Yves Rambaud, member of the Ipsen Group’s Board of Directors

Paris, December 22, 2003 — Mr. Yves Rambaud is appointed a member of The Ipsen Group’s Board of Directors. He is also a Board Member of the companies « LE NICKEL SLN » and GEODIS and he is Chairman of "La Fédération des Minéraux et Métaux" (Minerals and Metals Union). From 1991 to March 2003, he was Chief Executive Officer of ERAMET.

A graduate from both "Ecole Polytechnique" and "Ecole des Mines de Paris", Mr. Yves Rambaud started his career at the National Mining and Geological Service in Paris. From 1967 to 1971, he was successfully Manager, then Deputy General Manager of PENARROYA (mining and metallurgic company). From 1971 to 1974, he became General Manager Nickel Activity of "SOCIETE LE NICKEL (SLN)" (belonging to the same group as PENARROYA). When the company "LE NICKEL" became the IMETAL Group, he was appointed General Manager in 1974, then became Chief Executive Officer from 1985 to 1991 of "LE NICKEL SLN" (metallurgic company). At the same time he was appointed Vice President and General Manager, then Chief Executive Officer of ERAMET-SLN, which since became ERAMET.

About Ipsen

Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and haematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centres: Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group’s website is www.ipsen.com


Source: Ipsen

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Roche acquires rights to diabetes compound from Ipsen

Paris (France) and Basel (Switzerland), 21 October 2003 — Roche and Ipsen today announced that the two companies have entered into a second agreement, following the one concluded December 2002, this time for Ipsen’s diabetes compound BIM 51077. BIM 51077 is a Glucagon-like-peptide-1 (GLP-1) analogue, currently in Phase I clinical studies for Type 2 diabetes. In addition to BIM 51077 itself, Roche has been granted rights to all future compounds to be discovered or licensed by Ipsen in this class of drugs.

According to the terms of the first agreement entered in December 2002, Roche already has worldwide rights, excluding Europe, to market Ipsen’s homocamptothecine class of compounds, a promising group of anticancer agents with lead compounds in development, such as diflomotecan and BN 80927.

"BIM 51077 is a very promising compound that will further strengthen our position in the diabetes market, with proven products such as Xenical," stated William M. Burns, Head of the Pharmaceutical Division at Roche, "We are very pleased to build upon our relationship with Ipsen. After just ten months of entering into our first collaboration, we have identified a further opportunity for collaboration. Working closely with partners and building upon existing relationships is a key business strategy for Roche."

"We are delighted to be signing a new agreement with Roche. This partnership, with such a highly respected company, confirms the quality of our research and reflects our corporate strategy to actively search for new alliances, particularly with quality partners," said Jean-Luc Bélingard, Ipsen’s President and CEO.


Terms of the Agreement

Under the terms of the agreement, Roche will have exclusive rights to market and sell BIM 51077 worldwide, except in Japan where Roche will share co-marketing rights with Teijin and in France where Ipsen has the option to co-market. Roche will reimburse the development and formulation work undertaken by Ipsen and will be responsible for all future clinical development. Ipsen will receive total payments of up to €202 million, consisting of €10 million in initial committed payments and additional payments contingent upon achievement of clinical, manufacturing, regulatory, and commercial milestones. Additionally, Ipsen will receive royalties on worldwide sales.

About BIM 51077

BIM 51077, a compound discovered by Ipsen Research and Development, is a GLP-1 receptor agonist, a new class of compounds under study for the treatment of Type 2 diabetes. Diabetic patients produce less insulin than non-diabetics, and clinical studies suggest that GLP-1 receptor agonists can increase insulin to near normal levels. GLP-1 incretin hormone is secreted naturally in response to food intake and acts to stimulate insulin production, suppress glucagon secretion, and slow gastric emptying in order to restore and sustain physiological blood glucose levels. The structure of BIM 51077 was optimized to provide extended duration of action while retaining the potency of the endogenous hormone.

Roche in Diabetes

Roche is committed to finding new medicines to treat metabolic diseases, with a strong emphasis on diabetes. In June 2003, Switzerland’s Federal Social Security Office (BSV) expanded reimbursement approval for Roche’s Xenical to include treatment of overweight Type 2 diabetics who are also being treated with one or more oral antidiabetic medicines. Xenical is the world's leading medicine for weight loss and weight control, and BSV’s expanded reimbursement approval underscores Xenical’s efficacy in treating overweight patients with Type 2 diabetes.

