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Management Report
Management Report

Research and Development

Bayer HealthCare Bayer Technology Services
Bayer CropScience Bayer Innovation
Bayer MaterialScience Triple-i: Inspiration, Ideas, Innovation
Research and Development Expenses by Subgroup in % (2006 in parentheses)
As a research-based company, the Bayer Group firmly believes in innovation as a key driver for future growth. We have the necessary resources in place to realize further growth opportunities for the future through research and development activities. In 2007 we invested a total of €2,578 million in research and development, compared with €2,297 million in the previous year. It is particularly important for us to develop new products that strengthen our core businesses while at the same time continuously optimizing our product portfolio and our manufacturing processes. Our research activities are closely aligned to the requirements of our markets, with customer needs and technological advances presenting opportunities for future innovation. With innovation projects in particular, our own research and development activities are supplemented by our international network of collaborations with leading universities, public-sector research institutes and partner companies. Through this pooling of expertise, we aim to rapidly translate new ideas into successful products.

Bayer HealthCare

In 2007 we invested €1,700 million (2006: €1,426 million) in R&D in the Pharmaceuticals and Consumer Health segments to lay the foundations for the introduction of further innovative products in the subgroup’s expanding markets. This represented 65.9 percent of the Bayer Group’s entire R&D expenditures and was equivalent to 11.5 percent of sales.

In connection with the integration of Schering AG, Berlin, Germany, we have carried out a strategic realignment and reorganized our global pharmaceutical research and development to adjust to the new situation. In drug discovery we now focus on four growth areas: oncology, cardiology, women’s healthcare and diagnostic imaging. The respective research activities are consolidated at three main sites: Berlin and Wuppertal, Germany, and Berkeley, California. The Berlin and Wuppertal locations have significant capabilities and activities in the identification of molecular targets and the development and optimization of lead substances, as well as in drug metabolism, pharmacokinetics, toxicology and clinical pharmacology. Berkeley is an important global research and development center for protein-based active ingredients and is home to the biotechnological ­production facility for infoKogenate®. Bayer HealthCare’s U.S. research sites in West Haven, Connecticut, and Richmond, California, have been or will be closed.

To drive the development of new substances to treat diseases where there is a high unmet medical need, we conducted clinical studies with several drug candidates from our research and development pipeline during 2007. Products we submitted to one or more regulatory authorities for registration or extension of the existing registration included infoXarelto® (prevention of venous thromboembolism following major orthopedic surgery), infoMenostar® transdermal VMS (menopause management), the E2/DNG project (contra­ception), the E2/LNG project (menopause management) and infoZevalin® (follicular lymphoma). The following table shows the drug candidates currently in Phase II or III of clinical ­testing:

Research and development projects (Phases III and II)

 IndicationStatus
Rivaroxaban/Xarelto®Prevention of venous thromboembolism in
medically ill, immobilized patients
Phase III
Rivaroxaban/Xarelto®Stroke prevention in atrial fibrillationPhase III
Rivaroxaban/Xarelto®Treatment of venous thromboembolismPhase III
Nexavar®MelanomaPhase III
Nexavar®Non-small-cell lung cancerPhase III
Bonefos®Prevention of bone metastasis in breast cancerPhase III
Zevalin®Aggressive non-Hodgkin’s lymphomaPhase III
YAZ® FlexFertility control (long cycle)Phase III
Combined oral contraceptive containing folateFertility controlPhase III
LCS (Levonorgestrel Contraceptive System)Intrauterine fertility controlPhase III
Mirena®MenorrhagiaPhase III
E2/DNGSupplementary indication:
dysfunctional uterine bleeding
Phase III
YAZ®Dysmenorrhea ( Japan )Phase III
Angeliq® low-lowMenopause managementPhase III
Visanne®EndometriosisPhase III
VEGF Trap-Eye Wet age-related macular degeneration (AMD)Phase III
AlemtuzumabMultiple sclerosisPhase III
Ultravist® 370Computed tomographyPhase III
Gadovist®Magnetic resonance imagingPhase III
Aspirin® i.v.Acute coronary syndromePhase III
Avelox®New indicationsPhase III
Adenosine A1 agonist Atrial fibrillation/stable angina pectorisPhase II
sGC activatorAcute heart failurePhase II
sGC stimulatorPulmonary hypertensionPhase II
sGC stimulator 2Heart failurePhase II
Rivaroxaban/Xarelto®Secondary prevention of
acute coronary syndrome/myocardial infarction
Phase II
Kogenate®Hemophilia
(formulation based on liposome technology)
Phase II
Nexavar®Breast cancerPhase II
Nexavar®Additional indicationsPhase II
L19-Interleukin 2Renal cell carcinomaPhase II
ZK-PRABreast cancerPhase II
Sagopilone (ZK-EPO) Lung/ovarian/breast/prostate cancerPhase II
FC PatchFertility controlPhase II
E2/DRSPFertility controlPhase II
Combined oral contraceptives/DHEAFertility controlPhase II
Valette® plusFertility controlPhase II
Spheramine®Parkinson’s diseasePhase II
Levitra® New indicationsPhase II
Amikacin InhalePneumoniaPhase II
Cipro InhaleLung infectionPhase II
We regularly evaluate our pharmaceutical research and development pipeline in order to prioritize the most promising projects.

