James (Jim) N. McGuire
Professional Experience:
Biologics and More Consulting, San Francisco Bay Area, USA, 2022-present
CEO
Independent consultant with broad expertise to help clients in charting an effective course from ideation to IND
Catalyst Biosciences, South San Francisco, USA, 2020-2022
Consultant (2022): Catalyst shut down all discovery activities (April 2022) and I am stayed on as a consultant to help company achieve their strategic goals
Executive Director (2022)
Research Project Lead (2020-2022)
Senior Director (2020-2022)
Leading efforts in bringing protease medicines to the market for the treatment of rare diseases with a focus on addressing dysregulation of the complement system
• Member of Senior Management Team
• Leading the drug discovery team (protein science and assays) in Translational Research- built from one to eight members over the last 18 months
• Scientific and project lead for complement factor I projects (CB 4332 and 2nd generation CFI)- have increased protease variant production by 800%
• Building drug discovery pipeline to deliver development candidates on a routine basis across complement biology using Catalyst’s protease platform
• Spearheading large external collaborations with Aarhus University (Denmark) and Newcastle University (UK)
• Senior scientific mentor to members of drug discovery team
• Assay subject matter expert for clinical trials (CB 4332 and MarzAA)
Novo Nordisk, Indianapolis, USA, 2020
Consultant (left to accept full-time position at Catalyst Biosciences)
Key part of building out new capabilities and progressing projects to lead candidate selection in an early discovery unit
• Responsible for expansion of lab activities that included the introduction of automation and high-content imaging
• Led establishment of new screening plans for drug discovery projects in cardiometabolic space
• Actively involved in post-IND publications for an obesity project
Novo Nordisk, Copenhagen, Denmark, 2008-2019
Principal Scientist (2014-2019)
Team Leader (2014)
Senior Scientist (2008-2014)
Subject matter expert in pharmacology and team lead (biology coordinator) for 13 programs that were advanced to the clinic and over 20 early-stage projects in the cardiometabolic space
• Delivered pharmacology packages to a key publication and formal feedback to authorities to support the approval of semaglutide as Ozempic for the treatment of diabetes as an injectable and recently approved as first-in-class orally-available peptide
• Pharmacology expert, biology coordinator (in vitro + in vivo) and/or steering group member in 13 projects that were progressed to lead candidate selection
• Designed and executed screening and in vivo/in vitro plans in over 20 early discovery projects
• Assay and data analysis development in a wide variety of applications (pharmacology, bioassays, biomarkers, ADME, enzymology, BBB transport, PK/PD prediction)
• Direct experience with complicated therapeutics: hPSC-derived organoids, BBB transport, tissue targeting, multi-agonism, bivalent molecular scaffolds, prodrugs, ADC and oral delivery of peptides
• Created successful bioassay-based methods to predict human PK and species translation
• Pioneered new technologies to increase throughput and information content- notably large-scale automation and state-of-the-art imaging platform
• Spearheaded establishment of multiple biochemical and cell-based assays including receptor binding, kinetics, GPCRs, tyrosine kinases, enzymes and serum albumin binding
• Manager for Receptor Pharmacology Team (20 direct reports) and Head of Automation and Screening Group (2-4 direct reports)
Steno Diabetes Hospital, Copenhagen, Denmark, 2006-2008
Senior Research Fellow
Group lead for biomarker basic research group with a focus on diabetes
• Group leader for proteomics biomarker discovery in diabetic nephropathy and type 2 diabetes
