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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Beaufour Ipsen and Roche to develop jointly and market Beaufour Ipsen’s novel anticancer drugs

Roche’s pipeline strengthened, with a fifth oncology transaction including a product in phase II Roche and Beaufour Ipsen (Paris, France) announced today that they have signed a global agreement to co-develop and market Beaufour Ipsen’s new anticancer candidates. Roche will have worldwide rights, excluding Europe, to market two Beaufour Ipsen products in development (diflomotecan and BN80927). Beaufour Ipsen retains these rights for Europe. In addition, mutual rights have been granted to future follow-on products in the same chemical family, the homocamptothecines, a new class of anticancer molecules discovered by Beaufour Ipsen.

Diflomotecan, which is entering Phase II clinical development, and a second compound (BN80927), currently in pre-clinical development, are being assessed for their efficacy in solid tumours, including colorectal, lung and breast cancer. Combination studies of diflomotecan and Roche’s Xeloda are expected to begin during the first quarter of 2003.

Diflomotecan is the first of a new generation of topoisomerase-1 inhibitors, with a proven mechanism of action, improved safety and efficacy profile. The second compound, BN80927, has a novel mechanism of action, including dual inhibition of topoisomerases I and II, and will be developed for a broad spectrum of indications.

"We are very pleased that Beaufour Ipsen has selected Roche to commercialise these promising drug candidates, especially in the US oncology market. With the completion of our fifth oncology deal this year and the continuous progress of our in-house pipeline, the strength of our portfolio continues to increase." said William M. Burns, Roche’s Head of Pharmaceuticals.

"We are delighted to be working with such a world class company and one of the world’s leading oncology companies to develop and market novel topoisomerase inhibitors discovered by Beaufour Ipsen" said Jean-Luc Belingard, CEO of the Beaufour Ipsen Group.


Financial Terms
Under the terms of the agreement Roche will have all rights to market and sell diflomotecan and BN80927 in the USA, Japan, and rest of the world, whereas Beaufour Ipsen will have the sole right to market and sell the products in Europe. Roche and Beaufour Ipsen will jointly pay all future research and development costs for selected indications according to their market potential. Beaufour Ipsen will receive up to US$150 million, consisting of over $20 million in committed payments, and additional payments contingent upon achievement of clinical, regulatory and commercial milestones. Beaufour Ipsen will receive royalties on net sales in the USA, Japan and rest of the world, while Roche will receive royalties on net sales in Europe.

About the Agreement
Roche and Beaufour Ipsen will jointly conduct clinical development of the products. The principal focus of the collaboration will be the clinical development and marketing of diflomotecan and BN80927. Roche and Beaufour Ipsen will also have mutual rights to follow-on compounds and improvements over the next three years. Any such products would also be co-developed and co-commercialised by Roche and Beaufour Ipsen for the treatment of cancer or other therapeutic areas.

Roche in Oncology
Roche is the world leader in oncology. Its franchise includes three drugs with survival benefit: MabThera (Rituximab), Xeloda (capecitabine), and Herceptin (Trastuzumab). It also includes NeoRecormon (epoetin beta), Roferon-A (interferon alfa-2a), and Kytril (granisetron HCL). In addition, Roche has entered several agreements in the current year with Antisoma, Kosan, Gryphon, and GeneMab to develop and commercialise various promising compounds in the oncology field. The Roche Group’s oncology program is supported by four Research sites (two in the USA, Germany and Japan) and five Development sites (two in the USA, UK, Switzerland and Japan).
Roche also offers a broad portfolio of tumor markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests running on the LightCycler. Within its Integrated Cancer Care Unit the company develops new tests which will have a significant impact on disease management of cancer patients in the future.

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-orientated healthcare groups. The company's two core businesses in pharmaceuticals and diagnostics provide innovative products and services, that address prevention, diagnosis and treatment of 3 diseases, thus enhancing people’s health and quality of life. The two core businesses achieved a turnover of 19.3 billion Swiss Francs in the first three quarters of 2002 and employed about 57,000 employees worldwide.

