Years of Research & Development

Annual Report 2007

Years of Research & Development

Since 1983, the focus of the Octapharma Group has been the continuous investment in research and development of human proteins for therapeutic use.

Content 4 Overview by the Chairman of the Group 6 The Management Board 8 Facts and Figures 10 Octapharma Milestones 13 25 Years of Research & Development 13 The Beginning 15 The Launch of octavi 17 Dr Schwinn joined Octapharma 19 Development of octaplas 19 The first R&D laboratories 21 Virus laboratories established 21 More products launched 23 Development of octagam 23 Investments in recombinant technology 25 New generation in R&D 25 Development of von Willebrand concentrate 27 New line of ICU products 29 Future generation of products 29 New scientific platform 29 R&D investments of EUR 42 million in 2008 31 Finance 31 - Key Figures of the Octapharma Group 33 - Income Statement of the Octapharma Group 34 - Balance Sheet of the Octapharma Group 36 - Cash Flow Statement of the Octapharma Group 37 The Auditor s Statement 39 Octapharma Contact Details

Company Snapshot Largest privately-owned plasma products company in the world 25 years focus on plasma products Manufacturing facilities in 5 countries Sales in more than 80 countries Sales of Euro 752 million in 2007 20% average annual growth since 1995

Foreword by Wolfgang Marguerre What better way to celebrate the 25th birthday of Octapharma than to look at the record results of 2007? Our sales of EUR 752 million have been 37% higher than the previous year and we have been able to successfully sell all our major products to the maximum, thus utilizing the expensive raw material human plasma to the optimal extent and producing at full capacity in our plants. We have also been able to maintain our company s debt-free status and in addition accumulate cash for future investments, even after significant investments in our factories and very substantial amounts in R&D and marketing. We have of course been helped by positive developments in the major global markets. However, we have even strengthened our position in established markets such as Europe and the United States. When sitting in my small home office in Paris in 1983, deciding on founding Octapharma, it was hard to imagine that our company would 25 years later be number three in plasma fractionation worldwide, employing almost 2000 people. The vision was clearly to establish something new and dynamic and it is with pride that I look back at those 25 years of continuous investment in research and development of plasma derivative products. These life-saving therapies have made a big difference to many patients lives. I am convinced that our 130-strong Research & Development team, together with their colleagues in the various divisions of the Octapharma Group, will continue to make a difference. I would like to especially thank everyone for their ability to stay entrepreneurial and innovative in this very competitive world. It is also with great pleasure that I see Octapharma being continuously valued as a serious partner by both authorities and patient organizations and I hope that this collaborative effort will continue for many years to come to the benefit of the medical community. Of the significant product developments coming out of Octapharma s research, I would in particular like to mention the fact that Octapharma is focused on developing human proteins, whether coming out of human plasma or out of human cell lines in the form of recombinant proteins. These proteins have been developed over millions of years of evolution and nature has done a very thorough job of optimizing the efficiency and reducing side effects. Octapharma is therefore continuously focused on bringing these proteins to the patients in the form of life-saving therapeutics in a way that respects the integrity of the proteins, but at the same time ensures that any potential virus transmission is avoided. This has meant continuous investment in optimizing purification and virus inactivation 4

methods, ensuring that the therapeutic value of the proteins stays intact. The nature of the plasma derivative business is such that due to the expensive raw material (human plasma), the financial gross margin can never come within the range of the classical pharmaceutical industry. However, due to the optimal utilization of the raw material, this year, by the selling of all important proteins contained in the plasma, we have been able to lift the group s results to a record even after substantial investments. Octapharma is a privately held company (since recently by my three children as well as by myself). I can assure you that the Octapharma Group will continue to retain the majority of its revenue. The investments required during the next four years to secure capacities, quality and new products are in excess of EUR 600 million Octapharma intends to take this challenge without the need for foreign-controlled financing instruments. 2008 will be a very exciting year to this effect. Octapharma has already started its partial vertical integration by owning plasma centers in Germany and the US, and it is our goal to be able to source 50% of the plasma needed from our own plasma centers by 2010. Therefore further investments will have to take place in this field of business over the next couple of years. The reason for the change in strategy is that with the rapid growth in demand for our products, it is unfortunately not possible for our suppliers (whether not-for-profit or for-profit organizations) to satisfy our plasma requirements. 2008 will also be the year in which the plasma R&D division in Vienna will obtain its own newly built R&D building. A project has been approved for a facility with 3000 m 2 of research space. The plasma-fractionation industry may need to further consolidate if opportunities occur, we are ready to react. Finally, I would like to take the opportunity to thank all our partners for the good co-operation during the last year and all employees of Octapharma for the interesting and fruitful teamwork. Wolfgang Marguerre Chairman of the Octapharma Group 5

The Octapharma Management Board Nicholas Jacobson Chief Operating Officer Octapharma Group Kim Björnstrup Deputy Chairman Octapharma Group Paulo Castro Member of the Board Frederic Marguerre Member of the Board Tobias Marguerre Managing Director Octapharma Nordic AB Wolfgang Marguerre Chairman Octapharma Group 6

The Management Board of the Octapharma Group is a diverse mix of Danish, British, Portuguese and German nationals. The fact that the Board is not dominated by one nationality ensures that management decisions are taken with the widest possible cultural representation. Reinhard Rettinghaus General Manager Octapharma Germany Karl Erik Clausen Chief Financial Officer Octapharma Group 7

