2016_may dotmatics ugm bob coner

4 Years In – How A Biotechnology Company Has Grown In Its Use Of

Dotmatics

Robert ConerMay 2016

May 20162NOT CONFIDENTIAL

Agenda

• Where we started• How we use Dotmatics now

– Design– Synthesis & Purification– Sample Logistics– Screening/Testing

• Extending Dotmatics Example


A Drug Discovery and Development CompanyOncology focused

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• World class scientific founder and experienced drug discovery team• Novel oncology project pipeline based on innovative science• Strong funding and venture capital support

• Commenced operation in August 2011• Based at the BioCenter in UTSW Dallas• More information at

http://pelotontherapeutics.com


Experienced Scientific and Business Team

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Multidisciplinary Drug Discovery Team• 33 employees, 17 Ph.D. level scientists, >100 years drug discovery experience• Scientific team members have delivered over 20 new chemical entities into

human clinical trials

Scientific Advisory BoardMichael S. Brown, M.D. Ralph J. DeBerardinis, M.D., Ph.D.William G. Kaelin, Jr., M.D. Thomas J. Kelly, M.D., Ph.D.David H. Johnson, M.D., F.A.C.P. Steven L. McKnight, Ph.D.

Board of DirectorsJohn CreecyDavid V. Goeddel, Ph.D.Leo Guthart, Ph.D.Tim Kutzkey, Ph.D.Frank McCormick, Ph.D.Brett Ringle, J.D.

Scientific CollaboratorsSally Comerford, Ph.D.Rick Bruick, Ph.D.Kevin Gardner, Ph.D.Robert Hammer, Ph.D.Ben Tu, Ph.D.

ManagementJohn Josey, Ph.D.James Rizzi, Ph.D.Eli Wallace, Ph.D.Michael Bakes, PMPNaseem Zojwalla, M.D.Tai Wong, Ph.D.


Where we started

Registry & Materials Inventory in Excel

Data Analysis inGraphpad

Data Shared inPowerPoint and stored on File Share

Paper notebooks for IP capture


Transitioning to Dotmatics

• Convert existing Excel file to SD file and Load with Register

• Start using ChemELN and Register compounds from there

• Setup assay data analysis protocols and start using Studies. Use BioELN to capture experiments.

• Use Browser to query and analyze data


Growth over time

• Use Nucleus to load HTS data and Vortex to analyze

• Added new projects• Added new assay data analysis protocols• “Side loaded” DMPK data• Barcode all reagent and sample containers

and use Inventory to manage location• Add custom extensions


Design Synthesis/Purification

Materials/Sample logisticsScreening/Testing

• Procure materials

• Synthesize

• Purify/characterize

• Prepare Sample

• Dissolve

• Dilute

• Distribute to screen

• Reduce raw data• Execute screen

• Develop the assay

• Select compounds to make

• Mine, search and invent analogs

• Analyze patternsProject Workflow & Tracking and

Decision making

• Assess design ideas

• Load data to dbs

• Procure reagents

Discovery Cycle


Initial load of HTS data


Analyze HTS data in Vortex

Next step: Resynthesize & test the hits…


Synthesis - ChemELN


Compound Registration – from ChemELN


Sample Logistics


Materials Management


Assay Data Processing and Publishing


Design – Analyze Data

Multiple tabs – all data in one place


Design – Analyze PK data (from Winnonlin)


Design – Analyze Stability Data


Behind the Scenes


Dotmatics Pivoter

Instead of trying to use Oracle’s PIVOT statement, you point and click


Example Pivot


Dotmatics Pivoter converts PK data from this


To this

Data here is output of Dotmatics Pivoter


Extending Dotmatics Example

• Several of our chemists came from other companies that had a method for automatically adding analytical data to their notebooks

• Requirements: - Take no longer than 24 hours to add spectra to Dotmatics after creation- Exclude certain spectra from being added- Indicate which spectra goes with which notebook and page- Work for both LC and NMR instruments- Never add spectra to a closed notebook page- Never add a spectra that has been removed manually from a page


Analytical instrumentation setup

Agilent LCMS

Agilent LC

Agilent NMR

Replication scripts

run twice daily

Windows File Share

Backup at Offsite Data

Center

Dotmatics Server

DotmaticsELN

Analytical attachment script runs once per day


Extending Dotmatics Example


• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after

creation- Exclude certain spectra from being added- Indicate which spectra goes with which notebook and page- Work for both LC and NMR instruments- Never add spectra to a closed notebook page- Never add a spectra that has been removed manually from a page


Agilent NMR


Agilent LC


Extending Dotmatics Sample


• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after creation ✓ Exclude certain spectra from being added

✓ Indicate which spectra goes with which notebook and page ✓ Work for both LC and NMR instruments

- Never add spectra to a closed notebook page - Never add a spectra that has been removed manually from a page


Processing Algorithm

• Python script runs periodically (using cron) on our Dotmatics server

• It walks the directory tree of the shared folder that contains all of our analytical data

• For each analytical pdf:– A SHA512 hash is calculated for the pdf and checked vs. the database, if found,

pdf is skipped. If not found, hash added to database.– Filename of pdf is analyzed to look for a notebook-page pattern. If not found,

skipped.– Using notebook and page, experiment is located in TM_EXPERIMENTS table

and EXPERIMENT ID extracted. If experiment is closed or not found, skip.– PDF is added to ELN_QCDATA table with EXPERIMENT ID– Studies ChemELN will read the PDF from the ELN_QCDATA table when the

experiment is opened


Table to record hashes of analytical pdfs


ELN_QCDATA table


CHEMELN page example


Overview


• Requirements: ✓ Take no longer than 24 hours to add spectra to Dotmatics after creation ✓ Exclude certain spectra from being added

✓ Indicate which spectra goes with which notebook and page ✓ Work for both LC and NMR instruments ✓ Never add spectra to a closed notebook page ✓ Never add a spectra that has been removed manually from a page


Summary of Dotmatics

• Grows with us• Supports the Discovery Cycle• Can be extended


Acknowledgments

Peloton Therapeutics, Inc. DotmaticsZhaodan CaoTzuling ChengRobert CzerwinskiXinlin DuBarry GogginJonas GrinaGuangzhou HanHeli HuangJohn Josey

James RizziStephen SchlachterHuiling TanBin WangKeshi WangPaul WehnShanhai XieRui XuHanbiao Yang

Alister CampbellPhil MounteneyDan Ormsby

Jason CastanadaTheresa Smith


Q & A

• Contact Information:– Robert Coner– Peloton Therapeutics– Manager, R&D Informatics– 2330 Inwood Drive, Suite 226, Dallas, TX 75235– [email protected]– Phone: +1-469-271-7811– https://www.linkedin.com/in/bobconer– Skypeid: conerbob

2016_may dotmatics ugm bob coner

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