During the past 18 years, I have discovered and developed novel medicine leads across all of AstraZeneca’s major disease areas: oncology, inflammation, respiratory and metabolism. 

What drives me is applying science and creativity to design new medicines that make a difference for patients. My first degree was in chemical engineering, and I was drawn to the concepts of molecular evolution and protein design and how to make something useful out of them. My PhD, from the Universität Zürich, is in molecular evolution, harnessing the concept of Darwinian evolution to create and evolve new proteins with novel functionality.

I started my biotech career in research in a small biotech company in Cambridge, discovering antibody medicines using those principles, before moving into clinical development as Product Development Team Leader. I was most recently Product Development Team Leader and Senior Director, R&D, in CVRM iMed, MedImmune. What motivates me today is knowing just how many people have worked extremely hard and sacrificed so much to make the discoveries that led to a clinical discovery.

At AstraZeneca, I initially continued my work in research to head up the Global Technology Department, and become a discovery platform expert for antibody, protein, peptide and nucleic acid-based biopharmaceuticals. Using design and directed evolution to create drug leads beyond just antibodies resulted in nearly half of the pre-clinical portfolio being biologics that were not standard monoclonal antibodies. It also led me to found a synthetic peptide discovery team that worked closely with our colleagues in cardiovascular and metabolism discovery. One of the molecules looked so exciting that, in 2013, I was able to take this peptide into clinical trials and generate the data that could transform it into a new medicine.

As Product Development Team Leader, my primary role today is to advance candidate drugs for type-2 diabetes, obesity, diabetic nephropathy and non-alcoholic steatohepatitis (NASH), from late-pre-clinical to clinical proof-of-concept, and to transition them to late-stage development. Through my Fellow position at the University of Cambridge, I continue supervising PhD students in a number of protein design and directed evolution projects to stay close to the science that led me onto my journey.

The great thing about creating new medicines is the intellectual work of designing a molecule to attack a disease in such a way that it makes a very significant, meaningful difference to the patient. Being able to demonstrate this first in animal models of the disease and finally in the clinic is incredibly rewarding.

What drives me is applying science and creativity to create new medicines that make a difference for patients.

Lutz Jermutus PhD Head of Projects

Award

2017 MedImmune President’s Award (project team award)

 

Award

2015 Honorary Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom

 

Award

2013 Industrial Fellow of Trinity Hall, University of Cambridge

 


Award

2009 Fellow of the Royal Society of Chemistry (FRSC) 

 


Award

1997 Graduate Kekulé Fellowship of Verband der Chemischen Industrie

 


Award

1991 Undergraduate scholarship of Studienstiftung des deutschen Volkes

 



CURRENT ROLE

Head of Projects

During my PhD, I perfected a technology called ribosome display for the design of novel antibody molecules. I then applied this technique to help create an antibody that is now in Phase III testing with our partner LEO Pharma for atopic dermatitis.

I led the work to significantly broaden the types of drugs AstraZeneca is able to create. Two decisions make me particularly proud because we took them against perceived wisdom at the time. The foundation of the peptide team resulted in the medicine I am currently leading in Phase II clinical trials. We also started a phenotypic screening effort where we looked first for antibodies and proteins with interesting function, and then tried to understand how they were doing it. This resulted in the discovery of the anti-CD73 antibody in oncology that is now in multiple Phase II studies.

The peptide drug candidate I am currently working on has potential across type 2 diabetes, obesity and NASH. It was the first peptide drug discovered and taken through development in AstraZeneca. I am proud that we were the first to describe the clinical activity of this dual-mechanism medicine and were able to publish our data in The Lancet. Publishing in a leading clinical journal could not be further away from my roots as a chemical engineer!

  Featured publications

Tailoring in vitro evolution for protein affinity or stability.

J. Hanes, L. Jermutus, S. Bornhauser-Weber, H.-R. Bosshard and A. Plückthun. (1998) Ribosome display selects and evolves high-affinity binding antibodies in vitro from immune libraries. Proc. Natl. Acad. Sci. USA 95:14130-14135.

Structure-based chimeric enzymes as an alternative to directed enzyme evolution: phytase as a test case.

L Jermutus, A. Honegger, F. Schwesinger, J.Hanes and A.Plückthun. (2001) Tailoring in vitro evolution for protein affinity or stability. Proc. Natl. Acad. Sci. USA 98:75-80.