Facts and Figures Founded in 1983 Mission For the safe and optimal use of human proteins Employees 1,827 Turnover EUR 752 million Headquarters Octapharma AG, Lachen, Switzerland Production - Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria - Octapharma SA, Lingolsheim, France - Octapharma AB, Stockholm, Sweden - Octapharma S.A. de C.V., Mexico City, Mexico - Octapharma Produktionsgesellschaft Deutschland mbh, Springe, Germany Research & Development - Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria - Frankfurter Innovationszentrum, Frankfurt, Germany - Charité Universitätsmedizin Berlin, Germany - Octagene GmbH, Munich, Germany (contract research) - Octapharma AB, Stockholm, Sweden Corporate Medical, Regulatory - Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria - Octapharma Vertrieb von Plasmaderivaten GmbH, Langenfeld, Germany International Corporate Marketing Octapharma AG, Lachen, Switzerland Subsidiaries & Representative Offices 28 Markets Europe, Asia, Middle East, USA, South America, Canada, Mexico, Australia, New Zealand Brands (registered trademarks) octaplas, octagam, octanate, octanyne, octaplex, octavi SD Optimum, octalbin, uniplas, rhesonativ, aunativ, gammonativ, atenativ, gammanorm, nanotiv, octonativ, octanine F, wilate 8

Innovations One of the world s first factor VIII concentrates AHF concentrate (KABI 1965 through acquisition) The first albumin-free genetically engineered factor VIII (development started by KABI in the 1980s through acquisition) For the safe and optimal use of human proteins First company to commercially implement solvent detergent (SD) technology for virus inactivation (1986) First SD virus-inactivated, standardised plasma for transfusion (1991) First liquid, ready-to-use intravenous immunoglobulin with a two year shelf-life at room temperature (1994) First virus-inactivated universally applicable transfusion plasma (2004) First double virus-inactivated von Willebrand factor concentrate product (2005) 9

Milestones Joint development contract for octaplas with New York Blood Center - Introduction of octaplas in Germany - International launch of octaplas First sale of octavi The first self-sufficiency contract is signed with Norway Introduction of octavi SD Plus (octate ) 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 Octapharma was founded by Wolfgang Marguerre - Acquisition of the Vienna production facility - International launch of octanyne First commercial SD virus-inactivated, high-purity factor VIII concentrate Introduction of octagam in Norway, Portugal and Israel 10

Registration of octagam in Germany Purchase of former Kabi Group in Sweden - Acquisition of five donor centers in Germany - US launch of albumin (human) Acquisition of Strasbourg facility (Aventis Behring) - European launch of octaplex - European launch of gammanorm - US launch of octagam - Australian launch of octagam 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Double virus-inactivated factor IX octanine F (SD & filtration) Opening of the first Octapharma donor center in Germany - Registration of octanate in Germany - International launch of octanate and octanine F - Long-term lease of German Red Cross plant in Springe, Germany (NSTOB) - German launch of wilate - Introduction of first virus-inactivated universally applicable transfusion plasma (uniplas ) - Acquisition of Mexican facility (Probifasa) 11

Sampling of lyophilized protein under controlled air moisture conditions in a glove box. Kim Björnstrup We continuously focus on human proteins since we believe that they are the optimal fit for the human body. Dr Jürgen Römisch We are always looking for new plasma proteins to extend therapeutic indications and to improve treatments. Our exciting new wound-healing project contributes to these objectives.

25 Years of Research & Development From the very beginning the success of the Octapharma Group has been based on the research and development of its own products. Today Octapharma employs more than 130 people dedicated to the research and development of plasma derivatives, and proteins which are produced in cell lines using fermentor technology. What differentiates Octapharma from the rest of the plasma fractionation industry is that Octapharma s research is based purely on the development of human proteins; not only are our plasma products of human origin, but so are our recombinant products. The recombinant products are produced on a human cell line as opposed to the traditional concept in recombinant technology (which uses murine cell lines). The focus on human proteins is deliberate since Octapharma firmly believes that proteins of human origin potentially have much better tolerability than proteins from cell lines of other mammals, hence our mission statement: for the safe and optimal use of human proteins. The Beginning The company was founded in 1983 by Mr Wolfgang Marguerre together with a colleague from the industry who however left the company in 1995. Previously, Mr Marguerre had been working in a large company in the plasma fractionation industry and was driven by an ambition to show that things could be done differently. The inspiration was an intimate knowledge of the haemophilia market and an understanding of the problems facing the haemophilia population (chiefly the availability of sufficient quantities of safe products). At this time, many people with haemophilia were still being treated with crude plasma fractions such as cryoprecipitate. Cryoprecipitate is the precipitate, rich in factor VIII, which forms when frozen human plasma is thawed. The major problem with such treatment was that the precipitate contained many other proteins which caused side effects. Secondly, cryoprecipitate was not virus-inactivated and therefore carried a high risk of transmitting viruses from the donors to the recipients. Various brands of the coagulation proteins factor VIII and factor IX were already on the market. However, the availability was not sufficient and the purity and the safety against viruses was not always guaranteed since several preparations did not even contain dedicated virus inactivation steps. At that time, the major concern was the transmission of hepatitis B, the most serious strain of liver disease, which can lead to liver cirrhosis, liver cancer and ultimately death. 13

Microscopy of cell cultures. Dr Bernard Horowitz In 1983, we had just made the initial trial runs of the solvent detergent (SD) technology and the collaboration with Octapharma presented an excellent opportunity to utilize our technology for the good of haemophilia patients. Dr Horst Schwinn When I saw Octapharma s ad in my local newspaper, I was rather amused. Then I gave it a second thought and told my wife that I had to talk to those people.