Roche is a leading supplier of products and services for diabetes monitoring and integrated diabetes management. Following the acquisition of Disetronic, the world’s second-largest manufacturer of insulin pumps, Roche’s diabetes portfolio will range from blood glucose meters for patient self-monitoring to sophisticated, programmable insulin pumps that allow patients to continuously administer insulin doses according to their individual needs. In 2002, Roche Diabetes Care, a business area of Roche Diagnostics, posted sales of 2.5 billion Swiss francs (+14% in local currencies), thanks to the continued success of the Accu-Chek product line.

Roche Business Development and Alliance Strategy

Roche’s research strategy is based on strong in-house research with centres in Japan, Europe and the USA and strategic alliances with Genentech and Chugai. Complementing and strengthening the Group’s dynamic R&D capabilities are over 50 scientific and commercial collaborations with biotech companies and universities, tailored alliances supplement these efforts in clearly defined focus areas. Roche has formed over 45 new partnerships, which span a wide range of therapeutic areas and technologies, making it an industry leader; a key element of this strategy is to enable its partners to achieve their vision while maintaining their cultural identity and entrepreneurial spirit.

Ipsen’s Active Search for New Alliances and Partnerships

Ipsen’s strategy for development is based on two main pillars: the high quality of its research and an active search for new alliances and partnerships. This new agreement with Roche reflects such strategy, validates the quality of the new molecules discovered by Ipsen’s researchers and confirms the Ipsen development model. Since January 2002, Ipsen has signed ten major licensing, research development and other partnership agreements and thus demonstrated its ability to form and develop alliances and partnerships with the leading pharmaceutical and biotech companies. The Group intends to continue this strategy in the future in order to enrich its product portfolio in its four targeted disease areas. These agreements help the Company to secure access to complementary technologies to those it already has, and at the same time provide new opportunities for international distribution, particularly in the United States and Japan.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market, the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche employs roughly 65,000 people in 150 countries. The Group has alliances and R&D agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

About Ipsen
Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and haematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centres: Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group's website is www.ipsen.com.


Source: Ipsen

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Octagen Corporation and Ipsen Commence Human Studies of Potential New Hemophilia Drug

Bala Cynwyd, PA., USA and Paris, France, September 4, 2003 — Octagen Corporation, a Philadelphia area biotechnology company, and Ipsen (formerly Beaufour Ipsen), a European pharmaceutical company announced today the start of a phase I human (clinical) trial of their recombinant porcine coagulation factor VIII for hemophilia A inhibitor patients. The drug, known internally as OBI-1, is being developed jointly by Octagen and Ipsen.

The phase I trial, to be conducted in up to 20 clinical centers throughout the United States of America and the United Kingdom, is designed to compare the safety and pharmacokinetics of single infusions of genetically engineered OBI-1 and the commercially available porcine factor VIII known as Hyate:C, a product derived from pig plasma and sold by Ipsen.

"A disorder that affects an estimated 350,000 people worldwide, hemophilia A is caused by a lack of a clotting factor protein known as factor VIII, a deficiency that results in periodic episodes of spontaneous bleeding" observed Richard Driansky, Octagen’s Chief Executive Officer. "These bleeding episodes are treated generally with replacement human factor VIII, which can either be genetically engineered or obtained from the pooled plasma of multiple donors. Approximately 25% of hemophiliacs develop antibodies or inhibitors to human factor VIII, which their immune systems see as foreign protein matter. As a result they can no longer be treated with human factor VIII" noted Mr. Driansky.

"Many inhibitor patients can be successfully treated with porcine factor VIII," said Dr. Alistair Stokes, Ipsen’s Executive Vice-President, Corporate Development. "The problem," added Dr. Stokes, "is that supplies of Hyate:C, the current commercial porcine factor VIII, have been constrained due to the necessity and difficulty of screening out extraneous material from the porcine plasma from which the product is derived. Since OBI-1 is a genetically engineered molecule, its production would not be hindered by that consideration" observed Dr. Stokes. "If proven safe and effective in clinical trials, OBI-1 would hold considerable promise both for hemophilia A inhibitor patients, as well as for so-called 'acquired' or 'autoantibody' patients. The latter group consists of individuals who do not have congenital hemophilia but who develop a severe and often life-threatening immune response to their own normal factor VIII" noted Dr. Stokes.


