Mads Krogsgaard Thomsen - Diabetes Care R&D
Slide 29 - Sources of innovation within Diabetes R&D at Novo Nordisk
Good morning Ladies and Gentlemen.
As our highest priority within R&D, Novo Nordisk has to maintain leadership in diabetes. The success in this respect, we believe, is evidenced by the number of diabetes compounds expected to reach first human dose or clinical proof-of-concept within this year.
However, before I go into more detail in this regard, I would like to highlight the need for a sustained commitment to innovation, as shown on this slide. It starts with a strong and unique insight into the pathophysiology of diabetes and from basic research, it spans across the balanced use of enabling technologies that turn novel concepts into reality in the form of investigative drugs. Even with these at hand, however, it is not until clinical research has been completed and outcomes data emerge that an unmet need in the medical community has become fulfilled.
75 years of commitment at Novo Nordisk has led to the most important innovations within Type 1 diabetes. Additionally, we decided a few years ago to expand this commitment in response to the alarming growth in Type 2 diabetes across the globe. Thus, major R&D resources were shifted into the discovery of a broad-ranging array of new, innovative therapeutics for Type 2 diabetes.
In support of this holistic strategy of targeting Type 2 diabetes from all relevant angles, the recently completed 53,000 man-year UK Prospective Diabetes Study of Type 2 diabetes concluded that strict glucose control leads to significantly fewer late complications and consequently treatment should be more intensive and include more combination therapy, utilising drugs with different actions, and also more frequent use of insulin in the treatment.
Slide 30 - Drug candidates in development for Type 2 diabetes.
In order to understand the need for more use of synergistic combination therapies we need to look at the natural history of the Type 2 diabetes. What directs the process leading to Type 2 diabetes? It is an interplay between genes, so-called diabetogenes, and environmental factors that - after a phase of impaired glucose tolerance (IGT) - induce diabetes once the insulin-producing beta-cells no longer respond to the demand for insulin. The IGT phase is often aggravated by dyslipiaemia and insulin resistance. With further beta-cell deterioration, oral treatment failure occurs and full or partial replacement with insulin is needed to compensate for the lack of insulin production. Throughout the process, the liver contributes by producing far too much glucose in the fasting state. The slide clearly demonstrates that Type 2 diabetes is a complicated, progressive disease that needs careful and individualised therapeutic attention. Our response to the challenge is clear: We currently have drug candidates in our development pipeline which target all the different factors contributing to Type 2 diabetes:
- appetite
- insulin resistance
- dyslipidaemia
- glucose production in the liver
- insulin secretion
- beta-cell stress
- insulin replacement and
- late complications
Slide 31 - Holistic approach to Type 2 diabetes drug discovery: Modulation of new targets
With the above in mind, we can take a look inside the body. On the next slide we can see that the level of blood glucose is in balance between how much is injected during meals on the one hand, and the handling by the body of glucose on the other hand, ie the amount of glucose taken up by tissues in response to insulin (decreasing blood glucose) and the amount of glucose released to the blood by the liver during fasting (increasing blood glucose). Thus, diabetes is in reality the result of an orchestra of tissues and organs that has an ill-functioning director - the unhealthy interplay between genes & environment, causing each part of the orchestra to either contribute to hyperglycaemia or fail to compensate for the unhealthy response of the neighbouring members of the orchestra. One needs to realise that attempts at correcting one individual contributing factor, is not likely to give long-term success in the management of Type 2 diabetes. Thus, we have set ourselves the ambitious R&D goal of making the orchestra of tissues play in harmony again, ideally giving hope for a future where persons with diabetes will 1) be able to secrete sufficient amounts of their own insulin in a physiological manner and 2) allow insulin to exert its full action on the insulin target tissues that are responsible for glucose and lipid metabolism: Liver, muscle and fat. In achieving the above, our long track record in understanding the biology of diabetes has aided us in dissecting out the most interesting projects among the long list of drug targets some of which are shown here on the slide: Membrane and nuclear receptors, enzymes and ion channels. Since our strategic decision was made to focus heavily on Type 2 diabetes, the outcome has been the filing of more than 250 diverse diabetes-related patent applications.
Slide 32 - Selected diabetes development projects at Novo Nordisk
We have now been into some detail regarding the diabetes research and development effort that is currently ongoing at Novo Nordisk. On the slide shown here, a summary of our extensive development pipeline is presented. Following the launch of NovoNorm®/Prandin™ last year, we expect launch of NovoRapid™ in a number of markets this year and also, that large scale Phase 3 studies of NovoMix™ and NN 304, our soluble, neutral, long-acting insulin analogue will continue into next year. Furthermore, as you can see, we hope that four compounds for diabetes may achieve clinical proof-of-concept, and that four others will enter clinical trials this year. Finally, the healthy mix of projects with respect to target diversity and positioning in the pipeline will continue as a result of our continued effort by hundreds of discovery researchers.
Slide 33 - Pulmonary insulin in the treatment of diabetes
As you will know we are working on development of an inhaled insulin formulation together with our collaborator, Aradigm. Regarding pulmonary insulin, a number of issues relating to the technology and long-term safety, efficacy and reproducibility of insulin inhalation will need to be addressed. We believe that the obvious market fit for this product, once these issues have been satisfactorily resolved, will be found within Type 2 diabetes where a large number of individuals, who have failed to achieve acceptable metabolic control when using oral agents, are reluctant to initiate insulin therapy due to fear of injection. In this important and currently ill-controlled segment, the meal-related insulin requirement can be adequately met by pulmonary administration and only the future will - in each individual patient - determine whether this meal-time treatment will suffice or alternatively, whether a bed-time injection of long-acting insulin is required in addition. In Type 1 diabetes, basal insulin injections are needed in any instance and individuals have at a young age become used to the convenience and accuracy of modern administration systems such as the NovoPen® and hence, the rationale for life-long pulmonary insulin administration may be less clear.
Slide 34 - Development stage projects for diabetes and R&D collaborations
Based on what I have just presented to you, we believe that Novo Nordisk currently has a pipeline of diabetes projects which is unparalleled in the pharmaceutical industry. In order to compare our effort in the area with that of our competitors, we have made a survey of annual reports, R&D databases, brokers' research, and other available sources of information. The result is shown graphically in my last slide where the horizontal axis shows the number of publicly known diabetes R&D collaborations and the vertical axis compares the number of development stage projects found in the diabetes pipeline of the leading companies. Novo Nordisk is in a leadership position with respect to portfolio size and has three out of our ten development projects based on R&D collaborations with biotech or pharmaceutical companies. As you may expect from our number of R&D collaborators, almost 25% of our discovery expenditure is devoted to extramural research. The newcomers that have recently entered the diabetes R&D arena have often made their entry in an opportunistic manner through licensing deals, giving access to compounds in different phases of development but not experience within this complex disease area. Diabetes has recently been defined by WHO to be a global epidemic that as demonstrated ao. in the UKPDS, associated with a big unmet medical need. Novo Nordisk has for several years realised that an integrative strategic view is needed when addressing Type 2 diabetes, and we believe that the size, robustness and innovation level of our diabetes R&D pipeline will secure that we can continue to fulfill unmet needs of persons with diabetes as we move into the next millennium.
And now I will give the word back to Kurt Anker Nielsen.