During his contacts with various plasma suppliers, Wolfgang Marguerre met with Red Cross organizations all over the world. He observed that many of the Red Cross organizations had fractionation plants which were primarily capable of producing albumin, had spare capacity but did not have the technology to produce purified and safe factor VIII preparations. For an entrepreneurial person like Mr Marguerre it was an opportunity to bring new and innovative technology into the Red Cross organizations and utilize their excess production capacity to produce factor VIII and other human proteins, not only from the plasma being collected by the Red Cross organizations, but also by other organizations such as the Statens Helse Service in Norway. The idea to create a new high-purity, virus-inactivated factor VIII preparation was at an advanced stage, but since Octapharma had no research laboratories and no employees, an inventive concept had to be developed. The initial step was to hire a bioscientist who had experience in the field of plasma protein purification and place him in the research laboratories of chosen Red Cross organizations in Europe, one of them being DRK Hagen in Germany. The idea was to make a pure factor VIII concentrate, virus-inactivated with a safe and effective method. The virus inactivation method chosen was the new solvent detergent (SD) technology developed by Drs Horowitz and Prince at the New York Blood Center. The Launch of octavi Although originally developed to prevent the transmission of hepatitis B and non-a, non-b hepatitis virus, the beauty of the SD technology is that it attacks the lipid coat of all lipid enveloped viruses, including HIV, hepatitis C and West Nile virus, but does not change the biological properties of the proteins. It took Octapharma s first research scientist, Mr Andy Smith, one and a half years to develop the first Octapharma factor VIII concentrate, Octa V.I., and combine it with the SD technology. When the HIV crisis hit the haemophilia world in 1984/85, Octapharma was ready with a solution. The SD technology in Octapharma s first purified factor VIII concentrate, introduced to prevent hepatitis B and non-a, non-b hepatitis virus transmission, also protected patients against HIV. Thus, the SD technology became the backbone of virus inactivation in all Octapharma s pharmaceutical products from the very start. Octapharma prides itself on never having been involved in any product liability case with its customers. 15

Filtration of a protein solution upon defined flow conditions. Monika Stadler When I started to work for Octapharma in 1990, their R&D laboratories were non-existent, but the reputation of Dr Schwinn was more than convincing. Dr Bernhard Kerner Prior to Octapharma acquiring Schwab, I had already had several contacts with Octapharma and I was convinced that their innovative approach would bring new life into our then state-owned company.

Due to its existing collaboration with the German Red Cross and other non-profit organizations, many partners immediately decided to implement the Octa V.I. technology in their facilities and agreements were made so that royalties would be paid to Octapharma. In addition, those organizations would rent to Octapharma their excess manufacturing capacity so that Octapharma could produce products for its self-sufficiency partners, i.e. organizations that had plasma available for fractionation but did not own their own manufacturing facilities. One of these collaborations is the selfsufficiency project with Statens Helse Service in Norway, which has been running since 1988. Octapharma first based the collaboration on production of plasma derivative products out of Norwegian plasma at CRTS Lille in France. Later, the production continued at Octapharma s own factory in Vienna and since 2004 at Octapharma Sweden AB. Additionally, all the plasma utilized for transfusion in Norway has been processed in Octapharma s Vienna plant since 1991 to ensure that the Norwegian transfusion plasma is virus-inactivated. See below for more details about this product (octaplas ). Octapharma s first factor VIII concentrate Octa V.I., whilst a major breakthrough, was still not as pure (free from other proteins) as could be desired. The next research project was therefore to increase the purity. The new generation of purified factor VIII (octavi ) went from a purity (specific activity) of 5 IU/mg to 100 IU/mg. This product (octavi ) included a novel method of purification and is still used in Octapharma s modern factor VIII concentrate octanate, which was further developed in 1995 to contain an additional inactivation step (dry heat treatment against non-lipid coated viruses such as hepatitis A and Parvovirus B19). Dr Schwinn joined Octapharma As the company rapidly took off, it was evident that an even bigger effort had to be made in developing additional pharmaceuticals out of the raw material human plasma in order to secure safe and optimal use. After having generated a strong cash flow based on contract manufacturing agreements and licensing income, the company decided to look for a person with extensive experience in protein purification. At that time, Dr Horst Schwinn, working at the reputable Behringwerke in Marburg, came to Octapharma s attention. It was, however, evident that it would be hard to motivate a person such as Dr Schwinn to join a small company which was just in its starting stage and a way to capture his attention had to be found. The solution was to insert an advert in a small local journal where Dr Schwinn was living. The advert was tailor-made for Dr Schwinn and the story goes that when Dr Schwinn saw this advert he thought that such a daring initiative had to be investigated. Octapharma s scheme worked and Dr Schwinn joined the company in 1988. 17

Cell clone cultivation in shaker flasks. Dr Lothar Biesert Georg Speyer Haus has a long common history with the Paul Ehrlich Institute, the official organization in Germany which evaluates the safety of plasmaderived products. What would be more logical than to place your GLP certified virus validation laboratories in this institution? Dr Thomas Gärtner The development of Octapharma s PCR pool tests over a short time period was an exciting challenge.

