PharmaMar Highlights Aplidin(R) Results at AACR

Washington D.c. (ots/PRNewswire) - PharmaMar today announces the presentation of five posters highlighting advances with three of its compounds at the 97th Annual Meeting of the American Association for Cancer Research (AACR), taking place in Washington from 1-5 April 2006. The posters include results from preclinical research on Aplidin(R), Zalypsis(R) and PM02734.

PharmaMar's highlights from this year's AACR meeting are as follows:


Aplidin (plitidepsin) is a cyclic peptide, originally isolated from the marine tunicate Aplidium albicans, now manufactured synthetically. It is a potent inducer of apoptosis.

Aplidin is being evaluated in Phase II clinical trials in solid and haematological malignancies, including paediatrics, in Europe, USA and Canada. More than 500 patients have been treated to date. A clinical programme of combination studies with Aplidin was initiated in the fall of 2005. 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.

One of the studies presented at AACR shows that in specific tumour xenografts, the combination of Aplidin with carboplatin demonstrated potentiation of antitumour activity over either drug administered as a monotherapy. Parenthetically, the combination of Aplidin and carboplatin is currently being explored in a Phase I clinical trial in patients with advanced solid and haematological tumours.

A second study analyzed Aplidin against a panel of human kidney tumour cell lines both in vitro and in vivo. In cytototoxicity assays in vitro, Aplidin demonstrated potency against human renal tumour cell lines. In a separate, dose-ranging study, human kidney tumours were implanted subcutaneously into athymic nude mice and were allowed to grow in situ. Animals were then randomized and drug treatment commenced. Aplidin, in combination with standard-of-care agents including interferon and interleukin, was tested in these pre-clinical models. Results of the study showed that Aplidin moderately potentiates the antitumour effect of either agent given as a monotherapy at the same dose in those renal tumour xenografts.

The third Aplidin study presented was aimed at characterizing the molecular basis of the resistance to Aplidin, which is an area of active investigation. Using a proteomic-based approach, 36 proteins were identified as differentially expressed between wild-type and Aplidin-resistant human cancer cells. The proteins detected, whose levels are altered in Aplidin resistant cells, are associated with regulation of cell survival, cellular transformation, redox state and actin cytoskeleton-membrane linkage. These proteins represent candidates to mediate the action or sensitivity of human cancer cells to this drug. The study concluded that further studies on the mechanism of action and sensitivity of human cancer cells to Aplidin need to be performed to confirm their role.

Dr Glynn Faircloth, VP Preclinical R&D, PharmaMar USA, said:

"The results seen in the Aplidin studies provide the best preclinical evidence yet for the drug's use in combination therapy. By examining the effects of Aplidin in combination studies, we hope to broaden its therapeutic potential in a number of different types of cancer, and to guide clinical combination studies in the near future. In addition, research at the molecular level provides information on protein candidates for further study of the mechanism of action of Aplidin and the sensitivity of human cancer cells to the drug. Taken together, these additional data become valuable tools to assist in the clinical development programme for this promising compound."


Zalypsis(R) (PM00104) is a new synthetic alkaloid related to Jorumycin and Renieramycins, currently in Phase I clinical trials. The objectives of the present studies were to investigate the influence of dose and dosing regimen on the toxicokinetics of Zalypsis in animal models, which was part of the evaluation to support Zalypsis multi-cycle toxicology studies. Preliminary insights into the mechanism of action of Zalypsis are exploring cycle changes, DNA binding properties, and transcriptional inhibition. Zalypsis has demonstrated a significant in vitro activity against solid and non-solid tumour cell lines as well as significant in vivo activity in several xenografted human cell lines in mice, such as breast and prostate.


The novel investigational agent PM02734, a member of the Kahalalide F family of compounds currently in Phase I clinical trials, shows in vitro antitumour activity against breast, colon, lung, neuroblastoma, prostate, sarcoma, and thyroid tumour cell lines. Pharmacokinetic (PK) studies in vivo demonstrate that PM02734 presents PK parameters i.e., drug exposure that differ among separate animal species. Follow up studies in breast and prostate tumours are underway to incorporate this information to optimize drug exposure for optimal activity.

About PharmaMar

PharmaMar is the world's leading biopharmaceutical company 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 designated Orphan Drug for soft tissue sarcomas and ovarian cancer by the European Commission (E.C.) and by the United States Food & Drug Administration (US FDA). Aplidin(R), in Phase II, designated Orphan Drug for acute lymphoblastic leukaemia and for multiple myeloma by the E.C. and by the FDA; Kahalalide F in Phase II, and ES-285, Zalypsis(R) and PM02734 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:

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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)