Notes to editor

Octagen

Founded in November 1997, Octagen’s mission is to develop and commercialize drugs to treat hemophilia and other disorders of the clotting process. OBI-1 was discovered by Dr. John S. Lollar, a renowned hemophilia researcher and Professor of Medicine at Emory University (Atlanta, USA). In 1998 Octagen entered into an exclusive worldwide license with Emory University to develop that drug. Later that year Octagen and Ipsen entered into an exclusive sublicense agreement, pursuant to which the two companies have been engaged in the development of OBI-1. Octagen, Ipsen, and Dr. Lollar have also been collaborating on an earlier stage project involving a recombinant and largely humanized version of factor VIII, OBI-2. That molecule is designed to reduce the incidence of inhibitor formation.

Octagen's website is www.octagen.com

Ipsen

Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and hematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centers Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group’s website is www.ipsen.com


Source: Ipsen

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Agreement between Teijin Limited and Ipsen for the development and the marketing of four Ipsen products in Japan

...and a new agent discovered by Teijin Limited in Europe Tokyo (Japan) and Paris (France), 7 July 2003 - Teijin Limited and Ipsen announced today the signature of a collaboration to develop and market four Ipsen products in Japan and Teijin's anti-gout agent, TMX-67 in Europe. As part of the agreement, Teijin will support the establishment of Ipsen’s presence in Japan with a mirror agreement for Europe. The collaboration foresees that sales of products in Japan and Europe will revert back to Ipsen and Teijin, respectively, in the future when the companies establish a local commercial presence.

The four products from Ipsen are a Glucagon-like peptide-1 analogue (GLP-1, code name: BIM51077) for which Teijin has been granted co-exclusive rights in Japan, a type 2-receptor selective somatostatin analogue (SSTR-2, code name: BIM23190), a parathyroid hormone 1-34 fragment analogue (PTH, code name: BIM44058), and a sustained-release formulation of a somatostatin analogue (Somatuline® Autogel®), for which Teijin has been granted exclusive rights in Japan.

Teijin will develop the analogues of GLP-1, SSTR-2, PTH and Somatuline® Autogel® as treatments for type II diabetes, diabetic retinopathy, severe osteoporosis, and acromegaly, respectively. By developing novel drugs having superior efficacy compared with competitive products currently under development, Teijin aims to provide patients suffering from these diseases with better solutions, taking advantage of Ipsen’s outstanding expertise in peptide technology and large molecule sustained-release formulation technology.

GLP-1 and SSTR-2 analogues are in phase I development and the PTH analogue is in preclinical development. Somatuline® Autogel® has been launched in several European countries including the UK and France, and is in phase III in the USA. Teijin will move forward with the development and sales of these products in Japan, in collaboration with Ipsen.

TMX-67 is a novel xanthine oxidase inhibitor discovered by Teijin with a novel molecular structure different from allopurinol, the only xanthine oxidase inhibitor currently available on the market. TMX-67 is expected to be safer and more effective than allopurinol at lower doses and is in phase III both in Japan (Teijin) and the USA (TAP Pharmaceutical Products Inc., Lakeforest, IL). The involvement of Ipsen will make it possible to develop TMX-67 in parallel in the three territories, Japan, the USA and Europe.

"The addition of GLP-1 and SSTR-2 analogues and Somatuline® Autogel® to Teijin’s product pipeline will help the company to establish a first-class cardiovascular and metabolic disease franchise in Japan. The addition of the PTH analogue to Teijin’s existing osteoporosis portfolio including Bonalon® and Onealfa® will enable Teijin to provide a total solution in osteoporosis management, in which Teijin aims at being the leading company. This collaboration will also enable us to establish a basis for the expansion into the European market with TMX-67 in collaboration with Ipsen, which has a solid foundation in the European pharmaceutical industry." said Shigeo Ohyagi, General Manager of Medical & Pharmaceutical Business Group, Teijin Group Senior Executive Officer.

"Our strategy is based on an active search for new alliances and partnerships, especially to reinforce Ipsen’s internationalization. This collaboration with Teijin, a leading pharmaceutical company in Japan, will allow us to develop our presence in Japan, the world’s second biggest market" said Jean-Luc Bélingard, President and CEO of the Ipsen Group.


Notes to editor

Teijin Limited

1. Establishment:	June 1918
2. Head Office:	6-7, Minami-hommachi, 1 chome, Chuo-ku, Osaka, 541-8587 Japan
3. Capital Stock:	¥70.787 billion (as of March 31, 2003)
4. Representative:	President & CEO Toru Nagashima
5. Number of Employees:	Consolidated 23,265 (as of March 31, 2003) Non-consolidated 2,938 (as of March 31, 2003)
6. Sales:	Consolidated ¥890.4 billion (Fiscal Year ended March 2003) Non-consolidated ¥127.4 billion (Fiscal Year ended March 2003)

7. Description of Business:
Teijin’s main areas of activity are the production and sales of fibres, chemicals and plastics, pharmaceuticals and medical products, as well as the home healthcare business. With respect to pharmaceuticals and medical products, Teijin has focused on respiratory, disease, bone calcium metabolism and cardiovascular / metabolism disorders, and markets throughout Japan. In the home health care field, Teijin is engaged in the home oxygen therapy business, marketing its oxygen concentrators throughout Japan.