Beaufour Ipsen in oncology
Endocrinology/oncology is a significant line of development for Beaufour Ipsen, representing 33.2% of its turnover in 2001. Sales are based on two major products, Decapeptyl, a sustainedrelease (28 days and 3 months) peptide analogue of the hypothalamus hormone (GnRH), mainly indicated in the treatment of prostate cancer, and Somatuline, a sustained-release (28 days) somatostatin peptide analogue and inhibitor of growth hormone used in the treatment of carcinoid tumors.

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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Genome express increases focus on integrated collaborative high throughput services and solutions

Company moves to strengthen position as link in partners' R&D value chain

Grenoble, France, November 15, 2002 - GENOME express, the developer of high value-added solutions for functional genomics and target discovery and validation, announces today that it is increasing its focus on integrated high throughput services and solutions for pharmaceutical, biotech and agri-food industries.

The company has already implemented a number of measures to support this strategy. These include the transfer of its oligonucleotide activity to Qbiogene, a Canadian company that develops and markets molecular biology and genomics products, and the recent launch of its proprietary Discriminative Analysis of Clone Signatures (DACS^TM) technology, a solution focusing on the discovery process of tissue- or cell-expressed genes.

"Remaining competitive and profitable in oligonucleotide activities would have demanded significant investment," said Yves Laurent, CEO of GENOME express. "We decided it would also be a distraction from our higher added value activities where we are engaged in the development and collaborative deployment of our unique integrated platform (genomics, gene profiling and proteomics, bioinformatics) to address real needs."

The recent launch of its Discriminative Analysis of Clone Signatures (DACS) technology is a good illustration of GENOME express' commitment to providing solutions offering real advantages to its customers and partners.

"In the fast-moving field of exploratory genomics, GENOME express intends to stay in the forefront of high value-added services," added Laurent. "Our new GE-DACS solution eliminates bottlenecks in the discovery process of genes expressed in tissue or in a cell and reduces the expense and time needed to generate resources and information for the expression analysis of these genes."

Future investments and collaborations will reinforce its already powerful in-house technology platforms and the company will continue to build a business that brings tangible, significant benefits to its customers. "We expect to make further exciting announcements that will show how GENOME express brings unique competitive advantages to its customers," concluded Laurent.


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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Genome express launches proprietary technology to speed up gene discovery

DACS (Discriminative Analysis of Clone Signatures) cuts cost of creating improved genomic resources and simplifies gene expression analysis

Grenoble, France, October 23, 2002 - GENOME express, the developer of high value-added solutions for functional genomics and target discovery and validation, announces today the availability of its new proprietary technology, DACS.

The first application of this innovative technology is GE-DACS^TM (Gene Expression DACS). GE-DACS^TM eliminates bottlenecks in the discovery process of genes expressed in tissue or in a cell. Unlike existing processes, which are both complicated and costly, DACS reduces the expense and time needed to generate resources and information for the expression analysis of these genes. These resources are mainly PCR products that are "ready-to-spot" for an analysis tool such as micro-arrays. Micro-arrays have become an essential tool in the study of complex diseases such as diabetes, cancer and obesity.

DACS thus provides a significant breakthrough compared with other processes such as SAGE¹. DACS not only speeds up the discovery process but also facilitates expression analysis without the need to access data relating to the organism in question (genomic sequence or EST² sequences).

Furthermore, as it is built on the generation of complementary DNA clones, DACS ensures these biological resources are kept intact, and a link to the information produced is established for each clone. If, during the discovery process, researchers suspect the implication of a particular gene in a disease, they can access the initial biological resource and begin an in-depth analysis.

The simplicity of the process means that for the first time, experiments can be reproduced with ease. This is crucial for differential expression analysis, for example gene expression in a normal cell compared to a cancerous cell.

While the first application of DACS is for the study of gene expression, this technology developed by GENOME express can be applied far more widely for use in genomics. Examples include genome sequencing finishing and structural differential genome analysis.

"GE-DACS^TM enriches our technology portfolio with the addition of high-throughput differential expression analysis," said Yves Laurent, CEO of GENOME express. "DACS is proof of GENOME express' ability to develop innovative proprietary tools linking molecular biology to bioinformatics."

¹ — SAGE - Serial Analysis of Gene Expression
² — EST - Expressed Sequence Tag


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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Genome express appoints François Pons as new business development manager

Functional genomics company will benefit from François Pons' pharma and biotech experience in creating and managing scientific and industry collaborations

Grenoble, France, September 23, 2002 - GENOME express, the developer of high value-added solutions for functional genomics, announces today the appointment of François Pons as Director of Business Development.