Development of octaplas When Dr Schwinn joined Octapharma, research was still being conducted at the facilities of DRK Hagen. In 1989, Octapharma again had an original idea which was to utilize the solvent detergent (SD) technology for virus inactivation of transfusion plasma (later octaplas ). Until then (and largely today), most transfusion plasma was tested for viruses but was not virus-inactivated. This means that undetected viruses can still be transfused to healthy patients by fresh frozen plasma (FFP). The research project for the introduction of the SD technology for the virus inactivation of transfusion plasma was not an easy task since it had to be ensured that all the proteins in plasma (which number several hundred) remain intact after the addition and removal of solvent detergent (SD). A novel method to extract the solvent detergent chemicals after treatment had to be developed which would not cause excessive damage to the proteins. Octapharma again went to the New York Blood Center (the owner of the patents on the SD technology), obtained an exclusive license for Europe and started to develop the product under Dr Schwinn s leadership. As part of this agreement, Octapharma financed the research of Dr Bonomo at the New York Blood Center who developed a method which could extract the detergent after virus inactivation of the plasma. The actual industrial development was made by Dr Schwinn at DRK Hagen in Germany and as a consequence, DRK Hagen acquired a license for solvent detergent (SD) treated plasma from Octapharma in 1989 and became a very important producer of this product in Germany. By then, Octapharma had grown to a size where investments in its own production and research facilities were becoming necessary. The next step was to find a plasma fractionation plant somewhere in Europe. At that time, the Austrian company, Chemie Linz, had a small fractionation plant ( Schwab ) near Vienna, Austria, for sale. The plant had capacity to fractionate 200 000 litres per year with a staff of 90 people. The first R&D laboratories When moving into the Schwab premises in Oberlaa, Vienna, in 1990, Octapharma could finally claim its own research laboratories for the first time. They consisted of approximately 50 m 2 laboratory space. The initial staff of the R&D department consisted of five people. The first assignment of the new research department was to implement the octavi technology into the plant and build a separate plant for the solvent detergent (SD) treated plasma, octaplas. This would enable Octapharma to finally produce its main products (octavi, albumin and octaplas ) in its own facilities. 19

Cell culture media preparation under sterile conditions. Iréne Agerkvist The assignment to commercially develop Octapharma s first recombinant product for the market is a challenge that the Swedish team willingly undertakes. Patrick Selosse octagam, with its excellent tolerability, is developed under the credo: if you respect the proteins, then the proteins will respect you.

Virus laboratories established Research and development in the plasma industry is not only focused on purification but also, as mentioned, on rendering the proteins safe and virus-free. The focus on this issue continued through the 1990s and Octapharma decided to rent laboratories at the famous Georg Speyer Haus in Germany in 1992 in order to create its own facility for validation and documentation of the virus inactivation methods utilized in its existing products and new developments. The first employee at Octapharma s laboratories at Georg Speyer Haus was Dr Lothar Biesert. More products launched The staff of Dr Biesert rapidly expanded and in 2004 the laboratories moved to FIZ in Frankfurt and now occupy a highly modern virus validation laboratory consisting of 250 m 2. The laboratory is GLP approved and conducts validation studies for all Octapharma s existing and future products in development. Until the mid-1990s, the most important proteins being produced from plasma were factor VIII and factor IX concentrates and Albumin. Octapharma, based on its own research and development, launched its high-purity and virus-inactivated concentrates, octanyne and octaplex, in 1990. Later, both products were re-launched with the addition of nanofiltration as an extra safety measure against non-lipid coated viruses such as hepatitis A and Parvovirus B19. As previously mentioned, a very important aspect in developing plasma proteins for human use is to ensure the integrity of the molecules. In 1995, it was therefore decided, in collaboration with the Freie Universität Berlin, today called Charité Hochschulmedizin Berlin, to create a molecular biochemistry laboratory under the leadership of Dr Christoph Kannicht. Dr Kannicht s biochemical unit today consists of a staff of five people who are in possession of the most modern research equipment in order to investigate the integrity and the mechanisms of the proteins developed, including recombinant proteins. The technologies utilized at this location include: dynamic light scattering (DLS) Fourier transform infrared spectroscopy (FTIR) two-dimensional difference gel electrophoresis (2D DIGE) matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI TOF MS) Biacore surface plasmon resonance measurement flow-based measurement of VWF-mediated platelet adhesion to collagen (flow-chamber system) fluorescence microscopy 21

Protein purification by chromatography and automated collection of fractions. Kristina Martinelle Process development for production of recombinant proteins is a new research field at Octapharma. Stefan Winge It has been exciting to utilize the purification experience related to plasma products on our novel recombinant factor VIII.

Development of octagam At the beginning of the 1990s, Octapharma began to develop an intravenous gammaglobulin (IVIG). This kind of product was already known to the market as the preferred treatment of serious diseases of the immune system such as PID (primary immune deficiency) and ITP. Until then, most IVIG products had to be refrigerated and were only available in lyophilized (powder) form and needed to be reconstituted before use. The goal of the research and development project was therefore to develop a virus-inactivated IVIG, which was both stable in liquid form and at room temperature so that the physician could use the product immediately without further preparation. A research team was established in Vienna in collaboration with Mr Patrick Selosse who had by then joined Octapharma as part of the technology transfer team responsible for transferring technology to Octapharma s licensees around the world. As a result, in 1993, Octapharma s leading product, octagam, was launched. Due to its unique and advanced purity, tolerability, safety and convenience features, this product is still state-of-the-art and considered one of the best in its class. Investments in recombinant technology Thanks to having more resources available to invest, Octapharma decided to start research into gene therapy for the treatment of Haemophilia A. In 1999 it was decided that the company should fully concentrate on the development of a recombinant factor VIII concentrate. Fundamental to this was the belief that the recombinant protein should be based on a human cell line to stay loyal to Octapharma s idea of developing human proteins. The research was conducted through the company Octagene in Munich, which today is managed by Mrs Carola Schröder with a staff of 25 people. The collaboration was a complete green field, meaning that everything had to be developed from scratch. The initial project (factor VIII) was a tremendous challenge. First, the ideal cell for producing the protein had to be identified and a completely new way to place the DNA strand responsible for producing the protein in the cell had to be constructed. 23