Some important development candidates in our pipeline are described below. Our innovative cancer drug infoNexavar® (sorafenib), developed jointly with Onyx Pharmaceuticals Inc., inhibits tumor growth by simultaneously blocking several serine/threonine and receptor tyrosine kinases in tumor cells. It also reduces the formation of new blood vessels that feed the tumor. We already market this product – first approved in December 2005 for the treatment of patients with advanced renal cell carcinoma – in more than 80 countries. In June 2007 we presented positive Phase III study results for the treatment of hepatocellular carcinoma with Nexavar®. Based on these data we obtained marketing authorization in this indication in Europe and the United States in the course of the year. Nexavar® is currently in various stages of clinical testing for the treatment of other tumor types.

In addition, our developmental product rivaroxaban (planned trade name: Xarelto®), a novel oral direct Factor Xa inhibitor, is being developed for the prevention and treatment of thrombotic events in order to address currently unmet needs in the anticoagulation market. This product is being jointly developed by Bayer HealthCare and Johnson & Johnson subsidiary Ortho-McNeil, Inc. under an agreement concluded in October 2005. Phase III clinical trials with Xarelto® were initiated in December 2005 for the prevention of venous thromboembolism (VTE) after major orthopedic surgery. In 2007 we applied to the European Medicines Agency (EMEA) for marketing approval for this indication. In 2006 we initiated Phase III clinical trials for the chronic indications of stroke prevention in atrial fibrillation and the treatment of venous thromboembolism and its secondary prevention. In 2007 we initiated the Phase III trial for the prevention of thrombosis in medically ill, immobilized patients. Phase II clinical trials for secondary prevention of acute coronary syndrome/myocardial infarction began in 2006.
 
An example of research and development activities in our Women’s Healthcare business unit is our product infoYAZ® from the drospirenone product family. Featuring an innovative, patent-protected therapeutic regime, YAZ® is the first oral contraceptive with two additional indications: acne and PMDD (premenstrual dysphoric disorder). In addition to the benefits of drospirenone, the gestagen contained in the product, YAZ® reduces the typical monthly hormone fluctuations seen with traditional contraceptives with a 21-day regimen. The product has already been approved for all three indications in the United States. In June 2007, YAZ® was approved in the Netherlands for fertility control and the treatment of acne. On the basis of this registration, an application has been submitted for the product to receive marketing approval for these two indications throughout Europe via the Mutual Recognition Procedure (MRP).

Our research and development efforts for biological products in the Hematology/Cardiology business unit focus on strengthening and expanding our recombinant Factor VIII product Kogenate®. Key research and product development projects include a new presentation of Kogenate® based on patented pegylated liposome technology as well as Kogenate® – Next Generation and the evaluation of gene therapy for hemophilia B.

In the Specialized Therapeutics business unit, the humanized monoclonal antibody ­alemtuzumab successfully completed Phase ii clinical trials and is now being tested in two global Phase III studies for the treatment of multiple sclerosis (MS). This novel approach to the treatment of the autoimmune disease MS is being developed in ­collaboration with Genzyme Corporation.