Before taking up this appointment with GENOME express, Pons acquired eight years' high-level experience in the industry. He was Director of business development and scientific communication at the Centre d'Immunologie Pierre Fabre, in Saint Julien en Genevois, on the French side of the border between France and Switzerland. At Pierre Fabre, Pons was closely involved in the negotiation of a number of partnerships and licensing agreements, as well as the setting up and management of research consortia in immunotherapy for cancer and infectious diseases. He was also active in managing investment projects. He originally joined Pierre Fabre as biotechnology licensing manager after a period in strategic marketing with Baxter Healthcare France. His academic qualifications include a master's degree in biochemistry and microbiology (Marseille-Luminy), a diploma in food biotechnology and industry (ENSAIA, Nancy, a French school of agronomy and food industry), and a master's in industrial engineering and management of technological innovation (École Centrale, Paris).

François Pons comes to GENOME express during a period of intensive development. He is responsible for relations with both industry and research establishments and will develop collaborative and partnership alliances with these bodies. His overall mission is to promote GENOME express's integrated genomics and proteomics platform.

"GENOME express is at the stage where it needs to market its know-how in a more targeted and personalized way," said Yves Laurent, CEO of GENOME express. "François Pons brings the skills and experience required for this new phase. He possesses a combination of salesmanship, experience in negotiating and setting up contracts, and understanding of the scientific and pharmaceutical industry environments. This, together with his sheer enthusiasm, will make him one of the key players in the success of GENOME express. We are truly pleased to have him on board."

"I am looking forward to working with the GENOME express team in a vital, fast-growing field," said François Pons. "The company has demonstrated considerable quality throughout its existence and the excellent team has made the right scientific and industry choices, positioning itself in the functional genomics space. These are all good reasons why I want to make my contribution to the company's future success."


About GENOME express
GENOME express, Grenoble, France, develops and markets high value-added solutions for functional genomics. Its expertise covers a variety of disciplines including microbiology (library manufacturing), molecular biology (high throughput sequencing) and bioinformatics (proprietary software). Under development are an integrated genomics and proteomics platform designed to enable GENOME express to engage in proprietary target discovery. Siparex Ventures was lead banker for the fund-raising with co-lead Sud Partners (Sudinnova's fund management arm). Other investors were 3i, the original institutional investor, the Compagnie Financière Edmond de Rothschild, Aquasourça, SPEF Venture and Biotek Partenaires. Since the 12.4&nbps;million euro financing round, the company has received a further million euro grant from France's innovation agency, Anvar. GENOME express is one of the four members of the Genostar consortium, a bioinformatics platform for exploratory genomics that offers a unified way of representing biological knowledge.

Source: Genome Express

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Prostate cancer: Signature of a partnership agreement between Beaufour Ipsen and UroGene

Paris and Evry-Genopole, FRANCE — July 17, 2002 – The pharmaceutical group Beaufour Ipsen and the biopharmaceutical company UroGene have just signed a partnership agreement for the functional and clinical evaluation of a class of molecules in the field of prostate cancer. UroGene will be contributing its molecular genomic know-how, its biological and clinical expertise, and its biological resources and data base, in order to implement this programme.

"This agreement is very pertinent to the Beaufour Ipsen Group strategy since oncology is one of our major lines of therapeutic research. This agreement with UroGene regarding an important medical application is very satisfactory" stated Christophe Thurieau, Director of Research of the Henri Beaufour Institute. "We are convinced that evaluating our molecules for prostate cancer will open the way to extremely promising new therapeutic possibilities. Cancer of the prostate concerns millions of men the world over. Combining our joint expertise and developing the tools required to provide specialist care will give new hope to patients and clinicians involved in the management of this disease."

"We are particularly pleased with the Beaufour Ipsen decision to join forces with us. They are very prominent in the treatment of prostatic cancer and this agreement concurs with our strategy — an integrated oncological and urological approach. It is also a further demonstration that the means and know-how available to us can advance the development of new therapeutics" declared Philippe Berthon, President and Chief Scientific Officer of UroGene. "Further to our own therapeutic development plans — from gene to treatment — in the field of urological tumours, such cooperative work on new molecules can provide timely solutions in the quest for innovative treatment at the clinical stage."


