To succeed in our objective to create a pipeline of novel, orally available drugs that address serious unmet medical needs, we have established a broad range of discovery capabilities in-house, including target validation, high-throughput screening, medicinal chemistry, computational chemistry, and pharmacological and ADME (absorption, distribution, metabolism and excretion) assessment. We augment these capabilities through collaborations with academic and contract laboratory resources with relevant expertise.

We select drug targets with strong preclinical or clinical validation in areas where we have the potential to generate either first-in-class molecules or compounds that are highly differentiated from existing treatments.

Our chemistry and biology efforts are highly integrated and are characterized by the rapid generation of relevant data on a broad and diverse range of compounds for each therapeutic target we pursue. This process allows our scientists to better understand, in real time, the potency and selectivity of the compounds, how they are likely to be absorbed and eliminated in the body, and to assess the potential safety of the compounds. We believe that this approach, along with stringent criteria for the selection of clinical candidates, will help us to select appropriate candidates for clinical development.

Given our chemistry-driven discovery process, our pipeline has grown to encompass multiple therapeutic areas: oncology, inflammation and diabetes. While our productivity has created a diverse pipeline, we conduct a limited number of discovery programs in parallel at any one time. This focus allows us to allocate resources to our selected programs at a level that we believe is competitive with much larger pharmaceutical companies. We believe this level of resource allocation, applied to the discovery process outlined above, has been critical to our success in our current programs, and that it remains a meaningful competitive advantage.

In all of our programs we strive to generate a diverse and broad range of proprietary compounds which we believe enhances the overall probability of success for our programs and creates the potential for multiple products.

Once our compounds reach clinical development, our objective, whenever possible, is to rapidly progress the lead candidate into a proof-of-concept clinical trial prior to initiating larger definitive Phase IIb clinical trials to quickly assess the therapeutic potential of the clinical candidate itself and its underlying mechanism.

Incyte’s Clinical Development and Regulatory Team

Our development teams are responsible for ensuring that our clinical candidates are expeditiously progressed from preclinical development and IND-enabling studies into Phase I and Phase II development. To efficiently and effectively keep place with the growth in our clinical pipeline, we have added new members to the development teams by internal transfers and by recruiting new employees with expertise in drug development including clinical trial design, statistics, regulatory affairs and project management. We have also built core internal process chemistry and formulation teams using this same strategy. Our internal multi-discipinary project teams also work with experienced external CROs with expertise in managing clinical trials, process chemistry, product formulation, and the manufacture of clinical trial supplies to support our drug development efforts.

Commercial Strategy

We intend to develop and commercialize some of our compounds on our own in selected markets where a company of our size can compete effectively, such as HIV, oncology, and certain inflammatory conditions. For programs that target large primary care indications such as diabetes and/or require lengthy and expensive clinical development plans, we may seek to form strategic alliances as we did with Pfizer for our CCR2 antagonist program.

Collaborative Research and License Agreement with Pfizer

Effective in January 2006, we entered a collaborative research and license agreement with Pfizer Inc. (“Pfizer”) for the pursuit of our CCR2 antagonist program.  Pfizer gained worldwide development and commercialization rights to our portfolio of CCR2 antagonist compounds.  Pfizer’s rights extend to the full scope of potential indications, with the exception of multiple sclerosis and autoimmune nephritides, where we retained worldwide rights, along with certain compounds.  We do not have obligations to Pfizer on preclinical development candidates we select for pursuit in these indications. 

Recent Decision to Out-License CCR5 Antagonist Program Confirms Focus on Near-term Value

While we have made good progress advancing our CCR5 antagonist, INCB9471, as a treatment for HIV and believe it has potential to become the best-in-class CCR5 antagonist, it is essential that we focus our resources on the programs that offer the greatest near-term value. Considering that this program is one of our more expensive, time- and labor-intensive efforts, and is now our only HIV product, in March 2008 we announced that we would not initiate Phase IIb trials and intend to pursue out-licensing options. 

JAK Inhibitor Program Is Now Our Highest Priority

Given the success we have achieved in the JAK inhibitor program for myelofibrosis, a rare life-threatening myeloproliferative disease for which there are no approved drug therapies, this program is now our highest priority. As this indication is likely to receive expedited FDA review and approval, the JAK program offers tremendous potential for creating near-term value. It is also a program we can develop and commercialize on our own. 

There is a growing body of preclinical and clinical evidence suggesting JAK inhibitors may have therapeutic value in other hematological conditions, solid tumors and multiple inflammatory conditions. Given this broad potential, and the fact we have one of the most advanced compounds in clinical development, we are aggressively moving INCB18424 forward in multiple indications (see pipeline).