R&D FROM THE OCEAN

Why does PharmaMar focus on the sea? The oceans cover 70% of the Earth's surface and account for 90% of the biosphere. Over millions of years myriads of marine life forms have evolved to produce a vast diversity of uniquely sophisticated chemical entities. Among these there are molecules with potent biological activities which have developed as a form of biochemical warfare to survive in a highly competitive environment. PharmaMar has recognized the anti-tumour potential of these molecules, and is actively developing them as innovative treatments for cancer.

To tap into the marine sources PharmaMar employs expert marine biologists who search the world oceans collecting small samples of local flora and fauna from selected locations. Collected samples are identified taxonomically, shipped back frozen to our research facilities in Madrid, and incorporated in PharmaMar´s unique biodiverse library already containing thousands of marine samples.

PharmaMar supports the protection, conservation and sustainable use of the precious resources from the sea. Our approach to drug discovery not only contributes to potential novel therapeutics from just a few grams of marine sample but also to the better knowledge of the local marine ecosystems and their conservation. Resulting information is centralised in our R&D database to optimise future exploration and is also shared with the local communities and academic centres.

PharmaMar has created a collaborative network to speed up research on its collection of potentially active agents. This network includes centres of marine biology and chemistry, which have facilitated access to marine samples (micro- as well as macro-organisms), and world-class basic science and clinical researchers..

Small sample portions are processed and tested in our biological model systems specifically developed for detecting anti-tumour activity. Fractionation of the samples by chromatographic techniques allow for rapid isolation of interesting molecules and fast-track elucidation of their chemical structure.

Molecules with interesting anti-tumour activity are then subject of medicinal chemistry programs to establish a convenient way for their production by chemical synthesis, thus avoiding the need for the natural source. These programs result in synthetic chemical analogues of the originally isolated marine molecules, giving rise to an entire family of active anti-tumour compounds and often with candidates with improved pharmacological profiles. The synthetic analogues also provide valuable insights into the structure vs activity relationship (SAR) which can be used for further refinement of the chemical structure and improved drug like properties (maximal activity and minimal side effects).

With this approach we continuously discover new molecules with unique modes of action (MoA), representing a significant opportunity for advances in basic science and most importantly, opening potential new avenues for the treatment of cancer.

In vivo model systems are used to determine the antitumor activities and pharmacokinetic and toxicological profiles of those molecules with promising in vitro biological anti-tumour activity. Lead candidates are then proposed to the regulatory agencies for entry in clinical trials.

PharmaMar has more than 870 patents granted including novel chemical structures, synthetic and product processes and therapeutic applications.

SELECTED REFERENCES

Jimeno J. et al., New Marine Derived Anticancer Therapeutics - A Journey from the Sea to Clinical Trials. Marine Drugs 1, 14-29 (2004)

Amador ML. et al., Progress in the development and acquisition of anticancer agents from marine Sources. Ann Oncol. 14(11), 1607-1615 (2003)

Donia M & Hamann MT., Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis. 3(6) 338-348 (2003)

García-Fernández, LF et al., The Marine Pharmacy: New Antitumoral Compounds from the Sea. Pharmaceutical News 9, 495-501 (2003)

Haefner & Burkhard, Drugs from the deep: marine natural products as drug candidates. Drug Discovery Today 8(12) 536-544 (2003)

Schwartsmann,G. et al., Marine-derived anticancer agents in clinical trials. Expert Opin Investig Drugs 12(8) 1367-1383 (2003)

Mayer,A.M.& Gustafson,K.R., Marine pharmacology in 2000: antitumor and cytotoxic compounds Int J Cancer 105(3) 291-299 (2003)

Jimeno, J. M., A clinical armamentarium of marine-derived anti-cancer compounds Anticancer Drugs 13 (Sup 1) S15-19 (2002)