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Work Experience

Seagen (2020-2024)

Director of Quantitative Pharmacology and Disposition (2020-2024)

Manager, platform model development, translational modeling support, and team building

  • Created workflows to automate the analysis and reporting of non-GLP studies.
  • Developed junior scientists in a growing group: created and ran training sessions for R and modeling and simulation tools; provided mentorship and career guidance.
  • Acted as a project team representative for preclinical programs.
  • Provided modeling and simulation support for projects and platforms from discovery through development.
  • Created validated NONMEM environment used by the quantitatively pharmacology group for regulatory submissions.
  • Authored module 2.6.4 and study reports for IND submissions.
  • Clinical pharmacology representative for early stage programs.

Amgen (2013-2020)

Preclinical Director, Discovery & Translational Sciences, PKDM, (2019-2020)

Principal Scientist, PKDM, San Francisco, Ca (2016-2019)

Manager, platform model development, and translational modeling support

  • Managed direct reports.
  • Responsible for module 2.6.4 in INDs for immune-oncology programs.
  • Project team representative typically supporting 8-12 programs in oncology and metabolic disorders from early discovery through FIH.
  • Supported product life-cycle management by evaluating feasibility of new indications and development of new molecules to support franchises.
  • Developed modeling tools to guide determination of antibody design goals for Therapeutic Discovery.
  • Automated analysis and reporting of common PKDM-related tasks (non-compartmental analysis, GLP-tox study design, etc.) run completely in free software (R) with web-based interfaces (Shiny).
  • Created workshop in R focusing on software and analysis techniques in the context of preclinical drug development.

Senior Scientist, Medical Sciences (2013-2016)

Translational modeling support

  • Provided the modeling support to combine indication specific parameters in non-human primates with human response to G-CSF to identify dosing regimens to support sBLAs for Acute Radiation Syndrome for Neupogen and Neulasta using the animal rule.
  • Mentored new project representatives in PKDM and CPMS with a focus on developing preclinical programs to support clinical advancement.
  • Managed and coordinated the outsourcing of project components to bring new knowledge and capabilities in house and make filing deadlines.
  • Developed translational modeling and simulation strategies for FIH dose projections to identify drugability liabilities.

Pfizer (2010-2013)

Principal Scientist, Systems Pharmacology (2010-2013)

Pfizer Inc, Pharmacokinetics Dynamics and Metabolism (PDM), Andover/Cambridge (2010-2013)

Provide modeling support for drug candidates from early discovery through Phase I

  • Incorporation of in vitro and in vivo data into systemic models of drug disposition and efficacy on indications spanning the Inflammatory & Autoimmunity, and Orphan & Genetic Diseases Research Units as well as the Centers for Therapeutic Innovation (Boston and La Jolla).
  • Provided modeling and simulation support to 15 project teams including: experimental design for parameter identification; linking physiology and pharmacology to provide comparative analysis of competitor compounds (both approved and in development) to ensure differentiability; analysis of different strategies to guide project teams in deciding which modality, technology, etc. to employ. -Developed a model generation system allowing description of models with simple text files that could then be used to create models in several formats (Matlab, ADAPT, Monolix, Berkeley Madonna, etc.) this included: a deployable GUI to be used by project teams, PDM project representatives, and analytical scientists; facilitated the transfer of models to the Clinical Pharmacology group when the project moves forward; makes models available to others within PDM in languages they are familiar with.
  • Created tools for bioanalytical scientists to promote assay development by quantifying aspects such as the effect of sample impurities on measurements, characterizing anti-drug antibody response, and the affinity and concentration of neutralizing antibodies.
  • Participated in due diligence teams by evaluating preclinical and clinical data identifying risks associated with in- licensing and asset acquisition.
  • Mentored interns, both within PDM and in the clinical pharmacology group, developing systems models to support projects in both early stage development as well as compounds currently in the clinic.