The portfolio of products emerging from our own research and development is supplemented by products inlicensed on a national, regional or global level. An example is the acquisition from U.S.-based ZymoGenetics, Inc., of commercialization rights outside the United States for recombinant human thrombin (rThrombin), which received marketing approval from the FDA in January 2008. The two companies plan to co-promote the product in the United States for an initial period of three years under the name infoRecothrom™ for the control of bleeding during surgery. In 2007 we entered into a partnership with Nektar Therapeutics Inc. to develop and commercialize an inhaled formulation of the antibiotic amikacin to treat pneumonia. Under the collaboration agreement entered into in 2006 with Regeneron Pharmaceuticals, Inc. on global development and marketing for the developmental product “VEGF Trap-Eye,” the product has now entered Phase III testing in age-related macular degeneration. “VEGF Trap-Eye” is a protein which, when applied locally to the eye, binds to or “traps” the vascular endothelial growth factor (VEGF) and blocks its activity. Bayer has the right to market the drug outside the United States upon regulatory approval.
 
The agreement signed in 2006 with Nuvelo Inc. to globally develop and market alfimeprase was terminated after the drug failed to meet its primary endpoints in two Phase III trials (NAPA 2 and SONOMA 2).
 
We manage the life cycles of commercialized products by identifying new indications and developing improved formulations in order to expand the scope of possible treatment opportunities.

In our Consumer Health segment, research and development activities of the Consumer Care Division at the Morristown, New Jersey, and Gaillard, France, sites focus on identifying, developing and commercializing non-prescription (over-the-counter = OTC) products. These efforts are centered on support for existing brands and the implementation of product-specific, clinical and regulatory development strategies that enable the successful exploitation of new technologies, the expansion of indications for existing products or the reclassification of current prescription medicines as OTC products. We introduced several new products to the market in 2007.

In the Diabetes Care Division, headquartered in Tarrytown, New York, we focus on strengthening core product lines and continuing our expansion into attractive segments of the diabetes market. The results of our internal development work and our collaborations with partners enable us to offer user-friendly blood glucose monitoring systems to meet the individual needs of people with diabetes.
 
The Animal Health Division focuses its research and development activities in Monheim, Germany, on antiinfectives and parasiticides as well as active ingredients for the treatment of non-infectious disorders such as renal failure, pain, cancer and congestive heart failure, particularly in companion animals.

Bayer CropScience

In 2007, €637 million (2006: €614 million), or about 24.7 percent of the Bayer Group’s research and development expenditures, was spent at Bayer CropScience. This is equivalent to 10.9 percent of the subgroup’s sales.

CropScience maintains a global network of research and development facilities. Our biggest R&D sites for crop protection products are located in Monheim and Frankfurt, Germany, and Lyon, France. The major research centers of the BioScience Business Group are located in Ghent, Belgium, and Haelen, Netherlands.

While research is concentrated at a small number of centrally located sites, our development activities take place both there and at field testing stations across the globe, to enable future products to be tested under the relevant regional climatic conditions. Breeding activities for our seed business are also carried out at various decentralized locations to take account of specific local market requirements.

In the Crop Protection segment we identify and develop innovative, safe and economically sustainable insecticides, fungicides and herbicides and carry out research projects in new areas of future importance, such as plant health or stress tolerance. In addition to conventional chemistry, biology and biochemistry, modern technologies such as genomics, high-throughput screening, bioinformatics and combinatorial chemistry play an important role in the identification of new lead structures. Collaborations with external parties supplement our own activities.

Once a compound is identified for development, its biological, environmental and toxicological profile is assessed.

We work to actively extend the applications for our products by developing seed ­treatments and continuously managing product life cycles. This includes developing new formulations for active ingredients and products that are already on the market so that they can be applied to additional crops or are easier to use.

