This document discusses harnessing quantitative systems pharmacology to deliver personalized medicine through the Microphysiology Systems Database (MPS-Db). The MPS-Db is presented as a solution for aggregating, analyzing, sharing, and modeling in vitro data from microphysiology systems (MPS) to accelerate drug development and implementation of personalized medicine approaches. Key features and capabilities of the MPS-Db are described, including supporting various model types, integrating with other databases, and performing data analysis, reproducibility evaluation, and computational modeling. Commercial and non-profit versions are discussed.

1. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Microphysiology,Systems,Database,(MPS6Db)
Non6Profit,and,Commercial,Versions
1
Mark,Schurdak,,PhD
Associate)Professor
Director)of)Operations
University)of)Pittsburgh)Drug)
Discovery)Institute
Bert,Gough,,PhD
Associate)Professor
Director)of)Informatics
University)of)Pittsburgh)Drug)
Discovery)Institute
D.,Lansing,Taylor,,PhD
Distinguished)Professor
Director
University)of)Pittsburgh)Drug)
Discovery)Institute
The,Microphysiology Systems,Database,(MPS6Db):
A"platform"for"aggregating,"analyzing,"sharing"and"
computationally"modeling"in"vitro"data
https://mps.csb.pitt.edu/

2. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Disclosure
2
Biosystics launched/in/Sept/2021/to/
sustain/the/public/MPS8Db/through/commercialization
I+am+an+officer+and+shareholder+of+BioSystics
Delivering+Actionable+Knowledge+That+Advances+Human+Health+and+Safety

3. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Agenda
3
• Introduction*to Microphysiology Systems*(MPS)*8 The*challenges
• Overview*of*the*MPS*Database*(MPS8Db)*– The*solution
• Live*tour*of*the*MPS8Db
• New*Portal*concepts
• Feedback*and*Discussion

4. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Level%of%Human%In#Vitro#Biomimetic%Structure/Function%
Static%
2D%Culture
Organoids%in%
Fluidic%MPS%
Static
Organoids
Integrated,%Fluidic%
Organ%MPS
Growing%and%Evolving%Live%Cell/Tissue%Experimental%Models%
That%Are%Applied%to%ADMEHTox and%Diseases%With%“Fit%for%Purpose”
Biomimetic,%
Fluidic%MPS
MPS%are%miniaturized%functional%models%of%organs%constructed%from%multiple%cell%types,%including%cell%lines,%primary%cells%or
pluripotent%stem%cells%from%human%or%animal%sources,%either%by%selfHassembly%or%supervised%organization%in%3D,%that%also%
includes%some%environmental%cues.
Static%
3D%Spheroids
Taylor'DL,'Gough'A,'Schurdak'ME,'Vernetti'et.al.''In:'Handbook'of'Experimental'Pharmacology.'2019.

5. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Disease&Models
ADME-TOX&Models
Selection&of&Cohorts&for&
Clinical&Trials….
The$Future$Is$Patient/Specific$Stem$Cells$to$Build$“You/on/a/Chip”
Creating&individualized&
human&organ&disease&and&
ADME-TOX&models

6. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine 6
The$Status$of$the$Field$of$MPS$and$the$New$Challenge$
Status$of$the$MPS$Field
We$now$have$a$large$and$growing$selection$of$more$powerful$In#Vitro#models$for$ADME@TOX$
and$diseases$that$are$beginning$to$generate$increasing$amounts$of$data$from$exploring$model$
variables$(e.g.$cells,$media,$matrices,$etc)$to$testing$safety$and$efficacy$of$therapeutics
New$Challenge
Ability$to$acquire,$manage,$analyze$and$share$data$and$metadata,$determine$reproducibility$of$data,$
compare$results$between$different$models$and$treatments,$integrate$data$from$other$databases$
(e.g.$animal$pre@clinical$data$and$drugs),$and$computationally$model$data$to$create$new$knowledge

7. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Model&Types&Supported&
In&the&MPS3Db
• 2D#microplates
• static#spheroids
• static#organoids
• microfluidic#organoids
• static#biomimetic
• microfluidic#biomimetic
• coupled#organs
• human6on6a6chip#
• human#and#animal#cell6
based#models
7
ChEMBL,&
Unichem,&
DrugBank
OpenFDA,
NAMCS/NHAMCS
Preclinical&Data
PubChem
EMA,&CT.gov,
Health&Canada
LiverTox
Clinical&&Data
Proprietary&Databases&
and&Tools
The&Solution&Is&the&MPS3Db:&
An&Integrated&Database,&Analytics&and&Modeling&Platform
MPS&Data
Output
Safety&and&Efficacy
Computational Models&of
ADME/Tox &&Disease&&
Reproducibility

8. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Accelerate(the(development(and(implementation(of(MPS(models
1. Explore*existing*experimental*models*(MPS),*metadata*and*data*on*growing*list*of*organs
2. Guide*the*design,*development*and/or*implementation*of*an*experimental*model*
3. Share*experimental*data*and*metadata*within*defined*groups
Manage(data(and(metadata(for(MPS(studies
1. Manage*large*experimental*data*sets*from*many*chips*or*plates*in*an*experimental*study
2. One*stop*location*for*all*data,*information*and*knowledge*on*experimental*models
3. Manage*drug*testing*results*for*efficacy*and*ADMEHTOX
Analyze(data,(evaluate(reproducibility,(and(establish(preclinical(and(clinical(concordance
1. Analyze*experimental*parameters*tested*and*link*to*specific*experiment/study
2. Harness*data*and*external*database*information*for*computational*modeling*of*disease*progression*and*ADMEHTOX
3. Determine*reproducibility*of*experimental*models*within*and*between*between*experiments/studies*
4. Compare*data*from*animal*ADMEHTOX*and*Disease*models*with*animal*and*human*MPS*models
Why(Does(the(Field(Need(the(MPS@Db?(
8

9. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Accelerate(the(development(and(implementation(of(MPS(models
1. Explore*existing*experimental*models*(MPS),*metadata*and*data*on*growing*list*of*organs
2. Guide*the*design,*development*and/or*implementation*of*an*experimental*model*
3. Share*experimental*data*and*metadata*within*defined*groups
Manage(data(and(metadata(for(MPS(studies
1. Manage*large*experimental*data*sets*from*many*chips*or*plates*in*an*experimental*study
2. One*stop*location*for*all*data,*information*and*knowledge*on*experimental*models
3. Manage*drug*testing*results*for*efficacy*and*ADMEHTOX
Analyze(data,(evaluate(reproducibility,(and(establish(preclinical(and(clinical(concordance
1. Analyze*experimental*parameters*tested*and*link*to*specific*experiment/study
2. Harness*data*and*external*database*information*for*computational*modeling*of*disease*progression*and*ADMEHTOX
3. Determine*reproducibility*of*experimental*models*within*and*between*between*experiments/studies*
4. Compare*data*from*animal*ADMEHTOX*and*Disease*models*with*animal*and*human*MPS*models
Why(Does(the(Field(Need(the(MPS@Db?(
9

10. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine 10
The$MPS(Db$Is$a$Single$Entry$System$Guiding$Users$Along$a$Simple,$Streamlined$
Workflow$to$Design,$Create,$Implement,$Analyze,$and$Document$MPS$Studies
Study$Design
and$Creation
Drug%Trials
Adverse%Events,%…
Simple%menus%facilitate%
metadata%entry%for%study%
details
Study$Implementation$
and$Data$Import
Setting%up%chips%or%
plates
Data%import,%
calibration%and%review%
tools
Data$Normalization$
And$Analysis
Graphing%and%Analysis
Intra@ &%Inter@
Reproducibility%Analysis
Statistics$and$Data$Modeling
One%and%Two%sample%Power%
Analysis
PBPK%Computational%
Modeling
Sharing$Data
Non@Profit%sharing%
options.
For@profit%sharing%
options.

11. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine 11
We#Formed#BioSystics#to#Develop#and#Market#a#
Commercial#Version#of#The#MPS>Db
For$companies$developing$and/or$using$MPS$experimental$models:
• Pharmaceutical.companies
• Biotech.companies
• Contract.Research.Organizations
For$proprietary$company$projects:
• Installation.behind.the.company$firewall
• Integration.with.company$databases
• Development.of.custom$features
Selected$data$can$easily$be$copied$to$the$public$MPS?Db$for$sharing$with$
collaborators$or$the$general$public.
! BioSystics$commercial$revenues$will$sustain$and$support$the$public$MPS?Db

12. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine 12
https://mps.csb.pitt.edu/
Objectives*of*the*Demonstration
• Introduce3the3website3Home3page,3navigation3and3workflow
• Viewing3models3
• Components3used3in3setting3up3studies
• How3to3review3studies3and3their3content
• Overview3of3Data3Analysis3tools
• Reproducibility,3power3analysis,3cytokines,3gene3expression
• Introduction3to3computational3modeling3features
• PK3Analysis
• Quick3tour3of3the3COVIDH193portal

13. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Stem%Cell%Portal%– Key%Feature%Is%a%List%of%Available%Stem%Cells,%Normal%
and%With%Disease%Specific%Mutations,%Including%Engineered%Cells
13
Stem%Cell%Information%Portal%
Stem Cell Centers
Biology Stem Cells Disease Models
• A"resource"for"finding"available"stem"cells,"for"use"in"the"development"of"MPS"Disease"models
• Includes%characteristics,%protocols,%mutation%status,%engineered%features%and%current%applications%of%specific%stem%cell%lots
• Follows"design"of"other"portals"for"ease"of"use
• Includes"profiles"of"Stem"Cell"Centers"that"can"be"filled"and"edited"by"the"Stem"Cell"Center"PI"or"their"designate

14. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
MPS$Preclinical$Trial$Portal$– Key$Features$Are$a$List$of$Preclinical$Trials
and$Available$Disease$Specific$Cohorts$of$Patient$Derived$Cells$
14
MPS$Preclinical$Trial$Information$Portal$
MPS Preclinical Centers
Biology Preclinical Trials
• A"resource"for"designing"and"implementing"MPS6based"preclinical"trials"for"drug"repurposing"and"discovery
• Compilation$of$MPS$preclinical$trials$(similar"to"clinicaltrials.gov,"but"more"like"AACT"(the"Clinical"Trials"Transformation"Initiative)
• Key$components$include$disease$specific$cohorts$of$patient$derived$primary$and$stem$cells$
• Follows"design"of"other"portals"for"ease"of"use
• Includes"profiles"of"centers"that"are"currently"implementing,"or"have"completed"a"preclinical"trials,"that"can"be"edited"by"the"center"
administrator

15. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Login,'Explore,'And'Provide'Feedback'On'The'MPS<Db
Login/Register
• https://mps.csb.pitt.edu
Please'provide'feedback,0
• Feedback0function0
• email0to0
• MPSHELP@pitt.edu
• gough@pitt.edu
15

16. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Schedule(an(Individual(Interactive(Online(Training:
16
•Feedback(function(
•email(to(
MPSHELP@pitt.edu
gough@pitt.edu

17. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Applications+Development+and+
Support+Team
Lawrence(Vernetti– Toxicologist,+Database+Applications
Joe(Maggiore(– Clinical+and+Commercialization
Aamil Shah(– Commercialization
Kathrin(Gassei(< Commercialization
Harold(Takyi(– Information+Systems+Manager+
Amanda(Maleski(– Administration+Manager
17
Core+Development+Team
Mark(Schurdak(–Multi<PI
Bert(Gough(– Multi<PI
Lans(Taylor@Multi<PI
Celeste(Reese(–Project+Manager
Larry(Peng(Zhang(– Software+Development+Manager
Luke(Bergenthal(– Database+Developer
Quinn(Wolter– Database+Developer
Sandra(Karcher(– Data+Analyst/Modeler
Mike(Castiglione(– Data+Analyst
Dillon(Gavlock(– Data+Analyst
Tongying Shun(– Lead+Statistician,+DBA
The(MPS@Db(Team
17

18. Harnessing Quantitative Systems Pharmacology to Deliver Personalized Medicine
Opportunities+for+Collaboration
• Adding&data&from&experimental&models&in&development&or&use&
at&the&NIDDK
• Adding&or&accessing&data&from&animal&models&and&clinical&trials
• What&would&you&like&to&see&in&the&MPSADb?
18