The Group’s website is http://www.teijin.co.jp

Ipsen

Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and hematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centers Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group’s website is www.ipsen.com


Source: Ipsen

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Ipsen research discovers a family of specific analogues of ghrelin, a hormone implicated in weight control

Paris, 24 June 2003. The 'Beaufour Ipsen' pharmaceutical group, renamed 'Ipsen', announced at the 85th Annual Meeting of The Endocrine Society held from 19 June to 22 June in Philadelphia (USA) that it has discovered a family of specific analogues of ghrelin, a hormone implicated in weight control, which, for the first time, do not stimulate growth hormone secretion.

Changes in body weight represent a major and increasing public health problem. The prevalence of obesity in the USA is 27.7% in men and 34% in women in the 20-74 year age group (source: National Health and Nutrition Examination Survey 1999-2000); whereas in most European countries it is approximately 10-20% in men and 15-25% in women (source: Danish National Board of Health Conference on Obesity, September 2002). Significant weight loss or cachexia is also an increasing cause of morbidity and mortality in the elderly, and persons with congestive heart failure or in some cancers.

Ghrelin is secreted by the stomach and stimulates the appetite. It has recently received media attention because high blood levels of ghrelin have been observed in individuals following weight loss from dieting, which may partially explain the difficulty in maintaining diet-induced weight loss. Ghrelin levels remain low in patients who have lost weight by undergoing gastric bypass surgery, and, again, this may partially explain the lack of appetite in these individuals. All these observations open the way to the research of new drugs which can treat weight pathologies such as the ghrelin agonists for cachexia and ghrelin antagonists for obesity.

Ghrelin also stimulates growth hormone and prolactin secretions by the pituitary gland, and cortisol and aldosterone secretion by the adrenal glands. If these additional effects can be desirable in certain pathologies, often they will lead to secondary effects in other pathologies (for example: augmentation of growth hormone is not desirable in the elderly with diabetes or in persons with cancer).

In this context, Ipsen research has for the first time synthesised a unique modified version of ghrelin analogues which conserves its regulator effect on appetite, but does not stimulate growth hormone secretion.

This discovery advances the possibility of producing ghrelin-based drugs for regulating appetite and body weight. For the first time this also suggests that differences may exist at the ghrelin receptor levels in different target tissues, which opens up a new field of research. This provides unique tools for researchers to increase the knowledge of ghrelin regulation and human body weight control.

This discovery has been made by Biomeasure Inc. (Boston, USA), one of four research centres of the Ipsen Group to discover drugs in neuroendocrinology. "This important discovery highlights the quality of our research in neuroendocrinology and our capacity to generate innovative molecules in this therapeutic area. At present, we are conducting pre-clinical tests on selected ghrelin analogues in order to enter them in the clinical evaluation phase in the near future" said Jacques-Pierre Moreau, Ipsen's CSO.


Ipsen

Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and hematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centers Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group’s website is www.ipsen.com


Source: Ipsen

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Ipsen to develop Spirogen’s novel anti-tumour agent

Paris and London, 22 May 2003. The "Beaufour Ipsen" pharmaceutical group, renamed "Ipsen", has acquired worldwide rights to develop a new and novel antitumour agent SJG-136, from Spirogen, a London-based biotechnology company. The agreement also provides Ipsen with exclusive access to three, selected gene targets as a platform for the synthesis and development of further anti-cancer drug candidates and a 20 percent equity stake in Spirogen.

SJG-136 spans six base pairs of DNA and has significant activity in a number of human tumour xenograft (animal) models including brain melanoma, breast, ovarian and colon tumours. The agent is currently in pre-clinical development with Cancer Research, UK and the National Cancer Institute in the United States of America (USA). Phase I clinical trials are planned for the third quarter of 2003 in the United Kingdom and the fourth quarter in the United States of America (USA).

Commenting on the agreement, Dr Alistair Stokes, Ipsen’s Executive Vice President, Corporate Development said: "We believe that SJG-136 has the potential to be an important addition to the anti-cancer therapeutic armoury. This agreement, after the one concluded with Roche last December, reflects the Group’s policy of seeking alliances that will help us gain access to new products and technologies in our core therapeutic areas".