Center for Protein Therapeutics, Pharmaceutical Sciences Department, SUNY Buffalo (2008-2010)

Postdoctoral Fellow

Developed multi-scale PKPD models of combination therapy for monoclonal antibody systems

  • Developed qualitative and quantitative models of signal transduction in B-cell lymphomas based on in vitro CD20 agonist data.
  • Created mechanistic PKPD model of single agent efficacy in mice that when modulated by the signal transduction model was capable of predicting the synergistic effects of two different combination regimens.
  • Mentored and trained graduate students in various aspects of modeling and simulation associated with PKPD systems.

US State Department, Peace Corps (2005-2007)

Peace Corps Volunteer in Samoa

Visiting lecturer in the Science Department at the National University of Samoa

  • Developed the curriculum for current courses in cellular and molecular biology, plant and animal physiology, and environmental chemistry.
  • Created new upper level physics courses in environmental physics and energy supplies which complemented the current
  • program in environmental science and allowed the creation of physics minor.
  • Provided training and teaching material to secondary school biology teachers preparing highschool level students for regional qualifying exams.

University of Pittsburgh, Department of Chemical Engineering (2000-2005)

Doctoral Candidate, Advisor: Prof. Robert S. Parker

Model–Based Design of Cancer Chemotherapy Treatment Schedules

  • Developed nonlinear pharmacokinetic and pharmacodynamic models of 9-Nitrocamptothecin in severe combined immunodeficient (SCID) mice bearing subcutaneously implanted HT29 human colon xenografts.
  • Designed a control algorithm which balanced the need to reduce tumor burden and avoid toxic side effects without violating clinical constraints to provide clinically relevant cancer chemotherapy drug schedule.
  • Ensured clinical relevance of results by interacting regularly with collaborators from several fields including clinical oncologists, animal pharmacologists, and technicians.

University of Arkansas, Fayetteville AR, Department of Chemical Engineering (1998-2000)

Graduate Student Researcher, Advisor: Prof. Robert R. Beitle

Using Optical Tweezers to Determine the Suitability of Chromatography Packing

  • Created actuators by covalently anchoring proteins to the surface of chemically active microspheres.
  • Designed a methodology to rapidly evaluate the suitability of chromatography packing while minimizing the amount of protein required for the evaluations.
  • Methodology refined to minimize the economic costs associated with developing protein purification procedures for expensive therapeutic proteins.

Education

Ph.D., Chemical Engineering, University of Pittsburgh, Pittsburgh, PA August 2005

M.S., Chemical Engineering, University of Arkansas, Fayetteville, AR August 2000

B.S., Chemical Engineering, University of Arkansas, Fayetteville, AR August 1998

Tool Development

Develop and maintain the ubiquity modeling and simulation tools to support model development and deployment in heterogeneous environments (2014-present).

Maintain the {ubiqiuty} R package, a complete modeling and simulation workflow to support preclinical and translational drug development (2017-present).

Maintain the {onbrand} R package, Automated reporting in Word and PowerPoint can require customization for each organizational template (2020-present).

Maintain the {nlmixr2rpt} R package, Generate reporting workflows around {nlmixr2} analyses with outputs in Word and PowerPoint (2020-present).

Maintain the {ruminate} R package, A pharmacometrics data transformation and analysis tool (2022-present).

Maintain the {formods} R package, Set of Shiny modules for general tasks (2022-present).

Member of the {nlmixr2} development team.

