Pierre Signore

• Lead the Pharmacology department to develop drug candidates for two platforms: 1/ small molecules that stabilize hypoxia-inducible factor (HIF) to treat myocardial infarction, heart failure, anemia, kidney disease and inflammatory bowel disease; and 2/ antibodies against connective tissue growth factor (CTGF) to treat fibrotic diseases. • Write pharmacodynamics and safety pharmacology sections of Investigational New Drug (IND) applications, Clinical Trial Applications (CTA) and New Drug Applications (NDA) for worldwide drug approval. Interact with European and Japanese corporate partners to design studies supporting NDA and to finalize study reports. Respond to queries from regulatory agencies during the approval process. • Interact with project leaders to establish annual project plans. Design in-vivo efficacy and safety studies to screen new drugs and select lead compounds. Give regular updates to project teams and corporate partners. • Supervise scientists during the development, validation and implementation of in-vivo models of myocardial infarction, congestive heart failure, chronic kidney disease, acute kidney injury, glucose tolerance, insulin sensitivity, liver fibrosis, lung fibrosis, kidney fibrosis and inflammatory bowel disease. Write protocols and reports. Mentor scientists with data analysis and presentations. • Select contract research organizations (CROs) and act as sponsor representative for preclinical studies performed outside the company.

• Identified paclitaxel as the lead compound for the first generation of drug-eluting stents to inhibit arterial restenosis. Designed and executed in vivo proof-of-concept studies. Gave scientific presentations to potential corporate partners that led to a co-exclusive license agreement with Boston Scientific Corp. and Cook Inc. for the development of paclitaxel-eluting stents. • Developed drug-eluting devices to prevent vascular graft stenosis. Designed and executed preclinical efficacy and safety studies internally and at CROs. Presented study results to major US medical device companies, which led to a license agreement with C.R. Bard, Inc. and its subsidiary IMPRA, Inc. • Project leader for the development of medical devices to treat vascular restenosis, atherosclerosis and aneurysms. Guided and coordinated product development efforts between the Pharmacology, Formulations, Analytical, Engineering, Cell Biology and Legal departments. Screened compounds and extended-release formulations for in vivo efficacy and safety. Demonstrated proof of concept in chronic animal models. Ensured that projects followed timelines and interacted with corporate partners to speed product development. • Led a group of preclinical scientists and surgeons who developed several surgical models of diseases in rodents and large mammals to study and treat vascular restenosis, vascular graft complications, stent-graft endoleaks and surgical adhesion.

Used pharmacological agents to alter the cardiovascular response to exercise. Showed that the parasympathetic system reduces cardiac sensitivity to adrenergic stimulation during hypoxia and that the cardiac responses to exercise in air and during apnea are controlled by different nervous pathways.

Set-up a research laboratory off the main campus to study cardiovascular responses in freely moving animals. Developed telemetry techniques to remotely monitor heart rate in exercising mammals. Mentored and supervised graduate students.