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Iain C Kilty, PhD

Vice President and Head of Preclinical, I&I Research Unit

I lead the Preclinical Group within Inflammation & Immunology, responsible for the portfolio from the point we invest in screening through to delivering the regulatory package for first in human studies. I joined Pfizer in 1996 and since then have had the opportunity to work across the pipeline from target hunting through to Ph2 development. The majority of this time has been focused on anti-inflammatory therapies across a range of chronic conditions, in disease areas including rheumatology, dermatology, gastroenterology and respiratory indications.

I have worked on both large and small molecules, delivered by various different routes including oral, inhaled, topical and injectable therapies. Of note, I have a specific interest in inflammatory signaling pathways and personally led a number of kinase inhibitor projects to the clinic including IRAK4, JAK and p38 programs in addition to other non-kinase small and large molecule programs. Throughout my career at Pfizer I have enjoyed working closely with academic or industrial key opinion leaders, both through direct collaboration and as part of industrial academic consortia.

I am an advocate for a primary focus on understanding human pathophysiology of inflammatory diseases by working with primary patient samples and have a keen interest in building translational understanding of the targets we invest in.

RESEARCH AREA(S)

The preclinical group supports both large and small molecule programs across our core diseases areas of rheumatology, dermatology and gastroenterology. We are interested in anti-inflammatory approaches in innate and adaptive immunity as well as well targets that would address the end stage fibrotic manifestations of many autoimmune diseases. Mechanistic areas of interest include cytokine signaling, innate receptor signaling, immunometabolism, tolerance induction, epithelial barrier function, modulation of checkpoint signaling and drivers of fibrosis.

Where possible, we focus on primary patient cells or biofluids to build understanding of our targets of interest and have also invested in complex in vitro and humanized in vivo models. In choosing targets we are somewhat modality agnostic and have access to core expertise in medicinal chemistry and biomedical design. Of note, we are currently working on oral, topical and systemically delivered therapies. There is a keen focus on translational strategies to support crisp clinical decision making as we transition our programs into development.

PUBLICATIONS

  1. Hill, A., Loh, P., Bharadwaj, R., Guinan, E., Lakhani, K., Kilty, I.and Jelinsky, J. (2017) “Stepwise Distributed Open Innovation Contests for Software Development - Acceleration of Genome-Wide Association Analysis” GigaScience doi: 10.1093/gigascience/gix009 https://www.ncbi.nlm.nih.gov/pubmed/28327993
  2. Jones, P., Storer, R, Sabnis, Y., Wakenhut, F., Whitlock, G., England, K., Mukaiyama, T., Dehnhardt, C., Coe, J., Kortum, S., Chrencik, J., Brown, D., Jones, R., Murphy, J., Yeoh, T., Morgan, P. and Kilty, I. (2017) "Design and Synthesis of a pan-JAK Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin" J.Med.Chem doi: 10.1021/acs.jmedchem.6b01634 https://www.ncbi.nlm.nih.gov/pubmed/2798383
  3. Lee, K., Ambler, C., Anderson, D., Boscoe, B., Brodfuehrer, J.,Bree, A.,Chang, J., Choi, C., Chung, S., Curran, K.,Day, J., Dehnhardt, C.,Dower, K.,Drozda, S., Frisbie, R., Gavrin, L., Goldberg, J.,Han, S.,Hegen, M.,Hepworth, D., Hope, H.,┴ Kamtekar, S., Kilty, IC, Lee, A., Lin, L.L., Lovering, F., Lowe, M.D., Mathias, J., Morgan, H., Murphy, E., Papaioannou, N.,Patny, A., Pierce, B.,Ramsey, S.,Rao, V., Saiah, E., Samardjiev, I.,Samas, B., Shen, M., Shin, J., Soutter, H., Strohbach, J.,Symanowicz, P.,Thomason, J.,Trzupek, J., Vargas, R., Vincent, F., Wrightstone, A., Yan, J.,Zapf, C.and Wright, S. (2017) “Discovery of Clinical Candidate 1{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design” J.Med.Chem doi: 10.1021/acs.jmedchem.7b00231 https://www.ncbi.nlm.nih.gov/pubmed/28498658
  4. Singh, D., Siew, L., Christensen, J., Plumb, J., Clarke, G., Greenaway, S., Clarke, N., Kilty, I. and Tan, L. (2015) “Different effects of oral and inhaled P38 MAPK inhibitors on corticosteroid resistant neutrophilic inflammation after inhaled LPS challenge in healthy subjects.” Eur.J.Clin.Pharm. doi:10.1007/s00228-015-1920-1 https://www.ncbi.nlm.nih.gov/pubmed/26265232
  5. Nicholson, G., Leaker, B., Holloway, R., Donnelly, L., Kilty, I.C. and Barnes P.J. (2016) “A novel flow cytometric based method to measure kinase inhibition in sputum from COPD subjects” B.M.J.Open Resp. Res. 3:e000140 doi:10.1136/bmjresp-2016-000140 https://www.ncbi.nlm.nih.gov/pubmed/27403320</li>

EDUCATION

University of Liverpool, PhD: “The Development of Two Distinct Differentiated Cell Lines with a Thermolabile Form of SV40 Large T Antigen,” 1996
University of Cambridge, Jesus College, Cantab Biochemistry, M.A., 1993
University of Cambridge, Jesus College, Cantab Biochemistry, B.A., 1992

AWARDS & HONORS

Pfizer Team Achievement Award for the (Topical JAK Program), 2016
Senior Editor Journal of Inflammation
Member of the Organizational Committee for the British Inflammation Research Association (BIRAs)
Member of the UK Government Asthma Advisory Group