The Crop Protection active ingredient pipeline currently contains 18 projects that the company aims to bring to market maturity by 2015, and a further 45 projects in early-stage research. The following new active ingredients from the R&D pipeline of Bayer CropScience received their first marketing approvals in various countries in 2007:
New active ingredientIndicationStatus
FlubendiamideInsecticideMarket introduction 2007
SpirotetramatInsecticideMarket introduction expected in 2008
TembotrioneHerbicideMarket introduction 2007
PyrasulfotoleHerbicideMarket introduction expected in 2008
Flubendiamide (major brand: infoBelt®) is a new insecticide for foliar application in annual and perennial crops, offering protection primarily against all major Lepidoptera species. It belongs to a new chemical class of substances (substituted phthalic acid diamides) with a novel mechanism of action. The substance is also highly effective against insects that are resistant to certain conventional insecticides. Flubendiamide is intended for worldwide use in vegetables, fruit, cotton, corn, beans, tea and a number of other crops.

Spirotetramat (major brand: infoMovento®) is Bayer CropScience’s third active ingredient from the ketoenols substance class. It is a highly effective systemic insecticide that offers protection against a broad spectrum of sucking insects. Spirotetramat protects pome and stone fruit, citrus fruit, grapes, nuts, vegetables and potatoes against pests such as aphids, cicadas, grape lice, mealybugs, whiteflies and cottony-cushion scales.

Tembotrione (major brand: infoLaudis®), from the triketone chemicals class, is absorbed by the plant through the leaves and can be used in corn to control a broad spectrum of weeds, including resistant varieties.

Pyrasulfotole (major brand: infoHuskie™), a member of the benzoylpyrazoles class, is a new herbicidal active ingredient offering farmers reliable control of a large number of broad-leaved weeds in cereals.
The compounds discovered in the course of crop protection research are also tested and evaluated by our Environmental Science unit to identify possible development potential for non-agricultural uses. Active ingredients from other companies may also be tested and purchased if suitable. Our current development projects include passive treatments such as gels and baits, formulations for pest control, new products for weed control, and active ingredient mixtures to control fungal diseases on turf and ornamental plants.

In 2007, Environmental Science introduced various new products for professional users and consumers. Key launches included the insecticide infoExemptor® (thiacloprid) for the green industry in Europe and the new herbicide infoDestiny® (iodosulfuron) in Japan.

Research activities in our BioScience unit are based on plant biotechnology and modern breeding methods designed to optimize the properties of our core crops – cotton, canola and rice – and our vegetable seeds.

We have a promising pipeline comprising more than 40 lead projects. Our research and development activities are focused on stress tolerance, yield increases and qualitative plant traits. For example, we are working to develop new canola oil profiles, tomatoes with improved processing characteristics, and new cotton varieties with enhanced fiber properties. Other projects are directed toward improving plants’ herbicide tolerance and their resistance to insect attack and diseases. We supplement our own research activities with research and licensing agreements, a key area here being the improvement and safeguarding of crop yields in stress situations by modulating specific genes in cotton, canola and rice.

The expansion of sales in our BioScience Business Group was supported by new product introductions in 2007.

Bayer MaterialScience

In 2007, Bayer MaterialScience spent €209 million (2006: €227 million) on research and development (not including joint development activities with customers) to further expand its leading position in market and process technology as a global supplier of high-quality customized materials and system solutions. The subgroup thus accounted for an 8.1 percent share of the Bayer Group’s total research and development expenditures, with R&D expenses amounting to 2.0 percent of sales. In the four MaterialScience business units – Polyurethanes; Polycarbonates; Thermoplastic Polyurethanes; and Coatings, Adhesives, Sealants – the latest technologies and production processes are used to develop new products and applications in close cooperation with our customers and other external partners.

The Polycarbonates business unit strives to develop new formulations and applications for its products and continually improve its manufacturing processes. In product devel­opment, we focus our activities on developing new blends, refining materials for optical data storage, developing modified base materials for polycarbonate sheets and modifying the surface of polycarbonates using various coating technologies. Examples include polycarbonate windows and roof elements for cars. Noteworthy applications for polycarbonate films are LCD diffuser films for flat screens and formable coated films for electronic and automotive applications. Soft-touch infoMakrofol® films are used in automotive interior components and mobile phone housings.