Publications

  • Liu, Shufang, Yingyi Li, Zhe Li, Shengjia Wu, John M. Harrold, and Dhaval K. Shah 2024. “Translational Two-Pore PBPK Model to Characterize Whole-Body Disposition of Different-Size Endogenous and Exogenous Proteins.” Journal of Pharmacokinetics and Pharmacodynamics, ahead of print, May. https://doi.org/10.1007/s10928-024-09922-x.
  • Kondic, Anna, Dean Bottino, John Harrold, et al. 2022. “Navigating Between Right, Wrong, and Relevant: The Use of Mathematical Modeling in Preclinical Decision Making.” Frontiers in Pharmacology 13. https://www.frontiersin.org/articles/10.3389/fphar.2022.860881.
  • Selvaggio, Gianluca, Silvia Parolo, Pranami Bora, et al. 2022. “Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model.” Frontiers in Oncology 12. https://www.frontiersin.org/articles/10.3389/fonc.2022.818641.
  • Pham, Elizabeth, Matthias Friedrich, Famke Aeffner, et al. 2021. “Preclinical Assessment of a MUC12-Targeted BiTE (Bispecific T-Cell Engager) Molecule.” Molecular Cancer Therapeutics 20 (10): 1977–87. https://doi.org/10.1158/1535-7163.MCT-21-0236.
  • Lu, Shu-Chen, Michelle Chen, Larissa Atangan, et al. 2021. “GIPR Antagonist Antibodies Conjugated to GLP-1 Peptide Are Bispecific Molecules That Decrease Weight in Obese Mice and Monkeys.” Cell Reports Medicine, April, 100263. https://doi.org/10.1016/j.xcrm.2021.100263.
  • Harrold, John, Per Olsson Gisleskog, Juan Jose Perez-Ruixo, et al. 2020. “Prediction of Survival Benefit of Filgrastim in Adult and Pediatric Patients with Acute Radiation Syndrome.” Clinical and Translational Science 13 (4): 807–17. https://doi.org/https://doi.org/10.1111/cts.12777.
  • Harrold, John, Per Olsson Gisleskog, Isabelle Delor, et al. 2020. “Quantification of Radiation Injury on Neutropenia and the Link Between Absolute Neutrophil Count Time Course and Overall Survival in Nonhuman Primates Treated with G-CSF.” Pharmaceutical Research 37 (6): 102. https://doi.org/10.1007/s11095-020-02839-3.
  • Melhem, Murad, Delor, Isabelle, Perez-Ruixo, Juan Jose, et al. 2018. “Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.” British Journal of Clinical Pharmacology 18 (9 Suppl): 529–15.
  • Krzyzanski, Wojciech, John M Harrold, Liviawati S Wu, and Juan Jose Perez-Ruixo 2016. “A Cell-Level Model of Pharmacodynamics-Mediated Drug Disposition.” Journal of Pharmacokinetics and Pharmacodynamics 43 (5): 513–27.
  • Tiwari, Abhinav, Anson K Abraham, John M Harrold, Anup Zutshi, and Pratap Singh 2016. “Optimal Affinity of a Monoclonal Antibody: Guiding Principles Using Mechanistic Modeling.” The AAPS Journal In Press.
  • Krzyzanski, Wojciech, Juan Jose Perez-Ruixo, and John Harrold 2015. “Pharmacodynamic Model for Chemoradiotherapy-Induced Thrombocytopenia in Mice.” Journal of Pharmacokinetics and Pharmacodynamics EPUB: 1–12.
  • Chudasama, Vaishali L, Anup Zutshi, Pratap Singh, Anson K Abraham, Donald E Mager, and John M Harrold 2015. “Simulations of Site-Specific Target-Mediated Pharmacokinetic Models for Guiding the Development of Bispecific Antibodies.” Journal of Pharmacokinetics and Pharmacodynamics 42 (1): 1–18.