Sample dilution for protein analysis. Tor-Einar Svae My long-term experience from both the scientific and commercial divisions of the company is very helpful in developing market access for our products. Dr Christoph Kannicht The basis of success for any protein-based company is the ability to understand the influence of its production and virus inactivation methods on the proteins.

The cell construct was ready for the industrial development phase in 2003. In 2002 Octapharma had acquired a part of the ex-pharmacia Group in Sweden, the old Kabi. In 2003, the commercial development of the project was moved from Munich to Sweden where researchers with knowledge in this field were located due to previous industrial projects of this nature. In 2003, more than 800 m 2 were set up for the project and an initial staff of 9 people were employed to upscaling the cell construct to industrial production scale. Today, the staff consists of more than 40 people and occupies more than 700 m 2 of research laboratories and 700 m 2 for offices etc. In addition, a pilot plant has been set up to provide products for the clinical trials to be started in 2008. A full commercial plant is in a conceptual phase and construction will be commenced in 2008. New generation in R&D When Dr Schwinn retired in 2000, Octapharma s research and development was taken over by Professor Djuro Josic who was followed in 2004 by Mr Tor-Einar Svae. Mr Svae had previously been in charge of Octapharma Norway s self-sufficiency project and managed numerous other positions in the company. Tor-Einar Svae was in charge of plasma R&D until 2007, when he was appointed Director of International Market Access. Development of von Willebrand concentrate During his employment at Octapharma, Dr Schwinn, along with his Vienna-based research team, was also the initiator of a novel factor VIII and von Willebrand concentrate. The goal was to create a high-purity von Willebrand / factor VIII preparation which would have a 1:1 ratio of the two proteins. This would present the ideal treatment concept for von Willebrand disease, a coagulation disorder which affects one in a hundred people. The product utilized a novel large-scale size exclusion technique for purification and also included two very robust virus inactivation methods, namely the solvent detergent (SD) technology and a novel concept of perma heat, a treatment of the lyophilized preparation for two hours at 100 C. After Dr Schwinn s retirement, the development of the product was continued under the leadership of Mr Tor-Einar Svae and later the present Director of R&D, Dr Jürgen Römisch. The product was launched in Germany in 2005 with great success and is now rapidly being launched in other European countries. The product is truly a new development in this field of therapy. 25

Optimized throughput screening of high producer cell clones. Carola Schröder The collaboration with Octapharma has been very fruitful and even enabled us to develop some unique independent technologies for the future. Dr Wolfgang Frenzel A thorough clinical development is the basis for a successful market introduction of a novel product.

In 2003, Mr Tor-Einar Svae was the main inventor of a novel product in the area of transfusion medicine, the virus-inactivated non-blood-type specific transfusion plasma (uniplas ). It is widely recognized that one of the main problems with the use of fresh frozen plasma is the risk of mismatched transfusion (mixing up blood types). Used as the backbone, the octaplas production process, a novel method, was developed and patented. This invention enabled the neutralization of the blood-type-specific antigens through a so-called optimal mix of blood types. The clinical development of the product has, however, been slow. After a very successful clinical trial in open heart surgery, the recruitment of patients in an IND-based US and Canadian trial has not been as fast as expected since the high volume indication pursued (spontaneous TTP) is a very rare disease with few patients eligible for enrolment. In 2004, the company set itself the ambitious goal of developing a new high-yield liquid IVIG with the same clinical properties as octagam but with a considerably higher yield of immunoglobulin from each litre of plasma. The development of this product was started by a group of researchers with the clear goal of improving the economics of plasma fractionation by the aforementioned yield increase exceeding 25%. The project also contained the challenge of improving the safety against both large and small non-lipid coated viruses. The result today is a product with a state-of-the-art virus inactivation profile that meets and exceeds the ambitious goal of yield improvement. New line of ICU products To complete Octapharma s portfolio of products for Intensive Care and Emergency Medicine, the development of a novel double virus-inactivated fibrinogen (to improve coagulation in major bleeding) was initiated in 2004. The major challenge has been to implement effective virus inactivation steps while still keeping a product which is convenient and easy to handle by clinicians. The product is now finally developed and is planned for IND (clinical development) in 2008. 27

Discussion of results in an analytical laboratory. Dr Andrea Buchacher Replicating the excellent profile of octagam was our goal for the new high-yield IVIG product and I believe we have succeeded. Dr Andrea Neisser-Svae The unique way, that we stabilize the wound-healing protein, is probably the secret of the efficacy that we have observed in vitro.

