Aplidin(R) Commences Combination Trials

Madrid (ots/PRNewswire) - - Further Steps in the Development of Aplidin(R) in Melanoma in First Line Therapy

PharmaMar announces the initiation of a programme of combination studies with Aplidin(R) (plitidepsin), PharmaMar's novel marine-derived anti-tumour agent, originally isolated from the tunicate Aplidium albicans.

Aplidin(R) in Combination with Dacarbazine (DTIC)

The first study is a Phase I/II trial of Aplidin in combination with DTIC, the standard agent for the treatment of metastatic malignant melanoma. This multicentre, randomised, open-label, clinical and pharmacokinetic trial will determine the recommended dose and assess efficacy of Aplidin(R) when administered alone or in combination with DTIC as a first-line therapy.

The preliminary results of a Phase II study, which demonstrated evidence of the anti-tumour activity of Aplidin(R) as a single agent in previously treated patients with advanced or metastatic melanoma, were presented at the ESMO Congress November 2004 in Vienna, Austria.

Aplidin in Combination with Carboplatin

The second of these combination studies will assess the safety and tolerability of Aplidin when administered in combination with carboplatin in patients with advanced solid and haematological tumours. The Phase I multicentre, open-label, dose-escalating, clinical and pharmacokinetic study will identify the maximum tolerated dose and recommended dose of Aplidin administered in combination with carboplatin to patients for whom there is no standard therapy.

Dr M.A. Izquierdo, Director of Clinical Development at PharmaMar, commented: "The previous observation of encouraging clinical activity in a heavily pre-treated population of patients with malignant melanoma warrants further investigation in first line therapy, both as a single agent or in combination with DTIC. With the initiation of these combination studies, we are seeking to broaden the therapeutic potential of Aplidin in a number of different tumour types. Further combination studies will be commenced in due course as we continue to explore the opportunities for this compound."

About Aplidin

Aplidin is a cyclic peptide, originally isolated from the marine tunicate Aplidium albicans, now manufactured synthetically. It induces apoptosis rapidly and consistently, inhibits VEGF secretion and blocks the cell-cycle.

It is currently being evaluated in Phase II trials in solid and haematological malignancies, including paediatrics. The clinical programme involves hospitals in Europe, Canada and the US. Approximately 500 patients have been treated to date. In preclinical development, human leukaemia, myeloma and lymphoma tumour cell lines were shown to be particularly sensitive to Aplidin. There is no evidence of cross-resistance with commonly used therapeutic agents for haematological malignancies.

Aplidin(R) shows no clinical evidence of relevant bone marrow toxicity. Its main side effects, muscular toxicity and liver biochemical alterations, are reversible and manageable. Hair loss and oral ulcers are infrequent.

About PharmaMar

PharmaMar is the world's leading biopharmaceutical companies in advancing cancer care through the discovery and development of innovative marine-derived medicines. PharmaMar's clinical portfolio currently includes: YONDELIS(R) (co-developed with Johnson & Johnson Pharmaceutical Research & Development) in Phase III clinical trials; it is also designated Orphan Drug for Soft Tissue Sarcomas by the European Commission (E.C.) in 2001 and by the Food & Drug Administration (FDA) in 2004, and Orphan Drug for ovarian cancer by the E.C. in 2003 and by the FDA in 2005. It also features Aplidin(R), in Phase II, designated Orphan Drug for acute lymphoblastic leukaemia by the E.C. in 2003 and by the FDA in 2004, and for multiple myeloma by the FDA and the EC in 2004; as well as Kahalalide F in Phase II, and ES-285 and Zalypsis(R) in Phase I clinical trials. PharmaMar, based in Madrid, Spain, is a subsidiary of the Zeltia Group (Spanish stock exchange, ZEL).

This press release is also available in the News section on PharmaMar's web site: http://www.pharmamar.com/en/press

For more information, contact:

Media: Lola Casals, PharmaMar Communication, tel.: +34-91-846-6000

Investors: Catherine Moukheibir, Zeltia Capital Markets Operations tel.: +34-91-444-4500

Rückfragen & Kontakt:

Media: Lola Casals, PharmaMar Communication, tel.: +34-91-846-6000.
Investors: Catherine Moukheibir, Zeltia Capital Markets Operations
tel.: +34-91-444-4500