Dr Chris Martin, CEO of Spirogen said: "The development of chemotherapeutics which target specific genes represents the cutting edge of molecular research. We are delighted to be working with Ipsen to develop such compounds for the oncology market. This agreement is in line with Spirogen’s strategy of developing drug candidates and its gene targeting technology in partnership with pharmaceutical companies while taking forward its own anti-cancer DNA sequence binding agents".


Notes to editor

Ipsen

Present in over 110 countries with a total staff of nearly 3700, the Ipsen Group had a turnover of €718 million in 2002, 27.1% outside Western Europe.

The Group is focused on developing innovative products in targeted disease areas: oncology, endocrinology, neurology and hematology. Ipsen currently has over 20 products on the market, including those marketed to specialists in disease areas that represent the main source of Ipsen’s future growth, as well as predominantly natural-based products that represent the historical base of the Group’s business in other disease areas. In 2002, 18.2% of Ipsen’s turnover was reinvested in Research and Development, carried out from 4 centers Paris, Boston, Barcelona and London by an international network of about 550 scientists.

The Group’s website is www.ipsen.com

Spirogen

Spirogen is a privately owned UK company, founded in 2001 by Professor David Thurston and Dr Phillip Howard (now at the School of Pharmacy, University of London), Professor John Hartley (University College London) and Dr Chris Martin. The company is pioneering the discovery and development of a unique class of low molecular weight sequence-specific DNA-interactive drugs designed to treat gene-mediated diseases.

Spirogen’s proprietary combinatorial chemistry-based platform technology forms the basis of a research effort that began over a decade ago to develop novel therapeutics with potential application in a number of markets. Spirogen’s initial investors were: Cambridge Research Bioventures (lead investor), Xenva Ltd, CRIL and Bloomsbury Bioseed Fund.

Spirogen's website is www.spirogen.com


Source: Ipsen

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Agreement between Beaufour Ipsen and Novartis Pharma for the marketing of two anti-hypertensive drugs, Nisis® and Nisisco® in France

Paris, May 14, 2003 — The Beaufour Ipsen Group announced today the singning in France of a marketing agreement with Novartis Pharma for two antihypertensive drugs Nisis® (valsartan) and Nisisco® (valsartan and hydrochlorothiazide). Since March 31, 2003, Beaufour Ipsen Pharma, the French subsidiary of the Group, promotes these products in France, its overseas departments and territories and in the Principalities of Monaco and Andorra. These two drugs were previously distributed by Aventis.

Already involved in the treatment of hypertension with Tenstaten® (cicletanine), this agreement reinforces Beaufour Ipsen’s expertise in cardiovascular diseases in these territories. This is also consistent with the Group’s strategy to strenghten its international development based on a solid position in France.

According to Christophe Jean, Executive Vice-President, Chief Operating Officer, Beaufour Ipsen Group "We are pleased to collaborate with Novartis Pharma, one of the world leaders in the treatment of arterial hypertension, a disease which affects 7.5 million people treated in France today. This agreement adds two major innovative medicines to our portfolio that have significant medical and scientific vcardiovascular field".

In 2002, Nisis and Nisisco had a turnover of more than €24 million (source : GERS), enhanced by the launch of Nisisco® 160-25 (160 mg of valsartan and 25 mg of hydrochlorothiazide) last February, which complements the product line already available to physicians.

These drugs are being further evaluated in a broad based clinical program with the participation of more than 38,000 patients. The purpose of the ongoing studies is to extend the present indications to hypertension post-infarct, and arterial hypertension associated with cardiovascular risks.


Notes to editor

Nisis®/Nisisco®

Nisis® and Nisisco® belong to the family of angiotensin II antagonists, representing the leading edge in the treatment of hypertension with the prospect of expanding their use.

Nisis® (active ingredient: valsartan) is indicated in the treatment of essential arterial hypertension (40 mg, 80 mg, 160 mg, packs of 28). Nisisco® 80 - 12,5 (80 mg of valsartan and 12,5 :mg of hydrochlorothiazide, packs of 28) is indicated after failure of a monotherapy by an angiotensin II antagonist or by hydrochlorothiazide and Nisisco 160 – 25 is indicated when a monotherapy by Nisis 160 or by the combination Nisisco 80 - 12.5 is insufficient.

Beaufour Ipsen

Present in over 80 countries with a total staff of 3423, the Beaufour Ipsen Group had a turnover of €704 million in 2001, 57% of which was outside France.