Future generation of products A host of other research and development projects are in the pipeline both in the area of plasma products and also human cell based recombinants. In the plasma area a 10% version of octagam is expected to be launched in 2008. A double virus-inactivated plasma product for the treatment of hard to heal wounds is in the late development phase. If the preclinical development programe currently being conducted confirms the in vitro results, it is expected that this product can go into clinical development in 2009. New scientific platform The scientific platform created at Octagene in Munich has enabled the company to offer Octapharma a range of new recombinant products based on a human cell line. The next product coming out of the collaboration is a factor IX protein for the treatment of Haemophilia B. The product went to the stage of commercial upscaling at the end of 2007 and will be transferred to the Stockholm team mid-2008. The product has, in its initial profile, shown to overcome the problems of recovery that affect the current product on the market. R&D investments of EUR 42 million in 2008 The research and development pipeline of Octagene is full and Octapharma is almost doubling its funding for new projects in 2008 by adding products such as a granulocyte colony-stimulating factor (G-CSF) and a von Willebrand factor / factor VIII with a prolonged half-life. With a research and development budget of Euro 42 million in 2008 (an increase of 78% over 2007), Octapharma is showing its commitment to continue to invest in products that will save and improve human lives. Octapharma will continue to work for the safe and optimal use of human proteins for many years to come. 29

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Key Figures of the Octapharma Group Years of Research & Development (Monetary figures in 1,000 EUR) 2007 2006 2005 2004 2003 Profit from operations 237,497 126,850 59,940 42,070 41,102 Net profit for the year 206,751 105,694 53,417 30,060 27,021 Year-end headcount 1,968 1,826 1,482 1,360 1,401 Return on average equity 45% 32% 18% 14% 14% Profit from operations per employee 130 77 42 31 29 Current ratio 404% 332% 261% 229% 229% Days of sales in receivables 106 108 109 112 102 Days of purchases in inventory 149 189 196 246 279 Cash flow from operations 209,822 85,406 80,864 35,511 4,769 Expenditures to ensure future prosperity 69,367 43,239 31,079 35,565 43,125 Research & development 23,582 19,544 15,291 12,248 14,836 Capital expenditures and investment in activities 45,785 23,695 15,788 23,317 28,289 31

Key Figures of the Octapharma Group Net sales 800,000 700,000 600,000 500,000 400,000 300,000 200,000 100,000 0 2000 2001 2002 2003 2004 2005 2006 2007 Operating income 250,000 200,000 150,000 100,000 50,000 0 2000 2001 2002 2003 2004 2005 2006 2007 Average headcount 2,000 1,800 1,600 1,400 1,200 1,000 800 600 400 200 0 2000 2001 2002 2003 2004 2005 2006 2007 32

Income Statement of the Octapharma Group Years of Research & Development (All figures in 1,000 EUR) 2007 2006 Gross sales 779,058 571,588 Sales deductions -26,978-24,643 Net sales 752,080 546,945 Cost of sales -412,616-324,286 Gross profit 339,464 222,659 Research & development -23,582-19,544 Selling & marketing -42,894-35,404 Regulatory affairs / quality audit -5,075-6,429 General & administration -32,076-32,555 Other income 3,366 2,078 Other expenses -1,706-3,955 Total operating expenses -101,967-95,809 Operating income 237,497 126,850 Non-operating income and expenses -4,172-4,873 Profit before taxes 233,325 121,977 Income tax expenses -26,574-16,283 Profit after taxes 206,751 105,694 Attributable to: Shareholders of Octapharma Nordic AB 206,751 101,842 Minority interest 0 3,852 Net profit for the year 206,751 105,694 33

Balance Sheet of the Octapharma Group (All figures in 1,000 EUR) 31.12.2007 31.12.2006 Assets Cash & cash equivalents 204,417 70,630 Trade receivables 225,276 169,865 Other receivables 1,727 2,720 Receivables from related parties 250 387 Inventory 153,650 164,582 Other current assets 16,162 13,421 Total current assets 601,482 421,605 Financial investments 6,171 4,007 Loans to related parties 500 750 Deferred tax assets 12,736 8,953 Investments in associates 2,766 0 Property, plant & equipment 135,004 114,235 Total fixed assets 157,177 127,945 Total assets 758,659 549,550 34

Years of Research & Development (All figures in 1,000 EUR) 31.12.2007 31.12.2006 Liabilities and equity Trade payables & other payables 55,591 51,885 Payables to related parties 2,072 10,298 Income tax payables 21,376 13,399 Accruals & short-term provisions 69,924 51,496 Total current liabilities 148,963 127,078 Deferred income 418 302 Provisions 49,962 42,110 Deferred tax liabilities 8,844 7,051 Total non-current liabilities 59,224 49,463 Total liabilities 208,187 176,541 Common stock 100 96 Retained earnings 556,534 376,527 Currency translation adjustment -6,162-3,614 Total shareholder s equity 550,472 373,009 Total liabilities and equity 758,659 549,550 35

Cash Flow Statement of the Octapharma Group (All figures in 1,000 EUR) 2007 2006 Net profit for the year 206,751 105,694 Depreciation on property, plant & equipment 20,056 15,399 Profit or loss on disposal of fixed assets -17 8 Impairment losses 1,159 2,499 Share of loss of associates 321 0 Changes in long-term provisions and deferred tax assets / liabilities 6,158 14,786 Cash flow before changes in working capital 234,428 138,386 (Increase) decrease of working capital -24,606-52,980 Net cash from operating activities 209,822 85,406 Investment in property, plant & equipment -42,698-21,561 Investment in business activities and other financial assets -6,335-2,134 Proceeds from sales of fixed assets and business activities 397 82 Net cash used in investing activities -48,636-23,613 Changes in loans 0-16,531 Dividends paid -26,740 0 Net cash used for financing activities -26,740-16,531 Effect of currency translation adjustments -659 220 Net change in cash & cash equivalents 133,787 45,482 Cash & cash equivalents beginning of period 70,630 25,148 Cash & cash equivalents end of period 204,417 70,630 36