  • Harrold, John M, and Anson K Abraham 2014. “Ubiquity: A Framework for Physiological/Mechanism-Based Pharmacokinetic/Pharmacodynamic Model Development and Deployment.” Journal of Pharmacokinetics and Pharmacodynamics 41 (2): 141–51.
  • Dwivedi, G, L Fitz, M Hegen, et al. 2014. “A Multiscale Model of Interleukin-6–Mediated Immune Regulation in Crohn’s Disease and Its Application in Drug Discovery and Development.” CPT: Pharmacometrics & Systems Pharmacology 3 (1): e89.
  • Harrold, Jm, M Ramanathan, and D E Mager 2013. “Network-Based Approaches in Drug Discovery and Early Development.” Clinical Pharmacology and Therapeutics, September.
  • Harrold, John M, Robert M Straubinger, and Donald E Mager 2012. “Combinatorial Chemotherapeutic Efficacy in Non-Hodgkin Lymphoma Can Be Predicted by a Signaling Model of CD20 Pharmacodynamics.” Cancer Research, March.
  • Vugmeyster, Yulia, John Harrold, and Xin Xu 2012. “Absorption, Distribution, Metabolism, and Excretion (ADME) Studies of Biotherapeutics for Autoimmune and Inflammatory Conditions.” The AAPS Journal 14 (4): 714–27.
  • Chudasama, V L, F Schaedeli Stark, J M Harrold, et al. 2012. “Semi-mechanistic population pharmacokinetic model of multivalent trastuzumab emtansine in patients with metastatic breast cancer.” Clinical Pharmacology and Therapeutics 92 (4): 520–27.
  • Vugmeyster, Yulia, Qin Wang, Xin Xu, et al. 2012. “Disposition of Human Recombinant Lubricin in Naive Rats and in a Rat Model of Post-traumatic Arthritis After Intra-articular or Intravenous Administration.” The AAPS Journal, January.
  • Kagan, Leonid, Anson K Abraham, John M Harrold, and Donald E Mager 2010. “Interspecies Scaling of Receptor-Mediated Pharmacokinetics and Pharmacodynamics of Type I Interferons.” Pharm Res, March.
  • Zhou, R, R Mazurchuk, J Tamburlin, J Harrold, D Mager, and R Straubinger 2009. “Differential Pharmacodynamic Effects of Paclitaxel Formulations in an Intracranial Rat Brain Tumor Model.” J Pharmacol Exp Ther, October.
  • Harrold, J, and R Parker 2009. “Clinically Relevant Cancer Chemotherapy Dose Scheduling via Mixed-Integer Optimization.” Computers and Chemical Engineering, January.
  • Parker, J. M. Harrold AND R. S. 2006. Clinically–Relevant Cancer Chemotherapy Treatment Scheduling Using Parameterized Mixed–Integer Programming. CACHE Corporation.
  • Harrold, J. M., and J. L. Eiseman AND E. Joseph AND S. Strychor AND W. C. Zamboni AND R. S. Parker 2005. “Control-Relevant Modeling of the Antitumor Effects of 9-Nitrocamptothecin in SCID Mice Bearing HT29 Human Colon Xenografts.” Journal of Pharmacokinetics and Pharmacodynamics 32: 65–83.
  • Parker, R. S., J. M. Harrold, J. L. Eiseman, et al. 2004. “Toward Model-Based Chemotherapy Treatment Design.” Edited by D. Z. D’Argenio. Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis, Volume III. Kluwer Academic Publishers.