Currently, the main areas of innovation in the Polyurethanes business unit are the development of new and improved polyether polyol types and blends, and the improvement of manufacturing processes for polyols and aromatic isocyanates. Our TDI facility in Caojing, China, due on stream in 2010, will employ gas-phase phosgenation, which uses between 40 and 60 percent less energy than previous processes. We are also investigating the feasibility of a new and highly efficient production process for MDI.

In product development, our activities are focused mainly on extending the applications for our polyurethane systems and improving their thermal insulation properties and flame retardance. The use of renewable raw materials also plays an important part. For example, we have developed polyols containing up to 70 percent by weight of renewable raw materials for use in mattresses, car seats and refrigerator insulation. One completely new application is a polyurethane foam system used to lay railroad ballast beds. The use of this innovative technology, which is currently being tested under regular rail traffic conditions, can result in a lower maintenance requirement for the railroad bed and also reduce train noise levels.

The Coatings, Adhesives, Sealants business unit focuses its research and development activities on developing polyurethane raw materials for the formulation of high performance coatings, adhesives and sealants, such as aliphatic and aromatic polyisocyanates and resin components. Important areas of research are raw materials for waterborne and UV-curing systems that help to conserve resources by obviating the need for organic ­solvents and reducing drying times for coatings. We are also collaborating with the U.S. company InPhase Technologies to develop holographic data-storage media with a ­capacity of 300 GB per first-generation disc. We are also working to open up more new applications in the areas of printing inks, cosmetics and medical technology.

Most research and development activities in the Thermoplastic Polyurethanes business unit are directed toward obtaining high-performance thermoplastic polyurethane resin granules and film products, such as solar-module films with very high transparency and UV stability.

The New Business section of MaterialScience constantly tracks and evaluates new technological and market trends, channeling the most promising ideas into research and development projects in order to create profitable business opportunities for the future or expand existing technology platforms. There are various approaches to implementing such projects, including collaboration with the business units or an external institution, or the establishment of an independent company as part of a “greenhouse” initiative. In a new technology initiative, Bayer in the fall of 2007 signed an agreement with Aachen Technical University concerning the establishment of a center for catalysis research in which novel catalytic processes are to be developed. Following the founding in 2006 of the start-up company LYTTRON for the production of three-dimensionally formable ­electroluminescent films, the internal start-up project infoBaytubes® was launched in 2007. We now manufacture multi-wall carbon nanotubes in a pilot facility with an annual capacity of 60 tons and market them under the trade name Baytubes®. Thus within a very short time, we have become one of the world’s leading suppliers of such products.

Bayer Technology Services

The Bayer subgroups work closely with Bayer Technology Services on engineering and technology solutions, particularly in the fields of process technology, plant engineering and automation. This service company develops and implements innovative technology platforms that speed up development work and help the subgroups to manufacture new products, design system solutions and develop production processes. International sourcing of know-how plays a key strategic role in this. It involves country-specific expertise in the implementation of capital expenditure projects, global access to innovations and public funding, and the recruiting of top international personnel. The establishment of collaborations with other companies and with research institutes also has an important part to play in this respect.

Bayer Innovation

Bayer Innovation investigates and evaluates innovation themes outside of the subgroups’ core activities and develops them into viable new businesses for the Bayer Group. The aim of Bayer Innovation is to incorporate Bayer’s core competencies in the fields of health care, nutrition and high-tech materials into projects that complement Bayer’s business portfolio, and to facilitate access to new and growing markets.

In 2007 Bayer Innovation focused on the manufacture of plant-made pharmaceuticals (PMP) and on novel concepts for the treatment of chronic wounds, such as wound dressings made from biodegradable silica gel fibers. The full potential of these technologies is being evaluated in close cooperation with Bayer HealthCare, Bayer CropScience, Bayer MaterialScience, Bayer Technology Services and external partners.

Triple-i: Inspiration, Ideas, Innovation

More than 3,000 suggestions have already been submitted in response to the innovation initiative launched by Bayer AG in 2006, entitled “Triple-i: Inspiration, Ideas, Innovation.” Many of these proposals are currently undergoing further evaluation by our subgroups. The initiative is designed to motivate employees throughout the Group to submit ideas for new products and thus help to strengthen Bayer’s innovation capability.
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