The Auditor s Statement Years of Research & Development KPMG Ltd Audit Badenerstrasse 172 P.O. Box Telephone +41 44 249 31 31 CH-8004 Zurich CH-8026 Zurich Fax +41 44 249 23 19 Internet www.kpmg.ch Octapharma Nordic AB, Stockholm Summarized consolidated financial statements 2007 As independent auditors, we have audited the consolidated financial statements of Octapharma Nordic AB, Stockholm, for the year ended December 31, 2007, from which the summarized consolidated financial statements were derived, in accordance with International Standards on Auditing. In our report dated February 25, 2008 we expressed an unqualified opinion on the consolidated financial statements in accordance with the International Financial Reporting Standards (IFRS) from which the summarized consolidated financial statements were derived. In our opinion, the accompanying summarized consolidated financial statements are consistent, in all material respects, with the consolidated financial statements from which they were derived. For a better understanding of the Company's financial position and the results of its operations for the period and of the scope of our audit, the summarized consolidated financial statements should be read in conjunction with the consolidated financial statements from which the summarized consolidated financial statements were derived and our audit report thereon. KPMG Ltd Fredy Luthiger Markus Ackermann Zurich, February 25, 2008 37

Octapharma Contact Details Headquarters Octapharma AG Kim Björnstrup Karl Erik Clausen Seidenstraße 2 CH-8853 Lachen Switzerland Tel. (+41) (55) 4 51 21 21 Fax (+41) (55) 4 51 21 10 kim.bjoernstrup@octapharma.ch karl.erik.clausen@octapharma.ch Australia Octapharma Australia Pty. Ltd. Simon Sestich Jones Bay Wharf 42/26-32 Pirrama Road Pyrmont NSW 2009 Australia Tel. (+61) 2 8572 5800 Fax (+61) 2 8572 5890 simon.sestich@octapharma.ch Austria Octapharma Pharmazeutika Produktionsgesellschaft m.b.h. Nicholas Jacobson, Bernhard Kerner, Rudolf Lukschanderl Oberlaaer Straße 235 A-1100 Vienna Austria Tel. (+43) (1) 610 32 0 Fax (+43) (1) 610 32 9300 nicholas.jacobson@octapharma.com bernhard.kerner@octapharma.com rudolf.lukschanderl@octapharma.com Octapharma Handelsges.m.b.H. Brigitte Aigner Oberlaaer Straße 235 A-1100 Vienna Austria Tel. (+43) (1) 533 566 312 Fax (+43) (1) 533 566 333 brigitte.aigner@octapharma.com Belgium Octapharma Benelux S.A./N.V. Laurent de Narbonne Rue de stalle 63/4 B-1180 Brussels Belgium Tel. (+32) (2) 3 73 08 90 Fax (+32) (2) 3 74 48 35 laurent.de-narbonne@octapharma.com Brazil Octapharma Brasil Ltda. Clóvis Bastos Av. Ayrton Senna, 1850 Sala 118, Barra da Tijuca 22775-001 Rio de Janeiro-RJ Brazil Tel. (+55) (21) 24 30 31 83 Fax (+55) (21) 24 21 16 91 clovisb@octapharma.com.br China Octapharma Beijing Representative Office Chao Yueyun Suite M-16 International Communication Building 52 NanDaJie ZhongGuanCun HaiDianQu Beijing 100081 China Tel. (+86) 10 621 69126 Fax (+86) 10 621 93528 chaoyy2003@sohu.com Canada Octapharma Canada Inc. Matt Riordan 171 East Liberty Street Suite 326 Toronto, Ontario M6K 3P6 Canada Tel. (+1) 416 531 5533 Fax (+1) 416 531 8891 matt.riordan@octapharma.ch Czech Republic Octapharma CZ s.r.o. Adriana Fifikova Na Strzi 65/1702 CZ-14000 Prague 4 Czech Republic Tel. (+420) 222 191521 Fax (+420) 222 191505 adriana.fifikova@octapharma.com Denmark Octapharma Nordic Anders Amossen Elersvägen 40 SE-112 75 Stockholm Sweden Tel. (+45) 317 168 77 Fax (+46) 8566 43011 anders.amossen@octapharma.se Finland Octapharma Nordic AB Janne Nissilä Rajatorpantie 41 C FI-01640 Vantaa Finland Tel. (+358) 8520 2710 Fax (+358) 8520 2713 janne.nissila@octapharma.fi France Octapharma S.A.S. Patrick Selosse / Nicolas Sciard 70-72 rue du Maréchal Foch BP 33 F-67381 Lingolsheim France Tel. (+33) (3) 88 78 89 89 Fax (+33) (3) 88 78 89 78 patrick.selosse@octapharma.fr nicolas.sciard@octapharma.fr Octapharma France S.A.S. Laurent de Narbonne 62 bis Avenue André Morizet F-92100 Boulogne France Tel. (+33) (1) 41 31 80 00 Fax (+33) (1) 41 31 80 01 laurent.de-narbonne@octapharma.com Germany Octapharma Vetrieb von Plasmaderivaten GmbH Reinhard Rettinghaus Elisabeth-Selbert-Straße 11 D-40764 Langenfeld Germany Tel. (+49) (21 73) 91 70 Fax (+49) (21 73) 91 71 11 reinhard.rettinghaus@octapharma.de Octapharma Vetrieb von Plasmaderivaten GmbH Niederlassung Dessau Sybille Werner Otto-Reuter-Straße 3 D-06847 Dessau Germany Tel. (+49) (3 40) 5 50 80 Fax (+49) (3 40) 5 50 81 11 sybille.werner@octapharma.de Octapharma Produktionsgesellschaft Deutschland mbh Gerold Rempeters Elisabeth-Selbert-Straße 11 D-40764 Langenfeld Germany Tel. (+49) (21 73) 91 70 Fax (+49) (21 73) 91 71 11 gerold.rempeters@octapharma.com Deutsche Gesellschaft für Humanplasma mbh Reinhard Rettinghaus Elisabeth-Selbert-Strasse 11 D-40764 Langenfeld Germany Tel. (+49) (21 73) 91 70 Fax (+49) (21 73) 91 71 11 reinhard.rettinghaus@octapharma.de Greece Octapharma Hellas SA George Kalbitzer 60, Posidonos Ave. 166 75 Glyfada Attiki Greece Tel. (+30) 210 89 86 500 Fax (+30) 210 89 86 044 octapharma.hellas@octapharma.gr