Probing a protein-protein interaction by in vitro evolution.

L. Jermutus, M. Tessier, L. Pasamontes, A. P.G.M. van Loon and M. Lehmann. (2001) Structure-based chimeric enzymes as an alternative to directed enzyme evolution: phytase as a test case. J. Biotechnol. 85:15-24.

Harnessing phage and ribosome display for antibody optimisation Trends Biotechnol.

G. Thom, A. Cockroft, A. Buchanan, C. Jobery Candotti, S. Cohen, D. Lowne, P. Monk, C. Shorrock-Hart, L. Jermutus and R. Minter. (2006) Probing a protein-protein interaction by in vitro evolution. Proc. Natl. Acad. Sci. USA 103:7619-7624.

Harnessing phage and ribosome display for antibody optimisation Trends Biotechnol.

P. Dufner, L. Jermutus, R. Minter. (2006) Harnessing phage and ribosome display for antibody optimisation Trends Biotechnol. 24:523-529.

Potent peptide mimetics of human IgG1-Fc.

S. Bonetto, L. Spadola, A. G. Buchanan, L. Jermutus, J. Lund. (2009) Potent peptide mimetics of human IgG1-Fc. FASEB J. 23:575-85.

Challenges and opportunities for non-antibody scaffold drugs Drug Discov.

R. Vazquez-Lombardi, T. G. Phan, C. Zimmermann, D. Lowe, L. Jermutus, D. Christ (2015) Challenges and opportunities for non-antibody scaffold drugs Drug Discov. Today 20:1271-1283.

Combinatorial screening identifies novel promiscuous Matrix Metalloprotease (MMP) activities that lead to inhibition of the therapeutic target IL-13 Chem.

C. Urbach, N. C. Gordon, I. Strickland, C. Joberty-Candotti, D. Lowne, F. Hollfelder, R. R. Minter , L. Jermutus (2015) Combinatorial screening identifies novel promiscuous Matrix Metalloprotease (MMP) activities that lead to inhibition of the therapeutic target IL-13 Chem. Biol. 22:1442-52.

Robust anti-obesity and metabolic effects of a GLP-1/glucagon co-agonist peptide in rodents and non-human primates Diabetes Obes. Metab.

S. Henderson, A. Konkar, D. Hornigold, M. Fritsch Fredin, R. Jansson-Lofmark, R. Jackson, J. Naylor, A. Rossi, M. Bednarek, N. Bhagroo, H. Salari, S. Will, S. Oldham, G. Hansen, J. Jelsing, H. Cucak, T. Klein, J. Grimsby, S. Maguire, L. Jermutus, C.Rondinone, M. Coghlan (2016) Robust anti-obesity and metabolic effects of a GLP-1/glucagon co-agonist peptide in rodents and non-human primates Diabetes Obes. Metab. 18:1176-1190.

A CD80-biased CTLA4-Ig fusion protein with superior in vivo efficacy at low, infrequent doses by simultaneous engineering of affinity, selectivity, stability and FcRn binding J. Immunol.

J. Douthwaite, J. Moisan,  C. Priventseev, B. Soskic, S. Sabbah, S. Cohen, A. Collinson, E. England, C. Huntington, B. Kemp, L. Zhuang, S. Hudak, G. Rees, D. Goldberg, C. Barton, L. Chang, I. Vainshtein, M. Liang, L. Iciek, P. Ambery, M. Peakman, T. Vaughan, T. Tree, D. Sansom, M. Bowen, R. Minter, L. Jermutus (2017) A CD80-biased CTLA4-Ig fusion protein with superior in vivo efficacy at low, infrequent doses by simultaneous engineering of affinity, selectivity, stability and FcRn binding J. Immunol. 198:528-537. Correction 199:1943.

LEAP2 is an endogenous antagonist of the ghrelin receptor Cell Metab.

X. Ge, H. Yang, M. Bednarek, H. Galon-Tilleman, P. Chen, M. Chen, S. Crawley, J. Lichtman, M. Saberi, H. Tian, L. Jermutus, J. Grimsby, C. Rondinone, D. Kaplan (2018) LEAP2 is an endogenous antagonist of the ghrelin receptor Cell Metab. 27:461-469.