Posters & Presentations

  • Patilea-Vrana, Gabriela, John Harrold, Joseph A. Ware, et al. 2023. “Abstract 5668: Using Clinical Utility Index (CUI) to Determine the Optimal Biological Dose of a Nonfucosylated Anti-TIGIT Antibody: A Proposed Alternative to Maximum Tolerated Dose (MTD).” Cancer Research 83 (7_Supplement): 5668. https://doi.org/10.1158/1538-7445.AM2023-5668.
  • Andrews, Elizabeth T., Stephanie C. Casey, Mohammad Farhad Amani, et al. 2022. “Abstract 6251: Evaluation of a Dual-Targeting BCMA-CS1 HLE BiTE® Molecule for Multiple Myeloma.” Cancer Research 82 (12_Supplement): 6251. https://doi.org/10.1158/1538-7445.AM2022-6251.
  • Li, Cong, Madeline Fort, Lingming Liang, et al. 2020. “718 AMG 509, a STEAP1 x CD3 Bispecific XmAb® 2+1 Immune Therapy, Exhibits Avidity-Driven Binding and Preferential Killing of High STEAP1-Expressing Prostate and Ewing Sarcoma Cancer Cells.” Journal for ImmunoTherapy of Cancer 8 (Suppl 3): A430–30.
  • Bailis, Julie M., Petra Lutterbuese, Oliver Thomas, et al. 2020. “Abstract 3364: Preclinical Evaluation of BiTE®immune Therapy Targeting MUC17 or CLDN18.2 for Gastric Cancer.” Cancer Research 80 (16_Supplement): 3364. https://doi.org/10.1158/1538-7445.AM2020-3364.
  • Harrold, John M 2019. “Leveraging Preclinical and Historic Clinical Data to Obtain Approval of G-CSF Treatments for Acute Radiation Syndrome Under the Animal Rule.” AAPS.
  • Ma, Lian, Luning Zhuang, Gene M Williams, et al. 2016. “Dosing Regimen Selection under the Animal Rule for Pegfilgrastim to Treat Patients with Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS).” ACoP.
  • Tiwari, Abhinav, Anson K Abraham, John M Harrold, Anup Zutshi, and Pratap Singh 2016. “Optimal Affinity of a Monoclonal Antibody: Guiding Principles Using Mechanistic Modeling.” AAPS:NBC, T2068.
  • Ma, L, GM Williams, Y Ouyang, et al. 2016. “Patients With Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS): Considerations on the Dose Selection for Filgrastim Under the Animal Rule.” ASCPT 99: S50–50.
  • Harrold, John M, Per Olsson Gisleskog, Isabelle Delor, et al. 2015. “Quantitative Characterization of the Effects of Acute Radiation and Treatment with Filgrastim (Neupogen) on Absolute Neutrophil Counts and Overall Survival in Non-Human Primates.” ACoP.
  • Abuqayyas, Lubna, and John M Harrold 2015. “A General Method for Initialization of Steady-States in Complex PK/PD Systems.” ACoP.
  • Wu, Liviawati, Wojciech Krzyzanski, Juan Jose Perez-Ruixo, and John M Harrold 2015. “Cell-Level Model of Pharmacodynamics-Mediated Drug Disposition: Application to Filgrastim (Neupogen).” ACoP.
  • Zhao, Xiaochen, John M Harrold, Leonid Kagan, Robert M Straubinger, and Donald E Mager 2013. “Predicting Combinatorial Efficacy of Rituximab and Doxorubicin in Non-Hodgkin Lymphoma Xenografts.” ACoP.
  • Harrold, John M 2011. “A Model for Combination Rituximab Therapy Based on Receptor Occupancy Driven Molecular Signal Transduction in Non-Hodgkin’s Lymphoma.” ACoP.
  • Mager, Donald E, and John M Harrold 2010. “Mechanistic Exposure-Response Model of Combination Rituximab Chemotherapy in Murine Lymphoma Xenografts.” The FASEB Journal.
  • Harrold, John M, and Donald E Mager 2009. “Mechanistic Modeling of Combination Rituximab and rhApo2L Chemotherapy in Mice Bearing Ramos Lymphoma Xenografts.” ACoP.
  • Parker, J. M. Harrold AND R. S. 2004. “An MILP Approach to Cancer Chemotherapy Dose Regime Design.” Proc. American Control Conf. (Boston, MA), Paper WeM10.5.
  • Harrold, J. M., J. L. Eiseman, W. C. Zamboni, and R. S. Parker 2004. Modeling of Toxicity Effects and Nonlinearities in Pharmacokinetics of 9-Nitrocamptothecin in Mice. Austin, TX.
  • Harrold, J. M., and R. S. Parker 2003. A Model–Based Approach to Chemotherapy Treatment Design. Case Western Reserve Cancer Center/University of Pittsburgh Cancer Institute/Josephine Ford Cancer Center Annual Research Collaboration Meeting.
  • Harrold, J. M., J. L. Eiseman, W. C. Zamboni, and R. S. Parker 2003. A Clinically Relevant Mixed Integer Approach to Cancer Chemotherapy Treatment Design. Paper 478a. San Francisco, CA.
  • Parker, J. M. Harrold AND J. L. Eiseman AND W. C. Zamboni AND Robert S 2002. A Pharmacokinetic/Pharmacodynamic Model of Cancer Chemotherapy in SCID Mice. Paper 347a. Indianapolis, IN.