phase II trials of single-agent Yondelis in relapsed ovarian cancer patients with a platinum-free interval between 6 to 12 months are consistent with the previously presented findings of the randomized trial OVA-301, where trabectedin + PLD demonstrated superior clinical benefit over PLD alone. The activity of Yondelis appears particularly enhanced in this important subset of patients with partially platinum-sensitive disease for whom there is a clear medical need of new, effective therapeutic options. An exploratory analysis in the subset of patients with partially platinumsensitive disease in OVA-301 shows a significant delay in time to subsequent platinum for patients randomized to the Yondelis combination. Relevant

2 survival prolongation counted from the time of subsequent platinum therapy was achieved in these patients. A phase II study of the Gynecologic Oncology Group (GOG) reports on the activity of trabectedin plus docetaxel in recurrent or persistent ovarian and primary peritoneal cancer. This combination is well tolerated and appears more active than single agent taxane therapy in patients with recurrent ovarian and peritoneal cancer after failure of multiple lines of prior chemotherapy. A placebo-controlled design study evaluated the potential effects of trabectedin on the QT interval of the electrocardiogram. A therapeutic dose of Yondelis did not prolong the QT interval in patients with advanced solid tumor malignancies. The safety and PK profile of Yondelis was similar to that observed in previous studies. These findings further confirm the favorable safety profile of Yondelis, which is devoid of any relevant cardiac toxicity, unlike some of the agents frequently used in patients with advanced sarcomas and ovarian cancer. Six abstracts provide updated information on Yondelis in soft tissue sarcoma: A large overview of data from a decade of experience with Yondelis as a single-agent in patients with advanced soft tissue sarcomas shows the important contribution of Yondelis in the therapeutic armamentarium of these rare malignancies. The results of the Yondelis expanded access programs are consistent with data generated in clinical trials, and corroborate the usefulness of such programs in offering patients the opportunity of gaining acces to a new agent before its regulatory approval, with comparable efficacy and safety. These findings highlight the importance of such expanded access programs in the clinical development of new agents while offering beneficial tools for patient care. Results of a pooled analysis of five single-agent phase II studies using the recommended dose in the treatment of advanced uterine leiomyosarcomas show that Yondelis has activity and is reasonably safe and well tolerated for these patients. Nearly one-third of the patients were progression-free for 6 months or longer, and over half (52%) of these heavily pretreated patients

3 were alive at one year. Such substantial activity in relapsed, advanced disease warrants prospective trials with Yondelis at earlier stages of uterine leiomyosarcomas. Surgery of residual disease of myxoid liposarcoma (MLS) patients responding to trabectedin shows that Yondelis provides prolonged tumor control in MLS. Therefore, Yondelis therapy may provide responding patients with the benefit of subsequent surgical rescue for their advanced sarcoma. In addition, a very relevant observation in this report relates to the favorable data with Yondelis re-treatment at progression in patients who discontinued Yondelis after having achieved a previous response. In these patients, re-treatment with Yondelis was associated with significant further tumor control. This strategy allows to maximize the benefits from this agent in a disease setting with limited treatment options. A retrospective analysis of 39 patients from three European institutions evaluated trabectedin in advanced, pretreated synovial sarcomas. In this series, Yondelis induced an overall response rate of 18% and a 23% progression-free survival at 6 months. These results are in line with those previously shown in liposarcomas and leiomyosarcomas, suggesting that Yondelis plays an important clinical role in pathological sarcoma subtypes other than liposarcoma and leiomyosarcoma. The European Commission approved Yondelis for platinum-sensitive ovarian cancer in September In 2007 the European Commission had approved Yondelis for soft tissue sarcoma. Clinical trials are under way to expand the use of Yondelis in sarcoma, including a trial as first-line treatment in patients with translocation-associated tumors and in children with Ewing sarcoma, rhabdomyosarcoma and other STS subtypes. Yondelis is also undergoing clinical trials in other solid tumors. Following the initial report on a phase II trial in metastatic breast cancer presented at ASCO 2009, data on 55 such patients are being presented at this year s ASCO providing the results of Yondelis in the other two cohorts of metastatic breast cancer patients, namely those with BRCA1/2 germ-line-mutated tumors and those

4 with HER2-overexpressed tumors after failure of anti-her therapy. Yondelis was active in both cohorts, with manageable safety profile. Complete efficacy data and associated translational research are being presented. In this prospective study, the results of the analysis of RNA expression are consistent with previous retrospective data in soft tissue sarcoma suggesting better outcomes with Yondelis therapy in patients with high XPG expression in their tumors. Two reports presented this year at ASCO provide new information about Aplidin (plitidepsin) for the treatment of patients with melanoma and on the safety profile of this agent: A pase II trial including 20 patients evaluated Aplidin alone or with dacarbazine as first-line treatment for advanced unresectable melanoma. Although weekly Aplidin as a single-agent did not show relevant activity, encouraging activity was documented when Aplidin was combined with dacarbazine. An extensive overview of the available safety data with single-agent Aplidin in 578 adult patients with advanced malignancies confirms the favorable tolerability profile and absence of relevant cardiac toxicity with this agent. About PharmaMar PharmaMar is Grupo Zeltia's biotechnology subsidiary; it is a world leader in discovering, developing and selling marine-based drugs to treat cancer. Yondelis is Spain's first anticancer drug. It is currently approved for soft tissue sarcoma in all 30 countires of the EEA and in 25 additional countries outside the EEA. Yondelis is also approved for patients with relapsed, platinum-sensitive ovarian cancer in the EEA and in five countries outside the EEA as well. Yondelis is approved in Switzerland for STS. Phase II clinical trials with Yondelis are underway in various solid tumors and paediatric cancers. PharmaMar has four other compounds in clinical development: Aplidin, Irvalec, Zalypsis and PM In addition, PharmaMar has a rich pipeline of preclinical candidates and a major R&D program. About Zeltia Zeltia S.A. is a world-leading biopharmaceutical company specialised in the development of marinebased drugs for use in oncology and central nervous system illnesses. Grupo Zeltia consists mainly of the following companies: PharmaMar, the world-leading biotechnology company in advancing cancer care through the discovery and development of innovative marine-derived medicines; Noscira, a biotech firm focused on discovering and developing new drugs against Alzheimer s disease and other

5 neurodegenerative central nervous system diseases; Genómica, Spain's leading molecular diagnostics company; Sylentis, dedicated to researching therapeutic applications of gene silencing (RNAi); and a chemical division comprising Zelnova and Xylazel, two highly profitable companies that are leaders in their respective market segments. Important note PharmaMar, which is headquartered in Madrid (Spain), is a subsidiary of Grupo Zeltia (Spanish stock exchange: ZEL), which has been listed on the Spanish Stock Exchange since 1963 and on Spain's Electronic Market since This document is a press release, not a prospectus. This document does not constitute or form part of an offering or invitation to sell or a solicitation to purchase, offer or subscribe shares of the company. Moreover, no reliance should be placed upon this document for any investment decision or contract and it does not constitute a recommendation of any type with regard to the shares of the company. For more information (Tel ) Media Relations Fernando Mugarza Capital Markets José Luis Moreno Florencia Radizza This note is also available at PharmaMar website: