:: Historically speaking :: Recent Times ::

Historically speaking

Our group originated at the end of the 1970´s under the direction of Dr J Domingo. During this period, the group concentrated mainly on the study of the mechanism of hepatocarcinogensis in experimental models. In 1989 the group took up a new initiative and incorporated Dr Ricardo Pérez Tomas as principle investigator (or lab/Group leader). The group started to focus on the study of growth factors and thanks to financial backing from CICYT, the group was able to implicate their studies on various growth factors including EGF, TGF-α and TGF-β as well as the receptor for the first two mentioned (EGF-R) in diverse models of hepatic cellular proliferation and induction of neoplasia. During this time we developed the most suitable techniques to perform these studies (immunocytochemistry, autoradiography at the optical and electronic level, electrophoresis, western blots, protein iodination, radio immunoassays, gel absorption chromatography, immunoprecipitation and binding experiments) for the characterisation of these growth factors. The fruits of this labour were communicated in national and international congresses as well as in various internationally recognised reviews and articles.

Recent times

We are interested in the characterization of novel anti-cancer drugs from bacterial origin, and then, in the study of their mechanism of action as well as in to assess the therapeutic potential of these molecules in the treatment of cancer.

The experiments we have performed with prodigiosin show this is a drug with anticancerigenous properties and interesting promising antitumoral features. We characterized the apoptotic and anticancerigenous effect of prodigiosin in several human cell lines of hematopoyetic (Montaner et al., 2000) and gastrointestinal origin (Montaner and Pérez-Tomás, 2001; Díaz Ruiz et al., 2001), as well as human chronic lymphocitic leukemia (LLC-B) using an ex vivo model. At this moment we are completing the studies with breast and lung human cancer cell lines (publications in preparation). We are also interested in the relationship between prodigiosin and the main pathways involved in the induction of apoptosis, such as MAP kinases (p-38 MAPK, SAPK/JNK and ERK1/2) (Montaner and Pérez-Tomás, 2002a,b), its effect in cell cycle (Pérez-Tomás and Montaner, 2003), caspase activation (Montaner and Pérez-Tomás, 2002c), and the interaction of prodigiosin with DNA (Montaner et al., 2003).

Recently, we characterized the red pigment prodigiosin and its apoptotic effect. We have also isolated and partially characterized the cyclic depsipeptide 514 (PCT 200202375), a new molecular entity that stimulates programmed cell death (apoptosis) in cancer cell lines, with little impact on the viability of non-cancer cells. We are currently interested in the characterization of cyclic depsipeptide 514-induced apoptosis, as well as the assessment of both, genic expression and the activation state of the proteins involved in such process, to allow the elucidation of the molecular mechanisms determining this molecule's specify of action.

Executive abstract of the project

1)  Objective

To present the enterprise project titled "Anticancer Microbial Drugs Development" for the interests of possible future investments.

2) Background

The enterprise project "Anticancer Microbial Drugs Development" (AMD Development) arose from the collaboration between two groups of scientific investigations at the University of Barcelona .

One side of the collaboration will be directed by Dr Ricardo Pérez Tomas and Doctor Beatriz Montaner Ramoneda, specialising in the study of antitumoral molecules originating from bacterial origin. The team is dedicated to the isolation of these molecules and studies of their activity in different cancer cell lines.

Dr Ernest Giralt Lledó who has vast experience in synthesis and structural studies of bioactive molecules will direct the other side of the collaboration. He is dedicated to the characterisation and synthetic design of these molecules.

The principle activity of "AMD Development" is the discovery and pre-clinical development of new products against cancer to sell to pharmaceutical companies that will be able to finalise their development and release them into the market.

3) Products

Two drugs are being developed at the moment (1281 antitumoral and antitumoral 514) and are described as follows:

3.1 antitumoral 514: This product has been isolated, characterised and presented for patent application No. P200202375.

Several experiments have been carried out on the activity of this molecule. Lung cancer (as well as others) has shown to have high response to this drug. It is one of the cancers that has the highest incidents in the modern world today and is calculated to have the highest increase in the forthcoming years. Besides, lung cancer is especially difficult to treat successfully which is why it has the lowest survival rate in most countries in the western world. This is why the excellent results that has been obtained concerning lung cancer cells and antitumoral 514 make it all the more relevant and spectacular.


To licentiate this drug, the following points have to be realised:

Determine the method of synthesis of this molecule and to obtain it in an industrial form. This would permit the extension of the patent to include the synthesis as well as the product (3-6 months).

Perform animal toxicity studies. This would enable necessary documentation to begin phase 1 trials (4-6 months).

Therefore a period of about 7-12 months will be required to licentiate this drug.

3.2 1281 antitumoral: This product has been isolated recently and its activity tested in various cancer cell lines. At the moment the product is being characterised, synthesised and studied at the pre-clinical level.

4) Enterprise project

As mentioned earlier, the general strategy of AMD Development is the discovery of new anticancer drugs and its pre-clinical development. Once the products are prepared for phase I trials, they will be licensed to companies that will continue with their development for release into the market.

The group of scientific investigation of Dr Ricardo Pérez Tomas and Dr Beatriz Montaner Ramoneda has performed studies that have led to the discovery of new antitumoral drugs from bacterial origin at a ratio of 1 or 2 drugs per year. Of these, its hoped that 50% will enter phase I clinical trials.

Once discovery and preliminary test have been performed, the molecules are characterised, synthesised and patents obtained for both the products and the methods of synthesis. Given the experience of the group headed by Dr Giralt to characterise and synthesise these products, patents will be obtained within approximately 1 year of obtaining the product.


Finally, the enterprise must develop an expertise necessary for carrying out pre-clinical trials that allow every product to enter 1 st phase clinical trials approximately one and a half year after discovery.

Market

The world market of anticancer drugs had an annual expenditure of 29.4 billion dollars in the year 2001 and is due to increase by an estimated 6.3% per year until it reaches 42.8 billion dollars in the year 2007.

On the other hand, many patents of anticancer drugs used today are due to expire in forthcoming years, therefore pharmaceutical companies will be looking out for the discovery of new products to maintain their leadership in the world market.

Directors

Dr Ricardo Pérez Tomas is responsible for running the operation with support from "The innovation centre of the foundation of Bosch i Gimpera, University of Barcelona ". Dr Ricardo Pérez Tomas is also responsible for the biomedical team. Dr Beatriz Montaner Romaneda is responsible for the fulfilment of biomedical experiments.

The team responsible for the synthesis of the drugs is made up of Dr Ernest Giralt and Dr Josep Maria Caba and Mr Marc Martinell will be responsible for the characterisation.

A general director of AMP Development will be appointed in the foreseeable future. The ideal candidate will be qualified in experimental science and MBA with industrial experience. The most important task of the general director will be to form licensed agreements with pharmaceutical companies for the development and future commercialisation of the AMP development products. The initial phase will be equally committed to the economic management of the project.

Necessity of investment.

Its has been calculated that the required investment to perform studies on antitumoral 514 for licensing is approximately 480,000€ and a further 120,000€ to maintain the investigation on antitumoral 1281 and future products.

The enterprise hopes obtain a grant of €300.000 through a creditor NEOTEC of CDTI and a further €300.000 will be contributed by venture capital.

All this data will be detailed in a company format that is currently being prepared.

Initial valuation of the project and starting strategy

Detailed valuation of the project will be presented in a company format, which is currently being elaborated.

The intention of the enterprise team will be to carry out the next financial step, which would be in the region of 1 - 1.5 million Euro for a period of about two years.