• Advisor for 4 students (two MSc and two PhD) and 2 technicians that led to 11 peer-reviewed articles
• Responsible for setting research agenda, securing funding and recruitment of students
Ciphergen Biosystems, Copenhagen, Denmark, 2000-2006
Manager of Biomarker Discovery Unit
Leader of biomarker discovery group focused on clinical proteomics and assay development with mass spectrometry
• Managed a biomarker discovery CRO working with the pharmaceutical industry
• Established state-of-the-art proteomics workflows for individual patient samples
• Oversaw internal efforts to establish peptide biomarkers for Alzheimer's disease that led to eight articles and two patents
Lundbeck, Copenhagen, Denmark, 1999-2000
Research Scientist
Drug metabolism group at Danish pharmaceutical company with focus on CNS
• Developed small molecule LC and LC-MS workflows in ADME
• Established GLP in the department
University of Copenhagen, Copenhagen, Denmark, 1996-1999
Postdoctoral Fellow
Focus on protein chemistry and enzymology
• Transitioned from analytical and organic chemistry (focus of PhD) to biology and biochemistry
Education:
University of Illinois, Urbana-Champaign — PhD
Harvey Mudd College — BSc
Publications and Patents:
1. “Preclinical exploration of combined glucagon inhibition and liver-preferential insulin for treatment of diabetes: will this increase the therapeutic window?” NK Roed, J McGuire, et al manuscript submitted
2. “Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: translational difficulties and pitfalls” L Simonsen, J Lau, T Kruse, T Guo, J McGuire, JF Jeppesen, K Niss, P Sauerberg, K Raun, CD de la Cour PLOS ONE 2022 (March 4, 2022)
3. “Complement factor i-related composition and methods” N Le Moan, GE Blouse, B Kumar, T Knudsen, JK Jensen, E Oldenburg, CR Schar, MJ Traylor, ES Furine, JC Way, A Jendroszek, A Sandikci, J McGuire, SR Iyer Patent (WO2021257480A3)
4. “Novel compounds for the treatment of obesity” NK Roed, A Gruhler, HS Ramirez-Andersen, S Padkjaer, MPB Sandrini, J Lau, P Bloch, A Secher, CB Jensen, J McGuire, AP Chambers Patent (WO2019243502A1)
5. “The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome” L Liljedahl, MH Pedersen, JN McGuire, P James Phys Reports 2019 (25 February 2019)
6. “α-Helix or β-Turn? An Investigation into N-Terminally Constrained Analogues of Glucagon-like Peptide 1 (GLP-1) and Exendin-4” A Oddo, S Mortensen, H Thøgersen, L De Maria, S Hennen, JN McGuire, J Kofoed, L Linderoth, S Reedtz-Runge Biochemistry 2018, 57(28), 4148-4154
7. “Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice” L Liljedahl, J Norlin, JN McGuire, P James Physiol Rep 2017, 5(6), e13187
8. “N-glyccosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models” L Liljedahl, MH Pedersen, J Norlin, JN McGuire, P James Clinical Proteomics 2016, 13:22
9. “Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide” J Lau, P Bloch, L Schäffer, I Pettersson, J Spetzler, J Kofoed, K Madsen, LB Knudsen, JN McGuire, DB Steensgaard, HM Strauss, DX Gram, SM Knudsen, FS Nielsen, P Thygesen, S Reedtz-Runge, T Kruse, J Med Chem 2015, 58(18), 7370-7380
10. “Protein Markers for the Differential Diagnosis of Vascular Dementia and Alzheimer’s Disease” AH Simonsen, NO Hagnelius, G Waldemar, TK Nilsson, JN McGuire Int J Proteomics 2012, 01/2012
11. “Characterization of membrane-shed microvesicles from cytokine-stimulated β-cells using proteomics strategies” G Palmisano, SS Jensen, MC LeBihan, J Laine, JN McGuire, F Pociot, MR Larsen Molecular & Cellular Proteomics 2012, 11(8), 230-243
12. “Serum amyloid A and C-reactive protein levels may predict microalbuminuria and macroalbuminuria in newly diagnosed type 1 diabetic patients” AJ Overgaard, JN McGuire, P Hovind, HH Parving, P Rossing, F Pociot J Diabetes Complications 2012, 08/2012
