THE THESIS - September 12, 2015.

“Egyes szakértők szerint 10 éven belül valóra válhatna az a még kissé futurisztikusnak tűnő kép, hogy mindenkiről egy genetikai polimorfizmus adattár áll rendelkezésre mondjuk a háziorvosnál, az beírja a komputerébe, hogy milyen hatású gyógyszert szeretne felírni az adott betegnek, majd a gép megadja, hogy melyik konkrét gyógyszer vagy gyógyszerek a leghatásosabbak, vagy lesz a legkevesebb, és legkevésbé veszélyes mellékhatásuk az

adott genetikai mintázattal rendelkező betegnél.”1

Prof. Dr. Szalai CsabaSemmelweis Egyetem, Általános orvostudományi Kar,

Genetikai, Sejt - és Immunbiológiai Intézet Intézetvezető helyettes

1. According to publication of Prof. Dr. Csaba Szalai (http://gyogyhirek.hu/farmakogenomika-a-jovo-igerete/)

Judit AlföldiInvenshure Hungary LLC.

OUTLINE

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About Invenshure and Invenshure Hungary LLC.

DEFINITIONS

● Genetics - the study of genes and genetic variation - mostly one gene

● Genomics - study of the whole genome - mostly more than one gene

● Pharmacogenetics - the study of the role of genetics in drug response - mostly one gene

● Pharmacogenomics - the study of the role of genetics in drug response - mostly more than one gene

GOALS OF PHARMACOGENOMICS

● Drug discovery and development

● Reveal adverse drug reaction

PHARMACOGENOMICS

Human genome project (1999-2003) 1

~ 3 300 000 000 DNA base pairs~ 20.000 genes~ 400 are target genes for drugs~ 23 genes covering around 340 drugs

1. http://www.ensembl.org/Homo_sapiens/Info/StatsTable

THE PROBLEM - DRUGS

>4 Billion 1

~48% Do not work as intended2

>95% of drug - response variability and susceptibility depends on genetic factors

1. According to IMS Institute for Healthcare Informatics2. Spear BB, Heath-Chiozzi M, Huff J. Trends Mol. Med.7, 201–204 (2001).

THE PROBLEM - ADR’s

NIH estimates ADR’s account for as much as● ~7% of all admissions● > 20% readmissions

● 4th leading cause of death● > $130B the annual cost of ADR’s (estimated

by the FDA) 1

1. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm110632.htm

OUR MISSION

Provide the ● Most Cost-effective, ● Comprehensive,● Personalized,Pharmacogenomics analysis that identifies optimal drug therapy for individual Patients.

OUTLINE - STEP

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About Invenshure and Invenshure Hungary LLC.

PATIENT’S PERSPECTIVE

STEP 1:Doctor orders the

test

STEP 2:Patient provides

cheek swab sample

STEP 3:Patient or doctor activates the kit

online

STEP 4:OneOme processes the sample & returns report to the doctor

OneOme video

OUTLINE - STEP

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About Invenshure and Invenshure Hungary LLC.

OneOme REPORT - USE WITH CAUTION

Content:● Patient’s personal information● Main categories with those drugs which

must be used with great caution according to patient’s genotypes

● Main categories with those drugs which must be used with caution according to patient’s genotypes

● L1, SL, SH, T marks

OneOme REPORT - USE AS DIRECTED

Content:● Main categories with those drugs which

can be used as directed according to patient’s genotypes

OneOme REPORT - GENOTYPES

Content:● Genes with their genotypes which might

affect phenotype and metabolism,○ metabolism (CYP) could be normal,

decreased or increased○ Genotype might cause normal

response or increased risk in phenotype

○ CYP3A4, CYP3A5, CYP2C9, CYP2D6

OneOme REPORT - CYP ENZYMES

Content:● CYP enzymes are encoded by CYP

genes responsible for metabolism and elimination of clinically used drugs

● CYP enzymes could be inducers or inhibitors

● Relation between examined drugs and CYP enzymes are shown in the list

OUTLINE - STEP

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About Invenshure and Invenshure Hungary LLC.

THE WEB PORTAL

Provides a web interface for ○ Institution (Institutional teams),○ Providers,○ Patients

to○ View,○ Order,○ Activate,○ Interact

with the report of genetic result.

THE WEB PORTAL - SIGN IN

● Different login form for○ Provider,○ Patient and○ Admin

● User Session management provided by Flask-Login

● OAuth2 authentication for Admins (LIMS, Scientists)

● Password meets HIPAA regulations

● Users are stored in database

THE WEB PORTAL - ORDERS

● List all orders associated with Provider’s clinical team

● The list is searchable● The doctor can

○ create an order,○ review an order,○ manage an order and○ interact with the result of the

PGx report.

THE WEB PORTAL - ORDER STATUSES

● Each orders has statuses,○ Test ordered○ Payment pending / received○ Kit shipped ( if necessary )○ Kit activated○ Arrived at laboratory○ Sample is processing○ Report generated

● Doctor can○ Download the generated report,○ Explore the generated report (Drug explorer)

THE WEB PORTAL - DRUG EXPLORER

● Drugs are grouped by diseases● List drugs which are correspond to

the patient’s PGx Report● Search and add drugs by name or

indication● Search and review patient’s

Medication history provided by SureScripts

● Indications are marked with icons● Possibility to generate report

THE WEB PORTAL - DRUG ALTERNATIVES

● Drug overview explains the reason of caution● Offers alternatives of the selected drug,

○ Use as directed,○ Use with caution○ Use with great caution

● Possibility to add alternative drugs to drug list

THE WEB PORTAL - DRUG TO DRUG INTERACTION

● Drug / Drug interaction information from Wolters Kluwer database

● Summary view of all drug / drug interactions

● Detailed view of each drug / drug interaction

OUTLINE - STEP

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About InvenShure and Invenshure Hungary LLC.

TECHNICAL BACKGROUND - ENVIRONMENTS

● Development○ Local environment○ Docker-compose / Docker○ MariaDb

● Staging / Testing and Production○ Cloud environment (Amazon services)

■ Elastik (Load Balancer)■ Private Subnet for Web portal■ RDS for MariaDB

THE SYSTEM

● Web portal with LIMS (Laboratory Information Management System) are the basic interfaces

● Salesforce is a CRM● BrainTree responsible for

payments● SureScripts responsible for

medication history● Databases

THE WEB PORTAL - SOFTWARE INFRASTRUCTURE

● Utilizes the Python 3 framework and uses MariaDB● Uses the following packages

○ Flask - a microframework for Python based on Werkzeug, Jinja 2○ Flask-Bootstrap - HTML, CSS, and JavaScript framework for Flask○ Flask-Login - provides user session management for Flask○ Flask-Mail - provides an interface to set up SMTP and send messages○ Flask-OAuth2-Login○ Flask-Script - provides support for writing external scripts in Flask○ Flask-SQLAlchemy - adds support for SQLAlchemy○ Flask-Admin - provides support to building an admin interface on top of

an existing data model○ SQLAlchemy - Python SQL toolkit and Object Relational Mapper ○ WTForms, Jinja2 , NodeJs

OUTLINE - STEP

● Introduction ● OneOme solution - Patient's perspective● OneOme Pharmacogenomics Report (PGx)● OneOme solution - Doctor's perspective● Technical background● About Invenshure and Invenshure Hungary LLC.

THE COMPANY

QUESTIONS?

Confidential. OneOme 2016.