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 Company 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 is reinvested in Research and Development. R&D is focused on four major areas (biologicals, peptides, therapeutic agents of low molecular weight and drug delivery technology) and is carried out from 4 research centres (Paris, Boston, Barcelona and London) by an international network of around 500 scientific staff. The Group is directing its research efforts towards disabling diseases where current treatments remain unsatisfactory. Beaufour Ipsen currently has a pipeline of 15 projects in development. The Group has also set up research partnerships with prestigious universities in the USA and Europe, mainly in France and in the United Kingdom.

UroGene is a biopharmaceutical company with extensive physio-pathological clinical expertise for the accelerated discovery and development of novel onco-urological drugs (prostate, kidney, bladder).

UroGene's three major assets in order to accelerate the process and reach these objectives are:

• UroBank, a tissue and data bank fuelling research projects and enabling early identification of new pertinent therapeutic targets
• A very efficient — and therefore time saving — therapeutic target validation process
• Complete integration of the research and development platform (genomics, functional biology, proteomics, and medicinal chemistry) so that new treatment projects can progress freely from early molecular gene identity studies to molecules in the clinical trial phase involving patients. Several specialised collaboration agreements have been signed to complement the UroGene platform.

At this point, UroGene is working on four of its own therapeutic development programmes (small molecules and peptides) and one programme in partnership.


Source: Ipsen

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New collaboration to develop treatments for inflammatory disease

The University of Cambridge, one of the world's leading centres for biomedical research, and Beaufour Ipsen Group, a European-based global pharmaceutical company, have joined forces to develop and commercialise chemokine inhibitory compounds. Dr David J Grainger, a Royal Society Fellow at the University of Cambridge, has identified a family of peptides and small molecules that exhibit the ability to inhibit migration of inflammatory cells. While the majority of reported chemokine inhibitors are specific for one or a selected group of chemokines, the compounds identified by Dr Grainger exhibit broad chemokine inhibitory activity. These compounds have demonstrated efficacy in a variety of animal models, including those for atherosclerosis, asthma, stroke, endotoxaemia and dermal inflammation.

Under the terms of the agreement negotiated by the University's Technology Transfer Office, Beaufour Ipsen will fund research in Dr Grainger's laboratory, located in the Department of Medicine, Clinical School of Medicine at the University of Cambridge, and make additional payments related to commercialisation of products resulting from Dr Grainger's research.

The University of Cambridge will provide Beaufour Ipsen with exclusive worldwide rights to develop and market the chemokine inhibitory compounds discovered by Dr Grainger. Beaufour Ipsen will manage all phases of product development, including clinical trials and regulatory submissions. Further details of the agreement were not disclosed by either party.

"We are delighted to be working with Dr Grainger to develop his chemokine inhibitory compounds, which will further expand Beaufour Ipsen's strong commitment to the development of peptide-based pharmaceuticals," said Dr Jacques-Pierre Moreau, Beaufour Ipsen Group Vice President Research and Development.

"Dr Grainger is a remarkable young investigator, and his chemokine inhibitory compounds show great promise in the treatment of chronic inflammatory diseases, as evidenced by Dr Grainger's numerous publications in peer-reviewed journals. We are particularly enthusiastic about the prospect of employing these compounds in the area of pulmonary fibrosis, and are involved in animal model studies of pulmonary fibrotic syndromes."

"This agreement illustrates the University's commitment to the formation of commercial partnerships which translate our laboratory discoveries into drugs capable of treating previously incurable conditions," said David Secher, Director of Research Services at the University of Cambridge.


Notes for editors

Chemokines are small proteins that regulate the immune system, particularly chemotaxis (cell migration due to a chemical gradient). To date, four families of chemokines have been identified, consisting of over 50 proteins that bind to one or more of the 13 known chemokine receptors. Recent studies have demonstrated a role for chemokines in the pathogenesis of several inflammation-associated diseases, including asthma and atherosclerosis.

The Department of Medicine, University of Cambridge, comprises some 12 divisions: from anaesthesia and endocrinology to rheumatology. All divisions are involved in research related to human disease, with the broad aim of understanding disease processes at the molecular and physiological level and applying this knowledge to clinical management.

