Over the past two decades, I’ve discovered and developed novel medicines across all of AstraZeneca’s major disease areas.
My first degree is in chemical engineering where I became interested in enzymes and molecular evolution. During my PhD I worked on methods to evolve protein variants with novel functionalities in the test tube. I then started my career in biotech before moving into R&D leadership and from there clinical development.
At AstraZeneca, I first headed up the Global Technology Department. The innovative drug modalities that we worked on ultimately contributed to over half of our research portfolio. I then had the opportunity to take one of the resulting drug leads, a dual agonist peptide, into clinical trials and help transform it into a new medicine.
Today, my primary role is to lead a team of drug developers. We are probing human biology with a range of modalities (small molecules, peptides, anti-sense nucleotides, siRNAs, proteins, antibodies) across all our indications (cardiovascular disease, heart failure, kidney diseases, liver and metabolic diseases). We take on projects in pre-clinical and lead them to clinical proof-of-concept and Phase III transition. As Fellow of Trinity Hall at the University of Cambridge I supervise graduate students on protein design and directed evolution topics which keeps me close to the science that started off my journey.
What drives me every day is combining science and creativity to design new medicines that make a difference to patients.
MedImmune President’s Award
Honorary Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom
Industrial Fellow of Trinity Hall, University of Cambridge
Served as Product Development Team Leader in MedImmune CVRM. The peptide drug candidate I am currently working on has potential across liver and kidney diseases. It was the first peptide drug discovered and taken through early development in AstraZeneca. I am proud that we were the first team to describe the pre-clinical and clinical efficacy of this dual-mechanism compound and were able to publish our data in Nature Metabolism and The Lancet.
Next in my career as Global Head of Technology in MedImmune Research, I led an R&D initiative to broaden the modalities we could use to create new medicines. Two decisions make me particularly proud because both went against perceived wisdom at the time: the start-up of a peptide team, using recombinant and synthetic approaches, resulted in four clinical leads for heart failure, kidney disease and metabolic disease. We also initiated a phenotypic screening team: we looked first for antibodies with interesting functions and then worked on understanding how they were doing it, resulting in two clinical leads in oncology and infectious disease.
During my PhD, I perfected a molecular approach for the design of novel antibody molecules. In my first industry position as Director of Protein Engineering, Cambridge Antibody Technology, I applied this technique to help create an antibody therapy targeting IL-13 which is now an approved medication for atopic dermatitis.
Technique for protein evolution in the test tube:
Tailoring in vitro evolution for protein affinity or stability. Jermutus L, Honegger A, Schwesinger F, Hanes J, Plückthun A. Proc Natl Acad Sci U S A. 2001;98(1):75-80. doi: 10.1073/pnas.011311398.
Discovery of antibodies against IL-13 including tralokinumab:
Probing a protein-protein interaction by in vitro evolution. Thom G, Cockroft AC, Buchanan AG, Candotti CJ, Cohen EZ, Lowne D, Monk P, Shorrock-Hart CP, Jermutus L, and Minter RR.
Peptide mimetics of human antibodies:
Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human FcyRI. Bonetto PS, Spadola L, Buchanan AG, Jermutus L, Lund J. 2009; 23(2):575-585. doi: 10.1096/fj.08-117069.
Phenotypic selection and discovery of oleclumab:
Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type. Rust S, Guillard S, Sachsenmeier K, Hay C, Davidson M, Karlsson A, Karlsson R, Brand E, Lowne D, Elvin J, Flynn M, Kurosawa G, Hollingsworth R, Jermutus L, Minter R. Mol Cancer. 2013; 13(12):11. doi: 10.1186/1476-4598-12-11.
Alternatives to human antibodies:
Challenges and opportunities for non-antibody scaffold drugs. Vazquez-Lombardi R, Phan TG, Zimmermann C, Lowe D, Jermutus L, Christ D. Drug Discov Today. 2015;20(10):1271-83. doi: 10.1016/j.drudis.2015.09.004.
Using proteases instead of antibodies as antagonists of IL-13:
Combinatorial screening identifies novel promiscuous Matrix Metalloprotease (MMP) activities that lead to inhibition of the therapeutic target IL-13. Urbach C, Gordon NC, Strickland I, Lowne D, Joberty-Candotti C, May R, Herath A, Hijnen D, Thijs JL, Bruijnzeel-Koomen CA, Minter RR, Hollfelder F, Jermutus L. Chem Biol. 2015;22(11):1442-1452. doi: 10.1016/j.chembiol.2015.09.013.
Using directed evolution to generate a novel therapeutic protein for Type 1 Diabetes:
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. Douthwaite D, Moisan J, Privezentzev C, Soskic B, Sabbah S, Cohen S, Collinson A, EliEngland E, Huntington C, Kemp B, Zhuang L, Hudak S, Rees DG, Goldberg D, Barton C, Chang L, Vainshtein I, Liang M, Iciek L, Ambery P, Peakman M, Vaughan TJ, Tree TIM, Sansom DM, Bowen MA, Minter RR and Jermutus L. J Immunol. 2017;198(1) 528-537. doi: https://doi.org/10.4049/jimmunol.1600682.
First clinical data of a dual agonist peptide, cotadutide, in Type 2 Diabetes:
MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Ambery P, Parker VE, Stumvoll M, Posch MG, Heise T, Plum-Moerschel L, Tsai LF, Robertson D, Jain M, Petrone M, Rondinone C, Hirshberg B, Jermutus L. Lancet. 2018;391(10140):2607-2618. doi: 10.1016/S0140-6736(18)30726-8.
Mechanism of action of cotadutide:
Resolution of NASH and hepatic fibrosis by the GLP-1R and GCGR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis. Boland ML, Laker RC, Mather K, Nawrocki A, Oldham S, Boland BB, Lewis H, Conway J, Naylor J, Guionaud S, Feigh M, Veidal SS, Lantier L, McGuinness OP, Grimsby J, Rondinone CM, Jermutus L, Larsen MR, Trevaskis JL, Rhodes CJ. Nat Metab. 2020;2(5):413-431. doi: 10.1038/s42255-020-0209-6.
Novel biomarker approach for treatments of Type 1 Diabetes:
Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes. Edner NM, Heuts F, Thomas N, Wang CJ, Petersone L, Kenefeck R, Kogimtzis A, Ovcinnikovs V, Ross EM, Ntavli E, Elfaki Y, Eichmann M, Baptista R, Ambery P, Jermutus L, Peakman M, Rosenthal M, Walker LSK. Nat Immunol. 2020;21(10):1244-1255. doi: 10.1038/s41590-020-0744-z.
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