Mexico Octapharma S.A. de C.V. Angel Sosa Calzada México Tacuba No. 1419 Col. Argentina Poniente C.P. 11230 México, D.F. México Tel. (+52) 55 53 99 56 44 Fax (+52) 55 55 27 05 27 angel.sosa@octapharma.com.mx New Zealand Octapharma New Zealand Limited Simon Sestich Lumley Center 88 Shortland Street Auckland New Zealand Tel. (+64) (2) 85 72 58 00 Fax (+64) (2) 85 72 58 90 simon.sestich@octapharma.ch Norway Octapharma AS John Erik Ørn Furubakken NO-2090 Hurdal Norway Tel. (+47) (63) 98 88 60 Fax (+47) (63) 98 88 65 administrasjon@octapharma.no Poland Octapharma AG Jaroslaw Czarnota Ilzecka 26 PL-02-135 Warsaw Poland Tel. (+48) 225 757 082 Fax (+48) 225 757 001 jaroslaw.czarnota@octapharma.se Portugal Octapharma Produtos Farmaceuticos, Lda. Paulo Castro Rua da Graca, 14 P-1170-169 Lisbon Portugal Tel. (+351) (21) 8 16 08 20 Fax (+351) (21) 8 16 08 30 paulo.castro@octapharma.pt Russia Octapharma Russia Mikhail Smirnov Office 1002, 10th Floor Regus Business Centre Smolensky Passage Smolenskaya sg., 3 Moscow 121099 Russian Federation Tel. (+7) 495 937 80 59 Fax. (+7) 495 937 82 76 mikhail.smirnov@octapharma.com Saudi Arabia Octapharma Regional Scientific Office Maher Abu Al-Rob Abdel Malik Bin Marwan St. P.O. Box 7633 Riyadh 11472 Saudi Arabia Tel. (+966) 50 3844897 Fax (+966) 1 2170319 maher@octapharma.com.sa Slovakia Octapharma AG, o.z.z.o. Miroslav Gresik Zochova 6/8 SK-811 03 Bratislava Slovakia Tel. (+421) 2 5464 6701 Fax (+421) 2 5441 8321 miroslav.gresik@octapharma.at Spain Octapharma S.A. Diego Garcia Parque Empresarial de San Fernando Edif. Berlin - planta Baja Av. Castilla 2 28830 San Fernando de Henares, Madrid Spain Tel. (+34) 91 6487298 Fax (+34) 91 6764263 diego.garcia@octapharma.es Sweden Octapharma AB Tobias Marguerre Olivier Clairotte Elersvägen 40 SE-11275 Stockholm Sweden Tel. (+46) 8 566 43000 Fax (+46) 8 566 43010 tobias.marguerre@octapharma.se olivier.clairotte@octapharma.se Octapharma Nordic AB Tobias Marguerre Elersvägen 40 SE-11275 Stockholm Sweden Tel. (+46) 8 566 43000 Fax (+46) 8 566 43010 tobias.marguerre@octapharma.se United Kingdom Octapharma Limited Sue Griffin The Zenith Building 26 Spring Gardens Manchester, M2 1AB United Kingdom Tel. (+44) 161 837 3770 Fax (+44) 161 837 3799 reception@octapharma.co.uk USA Octapharma USA, Inc. Flemming Nielsen 121 River St., 12th Floor Hoboken, New Jersey 07030 USA Tel. (+1) 201 604 1130 Fax (+1) 201 604 1131 flemming.nielsen@octapharma.com Plasma Procurement Services Inc. Dennis Curtin One Front Street, 35th Floor San Francisco, California 94111 USA Tel. (+1) 518 561 4400 Fax (+1) 518 561 4848 dwhite@soctlaw.com

Octapharma AG Seidenstraße 2 CH-8853 Lachen Switzerland Tel. (+41) (55) 4 51 21 21 Fax (+41) (55) 4 51 21 10 www.octapharma.com Editorial content: Octapharma AG, Kim Björnstrup Design, artwork, production: Concept Design, Robert Becker