The Technology Transfer Office (TTO) facilitates the commercial development of University intellectual property — and that arising from projects undertaken within the Cambridge-MIT Institute. Specialist technology transfer staff manage all aspects of patents, copyright and contractual arrangements. Income from patents and software exceeds £1 million a year and is growing. The TTO licenses patents and other intellectual property to existing companies, both large and small, as well as to spinouts formed to exploit University and CMI technology. Working together with venture capital funds, the TTO forms around five new companies each year. The University holds equity in over thirty such companies (see www.rsd.cam.ac.uk/tto).

Present in over 80 countries with a total staff of 3440, the Beaufour Ipsen Group had a turnover of more than €700 million in 2001, 58% of which was outside France. The Company specialises in endocrinology, oncology, neurology, haematology, cardiology and gastroenterology and has a portfolio of 30 products which are either peptides, derived from biotechnology, or based on natural sources. Approximately 16.5% of Beaufour Ipsen’s turnover is reinvested in research and development (see www.beaufour-ipsen.com).

Research is focused on four major areas (biologics, peptides, small molecule therapeutics and drug delivery systems) and is carried out from three research centres (Boston, Barcelona, Paris) by an international network of around 500 scientific staff. They are involved in discovering innovative therapeutic responses for the most refractory diseases and to in creating original molecules. Beaufour Ipsen currently has a pipeline of 16 projects in development. The Group has also set up research partnerships with prestigious universities in the USA and Europe, mainly in France and in the United Kingdom.

Except for the historical information presented, certain matters discussed in this press release relating to the development of our products and the results of our collaboration with Beaufour Ipsen are forward-looking statements. Forward-looking statements are based on the opinions and estimates of management at the time the statements are made. They are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release.


Source: Ipsen

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Beaufour Ipsen markets a new injection formulation of somatuline in the UK, France and Portugal

The Beaufour Ipsen Group has obtained authorisation to market a new sustained-release injection formulation of lanreotide, Somatuline Autogel, in the UK, France and Portugal.

Somatuline Autogel is used to control growth hormone (GH) levels in people with acromegaly and also to provide symptomatic relief for patients with neuroendocrine tumours. Clinical studies have shown that Somatuline Autogel provides sustained drug release for at least 28 days.

 

Source: Ipsen

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Corixa and Beaufour Ipsen collaborate to develop and commercialize corixa’s anergix.mg™ technology for the treatment of myasthenia gravis

Seattle and Paris, Jan. 15, 2002 — Corixa Corporation (Nasdaq: CRXA), a developer of immunotherapeutics, and Beaufour Ipsen Group a European based global pharmaceutical company , today announced a license, development and commercialization agreement for Corixa’s AnergiX.MGTM technology for the treatment of myasthenia gravis, a chronic autoimmune neuromuscular disease that causes varying degrees of weakness of the skeletal muscles of the body.

Under the terms of the agreement, Corixa will provide Beaufour Ipsen with exclusive worldwide rights to develop and market its AnergiX.MG technology for the treatment of myasthenia gravis. Beaufour Ipsen will manage product development, including clinical trials and regulatory submissions. Beaufour Ipsen will pay Corixa an up-front license fee, guaranteed research support, success-based milestone payments and royalties in the event of Beaufour Ipsen product sales. The collaboration will be overseen by a joint steering committee made up of representatives from both companies. Further details of the agreement were not disclosed by either party.

"Our agreement with Beaufour Ipsen demonstrates the continued value of the AnergiX technology originally obtained in the Anergen acquisition and further extends the therapy potential of Corixa technology," stated Steven Gillis, Ph.D., chairman and chief executive officer of Corixa. "We hope that our collaboration with Beaufour Ipsen will provide a much needed treatment for those suffering from this debilitating neuromuscular disorder."

"We are excited to be working with Corixa to develop the AnergiX.MG technology, which will further expand our dedication to the treatment of neuromuscular diseases" said Jacques-Pierre Moreau, Beaufour Ipsen group Vice President Research & Development. "We share in Corixa’s commitment to discovering and developing innovative technologies and look forward to the possibility of developing a novel treatment for myasthenia gravis patients."


About Myasthenia Gravis

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction — the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. Acetylcholine travels through the neuromuscular junction and binds to acetylcholine receptors that are activated and generate a muscle contraction. In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction that prevents the muscle contraction from occurring.

