Innovator Organizations in New Drug Development: Assessing the Sustainability of the Biopharmaceutical Industry  Michael S. Kinch, Ryan Moore  Cell Chemical Biology  Volume 23, Issue 6, Pages 644-653 (June 2016) DOI: 10.1016/j.chembiol.2016.05.013 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Entry and Exit of Biopharmaceutical Companies over Time (A) In an assessment of biopharmaceutical companies, the year of founding (Entry; shown in black) and acquisition (Exit, shown in red) is indicated from 1800 to the end of 2015. (B) The net effect of entries and exits is indicated, which reveals the growth and then stagnation of the pharmaceutical industry (1688 to 1970) and then the rise and consolidation of biotechnology (1971 to 2015). (C) The site of location for all innovator companies is shown on a decade-by-decade basis. (D) Given the dominance of North American innovators, this region was dissected by subdividing the continent into generally accepted geographic regions. Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 Innovator Acquisition Relates to Company Age but Not Time since First Approval (A) The average age (time from foundation until acquisition) is shown for all acquisition events from 1951 to 2015. The “date” indicates the date in which the acquisition took place. (B) The average time from a first FDA approval until acquisition is indicated for all acquired innovator companies. (C) The likelihood that a company will remain active in new pharmaceutical R&D and independent for the times indicated is shown for all companies that gained their first FDA approval in the decade shown. Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 3 Geographic Distribution of Acquired Companies (A) The location of all acquired innovators (1800 to 2015) is indicated. (B) The likelihood that an innovator will be acquired is assessed relative to its location (prior to the acquisition). Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 4 Geographic Analysis of Acquirers (A) The location of all acquirers (1800 to 2015). (B) The location of acquirers is shown relative to the year of acquisition, thus revealing an increase in European acquirers (shown in red) relative to their North American (blue) or Australasian (black) peers. (C) A summary of the regions hosting NME innovators and acquirers and the changes resulting from consolidation is shown, with emphasis on the impact that consolidation has had on the number and geographic distribution of innovators. Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 5 Analysis of Organizations that Acquired Biopharmaceutical Innovators (A) The five leading acquirers of organizations that had contributed to the research or development of at least one new molecular entity are shown. (B) The total number of acquirers, the organizations subject to acquisition and current status (active in research and/or independently operated) is summarized. Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 6 Relationship between the Age and the Geographic Location of Innovators The age of active and independent innovator companies is clustered into four groups and shown for the three major geographic areas. Note that whereas more than three-quarters of North American companies have been in existence for less than 50 years, the majority of European companies have been around for more than 50 years, while companies younger than 20 are practically non-existent in Australasia landscape. Cell Chemical Biology 2016 23, 644-653DOI: (10.1016/j.chembiol.2016.05.013) Copyright © 2016 Elsevier Ltd Terms and Conditions