13. “Association between protein signals and type 2 diabetes incidence” TM Jensen, DR Witte, D Pieragostino, JN McGuire, ED Schjerning, C Nardi, A Urbani, M Kivimaki, EJ Brunner, AG Tabak, D Vistisen Acta Diabetologica 2012, 02/2012
14. “Methods of detecting a fragment of neurosecretory protein VGF for diagnosing Alzheimer’s disease” Patent (US7749716B2)
15. “Plasma proteome analysis of patients with type 1 diabetes with diabetic nephropathy” AJ Overgaard, HG Hansen, M Lajer, L Pedersen, L Tarnow, P Rossing, JN McGuire & F Pociot Proteome Science 2010, 8:4
16. “Quantitative iTRAQ-Based Proteomic Identification of Candidate Biomarkers for Diabetic Nephropathy in Plasma of Type 1 Diabetic Patients” AJ Overgaard, TE Thingholm, MR Larsen, L Tarnow, P Rossing, JN McGuire, F Pociot Clinical Proteomics 2010, 6(4), 104-115
17. “Screening newborns for candidate biomarkers of type 1 diabetes” JN McGuire, S Eising, AM Wägner, F Pociot Archives Phys Biochem 2010, 116(4-5), 227-232
18. “Proteomic investigations of the ventriculo-lumbar gradient in human CSF” AH Simonsen, S Bech, I Laursen, L Salvesen, K Winge, G Waldemar, L Werdelin, JE Nielsen, JN McGuire, LE Hjermind J Neuroscience Methods 2010, 191(2), 244-248
19. “Finding diabetic nephropathy biomarkers in the plasma peptidome by high-throughput magnetic bead-processing and MALDI-TOF-MS analysis” HG Hansen, AJ Overgaard, M Lajer, F Hubalek, P Højrup, L Pedersen, L Tarnow, P Rossing, F Pociot, JN McGuire Proteomics Clinical Applications 2010, 4(8-9), 697-705
20. “Mass spectrometry is only one piece of the puzzle in clinical proteomics” JN McGuire, AJ Overgaard, F Pociot Briefings in Functional Genomics and Proteomics 2008, 7(1) 74-83
21. “A novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer’s dementia in patients with Mild Cognitive Impairment” AH Simonsen, JN McGuire, O Hansson, H Zetterberg, V Podust, H Davies, G Waldemar, L Minthon, K Blennow Archives of Neurology 2007, 64(3), 366-70
22. “A novel panel of cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer’s disease versus normal aging and frontotemporal dementia” AH Simonsen, JN McGuire, VN Podust, NO Hagnelius, TK Nilsson, E Kapaki, D Vassilopoulos, G Waldemar Dementia and Geriatric Cognitive Disorders 2007, 24, 434-440
23. “A-beta1-40 quantification in CSF: comparison between chromatographic and immunochemical methods” AH Simonsen, SF Hansson, U Reutschi, JN McGuire, H Davies, P Mehta, G Waldemar, H Zetterberg, N Andreasen, A Wallin, K Blennow Dement Geriatr Cogn Disord 2007, 23(4), 246-250
24. “Saposin D and FAM3C are biomarkers for Alzheimer’s disease”, Patent (WO/2006/113289)
25. “Identification of CSF biomarkers for frontotemporal dementia using SELDI-TOF” U Rüetschi, H Zetterberg, VN Podust, J Gottfries, S Li, AH Simonsen, JN McGuire, M Karlsson, L Rymo, H Davies, K Blennow Experimental Neurology 2005, 196, 273-281
26. “Efficacy and compatibility with mass spectrometry of methods for elution of proteins from sodium dodecyl sulfate-polyacrylamide gels and polyvinyldifluoride membranes” CS Jørgensen, M Jagd, BK Sørensen, JN McGuire, V Barkholt, P Højrup, G Houen Analytical Biochemistry 2004, 330, 87-97
27. “Potential for proteomic profiling of Helicobacter pylori and other Helicobacter spp. using a ProteinChip® array” SO Hynes, JN McGuire, T Wadstrom, FEMS Immun. Medical Microbiol 2003, 36, 151-158
28. “Acyl carrier protein (ACP) inhibition and other differences between beta-ketoacyl synthase (KAS) I and II” KA McGuire, JN McGuire, P von Wettstein-Knowles Biochem Soc Trans 2001, 28(6), 607-610
29. “Cremeomycin, a novel cytotoxic antibiotic from Streptomyces cremeus. Structure elucidation and biological activity” JN McGuire, SR Wilson, KL Rinehart J Antibiotics 1995, 48(6), 516-519
Structure: 4ZGM - semaglutide in complex with extracellular domain of hGLP-1R