About Corixa

Corixa is a developer of immunotherapeutics with a commitment to treating and preventing autoimmune diseases, cancer and infectious diseases by understanding and directing the immune system. Corixa is focused on immunotherapeutic products and has a broad technology platform enabling both fully integrated vaccine design and the use of its separate, proprietary product components on a stand-alone basis. Corixa currently has 16 programs in clinical development and 22 programs in preclinical development, including its most advanced product candidate, Bexxar®, a monoclonal antibody conjugated to a radioisotope.

The company partners with numerous developers and marketers of pharmaceuticals, targeting products that are Powered by Corixa^TM technology with the goal of making its potential products available to patients around the world. Corixa was founded in 1994 and is headquartered in Seattle, Washington, with additional operations in Hamilton, Montana and South San Francisco, California. For more information, please visit Corixa's Website at www.corixa.com or call the company's investor relations information line at 1.877.4CORIXA or 877/426-7492.

About Beaufour Ipsen

Beaufour Ipsen is an independent European ethical pharmaceutical company which, aside from a traditional line of natural products (Gingko Biloba extracts & clays), has successfully developed and commercialized a range of specialist and biotech derived pharmaceuticals. Beaufour Ipsen is a leader in the development and production of controlled release formulation for therapeutic peptides used in the treatment of hormone responsive illnesses. Beaufour Ipsen market Dysport a brand of Botulinum toxin prescribed for the treatment of motor disorders & muscle spasticity. The company has sales in 80 countries.

Forward Looking Statements

Except for the historical information presented, certain matters discussed in this press release relating to the development of our products and the results of our collaboration with Beaufour Ipsen are forward-looking statements. Forward-looking statements are based on the opinions and estimates of management at the time the statements are made. They are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Factors that could affect Corixa's actual results include, but are not limited to the failure of the AnergiX.MG program to result in a safe or efficacious product for treating myasthenia gravis, the failure of Beaufour Ipsen to devote sufficient resources to the development and commercialization of AnegiX.MG and the other "Factors Affecting Our Operating Results, Our Business and Our Stock Price," described in Corixa’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2001, copies of which are available from Corixa’s investor relations department. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release.


Source: Ipsen

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Jean-Luc Belingard is appointed Chief Executive Officer of Beaufour Ipsen

Paris/London, December 3, 2001 — Jean Luc Belingard has been appointed Chief Executive Officer of Beaufour Ipsen, the fifth largest French pharmaceutical company, by the Board of Directors, effective January 2, 2002, hence succeeding Stéphane François. In this capacity, he will drive Beaufour Ipsen towards new challenges. In particular, Jean-Luc Belingard will implement a strategy based on alliances and co-operations with other pharmaceutical and biotechnology companies, leading to an initial public offering towards 2003.

Given Jean-Luc Belingard's wide ranging experience and expertise, the Board of Directors of Beaufour Ipsen expresses full confidence that he can deliver on his ambitious growth plans for the company, whilst maintaining its identity and core values. Jean-Luc Belingard's track record will confer Beaufour Ipsen an ever stronger dynamism in the years to come.

Jean-Luc Belingard, 53, a graduate from HEC, the premier French business school, who holds an MBA from Cornell University. He has spent the past 27 years in the pharmaceutical industry, successively with Merck & Co (1974-81), Roche (1981-99) and more recently with bioMérieux-Pierre Fabre, the third largest French pharmaceutical company.

At Roche, Jean-Luc Belingard was the youngest management board chairman within the group, at the helm of the French affiliate (1983-90), and the youngest group executive committee member (1990-99) heading the diagnostics division which was made into the world's leading diagnostics company during his tenure, notably through the acquisition of the PCR technology from Cetus Corp in 1991 and the acquisition and successful integration of Boehringer Mannheim in 1997. In addition, from his time at Roche, Jean-Luc Belingard has been elected to, and still sits on the Boards of Directors of Celera Genomics (US) and Laboratory Corporation of America (US), as well as that of French biotechnology company Exonhit Therapeutics. Jean-Luc Belingard joined Pierre Fabre in 1999 as Vice-Chairman and CEO, and following the merger with bioMérieux in 2000, he became Chief Executive Officer of the newly-created bioMérieux-Pierre Fabre.