The Group specialises in oncology, haematology, neurology and endocrinology and has a portfolio of 30 products which are either peptides, derived from biotechnology, or based on natural sources. In 2001, 16.4% of Beaufour Ipsen’s turnover was reinvested in Research and Development (R&D).

The Group’s website is www.beaufour-ipsen.com


Source: Ipsen

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Christophe Jean, Executive Vice President, Chief Operating Officer of the Beaufour Ipsen Group

Paris, May 13, 2003 — Mr Christophe Jean is nominated Executive Vice President, Chief Operating Officer of the Beaufour Ipsen Group. Christophe Jean, 47 years old and a Harvard graduate, joined the pharmaceutical industry with Ciba-Geigy where he successively occupied Marketing (Brazil & Sweden) and General Management positions at an international level. He was subsequently nominated Worldwide Head of Financial Control and Information Technology and was a Member of the Pharmaceuticals Executive Committee. He held that position until after the merger between Ciba-Geigy and Sandoz to form Novartis and was then nominated Head of Europe, the Middle East and Africa. In 2000 he became President and CEO for the pharmaceutical activities of the Pierre Fabre Group.

In September 2002 he joined the Beaufour Ipsen Group where he was initially in charge of creating the Corporate Strategic Planning and Strategic Marketing departments. He is a Member of the Executive Committee and also oversees commercial operations and the development of the US and Japan markets.

About Beaufour Ipsen

Present in over 80 countries with a total staff of 3423, the Beaufour Ipsen Group had a turnover of €704 million in 2001, 57% of which was outside France.

The Group develops products for four targeted disease area franchises: oncology, endocrinology, neurology and haematology. It currently has a portfolio of 30 products on the market which are either peptides, derived from biotechnology, or products based on natural sources. In 2001, 16.4% of Beaufour Ipsen's turnover was reinvested in Research and Development, which is carried out in four research centres (Paris, Boston, Barcelona and London) by an international network of around 500 scientific staff.

The Group’s website is www.beaufour-ipsen.com


Source: Ipsen

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Beaufour Ipsen obtains the European Marketing Authorisation for NutropinAQ®, recombinant growth hormone

Paris, 18 March 2003 — The Beaufour Ipsen Group announced today that the company has obtained European Marketing Authorisation from the European Agency for the Evaluation of Medicinal Products (EMEA) on 24 February, 2003 for Nutropin AQ%reg; (somatropin [rDNA origin] solution for injection). The approved name in Europe is NutropinAq. This decision comes after the agreement signed in September 2002 with Genentech, a USA biotechnology company giving Beaufour Ipsen exclusive rights to market Nutropin AQ® and Nutropin AQ PenTM Cartridge in Europe and the rest of the world, excluding North America and Japan.

Nutropin AQ® is produced using recombinant DNA technology and has the same amino acid sequence as human growth hormone (GH) produced naturally in the human body. Nutropin AQ® is used for the treatment of GH deficiency, which occurs when the production of GH secreted by the pituitary gland, is disrupted.

"Pituitary-related endocrine disorders are a key therapeutic area for Beaufour Ipsen. This collaboration with Genentech has added an important product to our portfolio", said Dr Alistair Stokes, Group Vice-President, Corporate Development, Beaufour Ipsen.

Nutropin AQ® is the first ready-to-use liquid GH formulation approved in the USA and is supplied as 10mg of sterile liquid somatropin per vial or cartridge for exclusive use with the Nutropin AQ Pen^TM.

Beaufour Ipsen is preparing to submit the requisite regulatory dossier to gain approval to market Nutropin AQ Pen^TM Cartridge for use with the Nutropin AQ Pen^TM.

"We are pleased to collaborate with Beaufour Ipsen to market Nutropin AQ® and Nutropin AQ Pen^TM in Europe", said Joseph S. McCracken, Vice-President, Business and Commercial Development of Genentech. "This agreement continues our efforts in providing our family of growth hormone products to patients throughout the world".


Notes to editor

Beaufour Ipsen

Present in over 80 countries with a total staff of 3423, the Beaufour Ipsen Group had a turnover of €704 million in 2001, 57% of which was outside France.

The Group specialises in oncology, haematology, neurology and endocrinology and has a portfolio of 30 products which are either peptides, derived from biotechnology, or based on natural sources. In 2001, 16.4% of Beaufour Ipsen’s turnover was reinvested in Research and Development (R&D).

The Group’s website is www.beaufour-ipsen.com

Genentech

Genentech is a leading biotechnology company that discovers, develops, manufactures and commercialises biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products originated from or are based on Genentech science.

Genentech manufactures and commercialises ten biotechnology products directly in the USA. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA.

NutropinAq

NutropinAq is indicated for the treatment of:

• Long-term treatment of children with growth failure due to inadequate endogenous GH secretion
• Long-term treatment of growth failure associated with Turner syndrome
• Treatment of prepubertal children with growth failure associated with chronic renal insufficiency up to the time of renal transplantation
• Replacement of endogenous GH in adults with GH deficiency of either childhood or adult-onset aetiology. GH deficiency should be confirmed appropriately prior to treatment

Source: Ipsen

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New laboratory system at Genome Express brings speed, flexibility and improved cost performance to DNA sequencing

Grenoble, France, February 25, 2003 — GENOME express, the developer of high value-added solutions for functional genomics and target discovery has installed new sophisticated high performance hardware and software in its laboratories to ensure it continues to offer its clients the best and most cost-effective approaches to target discovery and validation, the company announced today. The new equipment is the Zymark Sciclone ALH, an Advanced Liquid Handling workstation that speeds up laboratory research by automating liquid handling and microplate management.

"The acquisition and installation of the Sciclone is part of our continuous policy of providing an internationally-competitive platform for the benefit of our customers and partners," said Jean-François Mouret, Chief Technical Officer at GENOME express. "The Sciclone brings speed and increases the flexibility in our sequencing and fragment analysis process from DNA template to purified and ready to load DNA products."

The Sciclone ALH is a high precision, easy-to-use instrument that performs a host of functions that previously required several separate devices. The new system will bring benefits to GENOME express customers and partners in many of the wide range of activities offered by the company. For example, GENOME express has recently launched a major new technology called DACS (Discriminative Analysis of Clone Signature). GENOME express is initially using DACS for the study of gene expression, but the company will also use it far more widely in genomics generally. "Examples include genome sequencing finishing and structural differential genome analysis," said Mouret. "All these applications will take advantage of the throughput, reproducibility and traceability provided by the Sciclone workstation. Our clients will save time and money directly from being able to access this technology."

"We are delighted to have GENOME express among the international users of the Sciclone," said Kevin Hrusovsky CEO at Zymark. "Coupled with the company's know-how in functional genomics, it will help give them a competitive edge in this burgeoning market."

It supplies eight-channel independent Z-axis probes, "on-the-fly" interchangeable 96 and 384 arrays, a compact 20-position deck, bulk dispensing capabilities and a unique design that offers effortless integration with other devices from all four sides of the system. The Sciclone ALH uses Zymark's CLARA^TM software to ensure evolving laboratory requirements are completed with as little effort as possible.


About Zymark
Zymark is a leading provider of automation solutions serving the worldwide life science, biotechnology and pharmaceutical industries. The company has introduced new automation paradigms that have empowered scientists to raise laboratory research to a new, more industrialized level. With these advances, Zymark has firmly established itself as a solutions provider with a single-minded goal of streamlining the entire drug discovery pipeline. Zymark provides direct sales, service and applications support throughout the world and hosts the annual ISLAR conference on laboratory automation. For more information about Zymark Corporation and its products, visit www.zymark.com

About DACS
DACS (Discriminative Analysis of Clone Signature) is the new proprietary technology provided by GENOME express. The technology, based on EST sequencing reduces cost while offering the same advantages. DACS marks only one nucleotide of the four composing DNA — A, C, G, T — and includes a capillary multiplex sequencing thus offering high-throughput (1536 samples per run). A patented signal analysis technology applied on sequencing results discriminates identical clones from the different ones, thus allowing the discovery of genes expressed.

For further information: http://www.genomex.com

About GENOME express
GENOME express, Grenoble, France, develops and markets high value-added solutions for functional genomics. The company offers a unique platform that integrates proprietary tools for genomics (discovery and identification of SNPs — Syn-Quence^TM), transcriptomics (gene expression analysis), and proteomics (identification of proteins using genome mapping of mass spectrometry data — Pep Map^TM). Building on its success and experience as a service provider, GENOME express is currently making its platform accessible to private sector researchers and academics in the biopharmaceutical sector. This will be done through partnerships and enable GENOME express customers to outsource their R&D projects either in part or totally. The company is also developing its own research to discover new targets for therapeutic or diagnostic applications in the fields of metabolic diseases such as diabetes or obesity, the central nervous system and bacterial genomics.

For further information: http://www.genomex.com

Source: Genome Express

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Appointment of Mrs Claire Giraut as Chief Financial Officer of the Beaufour Ipsen Group

Paris, 5 February 2003 — Mrs Claire Giraut was appointed Chief Financial Officer of the Beaufour Ipsen Group and, as Group Vice-President, Finance, Member of the Executive Committee. The Company Secretary and the Head of Group’s Information Systems (MIS) will also report directly to Mrs Giraut.