Beaufour Ipsen: Facts & Figures 2000

Sales (Euros): 653 million Euros including 352 million Euros outside of France

Number of employees: 3,440 including 1,770 outside of France

Worldwide direct presence in over 30 countries

4 Research and Development Centers: Paris, Boston, Barcelona, London

12 manufacturing sites: France, Europe, China

5 therapeutic categories:
— Endocrinology/Oncology
— Neurosciences
— Haematology
— Cardiovascular
— Gastro-intestintal tract

Worldwide leadership in extraction technologies:
— clay-based products
— Ginkgo biloba

World-class drug delivery expetise in peptides

R&D focus on 5 major areas:
— Endocrinology
— Oncology
— Metabolic diseases
— Neurosciences
— Haematology


Source: Ipsen

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Transgene presents encouraging Phase II cancer vaccine data at 22nd Annual San Antonio Breast Cancer Symposium

San Antonio, Texas, December 10, 1999 — At the 22nd Annual Breast Cancer Symposium, TRANSGENE (NASDAQ:TRGNY; Nouveau Marché: TRANSGENE) today presented the results from a Phase II clinical trial using the Company's cancer vaccine, VV-MUC1-IL2, in women with metastatic breast cancer. These data, combined with pre-clinical data and results from another clinical trial in men with prostate cancer, demonstrate a favorable safety profile and anti-tumor activity in selected patients with advanced cancer treated with VV-MUC1-IL2. VV-MUC1-IL2 is a cancer vaccine in which the genes for the tumor antigen MUC1 and the immune stimulant IL2 have been inserted into a vaccinia virus. Treatment with the vaccine is intended to induce a reaction by the body's immune system against the MUC1 tumor antigen. MUC1 has been detected in tumor tissues of a majority of patients with breast cancer, prostate cancer, as well as several other types of tumors.

The Phase II study presented by Dr. David Miles of the Imperial Cancer Research Fund at Guy's Hospital, London, was conducted in 31 patients at sites in the United Kingdom, France, Belgium, and Israel. Treatment with the vaccine resulted in objective tumor regression and a partial remission in two patients, both of whom had advanced metastatic disease that did not respond to either chemotherapy or hormonal therapy.

"These results are notable in that we saw systemic anti-tumor activity," said Dr, Miles. "The ability to induce a partial remission in patients with visceral metastases who have progressive disease after intensive chemotherapy is important evidence of the potential role of therapeutic vaccines in the treatment of cancer."

"The use of vaccines for advanced cancer could represent an important new avenue in cancer treatment," said Michael Ross, Vice President of Medical and Regulatory Affairs of TRANSGENE. "The MUC1 tumor antigen provides an avenue to attack breast cancer, prostate cancer as well as other types of cancers. TRANSGENE's proprietary vaccinia virus platform has enabled us to move this product forward very rapidly."

The MUC1 product is part of TRANSGENE's broader effort to develop technologies that will enhance the human immune system's ability to reject cancer cells. Utilizing the same vaccinia virus vector, TRANSGENE has a second cancer vaccine in clinical trials based on the MVA strain carrying the genes for antigens from the human papilloma virus (HPV) type 16, which is responsible for more than 50% of cases of cervical cancer. TRANSGENE's second major focus in oncology is the general enhancement of the body's immune response to cancer, with currently three products in clinical trials: Adenovirus-IL2, Vero-IL2, and Adenovirus-IFN-γ.

"We are extremely encouraged by TRANSGENE's clinical progress in each of our anti-cancer initiatives," said Bernard Gilly, President and Chief Executive Officer of TRANSGENE. "This continued success and our commitment to an extensive and diverse vector platform confirms our dedication to the field of gene therapy."


TRANSGENE, based in Strasbourg, France, with US offices near Boston, Massachusetts, is a leading integrated gene therapy company dedicated to the discovery and development of gene delivery technologies and gene therapy products for the treatment of acquired or inherited diseases for which there is no cure or adequate therapy at present. The Company's proprietary technology platform consist of multiple vector families with a special emphasis on vaccinia virus, adenovirus and synthetic vectors. TRANSGENE has entered in two significant partnerships with Schering-Plough and Human Genome Sciences.

Source: Transgène

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