Mrs Claire Giraut, 46, qualified as a Biotech Engineer. Her career has mainly been in Finance. Among her most recent assignments, she was Senior Executive VP Finance of the Coflexip Stena Offshore Group, world leader in subsea oil services, listed in France and in the USA.

About Beaufour Ipsen

Present in over 80 countries with a total staff of 3423, the Beaufour Ipsen Group had a turnover of €704 million in 2001, 57% of which was outside France.

The Group develops products for four targeted disease area franchises: oncology, endocrinology, neurology and haematology. It currently has a portfolio of 30 products on the market which are either peptides, derived from biotechnology, or products based on natural sources. In 2001, 16.4% of Beaufour Ipsen's turnover was reinvested in Research and Development, which is carried out in four research centres (Paris, Boston, Barcelona and London) by an international network of around 500 scientific staff.

The Group’s website is www.beaufour-ipsen.com


Source: Ipsen

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Reinforcing Ipsen's presence on the American market clinical programme is underway for Ipsen's botulinum toxin in aesthetic medicine with Inamed

Ipsen Limited, the UK-based pharmaceutical company and subsidiary of the Beaufour Ipsen Group has announced the beginning of Phase II clinical trials in the United States of America (USA) on its botulinum toxin type A for use in aesthetic medicine. "Patients have now been enrolled and are being treated in this important study of botulinum toxin" said Dr Gary Monheit, a Dermatologist in Birmingham, Alabama, and Co-Principal Investigator in the study.

This announcement follows the filing of an Investigational New Drug (IND) application in September 2002, and the signing in July 2002 of a definitive agreement with Inamed Corporation, a global medical device company based in California. The agreement gives Inamed exclusive rights to develop and distribute Ipsen’s botulinum toxin type A for cosmetic indications in the USA, Canada and Japan.

In the past few years, botulinum toxin type A in its purified form, has revolutionised the face of cosmetic dermatology. It is a simple, reliable, reproducible, non-invasive procedure that can be administered successfully to manage a variety of cosmetic issues.

Dr Alistair Stokes, Chief Executive Officer of Ipsen and Group Vice-President, Corporate Development, Beaufour Ipsen said "These trials are part of our worldwide strategy to develop botulinum toxin in aesthetic medicine. Inamed has an excellent reputation in this marketplace, and our relationship with the company will help us to achieve our goal of increasing the use of botulinum toxin as a cosmetic treatment".

"The market in the USA for botulinum toxins is projected to exceed $400 million in 2002 and approach $800 million by 2005. The partnership with Ipsen gives us the potential to expand our product portfolio for the customer in a significant way" said Nick Teti, Inamed’s Chairman, President and Chief Executive Officer.

The exact nature of the cosmetic indication that will be submitted by Inamed will depend on the outcome of the clinical trial programme.

Botulinum toxin will be manufactured by Ipsen Biopharm in Wrexham, North Wales and supplied to Inamed for distribution in North America and Japan. Ipsen Biopharm is the UK pharmaceutical manufacturing and distribution arm of the Beaufour Ipsen Group.


Notes to editor

Botulinum toxin

Beaufour Ipsen’s botulinum toxin type A (which is branded as Dysport®) is now licensed in 50 countries for a variety of neuromuscular indications including: cervical dystonia, blepharospasm, hemifacial spasm, and the treatment of dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy. In addition Dysport® is licensed in some countries for post-stroke spasticity and hyperhidrosis.

Beaufour Ipsen

Present in over 80 countries with a total staff of 3423, the Beaufour Ipsen Group had a turnover of €704 million in 2001, 57% of which was outside France.

The Group specialises in oncology, haematology, neurology and endocrinology and has a portfolio of 30 products which are either peptides, derived from biotechnology, or based on natural sources. In 2001, 16.4% of Beaufour Ipsen’s turnover was reinvested in Research and Development (R&D).

The Group’s website is www.beaufour-ipsen.com

Inamed Corporation

Inamed is a global medical device company engaged in the development, manufacturing and marketing of products for breast and facial aesthetics and obesity intervention. These products include breast implants for aesthetic augmentation and for reconstructive surgery following a mastectomy; a range of dermal products to correct facial wrinkles; and minimally invasive devices for obesity intervention, including the LAPBAND® System indicated for severe obesity.

The Company’s website is www.inamed.com


Source: Ipsen

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